Single Screening Test Research Articles

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis.

BackgroundSchistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting.Methodology/Principal findingsA retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone.ConclusionsThe rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.

Is Erythrocyte Protoporphyrin a Better Single Screening Test for Iron Deficiency Compared to Hemoglobin or Mean Cell Volume in Children and Women?

Hemoglobin (Hb), mean cell volume (MCV), and erythrocyte protoporphyrin (EP) are commonly used to screen for iron deficiency (ID), but systematic evaluation of the sensitivity and specificity of these tests is limited. The objective of this study is to determine the sensitivity and specificity of Hb, MCV, and EP measurements in screening for ID in preschool children, non-pregnant women 15–49 years of age, and pregnant women. Data from the National Health and Nutrition Examination Surveys (NHANES) (NHANES 2003–2006: n = 861, children three to five years of age; n = 3112, non-pregnant women 15 to 49 years of age. NHANES 1999–2006: n = 1150, pregnant women) were examined for this purpose. Children or women with blood lead ≥10 µg/dL or C-reactive protein (CRP) >5.0 mg/L were excluded. ID was defined as total body iron stores <0 mg/kg body weight, calculated from the ratio of soluble transferrin receptor (sTfR) to serum ferritin (SF). The receiver operating characteristic (ROC) curve was used to characterize the sensitivity and specificity of Hb, MCV, and EP measurements in screening for ID. In detecting ID in children three to five years of age, EP (Area under the Curve (AUC) 0.80) was superior to Hb (AUC 0.62) (p < 0.01) but not statistically different from MCV (AUC 0.73). In women, EP and Hb were comparable (non-pregnant AUC 0.86 and 0.84, respectively; pregnant 0.77 and 0.74, respectively), and both were better than MCV (non-pregnant AUC 0.80; pregnant 0.70) (p < 0.01). We concluded that the sensitivity and specificity of EP in screening for ID were consistently superior to or at least as effective as those of Hb and MCV in each population examined. For children three to five years of age, EP screening for ID was significantly better than Hb and similar to MCV. For both non-pregnant and pregnant women, the performance of EP and Hb were comparable; both were significantly superior to MCV.

Neuroanatomical and Neuropsychological Markers of Amnestic MCI: A Three-Year Longitudinal Study in Individuals Unaware of Cognitive Decline.

Structural brain changes underlying mild cognitive impairment (MCI) have been well-researched, but most previous studies required subjective cognitive complaints (SCC) as a diagnostic criterion, diagnosed MCI based on a single screening test or lacked analyses in relation to neuropsychological impairment. This longitudinal voxel-based morphometry study aimed to overcome these limitations: The relationship between regional gray matter (GM) atrophy and behavioral performance was investigated over the course of 3 years in individuals unaware of cognitive decline, identified as amnestic MCI based on an extensive neuropsychological test battery. Region of interest analyses revealed GM atrophy in the left amygdala, hippocampus, and parahippocampus in MCI individuals compared to normally aging participants, which was specifically related to verbal memory impairment and evident already at the first measurement point. These findings demonstrate that GM atrophy is detectable in individuals with amnestic MCI despite unawareness of beginning cognitive decline. Thus, individuals with GM atrophy in regions associated with verbal memory impairment do not necessarily need to experience SCC before meeting neuropsychological criteria for MCI. These results have important implications for future research and diagnostic procedures of MCI.

Eficacia de la prueba de detección del virus del papiloma humano (VPH) para el rastreo de cáncer de cuello uterino

Cervical cancer (CC) represents the second cause of cancer deaths in the world among women aged 35 to 64 years old.In Argentina there 4000 cases are diagnosed each year and around 1800 women die each year. The World HealthOrganization and Pan-American Health Organization propose a single screening test that, if positive, defines the ade-quate immediate treatment. Argentina’s Health Ministry incorporated in 2011 the Human Papilloma Virus (HPV) test(together with cytology) as a mean of early detection of CC in the province of Jujuy and later on other provinces. We conducted a bibliographic search of the evidence of diagnostic accuracy and effectiveness of HPV test. The resultshighlight that HPV testing has greater sensitivity and similar specificity compared to cytology and it is also effective inreducing CC mortality, therefore HPV testing should be used as first screening test for CC.

