Long-term outcomes of elderly hairy cell leukemia patients treated with cladribine.

Hairy cell leukemia (HCL) is a rare hematologic disorder characterized by pancytopenia and splenomegaly for which a single course of cladribine is highly effective in inducing complete remissions. However, there is limited real-world data on outcomes and complications among geriatric patients with HCL treated with cladribine. We conducted a retrospective review of all patients 70 years or older within the Scripps Clinic HCL Database at the time of first treatment with cladribine. Of the 45 patients meeting inclusion criteria, 32 (71%) achieved CR and 4 (9%) achieved PR. Of the 9 remaining patients, 7 achieved normalization of peripheral blood counts after a single course of cladribine (complete hematologic response, CHR) and 2 had no response. The median duration of response for all responders was 119 months. Nine (20%) patients relapsed with a median time to first relapse of 28 months. Ten patients subsequently developed 12 primary malignancies with an excess frequency (observed-to-expected ratio) of 0.85 (95% confidence interval, 0.48-1.49). Median overall survival for the entire cohort was 166 months from time of HCL diagnosis and 119 months from time of first cladribine administration. Forty patient deaths were observed; the standardized mortality ratio (observed-to-expected ratio) was 1.42 (95% confidence interval, 1.03-1.96), representing a statistically significant increase in the risk of death (P = .03). This study supports the high rate of complete and durable responses following a single course of cladribine in geriatric patients.

Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes.

BACKGROUND: Diabetes is an independent risk factor for atrial fibrillation (AF), which is associated with increases in mortality and morbidity, as well as a diminished quality of life. Renal involvement in diabetes is common, and since chronic kidney disease (CKD) shares several of the same putative mechanisms as AF, it may contribute to its increased risk in individuals with diabetes. The objective of this study is to identify the relationship between CKD and the rates of newly-diagnosed AF in individuals with diabetes taking part in a screening program using a self-applied wearable electrocardiogram (ECG) patch. MATERIALS AND METHODS: The study included 608 individuals with a diagnosis of diabetes among 1738 total actively monitored participants in the prospective mHealth Screening to Prevent Strokes (mSToPS) trial. Participants, without a prior diagnosis of AF, wore an ECG patch for 2 weeks, twice, over a 4-months period and followed clinically through claims data for 1 year. Definitions of CKD included ICD-9 or ICD-10 chronic renal failure diagnostic codes, and the Health Profile Database algorithm. Individuals requiring dialysis were excluded from trial enrollment. RESULTS: Ninety-six (15.8%) of study participants with diabetes also had a diagnosis of CKD. Over 12 months of follow-up, 19 new cases of AF were detected among the 608 participants. AF was newly diagnosed in 7.3% of participants with CKD and 2.3% in those without (P < 0.05) over 12 months of follow-up. In a univariate Cox proportional hazard regression analysis, the risk of incident AF was 3 times higher in individuals with CKD relative to those without CKD: hazard ratios (HR) 3.106 (95% CI 1.2-7.9). After adjusting for the effect of age, sex, and hypertension, the risk of incident AF was still significantly higher in those with CKD: HR 2.886 (95% CI 1.1-7.5). CONCLUSION: Among individuals with diabetes, CKD significantly increases the risk of incident AF. Identification of AF prior to clinical symptoms through active ECG screening could help to improve the clinical outcomes in individuals with CKD and diabetes.

Prognostic Implications of a Point-of-Care Ultrasound Examination on Hospital Ward Admission.

OBJECTIVES: Few data exist regarding the use of ultrasound (US) to risk stratify ward admissions. Therefore, we evaluated associations between a cardiopulmonary limited ultrasound examination (CLUE) on admission and subsequent hospital outcomes. METHODS: Over a 22-month period in a 300-bed hospital, CLUE data reviewed from a series of nonelective ward admissions were correlated with the composite outcome of a hospital stay of longer than 2 days, disposition to hospice, or death. The CLUE included 5 quick-look signs of left ventricular dysfunction, left atrial enlargement, lung B-lines, pleural effusions, and inferior vena cava plethora and had been performed as warranted by 1 of 31 US-trained admitting residents and then repeated by a cardiologist as the reference standard. The admitting condition, medical history, results of routine admission testing, and CLUE were assessed for an association with the outcome in univariate and multivariable models. RESULTS: Of 547 patients, the mean age ± SD was 62.9 ± 15.5 years; 59% were male; and the mean stay was 5.6 ± 8.1 days, with 355 (65%) lasting longer than 2 days and 21 (4%) having hospice disposition or death. An abnormal CLUE exam was found in 368 (67%) of patients, was related to the outcome (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.23-2.68; P = .001) when obtained by a resident or cardiologist, and was included in a best-fit multivariable model with renal failure (OR, 2.44; 95% CI, 1.44-4.14; P < .001), infection/sepsis (OR, 2.25; 95% CI, 1.17-4.32; P = .02), and chest pain (OR, 0.36; 95% CI, 0.21-0.61; P < .001). CONCLUSIONS: An abnormal admission point of care ultrasound exam was related to complex hospitalization, specifically a longer length of stay.

