Population Averages Research Articles

Single-Cell Transcriptomic Analysis of Normal and Malignant B Cells.

In the past decade, single-cell (sc) transcriptomics has overcome the limitations of bulk analysis by measuring gene expression in individual cells, not just a population average. This can identify diverse cell types and states within a sample with high resolution, even without prior purification. Various technologies exist, each with its own capture, barcoding, and library preparation methods. This chapter focuses on the analysis of normal and malignant mature B cells using the 10× Genomics 5' sc-gene expression in parallel with B cell immune repertoire profiling. By integrating the gene expression data from similar cells, the complete transcriptome for each population can be reconstructed, while the identification of the expressed immunoglobulin genes allows investigating clonotype evolution and the detection of tumor clones that share the same clonally rearranged B cell receptor sequence. Researchers are guided through both the experimental protocols and data analysis with a comprehensive, step-by-step walkthrough of how to use some of the more popular single-cell software tools.

The good, the bad and the ugly: What do we really do when we identify the best and the worst organisations?

Identifying high and poorly performing organisations is common practice in healthcare. Often this is done within a frequentist inferential framework where statistical techniques are used that acknowledge that observed performance...

A field study of donor behaviour in the Iranian kidney market

Iran has the world’s only government-regulated kidney market. We report the results of the first field study of donor behaviour in this unusual market. Participants have lower risk tolerance and higher patience levels than the Iranian average but display no difference in rationality from population averages and there is evidence of altruism among participants. We provide an examination of decision-making in extreme situations by individuals in this market, typically at the very bottom of the income distribution, and shed light on the sort of people likely to participate if other nations were to operate such markets.

Paired X‐Ray Micro CT Scanning and Individual Foraminifera Isotopic Analysis Reveal (De)coupled Changes in Carbonate Preservation and Temperature

AbstractThe composition and preservation state of biogenic carbonate archives, such as foraminiferal tests, record ocean chemistry during the lifetime of the organism and post‐depositional changes in ambient conditions via carbonate compensation. Depending upon the specific paleoclimate proxy, post‐depositional processes, including dissolution, may alter original paleoenvironmental signals captured by the foraminifer's test composition. Accordingly, quantifying dissolution independent of geochemical measurements can improve proxy interpretation. Developing independent tools may also be useful for investigating whether changes in paleoclimatic conditions are associated with changes in seawater carbonate chemistry. Such approaches can be improved further if they are applied to individual foraminiferal tests, as specimen‐to‐specimen differences can record higher‐frequency environmental changes compared to conventional bulk‐scale analyses. Here, we combine individual foraminiferal carbon and oxygen isotopic analyses (IFA) with X‐ray MicroCT Scanning to generate paired analyses of test density (a proxy for the extent of post‐depositional dissolution) and isotopic composition. As a proof‐of‐concept application of this approach, we analyze Globigerina bulloides tests from both coretop and latest Miocene/earliest Pliocene‐aged sediment from Ocean Drilling Project (ODP) Site 1088 (Agulhas Ridge). Our measurements and mixing model calculations show that within‐population differences in carbon and oxygen isotopic ratios are largely independent of dissolution extent. By comparing population averages from coretop and downcore sediments, we find that lower oxygen isotopic ratios (likely driven by higher calcification temperatures) are associated with greater extents of dissolution at ODP Site 1088. We interpret this finding to reflect coupled changes in carbonate chemistry and climatic conditions over million‐year timescales.

Diagnosis Based on Population Data versus Personalized Data: The Evolving Paradigm in Laboratory Medicine.

The diagnosis of diseases is a complex process involving the integration of multiple parameters obtained from various sources, including laboratory findings. The interpretation of laboratory data is inherently comparative, necessitating reliable references for accurate assessment. Different types of references, such as reference intervals, decision limits, action limits, and reference change values, are essential tools in the interpretation of laboratory data. Although these references are used to interpret individual laboratory data, they are typically derived from population data, which raises concerns about their reliability and consequently the accuracy of interpretation of individuals' laboratory data. The accuracy of diagnosis is critical to all subsequent steps in medical practice, making the estimate of reliable references a priority. For more precise interpretation, references should ideally be derived from an individual's own data rather than from population averages. This manuscript summarizes the current sources of references used in laboratory data interpretation, examines the references themselves, and discusses the transition from population-based laboratory medicine to personalized laboratory medicine.

An approach to analyze spatiotemporal patterns of gene expression at single-cell resolution in Candida albicans-infected mouse tongues.

