Consequences of the multipatient use of a single-patient capillary blood sampling device (CBSD)

Introduction/objectives: Multipatient use of a single-patient CBSD occurred inan outpatient clinic during 4 to 16 months before itsnotification. We looked for transmission of blood-bornepathogens among exposed patients.Methods: Exposed patients underwent serology testing for HBV,HCV and HIV. Patients with isolated anti-HBc receivedone dose of hepatitis B vaccine to look for a memoryimmune response. Possible transmissions were investigatedby mapping visits and sequencing of the viral genomeif needed.Results: Of 280 exposed patients, 9 had died without suspicionof blood-borne infection, 3 could not be tested, and 5declined investigations. Among the 263 (93%) testedpatients, 218 (83%) had negative results. We confirmeda known history of HCV infection in 6 patients (1 coinfectedby HIV), and also identified resolved HBVinfection in 37 patients, of whom 18 were alreadyknown. 2 patients were found to have a previouslyunknown HCV infection. According to the time elapsedfrom the closest previous visit of a HCV-infected potentialsource patient, we could rule out nosocomial transmissionin one case (14 weeks) but not in the other (1day). In the latter, however, transmission was deemedvery unlikely by 2 reference centers based on thesequences of the E1 and HVR1 regions of the virus.Conclusion: We did not identify any transmission of blood-bornepathogens in 263 patients exposed to a single-patientCBSD, despite the presence of potential source cases.Change of needle and disinfection of the device betweenpatients may have contributed to this outcome.Although we cannot exclude transmission of HBV, previousacquisition in endemic countries is a more likelyexplanation in this multi-national population.

The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia.

INTRODUCTION: Timely diagnosis of invasive candidiasis (IC) remains difficult as the clinical presentation is not specific and blood cultures lack sensitivity and need a long incubation time. Thus, non-culture-based methods for diagnosing IC have been developed. Mannan antigen (Mn) and anti-mannan antibodies (A-Mn) are present in patients with IC. On behalf of the Third European Conference on Infections in Leukemia, the performance of these tests was analysed and reviewed. METHODS: The literature was searched for studies using the commercially available sandwich enzyme-linked immunosorbent assays (Platelia™, Bio-Rad Laboratories, Marnes-la-Coquette, France) for detecting Mn and A-Mn in serum. The target condition of this review was IC defined according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity, specificity and diagnostic odds ratios (DOR) were calculated for Mn, A-Mn and combined Mn/A-Mn testing. RESULTS: Overall, 14 studies that comprised 453 patients and 767 controls were reviewed. The patient populations included in the studies were mainly haematological and cancer cases in seven studies and mainly intensive care unit and surgery cases in the other seven studies. All studies but one were retrospective in design. Mn sensitivity was 58% (95% confidence interval [CI], 53-62); specificity, 93% (95% CI, 91-94) and DOR, 18 (95% CI 12-28). A-Mn sensitivity was 59% (95% CI, 54-65); specificity, 83% (95% CI, 79-97) and DOR, 12 (95% CI 7-21). Combined Mn/A-Mn sensitivity was 83% (95% CI, 79-87); specificity, 86% (95% CI, 82-90) and DOR, 58 (95% CI 27-122). Significant heterogeneity of the studies was detected. The sensitivity of both Mn and A-Mn varied for different Candida species, and it was the highest for C. albicans, followed by C. glabrata and C. tropicalis. In 73% of 45 patients with candidemia, at least one of the serological tests was positive before the culture results, with mean time advantage being 6 days for Mn and 7 days for A-Mn. In 21 patients with hepatosplenic IC, 18 (86%) had Mn or A-Mn positive test results at a median of 16 days before radiological detection of liver or spleen lesions. CONCLUSIONS: Mn and A-Mn are useful for diagnosis of IC. The performance of combined Mn/A-Mn testing is superior to either Mn or A-Mn testing.

Statin use and peripheral blood progenitor cells mobilization in patients with multiple myeloma.