Associations between reliable changes in depression and changes in BMI, total body fatness and visceral adiposity during a 12-month weight loss trial.

We investigated associations between changes in depression and body composition over a 12-month weight loss trial. Of the 298 adults (BMI > 27 m/kg2), 219 with complete depression and body composition data were included. A 10-item Center for Epidemiologic Studies Depression Scale measured depression; dual-energy X-ray absorptiometry measured body composition. Multinomial logistic regression predicted reliable changes in depression by BMI, body fat (BF) and visceral adiposity (VAT). Multiplicative interaction terms tested modification by sex and ethnicity. Participants with increases in body composition were less likely to experience improvements in depression (BMI: RRR = 0.79 (0.68-0.91), p < 0.01; BF: RRR = 0.97 (0.94 - 0.99), p = 0.01; VAT: RRR = 0.99 (0.98-1.00), p = 0.02), but not worsening of depression (BMI: RRR = 1.29 (0.96-1.73), p = 0.10; BF: RRR = 1.04 (0.99-1.09), p = 0.15; VAT: RRR = 1.01 (1.00-1.03), p = 0.18). Sex and ethnicity interaction terms were not significant. However, the relationship was only significant among females, among non-Latinos for BMI and BF, and among Latinos for VAT. Our study supports the association between depression and obesity and highlights the need for longitudinal studies investigating VAT and depression in diverse ethnic groups.

Safety and outcomes of aspirin desensitization for aspirin-exacerbated respiratory disease: A single-center study.

BACKGROUND: Aspirin desensitization is an effective treatment option for aspirin-exacerbated respiratory disease. Aspirin desensitization protocol modifications have improved the safety and efficiency of this procedure, yet some providers remain reluctant to perform it. OBJECTIVE: The primary objective of this study was to evaluate the safety and outcomes of outpatient aspirin desensitization procedures. A secondary objective was to assess clinical characteristics that might predict reaction severity during aspirin desensitization. METHODS: Two hundred seventy-five patients underwent aspirin desensitization at Scripps Clinic between January 2009 and August 2015. Baseline patient characteristics and reaction results were analyzed in the 167 patients who reacted during desensitization. RESULTS: All of the 167 reactors, including 23 who were classified as severe reactors, were successfully desensitized in the outpatient setting. The average desensitization duration among reactors was 1.67 days, and the average duration for gastrointestinal reactors was 2.29 days. The mean baseline Sino-Nasal Outcome Test score was higher in severe reactors compared with nonsevere reactors (P = .05). Overall, patients receiving omalizumab had a similar reaction profile to those not receiving omalizumab. CONCLUSIONS: Most patients undergoing aspirin desensitization will have symptoms. It remains difficult to predict the severity of these symptoms. However, desensitization can be done safely and efficiently in an appropriately equipped outpatient setting. This treatment option should be made available to all patients with aspirin-exacerbated respiratory disease. The Sino-Nasal Outcome Test score might be able to predict more severe reactions and merits further study. Eight of the 9 patients receiving omalizumab reacted during desensitization, suggesting that it does not block reactions during aspirin desensitization.

Does Obesity Influence the Risk of Clostridium difficile Infection Among Patients with Ulcerative Colitis?