Candida albicans is a fungal pathobiont inhabiting multiple mucosal surfaces of the human body. Immunosuppression, antibiotic-induced microbial dysbiosis, or implanted medical devices can impair mucosal integrity enabling C. albicans to overgrow and disseminate, causing either mucosal diseases such as oropharyngeal candidiasis or life-threatening systemic infections. Profiling fungal genes that are expressed in the infected mucosa or in any other infected organ is paramount to understand pathogenesis. Ideally, these transcript profiling measurements should reveal the expression of any gene at the single-cell level. The resolution typically achieved with current approaches, however, limits most gene expression measurements to cell population averages. The approach described in this report provides a means to dissect fungal gene expression in infected tissues at single-cell resolution.

Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2.

[18F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [11C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k2 and [Formula: see text] (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [11C]UCB-J studies to accurately estimate [Formula: see text]. This study evaluated the suitability of these methods to estimate [18F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions. Seven healthy participants underwent 120-min PET scans on the HRRT scanner with [18F]SynVesT-1. Six participants underwent test and retest scans. Arterial blood sampling and metabolite analysis provided input functions for the 1TC model, serving as the gold standard for kinetic parameters values. SRTM, coupled SRTM (SRTMC) and SRTM2 estimated were applied to estimate [Formula: see text](ref: CS) and DVRCER(ref: CER) values. For SRTM2, the population average of [Formula: see text] was determined from the 1TC model applied to the reference region. Test-retest variability and minimum scan time were also calculated. The 1TC k2 (1/min) values for CS and CER were 0.031 ± 0.004 and 0.021 ± 0.002, respectively. Although SRTMC [Formula: see text] was much higher than 1TC [Formula: see text], SRTMC underestimated BPND(ref: CS) and DVRCER by an average of 3% and 1% across regions, respectively, due to similar bias in k2 and [Formula: see text] estimation. SRTM underestimated BPND(ref: CS) by an average of 3%, but with the CER as reference region, SRTM estimation was unstable and DVRCER underestimation varied by region (mean 10%). Using population average [Formula: see text] values, SRTM2 BPND and DVRCER showed the best agreement with 1TC estimates. Our findings support the use of population [Formula: see text] value in SRTM2 with [18F]SynVesT-1 for the estimation of [Formula: see text] or DVRCER, regardless of the choice of reference region.

Beyond SIRD models: a novel dynamic model for epidemics, relating infected with entries to health care units and application for identification and restraining policy.

Epidemic models of susceptibles, exposed, infected, recovered and deceased (SΕIRD) presume homogeneity, constant rates and fixed, bilinear structure. They produce short-range, single-peak responses, hardly attained under restrictive measures. Tuned via uncertain I,R,D data, they cannot faithfully represent long-range evolution. A robust epidemic model is presented that relates infected with the entry rate to health care units (HCUs) via population averages. Model uncertainty is circumvented by not presuming any specific model structure, or constant rates. The model is tuned via data of low uncertainty, by direct monitoring: (a) of entries to HCUs (accurately known, in contrast to delayed and non-reliable I,R,D data) and (b) of scaled model parameters, representing population averages. The model encompasses random propagation of infections, delayed, randomly distributed entries to HCUs and varying exodus of non-hospitalized, as disease severity subdues. It closely follows multi-pattern growth of epidemics with possible recurrency, viral strains and mutations, varying environmental conditions, immunity levels, control measures and efficacy thereof, including vaccination. The results enable real-time identification of infected and infection rate. They allow design of resilient, cost-effective policy in real time, targeting directly the key variable to be controlled (entries to HCUs) below current HCU capacity. As demonstrated in ex post case studies, the policy can lead to lower overall cost of epidemics, by balancing the trade-off between the social cost of infected and the economic contraction associated with social distancing and mobility restriction measures.

All-cause mortality and cause-specific death in U.S. long-lived siblings: data from the Long Life Family Study.

