Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis.

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert MTB/RIF Ultra qPCR test (Xpert Ultra) have exhibited less sensitivity with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample preprocessing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of Xpert Ultra performed on tongue swabs collected from 183 adults with presumed TB in Kampala, Uganda. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 77.8% (95% confidence interval [CI] 64.4-88.0) and specificity was 100.0% (95% CI, 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum mycobacterial culture, sensitivity was 72.4% (95% CI, 59.1-83.3) and specificity remained the same. Semi-quantitative Xpert Ultra results were generally lower with tongue swabs than with sputum, and cycle threshold values were higher. None of the eight sputum Xpert Ultra "trace" or "very low" results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.

A feasibility study of neoadjuvant talazoparib for operable breast cancer patients with a germline BRCA mutation demonstrates marked activity.

This study was undertaken to determine the feasibility of enrolling breast cancer patients on a single-agent-targeted therapy trial before neoadjuvant chemotherapy. Specifically, we evaluated talazoparib in patients harboring a deleterious BRCA mutation (BRCA+). Patients with a germline BRCA mutation and ≥1 cm, HER2-negative primary tumors were eligible. Study participants underwent a pretreatment biopsy, 2 months of talazoparib, off-study core biopsy, anthracycline, and taxane-based chemotherapy ± carboplatin, followed by surgery. Volumetric changes in tumor size were determined by ultrasound at 1 and 2 months of therapy. Success was defined as 20 patients accrued within 2 years and <33% experienced a grade 4 toxicity. The study was stopped early after 13 patients (BRCA1 + n = 10; BRCA2 + n = 3) were accrued within 8 months with no grade 4 toxicities and only one patient requiring dose reduction due to grade 3 neutropenia. The median age was 40 years (range 25-55) and clinical stage included I (n = 2), II (n = 9), and III (n = 2). Most tumors (n = 9) were hormone receptor-negative, and one of these was metaplastic. Decreases in tumor volume occurred in all patients following 2 months of talazoparib; the median was 88% (range 30-98%). Common toxicities were neutropenia, anemia, thrombocytopenia, nausea, dizziness, and fatigue. Single-agent-targeted therapy trials are feasible in BRCA+ patients. Given the rapid rate of accrual, profound response and favorable toxicity profile, the feasibility study was modified into a phase II study to determine pathologic complete response rates after 4-6 months of single-agent talazoparib.

Platelet transfusion: a clinical practice guideline from the AABB

BACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).(AU)

Development and usability testing of a web-based cancer symptom and quality-of-life support intervention.

The feasibility and acceptability of computerized screening and patient-reported outcome measures have been demonstrated in the literature. However, patient-centered management of health information entails two challenges: gathering and presenting data using "patient-tailored" methods and supporting "patient-control" of health information. The design and development of many symptom and quality-of-life information systems have not included opportunities for systematically collecting and analyzing user input. As part of a larger clinical trial, the Electronic Self-Report Assessment for Cancer-II project, participatory design approaches were used to build and test new features and interfaces for patient/caregiver users. The research questions centered on patient/caregiver preferences with regard to the following: (a) content, (b) user interface needs, (c) patient-oriented summary, and (d) patient-controlled sharing of information with family, caregivers, and clinicians. Mixed methods were used with an emphasis on qualitative approaches; focus groups and individual usability tests were the primary research methods. Focus group data were content analyzed, while individual usability sessions were assessed with both qualitative and quantitative methods. We identified 12 key patient/caregiver preferences through focus groups with 6 participants. We implemented seven of these preferences during the iterative design process. We deferred development for some of the preferences due to resource constraints. During individual usability testing (n = 8), we were able to identify 65 usability issues ranging from minor user confusion to critical errors that blocked task completion. The participatory development model that we used led to features and design revisions that were patient centered. We are currently evaluating new approaches for the application interface and for future research pathways. We encourage other researchers to adopt user-centered design approaches when building patient-centered technologies.

TU-E-217BCD-08: Extraction and Insertion of Tumor Masses in Cone Beam Breast CT Images.

