Symptom-free Individuals Research Articles

Functional and prognostic impacts of serum albumin with thoracic arterial calcification among asymptomatic individuals

Although several studies have demonstrated the cardiovascular (CV) implication of hypoalbuminemia and arterial calcification among hemodialysis patients, little is known regarding their cardiac correlates and relevant CV outcomes in asymptomatic individuals. We assessed the potential CV interrelation between serum albumin (SA) and aortic calcification. Among 2,723 asymptomatic individuals underwent cardiovascular health check-up, we assessed serum albumin (SA) level, thoracic aortic calcification (TAC) and coronary artery calcification (CAC) by multi-detector computed tomography, and ultrasound-determined carotid plaque burden. We related these measures to cardiac structure/function and CV outcomes. Lower SA level was associated with higher TAC score and volume rather than carotid plaque or coronary calcification burden in fully adjusted models. By categorizing the study population into 4 groups by SA (>, ≤ 4.6 mg/dL) and presence of TAC, subjects classified into low SA/TAC(+) category were oldest with highest prevalent CV disease. Both lower SA and TAC(+) were independently associated with impaired myocardial systolic/diastolic mechanics and higher CV events during a median of 6.6 years (IQR: 5.1, 6.8 years) follow-up. Participants classified into low SA/TAC(+) category showed highest risk for CV events (adjusted HR: 3.78 [95% CI: 2.11, 6.77], high SA/TAC[-] as reference) in fully adjusted Cox model. Among symptom-free individuals, TAC was closely associated with low SA concentration in relation to unfavorable cardiac mechanics and may serve as a useful prognosticator for adverse CV events.

Heart rate response to cognitive load as a marker of depression and increased anxiety.

Understanding the interplay between cardiovascular parameters, cognitive stress induced by increasing load, and mental well-being is vital for the development of integrated health strategies today. By monitoring physiological signals like electrocardiogram (ECG) and photoplethysmogram (PPG) in real time, researchers can discover how cognitive tasks influence both cardiovascular and mental health. Cardiac biomarkers resulting from cognitive strain act as indicators of autonomic nervous system function, potentially reflecting conditions related to heart and mental health, including depression and anxiety. The purpose of this study is to investigate how cognitive load affects ECG and PPG measurements and whether these can signal early cardiovascular changes during depression and anxiety disorders. Ninety participants aged 18 to 45 years, ranging from symptom-free individuals to those with diverse psychological conditions, were assessed using psychological questionnaires and anamnesis. ECG and PPG monitoring were conducted as volunteers engaged in a cognitive 1-back task consisting of two separate blocks, each with six progressively challenging levels. The participants' responses were analyzed to correlate physiological and psychological data with cognitive stressors and outcomes. The study confirmed a notable interdependence between anxiety and depression, and cardiovascular responses. Task accuracy decreased with increased task difficulty. A strong relationship between PPG-measured heart rate and markers of depression and trait anxiety was observed. Increasing task difficulty corresponded to an increase in heart rate, linked with elevated levels of depression and trait anxiety. A strong relationship between ECG-measured heart rate and anxiety attacks was observed. Increasing task difficulty corresponded to an increase in heart rate, linked with elevated levels of anxiety attacks, although this association decreased under more challenging conditions. The findings underscore the predictive importance of ECG and PPG heart rate parameters in mental health assessment, particularly depression and anxiety under cognitive stress induced by increasing load. We discuss mechanisms of sympathetic activation explaining these differences. Our research outcomes have implications for clinical assessments and wearable device algorithms for more precise, personalized mental health diagnostics.

Interosseous tendon inflammation in the hands of patients with clinically suspect arthralgia: analysis of MRI data from a prospective cohort study.

