Indeterminate test results of T-SPOT.TB performed under routine field conditions

Interferon-gamma release assays for the diagnosis of tuberculosis (TB) can give indeterminate results. The prevalence of indeterminate test results (ITRs) among T-SPOT.TB tests was assessed. A retrospective analysis of samples processed in 2005 was performed. ITRs were assessed by age, sex, immunosuppression, distance to the laboratory and season. A subgroup of tests performed for specific indications (contact tracing, migrants with positive tuberculin skin test, TB suspects and immunosuppression) were analysed separately. Of a total of 1,429 tests, 49 (3.4%) were indeterminate. ITRs were significantly associated with old age (>75 versus 5-75 yrs; odds ratio (OR) 7.97, 95% confidence interval (CI) 3.968-15.438) and the season during which samples were transported (autumn and winter versus spring and summer; OR 3.47, 95% CI 1.753-7.514). The incidence of ITR was 302 (2.0%) among TB contacts, 75 (1.6%) among immigrants, 156 (3.0%) in TB suspects and 32 (3.0%) among immunosuppressed patients. Sex, young age and distance to the laboratory were not associated with the rate of ITR. Of the 13 tests with ITR that were repeated, 10 gave a clear positive or negative result. Indeterminate test results with T-SPOT.TB under routine conditions were infrequent and more common in individuals aged >75 yrs than in children and younger adults. The incidence of indeterminate test results was low and similar among healthy tuberculosis contacts, immigrants with a positive tuberculin skin test, tuberculosis suspects and the immunosuppressed. The conditions of transportation may influence the incidence of indeterminate test results.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

The Alcohol Use Disorders Identification Test (AUDIT) as a screening tool for excessive drinking in primary care: reliability and validity of a French version.

BACKGROUND: Excessive drinking is a major problem in Western countries. AUDIT (Alcohol Use Disorders Identification Test) is a 10-item questionnaire developed as a transcultural screening tool to detect excessive alcohol consumption and dependence in primary health care settings. OBJECTIVES: The aim of the study is to validate a French version of the Alcohol Use Disorders Identification Test (AUDIT). METHODS: We conducted a validation cross-sectional study in three French-speaking areas (Paris, Geneva and Lausanne). We examined psychometric properties of AUDIT as its internal consistency, and its capacity to correctly diagnose alcohol abuse or dependence as defined by DSM-IV and to detect hazardous drinking (defined as alcohol intake >30 g pure ethanol per day for men and >20 g of pure ethanol per day for women). We calculated sensitivity, specificity, positive and negative predictive values and Receiver Operator Characteristic curves. Finally, we compared the ability of AUDIT to accurately detect "alcohol abuse/dependence" with that of CAGE and MAST. RESULTS: 1207 patients presenting to outpatient clinics (Switzerland, n = 580) or general practitioners' (France, n = 627) successively completed CAGE, MAST and AUDIT self-administered questionnaires, and were independently interviewed by a trained addiction specialist. AUDIT showed a good capacity to discriminate dependent patients (with AUDIT > or =13 for males, sensitivity 70.1%, specificity 95.2%, PPV 85.7%, NPV 94.7% and for females sensitivity 94.7%, specificity 98.2%, PPV 100%, NPV 99.8%); and hazardous drinkers (with AUDIT > or =7, for males sensitivity 83.5%, specificity 79.9%, PPV 55.0%, NPV 82.7% and with AUDIT > or =6 for females, sensitivity 81.2%, specificity 93.7%, PPV 64.0%, NPV 72.0%). AUDIT gives better results than MAST and CAGE for detecting "Alcohol abuse/dependence" as showed on the comparative ROC curves. CONCLUSIONS: The AUDIT questionnaire remains a good screening instrument for French-speaking primary care.

A new clinical test in diagnosing quadriceps tendon rupture.