PURPOSE: To develop and validate algorithms for extraction and insertion of three-dimensional (3D) profiles of tumor masses in cone beam breast CT (CBBCT) images to create simulated abnormality for evaluation with observer performance study. METHODS: A bench-top experimental CBBCT scanner was constructed and used to image mastectomy breast specimens with IRB approval. 5 sets of CBBCT images with confirmed tumor masses and 2 sets of normal CBBCT images were selected and used for this study. All CBBCT images were first corrected for cupping artifacts. The corrected images were then processed to reduce their noise levels and form the denoised images. The corrected and denoised CBBCT images for normal breasts were then segmented into adipose and glandular voxels. The images for abnormal breasts were reviewed by mammographers with the help of clinical images and reports to delineate the tumor masses and form 3D tumor maps. Using these maps, the 3D tumor profiles were rescaled to average glandular signals around the insertion locations in normal images. The boundaries of the 3D rescaled tumor profiles were smoothed to avoid sharp edge. The resultant 3D tumor profiles were inserted onto cupping artifact corrected normal CBBCT images by replacing the signals in adipose voxels near the insertion locations. The cupping artifacts were then added back to generate the simulated abnormal CBBCT images. These images were then visually compared with actual abnormal images for their degree of realism. RESULTS: Based on visual comparison, the simulated abnormal CBBCT images showed no significant difference in realism from actual abnormal CBBCT images. CONCLUSIONS: We have successfully demonstrated the technique to extract 3D tumor profiles from abnormal CBBCT images and insert them onto normal CBBCT images to form simulated abnormal images for use in observer performance study. This work was supported in part by grants CA104759, CA13852 and CA124585 from the NIH-NCI, a research grant EB00117 from the NIH-NIBIB, and a subcontract from NIST-ATP.

The reliability of measuring physical characteristics of spiculated masses on mammography.

The goal of this study was to assess the reliability of measurements of the physical characteristics of spiculated masses on mammography. The images used in this study were obtained from the Digital Database for Screening Mammography. Two experienced radiologists measured the properties of 21 images of spiculated masses. The length and width of all spicules and the major axis of the mass were measured. In addition, the observers counted the total number of spicules. Interobserver and intraobserver variability were evaluated using a hypothesis test for equivalence, the intraclass correlation coefficient (ICC) and Bland-Altman statistics. For an equivalence level of 30% of the mean of the senior radiologist's measurement, equivalence was achieved for the measurements of average spicule length (p<0.01), average spicule width (p = 0.03), the length of the major axis (p<0.01) and for the count of the number of spicules (p<0.01). Similarly, with the ICC analysis technique "excellent" inter-rater agreement was observed for the measurements of average spicule length (ICC = 0.770), the length of the major axis (ICC = 0.801) and for the count of the number of spicules (ICC = 0.780). "Fair to good" agreement was observed for the average spicule width (ICC = 0.561). Equivalence was also demonstrated for intraobserver measurements. Physical properties of spiculated masses can be measured reliably on mammography. The interobserver and intraobserver variability for this task is comparable with that reported for other measurements made on medical images.

Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P

Nodulus infarction mimicking acute peripheral vestibulopathy.

The authors report two patients with cerebellar infarctions in the territory of the medial branch of the posterior inferior cerebellar artery who had vertigo, spontaneous ipsilesional nystagmus, and contralesional truncal lateropulsion. Although one of the two patients had slight dysmetria, overall signs closely mimicked those of acute peripheral vestibulopathy. The authors suggest that interruption of nodulouvular inhibitory projections to vestibular nuclei may account for the vestibular signs.

Hemodynamic studies in early ischemic stroke: serial transcranial Doppler and magnetic resonance angiography evaluation.

BACKGROUND AND PURPOSE: After acute stroke, it is often standard practice to obtain magnetic resonance angiography (MRA) to seek evidence of a plausible stroke mechanism. However, hemodynamic patterns after acute ischemic stroke are variable and dynamic. We evaluated information obtained by serial transcranial Doppler ultrasonography (TCD) examinations within the first week after acute ischemic stroke and compared it with that obtained from a single MRA study. METHODS: Forty-seven patients (aged 61+/-7 years) with acute ischemic hemispheric stroke were examined. TCD was performed within 24 hours, from 24 to 48 hours, and 4 to 8 days after ictus. Norms for TCD examination were determined in an age-matched control group that included 41 subjects without cerebrovascular disease (aged 57+/-10 years). RESULTS: In 17 stroke patients, the results of initial TCD examination were normal, although TCD follow-up showed gradual deterioration of middle cerebral artery (MCA) for 1 patient with normal MRA. In 12 patients, initial TCD study and MRA showed MCA or posterior cerebral artery occlusion. Serial TCD examinations documented recanalization (6 patients), formation of a residual MCA stenosis (1 patient), or progressive deterioration of flow through a symptomatic MCA (1 patient), not evident on MRA. In 5 patients MRA was normal, but early TCD demonstrated signs of previous recanalization (transitory hyperemia, slow flow restoration). In 2 patients with MCA branch occlusion, MRA suggested occlusion but failed to document either improvement (1 patient) or deterioration (1 patient) of flow that was evident with serial TCD. In 4 patients with proximal MCA stenosis and 5 patients with internal carotid artery occlusion or stenosis, serial TCD demonstrated different patterns of collateralization and suggested dynamic collateralization patterns after stroke that were not evident on MRA. CONCLUSIONS: Serial TCD examination may reveal dynamic changes in cerebral circulation that may be missed on a single MRA study.