Comparison of Iadpsg And Dipsi Criteria for Diagnosis of Gestational Diabetes Mellitus

Aim: DIPSI (Diabetes in Pregnancy Study Group India ) guidelines recommends the non-fasting 75gms glucose tolerance test as a single step screening and diagnostic test for GDM. International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines states that when a pregnant women walks into the antenatal clinic in fasting state, fasting blood sugar has to be taken. Then 75gms oral glucose to be given and 1hr &2hr venous plasma glucose has to be taken. Fasting plasma glucose > 92mgs/dl, 1hr plasma glucose > 180mgs/dl or 2hr plasma glucose > 153mgs/dl diagnoses GDM. Our objective was to study the implications of implementing the IADPSG guidelines and DIPSI guidelines for screening and diagnosis of GDM in Indian population. Method: Prospective study of a total of 100 pregnant women attending AN clinic at GMKMCH, Salem from February 2016 to august 2016 underwent a 75gms OGTT in non-fasting state. Then after 2-3 days apart fasting, after 75gms glucose load 1hr & 2hr plasma glucose was taken. Venous plasma glucose was measured using an auto analyser and GDM was diagnosed by DIPSI and IADPSG criteria. Results: Among them 14% were diagnosed by DIPSI criteria. 9% were diagnosed by IADPSG criteria.4% were diagnosed by both. Diagnosis of GDM by IADPSG criteria leaves 5% undiagnosed which may be easily detected through DIPSI. Eventhough the DIPSI criteria detects more number of cases than IADPSG criteria, it is not statically significant. Because DIPSI method is practically easier to do which also detects more number of cases ,it is better than IADPSG method.

Abstract PR529

Background & Objectives: Airway management remains one of the most important responsibilities of an anaesthesiologist. The purpose of this study was to compare preoperative anaesthetic airway evaluation methods of Modified Mallampati Test (MMT) and Upper Lip Bite Test (ULBT) to predict difficult intubation with the direct laryngoscopy views obtained during tracheal intubations. Materials & Methods: 200 patients (of either sex aged between 18 years and 55 years) undergoing elective surgical procedures under general anaesthesia with endotracheal intubation were evaluated for both tests before surgery. An experienced anesthesiologist, unaware of preoperative airway evaluation, performed the laryngoscopy and grading (as per Cormack and Lehane’s classification). Sensitivity, specificity, accuracy, positive and negative predictive values of upper lip bite test and Modified Mallampati test were calculated. Results: On comparing both the tests, we found that, MMT is more sensitive (75.00%) than ULBT (25.00%), both tests had high specificity (MMT 91.30%; ULBT 95.11%). Positive predictive value was 42.86% for MMT while it was 30.77% for ULBT. Similarly negative predictive value was 97.67% and 93.58% for MMT and ULBT respectively. Accuracy of MMT was 90.00% for MMT while it was 89.5% for ULBT. Conclusion: Both the tests are poor predictors of difficult intubation (low positive predictive values) when used as single preoperative bedside screening tests. MMT is a better test at predicting difficult endotracheal intubation when compared to ULBT. Both the tests are better predictors of easy intubations rather than difficult intubations (high negative predictive value).

Evaluation of three competitive ELISAs and a fluorescence polarisation assay for the diagnosis of bovine brucellosis