PURPOSE: Statins have beneficial effects in patients after myocardial infarction and at least part of the benefit results from mobilization of marrow endothelial progenitors to repopulate damaged myocardial tissues. This study examines if statins may have the same effect in mobilizing marrow progenitors to be harvested and subsequently used in high-dose chemotherapy with progenitor cell rescue in multiple myeloma. METHODS: From 2006 to 2012, 86 patients with multiple myeloma were mobilized with the use of G-CSF and were retrospectively analyzed. Patients with other malignancies or mobilized with the use of chemotherapy or with plerixafor were excluded. RESULTS: The median age of the patients was 60 years. 72 patients had received one line of chemotherapy and 14 patients two or more lines of chemotherapy. Twenty patients were taking statins at the time of the harvest while 66 patients were not. In the group of patients taking statins the success rate of first leukapheresis (obtaining the target number of 4 × 10(6) CD34+ cells/kg) was 85 % while in the group not taking statins this rate was 63.6 %. Despite the comparatively small number of patients this difference approached statistical significance (χ (2) = 0.07). CONCLUSION: This retrospective analysis of 86 patients shows for the first time a possible benefit of statins for peripheral blood progenitor cells mobilization in patients with multiple myeloma. Larger studies would be required to clarify the issue. If their effectiveness is confirmed, statins could be a safe and cheaper addition to chemotherapy and plerixafor for peripheral hematopoietic stem cell mobilization.

Routine use of point-of-care tests: usefulness and application in clinical microbiology.

Point-of-care (POC) tests offer potentially substantial benefits for the management of infectious diseases, mainly by shortening the time to result and by making the test available at the bedside or at remote care centres. Commercial POC tests are already widely available for the diagnosis of bacterial and viral infections and for parasitic diseases, including malaria. Infectious diseases specialists and clinical microbiologists should be aware of the indications and limitations of each rapid test, so that they can use them appropriately and correctly interpret their results. The clinical applications and performance of the most relevant and commonly used POC tests are reviewed. Some of these tests exhibit insufficient sensitivity, and should therefore be coupled to confirmatory tests when the results are negative (e.g. Streptococcus pyogenes rapid antigen detection test), whereas the results of others need to be confirmed when positive (e.g. malaria). New molecular-based tests exhibit better sensitivity and specificity than former immunochromatographic assays (e.g. Streptococcus agalactiae detection). In the coming years, further evolution of POC tests may lead to new diagnostic approaches, such as panel testing, targeting not just a single pathogen, but all possible agents suspected in a specific clinical setting. To reach this goal, the development of serology-based and/or molecular-based microarrays/multiplexed tests will be needed. The availability of modern technology and new microfluidic devices will provide clinical microbiologists with the opportunity to be back at the bedside, proposing a large variety of POC tests that will allow quicker diagnosis and improved patient care.

Substance use and suicidal conduct: a study of adolescents hospitalized for suicide attempt and ideation.

AIM: To study the prevalence of psychoactive substance use disorder (PSUD) among suicidal adolescents, psychoactive substance intoxication at the moment of the attempt, and the association between PSUD at baseline and either occurrence of suicide or repetition of suicide attempt(s). METHODS: 186 adolescents aged 16 to 21 y hospitalized for suicide attempt or overwhelming suicidal ideation were included (T0); 148 of them were traced again for evaluations after 6 mo (T1) and/or 18 mo (T2). DSM-IV diagnoses were assessed each time using the Mini International Neuropsychiatric Interview. RESULTS: At T0, 39.2% of the subjects were found to have a PSUD. Among them, a significantly higher proportion was intoxicated at the time of the attempt than those without PSUD (44.3% vs 25.4%). Among the 148 adolescents who could be traced at either T1 or T2, two died from suicide and 30 repeated suicide attempts once or more times. A marginally significant association was found between death by suicide/repetition of suicide attempt and alcohol abuse/dependence at baseline (OR=3.3, 95% CI 0.7-15.0; OR=2.6, 95% CI 0.7-9.3). More than one suicide attempt before admission to hospital at T0 (OR=3.2, 95% CI 1.1-10.0) and age over 19 y at T0 (OR=3.2, 95% CI 1.1-9.2) were independently associated with the likelihood of death by suicide or repetition of suicide attempt. CONCLUSION: Among adolescents hospitalized for suicide attempt or overwhelming suicidal ideation, the risk of death or repetition of attempt is high and is associated with previous suicide attempts--especially among older adolescents--and also marginally associated with PSUD; these adolescents should be carefully evaluated for such risks and followed up once discharged from the hospital.

