ALLERGENIC RELATIONSHIP OF THE POLLENS OF DWARF AND GIANT RAGWEED TO SEVERAL OF THEIR BOTANIC RELATIVES.

PubMed

Simon, F A

1943-02-01

Thirty-eight of forty patients, allergic to the pollen of dwarf and giant ragweed, were found to be allergic also to the pollen of botanically related species. There was definite variation in the degree of reactivity to the various pollens in different patients. One additional patient reacted to dwarf ragweed but not to giant ragweed or to four other composites. Antibody neutralization studies in six cases indicated that (a) in four cases dwarf ragweed could have been the only sensitizing allergen. (b) In one case either dwarf or giant ragweed could have been the only sensitizing allergen. (c) In one case cosmos plus either of the ragweeds or some undetermined pollen could have been the sensitizing allergen, (d) In none of the six cases studied could cosmos, sunflower, goldenrod, or dandelion have been the only sensitizing allergens. The evidence presented supports the following concepts: (1) Hypersensitiveness of this type develops as the result of allergenic stimulation. (2) The pollens of the ragweeds and their botanic relatives contain, in addition to species-specific allergens, multiple common allergenic determinants which vary in their distribution among related species. (3) A person exposed simultaneously to a group of allergens may become sensitized to certain members of the group and not to others, while another person, exposed to the same group of allergens, may become sensitized to different members of the group.

Coagulation phenotypes in septic shock as evaluated by calibrated automated thrombography.

PubMed

Perrin, Julien; Charron, Cyril; François, Jean-Hugues; Cramer-Bordé, Elisabeth; Lévy, Bruno; Borgel, Delphine; Vieillard-Baron, Antoine

2015-01-01

Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis.

The work and social adjustment scale: reliability, sensitivity and value.

PubMed

Zahra, Daniel; Qureshi, Adam; Henley, William; Taylor, Rod; Quinn, Cath; Pooler, Jill; Hardy, Gillian; Newbold, Alexandra; Byng, Richard

2014-06-01

To investigate the psychometric properties of the Work and Social Adjustment Scale (WSAS) as an outcome measure for the Improving Access to Psychological Therapy programme, assessing its value as an addition to the Patient Health (PHQ-9) and Generalised Anxiety Disorder questionnaires (GAD-7). Little research has investigated these properties to date. Reliability and responsiveness to change were assessed using data from 4,835 patients. Principal components analysis was used to determine whether the WSAS measures a factor distinct from the PHQ-9 and GAD-7. The WSAS measures a distinct social functioning factor, has high internal reliability, and is sensitive to treatment effects. The WSAS, PHQ-9 and GAD-7 perform comparably on measures of reliability and sensitivity. The WSAS also measures a distinct social functioning component suggesting it has potential as an additional outcome measure.

Added diagnostic value of magnetoencephalography (MEG) in patients suspected for epilepsy, where previous, extensive EEG workup was unrevealing.

PubMed

Duez, Lene; Beniczky, Sándor; Tankisi, Hatice; Hansen, Peter Orm; Sidenius, Per; Sabers, Anne; Fuglsang-Frederiksen, Anders

2016-10-01

To elucidate the possible additional diagnostic yield of MEG in the workup of patients with suspected epilepsy, where repeated EEGs, including sleep-recordings failed to identify abnormalities. Fifty-two consecutive patients with clinical suspicion of epilepsy and at least three normal EEGs, including sleep-EEG, were prospectively analyzed. The reference standard was inferred from the diagnosis obtained from the medical charts, after at least one-year follow-up. MEG (306-channel, whole-head) and simultaneous EEG (MEG-EEG) was recorded for one hour. The added sensitivity of MEG was calculated from the cases where abnormalities were seen in MEG but not EEG. Twenty-two patients had the diagnosis epilepsy according to the reference standard. MEG-EEG detected abnormalities, and supported the diagnosis in nine of the 22 patients with the diagnosis epilepsy at one-year follow-up. Sensitivity of MEG-EEG was 41%. The added sensitivity of MEG was 18%. MEG-EEG was normal in 28 of the 30 patients categorized as 'not epilepsy' at one year follow-up, yielding a specificity of 93%. MEG provides additional diagnostic information in patients suspected for epilepsy, where repeated EEG recordings fail to demonstrate abnormality. MEG should be included in the diagnostic workup of patients where the conventional, widely available methods are unrevealing. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography.

PubMed

Ernst, Marielle; Romero, Javier M; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54-95%) while specificity was high 91% (95%-CI, 82-96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60-98%) and specificity of 84% (95%-CI, 74-90%). In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

PubMed Central

Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

2016-01-01

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

Celiac symptoms in patients with fibromyalgia: a cross-sectional study.

PubMed

García-Leiva, Juan Miguel; Carrasco, Jorge Luis Ordóñez; Slim, Mahmoud; Calandre, Elena P

2015-03-01

Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms including gastrointestinal manifestations of nonspecific nature. Celiac disease and nongluten sensitivity frequently evolve in adults with gastrointestinal and extraintestinal symptoms similar to those found among patients with fibromyalgia. The objective of the present study was to evaluate the presence of celiac-type symptoms among patients with fibromyalgia in comparison with healthy subjects and with those experienced by adult celiac patients and subjects with gluten sensitivity. A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001). Regarding the existing data in the literature, the prevalence of fatigue, depression, cognitive symptoms and cutaneous lesions predominated among patients with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher among patients with fibromyalgia compared to gluten-sensitive patients and was similar among patients with fibromyalgia and celiac disease patient. The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiac disease or nonceliac gluten intolerance.

Egg hypersensitivity and measles-mumps-rubella vaccine administration.

PubMed

Beck, S A; Williams, L W; Shirrell, M A; Burks, A W

1991-11-01

Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokine Profile of Patients with Allergic Rhinitis Caused by Pollen, Mite, and Microbial Allergen Sensitization.

PubMed

Tyurin, Yury A; Lissovskaya, Svetlana A; Fassahov, Rustem S; Mustafin, Ilshat G; Shamsutdinov, Anton F; Shilova, Marina A; Rizvanov, Albert A

2017-01-01

Allergic rhinitis (AR) is especially prevalent among the population of large cities. Immunologically, the airway epithelium is a region where the population of allergen-presenting cells concentrates. These cells actively express a group of receptors of the innate immune system. A specific cytokine profile is its representation. The study was aimed at evaluating the cytokine profile in patients with seasonal and perennial allergic rhinitis. The cytokine profile of nasal secretion and blood serum of 44 patients with AR was studied. 24 of them had seasonal allergic rhinitis (SAR), and 20 patients suffered from perennial allergic rhinitis (PAR). The patients' age ranged from 4 to 60 years. It was determined in our study that the activation of the GM-CSF production retained in patients with PAR sensitized to mite allergen components ( Dermatophagoides pteronyssinus ). There was a higher production profile of TNF- α and TSLP in nasal secretion in the patients with perennial allergic rhinitis and additional high sensitization to SEs. Sensitization to mold fungal allergen components significantly increases in patients with seasonal allergic rhinitis. They demonstrated high level of sensitization to the Aspergillus fumigatus component m3. Thus, along with other clinical trials, the study performed would clarify some aspects of molecular pathogenesis of human allergic rhinitis.

Central sensitization: Implications for the diagnosis and treatment of pain

PubMed Central

Woolf, Clifford J

2010-01-01

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and postsurgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk both of developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity. PMID:20961685

Performance of two immunochromatographic tests for diagnosis of visceral leishmaniasis in patients coinfected with HIV.

PubMed

da Silva, Mauro Roberto Biá; Brandão, Natália Alberto Alves; Colovati, Marco; de Sousa, Margella Marconcine Pinheiro; de Lima, Larissa Coelho; Dorta, Miriam Leandro; Ribeiro-Dias, Fátima; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Oliveira, Milton Adriano Pelli

2018-02-01

Because of visceral leishmaniasis (VL) urbanization and spreading of the human immunodeficiency virus (HIV) infection to rural areas, coinfection has become more common. Here, we compared the accuracy of Kalazar Detect® (KD), an rK39-based immunochromatographic (IC) test, and OrangeLife® (OL), an rK39 + rK28 IC test, for diagnosing VL in patients coinfected with HIV in an endemic area in Brazil. Seventy-six VL patients and 40 patients with other diseases, of which 31 and 21 patients, respectively, were infected with HIV, were examined. The sensitivity of OL and KD tests was 88.89 and 95.45%, respectively, in patients without HIV. The sensitivity dropped to 67.74 and 61.29%, respectively, in coinfected patients. The decrease in sensitivity was not related to a decrease in the production of Leishmania-specific IgG. Because of the low sensitivity of rk39 test in HIV-infected patients, we suggest that patients with negative rK39 results should undergo further investigation with additional serological tests that are not based only on the rK39 antigen and examination of bone marrow aspirates.

Rotator cuff crepitus: could Codman really feel a cuff tear?

PubMed

Ponce, Brent A; Kundukulam, Joseph A; Sheppard, Evan D; Determann, Jason R; McGwin, Gerald; Narducci, Carl A; Crowther, Marshall J

2014-07-01

The objective of this study was to assess the accuracy of palpating crepitus to diagnose rotator cuff tears. Seventy consecutive consenting patients who presented with shoulder pain and no previous imaging or surgery on the affected shoulder were prospectively enrolled during a 10-month period. A standardized patient history and examination, including the crepitus test, were recorded in addition to obtaining standard radiographs. Additional imaging after initial evaluation was performed with magnetic resonance imaging and interpreted by a musculoskeletal radiologist blinded to the examination findings. Statistical analysis was used to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the crepitus test in the clinical diagnosis of a rotator cuff tear. Sixty-three patients had histories, examinations, and imaging studies available for analysis. The crepitus test had a sensitivity of 67%, specificity of 80%, PPV of 91%, and NPV of 43% for all types of rotator cuff tears. The sensitivity and specificity for full-thickness or high-grade partial tears was 82% and 73%, respectively; the PPV and NPV were 77% and 79%. Increasing age improved accuracy as the presence of crepitus in patients older than 55 years had a sensitivity of 76%, specificity of 100%, PPV of 100%, and NPV of 38%. The crepitus test has a favorable sensitivity, specificity, PPV, and NPV to assess the integrity of the rotator cuff and may be a useful examination in the clinical diagnosis of a rotator cuff tear. Published by Mosby, Inc.

Can the efficiency of modified Alvarado scoring system in the diagnosis acute appendicitis be increased with tenesmus?

PubMed

Bulus, Hakan; Tas, Adnan; Morkavuk, Baris; Koklu, Seyfettin; Soy, Derya; Coskun, Ali

2013-01-01

Acute appendicitis is one of the main pathological conditions requiring emergency surgical intervention. The most widely accepted scoring system is modified Alvarado scoring system (MASS). In this study we aimed to improve the efficiency of MASS by adding a new parameter and to evaluate its efficiency in the diagnosis of acute appendicitis. This study included 158 patients who underwent acute appendectomy in Keçiören Training and Research Hospital General Surgery Department. In addition to criteria of MASS, all patients were questioned about the presence of tenesmus. The validity of MASS and MASS with additional parameter was evaluated with respect to sensitivity, specificity and positive and negative predictive values. Accuracy rates of MASS, clinical findings, ultrasonography and MASS with additional parameter in the diagnosis of acute appendicitis were 64, 76, 85 and 80 %. False positivity rates for clinical findings, MASS and MASS with additional parameter in the diagnosis of acute appendicitis were 17, 26 and 10 %, respectively. Sensitivity and specificity of clinical findings in the diagnosis of acute appendicitis were 83 and 66 %, respectively. Sensitivity and specificity of MASS in the diagnosis of acute appendicitis were 74 and 39 %, respectively, and those of MASS with additional parameter were appendicitis increased to 83 and 66 %, respectively. MASS is a simple, cheap and objective scoring system and does not require expertise. When tenesmus is added to standard MASS, rates of accuracy, sensitivity and specificity become better than those in MASS in the diagnosis of acute appendicitis.

Abnormal IgG4 antibody response to aeroallergens in allergic patients.

PubMed

Jeannin, P; Delneste, Y; Tillie-Leblond, I; Wallaert, B; carlier, A; Pestel, J; Tonnel, A B

1994-01-01

Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders.

Component resolution reveals additional major allergens in patients with honeybee venom allergy.

PubMed

Köhler, Julian; Blank, Simon; Müller, Sabine; Bantleon, Frank; Frick, Marcel; Huss-Marp, Johannes; Lidholm, Jonas; Spillner, Edzard; Jakob, Thilo

2014-05-01

Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen-specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3- and Api m 10-specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma.

PubMed

Weber, Andreas; von Weyhern, Claus; Fend, Falko; Schneider, Jochen; Neu, Bruno; Meining, Alexander; Weidenbach, Hans; Schmid, Roland M; Prinz, Christian

2008-02-21

To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma. Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005. Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology). Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.

Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

PubMed

Helås, T; Sagafos, D; Kleggetveit, I P; Quiding, H; Jönsson, B; Segerdahl, M; Zhang, Z; Salter, H; Schmelz, M; Jørum, E

2017-09-01

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits Na V 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na V 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in Na V 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the Na V 1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in EM patients with mutations in Na V 1.7, 1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls. © 2017 European Pain Federation - EFIC®.

[Psychosocial stressors and pain sensitivity in chronic pain disorder with somatic and psychological factors (F45.41)].

PubMed

Studer, M; Stewart, J; Egloff, N; Zürcher, E; von Känel, R; Brodbeck, J; Grosse Holtforth, M

2017-02-01

Increased pain sensitivity is characteristic for patients with chronic pain disorder with somatic and psychological factors (F45.41). Persistent stress can induce, sustain, and intensify pain sensitivity, thereby modulating pain perception. In this context, it would be favorable to investigate which psychosocial stressors are empirically linked to pain sensitivity. The aim of this study was to examine the relationship between psychosocial stressors and pain sensitivity in a naturalistic sample of patients with chronic pain disorder with somatic and psychological factors (F45.41). We assessed 166 patients with chronic pain disorder with somatic and psychological factors (F45.41) at entry into an inpatient pain clinic. Pain sensitivity was measured with a pain provocation test (Algopeg) at the middle finger and earlobe. Stressors assessed were exposure to war experiences, adverse childhood experiences, illness-related inability to work, relationship problems, and potentially life-threatening accidents. Correlation analyses and structural equation modeling were used to examine which stressors showed the strongest prediction of pain sensitivity. Patients exhibited generally heightened pain sensitivity. Both exposure to war and illness-related inability to work showed significant bivariate correlations with pain sensitivity. In addition to age, they also predicted a further increase in pain sensitivity in the structural equation model. Bearing in mind the limitations of this cross-sectional study, these findings may contribute to a better understanding of the link between psychosocial stressors and pain sensitivity.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography

PubMed Central

Ernst, Marielle; Romero, Javier M.; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

Purpose The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. Materials and Methods 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Results Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%). Conclusion In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT. PMID:26479718

Comparison of Four Views to Single-view Ultrasound Protocols to Identify Clinically Significant Pneumothorax.

PubMed

Helland, Gregg; Gaspari, Romolo; Licciardo, Samuel; Sanseverino, Alexandra; Torres, Ulises; Emhoff, Timothy; Blehar, David

2016-10-01

Ultrasound (US) has been shown to be effective at identifying a pneumothorax (PTX); however, the additional value of adding multiple views has not been studied. Single- and four-view protocols have both been described in the literature. The objective of this study was to compare the diagnostic accuracy of single-view versus four-view lung US to detect clinically significant PTX in trauma patients. This was a randomized, prospective trial on trauma patients. Adult patients with acute traumatic injury undergoing computed tomography (CT) scan of the chest were eligible for enrollment. Patients were randomized to a single view or four views of each hemithorax prior to any imaging. USs were performed and interpreted by credentialed physicians using a 7.5-Mhz linear array transducer on a portable US machine with digital clips recorded for later review. Attending radiologist interpretation of the chest CT was reviewed for presence or absence of PTX with descriptions of small foci of air or minimal PTX categorized as clinically insignificant. A total of 260 patients were enrolled over a 2-year period. A total of 139 patients received a single view of each chest wall and 121 patients received four views. There were a total of 49 patients that had a PTX (19%), and 29 of these were clinically significant (11%). In diagnosis of any PTX, both single-view and four-view techniques showed poor sensitivity (54.2 and 68%) but high specificity (99 and 98%). For clinically significant PTX, single-view US demonstrated a sensitivity of 93% (95% confidence interval [CI] = 64.1% to 99.6%) and a specificity of 99.2% (95% CI = 95.5% to 99.9%), with sensitivity of 93.3% (95% CI = 66% to 99.7%) and specificity of 98% (95% CI = 92.1% to 99.7%) for four views. Single-view and four-view chest wall USs demonstrate comparable sensitivity and specificity for PTX. The additional time to obtain four views should be weighed against the absence of additional diagnostic yield over a single view when using US to identify a clinically significant PTX. © 2016 by the Society for Academic Emergency Medicine.

Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: first experience in an emergency department of a general hospital.

PubMed

Lotze, Ulrich; Lemm, Holger; Heyer, Anke; Müller, Karin

2011-01-01

The purpose of this observational study was to test the diagnostic performance of the Elecsys® troponin T high-sensitive system combined with copeptin measurement for early exclusion of acute myocardial infarction (MI) in clinical practice. Troponin T high-sensitive (diagnostic cutoff: <14 pg/mL) and copeptin (diagnostic cutoff: <14 pmol/L) levels were determined at admission in addition to other routine laboratory parameters in patients with suspected acute MI presenting to the emergency department of a general hospital over a period of five months. Data from 142 consecutive patients (mean age 71.2 ± 13.5 years, 76 men) were analyzed. Final diagnoses were acute MI in 13 patients (nine ST elevation MI, four non-ST elevation MI, 9.2%) unstable angina pectoris in three (2.1%), cardiac symptoms not primarily associated with myocardial ischemia in 79 (55.6%), and noncardiac disease in 47 patients (33.1%). The patients with acute MI were younger and had higher troponin T high-sensitive and copeptin values than patients without acute MI. Seventeen patients had very high copeptin values (>150 pmol/L), one of whom had a level of >700 pmol/L and died of pulmonary embolism. A troponin T high-sensitive level of <14 pg/mL in combination with copeptin <14 pmol/L at initial presentation ruled out acute MI in 45 of the 142 patients (31.7%), each with a sensitivity and negative predictive value of 100%. According to this early experience, a single determination of troponin T high-sensitive and copeptin may enable early and accurate exclusion of acute MI in one third of patients, even in an emergency department of a general hospital.

Allergen Chip Diagnosis for Soy-Allergic Patients: Gly m 4 as a Marker for Severe Food-Allergic Reactions to Soy

PubMed Central

Berneder, M.; Bublin, M.; Hoffmann-Sommergruber, K.; Hawranek, T.; Lang, R.

2016-01-01

Background Gly m 5 and Gly m 6 are known to induce severe reactions in soy-allergic patients. For birch pollen (BP)-allergic patients, the Bet v 1 homologous allergen Gly m 4 is also a potential trigger of generalized severe reactions upon soy consumption. Therefore, reliable component-resolved diagnosis of soy allergy is needed. Methods IgE reactivity from sera of 20 patients from a BP environment with reported soy allergy was assessed. Skin prick tests (SPT) with BP and soy drink were performed. Specific IgE for BP, soy, Bet v 1 and Gly m 4 was analyzed by ImmunoCAP. In addition, ISAC microarray profiling was performed. Results Nineteen of 20 patients were BP allergic (positive SPT and/or CAP results for BP extract and Bet v 1). Eighteen soy-allergic patients were tested positive with soy drink in SPT. Soy CAP results were negative in the majority of tests (15/20), whereas 19/20 sera had specific IgE to Gly m 4. In the microarray approach, 14/20 sera displayed Gly m 4-specific IgE, the additional 6 sera had IgE levels below 0.3 ISAC standardized units. The BP-negative serum had Gly m 5- and Gly m 6-specific IgE which correlated with positive soy ImmunoCAP. Conclusions Soy sensitization detected by SPT and Gly m 4 ImmunoCAP were in good qualitative agreement with ISAC results. Soy ImmunoCAP was only specific for Gly m 5 and Gly m 6 sensitization. Gly m 4 ImmunoCAP has a higher sensitivity than ImmunoCAP ISAC. In this patient cohort, Gly m 4 sensitization was linked to the development of severe and generalized allergic reactions upon soy consumption. PMID:23548307

Olfactory dysfunction affects thresholds to trigeminal chemosensory sensations.

PubMed

Frasnelli, J; Schuster, B; Hummel, T

2010-01-14

Next to olfaction and gustation, the trigeminal system represents a third chemosensory system. These senses are interconnected; a loss of olfactory function also leads to a reduced sensitivity in the trigeminal chemosensory system. However, most studies so far focused on comparing trigeminal sensitivity to suprathreshold stimuli; much less data is available with regard to trigeminal sensitivity in the perithreshold range. Therefore we assessed detection thresholds for CO(2), a relatively pure trigeminal stimulus in controls and in patients with olfactory dysfunction (OD). We could show that OD patients exhibit higher detection thresholds than controls. In addition, we were able to explore the effects of different etiologies of smell loss on trigeminal detection thresholds. We could show that in younger subjects, patients suffering from olfactory loss due to head trauma are more severely impaired with regard to their trigeminal sensitivity than patients with isolated congenital anosmia. In older patients, we could not observe any differences between different etiologies, probably due to the well known age-related decrease of trigeminal sensitivity. Furthermore we could show that a betterment of the OD was accompanied by decreased thresholds. This was most evident in patients with postviral OD. In conclusion, factors such as age, olfactory status and etiology of olfactory disorder can affect responsiveness to perithreshold trigeminal chemosensory stimuli. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Performance of the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria in Thai patients.

PubMed

Louthrenoo, Worawit; Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya

2017-05-01

To evaluate the sensitivity and specificity of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in Thai patients presenting with acute arthritis in a real-life setting. Data were analyzed on consecutive patients presenting with arthritis of less than 2 weeks duration. Sensitivity and specificity were calculated by using the presence of monosodium urate (MSU) crystals in the synovial fluid or tissue aspirate as gold standard for gout diagnosis. Subgroup analysis was performed in patients with early disease (≤2 years), established disease (>2 years), and those without tophus. Additional analysis also was performed in non-tophaceous gout patients, and patients with acute calcium pyrophosphate dihydrate crystal arthritis were used as controls. One hundred and nine gout and 74 non-gout patients participated in this study. Full ACR/EULAR classification criteria had sensitivity and specificity of 90.2 and 90.0%, respectively; and 90.2 and 85.0%, respectively, when synovial fluid microscopy was excluded. Clinical-only criteria yielded sensitivity and specificity of 79.8 and 87.8%, respectively. The criteria performed well among patients with early and non-tophaceous disease, but had lower specificity in patients with established disease. The variation of serum uric acid level was a major limitation of the classification criteria. The ACR/EULAR classification criteria had high sensitivity and specificity in Thai patients presenting with acute arthritis, even when clinical criteria alone were used.

Prevalence of and risk factors for latex sensitization in patients with spina bifida.

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Mezzetti, P; Cianferoni, A; Danti, A D; Mercurella, A; Vierucci, A

1998-11-01

We determined the prevalence of and risk factors for latex sensitization in patients with spina bifida. A total of 59 consecutive subjects 2 to 40 years old with spina bifida answered a questionnaire, and underwent a latex skin prick test and determination of serum IgE specific for latex by RAST CAP radioimmunoassay. We also noted the relationships of total serum IgE skin prick tests to common air and food allergens. In addition, skin prick plus prick tests were also done with fresh foods, including kiwi, pear, orange, almond, pineapple, apple, tomato and banana. Latex sensitization was present in 15 patients (25%) according to the presence of IgE specific to latex, as detected by a skin prick test in 9 and/or RAST CAP in 13. Five latex sensitized patients (33.3%) had clinical manifestations, such as urticaria, conjuctivitis, angioedema, rhinitis and bronchial asthma, while using a latex glove and inflating a latex balloon. Atopy was present in 21 patients (35.6%). In 14 patients (23%) 1 or more skin tests were positive for fresh foods using a prick plus prick technique. Tomato, kiwi, and pear were the most common skin test positive foods. Univariate analysis revealed that a history of 5 or more operations, atopy and positive prick plus prick tests results for pear and kiwi were significantly associated with latex sensitization. Multivariate analysis demonstrated that only atopy and a history of 5 or more operations were significantly and independently associated with latex sensitization. A fourth of the patients with spina bifida were sensitized to latex. Atopy and an elevated number of operations were significant and independent predictors of latex sensitization in these cases.

Novel autoantibody markers for early and seronegative rheumatoid arthritis.

PubMed

Somers, Klaartje; Geusens, Piet; Elewaut, Dirk; De Keyser, Filip; Rummens, Jean-Luc; Coenen, Marieke; Blom, Marlies; Stinissen, Piet; Somers, Veerle

2011-02-01

Approximately one-third of rheumatoid arthritis (RA) patients are seronegative for the 2 serological RA markers, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP). Moreover, the sensitivities of both markers are lower in the diagnostically important early disease phase. The aim of this study was to identify additional autoantibody markers for early RA and for RF-negative, ACCP-negative (seronegative) RA. We screened an RA synovium cDNA phage display library with autoantibodies in plasma from 10 early (symptoms of maximum 1 year) and 10 seronegative (RF-negative, ACCP-negative) RA patients with validation in 72 additional RA patients and 121 controls (38 healthy controls, 43 patients with other inflammatory rheumatic diseases, 20 osteoarthritis patients and 20 subjects with mechanical joint complaints). Fourteen novel autoantibodies were identified that showed a 54% sensitivity and 90% specificity for RA. For 11 of these autoantibodies, an exclusive presence was demonstrated in RA patients (100% specificity, 37% sensitivity) as compared to controls. All early RA patients were positive for at least one of the identified autoantibodies and antibody-positivity was associated with a shorter disease duration (P = 0.0087). 52% of RA patients who initially tested negative for RF and ACCP, tested positive for at least one of the 14 novel autoantibodies, resulting in a 19% increase in sensitivity compared to current serological testing. Moreover, 5 identified autoantibodies were detected more frequently in seronegative RA patients, indicating that these autoantibodies constitute novel candidate markers for this RA subtype. We demonstrated that the targets of 3 of these 5 autoantibodies had an increased expression in RA synovial tissue compared to control synovial tissue, pointing towards a biological rationale for these auto antibody targets in RA. In conclusion, we identified novel candidate autoantibody markers for RA that can be detected in early and seronegative RA patients indicating the potential added value for RA diagnostics. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Effects of Instrumentation on Urine Cytology and CK-20 Analysis for the Detection of Bladder Cancer.

PubMed

Wegelin, Olivier; Bartels, Diny W M; Tromp, Ellen; Kuypers, Karel C; van Melick, Harm H E

2015-10-01

To evaluate the effects of cystoscopy on urine cytology and additional cytokeratin-20 (CK-20) staining in patients presenting with gross hematuria. For 83 patients presenting with gross hematuria, spontaneous and instrumented paired urine samples were analyzed. Three patients were excluded. Spontaneous samples were collected within 1 hour before cystoscopy, and the instrumented samples were tapped through the cystoscope. Subsequently, patients underwent cystoscopic evaluation and imaging of the urinary tract. If tumor suspicious lesions were found on cystoscopy or imaging, subjects underwent transurethral resection or ureterorenoscopy. Two blinded uropathological reviewers (DB, KK) evaluated 160 urine samples. Reference standards were results of cystoscopy, imaging, or histopathology. Thirty-seven patients (46.3%) underwent transurethral resection or ureterorenoscopy procedures. In 30 patients (37.5%) tumor presence was confirmed by histopathology. The specificity of urine analysis was significantly higher for spontaneous samples than instrumented samples for both cytology alone (94% vs 72%, P = .01) and for cytology combined with CK-20 analysis (98% vs 84%, P = .02). The difference in sensitivity between spontaneous and instrumented samples was not significant for both cytology alone (40% vs 53%) and combined with CK-20 analysis (67% vs 67%). The addition of CK-20 analysis to cytology significantly increases test sensitivity in spontaneous urine cytology (67% vs 40%, P = .03). Instrumentation significantly decreases specificity of urine cytology. This may lead to unnecessary diagnostic procedures. Additional CK-20 staining in spontaneous urine cytology significantly increases sensitivity but did not improve the already high specificity. We suggest performing urine cytology and CK-20 analysis on spontaneously voided urine. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of Left Atrial Appendage Thrombi in Patients With Persistent and Long-Standing Persistent Atrial Fibrillation Using Intra-Cardiac Echocardiography and Cardiac Computed Tomography.

PubMed

Ikegami, Yukinori; Tanimoto, Kojiro; Inagawa, Kohei; Shiraishi, Yasuyuki; Fuse, Jun; Sakamoto, Munehisa; Momiyama, Yukihiko; Takatsuki, Seiji

2017-12-25

Intracardiac echocardiography (ICE) and cardiac computed tomography (CCT), in addition to standard transesophageal echocardiography (TEE), have been used to identify left atrial (LA) thrombi prior to ablation for atrial fibrillation (AF). The clinical advantages of this, however, remain unclear. This study therefore investigated the advantages of additional pre-procedural LA appendage (LAA) thrombus evaluation using ICE and the clinical value of CCT in persistent and long-standing persistent AF.Methods and Results:We analyzed data from 108 consecutive patients with persistent and long-standing persistent AF who were scheduled to undergo AF ablation. TEE was performed within 24 h prior to ablation. ICE was performed for 97 patients in whom a thrombus was not detected on TEE. CCT was performed in 95 patients. Thrombus or sludge was detected on TEE in 11 patients (10.3%), for whom ablation was cancelled. Four additional patients were diagnosed with LAA thrombus on ICE. When TEE and ICE were used as the reference for thrombus detection, the sensitivity, specificity, positive predictive value, and negative predictive value of CCT for identifying contrast defects in the LAA were 100%, 81.0%, 40.7%, and 100%, respectively. ICE combined with TEE increased the detection rate of LAA thrombi in patients with persistent and long-standing persistent AF. Moreover, CCT had high sensitivity and negative predictive value for LAA thrombus detection.

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study.

PubMed

Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B; Zorumski, Charles F; Conway, Charles; Nagele, Peter

2017-04-01

While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new cardiac troponin elevation after electroconvulsive therapy, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia.

Beer, Cider, and Wine Allergy

PubMed Central

Tadros, Susan

2017-01-01

Background. Allergy to beer is often due to specific proteins in barley and sometimes to lipid transfer protein. Allergy to wine is frequently due to a sensitivity to grape proteins. We present a rare case of allergy to beer, wine, and cider resulting from IgE reactivity to yeasts and moulds which also explained the patient's additional sensitivity to yeast extracts and blue cheese. Case Presentation. The patient's symptoms included throat and facial itching accompanied by mild wheeze and severe urticaria. Diagnosis of allergy to yeast was confirmed by specific IgE testing as well as that to relevant foods and beverages. The patient's ongoing management included advice to avoid beer, wine, and other food groups containing specific yeasts, in addition to carrying a short acting nonsedating antihistamine as well as an adrenaline autoinjector. Conclusions. Cases of yeast allergy are extremely rare in medical literature but may be underrecognised and should be considered in patients presenting with reactions to alcoholic beverages and other yeast-containing products. PMID:28396809

Beer, Cider, and Wine Allergy.

PubMed

Bansal, Rhea A; Tadros, Susan; Bansal, Amolak S

2017-01-01

Background . Allergy to beer is often due to specific proteins in barley and sometimes to lipid transfer protein. Allergy to wine is frequently due to a sensitivity to grape proteins. We present a rare case of allergy to beer, wine, and cider resulting from IgE reactivity to yeasts and moulds which also explained the patient's additional sensitivity to yeast extracts and blue cheese. Case Presentation . The patient's symptoms included throat and facial itching accompanied by mild wheeze and severe urticaria. Diagnosis of allergy to yeast was confirmed by specific IgE testing as well as that to relevant foods and beverages. The patient's ongoing management included advice to avoid beer, wine, and other food groups containing specific yeasts, in addition to carrying a short acting nonsedating antihistamine as well as an adrenaline autoinjector. Conclusions . Cases of yeast allergy are extremely rare in medical literature but may be underrecognised and should be considered in patients presenting with reactions to alcoholic beverages and other yeast-containing products.

The NEXUS criteria are insufficient to exclude cervical spine fractures in older blunt trauma patients.

PubMed

Paykin, Gabriel; O'Reilly, Gerard; Ackland, Helen M; Mitra, Biswadev

2017-05-01

The National Emergency X-Radiography Utilization Study (NEXUS) criteria are used to assess the need for imaging to evaluate cervical spine integrity after injury. The aim of this study was to assess the sensitivity of the NEXUS criteria in older blunt trauma patients. Patients aged 65 years or older presenting between 1st July 2010 and 30th June 2014 and diagnosed with cervical spine fractures were identified from the institutional trauma registry. Clinical examination findings were extracted from electronic medical records. Data on the NEXUS criteria were collected and sensitivity of the rule to exclude a fracture was calculated. Over the study period 231,018 patients presented to The Alfred Emergency & Trauma Centre, of whom 14,340 met the institutional trauma registry inclusion criteria and 4035 were aged ≥65years old. Among these, 468 patients were diagnosed with cervical spine fractures, of whom 21 were determined to be NEXUS negative. The NEXUS criteria performed with a sensitivity of 94.8% [95% CI: 92.1%-96.7%] on complete case analysis in older blunt trauma patients. One-way sensitivity analysis resulted in a maximum sensitivity limit of 95.5% [95% CI: 93.2%-97.2%]. Compared with the general adult blunt trauma population, the NEXUS criteria are less sensitive in excluding cervical spine fractures in older blunt trauma patients. We therefore suggest that liberal imaging be considered for older patients regardless of history or examination findings and that the addition of an age criterion to the NEXUS criteria be investigated in future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitization to Alternaria and Cladosporium in patients with respiratory allergy and outdoor counts of mold spores in Ankara atmosphere, Turkey.

PubMed

Bavbek, Sevim; Erkekol, Ferda Oner; Ceter, Talip; Mungan, Dilşad; Ozer, Faruk; Pinar, Münevver; Misirligil, Zeynep

2006-08-01

Sensitization to Alternaria and Cladosporium has been reported to be 3% to 30% in European countries. However, in Turkey, there is limited data about the prevalence of sensitization to these molds and the intensity of the two mold spores in Ankara atmosphere. This study was designed to evaluate the sensitization to Alternaria and Cladosporium in patients with respiratory allergy in Ankara and also the concentration of the two molds in Ankara atmosphere. Allergic rhinitis and asthma patients living in Ankara were included in the study. Demographic and diagnostic data of the patients were recorded. A skin prick test with extracts supplied by three different laboratories was used to evaluate the sensitization to Alternaria and Cladosporium. Mold spores were measured using a Burkard 7-day recording volumetric spore trap in Ankara atmosphere during a year. Overall sensitization to the two molds was found to be 14.8%, and isolated Alternaria or Cladosporiumsensitization was 3%. Considering the positive reaction to at least one of the three suppliers, the sensitization rate was 11.9% and 8.1% for Alternaria and Cladosporium, respectively. Cochran's Q homogenization test demonstrated that the positive and negative reaction were not homogeneous among three laboratories. The total number of mold spores in Ankara atmosphere was 429,264 spores/m3 of which 75.5% and 6% were constituted by Cladosporium and Alternaria, respectively. The prevalence of Cladosporium and Alternaria sensitization in respiratory allergy patients is quite similar to European countries; however, our data indicate that commercial mold extracts should be standardized to establish the real sensitization rates. Additionally, considering the great numbers of these mold spores in Ankara atmosphere, long-term follow-up studies are needed to evaluate the relationship between the mold load and sensitization patterns.

Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma

PubMed Central

Weber, Andreas; von Weyhern, Claus; Fend, Falko; Schneider, Jochen; Neu, Bruno; Meining, Alexander; Weidenbach, Hans; Schmid, Roland M; Prinz, Christian

2008-01-01

AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma. METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005. RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology). CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings. PMID:18286693

Spot sign on 90-second delayed computed tomography angiography improves sensitivity for hematoma expansion and mortality: prospective study.

PubMed

Ciura, Viesha A; Brouwers, H Bart; Pizzolato, Raffaella; Ortiz, Claudia J; Rosand, Jonathan; Goldstein, Joshua N; Greenberg, Steven M; Pomerantz, Stuart R; Gonzalez, R Gilberto; Romero, Javier M

2014-11-01

The computed tomography angiography (CTA) spot sign is a validated biomarker for poor outcome and hematoma expansion in intracerebral hemorrhage. The spot sign has proven to be a dynamic entity, with multimodal imaging proving to be of additional value. We investigated whether the addition of a 90-second delayed CTA acquisition would capture additional intracerebral hemorrhage patients with the spot sign and increase the sensitivity of the spot sign. We prospectively enrolled consecutive intracerebral hemorrhage patients undergoing first pass and 90-second delayed CTA for 18 months at a single academic center. Univariate and multivariate logistic regression were performed to assess clinical and neuroimaging covariates for relationship with hematoma expansion and mortality. Sensitivity of the spot sign for hematoma expansion on first pass CTA was 55%, which increased to 64% if the spot sign was present on either CTA acquisition. In multivariate analysis the spot sign presence was associated with significant hematoma expansion: odds ratio, 17.7 (95% confidence interval, 3.7-84.2; P=0.0004), 8.3 (95% confidence interval, 2.0-33.4; P=0.004), and 12.0 (95% confidence interval, 2.9-50.5; P=0.0008) if present on first pass, delayed, or either CTA acquisition, respectively. Spot sign presence on either acquisitions was also significant for mortality. We demonstrate improved sensitivity for predicting hematoma expansion and poor outcome by adding a 90-second delayed CTA, which may enhance selection of patients who may benefit from hemostatic therapy. © 2014 American Heart Association, Inc.

Association of Dark-Adapted Visual Function with Retinal Structural Changes in Patients with Stargardt Disease

PubMed Central

Salvatore, Serena; Fishman, Gerald A.; McAnany, J. Jason; Genead, Mohamed A.

2014-01-01

Purpose To evaluate dark-adapted retinal sensitivity in patients with Stargardt disease (STGD1) using a modified MP-1 microperimeter (MP-1S) and to compare the sensitivity loss with structural changes observed by spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscope (cSLO) infrared imaging. Methods Twelve STGD1 patients and 10 normally sighted controls participated. Dark-adapted mean sensitivity (MS) was obtained using a MP-1S. Additionally, MS percent difference between the patients and the controls was obtained. Sensitivity results were superimposed on cSLO infrared images and compared with corresponding SD-OCT scans. Results Dark-adapted MS±SD was 8.34±1.54 dB for the controls and 3.68±1.74 dB for STGD1(p<0.001). There was a significant reduction in MS of 24.0% in STGD1. Sensitivity reductions were observed in areas that showed changes on cSLO infrared images and on SD-OCT, including disorganizational loss of the retinal pigment epithelium, and abnormal photoreceptor inner-segment ellipsoid (ISe) and external limiting membrane reflectance band. Conclusions With topographical accuracy, dark-adapted sensitivity measurements can be made in STGD1 and normal controls with the MP-1S. Sensitivity loss is associated with structural changes. This finding can be useful for the determination of optimal areas for potential improvement of retinal function in Stargardt patients. PMID:24280667

miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Zhiwei, E-mail: carlhe@126.com; Liu, Yi, E-mail: cassieliu@126.com; Xiao, Bing, E-mail: rockg714@aliyun.com

2015-02-13

A large proportion of the NSCLC patients were insensitive to radiotherapy, but the exact mechanism is still unclear. This study explored the role of miR-25 in regulating sensitivity of NSCLC cells to ionizing radiation (IR) and its downstream targets. Based on measurement in tumor samples from NSCLC patients, this study found that miR-25 expression is upregulated in both NSCLC and radio-resistant NSCLC patients compared the healthy and radio-sensitive controls. In addition, BTG expression was found negatively correlated with miR-25a expression in the both tissues and cells. By applying luciferase reporter assay, we verified two putative binding sites between miR-25 andmore » BTG2. Therefore, BTG2 is a directly target of miR-25 in NSCLC cancer. By applying loss-and-gain function analysis in NSCLC cell lines, we demonstrated that miR-25-BTG2 axis could directly regulated BTG2 expression and affect radiotherapy sensitivity of NSCLC cells. - Highlights: • miR-25 is upregulated, while BTG2 is downregulated in radioresistant NSCLC patients. • miR-25 modulates sensitivity to radiation induced apoptosis. • miR-25 directly targets BTG2 and suppresses its expression. • miR-25 modulates sensitivity to radiotherapy through inhibiting BTG2 expression.« less

Evaluation of diagnostic serological results in cases of suspected primary syphilis infection.

PubMed

Gratzer, Beau; Pohl, Daniel; Hotton, Anna L

2014-05-01

Reverse sequence screening for syphilis, in which an automatable treponemal assay (enzyme immunoassay [EIA]/chemiluminescence assay [CIA]) is performed first and followed by a nontreponemal test for reactive specimens, has been used increasingly in the United States. The EIA is objective, efficient, and believed to be more sensitive than the rapid plasma reagin (RPR) because treponemal antibodies appear before nontreponemal antibodies. We sought to compare the sensitivity of a commonly used EIA, the Trep-Sure EIA (TS-EIA), to the RPR in cases of suspected primary syphilis infection in our clinic. A retrospective medical record review of patients with sexually transmitted infection clinic visits from January 2009 to December 2011 was conducted, and 52 patients met the following inclusion criteria: suspected primary syphilis symptoms, at least 1 positive syphilis test result at visit, and no history of syphilis. Sensitivity analyses compared the TS-EIA and RPR, using the reference standard of concordantly positive/reactive TS-EIA/RPR or positive fluorescent treponemal antibody absorption test (FTA-ABS) result. We considered equivocal TS-EIA results to be positive for sensitivity calculations because such results typically reflex to additional testing and therefore may still result in identifying new infections. Twenty-eight (53.8%) of the 52 patients had a positive or equivocal TS-EIA. Twenty-five (89.3%) of those were RPR reactive; the remaining 3 (10.7%) were RPR nonreactive, FTA-ABS positive. Forty patients (76.9%) had a positive RPR, including 15 patients (37.5%) with negative TS-EIA results; all 15 were FTA-ABS positive. Nine additional patients were TS-EIA negative and RPR nonreactive but had a positive FTA-ABS result. The RPR was significantly more sensitive than the EIA (76.9% vs. 53.8%, P = 0.005). Trep-Sure EIA positivity was also significantly associated with higher median RPR titer (P = 0.011). Use of the TS-EIA may result in underdetection of primary syphilis compared with the RPR. Further evaluation of the sensitivity of the TS-EIA in high-morbidity settings is warranted before the adoption of reverse sequence screening algorithms.

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing

PubMed Central

Shtessel, Maria; Lobell, Elizabeth; Hudes, Golda; Rosenstreich, David; de Vos, Gabriele

2017-01-01

Background: Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. Objective: To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. Methods: SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. Results: A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357–4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. Conclusion: IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed. PMID:28583228

Diagnosing environmental allergies: Comparison of skin-prick, intradermal, and serum specific immunoglobulin E testing.

PubMed

Ferastraoaru, Denisa; Shtessel, Maria; Lobell, Elizabeth; Hudes, Golda; Rosenstreich, David; de Vos, Gabriele

2017-06-01

Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357-4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed.

Effects of pirfenidone on increased cough reflex sensitivity in guinea pigs.

PubMed

Okazaki, Akihito; Ohkura, Noriyuki; Fujimura, Masaki; Katayama, Nobuyuki; Kasahara, Kazuo

2013-10-01

Pirfenidone, an antifibrotic drug with anti-inflammatory and antioxidant effects, delays fibrosis in idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater cough reflex sensitivity to inhaled capsaicin than healthy people, and cough is an independent predictor of IPF disease progression; however, the effects of pirfenidone on cough reflex sensitivity are unknown. After challenge with an aerosolized antigen in actively sensitized guinea pigs, pirfenidone was administered intraperitoneally, and the cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected. Pirfenidone suppressed the capsaicin-induced increase in cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of prostaglandin E2, substance P, and leukotriene B4, but not histamine, in the BAL fluid were dose dependently suppressed by pirfenidone. The decrease in neutral endopeptidase activity in the tracheal tissue was also alleviated by pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced. These results suggest that pirfenidone ameliorates isolated cough based on increased cough reflex sensitivity associated with allergic airway diseases, and potentially relieve chronic cough in IPF patients who often have increased cough reflex sensitivity. Prospective studies on cough-relieving effects of pirfenidone in patients with IPF are therefore warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advances in asthma in 2016: Designing individualized approaches to management.

PubMed

Anderson, William C; Apter, Andrea J; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2017-09-01

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Functional and Morphological Correlations before and after Video-Documented 23-Gauge Pars Plana Vitrectomy with Membrane and ILM Peeling in Patients with Macular Pucker.

PubMed

Mayer, Wolfgang J; Fazekas, Clara; Schumann, Ricarda; Wolf, Armin; Compera, Denise; Kampik, Anselm; Haritoglou, Christos

2015-01-01

Purpose. To assess functional and morphological alterations following video-documented surgery for epiretinal membranes. Methods. Forty-two patients underwent video-documented 23-gauge vitrectomy with peeling of epiretinal (ERM) and inner limiting membrane (ILM). Patient assessment was performed before and 3 and 6 months including best corrected visual acuity (BCVA), slit lamp biomicroscopy, SD-OCT, and central 2° and 18° microperimetry. In addition, all video-documented areas of peeling on the retinal surface were evaluated postoperatively using an additional focal 2° microperimetry. Retinal sensitivity and BCVA were correlated with morphological changes (EZ and ELM) in the foveal region and in regions of membrane peeling. Results. Overall, BCVA increased from 0.6 (±0.2) to 0.2 (±0.2) logMAR after 6 months with an increase in retinal sensitivity (17.9 ± 2.7 dB to 26.8 ± 3.1 dB, p < 0.01). We observed a significant correlation between the integrity of the EZ but not of the ELM and the retinal sensitivity, overall and in peeling areas (p < 0.05). However, no significant correlation between alterations in the area of peeling and overall retinal sensitivity regarding visual acuity gain could be observed after 6 months (p > 0.05). In contrast, overall postoperative retinal sensitivity was significantly decreased in patients with a visual acuity gain lower than 2 lines (p < 0.05) correlating with EZ defects seen in OCT. Conclusions. Mechanical trauma of epiretinal membrane and ILM peeling due to the use of intraocular forceps may affect the outer retinal structure. Nevertheless, these changes seem to have no significant impact on postoperative functional outcome.

New food allergies in a European non-Mediterranean region: is Cannabis sativa to blame?

PubMed

Ebo, D G; Swerts, S; Sabato, V; Hagendorens, M M; Bridts, C H; Jorens, P G; De Clerck, L S

2013-01-01

Allergy to fruit and vegetables exhibit geographic variation regarding the severity of symptoms and depending on the sensitization profile of the patient. These sensitization profiles and routes remain incompletely understood. Cannabis is a very popular drug and derived from Cannabis sativa, a plant containing lipid transfer proteins (LTP) also known as important allergens in plant and fruit allergies. In this study we sought to elucidate a potential connection between C. sativa allergy and plant food allergies. A case-control study involving 21 patients consulting for plant food allergies. Twelve patients were cannabis allergic and 9 had a pollen or latex allergy without cannabis allergy. Testing for cannabis IgE implied measurement of specific IgE, skin testing and basophil activation tests. Allergen component analysis was performed with a microarray technique. Plant food allergy in patients with documented cannabis allergy had more severe reactions than patients without cannabis allergy and frequently implied fruits and vegetables that are not observed in a (birch) pollen-related food syndrome. With the exception of 1 patient with cannabis allergy, all were sensitized to nonspecific (ns)-LTP. Our data suggest that illicit cannabis abuse can result in cannabis allergy with sensitization to ns-LTP. This sensitization might result in various plant-food allergies. Additional collaborative studies in different geographical areas are needed to further elucidate on this hypothesis. Copyright © 2013 S. Karger AG, Basel.

Development and testing of culturally sensitive patient information material for Turkish, Polish, Russian and Italian migrants with depression or chronic low back pain (KULTINFO): study protocol for a double-blind randomized controlled trial.

PubMed

Hölzel, Lars P; Ries, Zivile; Zill, Jördis M; Kriston, Levente; Dirmaier, Jörg; Härter, Martin; Bermejo, Isaac

2014-07-04

Many of the approximately 15 million people with a migration background living in Germany (19% of the population) are inadequately reached by existing healthcare provision. In the literature, the necessity for cultural adaptation of information material for patients with a migration background is often cited as a measure for improving healthcare.In this study, culturally sensitive information material will be developed and evaluated for patients with a migration background and depression or chronic low back pain. In this respect, it will be examined whether culturally sensitive information material is judged as more useful by the patients than standard translated patient information without cultural adaptation. The implementation and evaluation of culturally sensitive patient information material will occur in the framework of a double-blind randomized controlled parallel-group study in four study centres in Germany. Primary care patients with a Turkish, Polish, Russian or Italian migration background with a diagnosis of depressive disorder or chronic low back pain will be included and randomly allocated to the intervention group or the control group. In the intervention group, culturally sensitive patient information will be handed to the patient at the end of the physician consultation, while in the control group, standard translated patient information material will be provided. The patients will be surveyed by means of questionnaires following the consultation as well as after 8 weeks and 6 months. In addition to the primary outcome (subjective usefulness), several patient- and physician-rated secondary outcomes will be considered. The study will provide an empirical answer to the question of whether persons with a migration background perceive culturally sensitive patient information material as more useful than translated information material without cultural adaptation. Deutsches Register Klinischer Studien (DRKS-ID) DRKS00004241 and Universal Trial Number (UTN) U1111-1135-8043.

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

PubMed Central

Qian, Yushen; Pollom, Erqi L.; King, Martin T.; Dudley, Sara A.; Shaffer, Jenny L.; Chang, Daniel T.; Gibbs, Iris C.; Goldhaber-Fiebert, Jeremy D.; Horst, Kathleen C.

2016-01-01

Purpose The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. Patient and Methods We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. Results Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. Conclusion THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States. PMID:26351332

Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis

PubMed Central

Phi, Xuan-Anh; Saadatmand, Sepideh; De Bock, Geertruida H; Warner, Ellen; Sardanelli, Francesco; Leach, Martin O; Riedl, Christopher C; Trop, Isabelle; Hooning, Maartje J; Mandel, Rodica; Santoro, Filippo; Kwan-Lim, Gek; Helbich, Thomas H; Tilanus-Linthorst, Madeleine MA; van den Heuvel, Edwin R; Houssami, Nehmat

2016-01-01

Background: We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials. Methods: Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated. Results: In BRCA1/2 mutation carriers of all ages (BRCA1=1219 and BRCA2=732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P>0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening. Conclusions: Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering. PMID:26908327

Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis.

PubMed

Phi, Xuan-Anh; Saadatmand, Sepideh; De Bock, Geertruida H; Warner, Ellen; Sardanelli, Francesco; Leach, Martin O; Riedl, Christopher C; Trop, Isabelle; Hooning, Maartje J; Mandel, Rodica; Santoro, Filippo; Kwan-Lim, Gek; Helbich, Thomas H; Tilanus-Linthorst, Madeleine M A; van den Heuvel, Edwin R; Houssami, Nehmat

2016-03-15

We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials. Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated. In BRCA1/2 mutation carriers of all ages (BRCA1 = 1,219 and BRCA2 = 732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P > 0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening. Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽ 40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering.

Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department.

PubMed

Bahrmann, Philipp; Bahrmann, Anke; Breithardt, Ole-A; Daniel, Werner G; Christ, Michael; Sieber, Cornel C; Bertsch, Thomas

2013-06-01

Identifying older patients with non-ST- elevation myocardial infarction (NSTEMI) within the very large proportion with elevated high-sensitive cardiac troponin T (hs-cTnT) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department (ED). We prospectively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive (copeptin-us) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients. We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED. In addition to clinical examination, copeptin-us and hs-cTnT were measured at admission. Two cardiologists independently adjudicated the final diagnosis of NSTEMI after reviewing all available data. All patients were followed up for cardiovascular-related death within the following 12 months. NSTEMI was diagnosed in 38 (12%) patients (age 81±6 years). The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21% vs. 19% to rule in NSTEMI. The combination of copeptin-us <14 pmol/L and hs-cTnT <0.014 µg/L compared to hs-cTnT <0.014 µg/L alone had a negative predictive value of 100% vs. 99% to rule out NSTEMI. Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome. When copeptin-us ≥14 pmol/L was added, the net reclassification improvement for outcome was not significant (p=0.809). In unselected older patients presenting to the ED, the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone.

Additive value of 3T cardiovascular magnetic resonance coronary angiography for detecting coronary artery disease.

PubMed

Zhang, Lijun; Song, Xiantao; Dong, Li; Li, Jianan; Dou, Ruiyu; Fan, Zhanming; An, Jing; Li, Debiao

2018-04-30

The purpose of the work was to evaluate the incremental diagnostic value of free-breathing, contrast-enhanced, whole-heart, 3 T cardiovascular magnetic resonance coronary angiography (CE-MRCA) to stress/rest myocardial perfusion imaging (MPI) and late gadolinium enhancement (LGE) imaging for detecting coronary artery disease (CAD). Fifty-one patients with suspected CAD underwent a comprehensive cardiovascular magnetic resonance (CMR) examination (CE-MRCA, MPI, and LGE). The additive diagnostic value of MRCA to MPI and LGE was evaluated using invasive x-ray coronary angiography (XA) as the standard for defining functionally significant CAD (≥ 50% stenosis in vessels > 2 mm in diameter). 90.2% (46/51) patients (54.0 ± 11.5 years; 71.7% men) completed CE-MRCA successfully. On per-patient basis, compared to MPI/LGE alone or MPI alone, the addition of MRCA resulted in higher sensitivity (100% vs. 76.5%, p < 0.01), no change in specificity (58.3% vs. 66.7%, p = 0.6), and higher accuracy (89.1% vs 73.9%, p < 0.01) for CAD detection (prevalence = 73.9%). Compared to LGE alone, the addition of CE-MRCA resulted in higher sensitivity (97.1% vs. 41.2%, p < 0.01), inferior specificity (83.3% vs. 91.7%, p = 0.02), and higher diagnostic accuracy (93.5% vs. 54.3%, p < 0.01). The inclusion of successful free-breathing, whole-heart, 3 T CE-MRCA significantly improved the sensitivity and diagnostic accuracy as compared to MPI and LGE alone for CAD detection.

Sensitization to reactive diluents and hardeners in epoxy resin systems. IVDK data 2002-2011. Part I: reaction frequencies.

PubMed

Geier, Johannes; Lessmann, Holger; Hillen, Uwe; Skudlik, Christoph; Jappe, Uta

2016-02-01

Epoxy resin systems (ERSs), consisting of resins, reactive diluents, and hardeners, are indispensable in many branches of industry. In order to develop less sensitizing ERS formulations, knowledge of the sensitizing properties of single components is mandatory. To analyse the frequency of sensitization in the patients concerned, as one integral part of a research project on the sensitizing potency of epoxy resin compounds (FP-0324). A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002-2011, and a comparison of reaction frequencies with (surrogate) exposure data, were performed. Almost half of the patients sensitized to epoxy resin were additionally sensitized to reactive diluents or hardeners. Among the reactive diluents, 1,6-hexanediol diglycidyl ether was the most frequent allergen, followed by 1,4-butanediol diglycidyl ether, phenyl glycidyl ether, and p-tert-butylphenyl glycidyl ether. Among the hardeners, m-xylylene diamine (MXDA) and isophorone diamine (IPDA) were the most frequent allergens. According to the calculated exposure-related frequency of sensitization, MXDA seems to be a far more important sensitizer than IPDA. Up to 60% of the patients sensitized to hardeners and 15-20% of those sensitized to reactive diluents do not react to epoxy resin. In cases of suspected contact allergy to an ERS, a complete epoxy resin series must be patch tested from the start. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acetylsalicylic Acid Produces Different Effects on the Production of Active Oxygen Species by Activated Platelets in Different Inflammatory Diseases.

PubMed

Gabbasov, Z A; Kogan-Yasny, V V; Lakhno, D A; Kagan, L G; Ryzhkova, E V; Vasilieva, E Yu; Shpektor, A V

2017-11-01

We studied the effect of acetylsalicylic acid on ROS generation by platelets in patients after surgical interventions and in patients with bronchial asthma was studied. Platelets stimulated with platelet-activating factor are characterized by weak luminol-enhanced chemiluminescence in healthy people and patients after operations with laparoscopic incisions. Addition of platelet activation factor to platelet samples from patients after open abdominal surgery caused intensive chemiluminescence that was suppressed after platelet incubation with acetylsalicylic acid. At the same time, platelets of patients with aspirin-sensitive asthma did not respond to addition of platelet activating factor, but after incubation with acetylsalicylic acid, an intensive burst of chemiluminescence was detected with a maximum in 5-10 sec after the addition of a platelet-activating factor. In patients with bronchial asthma tolerant to aspirin, platelet activation factor did not induce chemiluminescence irrespective of incubation with acetylsalicylic acid.

Is the performance of MRI in preoperative staging of breast cancer independent of clinical and histological factors? A subgroup analysis.

PubMed

Carreira Gómez, C; Zamora Romero, J; Gil de Miguel, A; Chiva de Agustín, M; Plana Farrás, M N; Martínez González, J

2015-01-01

To determine whether preoperative breast MRI is more useful in patients according to their breast density, age, menopausal status, and biopsy findings of carcinoma in situ. We retrospectively studied 264 patients treated for breast cancer who had undergone mammography, ultrasonography, and MRI. We compared the size of the tumor on the three techniques and the sensitivity of the techniques for detecting additional lesions both in the overall group and in subgroups of patients classified according to their breast density, age, menopausal status, and histological findings of intraductal carcinoma. The definitive histological diagnosis was used as the gold standard. MRI was the technique that was most concordant with the histological findings for the size of the lesion, and it was also the technique that detected the most additional lesions. With MRI, we observed no differences in lesion size between the overall group and the subgroups in which MRI provided added value. Likewise, we observed no differences in the number of additional lesions detected in the overall group except for multicentric lesions, which was larger in older patients (P=.02). In the subgroup of patients in which MRI provided added value, the sensitivity for bilateral lesions was higher in patients with fatty breasts (P=.04). Multifocal lesions were detected significantly better in premenopausal patients (P=.03). MRI is better than mammography and better than ultrasonography for establishing the size of the tumor and for detecting additional lesions. Our results did not identify any subgroups in which the technique was more useful. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin in the evaluation of acute chest pain of uncertain etiology. A PITAGORAS substudy.

PubMed

Sanchis, Juan; Bardají, Alfredo; Bosch, Xavier; Loma-Osorio, Pablo; Marín, Francisco; Sánchez, Pedro L; Calvo, Francisco; Avanzas, Pablo; Hernández, Carolina; Serrano, Silvia; Carratalá, Arturo; Barrabés, José A

2013-07-01

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients. A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event. Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide. In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Risk factors for infection in the trauma patient.

PubMed Central

Morgan, A. S.

1992-01-01

The most common cause of late death following trauma is sepsis. The traumatized patient has a significant increased risk of infection. Transfusion, hypotension, and prolonged ventilatory support are predictive of septic complications. In addition, the trauma patient has a higher predisposition to pneumonia than nontrauma patients (18% versus 3% incidence of pneumonia, P < .001). Additional risk factors include the degree of nutrition status and the type of medications used during surgery. Immunologic depression may be an additional risk factor. There is mounting evidence that trauma can result in host defense abnormalities. To prevent the significant mortality caused by sepsis, close surveillance must be maintained, nutritional status must be optimal, and liberal use of antibiotics should be discouraged. Their use should be guided by appropriate cultures and sensitivities. PMID:1296993

Variability of Offending Allergens of Allergic Rhinitis According to Age: Optimization of Skin Prick Test Allergens

PubMed Central

Lee, Ji-Eun; Ahn, Jae-Chul; Han, Doo Hee; Kim, Dong-Young; Kim, Jung-Whun; Cho, Sang-Heon; Park, Heung-Woo

2014-01-01

Purpose This study evaluates offending allergens in patients with allergic rhinitis (AR) according to age that establish a minimal panel for skin prick test (SPT) allergens required to identify if a patient is sensitized. Methods We retrospectively analyzed SPT results according to age to determine the minimum test battery panel necessary to screen at least 93%-95% of AR patients. Allergic skin tests (common airborne indoor and outdoor allergens) were performed on 7,182 patients from January 2007 to June 2011. All patients were classified into 9 groups according to age; subsequently, we investigated offending allergens by age group. Results A total of 5,032 (70.1%) patients were found sensitized to at least one of the 55 aeroallergen extracts tested. The annual ranking of offending allergens was not significantly different from each other over the past 5 years. House dust mites (HDM) were the most prevalent allergens ranked from first to third for all 5 years. The allergens in the minimum test panel differed slightly among all age groups; in addition, the types of sensitized allergen sources were more diverse in the older versus younger age group. HDM covered a larger proportion of the sensitized allergens in the younger age group versus the older age group. Testing with 5 allergens (Dermatophagoides farinae, Tetranychus urticae, oak, mugwort and cockroach) adequately identified over 90% of the sensitized patients. Conclusions A SPT with around 5-7 allergens adequately detected most of the sensitization in the majority of the age groups in Korea. However, this study suggests that physicians perform the SPT with appropriately selected allergens in each age category for the screening of AR. PMID:24404393

Variability of offending allergens of allergic rhinitis according to age: optimization of skin prick test allergens.

PubMed

Lee, Ji-Eun; Ahn, Jae-Chul; Han, Doo Hee; Kim, Dong-Young; Kim, Jung-Whun; Cho, Sang-Heon; Park, Heung-Woo; Rhee, Chae-Seo

2014-01-01

This study evaluates offending allergens in patients with allergic rhinitis (AR) according to age that establish a minimal panel for skin prick test (SPT) allergens required to identify if a patient is sensitized. We retrospectively analyzed SPT results according to age to determine the minimum test battery panel necessary to screen at least 93%-95% of AR patients. Allergic skin tests (common airborne indoor and outdoor allergens) were performed on 7,182 patients from January 2007 to June 2011. All patients were classified into 9 groups according to age; subsequently, we investigated offending allergens by age group. A total of 5,032 (70.1%) patients were found sensitized to at least one of the 55 aeroallergen extracts tested. The annual ranking of offending allergens was not significantly different from each other over the past 5 years. House dust mites (HDM) were the most prevalent allergens ranked from first to third for all 5 years. The allergens in the minimum test panel differed slightly among all age groups; in addition, the types of sensitized allergen sources were more diverse in the older versus younger age group. HDM covered a larger proportion of the sensitized allergens in the younger age group versus the older age group. Testing with 5 allergens (Dermatophagoides farinae, Tetranychus urticae, oak, mugwort and cockroach) adequately identified over 90% of the sensitized patients. A SPT with around 5-7 allergens adequately detected most of the sensitization in the majority of the age groups in Korea. However, this study suggests that physicians perform the SPT with appropriately selected allergens in each age category for the screening of AR.

Allergic contact dermatitis caused by isobornyl acrylate in OmniPod, an innovative tubeless insulin pump.

PubMed

Raison-Peyron, Nadia; Mowitz, Martin; Bonardel, Nathalie; Aerts, Olivier; Bruze, Magnus

2018-04-10

The frequency of allergic contact dermatitis caused by (meth)acrylates is increasing worldwide, and isobornyl acrylate (IBOA) has been identified as a culprit sensitizer in FreeStyle Libre, a medical device used by diabetic patients. To report on 4 patients sensitized to IBOA contained in OmniPod, a new, tubeless insulin pump, and to describe the clinical and chemical analytical work-up. Four patients with eczematous skin eruptions after using OmniPod, including 2 with previous adverse skin reactions to FreeStyle Libre, were patch tested with a baseline series and additional (meth)acrylates, including IBOA in several concentrations and/or vehicles. Gas chromatography-mass spectrometry (GC-MS) was used to identify the presence of IBOA in OmniPod. All patients were shown to be sensitized to IBOA. GC-MS identified IBOA in OmniPod, with the highest concentrations being found in the unit itself and not in the adhesive patch. The OmniPod tubeless insulin pump is another source of IBOA, and its use may lead to primary sensitization to this acrylate, or may provoke elicitation of allergic contact dermatitis in previously sensitized patients. Our cases highlight the need to obtain satisfactory cooperation from pharmaceutical companies involved in the manufacture of these widely used medical devices. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients

PubMed Central

PAPADOPOULOU, EIRINI; TSOULOS, NIKOLAOS; TSIRIGOTI, ANGELIKI; APESSOS, ANGELA; AGIANNITOPOULOS, KONSTANTINOS; METAXA-MARIATOU, VASILIKI; ZAROGOULIDIS, KONSTANTINOS; ZAROGOULIDIS, PAVLOS; KASARAKIS, DIMITRIOS; KAKOLYRIS, STYLIANOS; DAHABREH, JUBRAIL; VLASTOS, FOTIS; ZOUBLIOS, CHARALAMPOS; RAPTI, AGGELIKI; PAPAGEORGIOU, NIKI GEORGATOU; VELDEKIS, DIMITRIOS; GAGA, MINA; ARAVANTINOS, GERASIMOS; KARAVASILIS, VASILEIOS; KARAGIANNIDIS, NAPOLEON; NASIOULAS, GEORGE

2015-01-01

It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18–21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of EGFR mutations. Furthermore, KRAS mutation analysis in patients with a known smoking history revealed no difference in mutation frequency according to smoking status; however, a different mutation spectrum was observed. PMID:26622815

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Evaluation and construction of diagnostic criteria for inclusion body myositis

PubMed Central

Mammen, Andrew L.; Amato, Anthony A.; Weiss, Michael D.; Needham, Merrilee

2014-01-01

Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%–84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). Conclusions: Published expert consensus–derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence: This study provides Class II evidence that published expert consensus–derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities. PMID:24975859

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

PubMed Central

Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

[Effects of critical ultrasonic management of Peking Union Medical College Hospital on the etiological diagnosis of patients with acute respiratory failure].

PubMed

Zhao, Hua; Wang, Xiaoting; Liu, Dawei; Zhang, Hongmin; He, Huaiwu; Long, Yun

2015-12-15

To evaluate the diagnostic value and potential therapeutic impact of Peking Union Medical College Hospital critical ultrasonic management (PCUM) in the early management of critically ill patients with acute respiratory failure (ARF). Patients admitted into the ICU of Peking Union Medical College Hospital for ARF were consecutively recruited over a 18-month period. Patients were randomly divided into conventional group and PCUM group (critical care ultrasonic examination was added in addition to conventional examinations). The two groups were compared with respect to time to preliminary diagnosis, time to final diagnosis, diagnostic accuracy, time to treatment response, time to other examination. A total of 187 patients were included in this study. The two groups showed no significant differences in general clinical information or final diagnosis (P > 0.05). The PCUM group had a shorter time to preliminary diagnosis, time to final diagnosis, time to treatment response, time to X-ray/CT examination, and a higher diagnostic accuracy than the conventional group (P < 0.001). PCUM had high sensitivity and specificity for the diagnosis of acute respiratory distress syndrome (ARDS) (sensitivity 92.0%, specificity 98.5%), acute pulmonary edema (sensitivity 94.7%, specificity 96.1%), pulmonary consolidation (sensitivity 85.7%, specificity 98.6%), COPD/asthma (sensitivity 84.2%, specificity 98.7%). The PCUM is seem to be an attractive complementary diagnostic tool and able to contribute to an early therapeutic decision for the patients with ARF.

Contact allergies in haemodialysis patients: a prospective study of 75 patients.

PubMed

Gaudy-Marqueste, C; Jouhet, C; Castelain, M; Brunet, P; Berland, Y; Grob, J J; Richard, M A

2009-02-01

Haemodialysis exposes patients to many potentially sensitizing allergens. The primary objective of this study was to evaluate the prevalence of delayed hypersensitivity in a population of haemodialysis patients. Secondary objectives were to identify the possible risk factors for contact sensitization and to propose a series of skin tests adapted to haemodialysis patients. A prospective monocentric study was carried out in a nonselected population of haemodialysis patients. For each patient, medical history of atopy and allergic contact dermatitis, ongoing treatments (including topical ones), presence of eczema at the site of vascular access for haemodialysis were recorded. Allergological investigation included delayed hypersensitivity tests (European Environmental and Contact Dermatitis Research Group battery, tests GERDA, additional list and a battery of antiseptics and other dialysis-specific allergens) and latex skin prick test. Seventy-five patients (41 men, 34 women, mean age of 65 years old), with a mean 3.8 years under dialysis, were included. Nineteen patients (25%) had at least one positive skin test and 13 (17%) a positive patch test to at least one allergen relative to dialysis process including eight tests to lidocaine-prilocaine cream and three to povidone-iodine. Tests results seemed clinically relevant since nine patients had localized pruritus at the fistula site and six patients active eczema around it. Contact sensitizations are frequent in haemodialysis patients and are linked to vascular access conditioning especially the use of lidocaine-prilocaine cream. Designing a specific test battery could help to diagnose the potential allergens and subsequently to give advice to avoid contact with sensitizing agents.

Positron emission mammography in breast cancer presurgical planning: comparisons with magnetic resonance imaging

PubMed Central

Narayanan, Deepa; Kalinyak, Judith E.; The, Juliette; Velasquez, Maria Victoria; Kahn, Simone; Saady, Matthew; Mahal, Ravinder; Chrystal, Larraine

2010-01-01

Purpose The objective of this study was to compare the performance characteristics of 18F-fluorodeoxyglucose (FDG) positron emission mammography (PEM) with breast magnetic resonance imaging (MRI) as a presurgical imaging and planning option for index and ipsilateral lesions in patients with newly diagnosed, biopsy-proven breast cancer. Methods Two hundred and eight women >25 years of age (median age = 59.7 ± 14.1 years) with biopsy-proven primary breast cancer enrolled in this prospective, single-site study. MRI, PEM, and whole-body positron emission tomography (WBPET) were conducted on each patient within 7 business days. PEM and WBPET images were acquired on the same day after intravenous administration of 370 MBq of FDG (median = 432.9 MBq). PEM and MRI images were blindly evaluated, compared with final surgical histopathology, and the sensitivity determined. Substudy analysis compared the sensitivity of PEM versus MRI in patients with different menopausal status, breast density, and use of hormone replacement therapy (HRT) as well as determination of performance characteristics for additional ipsilateral lesion detection. Results Two hundred and eight patients enrolled in the study of which 87% (182/208) were analyzable. Of these analyzable patients, 26.4% (48/182), 7.1% (13/182), and 64.2% (120/182) were pre-, peri-, and postmenopausal, respectively, and 48.4% (88/182) had extremely or heterogeneously dense breast tissue, while 33.5% (61/182) had a history of HRT use. Ninety-two percent (167/182) underwent core biopsy for index lesion diagnosis. Invasive cancer was found in 77.5% (141/182), while ductal carcinoma in situ (DCIS) and/or Paget’s disease were found in 22.5% (41/182) of patients. Both PEM and MRI had index lesion depiction sensitivity of 92.8% and both were significantly better than WBPET (67.9%, p < 0.001, McNemar’s test). For index lesions, PEM and MRI had equivalent sensitivity of various tumors, categorized by tumor stage as well as similar invasive tumor size predictions with Spearman's correlation coefficient of 0.61 for both PEM and MRI compared to surgical pathology. Menopausal status, breast density, and HRT did not influence the sensitivity of PEM or MRI. For 67 additional unsuspected ipsilateral lesions or multifocal lesions, PEM had sensitivity of 85% (34/40) and specificity of 74%, (20/27) compared to MRI's sensitivity of 98% (39/40) and specificity of 48% (13/27) [p = 0.074, for sensitivity; p = 0.096 for specificity] Conclusion PEM is a good alternative to MRI as a presurgical breast imaging option and its performance characteristics are not affected by patient menopausal/hormonal status or breast density. PMID:20871992

Positron emission mammography in breast cancer presurgical planning: comparisons with magnetic resonance imaging.

PubMed

Schilling, Kathy; Narayanan, Deepa; Kalinyak, Judith E; The, Juliette; Velasquez, Maria Victoria; Kahn, Simone; Saady, Matthew; Mahal, Ravinder; Chrystal, Larraine

2011-01-01

The objective of this study was to compare the performance characteristics of (18)F-fluorodeoxyglucose (FDG) positron emission mammography (PEM) with breast magnetic resonance imaging (MRI) as a presurgical imaging and planning option for index and ipsilateral lesions in patients with newly diagnosed, biopsy-proven breast cancer. Two hundred and eight women >25 years of age (median age = 59.7 ± 14.1 years) with biopsy-proven primary breast cancer enrolled in this prospective, single-site study. MRI, PEM, and whole-body positron emission tomography (WBPET) were conducted on each patient within 7 business days. PEM and WBPET images were acquired on the same day after intravenous administration of 370 MBq of FDG (median = 432.9 MBq). PEM and MRI images were blindly evaluated, compared with final surgical histopathology, and the sensitivity determined. Substudy analysis compared the sensitivity of PEM versus MRI in patients with different menopausal status, breast density, and use of hormone replacement therapy (HRT) as well as determination of performance characteristics for additional ipsilateral lesion detection. Two hundred and eight patients enrolled in the study of which 87% (182/208) were analyzable. Of these analyzable patients, 26.4% (48/182), 7.1% (13/182), and 64.2% (120/182) were pre-, peri-, and postmenopausal, respectively, and 48.4% (88/182) had extremely or heterogeneously dense breast tissue, while 33.5% (61/182) had a history of HRT use. Ninety-two percent (167/182) underwent core biopsy for index lesion diagnosis. Invasive cancer was found in 77.5% (141/182), while ductal carcinoma in situ (DCIS) and/or Paget's disease were found in 22.5% (41/182) of patients. Both PEM and MRI had index lesion depiction sensitivity of 92.8% and both were significantly better than WBPET (67.9%, p < 0.001, McNemar's test). For index lesions, PEM and MRI had equivalent sensitivity of various tumors, categorized by tumor stage as well as similar invasive tumor size predictions with Spearman's correlation coefficient of 0.61 for both PEM and MRI compared to surgical pathology. Menopausal status, breast density, and HRT did not influence the sensitivity of PEM or MRI. For 67 additional unsuspected ipsilateral lesions or multifocal lesions, PEM had sensitivity of 85% (34/40) and specificity of 74%, (20/27) compared to MRI's sensitivity of 98% (39/40) and specificity of 48% (13/27) [p = 0.074, for sensitivity; p = 0.096 for specificity] PEM is a good alternative to MRI as a presurgical breast imaging option and its performance characteristics are not affected by patient menopausal/hormonal status or breast density.