This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern. In the Long Life Family Study (LLFS), 1,264 proband siblings (Mean age 90.1, SD 6.4) and 172 spouses (83.8, 7.2) from 511 U.S.-based families were recruited and followed over 12 years. Their survival function was compared with a birth cohort-, baseline age-, sex-, and race-matched pseudo sample from U.S. census data. To examine underlying and contributing causes, we examined in detail 338 deaths with complete death adjudication at the University of Pittsburgh Field Center through the year 2018. A familial effect on survival and death pattern was examined using mixed effect models. The LLFS siblings had better survival than the matched U.S. population average. They also had slightly but not significantly better survival than their spouses' (HR=1.18 [95%CI 0.94-1.49]) after adjusting for age and sex. Age at death ranged from 75-104 years, mean 91.4. The leading causes of death were cardiovascular disease (33.1%), dementia (22.2%), and cancer (10.7%). Mixed effect model shows a significant random effect of family in survival, with adjustment of baseline age and sex. There was no significant familial effect in the underlying cause of death or conditions directly contributing to death among siblings recruited by the University of Pittsburgh Field Center. Our findings demonstrate a higher survival in the LLFS siblings than the U.S. census data, with a familial component of survival. We did not find significant correspondence in causes of death between siblings within families.

Investigating grey matter volumetric trajectories through the lifespan at the individual level

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14–23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.

Patient-reported Outcomes Following Nonoperative Treatment of Pediatric First‐Time Patellar Dislocation

BackgroundPatellar instability is a common pediatric knee injury. The purpose of this study was to analyze PROMs (patient-reported outcome measures) after non-operative treatment following a first-time pediatric patellar dislocation. MethodsIn this single-center, retrospective study, patients <18 years old between January 2012 and December 2019 with a first-time patellar dislocation were evaluated. From this cohort, we included all those patients who initially underwent non-operative management and followed up for at least 1 year. Measures of patellar height and patellofemoral dysplasia were collected. Patient-reported outcome measures (PROMs) were collected at the initial and follow-up visit. Univariate and multivariate analyses were utilized to determine the rate and risk factors for recurrence and the changes in PROMs. Results176 knees were included in the initial analysis, and 80 in the pre- and post-PROM analysis. There was a 41% rate of recurrence at a mean of 16.4 months of follow-up. In a multivariate logistic regression model, trochlear dysplasia (OR:4.53, 95%CI: 1.61–12.7, P=0.004), patella alta (OR:4.27, 95%CI: 1.76–10.3, P<0.001), and tibial tubercle trochlear groove (TT-TG) > 15mm (OR:2.49, 95%CI: 1.3–6.03, P<0.001) were significant risk factors for recurrence. Patients with or without recurrence showed significant improvements in PROMs at 1 year follow-up. However, both groups had mean scores below the population average. Regardless of recurrence or not, KOOS-Child QoL scores ranked the lowest among all PROM scores at the final follow-up. ConclusionsThe findings of this study provide further evidence of the high rate of recurrent instability and important associated risk factors to consider. We also found that despite the overall improvement in all PROM subscales 1 year following the initial episode, both recurrence and no-recurrence groups demonstrated lower mean PROM scores than normal values. Furthermore, quality of life subscales showed the smallest improvement among all patients. Our results may be used to counsel patients and families regarding expectations after first-time and recurrent patellar dislocations. Key conceptsPatellar instability is one of the most common pediatric sports injuries with a high risk of recurrence.(1)In the absence of other factors, a first-time patellar dislocation is generally treated non-operatively, but the long-term outcomes are not clear.(2)In this study, we found a high risk of recurrent dislocation. In addition, while the PROMs improved for all patients, even patients without evidence of further instability demonstrated patient-reported outcomes lower than the general population.(3)Future research may reveal subtle residual instability or other factors as the reason for the lower functional status and also compare these outcomes with operative reconstruction. Level of evidenceCase series, Level IV

Three-dimensional morphometric and volumetric analysis of maxillary sinuses.