Bovine brucellosis is an infectious disease of worldwide public health and economic importance. The usual tests for the diagnosis of this disease include the Rose-Bengal test (RBT), complement fixation test (CFT), serum agglutination test (SAT) and indirect ELISA. New tests such as competitive ELISAs (C-ELISA) and fluorescence polarisation assay (FPA) have been developed. However, C-ELISA may correspond to different protocols and a wide variation may exist in their diagnostic performance. The aim of this study was to evaluate three commercially available C-ELISA kits (C-ELISA1–3) and FPA for the diagnosis of bovine brucellosis and compare test performance with RBT, CFT, indirect ELISA and FPA. Sera submitted to EU laboratories in 2011 from 5111 adult cattle were tested. Individual test sensitivities (Se) and specificities (Sp) were estimated. Threshold assessment using the receiver operating characteristic method was also performed.The most sensitive tests were FPA (99.0%; 95% confidence interval [CI], 97.9-100%), C-ELISA1 (98.4%; 95% CI, 97.0-99.8%) and RBT (97.7%; 95% CI, 95.9-99.3%). The most specific tests were CFT (99.98%; 95% CI, 99.93-100%), SAT (99.98%; 95% CI, 99.93-100%) and RBT (99.89%; 95% CI, 99.79-99.99%). Among the new tests, none of the three C-ELISA kits studied could be recommended as a single screening test because of their low specificity, especially when used in a herd. C-ELISA3 could not be recommended as confirmatory test on individual animals to determine whether false positive serological test results had occurred.

Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model

Tuberculosis (TB) remains a major global public health problem, and improved treatments are needed to shorten duration of therapy, decrease disease burden, improve compliance, and combat emergence of drug resistance. Ideally, the most effective regimen would be identified by a systematic and comprehensive combinatorial search of large numbers of TB drugs. However, optimization of regimens by standard methods is challenging, especially as the number of drugs increases, because of the extremely large number of drug-dose combinations requiring testing. Herein, we used an optimization platform, feedback system control (FSC) methodology, to identify improved drug-dose combinations for TB treatment using a fluorescence-based human macrophage cell culture model of TB, in which macrophages are infected with isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible green fluorescent protein (GFP)-expressing Mycobacterium tuberculosis (Mtb). On the basis of only a single screening test and three iterations, we identified highly efficacious three- and four-drug combinations. To verify the efficacy of these combinations, we further evaluated them using a methodologically independent assay for intramacrophage killing of Mtb; the optimized combinations showed greater efficacy than the current standard TB drug regimen. Surprisingly, all top three- and four-drug optimized regimens included the third-line drug clofazimine, and none included the first-line drugs isoniazid and rifampin, which had insignificant or antagonistic impacts on efficacy. Because top regimens also did not include a fluoroquinolone or aminoglycoside, they are potentially of use for treating many cases of multidrug- and extensively drug-resistant TB. Our study shows the power of an FSC platform to identify promising previously unidentified drug-dose combinations for treatment of TB.

Sporadic Creutzfeldt–Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay

Protein 14-3-3 is a reliable marker of rapid neuronal damage, specifically increased in cerebrospinal fluid (CSF) of sporadic Creutzfeldt–Jakob disease (sCJD) patients. Its detection is usually performed by Western Blot (WB), prone to methodological issues. Our aim was to evaluate the diagnostic performance of a recently developed quantitative enzyme-linked immunosorbent (ELISA) assay for 14-3-3γ, in comparison with WB and other neurodegeneration markers. CSF samples from 145 patients with suspicion of prion disease, later classified as definite sCJD (n=72) or Non-prion diseases (Non-CJD; n=73) comprised our population. 14-3-3 protein was determined by WB and ELISA. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) were also evaluated. Apolipoprotein E gene (ApoE) and prionic protein gene (PRNP) genotyping was assessed. ELISA 14-3-3γ levels were significantly increased in sCJD compared to Non-CJD patients (p<0.001), showing very good accuracy (AUC=0.982; sensitivity=97%; specificity=94%), and matching WB results in 81% of all cases. It strongly correlated with t-Tau and p-Tau (p<0.0001), showing slightly higher specificity (14-3-3 WB – 63%; Tau – 90%; p-Tau/t-Tau ratio – 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results.