INTRODUCTION: Extensor mechanism ruptures might be easily overlooked and misdiagnosed, and delayed diagnosis of quadriceps tendon rupture is frequent. However, the literature recommends early surgical repair within 72 h. PATIENTS AND METHODS: This paper describes a new simple clinical diagnostic test that directly evaluates the integrity of the distal 5 cm of the quadriceps tendon itself. It consists of inserting a needle in the tendon, proximal to the suspected rupture and mobilising the knee joint. RESULTS: The suspected ruptured quadriceps tendons with a positive 'needle' diagnostic test were confirmed intra-operatively. CONCLUSIONS: This minimally invasive and easily available technique should be considered in the diagnostic work-up and treatment planning of patients with suspected tears of the quadriceps tendon.

Penser un modèle de complémentarité de trois épreuves projectives (Hand-Test, Rorschach et TAT) dans une perspective psychodynamique : un défi méthodologique et épistémologique

L'idée de complémentarité de certaines épreuves projectives s'est dessinée dès les années 1960, telles que Rorschach - test du Village, Rorschach - CAT et enfin Rorschach - TAT. L'essentiel des dispositifs projectifs mobilise les épreuves de Rorschach et de TAT dont la complémentarité a été largement pointée, notamment, par Anzieu et Chabert (1983), Chabert (1998), Roman (2006, 2007, 2009) et Emmanuelli et Azoulay (2001, 2008, 2009). Les épreuves de Hand-Test, Rorschach et TAT opèrent selon des dynamiques différentes à partir de consignes, sorte d'« injonction à imaginer » (Roman, 2008). Le défi méthodologique et épistémologique est d'envisager une complémentarité entre ces trois épreuves projectives, complémentarité qui ne va pas de soi dans la mesure où le Hand-Test a été pensé à partir du modèle de l'Analyse Structurale, le Rorschach et le TAT dans une perspective psychodynamique. L'enjeu du défi est de parvenir à se dégager du modèle de l'Analyse Structurale, d'une dimension déterministe et inscrire le Hand-Test dans une dimension processuelle d'une part, et de croiser ces trois épreuves afin de parvenir à mettre en avant les ressources du sujet quant à l'émergence de potentialités de transformations bien souvent, trop souvent, reléguées au second plan, voire négligées, lors de la prise en charge institutionnelle d'autre part. Ainsi, l'approche de la complémentarité des épreuves se trouve au service d'une compréhension de l'évolution du rapport à l'agir chez les adolescents. L'écart qui se donne à voir entre la conception des épreuves projectives envisagées dans une perspective psychodynamique et la manière d'appréhender le Hand-Test constitue le défi méthodologique et épistémologique que nous proposons de discuter.

Rifaximin treatment for the irritable bowel syndrome with a positive lactulose hydrogen breath test improves symptoms for at least 3 months.

BACKGROUND: While rifaximin was able to improve symptoms in patients with irritable bowel syndrome (IBS) in phase III trials, these results are yet to be repeated in phase IV studies. AIM: To evaluate the treatment response to rifaximin in IBS patients in a phase IV trial. METHODS: IBS patients underwent lactulose hydrogen breath testing (LHBT). LHBT-positive patients were treated with rifaximin for 14 days. Prior to treatment as well as at week 4 and 14 following the start of rifaximin treatment, patients completed a questionnaire assessing symptom severity on a Likert scale from 0 to 10. RESULTS: One hundred and six of 150 IBS patients (71%) were LHBT-positive and treated with rifaximin. As assessed at week 4 following commencement of the therapy, rifaximin provided significant improvement of the following IBS-associated symptoms: bloating (5.5±2.6 before the start of the treatment vs. 3.6±2.7 at week 4, P<0.001), flatulence (5.0±2.7 vs. 4.0±2.7, P=0.015), diarrhoea (2.9±2.4 vs. 2.0±2.4, P=0.005) and abdominal pain (4.8±2.7 vs. 3.3±2.5, P<0.001). Overall well-being also significantly improved (3.9 ± 2.4 vs. 2.7 ± 2.3, P < 0.001). Similar improvements in IBS symptoms were obtained at week 14. Eighty-six per cent of patients undergoing repetitive LHBT (55/64) tested negative at week 4. CONCLUSIONS: We found a high percentage of LHBT-positive IBS patients. IBS-associated symptoms (bloating, flatulence, diarrhoea, pain) were improved for a period of 3 months following 2 weeks of treatment with rifaximin. We conclude that rifaximin treatment alleviates symptoms in LHBT-positive IBS patients.