Highly sensitive detection of ESR1 mutations in cell-free DNA from patients with metastatic breast cancer using molecular barcode sequencing.

PubMed

Masunaga, Nanae; Kagara, Naofumi; Motooka, Daisuke; Nakamura, Shota; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

2018-01-01

We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR). MB-NGS showed a higher sensitivity (0.1%) than NGS without barcode (1%) by reducing background errors. Of the cfDNA samples from 34 patients with metastatic breast cancer, NGS without barcode revealed seven mutations in six patients (17.6%) and MB-NGS revealed six additional mutations including three mutations not reported in the COSMIC database of breast cancer, resulting in total 13 ESR1 mutations in ten patients (29.4%). Regarding the three hotspot mutations, all the patients with mutations detected by MB-NGS had identical mutations detected by droplet digital PCR (ddPCR), and mutant allele frequency correlated very well between both (r = 0.850, p < 0.01). Moreover, all the patients without these mutations by MB-NGS were found to have no mutations by ddPCR. In conclusion, MB-NGS could successfully detect ESR1 mutations in cfDNA with a higher sensitivity of 0.1% than conventional NGS and was considered as clinically useful as ddPCR.

[Laboratory diagnosis of auto-immune hemolytic anemia: characteristics of the manual direct test of Polybrene].

PubMed

Braga, G W; Bordin, J O; Moreira Júnior, G; Kuroda, A

1998-01-01

The direct manual Polybrene test (DPT) and the direct antiglobulin tests (DAT) were employed to detect antibody sensitizing red blood cell (RCB) in patients with clinical and laboratorial findings of autoimmune hemolytic anemia (AIHA). To compare the sensitivity and specificity of DPT and DAT in the diagnosis of AIHA. Eighteen consecutive patients with diagnosis of AIHA were evaluated. The control group consisted of 20 normal volunteers blood donors and 20 patients with sickle cell anemia. All patients and controls were submitted to DPT and DAT. All DAT positive samples were further tested using monospecific reagents (anti-IgG heavy chain and anti-C3d). Positive samples for either DPT or DAT were evaluated by eluate technique using. The dichloromethane (DCM). The DAT was positive in 14 patients and negative in 4 subjects, while the DPT was positive in 17 patients and negative in 1 individual who had a positive DAT owing to complement (C3d). All positive eluates performed with DCM showed RBC autoantibodies with presumed "anti-Rh" specificity. The sensitivity rate of the DPT (94%) was significantly (p < 0.05) higher than the sensitivity rate of DAT (78%) to determine whether IgG was bound in vivo, but no difference was found regarding the specificity of the two tests. 1) The DPT is more sensitive than the DAT in detecting IgG autoantibody on the RBCs of patients with AIHA; 2) because of its simplicity and rapidity, the DPT is a useful additional screening test for the investigation of Coombs-negative AIHA.

Pulse oximetry in the evaluation of peripheral vascular disease.

PubMed

Jawahar, D; Rachamalla, H R; Rafalowski, A; Ilkhani, R; Bharathan, T; Anandarao, N

1997-08-01

The role of pulse oximetry in the evaluation of peripheral vascular disease (PVD) was investigated. In addition, the value of elevating the limb to improve the sensitivity of detection of PVD by the pulse oximeter was also determined. Pulse oximetry reading in the toes were obtained in 40 young, healthy volunteers and in 40 randomly selected patients referred to the vascular investigation laboratory over a period of two months. All 40 healthy volunteers had normal pulse oximetry readings. Normal pulse oximetry reading in the toes was defined as > 95% O2 Sat and +/-2 of finger pulse oximetry reading. In all 40 patients, pulse oximetry readings were either normal or not detected at all. Since there was no gradation in decrease in the pulse oximetry reading with severity of disease or with elevation of the patient's lower extremity, an absent or no reading was considered as an abnormal result from the test. The frequency of abnormal pulse oximetry readings increased significantly in groups with abnormal ankle-brachial pressure index (ABPI) and also varied significantly with elevation of the patients' lower limbs. In patients with no PVD detected by Doppler (ABPI > 0.9), pulse oximetry readings were normal in all. However, in patients with moderate PVD (ABPI, 0.5-0.9), 84% of the patients' lower limbs had normal pulse oximetry readings and 16% had an abnormal reading at baseline level (flat). An additional 12% of the lower limbs in this group had an abnormal reading on elevation of the limb to 12 inches. In patients with severe PVD (ABPI < 0.5), 54% of the patients' lower limbs had an abnormal reading at baseline and an additional 23% had an abnormal reading at elevation of the limb to 12 inches. In conclusion, pulse oximetry was not a sensitive test for detecting early PVD.

Comparative evaluation of two rapid Salmonella-IgM tests and blood culture in the diagnosis of enteric fever.

PubMed

Prasad, K J; Oberoi, J K; Goel, N; Wattal, C

2015-01-01

Enteric fever is a major public health problem in developing countries like India. An early and accurate diagnosis is necessary for a prompt and effective treatment. We have evaluated the diagnostic accuracy of two Rapid Salmonella-IgM tests (Typhidot-IgM and Enteroscreen-IgM) as compared to blood culture in rapid and early diagnosis of enteric fever. A total of 2,699 patients' serum samples were tested by Rapid Salmonella-IgM tests and blood culture. Patients were divided into two groups. Test group - patients with enteric fever and blood culture positives for Salmonella Typhi; and three types of Controls, i.e. patients with non-enteric fever illnesses, normal healthy controls and patients positive for S. Paratyphi- A. In addition to this we have also evaluated the significance of positive Salmonella-IgM tests among blood culture-negative cases. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Typhidot-IgM test and Enteroscreen-IgM test considering blood culture as gold standard were 97.29% and 88.13%, 97.40% and 87.83%, 98.18% and 92.03%, 96.15% and 82.27%, respectively. Typhidot-IgM test was found to be significantly more sensitive and specific as compared to Enteroscreen-IgM. Among blood culture-negative patients, Rapid Salmonella-IgM tests detected 72.25% additional cases of enteric fever. Although the Rapid Salmonella-IgM tests are meant to diagnose S. Typhi only, but these tests detect S. Paratyphi- A also. Thirty-eight patients who were blood culture-positive for S. Paratyphi- A were also positive by Rapid Salmonella-IgM tests. Rapid Salmonella-IgM tests offer an advantage of increased sensitivity, rapidity, early diagnosis and simplicity over blood culture.

Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker.

PubMed

Tanko, Zita; Shab, Arna; Diepgen, Thomas Ludwig; Weisshaar, Elke

2009-06-01

Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.

2013 American College of Rheumatology/European League against rheumatism classification criteria for systemic sclerosis outperform the 1980 criteria: data from the Canadian Scleroderma Research Group.

PubMed

Alhajeri, Hebah; Hudson, Marie; Fritzler, Marvin; Pope, Janet; Tatibouet, Solène; Markland, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Kaminska, Elzbieta; Masetto, Ariel; Sutton, Evelyn; Mathieu, Jean-Pierre; Ligier, Sophie; Grodzicky, Tamara; LeClercq, Sharon; Thorne, Carter; Gyger, Geneviève; Smith, Douglas; Fortin, Paul R; Larché, Maggie; Baron, Murray

2015-04-01

The goal of this study was to determine the sensitivity of the new 2013 classification criteria for systemic sclerosis (SSc; scleroderma) in an independent cohort of SSc subjects and to assess the contribution of individual items of the criteria to the overall sensitivity. SSc subjects from the Canadian Scleroderma Research Group cohort were assessed. Sensitivity was determined in several subgroups of patients. In patients without the criterion of skin thickening proximal to the metacarpophalangeal (MCP) joints, we recalculated sensitivity after removing the individual criterion. A total of 724 SSc patients were included. Most were women (86%), mean age was 55.8 years, mean disease duration was 10.9 years, and 59% had limited cutaneous SSc (lcSSc). Overall, the sensitivity of the 2013 criteria was 98.3% compared to 88.3% for the 1980 criteria. This pattern was consistent among those with lcSSc (98.8% versus 85.6%), anticentromere antibodies (98.9% versus 79.8%), disease duration ≤3 years (98.7% versus 84.7%), and no skin involvement proximal to the MCP joints (97% versus 60%). In the latter subgroup, removing Raynaud's phenomenon and sclerodactyly from the criteria reduced the sensitivity to 77% and 79%, respectively. Removing both sclerodactyly and puffy fingers reduced the sensitivity to 62%. The 2013 SSc classification criteria classify more SSc patients than the 1980 criteria. The improvement in sensitivity is most striking in those with lcSSc, especially those without skin involvement proximal to the MCP joints. The addition of Raynaud's phenomenon and puffy fingers to the 2013 criteria accounts for important gains in sensitivity. Copyright © 2015 by the American College of Rheumatology.

Is the European standard series suitable for patch testing in Riyadh, Saudi Arabia?

PubMed

el-Rab, M O; al-Sheikh, O A

1995-11-01

Due to the lack of a regional patch test series in our geographical area, the suitability of the European standard series was evaluated by patch testing dermatitis patients in Riyadh, Saudi Arabia. Of 240 consecutive patients with various forms of dermatitis, 136 (57%) showed 1 or more positive patch tests, women, 74 (54%), slightly outnumbering men, 62 (46%). Positive reactions were found to 21 of the 22 items in the test series. Sensitization was most common to nickel sulfate (51 = 37.5%), potassium dichromate (48 = 35%) and cobalt chloride (43 = 32%) The frequency of sensitization to nickel was higher in women (41 = 30%) while that to dichromate was higher in men (39 = 29%). Less reactions were found to fragrance mix (21 = 15%), formaldehyde (15 = 11%) and neomycin sulfate (15 = 11%). Sensitization to other allergens ranged between 10 and 1%. Less than 1% of patients (0.7%) reacted to benzocaine and none to primin. The frequency of occurrence of multiple sensitivities is also presented. We conclude that the European standard series is suitable for patch testing dermatitis patients in our region, with the exception of benzocaine and primin. The addition of 3 allergens that could be of local relevance is discussed.

Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and missed by the current fragrance mix.

PubMed

Frosch, Peter J; Pirker, Claudia; Rastogi, Suresh C; Andersen, Klaus E; Bruze, Magnus; Svedman, Cecilia; Goossens, An; White, Ian R; Uter, Wolfgang; Arnau, Elena Giménez; Lepoittevin, Jean-Pierre; Menné, Torkil; Johansen, Jeanne Duus

2005-04-01

The currently used 8% fragrance mix (FM I) does not identify all patients with a positive history of adverse reactions to fragrances. A new FM II with 6 frequently used chemicals was evaluated in 1701 consecutive patients patch tested in 6 dermatological centres in Europe. FM II was tested in 3 concentrations - 28% FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral), 2% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%alpha-hexyl-cinnamic aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Positive reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied considerably between the 6 centres, with a mean value of 7.2% for FM I and means ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history - certain and none - values for sensitivity and specificity were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%; 28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%; 28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients with a certain history, a total of 7 patients were found reacting to FM II only. Conversely, in the group of patients without any fragrance history, there were significantly more positive reactions to FM I than to any concentration of FM II. In conclusion, the new FM II detects additional patients sensitive to fragrances missed by FM I; the number of false-positive reactions is lower with FM II than with FM I. Considering sensitivity, specificity and the frequency of doubtful reactions, the medium concentration, 14% FM II, seems to be the most appropriate diagnostic screening tool.

Costs of trastuzumab in combination with chemotherapy for HER2-positive advanced gastric or gastroesophageal junction cancer: an economic evaluation in the Chinese context.

PubMed

Wu, Bin; Ye, Ming; Chen, Huafeng; Shen, Jinfang F

2012-02-01

Adding trastuzumab to a conventional regimen of chemotherapy can improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (GEJ) cancer, but the economic impact of this practice is unknown. The purpose of this cost-effectiveness analysis was to estimate the effects of adding trastuzumab to standard chemotherapy in patients with HER2-positive advanced gastric or GEJ cancer on health and economic outcomes in China. A Markov model was developed to simulate the clinical course of typical patients with HER2-positive advanced gastric or GEJ cancer. Five-year quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Model inputs were derived from the published literature and government sources. Direct costs were estimated from the perspective of Chinese society. One-way and probabilistic sensitivity analyses were conducted. On baseline analysis, the addition of trastuzumab increased cost and QALY by $56,004.30 (year-2010 US $) and 0.18, respectively, relative to conventional chemotherapy, resulting in an ICER of $251,667.10/QALY gained. Probabilistic sensitivity analyses supported that the addition of trastuzumab was not cost-effective. Budgetary impact analysis estimated that the annual increase in fiscal expenditures would be ~$1 billion. On univariate sensitivity analysis, the median overall survival time for conventional chemotherapy was the most influential factor with respect to the robustness of the model. The findings from the present analysis suggest that the addition of trastuzumab to conventional chemotherapy might not be cost-effective in patients with HER2-positive advanced gastric or GEJ cancer. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Vertically Aligned Nitrogen-Doped Carbon Nanotube Carpet Electrodes: Highly Sensitive Interfaces for the Analysis of Serum from Patients with Inflammatory Bowel Disease.

PubMed

Wang, Qian; Subramanian, Palaniappan; Schechter, Alex; Teblum, Eti; Yemini, Reut; Nessim, Gilbert Daniel; Vasilescu, Alina; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine

2016-04-20

The number of patients suffering from inflammatory bowel disease (IBD) is increasing worldwide. The development of noninvasive tests that are rapid, sensitive, specific, and simple would allow preventing patient discomfort, delay in diagnosis, and the follow-up of the status of the disease. Herein, we show the interest of vertically aligned nitrogen-doped carbon nanotube (VA-NCNT) electrodes for the required sensitive electrochemical detection of lysozyme in serum, a protein that is up-regulated in IBD. To achieve selective lysozyme detection, biotinylated lysozyme aptamers were covalently immobilized onto the VA-NCNTs. Detection of lysozyme in serum was achieved by measuring the decrease in the peak current of the Fe(CN)6(3-/4-) redox couple by differential pulse voltammetry upon addition of the analyte. We achieved a detection limit as low as 100 fM with a linear range up to 7 pM, in line with the required demands for the determination of lysozyme level in patients suffering from IBD. We attained the sensitive detection of biomarkers in clinical samples of healthy patients and individuals suffering from IBD and compared the results to a classical turbidimetric assay. The results clearly indicate that the newly developed sensor allows for a reliable and efficient analysis of lysozyme in serum.

Scanning laser densitometry and color perimetry demonstrate reduced photopigment density and sensitivity in two patients with retinal degeneration.

PubMed

Tornow, R P; Stilling, R; Zrenner, E

1999-10-01

To test the feasibility of scanning laser densitometry with a modified Rodenstock scanning laser ophthalmoscope (SLO) to measure the rod and cone photopigment distribution in patients with retinal diseases. Scanning laser densitometry was performed using a modified Rodenstock scanning laser ophthalmoscope. The distribution of the photopigments was calculated from dark adapted and bleached images taken with the 514 nm laser of the SLO. This wavelength is absorbed by rod and cone photopigments. Discrimination is possible due to their different spatial distribution. Additionally, to measure retinal sensitivity profiles, dark adapted two color static perimetry with a Tübinger manual perimeter was performed along the horizontal meridian with 1 degree spacing. A patient with retinitis pigmentosa had slightly reduced photopigment density within the central +/- 5 degrees but no detectable photopigment for eccentricities beyond 5 degrees. A patient with cone dystrophy had nearly normal pigment density beyond +/- 5 degrees, but considerably reduced photopigment density within the central +/- 5 degrees. Within the central +/- 5 degrees, the patient with retinitis pigmentosa had normal sensitivity for the red stimulus and reduced sensitivity for the green stimulus. There was no measurable function beyond 7 degrees. The patient with cone dystrophy had normal sensitivity for the green stimulus outside the foveal center and reduced sensitivity for the red stimulus at the foveal center. The results of color perimetry for this patient with a central scotoma were probably influenced by eccentric fixation. Scanning laser densitometry with a modified Rodenstock SLO is a useful method to assess the human photopigment distribution. Densitometry results were confirmed by dark adapted two color static perimetry. Photopigment distribution and retinal sensitivity profiles can be measured with high spatial resolution. This may help to measure exactly the temporal development of retinal diseases and to test the success of different therapeutic treatments. Both methods have limitations at the present state of development. However, some of these limitations can be overcome by further improving the instruments.

Use of capture-based next-generation sequencing to detect ALK fusion in plasma cell-free DNA of patients with non-small-cell lung cancer.

PubMed

Cui, Shaohua; Zhang, Wei; Xiong, Liwen; Pan, Feng; Niu, Yanjie; Chu, Tianqing; Wang, Huimin; Zhao, Yizhuo; Jiang, Liyan

2017-01-10

Capture-based next-generation sequencing (NGS) is a potentially useful diagnostic method to measure tumor tissue DNA in blood as it can identify concordant mutations between cell-free DNA (cfDNA) and primary tumor DNA in lung cancer patients. In this study, the sensitivity, specificity and accuracy of capture-based NGS for detecting ALK fusion in plasma cfDNA was assessed. 24 patients with tissue ALK-positivity and 15 who did not harbor ALK fusion were enrolled. 13 ALK-positive samples were identified by capture-based NGS among the 24 samples with tissue ALK-positivity. In addition to EML4-ALK, 2 rare fusion types (FAM179A-ALK and COL25A1-ALK) were also identified. The overall sensitivity, specificity and accuracy for all cases were 54.2%, 100% and 71.8%, respectively. For patients without distant metastasis (M0-M1a) and patients with distant metastasis (M1b), the sensitivities were 28.6% and 64.7%, respectively. In the 15 patients who received crizotinib, the estimated median PFS was 9.93 months. Thus, captured-based NGS has acceptable sensitivity and excellent specificity for the detection of ALK fusion in plasma cfDNA, especially for patients with distant metastasis. This non-invasive method is clinically feasible for detecting ALK fusion in patients with advanced-stage NSCLC who cannot undergo traumatic examinations or have insufficient tissue samples for molecular tests.

Adding Debriefing to Objective Structured Clinical Examinations to Enhance Disability Cultural Sensitivity in Pharmacy Students

ERIC Educational Resources Information Center

Smith, Mark Joseph

2016-01-01

Debriefing was added to the design of an objective structured clinical examination (OSCE) after second-year pharmacy students performed poorly at considering patient disability in planning for patient care. This mixed-methods study examines secondary data to explore whether and how the addition of a debriefing to an OSCE impacted pharmacy…

Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic noncancer pain.

PubMed

Markman, John D; Barbosa, William A; Gewandter, Jennifer S; Frazer, Maria; Rast, Shirley; Dugan, Michelle; Nandigam, Kiran; Villareal, Armando; Kwong, Tai C

2015-06-01

To determine whether the prevailing liquid chromatography and tandem mass spectroscopy assay (LC-MS/MS) assay designed to monitor buprenorphine compliance of the sublingual formulation used in the substance abuse treatment setting can be extrapolated to the transdermal formulation used in the chronic pain treatment setting, which is 1000-fold less concentrated. Retrospective chart review. Self-reported compliant patients using the transdermal or sublingual formulations of buprenorhphine. Transdermal patch application was also visually confirmed during clinic visits. Urine drug test results from a LC-MS/MS were compared between samples from transdermal and sublingual patients. While all sublingual patients tested positive for at least one metabolite of buprenorphine, only 69% of the transdermal patients did so. In addition, the most abundant metabolite in the transdermal patients was buprenorphine-glucuronide, as compared with norbuprenorphine-glucuronide in sublingual patients. These data suggest that currently available urine drug tests for buprenorphine, including the more expensive LC-MS/MS based assays, may not be sufficiently sensitive to detect the metabolites from transdermal buprenorphine patients. This study highlights the need to evaluate the value and sensitivity of urine drug tests given the wide range of buprenorphine dosing in clinical practice. These results underscore the need for additional cost benefit analyses comparing different confirmatory drug testing techniques including many commercially available drug testing options. © 2014 Wiley Periodicals, Inc. Wiley Periodicals, Inc.

Changes in color vision and contrast sensitivity after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy.

PubMed

Cabrerizo, Javier; Livny, Eitan; Musa, Fayyaz U; Leeuwenburgh, Paulien; van Dijk, Korine; Melles, Gerrit R J

2014-10-01

The aim of this study is to evaluate contrast sensitivity, color vision, and subjective patient satisfaction after Descemet membrane endothelial keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED). From a group of 500 DMEK surgeries performed in our center, patients with a history of bilateral FED and unilateral DMEK were identified. A total of 29 patients were included in the study and divided into 2 groups: phakic (n = 12) and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED-affected eye. In addition, a control group of 10 healthy eyes of 10 patients was included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color vision tests were performed. Subjective optical quality was graded with a questionnaire. Compared with untreated FED-affected eyes, best spectacle-corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P = 0.030 and P < 0.001, respectively); a similar result was obtained for contrast sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ between untreated FED-affected and DMEK-operated eyes in the phakic group (P = 0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic group (P < 0.001) and in the pseudophakic group (P < 0.001). In FED, DMEK may not only be effective for obtaining a higher visual acuity but particularly improving the contrast sensitivity may also lead to better subjective optical performance. Although frequently mentioned spontaneously by patients, an objective change in color vision could not be substantiated. Hence, quantifying contrast sensitivity before surgery may aid in the decision for surgery, and in the evaluation of surgical outcome.

Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux.

PubMed

Massanyi, Eric Z; Preece, Janae; Gupta, Angela; Lin, Susan M; Wang, Ming-Hsien

2013-10-01

To assess the sensitivity and negative predictive value (NPV) of screening renal and bladder ultrasound (RBUS) after initial febrile urinary tract infection (UTI) among patients with clinically significant vesicoureteral reflux (VUR). A retrospective review was performed of all children <2 years of age who presented with a febrile UTI between 2004 and 2011. The sensitivity and NPV of initial RBUS was calculated among patients who were found to have high-grade (IV-V) VUR. Additionally, initial RBUS among patients with evidence of photopenia on dimercaptosuccinic acid (DMSA) scan or who underwent surgical intervention were reviewed. One hundred forty-four patients with febrile UTI were identified; available RBUS, voiding cystourethrogram (VCUG), and DMSA results for each kidney were reviewed. One hundred fifty-eight kidneys had evidence of VUR on VCUG, and initial RBUS demonstrated abnormality in 25 (sensitivity 0.17). Forty-five kidneys had high-grade VUR and RBUS revealed abnormality in 16 (sensitivity 0.36). One hundred seventy-eight kidneys had no evidence of abnormality on initial RBUS, and 136 (76%) were found to have VUR (NPV 0.24), of which 31 had high-grade VUR (NPV 0.83). Seven kidneys had scarring on DMSA and initial RBUS was normal in 4 (57%). Twelve of 19 patients (63%) who eventually underwent surgical intervention had a normal initial RBUS. RBUS has poor sensitivity and NPV for detecting high-grade VUR in patients <2 years who present with a febrile UTI. A significant number of patients who were diagnosed with high-grade VUR, renal scarring, or underwent surgical correction of VUR had a negative screening RBUS. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of Endocrine Tests. C: glucagon and clonidine test in phaeochromocytoma.

PubMed

Bisschop, P H; Corssmit, E P M; Baas, S J; Serlie, M J; Endert, E; Wiersinga, W M; Fliers, E

2009-03-01

The diagnosis of phaeochromocytoma is based on the demonstration of catecholamine excess. Urine and plasma metanephrine measurements are highly sensitive tests for the diagnosis of phaeochromocytoma, but moderate elevations in metanephrines lack optimal specificity. In this study we aimed to evaluate the diagnostic value of additional tests, i.e. glucagon stimulation and clonidine suppression test, in patients with moderately elevated catecholamines and/or metanephrines. Patients with suspected phaeochromocytoma with moderately elevated catecholamines and/or metanephrines in plasma or urine were subjected to the glucagon stimulation and clonidine suppression test. The presence of phaeochromocytoma was confirmed by histology and the absence by a disease-free extended follow-up. Fifty-five patients were included. Phaeochromocytoma was diagnosed in 11 patients. The follow-up period in patients without phaeochromocytoma was 56 (19 to 154) months. The sensitivity of the glucagon test was 30% and the specificity 100%. The clonidine test had no discriminative power, because the area under the ROC curve was not significantly different from 0.5. The clonidine suppression test without normetanephrine measurements and the glucagon stimulation test are not sensitive enough to safely exclude phaeochromocytoma in patients with mildly elevated plasma or urine catecholamines.

The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis.

PubMed

Rolim, Ana Luiza R; Lindsey, Susan C; Kunii, Ilda S; Crispim, Felipe; Moisés, Regina Célia M S; Maciel, Rui M B; Dias-da-Silva, Magnus R

2014-10-01

Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called thyrotoxic periodic paralysis (TPP) and is characterised by transient hypokalaemia and hypophosphataemia under high thyroid hormone levels that is frequently precipitated by carbohydrate load. The sulphonylurea receptor 1 (SUR1 (ABCC8)) is an essential regulatory subunit of the β-cell ATP-sensitive K(+) channel that controls insulin secretion after feeding. Additionally, the SUR1 Ala1369Ser variant appears to be associated with insulin sensitivity. We examined the ABCC8 gene at the single nucleotide level using PCR-restriction fragment length polymorphism (RFLP) analysis to determine its allelic variant frequency and calculated the frequency of the Ala1369Ser C-allele variant in a cohort of 36 Brazilian TPP patients in comparison with 32 controls presenting with thyrotoxicosis without paralysis (TWP). We verified that the frequency of the alanine 1369 C-allele was significantly higher in TPP patients than in TWP patients (61.1 vs 34.4%, odds ratio (OR)=3.42, P=0.039) and was significantly more common than the minor allele frequency observed in the general population from the 1000 Genomes database (61.1 vs 29.0%, OR=4.87, P<0.005). Additionally, the C-allele frequency was similar between TWP patients and the general population (34.4 vs 29%, OR=1.42, P=0.325). We have demonstrated that SUR1 alanine 1369 variant is associated with allelic susceptibility to TPP. We suggest that the hyperinsulinaemia that is observed in TPP may be linked to the ATP-sensitive K(+)/SUR1 alanine variant and, therefore, contribute to the major feedforward precipitating factors in the pathophysiology of TPP. © 2014 Society for Endocrinology.

Performance of an automated electronic acute lung injury screening system in intensive care unit patients.

PubMed

Koenig, Helen C; Finkel, Barbara B; Khalsa, Satjeet S; Lanken, Paul N; Prasad, Meeta; Urbani, Richard; Fuchs, Barry D

2011-01-01

Lung protective ventilation reduces mortality in patients with acute lung injury, but underrecognition of acute lung injury has limited its use. We recently validated an automated electronic acute lung injury surveillance system in patients with major trauma in a single intensive care unit. In this study, we assessed the system's performance as a prospective acute lung injury screening tool in a diverse population of intensive care unit patients. Patients were screened prospectively for acute lung injury over 21 wks by the automated system and by an experienced research coordinator who manually screened subjects for enrollment in Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) trials. Performance of the automated system was assessed by comparing its results with the manual screening process. Discordant results were adjudicated blindly by two physician reviewers. In addition, a sensitivity analysis using a range of assumptions was conducted to better estimate the system's performance. The Hospital of the University of Pennsylvania, an academic medical center and ARDSNet center (1994-2006). Intubated patients in medical and surgical intensive care units. None. Of 1270 patients screened, 84 were identified with acute lung injury (incidence of 6.6%). The automated screening system had a sensitivity of 97.6% (95% confidence interval, 96.8-98.4%) and a specificity of 97.6% (95% confidence interval, 96.8-98.4%). The manual screening algorithm had a sensitivity of 57.1% (95% confidence interval, 54.5-59.8%) and a specificity of 99.7% (95% confidence interval, 99.4-100%). Sensitivity analysis demonstrated a range for sensitivity of 75.0-97.6% of the automated system under varying assumptions. Under all assumptions, the automated system demonstrated higher sensitivity than and comparable specificity to the manual screening method. An automated electronic system identified patients with acute lung injury with high sensitivity and specificity in diverse intensive care units of a large academic medical center. Further studies are needed to evaluate the effect of automated prompts that such a system can initiate on the use of lung protective ventilation in patients with acute lung injury.

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

PubMed

Suzuki, Cibele; Lopes da Silva, Nilceia; Kumar, Praveen; Pathak, Purnima; Ong, Siew Hwa

2017-08-01

Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross domestic product.

Economic evaluation of osteoporosis liaison service for secondary fracture prevention in postmenopausal osteoporosis patients with previous hip fracture in Japan.

PubMed

Moriwaki, K; Noto, S

2017-02-01

A model-based cost-effectiveness analysis was performed to evaluate the cost-effectiveness of secondary fracture prevention by osteoporosis liaison service (OLS) relative to no therapy in patients with osteoporosis and a history of hip fracture. Secondary fracture prevention by OLS is cost-effective in Japanese women with osteoporosis who have suffered a hip fracture. The purpose of this study was to estimate, from the perspective of Japan's healthcare system, the cost-effectiveness of secondary fracture prevention by OLS relative to no therapy in patients with osteoporosis and a history of hip fracture. A patient-level state transition model was developed to predict lifetime costs and quality-adjusted life years (QALYs) in patients with or without secondary fracture prevention by OLS. The incremental cost-effectiveness ratio (ICER) of secondary fracture prevention compared with no therapy was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. Compared with no therapy, secondary fracture prevention in patients aged 65 with T-score of -2.5 resulted in an additional lifetime cost of $3396 per person and conferred an additional 0.118 QALY, resulting in an ICER of $28,880 per QALY gained. Deterministic sensitivity analyses showed that treatment duration and offset time strongly affect the cost-effectiveness of OLS. According to the results of scenario analyses, secondary fracture prevention by OLS was cost-saving compared with no therapy in patients with a family history of hip fracture and high alcohol intake. Secondary fracture prevention by OLS is cost-effective in Japanese women with osteoporosis who have suffered a hip fracture. In addition, secondary fracture prevention is less expensive than no therapy in high-risk patients with multiple risk factors.

Down-regulation of FcεRI-mediated CD63 basophil response during short-term VIT determined venom-nonspecific desensitization.

PubMed

Čelesnik Smodiš, Nina; Šilar, Mira; Eržen, Renato; Rijavec, Matija; Košnik, Mitja; Korošec, Peter

2014-01-01

We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific.

Down-Regulation of FcεRI-Mediated CD63 Basophil Response during Short-Term VIT Determined Venom-Nonspecific Desensitization

PubMed Central

Čelesnik Smodiš, Nina; Šilar, Mira; Eržen, Renato; Rijavec, Matija; Košnik, Mitja; Korošec, Peter

2014-01-01

Background We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. Methods In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. Results We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Conclusions Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific. PMID:24733549

[Pneumonia in immunosuppressed patients].

PubMed

Solyanik, O; Gaass, T; Hellbach, K; Dinkel, J

2017-01-01

Pulmonary infections are a common complication in immunosuppressed patients with a frequently fatal prognosis despite modern prophylactic therapy. An early and correct diagnosis is important for initiation of the appropriate therapy. Chest radiography is the preferred initial imaging examination but is not accurate enough for the detection of pulmonary infections in immunosuppressed patients. Pneumonia is caused by a broad spectrum of pathogens in immunocompromised patients. In addition to imaging, the clinical history and epidemiology also play an important role in the diagnostics. Using epidemiological and anamnestic information, computed tomography (CT) shows a significantly better sensitivity and specificity particularly for the diagnosis of atypical forms of pneumonia. Due to the exact imaging of the different infiltration patterns CT provides an increased sensitivity with respect to the etiological classification of pulmonary infections. This article reviews in particular the radiological findings of commonly occurring pulmonary infections in immunosuppressed patients.

Validation Study of a Predictive Algorithm to Evaluate Opioid Use Disorder in a Primary Care Setting

PubMed Central

Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Tedtaotao, Maria; Smith, Gregory A.

2017-01-01

Background: Opioid abuse in chronic pain patients is a major public health issue. Primary care providers are frequently the first to prescribe opioids to patients suffering from pain, yet do not always have the time or resources to adequately evaluate the risk of opioid use disorder (OUD). Purpose: This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm (“profile”) incorporating phenotypic and, more uniquely, genotypic risk factors. Methods and Results: In a validation study with 452 participants diagnosed with OUD and 1237 controls, the algorithm successfully categorized patients at high and moderate risk of OUD with 91.8% sensitivity. Regardless of changes in the prevalence of OUD, sensitivity of the algorithm remained >90%. Conclusion: The algorithm correctly stratifies primary care patients into low-, moderate-, and high-risk categories to appropriately identify patients in need for additional guidance, monitoring, or treatment changes. PMID:28890908

Validation Study of a Predictive Algorithm to Evaluate Opioid Use Disorder in a Primary Care Setting.

PubMed

Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Tedtaotao, Maria; Smith, Gregory A; Brenton, Ashley

2017-01-01

Opioid abuse in chronic pain patients is a major public health issue. Primary care providers are frequently the first to prescribe opioids to patients suffering from pain, yet do not always have the time or resources to adequately evaluate the risk of opioid use disorder (OUD). This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm ("profile") incorporating phenotypic and, more uniquely, genotypic risk factors. In a validation study with 452 participants diagnosed with OUD and 1237 controls, the algorithm successfully categorized patients at high and moderate risk of OUD with 91.8% sensitivity. Regardless of changes in the prevalence of OUD, sensitivity of the algorithm remained >90%. The algorithm correctly stratifies primary care patients into low-, moderate-, and high-risk categories to appropriately identify patients in need for additional guidance, monitoring, or treatment changes.

Noninvasive ergonovine maleate provocative testing for coronary artery spasm: the need for routine thallium-201 imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shanes, J.G.; Krone, R.J.; Fisher, K.

1983-01-01

We administered ergonovine and used both electrocardiographic monitoring and thallium-/sup 201/ (/sup 201/Tl) imaging to detect reversible ischemia in 100 patients. Patients already established as having coronary artery spasm and those with nonbypassed, proximal, high-grade coronary artery stenosis were excluded. No complication occurred in any patient. The use of thallium imaging in addition to electrocardiographic monitoring resulted in a higher degree of sensitivity than did ECG monitoring alone. Fourteen patients demonstrated evidence of coronary artery spasm as documented by /sup 201/Tl imaging but of the 14, significant ECG changes occurred in only 50%, and classic ST segment elevation in 21%.more » Thus, in carefully selected patients the noninvasive provocation of coronary spasm can be accomplished safely, but ECG monitoring must be combined with thallium-/sup 201/ imaging to achieve an acceptable degree of sensitivity.« less

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

PubMed

Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-07-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Radiopharmaceuticals for SPECT cancer detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chernov, V. I., E-mail: chernov@oncology.tomsk.ru; Medvedeva, A. A., E-mail: tickayaAA@oncology.tomsk.ru; Zelchan, R. V., E-mail: r.zelchan@yandex.ru

2016-08-02

The purpose of the study was to assess the efficacy of single photon emission computed tomography (SPECT) with {sup 199}Tl and {sup 99}mTc-MIBI in the detection of breast, laryngeal and hypopharyngeal cancers. A total of 220 patients were included into the study: 120 patients with breast lesions (100 patients with breast cancer and 20 patients with benign breast tumors) and 100 patients with laryngeal/hypopharyngeal diseases (80 patients with laryngeal/hypopharyngeal cancer and 20 patients with benign laryngeal/hypopharyngeal lesions). No abnormal {sup 199}Tl uptake was seen in all patients with benign breast and laryngeal lesions, indicating a 100% specificity of {sup 199}Tlmore » SPECT. In the breast cancer patients, the increased {sup 199}Tl uptake in the breast was visualized in 94.8% patients, {sup 99m}Tc-MIBI—in 93.4% patients. The increased {sup 199}Tl uptake in axillary lymph nodes was detected in 60% patients, and {sup 99m}Tc-MIBI—in 93.1% patients. In patients with laryngeal/hypopharyngeal cancer, the sensitivity of SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI was 95%. The {sup 199}Tl SPECT sensitivity in identification of regional lymph node metastases in the patients with laryngeal/hypopharyngeal cancer was 75% and the {sup 99m}Tc-MIBI SPECT sensitivity was 17%. The data obtained showed that SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI can be used as one of the additional imaging methods in detection of tumors.« less

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis.

PubMed

Enden, T; Resch, S; White, C; Wik, H S; Kløw, N E; Sandset, P M

2013-06-01

Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64,709 for additional CDT and $51,866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20,429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55,000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50,000/QALY gained. Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding. © 2013 International Society on Thrombosis and Haemostasis.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis

PubMed Central

ENDEN, T.; RESCH, S.; WHITE, C.; WIK, H. S.; KLØW, N. E.; SANDSET, P. M.

2013-01-01

Summary Background Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). Objectives To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Methods Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). Results In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64 709 for additional CDT and $51 866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20 429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55 000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50 000/QALY gained. Conclusions Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding. PMID:23452204

Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia.

PubMed

Benussi, Alberto; Di Lorenzo, Francesco; Dell'Era, Valentina; Cosseddu, Maura; Alberici, Antonella; Caratozzolo, Salvatore; Cotelli, Maria Sofia; Micheli, Anna; Rozzini, Luca; Depari, Alessandro; Flammini, Alessandra; Ponzo, Viviana; Martorana, Alessandro; Caltagirone, Carlo; Padovani, Alessandro; Koch, Giacomo; Borroni, Barbara

2017-08-15

To determine whether a transcranial magnetic stimulation (TMS) multiparadigm approach can be used to distinguish Alzheimer disease (AD) from frontotemporal dementia (FTD). Paired-pulse TMS was used to investigate short-interval intracortical inhibition (SICI) and facilitation (ICF), long-interval intracortical inhibition, and short-latency afferent inhibition (SAI) to measure the activity of different intracortical circuits in patients with AD, patients with FTD, and healthy controls (HC). The primary outcome measures were sensitivity and specificity of TMS measures, derived from receiver operating curve analysis. A total of 175 participants met the inclusion criteria. We diagnosed 79 patients with AD, 64 patients with FTD, and 32 HC. We found that while patients with AD are characterized by a specific impairment of SAI, FTD shows a remarkable dysfunction of SICI-ICF intracortical circuits. With the use of the best indexes, TMS differentiated FTD from AD with a sensitivity of 91.8% and specificity of 88.6%, AD from HC with a sensitivity of 84.8% and specificity of 90.6%, and FTD from HC with a sensitivity of 90.2% and specificity of 78.1%. These results were confirmed in patients with mild disease. TMS is a noninvasive procedure that reliably distinguishes AD from FTD and HC and, if these findings are replicated in larger studies, could represent a useful additional diagnostic tool for clinical practice. This study provides Class III evidence that TMS measures can distinguish patients with AD from those with FTD. © 2017 American Academy of Neurology.

Analysis of occlusal variables, dental attrition, and age for distinguishing healthy controls from female patients with intracapsular temporomandibular disorders.

PubMed

Seligman, D A; Pullinger, A G

2000-01-01

Confusion about the relationship of occlusion to temporomandibular disorders (TMD) persists. This study attempted to identify occlusal and attrition factors plus age that would characterize asymptomatic normal female subjects. A total of 124 female patients with intracapsular TMD were compared with 47 asymptomatic female controls for associations to 9 occlusal factors, 3 attrition severity measures, and age using classification tree, multiple stepwise logistic regression, and univariate analyses. Models were tested for accuracy (sensitivity and specificity) and total contribution to the variance. The classification tree model had 4 terminal nodes that used only anterior attrition and age. "Normals" were mainly characterized by low attrition levels, whereas patients had higher attrition and tended to be younger. The tree model was only moderately useful (sensitivity 63%, specificity 94%) in predicting normals. The logistic regression model incorporated unilateral posterior crossbite and mediotrusive attrition severity in addition to the 2 factors in the tree, but was slightly less accurate than the tree (sensitivity 51%, specificity 90%). When only occlusal factors were considered in the analysis, normals were additionally characterized by a lack of anterior open bite, smaller overjet, and smaller RCP-ICP slides. The log likelihood accounted for was similar for both the tree (pseudo R(2) = 29.38%; mean deviance = 0.95) and the multiple logistic regression (Cox Snell R(2) = 30.3%, mean deviance = 0.84) models. The occlusal and attrition factors studied were only moderately useful in differentiating normals from TMD patients.

Central Sensitization Inventory as a Predictor of Worse Quality of Life Measures and Increased Length of Stay Following Spinal Fusion.

PubMed

Bennett, E Emily; Walsh, Kevin M; Thompson, Nicolas R; Krishnaney, Ajit A

2017-08-01

Central sensitization is abnormal and intense enhancement of pain mechanism by the central nervous system. Patients with central sensitization may be at higher risk of poor outcomes after spinal fusion. The Central Sensitivity Inventory (CSI) was developed to identify and quantify key symptoms related to central sensitization. In 664 patients who underwent thoracic and/or lumbar fusion, we evaluated retrospectively pretreatment CSI as a predictor of postoperative quality of life measures, length of stay, and discharge status. Preoperative Pain Disability Questionnaire scores, Patient Health Questionnaire-9 scores, and EuroQol-5 Dimensions index scores were significantly worse in patients with preoperative CSI ≥40 compared with patients with preoperative CSI <40 (P < 0.0001 for all). After adjusting for demographic variables, operation duration, and preoperative health status, preoperative CSI was significantly associated with higher postoperative Pain Disability Questionnaire total score (unadjusted P < 0.001, adjusted P = 0.009), higher postoperative Patient Health Questionnaire-9 score (unadjusted P < 0.001, adjusted P = 0.001), and lower postoperative EuroQol-5 Dimensions index (unadjusted P < 0.001, adjusted P = 0.001). For each 10-unit increase in CSI, average length of stay increased by 6.4% (95% confidence interval 0.4%-12.6%, P = 0.035). The odds of being discharged home after adjusting for confounders was not statistically related to preoperative CSI (P = 0.0709). Preoperative CSI was associated with worse quality of life outcomes and increased length of stay after spinal fusions. CSI may be an additional measure in evaluating patients preoperatively to better predict successful spinal fusion outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk factors for an additional port in single-incision laparoscopic cholecystectomy in patients with cholecystitis.

PubMed

Araki, Kenichiro; Shirabe, Ken; Watanabe, Akira; Kubo, Norio; Sasaki, Shigeru; Suzuki, Hideki; Asao, Takayuki; Kuwano, Hiroyuki

2017-01-01

Although single-incision laparoscopic cholecystectomy is now widely performed in patients with cholecystitis, some cases require an additional port to complete the procedure. In this study, we focused on risk factor of additional port in this surgery. We performed single-incision cholecystectomy in 75 patients with acute cholecystitis or after cholecystitis between 2010 and 2014 at Gunma University Hospital. Surgical indications followed the TG13 guidelines. Our standard procedure for single-incision cholecystectomy routinely uses two needlescopic devices. We used logistic regression analysis to identify the risk factors associated with use of an additional full-size port (5 or 10 mm). Surgical outcome was acceptable without biliary injury. Nine patients (12.0%) required an additional port, and one patient (1.3%) required conversion to open cholecystectomy because of severe adhesions around the cystic duct and common bile duct. In multivariate analysis, high C-reactive protein (CRP) values (>7.0 mg/dl) during cholecystitis attacks were significantly correlated with the need for an additional port (P = 0.009), with a sensitivity of 55.6%, specificity of 98.5%, and accuracy of 93.3%. This study indicated that the severe inflammation indicated by high CRP values during cholecystitis attacks predicts the need for an additional port. J. Med. Invest. 64: 245-249, August, 2017.

Effects of supplementation with omega-3 on insulin sensitivity and non-esterified free fatty acid (NEFA) in type 2 diabetic patients.

PubMed

Farsi, Payam Farahbakhsh; Djazayery, Abolghassem; Eshraghian, Mohammad Reza; Koohdani, Fariba; Saboor-Yaraghi, Ali Akbar; Derakhshanian, Hoda; Zarei, Mahnaz; Javanbakht, Mohammad Hassan; Djalali, Mahmoud

2014-06-01

The aim of this study was to determine the role of omega-3 supplementation on NEFA concentration, insulin sensitivity and resistance, and glucose and lipid metabolism in type 2 diabetic patients. Forty-four type 2 diabetic patients were randomly recruited into two groups. Group A received 4 g/day omega-3 soft gels, and group B received a placebo for 10 wks. Blood samples were collected after 12-h fast. Physical activity records, three-day food records, and anthropometric measurements were obtained from all participants at the beginning and end of the study. Omega-3 supplementation caused a significant reduction in NEFA in the intervention group compared with the placebo group (P = 0.009). Additionally, the administration of omega-3 resulted in significantly greater changes (Diff) for the intervention group in various parameters, such as insulin and Quicki indices compared with the placebo group (P < 0.05). Omega-3 fatty acid supplementation in type 2 diabetic patients improved insulin sensitivity, probably due to the decrease in NEFA concentrations.

Increased interleukin-10 levels correlate with bacteremia and sepsis in febrile neutropenia pediatric oncology patients.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2012-03-01

Early diagnosis of bacteremia and sepsis in pediatric oncology patients with febrile neutropenia still remains unresolved task due to lack of sensitive and specific laboratory markers particularly at the beginning of the infectious process. The objective of our study was to assess the potentiality of interleukin-10 (IL-10) to predict or exclude bacteremia or sepsis at the beginning of febrile episode in childhood oncology patients. A total of 36 febrile neutropenic episodes in 24 children were studied. Serum samples were collected after confirmation of febrile neutropenia and analyzed using automated random access analyzer. The sensitivity of IL-10 was 73% and specificity - 92% (cut-off=18pg/ml, area under the curve - 0.87, 95% CI for sensitivity 39-94%, 95% CI for specificity 74-99%) with negative predictive value (NPV) - 83%. IL-10 evaluation might be used as an additional diagnostic tool for clinicians in excluding bacteremia or clinical sepsis in oncology patients with febrile neutropenia because of high NPV and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Estimating the Added Utility of Highly Sensitive Histidine-Rich Protein 2 Detection in Outpatient Clinics in Sub-Saharan Africa.

PubMed

Plucinski, Mateusz M; Rogier, Eric; Dimbu, Pedro Rafael; Fortes, Filomeno; Halsey, Eric S; Aidoo, Michael

2017-10-01

Most malaria testing is by rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein 2 (HRP2). Recently, several RDT manufacturers have developed highly sensitive RDTs (hsRDTs), promising a limit of detection (LOD) orders of magnitude lower than conventional RDTs. To model the added utility of hsRDTs, HRP2 concentration in Angolan outpatients was measured quantitatively using an ultrasensitive bead-based assay. The distribution of HRP2 concentration was bimodal in both afebrile and febrile patients. The conventional RDT was able to detect 81% of all HRP2-positive febrile patients and 52-77% of HRP2-positive afebrile patients. The added utility of hsRDTs was estimated to be greater in afebrile patients, where an hsRDT with a LOD of 200 pg/mL would detect an additional 50-60% of HRP2-positive persons compared with a conventional RDT with a LOD of 3,000 pg/mL. In febrile patients, the hsRDT would detect an additional 10-20% of cases. Conventional RDTs already capture the vast majority of symptomatic HRP2-positive individuals, and hsRDTs would have to reach a sufficiently low LOD approaching 200 pg/mL to provide added utility in identifying HRP2-positive, asymptomatic individuals.

Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients

PubMed Central

Carmona-Bayonas, A; Gómez, J; González-Billalabeitia, E; Canteras, M; Navarrete, A; Gonzálvez, M L; Vicente, V; Ayala de la Peña, F

2011-01-01

Background: Predictive models to identify low-risk febrile neutropenia (FN) have been developed with heterogeneous samples, which included stable and unstable patients, solid tumours, acute leukaemia and bone marrow transplantation. These models fail to recognise 5–15% of cases with unexpected complications, and literature specifically addressing apparently stable patients (ASPs) is scarce. Methods: We reviewed 861 episodes of FN in outpatients with solid tumours, including 692 (80%) episodes with apparent clinical stability. We aimed to investigate the prognosis of this latter group and explore the possibility of stratifying it according to the presenting features. A case–control study was performed and the MASCC index was evaluated. Results: The rates of complications and bacteraemia in ASPs were 7.3% and 6.2%, respectively. The MASCC index yielded a low sensitivity to detect complications (36%). Prognostic factors were identified: ECOG performance status ⩾2, chronic bronchitis, chronic heart failure, stomatitis NCI grade ⩾2, monocytes <200 mm−3 and stress hyperglycaemia. Conclusion: A very simple assessment is useful to classify the patients with FN according to the risk of complications. A few additional variables may predict the clinical course of the patients. We additionally show that the MASCC index applied to this specific group has a low sensitivity to predict complications. PMID:21811253

Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer.

PubMed

Acevedo, Joseph R; Fero, Katherine E; Wilson, Bayard; Sacco, Assuntina G; Mell, Loren K; Coffey, Charles S; Murphy, James D

2016-11-10

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.

Diagnostic power of longitudinal strain at rest for the detection of obstructive coronary artery disease in patients with type 2 diabetes mellitus.

PubMed

Zuo, Houjuan; Yan, Jiangtao; Zeng, Hesong; Li, Wenyu; Li, Pengcheng; Liu, Zhengxiang; Cui, Guanglin; Lv, Jiagao; Wang, Daowen; Wang, Hong

2015-01-01

Global longitudinal strain (GLS) measured by 2-D speckle-tracking echocardiography (2-D STE) at rest has been recognized as a sensitive parameter in the detection of significant coronary artery disease (CAD). However, the diagnostic power of 2-D STE in the detection of significant CAD in patients with diabetes mellitus is unknown. Two-dimensional STE features were studied in total of 143 consecutive patients who underwent echocardiography and coronary angiography. Left ventricular global and segmental peak systolic longitudinal strains (PSLSs) were quantified by speckle-tracking imaging. In the presence of obstructive CAD (defined as stenosis ≥75%), global PSLS was significantly lower in patients with diabetes mellitus than in patients without (16.65 ± 2.29% vs. 17.32 ± 2.27%, p < 0.05). Receiver operating characteristic analysis revealed that global PSLS could effectively detect obstructive CAD in patients without diabetes mellitus (cutoff value: -18.35%, sensitivity: 78.8%, specificity: 77.5%). However, global PSLS could detect obstructive CAD in diabetic patients at a lower cutoff value with inadequate sensitivity and specificity (cutoff value: -17.15%; sensitivity: 61.1%, specificity: 52.9%). In addition, the results for segmental PSLS were similar to those for global PSLS. In conclusion, global and segmental PSLSs at rest were significantly lower in patients with both obstructive CAD and diabetes mellitus than in patients with obstructive CAD only; thus, PSLSs at rest might not be a useful parameter in the detection of obstructive CAD in patients with diabetes mellitus. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Subgroup Economic Evaluation of Radiotherapy for Breast Cancer After Mastectomy.

PubMed

Wan, Xiaomin; Peng, Liubao; Ma, Jinan; Chen, Gannong; Li, Yuanjian

2015-11-01

A recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group found significant improvements achieved by postmastectomy radiotherapy (PMRT) for patients with breast cancer with 1 to 3 positive nodes (pN1-3). It is unclear whether PMRT is cost-effective for subgroups of patients with positive nodes. To determine the cost-effectiveness of PMRT for subgroups of patients with breast cancer with positive nodes. A semi-Markov model was constructed to estimate the expected lifetime costs, life expectancy, and quality-adjusted life-years for patients receiving or not receiving radiation therapy. Clinical and health utilities data were from meta-analyses by the Early Breast Cancer Trialists' Collaborative Group or randomized clinical trials. Costs were estimated from the perspective of the Chinese society. One-way and probabilistic sensitivity analyses were performed. The incremental cost-effective ratio was estimated as $7984, $4043, $3572, and $19,021 per quality-adjusted life-year for patients with positive nodes (pN+), patients with pN1-3, patients with pN1-3 who received systemic therapy, and patients with >4 positive nodes (pN4+), respectively. According to World Health Organization recommendations, these incremental cost-effective ratios were judged as cost-effective. However, the results of one-way sensitivity analyses suggested that the results were highly sensitive to the relative effectiveness of PMRT (rate ratio). We determined that the results were highly sensitive to the rate ratio. However, the addition of PMRT for patients with pN1-3 in China has a reasonable chance to be cost-effective and may be judged as an efficient deployment of limited health resource, and the risk and uncertainty of PMRT are relatively greater for patients with pN4+. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Efficacy of 67 gallium ECT imaging in lymphoma, infection, and lung carcinoma: A comparison with planar imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harwood, S.J.; Anderson, M.W.; Klein, R.C.

1984-01-01

Emission computed tomography (ECT) studies were performed on a GE 400 A/T camera and ADAC computers (system 3 and system 3300). Thirty-three sets of ECT and planar images were obtained in 20 patients over a six month period. Imaging was performed 48 hours after the intravenous administration of 5 mc of Gallium 67 citrate. No bowel preparation was employed. Comparison is made of the initial nuclear medicine report derived from planar and ECT imaging aided by clinical knowledge versus the consensus opinion of two nuclear medicine physicians reading the planar images along with minimal clinical information. The lymphoma series consistsmore » of 18 scans in 10 patients. There were 5 scans in which a false negative planar interpretation was changed to a true positive ECT interpretation. Sensitivity of planar imaging for lymphoma was 58% which rose to 100% with addition of ECT information. There were no false positives by either technique. There were 5 sets of scans in 5 lung carcinoma patients. Sensitivity of the planar images was 60% because of 2 false negative results. Sensitivity of the ECT technique was 100%. There were no false positives. The infection series consists of 10 scans in 5 patients. Sensitivity of ECT was 100%, sensitivity of planar was 66%. There was 1 false positive planar. For the total series the accuracy of planar imaging was 69% and the predictive value of a negative planar interpretation was 44%. Corresponding values for ECT imaging were 100%. The authors' experience demonstrates significant increase in sensitivity without loss of specificity resulting from the use of Emission Computed Tomography in both chest and abdomen in patients with lymphoma, infection, and lung cancer.« less

99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors.

PubMed

Gabriel, M; Muehllechner, P; Decristoforo, C; von Guggenberg, E; Kendler, D; Prommegger, R; Profanter, C; Moncayo, R; Virgolini, I

2005-09-01

To evaluate the use of 99mTc-EDDA-hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC) for staging and follow-up of neuroendocrine gastro-entero-pancreatic (GEP) tumors with special focus on the acquisition protocol including single photon emission computed tomography (SPECT). Eighty-eight patients (37 female, 51 male; age range: 16 to 81 years; mean age: 56.3 years) were studied: 42 patients for staging after initial histological confirmation and 46 patients during post-therapy follow-up. An average activity of 400 MBq of the radiopharmaceutical was injected. All tumors originated from neuroendocrine tissue of the gastroenteropancreatic tract. Whole body scintigrams at 4 h postinjection and SPECT of the abdomen were obtained in all patients. Additional planar images of the abdomen were acquired at 2 h after injection in 68 patients. The Tc-TOC scan result was true-positive in 56 patients, true-negative in 17, false-negative in 14, and false-positive in 1 patient. The false-positive finding was caused by a colonic adenoma. Overall, a scan sensitivity of 80% (56/70 patients), specificity of 94.4% (17/18 patients) and accuracy of 82.9% (73/88 patients) were calculated on patient basis. In total, Tc-TOC detected 357 foci in 69 patients. In 7 patients equivocal findings were observed in the bowel at 4 h postinjection without corresponding tracer uptake in the scan 2 h earlier, meaning that these abnormal findings were correctly classified as non-malignant. In addition to planar views, SPECT revealed further 62 lesions. Tc-TOC with one-day, dual-time acquisition protocol is an accurate staging procedure in patients with neuroendocrine GEP tumors. SPECT shows high sensitivity for detection of abdominal lesions, while earlier images improve the reliability of abnormal abdominal findings.

Preemptive use of etodolac on tooth sensitivity after in-office bleaching: a randomized clinical trial

PubMed Central

Vaez, Savil Costa; Faria-e-Silva, André Luís; Loguércio, Alessandro Dourado; Fernandes, Micaelle Tenório Guedes; Nahsan, Flávia Pardo Salata

2018-01-01

Abstract Purpose This study determined the effectiveness of the preemptive administration of etodolac on risk and intensity of tooth sensitivity and the bleaching effect caused by in-office bleaching using 35% hydrogen peroxide. Material and methods Fifty patients were selected for this tripleblind, randomized, crossover, and placebo-controlled clinical trial. Etodolac (400 mg) or placebo was administrated in a single-dose 1 hour prior to the bleaching procedure. The whitening treatment with 35% hydrogen peroxide was carried out in two sessions with a 7-day interval. Tooth sensitivity was assessed before, during, and 24 hours after the procedure using the analog visual scale and the verbal rating scale. Color alteration was assessed by a bleach guide scale, 7 days after each session. Relative risk of sensitivity was calculated and adjusted by session, while overall risk was compared by the McNemar's test. Data on the sensitivity level of both scales and color shade were subjected to Friedman, Wilcoxon, and Mann-Whitney tests, respectively (α=0.05). Results The preemptive administration of etodolac did not affect the risk of tooth sensitivity and the level of sensitivity reported, regardless of the time of evaluation and scale used. The sequence of treatment allocation did not affect bleaching effectiveness, while the second session resulted in additional color modification. The preemptive administration of etodolac in a single dose 1 hour prior to in-office tooth bleaching did not alter tooth color, and the risk and intensity of tooth sensitivity reported by patients. Conclusion A single-dose preemptive administration of 400 mg of etodolac did not affect either risk of tooth sensitivity or level of sensitivity reported by patients, during or after the in-office tooth bleaching procedure. PMID:29412363

Preemptive use of etodolac on tooth sensitivity after in-office bleaching: a randomized clinical trial.

PubMed

Vaez, Savil Costa; Faria-E-Silva, André Luís; Loguércio, Alessandro Dourado; Fernandes, Micaelle Tenório Guedes; Nahsan, Flávia Pardo Salata

2018-02-01

This study determined the effectiveness of the preemptive administration of etodolac on risk and intensity of tooth sensitivity and the bleaching effect caused by in-office bleaching using 35% hydrogen peroxide. Fifty patients were selected for this tripleblind, randomized, crossover, and placebo-controlled clinical trial. Etodolac (400 mg) or placebo was administrated in a single-dose 1 hour prior to the bleaching procedure. The whitening treatment with 35% hydrogen peroxide was carried out in two sessions with a 7-day interval. Tooth sensitivity was assessed before, during, and 24 hours after the procedure using the analog visual scale and the verbal rating scale. Color alteration was assessed by a bleach guide scale, 7 days after each session. Relative risk of sensitivity was calculated and adjusted by session, while overall risk was compared by the McNemar's test. Data on the sensitivity level of both scales and color shade were subjected to Friedman, Wilcoxon, and Mann-Whitney tests, respectively (α=0.05). The preemptive administration of etodolac did not affect the risk of tooth sensitivity and the level of sensitivity reported, regardless of the time of evaluation and scale used. The sequence of treatment allocation did not affect bleaching effectiveness, while the second session resulted in additional color modification. The preemptive administration of etodolac in a single dose 1 hour prior to in-office tooth bleaching did not alter tooth color, and the risk and intensity of tooth sensitivity reported by patients. A single-dose preemptive administration of 400 mg of etodolac did not affect either risk of tooth sensitivity or level of sensitivity reported by patients, during or after the in-office tooth bleaching procedure.

['How strange is the patient to me?'

PubMed

Karger, André; Lindtner-Rudolph, Heide; Mroczynski, Robert; Ziem, Alexander; Joksimovic, Ljiljana

2017-09-01

'How strange is the patient to me?' Physicians' attitudes and expectations toward treating patients with a migration background Objectives: Undergraduate and postgraduate training in cultural competence remains a challenging issue. It might be useful to integrate culturally sensitive learning objectives in existing curricula. As part of a needs assessment, this qualitative study examined the prototypical experiences in clinical routines with patients with a migration background. Twenty physicians took part in half-structured narrative interviews, which were then analyzed by linguistic-ethnographic conversation analysis. The main reasons for difficulties in patient-physician relation proved to be language barriers. Assignments of professional interpreters were rated critically. Physicians attributed the responsibility for successful communication mainly to the patient. The physicians saw little need for training in cultural competence. The integration of learning objectives related to cultural sensibility in existing curricula would seem to be useful, especially because the physicians interviewed reported little need for additional training on their own. The importance of implied negative attitudes and stereotypes in creating a culturally sensitive approach should be taken into account.

Using the emergency department as a screening site for high blood pressure. A method for improving hypertension detection and appropriate referral.

PubMed

Mamon, J; Green, L; Levine, D M; Gibson, G; Gurley, H T

1987-08-01

This study describes the development and testing of a high blood pressure protocol for use in emergency departments (ED) to enhance detection of those patients appropriate for subsequent referral. The protocol involves two serial blood pressure measurements and a patient interview to determine: 1) previous history of high blood pressure (HBP), 2) treatment in past year for HBP, and 3) usual source of medical care. The accuracy of patient reporting was validated by comparison with the patients' hospital record (reflecting outpatient and inpatient visits). Results indicate that these self-reports have high levels of sensitivity (range 90-100%) and specificity (range 79-96%). Use of the additional patient information increased the sensitivity of the screening protocol in identifying when and where a patient should be referred. Use of this methodology indicates that the protocol is a simple and effective method for HBP screening. The findings also suggest that the ED is an ideal site for screening the "hard-to-reach" hypertensive population.

Clinical value of whole body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in the detection of metastatic bladder cancer.

PubMed

Yang, Zhongyi; Pan, Lingling; Cheng, Jingyi; Hu, Silong; Xu, Junyan; Ye, Dingwei; Zhang, Yingjian

2012-07-01

To investigate the value of whole-body fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for the detection of metastatic bladder cancer. From December 2006 to August 2010, 60 bladder cancer patients (median age 60.5 years old, range 32-96) underwent whole body positron emission tomography/computed tomography positron emission tomography/computed tomography. The diagnostic accuracy was assessed by performing both organ-based and patient-based analyses. Identified lesions were further studied by biopsy or clinically followed for at least 6 months. One hundred and thirty-four suspicious lesions were identified. Among them, 4 primary cancers (2 pancreatic cancers, 1 colonic and 1 nasopharyngeal cancer) were incidentally detected, and the patients could be treated on time. For the remaining 130 lesions, positron emission tomography/computed tomography detected 118 true positive lesions (sensitivity = 95.9%). On the patient-based analysis, the overall sensitivity and specificity resulted to be 87.1% and 89.7%, respectively. There was no difference of sensitivity and specificity in patients with or without adjuvant treatment in terms of detection of metastatic sites by positron emission tomography/computed tomography. Compared with conventional imaging modality, positron emission tomography/computed tomography correctly changed the management in 15 patients (25.0%). Positron emission tomography/computed tomography has excellent sensitivity and specificity in the detection of metastatic bladder cancer and it provides additional diagnostic information compared to standard imaging techniques. © 2012 The Japanese Urological Association.

Increase in sensitization to oil of turpentine: recent data from a multicenter study on 45,005 patients from the German-Austrian Information Network of Departments of Dermatology (IVDK).

PubMed

Treudler, R; Richter, G; Geier, J; Schnuch, A; Orfanos, C E; Tebbe, B

2000-02-01

Contact allergy to oil of turpentine was reported to have become rare. However, the evaluation of standardized data of 45,005 patients tested 1992-1997 in 30 Dermatological Centers associated with the German-Austrian Information Network of Departments of Dermatology (IVDK) showed an increase in positive patch test reactions to turpentine from 0.5% during the years 1992-1995, up to 1.7% in 1996 and 3.1% in 1997. In particular, 17,347 patients tested in 1996-1997 were evaluated in detail by comparing 431 individuals with positive patch test reactions with the rest of the group found negative to turpentine. Using the so-called MOAHLFA index, the following characteristics were shown. Turpentine allergy (a) was found to be significantly less frequent in men and in patients with occupational dermatitis, (b) showed no difference in its association with atopic dermatitis, (c) patients with turpentine allergy had significantly less symptoms of the hands, more symptoms of the legs or in the face and (d) were significantly more often aged over 60 years. Also, patients sensitized to turpentine had increased rates of additional sensitizations. The definite reason for the increase in turpentine sensitization in the population tested here is not clear. Therefore, a detailed exposure analysis is necessary; the new increase in turpentine allergies may be due to popular topical remedies or household chemicals.

Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merkel, K.D.; Brown, M.L.; Dewanjee, M.K.

We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracymore » was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.« less

Adding retinal photography to screening for diabetic retinopathy: a prospective study in primary care.

PubMed

O'Hare, J P; Hopper, A; Madhaven, C; Charny, M; Purewell, T S; Harney, B; Griffiths, J

1996-03-16

To evaluate whether adding retinal photography improved community screening for diabetic retinopathy. Mobile screening unit at rural and urban general practices in south west England. 1010 diabetic patients from primary care. Prospective study; patients were examined by ophthalmoscopy by general practitioners or opticians without fundal photographs and again with photographs, and assessments were compared to those of an ophthalmologist. Whether fundal photography improved the sensitivity of detection of retinopathy and referrable diabetic retinopathy, and whether this sensitivity could be improved by including a review of the films by the specialist. Diabetic retinopathy was detected by the ophthalmologist in 205 patients (20.5%) and referrable retinopathy in 49 (4.9%). The sensitivity of the general practitioners and opticians for referrable retinopathy with ophthalmoscopy was 65%, and improved to 84% with retinal photographs. General practitioners' sensitivity in detecting background retinopathy improved with photographs from 22% to 65%; opticians' sensitivity in detecting background retinopathy improved from 43% to 71%. The sensitivity of detecting referrable retinopathy by general practitioners improved from 56% to 80% with photographs; for opticians it improved from 75% to 88%. Combining modalities of screening by providing photography with specialist review of all films in addition to direct ophthalmoscopy through dilated pupils improves assessment and referral for diabetic retinopathy by general practitioners and opticians. With further training and experience, primary care screeners should be able to achieve a sensitivity that will achieve an effective, acceptable, and economical community based screening programme for this condition.

Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

PubMed

Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

2016-01-01

Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.

Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow-up.

PubMed

Dalla Vecchia, Laura; Barbic, Franca; Galli, Andrea; Pisacreta, Massimo; Gornati, Rosella; Porretta, Tiziano; Porta, Alberto; Furlan, Raffaello

2013-06-15

Carotid surgery variably modifies carotid afferent innervation, thus affecting arterial baroreceptor sensitivity. Low arterial baroreflex sensitivity is a well-known independent risk factor for cardiovascular diseases. The aim of this study was to assess the 4-mo effects of carotid endarterectomy (CEA) on arterial baroreceptor sensitivity and cardiovascular autonomic profile in patients with unilateral carotid stenosis. We enrolled 20 patients (72 ± 8 yr) with unilateral >70% carotid stenosis. ECG, beat-by-beat blood pressure, and respiration were continuously recorded before and 126 ± 9 days after CEA, at rest and during a 75° head-up tilt. Both pharmacological (modified Oxford technique, BRS) and spontaneous (index α, spectral analysis) arterial baroreflex sensitivity were assessed. Cardiovascular autonomic profile was evaluated by plasma catecholamines and spectral indexes of cardiac sympathovagal modulation [low-frequency R-R interval (LFRR), low frequency-to high frequency ratio (LF/HF), high-frequency R-R interval (HFRR)] and sympathetic vasomotor control [low-frequency systolic arterial pressure (LFSAP)] obtained from heart rate and SAP variability. After CEA, both the index α and BRS were higher (P < 0.02) at rest. SAP variance decreased both at rest and during tilt (P < 0.02). Before surgery, tilt did not modify the autonomic profile compared with baseline. After CEA, tilt increased LF/HF and LFSAP and reduced HFRR compared with rest (P < 0.02). Four months after CEA was performed, arterial baroreflex sensitivity was enhanced. Accordingly, the patients' autonomic profile had shifted toward reduced cardiac and vascular sympathetic activation and enhanced cardiac vagal activity. The capability to increase cardiovascular sympathetic activation in response to orthostasis was restored. Baroreceptor sensitivity improvement might play an additional role in the more favorable outcome observed in patients after carotid surgery.

Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests.

PubMed

Korman, Jessica D; Volenberg, Irene; Balko, Jody; Webster, Joe; Schiodt, Frank V; Squires, Robert H; Fontana, Robert J; Lee, William M; Schilsky, Michael L

2008-10-01

Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp <20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 microg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio >2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.

Slow Temporal Summation of Pain for Assessment of Central Pain Sensitivity and Clinical Pain of Fibromyalgia Patients

PubMed Central

Staud, Roland; Weyl, Elizabeth E.; Riley, Joseph L.; Fillingim, Roger B.

2014-01-01

Background In healthy individuals slow temporal summation of pain or wind-up (WU) can be evoked by repetitive heat-pulses at frequencies of ≥.33 Hz. Previous WU studies have used various stimulus frequencies and intensities to characterize central sensitization of human subjects including fibromyalgia (FM) patients. However, many trials demonstrated considerable WU-variability including zero WU or even wind-down (WD) at stimulus intensities sufficient for activating C-nociceptors. Additionally, few WU-protocols have controlled for contributions of individual pain sensitivity to WU-magnitude, which is critical for WU-comparisons. We hypothesized that integration of 3 different WU-trains into a single WU-response function (WU-RF) would not only control for individuals’ pain sensitivity but also better characterize their central pain responding including WU and WD. Methods 33 normal controls (NC) and 38 FM patients participated in a study of heat-WU. We systematically varied stimulus intensities of.4 Hz heat-pulse trains applied to the hands. Pain summation was calculated as difference scores of 1st and 5th heat-pulse ratings. WU-difference (WU-Δ) scores related to 3 heat-pulse trains (44°C, 46°C, 48°C) were integrated into WU-response functions whose slopes were used to assess group differences in central pain sensitivity. WU-aftersensations (WU-AS) at 15 s and 30 s were used to predict clinical FM pain intensity. Results WU-Δ scores linearly accelerated with increasing stimulus intensity (p<.001) in both groups of subjects (FM>NC) from WD to WU. Slope of WU-RF, which is representative of central pain sensitivity, was significantly steeper in FM patients than NC (p<.003). WU-AS predicted clinical FM pain intensity (Pearson’s r = .4; p<.04). Conclusions Compared to single WU series, WU-RFs integrate individuals’ pain sensitivity as well as WU and WD. Slope of WU-RFs was significantly different between FM patients and NC. Therefore WU-RF may be useful for assessing central sensitization of chronic pain patients in research and clinical practice. PMID:24558475

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

PubMed

Dreizin, David; Boscak, Alexis R; Anstadt, Michael J; Tirada, Nikki; Chiu, William C; Munera, Felipe; Bodanapally, Uttam K; Hornick, Michael; Stein, Deborah M

2016-12-01

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. © RSNA, 2016.

Epi proColon® 2.0 CE: A Blood-Based Screening Test for Colorectal Cancer.

PubMed

Lamb, Yvette N; Dhillon, Sohita

2017-04-01

Epi proColon ® 2.0 CE is a blood-based test designed to aid in the early detection of colorectal cancer. The test comprises a qualitative assay for the polymerase chain reaction (PCR) detection of methylated Septin9 DNA, the presence of which is associated with colorectal cancer: however, positive results should be verified by colonoscopy or sigmoidoscopy. Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with high clinical sensitivity and specificity in pivotal case-control studies. The sensitivity of the test did not appear to be affected by the tumour location or by patient age or gender. In addition, limited data suggest that Epi proColon ® 2.0 CE discriminated between patients with colorectal cancer and healthy controls with higher sensitivity and generally similar specificity to that of the faecal immunochemical test, and with higher sensitivity and specificity to that of the guaiac-based faecal occult blood test (statistical data not available). In an observational study, most patients who refused colonoscopy for screening accepted a non-invasive test option as an alternative, and preferred Epi proColon ® 2.0 CE over a stool-based test. Large prospective trials of Epi proColon ® 2.0 CE in a screening setting will be required to further elucidate the cost-effectiveness of the test. Nevertheless, currently available data suggests that Epi proColon ® 2.0 CE has the potential to be a sensitive and convenient screening option for patients refusing screening by colonoscopy.

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Costa, F.; Furlan, R.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1999-01-01

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Should gram stains have a role in diagnosing hip arthroplasty infections?

PubMed

Johnson, Aaron J; Zywiel, Michael G; Stroh, D Alex; Marker, David R; Mont, Michael A

2010-09-01

The utility of Gram stains in diagnosing periprosthetic infections following total hip arthroplasty has recently been questioned. Several studies report low sensitivity of the test, and its poor ability to either confirm or rule out infection in patients undergoing revision total hip arthroplasty. Despite this, many institutions including that of the senior author continue to perform Gram stains during revision total hip arthroplasty. We assessed the sensitivity, specificity, accuracy, and positive and negative predictive values of Gram stains from surgical-site samplings taken from procedures on patients with both infected and aseptic revision total hip arthroplasties. A review was performed on patients who underwent revision total hip arthroplasty between 2000 and 2007. Eighty-two Gram stains were performed on patients who had infected total hip arthroplasties and underwent revision procedures. Additionally, of the 410 revision total hip arthroplasties performed on patients who were confirmed infection-free, 120 Gram stains were performed. Patients were diagnosed as infected using multiple criteria at the time of surgery. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated from these Gram stain results. The Gram stain demonstrated a sensitivity and specificity of 9.8% and 100%, respectively. In this series, the Gram stain had a negative predictive value of 62%, a positive predictive value of 100%, and an accuracy of 63%. Gram stains obtained from surgical-site samples had poor sensitivity and poor negative predictive value. Based on these findings, as well as those of other authors, we believe that Gram stains should no longer be considered for diagnosing infections in revision total hip arthroplasty. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Aspergillus Galactomannan Enzyme Immunoassay and Quantitative PCR for Diagnosis of Invasive Aspergillosis with Bronchoalveolar Lavage Fluid

PubMed Central

Musher, Benjamin; Fredricks, David; Leisenring, Wendy; Balajee, S. Arunmozhi; Smith, Caitlin; Marr, Kieren A.