Prevalence of Low VWF, VWD, and Isolated Collagen Binding Defects in Subjects Undergoing Evaluation for VWD

Laboratory testing of von Willebrand disease (VWD) continues to be a complicated and much debated subject. There are multiple tests recommended to assess varying aspects of von Willebrand factor (VWF) function, and no single test that identifies all VWD. In order to investigate the relative effectiveness of VWF laboratory testing, we examined a series of samples sent to a central reference laboratory for a VWD screen, which included VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), factor VIII activity (FVIII), and quantitative analysis of multimer distribution. Institutional review board approval was obtained to add testing for VWF binding to collagens 3, 4, and 6 (VWF:CB3, VWF:CB4, and VWF:CB6). Although no additional clinical information was available on the subjects, we presume that some degree of bleeding symptoms were present to drive clinical ordering of the VWD screen. A total of 882 subjects had results available for all the indicated VWF assays.With regard to VWF levels, 24% of subjects had VWF:RCo below the assay's lower limit of normal (54 IU/dL) and 16% had VWF:Ag below the assay's lower limit of normal (50 IU/dL), classified here as "Low VWF". Only 2% of subjects had either VWF:Ag or VWF:RCo < 30 IU/dL, consistent with the NHLBI's published guidelines on diagnosis of VWD. Only one subject (01.%) had an isolated defect in binding to collagen 3, defined as a VWF:CB/VWF:Ag ratio <0.5 and normal multimer distribution. However, 13 subjects (1.5%) had an isolated defect in binding collagens 4 and/or 6. Concordance between collagen 4 and 6 levels was observed for all subjects, although differences in collagen 3 vs collagens 4 and 6 were observed.With regard to multimer distribution, 2% of subjects had an abnormal multimer distribution including loss of high molecular weight or borderline abnormal multimer structure (defined as loss of the very highest molecular weight multimers). Of the subjects with abnormal multimer distribution, 82% had either abnormal VWF:RCo/VWF:Ag or VWF:CB/VWF:Ag ratios, leaving only 0.3% of the study population with an abnormal multimer distribution that would not have been suspected without formal multimer testing. Only 1% would be considered for a diagnosis of type 2A or type 2B. However, those subjects with loss of the very highest molecular weight multimers may represent acquired abnormalities related to sample processing defects rather than true structural abnormalities. 22 subjects (2.5%) had low VWF and a discrepancy between VWF:Ag and VWF:RCo suspicious for a diagnosis of type 2M VWD.Low VWF is a not uncommon finding in subjects undergoing evaluation for VWD. Although this data cannot confirm the degree of clinical symptoms present in the subjects under study, it is certainly consistent with the idea that specific screening for VWD is of high utility in patients presenting with bleeding complaints. A limitation of this study, however, is that laboratory data cannot be directly linked to phenotype, and it is possible that only patients at high risk of having VWD were screened and therefore the risk in the general population is much lower. Multimer defects were uncommon, and generally but not always confirmed by low collagen binding, which may be dependent upon the degree of structural abnormality, missing very subtle abnormalities. However, the use of two multimer-dependent screening tests (VWF:RCo and VWF:CB) improved the detection of multimer defects. In subjects with normal multimer distribution, defects in collagen 4 or 6 binding were far more common than defects in collagen 3 binding, and of equivalent frequency to low VWF levels. VWF collagen binding is not often included in the diagnostic workup for suspected VWD patients, but our data indicate that isolated defects in VWF binding to collagens 3 and 4 or 6 may be overlooked. Although this study did not confirm bleeding symptoms, our previously reported data indicate that subjects with VWF collagen binding defects may have increased bleeding symptoms. This data confirms the lack of a single screening test for VWD, and suggests that in order to fully exclude a diagnosis of VWD, a broad spectrum of assays is required. DisclosuresFriedman:CSL Behring: Consultancy; Instrumentation Laboratories: Consultancy; Novo Nordisk: Consultancy; Alexion: Speakers Bureau. Flood:Baxter: Consultancy; CSL Behring: Consultancy.

Besonderheiten der postoperativen Peritonitis

Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity.

Is YKL-40 (CHI3-L1) a new possible biomarker prognosticator in high grade glioma?