Staffing and pattern of mechanical restraint use across a multiple hospital system.

BACKGROUND: In an effort to enhance patient safety in acute care settings, governmental and regulatory agencies have established initiatives aimed at limiting the use of mechanical restraints. Concurrently, hospital staffing levels are undergoing changes raising concerns about the impact these changes may have on restraint use. No studies to date have described the impact these two initiatives have had on restraint use in acute care hospitals. OBJECTIVES: To determine across a multiple hospital system: (a) the rates, frequencies, duration, and timing of restraint use, and (b) the relationship between restraint use and staffing. METHODS: This was a secondary analysis of prospective, observational data from a large outcomes database for 10 acute care hospitals. Monthly data were obtained from 94 patient care units for periods ranging from 1-12 months for a total of 566 cumulative months during 1999. RESULTS: The system restraint application duration rate (total restraint hours/total possible hours) was 2.8% (hospital ranges: 0.3-4.4%). More restraints were applied on night shifts (48.8%; n = 5,296) than on day (33.5%; n = 3,634) or evening shifts (17.7%; n = 1,926) (p < .0001) and most applied at midnight (31.7%; n = 3,441) followed by 0600-0900 (33.3%; n = 3,614). There was a weak positive relationship between staffing and restraint use (r = 0.276, p = .0001) at the system level and units with higher staffing levels also had higher baseline restraint use (p < .0001). CONCLUSIONS: Restraint frequency, duration, and timing may have been altered by recent initiatives, and there is beginning evidence that differences exist between community, rural, and tertiary hospitals. While there is a weak positive relationship between higher staffing and restraint use at the system and unit level, further exploration of the influence of other factors, specifically patient acuity, are in order. The finding of unit variability and consistent restraint application times provides a starting point for further quality initiatives or research interventions aimed at restraint reduction.

Brain volume changes on longitudinal magnetic resonance imaging in normal older people.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.

A prospective study of cerebral white matter abnormalities in older people with gait dysfunction.

OBJECTIVES: The authors previously reported cross-sectional data suggesting a relationship between cerebral white matter hyperintensities (WMH) and gait and balance dysfunction in older people. There have been no longitudinal MRI studies to address this issue. The current study compared progression of WMH in subjects with gait and balance dysfunction with that in healthy subjects. METHODS: Two brain MRI were performed on 70 healthy, ambulatory subjects (mean baseline age 79, range 74 to 88) with no identifiable neurologic disease. The mean time between MRI was 4 years. Gait and balance were quantified using the Tinetti Balance and Mobility Scale, and falls were documented each year. On T2-weighted MRI, total hyperintense volume (HV) within three periventricular levels was estimated using the Cavalieri principle, and WMH were graded (0 to 4) using an established semiquantitative scale. RESULTS: Compared with those with normal gait and balance, subjects whose Tinetti scores dropped markedly (> 4 points) between first and second MRI showed a significantly greater mean increase in HV during follow-up. The larger group of subjects with an abnormal Tinetti score (< 24) at the time of second MRI showed a significantly greater mean increase in HV, compared with those with normal gait and balance at follow-up. Subjects with marked WMH at baseline showed significantly greater increase in HV over time. Subjects with abnormal Tinetti scores had significantly more falls than subjects with normal Tinetti scores. CONCLUSIONS: Some older people develop gait and balance dysfunction that is associated with gradual onset of cerebral white matter disease.

Bilateral sudden deafness as a prodrome of anterior inferior cerebellar artery infarction.