Neuro-mechanical and metabolic adjustments to the repeated anaerobic sprint test in professional football players.

PURPOSE: This study aimed to determine the neuro-mechanical and metabolic adjustments in the lower limbs induced by the running anaerobic sprint test (the so-called RAST). METHODS: Eight professional football players performed 6 × 35 m sprints interspersed with 10 s of active recovery on artificial turf with their football shoes. Sprinting mechanics (plantar pressure insoles), root mean square activity of the vastus lateralis (VL), rectus femoris (RF), and biceps femoris (BF) muscles (surface electromyography, EMG) and VL muscle oxygenation (near-infrared spectroscopy) were monitored continuously. RESULTS: Sprint time, contact time and total stride duration increased from the first to the last repetition (+17.4, +20.0 and +16.6 %; all P < 0.05), while flight time and stride length remained constant. Stride frequency (-13.9 %; P < 0.001) and vertical stiffness decreased (-27.2 %; P < 0.001) across trials. Root mean square EMG activities of RF and BF (-18.7 and -18.1 %; P < 0.01 and 0.001, respectively), but not VL (-1.2 %; P > 0.05), decreased over sprint repetitions and were correlated with the increase in running time (r = -0.82 and -0.90; both P < 0.05). Together with a better maintenance of RF and BF muscles activation levels over sprint repetitions, players with a better repeated-sprint performance (lower cumulated times) also displayed faster muscle de- (during sprints) and re-oxygenation (during recovery) rates (r = -0.74 and -0.84; P < 0.05 and 0.01, respectively). CONCLUSION: The repeated anaerobic sprint test leads to substantial alterations in stride mechanics and leg-spring behaviour. Our results also strengthen the link between repeated-sprint ability and the change in neuromuscular activation as well as in muscle de- and re-oxygenation rates.

Educational intervention for parents of adolescents with chronic illness: a pre-post test pilot study.

OBJECTIVE: This pilot experimental study tested the feasibility and intended effect of an educational intervention for parents to help them assist their adolescent child with chronic illness (CI) in becoming autonomous. METHODS: A two-phase pre-post pilot intervention study targeting parents of adolescents with CI was conducted. Parents were allocated to group 1 and 2 and received the four-module intervention consecutively. Intended effect was measured through online questionnaires for parents and adolescents before, at 2 months after, and at 4-6 months after the intervention. Feasibility was assessed through an evaluation questionnaire for parents. RESULTS: The most useful considered modules concerned the future of the adolescent and parents and social life. The most valued aspect was to exchange with other parents going through similar problems and receiving a new outlook on their relationship with their child. For parents, improvement trends appeared for shared management, parent protection, and self-efficacy, and worsening trends appeared for coping skills, parental perception of child vulnerability, and parental stress. For adolescents, improvement trends appeared for self-efficacy and parental bonding and worsening trends appeared for shared management and coping skills. CONCLUSION: Parents could benefit from peer-to-peer support and education as they support the needed autonomy development of their child. Future studies should test an online platform for parents to find peer support at all times and places.

Discrepancy between Visual Acuity and Microperimetry in AMD Patients: Visual Acuity Appears as an Inadequate Parameter to Test Macular Function.

BACKGROUND: Best corrected visual acuity (BCVA) of 0.8 or above in AMD patients can sometimes correspond to poor macular function inducing a serious visual handicap. Microperimetry can be used to objectivize this difference. PATIENTS AND METHODS: A retrospective study was undertaken on 233 files of AMD patients of whom 82 had had a microperimetry. BCVA was compared with microperimetry performance. All examinations were performed in an identical setting by the same team of 3 persons. RESULTS: Among the 82 patients included, 32 (39.0%) had a BCVA equal to or above 0.8 even though their microperimetry performance was lower than 200/560 db. 10 of them (12.2% of total) had an even poorer microperimetry below 120/560 db indicating poor macular function. CONCLUSIONS: More than a third of the AMD patients had a bad or very bad microperimetry performance in parallel with a good visual acuity. Microperimetry is a valuable tool to assess and follow real macular function in AMD patients when visual acuity alone can be misleading.