Abstract A biomarker is “a naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process, disease, etc. can be identified” and it could be used a measurable indicator for the presence or severity of disease state. YKL-40 is a secreted glycoprotein associated with extracellular matrix, a member of the mammalian chitinase-like proteins that is expressed in a several types of solid tumors. Although the implication of this biomarker in tissue remodeling processes or the role in cancer cell proliferation, invasiveness, angiogenesis, and remodeling of the extracellular matrix is going to be well recognized, the regulation and role in glioblastoma multiforme (GBM) progression remains unknown. Using the serum level of YKL-40 as a single screening test in cancer cannot be used, but in association with other tumoral biomarkers and imaging techniques can be a useful tool as a “prognosticator.” Moreover, elucidation of the YKL-40 functions could be an attractive target for antitumor therapy.

The Use of NESTROFT for Screening Pregnant Women for Detection of β-Thalassemia Carriers

The thalassemias and sickle cell disorders are widely distributed in India and cause a significant health burden [1, 2]. Community control programmes are the only way to reduce this burden. Screening for identification of carriers forms an integral component of a prevention programme [1, 2]. The often-debated questions are whom to screen and which would be the most appropriate technology to be used. The individuals targeted for screening in most studies include school or university students, newly-married couples, pregnant women, extended family members of a thalassemia major child, or members of communities where the prevalence of b-thalassemia carriers is higher than the average of 3 %–4 % in the Indian population. Pregnant women would be the most appropriate group as they are the ones at immediate risk but they often come late in the second trimester of pregnancy to the antenatal clinic for their first visit, especially in public hospitals, and it is often difficult to get their husbands for testing [3]. All these target groups have been screened in India by different centers [4–7]. Premarital screening is largely not acceptable due to fear of stigmatization. The technologies used for screening and diagnosis, include the following: Naked eye single tube red cell osmotic fragility test (NESTROFT); red cell indices; discriminant functions; flow cytometric osmotic fragility; and hemoglobin analysis by high-performance liquid chromatography (HPLC), capillary electrophoresis, or cellulose acetate electrophoresis for estimation of Hb A2, Hb F or other hemoglobin variants. A combination of these methods has been used by different investigators and each one has its advantages and limitations [8–13]. NESTROFT has been used as a primary screening test for population screening in many studies after Kattamis et al. first showed that a 0.36 % saline solution was sensitive and effectively detected more than 96 % of b-thalassemia carriers on screening [14]. The ideal approach would be to measure the red cell indices and quantitate Hb A2, Hb F, and any other hemoglobin variant by HPLC or capillary electrophoresis in every individual to ensure that all b-thalassemia heterozygotes as well as carriers of abnormal hemoglobins are identified. However, this is not a cost-effective strategy for massscreening programmes in a large country. Moreover, even with this ideal strategy, around 2 % of b-thalassemia heterozygotes who have normal red cell indices, and/or normal or borderline Hb A2 levels will be missed. NESTROFT has a high sensitivity but lower specificity as shown in several studies [8–13]. Using NESTROFT as a single first-line screening test has some limitations. Although it has a high negative predictive value, few bthalassemia carriers have been missed in different studies. In a quality control evaluation done during the large multicenter study of Indian Council of Medical Research (ICMR) under the Jai Vigyan programme, the main reasons for higher number of false negatives at some centers were the quality of water used, inaccurate dilution of the buffer, and frequent change of technicians. It was also shown that if NESTROFT was combined with measuring red cell indices in the first step itself using mean corpuscular volume (MCV) \80 fL and mean corpuscular hemoglobin (MHC)\27 pg as cut-off values, the b-thalassemia carriers & Roshan B. Colah colahrb@gmail.com

Reliability of dipstick assay in predicting urinary tract infection.