2004-01-01

Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in hematopoietic stem cell transplant patients. Diagnosis requires microbiological or histopathologic demonstration of the organism in tissues; however, cultivation of Aspergillus species from respiratory secretions has low diagnostic sensitivity. Assays to detect Aspergillus antigen or DNA in bronchoalveolar lavage (BAL) fluid could facilitate earlier diagnosis, thereby guiding optimal therapy and obviating the need for additional costly and potentially morbid diagnostic evaluation. We evaluated the performance of a galactomannan enzyme immunoassay (GM EIA; Bio-Rad) by using a range of index cutoffs to define positivity and a quantitative PCR (qPCR) assay for the detection of Aspergillus species from BAL samples of patients with proven and probable IPA (case patients; n = 49) and without IPA (control patients; n = 50). The sensitivity of the GM EIA was 61% with an index cutoff of 1.0 and 76% with an index cutoff of 0.5; the corresponding specificities were 98 and 94%, respectively. The sensitivity and specificity of qPCR assay were 67 and 100%, respectively. The sensitivity with 22 culture-negative BAL specimens from patients with IPA was 41% for GM EIA with an index cutoff of 1.0, 59% for GM EIA with an index cutoff of 0.5, and 36% for qPCR assay. GM EIA indices and DNA quantities corresponded to BAL fungal burdens, with culture-positive samples having larger amounts of antigen and DNA compared to culture-negative samples. GM EIA and qPCR assay add to the sensitivity of BAL for diagnosing IPA in high-risk patients, with excellent specificity. Adjunctive use of these tests may reduce dependence on invasive diagnostic procedures. PMID:15583275

Culture-sensitive psychotraumatology

PubMed Central

Schnyder, Ulrich; Bryant, Richard A.; Ehlers, Anke; Foa, Edna B.; Hasan, Aram; Mwiti, Gladys; Kristensen, Christian H.; Neuner, Frank; Oe, Misari; Yule, William

2016-01-01

Background Although there is some evidence of the posttraumatic stress disorder (PTSD) construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-)stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions In summary, culture-sensitive psychotraumatology means assuming an empathic and non-judgmental attitude, trying to understand each individual's cultural background. Highlights of the article Cultural sensitivity is required to successfully treat trauma survivors. Empirically supported treatments may need to be modified depending on the patient’s cultural background. In addition to talking, patients may write or use other ways of accessing the traumatic memories such as painting, dancing, or singing. In low and middle income countries, dissemination of evidence-based treatments is frequently impeded by limited resources and poor health infrastructure. Beware of cultural stereotyping! PMID:27473520

Successful Renal Transplantation with Desensitization in Highly Sensitized Patients: A Single Center Experience

PubMed Central

Yoon, Hye Eun; Hyoung, Bok Jin; Hwang, Hyeon Seok; Lee, So Young; Jeon, Youn Joo; Song, Joon Chang; Oh, Eun-Jee; Park, Sun Cheol; Choi, Bum Soon; Moon, In Sung; Kim, Yong Soo

2009-01-01

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients. PMID:19194545

Postmenopausal bleeding: value of imaging.

PubMed

Reinhold, Caroline; Khalili, Ida

2002-05-01

Endovaginal sonography in combination with HSG is an effective screening tool in evaluating patients with postmenopausal bleeding. Endovaginal sonography is highly sensitive for detecting endometrial carcinoma and can identify patients at low risk for endometrial disease obviating the need for endometrial sampling in this subgroup of patients. In patients with abnormal findings at sonography, a detailed morphologic analysis can be used to determine which patients can undergo blind endometrial sampling successfully versus those who would benefit from hysteroscopic guidance. In patients in whom endovaginal sonography and HSG are inadequate, MRI may provide additional information on the appearance of the endometrium, particularly in patients in whom endometrial sampling is difficult (eg, patients with cervical stenosis).

New Perspectives on the Diagnosis of Allergy to Anisakis spp.

PubMed

Moneo, Ignacio; Carballeda-Sangiao, Noelia; González-Muñoz, Miguel

2017-05-01

To compare the prevalence of sensitization in different countries based on specific IgE values and to evaluate the use of isolated native or recombinant allergens for diagnosis. Isolated allergens help in the diagnosis of truly sensitized patients avoiding false positives due to cross-reactions. Their use is therefore highly recommended, especially when used as a combination of several relevant allergens. The use of purified allergens allows an accurate diagnosis and this has led to three important findings: (1) in addition to the digestive route of sensitization, occupational and non-digestive exposure seems to be clinically relevant. (2) The parasite appears as an important agent for chronic urticaria. And (3) in endemic countries, the amount of highly sensitized subjects in the general population could be as high as 7%. Adequate information to asymptomatic patients on fish consumption habits would avoid new contacts with parasite allergens and decrease their specific IgE levels and consequently the appearance of acute or chronic episodes induced by the parasite.

Evaluation of a rapid immunochromatographic ODK-0901 test for detection of pneumococcal antigen in middle ear fluids and nasopharyngeal secretions.

PubMed

Hotomi, Muneki; Togawa, Akihisa; Takei, Shin; Sugita, Gen; Sugita, Rinya; Kono, Masamitsu; Fujimaki, Yutaka; Kamide, Yosuke; Uchizono, Akihiro; Kanesada, Keiko; Sawada, Shoichi; Okitsu, Naohiro; Tanaka, Yumi; Saijo, Yoko; Yamanaka, Noboru

2012-01-01

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs.

Evaluation of a Rapid Immunochromatographic ODK-0901 Test for Detection of Pneumococcal Antigen in Middle Ear Fluids and Nasopharyngeal Secretions

PubMed Central

Hotomi, Muneki; Togawa, Akihisa; Takei, Shin; Sugita, Gen; Sugita, Rinya; Kono, Masamitsu; Fujimaki, Yutaka; Kamide, Yosuke; Uchizono, Akihiro; Kanesada, Keiko; Sawada, Shoichi; Okitsu, Naohiro; Tanaka, Yumi; Saijo, Yoko; Yamanaka, Noboru

2012-01-01

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs. PMID:22448257

Contribution of a new electrophysiologic test to Morton's neuroma diagnosis.

PubMed

Pardal-Fernández, José Manuel; Palazón-García, Elena; Hernández-Fernández, Francisco; de Cabo, Carlos

2014-06-01

Morton's neuroma causes metatarsalgia due to the interdigital neuropathy. The small nerve diameter compromises their evaluation in image studies. To overcome this problem we propose a new electrophysiological test. We conducted a prospective case-control study performing a orthodromic electroneurography using subdermal electrodes in controls and patients to assess the validity. Additionally all patients were tested with magnetic resonance. Some patients required surgery and subsequent histological evaluation. The new ENG procedure showed higher sensitivity and specificity. Methodological standardization was easy and the test was well tolerated by the subjects. Our test demonstrated remarkable diagnostic efficiency, and also was able to identify symptomatic patients undetected by magnetic resonance, which underlines the lack of correlation between the size and intensity of the lesion. This new electrophysiological method appears to be a highly sensitivity, well-tolerated, simple and low-cost for Morton's neuroma diagnosis. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Rectal mucosal electrosensitivity - what is being tested?

PubMed

Meagher, A P; Kennedy, M L; Lubowski, D Z

1996-01-01

The results of rectal mucosal electrosensitivity (RME) testing have been used to support theories regarding the aetiology of both idiopathic constipation and bowel dysfunction following rectopexy. The aim of this study was to assess the validity of tests of RME. Sixty-eight patients, comprising three groups (group 1: 50 patients undergoing assessment in the Anorectal Physiology Unit, group 2: 10 patients with coloanal or ileoanal anastomosis, group 3: 8 patients with a stoma) underwent mucosal electrosensitivity testing, with the threshold stimulus required to elicit sensation being recorded. In addition the RME was measured in groups 1 and 2 when placing the electrode, mounted on a catheter with a central wire, against the anterior, posterior, right and left rectal or neorectal walls. To asses the influence on this test of loss of mucosal contact due to faeces, a further 8 cases with a normal rectum had RME performed with and without a layer of water soaked gauze around the electrode to stimulate faeces and prevent the electrode from making contact with the rectal mucosa. There was marked variance in the sensitivity of the different regions of rectal wall tested (P < 0.001). In group 1 patients the mean sensitivities were: central 36.6 mA, anterior 27.4 mA, posterior 37.9 mA, right 22.3 mA and left 25.6 mA. This circumferential variation suggests that the pelvic floor rather than rectal mucosa was being stimulated. All patients in group 2 had recordable sensitivities, and the mean sensitivity threshold was significantly higher than group 1 patients in the central (P = 0.03), right (P = 0.03) and left (P = 0.007) positions. In group 3 the sensitivity was greater within the stoma at the level of the abdominal wall muscle than intra-abdominally or subcutaneously, again suggesting an extra-colonic origin of the sensation. The sensitivity threshold was significantly greater with the electrode wrapped in gauze (P < 0.01), and loss of mucosal contact was not detected by the EMG machine. Therefore RME testing would seem not to measure mucosal sensitivity, and is probably influenced by the presence of faeces.

CSF soluble amyloid precursor proteins in the diagnosis of incipient Alzheimer disease.

PubMed

Perneczky, R; Tsolakidou, A; Arnold, A; Diehl-Schmid, J; Grimmer, T; Förstl, H; Kurz, A; Alexopoulos, P

2011-07-05

To explore if soluble amyloid precursor proteins (sAPP) in CSF improve the identification of patients with incipient Alzheimer disease (AD) in a group of patients with mild cognitive impairment (MCI). A cohort study with follow-up assessments of 58 patients with MCI with baseline CSF sampling was conducted: 21 patients had progressed to probable AD (MCI-AD), 27 still had MCI, 8 had reverted to normal (MCI-NAD), and 2 patients with frontotemporal dementia (FTD) were excluded. Sixteen additional patients with FTD were included to explore the specificity of the CSF markers. CSF concentrations of sAPPα, sAPPβ, tau, and Aβ(1-42) were measured with sensitive and specific ELISAs. Associations between diagnostic status, CSF protein concentrations, and other patient characteristics were explored using multiple logistic regression analyses with stepwise variable selection. The optimal sensitivity and specificity of the best models were derived from receiver operating characteristic curves. The MCI-AD group had significantly higher sAPPβ concentrations than the MCI-NAD and the FTD groups. A combination of sAPPβ, tau, and age differentiated the MCI-AD and the MCI-NAD groups with a sensitivity of 80.00% and a specificity of 81.00%. The best model for the differentiation of the MCI-AD and the FTD groups included sAPPβ and tau, and showed a sensitivity of 95.20% and a specificity of 81.20%. Aβ(1-42) and sAPPα did not significantly contribute to the models. These findings suggest that sAPPβ may be clinically useful, and superior to Aβ(1-42), in the early and differential diagnosis of incipient AD.

Non-mix fragrances are top sensitizers in consecutive dermatitis patients - a cross-sectional study of the 26 EU-labelled fragrance allergens.

PubMed

Bennike, Niels H; Zachariae, Claus; Johansen, Jeanne D

2017-11-01

For cosmetics, it is mandatory to label 26 fragrance substances, including all constituents of fragrance mix I (FM I) and fragrance mix II (FM II). Earlier reports have not included oxidized R-limonene [hydroperoxides of R-limonene (Lim-OOH)] and oxidized linalool [hydroperoxides of linalool (Lin-OOH)], and breakdown testing of FM I and FM II has mainly been performed in selected, mix-positive patients. To report the prevalence of sensitization to the 26 fragrances, and to assess concomitant reactivity to FM I and/or FM II. A cross-sectional study on consecutive dermatitis patients patch tested with the 26 fragrances and the European baseline series from 2010 to 2015 at a single university clinic was performed. Of 6004 patients, 940 (15.7%, 95%CI: 14.7-16.6%) were fragrance-sensitized. Regarding the single fragrances, most patients were sensitized to Lin-OOH (3.9%), Evernia furfuracea (3.0%), Lim-OOH (2.5%), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (2.1%). Significantly fewer patients were 'FM I-positive and constituent-positive' than 'FM II-positive and constituent-positive' (32.7% versus 57.0%, p < 0.0001). Additionally, significantly more patients were 'FM II-negative but constituent-positive' than 'FM I-negative but constituent-positive' (12.4% versus 3.2%, p = 0.0008). Non-mix fragrances are the most important single fragrance allergens among consecutive patients. The test concentration of the single FM I constituents should be increased when possible. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Extracolonic findings (ECF) on CT colonography (CTC) in patients presenting with colorectal symptoms.

PubMed

Badiani, Sarit; Tomas-Hernandez, Silvia; Karandikar, Sharad; Roy-Choudhury, Shuvro

2013-10-01

Computed tomographic colonography (CTC) is now an established method for imaging the colon and rectum in the screening and symptomatic setting. Additional benefit of CTC is the ability to assess for extracolonic findings especially in patients presenting with colorectal symptoms. To determine prevalence of extracolonic findings (ECF) in symptomatic patients undergoing CTC and determine accuracy of CTC for exclusion of significant abdominal disease and extracolonic malignancy (ECM). A total of 1359 unenhanced prone and postcontrast supine CTC studies were performed between March 2002 and December 2007. ECF were retrospectively classified according to C-RADS criteria into E1 to E4 findings. For ECM, a gold standard of clinical and/or radiological follow-up supplemented with data from the regional cancer registry with a median follow-up of 42 months was created. Sensitivity and negative predictive values for ECM was calculated. Following exclusions, 1177 CTCs were analyzed. Of 1423 extracolonic findings reported, 328/1423 (23%) E3 and 100/1423 (7%) E4 (including six eventual FP studies) findings were identified. Thirty-two ECMs were confirmed following further investigations. Seven further small ECMs were detected during the entire follow-up, of which two were potentially visible in retrospect (false-negative studies). Additional tests were generated from 55/1177 (4.7%) studies. Sensitivity and negative predictive value for ECM was 94.1% (95% CI 78.9-98.9%) and 99.8% (95% CI 99.3-99.9%), respectively. One in 37 patients were found to have an ECM. Two potentially detectable cancers were missed. Only a small proportion of patients underwent additional work-up.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craswell, P.W.; Price, J.; Boyle, P.D.

EDTA (calcium disodium edetate) lead mobilization and x-ray fluorescence (XRF) finger bone lead tests were done in 42 patients with chronic renal failure and without persisting lead intoxication. Nineteen of 23 patients with gout and 8 of 19 without gout had positive EDTA lead mobilization tests. Those patients with gout excreted significantly more excess lead chelate than those without gout. In the gout group 17 patients denied any childhood or industrial exposure to lead. They had a greater number of positive tests and excreted significantly more excess lead chelate than 14 patients with neither gout nor lead exposure. These resultsmore » confirm that gout in the presence of chronic renal failure is a useful marker of chronic lead poisoning. Of 27 patients with positive lead mobilization tests, only 13 had elevated XRF finger bone lead concentrations (sensitivity 48%). Three of 15 patients with negative lead mobilization tests had elevated XRF finger bone lead concentrations (specificity 80%). Although the XRF finger bone lead test is a convenient noninvasive addition to the diagnostic evaluation of patients with chronic renal failure and gout, its application is limited due to the lack of sensitivity of the method.« less

Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

PubMed Central

Meeus, Mira

2006-01-01

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc. PMID:17115100

Molecular diagnosis of bloodstream infections in onco-haematology patients with PCR/ESI-MS technology.

PubMed

Jordana-Lluch, Elena; Rivaya, Belén; Marcó, Clara; Giménez, Montserrat; Quesada, Mª Dolores; Escobedo, Agustín; Batlle, Montserrat; Martró, Elisa; Ausina, Vicente

2017-02-01

Onco-haematological patients are prone to develop infections, and antibiotic prophylaxis may lead to negative blood cultures. Thus, the microbiological diagnosis and subsequent administration of a targeted antimicrobial therapy is often difficult. The goal of this study was to evaluate the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of bloodstream infections in this patient group. A total of 463 whole blood specimens from different sepsis episodes in 429 patients were analysed using the PCR/ESI-MS platform, comparing the results with those of blood culture and other clinically relevant information. The sensitivity of PCR/ESI-MS by specimen (excluding polymicrobial infections, n = 25) in comparison with blood culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in haematological patients. When comparing with a clinical infection criterion, overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%) than in haematological patients (67.7%). Thirty-one microorganisms isolated by culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens not isolated by culture were detected moleculary. PCR/ESI-MS offers a reliable identification of pathogens directly from whole blood. While additional studies are needed to confirm our findings, the system showed a lower sensitivity in onco-haematological patients in comparison with previously reported results in patients from the Intensive Care Unit. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

PubMed

Martino, David; Dang, Thanh; Sexton-Oates, Alexandra; Prescott, Susan; Tang, Mimi L K; Dharmage, Shyamali; Gurrin, Lyle; Koplin, Jennifer; Ponsonby, Anne-Louise; Allen, Katrina J; Saffery, Richard

2015-05-01

The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

MRI monitoring of focused ultrasound sonications near metallic hardware.

PubMed

Weber, Hans; Ghanouni, Pejman; Pascal-Tenorio, Aurea; Pauly, Kim Butts; Hargreaves, Brian A

2018-07-01

To explore the temperature-induced signal change in two-dimensional multi-spectral imaging (2DMSI) for fast thermometry near metallic hardware to enable MR-guided focused ultrasound surgery (MRgFUS) in patients with implanted metallic hardware. 2DMSI was optimized for temperature sensitivity and applied to monitor focus ultrasound surgery (FUS) sonications near metallic hardware in phantoms and ex vivo porcine muscle tissue. Further, we evaluated its temperature sensitivity for in vivo muscle in patients without metallic hardware. In addition, we performed a comparison of temperature sensitivity between 2DMSI and conventional proton-resonance-frequency-shift (PRFS) thermometry at different distances from metal devices and different signal-to-noise ratios (SNR). 2DMSI thermometry enabled visualization of short ultrasound sonications near metallic hardware. Calibration using in vivo muscle yielded a constant temperature sensitivity for temperatures below 43 °C. For an off-resonance coverage of ± 6 kHz, we achieved a temperature sensitivity of 1.45%/K, resulting in a minimum detectable temperature change of ∼2.5 K for an SNR of 100 with a temporal resolution of 6 s per frame. The proposed 2DMSI thermometry has the potential to allow MR-guided FUS treatments of patients with metallic hardware and therefore expand its reach to a larger patient population. Magn Reson Med 80:259-271, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291.

PubMed

Thress, Kenneth S; Brant, Roz; Carr, T Hedley; Dearden, Simon; Jenkins, Suzanne; Brown, Helen; Hammett, Tracey; Cantarini, Mireille; Barrett, J Carl

2015-12-01

To assess the ability of different technology platforms to detect epidermal growth factor receptor (EGFR) mutations, including T790M, from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients. A comparison of multiple platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples were collected from patients entering the ongoing AURA trial (NCT01802632), investigating the safety, tolerability, and efficacy of AZD9291 in patients with EGFR-sensitizing mutation-positive NSCLC. Plasma was collected prior to AZD9291 dosing but following clinical progression on a previous EGFR-tyrosine kinase inhibitor (TKI). Extracted ctDNA was analyzed using two non-digital platforms (cobas(®) EGFR Mutation Test and therascreen™ EGFR amplification refractory mutation system assay) and two digital platforms (Droplet Digital™ PCR and BEAMing digital PCR [dPCR]). Preliminary assessment (38 samples) was conducted using all four platforms. For EGFR-TKI-sensitizing mutations, high sensitivity (78-100%) and specificity (93-100%) were observed using tissue as a non-reference standard. For the T790M mutation, the digital platforms outperformed the non-digital platforms. Subsequent assessment using 72 additional baseline plasma samples was conducted using the cobas(®) EGFR Mutation Test and BEAMing dPCR. The two platforms demonstrated high sensitivity (82-87%) and specificity (97%) for EGFR-sensitizing mutations. For the T790M mutation, the sensitivity and specificity were 73% and 67%, respectively, with the cobas(®) EGFR Mutation Test, and 81% and 58%, respectively, with BEAMing dPCR. Concordance between the platforms was >90%, showing that multiple platforms are capable of sensitive and specific detection of EGFR-TKI-sensitizing mutations from NSCLC patient plasma. The cobas(®) EGFR Mutation Test and BEAMing dPCR demonstrate a high sensitivity for T790M mutation detection. Genomic heterogeneity of T790M-mediated resistance may explain the reduced specificity observed with plasma-based detection of T790M mutations versus tissue. These data support the use of both platforms in the AZD9291 clinical development program. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

PubMed Central

Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa

2015-01-01

Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional clinical studies of MEK inhibitors in this disease. PMID:26324360

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Asking For Help is Helpful: Validation of a Brief Lifestyle and Mood Assessment Tool in Primary Health Care

PubMed Central

Goodyear-Smith, Felicity; Arroll, Bruce; Coupe, Nicole

2009-01-01

PURPOSE The short, validated, self-administered, Case-finding and Help Assessment Tool (CHAT) for lifestyle and mental health assessment of adult patients in primary health care addresses inactivity, tobacco use, alcohol and other drug misuse, problem gambling, depression, anxiety and stress, abuse, and anger problems. For each issue patients are asked whether they would like help, either during the consultation or at a later date. This study aims to assess the value of the help question. METHODS Validation of the CHAT was conducted according to the STAndards for Reporting of Diagnostic accuracy studies statement for diagnostic tests. The setting was Auckland primary care practices with populations ranging from socioeconomically advantaged to deprived. Participants were 755 consecutive primary care patients who completed the CHAT plus the help question and reference standards. Sensitivity, specificity, and likelihood ratios with and without the addition of help the question were calculated. RESULTS Sensitivity ranged from 80% to 98% for the more-common conditions (depression, nicotine dependency, anxiety, problematic drinking). For each condition, specificity increased with the addition of the help question: depression increased from 73% to 98%; anxiety 77% to 99%; drinking 85% to 99%; verbal anger 92% to 99%; verbal abuse 97% to 99%; problematic drinking and gambling 98% to 99%. CONCLUSIONS The help question increased specificity without compromising sensitivity and reduced false positives, thereby increasing the positive predictive value. It allowed patients with comorbidities to prioritize issues they wished to address, indicate their readiness to change, promote self-determination, and give the clinician an indication of which topics to pursue. PMID:19433841

Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.

PubMed

Masson, Serge; Caironi, Pietro; Fanizza, Caterina; Carrer, Sara; Caricato, Anselmo; Fassini, Paola; Vago, Tarcisio; Romero, Marilena; Tognoni, Gianni; Gattinoni, Luciano; Latini, Roberto

2016-04-01

Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). Forty ICUs in Italy. Nine hundred and ninety-five patients with severe sepsis or septic shock. Randomization to albumin and crystalloid solutions or crystalloid solutions alone. Plasma concentrations of N- terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrollment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of supporting therapy.

Cost-effectiveness of training rural providers to identify and treat patients at risk for fragility fractures.

PubMed

Nelson, S D; Nelson, R E; Cannon, G W; Lawrence, P; Battistone, M J; Grotzke, M; Rosenblum, Y; LaFleur, J

2014-12-01

This is a cost-effectiveness analysis of training rural providers to identify and treat osteoporosis. Results showed a slight cost savings, increase in life years, increase in treatment rates, and decrease in fracture incidence. However, the results were sensitive to small differences in effectiveness, being cost-effective in 70 % of simulations during probabilistic sensitivity analysis. We evaluated the cost-effectiveness of training rural providers to identify and treat veterans at risk for fragility fractures relative to referring these patients to an urban medical center for specialist care. The model evaluated the impact of training on patient life years, quality-adjusted life years (QALYs), treatment rates, fracture incidence, and costs from the perspective of the Department of Veterans Affairs. We constructed a Markov microsimulation model to compare costs and outcomes of a hypothetical cohort of veterans seen by rural providers. Parameter estimates were derived from previously published studies, and we conducted one-way and probabilistic sensitivity analyses on the parameter inputs. Base-case analysis showed that training resulted in no additional costs and an extra 0.083 life years (0.054 QALYs). Our model projected that as a result of training, more patients with osteoporosis would receive treatment (81.3 vs. 12.2 %), and all patients would have a lower incidence of fractures per 1,000 patient years (hip, 1.628 vs. 1.913; clinical vertebral, 0.566 vs. 1.037) when seen by a trained provider compared to an untrained provider. Results remained consistent in one-way sensitivity analysis and in probabilistic sensitivity analyses, training rural providers was cost-effective (less than $50,000/QALY) in 70 % of the simulations. Training rural providers to identify and treat veterans at risk for fragility fractures has a potential to be cost-effective, but the results are sensitive to small differences in effectiveness. It appears that provider education alone is not enough to make a significant difference in fragility fracture rates among veterans.

Study of Pre-disposing Factors of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Antibiotic Prescribing Pattern with Reference to Antibiotic Sensitivity Test.

PubMed

Shrestha, R; Shrestha, B; Shakya Shrestha, S; Pant, A; Prajapati, B; Karmacharya, B M

2015-01-01

Background Chronic Obstructive Pulmonary Disease (COPD) affects about 329 million people worldwide, which is nearly 5% of the entire global population. In the context of Nepal, COPD accounts for 43% of the non-communicable disease burden and 2.56% of hospitalizations. Various pre-disposing factors like bacterial, viral, fungal, smoking, occupational exposures and genetic factors have been proposed to precipitate COPD and its exacerbation though, the definitive pre-disposing factors and factors related to acute exacerbation have not been determined in the context of Nepal. Objective To find out the pre-disposing factors and the related causative agents for COPD. Method A cross sectional study was conducted in a tertiary care hospital. Patients of all age group who were diagnosed as COPD and admitted in the hospital were included in this study. Patients were interviewed using structured questionnaire. The sociodemographic data including personal and medical history were recorded from those participants. In addition, sputum from those patients was sent for culture to investigate the possible responsible pathogens as well as its antibiotic sensitivity pattern. Result A total of 150 patients having Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) who have admitted from either emergency or out-patient department of the hospital were included in this study. Among the total number of patients, more than half of them were female (n=82). In addition, analysis of occupations shows that most of them were either farmer (36.0%) or housewife (30.7%). In total studied patients (n=150), most of them were using traditional firewood (83%) for cooking purpose and majority of patients (91%) were smokers. Most of the sputum samples show growth of gram-positive cocci (26.7%) and gram negative bacilli (27.5%). Considering the overall sensitivity pattern, the higher sensitivity was recorded for Co-trimoxazole and Ciprofloxacin while higher rate of resistance was noted for Penicillin group of drugs. The most widely used antibiotics were found to be Cephalosporin group of drugs (68%). Conclusion The present study revealed that the case of COPD is more in female and the commonest pre-disposing factor is found to be smoke/firewood. Cephalosporin group of drugs is the most commonly prescribed drug.

Sensitivity of endoscopic ultrasound, multidetector computed tomography, and magnetic resonance cholangiopancreatography in the diagnosis of pancreas divisum: a tertiary center experience.

PubMed

Kushnir, Vladimir M; Wani, Sachin B; Fowler, Kathryn; Menias, Christine; Varma, Rakesh; Narra, Vamsi; Hovis, Christine; Murad, Faris M; Mullady, Daniel K; Jonnalagadda, Sreenivasa S; Early, Dayna S; Edmundowicz, Steven A; Azar, Riad R

2013-04-01

There are limited data comparing imaging modalities in the diagnosis of pancreas divisum. We aimed to: (1) evaluate the sensitivity of endoscopic ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP), and multidetector computed tomography (MDCT) for pancreas divisum; and (2) assess interobserver agreement (IOA) among expert radiologists for detecting pancreas divisum on MDCT and MRCP. For this retrospective cohort study, we identified 45 consecutive patients with pancreaticobiliary symptoms and pancreas divisum established by endoscopic retrograde pancreatography who underwent EUS and cross-sectional imaging. The control group was composed of patients without pancreas divisum who underwent endoscopic retrograde pancreatography and cross-sectional imaging. The sensitivity of EUS for pancreas divisum was 86.7%, significantly higher than the sensitivity reported in the medical records for MDCT (15.5%) or MRCP (60%) (P < 0.001 for each). On review by expert radiologists, the sensitivity of MDCT increased to 83.3% in cases where the pancreatic duct was visualized, with fair IOA (κ = 0.34). Expert review of MRCPs did not identify any additional cases of pancreas divisum; IOA was moderate (κ = 0.43). Endoscopic ultrasound is a sensitive test for diagnosing pancreas divisum and is superior to MDCT and MRCP. Review of MDCT studies by expert radiologists substantially raises its sensitivity for pancreas divisum.

Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology

PubMed Central

McShane, R; Nagy, Z; Esiri, M; King, E; Joachim, C; Sullivan, N; Smith, A

2001-01-01

OBJECTIVES—To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated.
METHODS—The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease.
RESULTS—Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance.
CONCLUSION—Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.

 PMID:11385006

High-resolution melting (HRM) re-analysis of a polyposis patients cohort reveals previously undetected heterozygous and mosaic APC gene mutations.

PubMed

Out, Astrid A; van Minderhout, Ivonne J H M; van der Stoep, Nienke; van Bommel, Lysette S R; Kluijt, Irma; Aalfs, Cora; Voorendt, Marsha; Vossen, Rolf H A M; Nielsen, Maartje; Vasen, Hans F A; Morreau, Hans; Devilee, Peter; Tops, Carli M J; Hes, Frederik J

2015-06-01

Familial adenomatous polyposis is most frequently caused by pathogenic variants in either the APC gene or the MUTYH gene. The detection rate of pathogenic variants depends on the severity of the phenotype and sensitivity of the screening method, including sensitivity for mosaic variants. For 171 patients with multiple colorectal polyps without previously detectable pathogenic variant, APC was reanalyzed in leukocyte DNA by one uniform technique: high-resolution melting (HRM) analysis. Serial dilution of heterozygous DNA resulted in a lowest detectable allelic fraction of 6% for the majority of variants. HRM analysis and subsequent sequencing detected pathogenic fully heterozygous APC variants in 10 (6%) of the patients and pathogenic mosaic variants in 2 (1%). All these variants were previously missed by various conventional scanning methods. In parallel, HRM APC scanning was applied to DNA isolated from polyp tissue of two additional patients with apparently sporadic polyposis and without detectable pathogenic APC variant in leukocyte DNA. In both patients a pathogenic mosaic APC variant was present in multiple polyps. The detection of pathogenic APC variants in 7% of the patients, including mosaics, illustrates the usefulness of a complete APC gene reanalysis of previously tested patients, by a supplementary scanning method. HRM is a sensitive and fast pre-screening method for reliable detection of heterozygous and mosaic variants, which can be applied to leukocyte and polyp derived DNA.

Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

PubMed

Delea, Thomas E; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

2007-01-01

Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. Results of this analysis of the cost effectiveness of oral deferasirox versus infusional deferoxamine suggest that deferasirox is a cost effective iron chelator from a US healthcare perspective.

Clinical Value of a One-Stop-Shop Low-Dose Lung Screening Combined with (18)F-FDG PET/CT for the Detection of Metastatic Lung Nodules from Colorectal Cancer.

PubMed

Han, Yeon-Hee; Lim, Seok Tae; Jeong, Hwan-Jeong; Sohn, Myung-Hee

2016-06-01

The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with (18)F-fluoro-2-deoxyglucose positron emission tomography with CT ((18)F-FDG PET/CT) compared with conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with (18)F-FDG PET/CT. Forty-five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had ≤5 metastatic lung nodules and the other 20 patients had >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with ≤5 nodules were evaluated by conventional lung setting image of (18)F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of (18)F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. Of the 120 nodules in the 25 patients with ≤5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of (18)F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were <1 cm in size. The sensitivity, specificity, and diagnostic accuracy of the modalities were 60.6 %, 85.2 %, and 71.1 % for conventional lung setting image and 83.3 %, 88.9 %, and 85.8 % for additional LD-HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional lung setting image and additional LD-HRCT were 0.712 and 0.827 respectively. Additional LD-HRCT with maximum inspiration was superior to conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer (P < 0.05).

Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax.

PubMed

Matulis, S M; Gupta, V A; Nooka, A K; Hollen, H V; Kaufman, J L; Lonial, S; Boise, L H

2016-05-01

Venetoclax (ABT-199), a specific inhibitor of the anti-apoptotic protein Bcl-2, is currently in phase I clinical trials for multiple myeloma. The results suggest that venetoclax is only active in a small cohort of patients therefore we wanted to determine its efficacy when used in combination. Combining venetoclax with melphalan or carfilzomib produced additive or better cell death in four of the five cell lines tested. The most striking results were seen with dexamethasone (Dex). Co-treatment of human myeloma cell lines and primary patient samples, with Dex and venetoclax, significantly increased cell death over venetoclax alone in four of the five cell lines, and in all patient samples tested. The mechanism by which this occurs is an increase in the expression of both Bcl-2 and Bim upon addition of Dex. This results in alterations in Bim binding to anti-apoptotic proteins. Dex shifts Bim binding towards Bcl-2 resulting in increased sensitivity to venetoclax. These data suggest that knowledge of drug-induced alterations of Bim-binding patterns may help inform better combination drug regimens. Furthermore, the data indicate combining this novel therapeutic with Dex could be an effective therapy for a broader range of patients than would be predicted by single-agent activity.

Dexamethasone treatment promotes Bcl-2-dependence in multiple myeloma resulting in sensitivity to Venetoclax

PubMed Central

Matulis, Shannon M.; Gupta, Vikas A.; Nooka, Ajay K.; Von Hollen, Hayley; Kaufman, Jonathan L.; Lonial, Sagar; Boise, Lawrence H.

2015-01-01

Venetoclax (ABT-199), a specific inhibitor of the anti-apoptotic protein Bcl-2, is currently in phase I clinical trials for multiple myeloma. Results suggest that venetoclax is only active in a small cohort of patients therefore we wanted to determine its efficacy when used in combination. Combining venetoclax with melphalan or carfilzomib produced additive or better cell death in 4 of the 5 cell lines tested. The most striking results were seen with dexamethasone. Co-treatment of human myeloma cell lines and primary patient samples, with dexamethasone and venetoclax significantly increased cell death over venetoclax alone in 4 of the 5 cell lines, and in all patient samples tested. The mechanism by which this occurs is an increase in the expression of both Bcl-2 and Bim upon addition of dexamethasone. This results in alterations in Bim binding to anti-apoptotic proteins. Dexamethasone shifts Bim binding towards Bcl-2 resulting in increased sensitivity to venetoclax. These data suggest that knowledge of drug-induced alterations of Bim binding patterns may help inform better combination drug regimens. Furthermore, the data indicate combining this novel therapeutic with dexamethasone could be an effective therapy for a broader range of patients than would be predicted by single agent activity. PMID:26707935

Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts.

PubMed

Liao, Katherine P; Ananthakrishnan, Ashwin N; Kumar, Vishesh; Xia, Zongqi; Cagan, Andrew; Gainer, Vivian S; Goryachev, Sergey; Chen, Pei; Savova, Guergana K; Agniel, Denis; Churchill, Susanne; Lee, Jaeyoung; Murphy, Shawn N; Plenge, Robert M; Szolovits, Peter; Kohane, Isaac; Shaw, Stanley Y; Karlson, Elizabeth W; Cai, Tianxi

2015-01-01

Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM.

Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts

PubMed Central

Liao, Katherine P.; Ananthakrishnan, Ashwin N.; Kumar, Vishesh; Xia, Zongqi; Cagan, Andrew; Gainer, Vivian S.; Goryachev, Sergey; Chen, Pei; Savova, Guergana K.; Agniel, Denis; Churchill, Susanne; Lee, Jaeyoung; Murphy, Shawn N.; Plenge, Robert M.; Szolovits, Peter; Kohane, Isaac; Shaw, Stanley Y.; Karlson, Elizabeth W.; Cai, Tianxi

2015-01-01

Background Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. Methods and Results We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. Conclusions We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM. PMID:26301417

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus

PubMed Central

Zhao, Ming; Zhou, Yin; Zhu, Bochen; Wan, Mengjie; Jiang, Tingting; Tan, Qiqun; Liu, Yan; Jiang, Juqing; Luo, Shuaihantian; Tan, Yixin; Wu, Haijing; Renauer, Paul; Gutiérrez, Maria del Mar Ayala; Palma, Maria Jesús Castillo; Castro, Rafaela Ortega; Fernández-Roldán, Concepción; Raya, Enrique; Faria, Raquel; Carvalho, Claudia; Alarcón-Riquelme, Marta E; Xiang, Zhongyuan; Chen, Jinwei; Li, Fen; Ling, Guanghui; Zhao, Hongjun; Liao, Xiangping; Lin, Youkun; Sawalha, Amr H; Lu, Qianjin

2016-01-01

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. Methods IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren’s syndrome (pSS) were used for validation. Results Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. Conclusions The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE. PMID:26787370

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus.

PubMed

Zhao, Ming; Zhou, Yin; Zhu, Bochen; Wan, Mengjie; Jiang, Tingting; Tan, Qiqun; Liu, Yan; Jiang, Juqing; Luo, Shuaihantian; Tan, Yixin; Wu, Haijing; Renauer, Paul; Del Mar Ayala Gutiérrez, Maria; Castillo Palma, Maria Jesús; Ortega Castro, Rafaela; Fernández-Roldán, Concepción; Raya, Enrique; Faria, Raquel; Carvalho, Claudia; Alarcón-Riquelme, Marta E; Xiang, Zhongyuan; Chen, Jinwei; Li, Fen; Ling, Guanghui; Zhao, Hongjun; Liao, Xiangping; Lin, Youkun; Sawalha, Amr H; Lu, Qianjin

2016-11-01

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment.

PubMed

Leonard, Alexandra; Guttman-Yassky, Emma

2018-05-12

Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.

Additional corpus biopsy enhances the detection of Helicobacter pylori infection in a background of gastritis with atrophy

PubMed Central

2012-01-01

Background The best sites for biopsy-based tests to evaluate H. pylori infection in gastritis with atrophy are not well known. This study aimed to evaluate the site and sensitivity of biopsy-based tests in terms of degree of gastritis with atrophy. Methods One hundred and sixty-four (164) uninvestigated dyspepsia patients were enrolled. Biopsy-based tests (i.e., culture, histology Giemsa stain and rapid urease test) and non-invasive tests (anti-H. pylori IgG) were performed. The gold standard of H. pylori infection was defined according to previous criteria. The sensitivity, specificity, positive predictive rate and negative predictive rate of biopsy-based tests at the gastric antrum and body were calculated in terms of degree of gastritis with atrophy. Results The prevalence rate of H. pylori infection in the 164 patients was 63.4%. Gastritis with atrophy was significantly higher at the antrum than at the body (76% vs. 31%; p<0.001). The sensitivity of biopsy-based test decreased when the degree of gastritis with atrophy increased regardless of biopsy site (for normal, mild, moderate, and severe gastritis with atrophy, the sensitivity of histology Giemsa stain was 100%, 100%, 88%, and 66%, respectively, and 100%, 97%, 91%, and 66%, respectively, for rapid urease test). In moderate to severe antrum or body gastritis with atrophy, additional corpus biopsy resulted in increased sensitivity to 16.67% compare to single antrum biopsy. Conclusions In moderate to severe gastritis with atrophy, biopsy-based test should include the corpus for avoiding false negative results. PMID:23272897

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer

PubMed Central

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-01-01

Purpose This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). Materials and Methods We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). Results In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Conclusion Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID:27669704

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer.

PubMed

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-07-01

This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

Detection of soft-tissue sarcoma recurrence: added value of functional MR imaging techniques at 3.0 T.

PubMed

Del Grande, Filippo; Subhawong, Ty; Weber, Kristy; Aro, Michael; Mugera, Charles; Fayad, Laura M

2014-05-01

To determine the added value of functional magnetic resonance (MR) sequences (dynamic contrast material-enhanced [DCE] and quantitative diffusion-weighted [DW] imaging with apparent diffusion coefficient [ADC] mapping) for the detection of recurrent soft-tissue sarcomas following surgical resection. This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. Thirty-seven patients referred for postoperative surveillance after resection of soft-tissue sarcoma (35 with high-grade sarcoma) were studied. Imaging at 3.0 T included conventional (T1-weighted, fluid-sensitive, and contrast-enhanced T1-weighted imaging) and functional (DCE MR imaging, DW imaging with ADC mapping) sequences. Recurrences were confirmed with biopsy or resection. A disease-free state was determined with at least 6 months of follow-up. Two readers independently recorded the signal and morphologic characteristics with conventional sequences, the presence or absence of arterial enhancement at DCE MR imaging, and ADCs of the surgical bed. The accuracy of conventional MR imaging in the detection of recurrence was compared with that with the addition of functional sequences. The Fisher exact and Wilcoxon rank sum tests were used to define the accuracy of imaging features, the Cohen κ and Lin interclass correlation were used to define interobserver variability, and receiver operating characteristic analysis was used to define a threshold to detect recurrence and assess reader confidence after the addition of functional imaging to conventional sequences. There were six histologically proved recurrences in 37 patients. Sensitivity and specificity of MR imaging in the detection of tumor recurrence were 100% (six of six patients) and 52% (16 of 31 patients), respectively, with conventional sequences, 100% (six of six patients) and 97% (30 of 31 patients) with the addition of DCE MR imaging, and 60% (three of five patients) and 97% (30 of 31 patients) with the addition of DW imaging and ADC mapping. The average ADC of recurrence (1.08 mm(2)/sec ± 0.19) was significantly different from those of postoperative scarring (0.9 mm(2)/sec ± 0.00) and hematomas (2.34 mm(2)/sec ± 0.72) (P = .03 for both). The addition of functional MR sequences to a routine MR protocol, in particular DCE MR imaging, offers a specificity of more than 95% for distinguishing recurrent sarcoma from postsurgical scarring.

The HEART score with high-sensitive troponin T at presentation: ruling out patients with chest pain in the emergency room.

PubMed

Santi, Luca; Farina, Gabriele; Gramenzi, Annagiulia; Trevisani, Franco; Baccini, Margherita; Bernardi, Mauro; Cavazza, Mario

2017-04-01

The HEART score is a simple scoring system, ranging from 0 to 10, specifically developed for risk stratification of patients with undifferentiated chest pain. It has been validated for the conventional troponin, but not for high-sensitive troponin. We assess a modified version of the HEART score using a single high-sensitivity troponin T dosage at presentation, regardless of symptom duration, and with different ECG criteria to evaluate if the patients with a low HEART score could be safely discharged early. The secondary aim was to confirm a statistically significant difference in each HEART score group (low 0-3, intermediate 4-6, high 7-10) in the occurrence of major adverse cardiac events at 30 and 180 days. We retrospectively analyzed the HEART score of 1597 consecutive patients admitted to the Emergency Department of our Hospital for chest pain between January 1 and June 30, 2014. Of these, 190 did not meet the inclusion criteria and 29 were lost to follow-up. None of the 512 (37.2 %) patients with a low HEART score had an event within 180 days. The difference between the cumulative incidences of events in the three HEART score groups was statistically significant (P < 0.0001). We demonstrate that it might be possible to safely discharge Emergency Department chest pain patients with a low modified HEART score after an initial determination of high-sensitive troponin T, without a prolonged observation period or an additional cardiac testing.

[Evaluation of ICT malaria immunochromatographic Binax NOW ICT P.f/P.v test for rapid diagnosis of malaria in a Colombian endemic area].

PubMed

Pabón, Adriana; Alvarez, Gonzalo; Yánez, Jorge; Céspedes, Carlos; Rodríguez, Yensa; Restrepo, Angela; Blair, Silvia

2007-06-01

One of the strategies to reduce malarial morbidity and mortality is to make an early diagnosis, using simple rapid tests which are highly sensitive and specific. Furthermore, the tests must be easy to perform and understand by local people in such a way that a suitable and prompt antimalarial treatment is guaranteed. The sensitivity and specificity was determined for the immuno-chromographic malaria dipstick (ICT Pf/Pv) test for the rapid diagnosis of malaria in Turbo, Antioquia. The sample consisted of 171 patients distributed into two groups: the first group was 118 patients with acute febrile syndrome compatible with malaria to which ICT Pf/Pv and thick smears were applied simultaneously; a second group was 53 patients with positive diagnosis by thick smear, with follow-up on the 4th and 7th days after beginning treatment. Sensitivity and specificity of the ICT Pf/Pv test for Plasmodium falciparum infections were 54.2% (95%CI: 52.0-53.4%) and 93.6% (95%CI: 93.1-94.2%), respectively. In addition, for Plasmodium vivax the sensitivity and specificity were 80% (95%CI: 77.9-82.1%) and 100% (95%CI: 99.5-100%); there was a 21.4% loss of sensitivity for P. falciparum 21.4% and a 33% loss for P. vivax malaria with parasitaemias under 500 parasites/ul. For the confirmatory test, ICT Pf/Pv showed a global sensitivity of 71.6% with 20.7% false positive and 5.6% false negative results. During follow-up, ICT showed 36% and 34% false positive results for day 4 and 7, respectively. The ICT Pf/Pv test has a poor sensitivity for P. falciparum malaria and its capacity to detect parasitemias under 500 parasites/ul is minimal. As a confirmatory test, the ICT Pf/Pv has a good sensitivity for P. falciparum. Its use for patient follow-up is not recommended.

Comparison of mortality prediction models in burns ICU patients in Pinderfields Hospital over 3 years.

PubMed

Douglas, Helen E; Ratcliffe, Andrew; Sandhu, Rajdeep; Anwar, Umair

2015-02-01

Many different burns mortality prediction models exist; however most agree that important factors that can be weighted include the age of the patient, the total percentage of body surface area burned and the presence or absence of smoke inhalation. A retrospective review of all burns primarily admitted to Pinderfields Burns ICU under joint care of burns surgeons and intensivists for the past 3 years was completed. Predicted mortality was calculated using the revised Baux score (2010), the Belgian Outcome in Burn Injury score (2009) and the Boston group score by Ryan et al. (1998). Additionally 28 of the 48 patients had APACHE II scores recorded on admission and the predicted and actual mortality of this group were compared. The Belgian score had the highest sensitivity and negative predictive value (72%/85%); followed by the Boston score (66%/78%) and then the revised Baux score (53%/70%). APACHE II scores had higher sensitivity (81%) and NPV (92%) than any of the burns scores. In our group of burns ICU patients the Belgian model was the most sensitive and specific predictor of mortality. In our subgroup of patients with APACHE II data, this score more accurately predicted survival and mortality. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Effects of additional oxazepam in long-term users of oxazepam.

PubMed

Voshaar, Richard C Oude; Verkes, Robbert-Jan; van Luijtelaar, Gilles L J M; Edelbroek, Peter M; Zitman, Frans G

2005-02-01

Although additional dosages of benzodiazepines in long-term users of benzodiazepines are common, it is unknown whether these additional dosages resort any effect. The effects of an additional 20-mg dosage oxazepam were assessed in a double-blind, balanced-order, crossover randomized study comparing 16 long-term users of oxazepam (patients) with 18 benzodiazepine-naive controls (controls). The effects of 10 and 30 mg oxazepam were assessed at pretest and 2.5 hours after drug administration on: (a) saccadic eye movements as proxy for the sedative effect, (b) acoustic startle response (ASR) as proxy for the anxiolytic effects, (c) memory, (d) reaction time tasks, and (e) subjective measurements. Dose-related effects were found in patients on the peak velocity of saccadic eye movement and on response probability, respectively peak amplitude of the ASR. Comparison with controls, however, suggests that in patients the sedative effects might be mixed up with suppression of sedative withdrawal symptoms, whereas patients were as sensitive as benzodiazepine-naive controls for the effects of an additional dosage on the ASR. Neither 10 nor 30 mg oxazepam challenge affected the reaction time tasks in patients, whereas controls show a dose-related impairment. The memory impairing effects, however, did not differ significantly between patients and controls. In contrast to controls, patients could not discriminate between a 10- and 30-mg dosage as assessed by visual analogue scales and the STAI-DY-1, which might indicate a placebo effect in the 10-mg challenge in patients. We conclude that additional dosages of oxazepam still exert pronounced effects after daily use for more than 10 years.

Deciphering the Sensitivity and Specificity of the Implantable Doppler in Free Flap Monitoring.

PubMed

Chang, Edward I; Ibrahim, Amir; Zhang, Hong; Liu, Jun; Nguyen, Alexander T; Reece, Gregory P; Yu, Peirong

2015-11-19

The efficacy of implantable Dopplers (iD) remains an area of considerable debate. Our study aims to decipher the sensitivity and specificity of the iD for free flap monitoring. A retrospective review of all free flaps with an iD was performed between 2000-2012. A Cook-Swartz iD was used in 439 patients (head and neck: n=364, breast: n=53, and extremity: n=22), and demonstrated equivalent sensitivity and specificity between flap types. The overall sensitivity and specificity was 77.8% and 88.4% respectively. The iD was placed on the artery in 267 patients, the vein in 101 patients, and 71 patients had a Doppler placed on both the artery and vein with significantly greater specificity for monitoring the artery than the vein (94.2% vs. 74.0%, p<0.001), but no difference between monitoring both the artery and the vein. Venous monitoring was significantly associated with a takeback (OR: 3.17, CI: 1.70-5.91; p=0.0003). There were 284 flaps that also had a monitoring segment in addition to the iD which significantly increased specificity for microvascular complications (OR: 17.71, CI: 3.39-92.23; p=0.0006). The specificity (90.5% vs. 84.8%) and sensitivity (80.0% vs. 66.7%) were significantly higher for clinically monitored flaps. The takeback rate was 13.0%, with positive findings in 59.6%, and 5.2% total flap loss. The use of implantable Dopplers has high sensitivity and specificity for buried free flap despite positive findings in less than 60% of take backs. Monitoring the artery is preferable to the vein, but clinical exam remains the gold standard for flap monitoring.

Deciphering the Sensitivity and Specificity of the Implantable Doppler Probe in Free Flap Monitoring.

PubMed

Chang, Edward I; Ibrahim, Amir; Zhang, Hong; Liu, Jun; Nguyen, Alexander T; Reece, Gregory P; Yu, Peirong

2016-03-01

The efficacy of implantable Doppler probes remains an area of considerable debate. This study aims to decipher its sensitivity and specificity for free flap monitoring. A retrospective review of all free flaps with an implantable Doppler probe was performed between 2000 and 2012. A Cook-Swartz implantable Doppler probe was used in 439 patients (head and neck, n = 364; breast, n = 53; extremity, n = 22), and demonstrated equivalent sensitivity and specificity between flap types. The overall sensitivity and specificity were 77.8 percent and 88.4 percent, respectively. The artery was monitored in 267 patients, compared to venous monitoring in 101 patients, and in 71 patients both the artery and vein were monitored. Arterial monitoring had significantly greater specificity than venous monitoring, (94.2 percent versus 74.0 percent; p < 0.001), but no benefit was found in monitoring both the artery and the vein. Venous monitoring was significantly associated with reoperation (OR, 3.17; 95 percent CI, 1.70 to 5.91; p = 0.0003). There were 284 flaps that had a monitoring segment in addition to the implantable Doppler probe that significantly increased overall specificity for microvascular complications (OR, 17.71; 95 percent CI, 3.39 to 92.23; p = 0.0006). The specificity (90.5 percent versus 84.8 percent) and sensitivity (80.0 percent versus 66.7 percent) were significantly higher for clinically monitored flaps. The take-back rate was 13.0 percent, with positive findings in 59.6 percent, and 5.2 percent total flap loss. The use of implantable Doppler probes has high sensitivity and specificity for buried free flaps despite positive findings in less than 60 percent of take-backs. Monitoring the artery is recommended, but clinical examination remains the gold standard for flap monitoring. Diagnostic, IV.

Evaluation of the articular cartilage of the knee joint: value of adding a T2 mapping sequence to a routine MR imaging protocol.

PubMed

Kijowski, Richard; Blankenbaker, Donna G; Munoz Del Rio, Alejandro; Baer, Geoffrey S; Graf, Ben K

2013-05-01

To determine whether the addition of a T2 mapping sequence to a routine magnetic resonance (MR) imaging protocol could improve diagnostic performance in the detection of surgically confirmed cartilage lesions within the knee joint at 3.0 T. This prospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The study group consisted of 150 patients (76 male and 74 female patients with an average age of 41.2 and 41.5 years, respectively) who underwent MR imaging and arthroscopy of the knee joint. MR imaging was performed at 3.0 T by using a routine protocol with the addition of a sagittal T2 mapping sequence. Images from all MR examinations were reviewed in consensus by two radiologists before surgery to determine the presence or absence of cartilage lesions on each articular surface, first by using the routine MR protocol alone and then by using the routine MR protocol with T2 maps. Each articular surface was then evaluated at arthroscopy. Generalized estimating equation models were used to compare the sensitivity and specificity of the routine MR imaging protocol with and without T2 maps in the detection of surgically confirmed cartilage lesions. The sensitivity and specificity in the detection of 351 cartilage lesions were 74.6% and 97.8%, respectively, for the routine MR protocol alone and 88.9% and 93.1% for the routine MR protocol with T2 maps. Differences in sensitivity and specificity were statistically significant (P < .001). The addition of T2 maps to the routine MR imaging protocol significantly improved the sensitivity in the detection of 24 areas of cartilage softening (from 4.2% to 62%, P < .001), 41 areas of cartilage fibrillation (from 20% to 66%, P < .001), and 96 superficial partial-thickness cartilage defects (from 71% to 88%, P = .004). The addition of a T2 mapping sequence to a routine MR protocol at 3.0 T improved sensitivity in the detection of cartilage lesions within the knee joint from 74.6% to 88.9%, with only a small reduction in specificity. The greatest improvement in sensitivity with use of the T2 maps was in the identification of early cartilage degeneration. © RSNA, 2013.

Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity

PubMed Central

Kråkenes, Jostein; Brauckhoff, Katrin; Haugland, Hans Kristian; Heinecke, Achim; Akslen, Lars A; Varhaug, Jan Erik; Brauckhoff, Michael

2015-01-01

Background Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131). Purpose To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT. Material and Methods Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard. Results Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%). Conclusion In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed. PMID:25770086

A Novel Extraction Method Combining Plasma with a Whole-Blood Fraction Shows Excellent Sensitivity and Reproducibility for Patients at High Risk for Invasive Aspergillosis

PubMed Central

Springer, Jan; Schloßnagel, Hannes; Heinz, Werner; Doedt, Thomas; Soeller, Rainer; Einsele, Hermann

2012-01-01

Diagnosis of invasive aspergillosis (IA) is still a major problem in routine clinical practice. Early diagnosis is essential for a good patient prognosis. PCR is a highly sensitive method for the detection of nucleic acids and could play an important role in improving the diagnosis of fungal infections. Therefore, a novel DNA extraction method, ultraclean production (UCP), was developed allowing purification of both cellular and cell-free circulating fungal DNA. In this prospective study we evaluated the commercially available UCP extraction system and compared it to an in-house system. Sixty-three patients at high risk for IA were screened twice weekly, and DNA extracted by both methods was cross-analyzed, in triplicate, by two different real-time PCR assays. The negative predictive values were high for all methods (94.3 to 100%), qualifying them as screening methods, but the sensitivity and diagnostic odds ratios were higher using the UCP extraction method. Sensitivity ranged from 33.3 to 66.7% using the in-house extracts to 100% using the UCP extraction method. Most of the unclassified patients showed no positive PCR results; however, single-positive PCR replicates were observed in some cases. These can bear clinical relevance but should be interpreted with additional clinical and laboratory data. The PCR assays from the UCP extracts showed greater reproducibility than the in-house method for probable IA patients. The standardized UCP extraction method yielded superior results, with regard to sensitivity and reproducibility, than the in-house method. This was independent of the PCR assay used to detect fungal DNA in the sample extracts. PMID:22593600

Familial Breast/Ovarian Cancer and BRCA1/2 Genetic Screening: The Role of Immunohistochemistry as an Additional Method in the Selection of Patients

PubMed Central

Vaz, Fátima H.; Machado, Patrícia M.; Brandão, Rita D.; Laranjeira, Cátia T.; Eugénio, Joana S.; Fernandes, Aires H.; André, Saudade P.

2007-01-01

Only 20–25% of families screened for BRCA1/2 mutations are found positive. Because only a positive result is informative, we studied the role of BRCA1/2 immunohistochemistry as an additional method for patient selection. From 53 high-risk-affected probands, 18 (34%) had available paraffin blocks of their tumors and were selected for this study. Mutation screening was done by conformation-sensitive gel electrophoresis and multiplex ligation-dependent probe amplification. For immunohistochemistry, 21 neoplastic specimens (15 breast carcinomas, 5 ovary neoplasms, and 1 rectal adenocarcinoma) were analyzed with BRCA1 (monoclonal antibody, Ab-1, oncogene) and BRCA2 (polyclonal antibody, Ab-2, oncogene) antibodies. Absence of the BRCA1 protein was confirmed in negative tumors by Western blotting. Seven patients were positive for BRCA1/2 mutations: 5 for BRCA1 and 2 for BRCA2. Four out of five positive patients had tumors negative for BRCA1 immunostaining, and the remaining 13 BRCA1-negative patients had positive BRCA1 immunostaining in all tumor samples. Sensitivity to predict for BRCA1 mutation carriers was 80%, and specificity was 100%, with a positive predictive value of 100% and a negative predictive value of 93%. This correlation was statistically significant (p=0.001). No correlation was observed for BRCA2. If larger studies confirm these results, high-risk patients with BRCA1-negative tumors should be screened first for this gene. PMID:17625228

Value for money? Array genomic hybridization for diagnostic testing for genetic causes of intellectual disability.

PubMed

Regier, Dean A; Friedman, Jan M; Marra, Carlo A

2010-05-14

Array genomic hybridization (AGH) provides a higher detection rate than does conventional cytogenetic testing when searching for chromosomal imbalance causing intellectual disability (ID). AGH is more costly than conventional cytogenetic testing, and it remains unclear whether AGH provides good value for money. Decision analytic modeling was used to evaluate the trade-off between costs, clinical effectiveness, and benefit of an AGH testing strategy compared to a conventional testing strategy. The trade-off between cost and effectiveness was expressed via the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis was performed via Monte Carlo simulation. The baseline AGH testing strategy led to an average cost increase of $217 (95% CI $172-$261) per patient and an additional 8.2 diagnoses in every 100 tested (0.082; 95% CI 0.044-0.119). The mean incremental cost per additional diagnosis was $2646 (95% CI $1619-$5296). Probabilistic sensitivity analysis demonstrated that there was a 95% probability that AGH would be cost effective if decision makers were willing to pay $4550 for an additional diagnosis. Our model suggests that using AGH instead of conventional karyotyping for most ID patients provides good value for money. Deterministic sensitivity analysis found that employing AGH after first-line cytogenetic testing had proven uninformative did not provide good value for money when compared to using AGH as first-line testing. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

EUS-FNA for suspected malignant biliary strictures after negative endoscopic transpapillary brush cytology and forceps biopsy.

PubMed

Ohshima, Yasuhiro; Yasuda, Ichiro; Kawakami, Hiroshi; Kuwatani, Masaki; Mukai, Tsuyoshi; Iwashita, Takuji; Doi, Shinpei; Nakashima, Masanori; Hirose, Yoshinobu; Asaka, Masahiro; Moriwaki, Hisataka

2011-07-01

Endoscopic transpapillary brush cytology and forceps biopsy are widely used for the pathological diagnosis of suspected malignant biliary strictures (MBS). However, the sensitivity of these methods remains insufficient, and it can be difficult to confirm the diagnosis. We aimed to evaluate the diagnostic ability of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and the impact of this technique on clinical management in patients with suspected MBS where endoscopic brush cytology and biopsy yielded negative results. This study included 225 consecutive patients with suspected MBS, who underwent endoscopic brush cytology and biopsy at our institutions. Negative results were obtained for these pathological tests in 75 patients, and EUS-FNA was performed in 22 of these patients. We retrospectively compared the EUS-FNA results with the final diagnosis and examined the influence of the EUS-FNA diagnosis on treatment selection. FNA specimens were successfully obtained in all patients, and the pathological results confirmed malignancy in 16 cases and predicted that the other 6 cases were benign. Of the 6 cases that were suspected to be benign, 3 patients were diagnosed with xanthogranulomatous cholecystitis by surgical pathology, and the remaining 3 patients were diagnosed with benign diseases at a follow-up after 12-18 months. Thus, the EUS-FNA-based diagnosis was proven correct for all the patients. In addition, the treatment strategy was altered as a result of the EUS-FNA results in the above 6 patients (27%). EUS-FNA is a sensitive and safe diagnostic modality for patients with suspected MBS and can be an additional option in cases where endoscopic brush cytology and biopsy have produced negative results.

AMP-activated Protein Kinase (AMPK): Does This Master Regulator of Cellular Energy State Distinguish Insulin Sensitive from Insulin Resistant Obesity?

PubMed Central

Valentine, Rudy J.; Ruderman, Neil B.

2014-01-01

Although a correlation exists between obesity and insulin resistance, roughly 25 % of obese individuals are insulin sensitive. AMP-activated protein kinase (AMPK) is a cellular energy sensor that among its many actions, integrates diverse physiological signals to restore energy balance. In addition, in many situations it also increases insulin sensitivity. In this context, AMPK activity is decreased in very obese individuals undergoing bariatric surgery who are insulin resistant compared to equally obese patients who are insulin sensitive. In this review, we will both explore what distinguishes these individuals, and evaluate the evidence that diminished AMPK is associated with insulin resistance and metabolic syndrome-associated disorders in other circumstances. PMID:24891985

Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients.

PubMed

Fillaux, Judith; Brémont, François; Murris, Marléne; Cassaing, Sophie; Rittié, Jean-Luc; Tétu, Laurent; Segonds, Christine; Abbal, Michel; Bieth, Eric; Berry, Antoine; Pipy, Bernard; Magnaval, Jean-François

2012-11-01

Cystic fibrosis (CF) patients presenting with persistent carriage of, or sensitization to, Aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to assess Aspergillus-related status modulating the forced expiratory volume in 1 s (FEV₁) of CF patients. From 1995 to 2007, 251 patients were evaluated. Demographic data, cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations, body mass index, and FEV(1) were recorded. The presence of A. fumigatus and Pseudomonas aeruginosa in sputum and the levels of A. fumigatus precipitin, total IgE (t-IgE), and specific anti-A. fumigatus IgE (Af-IgE) were determined. Patients were divided into 3 groups: (1) ABPA: A. fumigatus precipitin ≥3 lines, Af-IgE > 0.35 IU/ml, and t-IgE ≥500 IU/ml; (2) sensitization: Af-IgE > 0.35 IU/ml but t-IgE < 500 IU/ml; and (3) persistent carriage: Af-IgE ≤ 0.35 IU/ml with either an A. fumigatus persistent positive culture or an A. fumigatus precipitin ≥3 lines, provided this serological finding had been found associated with at least 1 A. fumigatus-positive culture. The remaining patients represented the control group. A multivariate analysis was carried out with FEV(1) as the outcome variable. ABPA, sensitization, and persistent carriage were significantly associated with a larger decline in FEV₁ compared with the control group, with odds ratios of 15.9, 14.9, and 10.7, respectively. This association was independent of other associated factors (P. aeruginosa transient detection, age, being underweight, and low FEV₁ at baseline). In addition to ABPA, sensitization and persistent carriage appear to have an impact on pulmonary function in CF patients.

Sensitivity of self-reported opioid use in case-control studies: Healthy individuals versus hospitalized patients.

PubMed

Rashidian, Hamideh; Hadji, Maryam; Marzban, Maryam; Gholipour, Mahin; Rahimi-Movaghar, Afarin; Kamangar, Farin; Malekzadeh, Reza; Weiderpass, Elisabete; Rezaianzadeh, Abbas; Moradi, Abdolvahab; Babhadi-Ashar, Nima; Ghiasvand, Reza; Khavari-Daneshvar, Hossein; Haghdoost, Ali Akbar; Zendehdel, Kazem

2017-01-01

Several case-control studies have shown associations between the risk of different cancers and self-reported opium use. Inquiring into relatively sensitive issues, such as the history of drug use, is usually prone to information bias. However, in order to justify the findings of these types of studies, we have to quantify the level of such a negative bias. In current study, we aimed to evaluate sensitivity of self-reported opioid use and suggest suitable types of control groups for case-control studies on opioid use and the risk of cancer. In order to compare the validity of the self-reported opioid use, we cross-validated the response of two groups of subjects 1) 178 hospitalized patients and 2) 186 healthy individuals with the results of their tests using urine rapid drug screen (URDS) and thin layer chromatography (TLC). The questioners were asked by trained interviewers to maximize the validity of responses; healthy individuals were selected from the companions of patients in hospitals. Self-reported regular opioid use was 36.5% in hospitalized patients 19.3% in healthy individuals (p-value> 0.001).The reported frequencies of opioid use in the past 72 hours were 21.4% and 11.8% in hospitalized patients and healthy individuals respectively. Comparing their responses with the results of urine tests showed a sensitivity of 77% and 69% among hospitalized patients and healthy individuals for self-reports (p-value = 0.4). Having corrected based on the mentioned sensitivities; the frequency of opioid regular use was 47% and 28% in hospitalized patients and healthy individuals, respectively. Regular opioid use among hospitalized patients was significantly higher than in healthy individuals (p-value> 0.001). Our findings showed that the level of opioid use under-reporting in hospitalized patients and healthy individuals was considerable but comparable. In addition, the frequency of regular opioid use among hospitalized patients was significantly higher than that in the general population. Altogether, it seems that, without corrections for these differences and biases, the results of many studies including case-control studies on opioid use might distort findings substantially.

Sensitivity of self-reported opioid use in case-control studies: Healthy individuals versus hospitalized patients

PubMed Central

Rashidian, Hamideh; Hadji, Maryam; Marzban, Maryam; Gholipour, Mahin; Rahimi-Movaghar, Afarin; Kamangar, Farin; Malekzadeh, Reza; Weiderpass, Elisabete; Rezaianzadeh, Abbas; Moradi, Abdolvahab; Babhadi-Ashar, Nima; Ghiasvand, Reza; Khavari-Daneshvar, Hossein; Haghdoost, Ali Akbar; Zendehdel, Kazem

2017-01-01

Background Several case-control studies have shown associations between the risk of different cancers and self-reported opium use. Inquiring into relatively sensitive issues, such as the history of drug use, is usually prone to information bias. However, in order to justify the findings of these types of studies, we have to quantify the level of such a negative bias. In current study, we aimed to evaluate sensitivity of self-reported opioid use and suggest suitable types of control groups for case-control studies on opioid use and the risk of cancer. Methods In order to compare the validity of the self-reported opioid use, we cross-validated the response of two groups of subjects 1) 178 hospitalized patients and 2) 186 healthy individuals with the results of their tests using urine rapid drug screen (URDS) and thin layer chromatography (TLC). The questioners were asked by trained interviewers to maximize the validity of responses; healthy individuals were selected from the companions of patients in hospitals. Results Self-reported regular opioid use was 36.5% in hospitalized patients 19.3% in healthy individuals (p-value> 0.001).The reported frequencies of opioid use in the past 72 hours were 21.4% and 11.8% in hospitalized patients and healthy individuals respectively. Comparing their responses with the results of urine tests showed a sensitivity of 77% and 69% among hospitalized patients and healthy individuals for self-reports (p-value = 0.4). Having corrected based on the mentioned sensitivities; the frequency of opioid regular use was 47% and 28% in hospitalized patients and healthy individuals, respectively. Regular opioid use among hospitalized patients was significantly higher than in healthy individuals (p-value> 0.001). Conclusion Our findings showed that the level of opioid use under-reporting in hospitalized patients and healthy individuals was considerable but comparable. In addition, the frequency of regular opioid use among hospitalized patients was significantly higher than that in the general population. Altogether, it seems that, without corrections for these differences and biases, the results of many studies including case-control studies on opioid use might distort findings substantially. PMID:28854228

RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia.

PubMed

Abraham, Ajay; Varatharajan, Savitha; Karathedath, Sreeja; Philip, Chepsy; Lakshmi, Kavitha M; Jayavelu, Ashok Kumar; Mohanan, Ezhilpavai; Janet, Nancy Beryl; Srivastava, Vivi M; Shaji, Ramachandran V; Zhang, Wei; Abraham, Aby; Viswabandya, Auro; George, Biju; Chandy, Mammen; Srivastava, Alok; Mathews, Vikram; Balasubramanian, Poonkuzhali

2015-07-01

Variation in terms of outcome and toxic side effects of treatment exists among acute myeloid leukemia (AML) patients on chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Candidate Ara-C metabolizing gene expression in primary AML cells is proposed to account for this variation. Ex vivo Ara-C sensitivity was determined in primary AML samples using MTT assay. mRNA expression of candidate Ara-C metabolizing genes were evaluated by RQPCR analysis. Global gene expression profiling was carried out for identifying differentially expressed genes between exvivo Ara-C sensitive and resistant samples. Wide interindividual variations in ex vivo Ara-C cytotoxicity were observed among samples from patients with AML and were stratified into sensitive, intermediately sensitive and resistant, based on IC50 values obtained by MTT assay. RNA expression of deoxycytidine kinase (DCK), human equilibrative nucleoside transporter-1 (ENT1) and ribonucleotide reductase M1 (RRM1) were significantly higher and cytidine deaminase (CDA) was significantly lower in ex vivo Ara-C sensitive samples. Higher DCK and RRM1 expression in AML patient's blast correlated with better DFS. Ara-C resistance index (RI), a mathematically derived quotient was proposed based on candidate gene expression pattern. Ara-C ex vivo sensitive samples were found to have significantly lower RI compared with resistant as well as samples from patients presenting with relapse. Patients with low RI supposedly highly sensitive to Ara-C were found to have higher incidence of induction death (p = 0.002; RR: 4.35 [95% CI: 1.69-11.22]). Global gene expression profiling undertaken to find out additional contributors of Ara-C resistance identified many apoptosis as well as metabolic pathway genes to be differentially expressed between Ara-C resistant and sensitive samples. This study highlights the importance of evaluating expression of candidate Ara-C metabolizing genes in predicting ex vivo drug response as well as treatment outcome. RI could be a predictor of ex vivo Ara-C response irrespective of cytogenetic and molecular risk groups and a potential biomarker for AML treatment outcome and toxicity. Original submitted 22 December 2014; Revision submitted 9 April 2015.

The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity.

PubMed

Nyfeler, B; Pichler, W J

1997-02-01

The diagnosis of a drug allergy is mainly based upon a very detailed history and the clinical findings. In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug. One of the in vitro tests is the lymphocyte transformation test (LTT), which can reveal a sensitization of T-cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain drug. To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drug allergy in whom a LTT was performed were retrospectively analysed. Based on the history and provocation tests, the probability (P) of a drug allergy was estimated to be > 0.9, 0.5-0.9, 0.1-0.5 or < 0.1, and was put in relation to a positive or negative LTT. Seventy-eight of 100 patients with a very likely drug allergy (P > 0.9) had a positive LTT, which indicates a sensitivity of 78%. If allergies to betalactam-antibiotics were analysed separately, the sensitivity was 74.4%. Fifteen of 102 patients where a classical drug allergy could be excluded (P < 0.1), had nevertheless a positive LTT (specificity thus 85%). The majority of these cases were classified as so-called pseudo-allergic reaction to NSAIDs. Patients with a clear history and clinical findings for a cotrimoxazole-related allergy, all had a positive LTT (6/6), and in patients who reacted to drugs containing proteins, sensitization could be demonstrated as well (i.e. hen's egg lysozyme, 7/7). In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%). Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drug allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drug allergies, able to support the diagnosis of a drug allergy and to pinpoint the relevant drug.

Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective analysis.

PubMed

Guarnotta, Valentina; Ciresi, Alessandro; Pillitteri, Giuseppe; Giordano, Carla

2018-05-01

Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement of anthropometric and metabolic parameters. The aim of the study was to evaluate the effects of DR-HC on insulin secretion and sensitivity and cardiometabolic risk, indirectly expressed by the visceral adiposity index (VAI). Retrospective analysis of 49 patients, 13 with primary and 36 with secondary adrenal insufficiency (AI), respectively, on conventional glucocorticoid treatment at baseline and switched to DR-HC for 36 months. Overall, 24 patients had AI-pre-diabetes (impaired fasting glucose, impaired glucose tolerance and the combination), and 25 had AI-normal glucose tolerance (NGT). Clinical and metabolic parameters, including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia, AUC 2 h insulinaemia , oral disposition index [Dio] and ISI-Matsuda), were evaluated. In patients with AI-NGT and AI-prediabetes, a significant decrease in BMI (P = .017 and P < .001), waist circumference (P = .008 and P < .001), HbA1c (P = .034 and P = .001) and a significant increase in HDL-C (P = .036 and P = .043) was, respectively, observed. In addition, in prediabetic patients, only we found a significant decrease in insulinaemia (P = .014), AUC 2 h insulinaemia (P = .038) and VAI (P = .001), in concomitance with a significant increase in DIo (P = .041) and ISI-Matsuda (P = .038). Long-term DR-HC therapy is associated with an improvement in insulin secretion and sensitivity in patients with prediabetes. However, all patients appear to benefit from the treatment in terms of improvement of metabolic and anthropometric parameters. Larger studies are required to confirm our preliminary data. © 2018 John Wiley & Sons Ltd.

Pharyngeal chemosensitivity in patients with obstructive sleep apnea and healthy subjects.

PubMed

Heiser, Clemens; Zimmermann, Ingo; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A

2013-09-01

Signs of pharyngeal neurodegeneration have been detected in patients with obstructive sleep apnea (OSA). Along with this neurodegeneration, a decreased pharyngeal sensitivity to mechanical stimulation has been described. The decreased sensitivity may play a role in the pathophysiology of this disease. The aim of the study was to investigate the chemosensitivity of the pharyngeal mucosa in patients with OSA compared with controls. Healthy controls and patients with OSA (age: 30-60 years) were included. Testing of oropharyngeal chemosensitivity was performed with subjective intensity ratings of capsaicin (SIR, visual analogue scale 0-10), air puffs (presented with an olfactometer), and stimulation with CO2 at the posterior pharyngeal wall. A 2-point discrimination test at the soft palate, an intensity rating of capsaicin at the tongue, and a nasal lateralization test were performed. Twenty-six patients with OSA and 18 healthy controls were included. No differences were detected in the SIR of capsaicin at the tongue or in the nasal lateralization test. At the pharynx, a decreased sensitivity to capsaicin (OSA: 6.8 ± 2.3; healthy control: 8.6 ± 1.3), air puffs (OSA: 2.8 ± 1.9; healthy control: 4.2 ± 1.6), and stimulation with CO2 (OSA: 1.5 ± 1.7; healthy control: 2.8 ± 1.8) were demonstrated in patients with OSA (all P < 0.05). Two-point discrimination at the soft palate was reduced with statistical significance in the OSA group (OSA: 11.5 ± 5.4 mm; healthy control: 5.0 ± 2.4 mm). The results suggest reduced pharyngeal chemosensitivity in OSA patients in addition to the reduced mechanical pharyngeal sensitivity shown with 2-point discrimination. This demonstrates peripheral neurodegeneration in the context of this disease.