BACKGROUND: Patients with ulcerative colitis (UC) are at an increased risk of Clostridium difficile infection (CDI) compared with the general population. Recent data suggest that obesity also increases the risk of CDI. AIMS: To examine whether obesity influences the risk of CDI among patients with UC. STUDY: We conducted a retrospective cross-sectional study of UC patients seen in gastroenterology clinic between January 1, 2014, and December 31, 2015. Records were reviewed for patients with the diagnosis of UC prior to 2014, and the first diagnosis of CDI between January 1, 2014, and December 31, 2015. Using body mass index (BMI), patients were classified into underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30). Age-adjusted and multivariate logistic regression was performed including gender, tobacco use, UC disease duration, medication exposure, and vitamin D deficiency. RESULTS: Of the 636 patients with UC, 114 (18%) were obese, 232 (36%) overweight, 274 (43%) normal weight, and 16 (2.5%) underweight. Nineteen patients (3.0%) developed CDI during the study period. CDI risk was not associated with BMI (OR 0.90, 95% CI 0.79-1.02). Compared to normal weight patients, risk of CDI was not influenced by being obese (multivariate OR 0.63, 95% CI 0.15-2.58), overweight (multivariate OR 0.33, 95% CI 0.08-1.30), or underweight (multivariate OR 2.98, 95% CI 0.45-19.83). CDI was associated with ever use of TNF therapy (multivariate OR 6.09, 95% CI 2.07-17.93) but not vedolizumab (multivariate OR 0.76, 95% CI 0.08-7.36). CONCLUSIONS: Obesity does not appear to be associated with the risk of C. difficile infection among patients with UC.

Effect of a Home-Based Wearable Continuous ECG Monitoring Patch on Detection of Undiagnosed Atrial Fibrillation: The mSToPS Randomized Clinical Trial.

Importance: Opportunistic screening for atrial fibrillation (AF) is recommended, and improved methods of early identification could allow for the initiation of appropriate therapies to prevent the adverse health outcomes associated with AF. Objective: To determine the effect of a self-applied wearable electrocardiogram (ECG) patch in detecting AF and the clinical consequences associated with such a detection strategy. Design, Setting, and Participants: A direct-to-participant randomized clinical trial and prospective matched observational cohort study were conducted among members of a large national health plan. Recruitment began November 17, 2015, and was completed on October 4, 2016, and 1-year claims-based follow-up concluded in January 2018. For the clinical trial, 2659 individuals were randomized to active home-based monitoring to start immediately or delayed by 4 months. For the observational study, 2 deidentified age-, sex- and CHA2DS2-VASc-matched controls were selected for each actively monitored individual. Interventions: The actively monitored cohort wore a self-applied continuous ECG monitoring patch at home during routine activities for up to 4 weeks, initiated either immediately after enrolling (n = 1364) or delayed for 4 months after enrollment (n = 1291). Main Outcomes and Measures: The primary end point was the incidence of a new diagnosis of AF at 4 months among those randomized to immediate monitoring vs delayed monitoring. A secondary end point was new AF diagnosis at 1 year in the combined actively monitored groups vs matched observational controls. Other outcomes included new prescriptions for anticoagulants and health care utilization (outpatient cardiology visits, primary care visits, or AF-related emergency department visits and hospitalizations) at 1 year. Results: The randomized groups included 2659 participants (mean [SD] age, 72.4 [7.3] years; 38.6% women), of whom 1738 (65.4%) completed active monitoring. The observational study comprised 5214 (mean [SD] age, 73.7 [7.0] years; 40.5% women; median CHA2DS2-VASc score, 3.0), including 1738 actively monitored individuals from the randomized trial and 3476 matched controls. In the randomized study, new AF was identified by 4 months in 3.9% (53/1366) of the immediate group vs 0.9% (12/1293) in the delayed group (absolute difference, 3.0% [95% CI, 1.8%-4.1%]). At 1 year, AF was newly diagnosed in 109 monitored (6.7 per 100 person-years) and 81 unmonitored (2.6 per 100 person-years; difference, 4.1 [95% CI, 3.9-4.2]) individuals. Active monitoring was associated with increased initiation of anticoagulants (5.7 vs 3.7 per 100 person-years; difference, 2.0 [95% CI, 1.9-2.2]), outpatient cardiology visits (33.5 vs 26.0 per 100 person-years; difference, 7.5 [95% CI, 7.2-7.9), and primary care visits (83.5 vs 82.6 per 100 person-years; difference, 0.9 [95% CI, 0.4-1.5]). There was no difference in AF-related emergency department visits and hospitalizations (1.3 vs 1.4 per 100 person-years; difference, 0.1 [95% CI, -0.1 to 0]). Conclusions and Relevance: Among individuals at high risk for AF, immediate monitoring with a home-based wearable ECG sensor patch, compared with delayed monitoring, resulted in a higher rate of AF diagnosis after 4 months. Monitored individuals, compared with nonmonitored controls, had higher rates of AF diagnosis, greater initiation of anticoagulants, but also increased health care resource utilization at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT02506244.