Aims:Urine dipstick analysis is a quick, cheap and a useful test in predicting Urinary Tract Infection (UTI) in hospitalized patients. Our aim is to evaluate the reliability (sensitivity) of urine dipstick analysis against urine culture in the diagnosis of UTI.Materials and Methods:Patients admitted to our hospital suspected of having UTI, with positive urine cultures were included in this study from a 2-year period (January 2011 to December 2012). Dipstick urinalysis was done using multistix 10 SG (Siemens) and clinitek advantus analyzer. The sensitivity of dipstick nitrites, leukocyte esterase and blood in these culture-positive UTI patients was calculated retrospectively.Results:Urine dipstick analysis of 635 urine culture-positive patients was studied. The sensitivity of nitrite alone and leukocyte esterase alone were 23.31% and 48.5%, respectively. The sensitivity of blood alone in positive urine culture was 63.94%, which was the highest sensitivity for a single screening test. The presence of leukocyte esterase and/or blood increased the sensitivity to 72.28%. The sensitivity was found to be the highest when nitrite, leukocyte and blood were considered together.Conclusions:Nitrite test and leukocyte esterase test when used individually is not reliable to rule out UTI. Hence, symptomatic UTI patients with negative dipstick assay should be subjected to urine culture for a proper management.

Metabolome Profiling by HRMAS NMR Spectroscopy of Pheochromocytomas and Paragangliomas Detects SDH Deficiency: Clinical and Pathophysiological Implications

Succinate dehydrogenase gene (SDHx) mutations increase susceptibility to develop pheochromocytomas/paragangliomas (PHEOs/PGLs). In the present study, we evaluate the performance and clinical applications of 1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy–based global metabolomic profiling in a large series of PHEOs/PGLs of different genetic backgrounds. Eighty-seven PHEOs/PGLs (48 sporadic/23 SDHx/7 von Hippel-Lindau/5 REarranged during Transfection/3 neurofibromatosis type 1/1 hypoxia-inducible factor 2α), one SDHD variant of unknown significance, and two Carney triad (CTr)–related tumors were analyzed by HRMAS-NMR spectroscopy. Compared to sporadic, SDHx-related PHEOs/PGLs exhibit a specific metabolic signature characterized by increased levels of succinate (P < .0001), methionine (P = .002), glutamine (P = .002), and myoinositol (P < .0007) and decreased levels of glutamate (P < .0007), regardless of their location and catecholamine levels. Uniquely, ATP/ascorbate/glutathione was found to be associated with the secretory phenotype of PHEOs/PGLs, regardless of their genotype (P < .0007). The use of succinate as a single screening test retained excellent accuracy in distinguishing SDHx versus non–SDHx-related tumors (sensitivity/specificity: 100/100%). Moreover, the quantification of succinate could be considered a diagnostic alternative for assessing SDHx-related mutations of unknown pathogenicity. We were also able, for the first time, to uncover an SDH-like pattern in the two CTr-related PGLs. The present study demonstrates that HRMAS-NMR provides important information for SDHx-related PHEO/PGL characterization. Besides the high succinate–low glutamate hallmark, SDHx tumors also exhibit high values of methionine, a finding consistent with the hypermethylation pattern of these tumors. We also found important levels of glutamine, suggesting that glutamine metabolism might be involved in the pathogenesis of SDHx-related PHEOs/PGLs.

Asymptomatic bacteriuria in women attending an antenatal clinic at a tertiary care centre

Objective . To compare the diagnostic performance of urine microscopy, leucocyte esterase and nitrite dipstick tests and various combinations of these as screening tests for asymptomatic bacteriuria in pregnancy. Methods . Pregnant women (N=800) attending an antenatal clinic were recruited at their first visit. Urine microscopy, culture and dipstick testing were performed on a random clean-catch midstream urine sample. A count of >105 colony-forming units of a single organism per millilitre of urine was taken as significant. Dipstick results were read as positive according to the manufacturer’s instructions. Results . A total of 800 eligible women were screened. The prevalence of asymptomatic bacteriuria as diagnosed by urine culture was 5.0% (n=40). Escherichia coli was the most prevalent uropathogen isolated by culture (60.0%). Neither urine microscopy nor the leucocyte test was found to be sufficiently sensitive to be used as a single screening test for asymptomatic bacteriuria in pregnant patients. The nitrite test alone had a sensitivity of 82.5% and a specificity of 99.9%. Combined dipstick testing had an improved sensitivity of 87.3% and a specificity of 96.2%. Addition of urine microscopy to combined dipstick testing increased the sensitivity to 95.0%, and the specificity became 92.4%. Conclusion . Combined dipstick testing is a useful screening test for asymptomatic bacteriuria in pregnancy. Addition of urine microscopy to combined dipstick testing further improves its diagnostic performance.