Diagnostic Accuracy of Full-Body Linear X-Ray Scanning in Multiple Trauma Patients in Comparison to Computed Tomography.

PubMed

Jöres, A P W; Heverhagen, J T; Bonél, H; Exadaktylos, A; Klink, T

2016-02-01

The purpose of this study was to evaluate the diagnostic accuracy of full-body linear X-ray scanning (LS) in multiple trauma patients in comparison to 128-multislice computed tomography (MSCT). 106 multiple trauma patients (female: 33; male: 73) were retrospectively included in this study. All patients underwent LS of the whole body, including extremities, and MSCT covering the neck, thorax, abdomen, and pelvis. The diagnostic accuracy of LS for the detection of fractures of the truncal skeleton and pneumothoraces was evaluated in comparison to MSCT by two observers in consensus. Extremity fractures detected by LS were documented. The overall sensitivity of LS was 49.2 %, the specificity was 93.3 %, the positive predictive value was 91 %, and the negative predictive value was 57.5 %. The overall sensitivity for vertebral fractures was 16.7 %, and the specificity was 100 %. The sensitivity was 48.7 % and the specificity 98.2 % for all other fractures. Pneumothoraces were detected in 12 patients by CT, but not by LS. 40 extremity fractures were detected by LS, of which 4 fractures were dislocated, and 2 were fully covered by MSCT. The diagnostic accuracy of LS is limited in the evaluation of acute trauma of the truncal skeleton. LS allows fast whole-body X-ray imaging, and may be valuable for detecting extremity fractures in trauma patients in addition to MSCT.  The overall sensitivity of LS for truncal skeleton injuries in multiple-trauma patients was < 50 %. The diagnostic reference standard MSCT is the preferred and reliable imaging modality. LS may be valuable for quick detection of extremity fractures. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of an Epigenetic Profile for the Detection of Bladder Cancer in Patients with Hematuria.

PubMed

van Kessel, Kim E M; Van Neste, Leander; Lurkin, Irene; Zwarthoff, Ellen C; Van Criekinge, Wim

2016-03-01

Many patients enter the care cycle with gross or microscopic hematuria and undergo cystoscopy to rule out bladder cancer. Sensitivity of this invasive examination is limited, leaving many patients at risk for undetected cancer. To improve current clinical practice more sensitive and noninvasive screening methods should be applied. A total of 154 urine samples were collected from patients with hematuria, including 80 without and 74 with bladder cancer. DNA from cells in the urine was epigenetically profiled using 2 independent assays. Methylation specific polymerase chain reaction was performed on TWIST1. SNaPshot™ methylation analysis was done for different loci of OTX1 and ONECUT2. Additionally all samples were analyzed for mutation status of TERT (telomerase reverse transcriptase), PIK3CA, FGFR3 (fibroblast growth factor receptor 3), HRAS, KRAS and NRAS. The combination of TWIST1, ONECUT2 (2 loci) and OTX1 resulted in the best overall performing panel. Logistic regression analysis on these methylation markers, mutation status of FGFR3, TERT and HRAS, and patient age resulted in an accurate model with 97% sensitivity, 83% specificity and an AUC of 0.93 (95% CI 0.88-0.98). Internal validation led to an optimism corrected AUC of 0.92. With an estimated bladder cancer prevalence of 5% to 10% in a hematuria cohort the assay resulted in a 99.6% to 99.9% negative predictive value. Epigenetic profiling using TWIST1, ONECUT2 and OTX1 results in a high sensitivity and specificity. Accurate risk prediction might result in less extensive and invasive examination of patients at low risk, thereby reducing unnecessary patient burden and health care costs. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chlorhexidine allergy in four specialist allergy centres in the United Kingdom, 2009–13: clinical features and diagnostic tests

PubMed Central

Helbert, M.; Sargur, R.; Swallow, K.; Harper, N.; Garcez, T.; Savic, S.; Savic, L.; Eren, E.

2017-01-01

Summary We describe an observational survey of diagnostic pathways in 104 patients attending four specialist allergy clinics in the United Kingdom following perioperative hypersensitivity reactions to chlorhexidine reactions. The majority were life‐threatening. Men undergoing urological or cardiothoracic surgery predominated. Skin prick testing and specific immunoglobulin (sIg)E testing were the most common tests used for diagnosis. Fifty‐three per cent of diagnoses were made on the basis of a single positive test. Where multiple tests were performed the sensitivity of intradermal, basophil activation and skin prick testing was 68% (50–86%), 50% (10–90%) and 35% (17–55%), respectively. Seven per cent were negative on screening tests initially, and 12 cases were only positive for a single test despite multiple testing. Intradermal tests appeared most sensitive in this context. Additional sensitization to other substances used perioperatively, particularly neuromuscular blocking agents (NMBA), was found in 28 patients, emphasizing the need to test for possible allergy to all drugs to which the patient was exposed even where chlorhexidine is positive. PMID:28194756

Pain Processing after Social Exclusion and Its Relation to Rejection Sensitivity in Borderline Personality Disorder

PubMed Central

Bungert, Melanie; Koppe, Georgia; Niedtfeld, Inga; Vollstädt-Klein, Sabine; Schmahl, Christian

2015-01-01

Objective There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that “social pain,” as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity. Method Twenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity. Results Higher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala. Discussion Despite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls. PMID:26241850

Trial Comparing a Combined Regimen of Amikacin and Ciprofloxacin to Ciprofloxacin Alone as Transrectal Prostate Biopsy Prophylaxis in the Era of High Fluoroquinolone-Resistant Rectal Flora.

PubMed

Son, Kyung Chul; Chung, Ho Seok; Jung, Seung Il; Kim, Myung Soo; Hwang, Eu Chang; Kim, Jin Woong; Kwon, Dong Deuk

2018-04-09

To investigate whether addition of amikacin to fluoroquinolone (FQ) antimicrobial prophylaxis reduces infections after transrectal ultrasound-guided prostate biopsy (TRUSPB). A total of 503 patients undergoing rectal swab were divided into three groups. Patients with FQ-sensitive rectal flora (group 1, n = 248) were administered ciprofloxacin before TRUSPB, and patients with FQ-resistant rectal flora were either administered ciprofloxacin (group 2, n = 97) or amikacin and ciprofloxacin (group 3, n = 158) before TRUSPB. Based on the rectal swab, FQ resistance was 54.9%, and extended-spectrum β-lactamase (ESBL) positivity was 17.2%. The incidence of infectious complication in group 1 was 1.6%. Groups 2 and 3, with FQ-resistant rectal flora, tended to have increased infectious complications (5.2% and 4.4%, respectively) but the difference between those results is not statistically significant. The most common pathogens of infectious complications in patients with FQ-resistant rectal flora were FQ-resistant and ESBL-producing Escherichia coli. E. coli pathogens isolated in Group 3 were amikacin-susceptible species. The operation history and ESBL positivity of rectal flora increased the incidence of infectious complications (odds ratio [OR] = 3.68; P = 0.035 and OR = 4.02; P = 0.008, respectively). DM and antibiotics exposure were risk factors for FQ resistance (OR = 2.19; P = 0.002) and ESBL positivity of rectal flora (OR = 2.96; P = 0.005), respectively. Addition of amikacin to ciprofloxacin prophylaxis could not reduce infectious complications in patients with FQ-resistant rectal flora. Despite the amikacin sensitivity of infectious complications, single-dose amikacin addition to ciprofloxacin prophylaxis has limitations. © 2018 The Korean Academy of Medical Sciences.

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

PubMed

Lenz, Max; Krychtiuk, Konstantin A; Goliasch, Georg; Distelmaier, Klaus; Wojta, Johann; Heinz, Gottfried; Speidl, Walter S

2018-04-01

Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors ( p<0.01). An elevation of both markers exhibited an additive effect on mortality, as those with both NT-proBNP and TnT levels above the median had a 30-day mortality rate of 51.0%, while those with both markers below the median had a 16.7% mortality rate (hazard ratio 3.7). These findings were independent of demographic and clinical parameters ( p<0.05). Our findings regarding the individual predictive properties of NT-proBNP and TnT are in line with literature. However, we were able to highlight that they exhibit additive prognostic potential which exceeds their individual value. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Cost-effectiveness analysis of implants versus autologous perforator flaps using the BREAST-Q.

PubMed

Matros, Evan; Albornoz, Claudia R; Razdan, Shantanu N; Mehrara, Babak J; Macadam, Sheina A; Ro, Teresa; McCarthy, Colleen M; Disa, Joseph J; Cordeiro, Peter G; Pusic, Andrea L

2015-04-01

Reimbursement has been recognized as a physician barrier to autologous reconstruction. Autologous reconstructions are more expensive than prosthetic reconstructions, but provide greater health-related quality of life. The authors' hypothesis is that autologous tissue reconstructions are cost-effective compared with prosthetic techniques when considering health-related quality of life and patient satisfaction. A cost-effectiveness analysis from the payer perspective, including patient input, was performed for unilateral and bilateral reconstructions with deep inferior epigastric perforator (DIEP) flaps and implants. The effectiveness measure was derived using the BREAST-Q and interpreted as the cost for obtaining 1 year of perfect breast health-related quality-adjusted life-year. Costs were obtained from the 2010 Nationwide Inpatient Sample. The incremental cost-effectiveness ratio was generated. A sensitivity analysis for age and stage at diagnosis was performed. BREAST-Q scores from 309 patients with implants and 217 DIEP flap reconstructions were included. The additional cost for obtaining 1 year of perfect breast-related health for a unilateral DIEP flap compared with implant reconstruction was $11,941. For bilateral DIEP flaps compared with implant reconstructions, the cost for an additional breast health-related quality-adjusted life-year was $28,017. The sensitivity analysis demonstrated that the cost for an additional breast health-related quality-adjusted life-year for DIEP flaps compared with implants was less for younger patients and earlier stage breast cancer. DIEP flaps are cost-effective compared with implants, especially for unilateral reconstructions. Cost-effectiveness of autologous techniques is maximized in women with longer life expectancy. Patient-reported outcomes findings can be incorporated into cost-effectiveness analyses to demonstrate the relative value of reconstructive procedures.

Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung

Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitoticmore » drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.« less

The additional lateralizing and localizing value of the postictal EEG in frontal lobe epilepsy.

PubMed

Whitehead, Kimberley; Gollwitzer, Stephanie; Millward, Helen; Wehner, Tim; Scott, Catherine; Diehl, Beate

2016-03-01

The aim of this study was to describe the additional lateralizing and localizing value of the postictal EEG in frontal lobe epilepsy (FLE). The ictal EEG in FLE is frequently challenging to localize. We identified patients investigated for epilepsy surgery with unilateral FLE based on consistent semiology, a clear lesion and/or with frontal onset on intracranial EEG. A one hour section of postictal EEG was analyzed by two raters for new or activated EEG features and it was assessed whether these features offered additional information when compared to the ictal EEG. Postictal features assessed included asymmetrical return of the posterior dominant rhythm and potentiated lateralized or regional frontal slowing, spikes or sharp waves. Thirty-eight patients were included who had a combined total of ninety-six seizures. 47/96 (49%) postictal periods contained correctly lateralizing or localizing information. The sensitivity for asymmetrical return of the posterior dominant rhythm was 24%. The sensitivity for regional frontal slow and frontal spikes was 23% and 20% respectively. Further analysis showed that in 14/38 (39%) patients, at least one seizure with an unhelpful ictal EEG was followed by postictal EEG features that added new localizing or lateralizing information. A subgroup of 11 patients who were ⩾1 year seizure-free (ILAE class 1) and thus classified as having a 'gold-standard' FLE diagnosis were analyzed separately and it was found that 14/30 of their seizures (47%) had extra postictal information. The new postictal information was always concordant with the ultimate diagnosis, except for asymmetric postictal return of background activity ipsilateral to the epileptogenic zone in three patients. This study shows that a close examination of the postictal EEG can offer additional information which can contribute to the identification of a potentially resectable epileptogenic zone. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Prosody impairment and associated affective and behavioral disturbances in Alzheimer's disease.

PubMed

Roberts, V J; Ingram, S M; Lamar, M; Green, R C

1996-12-01

We examined the ability to produce, repeat, and comprehend emotional prosody in 20 patients with Alzheimer's disease (AD) and in 11 elderly normal control subjects. In addition, caregivers of AD patients completed affective and behavioral measures with reference to the patient. Relative to control subjects, comprehension of emotional prosody was marginally impaired in mildly demented AD patients, whereas production, comprehension, and repetition of emotional prosody were significantly impaired in moderately demented AD patients. The moderately demented patients performed significantly poorer than the mildly demented patients on the production and repetition tasks. In contrast, there was no significance difference between the two groups on the prosody comprehension task. Additional analyses revealed an inverse relationship between the ability to correctly produce and repeat emotional prosody and the frequency of agitated behaviors and depressive symptomatology in moderately demented patients. This latter findings suggests that the inability to communicate emotional message is associated with disturbances in mood and behavior in AD patients. Implications for the management of disruptive behavior in agitated and aprosodic AD patients include the development of caregiver sensitivity to unexpressed emotion and caregiver assistance with emotional expression.

Magnetoencephalography for the Detection of Intervention Effects of a Specific Nutrient Combination in Patients with Mild Alzheimer’s Disease: Results from an Exploratory Double-Blind, Randomized, Controlled Study

PubMed Central

van Straaten, Elisabeth C. W.; de Waal, Hanneke; Lansbergen, Marieke M.; Scheltens, Philip; Maestu, Fernando; Nowak, Rafal; Hillebrand, Arjan; Stam, Cornelis J.

2016-01-01

Synaptic loss is an early pathological finding in Alzheimer’s disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn® Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity, and networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity, and graph theoretical aspects of MEG from the exploratory 24-week, double-blind, randomized, controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug naïve patients with mild AD were compared between a test group (n = 27), receiving Souvenaid, and a control group (n = 28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination. Peak frequencies of MEG were compared with EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared with EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further. PMID:27799918

Magnetoencephalography for the Detection of Intervention Effects of a Specific Nutrient Combination in Patients with Mild Alzheimer's Disease: Results from an Exploratory Double-Blind, Randomized, Controlled Study.

PubMed

van Straaten, Elisabeth C W; de Waal, Hanneke; Lansbergen, Marieke M; Scheltens, Philip; Maestu, Fernando; Nowak, Rafal; Hillebrand, Arjan; Stam, Cornelis J

2016-01-01

Synaptic loss is an early pathological finding in Alzheimer's disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn ® Connect, which is designed to enhance synapse formation and function. Here, we explore the value of MEG, with higher spatial resolution than EEG, in identifying intervention effects of the nutrient combination by comparing MEG spectral measures, functional connectivity, and networks between an intervention and a control group. Quantitative markers describing spectral properties, functional connectivity, and graph theoretical aspects of MEG from the exploratory 24-week, double-blind, randomized, controlled Souvenir II MEG sub-study (NTR1975, http://www.trialregister.nl) in drug naïve patients with mild AD were compared between a test group ( n  = 27), receiving Souvenaid, and a control group ( n  = 28), receiving an isocaloric control product. The groups were unbalanced at screening with respect to Mini-Mental State Examination. Peak frequencies of MEG were compared with EEG peak frequencies, recorded in the same patients at similar time points, were compared with respect to sensitivity to intervention effects. No consistent statistically significant intervention effects were detected. In addition, we found no difference in sensitivity between MEG and EEG peak frequency. This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity, possibly due to small sample size and unbalanced study groups. We found no indication that the difference could be attributed to a lack of sensitivity of MEG compared with EEG. MEG in randomized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further.

Healthcare expenditures and patient satisfaction: cost and quality from the consumer's perspective in the US.

PubMed

Fu, Alex Z; Wang, Nan

2008-05-01

Both cost and quality of healthcare are major concerns in the United States. Using patient satisfaction as a quality indicator, we seek to identify the relationship between healthcare cost and quality from the perspective of the community-dwelling population in the United States. We examined a nationally representative sample of 13,980 adults (age >or= 18 years) in the 2003 Medical Expenditure Panel Survey (MEPS). Given the idiosyncrasies of the cost data distribution, a recently developed extended estimating equation (EEE) model was employed to identify the relationship between patient satisfaction and healthcare expenditure, after controlling for individual demographic covariates, co-morbidity profile, and functional and activity limitations. A series of sensitivity analyses were conducted, in addition, to verify the identified relationship. All statistics were adjusted using the proper sampling weight from the MEPS data. Average annual healthcare expenditures for 2003 ranged between $3923 and $6073 when grouped by patient satisfaction ratings with a mean value $4779 for all individuals who rated perceived satisfaction of their healthcare. We found that there is no statistically significant relationship between patient satisfaction and total healthcare expenditure (p = 0.60) and a non-monotonic relationship is not identified either. All sensitivity analyses results revealed a lack of relationship between patient satisfaction and healthcare expenditures. Patient satisfaction might not reflect the quality of healthcare from an objective clinical standpoint. The identified cost-satisfaction relationship may not be extrapolated to other quality indicators. Due to the cross-sectional study design, no causal relationship could be inferred between patient satisfaction and healthcare expenditure. Our study adds to the literature on health care cost and quality by suggesting that the improvement of patient satisfaction may not require additional health care spending.

Labor characteristics and program costs of a successful diabetes disease management program.

PubMed

Rothman, Russell L; So, Stephanie A; Shin, John; Malone, Robert M; Bryant, Betsy; Dewalt, Darren A; Pignone, Michael P; Dittus, Robert S

2006-05-01

Organizations have invested in disease management programs to improve quality and to reduce costs, but little is known about the labor characteristics and the program costs necessary to implement a program. To examine the labor characteristics and the program costs of a successful diabetes disease management program. We performed a labor and cost analysis within a randomized controlled trial of a primary care-based diabetes disease management intervention. Participants included 217 patients with type 2 diabetes mellitus and poor glycemic control (glycosylated hemoglobin levels, > or = 8.0%). The intervention group received 12 months of intensive management from clinical pharmacists and a diabetes care coordinator who provided education, applied algorithms for medication management, and addressed barriers to care. The control group attended a single session led by pharmacists, followed by usual care from their primary providers. The process outcomes included the number of patient care-related activities, time spent per patient, and number of drug titrations or additions. The program costs were calculated based on Bureau of Labor Statistics wage data using a sensitivity analysis. The disease management team performed a mean of 4.0 care-related activities for a mean of 38.6 minutes per patient per month for intervention patients and performed a mean of 1.1 care-related activities for a mean of 10.7 minutes per patient per month for control patients (P < .001). Intervention patients had a median of 7 drug titrations or additions during the study. The incremental program cost for the intervention was 36.97 dollars (sensitivity analysis, 6.22 dollars-88.56 dollars) per patient per month. A successful diabetes disease management program can be integrated into an academic clinic for modest labor and cost.

Multicenter study of QuantiFERON®-TB Gold Plus in patients with active tuberculosis.

PubMed

Horne, D J; Jones, B E; Kamada, A; Fukushima, K; Winthrop, K L; Siegel, S A R; Kovacs, A; Anthony, P; Meekin, K A; Bhat, S; Kerndt, P; Chang, A; Koelle, D M; Narita, M

2018-06-01

QuantiFERON®-TB Gold Plus (QFT-Plus), recently approved for use in the United States, is a new-generation QuantiFERON assay that differs from its predecessors in that it uses an additional antigen tube containing peptides to elicit both CD8+ and CD4+ T-lymphocyte responses. To assess the sensitivity of QFT-Plus compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) in participants with active TB. Adult patients with active TB at three US and two Japanese sites were eligible for this study if they had culture-confirmed TB and were either untreated or had received 14 days of anti-tuberculosis treatment. We enrolled 164 participants, nine of whom had indeterminate results. Excluding indeterminate values, there were 150 QFT-GIT-positive results among 159 tests and 146 QFT-Plus-positive results among 157 tests, with sensitivities of respectively 94.3% (95%CI 89.5-97.4) and 93.02% (95%CI 87.8-96.5%). The estimated sensitivities for the two tests were not significantly different (P = 0.16). Overall test agreement was 98.7%, with a κ statistic of 0.89 (95%CI 0.75-1.00). In this multisite study, we found that QFT-Plus had similar sensitivity to QFT-GIT in adult patients with active TB.

Identification of dysphagia using the Toronto Bedside Swallowing Screening Test (TOR-BSST©): are 10 teaspoons of water necessary?

PubMed

Martino, Rosemary; Maki, Ellen; Diamant, Nicholas

2014-06-01

Dysphagia screening often includes administration of water. This study assessed the accuracy in identifying dysphagia with each additional teaspoon of water. The original research of the TOR-BSST(©) permitted this assessment. Trained nurses from acute and rehabilitation facilities prospectively administered the TOR-BSST(©) to 311 eligible stroke inpatients. A sensitivity analysis was conducted for the water item using 10 teaspoons plus a sip as the standard. The proportion of positive screenings was 59.2% in acute and 38.5% in rehabilitation. Of all four items that form the TOR-BSST(©), the water swallow item contributed to the identification of dysphagia in 42.7% in acute and 29.0% in rehabilitation patients. Across all patients, dysphagia accuracy was that five teaspoons resulted in a sensitivity of 79% (95% confidence interval [CI] = 70-86), eight a sensitivity of 92% (95% CI = 85-96) and 10 a sensitivity of 96% (95% CI = 90-99). Although a primary contributor, the water swallow item alone does not identify all patients with dysphagia. For a water swallow to accurately identify dysphagia, it is critical to administer 10 teaspoons. The TOR-BSST(©) water swallow item contributes largely to the total TOR-BSST(©)'s screening score and in making the test highly accurate and reliable.

Culture-sensitive psychotraumatology.

PubMed

Schnyder, Ulrich; Bryant, Richard A; Ehlers, Anke; Foa, Edna B; Hasan, Aram; Mwiti, Gladys; Kristensen, Christian H; Neuner, Frank; Oe, Misari; Yule, William

2016-01-01

Although there is some evidence of the posttraumatic stress disorder (PTSD) construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-)stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. In summary, culture-sensitive psychotraumatology means assuming an empathic and non-judgmental attitude, trying to understand each individual's cultural background.

Diagnostic accuracy and turnaround time of the Xpert MTB/RIF assay in routine clinical practice.

PubMed

Kwak, Nakwon; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Lee, Sang-Min; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Yim, Jae-Joon

2013-01-01

The Xpert MTB/RIF assay was introduced for timely and accurate detection of tuberculosis (TB). The aim of this study was to determine the diagnostic accuracy and turnaround time (TAT) of Xpert MTB/RIF assay in clinical practice in South Korea. We retrospectively reviewed the medical records of patients in whom Xpert MTB/RIF assay using sputum were requested. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of pulmonary tuberculosis (PTB) and detection of rifampicin resistance were calculated. In addition, TAT of Xpert MTB/RIF assay was compared with those of other tests. Total 681 patients in whom Xpert MTB/RIF assay was requested were included in the analysis. The sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay for diagnosis of PTB were 79.5% (124/156), 100.0% (505/505), 100.0% (124/124) and 94.0% (505/537), respectively. Those for the detection of rifampicin resistance were 57.1% (8/14), 100.0% (113/113), 100.0% (8/8) and 94.9% (113/119), respectively. The median TAT of Xpert MTB/RIF assay to the report of results and results confirmed by physicians in outpatient settings were 0 (0-1) and 6 (3-7) days, respectively. Median time to treatment after initial evaluation was 7 (4-9) days in patients with Xpert MTB/RIF assay, but was 21 (7-33.5) days in patients without Xpert MTB/RIF assay. Xpert MTB/RIF assay showed acceptable sensitivity and excellent specificity for the diagnosis of PTB and detection of rifampicin resistance in areas with intermediate TB burden. Additionally, the assay decreased time to the initiation of anti-TB drugs through shorter TAT.

Diagnostic Accuracy and Turnaround Time of the Xpert MTB/RIF Assay in Routine Clinical Practice

PubMed Central

Kwak, Nakwon; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Lee, Sang-Min; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Yim, Jae-Joon

2013-01-01

The Xpert MTB/RIF assay was introduced for timely and accurate detection of tuberculosis (TB). The aim of this study was to determine the diagnostic accuracy and turnaround time (TAT) of Xpert MTB/RIF assay in clinical practice in South Korea. We retrospectively reviewed the medical records of patients in whom Xpert MTB/RIF assay using sputum were requested. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of pulmonary tuberculosis (PTB) and detection of rifampicin resistance were calculated. In addition, TAT of Xpert MTB/RIF assay was compared with those of other tests. Total 681 patients in whom Xpert MTB/RIF assay was requested were included in the analysis. The sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay for diagnosis of PTB were 79.5% (124/156), 100.0% (505/505), 100.0% (124/124) and 94.0% (505/537), respectively. Those for the detection of rifampicin resistance were 57.1% (8/14), 100.0% (113/113), 100.0% (8/8) and 94.9% (113/119), respectively. The median TAT of Xpert MTB/RIF assay to the report of results and results confirmed by physicians in outpatient settings were 0 (0–1) and 6 (3–7) days, respectively. Median time to treatment after initial evaluation was 7 (4–9) days in patients with Xpert MTB/RIF assay, but was 21 (7–33.5) days in patients without Xpert MTB/RIF assay. Xpert MTB/RIF assay showed acceptable sensitivity and excellent specificity for the diagnosis of PTB and detection of rifampicin resistance in areas with intermediate TB burden. Additionally, the assay decreased time to the initiation of anti-TB drugs through shorter TAT. PMID:24204834

Cost effectiveness of alternative imaging strategies for the diagnosis of small-bowel Crohn's disease.

PubMed

Levesque, Barrett G; Cipriano, Lauren E; Chang, Steven L; Lee, Keane K; Owens, Douglas K; Garber, Alan M

2010-03-01

The cost effectiveness of alternative approaches to the diagnosis of small-bowel Crohn's disease is unknown. This study evaluates whether computed tomographic enterography (CTE) is a cost-effective alternative to small-bowel follow-through (SBFT) and whether capsule endoscopy is a cost-effective third test in patients in whom a high suspicion of disease remains after 2 previous negative tests. A decision-analytic model was developed to compare the lifetime costs and benefits of each diagnostic strategy. Patients were considered with low (20%) and high (75%) pretest probability of small-bowel Crohn's disease. Effectiveness was measured in quality-adjusted life-years (QALYs) gained. Parameter assumptions were tested with sensitivity analyses. With a moderate to high pretest probability of small-bowel Crohn's disease, and a higher likelihood of isolated jejunal disease, follow-up evaluation with CTE has an incremental cost-effectiveness ratio of less than $54,000/QALY-gained compared with SBFT. The addition of capsule endoscopy after ileocolonoscopy and negative CTE or SBFT costs greater than $500,000 per QALY-gained in all scenarios. Results were not sensitive to costs of tests or complications but were sensitive to test accuracies. The cost effectiveness of strategies depends critically on the pretest probability of Crohn's disease and if the terminal ileum is examined at ileocolonoscopy. CTE is a cost-effective alternative to SBFT in patients with moderate to high suspicion of small-bowel Crohn's disease. The addition of capsule endoscopy as a third test is not a cost-effective third test, even in patients with high pretest probability of disease. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

An economic evaluation based on a randomized placebo-controlled trial of varenicline in smokers with cardiovascular disease: results for Belgium, Spain, Portugal, and Italy.

PubMed

Wilson, Koo; Hettle, Robert; Marbaix, Sophie; Diaz Cerezo, Silvia; Ines, Monica; Santoni, Laura; Annemans, Lieven; Prignot, Jacques; Lopez de Sa, Esteban

2012-10-01

An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer's perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer's perspective, incremental cost effectiveness ratios were € 6120 (Belgium), € 5151 (Spain), € 5357 (Portugal), and € 5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD.

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Intrinsic Limitations to Unilateral Parathyroid Exploration

PubMed Central

Moore, Francis D.; Mannting, Finn; Tanasijevic, Milenko

1999-01-01

Objective To evaluate a method of limited parathyroid exploration for primary hyperparathyroidism. Summary Background Data Although preoperative localization of parathyroid adenomas has become sensitive enough for clinical practice, it has not achieved success as the basis for limited parathyroid exploration, because multiglandular disease is routinely underdiagnosed. The rapid intraoperative parathyroid hormone assay is sensitive for multiglandular disease, because hormone levels will not fall within 10 minutes of adenoma removal if additional abnormal tissue is present. A combination technique in which the exploration is limited according to the localization studies and the success is confirmed with the parathyroid hormone assay has promise for producing a high rate of curative limited parathyroid explorations. Methods Forty-eight consecutive patients with primary hyperparathyroidism and indications for surgery underwent preoperative localization. After tests, 45 patients underwent unilateral parathyroid exploration and confirmation of the success of unilateral exploration during surgery using the rapid parathyroid hormone assay. The intraoperative management of these patients and their follow-up to 3 months was recorded. Results Thirty-two of the 48 patients (67%) had successful unilateral exploration as gauged by a marked drop in parathyroid hormone levels during the procedure and by 3-month clinical follow-up. Of the 16 patients who ultimately underwent bilateral exploration, 7 had parathyroid hormone levels that did not fall after adenoma removal. Of these seven, five were found to have a second adenoma and two had slow metabolism of hormone with no additional abnormal tissue found. In 5 of the 16 patients, bilateral exploration was performed for erroneous localization. Four additional patients underwent bilateral exploration for improved exposure or negative results on localization tests. Conclusions These results show that unilateral parathyroid exploration is limited by the intrinsic 15% rate of multiglandular primary hyperparathyroidism, combined with the imperfections of preoperative localizing techniques. Although an 85% rate of unilateral exploration can theoretically be obtained for unselected cases, the other vagaries of the technique make a 70% rate a more reasonable expectation. PMID:10493485

Searching for the best real-time RT-PCRs to detect Zika virus infections: the importance of comparing several protocols.

PubMed

de Moraes, F M; Espósito, D L A; Klein, T M; da Fonseca, B A L

2018-01-01

Clinical manifestations of Zika, dengue, and chikungunya virus infections are very similar, making it difficult to reach a diagnosis based only on clinical grounds. In addition, there is an intense cross-reactivity between antibodies directed to Zika virus and other flaviviruses, and an accurate Zika diagnosis is best achieved by real-time RT-PCR. However, some real-time RT-PCR show better performance than others. To reach the best possible Zika diagnosis, the analytic sensitivity of some probe-based real-time RT-PCR amplifying Zika virus RNA was evaluated in spiked and clinical samples. We evaluated primers and probes to detect Zika virus, which had been published before, and tested sensitivity using serum spiked and patient samples by real-time RT-PCR. When tested against spiked samples, the previously described primers showed different sensitivity, with very similar results when samples from patients (serum and urine) were analyzed. Real-time RT-PCR designed to amplify Zika virus NS1 showed the best analytical sensitivity for all samples.

The Major Soybean Allergen Gly m Bd 28K Induces Hypersensitivity Reactions in Mice Sensitized to Cow's Milk Proteins.

PubMed

Candreva, Ángela María; Smaldini, Paola Lorena; Curciarello, Renata; Fossati, Carlos Alberto; Docena, Guillermo Horacio; Petruccelli, Silvana

2016-02-24

Reactions to soy have been reported in a proportion of patients with IgE-mediated cow's milk allergy (CMA). In this work, we analyzed if Gly m Bd 28K/P28, one of the major soybean allergens, is a cross-reactive allergen with cow milk proteins (CMP). We showed that P28 was recognized by IgE sera from CMA patients and activated human peripheral basophils degranulation. Moreover, IgE sera of mice exclusively sensitized to CMP recognized P28. Splenocytes from sensitized animals secreted IL-5 and IL-13 when incubated with CMP or soy proteins, but only IL-13 when treated with P28. In addition, a skin test was strongly positive for CMP and weakly positive for P28. Remarkably, milk-sensitized mice showed hypersensitivity symptoms following sublingual challenge with P28 or CMP. With the use of bioinformatics' tools seven putative cross-reactive epitopes were identified. In conclusion, using in vitro and in vivo tests we demonstrated that P28 is a novel cross-reactive allergen with CMP.

Nuclear magnetic resonance diagnosis of an anaplastic astrocytoma.

PubMed

Jackson, J A; Derman, H S; Harper, R L; Willcott, M R; Ford, J J; Schneiders, N J; McCrary, J A; Kelly, A; Bryan, R N

1984-01-01

A patient presented with an 8-month history of a progressive left homonymous visual field deficit, left hemiparesis, and a left thalamocortical sensory deficit that was not detectable by repeated conventional neurodiagnostic evaluations. Proton nuclear magnetic resonance (NMR) imaging revealed a right parietal lesion characterized by a prolonged T2 (spin-spin relaxation time). At surgery, the mass proved to be an anaplastic astrocytoma. NMR appears to be more sensitive than x-ray computerized tomography scanning in some patients with malignant gliomas and offers the clinician an additional probe with which to evaluate these patients.

Chromatic-achromatic perimetry in four clinic cases: Glaucoma and diabetes.

PubMed

Cabezos, Inmaculada; Luque, Maria Jos; de Fez, Dolores; Moncho, Vicenta; Camps, Vicente

2015-02-01

Some diseases that affect the visual system may show loss of chromatic-achromatic sensitivity before obvious physical signs appear in the usual examination of the eye's posterior segment. A perimetric study has been conducted with four typical patients with glaucoma and diabetes, at different stages of the disease. In addition to the standard white-on-white (standard automated perimetry [SAP]), a test battery has been used to study patient's contrast sensitivity, using stimuli with different chromatic, spatial, and temporal content (multichannel perimetry). The choice of stimuli tries to maximize the response of different visual mechanisms: Achromatic (parvocellular and magnocellular origin); chromatic red-green (parvocellular origin); and chromatic blue-yellow (koniocellular origin). The results seem to indicate losses in the achromatic-parvocellular perimetry and both chromatic perimetry tests, undetected by conventional SAP. Our results illustrate that our patients without visible retinal alterations show signs of suspicion in multichannel perimetry.

A Personalized Approach of Patient-Health Care Provider Communication Regarding Colorectal Cancer Screening Options.

PubMed

Sava, M Gabriela; Dolan, James G; May, Jerrold H; Vargas, Luis G

2018-07-01

Current colorectal cancer screening guidelines by the US Preventive Services Task Force endorse multiple options for average-risk patients and recommend that screening choices should be guided by individual patient preferences. Implementing these recommendations in practice is challenging because they depend on accurate and efficient elicitation and assessment of preferences from patients who are facing a novel task. To present a methodology for analyzing the sensitivity and stability of a patient's preferences regarding colorectal cancer screening options and to provide a starting point for a personalized discussion between the patient and the health care provider about the selection of the appropriate screening option. This research is a secondary analysis of patient preference data collected as part of a previous study. We propose new measures of preference sensitivity and stability that can be used to determine if additional information provided would result in a change to the initially most preferred colorectal cancer screening option. Illustrative results of applying the methodology to the preferences of 2 patients, of different ages, are provided. The results show that different combinations of screening options are viable for each patient and that the health care provider should emphasize different information during the medical decision-making process. Sensitivity and stability analysis can supply health care providers with key topics to focus on when communicating with a patient and the degree of emphasis to place on each of them to accomplish specific goals. The insights provided by the analysis can be used by health care providers to approach communication with patients in a more personalized way, by taking into consideration patients' preferences before adding their own expertise to the discussion.

Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients.

PubMed

Held, M; Laubscher, M; Workman, L; Zar, H J; Dunn, R

2017-09-22

GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225). GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Marcelo E.; Sztejnberg, Manuel L.; Gonzalez, Sara J.

2011-12-15

Purpose: A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comision Nacional de Energia Atomica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. Methods: The first calibration of the detector was done with themore » well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Results: Local mixed-field thermal neutron sensitivities and global thermal and mixed-field thermal neutron sensitivities derived from measurements performed at the RA-6 were compared and no significant differences were found. Global RA-6-based thermal neutron sensitivity showed agreement with pure thermal neutron sensitivity measurements performed in the RA-3 spectrum. Additionally, the detector response proved nearly unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal (considered for calibration calculations at RA-3) neutron source descriptions. The results confirm that the special design of the Rh SPND can be considered as having a pure thermal response for neutron spectra with epithermal-to-thermal flux ratios up to 12%. In addition, the linear response of the detector to thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95 {+-} 0.05 x 10{sup -21} A n{sup -1}{center_dot}cm{sup 2}{center_dot}s. This sensitivity can be used in spectra with up to 21% epithermal-to-thermal flux ratio without significant error due to epithermal neutron and gamma induced effects. The values of the measured fluxes in clinical applications had discrepancies with calculated results that were in the range of -25% to +30%, which shows the importance of a local on-line independent measurement as part of a treatment planning quality control system. Conclusions: The usefulness of the CNEA Rh SPND for the on-line local measurement of thermal neutron flux on BNCT patients has been demonstrated based on an appropriate neutron spectra calibration and clinical applications.« less

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments.

PubMed

Miller, Marcelo E; Sztejnberg, Manuel L; González, Sara J; Thorp, Silvia I; Longhino, Juan M; Estryk, Guillermo

2011-12-01

A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comisión Nacional de Energía Atómica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Local mixed-field thermal neutron sensitivities and global thermal and mixed-field thermal neutron sensitivities derived from measurements performed at the RA-6 were compared and no significant differences were found. Global RA-6-based thermal neutron sensitivity showed agreement with pure thermal neutron sensitivity measurements performed in the RA-3 spectrum. Additionally, the detector response proved nearly unchanged by differences in neutron spectra from real (RA-6 BNCT beam) and ideal (considered for calibration calculations at RA-3) neutron source descriptions. The results confirm that the special design of the Rh SPND can be considered as having a pure thermal response for neutron spectra with epithermal-to-thermal flux ratios up to 12%. In addition, the linear response of the detector to thermal flux allows the use of a mixed-field thermal neutron sensitivity of 1.95 ± 0.05 × 10(-21) A n(-1)[middle dot]cm² [middle dot]s. This sensitivity can be used in spectra with up to 21% epithermal-to-thermal flux ratio without significant error due to epithermal neutron and gamma induced effects. The values of the measured fluxes in clinical applications had discrepancies with calculated results that were in the range of -25% to +30%, which shows the importance of a local on-line independent measurement as part of a treatment planning quality control system. The usefulness of the CNEA Rh SPND for the on-line local measurement of thermal neutron flux on BNCT patients has been demonstrated based on an appropriate neutron spectra calibration and clinical applications.

SENSITIVITY OF ENDOSCOPIC ULTRASOUND, MULTIDETECTOR COMPUTER TOMOGRAPHY AND MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY IN THE DIAGNOSIS OF PANCREAS DIVISUM: A TERTIARY CENTER EXPERIENCE

PubMed Central

Kushnir, Vladimir M.; Wani, Sachin B.; Fowler, Kathryn; Menias, Christine; Varma, Rakesh; Narra, Vamsi; Hovis, Christine; Murad, Faris; Mullady, Daniel; Jonnalagadda, Sreenivasa S.; Early, Dayna S.; Edmundowicz, Steven A.; Azar, Riad R.

2014-01-01

OBJECTIVES There are limited data comparing imaging modalities in the diagnosis of pancreas divisum. We aimed to: 1. Evaluate the sensitivity of endoscopic ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP) and multi-detector computed tomography (MDCT) for pancreas divisum. 2. Assess interobserver agreement (IOA) among expert radiologists for detecting pancreas divisum on MDCT and MRCP. METHODS For this retrospective cohort study, we identified 45 consecutive patients with pancreaticobiliary symptoms and pancreas divisum established by endoscopic retrograde pancreatography (ERP) who underwent EUS and cross-sectional imaging. The control group was composed of patients without pancreas divisum who underwent ERP and cross-sectional imaging. RESULTS The sensitivity of EUS for pancreas divisum was 86.7%, significantly higher than sensitivity reported in the medical records for MDCT (15.5%) or MRCP (60%) [p<0.001 for each]. On review by expert radiologists the sensitivity of MDCT increased to 83.3% in cases where the pancreatic duct was visualized, with fair IOA (қ=0.34). Expert review of MRCPs did not identify any additional cases of pancreas divisum; IOA was moderate (қ=0.43). CONCLUSIONS EUS is a sensitive test for diagnosing pancreas divisum and is superior to MDCT and MRCP. Review of MDCT studies by expert radiologists substantially raises its sensitivity for pancreas divisum. PMID:23211370

Surrogate markers of subtle renal injury in patients with visceral leishmaniasis.

PubMed

Elnojomi, N A A; Musa, A M; Younis, B M; Elfaki, M E E; El-Hassan, A M; Khalil, E A G

2010-09-01

Sudanese visceral leishmaniasis (VL) is a disease of children that is characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and renal injury. Microalbuminuria (MA) and urinary retinol binding protein (urRBP) are useful markers for glomerular and tubular dysfunctions, respectively. We report the prevalence of subtle renal injury in 88 parasitologically confirmed VL patients in a cross-sectional and hospital-based study. Blood and urine were collected before treatment for hematological, biochemical profiles in addition to MA and urRBP measurement using competitive solid phase, sandwich enzyme-linked immune sorbent assay (ELISA), and immunoturbidometry. All the patients had normal serum urea and creatinine levels and no detectable urRBP. However, 40% of the patients had MA detected by ELISA, and 42% were reactive with turbidometry. The sensitivity, specificity, positive and negative predictive values for MA turbidometric technique were calculated as 100%; 96%; 95% and 100%, respectively. In conclusion; subtle renal injury in VL is mainly glomerular. Turbidometry for MA measurement is a simple, inexpensive, sensitive, and specific technique with high predictive values.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder.

PubMed

Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

2017-01-01

Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes.

Deep Brain Stimulation for Parkinson’s Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis

PubMed Central

Fundament, Tomasz; Eldridge, Paul R.; Green, Alexander L.; Whone, Alan L.; Taylor, Rod S.; Williams, Adrian C.; Schuepbach, W. M. Michael

2016-01-01

Background Parkinson’s disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. Methods We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Results Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. Conclusion These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications. PMID:27441637

Comorbid internet addiction in male clients of inpatient addiction rehabilitation centers: psychiatric symptoms and mental comorbidity.

PubMed

Wölfling, Klaus; Beutel, Manfred E; Koch, Andreas; Dickenhorst, Ulrike; Müller, Kai W

2013-11-01

Addictive Internet use has recently been proposed to be included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Still, little is known about its nosological features, including comorbidity with other mental disorders and disorder-specific psychopathological symptoms. To investigate whether Internet addiction (IA) is an issue in patients in addiction treatment, 1826 clients were surveyed in 15 inpatient rehabilitation centers. Male patients meeting criteria for comorbid IA (n = 71) were compared with a matched control group of male patients treated for alcohol addiction without addictive Internet use (n = 58). The SCL-90-R, the Patient Health Questionnaire, and the seven-item Generalized Anxiety Disorder were used to assess associated psychiatric symptoms and further comorbid disorders. Comorbid IA was associated with higher levels of psychosocial symptoms, especially depression, obsessive-compulsive symptoms, and interpersonal sensitivity. Moreover, the patients with IA more frequently met criteria for additional mental disorders. They display higher rates of psychiatric symptoms, especially depression, and might be in need of additional therapeutic treatment. In rehabilitation centers, a regular screening for IA is recommended to identify patients with this (non-substance-related) addiction and supply them with additional disorder-specific treatment.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT).

PubMed

Lee, Adria D; Cassiday, Pamela K; Pawloski, Lucia C; Tatti, Kathleen M; Martin, Monte D; Briere, Elizabeth C; Tondella, M Lucia; Martin, Stacey W

2018-01-01

The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2-4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods-pertussis culture as the "gold standard," composite reference standard analysis (CRS), and latent class analysis (LCA). Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

Is there a role for pre-operative contrast-enhanced magnetic resonance imaging for radical surgery in malignant pleural mesothelioma?

PubMed

Stewart, Duncan; Waller, David; Edwards, John; Jeyapalan, Kanagaratnam; Entwisle, James

2003-12-01

To assess the use of contrast-enhanced magnetic resonance imaging (CEMRI) in addition to computed tomography in the pre-operative assessment of patients for radical surgery in malignant pleural mesothelioma. Over a 45-month period, 51 of 76 patients assessed (69 men and seven women), underwent extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative pathological stage was correlated with radiological staging, with particular emphasis on tumour resectability. Seventeen (22%) patients were found on CEMRI to have unresectable, but histologically unconfirmed disease, not previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but pathological nodal data were incomplete in three, so excluding these patients from further analyses. The median pre-operative interval after CEMRI was 17 days. Two patients were found to have unexpectedly extensive disease at thoracotomy, thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the International Mesothelioma Interest Group system, tumour stage was correctly predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely due to the underestimation of pericardial involvement, but this did not affect resectability and had no significant effect on prognosis. Nodal stage was correctly identified in 60% of patients. CEMRI was successful in predicting pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%), but less so in identifying tumour stage T2 or less (sensitivity of 23%; specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%). CEMRI is most useful in the differentiation of T3 and T4 disease and may be unnecessary at earlier stages. Its multiplanar tumour localisation abilities are of value in the assessment of resectability. It is unlikely to contribute significantly to nodal staging, but it remains a valuable adjunct in the selection of patients for radical surgery.

More experiences with the Tzanck smear test: cytologic findings in cutaneous granulomatous disorders.

PubMed

Durdu, Murat; Baba, Mete; Seçkin, Deniz

2009-09-01

Granulomatous dermatitis is a distinctive histopathologic cutaneous reaction pattern against various infectious and noninfectious agents. Cytologically, granulomatous dermatitis shows granulomas and multinucleated giant cells. Various etiologic agents of granulomatous diseases can also be identified. We aimed to investigate Tzanck smear findings in granulomatous skin diseases. Patients who had granulomas and/or multinucleated giant cells of Langhans, foreign body- and/or Touton type in Tzanck smear tests were included in the study. In these patients, Tzanck preparations were then further evaluated for additional cytologic findings. Samples stained with May-Grünwald-Giemsa stain were evaluated by the same dermatologist throughout the study. In some patients, methylene blue, Gram and/or Erlich-Ziehl-Nielsen stains were also performed. In all of the study cases, the final diagnosis was established after the evaluation of clinical and laboratory findings (including, when appropriate, potassium hydroxide examination; bacterial, leishmanial, and fungal cultures; histopathology; tuberculosis and leishmania polymerase chain reaction). We also calculated the sensitivity and specificity of the Leishman-Donovan body for cutaneous leishmaniasis. Over a 2-year period, 94 of 950 patients (9.9%) in whom Tzanck smear tests were performed had cytologic findings consistent with a granulomatous reaction. In 74 (78.7%) and 20 (21.3%) patients, the granulomatous reaction was due to infectious and noninfectious causes, respectively. Infectious causes included cutaneous leishmaniasis in 65 patients (87.8%), candidal granuloma in two patients, botyromycosis in two patients, and aspergillosis, blastomycosis, mucormycosis, leprosy, and cutaneous tuberculosis in one patient each. In 58 of 74 patients (78.4%) with infectious granulomatous dermatitis, the causes of the granulomas were identified. Noninfectious granulomatous reactions were due to granuloma annulare in 7 patients, sarcoidosis in 5 patients, a foreign body in 4 patients, necrobiosis lipoidica in 2 patients, and juvenile xanthogranuloma in 2 patients. In 17 of 20 patients (85%) with noninfectious granulomatous reactions, the cytologic findings were characteristic of the final diagnoses. The sensitivity and specificity of Leishman-Donovan bodies for cutaneous leishmaniasis were 76.9% and 100%, respectively. All of the samples were evaluated by the same dermatologist throughout the study; therefore no comment could be made regarding the reliability of the Tzanck smear test. In addition, the sensitivity and specificity of Tzanck smear test findings for diseases other than cutaneous leishmaniasis could not be calculated because of an insufficient number of patients. The Tzanck smear test may be a useful diagnostic tool for certain granulomatous skin diseases.

18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques.

PubMed

Koolen, Bas B; Vrancken Peeters, Marie-Jeanne T F D; Aukema, Tjeerd S; Vogel, Wouter V; Oldenburg, Hester S A; van der Hage, Jos A; Hoefnagel, Cornelis A; Stokkel, Marcel P M; Loo, Claudette E; Rodenhuis, Sjoerd; Rutgers, Emiel J Th; Valdés Olmos, Renato A

2012-01-01

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6 months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0 months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

The impact of extended electrodiagnostic studies in Ulnar Neuropathy at the elbow

PubMed Central

Todnem, Kari; Michler, Ralf Peter; Wader, Tony Eugen; Engstrøm, Morten; Sand, Trond

2009-01-01

Background This study aimed to explore the value of extended motor nerve conduction studies in patients with ulnar nerve entrapment at the elbow (UNE) in order to find the most sensitive and least time-consuming method. We wanted to evaluate the utility of examining both the sensory branch from the fifth finger and the dorsal branch of the ulnar nerve. Further we intended to study the clinical symptoms and findings, and a possible correlation between the neurophysiological findings and pain. Methods The study was prospective, and 127 UNE patients who were selected consecutively from the list of patients, had a clinical and electrodiagnostic examination. Data from the most symptomatic arm were analysed and compared to the department's reference limits. Student's t - test, chi-square tests and multiple regression models were used. Two-side p-values < 0.05 were considered as significant. Results Ulnar paresthesias (96%) were more common than pain (60%). Reduced ulnar sensitivity (86%) and muscle strength (48%) were the most common clinical findings. Adding a third stimulation site in the elbow mid-sulcus for motor conduction velocity (MCV) to abductor digiti minimi (ADM) increased the electrodiagnostic sensitivity from 80% to 96%. Additional recording of ulnar MCV to the first dorsal interosseus muscle (FDI) increased the sensitivity from 96% to 98%. The ulnar fifth finger and dorsal branch sensory studies were abnormal in 39% and 30% of patients, respectively. Abnormal electromyography in FDI was found in 49% of the patients. Patients with and without pain had generally similar conduction velocity parameter means. Conclusion We recommend three stimulation sites at the elbow for MCV to ADM. Recording from FDI is not routinely indicated. Sensory studies and electromyography do not contribute much to the sensitivity of the electrodiagnostic evaluation, but they are useful to document axonal degeneration. Most conduction parameters are unrelated to the presence of pain. PMID:19814833

Proteins associated with EGFR-TKIs resistance in patients with non-small cell lung cancer revealed by mass spectrometry.

PubMed

Yang, Shaoyu; Chen, Xueqin; Pan, Yuelong; Yu, Jiekai; Li, Xin; Ma, Shenglin

2016-11-01

The present study aimed to identify potential serum biomarkers for predicting the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs). A total of 61 samples were collected and analyzed using the integrated approach of magnetic bead‑based weak cation exchange chromatography and matrix‑assisted laser desorption/ionization‑time of flight‑mass spectrometry. The Zhejiang University Protein Chip Data Analysis system was used to identify the protein spectra of patients that are resistant and sensitive to EGFR‑TKIs. Furthermore, a support vector machine was used to construct a predictive model with high accuracy. The model was trained using 46 samples and tested with the remaining 15 samples. In addition, the ExPASy Bioinformatics Resource Portal was used to search potential candidate proteins for peaks in the predictive model. Seven mass/charge (m/z) peaks at 3,264, 9,156, 9,172, 3,964, 9,451, 4,295 and 3,983 Da, were identified as significantly different peaks between the EGFR‑TKIs sensitive and resistant groups. A predictive model was generated with three protein peaks at 3,264, 9,451 and 4,295 Da (m/z). This three‑peak model was capable of distinguishing EGFR‑TKIs resistant patients from sensitive patients with a specificity of 80% and a sensitivity of 80.77%. Furthermore, in a blind test, this model exhibited a high specificity (80%) and a high sensitivity (90%). Apelin, TYRO protein tyrosine kinase‑binding protein and big endothelin‑1 may be potential candidates for the proteins identified with an m/z of 3,264, 9,451 and 4,295 Da, respectively. The predictive model used in the present study may provide an improved understanding of the pathogenesis of NSCLC, and may provide insights for the development of TKI treatment plans tailored to specific patients.

Sensitivity and Specificity of Interictal EEG-fMRI for Detecting the Ictal Onset Zone at Different Statistical Thresholds

PubMed Central

Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim

2014-01-01

There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4–3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ. PMID:25101049

Oral Administration of Forskolin, Homotaurine, Carnosine, and Folic Acid in Patients with Primary Open Angle Glaucoma: Changes in Intraocular Pressure, Pattern Electroretinogram Amplitude, and Foveal Sensitivity.

PubMed

Mutolo, Maria Giulia; Albanese, Giuseppe; Rusciano, Dario; Pescosolido, Nicola

2016-04-01

To evaluate the effects of a food supplement containing forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, B6, and magnesium in patients with primary open angle glaucoma (POAG) already in treatment and compensated by intraocular pressure (IOP)-lowering drugs, during a period of 12 months. Twenty-two patients (44 eyes) with POAG, with their IOP compensated by topical drugs, were enrolled and randomly assigned to the food supplement or control treatment group. The additional food supplement treatment consisted of 2 tablets per day (1 in the morning, 1 in the evening) given for 1 year of a balanced association of homotaurine, Coleus forskohlii root extract, L-carnosine, folic acid, vitamins B1, B2, B6, and magnesium. Pattern Electroretinogram (PERG) amplitude, foveal sensitivity obtained with the visual field analyzer frequency doubling technology, and IOP were detected at enrollment (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). We observed in treated patients a significant further decrease of IOP and an improvement of PERG amplitude at 6, 9, and 12 months, and foveal sensitivity at 12 months. All values remained substantially stable in control patients. The results of the present pilot study indicate that the components of the food supplement reach the eye in a detectable manner, as evidenced by the effects on the IOP. Moreover, they suggest a short-term neuroactive effect, as indicated by the improvement of PERG amplitude and foveal sensitivity in treated, but not in control patients.

Tactile allodynia in patients with lumbar radicular pain (sciatica).

PubMed

Defrin, Ruth; Devor, Marshall; Brill, Silviu

2014-12-01

We report a novel symptom in many patients with low back pain (LBP) that sheds new light on the underlying pain mechanism. By means of quantitative sensory testing, we compared patients with radicular LBP (sciatica), axial LBP (LBP without radiation into the leg), and healthy controls, searching for cutaneous allodynia in response to weak tactile and cooling stimuli on the leg and low back. Most patients with radicular pain (~60%) reported static and dynamic tactile allodynia, as well as cooling allodynia, on the leg, often extending into the foot. Some also reported allodynia on the low back. In axial LBP, allodynia was almost exclusively on the back. The degree of dynamic tactile allodynia correlated with the degree of background pain. The presence of allodynia suggests that the peripheral nerve generators of background leg and back pain have also induced central sensitization. The distal (foot) location of the allodynia in patients who have it indicates that the nociceptive drive that maintains the central sensitization arises paraspinally (ectopically) in injured ventral ramus afferents; this is not an instance of somatic referred pain. The presence of central sensitization also provides the first cogent account of shooting pain in sciatica as a wave of activity sweeping vectorially across the width of the sensitized dorsal horn. Finally, the results endorse leg allodynia as a pain biomarker in animal research on LBP, which is commonly used but has not been previously validated. In addition to informing the underlying mechanism of LBP, bedside mapping of allodynia might have practical implications for prognosis and treatment. How can you tell whether pain radiating into the leg in a patient with sciatica is neuropathic, ie, due to nerve injury? Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

A randomized trial of standardized nursing patient assessment using wireless devices.

PubMed

Dykes, Patricia C; Carroll, Diane L; Benoit, Angela; Coakley, Amanda; Chang, Frank; Empoliti, Joanne; Gallagher, Joan; Lasala, Cynthia; O'Malley, Rosemary; Rath, Greg; Silva, Judy; Li, Qi

2007-10-11

A complete and accurate patient assessment database is essential for effective communication, problem identification, planning and evaluation of patient status. When employed consistently for point-of-care documentation, information systems are associated with completeness and quality of documentation. The purpose of this paper is to report on the findings of a randomized, cross-over study conducted to evaluate the adequacy of a standard patient assessment module to support problem identification, care planning and tracking of nursing sensitive patient outcomes. The feasibility of wireless devices to support patient assessment data collection at the point-of-care was evaluated using wireless PDAs and tablet PCs. Seventy-nine (79) nurses from two patient care units at Massachusetts General Hospital (Boston, MA) were recruited into the study and randomized to complete patient assessment using wireless or paper devices. At the end of six weeks, nurses who where randomized to the paper assessment module were assigned to a device and those who used a device were assigned to paper for an additional six weeks. Impact was evaluated with regard to data capture, workflow implications and nurse satisfaction. Findings suggest that a standard patient assessment set promotes patient sensitive and quality data capture, which is augmented by the use of wireless devices.

A Randomized Trial of Standardized Nursing Patient Assessment Using Wireless Devices

PubMed Central

Dykes, Patricia C.; Carroll, Diane L.; Benoit, Angela; Coakley, Amanda; Chang, Frank; Empoliti, Joanne; Gallagher, Joan; Lasala, Cynthia; O’Malley, Rosemary; Rath, Greg; Silva, Judy; Li, Qi

2007-01-01

A complete and accurate patient assessment database is essential for effective communication, problem identification, planning and evaluation of patient status. When employed consistently for point-of-care documentation, information systems are associated with completeness and quality of documentation. The purpose of this paper is to report on the findings of a randomized, cross-over study conducted to evaluate the adequacy of a standard patient assessment module to support problem identification, care planning and tracking of nursing sensitive patient outcomes. The feasibility of wireless devices to support patient assessment data collection at the point-of-care was evaluated using wireless PDAs and tablet PCs. Seventy-nine (79) nurses from two patient care units at Massachusetts General Hospital (Boston, MA) were recruited into the study and randomized to complete patient assessment using wireless or paper devices. At the end of six weeks, nurses who where randomized to the paper assessment module were assigned to a device and those who used a device were assigned to paper for an additional six weeks. Impact was evaluated with regard to data capture, workflow implications and nurse satisfaction. Findings suggest that a standard patient assessment set promotes patient sensitive and quality data capture, which is augmented by the use of wireless devices. PMID:18693827

First- and second-order contrast sensitivity functions reveal disrupted visual processing following mild traumatic brain injury.

PubMed

Spiegel, Daniel P; Reynaud, Alexandre; Ruiz, Tatiana; Laguë-Beauvais, Maude; Hess, Robert; Farivar, Reza

2016-05-01

Vision is disrupted by traumatic brain injury (TBI), with vision-related complaints being amongst the most common in this population. Based on the neural responses of early visual cortical areas, injury to the visual cortex would be predicted to affect both 1(st) order and 2(nd) order contrast sensitivity functions (CSFs)-the height and/or the cut-off of the CSF are expected to be affected by TBI. Previous studies have reported disruptions only in 2(nd) order contrast sensitivity, but using a narrow range of parameters and divergent methodologies-no study has characterized the effect of TBI on the full CSF for both 1(st) and 2(nd) order stimuli. Such information is needed to properly understand the effect of TBI on contrast perception, which underlies all visual processing. Using a unified framework based on the quick contrast sensitivity function, we measured full CSFs for static and dynamic 1(st) and 2(nd) order stimuli. Our results provide a unique dataset showing alterations in sensitivity for both 1(st) and 2(nd) order visual stimuli. In particular, we show that TBI patients have increased sensitivity for 1(st) order motion stimuli and decreased sensitivity to orientation-defined and contrast-defined 2(nd) order stimuli. In addition, our data suggest that TBI patients' sensitivity for both 1(st) order stimuli and 2(nd) order contrast-defined stimuli is shifted towards higher spatial frequencies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Distribution of inhalant allergies in pediatric patients presenting with allergic complaints in the Eastern Anatolia Region.

PubMed

Kilic, Mehmet; Taskin, Erdal

2016-08-01

The objective of this study was to define the distribution of inhalant allergens in pediatric patients in whom sensitization was diagnosed with a skin prick test (SPT) who had presented with allergic complaints. In addition, the correlation between the inhalant allergens detected on the SPT and the patients' demographic features, diagnosis, and laboratory findings was defined. A total of 1415 children among the 4056 patients who presented at a clinic in the Eastern Anatolia region with allergic complaints and who had undergone an SPT were included in this study. On the SPT, sensitization to grass pollens was found in 60.1%, cereals pollens in 57.2%, and Dermatophagoides farinae in 21.8% of the patients. Furthermore, on the SPT, incidence of asthma development was 3.96 times higher (odds ratio 3.96, 95% CI: 1.77-6.83; P=0.001) in patients who were allergic to Dermatophagoides farinae. In our study, differences were found in the study region compared to data from around the world and other regions in Turkey in terms of the distribution of allergies and variations in allergens in patients diagnosed due to variations in climate and plants.

Molecular diagnosis of toxoplasmosis in immunocompromised patients.

PubMed

Robert-Gangneux, Florence; Belaz, Sorya

2016-08-01

Toxoplasmosis in immunocompromised patients is associated with a high mortality rate. Molecular techniques are important tools to diagnose acute disease in immunocompromised patients, but there are various methods with variable efficiency. Some of them have been validated for the diagnosis of congenital toxoplasmosis, but the impact of their use has not been evaluated in immunocompromised patients. Toxoplasmosis is of increasing importance in non-HIV immunocompromised patients. In addition, the picture of disease shows greater severity in South America, both in immunocompetent study participants and in congenitally infected infants. These epidemiological differences could influence the sensitivity of diagnostic methods. This review analyzes recent data on molecular diagnosis and compares them with older ones, in light of progress gained in molecular techniques and of recent epidemiological findings. Most recent studies were conducted in South America and used PCR targeting the B1 gene. PCR on blood could allow diagnosing a significant proportion of patients with ocular toxoplasmosis in Brazil. Quantitative PCR methods with specific probes should be used to improve sensitivity and warrant specificity. Performance of quantitative PCR targeting the repeated 529 bp sequence for the diagnosis of toxoplasmosis in immunocompromised patients needs evaluation in field studies in South America and in western countries.

Carpal tunnel syndrome: Investigating the sensitivity of initial-diagnosis with electro-diagnostic tests in 600 cases and associated risk factors especially manual milking.

PubMed

Tunç, Abdulkadir; Güngen, Belma Doğan

2017-01-01

Electro-diagnostic studies are the most reliable methods in diagnosis of carpal tunnel syndrome (CTS). Although there are many risk factors associated with CTS, there are a limited number of studies in the literature indicating that manual milking, which is frequently seen in Turkey, is a risk factor for CTS. The purpose of this study was to evaluate demographic findings of cases referred due to initial diagnosis of CTS as well as aetiological data especially manual milking and to investigate the sensitivity of initial diagnosis of CTS. Six hundred patients, who were referred to our electromyography laboratory due to initial diagnosis of CTS, were included. Demographic findings, duration of complaints, existence of diabetes mellitus, and manual milking histories of all patients were recorded. Sensitivity of initial diagnosis was investigated based on electro-diagnostic test results. According to electro-diagnostic test results, 289 of the patients were diagnosed with CTS (48.17%). 110 (18.3%) of 600 patients had a history of manual milking. In 94 of this group (85.4%), CTS was detected. Statistically significant correlation was found between CTS and age, female gender, duration of complaints, obesity and manual milking. This study confirms that manual milking is an important risk factor for CTS in addition to female gender, age, symptom duration and obesity. The fact that sensitivity of initial diagnosis of CTS was found to be low according to electro-diagnostic test results indicates importance of detailed clinical evaluation.

The diagnostic performance and added value of (18)F-FDG PET/CT in the detection of liver metastases in recurrent colorectal carcinoma patients.

PubMed

Odalovic, Strahinja; Artiko, Vera; Sobic-Saranovic, Dragana; Stojiljkovic, Milica; Petrovic, Milorad; Petrovic, Nebojsa; Kozarevic, Nebojsa; Grozdic-Milojevic, Isidora; Obradovic, Vladimir

2015-01-01

The aim of this study was to assess the value of (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT in detection of liver metastases in patients with suspected recurrent colorectal carcinoma, as well as to compare diagnostic performance of (18)F-FDG PET/CT with conventional imaging methods (MDCT). This study included 73 patients with resected primary colorectal adenocarcinoma referred for (18)F-FDG PET/CT to the National PET Center, at the Clinical Center of Serbia, Belgrade, from January 2010 to May 2013, with suspicion of recurrence. The patients underwent (18)F-FDG PET/CT examination on a 64-slice hybrid PET/CT scanner (Biograph, TruePoint64, Siemens Medical Solutions, Inc. USA). Prior to (18)F-FDG PET/CT all patients underwent contrast-enhanced MDCT. Findings of (18)F-FDG PET/CT and MDCT were compared to findings of subsequent histopathological examinations or with results of clinical and imaging follow-up over at least six months. Final diagnosis of liver metastases of colorectal cancer was made either by histopathological examination of specimen after biopsy or surgery, or based on clinical, laboratory and imaging evaluation during first six months after PET/CT scan. In detection of liver metastases (18)F-FDG PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 83.3%, 95.3%, 92.6%, 89.1% and 90.4%, respectively. In addition, MDCT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy in detection of liver metastases of 60%, 88.4%, 78.3%, 76% and 76.7%, respectively. There was significant difference in sensitivity (83.3% vs 60%; P=0.045) between these two methods. In addition, significant difference was observed in accuracy between PET/CT and MDCT (90.4% vs 76.7%; P=0.016). The higher specificity in visualization of liver metastases was also achieved by (18)F-FDG PET/CT compared to MDCT (95.3% vs 88.4%), but this difference was not significant (P=0.37). (18)F-FDG PET/CT was highly sensitive, specific and accurate method in detection of liver metastases in patients with suspected recurrent colorectal carcinoma in our study. This hybrid imaging showed superior diagnostic performance in evaluation of suspected colorectal cancer liver metastases compared to conventional imaging.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

PubMed Central

Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

2017-01-01

Background Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). Patients and methods The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. PMID:28572737

A Representation for Gaining Insight into Clinical Decision Models

PubMed Central

Jimison, Holly B.

1988-01-01

For many medical domains uncertainty and patient preferences are important components of decision making. Decision theory is useful as a representation for such medical models in computer decision aids, but the methodology has typically had poor performance in the areas of explanation and user interface. The additional representation of probabilities and utilities as random variables serves to provide a framework for graphical and text insight into complicated decision models. The approach allows for efficient customization of a generic model that describes the general patient population of interest to a patient- specific model. Monte Carlo simulation is used to calculate the expected value of information and sensitivity for each model variable, thus providing a metric for deciding what to emphasize in the graphics and text summary. The computer-generated explanation includes variables that are sensitive with respect to the decision or that deviate significantly from what is typically observed. These techniques serve to keep the assessment and explanation of the patient's decision model concise, allowing the user to focus on the most important aspects for that patient.

Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer

PubMed Central

Stefanou, Dimitra T.; Bamias, Aristotelis; Episkopou, Hara; Kyrtopoulos, Soterios A.; Likka, Maria; Kalampokas, Theodore; Photiou, Stylianos; Gavalas, Nikos; Sfikakis, Petros P.; Dimopoulos, Meletios A.; Souliotis, Vassilis L.

2015-01-01

Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that perturbations of DNA repair pathways as measured in PBMCs from OC patients correlate with the drug sensitivity of these cells and reflect the individualized response to platinum-based chemotherapy. PMID:25659114

Diagnostic value of the basophil activation test in evaluating Hymenoptera venom sensitization.

PubMed

Peternelj, Andreja; Silar, Mira; Bajrovic, Nissera; Adamic, Katja; Music, Ema; Kosnik, Mitja; Korosec, Peter

2009-01-01

Diagnosis of allergy to Hymenoptera venom is usually confirmed with skin testing and measurement of specific serum IgE antibody, tests which are sometimes inconclusive. In these cases, additional in vitro tests are necessary. The aim of this study was to show the applicability of the basophil activation test in detecting sensitization to Hymenoptera venom and to compare the test sensitivity and clinical positive-predictive value with skin prick tests and measurement of allergen-specific serum IgE. This prospective study was conducted between June 2004 and December 2007 and included a large group of 204 patients. All patients had a history of at least one systemic allergic reaction of Müller grades II-IV after a Hymenoptera sting. We compared results of the basophil activation test, specific serum IgE and skin prick tests with patients' clinical history and data on culprit insects. The overall clinical sensitivities of the basophil activation test, specific serum IgE and skin prick tests were 90%, 76% and 64%, respectively; the clinical positive-predictive values of the three tests were 79%, 73% and 78% for bee venom, 86%, 59% and 43% for wasp venom; and 84%, 77% and 22% for both venoms. Our results revealed a higher clinical sensitivity and comparable or better clinical positive-predictive value of basophil activation tests than skin prick tests and allergen-specific serum IgE in the detection of allergy to Hymenoptera venom.

Sensitivity and Specificity of Fenyö-Lindberg and Teicher Scores in the Diagnosis of Acute Appendicitis in Women

PubMed

Madžar, Zrinko; Kopljar, Mario; Madžar, Tomislav; Mesić, Marko; Mužina Mišić, Dubravka; Čiček, Slaven; Zovak, Mario

2016-12-01

The aim of the study was to assess diagnostic accuracy (sensitivity and specificity) of Fenyö-Lindberg and Teicher scores for distinguishing patients that need immediate surgical treatment from the others, in a female population from an urban setting. The study prospectively included 130 female patients admitted to the emergency department with abdominal pain indicating acute appendicitis. The scores and parameters of validity were calculated and compared to definitive diagnosis. For Fenyö-Lindberg score of -17 or less, 84.5% sensitivity, 55.6% specificity, 87.9% positive predictive value (PPV) and 48.4% negative predictive value (NPV) were recorded. For cut-off value greater or equal to -2, there was 59.2% sensitivity, 77.8% specificity, 91% PPV and 33.3% NPV. The Receiver Operating Characteristic (ROC) curve analysis of Fenyö-Lindberg score showed that the best single cut-off value for discriminating acute appendicitis in the study population was -15. For Teicher score, values greater than -3 yielded 89.3% sensitivity and 22.2% specificity, 81.4% PPV and 35.3% NPV. In conclusion, Fenyö-Lindberg score could be used as an additional tool to exclude appendicitis and avoid unnecessary appendectomies. Teicher score may help in recognizing patients with appendicitis. None of the two scores can indicate or decline appendectomy in all cases. Scoring systems may be useful for pointing to important clinical signs and symptoms in specific subpopulations.

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma.

PubMed

Flores-Montero, J; Sanoja-Flores, L; Paiva, B; Puig, N; García-Sánchez, O; Böttcher, S; van der Velden, V H J; Pérez-Morán, J-J; Vidriales, M-B; García-Sanz, R; Jimenez, C; González, M; Martínez-López, J; Corral-Mateos, A; Grigore, G-E; Fluxá, R; Pontes, R; Caetano, J; Sedek, L; Del Cañizo, M-C; Bladé, J; Lahuerta, J-J; Aguilar, C; Bárez, A; García-Mateo, A; Labrador, J; Leoz, P; Aguilera-Sanz, C; San-Miguel, J; Mateos, M-V; Durie, B; van Dongen, J J M; Orfao, A

2017-10-01

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10 7 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.

Connexin 43 inhibition sensitizes chemoresistant glioblastoma cells to temozolomide

PubMed Central

Murphy, Susan F; Varghese, Robin T; Lamouille, Samy; Guo, Sujuan; Pridham, Kevin J; Kanabur, Pratik; Osimani, Alyssa M; Sharma, Shaan; Jourdan, Jane; Rodgers, Cara M; Simonds, Gary R; Gourdie, Robert G; Sheng, Zhi

2015-01-01

Resistance of glioblastoma (GBM) to the front-line chemotherapeutic agent temozolomide (TMZ) continues to challenge GBM treatment efforts. The repair of TMZ-induced DNA damage by O-6-methylguanine-DNA methyltransferase (MGMT) confers one mechanism of TMZ resistance. Paradoxically, MGMT-deficient GBM patients survive longer despite still developing resistance to TMZ. Recent studies indicate that the gap junction protein connexin 43 (Cx43) renders GBM cells resistant to TMZ through its carboxyl terminus (CT). In this study, we report insights into how Cx43 promotes TMZ resistance. Cx43 levels were inversely correlated with TMZ sensitivity of GBM cells, including GBM stem cells. Moreover, Cx43 levels inversely correlated with patient survival, including as observed in MGMT-deficient GBM patients. Addition of the C-terminal peptide mimetic αCT1, a selective inhibitor of Cx43 channels, sensitized human MGMT-deficient and TMZ-resistant GBM cells to TMZ treatment. Moreover, combining αCT1 with TMZ blocked AKT/mTOR signaling, induced autophagy and apoptosis in TMZ-resistant GBM cells. Our findings suggest that Cx43 may offer a biomarker to predict the survival of patients with MGMT-independent TMZ resistance, and that combining a Cx43 inhibitor with TMZ could enhance therapeutic responses in GBM and perhaps other TMZ-resistant cancers. PMID:26542214

Vital signs in older patients: age-related changes.

PubMed

Chester, Jennifer Gonik; Rudolph, James L

2011-06-01

Vital signs are objective measures of physiological function that are used to monitor acute and chronic disease and thus serve as a basic communication tool about patient status. The purpose of this analysis was to review age-related changes of traditional vital signs (blood pressure, pulse, respiratory rate, and temperature) with a focus on age-related molecular changes, organ system changes, systemic changes, and altered compensation to stressors. The review found that numerous physiological and pathological changes may occur with age and alter vital signs. These changes tend to reduce the ability of organ systems to adapt to physiological stressors, particularly in frail older patients. Because of the diversity of age-related physiological changes and comorbidities in an individual, single-point measurements of vital signs have less sensitivity in detecting disease processes. However, serial vital sign assessments may have increased sensitivity, especially when viewed in the context of individualized reference ranges. Vital sign change with age may be subtle because of reduced physiological ranges. However, change from an individual reference range may indicate important warning signs and thus may require additional evaluation to understand potential underlying pathological processes. As a result, individualized reference ranges may provide improved sensitivity in frail, older patients. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

PubMed

Hanna, T P; Shafiq, J; Delaney, G P; Vinod, S K; Thompson, S R; Barton, M B

2018-02-01

To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax.