The maxillary sinus is a pyramid-shaped cavity with varying shapes, sizes, and capacities. Its dimensions grow gradually and develop until early adulthood. Anatomical knowledge of the maxillary sinus is essential to understanding sinonasal disorders, planning surgical procedures and preventing complications. Awareness of the sinus's proximity to critical structures helps avoid injuries during surgery. The European, Korean, and Sri Lankan population study parameters show varying results and do not necessarily apply to the Indian population. The standard morphometric data of the maxillary sinus is scanty in the Indian population. The study aimed to determine the volume and morphometry of the maxillary sinus along with gender differences in the Eastern population of the Indian. A retrospective cross-sectional study was conducted using cone beam computed tomography data of maxillary sinuses of 100 normal individuals. The data were analysed after the three-dimensional reconstruction of digital imaging and communications in medicine (DICOM) images with the help of DICOM to print and Geomagic freeform software in the Anatomy department. The different linear morphometric variables and volume of the maxillary sinus were studied. SPSS version 27.0. was utilised for statistical analyses. The mean values of Antero-posterior diameter, Transverse diameter, Craniocaudal diameters, the height of ostium from the floor and volume of the maxillary sinus in males on the right side are 36.61 mm, 20.7 mm, 40.31 mm, 26.02 mm and 16055.24 mm³ and on the left side are 37.17 mm, 20.17 mm, 40.73 mm, 26.91 mm and 15712.66 mm³ whereas in females the values on the right side are 38.10 mm, 21.56 mm, 38.96 mm, 25.81 mm and 14687.78 mm³ and on left side are 38.23 mm, 21.53 mm, 38.48 mm, 25.28 mm and 14203.13 mm3 respectively. The side-to-side parameter differences were non-significant within the male and female groups, respectively. The females had significantly (p < 0.05) larger transverse diameters than males in both the right and left maxillary sinuses. The males tend to have a slightly larger mean craniocaudal diameter than females, but the difference was found statistically significant (p < 0.05) only in the left maxillary sinus. The gender differentiation based on the measured parameters of bilateral maxillary sinus accuracy rate was 89.4% in males and 61.8% in females. These parameters serve as a standard or reference point, allowing radiologists and surgeons to compare individual patient scans to population averages and aid in better clinical outcomes. The mean values of different parameters of the maxillary sinus may be utilised to differentiate various suspected sinus pathologies, which is helpful for functional endoscopic sinus surgery. Gender differentiation can be done more accurately by forensic experts using Maxillary sinus transverse diameter bilaterally, followed by craniocaudal diameter of the left side sinus for predicting the gender of an unknown maxilla.

P-485 An exploration of psychological, emotional and social wellbeing among donor conceived young adults in the UK

Abstract Study question Do donor conceived young adults differ from those not donor conceived on key indicators of wellbeing? Summary answer In contrast to findings in childhood and adolescence, young adulthood may prove to be a challenging time for donor conceived individuals and influence their wellbeing. What is known already Although research has shown that the psychological adjustment of donor conceived children and adolescents generally does not differ to those conceived in more traditional circumstances, most studies have focussed on the family factors that are associated with an absence of adjustment problems amongst this population. Little research has explored social factors and broader definitions of wellbeing including positive wellbeing and life satisfaction. Further, few studies have focused on young adulthood; a time at which identity exploration is often heightened. Study design, size, duration Data were collected via an anonymous online survey between January and August 2022. The survey was designed in consultation with two community partners in the UK, the Donor Conception Network (DCN) and Donor Conceived Register Registrants’ Panel (DCRRP) and was piloted by donor conceived adults. Participants were recruited with assistance from the community partners and via social media and snowballing. All participants provided written consent to take part in the survey. Participants/materials, setting, methods 92 young adults (18-30 years-old) in the UK took part, of which 80% identified as female. 41 participants were donor conceived and 51 were not. The majority (78%) of donor conceived young adults were conceived by sperm donation. All participants were asked demographic information and completed standardised questionnaires of mental health, satisfaction with life, gratitude, mastery, collective self-esteem, identity confusion, and resilience. Adapted measures of stigma and pride were also administered to donor conceived participants. Main results and the role of chance Donor conceived participants reported less gratitude about their circumstances than participants who were not donor conceived, t(90) = 3.47, p&amp;lt;0.001, felt less control over their life and future, t(90)=-2.58, p=0.01, felt their social groups were not as central to their identity, t(90)=-2.81, p&amp;lt;0.01, reported lower general wellbeing, t(90)=-2.78, p&amp;lt;0.01, and lower satisfaction with life, t(73.81)=-3.59, p&amp;lt;0.001. No differences were found on measures of acceptance of identity or resilience. Among the donor conceived young adults, 18 (44%) reported that they felt they had always known they were donor conceived, whereas 23 (56%) could remember the point at which they were told (ranging from 9-27 years). Participants who reported having always known about being donor conceived had lower scores on the adapted stigma measure, t(39),=2.83, p&amp;lt;0.01, and higher scores on the adapted pride measure, t(39)=-2.68, p&amp;lt;0.05. Stigma was negatively correlated with general wellbeing, r(39)=-4.6, p &amp;lt; 0.01. Limitations, reasons for caution The relatively small sample was self-selected and partly recruited via support organisations for donor conceived people and lacked diversity regarding participant gender and donation type. Though the donor conceived young adults scored lower on wellbeing measures, the scores were close to population averages. The data is cross-sectional. Wider implications of the findings Findings suggest that greater support, which recognises and is tailored to the needs of donor conceived young adults, is needed. Such support resources should specifically consider findings relating to the relationship between disclosure and wellbeing, and stigma and wellbeing, for donor conceived people in young adulthood. Trial registration number Not applicable

Bootstrapping cascaded random matrix models: Correlations in permutations of matrix products.