BACKGROUND: Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery is known to be associated with hearing loss, facial weakness, ataxia, nystagmus, and hypalgesia. There have been few reports on bilateral deafness and vertebrobasilar occlusive disease. Furthermore, previous reports have not emphasized the inner ear as a localization of bilateral deafness. OBJECTIVE: To describe the presentation of acute ischemic stroke in the distribution of the anterior inferior cerebellar artery as sudden bilateral hearing loss with minimal associated signs. DESIGN AND SETTING: Case report and tertiary care hospital. PATIENT: A 66-year-old man with diabetes mellitus developed sudden bilateral deafness, unilateral tinnitus, and vertigo 7 days before the onset of dysarthria, facial weakness, and ataxia. T2-weighted magnetic resonance imaging scans showed hyperintensities in the right lateral pons and right middle cerebral peduncle and a possible abnormality of the left middle cerebellar peduncle. A magnetic resonance angiogram showed moderately severe stenosis of the distal vertebral artery and middle third of the basilar artery. The patient's right limb coordination and gait improved steadily over several weeks, but there was no improvement in hearing in his right ear. CONCLUSIONS: The relatively isolated onset of deafness as well as the severity and persistence of the hearing loss led us to conclude that the hearing loss in this case was likely due to prominent hypoperfusion of the internal auditory artery, with labyrinthine infarction as the earliest event. Vertebrobasilar occlusive disease should be considered in the differential diagnosis of sudden bilateral deafness.

Atrial fibrillation: prevalence after minimally invasive direct and standard coronary artery bypass.

BACKGROUND: This study identified and compared the prevalence of new-onset atrial fibrillation (AFIB) following standard coronary artery bypass grafting (SCABG) with cardiopulmonary bypass (CPB) and minimally invasive direct vision coronary artery bypass grafting (MIDCAB) without CPB. A further comparison was made between AFIB prevalence in SCABG and MIDCAB subjects with two or fewer bypasses. METHODS: This is a retrospective, comparative survey. Patients with new-onset AFIB who underwent SCABG or MIDCAB alone were identified electronically using a triangulated method (International Classification of Diseases, 9th revision, Clinical Modification [ICD-9 CM] code; clinical database word search; and pharmacy database drug search). RESULTS: The total sample (n = 814; 94 MIDCAB, 720 SCABG) exhibited a trend toward lower AFIB prevalence in MIDCAB (23.4%) versus SCABG (33.1%) subjects (p = 0.059). AFIB prevalence in the SCABG subset with two or less vessel bypasses (n = 98; n = 18 single vessel, n = 80 double vessels) and MIDCAB subjects (n = 94; n = 90 single vessels, n = 4 double vessels) was almost identical (SCABG subset 24.5% versus MIDCAB 23.4%, p = 0.860). Slightly more than half (56.9%) of new-onset AFIB subjects were identified by ICD-9 CM codes, with the remainder by word search (37.7%) or procainamide query (5.4%). CONCLUSIONS: In this sample, the number of vessels bypassed seemed to have a greater influence on AFIB prevalence than the application of CPB or the surgical approach. Retrospective identification of AFIB cases by ICD-9 CM code grossly underestimated AFIB prevalence.

Benchmarking patient outcomes.

PURPOSE: To examine the usefulness of three types of benchmarking for interpreting patient outcome data. DESIGN: This study was part of a multiyear, multihospital longitudinal survey of 10 patient outcomes. The patient outcome used for this methodologic presentation was central line infections (CLI). The sample included eight hospitals in an integrated healthcare system, with a range in size from 144 to 861 beds. The unit of analysis for CLI was the number of line days, with the CLI rate defined as the number of infections per 1,000 patient-line days per month. METHODS: Data on each outcome were collected at the unit level according to standardized protocols. Results were submitted via standardized electronic forms to a central data management center. Data for this presentation were analyzed using a Bayesian hierarchical Poisson model. Results are presented for each hospital and the system as a whole. FINDINGS: In comparison to published benchmarks, hospital performances were mixed with regard to CLI. Five of the 8 hospitals exceeded 2.2 infections per 1,000 patient-line days. When benchmarks were established for each hospital using 95% credible intervals, hospitals did reasonably well with only isolated months reaching or going beyond the benchmark limits. When the entire system was used to establish benchmarks with the 95% credible intervals, the hospitals that reached or exceeded the benchmark limits remained the same, but some hospitals had CLI rates more frequently in the upper 50% of the benchmarking limits. CONCLUSIONS: Benchmarking of quality indicators can be accomplished in a variety of ways as a means to quantify patient care and identify areas needing attention and improvement. Hospital-specific and system-wide benchmarks provide relevant feedback for improving performance at individual hospitals.