PubMed

Montero, Joan; Stephansky, Jason; Cai, Tianyu; Griffin, Gabriel K; Cabal-Hierro, Lucia; Togami, Katsuhiro; Hogdal, Leah J; Galinsky, Ilene; Morgan, Elizabeth A; Aster, Jon C; Davids, Matthew S; LeBoeuf, Nicole R; Stone, Richard M; Konopleva, Marina; Pemmaraju, Naveen; Letai, Anthony; Lane, Andrew A

2017-02-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and were uniformly sensitive to the BCL2 inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, and dynamic BH3 profiling. Animals bearing BPDCN patient-derived xenografts had disease responses and improved survival after venetoclax treatment in vivo Finally, we report on 2 patients with relapsed/refractory BPDCN who received venetoclax off-label and experienced significant disease responses. We propose that venetoclax or other BCL2 inhibitors undergo expedited clinical evaluation in BPDCN, alone or in combination with other therapies. In addition, these data illustrate an example of precision medicine to predict treatment response using ex vivo functional assessment of primary tumor tissue, without requiring a genetic biomarker. Therapy for BPDCN is inadequate, and survival in patients with the disease is poor. We used primary tumor cell functional profiling to predict BCL2 antagonist sensitivity as a common feature of BPDCN, and demonstrated in vivo clinical activity of venetoclax in patient-derived xenografts and in 2 patients with relapsed chemotherapy-refractory disease. Cancer Discov; 7(2); 156-64. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115. ©2016 American Association for Cancer Research.

Development of a Metabolic Biosignature for Detection of Early Lyme Disease

PubMed Central

Molins, Claudia R.; Ashton, Laura V.; Wormser, Gary P.; Hess, Ann M.; Delorey, Mark J.; Mahapatra, Sebabrata; Schriefer, Martin E.; Belisle, John T.

2015-01-01

Background. Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%–40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Methods. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Results. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%–95%), and a specificity of 95% (90%–100%). Importantly, the metabolic biosignature correctly classified 77%–95% of the of serology negative Lyme disease patients. Conclusions. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining high specificity. PMID:25761869

A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

PubMed

Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

2016-12-01

An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Automated detection using natural language processing of radiologists recommendations for additional imaging of incidental findings.

PubMed

Dutta, Sayon; Long, William J; Brown, David F M; Reisner, Andrew T

2013-08-01

As use of radiology studies increases, there is a concurrent increase in incidental findings (eg, lung nodules) for which the radiologist issues recommendations for additional imaging for follow-up. Busy emergency physicians may be challenged to carefully communicate recommendations for additional imaging not relevant to the patient's primary evaluation. The emergence of electronic health records and natural language processing algorithms may help address this quality gap. We seek to describe recommendations for additional imaging from our institution and develop and validate an automated natural language processing algorithm to reliably identify recommendations for additional imaging. We developed a natural language processing algorithm to detect recommendations for additional imaging, using 3 iterative cycles of training and validation. The third cycle used 3,235 radiology reports (1,600 for algorithm training and 1,635 for validation) of discharged emergency department (ED) patients from which we determined the incidence of discharge-relevant recommendations for additional imaging and the frequency of appropriate discharge documentation. The test characteristics of the 3 natural language processing algorithm iterations were compared, using blinded chart review as the criterion standard. Discharge-relevant recommendations for additional imaging were found in 4.5% (95% confidence interval [CI] 3.5% to 5.5%) of ED radiology reports, but 51% (95% CI 43% to 59%) of discharge instructions failed to note those findings. The final natural language processing algorithm had 89% (95% CI 82% to 94%) sensitivity and 98% (95% CI 97% to 98%) specificity for detecting recommendations for additional imaging. For discharge-relevant recommendations for additional imaging, sensitivity improved to 97% (95% CI 89% to 100%). Recommendations for additional imaging are common, and failure to document relevant recommendations for additional imaging in ED discharge instructions occurs frequently. The natural language processing algorithm's performance improved with each iteration and offers a promising error-prevention tool. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients.

PubMed

Erb, S; Frei, R; Strandén, A M; Dangel, M; Tschudin-Sutter, S; Widmer, A F

2015-11-01

The optimal approach in laboratory diagnosis of Clostridium difficile infection (CDI) is still not well defined. Toxigenic culture (TC) or alternatively fecal toxin assay by cell cytotoxicity neutralization assay are considered to be the reference standard, but these methods are time-consuming and labor intensive. In many medical centers, diagnosis of CDI is therefore still based on fecal toxin A/B enzyme immunoassay (EIA) directly from stool alone, balancing cost and speed against limited diagnostic sensitivity. The aim of the study was to assess in which patient population the additional workload of TC is justified. All consecutive stool specimens submitted for diagnosis of suspected CDI between 2004 and 2011 at a tertiary-care center were examined by toxin EIA and TC. Clinical data of patients with established diagnosis of CDI were collected in a standardized case-report form. From 12,481 stool specimens submitted to the microbiologic laboratory, 480 (3.8%) fulfilled CDI criteria; 274 (57.1%) were diagnosed by toxin EIA; and an additional 206 (42.9%) were diagnosed by TC when toxin EIA was negative. Independent predictors for negative toxin EIA but positive TC were high-dose corticosteroids (odds ratio (OR) 2.97, 95% confidence interval (CI) 1.50-5.90, p 0.002), leukocytopenia <1000/μL (OR 2.52, 95% CI 1.22-5.23, p 0.013) and nonsevere CDI (OR 2.21, 95% CI 1.39-3.50, p 0.001). There was no difference in outcomes such as in-hospital mortality and recurrence between both groups. In conclusion, negative toxin EIA does not rule out CDI in immunocompromised patients in the setting of relevant clinical symptoms. Methods with improved sensitivity such as TC or PCR should be used, particularly in this patient population. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Sensitivity and specificity of a new scoring system for diabetic macular oedema detection using a confocal laser imaging system

PubMed Central

Tong, L; Ang, A; Vernon, S; Zambarakji, H; Bhan, A; Sung, V; Page, S

2001-01-01

AIM—To assess the use of the Heidelberg retina tomograph (HRT) in screening for sight threatening diabetic macular oedema in a hospital diabetic clinic, using a new subjective analysis system (SCORE).
METHODS—200 eyes of 100 consecutive diabetic patients attending a diabetologist's clinic were studied, all eyes had an acuity of 6/9 or better. All patients underwent clinical examination by an ophthalmologist. Using the HRT, one good scan was obtained for each eye centred on the fovea. A System for Classification and Ordering of Retinal Edema (SCORE) was developed using subjective assessment of the colour map and the reflectivity image. The interobserver agreement of using this method to detect macular oedema was assessed by two observers (ophthalmic trainees) who were familiarised with SCORE by studying standard pictures of eyes not in the study. All scans were graded from 0-6 and test positive cases were defined as having a SCORE value of 0-2. The sensitivity of SCORE was assessed by pooling the data with an additional 88 scans of 88 eyes in order to reduce the confidence interval of the index.
RESULTS—12 eyes in eight out of the 100 patients had macular oedema clinically. Three scans in three patients could not be analysed because of poor scan quality. In the additional group of scans 76 out of 88 eyes had macular oedema clinically. The scoring system had a specificity of 99% (95% CI 96-100) and sensitivity of 67% (95% CI 57-76). The predictive value of a negative test was 87% (95% CI 82-99), and that of a positive test was 95% (95% CI 86-99). The mean difference of the SCORE value between two observers was -0.2 (95% CI -0.5 to +0.07).
CONCLUSIONS—These data suggest that SCORE is potentially useful for detecting diabetic macular oedema in hospital diabetic patients.

 PMID:11133709

Ultrasonographic detection of regional lymph node metastases in patients with intermediate or thick malignant melanoma.

PubMed

Brountzos, Elias N; Panagiotou, Irene E; Bafaloukos, Dimitrios I; Kelekis, Dimitrios A

2003-01-01

Careful monitoring of regional lymph nodes and early detection of metastases in malignant melanoma patients has an impact on their survival, since it may permit beneficial surgical therapy. Palpation is routinely used in clinical practice. The value of ultrasonography for routine follow-up of melanoma patients, still, is not generally accepted. The aim of our study was to assess the sensitivity and specificity of ultrasound and clinical examination respectively, in the detection of melanoma regional node metastases. Additionally, we evaluated whether early detection of metastases improved overall survival. One hundred and forty-eight melanoma patients with an intermediate or thick primary lesion were followed between January 1997 and May 2001. Clinical examination and concomitant regional lymph node ultrasonography were performed, every 3-4 months. If suspicious findings were identified, regional lymph node dissection was undertaken. Forty-four from the initial 148 patients relapsed with regional lymph nodal metastases. In 11 patients (25%) palpation failed to reveal the disease and metastases were depicted only by ultrasonography. In only 1 patient ultrasonography was false-negative. The sensitivity and specificity of palpation were 72.7 and 97% respectively, while those of ultrasonography were 97.7 (p<0.001) and 98% respectively. Ultrasonography was more sensitive in detecting lymph node metastases in the axilla (100%) and the groin (93.3%). When overall survival of patients presenting with local-regional recurrence was calculated--depending on the number of involved lymph nodes--a survival benefit (p<0.05) was found for patients with only one lymph node metastasis. In conclusion, ultrasonography is superior to clinical examination in the early detection of regional lymph node metastases from an intermediate or thick malignant melanoma and should be a part of those patients' surveillance.

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PubMed

Mardor, Yael; Pfeffer, Raphael; Spiegelmann, Roberto; Roth, Yiftach; Maier, Stephan E; Nissim, Ouzi; Berger, Raanan; Glicksman, Ami; Baram, Jacob; Orenstein, Arie; Cohen, Jack S; Tichler, Thomas

2003-03-15

To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Thymic stromal lymphopoietin expression is increased in nasal epithelial cells of patients with mugwort pollen sensitive-seasonal allergic rhinitis.

PubMed

Zhu, Dong-dong; Zhu, Xue-wei; Jiang, Xiao-dan; Dong, Zhen

2009-10-05

Excessive expression of thymic stromal lymphopoietin (TSLP) has been demonstrated in asthmatic airway epithelia and in nasal epithelia from animal models of allergic rhinitis (AR), but the evidence of expression of TSLP in nasal epithelial cells (NECs) of patients with AR is lacking. We aimed to investigate the expression of TSLP in NECs of patients with mugwort sensitive-seasonal AR and determine whether it is associated with severity of symptoms and the number of infiltrated eosinophils in nasal mucosa. NECs specimens were obtained by scraping with plastic curettes from the nasal inferior turbinates of patients with mugwort pollen sensitive-seasonal AR (n = 22) and nonallergic controls (n = 11) during last peak mugwort pollen season. The severity of nasal symptom was assessed using a Visual Analog Scale (VAS). In addition, serum mugwort pollen IgE levels were tested from each patient. In situ hybridization (ISH) was performed to test the messenger RNA (mRNA) of TSLP in the NECs. Furthermore, immunohistochemical staining (IHC) was scored to evaluate the expression of TSLP and eosinophil cell count was made by May-Grünwald/Giemsa staining. The correlation between expression of TSLP and all other parameters was analyzed in this study. The mRNA level of TSLP was significantly increased in NECs of patients with AR compared with the nonallergic control group (P < 0.05). In addition, IHC results showed that expression of TSLP in NECs from patients with AR was up-regulated which was correlated with VAS score (r = 0.598; P < 0.05) and nasal eosinophils count (r = 0.702; P < 0.05), but it was unrelated with mugwort pollen specific IgE level. These preliminary findings indicate a potential relationship between TSLP expression, severity of symptoms and nasal eosinophils count in pathogenesis of AR, but TSLP expression did not correlate with mugwort pollen specific IgE level. The elevated expression of TSLP might play a critical role in local atopical responses of AR. In the future, the TSLP has the potential to be one of the most important molecular markers for AR diagnoses and assessment.

Cognitive Performance Is Related to Central Sensitization and Health-related Quality of Life in Patients with Chronic Whiplash-Associated Disorders and Fibromyalgia.

PubMed

Coppieters, Iris; Ickmans, Kelly; Cagnie, Barbara; Nijs, Jo; De Pauw, Robby; Noten, Suzie; Meeus, Mira

2015-01-01

A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients. (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups. A case-control study was conducted. The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp. Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]). Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P < 0.017). CPM was comparable between the 3 groups. Cognitive performance was significantly related to central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P < 0.05). Decreased cognitive performance was related to deficient central pain modulation in healthy controls. Further, significant correlations between decreased cognitive performance and reduced health-related QoL were revealed among all study groups. Additionally, FM patients showed correlations between cognitive impairment and increased health-related QoL. Remarkably, impaired selective attention and working memory were related to less TS, whereas impaired sustained attention was correlated with dysfunctional CPM in FM patients. Based on the current cross-sectional study no firm conclusions can be drawn on the causality of the relations. In conclusion, this paper has demonstrated significant cognitive deficits, signs of CS, and reduced health-related QoL in chronic WAD and FM patients compared to healthy individuals. Significant relations between cognitive performance and CS as well as health-related QoL were demonstrated. These results provide preliminary evidence for the clinical importance of objectively measured cognitive deficits in patients with chronic WAD and FM. Chronic pain, fibromyalgia, whiplash, central sensitization, conditioned pain modulation, temporal summation, cognition, quality of life.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

PubMed

Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

Increased detection of smear-negative pulmonary tuberculosis by GeneXpert MTB/RIF® assay after bleach concentration.

PubMed

Tadesse, Mulualem; Aragaw, Dossegnaw; Rigouts, Leen; Abebe, Gemeda

2016-06-01

The GeneXpert MTB/RIF assay (Xpert) was endorsed as the initial diagnostic tool in people suspected of human immunodeficiency virus-associated or drug-resistant tuberculosis (TB). However, information regarding the performance of Xpert for diagnosing smear-negative TB in high burden settings remains limited. We evaluated the diagnostic accuracy of Xpert and the impact of bleach concentration on the performance of Xpert using smear-negative sputum samples from human immunodeficiency virus-negative patients. One spot and one morning smear-negative sputum samples per patient were examined using Xpert and culture at the Mycobacteriology Research Center of Jimma University, Ethiopia. The sputum culture on both Löwenstein-Jensen and/or Mycobacteria Growth Indicator Tube was the gold-standard. Of 185 smear-negative presumptive pulmonary TB cases, 19 (10.3%) had culture-proven TB. The sensitivity of Xpert on spot and morning sputum was similar (63.2%). Testing two specimens per patient insignificantly increased the sensitivity of Xpert. Bleach concentration and pelleting improved the sensitivity of Xpert over unprocessed sputum in paired samples (73.8% vs. 63.2%) without affecting the specificity (95%). Bleach concentration and pelleting allowed an additional seven cases of TB (missed on the first and second direct Xperts) to be detected, five of which were from culture-negative cases. Testing of a single sputum sample by Xpert can reach reasonable sensitivity and results would be available on the same day, avoiding loss of patients and treatment delay. The sensitivity of Xpert was improved after bleach concentration and pelleting, although its added value needs further study on a larger scale. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

[Husband to wife kidney transplantation in five multiparous women: sensitization or tolerance after pregnancy?].

PubMed

Ortiz-Arroyo, Víctor M; Granados, Julio; Uribe-Uribe, Norma; de Leo, Claudia; Castelán, Natalia; González, Norma; López, Mayra; Alberú, Josefina

2004-01-01

Pregnancy is a known cause of immunological sensitization and it has been reported graft survival to be lower in husband to wife kidney transplantation if the wife had been pregnant (mutual children) as compare to those cases without pregnancies. Previous exposure to husband HLA antigens during pregnancies may lead to specific sensitization to subsequent allografts. To communicate the fate of kidney allograft in husband to wife transplantation when the recipient had been pregnant. From 682 renal transplants performed at INCMNSZ 5 corresponded to husband to wife transplants. All the recipients were multiparous and had received multiple blood transfusions. Pretransplantation lymphocytotoxic cross-match testing were performed by complement dependent citotoxicity with antihuman globulin added (AHG-CDC), being negative in all cases for T and B cells. All the patients received triple-drug immunosuppressive therapy, additionally, anti-IL2R monoclonal antibodies were used in two cases. Two patients developed: accelerated acute rejection (case 1), and acute humoral rejection (case 5), respectively. Graft in these patients were loss to rejection and transplant nephrectomy accomplished. The remaining three patients (cases 2, 3, and 4) has not had any rejection episode, and have had excellent graft outcome at 34, 30, and 21 months posttransplant, respectively. Why under similar conditions some husband to wife kidney transplant recipients developed an adverse humoral immunological events while others maintain excellent long-term graft outcome? Is it possible to speculate that for some women pregnancy is in fact a sensitizing event, while in others it promotes "immunological acceptance"? At present there is no a test that characterized one and other group. Even though pretransplantation cross-match testing by flow cytometry is more sensitive than AHG-CDC, its negative result is by no means an absolute guarantee that an adverse anamnestic immunological event will not occur.

Epidemiological data on airborne contact dermatitis - results of the IVDK.

PubMed

Breuer, Kristine; Uter, Wolfgang; Geier, Johannes

2015-10-01

Airborne contact dermatitis (AirbCD) is not uncommon, according to a large number of published case reports and review articles. Epidemiological data on AirbCD based on larger clinical samples have not yet been published. To investigate demographic characteristics and patch test reactivity in patients diagnosed with both occupational and non-occupational AirbCD. A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 1994-2013, including 201 344 consecutively patch tested patients, was performed. One thousand two hundred and three patients (0.6%) were diagnosed with AirbCD, 421 (35.0%) of these with an occupational background. Occupational dermatitis and face involvement were more prevalent than in patients without AirbCD (n = 200 141). Sensitization to epoxy resin and sensitization to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) were significantly associated with AirbCD, and there was a trend for sensitization to Compositae mix and/or sesquiterpene lactone mix to be associated with AirbCD. Adhesives, plastics, construction materials, paints and varnishes in occupational cases, and plants in non-occupational cases, were the most commonly documented culprit product categories. AirbCD is more common in patients with occupational dermatitis than in patients with non-occupational dermatitis. In our clinical sample, components of epoxy resin systems, MCI/MI and Compositae allergens were the most important contact allergens associated with AirbCD. Patch testing with additional allergens is important. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-resolution endoscopy plus chromoendoscopy or narrow-band imaging in Barrett's esophagus: a prospective randomized crossover study.

PubMed

Kara, M A; Peters, F P; Rosmolen, W D; Krishnadath, K K; ten Kate, F J; Fockens, P; Bergman, J J G H

2005-10-01

High-resolution endoscopy (HRE) may improve the detection of early neoplasia in Barrett's esophagus. Indigo carmine chromoendoscopy (ICC) and narrow-band imaging (NBI) may be useful techniques to complement HRE. The aim of this study was to compare HRE-ICC with HRE-NBI for the detection of high-grade dysplasia or early cancer (HGD/EC) in patients with Barrett's esophagus. Twenty-eight patients with Barrett's esophagus underwent HRE-ICC and HRE-NBI (separated by 6 - 8 weeks) in a randomized sequence. The two procedures were performed by two different endoscopists, who were blinded to the findings of the other examination. Targeted biopsies were taken from all detected lesions, followed by four-quadrant biopsies at 2-cm intervals. Biopsy evaluation was supervised by a single expert pathologist, who was blinded to the imaging technique used. Fourteen patients were diagnosed with HGD/EC. The sensitivity for HGD/EC was 93 % and 86 % for HRE-ICC and HRE-NBI, respectively. Targeted biopsies had a sensitivity of 79 % with HRE alone. HGD was diagnosed from random biopsies alone in only one patient. ICC and NBI detected a limited number of additional lesions occult to HRE, but these lesions did not alter the sensitivity for identifying patients with HGD/EC. In most patients with high-grade dysplasia or early cancer in Barrett's esophagus, subtle lesions can be identified with high-resolution endoscopy. Indigo carmine chromoendoscopy and narrow-band imaging are comparable as adjuncts to high-resolution endoscopy.

Cross-reactions between xanthates and rubber additives.

PubMed

Sasseville, Denis; Al-Sowaidi, Mowza; Moreau, Linda

2007-09-01

We previously described allergic contact dermatitis from xanthates used in the recovery of metals from mining ores. We observed cross-reactions with carbamates, believed to be due to the common "dithio" nucleus shared by both groups. The present study was undertaken to establish the rate of cross-reactions between xanthates and rubber additives. Between November 2002 and December 2005, 1,220 consecutive patients were patch-tested with sodium isopropyl xanthate 10% in petrolatum (pet) and with potassium amyl xanthate 10% pet and later 5% pet, in addition to the North American Contact Dermatitis Group standard series and other series as required by their conditions. Fifty-one patients reacted to xanthates, carbamates, or thiurams; 26 reacted to xanthates only, and these reactions were felt to be irritant. Twenty-five patients reacted to xanthates and/or to one or more of the rubber additives, 12 had positive reactions to xanthates and to either carba mix or thiuram mix, 10 reacted to xanthates and carba mix, 9 reacted to xanthates and thiuram mix, and 8 showed positive reactions to xanthates and both mixes. However, 13 patients had positive reactions to carba mix and thiuram mix but did not react to xanthates. Six patients reacted to other rubber additives such as mercaptobenzothiazole, black rubber mix, and mixed dialkyl thioureas. Five of these patients also reacted to xanthates, 4 reacted to xanthates and carba mix, and 3 reacted to xanthates, carba mix, and thiuram mix. Of patients sensitized to carbamates, thiurams, or mercaptobenzothiazole, 50% exhibit cross-reactions with xanthates. Xanthates are irritants, and their patch-test concentrations should be lowered to 5% or less.

Characterization and classification of lupus patients based on plasma thermograms

PubMed Central

Chaires, Jonathan B.; Mekmaysy, Chongkham S.; DeLeeuw, Lynn; Sivils, Kathy L.; Harley, John B.; Rovin, Brad H.; Kulasekera, K. B.; Jarjour, Wael N.

2017-01-01

Objective Plasma thermograms (thermal stability profiles of blood plasma) are being utilized as a new diagnostic approach for clinical assessment. In this study, we investigated the ability of plasma thermograms to classify systemic lupus erythematosus (SLE) patients versus non SLE controls using a sample of 300 SLE and 300 control subjects from the Lupus Family Registry and Repository. Additionally, we evaluated the heterogeneity of thermograms along age, sex, ethnicity, concurrent health conditions and SLE diagnostic criteria. Methods Thermograms were visualized graphically for important differences between covariates and summarized using various measures. A modified linear discriminant analysis was used to segregate SLE versus control subjects on the basis of the thermograms. Classification accuracy was measured based on multiple training/test splits of the data and compared to classification based on SLE serological markers. Results Median sensitivity, specificity, and overall accuracy based on classification using plasma thermograms was 86%, 83%, and 84% compared to 78%, 95%, and 86% based on a combination of five antibody tests. Combining thermogram and serology information together improved sensitivity from 78% to 86% and overall accuracy from 86% to 89% relative to serology alone. Predictive accuracy of thermograms for distinguishing SLE and osteoarthritis / rheumatoid arthritis patients was comparable. Both gender and anemia significantly interacted with disease status for plasma thermograms (p<0.001), with greater separation between SLE and control thermograms for females relative to males and for patients with anemia relative to patients without anemia. Conclusion Plasma thermograms constitute an additional biomarker which may help improve diagnosis of SLE patients, particularly when coupled with standard diagnostic testing. Differences in thermograms according to patient sex, ethnicity, clinical and environmental factors are important considerations for application of thermograms in a clinical setting. PMID:29149219

Cost-effectiveness analysis of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome in Colombia.

PubMed

Mejía, Aurelio; Senior, Juan Manuel; Ceballos, Mateo; Atehortúa, Sara; Toro, Juan Manuel; Saldarriaga, Clara; Mejía, María Elena; Ramírez, Carolina

2015-01-01

Acute coronary syndrome is one of the most frequent medical emergencies in developing countries. To determine, from the perspective of the Colombian health system, the cost-effectiveness of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome. We conducted a cost-effectiveness analysis from the perspective of the Colombian health system comparing ticagrelor and clopidogrel for the treatment of patients with acute coronary syndrome. To estimate the expected costs and outcomes, a Markov model was constructed in which patients could remain stable without experiencing new cardiovascular events, suffer from a new event, or die. For the baseline case, a 10-year time horizon and a discount ratio of 3% for costs and benefits were adopted. The transition probabilities were extracted from the PLATO (Platelet Inhibition and Patient Outcomes) clinical trial. Vital statistics were drawn from the Departmento Administrativo Nacional de Estadística (DANE) and additional information from Colombian patients included in the Access registry. To identify and measure resource use, a standard case was built by consulting guidelines and protocols. Unit costs were obtained from Colombian rate lists. A probabilistic sensitivity analysis was conducted in which costs were represented by a triangular distribution, and the effectiveness through a beta distribution. In the base case, the additional cost per quality-adjusted life-year gained with ticagrelor was COP$ 28,411,503. The results were sensitive to changes in the time horizon and the unit cost of clopidogrel. For a willingness-to-pay equivalent to three times the Colombian per capita gross domestic product, the probability of ticagrelor being cost-effective was 75%. Ticagrelor is a cost-effective strategy for the treatment of patients with acute coronary syndrome in Colombia.

No effect of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia.

PubMed

Navarrete-Cortes, Adrian; Ble-Castillo, Jorge L; Guerrero-Romero, Fernando; Cordova-Uscanga, Ruben; Juárez-Rojop, Isela E; Aguilar-Mariscal, Hidemi; Tovilla-Zarate, Carlos Alfonso; Lopez-Guevara, Maria Del Rocio

2014-01-01

There are limited and conflicting data from clinical trials concerning the beneficial effects of magnesium supplementation on diabetic patients. We investigated the effects of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia. A total of 98 normomagnesemic subjects with type 2 diabetes were enrolled in a randomized, crossover, double-blind, placebo-controlled trial. Participants were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for three months, followed by a three-month washout period. Treatment assignments were then reversed over an additional three months of follow-up. The primary endpoint was a reduction in fasting glucose and HbA1c. A total of 56 subjects completed the follow-up in the magnesium and placebo supplementation groups. Urinary magnesium excretion was increased following magnesium supplementation in the intervention group compared with the placebo group (p = 0.0002). Fasting glucose, HbA1c, insulin and HOMA-IR, as well as lipid profile, did not change significantly during treatment. We concluded that magnesium supplementation does not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia.

Broncho-Vaxom and spontaneous allergic autocytotoxicity (spACT) in bronchial asthma associated with food hypersensitivity.

PubMed

Podleski, W K

1986-01-01

Spontaneous allergic autocytotoxicity (spACT) of white blood cells (WBC) was assessed in six bronchial asthma patients and eighteen normal control individuals. The observed alterations of non-primed WBC membrane were revealed as an increased uptake of trypan blue exclusion dye, an indicator of death cells. The phenomenon of spACT might be associated with a lack of T suppressor cell intervention, increased refractoriness of WBC membrane leading to its increased permeability and enhanced releasability of chemical mediators of anaphylaxis, which probably bypasses IgE events. In six bronchial asthma patients, three were sensitive toward wheat, two had cow milk sensitivity, and one had corn sensitivity. When WBC of these patients were studied in the direct ACT assay, an additional augmentation of spACT effect by specific food antigens was observed. Surprisingly, Broncho-Vaxom (BX) did not inhibit or enhance spACT. However, BX has antagonistic activity toward direct ACT response in the dose-dependent concentration as previously reported. Our preliminary clinical experience leads us to believe that the spACT assay can serve as a useful clinical discriminator of potential responders versus non-responders to therapy with new agents, when WBC disintegration by autoinduction is involved.

Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia.

PubMed

Dehghan-Nayeri, Nasrin; Eshghi, Peyman; Pour, Kourosh Goudarzi; Rezaei-Tavirani, Mostafa; Omrani, Mir Davood; Gharehbaghian, Ahmad

2017-07-01

Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE-MALDI-TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.

A study of the effects of long-term use on individual sensitivity to temazepam and lorazepam in a clinical population.

PubMed

van Steveninck, A L; Wallnöfer, A E; Schoemaker, R C; Pieters, M S; Danhof, M; van Gerven, J M; Cohen, A F

1997-09-01

The central effects of benzodiazepines may be attenuated after chronic use by changes in pharmacokinetics, pharmacodynamics or both. This attenuation may be influenced by the dosing pattern and the characteristics of the user population. The objectives of this study were to evaluate drug sensitivity in long-term users of temazepam and lorazepam in a clinical population. The sensitivity to benzodiazepine effects in chronic users (1-20 years) of lorazepam (n = 14) or temazepam (n = 13) was evaluated in comparison with age and sex matched controls. Drug sensitivity was evaluated by plasma concentration in relation to saccadic eye movement parameters, postural stability and visual analogue scales. Pharmacokinetics of lorazepam and temazepam did not differ between patients and control subjects. Chronic users of lorazepam showed clear evidence of reduced sensitivity, indicated by lack of any pharmacodynamic difference between patients and controls at baseline, when drug concentrations were similar to the peak values attained in the control subjects after administration of 1-2.5 mg of lorazepam. In addition, there was a two- to four fold reduction in the slopes of concentration-effect plots for measures of saccadic eye movements and body sway (all; P < or = 0.01). By contrast, sensitivity in chronic users of temazepam was not different from controls. The difference between the temazepam and the lorazepam group appears to be associated with a more continuous drug exposure in the latter, due to the longer half-life and a more frequent intake of lorazepam. This pattern of use may be partly related to the more anxious personality traits that were observed in the chronic users of lorazepam. Chronic users of lorazepam show evidence of tolerance to sedative effects in comparison with healthy controls. Tolerance does not occur in chronic users of temazepam. The difference may be related to pharmacological properties, in addition to different patterns of use, associated with psychological factors.

Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

PubMed

Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James

2017-01-01

Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.

Role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in evaluating patients with pheochromocytoma.

PubMed

Bandopadhyaya, G P; Kumar, Abhishek; Kumari, Jyotsana

2015-01-01

The aim of this retrospective study was to evaluate role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in patients with pheochromocytoma. The patients with diagnosis of pheochromocytoma based on radiological and biochemical markers were retrospectively selected for the study. These patients had undergone both (131)I-MIBG scintigraphy and (18)F-DOPA PET/CT. The imaging findings were compared to patient histopathology reports, biochemical markers and clinical follow up whenever available to establish the diagnosis. (131)I-MIBG showed a sensitivity of 68% and specificity of 100%. (18)F-DOPA PET/CT showed a sensitivity of 82% and specificity of 100%. (18)F-DOPA was better at localizing and finding more no of lesions as compared to (131)I-MIBG scintigraphy. (18)F-DOPA also is a better study in evaluation of paragangliomas. (18)F-DOPA PET/CT seems to be a better modality in comparison to (131)I-MIBG scintigraphy in the evaluation of pheochromocytoma/paraganglioma. At this point both these tracers seem to have mutually additive role in these patients and essential investigations with diagnosis and follow-up of this disease.

Sources of sensitization, cross-reactions, and occupational sensitization to topical anaesthetics among general dermatology patients.

PubMed

Jussi, Liippo; Lammintausta, Kaija

2009-03-01

Contact sensitization to local anaesthetics is often from topical medicaments. Occupational sensitization to topical anaesthetics may occur in certain occupations. The aim of the study was to analyse the occurrence of contact sensitization to topical anaesthetics in general dermatology patients. Patch testing with topical anaesthetics was carried out in 620 patients. Possible sources of sensitization and the clinical histories of the patients are analysed. Positive patch test reactions to one or more topical anaesthetics were seen in 25/620 patients. Dibucaine reactions were most common (20/25), and lidocaine sensitization was seen in two patients. Six patients had reactions to ester-type and/or amide-type anaesthetics concurrently. Local preparations for perianal conditions were the most common sensitizers. One patient had developed occupational sensitization to procaine with multiple cross-reactions and with concurrent penicillin sensitization from procaine penicillin. Dibucaine-containing perianal medicaments are the major source of contact sensitization to topical anaesthetics. Although sensitization to multiple anaesthetics can be seen, cross-reactions are possible. Contact sensitization to lidocaine is not common, and possible cross-reactions should be determined when reactions to lidocaine are seen. Occupational procaine sensitization from veterinary medicaments is a risk among animal workers.

"Cold air" and/or "talking" as cough triggers, a sign for the diagnosis of cough variant asthma.

PubMed

Kanemitsu, Yoshihiro; Matsumoto, Hisako; Osman, Nuriamina; Oguma, Tsuyoshi; Nagasaki, Tadao; Izuhara, Yumi; Ito, Isao; Tajiri, Tomoko; Iwata, Toshiyuki; Niimi, Akio; Mishima, Michiaki

2016-11-01

Fractional exhaled nitric oxide (FeNO) is considered an alternative marker of eosinophilic airway inflammation and is sometimes incorporated in the diagnosis of asthma. However, many patients with cough variant asthma (CVA) demonstrate an FeNO in the normal range. Therefore, additional information is needed to confirm the diagnosis of CVA, particularly in patients with low FeNO levels. We aimed to investigate the feasibility of using cough triggers to help diagnose CVA. We studied 163 patients presenting with prolonged/chronic cough alone (including 104 CVA patients) who underwent FeNO measurements and an airway responsiveness test, and answered a questionnaire listing 18 cough triggers. The sensitivity and specificity of FeNO levels and cough triggers for the diagnosis of CVA were determined. CVA patients showed higher FeNO levels than non-CVA patients. When the cut-off value of FeNO levels for the diagnosis of CVA was set at 22ppb, its sensitivity was 57%. CVA patients more frequently responded to "cold air" and "talking" as cough triggers than non-CVA patients. When the analysis was confined to those with a low FeNO (<22ppb) group, the sensitivity and positive predictive values of "cold air" and "talking" for the diagnosis of CVA were 36% and 70% for "cold air", and 44% and 74% for "talking", respectively. Their specificity was 81%. "Cold air" was associated with airway hyperresponsiveness in all patients with an emphasis on those with low FeNO levels. "Cold air" and/or "talking" as cough triggers could be signs for the diagnosis of CVA, particularly when FeNO levels are low. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study.

PubMed

Ward, J E; Karrison, T; Chatta, G; Hussain, M; Shevrin, D; Szmulewitz, R Z; O'Donnell, P H; Stadler, W M; Posadas, E M

2012-03-01

Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off period would result in prolonged time to PSA failure. Men with biochemically recurrent prostate cancer, whose PSA was <0.5 ng ml(-1) after 6 months of androgen deprivation therapy were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng ml(-1). Thirty-seven patients were randomized. Of 18 patients randomized to pazopanib, at the time of study closure, 4 had progressive disease, 1 remained on treatment and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had progressive disease, 7 remained under protocol-defined observation and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Because of high dropout rates in both arms, the study was halted. IAS is a treatment approach that may facilitate investigation of novel agents in the hormone-sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience to reduce the dropout rate.

Evaluating the diagnostic accuracy of the Xpert MTB/RIF assay on bronchoalveolar lavage fluid: A retrospective study.

PubMed

Lu, Yanjun; Zhu, Yaowu; Shen, Na; Tian, Lei; Sun, Ziyong

2018-02-08

Limited data on the diagnostic accuracy of the Xpert MTB/RIF assay using bronchoalveolar lavage fluid from patients with suspected pulmonary tuberculosis (PTB) have been reported in China. Therefore, a retrospective study was designed to evaluate the diagnostic accuracy of this assay. Clinical, radiological, and microbiological characteristics of 238 patients with suspected PTB were reviewed retrospectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of active PTB were calculated for the Xpert MTB/RIF assay using TB culture or final diagnosis based on clinical and radiological evaluation as the reference standard. The sensitivity and specificity of the Xpert MTB/RIF assay were 84.5% and 98.9%, respectively, and those for smear microscopy were 36.2% and 100%, respectively, when compared to the culture method. However, compared with the sensitivity and specificity of final diagnosis based on clinical and radiological evaluation, the sensitivity and specificity of the assay were 72.9% and 98.7%, respectively, which were significantly higher than those for smear microscopy. The Xpert MTB/RIF assay on bronchoalveolar lavage fluid could serve as an additional rapid diagnostic tool for PTB in a high TB-burden country and improve the time to TB treatment initiation in patients with PTB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Detection of liver metastasis: is diffusion-weighted imaging needed in Gd-EOB-DTPA-enhanced MR imaging for evaluation of colorectal liver metastases?

PubMed

Tajima, Taku; Akahane, Masaaki; Takao, Hidemasa; Akai, Hiroyuki; Kiryu, Shigeru; Imamura, Hiroshi; Watanabe, Yasushi; Kokudo, Norihiro; Ohtomo, Kuni

2012-10-01

We compared diagnostic ability for detecting hepatic metastases between gadolinium ethoxy benzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) on a 1.5-T system, and determined whether DWI is necessary in Gd-EOB-DTPA-enhanced MRI for diagnosing colorectal liver metastases. We assessed 29 consecutive prospectively enrolled patients with suspected metachronous colorectal liver metastases; all patients underwent surgery and had preoperative Gd-EOB-DTPA-enhanced MRI. Overall detection rate, sensitivity for detecting metastases and benign lesions, positive predictive value, and diagnostic accuracy (Az value) were compared among three image sets [unenhanced MRI (DWI set), Gd-EOB-DTPA-enhanced MRI excluding DWI (EOB set), and combined set]. Gd-EOB-DTPA-enhanced MRI yielded better overall detection rate (77.8-79.0 %) and sensitivity (87.1-89.4 %) for detecting metastases than the DWI set (55.9 % and 64.7 %, respectively) for one observer (P < 0.001). No statistically significant difference was seen between the EOB and combined sets, although several metastases were newly detected on additional DWI. Gd-EOB-DTPA-enhanced MRI yielded a better overall detection rate and higher sensitivity for detecting metastases compared with unenhanced MRI. Additional DWI may be able to reduce oversight of lesions in Gd-EOB-DTPA-enhanced 1.5-T MRI for detecting colorectal liver metastases.

The role of pleural fluid MAGE RT-nested PCR in the diagnosis of malignant pleural effusion.

PubMed

Jeon, Eun Ju; Park, Hye Kyeong; Jeon, Kyeongman; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung; Ki, Chang-Seok; Kim, Jong-Won; Shim, Young Mog; Um, Sang-Won

2012-11-01

  Melanoma antigen (MAGE) genes are expressed in tumor cells, the testis and the placenta. The purpose of this prospective study was to investigate the sensitivity, specificity, and accuracy of the carcinoembryonic antigen (CEA), MAGE reverse transcriptase-nested polymerase chain reaction (RT-nested PCR), and cytology of pleural fluid in the diagnosis of malignant pleural effusion.   Patients in whom unilateral pleural effusion was identified on chest radiography from January to December 2009 were included in the study. MAGE genes were analyzed by RT-nested PCR using MAGE A1-6 common primers.   Of 81 enrolled patients, 46 were diagnosed as malignant pleural effusion, and 24 were diagnosed as benign pleural effusion. The diagnoses of 11 patients were not confirmed in this study. The diagnostic sensitivity, specificity, and accuracy of MAGE RT-nested PCR were 61.4%, 95.7%, and 73.1%, respectively. The diagnostic sensitivities of cytology and CEA (>5 ng/mL) were 61.4% and 75.0%, respectively. Among 17 patients with negative cytology who had malignant pleural effusion, 12 and 10 patients were positive for CEA (>5.0 ng/mL) and MAGE RT-nested PCR, respectively. However, of five patients with malignant pleural effusion that was not recognized by cytology and CEA, MAGE RT-nested PCR correctly predicted a malignant etiology in only one additional patient (20%).   MAGE RT-nested PCR seems to add little on the combination of conventional methods in the diagnosis of malignant effusion. © 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty. Ltd.

Clinical validation of the nursing diagnosis of ineffective protection in haemodialysis patients.

PubMed

de Sá Tinôco, Jéssica Dantas; de Paiva, Maria das Graças Mariano Nunes; de Queiroz Frazão, Cecília Maria Farias; Lucio, Kadyjina Daiane Batista; Fernandes, Maria Isabel da Conceição Dias; de Oliveira Lopes, Marcos Venicios; de Carvalho Lira, Ana Luisa Brandão

2018-01-01

To evaluate the clinical validity of indicators of the nursing diagnosis of "ineffective protection" in haemodialysis patients. Haemodialysis patients have reduced protection. Studies on the nursing diagnosis of "ineffective protection" are scarce in the literature. The use of indicators to diagnose "ineffective protection" could improve the care of haemodialysis patients. The clinical usefulness of the indicators requires clinical validation. This was a diagnostic accuracy study. This study assessed a sample of 200 patients undergoing haemodialysis in a reference clinic for nephrology during the first half of 2015. Operational definitions were created for each clinical indicator based on concept analysis and content validation by experts for these indicators. Diagnostic accuracy measurement was performed with latent class analysis with randomised effects. The clinical indicator of "fatigue" had high sensitivity (p = .999) and specificity (p = 1.000) for the identification of "ineffective protection." Additionally, "maladaptive response to stress" (p = .711) and "coagulation change" (p = .653) were sensitive indicators. The main indicators that showed high specificity were "fever" (p = .987), "increased number of hospitalisations" (p = .911), "weakness" (p = .937), "infected vascular access" (p = .962) and "vascular access dysfunction" (p = .722). A set of nine clinical indicators of "ineffective protection" were accurate and statistically significant for haemodialysis patients. Three clinical indicators showed sensitivity, and six indicators showed specificity. Accurate measures for nursing diagnoses can help nurses confirm or rule out the probability of the occurrence of "ineffective protection" in patients undergoing haemodialysis. © 2017 John Wiley & Sons Ltd.

The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

PubMed Central

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2011-01-01

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI. PMID:21209786

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

PubMed

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2010-12-26

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

Prophylactic platelet transfusions in patients with blood malignancies: cost analysis of a randomized trial.

PubMed

Campbell, Helen E; Estcourt, Lise J; Stokes, Elizabeth A; Llewelyn, Charlotte A; Murphy, Michael F; Wood, Erica M; Stanworth, Simon J

2014-10-01

This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts <10 × 10(9) /L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (autoHSCT) and chemotherapy/allogeneic HSCT (chemo/alloHSCT) patients. Data were collected to 30 days on PLT and red blood cell (RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables. Across the whole trial no prophylaxis saved costs compared to prophylaxis: -$1760 per patient (95% confidence interval [CI], -$3250 to -$249; p < 0.05). For autoHSCT patients there was no cost difference between arms: -$110 per patient (95% CI, -$1648 to $1565; p = 0.89). For chemo/alloHSCT patients no prophylaxis cost significantly less than prophylaxis: -$5686 per patient (95% CI, -$8580 to -$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/alloHSCT patients reduced cost differences to -$941 per patient (p = 0.21) across the whole trial and -$2927 per patient (p < 0.05) in chemo/alloHSCT subgroup. It is unclear whether a no-prophylaxis policy saves costs overall. In chemo/alloHSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In autoHSCT patients savings generated through lower PLT use in no-prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost-effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient-reported outcomes are warranted. © 2014 AABB.

Computational Analysis of Epidermal Growth Factor Receptor Mutations Predicts Differential Drug Sensitivity Profiles toward Kinase Inhibitors.

PubMed

Akula, Sravani; Kamasani, Swapna; Sivan, Sree Kanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

2018-05-01

A significant proportion of patients with lung cancer carry mutations in the EGFR kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain has been shown to cause enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less frequent (uncommon) mutations in the EGFR kinase domain with potential implications in treatment response have also been reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity or resistance. A large-scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed, and drug sensitivity profiles for each mutant toward seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity toward each drug as compared with that of adenosine triphosphate was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental, and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity toward first- and next-generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations toward multiple inhibitors, which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

SPECT/CT with 99mTc-MAA in radioembolization with 90Y microspheres in patients with hepatocellular cancer.

PubMed

Hamami, Monia E; Poeppel, Thorsten D; Müller, Stephan; Heusner, Till; Bockisch, Andreas; Hilgard, Philipp; Antoch, Gerald

2009-05-01

Radioembolization with (90)Y microspheres is a novel treatment for hepatic tumors. Generally, hepatic arteriography and (99m)Tc-macroaggregated albumin (MAA) scanning are performed before selective internal radiation therapy to detect extrahepatic shunting to the lung or the gastrointestinal tract. Whereas previous studies have used only planar or SPECT scans, the present study used (99m)Tc-MAA SPECT/CT scintigraphy (SPECT with integrated low-dose CT) to evaluate whether SPECT/CT and additional diagnostic contrast-enhanced CT before radioembolization with (90)Y microspheres are superior to SPECT or planar imaging alone for detection of gastrointestinal shunting. In a prospective study, we enrolled 58 patients (mean age, 66 y; SD, 12 y; 10 women and 48 men) with hepatocellular carcinoma who underwent hepatic arteriography and scintigraphy with (99m)Tc-MAA using planar imaging, SPECT, and SPECT with integrated low-dose CT of the upper abdomen (acquired with a hybrid SPECT/CT camera). The ability of the different imaging modalities to detect extrahepatic MAA shunting was compared. Patient follow-up of a mean of 180 d served as the standard of reference. Gastrointestinal shunting was revealed by planar imaging in 4, by SPECT in 9, and by SPECT/CT in 16 of the 68 examinations. For planar imaging, the sensitivity for detection of gastrointestinal shunting was 25%, the specificity 87%, and the accuracy 72%. For SPECT without CT, the sensitivity was 56%, the specificity 87%, and the accuracy 79%. SPECT with CT fusion had a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%. In 3 patients, MAA deposits in the portal vein could accurately be attributed to tumor thrombus only with additional information from contrast-enhanced CT. The follow-up did not show any gastrointestinal complications. SPECT with integrated low-dose CT using (99m)Tc-MAA is beneficial in radioembolization with (90)Y microspheres because it increases the sensitivity and specificity of (99m)Tc-MAA SPECT when detecting extrahepatic arterial shunting. The overall low risk of gastrointestinal complications in radioembolization may therefore be further reduced by SPECT/CT.

Quality of vision, patient satisfaction and long-term visual function after bilateral implantation of a low addition multifocal intraocular lens.

PubMed

Pedrotti, Emilio; Mastropasqua, Rodolfo; Bonetto, Jacopo; Demasi, Christian; Aiello, Francesco; Nucci, Carlo; Mariotti, Cesare; Marchini, Giorgio

2017-07-17

The aim of the current study was to compare the quality of vision, contrast sensitivity and patient satisfaction with a biaspheric, segmented, rotationally asymmetric IOL (Lentis Comfort LS-313 MF 15-Oculentis GmbH, Berlin, Germany) as opposed to those of a monofocal IOL. This prospective single-blind comparative study included two groups of patients affected by bilateral senile cataract who underwent lens extraction and IOL implantation. The first group received a bilateral implantation of a monofocal IOL, and the second group received a bilateral implantation of the Comfort IOL. Twelve months after surgery uncorrected and corrected visual acuity at different distances (30, 50, 70 cm and 4 m), defocus curve and contrast sensitivity were assessed. Patient's satisfaction and spectacle independence were evaluated by mean of the NEI RQL-42 questionnaire. No significant differences were found between the groups in terms of near vision. The group of patients implanted with a Comfort IOL obtained the best results at intermediate distances (50 and 70 cm P < .001). Both groups showed an excellent uncorrected distance visual acuity (4 m). No statistically significant differences were found in terms of corrected near, intermediate and distance visual acuity. Concerning contrast sensitivity, no statistically significant differences between the groups were observed at any cycles per degree. The NEI RQL-42 questionnaire showed statistically significant differences between the group for "near vision" (P = .015), "dependence on correction" (P = .048) and "suboptimal correction" (P < .001) subscales. Our findings indicated that the Comfort IOL +1.5 D provides a good intermediate spectacle independence together with a high quality of vision, with a low amount of subjective symptoms and a contrast sensitivity similar to those obtained with a monofocal IOL.

Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis.

PubMed

Greiner, Georg; Gurbisz, Michael; Ratzinger, Franz; Witzeneder, Nadine; Simonitsch-Klupp, Ingrid; Mitterbauer-Hohendanner, Gerlinde; Mayerhofer, Matthias; Müllauer, Leonhard; Sperr, Wolfgang R; Valent, Peter; Hoermann, Gregor

2018-03-01

The analytically sensitive detection of KIT D816V in blood and bone marrow is important for diagnosing systemic mastocytosis (SM). Additionally, precise quantification of the KIT D816V variant allele fraction (VAF) is relevant clinically because it helps to predict multilineage involvement and prognosis in cases of advanced SM. Digital PCR (dPCR) is a promising new method for sensitive detection and accurate quantification of somatic mutations. We performed a validation study of dPCR for KIT D816V on 302 peripheral blood and bone marrow samples from 156 patients with mastocytosis for comparison with melting curve analysis after peptide nucleic acid-mediated PCR clamping (clamp-PCR) and allele-specific quantitative real-time PCR (qPCR). dPCR showed a limit of detection of 0.01% VAF with a mean CV of 8.5% and identified the mutation in 90% of patients compared with 70% for clamp-PCR ( P < 0.001). Moreover, dPCR for KIT D816V was highly concordant with qPCR without systematic deviation of results, and confirmed the clinical value of KIT D816V VAF measurements. Thus, patients with advanced SM showed a significantly higher KIT D816V VAF (median, 2.43%) compared with patients with indolent SM (median, 0.14%; P < 0.001). Moreover, dPCR confirmed the prognostic significance of a high KIT D816V VAF regarding survival ( P < 0.001). dPCR for KIT D816V provides a high degree of precision and sensitivity combined with the potential for interlaboratory standardization, which is crucial for the implementation of KIT D816V allele burden measurement. Thus, dPCR is suitable as a new method for KIT D816V testing in patients with mastocytosis. © 2017 American Association for Clinical Chemistry.

The sensitivity and specificity of frozen-section histopathology in the management of benign oral and maxillofacial lesions.

PubMed

Aronovich, Sharon; Kim, Roderick Y

2014-05-01

The management of odontogenic cysts and tumors typically requires a biopsy, which may present significant challenges and prompt an additional visit to the operating room before definitive treatment. The aim of this study was to determine the validity of frozen-section diagnosis in the management of benign oral and maxillofacial lesions, allowing intraoperative diagnosis followed by definitive treatment under the same general anesthetic. A retrospective chart review of patients treated at the University of Michigan Health System was performed. Patients of all ages who had a diagnosis of a benign maxillofacial lesion by frozen-section and permanent histopathology reports were included for analysis. Patients were identified using the Current Procedural Terminology code for enucleation and curettage and International Classification of Diseases, Ninth Revision codes for benign cysts or tumors of skull, face, or lower jaw. Of 450 patients reviewed, 214 had intraoperative frozen-section examination available for comparison with permanent histopathology. There were 121 men (56.5%) and 93 women (43.5%), with a mean age of 41 years. Compared with final permanent histopathology, the overall sensitivity of frozen sections was 92.1%. Frozen-section histopathology had a sensitivity greater than 90% and a specificity greater than 95% for the diagnosis of dentigerous cyst and keratocyst odontogenic tumor. In this study of 214 patients with benign maxillofacial lesions, frozen-section histopathology was found to be a valid diagnostic modality with high sensitivity, specificity, and positive and negative predictive values. These results and analysis support the use of frozen-section histopathology for the treatment of benign maxillofacial lesions and underscore its value in the management of these lesions. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Sadness might isolate you in a non-smelling world: olfactory perception and depression

PubMed Central

Schablitzky, Sylvia; Pause, Bettina M.

2014-01-01

Major depressive disorder (MDD) occurs with a high prevalence among mental illnesses. MDD patients experience sadness and hopelessness, with blunted affective reactivity. However, such depressive episodes are also key symptoms in other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective Disorder (SAD). Moreover, depressive symptoms can also be found in healthy individuals, but are experienced as less severe or for a shorter duration than in patients. Here, it is aimed to summarize studies investigating odor perception in depression, including depressive states in healthy individuals and patient populations. Odor perception in depression has been assessed with psychophysical methods (olfactory sensitivity, odor identification, and discrimination), and odor ratings (intensity, emotional valence, familiarity). In addition, some studies investigated affective reactions to odors, and physiological and anatomical correlates of odor perception in depression. The summary reveals that MDD is associated with reduced olfactory sensitivity. However, odor identification and discrimination scores seem to be unaffected by depression. The reduced olfactory sensitivity might be associated with a reduced ability to encode olfactory information and a reduced volume of the olfactory bulb. While similar processes seem to occur in healthy individuals experiencing depressive states, they have not been observed in BPD or SAD patients. However, in order to conclude that the reduced olfactory sensitivity is directly linked to depression, it is suggested that studies should implement control measures of cognitive performances or perceptual abilities in other stimulus modalities. It is concluded that the reduced olfactory performance in MDD patients seems to be disorder-, modality-, and test-specific, and that the application of an appropriate olfactory and cognitive test-battery might be highly useful in the differential diagnosis of MDD. PMID:24570666

Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling.

PubMed

Plagnol, Vincent; Woodhouse, Samuel; Howarth, Karen; Lensing, Stefanie; Smith, Matt; Epstein, Michael; Madi, Mikidache; Smalley, Sarah; Leroy, Catherine; Hinton, Jonathan; de Kievit, Frank; Musgrave-Brown, Esther; Herd, Colin; Baker-Neblett, Katherine; Brennan, Will; Dimitrov, Peter; Campbell, Nathan; Morris, Clive; Rosenfeld, Nitzan; Clark, James; Gale, Davina; Platt, Jamie; Calaway, John; Jones, Greg; Forshew, Tim

2018-01-01

Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications.

Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling

PubMed Central

Howarth, Karen; Lensing, Stefanie; Smith, Matt; Epstein, Michael; Madi, Mikidache; Smalley, Sarah; Leroy, Catherine; Hinton, Jonathan; de Kievit, Frank; Musgrave-Brown, Esther; Herd, Colin; Baker-Neblett, Katherine; Brennan, Will; Dimitrov, Peter; Campbell, Nathan; Morris, Clive; Rosenfeld, Nitzan; Clark, James; Gale, Davina; Platt, Jamie; Calaway, John; Jones, Greg

2018-01-01

Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications. PMID:29543828

Dark-Adapted Chromatic Perimetry for Measuring Rod Visual Fields in Patients with Retinitis Pigmentosa

PubMed Central

Bennett, Lea D.; Klein, Martin; Locke, Kirsten G.; Kiser, Kelly; Birch, David G.

2017-01-01

Purpose Although rod photoreceptors are initially affected in retinitis pigmentosa (RP), the full-field of rod vision is not routinely characterized due to the unavailability of commercial devices detecting rod sensitivity. The purpose of this study was to quantify rod-mediated vision in the peripheral field from patients with RP using a new commercially available perimeter. Methods Participants had one eye dilated and dark-adapted for 45 minutes. A dark-adapted chromatic (DAC) perimeter tested 80 loci 144° horizontally and 72° vertically with cyan stimuli. The number of rod-mediated loci (RML) were analyzed based on normal cone sensitivity (method 1) and associated with full-field electroretinography (ERG) responses by Pearson's r correlation and linear regression. In a second cohort of patients with RP, RML were identified by two-color perimetry (cyan and red; method 2). The two methods for ascribing rod function were compared by Bland-Altman analysis. Results Method 1 RML were correlated with responses to the 0.01 cd.s/m2 flash (P < 0.001), while total sensitivity to the cyan stimulus showed correlation with responses to the 3.0 cd.s/m2 flash (P < 0.0001). Method 2 detected a mean of 10 additional RML compared to method 1. Conclusions Scotopic fields measured with the DAC detected rod sensitivity across the full visual field, even in some patients who had nondetectable rod ERGs. Two-color perimetry is warranted when sensitivity to the cyan stimulus is reduced to ≤20 dB to get a true estimation of rod function. Translational Relevance Many genetic forms of retinitis pigmentosa (RP) are caused by mutations in rod-specific genes. However, treatment trials for patients with RP have relied primarily on photopic (cone-mediated) tests as outcome measures because there are a limited number of available testing methods designed to evaluate rod function. Thus, efficient methods for quantifying rod-mediated vision are needed for the rapidly increasing numbers of clinical trials. PMID:28798898

Sensitivity and specificity of linear array intraoperative ultrasound in glioblastoma surgery: a comparative study with high field intraoperative MRI and conventional sector array ultrasound.

PubMed

Coburger, Jan; Scheuerle, Angelika; Kapapa, Thomas; Engelke, Jens; Thal, Dietmar Rudolf; Wirtz, Christian R; König, Ralph

2015-07-01

Linear array intraoperative ultrasound (lioUS) is an emerging technology for intracranial use. We evaluated sensitivity and specificity of lioUS to detect residual tumor in patients harboring a glioblastoma. After near total resection in 20 patients, residual tumor detection using lioUS, conventional intraoperative ultrasound (cioUS), and gadopentetic-diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced intraoperative MRI (iMRI) were compared. Sensitivity and specificity were calculated based on 68 navigated biopsies. Receiver operator characteristic (ROC) curves and correlation with histopathological findings of each imaging modality were calculated. Additionally, results were evaluated in the subgroup of recurrent disease (23 biopsies in 8 patients). Sensitivity of lioUS (76 %) was significantly higher compared with iMRI (55 %) and cioUS (24 %). Specificity of lioUS (58 %) was significantly lower than in cioUS (96 %), while there was no significant difference to iMRI (74 %). All imaging modalities correlated significantly with histopathological findings. In the subgroup of recurrent disease, sensitivity and specificity decreased in all modalities. However, cioUS showed significant lower values than iMRI and lioUS. In ROC curves, lioUS showed a higher area und the curve (AUC) in comparison with iMRI and cioUS. We found similar results in the subgroup of recurrent disease. Tumor detection using a lioUS is significantly superior to cioUS. Overall test performance in lioUS is comparable with results of iMRI. While, the latter has a higher specificity and a significantly lower sensitivity in comparison with lioUS.

Nosographic analysis of osmophobia and field testing of diagnostic criteria including osmophobia.

PubMed

Chalmer, Mona Ameri; Hansen, Thomas Folkmann; Olesen, Jes

2018-01-01

Introduction Osmophobia has been suggested as an additional symptom of migraine without aura, and a high prevalence of osmophobia of up to 50% has been reported in the literature. We conducted a nosographic study of osmophobia in all migraineurs and tension-type headache patients and a field testing of suggested diagnostic criteria of osmophobia, presented in the appendix of the second edition of The International Classification of Headache Disorders and suggested by Silva-Néto et al. and Wang et al ., in migraine without aura and tension-type headache patients (n = 1934). Materials and methods Each patient received a validated semi-structured interview. All subjects fulfilled the diagnostic criteria of the second edition of The International Classification of Headache Disorders for migraine or tension-type headache. Statistical analyses were performed using statistical software R. The statistical R package "Caret" was used to construct a confusion matrix and retrieve sensitivity, which is defined as the suggested criteria's ability to correctly diagnose migraine without aura patients, and specificity, defined as the suggested criteria's ability to not wrongly diagnose tension-type headache patients. Results Osmophobia was present in 33.5% of patients with migraine with aura, in 36.0% of patients with migraine without aura, and in 1.2% of patients with tension-type headache. All migraineurs with osmophobia also fulfilled the current criteria for migraine by having nausea or photophobia and phonophobia. The appendix criteria had a sensitivity of 0.96 and a specificity of 0.99 for migraine without aura, and a sensitivity of 0.65 and a specificity of 0.99 for probable migraine without aura. Both the criteria by Silva-Néto et al. and Wang et al. had a sensitivity of 0.98 and a specificity of 0.99 for migraine without aura, and a sensitivity of 0.66 and a specificity of 0.99 for probable migraine without aura. Discussion This study demonstrates the remarkable specificity of osmophobia. The criteria by Silva-Néto et al. and Wang et al. both had a higher sensitivity than the appendix criteria for migraine without aura; all three criteria had a low sensitivity for probable migraine without aura. However, neither the appendix criteria nor the criteria by Silva-Néto et al. or Wang et al. added any extra patients that would not have been diagnosed by the current diagnostic criteria for migraine. Osmophobia is a valuable symptom that may be useful to differentiate between migraine without aura and tension-type headache in difficult clinical cases. Conclusion Our results do not suggest that alterations of the current diagnostic criteria for migraine without aura are needed.

Evaluation of qPCR-Based Assays for Leprosy Diagnosis Directly in Clinical Specimens

PubMed Central

Sarno, Euzenir Nunes; Moraes, Milton Ozório

2011-01-01

The increased reliability and efficiency of the quantitative polymerase chain reaction (qPCR) makes it a promising tool for performing large-scale screening for infectious disease among high-risk individuals. To date, no study has evaluated the specificity and sensitivity of different qPCR assays for leprosy diagnosis using a range of clinical samples that could bias molecular results such as difficult-to-diagnose cases. In this study, qPCR assays amplifying different M. leprae gene targets, sodA, 16S rRNA, RLEP and Ag 85B were compared for leprosy differential diagnosis. qPCR assays were performed on frozen skin biopsy samples from a total of 62 patients: 21 untreated multibacillary (MB), 26 untreated paucibacillary (PB) leprosy patients, as well as 10 patients suffering from other dermatological diseases and 5 healthy donors. To develop standardized protocols and to overcome the bias resulted from using chromosome count cutoffs arbitrarily defined for different assays, decision tree classifiers were used to estimate optimum cutoffs and to evaluate the assays. As a result, we found a decreasing sensitivity for Ag 85B (66.1%), 16S rRNA (62.9%), and sodA (59.7%) optimized assay classifiers, but with similar maximum specificity for leprosy diagnosis. Conversely, the RLEP assay showed to be the most sensitive (87.1%). Moreover, RLEP assay was positive for 3 samples of patients originally not diagnosed as having leprosy, but these patients developed leprosy 5–10 years after the collection of the biopsy. In addition, 4 other samples of patients clinically classified as non-leprosy presented detectable chromosome counts in their samples by the RLEP assay suggesting that those patients either had leprosy that was misdiagnosed or a subclinical state of leprosy. Overall, these results are encouraging and suggest that RLEP assay could be useful as a sensitive diagnostic test to detect M. leprae infection before major clinical manifestations. PMID:22022631

Mannitol Enhances Antibiotic Sensitivity of Persister Bacteria in Pseudomonas aeruginosa Biofilms

PubMed Central

Barraud, Nicolas; Buson, Alberto; Jarolimek, Wolfgang; Rice, Scott A.

2013-01-01

The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF) patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichia coli by generating a proton-motive force (PMF), suggesting a potential new strategy to improve antibiotic therapy and reduce disease progression in CF. Here, we used the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa persister cells during biofilm growth. Incubation with mannitol (10–40 mM) increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of mannitol to pre-grown biofilms was able to revert the persister phenotype and improve the efficacy of tobramycin. This effect was blocked by the addition of a PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol. Addition of glucose and NaCl at high osmolarity also improved the efficacy of tobramycin although to a lesser extent compared to mannitol. Therefore, the primary effect of mannitol in reverting biofilm associated persister cells appears to be an active, physiological response, associated with a minor contribution of osmotic stress. Mannitol was tested against clinically relevant strains, showing that biofilms containing a subpopulation of persister cells are better killed in the presence of mannitol, but a clinical strain with a high resistance to tobramycin was not affected by mannitol. Overall, these results suggest that in addition to improvements in lung function by facilitating mucus clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and does so through an active, physiological response. PMID:24349568

Use of the Photo-Electromyogram to Objectively Diagnose and Monitor Treatment of Post-TBI Light Sensitivity

DTIC Science & Technology

2014-10-01

Iowa neuro -ophthalmology clinics. In addition, we can access the University of Iowa Hospital patient database by diagnosis allowing us to obtain an...remains uncut. The caudal incision is just large enough for the transmitter to pass through while the rostral incision is just large enough for the

Psychological adaptation to ICDs and the influence of anxiety sensitivity.

PubMed

Lemon, Jim; Edelman, Sarah

2007-03-01

Forty-nine patients scheduled for implantable cardioverter defibrillator (ICD) implantation completed self-report psychological questionnaires prior to surgery and at 2, 4 and 6 months after surgery. The most common psychological problem identified was anxiety, with clinically significant cases based on the Depression Anxiety and Stress Scale (DASS) ranging between 26% and 34%. Clinically significant depression ranged between 8% and 20%. Anxiety sensitivity was associated with high levels of anxiety, depression and stress at baseline, but not at follow-up assessments. It is possible that within this population anxiety sensitivity is associated with distress during high-threat situations, but the relationship diminishes once the threat has passed. In addition, the reassurance provided by the ICD may reduce negative perceptions of symptoms, promoting psychological adaptation.

Analysis of feline and canine allergen components in patients sensitized to pets.

PubMed

Ukleja-Sokołowska, Natalia; Gawrońska-Ukleja, Ewa; Żbikowska-Gotz, Magdalena; Socha, Ewa; Lis, Kinga; Sokołowski, Łukasz; Kuźmiński, Andrzej; Bartuzi, Zbigniew

2016-01-01

Component resolved allergen diagnosis allows for a precise evaluation of the sensitization profiles of patients sensitized to felines and canines. An accurate interpretation of these results allows better insight into the evolution of a given patients sensitizations, and allows for a more precise evaluation of their prognoses. 70 patients (42 women and 28 men, aged 18-65, with the average of 35.5) with a positive feline or canine allergy diagnosis were included in the research group. 30 patients with a negative allergy diagnosis were included in the control group. The total IgE levels of all patients with allergies as well as their allergen-specific IgE to feline and canine allergens were measured. Specific IgE levels to canine (Can f 1, Can f 2, Can f 3, Can f 5) and feline (Fel d 1, Fel d 2, Fel d 4) allergen components were also measured with the use of the ImmunoCap method. Monosensitization for only one canine or feline component was found in 30% of patients. As predicted, the main feline allergen was Fel d 1, which sensitized as many as 93.9% of patients sensitized to felines. Among 65 patients sensitized to at least one feline component, for 30 patients (46.2%) the only sensitizing feline component was Fel d 1. Only 19 patients in that group (63.3%) were not simultaneously sensitized to dogs and 11 (36.7%), the isolated sensitization to feline Fel d 1 notwithstanding, displayed concurrent sensitizations to one of the canine allergen components. Fel d 4 sensitized 49.2% of the research group.64.3% of patients sensitized to canine components had heightened levels of specific IgE to Can f 1. Monosensitization in that group occurred for 32.1% of the patients. Sensitization to Can f 5 was observed among 52.4% of the patients. Concurrent sensitizations to a few allergic components, not only cross-reactive but also originating in different protein families, are a significant problem for patients sensitized to animals.

Assessment of nasalance and nasality in patients with a repaired cleft palate.

PubMed

Sinko, Klaus; Gruber, Maike; Jagsch, Reinhold; Roesner, Imme; Baumann, Arnulf; Wutzl, Arno; Denk-Linnert, Doris-Maria

2017-07-01

In patients with a repaired cleft palate, nasality is typically diagnosed by speech language pathologists. In addition, there are various instruments to objectively diagnose nasalance. To explore the potential of nasalance measurements after cleft palate repair by NasalView ® , we correlated perceptual nasality and instrumentally measured nasalance of eight speech items and determined the relationship between sensitivity and specificity of the nasalance measures by receiver-operating characteristics (ROC) analyses and AUC (area under the curve) computation for each single test item and specific item groups. We recruited patients with a primarily repaired cleft palate receiving speech therapy during follow-up. During a single day visit, perceptive and instrumental assessments were obtained in 36 patients and analyzed. The individual perceptual nasality was assigned to one of four categories; the corresponding instrumental nasalance measures for the eight specific speech items were expressed on a metric scale (1-100). With reference to the perceptual diagnoses, we observed 3 nasal and one oral test item with high sensitivity. However, the specificity of the nasality indicating measures was rather low. The four best speech items with the highest sensitivity provided scores ranging from 96.43 to 100%, while the averaged sensitivity of all eight items was below 90%. We conclude that perceptive evaluation of nasality remains state of the art. For clinical follow-up, instrumental nasalance assessment can objectively document subtle changes by analysis of four speech items only. Further studies are warranted to determine the applicability of instrumental nasalance measures in the clinical routine, using discriminative items only.

Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?

PubMed

Deirmengian, Carl; Kardos, Keith; Kilmartin, Patrick; Cameron, Alexander; Schiller, Kevin; Parvizi, Javad

2014-11-01

The diagnosis of periprosthetic joint infection (PJI) remains a serious clinical challenge. There is a pressing need for improved diagnostic testing methods; biomarkers offer one potentially promising approach. We evaluated the diagnostic characteristics of 16 promising synovial fluid biomarkers for the diagnosis of PJI. Synovial fluid was collected from 95 patients meeting the inclusion criteria of this prospective diagnostic study. All patients were being evaluated for a revision hip or knee arthroplasty, including patients with systemic inflammatory disease and those already receiving antibiotic treatment. The Musculoskeletal Infection Society (MSIS) definition was used to classify 29 PJIs and 66 aseptic joints. Synovial fluid samples were tested by immunoassay for 16 biomarkers optimized for use in synovial fluid. Sensitivity, specificity, and receiver operating characteristic curve analysis were performed to assess for diagnostic performance. Five biomarkers, including human α-defensin 1-3, neutrophil elastase 2, bactericidal/permeability-increasing protein, neutrophil gelatinase-associated lipocalin, and lactoferrin, correctly predicted the MSIS classification of all patients in this study, with 100% sensitivity and specificity for the diagnosis of PJI. An additional eight biomarkers demonstrated excellent diagnostic strength, with an area under the curve of greater than 0.9. Synovial fluid biomarkers exhibit a high accuracy in diagnosing PJI, even when including patients with systemic inflammatory disease and those receiving antibiotic treatment. Considering that these biomarkers match the results of the more complex MSIS definition of PJI, we believe that synovial fluid biomarkers can be a valuable addition to the methods utilized for the diagnosis of infection. Level II, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Visual representation of statistical information improves diagnostic inferences in doctors and their patients.

PubMed

Garcia-Retamero, Rocio; Hoffrage, Ulrich

2013-04-01

Doctors and patients have difficulty inferring the predictive value of a medical test from information about the prevalence of a disease and the sensitivity and false-positive rate of the test. Previous research has established that communicating such information in a format the human mind is adapted to-namely natural frequencies-as compared to probabilities, boosts accuracy of diagnostic inferences. In a study, we investigated to what extent these inferences can be improved-beyond the effect of natural frequencies-by providing visual aids. Participants were 81 doctors and 81 patients who made diagnostic inferences about three medical tests on the basis of information about prevalence of a disease, and the sensitivity and false-positive rate of the tests. Half of the participants received the information in natural frequencies, while the other half received the information in probabilities. Half of the participants only received numerical information, while the other half additionally received a visual aid representing the numerical information. In addition, participants completed a numeracy scale. Our study showed three important findings: (1) doctors and patients made more accurate inferences when information was communicated in natural frequencies as compared to probabilities; (2) visual aids boosted accuracy even when the information was provided in natural frequencies; and (3) doctors were more accurate in their diagnostic inferences than patients, though differences in accuracy disappeared when differences in numerical skills were controlled for. Our findings have important implications for medical practice as they suggest suitable ways to communicate quantitative medical data. Copyright © 2013 Elsevier Ltd. All rights reserved.

Peripheral nerve ultrasound scoring systems: benchmarking and comparative analysis.

PubMed

Grimm, Alexander; Rattay, Tim W; Winter, Natalie; Axer, Hubertus

2017-02-01

Ultrasound of the nerves is an additive diagnostic tool to evaluate polyneuropathy. Recently, the need for standardized scoring systems has widely been discussed; different scores are described so far. Therefore, 327 patients with polyneuropathy were analyzed by ultrasound in our laboratory. Consequently, several ultrasound scoring tools were applied, i.e., the nerve pattern classification according to Padua et al. in all patients with CIDP and variants, the Bochum ultrasound score (BUS) and the neuritis ultrasound protocol in immune-mediated neuritis, the ultrasound pattern sum score, the homogeneity score, and the nerve enlargement distribution score in all neuropathies if possible. For all scores good accuracy was found. Most patients with CIDP revealed hypoechoic enlarged nerves (Class 1), the BUS/NUP was useful to identify GBS (sensitivity >85%), MMN (100%) and CIDP (>70%), while the UPSS showed high sensitivity and positive/negative predictive values (N/PPV) in the diagnosis of GBS (>70%), CIDP (>85%) and axonal non-inflammatory neuropathies (>90%). Homogeneous nerves were found in most CMT1 patients (66.7%), while immune-mediated neuropathies mostly show regional nerve enlargement. The HS was suitable to identify CMT patients with an HS ≥5 points. All scores were easily applicable with high accuracy. The former-reported results could be similarly confirmed. However, all sores have some incompleteness concerning unselected polyneuropathy population, particularly rare and focal types. Scoring systems are useful and easily applicable. They show high accuracy in certain neuropathies, but also offer some gaps and can, therefore, only be used in addition to standard diagnostic routines such as electrophysiology.

Screening for obstructive sleep apnea syndrome in patients with type 2 diabetes mellitus: a prospective study on sensitivity of Berlin and STOP-Bang questionnaires.

PubMed

Westlake, Katerina; Plihalova, Andrea; Pretl, Martin; Lattova, Zuzana; Polak, Jan

2016-10-01

Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes mellitus representing an additional risk factor for already increased cardiovascular mortality. As cardiovascular diseases are the main cause of death in this population, there is a need to identify patients with moderate to severe OSA indicated for treatment. We aimed to evaluate the performance of the Berlin, STOP, and STOP-Bang screening questionnaires in a population of patients with Type 2 diabetes mellitus. 294 consecutive patients with Type 2 diabetes mellitus filled in the questionnaires and underwent overnight home sleep monitoring using a type IV sleep monitor. Severe, moderate, and mild OSA was found in 31 (10%), 61 (21%), and 121 (41%) patients, respectively. The questionnaires showed a similar sensitivity and specificity for AHI ≥ 15: 0.69 and 0.50 for Berlin, 0.65 and 0.49 for STOP, and 0.59 and 0.68 for STOP-Bang. However, the performance of the STOP-Bang questionnaire was different in men vs. women, sensitivity being 0.74 vs. 0.29 (p < 0.05) and specificity 0.56 vs. 0.82 (p < 0.05). Even the best-performing Berlin questionnaire failed to identify 31% of patients with moderate to severe OSA as being at high risk of OSA, thus preventing them from receiving a correct diagnosis and treatment. Considering that patients with Type 2 diabetes mellitus are at high risk of cardiovascular mortality and also have a high prevalence of moderate to severe OSA, we find screening based on the questionnaires suboptimal and suggest that OSA screening should be performed using home sleep monitoring devices. Copyright © 2016 Elsevier B.V. All rights reserved.