Influence of smoking on the antiplatelet effect of clopidogrel differs according to clopidogrel dose: Insights from the GRAVITAS trial.

OBJECTIVE: To examine the influence of smoking on the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI). BACKGROUND: Certain studies suggest smokers may have enhanced clopidogrel-induced platelet inhibition compared to non-smokers after PCI. Whether this is affected by clopidogrel dose is unknown. METHODS: In this study, we conducted an analysis of 5,429 patients in the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Platelet reactivity was assessed 12-24 hr after PCI (baseline). Patients with high on-treatment platelet reactivity (OTR) (P2Y12 reaction units [PRU] ≥ 230) were randomized to clopidogrel 75 mg or 150 mg daily. Reactivity was subsequently assessed at 30-days, and 6-months. Patients were stratified by smoking status. RESULTS: Smoking was independently associated with lower PRU (P = 0.001), and smokers were less likely to have high OTR (odds ratio 0.80, 95% confidence interval 0.68-0.94; P = 0.006) at baseline. Among patients assigned to clopidogrel 75 mg, smokers had lower PRU and were less likely to still have high OTR at 30-days (P < 0.001) and 6-months (P < 0.001). However, in patients assigned clopidogrel 150 mg, PRU and high OTR did not differ by smoking status at any time. Tests demonstrated an interaction between smoking and dose at 30 days (P = 0.007), and a trend at 6-months (P = 0.098). CONCLUSIONS: Smokers treated with clopidogrel exhibit reduced platelet reactivity and are less likely to have persistent high OTR than non-smokers. This difference is mitigated by clopidogrel 150 mg, indicating non-smokers may require double-dose therapy to achieve a similar antiplatelet effect after PCI. © 2016 Wiley Periodicals, Inc.

Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial.

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF.

Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series.

Hairy cell leukemia (HCL) is a rare, indolent B-cell disorder in which single courses of cladribine induce high rates of complete responses. We report on 88 young HCL patients (≤40 years of age at diagnosis) treated with cladribine from the Scripps Clinic HCL Database, of whom 83 were evaluable for response. Seventy-three patients (88%) achieved an initial complete response and 10 (12%) a partial response, with a median response duration of 57 months. Forty-eight patients (58%) relapsed, with a median time to first relapse for all responders of 54 months. Eight patients developed 11 second primary malignancies with an excess frequency of 1.60 (95% confidence interval, 0.80-2.89). Thirteen (15%) patients died with a mortality ratio compared with age-matched normals of 1.85 (95% confidence interval, 1.07-3.18). Median overall survival for all patients following the first cladribine course was 231 months, and 251 months from diagnosis. Single courses of cladribine induce high rates of complete and durable responses in the majority of young HCL patients and are therefore recommended for HCL patients regardless of age.

Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a common pain disorder characterized by nociceptive dysregulation. The basic biology of FM is poorly understood. Herein we have used agnostic gene expression as a potential probe for informing its underlying biology and the development of a proof-of-concept diagnostic gene expression signature. METHODS: We analyzed RNA expression in 70 FM patients and 70 healthy controls. The isolated RNA was amplified and hybridized to Affymetrix® Human Gene 1.1 ST Peg arrays. The data was analyzed using Partek Genomics Suite version 6.6. RESULTS: Fibromyalgia patients exhibited a differential expression of 421 genes (p<0.001), several relevant to pathways for pain processing, such as glutamine/glutamate signaling and axonal development. There was also an upregulation of several inflammatory pathways and downregulation of pathways related to hypersensitivity and allergy. Using rigorous diagnostic modeling strategies, we show "locked" gene signatures discovered on Training and Test cohorts, that have a mean Area Under the Curve (AUC) of 0.81 on randomized, independent external data cohorts. Lastly, we identified a subset of 10 probesets that provided a diagnostic sensitivity for FM of 95% and a specificity of 96%. We also show that the signatures for FM were very specific to FM rather than common FM comorbidities. CONCLUSIONS: These findings provide new insights relevant to the pathogenesis of FM, and provide several testable hypotheses that warrant further exploration and also establish the foundation for a first blood-based molecular signature in FM that needs to be validated in larger cohorts of patients.