Does phylogeographic structure relate to climatic niche divergence? A test using maritime pine (Pinus pinaster Ait.)

Aim To disentangle the effects of environmental and geographical processes driving phylogenetic distances among clades of maritime pine (Pinus pinaster). To assess the implications for conservation management of combining molecular information with species distribution models (SDMs; which predict species distribution based on known occurrence records and on environmental variables). Location Western Mediterranean Basin and European Atlantic coast. Methods We undertook two cluster analyses for eight genetically defined pine clades based on climatic niche and genetic similarities. We assessed niche similarity by means of a principal component analysis and Schoener's D metric. To calculate genetic similarity, we used the unweighted pair group method with arithmetic mean based on Nei's distance using 266 single nucleotide polymorphisms. We then assessed the contribution of environmental and geographical distances to phylogenetic distance by means of Mantel regression with variance partitioning. Finally, we compared the projection obtained from SDMs fitted from the species level (SDMsp) and composed from the eight clade-level models (SDMcm). Results Genetically and environmentally defined clusters were identical. Environmental and geographical distances explained 12.6% of the phylogenetic distance variation and, overall, geographical and environmental overlap among clades was low. Large differences were detected between SDMsp and SDMcm (57.75% of disagreement in the areas predicted as suitable). Main conclusions The genetic structure within the maritime pine subspecies complex is primarily a consequence of its demographic history, as seen by the high proportion of unexplained variation in phylogenetic distances. Nevertheless, our results highlight the contribution of local environmental adaptation in shaping the lower-order, phylogeographical distribution patterns and spatial genetic structure of maritime pine: (1) genetically and environmentally defined clusters are consistent, and (2) environment, rather than geography, explained a higher proportion of variation in phylogenetic distance. SDMs, key tools in conservation management, better characterize the fundamental niche of the species when they include molecular information.

Clinical utility of a molecular test in adjuvant treatment decision making in women with endocrine-sensitive early stage breast cancer: a retrospective, single center one year experience

Background. Molecular tests for breast cancer (BC) risk assessment are reimbursed by health insurances in Switzerland since the beginning of year 2015. The main current role of these tests is to help oncologists to decide about the usefulness of adjuvant chemotherapy in patients with early stage endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-negative BC. These gene expression signatures aim at predicting the risk of recurrence in this subgroup. One of them (OncotypeDx/OT) also predicts distant metastases rate with or without the addition of cytotoxic chemotherapy to endocrine therapy. The clinical utility of these tests -in addition to existing so-called "clinico-pathological" prognostic and predictive criteria (e.g. stage, grade, biomarkers status)-is still debated. We report a single center one year experience of the use of one molecular test (OT) in clinical decision making. Methods. We extracted from the CHUV Breast Cancer Center data base the total number of BC cases with estrogen-receptor positive (ER+), HER2-negative early breast cancer (node negative (pN0) disease or micrometastases in up to 3 lymph nodes) operated between September 2014 and August 2015. For the cases from this group in which a molecular test had been decided by the tumor board, we collected the clinicopathologic parameters, the initial tumor board decision, and the final adjuvant systemic therapy decision. Results. A molecular test (OT) was done in 12.2% of patients with ER + HER2 negative early BC. The median age was 57.4 years and the median invasive tumor size was 1.7 cm. These patients were classified by ODX testing (Recurrence Score) into low-, intermediate-, and high risk groups, respectively in 27.2%, 63.6% and 9% of cases. Treatment recommendations changed in 18.2%, predominantly from chemotherapyendocrine therapy to endocrine treatment alone. Of 8 patients originally recommended chemotherapy, 25% were recommended endocrine treatment alone after receiving the Recurrence Score result. Conclusions. Though reimbursed by health insurances since January 2015, molecular tests are used moderately in our institution as per the decision of the multidisciplinary tumor board. It's mainly used to obtain a complementary confirmation supporting the decision of no chemotherapy. The OncotypeDx Recurrence Score results were in the intermediate group in 66% of the 9 tested cases but contributed to avoid chemotherapy in 2 patients during the last 12 months.