Cost effectiveness of mesh prophylaxis to prevent parastomal hernia in patients undergoing permanent colostomy for rectal cancer.

PubMed

Lee, Lawrence; Saleem, Abdulaziz; Landry, Tara; Latimer, Eric; Chaudhury, Prosanto; Feldman, Liane S

2014-01-01

Parastomal hernia (PSH) is common after stoma formation. Studies have reported that mesh prophylaxis reduces PSH, but there are no cost-effectiveness data. Our objective was to determine the cost effectiveness of mesh prophylaxis vs no prophylaxis to prevent PSH in patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer. Using a cohort Markov model, we modeled the costs and effectiveness of mesh prophylaxis vs no prophylaxis at the index operation in a cohort of 60-year-old patients undergoing abdominoperineal resection for rectal cancer during a time horizon of 5 years. Costs were expressed in 2012 Canadian dollars (CAD$) and effectiveness in quality-adjusted life years. Deterministic and probabilistic sensitivity analyses were performed. In patients with stage I to III rectal cancer, prophylactic mesh was dominant (less costly and more effective) compared with no mesh. In patients with stage IV disease, mesh prophylaxis was associated with higher cost (CAD$495 more) and minimally increased effectiveness (0.05 additional quality-adjusted life years), resulting in an incremental cost-effectiveness ratio of CAD$10,818 per quality-adjusted life year. On sensitivity analyses, the decision was sensitive to the probability of mesh infection and the cost of the mesh, and method of diagnosing PSH. In patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer, mesh prophylaxis might be the less costly and more effective strategy compared with no mesh to prevent PSH in patients with stage I to III disease, and might be cost effective in patients with stage IV disease. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Development of a metabolic biosignature for detection of early Lyme disease.

PubMed

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Hess, Ann M; Delorey, Mark J; Mahapatra, Sebabrata; Schriefer, Martin E; Belisle, John T

2015-06-15

Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%-40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%-95%), and a specificity of 95% (90%-100%). Importantly, the metabolic biosignature correctly classified 77%-95% of the of serology negative Lyme disease patients. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining high specificity. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

M'kacher, Radhia; Bennaceur-Griscelli, Annelise; Girinsky, Theodore

Purpose: To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. Methods and Materials: Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatmentmore » (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. Results: Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; <6 kb in 18% in HL patients), increased spontaneous chromosomal abnormalities, and increased in vitro radiation sensitivity (p < 10{sup -4} each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations. Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. Conclusions: An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients.« less

Radiation exposure reduction by use of Kevlar cassettes in the neonatal nursery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herman, M.W.; Mak, H.K.; Lachman, R.S.

1987-05-01

A study was performed to determine whether the use of Kevlar cassettes in the neonatal intensive care nursery would reduce radiation exposure to patients. The radiation dose to the neonates was measured by using thermoluminescent dosimeters. In addition, the attenuation of the Kevlar cassettes and the sensitivity of the film-screen combination were compared with the previously used system. The greatest radiation reduction using a mobile X-ray unit was 27%; based on sensitivity measurements, the theoretical reduction averaged 38%. The reduction in radiation exposure resulted from reduced attenuation by the Kevlar cassette.

Radiation exposure reduction by use of Kevlar cassettes in the neonatal nursery.

PubMed

Herman, M W; Mak, H K; Lachman, R S

1987-05-01

A study was performed to determine whether the use of Kevlar cassettes in the neonatal intensive care nursery would reduce radiation exposure to patients. The radiation dose to the neonates was measured by using thermoluminescent dosimeters. In addition, the attenuation of the Kevlar cassettes and the sensitivity of the film-screen combination were compared with the previously used system. The greatest radiation reduction using a mobile X-ray unit was 27%; based on sensitivity measurements, the theoretical reduction averaged 38%. The reduction in radiation exposure resulted from reduced attenuation by the Kevlar cassette.

Is whole-body fluorine-18 fluorodeoxyglucose PET/CT plus additional pelvic images (oral hydration-voiding-refilling) useful for detecting recurrent bladder cancer?

PubMed

Yang, Zhongyi; Cheng, Jingyi; Pan, Lingling; Hu, Silong; Xu, Junyan; Zhang, Yongping; Wang, Mingwei; Zhang, Jianping; Ye, Dingwei; Zhang, Yingjian

2012-08-01

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers. From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months. Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively. PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

Molecular Tools for Diagnosis of Visceral Leishmaniasis: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

PubMed Central

de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.

2014-01-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. PMID:24829226

Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2′-deoxyguanosine by UPLC-MS/MS Analysis

PubMed Central

Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

2016-01-01

Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7−5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC. PMID:27585556

Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2‧-deoxyguanosine by UPLC-MS/MS Analysis

NASA Astrophysics Data System (ADS)

Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

2016-09-01

Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2‧-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7-5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC.

Increased pain sensitivity is not associated with electrodiagnostic findings in women with carpal tunnel syndrome.

PubMed

de la Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César; Laguarta-Val, Sofia; Alonso-Blanco, Cristina; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Pareja, Juan A

2011-01-01

To determine the differences in widespread pressure pain and thermal hypersensitivity in women with minimal, moderate, and severe carpal tunnel syndrome (CTS) and healthy controls. A total of 72 women with CTS (19 with minimal, 18 with moderate, and 35 with severe) and 19 healthy age-matched women participated. Pressure pain thresholds were bilaterally assessed over the median, ulnar, and radial nerves, the C5 to C6 zygapophyseal joint, the carpal tunnel, and the tibialis anterior muscle. In addition, warm and cold detection thresholds and heat and cold pain thresholds were bilaterally assessed over the carpal tunnel and the thenar eminence. All outcome parameters were assessed by an assessor blinded to the participant's condition. No significant differences in pain parameters among patients with minimal, moderate, and severe CTS were found. The results showed that PPT were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, C5 to C6 zygapophyseal joint, and the tibialis anterior muscle in patients with minimal, moderate, or severe CTS as compared with healthy controls (all, P<0.001). In addition, patients with CTS also showed lower heat pain threshold and reduced cold pain threshold compared with controls (P<0.001). No significant sensory differences between minimal, moderate, or severe CTS were found. The similar widespread pressure and thermal hypersensitivity in patients with minimal, moderate, or severe CTS and pain intensity suggests that increased pain sensitivity is not related to electrodiagnostic findings.

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

PubMed

Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

1982-01-01

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Incremental value of 99mTc-HYNIC-TOC SPECT/CT over whole-body planar scintigraphy and SPECT in patients with neuroendocrine tumours.

PubMed

Trogrlic, Mate; Težak, Stanko

2017-06-12

The aim of this study was to evaluate the additional value of 99m Tc-HYNIC-TOC SPECT/CT over planar whole-body (WB) scintigraphy and SPECT alone in the detection and accurate localisation of neuroendocrine tumour (NET) lesions. This study included 65 patients with a definitive histological diagnosis of NET prior to scintigraphy. Planar WB scintigraphy, SPECT, and SPECT/CT images were acquired at 4 h post-administration of 670 MBq 99m Tc-HYNIC-TOC. Additional SPECT images at 10 min after tracer administration were also acquired. Clinical and imaging follow-up findings were considered as the reference standards (minimum follow-up period, 15 months). Patient and lesion-based analyses of the efficacies of the imaging modalities were performed. While 38 patients exhibited metastasis of NETs, 27 presented no evidence of metastasis. Upon patient-based analysis, the sensitivity and specificity of SPECT/CT were found to be 88.9 and 79.3 %, respectively. The diagnostic accuracies of WB scintigraphy, 4h-SPECT, and SPECT/CT were 72.3, 73.8, and 84.6 %, respectively. The area under curve (AUC) value for SPECT/CT (0.84) was the highest, followed by those for 4h-SPECT (0.75) and WB scintigraphy (0.74). The accuracy and AUC values of SPECT/CT were significantly better compared to those of WB scintigraphy (p < 0.001), 10 min-SPECT (p < 0.001), and 4 h-SPECT (p = 0.001). The findings of SPECT/CT led to the change in treatment plan of 11 patients (16.9 %). The sensitivity and diagnostic accuracy of SPECT/CT in the evaluation of NET lesions outperforms planar WB imaging or SPECT alone.

Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome.

PubMed

Bien, C G; Mirzadjanova, Z; Baumgartner, C; Onugoren, M D; Grunwald, T; Holtkamp, M; Isenmann, S; Kermer, P; Melzer, N; Naumann, M; Riepe, M; Schäbitz, W R; von Oertzen, T J; von Podewils, F; Rauschka, H; May, T W

2017-01-01

To clarify the relevance of titres of IgG antibodies against contactin-associated protein-2 (CASPR2) in diagnosing anti-CASPR2 encephalitis and to describe features and outcomes. This was a retrospective analysis of 64 patients with CASPR2 antibodies, categorized independently as 'autoimmune encephalitis' or 'other disease'. Logistic regression methods were performed to identify potential predictors of 'autoimmune encephalitis' in addition to CASPR2 antibodies. An upfront CASPR2 antibody serum titre cut-off at ≥1:200 had a diagnostic sensitivity of 85% and a specificity of 81%. Logistic regression analyses indicated that, in addition to titre, encephalitic magnetic resonance imaging (MRI) was a significant predictor of 'autoimmune encephalitis' (Nagelkerke's R 2 = 0.81, P < 0.001) with high sensitivity (84%) and very high specificity (100%). Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2 encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2). Median modified Rankin score (mRS) at diagnosis was 3 (range 1-4). Twenty patients were male; median age was 64 (range 54-75) years; 5/15 patients with cerebrospinal fluid data had intrathecal CASPR2 antibody synthesis, and 12/19 with follow-ups >3 months (median 12 months, range 4-43 months) improved by ≥1 mRS point resulting in a median mRS of 2 (range 0-6; one death; all but one having received immunotherapy); and 2/15 patients with follow-up MRI developed hippocampal atrophy. Only higher CASPR2 serum antibody titres indicate anti-CASPR2 encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2 encephalitis has characteristic features and a favourable outcome with immunotherapy. © 2016 EAN.

Diagnostic value of a heart-type fatty acid-binding protein (H-FABP) bedside test in suspected acute coronary syndrome in primary care.

PubMed

Bruins Slot, M H E; Rutten, F H; van der Heijden, G J M G; Doevendans, P A; Mast, E G; Bredero, A C; van der Spoel, O P; Glatz, J F C; Hoes, A W

2013-09-30

To determine the diagnostic accuracy of a rapid heart-type fatty acid-binding protein (H-FABP) test in patients suspected of acute coronary syndrome (ACS) in primary care. General practitioners included 298 patients suspected of ACS. In all patients, whether referred to hospital or not, ECG and cardiac biomarker testing was performed. ACS was determined in accordance with international guidelines. Multivariate analysis was used to determine the value of H-FABP in addition to clinical findings. Mean patient age was 66 years (SD 14), 52% was female and 66 patients (22%) were diagnosed with ACS. The H-FABP bedside test was performed within 24h (median 3.1, IQR 1.5 to 7.1) after symptom onset. The positive predictive value (PPV) of H-FABP was 65% (95% confidence interval (CI) 50-78). The negative predictive value (NPV) was 85% (95% CI 80-88). Sensitivity was 39% (29-51%) and specificity 94% (90-96%). Within 6h after symptom onset, the PPV was 72% (55-84) and the NPV was 83% (77-88), sensitivity 43% (31-57%) and specificity 94% (89-97%). Adding the H-FABP test to a diagnostic model for ACS led to an increase in the area under the receiver operating curve from 0.66 (95% CI 0.58-0.73) to 0.75 (95% CI 0.68-0.82). The H-FABP rapid test provides modest additional diagnostic certainty in primary care. It cannot be used to safely exclude rule out ACS. The test can only be used safely in patients otherwise NOT referred to hospital by the GP, as an extra precaution not to miss ACS ('rule in'). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Intestinal Microbiota Distinguish Gout Patients from Healthy Humans

PubMed Central

Guo, Zhuang; Zhang, Jiachao; Wang, Zhanli; Ang, Kay Ying; Huang, Shi; Hou, Qiangchuan; Su, Xiaoquan; Qiao, Jianmin; Zheng, Yi; Wang, Lifeng; Koh, Eileen; Danliang, Ho; Xu, Jian; Lee, Yuan Kun; Zhang, Heping

2016-01-01

Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota. PMID:26852926

The financial and health burden of diabetic ambulatory care sensitive hospitalisations in Mexico.

PubMed

Lugo-Palacios, David G; Cairns, John

2016-01-01

To estimate the financial and health burden of diabetic ambulatory care sensitive hospitalisations (ACSH) in Mexico during 2001-2011. We identified ACSH due to diabetic complications in general hospitals run by local health ministries and estimated their financial cost using diagnostic related groups. The health burden estimation assumes that patients would not have experienced complications if they had received appropriate primary care and computes the associated Disability-Adjusted Life Years (DALYs). The financial cost of diabetic ACSH increased by 125% in real terms and their health burden in 2010 accounted for 4.2% of total DALYs associated with diabetes in Mexico. Avoiding preventable hospitalisations could free resources within the health system for other health purposes. In addition, patients with ACSH suffer preventable losses of health that should be considered when assessing the performance of any primary care intervention.

Tailoring Antibody Testing and How to Use it in the Calculated Panel Reactive Antibody Era: The Northwestern University Experience

PubMed Central

Tambur, Anat R.; Leventhal, Joseph; Kaufman, Dixon B.; Friedewald, John; Miller, Joshua; Abecassis, Michael M.

2014-01-01

Background Patients with human leukocyte antigen antibodies constitute a significantly disadvantaged population among those awaiting renal transplantation. We speculated that more understanding of the patients’ antibody makeup would allow a more “immunologic” evaluation of crossmatch data, facilitate the use of virtual crossmatch (XM), and lead to more transplantability of these patients. Methods We retrospectively compared the transplantability and transplant outcome of two consecutive patient populations transplanted in our center. Group I (n=374) was evaluated using solid-phase base testing for determination of percentage panel reactive antibody (“PRA screen”) with limited antibody identification testing. Group II (n=333) was tested in a more comprehensive manner with major emphasis on antibody identification, antibody strength assignment, and the use of pronase for crossmatch. Results Given this approach, 49% (166/333) of the transplanted patients in group II were sensitized compared with 40% (150/374) of the recipients in group I; P=0.012. Transplant outcome at 1-year posttransplant was similar in both groups. Conclusions We conclude that comprehensive evaluation of human leukocyte antigen sensitization and application of immunologic in analyzing compatibility between donor and recipient can increase the transplantability of sensitized patients while maintaining similar outcome. Our approach is in line with United Network for Organ Sharing new guidelines for calculated panel reactive antibody and virtual XM analysis. We hope this report will prompt additional transplant programs to consider how they will use the new United Network for Organ Sharing algorithms. PMID:18946342

Half-Unit Insulin Pens: Disease Management in Patients With Diabetes Who Are Sensitive to Insulin.

PubMed

Klonoff, David C; Nayberg, Irina; Stauder, Udo; Oualali, Hamid; Domenger, Catherine

2017-05-01

Insulin pens represent a significant technological advancement in diabetes management. While the vast majority have been designed with 1U-dosing increments, improved accuracy and precision facilitated by half-unit increments may be particularly significant in specific patients who are sensitive to insulin. These include patients with low insulin requirements and in those requiring more precise dose adjustments, such as the pediatric patient population. This review summarized functional characteristics of insulin half-unit pens (HUPs) and their effect on user experience. The literature search was restricted to articles published in English between January 1, 2000, and January 1, 2015. A total of 17 publications met the set criteria and were included in the review. Overall, studies outlined characteristics for 4 insulin HUPs. Based on their functionality, the pens were generally similar and all met the ISO 11608-1 criteria for accuracy. However, some had specific advantageous features in terms of size, weight, design, dialing torque, and injection force. Although limited, the currently available user preference studies in children and adolescents with diabetes and their carers suggest that the selection of an HUP is likely to be influenced by a combination of factors such as these, in addition to the prescribed insulin and dosing regimen. Insulin HUPs are likely to be a key diabetes management tool for patients who are sensitive to insulin; specific pen features may further advance diabetes management in these populations.

Effect of Pioglitazone on Cardio-Metabolic Risk in Patients with Obstructive Sleep Apnea

PubMed Central

Liu, Alice; Abbasi, Fahim; Kim, Sun H.; Ariel, Danit; Lamendola, Cindy; Cardell, James; Xu, Shiming; Patel, Shailja; Tomasso, Vanessa; Mojaddidi, Hafasa; Grove, Kaylene; Tsao, Philip S.; Kushida, Clete A.; Reaven, Gerald M.

2017-01-01

Prevalence of insulin resistance is increased in patients with obstructive sleep apnea (OSA). Since insulin resistance is an independent predictor of cardiovascular disease (CVD), this study was initiated to see if pioglitazone administration would improve insulin sensitivity, and thereby decrease risk of CVD in overweight/obese, nondiabetic, insulin-resistant patients with untreated OSA. Patients (n=30) were administered pioglitazone (45 mg/day) for 8 weeks, and measurements were made before and after intervention of insulin action (insulin-mediated glucose uptake by the insulin suppression test), C-reactive protein, lipid/lipoprotein profile, and gene expression profile of peri-umbilical subcutaneous fat tissue. Insulin sensitivity increased 31% (p<0.001) among pioglitazone-treated individuals, associated with a decrease in C-reactive protein concentration (p≤ 0.001), a decrease in plasma triglyceride and increase in high-density lipoprotein cholesterol concentrations (p≤ 0.001), accompanied by significant changes in apolipoprotein A1 and B concentrations and lipoprotein subclasses known to decrease CVD risk. In addition, subcutaneous adipose tissue gene expression profile showed a 1.6-fold (p<0.01) increase in GLUT4 expression, as well as decreased expression in 5 of 9 inflammatory genes (p<0.05). In conclusion, enhanced insulin sensitivity can significantly decrease multiple cardio-metabolic risk factors in patients with untreated OSA, consistent with the view that coexisting insulin resistance plays an important role in the association between OSA and increased risk of CVD. PMID:28219664

Use of Multiplex Real-Time PCR To Diagnose Scrub Typhus.

PubMed

Tantibhedhyangkul, Wiwit; Wongsawat, Ekkarat; Silpasakorn, Saowaluk; Waywa, Duangdao; Saenyasiri, Nuttawut; Suesuay, Jintapa; Thipmontree, Wilawan; Suputtamongkol, Yupin

2017-05-01

Scrub typhus, caused by Orientia tsutsugamushi , is a common cause of acute undifferentiated febrile illness in the Asia-Pacific region. However, its nonspecific clinical manifestation often prevents early diagnosis. We propose the use of PCR and serologic tests as diagnostic tools. Here, we developed a multiplex real-time PCR assay using hydrolysis (TaqMan) probes targeting O. tsutsugamushi 47-kDa, groEL , and human interferon beta (IFN-β gene) genes to improve early diagnosis of scrub typhus. The amplification efficiency was higher than 94%, and the lower detection limit was 10 copies per reaction. We used a human gene as an internal DNA quality and quantity control. To determine the sensitivity of this PCR assay, we selected patients with confirmed scrub typhus who exhibited a clear 4-fold increase in the level of IgG and/or IgM. The PCR assay result was positive in 45 of 52 patients, indicating a sensitivity of 86.5% (95% confidence interval [CI]: 74.2 to 94.4). The PCR assessment was negative for all 136 non-scrub typhus patients, indicating a specificity of 100% (95% CI: 97.3 to 100). In addition, this test helped diagnose patients with inconclusive immunofluorescence assay (IFA) results and using single blood samples. In conclusion, the real-time PCR assay proposed here is sensitive and specific in diagnosing scrub typhus. Combining PCR and serologic tests will improve the diagnosis of scrub typhus among patients presenting with acute febrile illness. Copyright © 2017 American Society for Microbiology.

A cost-effectiveness analysis of parecoxib in the management of postoperative pain in the Greek health care setting.

PubMed

Athanasakis, Kostas; Petrakis, Ioannis; Vitsou, Elli; Pimenidou, Apostolia; Kyriopoulos, John

2013-08-01

Postoperative pain management represents a significant factor of morbidity and reduced quality of life for patients, as well as a situation that substantially increases perioperative costs. Available analgesia treatments improve patient outcomes and reduce resource use associated with pain management, although with varying costs and adverse effects. The aim of this analysis was to assess the costs and patient outcomes of parecoxib used in combination with opioids versus use of opioids alone (monotherapy) in the postoperative treatment of surgical patients in Greece. A model comparing parecoxib plus opioid treatment versus opioids alone was developed that simulated the first 3 days postsurgery. Clinical efficacy was based on a Phase III, randomized, double-blind, clinical trial that also provided the frequencies of the occurrence of clinically meaningful events (CMEs) related to opioid use for both treatment arms. Resource use associated with each CME was elicited via strictly structured questionnaire-based interviews conducted by a panel of experts (surgeons and anesthesiologists), and costs were determined from the perspective of Social Insurance in Greece (2012 euros). Treatment effectiveness was calculated in summed pain intensity scores. A series of 1-way sensitivity analyses were conducted to check the robustness of the outcomes. Patients treated with parecoxib plus opioids had lower summed pain intensity scores (59.20 vs 80.80) and fewer CMEs (0.62 vs 1.04 per patient) compared with opioids alone for a 3-day period. This outcome led to a full offset of the excess cost of the addition of parecoxib and led to potential savings of €858 per patient compared with opioid use alone. Savings were mainly attributable to decreased CMEs due to reduced intensive care unit and general ward bed-days as well as to reduced physician and nurse time. Results were sensitive with regard to probabilities of occurrence or co-occurrence of CMEs (≥2 CMEs occurring simultaneously), although only to a small extent. Medication costs had a minimal impact on the results of the sensitivity analysis. Parecoxib may be a useful addition to opioid treatment by improving postoperative analgesic management, reducing opioid-related adverse events, and lowering per-patient treatment costs. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Visual performance after the implantation of a new trifocal intraocular lens

PubMed Central

Vryghem, Jérôme C; Heireman, Steven

2013-01-01

Purpose To evaluate the subjective and objective visual results after the implantation of a new trifocal diffractive intraocular lens. Methods A new trifocal diffractive intraocular lens was designed combining two superimposed diffractive profiles: one with +1.75 diopters (D) addition for intermediate vision and the other with +3.50 D addition for near vision. Fifty eyes of 25 patients that were operated on by one surgeon are included in this study. The uncorrected and best distance-corrected monocular and binocular, near, intermediate, and distance visual acuities, contrast sensitivity, and defocus curves were measured 6 months postoperatively. In addition to the standard clinical follow-up, a questionnaire evaluating individual satisfaction and quality of life was submitted to the patients. Results The mean age of patients at the time of surgery was 70 ± 10 years. The mean uncorrected and corrected monocular distance visual acuity (VA) were LogMAR 0.06 ± 0.10 and LogMAR 0.00 ± 0.08, respectively. The outcomes for the binocular uncorrected distance visual acuity were almost the same (LogMAR −0.04 ± 0.09). LogMAR −010 ± 0.15 and 0.02 ± 0.06 were measured for the binocular uncorrected intermediate and near VA, respectively. The distance-corrected visual acuity was maintained in mesopic conditions. The contrast sensitivity was similar to that obtained after implantation of a bifocal intraocular lens and did not decrease in mesopic conditions. The binocular defocus curve confirms good VA even in the intermediate distance range, with a moderate decrease of less than LogMAR 0.2 at −1.5 D, with respect to the best distance VA at 0 D defocus. Patient satisfaction was high. No discrepancy between the objective and subjective outcomes was evidenced. Conclusion The introduction of a third focus in diffractive multifocal intraocular lenses improves the intermediate vision with minimal visual discomfort for the patient. PMID:24124348

Interpersonal sensitivity mediates the effects of child abuse and affective temperaments on depressive symptoms in the general adult population.

PubMed

Otsuka, Ayano; Takaesu, Yoshikazu; Sato, Mitsuhiko; Masuya, Jiro; Ichiki, Masahiko; Kusumi, Ichiro; Inoue, Takeshi

2017-01-01

Recent studies have suggested that multiple factors interact with the onset and prognosis of major depressive disorders. In this study, we investigated how child abuse, affective temperaments, and interpersonal sensitivity are interrelated, and how they affect depressive symptoms in the general adult population. A total of 415 volunteers from the general adult population completed the Patient Health Questionnaire-9, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which are all self-administered questionnaires. Data were subjected to structural equation modeling (Mplus), and single and multiple regression analyses. The effect of child abuse on depressive symptoms was mediated by interpersonal sensitivity and 4 affective temperaments, including depressive, cyclothymic, anxious, and irritable temperaments. In addition, the effect of these temperaments on depressive symptoms was mediated by interpersonal sensitivity, indicating the indirect enhancement of depressive symptoms. In contrast to these 4 temperaments, the hyperthymic temperament did not mediate the effect of child abuse on depressive symptoms; its effect was not mediated by interpersonal sensitivity. However, a greater hyperthymic temperament predicted decreased depressive symptoms and interpersonal sensitivity, independent of any mediation effect. Because this is a cross-sectional study, long-term prospective studies are necessary to confirm its findings. Therefore, recall bias should be considered when interpreting the results. As the subjects were adults from the general population, the results may not be generalizable towards all patients with major depression. This study suggests that child abuse and affective temperaments affect depressive symptoms partly through interpersonal sensitivity. Interpersonal sensitivity may have a major role in forming the link between abuse, affective temperament, and depression.

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

PubMed

Fürbass, F; Ossenblok, P; Hartmann, M; Perko, H; Skupch, A M; Lindinger, G; Elezi, L; Pataraia, E; Colon, A J; Baumgartner, C; Kluge, T

2015-06-01

A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases.

PubMed

Naessens, James M; Visscher, Sue L; Peterson, Stephanie M; Swanson, Kristi M; Johnson, Matthew G; Rahman, Parvez A; Schindler, Joe; Sonneborn, Mark; Fry, Donald E; Pine, Michael

2015-08-01

Assess algorithms for linking patients across de-identified databases without compromising confidentiality. Hospital discharges from 11 Mayo Clinic hospitals during January 2008-September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications. © Health Research and Educational Trust.

Hybrid Parallel-Slant Hole Collimators for SPECT Imaging

NASA Astrophysics Data System (ADS)

Bai, Chuanyong; Shao, Ling; Ye, Jinghan; Durbin, M.; Petrillo, M.

2004-06-01

We propose a new collimator geometry, the hybrid parallel-slant (HPS) hole geometry, to improve sensitivity for SPECT imaging with large field of view (LFOV) gamma cameras. A HPS collimator has one segment with parallel holes and one or more segments with slant holes. The collimator can be mounted on a conventional SPECT LFOV system that uses parallel-beam collimators, and no additional detector or collimator motion is required for data acquisition. The parallel segment of the collimator allows for the acquisition of a complete data set of the organs-of-interest and the slant segments provide additional data. In this work, simulation studies of an MCAT phantom were performed with a HPS collimator with one slant segment. The slant direction points from patient head to patient feet with a slant angle of 30/spl deg/. We simulated 64 projection views over 180/spl deg/ with the modeling of nonuniform attenuation effect, and then reconstructed images using an MLEM algorithm that incorporated the hybrid geometry. It was shown that sensitivity to the cardiac region of the phantom was increased by approximately 50% when using the HPS collimator compared with a parallel-hole collimator. No visible artifacts were observed in the myocardium and the signal-to-noise ratio (SNR) of the myocardium walls was improved. Compared with collimators with other geometries, using a HPS collimator has the following advantages: (a) significant sensitivity increase; (b) a complete data set obtained from the parallel segment that allows for artifact-free image reconstruction; and (c) no additional collimator or detector motion. This work demonstrates the potential value of hybrid geometry in collimator design for LFOV SPECT imaging.

The role of natural color additives in food allergy.

PubMed

Lucas, C D; Hallagan, J B; Taylor, S L

2001-01-01

A critical evaluation of the available information demonstrates that reactions to natural color additives are rare. Studies of turmeric and carotenoid pigments administered in mixtures with other food colorings failed to definitely identify reactions to either color additive. For carotenoids, the one case report of an adverse reaction was not conclusive. An anaphylactic reaction to saffron does suggest an IgE-mediated reaction, but the high use of saffron as compared with this single report of an adverse reaction suggests that sensitivity to saffron is extremely rare. Numerous reports of reactions to grapes or grape products have been reported in the literature, but no reports of sensitivities to grape skin extract or grape color extract were found. In rare cases, annatto dye may provoke a severe, adverse reaction in individuals with an uncommon hypersensitivity, and may aggravate the symptoms of patients suffering from recurrent urticaria. In its long history of use, there has been only one reported case of anaphylaxis resulting from the ingestion of annatto. Studies designed to investigate the role of annatto in recurrent urticaria sufferers were limited due to the absence of double-blind challenge and placebo controls. A number of cases of adverse reactions to carmine following ingestion have been reported in the literature. These adverse reactions suggest an IgE-mediated hypersensitivity. In many of the reported cases, the cause of sensitization to carmine was topical exposure from the use of carmine-containing cosmetics or occupational exposure to carmine and not from ingestion of carmine-containing foods and beverages. Following sensitization, affected individuals would be sensitive to carmine and the amounts present in foods and beverages could elicit allergic reactions. It is not known whether all individuals with carmine sensitivity induced through topical use are sensitive to the ingestion of carmine in foods. However, reactions to carmine solely because of ingestion are likely to be exceedingly rare due to the low use levels of carmine in foods and beverages. Despite their widespread use in food products, few reports of allergic reactions following ingestion have been reported for the majority of natural color additives. It is concluded that the ingestion of natural color additives presents a very low risk of provoking adverse reactions.

Brain imaging of pain sensitization in patients with knee osteoarthritis.

PubMed

Pujol, Jesus; Martínez-Vilavella, Gerard; Llorente-Onaindia, Jone; Harrison, Ben J; López-Solà, Marina; López-Ruiz, Marina; Blanco-Hinojo, Laura; Benito, Pere; Deus, Joan; Monfort, Jordi

2017-09-01

A relevant aspect in osteoarthritic pain is neural sensitization. This phenomenon involves augmented responsiveness to painful stimulation and may entail a clinically worse prognosis. We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis. Sixty patients were recruited and pain sensitization was clinically defined on the basis of regional spreading of pain (spreading sensitization) and increased pain response to repeated stimulation (temporal summation). Functional magnetic resonance imaging testing involved assessing brain responses to both pressure and heat stimulation. Thirty-three patients (55%) showed regional pain spreading (simple sensitization) and 19 patients (32%) showed both regional spreading and temporal summation. Sensitized patients were more commonly women. Direct painful pressure stimulation of the joint (articular interline) robustly activated all of the neural elements typically involved in pain perception, but did not differentiate sensitized and nonsensitized patients. Painful pressure stimulation on the anterior tibial surface (sensitized site) evoked greater activation in sensitized patients in regions typically involved in pain and also beyond these regions, extending to the auditory, visual, and ventral sensorimotor cortices. Painful heat stimulation of the volar forearm did not discriminate the sensitization phenomenon. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT)

PubMed Central

Cassiday, Pamela K.; Pawloski, Lucia C.; Tatti, Kathleen M.; Martin, Monte D.; Briere, Elizabeth C.; Tondella, M. Lucia; Martin, Stacey W.

2018-01-01

Introduction The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Methods Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2–4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods—pertussis culture as the “gold standard,” composite reference standard analysis (CRS), and latent class analysis (LCA). Results Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Conclusions Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis. PMID:29652945

Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization.

PubMed

Ónodi-Nagy, Katinka; Kinyó, Ágnes; Meszes, Angéla; Garaczi, Edina; Kemény, Lajos; Bata-Csörgő, Zsuzsanna

2015-01-01

It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis. Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin's main antigens. Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients. Our data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.

Diagnostic value of isoproterenol testing in arrhythmogenic right ventricular cardiomyopathy.

PubMed

Denis, Arnaud; Sacher, Frédéric; Derval, Nicolas; Lim, Han S; Cochet, Hubert; Shah, Ashok J; Daly, Matthew; Pillois, Xavier; Ramoul, Khaled; Komatsu, Yuki; Zemmoura, Adlane; Amraoui, Sana; Ritter, Philippe; Ploux, Sylvain; Bordachar, Pierre; Hocini, Mélèze; Jaïs, Pierre; Haïssaguerre, Michel

2014-08-01

Although the Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) have recently been updated, the diagnosis remains challenging in the early stages. The aim of this study was to evaluate the diagnostic value of β-adrenergic stimulation in ARVC. We evaluated 412 consecutive patients (213 men, age 41.5±16 years) referred for premature ventricular contractions evaluation or suspected ARVC. Isoproterenol testing was performed with continuous infusion of isoproterenol (45 μg/min) for 3 minutes. It was considered positive if there were either (1) polymorphic premature ventricular contractions with ≥1 couplet or (2) sustained or nonsustained ventricular tachycardia with left bundle branch block excluding right ventricular outflow tract ventricular tachycardia. ARVC was diagnosed in 35 patients at initial evaluation (23 men, aged 42±15 years). Isoproterenol testing was positive in 32 of 35 (91.4%) patients with ARVC and in 42 of 377 (11.1%) patients without ARVC (P<0.0001). Sensitivity, specificity, positive, and negative predictive values of isoproterenol testing to diagnose ARVC were 91.4%, 88.9%, 43.2%, and 99.1%, respectively. During a mean follow-up period of 5.6±4.4 years, 6 additional patients met diagnostic criteria for ARVC. Importantly, initial isoproterenol testing was positive in 6 of 6 (100%) of these patients. Survival free from ARVC diagnosis was significantly lower in the positive isoproterenol group than in the negative isoproterenol group (P<0.0001, exact log-rank test). Ventricular arrhythmogenicity during isoproterenol testing is highly sensitive (sensitivity, 91.4%) for the diagnosis of ARVC, particularly in its early stages. © 2014 American Heart Association, Inc.

A methodological approach based on gold-nanoparticles followed by matrix assisted laser desorption ionization time of flight mass spectrometry for the analysis of urine profiling of knee osteoarthritis.

PubMed

López-Cortés, Rubén; Formigo, Jacobo; Reboiro-Jato, Miguel; Fdez-Riverola, Florentino; Blanco, Francisco J; Lodeiro, Carlos; Oliveira, Elisabete; Capelo, J L; Santos, H M

2016-04-01

The aim of this work is to develop a nanoparticle-based methodology to find out biomarkers of diagnostic for knee osteoarthritis, KOA, through the use of matrix assisted laser desorption ionization time-of-flight-based mass spectrometry profiling. Urine samples used for this study were obtained from KOA patients (42 patients), patients with prosthesis (58 patients), and controls (36 individuals) with no history of joint disease. Gold-nano particle MALDI-based urine profiling was optimized and then applied over the 136 individuals. Jaccard index and 10 different classifiers over MALDI MS datasets were used to find out potential biomarkers. Then, the specificity and sensitivity of the method were evaluated. The presence of ten m/z signals as potential biomarkers in the healthy versus non-healthy approach suggests that patients (KOA and prosthesis) are differentiable from the healthy volunteers through profiling. The automatic diagnostic study confirmed these preliminary conclusions. The sensitivity and the specificity for the urine profiling criteria here reported, achieved by the C4.5 classifier, is 97% and 69% respectively. Thus, it is confirmed the utility of the method proposed in this work as an additional fast, non-expensive and robust test for KOA diagnostic. When the proposed method is compared with those used in common practice it is found that sensitivity is the highest, thus with a low false negative rate for diagnostic KOA patients in the population studied. Specificity is lower but in the range accepted for diagnostic objectives. Copyright © 2016. Published by Elsevier B.V.

Underestimation of substance abuse in psychiatric patients by conventional hospital screening.

PubMed

Reidy, Lisa J; Junquera, Patricia; Van Dijck, Karolien; Steele, Bernard W; Nemeroff, Charles B

2014-12-01

Psychiatric diagnosis mainly relies on behavioral signs and symptoms. Substance abuse can mimic the clinical presentation of primary psychiatric disorders and can also complicate the management of psychiatric patients. The reliability and accuracy of urine toxicology is a vital tool in the optimal treatment of these patients. Current demographics of substance abuse suggest that in addition to the most conventional drugs of abuse (e.g. cocaine, cannabis) that are of concern to treating physicians, prescription medications and new designer drugs also should be when evaluating patients who present with symptoms of psychosis/drug addiction or altered mental status. Urine samples from 220 psychiatric inpatients admitted to either an acute drug and alcohol unit or acute psychiatric unit were analyzed for drugs by the standard hospital assay (KIMS) and by a more sensitive ELISA and GC-MS basic drug screening protocol. The standard hospital toxicology (KIMS) was inferior to the ELISA and GC-MS methods in terms of both assay sensitivity and in detecting a broader number of drugs. The KIMS tests failed to identify opiates and amphetamine/methamphetamine in 50% of the patients. The KIMS screen did not identify zolpidem, buprenorphine and a number of synthetic drugs of abuse including cathinone and tryptamines. In order to reliably identify substance abuse in patients with altered mental status in inpatient settings, analytical methodologies with adequate assay sensitivity and range to detect the vast majority of commonly abused illicit drugs and prescription medications are required for optimal clinical assessment and treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

The frail elderly: a matter of caring.

PubMed

Erlen, Judith A

2007-01-01

Nurses caring for patients with orthopaedic problems often encounter elderly patients in their caseload. These patients have variable levels of functioning; some may be frail and, therefore, require greater assistance and possibly more time with their care. This loss of function and need for more assistance increases their vulnerability and creates challenges for nurses and other healthcare providers who are delivering patient care. This article offers a brief description of the frail elderly and examines their increasing vulnerability and their need for additional protection, preserving their dignity and respecting their autonomy, and how caring helps to guide nurses in addressing the special needs of this particularly vulnerable patient population. Sensitivity, patience, trust, compassion, and clinical competence matter when caring for the frail elderly.

The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.

PubMed

Lee, Jinwoo; Choi, Sun Mi; Lee, Chang-Hoon; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

2017-06-01

Diagnosis of intrathoracic tuberculosis (TB) lymphadenitis remains a challenge because of difficulties in obtaining adequate tissue and the lack of a sensitive test. Recently, Xpert MTB/RIF assay is being used for rapid diagnosis of pulmonary TB, but it has not yet been widely validated in intrathoracic TB lymphadenitis. The aim of this study was to assess the additional role of Xpert MTB/RIF in diagnosing intrathoracic TB lymphadenitis using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen. Consecutive patients who underwent Xpert MTB/RIF assay using EBUS-TBNA specimen from January 2012 and November 2013 at a tertiary referral hospital were recruited. Among them, the cases with malignant lymph nodes were excluded. Among 73 patients, 13 (17.8%) cases were diagnosed with intrathoracic TB lymphadenitis. In detail, 10 patients were diagnosed using conventional methods only (histology or AFB culture) and 3 patients were additionally diagnosed when adding Xpert MTB/RIF assay. The median time to diagnosis using Xpert MTB/RIF (1 day) was shorter than conventional methods (3 days for histology, 14 days for AFB culture). Rifampin resistance was not detected in any patients. In patients with enlarged intrathoracic lymph nodes and low suspicion of malignancy, combination of conventional diagnostic methods with Xpert MTB/RIF could lead to additional and rapid diagnosis of intrathoracic TB lymphadenitis. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Polysensitization and individual susceptibility to allergic contact dermatitis.

PubMed

Gosnell, Amy L; Schmotzer, Brian; Nedorost, Susan T

2015-01-01

Patients with allergic contact dermatitis to 1 antigen have been shown to be at increased risk of developing delayed type hypersensitivity reactions to additional antigens. Both environmental and genetic factors likely influence the risk of sensitization. The aim of this study was to determine whether polysensitization occurs at a higher frequency than would be expected based on chance and whether polysensitization occurs more often in subsets of patients with hand involvement and atopic dermatitis. From a database of patch test results from a single practitioner, the probability of having positive reactions to 3 or more unrelated allergens was calculated under the assumption that positive reactions are independent and compared with the observed proportion having positive reactions to 3 or more unrelated allergens. The analysis was repeated excluding patients with leg involvement as a proxy for venous insufficiency dermatitis. The proportion of patients from the polysensitized and nonpolysensitized cohorts with either hand involvement or a history of atopic dermatitis was also calculated. Polysensitization occurs more often than expected based on chance. Polysensitized patients were more likely to have hand dermatitis. Atopic dermatitis was not significantly associated with polysensitization in this analysis. Polysensitized individuals may represent a phenotype with increased genetic susceptibility to sensitization.

[RAGWEED ALLERGY IN THE SOUTH OF RUSSIA - IN THE CHECHEN REPUBLIC].

PubMed

Macharadze, D; Janaeva, H; Avilov, K

2017-05-01

Allergy to ragweed pollen and other weeds is a global problem due to the rapid spread of these grasses around the world. In addition, pollen of short ragweed (Ambrosia, Amb) and mugwort (Artemisia, Art) - one of the main causes of respiratory allergy - seasonal allergic rhinoconjunctivitis (hay fever) with/without bronchial asthma patients living in the South of Russia. Epidemiological studies on the prevalence of Allergy to Amb and Art among patients living in Chechen Republic, absent. Aim - of this retrospective study was to investigate the prevalence of sensitization to weed pollen in patients of Chechnya. We surveyed аllergy (skin prick tests with 13 inhalant allergens) from 845 patients aged 4-68 years, in Urus-Martan for the period 2013-2016 yrs. Polisensitization was defined as the presence of positive skin tests to 2 or more extracts of different groups of allergens. ~26% and 21% of patients in the Chechen Republic have an allergy to Amb and Art, respectively. Further studies at the molecular level will help to establish the geographical variation of the sensitization profile to the major component of Amb and Art, which could have clinical significance in the proper selection of specific immunotherapy.

Cost-effectiveness of one-time genetic testing to minimize lifetime adverse drug reactions.

PubMed

Alagoz, O; Durham, D; Kasirajan, K

2016-04-01

We evaluated the cost-effectiveness of one-time pharmacogenomic testing for preventing adverse drug reactions (ADRs) over a patient's lifetime. We developed a Markov-based Monte Carlo microsimulation model to represent the ADR events in the lifetime of each patient. The base-case considered a 40-year-old patient. We measured health outcomes in life years (LYs) and quality-adjusted LYs (QALYs) and estimated costs using 2013 US$. In the base-case, one-time genetic testing had an incremental cost-effectiveness ratio (ICER) of $43,165 (95% confidence interval (CI) is ($42,769,$43,561)) per additional LY and $53,680 per additional QALY (95% CI is ($53,182,$54,179)), hence under the base-case one-time genetic testing is cost-effective. The ICER values were most sensitive to the average probability of death due to ADR, reduction in ADR rate due to genetic testing, mean ADR rate and cost of genetic testing.

Antibiogram for Periprosthetic Infections: A Tool for Better Informed Selection of Empiric Antibiotics for Surgical Site Infections.

PubMed

Chidester, Jeremy R; Danci, Ioana; Lewis, Priya; Biskup, Nataliya; Kim, Hahns; Gupta, Subhas

2016-05-01

Periprosthetic infection after breast reconstruction is not an uncommon complication, with incidence up to 24%. These infections are often treated empirically without knowing the causative bacteria or its sensitivities to various antibiotics. Even if cultures are obtained, results may not be available for several days. A retrospective chart review of 553 patients at a single institution between January 2009 and July 2014 was performed, identifying patients who (1) underwent implant-based breast reconstruction and subsequently suffered an infection and (2) had cultures available with sensitivities. We reviewed patient demographics, implant characteristics, prophylactic intravenous antibiotics, oral antibiotic maintenance used, microbiologic details, and outcomes. The goal was to identify the most common causative bacteria, as well as their sensitivities to commonly used antibiotics, to help guide antibiotic decision-making. Of the 553 patients who underwent implant-based reconstruction, 114 (20.6%) patients suffered periprosthetic infections. Of these patients, 32 (28.1%) patients (56 reconstructions, with 33 tissue expanders and 23 implants) had cultures performed revealing 43 bacterial species, with the most common being Staphylococcus aureus (23.2%) and Pseudomonas aeruginosa (26.8%). Ceftazidime and piperacillin/tazobactam were equally effective covering 100% of Pseudomonas, enteric, and atypical organisms (P = 1), whereas vancomycin covered 100% of gram-positive organisms. Trimethoprim/sulfamethoxazole covered 100% of S. aureus, whereas clindamycin only covered 71% of S. aureus (P = 0.03). Additionally, trimethoprim/sulfamethoxazole was better able to cover atypical and enteric organisms. Ciprofloxacin covered 71% of Pseudomonas compared with 56% for levofloxacin (P = 0.14). Interestingly, cephalexin, a common choice for perioperative prophylaxis, was highly ineffective for gram-positive species in patients who later returned with infections. This study supports the efficacy of current intravenous antibiotics protocols but questions the efficacy of both clindamycin and levofloxacin in empirically treating periprosthetic infections and cephalexin in providing effective perioperative prophylaxis against skin flora. Because bacterial sensitivities vary by location and patient population, this study encourages other centers to develop their own antibiogram specifically tailored to periprosthetic infections to improve antimicrobial decision making and potentially improve implant salvage.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.

PubMed

Larson, Bruce A; Rockers, Peter C; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K; Cassim, Naseem; Coetzee, Lindi M; Greene, Gregory S; Chiller, Tom M; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P

2016-01-01

In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

PubMed Central

Rockers, Peter C.; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K.; Cassim, Naseem; Coetzee, Lindi M.; Greene, Gregory S.; Chiller, Tom M.; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P.

2016-01-01

Background In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. Methods We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. Results In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). Conclusions In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved. PMID:27390864

Gamma-camera 18F-FDG PET in diagnosis and staging of patients presenting with suspected lung cancer and comparison with dedicated PET.

PubMed

Oturai, Peter S; Mortensen, Jann; Enevoldsen, Henriette; Eigtved, Annika; Backer, Vibeke; Olesen, Knud P; Nielsen, Henrik W; Hansen, Hanne; Stentoft, Poul; Friberg, Lars

2004-08-01

It is not clear whether high-quality coincidence gamma-PET (gPET) cameras can provide clinical data comparable with data obtained with dedicated PET (dPET) cameras in the primary diagnostic work-up of patients with suspected lung cancer. This study focuses on 2 main issues: direct comparison between foci resolved with the 2 different PET scanners and the diagnostic accuracy compared with final diagnosis determined by the combined information from all other investigations and clinical follow-up. Eighty-six patients were recruited to this study through a routine diagnostic program. They all had changes on their chest radiographs, suggesting malignant lung tumor. In addition to the standard diagnostic program, each patient had 2 PET scans that were performed on the same day. After administration of 419 MBq (range = 305-547 MBq) (18)F-FDG, patients were scanned in a dedicated PET scanner about 1 h after FDG administration and in a dual-head coincidence gamma-camera about 3 h after tracer injection. Images from the 2 scans were evaluated in a blinded set-up and compared with the final outcome. Malignant intrathoracic disease was found in 52 patients, and 47 patients had primary lung cancers. dPET detected all patients as having malignancies (sensitivity, 100%; specificity, 50%), whereas gPET missed one patient (sensitivity, 98%; specificity, 56%). For evaluating regional lymph node involvement, sensitivity and specificity rates were 78% and 84% for dPET and 61% and 90% for gPET, respectively. When comparing the 2 PET techniques with clinical tumor stage (TNM), full agreement was obtained in 64% of the patients (Cohen's kappa = 0.56). Comparing categorization of the patients into clinical relevant stages (no malignancy/malignancy suitable for treatment with curative intent/nontreatable malignancy), resulted in full agreement in 81% (Cohen's kappa = 0.71) of patients. Comparing results from a recent generation of gPET cameras obtained about 2 h later than those of dPET, there was a fairly good agreement with regard to detecting primary lung tumors but slightly reduced sensitivity in detecting smaller malignant lesions such as lymph nodes. Depending on the population to be investigated, and if dPET is not available, gPET might provide significant diagnostic information in patients in whom lung cancer is suspected.

Endoscopic bursectomy for the treatment of septic pre-patellar bursitis: a case series.

PubMed

Dillon, John P; Freedman, Ilan; Tan, James S M; Mitchell, David; English, Shaun

2012-07-01

Operative treatment for septic pre-patellar bursitis generally involves open debridement in addition to an extended course of intravenous antibiotics. Skin necrosis and wound breakdown are potential complications of this procedure in addition to scar sensitivity and a prolonged recovery. We report endoscopic bursectomy for the treatment of septic pre-patellar bursitis in eight patients over a 3-year period. All patients had microbiological confirmation of an infective process. The average age was 36 years (23-68 years). The average hospital stay was 6 days (4-9 days). No patient had a recurrence or complained of tenderness or hypoaesthesia around their wound. No patient experienced wound complications or skin necrosis. The average return to work time was 18 days (7-22 days). We conclude that endoscopic bursectomy is a safe and effective treatment for septic pre-patellar bursitis with a shortened hospital stay and a quicker return to work than conventional open debridement.

Neuropad for the detection of cardiovascular autonomic neuropathy in patients with type 2 diabetes.

PubMed

Mendivil, Carlos O; Kattah, William; Orduz, Arturo; Tique, Claudia; Cárdenas, José L; Patiño, Jorge E

2016-01-01

Cardiovascular autonomic neuropathy (CAN) is a prevalent and neglected chronic complication of diabetes, with a large impact on morbidity and mortality. Part of the reason why it is not detected and treated opportunely is because of the complexity of the tests required for its diagnosis. We evaluated the Neuropad®, a test based on sudomotor function, as a screening tool for CAN in adult patients with type 2 diabetes in Bogotá, Colombia. This was a cross-sectional evaluation of Neuropad® for the detection of CAN. Patients were 20-75years of age and did not suffer from any other type of neuropathy. CAN was diagnosed using the Ewing battery of tests for R-R variability during deep breathing, Valsalva and lying-to-standing maneuvers. Additionally, distal symmetric polyneuropathy (DSP) was diagnosed using a sign-based scale (Michigan Neuropathy Disability Score - NDS) and a symptom-based score (Total Symptom Score - TSS). The primary outcome was the sensitivity and specificity of the Neuropad® for the diagnosis of CAN, and secondary outcomes were the sensitivity and specificity of Neuropad® for DSP. We studied 154 patients (74 men and 80 women). Prevalence of CAN was extremely high (68.0% of study participants), but also DSP was prevalent, particularly according to the signs-based definition (45%). The sensitivity of the Neuropad® for any degree of CAN was 70.1%, being slightly higher for the deep breathing and Valsalva tests than for lying-to-standing. The specificity of the Neuropad® for any type of CAN was only 37.0%, as expected for a screening exam. The negative predictive value was higher for the deep breathing and Valsalva tests (69.4 and 81.6%, respectively). Neuropad showed also a good sensitivity and negative predictive value for DSP. The sensitivity and specificity of Neuropad were better among men, and among patients with diabetes duration above the group median. The Neuropad is a simple and inexpensive device that demonstrated an adequate performance as a screening tool for cardiovascular autonomic neuropathy in Latin American patients with DM2. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease.

PubMed

Rohof, Wout O; Bennink, Roelof J; de Jonge, Hugo; Boeckxstaens, Guy E

2014-10-01

Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of the acid pocket. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Anticarbohydrate antibodies as markers of inflammatory bowel disease in a Central European cohort.

PubMed

Malickova, Karin; Lakatos, Peter L; Bortlik, Martin; Komarek, Viktor; Janatkova, Ivana; Lukas, Milan

2010-02-01

The study discusses the role of antichitobioside carbohydrate antibody (ACCA), antilaminaribioside carbohydrate antibodies (ALCA), and antimannobioside carbohydrate antibodies (AMCA) in Central European patients with inflammatory bowel disease (IBD). Twohundred and seventy-two serum samples were used - 116 Crohn's disease (CD), 84 ulcerative colitis, and 72 healthy control samples. All samples were evaluated using enzyme-linked immunosorbent assay for the following four anticarbohydrate assays: ACCA, ALCA, AMCA, and anti-Saccharomyces cerevisiae antibodies (gASCA). gASCA antibodies showed the highest sensitivity (67%) for a CD diagnosis, followed by AMCA (31%), ACCA (27%), and ALCA (25%). Positivity of at least one of the four assays increased the overall sensitivity of antibody testing in CD up to 85.5%. Mean serum gASCA levels were significantly higher in CD patients who were younger at diagnosis and had a longer disease duration before blood sampling (P<0.001). In nonstricturing, nonpenetrating CD, serum gASCA levels were lower than in patients with stricturing and/or penetrating behavior (P<0.05). The strongest association of gASCA was found with ileocolonic CD and with upper gastrointestinal disease (P<0.001). No association between anticarbohydrate (AMCA, ACCA, and ALCA) antibodies and CD location, behavior, age at onset, and disease duration was found; however, that sample size of some of our subgroups was probably too small to make firm conclusions on associations with all CD phenotypes. None of the assessed anticarbohydrate assays was predictive of colonic CD in patients in whom the distinction between CD and ulcerative colitis is not obvious using routine diagnostic methods. There was no relationship between the presence or concentration of anticarbohydrate antibodies and the inflammation measured by C-reactive protein levels. The use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns. The addition of AMCA, ALCA, and ACCA assays as IBD serology markers improves the overall sensitivity of immunological examinations in IBD; however, anticarbohydrate assays are not helpful for predicting CD behavior.

Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism.

PubMed

Moores, L; Kline, J; Portillo, A K; Resano, S; Vicente, A; Arrieta, P; Corres, J; Tapson, V; Yusen, R D; Jiménez, D

2016-01-01

ESSENTIALS: When high probability of pulmonary embolism (PE), sensitivity of computed tomography (CT) is unclear. We investigated the sensitivity of multidetector CT among 134 patients with a high probability of PE. A normal CT alone may not safely exclude PE in patients with a high clinical pretest probability. In patients with no clear alternative diagnosis after CTPA, further testing should be strongly considered. Whether patients with a negative multidetector computed tomographic pulmonary angiography (CTPA) result and a high clinical pretest probability of pulmonary embolism (PE) should be further investigated is controversial. This was a prospective investigation of the sensitivity of multidetector CTPA among patients with a priori clinical assessment of a high probability of PE according to the Wells criteria. Among patients with a negative CTPA result, the diagnosis of PE required at least one of the following conditions: ventilation/perfusion lung scan showing a high probability of PE in a patient with no history of PE, abnormal findings on venous ultrasonography in a patient without previous deep vein thrombosis at that site, or the occurrence of venous thromboembolism (VTE) in a 3-month follow-up period after anticoagulation was withheld because of a negative multidetector CTPA result. We identified 498 patients with a priori clinical assessment of a high probability of PE and a completed CTPA study. CTPA excluded PE in 134 patients; in these patients, the pooled incidence of VTE was 5.2% (seven of 134 patients; 95% confidence interval [CI] 1.5-9.0). Five patients had VTEs that were confirmed by an additional imaging test despite a negative CTPA result (five of 48 patients; 10.4%; 95% CI 1.8-19.1), and two patients had objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months (two of 86 patients; 2.3%; 95% CI 0-5.5). None of the patients had a fatal PE during follow-up. A normal multidetector CTPA result alone may not safely exclude PE in patients with a high clinical pretest probability. © 2015 International Society on Thrombosis and Haemostasis.

Use of hexyl isocyanate antigen to detect antibodies to hexamethylene diisocyanate (HDI) in sensitized guinea pigs and in a sensitized worker.

PubMed

Karol, M H; Hauth, B A

1982-01-01

Hypersensitivity to hexamethylene diisocyanate (HDI) has been reported following occupational exposure. Diagnosis of sensitivity is usually made from clinical evaluation of symptomatology. An in vitro serologic assay for HDI sensitivity was developed by immunizing guinea pigs with HDI and with hexyl isocyanate (HMI). Animals injected intradermally with HMI produced hapten-specific antibodies whereas guinea pigs injected with HDI produced antibodies specific for larger determinants which included the HDI hapten. The larger determinants were assumed to be composed of portions of "self" molecules which reacted in vivo with HDI. Serum albumin appeared to be one such molecule. No cross reactions were noted between antibodies to HDI and another widely used industrial isocyanate, toluene diisocyanate (TDI). Antigens effective in detecting antibodies to HDI or HMI were tested for ability to detect reaginic antibodies in a worker with clinical "HDI" asthma. Using a radioimmunoassay (RAST), antibodies reacted with conjugates containing either HDI or HMI as haptens. In addition, the prevalance of HDI polyisocyanates (Desmodur N) in spray paints prompted its use as a hapten. Antibodies reacted with Desmodur N antigen conjugates in RAST. RAST inhibition further indicated that Desmodur N antigen reacted more readily with the patient's antibodies than did HDI or HMI antigens. These results suggest that the patient may have been exposed to HDI polyisocyanates in spray paint application. Use of Rast inhibition for diagnosis of sensitivity may indicate the precise sensitizing agent within a mixture.

Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts.

PubMed

Calabrese, Emma; Maaser, Christian; Zorzi, Francesca; Kannengiesser, Klaus; Hanauer, Stephen B; Bruining, David H; Iacucci, Marietta; Maconi, Giovanni; Novak, Kerri L; Panaccione, Remo; Strobel, Deike; Wilson, Stephanie R; Watanabe, Mamoru; Pallone, Francesco; Ghosh, Subrata

2016-05-01

Bowel ultrasonography (US) is considered a useful technique for assessing mural inflammation and complications in Crohn's disease (CD). The aim of this review is to appraise the evidence on the accuracy of bowel US for CD. In addition, we aim to provide recommendations for its optimal use. Publications were identified by literature search from 1992 to 2014 and selected based on predefined criteria: 15 or more patients; bowel US for diagnosing CD, complications, postoperative recurrence, activity; adequate reference standards; prospective study design; data reported to allow calculation of sensitivity, specificity, agreement, or correlation values; articles published in English. The search yielded 655 articles, of which 63 were found to be eligible and retrieved as full-text articles for analysis. Bowel US showed 79.7% sensitivity and 96.7% specificity for the diagnosis of suspected CD, and 89% sensitivity and 94.3% specificity for initial assessment in established patients with CD. Bowel US identified ileal CD with 92.7% sensitivity, 88.2% specificity, and colon CD with 81.8% sensitivity, 95.3% specificity, with lower accuracy for detecting proximal lesions. The oral contrast agent improves the sensitivity and specificity in determining CD lesions and in assessing sites and extent. Bowel US is a tool for evaluation of CD lesions in terms of complications, postoperative recurrence, and monitoring response to medical therapy; it reliably detects postoperative recurrence and complications, as well as offers the possibility of monitoring disease progression.

Dolichandrone platycalyx: New entomophilous pollen--A report on pollen sensitization in allergic individuals.

PubMed

Mridula, P A; Mahesh, P A; Abraham, Jacob N; Amrutha, D H; Agashe, S N; Sitesh, Roy; Vedanthan, P K

2011-01-01

Dolichandrone platycalyx, commonly known as Nile trumpet tree, is believed to have originated in East Africa. However, this and the variants of this tree are found in Europe, Asia, and America (California and Florida). The tree mostly grows in tropical climates, but temperate species are also found. This study was designed to evaluate the allergenicity of D. platycalyx, one of the most common entomophilous avenue trees in Karnataka state, and to determine the pollen production of D. platycalyx. All of the patients with allergic rhinitis and asthma attending a tertiary care center in South India during August 2007 to March 2008 underwent a detailed clinical evaluation and skin-prick testing to common allergens along with D. platycalyx. Control subjects without any symptoms of respiratory allergy also underwent skin testing. The pollen counts were determined for a mature unopened flower of D. platycalyx. A total of 317 subjects with respiratory allergy and 30 controls were included in the study. A significant percentage (16.1%) of patients evaluated were observed to be sensitive to Dolichandrone pollen extract by skin-prick testing, whereas none of the control subjects were found to be sensitized. D. platycalyx was the fourth most common sensitizer after Parthenium hysterophorus, Prosopis juliflora, and Artemesia vulgaris. D. platycalyx was found to be a moderate pollen producer at 66,000 pollens/flower. Sensitization to D. platycalyx is common in subjects with respiratory allergies. The clinical relevance of this sensitization and other entomophilous plants needs additional study.

Agreement between patients' self-report and medical records for vaccination: the PGRx database.

PubMed

Grimaldi-Bensouda, Lamiae; Aubrun, Elodie; Leighton, Pamela; Benichou, Jacques; Rossignol, Michel; Abenhaim, Lucien

2013-03-01

Patients' self-reported vaccine exposure (PS) may be subject to memory errors and other biases. Physicians' prescription records and other medical records (MR) do not capture noncompliance with vaccination. This study compared PS with MR for influenza, 23-valent pneumococcal, and human papillomavirus (HPV) vaccines. The Pharmacoepidemiologic General Research Extension (PGRx) database uses a network of over 300 general practitioners across France, who systematically recruit an age- and sex-stratified sample of patients (≥ 14 years old), without reference to their diagnoses or prescriptions. Patients received a structured telephone interview, combined with an interview guide listing vaccines commonly given. Patients' self-reported vaccination in the 3 years before their recruitment was compared with medical records kept by the physician or the patient. Concordance between PS and MR was assessed for 7613 patients for whom both sources of information were available. Agreement within 3 years before the recruitment date was substantial for influenza vaccines (prevalence and bias-adjusted kappa [PABAK] = 0.74, sensitivity PS relative to MR 81.5%) and high for 23-valent pneumococcal vaccines (PABAK = 0.98, sensitivity PS 49.6) and HPV vaccines (PABAK = 0.92, sensitivity PS 91.6). In adjusted analyses, agreement varied with sociodemographic and health-related factors, particularly for influenza and 23-valent pneumococcal vaccines. The PGRx method for drug exposure assessment is a new tool in pharmacoepidemiology that shows substantial to high agreement between PS and MR for exposure to various vaccines. Our finding of high agreement between PS and MR for HPV vaccination status in young women is a significant addition to the literature. Copyright © 2013 John Wiley & Sons, Ltd.

Demonstration of the test-retest reliability and sensitivity of the Lower Limb Functional Index-10 as a measure of functional recovery post burn injury: a cross-sectional repeated measures study design.

PubMed

Ryland, Margaret E; Grisbrook, Tiffany L; Wood, Fiona M; Phillips, Michael; Edgar, Dale W

2016-01-01

Lower limb burns can significantly delay recovery of function. Measuring lower limb functional outcomes is challenging in the unique burn patient population and necessitates the use of reliable and valid tools. The aims of this study were to examine the test-retest reliability, sensitivity, and internal consistency of Sections 1 and 3 of the Lower Limb Functional Index-10 (LLFI-10) questionnaire for measuring functional ability in patients with lower limb burns over time. Twenty-nine adult patients who had sustained a lower limb burn injury in the previous 12 months completed the test-retest procedure of the study. In addition, the minimal detectable change (MDC) was calculated for Section 1 and 3 of the LLFI-10. Section 1 is focused on the activity limitations experienced by patients with a lower limb disorder whereas Section 3 involves patients indicating their current percentage of pre-injury duties. Section 1 of the LLFI-10 demonstrated excellent test-retest reliability (intra-class correlation coefficient (ICC) 0.98, 95 % CI 0.96-0.99) whilst Section 3 demonstrated high test-retest reliability (ICC 0.88, 95 % CI 0.79-0.94). MDC scores for Sections 1 and 3 were 1.27 points and 30.22 %, respectively. Internal consistency was demonstrated with a significant negative association (r s  = -0.83) between Sections 1 and 3 of the LLFI-10 (p < 0.001). This study demonstrates that Section 1 and 3 of the LLFI-10 are reliable for measuring functional ability in patients who have sustained lower limb burns in the previous 12 months, and furthermore, Section 1 is sensitive to changes in patient function over time.

The Potential Utility of the Patient Health Questionnaire as a Screener for Psychiatric Comorbidity in a Chronic Disabling Occupational Musculoskeletal Disorder Population.

PubMed

Asih, Sali; Mayer, Tom G; Bradford, E McKenna; Neblett, Randy; Williams, Mark J; Hartzell, Meredith M; Gatchel, Robert J

2016-02-01

The patient health questionnaire (PHQ) is designed for screening psychopathology in primary care settings. However, little is known about its clinical utility in other chronic pain populations, which usually have high psychiatric comorbidities. A consecutive cohort of 546 patients with chronic disabling occupational musculoskeletal disorder (CDOMD) was administered and compared upon psychosocial assessments, including the PHQ and a structured clinical interview for DSM-IV (SCID). Four PHQ modules were assessed: major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD), and alcohol use disorders (AUD) [including both alcohol abuse and dependence]. Based on the SCID diagnosis, sensitivity and specificity were determined. The specificity of the PHQ ranged from moderate to high for all 4 PHQ modules (MDD, 0.79; GAD, 0.67; PD, 0.89; AUD, 0.97). However, the sensitivity was relatively low: MDD (0.58); GAD (0.61); PD (0.49); and AUD (0.24). The PHQ was also associated with psychosocial variables. Patients whose PHQ showed MDD, GAD, or PD reported significantly more depressive symptoms and perceived disability than patients who did not (Ps < 0.001). Patients with MDD or GAD reported significantly higher pain than those without (Ps < 0.001). The strong specificity of the PHQ appears to be its primary strength for this cohort. Due to its high specificity, the PHQ could be employed as an additional screening tool to help rule out potential psychiatric comorbidity in patients with CDOMD. The low sensitivity of the PHQ in this population, however, remains a weakness of the PHQ. © 2015 World Institute of Pain.

Femur fractures should not be considered distracting injuries for cervical spine assessment.

PubMed

Dahlquist, Robert T; Fischer, Peter E; Desai, Harsh; Rogers, Amelia; Christmas, A Britton; Gibbs, Michael A; Sing, Ronald F

2015-12-01

The National Emergency X-Radiography Utilization Study (NEXUS) clinical decision rule is extremely sensitive for clearance of cervical spine (C-spine) injury in blunt trauma patients with distracting injuries. We sought to determine whether the NEXUS criteria would maintain sensitivity for blunt trauma patients when femur fractures were not considered a distracting injury and an absolute indication for diagnostic imaging. We retrospectively analyzed blunt trauma patients with at least 1 femur fracture who presented to our emergency department as trauma activations from 2009 to 2011 and underwent C-spine injury evaluation. Presence of C-spine injury requiring surgical intervention was evaluated. Of 566 trauma patients included, 77 (13.6%) were younger than 18 years. Cervical spine injury was diagnosed in 53 (9.4%) of 566. A total of 241 patients (42.6%) had positive NEXUS findings in addition to distracting injury; 51 (21.2%) of these had C-spine injuries. Of 325 patients (57.4%) with femur fractures who were otherwise NEXUS negative, only 2 (0.6%) had C-spine injuries (95% confidence interval [CI], 0.2%-2.2%); both were stable and required no operative intervention. Use of NEXUS criteria, excluding femur fracture as an indication for imaging, detected all significant injuries with a sensitivity for any C-spine injury of 96.2% (95% CI, 85.9%-99.3%) and negative predictive value of 99.4% (95% CI, 97.6%-99.9%). In our patient population, all significant C-spine injuries were identified by NEXUS criteria without considering the femur fracture a distracting injury and indication for computed tomographic imaging. Reconsidering femur fracture in this context may decrease radiation exposure and health care expenditure with little risk of missed diagnoses. Copyright © 2015 Elsevier Inc. All rights reserved.

A Phase 2 Trial of Flavopiridol (Alvocidib) and Cisplatin in Platin-Resistant Ovarian and Primary Peritoneal Carcinoma: MC0261

PubMed Central

Bible, Keith C.; Peethambaram, Prema P.; Oberg, Ann L.; Maples, William; Groteluschen, David L.; Boente, Matthew; Burton, Jill K.; Gomez Dahl, Leigh C.; Tibodeau, Jennifer D.; Isham, Crescent R.; Maguire, Jacie L.; Shridhar, Viji; Kukla, Andrea K.; Voll, Kalli J.; Mauer, Mathew J.; Colevas, Alexander D.; Wright, John; Doyle, L. Austin; Erlichman, Charles

2014-01-01

Purpose Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. Methods A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression > vs. ≤6 months following prior platin-based therapy). Measurable disease (RECIST) - or evaluable disease plus CA125 >2× post-treatment nadir - and ECOG performance ≤2 were required. Results Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2–12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. Conclusions The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study. PMID:22664059

Serologic reactivity to purified recombinant and native 29-kilodalton peripheral membrane protein of pathogenic Entamoeba histolytica.

PubMed Central

Flores, B M; Reed, S L; Ravdin, J I; Torian, B E

1993-01-01

The 29-kDa peripheral membrane protein of Entamoeba histolytica has recently been demonstrated to have epitopes on pathogenic clinical isolates which were not detected by monoclonal antibodies on nonpathogenic isolates. To analyze the serological response to this protein, we tested 93 serum specimens (from 33 patients with amebic liver abscess, 7 patients with colitis, 2 patients with ameboma, 18 individuals harboring a nonpathogenic zymodeme strain, 10 healthy Mexican migrant workers, and 23 healthy controls) by enzyme-linked immunosorbent assay (ELISA) using immunoaffinity-purified native or recombinant protein. When tested by ELISA with the native antigen, 79% (26 of 33) of the serum specimens from patients with amebic liver abscess, 4 of 9 serum specimens from symptomatic patients with colitis or ameboma, and serum from one migrant worker were positive. None of the 18 subjects harboring a nonpathogenic strain or 23 control individuals were seropositive to the native antigen (sensitivity, 71%; specificity, 98%). Of 30 serum specimens from patients with amebic liver abscess tested with recombinant antigen, 27 were seropositive (90%). In addition, six patients with colitis or ameboma and two individuals who harbored a nonpathogenic strain were seropositive to the recombinant antigen. One healthy Mexican migrant worker tested positive by both ELISAs (sensitivity, 87%; specificity, 94%). Immunoblotting of 51 serum specimens to sodium dodecyl sulfate-denatured native 29-kDa protein was less sensitive (65%) than ELISA in detecting serum antibodies to the antigen. These results suggest a similar antibody response to native and recombinant antigens (r = 0.86) and support the potential utility of a quantitative assay with defined recombinant antigen for the serodiagnosis of invasive amebiasis in nonendemic areas in conjunction with other diagnostic tools. Images PMID:8314979

The role of specific visual subfields in collisions with oncoming cars during simulated driving in patients with advanced glaucoma

PubMed Central

Kunimatsu-Sanuki, Shiho; Iwase, Aiko; Araie, Makoto; Aoki, Yuki; Hara, Takeshi; Fukuchi, Takeo; Udagawa, Sachiko; Ohkubo, Shinji; Sugiyama, Kazuhisa; Matsumoto, Chota; Nakazawa, Toru; Yamaguchi, Takuhiro; Ono, Hiroshi

2017-01-01

Background/aims To assess the role of specific visual subfields in collisions with oncoming cars during simulated driving in patients with advanced glaucoma. Methods Normal subjects and patients with glaucoma with mean deviation <–12 dB in both eyes (Humphrey Field Analyzer 24-2 SITA-S program) used a driving simulator (DS; Honda Motor, Tokyo). Two scenarios in which oncoming cars turned right crossing the driver's path were chosen. We compared the binocular integrated visual field (IVF) in the patients who were involved in collisions and those who were not. We performed a multivariate logistic regression analysis; the dependent parameter was collision involvement, and the independent parameters were age, visual acuity and mean sensitivity of the IVF subfields. Results The study included 43 normal subjects and 100 patients with advanced glaucoma. And, 5 of the 100 patients with advanced glaucoma experienced simulator sickness during the main test and were thus excluded. In total, 95 patients with advanced glaucoma and 43 normal subjects completed the main test of DS. Advanced glaucoma patients had significantly more collisions than normal patients in one or both DS scenarios (p<0.001). The patients with advanced glaucoma who were involved in collisions were older (p=0.050) and had worse visual acuity in the better eye (p<0.001) and had lower mean IVF sensitivity in the inferior hemifield, both 0°–12° and 13°–24° in comparison with who were not involved in collisions (p=0.012 and p=0.034). A logistic regression analysis revealed that collision involvement was significantly associated with decreased inferior IVF mean sensitivity from 13° to 24° (p=0.041), in addition to older age and lower visual acuity (p=0.018 and p<0.001). Conclusions Our data suggest that the inferior hemifield was associated with the incidence of motor vehicle collisions with oncoming cars in patients with advanced glaucoma. PMID:28400370

Hyperinsulinism–hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype–phenotype correlations

PubMed Central

Kapoor, Ritika R; Flanagan, Sarah E; Fulton, Piers; Chakrapani, Anupam; Chadefaux, Bernadette; Ben-Omran, Tawfeg; Banerjee, Indraneel; Shield, Julian P; Ellard, Sian; Hussain, Khalid

2009-01-01

Background Activating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion. Objectives To study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA. Patients and methods Twenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed. Results Heterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 μmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified. Conclusion Patients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations. PMID:19690084

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

PubMed

Bhorade, S M; Sandesara, C; Garrity, E R; Vigneswaran, W T; Norwick, L; Alkan, S; Husain, A N; McCabe, M A; Yeldandi, V

2001-09-01

We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

PubMed

McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

2015-01-01

The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration.

PubMed

Reder, Nicholas P; Davis, Christopher S; Kovacs, Elizabeth J; Fisichella, P Marco

2014-06-01

Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome after lung transplantation. Unfortunately, the identification of patients with GERD who aspirate still lacks clear diagnostic indicators. The authors hypothesized that symptoms of GERD and detection of pepsin and bile acids in the bronchoalveolar lavage fluid (BAL) and exhaled breath condensate (EBC) are effective for identifying lung transplantation patients with GERD-induced aspiration. From November 2009 to November 2010, 85 lung transplantation patients undergoing surveillance bronchoscopy were prospectively enrolled. For these patients, self-reported symptoms of GERD were correlated with levels of pepsin and bile acids in BAL and EBC and with GERD status assessed by 24-h pH monitoring. The sensitivity and specificity of pepsin and bile acids in BAL and EBC also were compared with the presence of GERD in 24-h pH monitoring. The typical symptoms of GERD (heartburn and regurgitation) had modest sensitivity and specificity for detecting GERD and aspiration. The atypical symptoms of GERD (aspiration and bronchitis) showed better identification of aspiration as measured by detection of pepsin and bile acids in BAL. The sensitivity and specificity of pepsin in BAL compared with GERD by 24-h pH monitoring were respectively 60 and 45 %, whereas the sensitivity and specificity of bile acids in BAL were 67 and 80 %. These data indicate that the measurement of pepsin and bile acids in BAL can provide additional data for identifying lung transplantation patients at risk for GERD-induced aspiration compared with symptoms or 24-h pH monitoring alone. These results support a diagnostic role for detecting markers of aspiration in BAL, but this must be validated in larger studies.