How Consumers and Physicians View New Medical Technology: Comparative Survey.

BACKGROUND: As a result of the digital revolution coming to medicine, a number of new tools are becoming available and are starting to be introduced in clinical practice. OBJECTIVE: We aim to assess health care professional and consumer attitudes toward new medical technology including smartphones, genetic testing, privacy, and patient-accessible electronic health records. METHODS: We performed a survey with 1406 health care providers and 1102 consumer responders. RESULTS: Consumers who completed the survey were more likely to prefer new technologies for a medical diagnosis (437/1102, 39.66%) compared with providers (194/1406, 13.80%; P<.001), with more providers (393/1406, 27.95%) than consumers (175/1102, 15.88%) reporting feeling uneasy about using technology for a diagnosis. Both providers and consumers supported genetic testing for various purposes, with providers (1234/1406, 87.77%) being significantly more likely than consumers (806/1102, 73.14%) to support genetic testing when planning to have a baby (P<.001). Similarly, 91.68% (1289/1406) of providers and 81.22% (895/1102) of consumers supported diagnosing problems in a fetus (P<.001). Among providers, 90.33% (1270/1406) were concerned that patients would experience anxiety after accessing health records, and 81.95% (1149/1406) felt it would lead to requests for unnecessary medical evaluations, but only 34.30% (378/1102; P<.001) and 24.59% (271/1102; P<.001) of consumers expressed the same concerns, respectively. Physicians (137/827, 16.6%) reported less concern about the use of technology for diagnosis compared to medical students (21/235, 8.9%; P=.03) and also more frequently felt that patients owned their medical record (323/827, 39.1%; and 30/235, 12.8%, respectively; P<.001). CONCLUSIONS: Consumers and health professionals differ significantly and broadly in their views of emerging medical technology, with more enthusiasm and support expressed by consumers.

Prevalence and treatment of latent tuberculosis infection among newly arrived refugees in San Diego County, January 2010-October 2012.

OBJECTIVES: We determined the prevalence and treatment rates of latent tuberculosis infection (LTBI) in newly arrived refugees in San Diego County, California, and assessed demographic and clinical characteristics associated with these outcomes. METHODS: We analyzed data from LTBI screening results of 4280 refugees resettled in San Diego County between January 2010 and October 2012. Using multivariate logistic regression, we calculated the associations between demographic and clinical risk factors and the outcomes of LTBI diagnosis and LTBI treatment initiation. RESULTS: The prevalence of LTBI was highest among refugees from sub-Saharan Africa (43%) and was associated with current smoking and having a clinical comorbidity that increases the risk for active tuberculosis. Although refugees from sub-Saharan Africa had the highest prevalence of infection, they were significantly less likely to initiate treatment than refugees from the Middle East. Refugees with postsecondary education were significantly more likely to initiate LTBI treatment. CONCLUSIONS: Public health strategies are needed to increase treatment rates among high-risk refugees with LTBI. Particular attention is required among refugees from sub-Saharan Africa and those with less education.

Objectively measured peri-vaccination sleep does not predict COVID-19 breakthrough infection.

Prior studies have shown that sleep duration peri-vaccination influences an individual's antibody response. However, whether peri-vaccination sleep affects real-world vaccine effectiveness is unknown. Here, we tested whether objectively measured sleep around COVID-19 vaccination affected breakthrough infection rates. DETECT is a study of digitally recruited participants who report COVID-19-related information, including vaccination and illness data. Objective sleep data are also recorded through activity trackers. We compared the impact of sleep duration, sleep efficiency, and frequency of awakenings on reported breakthrough infection after the 2nd vaccination and 1st COVID-19 booster. Logistic regression models were created to examine if sleep metrics predicted COVID-19 breakthrough infection independent of age and gender. Self-reported breakthrough COVID-19 infection following 2nd COVID-19 vaccination and 1st booster. 256 out of 5265 individuals reported a breakthrough infection after the 2nd vaccine, and 581 out of 2583 individuals reported a breakthrough after the 1st booster. There was no difference in sleep duration between those with and without breakthrough infection. Increased awakening frequency was associated with breakthrough infection after the 1st booster with 3.01 ± 0.65 awakenings/hour in the breakthrough group compared to 2.82 ± 0.65 awakenings/hour in those without breakthrough (P < 0.001). Cox proportional hazards modeling showed that age < 60 years (hazard ratio 2.15, P < 0.001) and frequency of awakenings (hazard ratio 1.17, P = 0.019) were associated with breakthrough infection after the 1st booster. Sleep duration was not associated with breakthrough infection after COVID vaccination. While increased awakening frequency during sleep was associated with breakthrough infection beyond traditional risk factors, the clinical implications of this finding are unclear.

Toward implementation of quorum sensing autoinducers as biomarkers for infectious disease states.

The opportunistic bacterial pathogen Pseudomonas aeruginosa causes chronic lung infections in cystic fibrosis (CF) patients. Importantly, virulence factor expression and biofilm formation in P. aeruginosa is coordinated by quorum sensing (QS) and one of the key QS signaling molecules is 3-oxo-C12-HSL. Remarkably, a tetramic acid, (C12-TA), with antibacterial properties is formed spontaneously from 3-oxo-C12-HSL under physiological conditions. Seeking to better understand this relationship, we sought to investigate whether 3-oxo-C12-HSL and C12-TA may be contributing factors to the overall pathogenicity of P. aeruginosa in CF individuals and if their detection and quantitation in sputum samples might be used as an indicator to assess disease states and monitor therapy success in CF patients. To this end, 3-oxo-C12-HSL and C12-TA concentrations were initially analyzed in P. aeruginosa flow cell biofilms using liquid chromatography coupled with mass spectrometry (LC-MS). A liquid chromatography tandem mass spectrometry (LC-MS/MS)-based method was then developed and validated for their detection and quantification in the sputa of CF patients. To the best of our knowledge, this is the first report to show the presence of both the quorum sensing molecule (3-oxo-C12-HSL) and its rearranged product (C12-TA) in human clinical samples such as sputum. A total of 47 sputum samples from 20 CF and 2 non-CF individuals were analyzed. 3-Oxo-C12-HSL was detected and quantified in 45 samples with concentrations ranging from 20 to >1000 nM; C12-TA was found in 14 samples (13-900 nM). On the basis of our findings, quorum sensing autoinducers merit further investigation as biomarkers for infectious disease states.

Mobile Health and Preventive Medicine.

Wearable devices providing health-related data (mobile health [mHealth]) have grown in numbers and types of data available over the past 2 decades. Applications in prevention with some of the longest track records are activity trackers to promote fitness (primary prevention), mobile electrocardiogram devices to detect arrhythmias (secondary prevention), and continuous glucose monitoring to improve glycemic control in type 2 diabetes (tertiary prevention). Continued integration of multiple diverse data streams and improved interfaces with individuals (such as artificial intelligence-driven health coaches), and health care teams (as in the hospital-at-home concept), promise to optimize use of mHealth to improve clinical and public health outcomes.

Genetic screening for low-penetrance variants in protein-coding genes.

Genetic testing holds great promise as a screening tool to identify persons at risk for a disease at the presymptomatic stage. However, the complexities of gene-disease associations, even in single-gene diseases, pose important challenges. These challenges include defining the role of screening for mutations that have low penetrance, which cause disease in only a minority of patients with the genotype. On the basis of the high rate of false positives, medical expert panels to date have largely discouraged genetic testing for low-penetrance mutations for use in population-based screening, although official recommendations currently exist for only a few genes. We examine the relatively limited experience of population-based screening for low-penetrance mutations in clinical settings to date, including screening for glucose-6-phosphate dehydrogenase deficiency and a low-penetrance mutation for cystic fibrosis in newborns, type 1 Gaucher disease carrier screening, and screening for adults for hemochromatosis. The trend toward recommending restricting use of these tests by medical experts is contrasted with the growing availability of genetic tests, including those for low-penetrance mutations, through direct-to-consumer outlets.

Effects of long-term cryopreservation on peripheral blood progenitor cells.

BACKGROUND AIMS: The long-term stability of cryopreserved peripheral blood progenitor cells is an important issue for patients experiencing disease relapse. However, there is no consensus on how to evaluate the long-term effects of cryopreservation. We describe the effect of cryopreservation on viability and progenitor colony activity from 87 individual samples processed at the Scripps Green Hospital Stem Cell Processing Center (La Jolla, CA, USA). METHODS: We randomly selected 87 peripheral blood hematopoietic stem cell (PBHSC) samples from 60 patients and evaluated the effect of cryopreservation on sample viability and red and white cell colony activity after < 24 h and 7, 10 and 15 years of cryopreservation. Viability was assayed via trypan blue dye exclusion and activity was measured following 14 days of culture. RESULTS: An age at collection older than 50 years may result in suboptimal activity and viability following long-term cryopreservation, while gender and disease status had no effect. Cryopreservation did not significantly affect white or red cell activity following 10 years of cryopreservation. However, for samples stored longer than 10 years, viability and activity significantly decreased. We noted a positive association between higher pre-cryopreservation %CD34 count and colony activity. CONCLUSIONS: Cryopreservation of peripheral blood progenitor cells for up to 10 years results in no loss of clonogenic capacity, as determined by culture activity, although longer durations of storage may affect activity. Until validated methods are developed, cryopreserved grafts should be evaluated based on pre-freeze CD34(+) cell counts as assayed by flow cytometry, and post-thaw sample evaluation should be reserved for patients identified as poor mobilizers.

Determination of clinical and demographic predictors of laboratory-confirmed influenza with subtype analysis.

BACKGROUND: Rapid influenza diagnosis is important for early identification of outbreaks, effective management of high-risk contacts, appropriate antiviral use, decreased inappropriate antibiotic use and avoidance of unnecessary laboratory testing. Given the inconsistent performance of many rapid influenza tests, clinical diagnosis remains integral for optimizing influenza management. However, reliable clinical diagnostic methods are not well-established. This study assesses predictors of influenza, and its various subtypes, in a broad population at the point of care, across age groups, then evaluates the performance of clinical case definitions composed of identified predictors. METHODS: Respiratory specimens and demographic and clinical data were obtained from 3- to 80-year-old US military family members presenting for care with influenza-like illness (ILI) from November 2007 to April 2008. Molecular and virus isolation techniques were used to detect and subtype influenza viruses. Associations between influenza diagnosis and demographic/clinical parameters were assessed by logistic regression, including influenza type and subtype analyses. The predictive values of multiple combinations of identified clinical predictors (case definitions), and the Centers for Disease Control and Prevention (CDC) ILI case definition, were estimated. RESULTS: Of 789 subjects, 220 (28%) had laboratory-confirmed influenza (51 A(H1), 46 A(H3), 19 A(unsubtypeable), 67 B, 1 AB coinfection), with the proportion of influenza A to B cases highest among 6- to 17-year-olds (p = 0.019). Independent predictors of influenza included fever, cough, acute onset, body aches, and vaccination status among 6- to 49-year-olds, only vaccination among 3- to 5-year-olds, and only fever among 50- to 80-year-olds. Among 6- to 49-year-olds, some clinical case definitions were highly sensitive (100.0%) or specific (98.6%), but none had both parameters over 60%, though many performed better than the CDC ILI case definition (sensitivity 37.7%, 95% confidence interval 33.6-41.9% in total study population). CONCLUSIONS: Patterns of influenza predictors differed across age groups, with most predictors identified among 6- to 49-year-olds. No combination of clinical and demographic predictors served as a reliable diagnostic case definition in the population and influenza season studied. A standardized clinical case definition combined with a point-of-care laboratory test may be the optimal rapid diagnostic strategy available.

Erythropoietin, GDF15, IL6, hepcidin and testosterone levels in a large cohort of elderly individuals with anaemia of known and unknown cause.

Epidemiologic studies have documented an increasing frequency of anaemia in individuals 65 yrs and older. Elderly individuals with anaemia have been categorised into the following: those with chronic disease, those with iron, B12 or folate deficiency and those with anaemia of unknown aetiology (AUE). There is considerable interest and debate as to whether AUE has an inflammatory component, is caused by cytokine dysregulation affecting production or response to erythropoietin (EPO) or iron availability or represents a novel pathologic process. Here, we compare a large cohort of AUE cases with a matched, non-anaemic control group and with individuals who have anaemia of defined cause. IL-6, hepcidin, GDF15, EPO and testosterone levels were compared. IL6 and hepcidin levels did not differ significantly between AUE and control groups, indicating that inflammation or iron restriction is not central feature of anaemia in this group. GDF15 levels were significantly elevated when comparing AUE with controls and were markedly elevated in patients with renal disease. Testosterone levels were lower in men from the AUE group compared with non-anaemic controls. EPO levels in the AUE group were increased relative to controls but were inappropriately low for the degree of anaemia. Our data indicate that an impaired EPO response, in the absence of evidence for iron restriction or inflammation, is characteristic of AUE.