Substance use and suicidal conducts : a study of adolescents hospitalized for suicide attempt and ideation

RESUME Objectifs: Etudier la prévalence des troubles liés à l'utilisation de substances psychoatives parmi des adolescents suicidaires; évaluer l'influence de la prise de substances psychoactives sur le geste suicidaire; analyser l'association entre les troubles liés à l'utilisation de substances psychoactives et le risque de récidive de la conduite suicidaire. Méthode: 186 adolescents, âgés de 16 à 21 ans, hospitalisés pour tentative de suicide ou idées suicidaires envahissantes, ont été inclus. Parmi eux, 148 ont été revus pour évaluation à 6 et/ou 18 mois. Des diagnostics psychiatriques, basés sur les critères du DSM-IV, ont été posés à l'aide d'un questionnaire, le MINI (Mini International Neuropsychiatric Interview). Résultats: A l'inclusion, 39.2% des sujets avaient un trouble lié à l'utilisation de substances psychoactives. Parmi eux, une proportion significativement plus élevée était sous l'influence d'alcool ou drogue au moment de la tentative de suicide (44.3% versus 25.4%). Des 148 adolescents suivis et revus à 6 ou 18 mois, 2 sont décédés par suicide et il y a eu 30 récidives de tentative de suicide durant l'étude. Une association significative a été trouvée entre les récidives de suicide et un diagnostic d'abus/dépendance à l'alcool à l'inclusion (OR=3.3; CI 0.7-15.0; 0R=2.6, CI 0.7-9.3). Des antécédents de plusieurs tentatives de suicide (OR=3.2; CI 1.1-10.0) et un âge supérieur à 19 ans (OR=3.2; CI 1.1-9.2) à l'inclusion étaient associés à la probabilité de mort par suicide ou de récidive de tentative de suicide. Conclusion: Parmi les adolescents hospitalisés pour tentative de suicide ou idées suicidaires envahissantes, le risque de décès ou de récidive est important. Ce risque est associé, entre autres, à des antécédents suicidaires et au diagnostic de trouble lié à l'utilisation de substances psychoactives. Le risque suicidaire ainsi que la consommation de substances psychoactives devrait être évalué chez les adolescents. De plus, les sujets jugés à risque devraient être suivis systématiquement après une hospitalisation pour conduite suicidaire. ABSTRACT Aim: To study the prevalence of psychoactive substance use disorder (PSUD) among suicidal adolescents, psychoactive substance intoxication at the moment of the attempt and the association between PSUD at baseline and either occurrence of suicide or repetition of suicide attempt(s). Methods: 186 adolescents aged 16 to 21 hospitalised for suicide attempt or overwhelming suicidal ideation were included (TO); 148 of them were traced again for evaluations after 6 months and/or 18 months. DSM-IV diagnoses were assessed each time using the Mini International Neuropsychiatric Interview. Results: At TO, 39.2% of the subjects were found to have a PSUD. Among them, a significantly higher proportion was intoxicated at the time of the attempt than those without PSUD (44-.3% vs. 25.4%). Among the 148 adolescents who could be traced at either Ti or T2, two died from suicide and 30 repeated suicide attempt once or more time. A marginally significant association was found between death by suicide/repetition of suicide attempt and alcohol abuse/dependence at baseline (0R=3.3; CI 0.7-15.0; 0R=2.6, CI 0.7-9.3). More than one suicide attempt before admission to hospital at TO (OR=3.2; CI 1.1-10.0) and age over 19 at TO (0R=3.2; CI 1.1-9.2) were independently associated with the likelihood of death by suicide or repetition of suicide attempt. Conclusion: Among adolescents hospitalised for suicide attempt or overwhelming suicidal ideation, the risk of death or repetition of attempt is high and is associated with previous suicide attempts - especially among older adolescents - and also marginally associated with PSUD; these adolescents should be carefully evaluated for such risks and followed up once discharged from the hospital.

Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study.

OBJECTIVES: We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS: A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART.

Is Internet use unhealthy? A cross-sectional study of adolescent Internet overuse.

OBJECTIVE: To assess whether problematic internet use is associated with somatic complaints and whether this association remains when checking for internet activity among a random sample of adolescents living in the canton of Vaud, Switzerland. METHODS: Cross-sectional survey of 3,067 8th graders (50.3% females) divided into average (n = 2,708) and problematic (n = 359) Internet users and compared for somatic complaints (backache, overweight, headaches, musculoskeletal pain, sleep problems and sight problems) controlling for sociodemographic and internet-related variables. Logistic regressions were performed for each complaint and for all of them simultaneously controlling variables significant at the bivariate level. RESULTS: At the multivariate level, when taken separately, problematic internet users were more likely to have a chronic condition (adjusted odds ratio [aOR] with 95% CI: 1.58 [1.11:2.23]) and to report back pain (aOR: 1.46 [1.04:2.05]), overweight (aOR: 1.74 [1.03:2.93]), musculoskeletal pain (aOR: 1.36 [1.00:1.84]) and sleep problems (aOR: 2.16 [1.62:2.88]). When considered in the full model, only sleep problems remained significant (aOR: 2.03 [1.50:2.74]). CONCLUSIONS: Our results confirm that problematic internet users report health problems more frequently, with lack of sleep being the most strongly associated and seeming to act as mediator regarding the other ones. Clinicians should remember to screen for excessive internet use their patients complaining of sleep-related problems, back or musculoskeletal pain or overweight. Clinicians should advise parents to limit the amount of time their adolescent children can spend online for leisure activities. Furthermore, limiting the number of devices used to connect to the internet could help warrant enough sleeping time.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Real-time monitoring of protein conformational changes using a nano-mechanical sensor.

Proteins can switch between different conformations in response to stimuli, such as pH or temperature variations, or to the binding of ligands. Such plasticity and its kinetics can have a crucial functional role, and their characterization has taken center stage in protein research. As an example, Topoisomerases are particularly interesting enzymes capable of managing tangled and supercoiled double-stranded DNA, thus facilitating many physiological processes. In this work, we describe the use of a cantilever-based nanomotion sensor to characterize the dynamics of human topoisomerase II (Topo II) enzymes and their response to different kinds of ligands, such as ATP, which enhance the conformational dynamics. The sensitivity and time resolution of this sensor allow determining quantitatively the correlation between the ATP concentration and the rate of Topo II conformational changes. Furthermore, we show how to rationalize the experimental results in a comprehensive model that takes into account both the physics of the cantilever and the dynamics of the ATPase cycle of the enzyme, shedding light on the kinetics of the process. Finally, we study the effect of aclarubicin, an anticancer drug, demonstrating that it affects directly the Topo II molecule inhibiting its conformational changes. These results pave the way to a new way of studying the intrinsic dynamics of proteins and of protein complexes allowing new applications ranging from fundamental proteomics to drug discovery and development and possibly to clinical practice.

Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: A systematic review.

BACKGROUND: The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC). The results from these studies have been promising and the most updated version of ATA guidelines quoted for the first time that "FNA findings that are inconclusive or suggestive of MTC should have calcitonin measured in the FNA washout fluid." Here we aimed to systematically review published data on this topic to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the medical databases was conducted by searching for the terms "calcitonin" AND "washout." The search was updated until April 2015. RESULTS: Twelve relevant studies, published between 2007 and 2014, were found. Overall, 413 thyroid nodules or neck lymph nodes underwent FNA-calcitonin, 95 were MTC lesions and 93 (97.9%) of these were correctly detected by this measurement regardless of their cytologic report. CONCLUSIONS: The present study shows that the above ATA recommendation is well supported. Almost all MTC lesions are correctly detected by FNA-calcitonin and this technique should be used to avoid false negative or inconclusive results from cytology. The routine determination of serum calcitonin in patients undergoing FNA should improve the selection of patients at risk for MTC, guiding the use of FNA-calcitonin in the same FNA sample and providing useful information to the cytopathologist for the morphological assessment and the application of tailored ancillary tests.