Ability of physicians to diagnose influenza and usefulness of a rapid influenza antigen test in febrile returning travelers: A randomized controlled trial.

BACKGROUND: Fever is a frequent cause of medical consultation among returning travelers. The objectives of this study were to assess whether physicians were able to identify patients with influenza and whether the use of an influenza rapid diagnostic test (iRDT) modified the clinical management of such patients. METHODS: Randomized controlled trial conducted at 2 different Swiss hospitals between December 2008 and November 2012. Inclusion criteria were 1) age ≥18 years, 2) documented fever of ≥38 °C or anamnestic fever + cough or sore throat within the last 4 days, 3) illness occurring within 14 days after returning from a trip abroad, 4) no definitive alternative diagnosis. Physicians were asked to estimate the likelihood of influenza on clinical grounds, and a single nasopharyngeal swab was taken. Thereafter patients were randomized into 2 groups: i) patients with iRDT (BD Directigen A + B) performed on the nasopharyngeal swab, ii) patients receiving usual care. A quantitative PCR to detect influenza was done on all nasopharyngeal swabs after the recruitment period. Clinical management was evaluated on the basis of cost of medical care, number of X-rays requested and prescription of anti-infective drugs. RESULTS: 100 eligible patients were referred to the investigators. 93 patients had a naso-pharyngeal swab for a PCR and 28 (30%) swabs were positive for influenza. The median probability of influenza estimated by the physician was 70% for the PCR positive cases and 30% for the PCR negative cases (p < 0.001). The sensitivity of the iRDT was only 20%, and specificity 100%. Mean medical cost for the patients managed with iRDT and without iRDT were USD 581 (95%CI 454-707) and USD 661 (95%CI 522-800) respectively. 14/60 (23%) of the patients managed with iRDT were prescribed antibiotics versus 13/33 (39%) in the control group (p = 0.15). No patient received antiviral treatment. CONCLUSION: Influenza was a frequent cause of fever among these febrile returning travelers. Based on their clinical assessment, physicians had a higher level of suspicion for influenza in PCR positive cases. The iRDT used in this study showed a disappointingly low sensitivity and can therefore not be recommended for the management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00821626.

Predicting richness and composition in mountain insect communities at high resolution: a new test of the SESAM framework

Aim The aim of this study was to test different modelling approaches, including a new framework, for predicting the spatial distribution of richness and composition of two insect groups. Location The western Swiss Alps. Methods We compared two community modelling approaches: the classical method of stacking binary prediction obtained fromindividual species distribution models (binary stacked species distribution models, bS-SDMs), and various implementations of a recent framework (spatially explicit species assemblage modelling, SESAM) based on four steps that integrate the different drivers of the assembly process in a unique modelling procedure. We used: (1) five methods to create bS-SDM predictions; (2) two approaches for predicting species richness, by summing individual SDM probabilities or by modelling the number of species (i.e. richness) directly; and (3) five different biotic rules based either on ranking probabilities from SDMs or on community co-occurrence patterns. Combining these various options resulted in 47 implementations for each taxon. Results Species richness of the two taxonomic groups was predicted with good accuracy overall, and in most cases bS-SDM did not produce a biased prediction exceeding the actual number of species in each unit. In the prediction of community composition bS-SDM often also yielded the best evaluation score. In the case of poor performance of bS-SDM (i.e. when bS-SDM overestimated the prediction of richness) the SESAM framework improved predictions of species composition. Main conclusions Our results differed from previous findings using community-level models. First, we show that overprediction of richness by bS-SDM is not a general rule, thus highlighting the relevance of producing good individual SDMs to capture the ecological filters that are important for the assembly process. Second, we confirm the potential of SESAM when richness is overpredicted by bS-SDM; limiting the number of species for each unit and applying biotic rules (here using the ranking of SDM probabilities) can improve predictions of species composition

Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence.