Household Transmission of Mpox to Children and Adolescents, California, 2022.

BACKGROUND: In California, the 2022 mpox outbreak cumulated 5572 cases, 20% of US cases, as of November 28, 2022; 0.3% of cases were among children <16 years old. The secondary attack rate (SAR) for children sharing households with infected adults is unknown. METHODS: A line list of pediatric mpox household contacts aged <16 years reported through August 31, 2022 was created. It included demographic and clinical information on the contacts. Pediatric contact lists were crossmatched with the state vaccination database to identify those who received postexposure prophylaxis (PEP) with the JYNNEOS vaccine. RESULTS: We identified 129 pediatric household contacts with median age of 7 years (range, 0-15 years). Among 18 symptomatic contacts, 12 (66.7%) underwent mpox testing; 5 (41.2%) were confirmed cases, 6 (50%) were negative, and 1 (0.8%) had an indeterminate result. Six symptomatic children were not tested for mpox (33.3%). Overall, 6 infected contacts were identified, resulting in a SAR of 4.7% (6 of 129). The majority of pediatric household contacts and 4 of 6 infected children identified as Hispanic/Latino. Only 18 children (14%) reported receiving PEP. CONCLUSIONS: The SAR was overall low among pediatric household contacts; none had severe disease. This may be underestimated given low testing rates.

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK.

BACKGROUND: Black men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited. METHODS: This retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis. The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors. RESULTS: 730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70-79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men. CONCLUSIONS: More prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis.

OBJECTIVES: Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use. METHODS: A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research. RESULTS: Using serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children. CONCLUSIONS: For adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.

Exploring ethnic differences in the distribution of blood test results in healthy adult populations to inform earlier cancer detection: a systematic review.

BACKGROUND: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes. OBJECTIVE: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis. METHODS: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible. RESULTS: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women. CONCLUSIONS: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580.

Reduced Odds of Mpox-Associated Hospitalization Among Persons Who Received JYNNEOS Vaccine - California, May 2022-May 2023.

The effectiveness of 1 dose of JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic) against hospitalization for mpox (caused by Monkeypox virus), has been demonstrated; however, the impact of 2 doses on hospitalization risk, especially among persons infected with HIV, who are at higher risk for severe disease, is an important factor in evaluating vaccine effectiveness against mpox disease severity and Monkeypox virus infection. Surveillance data collected by the California Department of Public Health were used to evaluate whether receipt of 2 doses of JYNNEOS vaccine reduced the odds of hospitalization among persons with mpox. The odds of hospitalization among persons with mpox who had received 1 or 2 JYNNEOS doses were 0.27 (95% CI = 0.08-0.65) and 0.20 (95% CI = 0.01-0.90), respectively, compared with unvaccinated mpox patients. In mpox patients with HIV infection, the odds of hospitalization among those who had received 1 JYNNEOS vaccine dose was 0.28 (95% CI = 0.05-0.91) times that of those who were unvaccinated. No mpox-associated hospitalizations were identified among persons infected with HIV who had received 2 JYNNEOS vaccine doses. To optimize durable immunity, all eligible persons at risk for mpox, especially those infected with HIV, should complete the 2-dose JYNNEOS series.

Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact - Six U.S. Jurisdictions, November 1-December 14, 2022.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

Moderators of peak respiratory exchange ratio during exercise testing in children and adolescents with Fontan physiology.

OBJECTIVES: Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology. METHODS: Secondary analysis of a cross-sectional study of 8-18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio. RESULTS: Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative. CONCLUSION: Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient's ability to sustain high-intensity exercise.

Doctor-patient communication about blood tests: Qualitative interview study in general practice.

Context: Shared decision making is widely advocated, however most research focuses on treatment decisions. Evidence for shared decision-making in relation to diagnostic testing is limited to specific tests such as prostate specific antigen, screening and genetic tests. There is a lack of evidence regarding the relevance of shared decision-making to routine blood tests, despite increasing rates of laboratory testing in primary care. Objectives: To explore shared decision making and communication around routine blood tests in primary care. Study design: Qualitative interview study Setting: UK primary care Population studied: Qualitative interviews were undertaken with patients at two time points: (a) at or soon after their blood test and (b) after they had received their test results. We also undertook interviews with the patients' GPs who requested the tests. This gave us paired data which enabled to us to examine areas of congruence and dissonance between GPs' and patients' expectations, experience and understanding of testing. A total of 80 interviews with 28 patients and 19 doctors were completed, reflecting a range of socioeconomic and demographic characteristics. Interviews were digitally recorded, transcribed and analyzed using thematic analysis using a mixture of inductive and deductive coding and constant comparison. Results: There were no examples of shared decision making identified in any of the interviews, indeed patients were frequently unaware of which blood tests had been done and why. Barriers to a shared understanding of blood testing were identified including the complexity and technical nature of information, a lack of resources for information sharing and a perception that blood tests were low priority for information sharing. Doctors perceived that a paternalistic approach to testing could be justified to protect patients from anxiety. Misunderstanding and a lack of communication around testing and test results led to uncertainty, anxiety and frustration for patients. Conclusions: The results have implications, not just for models of shared decision making, but more fundamentally, informed consent. Shared decision-making for diagnostic testing differs from treatment decisions. Promoting a shared understanding and shared decision-making could help rationalize testing, potentially reducing unnecessary investigations and improving patient-centered care.

Blood tests in primary care: A qualitative study of communication and decision-making between doctors and patients.

OBJECTIVE: Blood tests are commonly used in primary care as a tool to aid diagnosis, and to offer reassurance and validation for patients. If doctors and patients do not have a shared understanding of the reasons for testing and the meaning of results, these aims may not be fulfilled. Shared decision-making is widely advocated; yet, most research focusses on treatment decisions rather than diagnostic decisions. The aim of this study was to explore communication and decision-making around diagnostic blood tests in primary care. METHODS: Qualitative interviews were undertaken with patients and clinicians in UK primary care. Patients were interviewed at the time of blood testing, with a follow-up interview after they received test results. Interviews with clinicians who requested the tests provided paired data to compare clinicians' and patients' expectations, experiences and understandings of tests. Interviews were analysed thematically using inductive and deductive coding. RESULTS: A total of 80 interviews with 28 patients and 19 doctors were completed. We identified a mismatch in expectations and understanding of tests, which led to downstream consequences including frustration, anxiety and uncertainty for patients. There was no evidence of shared decision-making in consultations preceding the decision to test. Doctors adopted a paternalistic approach, believing that they were protecting patients from anxiety. CONCLUSION: Patients were not able to develop informed preferences and did not perceive that choice is possible in decisions about testing, because they did not have sufficient information and a shared understanding of tests. A lack of shared understanding at the point of decision-making led to downstream consequences when test results did not fulfil patients' expectations. Although shared decision-making is recommended as best practice, it does not reflect the reality of doctors' and patients' accounts of testing; a broader model of shared understanding seems to be more relevant to the complexity of primary care diagnosis. PATIENT OR PUBLIC CONTRIBUTION: A patient and public involvement group comprising five participants with lived experience of blood testing in primary care met regularly during the study. They contributed to the development of the research objectives, planning recruitment methods, reviewing patient information leaflets and topic guides and also contributed to discussion of emerging themes at an early stage in the analysis process.

Heart Rate Recovery Following Exercise Testing in Pediatric Patients with Acyanotic Repaired Congenital Heart Disease.

Attenuated heart rate recovery (HRR) following peak exercise has been shown to be a predictor of mortality in populations of adults with Fontan palliation, coronary artery disease, heart failure, and heart transplantation. However, few have studied HRR in children and adolescents with congenital heart disease (CHD). This case-control study compared HRR patterns from exercise stress testing in children and adolescents with and without repaired acyanotic CHD (raCHD). Retrospective analysis included patients aged 10-18 years who had exercise testing between 2007 and 2017. The raCHD cohort included patients with Tetralogy of Fallot, transposition of the great arteries, coarctation, truncus arteriosus, atrioventricular septal defect, pulmonary outflow obstruction, aortic stenosis and/or insufficiency, or septal defects. Those in the control cohort were matched for age, sex, BMI, peak METs achieved, and peak heart rate (HR). HR at 1-min intervals throughout the 10-min recovery period and HRR patterns were analyzed. The study included n = 584 individuals (raCHD: n = 146), median age 14 years old, 67.1% male. The cohorts had similar resting and peak HRs. Linear mixed-effects models (LMM) suggested statistically significant cohort-by-time interaction for HR in exercise recovery, with the largest mean difference at minute-6 (2.9 bpm, p = 0.008). When comparing lesion types, LMM found no cohort or cohort-by-time interaction. While minute-6 of exercise recovery was statistically significant, the difference was 2.9 bpm and may not have clinical significance. These results suggest that HRR in pediatric raCHD patients should not vary from their healthy peers, and an attenuated HRR may not be directly attributed to underlying raCHD.

Practices and Procedures in Clinical Pediatric Exercise Laboratories in North America.

Interinstitutional differences in clinical pediatric exercise laboratory (CPEL) practices may affect patient care and efficacy of multicenter research. PURPOSE: To describe current practices/procedures in CPELs and explore differences in CPELs employing exercise physiologists to those that do not. METHODS: A 40-item survey was distributed to CPELs in North America focusing on (1) staffing; (2) exercise stress testing (EST) volumes, reporting, and interpretation; and (3) EST procedures/protocols. RESULTS: Of the 55 responses, 89% were in the United States, 85% were children's hospitals with university affiliation, and 58% were cardiology specific. Exercise physiologists were employed in 56% of CPELs, and 78% had master's degrees or higher. Certifications were required in most CPELs (92% emergency life-support, 27% professional, and 21% clinical). Median volume was 201 to 400 ESTs per year, 80% used treadmill, and 10% used cycle ergometer as primary modalities. Ninety-three percent of CPELs offered metabolic ESTs, 87% offered pulmonary function testing, 20% used institution-specific EST protocols, and 72% offered additional services such as cardiac/pulmonary rehabilitation. CPELS staffing exercise physiologists performed higher volumes of ESTs (P = .004), were more likely to perform metabolic ESTs (P = .028), participated in more research (P < .001), and provided services in addition to ESTs (P = .001). CONCLUSIONS: Heterogeneity in CPELs staffing and operation indicates need for standardization.

Metal-Encoded Polystyrene Microbeads as a Mass Cytometry Calibration/Normalization Standard Covering Channels from Yttrium (89 amu) to Bismuth (209 amu).

Mass cytometry (MC) measures metal isotope signals from single cells and bead samples. Since large numbers of isotopes can be employed as labels, mass cytometry is a powerful analytical technique for multiparameter cytometric assays. The calibration protocol in MC is a critical algorithm, which employs metal-encoded microbeads as an internal standard to correct the data for instrumental signal drift. The current generation of commercially available beads carries four lanthanide elements (cerium, europium, holmium, and lutetium). However, this is not sufficient to calibrate the full span of detection channels, ranging from yttrium (89 amu) to bismuth (209 amu), which are now available. To address this issue we prepared polystyrene microbeads encoded with seven elements (yttrium, indium, and bismuth in addition to the four lanthanides) by multistage dispersion polymerization for MC calibration and normalization. The bead synthesis conditions were optimized to obtain microbeads that were uniform in size and generated strong MC signal intensities at similar levels for the eight encoded isotopes. Metal ion leaching from the beads under storage and application conditions was also examined. We demonstrated that the precision of normalized MC signals in the MC detection channels was improved by employing seven-element-encoded microbeads as a standard.

What methods are being used to create an evidence base on the use of laboratory tests to monitor long-term conditions in primary care? A scoping review.

BACKGROUND: Studies have shown unwarranted variation in test ordering among GP practices and regions, which may lead to patient harm and increased health care costs. There is currently no robust evidence base to inform guidelines on monitoring long-term conditions. OBJECTIVES: To map the extent and nature of research that provides evidence on the use of laboratory tests to monitor long-term conditions in primary care, and to identify gaps in existing research. METHODS: We performed a scoping review-a relatively new approach for mapping research evidence across broad topics-using data abstraction forms and charting data according to a scoping framework. We searched CINAHL, EMBASE and MEDLINE to April 2019. We included studies that aimed to optimize the use of laboratory tests and determine costs, patient harm or variation related to testing in a primary care population with long-term conditions. RESULTS: Ninety-four studies were included. Forty percent aimed to describe variation in test ordering and 36% to investigate test performance. Renal function tests (35%), HbA1c (23%) and lipids (17%) were the most studied laboratory tests. Most studies applied a cohort design using routinely collected health care data (49%). We found gaps in research on strategies to optimize test use to improve patient outcomes, optimal testing intervals and patient harms caused by over-testing. CONCLUSIONS: Future research needs to address these gaps in evidence. High-level evidence is missing, i.e. randomized controlled trials comparing one monitoring strategy to another or quasi-experimental designs such as interrupted time series analysis if trials are not feasible.