The selection of a screening test for frailty identification in community-dwelling older adults.

Frailty in older Chinese has been less often studied and the selection of one screening test feasible in primary care and population survey is needed. We attempted to examine the sensitivity and specificity of each of the five Fried's criteria as a single screening test in the identification of frailty. We recruited 4000 community-dwelling Chinese adults 65 years or older stratified by 3 age-stratum and identified frailty as having 3 or more of Fried's criteria: underweight(BMI<18.5), handgrip strength(<lowest quintile), walking speed(<lowest quintile), self-reported exhaustion and low physical activity(PASE score<lowest quintile). The proportion of frailty in the 3 age groups (65-69 years, 70-74 years, 75 years and above) were 2.3%, 3.4% and 11.9% respectively in men and 1.4%, 2.6% and 11.6% in women. Among the 5 criteria, walking speed, grip strength and physical activity (PASE score) divided at their respective lowest quintile values, achieved similar Area Under Curve in the Receiver Operating Characteristics analysis. For walking speed, the sensitivity and specificity were 82.7% and 83.1% in men and 91.9% and 84.5% in women respectively. For grip strength, the corresponding values were 89.5% and 80.6% in men; and 84.5% and 81.9% in women. For physical activity, they were 83.7% and 83.5% in men; and 82.8% and 84.7% in women. Either walking speed or grip strength measurement may be suitable for frailty screening in primary care or population health survey. A cut-off value of 0.9 m/s in walking speed and 28 kg in grip strength for older men; and a corresponding value of 0.8 m/s and 18 kg for older women is recommended for the screening of frailty in community-dwelling older Chinese adults.

Screening for cervical cancer: a systematic review and meta-analysis

BackgroundThe systematic review on which this paper is based provided evidence for the Canadian Task Force on Preventive Health Care to update their guideline regarding screening for cervical cancer. In this article we highlight three questions covered in the full review that pertain to the effectiveness of screening for reducing cervical cancer mortality and incidence as well as optimal timing and frequency of screening.MethodsWe searched MEDLINE, Embase and Cochrane Central from 1995 to 2012 for relevant randomized controlled trials and observational studies with comparison groups. Eligible studies included women aged 15 to 70 years who were screened using conventional cytology, liquid-based cytology or human papillomavirus DNA tests. Relevance screening, data extraction, risk of bias analyses and quality assessments were performed in duplicate. We conducted a meta-analysis using a random-effects model on the one body of evidence that could be pooled.ResultsFrom the 15,145 screened citations, 27 papers (24 studies) were included; five older studies located in a United States Preventive Services Task Force review were also included. A randomized controlled trial in India showed even a single lifetime screening test significantly decreased the risk of mortality from and incidence of advanced cervical cancer compared to no screening (mortality: risk ratio 0.65, 95% confidence interval 0.47, 0.90; incidence: relative risk 0.56, 95% confidence interval 0.42, 0.75). Cytology screening was shown to be beneficial in a cohort study that found testing significantly reduced the risk of being diagnosed with invasive cervical cancer compared to no screening (risk ratio 0.38; 95% confidence interval 0.23, 0.63). Pooled evidence from a dozen case–control studies also indicated a significant protective effect of cytology screening (odds ratio 0.35; 95% confidence interval 0.30, 0.41). This review found no conclusive evidence for establishing optimal ages to start and stop cervical screening, or to determine how often to screen; however the available data suggests substantial protective effects for screening women 30 years and older and for intervals of up to five years.ConclusionsThe available evidence supports the conclusion that cervical screening does offer protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality.