Random matrix theory is a useful tool in the study of the physics of multiple scattering systems, often striking a balance between computation speed and physical rigour. Propagation of waves through thick disordered media, as arises, for example, in optical scattering or electron transport, typically necessitates cascading of multiple random matrices drawn from an underlying ensemble for thin media, greatly increasing the computational burden. Here we propose a dual pool based bootstrapping approach to speed up statistical studies of scattering in thick random media. We examine how potential matrix reuse in a pool based approach can impact statistical estimates of population averages. Specifically, we discuss how both bias and additional variance in the sample mean estimator are introduced through bootstrapping. In the diffusive scattering regime, the extra estimator variance is shown to originate from samples in which cascaded transfer matrices are permuted matrix products. Through analysis of the combinatorics and cycle structure of permutations we quantify the resulting correlations. Proofs of several analytic formulas enumerating the frequency with which correlations of different strengths occur are derived. Extension to the ballistic regime is briefly considered.

Time series generative adversarial network for muscle force prognostication using statistical outlier detection

AbstractMachine learning approaches, such as artificial neural networks (ANN), effectively perform various tasks and provide new predictive models for complicated physiological systems. Examples of Robotics applications involving direct human engagement, such as controlling prosthetic arms, athletic training, and investigating muscle physiology. It is now time for automated systems to take over modelling and monitoring tasks. However, there is a problem with the massive amount of time series data collected to build accurate forecasting systems. There may be inconsistencies in forecasting muscle forces due to the enormous amount of data. As a result, anomaly detection techniques play a significant role in detecting anomalous data. Detecting anomalies can help reduce redundancy and free up large storage space for storing relevant time‐series data. This paper employs several anomaly detection techniques, including Isolation Forest (iforest), K‐Nearest Neighbour (KNN), Open Support Vector Machine (OSVM), Histogram, and Local Outlier Factor (LOF). These techniques have been used by Long Short‐Term Memory (LSTM), Auto‐Regressive Integrated Moving Average (ARIMA), and Prophet models. The dataset used in this study contained raw measurements of body movements (kinematics) and the forces generated during walking (kinetics) of 57 healthy people (29 Female, 28 Male) without walking abnormalities or recent leg injuries. To increase the data samples, we used TimeGAN that generates synthetic time series data with temporal dependencies, aiding in training robust predictive models for muscle force prediction. The results are then compared with different evaluation metrics for five different samples. It is found that anomaly detection techniques with LSTM, ARIMA, and Prophet models provided better performance in forecasting muscle forces. The iforest method achieved the best Pearson's Correlation Coefficient (r) of 0.95, which is a competitive score with existing systems that perform between 0.7 and 0.9. The methodology provides a foundation for precision medicine, enhancing prognostic capability over relying solely on population averages.

Systemic versus local patterns of limb joint articular morphology inferred from relative distances from morphological centroid.

Joint morphogenesis is a complex process known to require the interaction of developmental cascades and mechanical loading, yet many details of this interaction are incompletely understood. While prior work has established populational patterns of joint morphological (co)variance, exploring how these patterns manifest within the individual provides information on the deployment of morphogenic processes as either systemic or local influences on joint shape. To better identify the patterns of variance-generating morphogenic processes, this study investigates the degree to which individual joint shapes deviate from population averages systematically across the body. Using three-dimensional landmark data from 200 adult skeletons, we ranked individuals based on their distances from morphological centroids for eight major joints. Spearman correlations assessed associations between ranks across various articular pairings, testing hypotheses regarding systemic versus localized variance. Results reveal low coordination between deviations observed in conarticular surfaces, functional analogs, and same-bone surfaces; however strong associations exist between antimeres, suggesting the left-right deployment of variance-generating morphogenic patterns is highly consistent. These results support a model of localized rather than systemic processes driving variation in joint shape. While more remains to be elucidated about the specifics of articular surface morphogenesis, these findings advance our understanding of the systems of variance generation at play during development and growth of our definitive joint morphology.