GP's perspectives on laboratory test use for monitoring long-term conditions: an audit of current testing practice.

BACKGROUND: We have shown previously that current recommendations in UK guidelines for monitoring long-term conditions are largely based on expert opinion. Due to a lack of robust evidence on optimal monitoring strategies and testing intervals, the guidelines are unclear and incomplete. This uncertainty may underly variation in testing that has been observed across the UK between GP practices and regions. METHODS: Our objective was to audit current testing practices of GPs in the UK; in particular, perspectives on laboratory tests for monitoring long-term conditions, the workload, and how confident GPs are in ordering and interpreting these tests. We designed an online survey consisting of multiple-choice and open-ended questions that was promoted on social media and in newsletters targeting GPs practicing in UK. The survey was live between October-November 2019. The results were analysed using a mixed-methods approach. RESULTS: The survey was completed by 550 GPs, of whom 69% had more than 10 years of experience. The majority spent more than 30 min per day on testing (78%), but only half of the respondents felt confident in dealing with abnormal results (53%). There was a high level of disagreement for whether liver function tests and full blood counts should be done 'routinely', 'sometimes', or 'never' in patients with a certain long-term condition. The free text comments revealed three common themes: (1) pressures that promote over-testing, i.e. guidelines or protocols, workload from secondary care, fear of missing something, patient expectations; (2) negative consequences of over-testing, i.e. increased workload and patient harm; and (3) uncertainties due to lack of evidence and unclear guidelines. CONCLUSION: These results confirm the variation that has been observed in test ordering data. The results also show that most GPs spent a significant part of their day ordering and interpreting monitoring tests. The lack of confidence in knowing how to act on abnormal test results underlines the urgent need for robust evidence on optimal testing and the development of clear and unambiguous testing recommendations. Uncertainties surrounding optimal testing has resulted in an over-use of tests, which leads to a waste of resources, increased GP workload and potential patient harm.

Physical Activity Patterns in Children and Adolescents With Heart Disease.

PURPOSE: To quantify the differences in daily physical activity (PA) patterns, intensity-specific volumes, and PA bouts in youth with and without heart disease (HD). METHODS: Seven-day PA was measured on children/adolescents with HD (n = 34; median age 12.4 y; 61.8% male; 70.6% single ventricle, 17.7% heart failure, and 11.8% pulmonary hypertension) and controls without HD (n = 22; median age 12.3 y; 59.1% male). Mean counts per minute were classified as sedentary, light, and moderate to vigorous PA (MVPA), and bouts of MVPA were calculated. PA was calculated separately for each hour of wear time from 8:00 to 22:00. Multilevel linear mixed modeling compared the outcomes, stratifying by group, time of day, and day part (presented as median percentage of valid wear time [interquartile range]). RESULTS: Compared with the controls, the HD group had more light PA (33.9% [15%] vs 29.6% [9.5%]), less MVPA (1.7% [2.5%] vs 3.2% [3.3%]), and more sporadic bouts (97.4% [5.7%] vs 89.9% [9.2%]), but fewer short (2.0% [3.9%] vs 7.1% [5.7%]) and medium-to-long bouts (0.0% [1.9%] vs 1.6% [4.6%]) of MVPA. The HD group was less active in the late afternoon, between 15:00 and 17:00 (P < .03). There were no differences between groups in sedentary time. CONCLUSION: Children/adolescents with HD exhibit differences in intensity-specific volumes, PA bouts, and daily PA patterns compared with controls.

The effect of muscle fatigue on wrist joint position sense in healthy adults.