Detection of color vision defects in chloroquine retinopathy.

PubMed

Vu, B L; Easterbrook, M; Hovis, J K

1999-09-01

The effect of chloroquine toxicity on color vision is unclear. The authors identified the color defects seen in chloroquine retinopathy and determined the sensitivity and specificity of clinical color vision tests for detecting the presence of previously diagnosed chloroquine retinopathy. Case-control study. Chloroquine retinopathy was defined using previously published criteria. Data from 30 patients with retinopathy and 25 patients using chloroquine but with no evidence of retinal toxicity were collected. All patients were tested with the following six clinical color vision tests: Ishihara, Farnsworth D-15, and Adams Desaturated-15 (Dsat-15), City University 2nd Edition (CU), Standard Pseudoisochromatic Plates Part 2 (SPP-2), and American Optical Hardy Rand Rittler (AO HRR). The number of failures was determined for each test. The types of color vision defects were classified as blue-yellow (BY), red-green (RG), or mixed RG and BY (mixed). Of the 30 patients with retinopathy, 28 (93.3%) of 30 patients failed at least 1 color vision test, demonstrating predominantly mixed defects. Five (25%) of 25 of the control subjects failed at least 1 test, and these defects were predominantly BY. The sensitivity and specificity of the tests are as follows: SPP-2 (93.3%, 88%), AO HRR (76.7%, 88%), Ishihara (43.3%, 96%), Dsat-15 (33.3%, 84%), D-15 (16.7%, 96%), and CU (20%, 92%). Color vision can be affected by chloroquine and should be tested routinely with a color vision test designed to detect both mild BY and protan RG defects to maximize sensitivity for toxicity. The SPP-2 and AO HRR are two tests that meet these criteria. The Ishihara has a low sensitivity, as do the D-15 tests and CU. All of the tests have similar specificity for chloroquine toxicity. If color vision defects are detected in patients at risk of developing chloroquine retinopathy, additional testing is indicated to rule out toxicity.

Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients.

PubMed

Ratzinger, Franz; Schuardt, Michael; Eichbichler, Katherina; Tsirkinidou, Irene; Bauer, Marlene; Haslacher, Helmuth; Mitteregger, Dieter; Binder, Michael; Burgmann, Heinz

2013-01-01

Physicians are regularly faced with severely ill patients at risk of developing infections. In literature, standard care wards are often neglected, although their patients frequently suffer from a systemic inflammatory response syndrome (SIRS) of unknown origin. Fast identification of patients with infections is vital, as they immediately require appropriate therapy. Further, tools with a high negative predictive value (NPV) to exclude infection or bacteremia are important to increase the cost effectiveness of microbiological examinations and to avoid inappropriate antibiotic treatment. In this prospective cohort study, 2,384 patients with suspected infections were screened for suffering from two or more SIRS criteria on standard care wards. The infection probability score (IPS) and sepsis biomarkers with discriminatory power were assessed regarding their capacity to identify infection or bacteremia. In this cohort finally consisting of 298 SIRS-patients, the infection prevalence was 72%. Bacteremia was found in 25% of cases. For the prediction of infection, the IPS yielded 0.51 ROC-AUC (30.1% sensitivity, 64.6% specificity). Among sepsis biomarkers, lipopolysaccharide binding protein (LBP) was the best parameter with 0.63 ROC-AUC (57.5% sensitivity, 67.1% specificity). For the prediction of bacteremia, the IPS performed slightly better with a ROC-AUC of 0.58 (21.3% sensitivity, 65% specificity). Procalcitonin was the best discriminator with 0.78 ROC-AUC, 86.3% sensitivity, 59.6% specificity and 92.9% NPV. Furthermore, bilirubin and LBP (ROC-AUC: 0.65, 0.62) might also be considered as useful parameters. In summary, the IPS and widely used infection parameters, including CRP or WBC, yielded a poor diagnostic performance for the detection of infection or bacteremia. Additional sepsis biomarkers do not aid in discriminating inflammation from infection. For the prediction of bacteremia procalcitonin, and bilirubin were the most promising parameters, which might be used as a rule for when to take blood cultures or using nucleic acid amplification tests for microbiological diagnostics.

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

Detection of lipopolysaccharides in serum using a waveguide-based optical biosensor

NASA Astrophysics Data System (ADS)

Noormohamed, Aneesa; Stromberg, Loreen R.; Anderson, Aaron S.; Karim, Zachary; Dighe, Priya; Kempaiah, Prakasha; Ong'echa, John M.; Perkins, Douglas J.; Doggett, Norman; McMahon, Benjamin; Mukundan, Harshini

2017-02-01

Direct ultra-sensitive detection of pathogen biomarkers in blood could provide a universal strategy for diagnosis of bacterial infections, which remain a leading cause of morbidity and mortality in many areas of the world. Many factors complicate diagnosis, including the presence of multiple co-infections in a given patient, and lack of infrastructure in rural settings. In some pediatric patients, such as those in areas with poor resources, an additional challenge exists with low sample volumes due to age and other health factors such as anemia and dehydration. Our team is working on developing novel diagnostic assays, with a waveguide-based biosensor platform, to rapidly and specifically identify pathogen biomarkers from small samples of serum or plasma, allowing for the timely and sensitive diagnosis of infection at the point of care. In addition to the platform, we have developed novel membrane insertion and lipoprotein capture assay methods, to capture lipidated pathogen biomarkers in aqueous blood, by virtue of their interactions with host lipoprotein carriers. Herein, we demonstrate our efforts to adapt the lipoprotein capture assay for the detection of small concentrations of pathogen-secreted lipopolysaccharides in aqueous blood, with the ultimate aim of diagnosing Gram-negative infections effectively.

Do prehospital discharge pacemaker checks provide any additional clinical benefit?

PubMed

Wheelan, Kevin R; Legge, Darlene M; Sakowski, Brent C; Bruce, Susan S; Roberts, David C; Johnston, L Murphy; Moore, B Jane; Beveridge, Thomas P; Wells, Peter J; Vallabahn, Ravi; Donsky, Michael S; Franklin, Jay O

2005-08-01

We performed a retrospective analysis of 250 records of consecutive, newly implanted, pacemaker patients from a single center to determine the rate of postimplant complications and observations discovered before and during the prehospital discharge evaluation. No observations occurred in 246 of 250 patients (98.4%) (1-sided 95% confidence interval 96.4%). Of the 250 patients, 4 had observations that were discovered at the prehospital discharge check and required reprogramming to increase the sensitivity safety margin (3 atrial and 1 ventricular). We documented only 1 complication that was discovered before the predischarge evaluation through telemetry and resulted in an atrial lead revision.

Polymerase chain reaction in the detection of tumor cells: new approaches in diagnosis and follow-up of patients with thyroid cancer.

PubMed

Bojunga, Jörg; Kusterer, Klaus; Schumm-Draeger, Petra-Maria; Usadel, Klaus-Henning

2002-12-01

Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increasing frequency. In addition to other measures, diagnosis is based on fine-needle aspiration cytology examination. Recently, new assays using reverse transcription-polymerase chain reaction (PCR) are being tested to improve sensitivity and specificity of primary diagnosis and detection of recurrent thyroid cancer. In the preoperative diagnosis of thyroid cancer, several tissue- and/or tumor-specific mRNA have been described and in several cases, a higher sensitivity and specificity could be achieved using molecular techniques compared to conventional methods. In the postoperative follow-up of patients with thyroid cancer, conflicting data have been published and the use of PCR techniques revealed several problems of the molecular approach, which are based on some technical as well as biologic limitations. Despite these problems, which are discussed in detail in this review, molecular techniques may nevertheless improve the sensitivity and accuracy of fine-needle aspiration of thyroid nodules, fine-needle aspiration of metastases, and detection of recurrent disease in peripheral blood samples.

Neuropathic pain in a Fabry disease rat model

PubMed Central

Miller, James J.; Aoki, Kazuhiro; Murphy, Carly A.; O’Hara, Crystal L.; Tiemeyer, Michael; Stucky, Cheryl L.; Dahms, Nancy M.

2018-01-01

Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge. Fabry rats had substantial serum and tissue accumulation of α-galactosyl glycosphingolipids and had pronounced mechanical pain behavior. Additionally, Fabry rat dorsal root ganglia displayed global N-glycan alterations, sensory neurons were laden with inclusions, and sensory neuron somata exhibited prominent sensitization to mechanical force. We found that the cation channel transient receptor potential ankyrin 1 (TRPA1) is sensitized in Fabry rat sensory neurons and that TRPA1 antagonism reversed the behavioral mechanical sensitization. This study points toward TRPA1 as a potentially novel target to treat the pain experienced by patients with Fabry disease. PMID:29563343

Improving on the diagnostic characteristics of echocardiography for pulmonary hypertension.

PubMed

Broderick-Forsgren, Kathleen; Davenport, Clemontina A; Sivak, Joseph A; Hargett, Charles William; Foster, Michael C; Monteagudo, Andrew; Armour, Alicia; Rajagopal, Sudarshan; Arges, Kristine; Velazquez, Eric J; Samad, Zainab

2017-09-01

This retrospective study evaluated the diagnostic characteristics of a combination of echocardiographic parameters for pulmonary hypertension (PH). Right ventricular systolic pressure (RVSP) estimation by echocardiography (echo) is used to screen for PH. However, the sensitivity of this method is suboptimal. We hypothesized that RVSP estimation in conjunction with other echo parameters would improve the value of echo for PH. The Duke Echo database was queried for adult patients with known or suspected PH who had undergone both echo and right heart catheterization (RHC) within a 24 h period between 1/1/2008 and 12/31/2013. Patients with complex congenital heart disease, heart transplantation, ventricular assist device, or on mechanical ventilation at time of study were excluded. Diagnostic characteristics of several echo parameters (right atrial enlargement, pulmonary artery (PA) enlargement, RV enlargement, RV dysfunction, and RVSP) for PH (mean PA pressure 25 mmHg on RHC) were evaluated among 1007 patients. RVSP ≥40 had a sensitivity of 77% (accuracy 77), while RVSP ≥35 had the highest sensitivity at 88% (81% accuracy). PA enlargement had the lowest sensitivity at 17%. The area under the curve (AUC) for RVSP was 0.844. A model including RVSP, RA, PA, RV enlargement and RV dysfunction had a higher AUC (AUC = 0.87) than RVSP alone. The value of echo as a screening test for PH is improved by a model incorporating a lower RVSP in addition to other right heart parameters. These findings need to be validated in prospective cohorts.

Characterization of Cannabis sativa allergens.

PubMed

Nayak, Ajay P; Green, Brett J; Sussman, Gordon; Berlin, Noam; Lata, Hemant; Chandra, Suman; ElSohly, Mahmoud A; Hettick, Justin M; Beezhold, Donald H

2013-07-01

Allergic sensitization to Cannabis sativa is rarely reported, but the increasing consumption of marijuana has resulted in an increase in the number of individuals who become sensitized. To date, little is known about the causal allergens associated with C sativa. To characterize marijuana allergens in different components of the C sativa plant using serum IgE from marijuana sensitized patients. Serum samples from 23 patients with a positive skin prick test result to a crude C sativa extract were evaluated. IgE reactivity was variable between patients and C sativa extracts. IgE reactivity to C sativa proteins in Western blots was heterogeneous and ranged from 10 to 70 kDa. Putative allergens derived from 2-dimensional gels were identified. Prominent IgE reactive bands included a 23-kDa oxygen-evolving enhancer protein 2 and a 50-kDa protein identified to be the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase. Additional proteins were identified in the proteomic analysis, including those from adenosine triphosphate synthase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and luminal binding protein (heat shock protein 70), suggesting these proteins are potential allergens. Deglycosylation studies helped refine protein allergen identification and demonstrated significant IgE antibodies against plant oligosaccharides that could help explain cross-reactivity. Identification and characterization of allergens from C sativa may be helpful in further understanding allergic sensitization to this plant species. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Evaluation of digital PCR for detecting low-level EGFR mutations in advanced lung adenocarcinoma patients: a cross-platform comparison study

PubMed Central

Liu, Bing; Li, Lei; Huang, Lixia; Li, Shaoli; Rao, Guanhua; Yu, Yang; Zhou, Yanbin

2017-01-01

Emerging evidence has indicated that circulating tumor DNA (ctDNA) from plasma could be used to analyze EGFR mutation status for NSCLC patients; however, due to the low level of ctDNA in plasma, highly sensitive approaches are required to detect low frequency mutations. In addition, the cutoff for the mutation abundance that can be detected in tumor tissue but cannot be detected in matched ctDNA is still unknown. To assess a highly sensitive method, we evaluated the use of digital PCR in the detection of EGFR mutations in tumor tissue from 47 advanced lung adenocarcinoma patients through comparison with NGS and ARMS. We determined the degree of concordance between tumor tissue DNA and paired ctDNA and analyzed the mutation abundance relationship between them. Digital PCR and Proton had a high sensitivity (96.00% vs. 100%) compared with that of ARMS in the detection of mutations in tumor tissue. Digital PCR outperformed Proton in identifying more low abundance mutations. The ctDNA detection rate of digital PCR was 87.50% in paired tumor tissue with a mutation abundance above 5% and 7.59% in paired tumor tissue with a mutation abundance below 5%. When the DNA mutation abundance of tumor tissue was above 3.81%, it could identify mutations in paired ctDNA with a high sensitivity. Digital PCR will help identify alternative methods for detecting low abundance mutations in tumor tissue DNA and plasma ctDNA. PMID:28978074

[How good are clinical investigative procedures for diagnosing meniscus lesions?].

PubMed

Jerosch, J; Riemer, S

2004-06-01

The purpose of this study was to evaluate different clinical meniscus tests. During 13 months we evaluated 64 patients with a suspected meniscus lesion in a prospective study. The age ranged from 16 to 76 years (average: 38.5 years). 66 % were male patients. Between the clinical examination and the arthroscopy there was no additional trauma to the knee. All patients were clinically examined in a standard manner by two independent orthopaedic surgeons. Clinical findings of the menisci were documented according to 12 well-described and commonly used meniscus tests. The arthroscopy was performed by a single surgeon who was not aware of the results of the clinical examination. This surgeon documented the intraarticular findings in a standardized operating report. A meniscus lesion/degeneration was documented when this was evident either by inspection or by palpation. The results showed either clinical meniscus tests with a high specificity and a low sensitivity or tests with a high sensitivity, but only a low specificity. We were not able to identify meniscus tests which showed both a high sensitivity and a high specificity. Even with access to MRI the clinical findings in knee joint with injured menisci still have a high diagnostic value. However, it seems to be necessary to combine different tests.

Evaluation of an immunochromatographic assay for the detection of anti-hepatitis A virus IgM

PubMed Central

2010-01-01

Background Hepatitis A virus (HAV) is a causative agent of acute hepatitis, which is transmitted by person-to-person contact and via the faecal-oral route. Acute HAV infection is usually confirmed by anti-HAV IgM detection. In order to detect anti-HAV IgM in the serum of patients infected with HAV, we developed a rapid assay based on immunochromatography (ICA) and evaluated the sensitivity of this assay by comparing it with a commercial microparticle enzyme immunoassay (MEIA) that is widely used for serological diagnosis. Results The newly developed ICA showed 100% sensitivity and specificity when used to test 150 anti-HAV IgM-positive sera collected from infected patients and 75 negative sera from healthy subjects. Also, the sensitivity of ICA is about 10 times higher than MEIA used in this study by determining end point to detect independent on infected genotype of HAV. In addition, the ICA was able to detect 1 positive sample from among 50 sera from acute hepatitis patients that had tested negative for anti-HAV IgM using the MEIA. Conclusion Conclusively, ICA for the detection of anti-HAV IgM will be very effective for rapid assay to apply clinical diagnosis and epidemiological investigation on epidemics due to the simplicity, rapidity and specificity. PMID:20637129

Implementation and evaluation of a low health literacy and culturally sensitive diabetes education program.

PubMed

Swavely, Deborah; Vorderstrasse, Allison; Maldonado, Edgardo; Eid, Sherrine; Etchason, Jeff

2014-01-01

Low health literacy is more prevalent in persons with limited education, members of ethnic minorities, and those who speak English as a second language, and is associated with multiple adverse diabetes-related health outcomes. This study examined the effectiveness of a low health literacy and culturally sensitive diabetes education program for economically and socially disadvantaged adult patients with type 2 diabetes. A pre-post prospective study design was used to examine outcomes over 12 months. Outcome measures included diabetes knowledge, self-efficacy, and self-care, measured using reliable and valid survey tools, and A1C. Over this period of time 277 patients were enrolled in the program, with 106 participants completing survey data. At the completion of the program patients had significant improvements in diabetes knowledge (p < .001), self-efficacy (p < .001), and three domains of self-care including diet (p < .001), foot care (p < .001), and exercise (p < .001). There were no significant improvements in the frequency of blood glucose testing (p = .345). Additionally, A1C values significantly improved 3 months after completing the program (p = .007). In conclusion, a diabetes education program designed to be culturally sensitive and meet the needs of individuals with low health literacy improves short-term outcomes. © 2013 National Association for Healthcare Quality.

Detection by PCR of Enteroviruses in Cerebrospinal Fluid during a Summer Outbreak of Aseptic Meningitis in Switzerland

PubMed Central

Gorgievski-Hrisoho, Meri; Schumacher, Jean-Daniel; Vilimonovic, Nevenka; Germann, Daniel; Matter, Lukas

1998-01-01

Enteroviruses (EV) are among the most common causes of aseptic meningitis. Standard diagnostic techniques are often too slow and lack sensitivity to be of clinical relevance. EV RNA can be detected within 5 h by a commercially available reverse transcription-PCR (RT-PCR) test kit. Cerebrospinal fluid (CSF) samples from 68 patients presenting with aseptic meningitis during a summer outbreak in Switzerland were examined in parallel with cell culture and commercial RT-PCR. RT-PCR was positive in all 16 CSF specimens positive by cell culture (100%). In addition, 42 of 52 (80%) CSF samples negative by cell culture were PCR positive. In 26 of these 42 (62%) patients, viral culture from other sites (throat swab or stool) was also positive. The CSF virus culture took 3 to 7 days to become positive. Echovirus 30 was the type most often isolated in this outbreak. The sensitivity of CSF RT-PCR based on clinical diagnosis during this aseptic meningitis outbreak in patients with negative bacterial culture results was 85%, i.e., considerably higher than the sensitivity of CSF virus culture (24%). We conclude that this commercial RT-PCR assay allows a positive diagnosis with minimal delay and may thus influence clinical decisions. PMID:9705364

The Relationship between Body Mass Index and Periodontitis in Arab Patients with Type 2 Diabetes Mellitus

PubMed Central

Awad, Manal; Rahman, Betul; Hasan, Haidar; Ali, Houssam

2015-01-01

Objective Our study sought to evaluate the association between periodontitis and body mass index (BMI) among patients with type 2 diabetes mellitus.  Methods In this cross-sectional case control study analysis of 186 diabetic patients, 112 patients had a body mass index ≥30kg/m2 and 74 control patients had BMI <30kg/m2. All participants underwent oral examinations including a full mouth recording of clinical attachment level (CAL). Information regarding HbA1c levels and high-sensitivity C-reactive protein (hs-CRP) were also gathered.  Results Over half (61%) of patients had a BMI ≥30. Of these 52% had CAL less than 2mm. Multivariate logistic regression analysis showed that there was no association between BMI and CAL. In addition, hs-CRP levels were significantly and positively associated with CAL (OR:1.06, 95% CI: 1.01, 1.12; p=0.007).  Conclusion Among patients with type 2 diabetes mellitus, there was no association between periodontitis and BMI. More studies are needed to further explore this relationship taking into consideration additional lifestyle factors. PMID:25829999

Accuracy of magnetic resonance imaging in the pre-operative staging of rectal adenocarcinoma: Experience from a regional Australian cancer center.

PubMed

White, Rohen; Ung, Kim Ann; Mathlum, Maitham

2013-12-01

Selection of the optimal treatment pathway in patients with rectal adenocarcinoma relies on accurate locoregional staging. This study aims to assess the accuracy of staging with magnetic resonance imaging (MRI) and in particular, its accuracy in differentiating patients with early stage disease from those with more advanced disease who benefit from a different treatment approach. Patients who were staged with MRI and received surgery as the first line of treatment for biopsy-proven adenocarcinoma of the rectum were identified. Comparison was made between the clinical stage on MRI and the pathological stage of the surgical specimen. The sensitivity, specificity and overall accuracy of MRI was assessed. In all, 58 eligible patients were identified. In 31% of patients, the extent of disease was underrepresented on preoperative MRI. Sensitivity, specificity and overall accuracy of anorectal MRI in detecting stage II/III disease status in this cohort was 59, 71 and 62%, respectively. MRI underestimated the pathological stage in many patients in this series who may have benefited from the addition of neoadjuvant radiotherapy to their management. This study supports further refinement of preoperative staging and demonstrates that impressive results from highly controlled settings may be difficult to reproduce in community practice. © 2012 Wiley Publishing Asia Pty Ltd.

The Effects of Safety Net Hospital Closures and Conversions on Patient Travel Distance to Hospital Services

PubMed Central

Bazzoli, Gloria J; Lee, Woolton; Hsieh, Hui-Min; Mobley, Lee Rivers

2012-01-01

Objective To examine the effects of safety net hospital (SNH) closure and for-profit conversion on uninsured, Medicaid, and racial/ethnic minorities. Data Sources/Extraction Methods Hospital discharge data for selected states merged with other sources. Study Design We examined travel distance for patients treated in urban hospitals for five diagnosis categories: ambulatory care sensitive conditions, referral sensitive conditions, marker conditions, births, and mental health and substance abuse. We assess how travel was affected for patients after SNH events. Our multivariate models controlled for patient, hospital, health system, and neighborhood characteristics. Principal Findings Our results suggested that certain groups of uninsured and Medicaid patients experienced greater disruption in patterns of care, especially Hispanic uninsured and Medicaid women hospitalized for births. In addition, relative to privately insured individuals in SNH event communities, greater travel for mental health and substance abuse care was present for the uninsured. Conclusions Closure or for-profit conversions of SNHs appear to have detrimental access effects on particular subgroups of disadvantaged populations, although our results are somewhat inconclusive due to potential power issues. Policy makers may need to pay special attention to these patient subgroups and also to easing transportation barriers when dealing with disruptions resulting from reductions in SNH resources. PMID:22091871

18F-FDG-PET/CT angiography in the diagnosis of infective endocarditis and cardiac device infection in adult patients with congenital heart disease and prosthetic material.

PubMed

Pizzi, María N; Dos-Subirà, L; Roque, Albert; Fernández-Hidalgo, Nuria; Cuéllar-Calabria, Hug; Pijuan Domènech, Antonia; Gonzàlez-Alujas, María T; Subirana-Domènech, M T; Miranda-Barrio, B; Ferreira-González, Ignacio; González-López, Juan J; Igual, Albert; Maisterra-Santos, Olga; García-Dorado, David; Castell-Conesa, Joan; Almirante, Benito; Escobar Amores, Manuel; Tornos, Pilar; Aguadé-Bruix, Santiago

2017-12-01

Infective endocarditis (IE) and cardiac device infection (CDI) are a major complication in the growing number of patients with congenital heart disease (CHD) reaching adulthood. We aimed to evaluate the added value of 18 F-FDG-PET/CT angiography (PET/CTA) in the diagnosis of IE-CDI in adults with CHD and intravascular or intracardiac prosthetic material, in whom echocardiography (ECHO) and modified Duke Criteria (DC) have limitations because of the patients' complex anatomy. A prospective study was conducted in a referral center with multidisciplinary IE and CHD Units. PET/CTA and ECHO findings were compared in consecutive adult (≥18years) patients with CHD who have prosthetic material and suspected IE-CDI. The initial diagnosis using the DC and the diagnosis with the additional PET/CTA data (DC+PET/CTA) were compared with the final diagnostic consensus established by an expert team at three months. Between November-2012 and April-2017, 25 patients (15 men; median age 40years) were included. Cases were initially classified as definite in 8 (32%), possible in 14 (56%) and rejected in 3 (12%). DC+PET/CTA allowed reclassification of 12/14 (86%) cases initially identified as possible IE. The sensitivity, specificity, PPV, NPV, and accuracy of DC at IE suspicion were 39.1%/83.3%/90.4%/25.5%/61.2%, respectively. The diagnostic performance increased significantly with addition of PET/CTA data: 87%/83.3%/95.4%/61.5%/85.1%, respectively. PET/CTA also provided an alternative diagnosis in 3 patients with rejected IE, and detected pulmonary embolisms in 3 patients. PET/CTA was a useful diagnostic tool in the complex group of adult patients with CHD who have cardiac or intravascular prosthetic material and suspected IE or CDI, providing added diagnostic value to the modified DC (increased sensitivity) and improving case classification. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Usefulness of neutrophil-to-lymphocyte ratio as a biomarker for diagnosing infections in patients with systemic lupus erythematosus.

PubMed

Kim, Hyoun-Ah; Jung, Ju-Yang; Suh, Chang-Hee

2017-11-01

Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have been investigated as disease activity markers for systemic lupus erythematosus (SLE). Hence, we investigated the clinical significance of these parameters in diagnosing infection in patients with SLE. In total, 120 patients with SLE, who were admitted to hospital due to disease flares or infection, were recruited for the study. Of the 120 patients, 60 had a concurrent infection (SLE with infection), while the remaining 60 patients were admitted with a flare without any evidence of infection (SLE with flare). NLR was higher in the patients with SLE with infection, compared to patients with SLE with flare (14.2 ± 15.4 versus 3.3 ± 2.2, p < 0.001). Additionally, PLR was higher in the SLE with infection group than in the SLE with flare group (357.7 ± 350.1 versus 231.7 ± 152.9, p = 0.012), but not MLR. In the SLE with infection group, C-reactive protein (CRP) levels positively correlated with NLR and PLR. NLR with a cut-off value of 5.70 and an area under the curve (AUC) of 0.872 indicated good sensitivity (75%) and specificity (90%), for the diagnosis of SLE with infection. CRP with a cut-off value of 1.28 mg/dL (AUC 0.942) showed the sensitivity (93.3%) and specificity (91.7%). NLR with a cut-off value of 5.70 and CRP with a cut-off value of 1.28 mg/dL showed the increased specificity (98.3%) than only CRP, but not significant. NLR could be a good additive marker for diagnosing infection in patients with SLE.

Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

PubMed Central

Kacerovsky-Bielesz, Gertrud; Chmelik, Marek; Ling, Charlotte; Pokan, Rochus; Szendroedi, Julia; Farukuoye, Michaela; Kacerovsky, Michaela; Schmid, Albrecht I.; Gruber, Stephan; Wolzt, Michael; Moser, Ewald; Pacini, Giovanni; Smekal, Gerhard; Groop, Leif; Roden, Michael

2009-01-01

OBJECTIVE We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms. RESEARCH DESIGN AND METHODS We studied 24 nonobese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using1H and31P magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O2uptake and insulin sensitivity. CONCLUSIONS The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. PMID:19265027

The Faces Symbol Test, a newly developed screening instrument to assess cognitive decline related to multiple sclerosis: first results of the Berlin Multi-Centre FST Validation Study.

PubMed

Scherer, P; Penner, I K; Rohr, A; Boldt, H; Ringel, I; Wilke-Burger, H; Burger-Deinerth, E; Isakowitsch, K; Zimmermann, M; Zahrnt, S; Hauser, R; Hilbert, K; Tiel-Wilck, K; Anvari, K; Behringer, A; Peglau, I; Friedrich, H; Plenio, A; Benesch, G; Ehret, R; Nippert, I; Finke, G; Schulz, I; Bergtholdt, B; Breitkopf, S; Kaskel, P; Reischies, F; Kugler, J

2007-04-01

Reliable, language-independent, short screening instruments to test for cognitive function in patients with multiple sclerosis (MS) remain rare, despite the high number of patients affected by cognitive decline. We developed a new, short screening instrument, the Faces Symbol Test (FST), and compared its diagnostic test characteristics with a composite of the Digit Symbol Substitution Test (DSST) and the Paced Auditory Serial Addition Test (PASAT), in 108 MS patients and 33 healthy controls. An Informant-Report Questionnaire, a Self-Report Questionnaire, and a neurologist's estimation of the Every Day Life Cognitive Status were also applied to the MS patients. The statistical analyses comprised of a receiver operating characteristic analysis for test accuracy and for confounding variables. The PASAT and DSST composite score estimated that 36.5% of the MS patients had cognitive impairment. The FST estimated that 40.7% of the MS patients were cognitively impaired (sensitivity 84%; specificity 85%). The FST, DSST and PASAT results were significantly correlated with the patients' physical impairment, as measured by the Expanded Disability Status Scale (EDSS). The results suggest that the FST might be a culture-free, sensitive, and practical short screening instrument for the detection of cognitive decline in patients with MS, including those in the early stages.

Head-to-Head Comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: A Prospective Study of 59 Patients with Neuroendocrine Tumors.

PubMed

Johnbeck, Camilla B; Knigge, Ulrich; Loft, Annika; Berthelsen, Anne K; Mortensen, Jann; Oturai, Peter; Langer, Seppo W; Elema, Dennis R; Kjaer, Andreas

2017-03-01

Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up, and treatment planning of neuroendocrine tumor (NET). PET-based tracers using 68 Ga as the radioisotope have in most centers replaced SPECT-based tracers as the gold standard. 64 Cu-DOTATATE is a new PET tracer that has been shown to be far superior to the SPECT tracer 111 In-diethylenetriaminepentaacetic acid-octreotide. Because of the advantages of 64 Cu over 68 Ga, we hypothesized that the tracer has a higher sensitivity than 68 Ga-based tracers. To test this hypothesis, we compared on a head-to-head basis the diagnostic performance of 64 Cu-DOTATATE with that of 68 Ga-DOTATOC in NET patients. Methods: Fifty-nine NET patients were scanned with both 64 Cu-DOTATATE and 68 Ga-DOTATOC PET/CT and compared on a head-to-head basis. Discordant lesions were verified during at least 30 mo of follow-up. Results: A total of 701 lesions were concordantly detected on both 64 Cu-DOTATATE and 68 Ga-DOTATOC PET/CT scans, whereas an additional 68 lesions were found by only one of the scans. 64 Cu-DOTATATE showed 42 lesions not found on 68 Ga-DOTATOC, of which 33 were found to be true-positive on follow-up. 68 Ga-DOTATOC showed 26 lesions not found on 64 Cu-DOTATATE, of which 7 were found to be true-positive on follow-up. False-positives were mainly lymph node lesions. Accordingly, 83% of the additional true lesions found on only one of the scans were found by 64 Cu-DOTATATE. On a patient-basis, additional true lesions were found by 64 Cu-DOTATATE and 68 Ga-DOTATOC in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusion: 64 Cu-DOTATATE has advantages over 68 Ga-DOTATOC in the detection of lesions in NET patients. Although patient-based sensitivity was the same for 64 Cu-DOTATATE and 68 Ga-DOTATOC in this cohort, significantly more lesions were detected by 64 Cu-DOTATATE. Furthermore, the shelf life of more than 24 h and the scanning window of at least 3 h make 64 Cu-DOTATATE favorable and easy to use in the clinical setting. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma

PubMed Central

Myers, Amy L.; Lin, Lin; Nancarrow, Derek J.; Wang, Zhuwen; Ferrer-Torres, Daysha; Thomas, Dafydd G.; Orringer, Mark B.; Lin, Jules; Reddy, Rishindra M.; Beer, David G.; Chang, Andrew C.

2015-01-01

Esophageal adenocarcinoma (EAC) patients commonly present with advanced stage disease and demonstrate resistance to therapy, with response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for improvement of clinical outcomes. IGFBP2 is a member of the IGFBP family of proteins that has been reported to modulate both IGF and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. In this study, high IGFBP2 expression was observed in a subset of primary EACs and was found to be significantly higher in patients with shorter disease-free intervals as well as in treatment-resistant EACs as compared to chemonaive EACs. Modulation of IGFBP2 expression in EAC cell lines promoted cell proliferation, migration and invasion, implicating a role in the metastatic potential of these cells. Additionally, knockdown of IGFBP2 sensitized EAC cells to cisplatin in a serum-dependent manner. Further in vitro exploration into this chemosensitization implicated both the AKT and ERK pathways. Silencing of IGFBP2 enhanced IGF1-induced immediate activation of AKT and reduced cisplatin-induced ERK activation. Addition of MEK1/2 (selumetinib or trametinib) or AKT (AKT Inhibitor VIII) inhibitors enhanced siIGFBP2-induced sensitization of EAC cells to cisplatin. These results suggest that targeted inhibition of IGFBP2 alone or together with either the MAPK or PI3K/AKT signaling pathway in IGFBP2-overexpressing EAC tumors may be an effective approach for sensitizing resistant EACs to standard neoadjuvant chemotherapy. PMID:26317790

Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.

PubMed

Yoshioka, Takahiro; Shien, Kazuhiko; Namba, Kei; Torigoe, Hidejiro; Sato, Hiroki; Tomida, Shuta; Yamamoto, Hiromasa; Asano, Hiroaki; Soh, Junichi; Tsukuda, Kazunori; Nagasaka, Takeshi; Fujiwara, Toshiyoshi; Toyooka, Shinichi

2018-04-01

Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-human epidermal growth factor receptor 2 (HER2) drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. First, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs. In the drug sensitivity analysis, both afatinib and neratinib produced an antitumor effect in most of the HER2-amplified cell lines. However, some cells were not sensitive to the drugs. When the molecular profiles of the cells were compared based on the drug sensitivities, we found that cancer cells with lower mRNA expression levels of IGFBP7, a tumor suppressor gene that inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R), were less sensitive to pan-HER inhibitors. A combination therapy consisting of pan-HER inhibitors and an IGF-1R inhibitor, picropodophyllin, showed a notable synergistic effect. Among 123 clinical samples, we found 19 cases of HER2 amplification and three cases of oncogenic mutations. In conclusion, afatinib and neratinib are promising therapeutic options for the treatment of HER2-amplified gastric cancer. In addition to HER2 amplification, IGFBP7 might be a biomarker of sensitivity to these drugs, and IGF-1R-targeting therapy can overcome drug insensitiveness in HER2-amplified gastric cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nielsen, Yousef W., E-mail: yujwni01@heh.regionh.d; Eiberg, Jonas P.; Logager, Vibeke B.

The purpose of this investigation was to determine if addition of infragenicular steady-state (SS) magnetic resonance angiography (MRA) to first-pass imaging improves diagnostic performance compared with first-pass imaging alone in patients with peripheral arterial disease (PAD) undergoing whole-body (WB) MRA. Twenty consecutive patients with PAD referred to digital-subtraction angiography (DSA) underwent WB-MRA. Using a bolus-chase technique, first-pass WB-MRA was performed from the supra-aortic vessels to the ankles. The blood-pool contrast agent gadofosveset trisodium was used at a dose of 0.03 mmol/kg body weight. Ten minutes after injection of the contrast agent, high-resolution (0.7-mm isotropic voxels) SS-MRA of the infragenicular arteriesmore » was performed. Using DSA as the 'gold standard,' sensitivities and specificities for detecting significant arterial stenoses ({>=}50% luminal narrowing) with first-pass WB-MRA, SS-MRA, and combined first-pass and SS-MRA were calculated. Kappa statistics were used to determine intermodality agreement between MRA and DSA. Overall sensitivity and specificity for detecting significant arterial stenoses with first-pass WB-MRA was 0.70 (95% confidence interval 0.61 to 0.78) and 0.97 (0.94 to 0.99), respectively. In first-pass WB-MRA, the lowest sensitivity was in the infragenicular region, with a value of 0.42 (0.23 to 0.63). Combined analysis of first-pass WB-MRA and SS-MRA increased sensitivity to 0.81 (0.60 to 0.93) in the infragenicular region, with specificity of 0.94 (0.88 to 0.97). Sensitivity and specificity for detecting significant arterial stenoses with isolated infragenicular SS-MRA was 0.47 (0.27 to 0.69) and 0.86 (0.78 to 0.91), respectively. Intermodality agreement between MRA and DSA in the infragenicular region was moderate for first-pass WB-MRA ({kappa} = 0.49), fair for SS-MRA ({kappa} = 0.31), and good for combined first-pass/SS-MRA ({kappa} = 0.71). Addition of infragenicular SS-MRA to first-pass WB MRA improves diagnostic performance.« less

The role of FDG PET/CT in patients with locoregional breast cancer recurrence: a comparison to conventional imaging techniques.

PubMed

Aukema, T S; Rutgers, E J Th; Vogel, W V; Teertstra, H J; Oldenburg, H S; Vrancken Peeters, M T F D; Wesseling, J; Russell, N S; Valdés Olmos, R A

2010-04-01

The aim of this study was to evaluate the impact of (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) on clinical management in patients with locoregional breast cancer recurrence amenable for locoregional treatment and to compare the PET/CT results with the conventional imaging data. From January 2006 to August 2008, all patients with locoregional breast cancer recurrence underwent whole-body PET/CT. PET/CT findings were compared with results of the conventional imaging techniques and final pathology. The impact of PET/CT results on clinical management was evaluated based on clinical decisions obtained from patient files. 56 patients were included. In 32 patients (57%) PET/CT revealed additional tumour localisations. Distant metastases were detected in 11 patients on conventional imaging and in 23 patients on PET/CT images (p < 0.01). In 25 patients (45%), PET/CT detected additional lesions not visible on conventional imaging. PET/CT had an impact on clinical management in 27 patients (48%) by detecting more extensive locoregional disease or distant metastases. In 20 patients (36%) extensive surgery was prevented and treatment was changed to palliative treatment. The sensitivity, specificity, accuracy, positive and negative predictive values of FDG PET/CT were respectively 97%, 92%, 95%, 94% and 96%. PET/CT, in addition to conventional imaging techniques, plays an important role in staging patients with locoregional breast cancer recurrence since its result changed the clinical management in almost half of the patients. PET/CT could potentially replace conventional staging imaging in patients with a locoregional breast cancer recurrence. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma.

PubMed

Brüggenjürgen, Bernd; Reinhold, Thomas; Brehler, Randolf; Laake, Eckard; Wiese, Günther; Machate, Ulrich; Willich, Stefan N

2008-09-01

Specific immunotherapy is the only potentially curative treatment in patients with allergic rhinitis and allergic asthma. Health economic evaluations on this treatment, particularly in a German context, are sparse. To evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in addition to symptomatic treatment (ST) compared with ST alone in a German health care setting. The analysis was performed as a health economic model calculation based on Markov models. In addition, we performed a concomitant expert board composed of allergy experts in pediatrics, dermatology, pneumology, and otolaryngology. The primary perspective of the study was societal. Additional sensitivity analyses were performed to prove our results for robustness. The SCIT and ST combination was associated with annual cost savings of Euro140 per patient. After 10 years of disease duration, SCIT and ST reach the breakeven point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787 per quality-adjusted life-year (QALY), with a range that depended on patient age (adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a third-party payer's perspective, SCIT was associated with slightly additional costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients. Additional SCIT was associated with improved medical outcomes and cost savings compared with symptomatic treatment alone according to a societal perspective. Taking a European accepted ICER threshold of up to Euro50,000 per QALY into account, additional SCIT is considered clearly cost-effective compared with routine care in Germany. The degree of cost-effectiveness is strongly affected by costs related to SCIT and the target population receiving such treatment.

Effectiveness of physical exam signs for early detection of critical illness in pediatric systemic inflammatory response syndrome.

PubMed

Scott, Halden F; Donoghue, Aaron J; Gaieski, David F; Marchese, Ronald F; Mistry, Rakesh D

2014-11-19

Early detection of compensated pediatric septic shock requires diagnostic tests that are sensitive and specific. Four physical exam signs are recommended for detecting pediatric septic shock prior to hypotension (cold extremities, mental status, capillary refill, peripheral pulse quality); this study tested their ability to detect patients who develop organ dysfunction among a cohort of undifferentiated pediatric systemic inflammatory response syndrome patients. A prospective cohort of 239 pediatric emergency department patients <19 years with fever and tachycardia and undergoing phlebotomy were enrolled. Physicians recorded initial physical exams on a standardized form. Abstraction of the medical record determined outcomes including organ dysfunction, intensive care unit stay, serious bacterial infection, and therapies. Organ dysfunction occurred in 13/239 (5.4%) patients. Presence of at least one sign was significantly associated with organ dysfunction (Relative Risk: 2.71, 95% CI: 1.05-6.99), and presence of at least two signs had a Relative Risk = 4.98 (95% CI: 1.82-13.58). The sensitivity of exam findings ranged from 8-54%, specificity from 84-98%. Signs were associated with increased risk of intensive care and fluid bolus, but not with serious bacterial infection, intravenous antibiotics or admission. Altered mental status and peripheral pulse quality were significantly associated with organ dysfunction, while abnormal capillary refill time and presence of cold, mottled extremities were not. Certain recommended physical exam signs were associated with increased risk of organ dysfunction, a rare outcome in this undifferentiated pediatric population with fever and tachycardia. Sensitivity was low, while specificity was high. Additional research into optimally sensitive and specific diagnostic strategies is needed.

Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis

PubMed Central

2014-01-01

Background There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB. Methods This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months. Results There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months. Conclusions We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests. PMID:24904240

Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI.

PubMed

Marshall, Helen; Horsley, Alex; Taylor, Chris J; Smith, Laurie; Hughes, David; Horn, Felix C; Swift, Andrew J; Parra-Robles, Juan; Hughes, Paul J; Norquay, Graham; Stewart, Neil J; Collier, Guilhem J; Teare, Dawn; Cunningham, Steve; Aldag, Ina; Wild, Jim M

2017-08-01

Hyperpolarised 3 He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6-16 years) with clinically stable mild cystic fibrosis (CF) (FEV 1 >-1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure-function relationships. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Blastic plasmacytoid dendritic cell neoplasm is dependent on BCL-2 and sensitive to venetoclax

PubMed Central

Montero, Joan; Stephansky, Jason; Cai, Tianyu; Griffin, Gabriel K.; Cabal-Hierro, Lucia; Togami, Katsuhiro; Hogdal, Leah J.; Galinsky, Ilene; Morgan, Elizabeth A.; Aster, Jon C.; Davids, Matthew S.; LeBoeuf, Nicole R.; Stone, Richard M.; Konopleva, Marina; Pemmaraju, Naveen; Letai, Anthony; Lane, Andrew A.

2017-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the anti-apoptotic protein BCL-2 and were uniformly sensitive to the BCL-2 inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, and dynamic BH3 profiling. Animals bearing BPDCN patient-derived xenografts had disease responses and improved survival after venetoclax treatment in vivo. Finally, we report on two patients with relapsed/refractory BPDCN who received venetoclax off-label and experienced significant disease responses. We propose that venetoclax or other BCL-2 inhibitors undergo expedited clinical evaluation in BPDCN, alone or in combination with other therapies. In addition, these data illustrate an example of precision medicine to predict treatment response using ex vivo functional assessment of primary tumor tissue, without requiring a genetic biomarker. PMID:27986708

Bedside ultrasonography for diagnosis of pneumothorax

PubMed Central

Chen, Lin

2015-01-01

Ultrasonography (US) has found its way into the critical care and emergency settings for the evaluation of acute respiratory failure conditions in recent years. It is useful for the diagnosis of varieties of abnormalities involving pleura and lung such as pleural effusion, alveolar interstitial syndrome, and pneumothorax (PTX). In addition to its reproducibility and timeliness, US has high sensitivity and specificity for the diagnosis of these conditions. The most widely used method for bedside evaluation of PTX is chest X-ray (CXR). However, the diagnostic sensitivity of CXR in detecting PTX is limited especially in occult PTX and when the patient is assumed supine position. Computed tomography (CT) is the gold standard in the evaluation of PTX, but is limited by its high radiation exposure and safety concerns in transporting critically ill patients. In this paper we review current advances in PTX diagnosis using US. PMID:26435925

Electrical impedance tomography.

PubMed

Costa, Eduardo L V; Lima, Raul Gonzalez; Amato, Marcelo B P

2009-02-01

Electrical impedance tomography (EIT) is a noninvasive, radiation-free monitoring tool that allows real-time imaging of ventilation. The purpose of this article is to discuss the fundamentals of EIT and to review the use of EIT in critical care patients. In addition to its established role in describing the distribution of alveolar ventilation, EIT has been shown to be a useful tool to detect lung collapse and monitor lung recruitment, both regionally and on a global basis. EIT has also been used to diagnose with high sensitivity incident pneumothoraces during mechanical ventilation. Additionally, with injection of hypertonic saline as a contrast agent, it is possible to estimate ventilation/perfusion distributions. EIT is cheap, noninvasive and allows continuous monitoring of ventilation. It is gaining acceptance as a valuable monitoring tool for the care of critical patients.

FAILURE OF RADIOACTIVE IODINE IN TREATMENT OF HYPERTHYROIDISM

PubMed Central

Schneider, David F.; Sonderman, Philip E.; Jones, Michaela F.; Ojomo, Kristin A.; Chen, Herbert; Jaume, Juan C.; Elson, Diane F.; Perlman, Scott B.; Sippel, Rebecca S.

2015-01-01

Introduction Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common, and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. Methods We conducted a retrospective review of patients treated with RAI from 2007–2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis. Results Of the 325 patients analyzed, 74 patients (22.8%) failed initial RAI treatment. 53 (71.6%) received additional RAI, 13 (17.6%) received additional RAI followed by surgery, and the remaining 8 (10.8%) were cured after thyroidectomy. The percentage of patients who failed decreased in a step-wise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses < 12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (HR 1.13, 95% CI 1.02–1.26, p=0.02) and methimazole treatment (HR 2.55, 95% CI 1.22–5.33, p=0.01) were associated with failure. Conclusions Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients. PMID:25001092

Failure of radioactive iodine in the treatment of hyperthyroidism.

PubMed

Schneider, David F; Sonderman, Philip E; Jones, Michaela F; Ojomo, Kristin A; Chen, Herbert; Jaume, Juan C; Elson, Diane F; Perlman, Scott B; Sippel, Rebecca S

2014-12-01

Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis. Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02-1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure. Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.).

PubMed

Reider, N; Komericki, P; Hausen, B M; Fritsch, P; Aberer, W

2001-11-01

Medical remedies of plant origin have gained increasing popularity in recent years. Both anaphylactic and eczematous allergic reactions are on the rise, accordingly. Arnica and marigold, both of the Compositae family, are in widespread use, but only limited data are available on their allergenic potential. We tested 443 consecutive patients, in addition to the European standard and other series, with Compositae mix, sesquiterpene lactone mix, arnica, marigold, and propolis. 5 subjects ( approximately 1.13%) reacted to arnica, 9 ( approximately 2.03%) to marigold. The Compositae mix was positive in 18 cases ( approximately 4.06%). Among them were 3 out of 5 individuals with a sensitization to arnica, and 4 out of 9 who reacted to marigold. Sensitization to arnica and marigold was often accompanied by reactions to nickel, Myroxylon Pereirae resin, fragrance mix, propolis, and colophonium. We conclude that Compositae allergy contributes significantly to the epidemiology of contact dermatitis and that sensitization to arnica and marigold cannot be assessed by testing with the Compositae or sesquiterpene mix alone. As extracts of these plants are frequently used in occupational and cosmetic products, patch testing with additional plant extracts or adjustment of the commercial Compositae mix to regional conditions is recommended.

Experiential, autonomic, and respiratory correlates of CO2 reactivity in individuals with high and low anxiety sensitivity.

PubMed

Blechert, Jens; Wilhelm, Frank H; Meuret, Alicia E; Wilhelm, Eva M; Roth, Walton T

2013-10-30

Psychometric studies indicate that anxiety sensitivity (AS) is a risk factor for anxiety disorders such as panic disorder (PD). To better understand the psychophysiological basis of AS and its relation to clinical anxiety, we examined whether high-AS individuals show similarly elevated reactivity to inhalations of carbon dioxide (CO2) as previously reported for PD and social phobia in this task. Healthy individuals with high and low AS were exposed to eight standardized inhalations of 20% CO2-enriched air, preceded and followed by inhalations of room air. Anxiety and dyspnea, in addition to autonomic and respiratory responses were measured every 15 s. Throughout the task, high AS participants showed a respiratory pattern of faster, shallower breathing and reduced inhalation of CO2 indicative of anticipatory or contextual anxiety. In addition, they showed elevated dyspnea responses to the second set of air inhalations accompanied by elevated heart rate, which could be due to sensitization or conditioning. Respiratory abnormalities seem to be common to high AS individuals and PD patients when considering previous findings with this task. Similarly, sensitization or conditioning of anxious and dyspneic symptoms might be common to high AS and clinical anxiety. Respiratory conditionability deserves greater attention in anxiety disorder research. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation and Comparison of Multiple Test Methods, Including Real-time PCR, for Legionella Detection in Clinical Specimens

PubMed Central

Peci, Adriana; Winter, Anne-Luise; Gubbay, Jonathan B.

2016-01-01

Legionella is a Gram-negative bacterium that can cause Pontiac fever, a mild upper respiratory infection and Legionnaire’s disease, a more severe illness. We aimed to compare the performance of urine antigen, culture, and polymerase chain reaction (PCR) test methods and to determine if sputum is an acceptable alternative to the use of more invasive bronchoalveolar lavage (BAL). Data for this study included specimens tested for Legionella at Public Health Ontario Laboratories from 1st January, 2010 to 30th April, 2014, as part of routine clinical testing. We found sensitivity of urinary antigen test (UAT) compared to culture to be 87%, specificity 94.7%, positive predictive value (PPV) 63.8%, and negative predictive value (NPV) 98.5%. Sensitivity of UAT compared to PCR was 74.7%, specificity 98.3%, PPV 77.7%, and NPV 98.1%. Out of 146 patients who had a Legionella-positive result by PCR, only 66 (45.2%) also had a positive result by culture. Sensitivity for culture was the same using either sputum or BAL (13.6%); sensitivity for PCR was 10.3% for sputum and 12.8% for BAL. Both sputum and BAL yield similar results regardless testing methods (Fisher Exact p-values = 1.0, for each test). In summary, all test methods have inherent weaknesses in identifying Legionella; therefore, more than one testing method should be used. Obtaining a single specimen type from patients with pneumonia limits the ability to diagnose Legionella, particularly when urine is the specimen type submitted. Given ease of collection and similar sensitivity to BAL, clinicians are encouraged to submit sputum in addition to urine when BAL submission is not practical from patients being tested for Legionella. PMID:27630979

Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy.

PubMed

de Ruiter, C M; van der Veer, C; Leeflang, M M G; Deborggraeve, S; Lucas, C; Adams, E R

2014-09-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Characterization and Plasma Measurement of the WE-14 Peptide in Patients with Pheochromocytoma

PubMed Central

Guillemot, Johann; Guérin, Marlène; Thouënnon, Erwan; Montéro-Hadjadje, Maité; Leprince, Jérôme; Lefebvre, Hervé; Klein, Marc; Muresan, Mihaela; Anouar, Youssef; Yon, Laurent

2014-01-01

Granins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors. The aim of the present study was to investigate the tumoral chromogranin A (CgA)-derived peptide WE-14 and the potential advantage to combine plasma WE-14 detection with the EM66 assay and the existing current CgA assay for the diagnosis of pheochromocytoma. Compared to healthy volunteers, plasma WE-14 levels were 5.4-fold higher in patients with pheochromocytoma, but returned to normal values after surgical resection of the tumor. Determination of plasma CgA and EM66 concentrations in the same group of patients revealed that the test assays for these markers had an overall 84% diagnostic sensitivity, which is identical to that determined for WE-14. However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays. By combining the results of the three assays, the sensitivity for the diagnosis of pheochromocytoma was increased to 95%. In fact, the combination of WE-14 with either CgA or EM66 test assays achieved 100% sensitivity for the diagnosis of paragangliomas and sporadic or malignant pheochromocytomas if taken separately to account for the heterogeneity of the tumor. These data indicate that WE-14 is produced in pheochromocytoma and secreted into the general circulation, and that elevated plasma WE-14 levels are correlated with the occurrence of this chromaffin cell tumor. In addition, in association with other biological markers, such as CgA and/or EM66, WE-14 measurement systematically improves the diagnostic sensitivity for pheochromocytoma. These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors. PMID:24523932

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer.

PubMed

Rosenthal, Eben L; Moore, Lindsay S; Tipirneni, Kiranya; de Boer, Esther; Stevens, Todd M; Hartman, Yolanda E; Carroll, William R; Zinn, Kurt R; Warram, Jason M

2017-08-15

Purpose: Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer. Experimental Design: Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients ( n = 12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1 mm) into their respective blocks, metastatic cancer was found in 8.1% of the recut nodal specimens, which altered staging in two of those cases. Conclusions: Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning. Clin Cancer Res; 23(16); 4744-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Optical biopsy of head and neck cancer using hyperspectral imaging and convolutional neural networks

NASA Astrophysics Data System (ADS)

Halicek, Martin; Little, James V.; Wang, Xu; Patel, Mihir; Griffith, Christopher C.; El-Deiry, Mark W.; Chen, Amy Y.; Fei, Baowei

2018-02-01

Successful outcomes of surgical cancer resection necessitate negative, cancer-free surgical margins. Currently, tissue samples are sent to pathology for diagnostic confirmation. Hyperspectral imaging (HSI) is an emerging, non-contact optical imaging technique. A reliable optical method could serve to diagnose and biopsy specimens in real-time. Using convolutional neural networks (CNNs) as a tissue classifier, we developed a method to use HSI to perform an optical biopsy of ex-vivo surgical specimens, collected from 21 patients undergoing surgical cancer resection. Training and testing on samples from different patients, the CNN can distinguish squamous cell carcinoma (SCCa) from normal aerodigestive tract tissues with an area under the curve (AUC) of 0.82, 81% accuracy, 81% sensitivity, and 80% specificity. Additionally, normal oral tissues can be sub-classified into epithelium, muscle, and glandular mucosa using a decision tree method, with an average AUC of 0.94, 90% accuracy, 93% sensitivity, and 89% specificity. After separately training on thyroid tissue, the CNN differentiates between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multi-nodular goiter (MNG) with an AUC of 0.93, 87% accuracy, 88% sensitivity, and 85% specificity. Classical-type papillary thyroid carcinoma is differentiated from benign MNG with an AUC of 0.91, 86% accuracy, 86% sensitivity, and 86% specificity. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multi-category diagnostic information for normal head-and-neck tissue, SCCa, and thyroid carcinomas. More patient data are needed in order to fully investigate the proposed technique to establish reliability and generalizability of the work.

Experimental Psychological Stress on Quantitative Sensory Testing Response in Patients with Temporomandibular Disorders.

PubMed

Araújo Oliveira Ferreira, Dyna Mara; Costa, Yuri Martins; de Quevedo, Henrique Müller; Bonjardim, Leonardo Rigoldi; Rodrigues Conti, Paulo César

2018-05-15

To assess the modulatory effects of experimental psychological stress on the somatosensory evaluation of myofascial temporomandibular disorder (TMD) patients. A total of 20 women with myofascial TMD and 20 age-matched healthy women were assessed by means of a standardized battery of quantitative sensory testing. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR), and pressure pain threshold (PPT) were performed on the facial skin overlying the masseter muscle. The variables were measured in three sessions: before (baseline) and immediately after the Paced Auditory Serial Addition Task (PASAT) (stress) and then after a washout period of 20 to 30 minutes (poststress). Mixed analysis of variance (ANOVA) was applied to the data, and the significance level was set at P = .050. A significant main effect of the experimental session on all thermal tests was found (ANOVA: F > 4.10, P < .017), where detection tests presented an increase in thresholds in the poststress session compared to baseline (CDT, P = .012; WDT, P = .040) and pain thresholds were reduced in the stress (CPT, P < .001; HPT, P = .001) and poststress sessions (CPT, P = .005; HPT, P = .006) compared to baseline. In addition, a significant main effect of the study group on all mechanical tests (MPT, WUR, and PPT) was found (ANOVA: F > 4.65, P < .037), where TMD patients were more sensitive than healthy volunteers. Acute mental stress conditioning can modulate thermal sensitivity of the skin overlying the masseter in myofascial TMD patients and healthy volunteers. Therefore, psychological stress should be considered in order to perform an unbiased somatosensory assessment of TMD patients.

Specific Infectious Organisms Associated With Poor Outcomes in Treatment for Hip Periprosthetic Infection.

PubMed

Cunningham, Daniel J; Kavolus, Joseph J; Bolognesi, Michael P; Wellman, Samuel S; Seyler, Thorsten M

2017-06-01

Periprosthetic hip infection treatment remains a significant challenge for orthopedics. Some studies have suggested that methicillin resistance and gram-negative organism type are associated with increased treatment failure. The aim of this research is to determine if specific organisms were associated with poor outcomes in treatment for hip periprosthetic infection. Records were reviewed of all patients between 2005 and 2015 who underwent treatment for infected partial or total hip arthroplasty. Characteristics of each patient's treatment course were determined including baseline characteristics, infecting organism(s), infection status at final follow-up, surgeries for infection, and time in hospital. Baseline characteristics and organisms that were associated with clinical outcomes in univariate analysis were incorporated into multivariable outcomes models. When compared with patients infected with other organism(s), patients infected with the following organisms had significantly decreased infection-free rates: Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA), and Proteus. Infection with certain organisms was associated with 1.13-2.58 additional surgeries: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, MRSA, Pseudomonas, Peptostreptococcus, Klebsiella, Candida, diphtheroids, Propionibacterium acnes, and Proteus species. Specific organisms were associated with 8.56-24.54 additional days in hospital for infection: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, Proteus, MRSA, Enterococcus, Pseudomonas, Klebsiella, beta-hemolytic Streptococcus, and diphtheroids. Higher comorbidity score was also associated with greater length of hospitalization. MRSA, Pseudomonas, and Proteus were associated with all 3 outcomes of lower infection-free rate, more surgery, and more time in hospital in treatment for hip periprosthetic infection. Organism-specific outcome information may help individualize patient-physician discussions about the expected course of treatment for hip periprosthetic infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Out-of-field in vivo dosimetry using TLD in SABR for primary kidney cancer involving mixed photon fields.

PubMed

Lonski, P; Keehan, S; Siva, S; Pham, D; Franich, R D; Taylor, M L; Kron, T

2017-05-01

To assess out-of-field dose using three different variants of LiF thermoluminescence dosimeters (TLD) for ten patients who underwent stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) and compare with treatment planning system (TPS) dose calculations. Thermoluminescent dosimeter (TLD) measurements were conducted at 20, 30, 40 and 50cm from isocentre on ten patients undergoing SABR for primary RCC. Three types of high-sensitivity LiF:Mg,Cu,P TLD material with different 6 Li/ 7 Li isotope ratios were used. Patient plans were calculated using Eclipse Anisotropic Analytical Algorithm (AAA) for clinical evaluation and recalculated using Pencil Beam Convolution (PBC) algorithm for comparison. Both AAA and PBC showed diminished accuracy for photon doses at increasing distance out-of-field. At 50cm, measured photon dose was 0.3cGy normalised to a 10Gy prescription on average with only small variation across all patients. This is likely due to the leakage component of the out-of-field dose. The 6 Li-enriched TLD materials showed increased signal attributable to additional neutron contribution. LiF:Mg,Cu,P TLD containing 6 Li is sensitive enough to measure out-of-field dose 50cm from isocentre however will over-estimate the photon component of out-of-field dose in high energy treatments due to the presence of thermal neutrons. 7 Li enriched materials which are insensitive to neutrons are therefore required for accurate photon dosimetry. Neutron signal has been shown here to increase with MUs and is higher for patients treated using certain non coplanar beam arrangements. Further work is required to convert this additional neutron signal to dose. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshioka, Yasuo; Ogawa, Kazuhiko, E-mail: kogawa@radonc.med.osaka-u.ac.jp; Oikawa, Hirobumi

Purpose: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. Methods and Materials: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS),more » and local control (LC) was investigated. Results: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT– group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT– group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT– group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. Conclusions: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.« less

Screening and prevention of venous thromboembolism in critically ill patients: a decision analysis and economic evaluation.

PubMed

Sud, Sachin; Mittmann, Nicole; Cook, Deborah J; Geerts, William; Chan, Brian; Dodek, Peter; Gould, Michael K; Guyatt, Gordon; Arabi, Yaseen; Fowler, Robert A

2011-12-01

Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality. To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients. A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios. In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses. Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.

Platelet response to aspirin 50 and 100 mg in patients with coronary heart disease over a five-year period.

PubMed

Berent, Robert; Auer, Johann; Franklin, Barry; Schmid, Peter; von Duvillard, Serge P

2011-09-01

Aspirin has been shown to decrease cardiovascular (CV) events by ∼25%. Despite aspirin therapy 10% to 20% of patients with arterial vascular disease develop atherothrombotic events. A meta-analysis of antiplatelet therapy showed a progressive decrease in clinical efficacy of aspirin after 2 years. Whether this is due to a decreased sensitivity to aspirin during long-term therapy remains unclear. A prospective randomized clinical trial with serial monitoring over 5 years was conducted in 100 patients with documented coronary heart disease. We investigated whether long-term treatment with aspirin 50 and 100 mg affects platelet response similarly. Occurrence of CV events was documented. Platelet sensitivity to aspirin, prostacyclin, and adenosine diphosphate-, collagen-, and epinephrine-induced platelet aggregation were evaluated over time. In addition, β-thromboglobulin and inflammatory markers were measured. Four patients were lost to follow-up and 10 patients died. Eleven patients developed nonfatal CV events. In the 2 groups platelet response to aspirin and the referenced variables remained unchanged over 5 years. In patients who developed CV events, the last monitoring interval revealed no difference in platelet response to aspirin. However, patients with nonfatal and fatal CV events showed increased inflammatory markers versus patients without CV events independent of aspirin 50 or 100 mg intake. In conclusion, our study revealed no difference in antiplatelet response to aspirin 50 versus 100 mg or CV events over 5 years in patients with coronary heart disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

PubMed Central

Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye.

PubMed

Perényi, Kristóf; Dienes, Lóránt; Kornafeld, Anna; Kovács, Balázs; Kiss, Huba J; Szepessy, Zsuzsanna; Nagy, Zoltán Z; Barsi, Árpád; Acosta, M Carmen; Gallar, Juana; Kovács, Illés

To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients. Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate. After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO 2 ; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05). Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.

The Value of Diffusion-Weighted Imaging in Combination With Conventional Magnetic Resonance Imaging for Improving Tumor Detection for Early Cervical Carcinoma Treated With Fertility-Sparing Surgery.

PubMed

Li, Xiulei; Wang, Ling; Li, Yong; Song, Peiji

2017-10-01

This study aimed to investigate the value of diffusion-weighted imaging (DWI) in combination with conventional magnetic resonance imaging (MRI) for improving tumor detection in young patients treated with fertility-sparing surgery because of early cervical carcinoma. Fifty-four patients with stage Ia or Ib1 cervical carcinoma were enrolled into this study. Magnetic resonance examinations were performed for these patients using conventional MRI (including T1-weighted imaging, T2-weighted imaging, and dynamic contrast-enhanced MRI) and DWI. The apparent diffusion coefficient (ADC) values of cervical carcinoma were analyzed quantitatively and compared with that of adjacent epithelium. Sensitivity, positive predictive value, and accuracy of 2 sets of MRI sequences were calculated on the basis of histologic results, and the diagnostic ability of conventional MRI/DWI combinations was compared with that of conventional MRI. The mean ADC value from cervical carcinoma (mean, 786 × 10 mm/s ± 100) was significantly lower than that from adjacent epithelium (mean, 1352 × 10 mm/s ± 147) (P = 0.01). When the threshold ADC value set as 1010 × 10 mm/s, the sensitivity and specificity for differentiating cervical carcinoma from nontumor epithelium were 78.2% and 67.2%, respectively. The sensitivity and accuracy of conventional MRI for tumor detection were 76.0% and 70.4%, whereas the sensitivity and accuracy of conventional MRI/DWI combinations were 91.7% and 90.7%, respectively. Conventional MRI/DWI combinations revealed a positive predictive value of 97.8% and only 4 false-negative findings. The addition of DWI to conventional MRI considerably improves the sensitivity and accuracy of tumor detection in young patients treated with fertility-sparing surgery, which supports the inclusion quantitative analysis of ADC value in routine MRI protocol before fertility-sparing surgery.

Effects of short-term inpatient treatment on sensitivity to a size contrast illusion in first-episode psychosis and multiple-episode schizophrenia.

PubMed

Silverstein, Steven M; Keane, Brian P; Wang, Yushi; Mikkilineni, Deepthi; Paterno, Danielle; Papathomas, Thomas V; Feigenson, Keith

2013-01-01

In the Ebbinghaus illusion, a shape appears larger than its actual size when surrounded by small shapes and smaller than its actual size when surrounded by large shapes. Resistance to this visual illusion has been previously reported in schizophrenia, and linked to disorganized symptoms and poorer prognosis in cross-sectional studies. It is unclear, however, when in the course of illness this resistance first emerges or how it varies longitudinally with illness phase. We addressed these issues by having first-episode psychosis patients, multiple-episode schizophrenia patients and healthy controls complete a psychophysical task at two different time points, corresponding to hospital admission and discharge for patients. The task required judging the relative size of two circular targets centered on either side of the screen. Targets were presented without context (baseline), or were surrounded by shapes that made the size judgment harder or easier (misleading and helpful contexts, respectively). Context sensitivity was operationalized as the amount of improvement relative to baseline in the helpful condition minus the amount of decrement relative to baseline in the misleading condition. At hospital admission, context sensitivity was lower in the multiple-episode group than in the other groups, and was marginally less in the first episode than in the control group. In addition, schizophrenia patients were significantly more and less accurate than the other groups in the misleading and helpful conditions, respectively. At discharge, all groups exhibited similar context sensitivity. In general, poorer context sensitivity was related to higher levels of disorganized symptoms, and lower level of depression, excitement, and positive symptoms. Resistance to the Ebbinghaus illusion, as a characteristic of the acute phase of illness in schizophrenia, increases in magnitude after the first episode of psychosis. This suggests that visual context processing is a state-marker in schizophrenia and a biomarker of relapse and recovery.

INFECTION RETARDANT COATINGS IMPACT ON BACTERIAL PRESENCE IN PENILE PROSTHESIS SURGERY: A MULTICENTER STUDY.

PubMed

Jani, Kavina; Smith, Christopher; Delk, John R; Carson, Culley C; Donatucci, Craig F; Cleves, Mario A; Wilson, Steven K; Henry, Gerard D

2018-06-09

To investigate patients for positive culture rates with or without IRC PPs and to examine changes in culture positive isolates found in patients presenting overt clinical infection. Cultures were obtained from PPs immediately upon surgical exposure of the pump. 236 patients were broken down into 2 groups, with each further divided into 2 groups. The non-infected group included 208 patients: 133 with uncoated PPs and 75 with IRC implants. The infected group included 28 patients: 16 with uncoated PP and 12 with IRC IPP. Additionally, sensitivity to the combination of tetracycline and rifampin were evaluated on all cultures. In the non-infected group, culture positive isolates were found in 85 patients with uncoated PP's and in 32 patients with IRC implants [p-value = 0.0003]. Cultures positive for Staphylococcus genus were found in 75 uncoated PP patients, while 20 patients with IRC implants had an isolate of this genus. In the infected group, culture positive isolates were found in 7 patients with uncoated PP and 6 patients with IRC IPPs [p-value = 1.000]. Positive cultures for Staphylococcus genus were found in 6 patients with uncoated PP, while 3 patients with IRC IPP had an isolate of this genus. All bacterial isolates were sensitive to the combination of tetracycline and rifampin. Positive bacterial cultures have been shown to be present on clinically uninfected IPPs at time of revision surgery. Culture isolates grown from patients with IRC IPPs reveal a non-traditional bacterial profile: fewer cultured isolates of Staphylococcus genus. Copyright © 2018. Published by Elsevier Inc.

Cardiothoracic ratio for prediction of left ventricular dilation: a systematic review and pooled analysis.

PubMed

Loomba, Rohit S; Shah, Parinda H; Nijhawan, Karan; Aggarwal, Saurabh; Arora, Rohit

2015-03-01

Increased cardiothoracic ratio noted on chest radiographs often prompts concern and further evaluation with additional imaging. This study pools available data assessing the utility of cardiothoracic ratio in predicting left ventricular dilation. A systematic review of the literature was conducted to identify studies comparing cardiothoracic ratio by chest x-ray to left ventricular dilation by echocardiography. Electronic databases were used to identify studies which were then assessed for quality and bias, with those with adequate quality and minimal bias ultimately being included in the pooled analysis. The pooled data were used to determine the sensitivity, specificity, positive predictive value and negative predictive value of cardiomegaly in predicting left ventricular dilation. A total of six studies consisting of 466 patients were included in this analysis. Cardiothoracic ratio had 83.3% sensitivity, 45.4% specificity, 43.5% positive predictive value and 82.7% negative predictive value. When a secondary analysis was conducted with a pediatric study excluded, a total of five studies consisting of 371 patients were included. Cardiothoracic ratio had 86.2% sensitivity, 25.2% specificity, 42.5% positive predictive value and 74.0% negative predictive value. Cardiothoracic ratio as determined by chest radiograph is sensitive but not specific for identifying left ventricular dilation. Cardiothoracic ratio also has a strong negative predictive value for identifying left ventricular dilation.

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines.

PubMed

D'Alessandro, Giandomenico; Cerritelli, Francesco; Cortelli, Pietro

2016-01-01

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate "reading system" able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways.

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines

PubMed Central

D'Alessandro, Giandomenico; Cerritelli, Francesco; Cortelli, Pietro

2016-01-01

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate “reading system” able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways. PMID:27013961

Streamlining the Evaluation of Low Back Pain in Children

PubMed Central

Auerbach, Joshua D.; Ahn, Jaimo; Zgonis, Miltiadis H.; Reddy, Sudheer C.; Ecker, Malcolm L.

2008-01-01

The workup of low back pain in children often results in overimaging so as not to miss organic back pain. The primary goal of this study was to identify which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain. Medical records from 100 consecutive patients between 2 and 18 years of age presenting with low back pain, without night pain or constitutional symptoms, were evaluated. A hyperextension test combined with a radiograph showed a negative predictive value of 0.81 and sensitivity of 0.90. The addition of a bone scan was highly effective in achieving good negative predictive value and sensitivity. Bone scans had perfect negative predictive value and sensitivity when symptom duration was less than 6 weeks. We identified a set of factors that is highly predictive for distinguishing organic back pain from mechanical back pain. Painless hyperextension combined with negative anteroposterior, lateral, and oblique lumbar radiographs and magnetic resonance images predicts mechanical back pain. For patients with nonneurologic back pain of less than 6 weeks duration, bone scan is the most useful screening test because it is accurate, accessible, inexpensive, and unlikely to require sedation. Level of Evidence: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18553213

A System Dynamics Approach to Modeling the Sensitivity of Inappropriate Emergency Department Utilization

NASA Astrophysics Data System (ADS)

Behr, Joshua G.; Diaz, Rafael

Non-urgent Emergency Department utilization has been attributed with increasing congestion in the flow and treatment of patients and, by extension, conditions the quality of care and profitability of the Emergency Department. Interventions designed to divert populations to more appropriate care may be cautiously received by operations managers due to uncertainty about the impact an adopted intervention may have on the two values of congestion and profitability. System Dynamics (SD) modeling and simulation may be used to measure the sensitivity of these two, often-competing, values of congestion and profitability and, thus, provide an additional layer of information designed to inform strategic decision making.

Recent advances in distal tubular potassium handling

PubMed Central

Rodan, Aylin R.; Cheng, Chih-Jen

2011-01-01

It is well known that sodium reabsorption and aldosterone play important roles in potassium secretion by the aldosterone-sensitive distal nephron. Sodium- and aldosterone-independent mechanisms also exist. This review focuses on some recent studies that provide novel insights into the sodium- and aldosterone-independent potassium secretion by the aldosterone-sensitive distal nephron. In addition, we discuss a study reporting on the regulation of the mammalian potassium kidney channel ROMK by intracellular and extracellular magnesium, which may be important in the pathogenesis of persistent hypokalemia in patients with concomitant potassium and magnesium deficiency. We also discuss outstanding questions and propose working models for future investigation. PMID:21270092

Number needed to treat and associated incremental costs of treatment with enzalutamide versus abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

PubMed

Massoudi, Marjan; Balk, Mark; Yang, Hongbo; Bui, Cat N; Pandya, Bhavik J; Guo, Jenny; Song, Yan; Wu, Eric Q; Brown, Bruce; Barlev, Arie; Flanders, Scott

2017-02-01

Enzalutamide (ENZA) and abiraterone acetate plus prednisone (AA) are approved second-generation hormone therapies for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). This study compared ENZA with AA in chemotherapy-naïve mCRPC by calculating the number needed to treat (NNT) and associated incremental costs to achieve one additional chemotherapy-naïve patient with mCRPC free of radiographic progression, chemotherapy, or death over a 1-year time horizon. Clinical outcomes were obtained from the PREVAIL and COU-AA-302 trials. Three outcomes were evaluated: radiographic progression-free survival, time to cytotoxic chemotherapy initiation, and overall survival at 1 year. NNT was calculated as the reciprocal of the outcome event rate difference for ENZA compared with AA. The incremental costs to achieve one additional outcome at 1 year were calculated as the difference in cost per treated patient multiplied by the NNT. Per-treated-patient costs were considered from a US payer perspective and included medications, monitoring, adverse events, post-progression treatments, and end-of-life care. Within a 1-year time horizon, the total cost per treated patient for ENZA was $2,666 less than AA. Compared with AA, treating 14 patients with ENZA resulted in one additional patient free of progression or death over 1 year; treating 26 patients with ENZA resulted in one additional patient with chemotherapy delayed over 1 year; and treating 91 patients with ENZA resulted in one additional patient free of death over 1 year. Therefore, ENZA is cost-effective compared with AA for all three outcomes evaluated, and the modeled results suggest ENZA is associated with potentially improved clinical outcomes in delaying chemotherapy initiation and disease progression for chemotherapy-naïve patients. The results are robust in sensitivity analyses, where the effect of changes in key model inputs and assumptions were tested. The results modeled in the present study suggest ENZA is cost-effective compared with AA for treating chemotherapy-naïve patients with mCRPC.

Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma.

PubMed

O'Driscoll, B R; Powell, G; Chew, F; Niven, R M; Miles, J F; Vyas, A; Denning, D W

2009-11-01

It has been shown that patients with allergic bronchopulmonary aspergillosis (ABPA) and patients with severe asthma with fungal sensitization (SAFS) can benefit from antifungal therapy. It is not known whether allergy skin prick tests (SPT) or specific IgE tests are more sensitive in the identification of patients who are sensitized to fungi and who are therefore candidates for antifungal therapy. To compare SPT and specific serum IgE tests for fungal sensitization in patients with severe asthma. We have undertaken SPT and specific serum IgE tests to six fungi (Aspergillus fumigatus, Candida albicans, Penicillium notatum, Cladosporium herbarum, Alternaria alternata and Botrytis cineria) and specific serum IgE test for Trichophyton in 121 patients with severe asthma (British Thoracic Society/SIGN steps 4 and 5). Sixty-six percent of patients were sensitized to one or more fungi based on SPT and/or specific serum IgE results. Positivity to SPT and/or specific serum IgE was as follows: A. fumigatus 45%, C. albicans 36%, P. notatum 29%, C. herbarum 24%, A. alternata 22%, B. cineria 18%, Trichophyton 17% (specific serum IgE only). Concordance between the tests was 77% overall but only 14-56% for individual fungi. Twenty-nine (24%) patients were sensitized to a single fungus and seven (6%) were sensitized to all seven fungal species. Fifty percent of patients were sensitized to fungal and non-fungal extracts, 21% were sensitized only to non-fungal extracts, 16% were sensitized only to fungal extracts and 13% had no positive tests. This study is consistent with previous reports that fungal sensitization is common in patients with severe asthma. At present, it remains necessary to undertake both SPT and specific serum IgE testing to identify all cases of fungal sensitization. This may be important in the identification of patients with ABPA and SAFS who may benefit from antifungal therapy.

Barnidipine compared to lercanidipine in addition to losartan on endothelial damage and oxidative stress parameters in patients with hypertension and type 2 diabetes mellitus.

PubMed

Derosa, Giuseppe; Mugellini, Amedeo; Pesce, Rosa Maria; D'Angelo, Angela; Maffioli, Pamela

2016-04-12

Essential hypertension has been extensively reported to cause endothelial dysfunction. The aim of this study was to evaluate the effects of barnidipine or lercanidipine, in addition to losartan, on some parameters indicative of endothelial damage and oxidative stress in hypertensive, type 2 diabetic patients. One hundred and fifty one patients were randomised to barnidipine, 20 mg/day, or lercanidipine, 20 mg/day, both in addition to losartan, 100 mg/day, for 6 months. We assessed BP every month, in addition, patients underwent ambulatory blood pressure monitoring (ABPM). We also assessed: fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), some markers such as high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), metalloproteinase-2 (MMP-2) and -9 (MMP-9), soluble vascular adhesion protein-1 (sVCAM-1), soluble intercellular adhesion protein-1 (sICAM-1), isoprostanes and paraoxonase-1 (PON-1). Both barnidipine and lercanidipine resulted in a significant reduction in blood pressure, even if the reduction obtained with barnidipine + losartan was greater than that obtained with lercanidipine + losartan. Data recorded with ABPM also showed a similar trend. Barnidipine + losartan reduced the levels of Hs-CRP, TNF-α, sVCAM-1, sICAM-1, and isoprostanes both compared to baseline and to lercanidipine + losartan. Barnidipine + losartan gave an improvement of some parameters indicative of endothelial damage and oxidative stress in diabetic and hypertensive patients. NCT02064218 , ClinicalTrials.gov.

Hypersensitivity of skin fibroblasts from basal cell nevus syndrome patients to killing by ultraviolet B but not by ultraviolet C radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Applegate, L.A.; Goldberg, L.H.; Ley, R.D.

Basal cell nevus syndrome (BCNS) is an autosomal dominant genetic disorder in which the afflicted individuals are extremely susceptible to sunlight-induced skin cancers, particularly basal cell carcinomas. However, the cellular and molecular basis for BCNS is unknown. To ascertain whether there is any relationship between genetic predisposition to skin cancer and increased sensitivity of somatic cells from BCNS patients to killing by UV radiation, we exposed skin fibroblasts established from unexposed skin biopsies of several BCNS and age- and sex-matched normal individuals to either UV-B (280-320 nm) or UV-C (254 nm) radiation and determined their survival. The results indicated thatmore » skin fibroblasts from BCNS patients were hypersensitive to killing by UV-B but not UV-C radiation as compared to skin fibroblasts from normal individuals. DNA repair studies indicated that the increased sensitivity of BCNS skin fibroblasts to killing by UV-B radiation was not due to a defect in the excision repair of pyrimidine dimers. These results indicate that there is an association between hypersensitivity of somatic cells to killing by UV-B radiation and the genetic predisposition to skin cancer in BCNS patients. In addition, these results suggest that DNA lesions (and repair processes) other than the pyrimidine dimer are also involved in the pathogenesis of sunlight-induced skin cancers in BCNS patients. More important, the UV-B sensitivity assay described here may be used as a diagnostic tool to identify presymptomatic individuals with BCNS.« less

Percutaneous CT-guided sacroiliac joint sampling for infection: aspiration, biopsy, and technique.

PubMed

Knipp, David; Simeone, F Joseph; Nelson, Sandra B; Huang, Ambrose J; Chang, Connie Y

2018-04-01

To evaluate methods of CT-guided sacroiliac joint sampling in patients with suspected infection. All CT-guided sacroiliac joint sampling procedures for suspected infection were reviewed for sampling type (aspiration, lavage aspiration, biopsy), microbiology results, and clinical and imaging follow-up. The primary gold standard was anatomic pathology. If pathology was not available, then positive blood culture with the same organism as SIJ sampling, imaging and clinical follow-up, or clinical follow-up only were used. Anterior and posterior joint distention was evaluated by MRI within 7 days of the procedure. A total of 34 patients (age 39 ± 20 (range, 6-75) years; 21 F, 13 M) were included. Aspiration samples only were obtained in 13/34 (38%) cases, biopsy samples only in 9/34 (26%) cases, and both samples in 12/34 (35%) cases. There was an overall 54% sensitivity and 86% specificity. For the aspiration samples, sensitivity and specificity were 60 and 81%, respectively, compared to 45 and 90% for the biopsy samples. In cases with both samples, biopsy did not add additional microbial information. Seventeen (17/34, 50%) patients had an MRI. The anterior joint was more distended than the posterior joint in 15/17 (88%) of patients, and this difference was significant (P = 0.0003). All of these 17 patients had an attempted aspiration by a posterior approach; 6/17 (35%) resulted in a successful aspiration. Aspiration of the sacroiliac joint has a higher sensitivity than biopsy and should always be attempted first. MRI may be helpful for procedure planning.

Isolation and characterization of circulating tumor cells from human gastric cancer patients.

PubMed

Yuan, Dandan; Chen, Liang; Li, Mingxing; Xia, Hongwei; Zhang, Yuchen; Chen, Tie; Xia, Rui; Tang, Qiulin; Gao, Fabao; Mo, Xianming; Liu, Ming; Bi, Feng

2015-04-01

Circulating tumor cells (CTCs) have been proved to be responsible for tumor metastasis and resistant to anticancer therapies. This study aims to isolate and characterize circulating tumor cells from human gastric cancer patients, and investigate characteristic differences between gastric CTCs and gastric cancer cell lines. We analyzed 31 cases of gastric cancer patients using anti-CD45 antibody-conjugated magnetic microbeads negative separation, combined with fluorescence activated cell sorter CD44 positive screening. Abilities of tumor formation, metastasis, invasion, migration, irradiation and drug sensitivity of CTCs and gastric cancer cell lines were detected and compared. Of all the 31 patients, CD44(+)/CD45(-)CTCs were isolated in 14 patients, of which 3 cases were stage IIA, 2 cases stage IIB, 2 cases stage IIIC and 7 cases stage IV. The malignant behavior was demonstrated by both clonogenetic assay and tumor xenograft in nude mice. Compared with human gastric cancer cell lines, the migration and invasion abilities of CTCs increased to 3.21-12.6-fold and 2.3-6.7-fold, respectively (all p values <0.05). In addition, the metastatic potential of CTCs is much higher in vivo than that of the control. Furthermore, CTCs were found to be relatively sensitive to FU, cisplatin and paclitaxel, but relatively resistant to irradiation, oxaliplatin, cetuximab and trastuzumab. CD44(+)/CD45(-) gastric CTCs were isolated and found to exhibit stronger malignant behavior when compared with human gastric cancer cell lines. Furthermore, CTCs cultured in vitro have potential implications in drug sensitivity screening for the future anticancer treatments.

Capsule endoscopy for the detection of oesophageal mucosal disorders: a comparison of two different ingestion protocols.

PubMed

De Jonge, Pieter J F; Van Eijck, Brechje C; Geldof, Han; Bekkering, Frank C; Essink-Bot, Marie-Louise; Polinder, Suzanne; Kuipers, Ernst J; Siersema, Peter D

2008-01-01

To assess the accuracy of a new ingestion protocol for capsule endoscopy (CE) in evaluating patients with gastro-oesophageal reflux disease (GORD). Oesophago-gastroduodenoscopy (OGD) was performed 1 week prior to CE. The first 28 subjects swallowed the capsule following the original ingestion protocol (OIP) and the subsequent 30 subjects following a simplified ingestion protocol (SIP). CE videos were reviewed by two independent investigators who were blinded to the OGD findings. Of 48 patients included, 24 were diagnosed with reflux oesophagitis (67% male, mean age 49.5+/-13 years) and 24 with Barrett oesophagus (BO) (88% male, 55.6+/-10 years) by OGD. In addition, 10 asymptomatic healthy controls (50% male, 45.8+/-7.1 years) were included. Oesophageal transit time was faster in patients using the SIP compared to the OIP (126+/-26 s versus 214+/-33; p=0.04). Complete evaluation of the Z-line was possible in 19/28 (68%) of the OIPs compared to 28/30 (93%) of the SIPs (p=0.04). Sensitivity for detecting any oesophageal abnormality was higher in the SIP group than in the OIP group (97% versus 89%; p=0.11). Overall, CE detected oesophagitis in 22/24 patients (sensitivity, 92%; specificity, 88%) and BO in 23/24 patients (sensitivity, 96%; specificity, 91%). Furthermore, 41/44 (93%) preferred CE over OGD and experienced less discomfort and pain during CE. CE is an accurate method for detecting mucosal oesophageal abnormalities. The new ingestion protocol improves the visualization of the Z-line, which is likely to increase the diagnostic yield of CE.

Rapid diagnosis of sepsis with TaqMan-Based multiplex real-time PCR.

PubMed

Liu, Chang-Feng; Shi, Xin-Ping; Chen, Yun; Jin, Ye; Zhang, Bing

2018-02-01

The survival rate of septic patients mainly depends on a rapid and reliable diagnosis. A rapid, broad range, specific and sensitive quantitative diagnostic test is the urgent need. Thus, we developed a TaqMan-Based Multiplex real-time PCR assays to identify bloodstream pathogens within a few hours. Primers and TaqMan probes were designed to be complementary to conserved regions in the 16S rDNA gene of different kinds of bacteria. To evaluate accurately, sensitively, and specifically, the known bacteria samples (Standard strains, whole blood samples) are determined by TaqMan-Based Multiplex real-time PCR. In addition, 30 blood samples taken from patients with clinical symptoms of sepsis were tested by TaqMan-Based Multiplex real-time PCR and blood culture. The mean frequency of positive for Multiplex real-time PCR was 96% at a concentration of 100 CFU/mL, and it was 100% at a concentration greater than 1000 CFU/mL. All the known blood samples and Standard strains were detected positively by TaqMan-Based Multiplex PCR, no PCR products were detected when DNAs from other bacterium were used in the multiplex assay. Among the 30 patients with clinical symptoms of sepsis, 18 patients were confirmed positive by Multiplex real-time PCR and seven patients were confirmed positive by blood culture. TaqMan-Based Multiplex real-time PCR assay with highly sensitivity, specificity and broad detection range, is a rapid and accurate method in the detection of bacterial pathogens of sepsis and should have a promising usage in the diagnosis of sepsis. © 2017 Wiley Periodicals, Inc.

Occupational contact dermatitis due to essential oils.

PubMed

Trattner, Akiva; David, Michael; Lazarov, Aneta

2008-05-01

Allergic contact dermatitis induced by the occupational use of products containing essential oils has not been studied comprehensively. The aim of the present report was to describe the characteristics, diagnosis, and outcome of 5 patients with occupational contact dermatitis because of essential oils attending our outpatient dermatology clinics over a 2-year period. These patients are added to the 11 cases reported thus far in the literature. The research shows that for proper diagnosis, patch tests with the standard series and the fragrance series should be performed, in addition to tests with the specific oils to which the patients were exposed. Patients should be instructed to avoid the allergens identified. Sensitization to essential oils has important implications for the occupational future of affected individuals.

No Evidence for Infection of UK Prostate Cancer Patients with XMRV, BK Virus, Trichomonas vaginalis or Human Papilloma Viruses

PubMed Central

Groom, Harriet C. T.; Warren, Anne Y.; Neal, David E.; Bishop, Kate N.

2012-01-01

The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer. PMID:22470540

No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.

PubMed

Groom, Harriet C T; Warren, Anne Y; Neal, David E; Bishop, Kate N

2012-01-01

The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.

Pneumonia risk stratification in tropical Australia: does the SMART-COP score apply?

PubMed

Davis, Joshua S; Cross, Gail B; Charles, Patrick G P; Currie, Bart J; Anstey, Nicholas M; Cheng, Allen C

2010-02-01

To examine the performance in tropical northern Australia of SMART-COP, a simple scoring system developed in temperate Australia to predict the need for intensive respiratory or vasopressor support (IRVS) in pneumonia patients. A prospective observational study of patients admitted to Royal Darwin Hospital in the Northern Territory with sepsis between August 2007 and May 2008. Chest x-rays were reviewed to confirm pneumonia, and each patient's SMART-COP score was assessed against the need for IRVS. Of 206 patients presenting with radiologically confirmed pneumonia, 184 were eligible for inclusion. The mean age of patients was 50.1 years, 65% were Indigenous and 56% were men. Overall, 38 patients (21%) required IRVS, and 18 patients (10%) died by Day 30. A SMART-COP score of >or= 3 had a sensitivity of only 71% for predicting the need for IRVS and 67% for 30-day mortality. As the variables most strongly associated with IRVS were serum albumin level < 35 g/L (odds ratio, 6.8) and Indigenous status (odds ratio, 2.3), we tested a modified scoring system (SMART-COP) that used a higher weighting for albumin and included Indigenous status. A SMART-COP score of >or= 3 had a sensitivity of 97% for IRVS and 100% for 30-day mortality. The SMART-COP score underestimates the severity of pneumonia in tropical northern Australia, but can be improved by using locally relevant additions.

Assessment of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Atopic Dermatitis Patients

PubMed Central

Jiang, Ying; Ma, Wencong

2017-01-01

Background To develop new strategies for identifying atopic dermatitis patients, a better understanding of the signs for chronic inflammatory status is needed. This study was designed to investigate whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are related to the severity of atopic dermatitis (AD) assessed by the Scoring Atopic Dermatitis (SCORAD) index. Material/Methods A retrospective study involving 80 AD patients and 45 healthy control subjects was performed. NLR, PLR, and the number of peripheral blood eosinophils were compared between AD patients and healthy controls, and correlations between these indexes and clinical characteristics were analyzed. Results NLR, PLR, and eosinophils in AD patients were all significantly higher than in healthy individuals. Among AD patients, NLR (p<0.001) and PLR (p<0.001), as contrasted with eosinophils (p=0.146), were correlated positively with SCORAD index. Additionally, an NLR level of 1.75 was determined as the predictive cut-off value of severe AD (SCORAD ≥51) (sensitivity 94.7%, specificity 58.6%, the area under the receiver-operating characteristic curve (AUROC) 0.778, p=0.001). For eosinophils, the sensitivity and specificity were 78.9% and 62.1%, respectively, and the AUROC was only 0.685 (p=0.032) in predicting high SCORAD. Conclusions NLR and PLR reflect inflammatory response and disease severity in AD patients. PMID:28306706

The hospital anxiety and depression rating scale: A cross-sectional study of psychometrics and case finding abilities in general practice

PubMed Central

Olssøn, Ingrid; Mykletun, Arnstein; Dahl, Alv A

2005-01-01

Background General practitioners' (GPs) diagnostic skills lead to underidentification of generalized anxiety disorders (GAD) and major depressive episodes (MDE). Supplement of brief questionnaires could improve the diagnostic accuracy of GPs for these common mental disorders. The aims of this study were to examine the usefulness of The Hospital Anxiety and Depression Rating Scale (HADS) for GPs by: 1) Examining its psychometrics in the GPs' setting; 2) Testing its case-finding properties compared to patient-rated GAD and MDE (DSM-IV); and 3) Comparing its case finding abilities to that of the GPs using Clinical Global Impression-Severity (CGI-S) rating. Methods In a cross-sectional survey study 1,781 patients in three consecutive days in September 2001 attended 141 GPs geographically spread in Norway. Sensitivity, specificity, optimal cut off score, and Area under the curve (AUC) for the HADS and the CGI-S were calculated with Generalized Anxiety Questionnaire (GAS-Q) as reference standard for GAD, and Depression Screening Questionnaire (DSQ) for MDE. Results The HADS-A had optimal cut off ≥8 (sensitivity 0.89, specificity 0.75), AUC 0.88 and 76% of patients were correctly classified in relation to GAD. The HADS-D had by optimal cut off ≥8 (sensitivity 0.80 and specificity 0.88) AUC 0.93 and 87% of the patients were correctly classified in relation to MDE. Proportions of the total correctly classified at the CGI-S optimal cut-off ≥3 were 83% of patients for GAD and 81% for MDE. Conclusion The results indicate that addition of the patients' HADS scores to GPs' information could improve their diagnostic accuracy of GAD and MDE. PMID:16351733

Alu–based cell-free DNA: a novel biomarker for screening of gastric cancer

PubMed Central

Zhao, Jianmei; Shen, Xianjuan; Jing, Rongrong; Yu, Juan; Li, Li; Shi, Yingjuan; Zhang, Lurong; Wang, Zhiwei; Cong, Hui

2017-01-01

Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay. The concentration of CFD was quantitated by bDNA-based Alu assay. CEA, CA19-9, C72-4 and CA50 concentrations were determined by ABBOTT ARCHITECT I2000 SR. We found the CFD concentrations have significant differences between GC patients, benign gastric disease (BGD) patients and healthy controls (P < 0.05). CFD were weakly correlated with CEA (r = −0.197, P < 0.05) or CA50 (r = 0.206, P < 0.05), and no correlation with CA19-9 (r = −0.061, P > 0.05) or CA72-4 (r = 0.011, P > 0.05). In addition, CFD concentrations were significantly higher in stage I GC patients than BGD patients and healthy controls (P < 0.05), but there was no significant difference in CEA, CA19-9 and CA50 among the three traditional tumor markers (P > 0.05). Our analysis showed that CFD was more sensitive than CEA, CA19-9, CA72-4 or CA50 in early screening of GC. Compared with CEA, CA19-9, CA72-4 and CA50, CFD may prove to be a better biomarker for the screening of GC, thus providing a sensitive biomarker for screening and monitoring progression of GC. PMID:28903321

The incidence of traumatic intracranial hemorrhage in head-injured older adults transported by EMS with and without anticoagulant or antiplatelet use.

PubMed

Nishijima, Daniel Kiden; Gaona, Samuel D; Waechter, Trent; Maloney, Ric; Blitz, Adam; Elms, Andrew R; Farrales, Roel D; Montoya, James; Bair, Troy; Howard, Calvin; Gilbert, Megan; Trajano, Renee; Hatchel, Kaela; Faul, Mark; Bell, Jeneita M; Coronado, Victor; Vinson, David R; Ballard, Dustin W; Tancredi, Daniel J; Garzon, Hernando; Mackey, Kevin E; Shahlaie, Kiarash; Holmes, James F

2017-11-06

Field triage guidelines recommend transport of head-injured patients on anticoagulants or antiplatelets to a higher-level trauma center based on studies suggesting a high incidence of traumatic intracranial hemorrhage (tICH). We compared the incidence of tICH in older adults transported by EMS with and without anticoagulation or antiplatelet use and evaluated the accuracies of different sets of field triage criteria to identify tICH. This was a prospective, observational study at 5 EMS agencies and 11 hospitals. Older adults (≥55 years) with head trauma and transported by EMS from Aug 2015 to Sept 2016 were eligible. EMS providers completed standardized data forms and patients were followed through ED or hospital discharge. We enrolled 1,304 patients; 1147 (88%) received a cranial CT scan and were eligible for analysis. 434 (33%) patients had anticoagulant or antiplatelet use and 112 (10%) had tICH. The incidence of tICH in patients with (11%, 95%CI 8-14%) and without (9%, 95%CI 7-11%) anticoagulant or antiplatelet use was similar. Anticoagulant or antiplatelet use was not predictive of tICH on adjusted analysis. Steps 1-3 criteria alone were not sensitive in identifying tICH (27%) while the addition of anticoagulant or antiplatelet criterion improved sensitivity (63%). Other derived sets of triage criteria were highly sensitive (>98%) but poorly specific (<11%). The incidence of tICH was similar between patients with and without anticoagulant or antiplatelet use. Use of anticoagulant or antiplatelet medications was not a risk factor for tICH. We were unable to identify a set of triage criteria that was accurate for trauma center need.

Sensitive detection of KIT D816V in patients with mastocytosis.

PubMed

Tan, Angela; Westerman, David; McArthur, Grant A; Lynch, Kevin; Waring, Paul; Dobrovic, Alexander

2006-12-01

The 2447 A > T pathogenic variation at codon 816 of exon 17 (D816V) in the KIT gene, occurring in systemic mastocytosis (SM), leads to constitutive activation of tyrosine kinase activity and confers resistance to the tyrosine kinase inhibitor imatinib mesylate. Thus detection of this variation in SM patients is important for determining treatment strategy, but because the population of malignant cells carrying this variation is often small relative to the normal cell population, standard molecular detection methods can be unsuccessful. We developed 2 methods for detection of KIT D816V in SM patients. The first uses enriched sequencing of mutant alleles (ESMA) after BsmAI restriction enzyme digestion, and the second uses an allele-specific competitive blocker PCR (ACB-PCR) assay. We used these methods to assess 26 patients undergoing evaluation for SM, 13 of whom had SM meeting WHO classification criteria (before variation testing), and we compared the results with those obtained by direct sequencing. The sensitivities of the ESMA and the ACB-PCR assays were 1% and 0.1%, respectively. According to the ACB-PCR assay results, 65% (17/26) of patients were positive for D816V. Of the 17 positive cases, only 23.5% (4/17) were detected by direct sequencing. ESMA detected 2 additional exon 17 pathogenic variations, D816Y and D816N, but detected only 12 (70.5%) of the 17 D816V-positive cases. Overall, 100% (15/15) of the WHO-classified SM cases were codon 816 pathogenic variation positive. These findings demonstrate that the ACB-PCR assay combined with ESMA is a rapid and highly sensitive approach for detection of KIT D816V in SM patients.

Heterozygous ABCC8 mutations are a cause of MODY.

PubMed

Bowman, P; Flanagan, S E; Edghill, E L; Damhuis, A; Shepherd, M H; Paisey, R; Hattersley, A T; Ellard, S

2012-01-01

The ABCC8 gene encodes the sulfonylurea receptor 1 (SUR1) subunit of the pancreatic beta cell ATP-sensitive potassium (K(ATP)) channel. Inactivating mutations cause congenital hyperinsulinism (CHI) and activating mutations cause transient neonatal diabetes (TNDM) or permanent neonatal diabetes (PNDM) that can usually be treated with sulfonylureas. Sulfonylurea sensitivity is also a feature of HNF1A and HNF4A MODY, but patients referred for genetic testing with clinical features of these types of diabetes do not always have mutations in the HNF1A/4A genes. Our aim was to establish whether mutations in the ABCC8 gene cause MODY that is responsive to sulfonylurea therapy. We sequenced the ABCC8 gene in 85 patients with a BMI <30 kg/m², no family history of neonatal diabetes and who were deemed sensitive to sulfonylureas by the referring clinician or were sulfonylurea-treated. All had tested negative for mutations in the HNF1A and HNF4A genes. ABCC8 mutations were found in seven of the 85 (8%) probands. Four patients were heterozygous for previously reported mutations and four novel mutations, E100K, G214R, Q485R and N1245D, were identified. Only four probands fulfilled MODY criteria, with two diagnosed after 25 years and one patient, who had no family history of diabetes, as a result of a proven de novo mutation. ABCC8 mutations can cause MODY in patients whose clinical features are similar to those with HNF1A/4A MODY. Therefore, sequencing of ABCC8 in addition to the known MODY genes should be considered if such features are present, to facilitate optimal clinical management of these patients.

Broad-Range PCR Coupled with Electrospray Ionization Time of Flight Mass Spectrometry for Detection of Bacteremia and Fungemia in Patients with Neutropenic Fever

PubMed Central

Maertens, J.; Bueselinck, K.; Lagrou, K.

2016-01-01

Infection is an important complication in patients with hematologic malignancies or solid tumors undergoing intensive cytotoxic chemotherapy. In only 20 to 30% of the febrile neutropenic episodes, an infectious agent is detected by conventional cultures. In this prospective study, the performance of broad-range PCR coupled with electrospray ionization time of flight mass spectrometry (PCR/ESI-MS) technology was compared to conventional blood cultures (BC) in a consecutive series of samples from high-risk hematology patients. In 74 patients, BC and a whole-blood sample for PCR/ESI-MS (Iridica BAC BSI; Abbott, Carlsbad, CA, USA) were collected at the start of each febrile neutropenic episode and, in case of persistent fever, also at day 5. During 100 different febrile episodes, 105 blood samples were collected and analyzed by PCR/ESI-MS. There was evidence of a bloodstream infection (BSI) in 36/105 cases (34%), based on 14 cases with both PCR/ESI-MS and BC positivity, 17 cases with BC positivity only, and 5 cases with PCR/ESI-MS positivity only. The sensitivity of PCR/ESI-MS was 45%, specificity was 93%, and the negative predictive value was 80% compared to blood culture. PCR/ESI-MS detected definite pathogens (Fusobacterium nucleatum and Streptococcus pneumoniae) missed by BC, whereas it missed both Gram-negative and Gram-positive organisms detected by BC. PCR/ESI-MS testing detected additional microorganisms but showed a low sensitivity (45%) compared to BC in neutropenic patients. Our results indicate a lower concordance between BC and PCR/ESI-MS in the neutropenic population than what has been previously reported in other patient groups with normal white blood cell distribution, and a lower sensitivity than other PCR-based methods. PMID:27440820

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

PubMed

Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

2018-04-10

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

Role of PCR method using IS6110 primer in detecting Mycobacterium tuberculosis among the clinically diagnosed childhood tuberculosis patients at an urban hospital in Dhaka, Bangladesh.

PubMed

Kabir, Senjuti; Uddin, Mohammad Khaja Mafij; Chisti, Mohammod Jobayer; Fannana, Tilka; Haque, Mohammad Enamul; Uddin, Muhammad Reaj; Banu, Sayera; Ahmed, Tahmeed

2018-03-01

Better methods are needed for the accurate detection of child tuberculosis (TB). This study compared different laboratory tests and evaluated IS6110 PCR for the detection of Mycobacterium tuberculosis (MTB) among clinically diagnosed child TB patients. A total of 102 paediatric patients (<15 years old) with clinically diagnosed TB were enrolled in this study. The patients were admitted to the icddr,b hospital in Dhaka between 2003 and 2005. Sputum/gastric lavage samples were collected for smear microscopy, culture (solid/Lowenstein-Jensen medium and liquid/MGIT), and IS6110 PCR testing. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of smear microscopy and PCR were compared to the two culture methods. Three patients were positive on smear microscopy (2.9%). MTB was detected by conventional culture in 15.7% (16/102), liquid culture in 14% (14/100), and IS6110 PCR in 61.8% (63/102). PCR detected an additional 45 patients who were undetected with the three other tests. Compared to conventional and liquid culture, respectively, smear microscopy showed sensitivity of 18.8% and 21.4%, specificity of 100% individually, PPV of 100% individually, and NPV of 86.9% and 88.7%, whereas PCR had sensitivity of 87.5% and 92.9%, specificity of 43% individually, PPV of 22.2% and 21%, and NPV of 94.9% and 97.4%. PCR can be useful compared to smear microscopy and culture methods and is applicable as a rapid screening test for child TB. A larger scale study is required to determine its diagnostic efficacy in improving the detection of child TB in the presence and absence of severe malnutrition. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study.

PubMed

Mehta, V; Snidvongs, S; Ghai, B; Langford, R; Wodehouse, T

2017-06-01

Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer.

PubMed

White-Al Habeeb, Nicole M A; Ho, Linh T; Olkhov-Mitsel, Ekaterina; Kron, Ken; Pethe, Vaijayanti; Lehman, Melanie; Jovanovic, Lidija; Fleshner, Neil; van der Kwast, Theodorus; Nelson, Colleen C; Bapat, Bharati

2014-09-15

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2'-deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

Analytical Validation of Quantitative Real-Time PCR Methods for Quantification of Trypanosoma cruzi DNA in Blood Samples from Chagas Disease Patients

PubMed Central

Ramírez, Juan Carlos; Cura, Carolina Inés; Moreira, Otacilio da Cruz; Lages-Silva, Eliane; Juiz, Natalia; Velázquez, Elsa; Ramírez, Juan David; Alberti, Anahí; Pavia, Paula; Flores-Chávez, María Delmans; Muñoz-Calderón, Arturo; Pérez-Morales, Deyanira; Santalla, José; Guedes, Paulo Marcos da Matta; Peneau, Julie; Marcet, Paula; Padilla, Carlos; Cruz-Robles, David; Valencia, Edward; Crisante, Gladys Elena; Greif, Gonzalo; Zulantay, Inés; Costales, Jaime Alfredo; Alvarez-Martínez, Miriam; Martínez, Norma Edith; Villarroel, Rodrigo; Villarroel, Sandro; Sánchez, Zunilda; Bisio, Margarita; Parrado, Rudy; Galvão, Lúcia Maria da Cunha; da Câmara, Antonia Cláudia Jácome; Espinoza, Bertha; de Noya, Belkisyole Alarcón; Puerta, Concepción; Riarte, Adelina; Diosque, Patricio; Sosa-Estani, Sergio; Guhl, Felipe; Ribeiro, Isabela; Aznar, Christine; Britto, Constança; Yadón, Zaida Estela; Schijman, Alejandro G.

2015-01-01

An international study was performed by 26 experienced PCR laboratories from 14 countries to assess the performance of duplex quantitative real-time PCR (qPCR) strategies on the basis of TaqMan probes for detection and quantification of parasitic loads in peripheral blood samples from Chagas disease patients. Two methods were studied: Satellite DNA (SatDNA) qPCR and kinetoplastid DNA (kDNA) qPCR. Both methods included an internal amplification control. Reportable range, analytical sensitivity, limits of detection and quantification, and precision were estimated according to international guidelines. In addition, inclusivity and exclusivity were estimated with DNA from stocks representing the different Trypanosoma cruzi discrete typing units and Trypanosoma rangeli and Leishmania spp. Both methods were challenged against 156 blood samples provided by the participant laboratories, including samples from acute and chronic patients with varied clinical findings, infected by oral route or vectorial transmission. kDNA qPCR showed better analytical sensitivity than SatDNA qPCR with limits of detection of 0.23 and 0.70 parasite equivalents/mL, respectively. Analyses of clinical samples revealed a high concordance in terms of sensitivity and parasitic loads determined by both SatDNA and kDNA qPCRs. This effort is a major step toward international validation of qPCR methods for the quantification of T. cruzi DNA in human blood samples, aiming to provide an accurate surrogate biomarker for diagnosis and treatment monitoring for patients with Chagas disease. PMID:26320872

MELISA-an in vitro tool for the study of metal allergy.

PubMed

Stejskal, V D; Cederbrant, K; Lindvall, A; Forsbeck, M

1994-10-01

The sensitizing properties of metals widely used in medical and dental care have been studied with the help of an optimized lymphocyte proliferative assay, MELISA. MELISA (memory lymphocyte immuno-stimulation assay) was originally developed for the screening of allergenic epitopes of drugs and other chemicals of low molecular weight, but has recently been adapted for the study of metal-induced sensitization. The patients studied suffered from various oral mucosal problems which were suspected to be caused by the release of metal ions from dental restorations. They were also troubled by chronic fatigue persisting over many years. One patient was also occupationally exposed to metals while working in a dental practice. Healthy subjects without any discomfort due to metal devices served as controls. In addition to metals used in dentistry, lymphocyte responses to organic mercurials used widely as preservatives in vaccines, eye/nose drops and contact lense fluids were studied. The results indicated that mercurials, as well as other metals such as gold or palladium, induce strong lymphocyte proliferative responses in patients with oral or systemic symptoms, but not in similarly exposed unaffected subjects. The results of MELISA performed with a pair of identical twins with chronic fatigue syndrome (CFS) indicated that metal-specific responses may be dependent on the genetics of the patient. Thus, many metals that are today accepted for use in medicine and dentistry carry a definite sensitizing risk for certain genetically predisposed individuals. Therefore, the use of these metals should be limited in the future.

Real-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study

PubMed Central

Mobarak, Lamiaa; Nabeel, Mohammed M.; Hassan, Ehsan; Omran, Dalia; Zakaria, Zeinab

2016-01-01

Background Hepatitis C virus is a worldwide problem. Noninvasive methods for liver fibrosis assessment as ultrasound-based approaches have emerged to replace liver biopsy. The aim of this study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC), compared with transient elastography and liver biopsy. Methods RTE, FibroScan and liver biopsy were performed in 50 CHC patients. In addition, aspartate aminotransferase to platelet ratio index (APRI) and routine laboratory values were included in the analysis. Results RTE was able to diagnose significant hepatic fibrosis (F ≥2) according to METAVIR scoring system at cut-off value of 2.49 with sensitivity 100%, specificity 66%, and area under the receiver-operating characteristics (AUROC) 0.8. FibroScan was able to predict significant fibrosis at cut-off value 7.5 KPa with sensitivity 88%, specificity 100%, and AUROC 0.94.APRI was able to predict significant hepatic fibrosis (F ≥2) with sensitivity 54%, specificity 80%, and AUROC 0.69. There was a significant positive correlation between the FibroScan score and RTE score (r=0.6, P=0.001). Conclusions Although FibroScan is superior in determining significant hepatic fibrosis, our data suggest that RTE may be a useful and promising noninvasive method for liver fibrosis assessment in CHC patients especially in cases with technical limitations for FibroScan. PMID:27366038

Real-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study.

PubMed

Mobarak, Lamiaa; Nabeel, Mohammed M; Hassan, Ehsan; Omran, Dalia; Zakaria, Zeinab

2016-01-01

Hepatitis C virus is a worldwide problem. Noninvasive methods for liver fibrosis assessment as ultrasound-based approaches have emerged to replace liver biopsy. The aim of this study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC), compared with transient elastography and liver biopsy. RTE, FibroScan and liver biopsy were performed in 50 CHC patients. In addition, aspartate aminotransferase to platelet ratio index (APRI) and routine laboratory values were included in the analysis. RTE was able to diagnose significant hepatic fibrosis (F ≥2) according to METAVIR scoring system at cut-off value of 2.49 with sensitivity 100%, specificity 66%, and area under the receiver-operating characteristics (AUROC) 0.8. FibroScan was able to predict significant fibrosis at cut-off value 7.5 KPa with sensitivity 88%, specificity 100%, and AUROC 0.94.APRI was able to predict significant hepatic fibrosis (F ≥2) with sensitivity 54%, specificity 80%, and AUROC 0.69. There was a significant positive correlation between the FibroScan score and RTE score (r=0.6, P=0.001). Although FibroScan is superior in determining significant hepatic fibrosis, our data suggest that RTE may be a useful and promising noninvasive method for liver fibrosis assessment in CHC patients especially in cases with technical limitations for FibroScan.

Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases

PubMed Central

Naessens, James M; Visscher, Sue L; Peterson, Stephanie M; Swanson, Kristi M; Johnson, Matthew G; Rahman, Parvez A; Schindler, Joe; Sonneborn, Mark; Fry, Donald E; Pine, Michael

2015-01-01

Objective Assess algorithms for linking patients across de-identified databases without compromising confidentiality. Data Sources/Study Setting Hospital discharges from 11 Mayo Clinic hospitals during January 2008–September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). Study Design Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. Data Collection/Extraction Methods De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). Principal Findings Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. Conclusion Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications. PMID:26073819

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients

PubMed Central

Liu, Chen; Guan, Zhao; Xu, Qinzhu; Zhao, Lei; Song, Ying; Wang, Hui

2016-01-01

Abstract Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests. Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed. The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values. Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by a TEG test. There were correlations between TEG parameters and corresponding conventional tests. K values can better predict elevated fibrinogen levels in aged fracture patients. PMID:27311005

Relation of thromboelastography parameters to conventional coagulation tests used to evaluate the hypercoagulable state of aged fracture patients.

PubMed

Liu, Chen; Guan, Zhao; Xu, Qinzhu; Zhao, Lei; Song, Ying; Wang, Hui

2016-06-01

Fractures are common among aged people, and rapid assessment of the coagulation status is important. The thromboelastography (TEG) test can give a series of coagulation parameters and has been widely used in clinics. In this research, we looked at fracture patients over 60 and compared their TEG results with those of healthy controls. Since there is a paucity of studies comparing TEG assessments with conventional coagulation tests, we aim to clarify the relationship between TEG values and the values given by conventional coagulation tests.Forty fracture patients (27 femur and 13 humerus) over 60 years old were included in the study. The change in their coagulation status was evaluated by TEG before surgery within 4 hours after the fracture. Changes in TEG parameters were analyzed compared with controls. Conventional coagulation test results for the patients, including activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, and platelets, were also acquired, and correlation analysis was done with TEG parameters, measuring similar aspects of the coagulation cascade. In addition, the sensitivity and specificity of TEG parameters for detecting raised fibrinogen levels were also analyzed.The K (time to 20 mm clot amplitude) and R (reaction time) values of aged fracture patients were lower than controls. The values for angle, maximal amplitude (MA), and coagulation index (CI) were raised compared with controls, indicating a hypercoagulable state. Correlation analysis showed that there were significant positive correlations between fibrinogen and MA/angle, between platelets and MA, and between APTT and R as well. There was significant negative correlation between fibrinogen and K. In addition, K values have better sensitivity and specificity for detecting elevated fibrinogen concentration than angle and MA values.Aged fracture patients tend to be in a hypercoagulable state, and this could be effectively reflected by a TEG test. There were correlations between TEG parameters and corresponding conventional tests. K values can better predict elevated fibrinogen levels in aged fracture patients.

Investigation into the quantitative and qualitative characteristics of choroidal melanoma through magnetic resonance imaging and B-scan ultrasound

PubMed Central

Papayiannis, Vassilis; Tsaousis, Konstantinos T; Kouskouras, Constantinos A; Haritanti, Afroditi; Diakonis, Vasilios F; Tsinopoulos, Ioannis T

2017-01-01

Objective To investigate the homogeneity and vascularity of choroidal melanoma through magnetic resonance imaging (MRI) and brightness modulation (B-mode) ultrasound scan and their correlation with dimensions of tumor, as well as to measure the sensitivity of both modalities in retinal detachment (RD) detection. Materials and methods This retrospective chart review included patients diagnosed with choroidal melanoma. All these patients underwent MRI scans using T2-weighted (T2-WI) and T1-weighted (T1-WI) sequences, before and after an intravenous injection of paramagnetic contrast material. The patients were also examined using a B-mode ultrasound scan, and the results from both modalities were compared (tumor homogeneity, tumor height, tumor base diameter, and tumor vascularity). Results Forty-two patients (mean age=65.33±12.51 years) with choroidal melanoma were included in the study. Homogeneity was confirmed in 16 patients through ultrasound scan, in 19 patients through T1-WI sequence, in 21 patients through T2-WI sequence, and in 25 patients through T1-WI sequence + contrast (gadolinium). Patients with homogenous tumors presented with lower (P=0.0045) mean height than that of those with nonhomogenous tumors, whereas no statistically significant difference was found for base diameter measurements (P=0.056). Patients with tumors of high vascularity presented with greater mean height (P=0.000638) and greater mean base diameter compared with those with tumors of low vascularity (P=0.019543). RD was detected in 26 patients through T1-WI sequence, in 13 patients through T2-WI sequence, in 26 patients through T1-WI sequence + contrast, and in 32 patients through ultrasound scan, which proved to be the most sensitive modality. Conclusion The height of choroidal melanoma was positively correlated with tumor’s homogeneity. Melanomas of greater height were found to be less homogenous, due to increased degeneration and higher occurrence of intratumoral hemorrhage. In addition, choroidal melanoma’s height was also positively correlated with the level of its vascularity. Finally, ultrasound scan was found to be more sensitive than MRI in the detection of RD. PMID:28860706

Cutaneous Sensibility Changes in Bell's Palsy Patients.

PubMed

Cárdenas Palacio, Carlos Andrés; Múnera Galarza, Francisco Alejandro

2017-05-01

Objective Bell's palsy is a cranial nerve VII dysfunction that renders the patient unable to control facial muscles from the affected side. Nevertheless, some patients have reported cutaneous changes in the paretic area. Therefore, cutaneous sensibility changes might be possible additional symptoms within the clinical presentation of this disorder. Accordingly, the aim of this research was to investigate the relationship between cutaneous sensibility and facial paralysis severity in these patients. Study Design Prospective longitudinal cohort study. Settings Tertiary care medical center. Subjects and Methods Twelve acute-onset Bell's palsy patients were enrolled from March to September 2009. In addition, 12 sex- and age-matched healthy volunteers were tested. Cutaneous sensibility was evaluated with pressure threshold and 2-point discrimination at 6 areas of the face. Facial paralysis severity was evaluated with the House-Brackmann scale. Results Statistically significant correlations based on the Spearman's test were found between facial paralysis severity and cutaneous sensitivity on forehead, eyelid, cheek, nose, and lip ( P < .05). Additionally, significant differences based on the Student's t test were observed between both sides of the face in 2-point discrimination on eyelid, cheek, and lip ( P < .05) in Bell's palsy patients but not in healthy subjects. Conclusion Such results suggest a possible relationship between the loss of motor control of the face and changes in facial sensory information processing. Such findings are worth further research about the neurophysiologic changes associated with the cutaneous sensibility disturbances of these patients.

High SPDEF May Identify Patients Who Will Have a Prolonged Response to Androgen Deprivation Therapy

PubMed Central

Haller, Andrew C.; Tan, Wei; Payne-Ondracek, Rochelle; Underwood, Willie; Tian, Lili; Morrison, Carl; Li, Fengzhi

2015-01-01

Background Due to the indolent nature of prostate cancer, new prognostic measures are needed to identify patients with life threatening disease. SAM pointed domain-containing Ets transcription factor (SPDEF) has been associated with good prognosis and demonstrates an intimate relationship with the androgen receptor (AR), however its role in prostate cancer progression remains unclear. Methods A tissue microarray constructed from cores of 713 consecutive radical prostatectomy specimens were immunohistochemically stained for SPDEF and correlated with progression free and metastatic free survival. In vitro studies assessed growth rate, migration, and sensitivity to bicalutamide to explore mechanisms behind the tissue microarray observations. Results Patients with high SPDEF demonstrate longer metastases free survival after receiving the standard of care (HR = 9.80, P = 0.006). SPDEF expression corresponded with bicalutamide growth inhibition and apoptosis induction in all cell lines studied. In addition, a feed-forward loop of AR-SPEF expression regulation is observed. Conclusions SPDEF may be clinically useful to identify patients who will have extended benefits from androgen deprivation therapy. In vitro observations suggest SPDEF mediates initial sensitivity to androgen deprivation therapy through both AR regulation and downstream events. PMID:24375440

Two cases of Bezold-Jarisch reflex induced by intra-arterial nitroglycerin in critical left main coronary artery stenosis.

PubMed

Shah, Sachin P; Waxman, Sergio

2013-01-01

The Bezold-Jarisch reflex, a well-described phenomenon, occurs upon the stimulation of intracardiac mechanoreceptors and is mediated by vagal afferent nerve fibers. Several factors can sensitize the cardiovascular system to develop this reflex, including acute myocardial ischemia, natriuretic peptides, and, rarely, nitroglycerin administration in the setting of acute myocardial infarction. The development of the Bezold-Jarisch reflex in the presence of severe coronary artery stenosis, specifically left main coronary artery stenosis, has not been described. We report 2 cases of patients who underwent elective coronary angiography and were given intra-arterial nitroglycerin during radial sheath insertion to reduce radial artery spasm. In both patients, bradycardia and hypotension developed along with diaphoresis, consistent with the Bezold-Jarisch reflex. Coronary angiography revealed critical (>90%) left main coronary artery stenosis in both patients. Critical left main coronary artery stenosis might sensitize mechanoreceptors or vagal afferents to the development of the Bezold-Jarisch reflex after intra-arterial nitroglycerin use; however, the mechanism of this possible relationship is unclear. In addition to discussing our patients' cases, we review the medical literature relevant to the Bezold-Jarisch reflex.

Treatment strategies for pelvic organ prolapse: a cost-effectiveness analysis.

PubMed

Hullfish, Kathie L; Trowbridge, Elisa R; Stukenborg, George J

2011-05-01

To compare the relative cost effectiveness of treatment decision alternatives for post-hysterectomy pelvic organ prolapse (POP). A Markov decision analysis model was used to assess and compare the relative cost effectiveness of expectant management, use of a pessary, and surgery for obtaining months of quality-adjusted life over 1 year. Sensitivity analysis was conducted to determine whether the results depended on specific estimates of patient utilities for pessary use, probabilities for complications and other events, and estimated costs. Only two treatment alternatives were found to be efficient choices: initial pessary use and vaginal reconstructive surgery (VRS). Pessary use (including patients that eventually transitioned to surgery) achieved 10.4 quality-adjusted months, at a cost of $10,000 per patient, while VRS obtained 11.4 quality-adjusted months, at $15,000 per patient. Sensitivity analysis demonstrated that these baseline results depended on several key estimates in the model. This analysis indicates that pessary use and VRS are the most cost-effective treatment alternatives for treating post-hysterectomy vaginal prolapse. Additional research is needed to standardize POP outcomes and complications, so that healthcare providers can best utilize cost information in balancing the risks and benefits of their treatment decisions.

Usefulness of Four Different Echinococcus granulosus Recombinant Antigens for Serodiagnosis of Unilocular Hydatid Disease (UHD) and Postsurgical Follow-Up of Patients Treated for UHD▿

PubMed Central

Hernández-González, Ana; Muro, Antonio; Barrera, Inmaculada; Ramos, Guillermo; Orduña, Antonio; Siles-Lucas, Mar

2008-01-01

Four different recombinant antigens derived from Echinococcus granulosus, designated B1t, B2t, E14t, and C317, were tested with enzyme-linked immunosorbent assays (ELISAs) for the detection of specific immunoglobulin G (IgG) in patients with unilocular hydatid disease (UHD). The results were compared to those obtained with hydatid fluid and were subjected to receiver operator characteristic analysis. The diagnostic performance of the above-listed proteins was defined with respect to their specificity, sensitivity, and predictive values (PV); the influence of cyst location; and usefulness in the follow-up of surgical treatment for UHD and in the determination of whether or not patients have been surgically cured of UHD. The best diagnostic results were obtained with the anti-B2t IgG ELISA, with 91.2% sensitivity, 93% specificity, and high positive and negative PV (89.4 and 94.2, respectively). In addition, this diagnostic tool proved to be useful for the follow-up of surgically treated UHD patients. The anti-B2t IgG ELISA may find an application in the serodiagnosis of UHD in clinical laboratories. PMID:17989342

A serum protein-based algorithm for the detection of Alzheimer disease.

PubMed

O'Bryant, Sid E; Xiao, Guanghua; Barber, Robert; Reisch, Joan; Doody, Rachelle; Fairchild, Thomas; Adams, Perrie; Waring, Steven; Diaz-Arrastia, Ramon

2010-09-01

To develop an algorithm that separates patients with Alzheimer disease (AD) from controls. Longitudinal case-control study. The Texas Alzheimer's Research Consortium project. Patients  We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls. Main Outcome Measure  The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score. The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD. When age, sex, education, and APOE status were added to the algorithm, the sensitivity, specificity, and area under the curve were 0.94, 0.84, and 0.95, respectively. These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses. Additionally, these markers consistently distinguished cases from controls in significant analysis of microarray, logistic regression, and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.

J2ME implementation of system for storing and accessing of sensitive data on patient's mobile device

NASA Astrophysics Data System (ADS)

Zabołotny, Wojciech M.; Wielgórski, Radosław; Nowik, Marcin

2011-10-01

This paper presents a system allowing to use a patient's mobile phone or PDA for storing of biomedical data, which then, during medical consultation or intervention may be used by the medical staff. The presented solution is aimed on providing both: reliable protection to sensitive patient's data, and easy access to information for authorized medical staff. In the presented system, data are stored in an encrypted form, and the encryption key is available only for authorized persons. The central authentication server verifies the current access rights of the person trying to obtain the information, before providing him or her with the key needed to access the patient's data. The key provided by the server is valid only for the particular device, which minimizes the risk of its misuse. For rare situations when no connection to the authentication server is available (e.g. intervention in the mountains or rural area), system assures an additional "emergency" method to access the encryption key in controlled, registered way. The system has been implemented in Java language and tested in the simulated environment provided by Sun Java Wireless Toolkit for CLDC.

Colon Capsule Endoscopy for the Detection of Colorectal Polyps: An Economic Analysis

PubMed Central

Palimaka, Stefan; Blackhouse, Gord; Goeree, Ron

2015-01-01

Background Colorectal cancer is a leading cause of mortality and morbidity in Ontario. Most cases of colorectal cancer are preventable through early diagnosis and the removal of precancerous polyps. Colon capsule endoscopy is a non-invasive test for detecting colorectal polyps. Objectives The objectives of this analysis were to evaluate the cost-effectiveness and the impact on the Ontario health budget of implementing colon capsule endoscopy for detecting advanced colorectal polyps among adult patients who have been referred for computed tomographic (CT) colonography. Methods We performed an original cost-effectiveness analysis to assess the additional cost of CT colonography and colon capsule endoscopy resulting from misdiagnoses. We generated diagnostic accuracy data from a clinical evidence-based analysis (reported separately), and we developed a deterministic Markov model to estimate the additional long-term costs and life-years lost due to false-negative results. We then also performed a budget impact analysis using data from Ontario administrative sources. One-year costs were estimated for CT colonography and colon capsule endoscopy (replacing all CT colonography procedures, and replacing only those CT colonography procedures in patients with an incomplete colonoscopy within the previous year). We conducted this analysis from the payer perspective. Results Using the point estimates of diagnostic accuracy from the head-to-head study between colon capsule endoscopy and CT colonography, we found the additional cost of false-positive results for colon capsule endoscopy to be $0.41 per patient, while additional false-negatives for the CT colonography arm generated an added cost of $116 per patient, with 0.0096 life-years lost per patient due to cancer. This results in an additional cost of $26,750 per life-year gained for colon capsule endoscopy compared with CT colonography. The total 1-year cost to replace all CT colonography procedures with colon capsule endoscopy in Ontario is about $2.72 million; replacing only those CT colonography procedures in patients with an incomplete colonoscopy in the previous year would cost about $740,600 in the first year. Limitations The difference in accuracy between colon capsule endoscopy and CT colonography was not statistically significant for the detection of advanced adenomas (≥ 10 mm in diameter), according to the head-to-head clinical study from which the diagnostic accuracy was taken. This leads to uncertainty in the economic analysis, with results highly sensitive to changes in diagnostic accuracy. Conclusions The cost-effectiveness of colon capsule endoscopy for use in patients referred for CT colonography is $26,750 per life-year, assuming an increased sensitivity of colon capsule endoscopy. Replacement of CT colonography with colon capsule endoscopy is associated with moderate costs to the health care system. PMID:26366240

Diagnosis and treatment of shock due to massive pulmonary embolism: approach with transesophageal echocardiography and intrapulmonary thrombolysis.

PubMed

Krivec, B; Voga, G; Zuran, I; Skale, R; Pareznik, R; Podbregar, M; Noc, M

1997-11-05

To evaluate the diagnostic value of transesophageal echocardiography (TEE) as an initial diagnostic tool in shocked patients. The second objective was to study therapeutic impact of intrapulmonary thrombolysis in patients with diagnosed massive pulmonary embolism. Prospective observational study. Medical ICU in 800-bed general hospital. Twenty-four consecutive patients with unexplained shock and distended jugular veins. In 18 patients, right ventricular dilatation with global or segmental hypokinesis was documented. In addition, central pulmonary thromboemboli (12 patients), reduced contrast flow in right pulmonary artery (one patient), and right ventricular free wall akinesis (one patient) were found. No additional echocardiographic findings were apparent in four patients. According to pulmonary scintigraphy or autopsy, sensitivity of TEE for diagnosis of massive pulmonary embolism (MPE) in patients with right ventricular dilatation was 92% and specificity was 100%. In patients without right ventricular dilatation, left ventricular dysfunction (four patients) or cardiac tamponade (two patients) was confirmed. Intrapulmonary thrombolysis was evaluated in 11 of 13 patients with MPE. Two patients died prior to attempted thrombolysis. Three patients received streptokinase and eight received urokinase. Twenty-four hours after beginning of treatment, total pulmonary resistance index significantly decreased for 59% and mean pulmonary artery pressure for 31%. Cardiac index increased for 74%. Nine of 11 patients receiving thrombolysis survived to hospital discharge. Bedside TEE is a valuable tool for diagnosis of MPE. It enables immediate intrapulmonary thrombolysis, which seems to be an effective therapeutic alternative in our group of patients with obstructive shock.

Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naive HIV-1-infected patients: the ANRS COPANA cohort.

PubMed

Boufassa, Faroudy; Goujard, Cécile; Viard, Jean-Paul; Carlier, Robert; Lefebvre, Bénédicte; Yeni, Patrick; Bouchaud, Olivier; Capeau, Jacqueline; Meyer, Laurence; Vigouroux, Corinne

2012-01-01

The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naive HIV-1-infected patients. We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4(+) T-cell counts (≤200/mm(3)). Patients with low CD4(+) T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4(+) T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4(+) T-cell count >500/mm(3) as the reference), in addition to older age (β: +0.26 for a 10-year increase; P=0.01) and higher BMI (β: +0.07 for a 1-kg/m(2) increase; P=0.003). In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for altered insulin sensitivity.

Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

PubMed

Han, Zhi-Gang; Tao, Jie; Yu, Ting-Ting; Shan, Li

2017-04-26

BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators. RESULTS The median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05), and survival time of patients with ABCC2 CT + TT was significantly longer than in patients with the CC gene (P<0.05). CONCLUSIONS Polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with advanced NSCLC who have received platinum-based chemotherapy. Additionally, this information could be used to guide the individualized treatment of Uygur patients with advanced NSCLC.

Evaluation of failing hemodialysis fistulas with multidetector CT angiography: comparison of different 3D planes.

PubMed

Karadeli, E; Tarhan, N C; Ulu, E M Kayahan; Tutar, N U; Basaran, O; Coskun, M; Niron, E A

2009-01-01

To evaluate failing hemodialysis fistula complications using 16-detector MDCTA, and to assess the accuracies of different 3D planes. Thirty patients (16 men, 14 women, aged 27-79 years) were referred for hemodialysis access dysfunction. Thirty-one MDCTA exams were done prior to fistulography. For MDCTA, contrast was administered (2mL/kg at 5mL/s) via a peripheral vein in the contralateral arm. Axial MIP, coronal MIP, and VRT images were constructed. Venous complications were evaluated on axial source images, on each 3D plane, and on all-planes together. Results were analyzed using McNemar test. Axial MIP, VRT and all-planes evaluations were most sensitive for fistula site detection (93%). Coronal MIP had the highest sensitivity, specificity and accuracy (35%, 96%, and 85%, respectively) for detecting venous stenosis. VRT and all-planes had the highest sensitivity and accuracy for detecting aneurysms (100%). All-planes and axial MIP were most sensitive for detecting venous occlusion (61% and 54%). Comparisons of detection frequencies for each venous pathology between the five categories of MDCTA revealed no significant differences (P>0.05). MDCTA additionally showed 3 partially thrombosed aneurysms, 4 anastomosis site stenosis and 12 arterial complications. MDCTA overall gives low sensitivity for detection of central vein stenosis and moderate sensitivity for occlusion. For most pathology, all-planes evaluation of MDCTA gives highest sensitivity and accuracy rates when compared to other planes. For venous stenosis and occlusion, MDCTA should be considered when ultrasonography and fistulography are inconclusive. MDCTA is helpful in identifying aneurysms, collaterals, partial venous thromboses and additional arterial, anastomosis site pathologies.

The impact of using informative priors in a Bayesian cost-effectiveness analysis: an application of endovascular versus open surgical repair for abdominal aortic aneurysms in high-risk patients.

PubMed

McCarron, C Elizabeth; Pullenayegum, Eleanor M; Thabane, Lehana; Goeree, Ron; Tarride, Jean-Eric

2013-04-01

Bayesian methods have been proposed as a way of synthesizing all available evidence to inform decision making. However, few practical applications of the use of Bayesian methods for combining patient-level data (i.e., trial) with additional evidence (e.g., literature) exist in the cost-effectiveness literature. The objective of this study was to compare a Bayesian cost-effectiveness analysis using informative priors to a standard non-Bayesian nonparametric method to assess the impact of incorporating additional information into a cost-effectiveness analysis. Patient-level data from a previously published nonrandomized study were analyzed using traditional nonparametric bootstrap techniques and bivariate normal Bayesian models with vague and informative priors. Two different types of informative priors were considered to reflect different valuations of the additional evidence relative to the patient-level data (i.e., "face value" and "skeptical"). The impact of using different distributions and valuations was assessed in a sensitivity analysis. Models were compared in terms of incremental net monetary benefit (INMB) and cost-effectiveness acceptability frontiers (CEAFs). The bootstrapping and Bayesian analyses using vague priors provided similar results. The most pronounced impact of incorporating the informative priors was the increase in estimated life years in the control arm relative to what was observed in the patient-level data alone. Consequently, the incremental difference in life years originally observed in the patient-level data was reduced, and the INMB and CEAF changed accordingly. The results of this study demonstrate the potential impact and importance of incorporating additional information into an analysis of patient-level data, suggesting this could alter decisions as to whether a treatment should be adopted and whether more information should be acquired.

Identification of miRNA-103 in the Cellular Fraction of Human Peripheral Blood as a Potential Biomarker for Malignant Mesothelioma – A Pilot Study

PubMed Central

Weber, Daniel G.; Johnen, Georg; Bryk, Oleksandr; Jöckel, Karl-Heinz; Brüning, Thomas

2012-01-01

Background To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma. Methodology/Principal Findings Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%. Conclusions/Significance The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study. PMID:22253921

Nuclear medicine in breast cancer diagnostics: Primary tumor and lymphatic metastasis

NASA Astrophysics Data System (ADS)

Sinilkin, I.; Medvedeva, A.; Chernov, V.; Slonimskaya, E.; Zelchan, R.; Bragina, O.

2017-09-01

The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer.

Culturally sensitive patient-centred educational programme for self-management of type 2 diabetes: a randomized controlled trial.

PubMed

Mohamed, Hashim; Al-Lenjawi, Badriya; Amuna, Paul; Zotor, Francis; Elmahdi, Hisham

2013-10-01

To assess the effectiveness of a culturally sensitive, structured education programme (CSSEP) on biomedical, knowledge, attitude and practice measures among Arabs with type two diabetes. A total of 430 patients with type II diabetes mellitus living in Doha, Qatar were enrolled in the study. They were randomized to either intervention (n = 215) or a control group (n = 215). A baseline and one-year interval levels of biomedical variables including HbA1C, lipid profile, urine for microalbuminuria; in addition to knowledge, attitude and practice (KAP) scores were prospectively measured. The intervention was based on theory of empowerment, health belief models and was culturally sensitive in relation to language (Arabic), food habits and health beliefs. It consisted of four educational sessions for each group of patients (10-20 patients per session), lasting for 3-4 h. The first session discussed diabetes pathophysiology and complications; while the second session discussed healthy life style incorporating the Idaho plate method; and the third session dealt with exercise benefits and goal setting and the fourth session concentrated enhancing attitude and practice using counselling techniques. Outcomes were assessed at base line and 12 months after intervention. After 12 months participation in the intervention was shown to have led to a statistically significant reduction in HbA1C in the (CSSEP) group (-0.55 mmol/L, P = 0.012), fasting blood sugar (-0.92 mmol/L, P = 0.022), body mass index (1.70, P = 0.001) and albumin/creatinine ratio (-3.09, P < 0.0001) but not in the control group. The intervention group also had improvement in Diabetes knowledge (5.9%, P < 0.0001), attitude (6.56%, P < 0.0001), and practice (6.52%, P = 0.0001). This study demonstrates the effectiveness of culturally sensitive, structured, group-based diabetes education in enhancing biomedical and behavioural outcomes in Diabetic patients. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Comparison of credible patients of very low intelligence and non-credible patients on neurocognitive performance validity indicators.

PubMed

Smith, Klayton; Boone, Kyle; Victor, Tara; Miora, Deborah; Cottingham, Maria; Ziegler, Elizabeth; Zeller, Michelle; Wright, Matthew

2014-01-01

The purpose of this archival study was to identify performance validity tests (PVTs) and standard IQ and neurocognitive test scores, which singly or in combination, differentiate credible patients of low IQ (FSIQ ≤ 75; n = 55) from non-credible patients. We compared the credible participants against a sample of 74 non-credible patients who appeared to have been attempting to feign low intelligence specifically (FSIQ ≤ 75), as well as a larger non-credible sample (n = 383) unselected for IQ. The entire non-credible group scored significantly higher than the credible participants on measures of verbal crystallized intelligence/semantic memory and manipulation of overlearned information, while the credible group performed significantly better on many processing speed and memory tests. Additionally, credible women showed faster finger-tapping speeds than non-credible women. The credible group also scored significantly higher than the non-credible subgroup with low IQ scores on measures of attention, visual perceptual/spatial tasks, processing speed, verbal learning/list learning, and visual memory, and credible women continued to outperform non-credible women on finger tapping. When cut-offs were selected to maintain approximately 90% specificity in the credible group, sensitivity rates were highest for verbal and visual memory measures (i.e., TOMM trials 1 and 2; Warrington Words correct and time; Rey Word Recognition Test total; RAVLT Effort Equation, Trial 5, total across learning trials, short delay, recognition, and RAVLT/RO discriminant function; and Digit Symbol recognition), followed by select attentional PVT scores (i.e., b Test omissions and time to recite four digits forward). When failure rates were tabulated across seven most sensitive scores, a cut-off of ≥ 2 failures was associated with 85.4% specificity and 85.7% sensitivity, while a cut-off of ≥ 3 failures resulted in 95.1% specificity and 66.0% sensitivity. Results are discussed in light of extant literature and directions for future research.

Minimal residual disease in acute lymphoblastic leukemia: optimal methods and clinical relevance, pitfalls and recent approaches.

PubMed

Salari, Fatemeh; Shahjahani, Mohammad; Shahrabi, Saeid; Saki, Najmaldin

2014-11-01

After advances in experimental and clinical testing, minimal residual disease (MRD) assay results are considered a determining factor in treatment of acute lymphoblastic leukemia patients. According to MRD assay results, bone marrow (BM) leukemic burden and the rate of its decline after treatment can be directly evaluated. Detailed knowledge of the leukemic burden in BM can minimize toxicity and treatment complications in patients by tailoring the therapeutic dose based on patients' conditions. In addition, reduction of MRD before allo-HSCT is an important prerequisite for reception of transplant by the patient. In direct examination of MRD by morphological methods (even by a professional hematologist), leukemic cells can be under- or over-estimated due to similarity with hematopoietic precursor cells. As a result, considering the importance of MRD, it is necessary to use other methods including flow cytometry, polymerase chain reaction (PCR) amplification and RQ-PCR to detect MRD. Each of these methods has its own advantages and disadvantages in terms of accuracy and sensitivity. In this review article, different MRD assay methods and their sensitivity, correlation of MRD assay results with clinical symptoms of the patient as well as pitfalls in results of these methods are evaluated. In the final section, recent advances in MRD have been addressed.

Lagged segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.

PubMed

Voss, Andreas; Fischer, Claudia; Schroeder, Rico; Figulla, Hans R; Goernig, Matthias

2012-07-01

The objectives of this study were to introduce a new type of heart-rate variability analysis improving risk stratification in patients with idiopathic dilated cardiomyopathy (DCM) and to provide additional information about impaired heart beat generation in these patients. Beat-to-beat intervals (BBI) of 30-min ECGs recorded from 91 DCM patients and 21 healthy subjects were analyzed applying the lagged segmented Poincaré plot analysis (LSPPA) method. LSPPA includes the Poincaré plot reconstruction with lags of 1-100, rotating the cloud of points, its normalized segmentation adapted to their standard deviations, and finally, a frequency-dependent clustering. The lags were combined into eight different clusters representing specific frequency bands within 0.012-1.153 Hz. Statistical differences between low- and high-risk DCM could be found within the clusters II-VIII (e.g., cluster IV: 0.033-0.038 Hz; p = 0.0002; sensitivity = 85.7 %; specificity = 71.4 %). The multivariate statistics led to a sensitivity of 92.9 %, specificity of 85.7 % and an area under the curve of 92.1 % discriminating these patient groups. We introduced the LSPPA method to investigate time correlations in BBI time series. We found that LSPPA contributes considerably to risk stratification in DCM and yields the highest discriminant power in the low and very low-frequency bands.

Possible Geomagnetic and Environmental Symptoms in the Area of Athens During the Solar Cycle No 22

NASA Astrophysics Data System (ADS)

Nastos, P. T.; Paliatsos, A. G.; Korbakis, G. K.; Tritakis, V. P.; Bergiannaki, A.; Psarros, K.; Paparrigopoulos, P.; Stafanis, K.

The goal of this research is to confirm possible influences of environmental and geomagnetic variability in psychiatric hygiene of sensitive and heavily psychological patients. Three yearly samples of psychological patients consisted by four thousand cases (4000) each have been studied. The patients have been filed by the psychiatric clinic of the Eginition hospital in Athens where the three samples have been compiled during three very characteristic years of the No 22 11-year cycle, the maximum (1989), the minimum (1996) and one intermediate year of the descending branch (1994). A file with five to eight psychological symptoms like depression, sleep disturbance anxiety, aggressiveness etc. is attached to every patient. Each of these symptoms is correlated to the local geomagnetic index (k-index), the international geomagnetic index (Dst) and the environmental index (DI, Discomfort Index) in both daily and monthly basis. A clear seasonal variation in almost all symptoms and samples is present with maximum at the end of summer (August/September) and minimum at the end of winter (February-March). In addition very significant correlations among DI, Dst and some psychological symptoms appear. The main conclusion is that meteorological and geomagnetic factors play a significant role in the formation of sensitive psychological patients, behavior

Benefit of cerebrospinal fluid spectrophotometry in the assessment of CT scan negative suspected subarachnoid haemorrhage: a diagnostic accuracy study.

PubMed

Hann, Angus; Chu, Kevin; Greenslade, Jaimi; Williams, Julian; Brown, Anthony

2015-01-01

This study aimed to determine if performing cerebrospinal fluid spectrophotometry in addition to visual inspection detects more ruptured cerebral aneurysms than performing cerebrospinal fluid visual inspection alone in patients with a normal head CT scan but suspected of suffering an aneurysmal subarachnoid haemorrhage (SAH). We performed a single-centre retrospective study of patients presenting to the emergency department of a tertiary hospital who underwent both head CT scan and lumbar puncture to exclude SAH. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of an approach utilising both spectrophotometry and visual inspection (combined approach) was compared to visual inspection alone. A total of 409 patients (mean age 37.8 years, 56.2% female) were recruited and six (1.5%) had a cerebral aneurysm on angiography. The sensitivity of visual inspection was 50% (95% confidence interval [CI]: 12.4-82.6%), specificity was 99% (95% CI: 97.5-99.7%), PPV was 42.9% (95% CI: 10.4-81.3%) and NPV was 99.2% (95% CI: 97.8-99.8%). The combined approach had a sensitivity of 100% (95% CI: 54.1-100%), specificity of 79.7% (95% CI: 75.4-83.5%), PPV of 6.8% (95% CI: 2.6-14.3%) and a NPV of 100% (95% CI: 98.8-100%). The sensitivity of the combined approach was not significantly different to that of visual inspection alone (p=0.25). Visual inspection had a significantly higher specificity than the combined approach (p<0.01). The combined approach detected more cases of aneurysmal SAH than visual inspection alone, however the difference in sensitivity was not statistically significant. Visual xanthochromia should prompt angiography because of a superior specificity and PPV. Due to its reduced sensitivity, caution should be applied when using only visual inspection of the supernatant. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

PubMed Central

Bacconi, Andrea; Richmond, Gregory S.; Baroldi, Michelle A.; Laffler, Thomas G.; Blyn, Lawrence B.; Carolan, Heather E.; Frinder, Mark R.; Toleno, Donna M.; Metzgar, David; Gutierrez, Jose R.; Massire, Christian; Rounds, Megan; Kennel, Natalie J.; Rothman, Richard E.; Peterson, Stephen; Carroll, Karen C.; Wakefield, Teresa; Ecker, David J.

2014-01-01

The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml whole-blood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections. PMID:24951806

Effect of negative emotions evoked by light, noise and taste on trigeminal thermal sensitivity.

PubMed

Yang, Guangju; Baad-Hansen, Lene; Wang, Kelun; Xie, Qiu-Fei; Svensson, Peter

2014-11-07

Patients with migraine often have impaired somatosensory function and experience headache attacks triggered by exogenous stimulus, such as light, sound or taste. This study aimed to assess the influence of three controlled conditioning stimuli (visual, auditory and gustatory stimuli and combined stimuli) on affective state and thermal sensitivity in healthy human participants. All participants attended four experimental sessions with visual, auditory and gustatory conditioning stimuli and combination of all stimuli, in a randomized sequence. In each session, the somatosensory sensitivity was tested in the perioral region with use of thermal stimuli with and without the conditioning stimuli. Positive and Negative Affect States (PANAS) were assessed before and after the tests. Subject based ratings of the conditioning and test stimuli in addition to skin temperature and heart rate as indicators of arousal responses were collected in real time during the tests. The three conditioning stimuli all induced significant increases in negative PANAS scores (paired t-test, P ≤0.016). Compared with baseline, the increases were in a near dose-dependent manner during visual and auditory conditioning stimulation. No significant effects of any single conditioning stimuli were observed on trigeminal thermal sensitivity (P ≥0.051) or arousal parameters (P ≥0.057). The effects of combined conditioning stimuli on subjective ratings (P ≤0.038) and negative affect (P = 0.011) were stronger than those of single stimuli. All three conditioning stimuli provided a simple way to evoke a negative affective state without physical arousal or influence on trigeminal thermal sensitivity. Multisensory conditioning had stronger effects but also failed to modulate thermal sensitivity, suggesting that so-called exogenous trigger stimuli e.g. bright light, noise, unpleasant taste in patients with migraine may require a predisposed or sensitized nervous system.

Didactic Content and Experiential Aging Simulation for Developing Patient-Centered Strategies and Empathy for Older Adults.

PubMed

Johnson, Carole E; Jilla, Anna Marie; Danhauer, Jeffrey L

2018-02-01

The number of people over 65 years of age is increasing, and many of those individuals will have sensorineural hearing loss in addition to other chronic health conditions. Future hearing health care providers need to be sensitive to the needs of elderly patients. The purpose of this article is to describe an experiential learning curriculum used in the Doctor of Audiology program in the Department of Communication Sciences and Disorders at the University of Oklahoma Health Sciences Center. The curriculum uses simulations of sensory disorders common in the elderly to transform knowledge and active experience into patient-centered, empathetic counseling skills and strategies to use with older adults with hearing loss.

Impact of disseminated tumor cells in gastrointestinal cancer.

PubMed

Thorban, Stefan; Rosenberg, Robert; Maak, Matthias; Friederichs, Jan; Gertler, Ralf; Siewert, Jörg-Rüdiger

2006-05-01

The detection of epithelial cells by sensitive immunological and molecular methods in blood, lymph nodes or bone marrow of gastrointestinal cancer patients may open a new approach to clinical metastasis research. The phenotypic and genomic characterization of these cells is of great value in the prediction of the further course of the disease and the monitoring of response to treatment. In addition, the role of ultrastaging in blood, lymph nodes and bone marrow of cancer patients for the indication of multimodal therapy is discussed in this review. The impact of prognostic or predictive factors for new treatment protocols in patients with gastrointestinal cancer was evaluated as well as the correlation with clinical factors.

Final report on the United States phase I clinical trial of the hypoxic cell radiosensitizer, misonidazole (Ro-07-0582; NSC No. 261037

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, T.L.; Wasserman, T.H.; Johnson, R.J.

1981-10-15

The hypoxic cell sensitizer misonidazole began phase I evaluation in the United States in July 1977. One hundred two patients received 104 individual courses of drug. Drug was administered from once to five times per week over time spans from one to six weeks. The individual doses ranged 1 to 5 g/m. The major toxicity noted was neurologic; 49% of evaluable courses showed peripheral neuropathy, and 9% of evaluable courses showed central nervous system effects and/or ototoxicity. In addition, 48 of 102 patients exhibited some degree of nausea and vomiting. The concomitant administration of dexamethasone and phenytoin sodium appeared tomore » lower the incidence of neuropathy. Observations of efficacy were made comparatively in five patients who had multiple lesions treated with and without misonidazole. All five showed increased response in the lesions treated with misonidazole. It is concluded that misonidazole is a reasonably safe and potentially effective hypoxic cell sensitizer whose dose-limiting toxicity is neurologic.« less

Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

PubMed

Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

2017-11-01

The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.