The state of the reproductive system of adolescent girls after vaccination against human papillomavirus using a quadrivalent vaccine

Background. Currently, oncological diseases and their possible prevention are being actively studied. Cancer mortality remains high. A national project “Healthcare” has been started in Russia, including the Federal projects “Fighting Cancer” and “Development of Children’s Health Care, including the creation of a modern infrastructure for providing medical care to children”. In a number of regions, girls can be vaccinated against the human papillomavirus (HPV). The main reason for refusing HPV vaccination is an unfounded fear of negatively affecting the fertility and other bad data. The aim of the study is an investigation of the reproductive system of adolescent girls with completed course of vaccination against HPV using quadrivalent vaccine. Methods. We selected 65 schoolgirls in Moscow by analyzing medical documentation data. All of them were vaccinated against HPV and examined by a gynecologist. The state of their reproductive system was assessed. Results. Most girls received the vaccine at the age of 12–13, according to the regional vaccination calendar of the city of Moscow. They were vaccinated with the quadrivalent vaccine twice with an interval of 6 months; no adverse event was noted. The mean period of time since vaccination was 2.7 ± 1.1 years. The mean age of menarche, mean menstrual cycle length, and mean bleeding time were normal in girls vaccinated against HPV. Among menstrual disorders, dysmenorrhea and oligomenorrhea were most often observed, but the data did not differ from the population average. The incidence of abnormal uterine bleeding and breast pathology was lower. No papillomas were detected. Pubertal development corresponded to age of all girls. Conclusion. It has been established that vaccination against the human papillomavirus does not have a negative impact on the reproductive system of teenage girls. However, additional dynamic studies are needed at different age periods of girls and women vaccinated against HPV to confirm the positive effect on the sexual sphere and formation of strong adherence to vaccination.

Advances in Addressing Patient Heterogeneity in Economic Evaluation: A Review of the Methods Literature.

Cost-effectiveness analyses commonly use population or sample averages, which can mask key differences across subgroups and may lead to suboptimal resource allocation. Despite there being several new methods developed over the last decade, there is no recent summary of what methods are available to researchers. This review sought to identify advances in methods for addressing patient heterogeneity in economic evaluations and to provide an overview of these methods. A literature search was conducted using the Econlit, Embase and MEDLINE databases to identify studies published after 2011 (date of a previous review on this topic). Eligible studies needed to have an explicit methodological focus, related to how patient heterogeneity can be accounted for within a full economic evaluation. Sixteen studies were included in the review. Methodologies were varied and included regression techniques, model design and value of information analysis. Recent publications have applied methodologies more commonly used in other fields, such as machine learning and causal forests. Commonly noted challenges associated with considering patient heterogeneity included data availability (e.g., sample size), statistical issues (e.g., risk of false positives) and practical factors (e.g., computation time). A range of methods are available to address patient heterogeneity in economic evaluation, with relevant methods differing according to research question, scope of the economic evaluation and data availability. Researchers need to be aware of the challenges associated with addressing patient heterogeneity (e.g., data availability) to ensure findings are meaningful and robust. Future research is needed to assess whether and how methods are being applied in practice.

Vectorial Analysis of Deep Plane Face and Neck Lift.

The vector of aging and consequently the vector of lift in rhytidectomy has aided surgeons in improving movement of tissues during facial rejuvenation procedures. The goal was to analyze the vector of lift in patients undergoing primary and revisional facelift to achieve proper vectorial lifting. Patients undergoing deep-plane facelift surgery were included for analysis. Intraoperative photographs and measurements were taken of the skin, superficial musculoaponeurotic system (SMAS), and platysmal suture suspension with mastoid crevasse inset. Measurements were compared between patients who were undergoing primary vs secondary surgery, site of lift, age, and gender. Seventy-one patients (90% female, mean age 57.8) with a total of 142 hemifaces were analyzed, 57 (73%) of which were primary and 14 (27%) secondary facelifts. The average vector of SMAS lifting was 70.8°. Females had a more vertical vector than males (71.3° vs 65.4°; P < .01). The average vectors of platysmal and skin lift were 87.0° and 58.2°, respectively. There was intrapatient difference between hemifaces. Despite there being more intersuture disparity in secondary cases than primary cases (16.9° vs 4.5°; P < .05), the mean vector of lifting was similar between them. Proper release of the deep plane helps determine the appropriate vectors of lift, without relying on guidelines based on population averages. Each patient presents with a unique vector required to correct their descent. This technique provides an optimal result by directly suspending against the vectors of greatest descent.

Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.MethodsCross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.ResultsOf 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.ConclusionsPatient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.