STUDY DESIGN: Pretest and posttest experimental study. INTRODUCTION: The effect of muscle fatigue on wrist joint position sense (JPS) has yet to be determined. PURPOSE OF THE STUDY: The primary aim was to determine whether muscle fatigue affects wrist JPS in healthy adults. The secondary aims were to compare the effect of muscle fatigue on younger and older adults JPS and determine the association between JPS rate of change and total muscle fatigue (TMF) rates postexercise. METHODS: Forty male and female healthy adults were assigned into younger (18-40 years) and older (41-65 years) groups. Preexercise and postexercise testing consisted of active wrist JPS, handgrip, and wrist extensor strength assessments. Muscle fatigue was induced via a calibrated gripper and wrist extension dumbbell exercises. Dependent variables were the JPS rate of change (ie, preexercise and postexercise), TMF rate (ie, grip and wrist extension average strength decline), and Borg Rating of Perceived Exertion scale scores. RESULTS: Postexercise wrist JPS test scores were significantly higher than preexercise. Exercises induced statistically significant TMF rates and Borg Rating of Perceived Exertion scores among all participants. No statistically significant age-group differences on JPS rate of change, and TMF rate was found. A statistically significant mild correlation (r = 0.425) existed between JPS rate of change and TMF rates. DISCUSSION: Postexercise fatigue significantly impairs wrist JPS in both younger and older adults. On average, an 18% muscle strength decline led to 215% wrist JPS deficit. CONCLUSIONS: Significant wrist proprioception deficits persist for ≤5 min following exertional exercises, regardless of age level.

Predictive value of inflammatory markers for cancer diagnosis in primary care: a prospective cohort study using electronic health records.

BACKGROUND: Early identification of cancer in primary care is important and challenging. This study examined the diagnostic utility of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate and plasma viscosity) for cancer diagnosis in primary care. METHODS: Cohort study of 160,000 patients with inflammatory marker testing in 2014, plus 40,000 untested matched controls, using Clinical Practice Research Datalink (CPRD), with Cancer Registry linkage. Primary outcome was one-year cancer incidence. RESULTS: Primary care patients with a raised inflammatory marker have a one-year cancer incidence of 3.53% (95% CI 3.37-3.70), compared to 1.50% (1.43-1.58) in those with normal inflammatory markers, and 0.97% (0.87-1.07) in untested controls. Cancer risk is greater with higher inflammatory marker levels, with older age and in men; risk rises further when a repeat test is abnormal but falls if it normalises. Men over 50 and women over 60 with raised inflammatory markers have a cancer risk which exceeds the 3% NICE threshold for urgent investigation. Sensitivities for cancer were 46.1% for CRP, 43.6% ESR and 49.7% for PV. CONCLUSION: Cancer should be considered in patients with raised inflammatory markers. However, inflammatory markers have a poor sensitivity for cancer and are therefore not useful as 'rule-out' test.

Tellurium-based mass cytometry barcode for live and fixed cells.

Mass cytometry is a revolutionary technology that allows for the simultaneous quantification of >40 different biomarkers with cellular resolution. The biomarkers are detected using metal-labeled antibodies as well as small-molecule probes of cell size, viability, and biochemical status. Barcoding is an important component of sample preparation because it reduces processing time, eliminates sample-to-sample variation, discriminates cell doublets, reduces the amount of antibody needed, and conserves sample. We developed a thiol-reactive tellurium-based barcode, TeMal. TeMal is nontoxic at working concentrations, compatible with metal-labeled antibodies, and can readily be applied to live or fixed cells, making it advantageous and complementary compared to existing barcoding reagents. We have demonstrated the utility of TeMal by barcoding microscale samples in situ to facilitate analysis of cells from an automated cell culture system using mass cytometry.

Aptamer-facilitated mass cytometry.

Mass cytometry is a novel cell-by-cell analysis technique, which uses elemental tags instead of fluorophores. Sample cells undergo rapid ionization in inductively coupled plasma and the ionized elemental tags are then analyzed by means of time-of-flight mass spectrometry. Benefits of the mass cytometry approach are in no need for compensation, the high number of detection channels (up to 100) and low background noise. In this work, we applied a biotinylated aptamer against human PTK7 receptor for characterization of positive (human acute lymphoblastic leukemia) and negative (human Burkitt's lymphoma) cells by a mass cytometry instrument. Our proof of principal experiments showed that biotinylated aptamers in conjunction with metal-labeled neutravidin can be successfully utilized for mass cytometry experiments at par with commercially available antibodies. Graphical abstract Biotinylated aptamers in conjunction with metal-labeled neutravidin bind to cell biomarkers, and then injected into the inductively coupled plasma (ICP) source, where cells are vaporized, atomized, and ionized in the plasma for subsequent mass spectrometry (MS) analysis of lanthanide metals.