The prevalence of HIV sero-positivity in late pregnancy among antenatal attendees with seronegative status in first half of pregnancy in Nnewi, South East Nigeria

Background: In sub-Saharan Africa, women and children are vulnerable to HIV/AIDS with about 61% of the infections occurring in women and about 90% of the pediatrics infection through Mother-to-child transmission (MTCT). Antenatal attendees in Nigeria are offered routine HIV testing and counselling on the first visit with opt-out option irrespective of the gestational age at contact. This appears commendable but, considering the national HIV prevalence of 4.6%, our large population of >140 million, the long period of seroconversion of the virus and the fact that pregnant women continue to indulge in activities like: unprotected sexual intercourse with single or multiple partners or men with multiple sexual partners or legal polygamy, cross generational sex, intercourse with sero-discordant partners that put them at risk of new infections; a single screening test on contact may not be sufficient to detect all maternal infections. Aim and Objectives: This is to perform a second HIV testing in antenatal women late in pregnancy and determined the sero-prevalence of HIV amongst those who tested negative in the first half of pregnancy. Materials and Methods: This is a prospective cross sectional study conducted among previously HIV negative pregnant women in Nnamdi Azikiwe University Teaching Hospital (NAUTH) Nnewi between November 2010 and February 2011. The rapid test kits: Determine, Stat Pak and Unigold were used for detection/diagnosis of HIV antibody. Semi structured questionnaire was used to collect socio-demographic data of the subjects. Descriptive analysis of the result was done using the SPSS version 16. Results: The HIV prevalence following repeat testing in late pregnancy was 3.91% (9/230). The mean HIV prevalence at antenatal booking during the study period was 20.64% (116/562). Conclusion: The study highlights the high prevalence of HIV among previously negative attendees in late pregnancy. It brings to the fore the enormity of missed opportunity associated with a single routine antibody rapid test for pregnant women on contact/early pregnancy. Therefore, routine repeat antenatal HIV testing and counselling in late pregnancy is strongly advocated.

Virtual Scanning: A New Medical Paradigm?

The medical profession adopts new medical technologies which are deemed necessary to diagnose and treat disease. The current range of technologies allows the clinician to make diagnostic conclusions although the scope, limitations and costs of such diagnostic techniques are often ignored. The aim of this review article is to consider the techniques currently used to diagnose health and to highlight a novel and innovative way of screening the health of the population using a non-invasive cognitive technique. In recent years there has been the emergence of many new medical technologies which adopt vague principles yet instead of reducing the cost of diagnosing disease, each new test adds to the complexity and cost of the healthcare system. In addition, each new test invariably introduces limitations/errors which can influence the test outcomes eg. (i) the genetic profile associated with diabetes differs according to the racial origins of each patient, (ii) diseases are often multi-systemic, therefore the association of one biomarker as a diagnostic indication may be inherently flawed, (iii) genetic screening is not fully reproducible due to profiling errors and (iv) the significance of phenotype is often overlooked. Researchers are working on ways to provide a single genetic screening test which can provide a complete medical diagnosis, companies are working on ways to diagnose state of health using an iPhone, etc. The approaches are invariably innovative yet may lack a fundamental scientific principle which can provide an accurate and reliable diagnostic indication. There is a need for technologies which improve the accuracy of diagnosis, overcome the limitations of current tests, and reduce the cost of diagnosing and treating disease. This article reviews one such technology: Virtual Scanning. Virtual Scanning is based upon three observations: (i) that sense perception, and in particular colour perception, is linked to the function of the autonomic nervous system; (ii) that autonomic dysfunction influences the coherent and synchronised function of the organ networks and ultimately affects cellular and molecular biology; and (iii) the stability of the autonomic nervous system is neurally regulated. Accordingly measurements of colour perception can be used with diagnostic effect and knowledge of the structure of the autonomic nervous system and physiological systems may be used to re-establish the stability of the autonomic nervous system. In summary, the author presents a number of case studies to illustrate the potential scope for Virtual Scanning. In particular how it can be used to diagnose and treat disease.