Inflammation around the tendons of interosseous muscles of the hand (interosseous tendon inflammation) was recently observed with MRI for the first time in patients with rheumatoid arthritis and in at-risk individuals with detectable anti-citrullinated protein antibodies, generating the hypothesis that interosseous tendon inflammation precedes clinical arthritis. To better understand the role of interosseous tendon inflammation during the development of rheumatoid arthritis, we studied the frequency of interosseous tendon inflammation in healthy individuals and in those with arthralgia that was suspected of progressing to rheumatoid arthritis (ie, clinically suspect arthralgia) and the association of interosseous tendon inflammation with other symptoms of inflamed joint tissues and with clinical arthritis development. Adult (age ≥18 years) patients who presented with clinically suspect arthralgia and symptom-free (control) individuals underwent contrast-enhanced hand MRI. MRIs were evaluated for interosseous tendon inflammation on the radial and ulnar sides of the second to fifth metacarpophalangeal joints, and for synovitis, tenosynovitis, and osteitis using the rheumatoid arthritis MRI scoring system. Patients with clinically suspect arthralgia were followed up for clinical arthritis development. The presence of local tenosynovium was examined using immunohistochemistry for anti-CD55 and anti-CD68 on tissue from the hands of three embalmed bodies donated for scientific research. The primary outcome for the cross-sectional part of the study was the presence of interosseous tendon inflammation on MRI. The primary outcome for the longitudinal part of the study was development of clinical arthritis. Between April 3, 2012, and May 20, 2020, 667 patients with clinically suspect arthralgia (mean age 44 years [SD 13], 504 [76%] were women and 163 [24%] were men) underwent contrast-enhanced hand MRI. Between Nov 1, 2013, and Nov 30, 2014, 193 symptom-free controls were recruited (mean age 50 years [SD 16], 136 [70%] were women and 57 [30%] were men). Two (1%) of 193 symptom-free controls had interosseous tendon inflammation. Immunohistochemistry of cadaveric hand tissues showed no tenosynovium surrounding interosseous tendons. At inclusion, 67 (10%) of 667 patients with clinically suspect arthralgia had interosseous tendon inflammation (p<0·0001 vs symptom-free controls). Interosseous tendon inflammation occurred more frequently if synovitis (odds ratio [OR] 2·2 [95% CI 1·2-4·2]), or tenosynovitis (OR 9·7 [5·5-17·0]), was present at metacarpophalangeal joints. A three-dimensional MRI reconstruction suggested confluency of interosseous tendon inflammation with metacarpophalangeal-flexor-tenosynovitis. 91 (16%) of 558 patients with clinically suspect arthralgia developed clinical arthritis during follow-up (median total follow-up 25·3 months [95% CI 25·1-25·5]). Patients with clinically suspect arthralgia with interosseous tendon inflammation had a higher risk of developing clinical arthritis (hazard ratio [HR] 4·5 [2·8-7·2]), which was attenuated but still significant after adjusting for concomitant synovitis, tenosynovitis, or osteitis (HR 1·7 [1·02-2·8]). Interosseous tendon inflammation is almost absent in symptom-free individuals but occurs in people with clinically suspect arthralgia, in whom it correlates with symptoms and is associated with the development of clinical arthritis. The absence of local tenosynovium suggests that interosseous tendon inflammation arises from expanding local subclinical inflammation in the pre-arthritis phase of rheumatoid arthritis. European Research Council and the Dutch Arthritis Society.

Quality of Life in Patients with Confirmed and Suspected Spontaneous Intracranial Hypotension (P3-12.002)

<h3>Objective:</h3> To assess the impact of spontaneous intracranial hypotension (SIH) on quality-of-life (QoL). <h3>Background:</h3> SIH is a debilitating condition that typically produces orthostatic headache and limits upright time. It is often difficult to detect, diagnose, and treat, profoundly affecting patients’ QoL. <h3>Design/Methods:</h3> We conducted a cross-sectional survey of patients with confirmed (n=59) and clinically suspected (n=36) SIH evaluated from 2016 to 2022. Participants completed the following validated measurements online (REDCap V 11.2.2): SF-36 (general well-being), PHQ-9 (depression), GAD-7 (anxiety), FACIT-Sp-12 (spiritual well-being), and HIT-6 (headache impact). Subsequently, willing participants were interviewed to administer the Columbia-Suicide Severity Rating Scale (C-SSRS) assessing suicidal behavior and ideation. <h3>Results:</h3> 95 of 234 patients (41%) meeting inclusion criteria completed the questionnaires. The average age was 51.1 years (SD: 15.5), predominantly female (69.5%), Caucasian (91.6%), and married (69.5%). 74.5% scored within the most severe headache category on the HIT-6. SF-36 scores were significantly worse (p &lt; 0.0001) compared to the general population. 49.1% scored in the moderate or worse depression range (&gt;10) and 25.4% scored for moderate or worse anxiety (&gt;10). FACIT scores strongly correlated (p&lt;0.001) with HIT-6 (−.54), SF-36 Mental Component (r=.66), PHQ-9 (r=−.65) and GAD-7 (r=−.65). 67 respondents completed the C-SSRS of whom 64.2% had endorsed a wish to be dead, and 22.4% had demonstrated suicidal behavior. Symptom-free SIH patients (n = 22) scored significantly better than symptomatic patients and similar to the general population. <h3>Conclusions:</h3> SIH is associated with severe headache pain and high rates of depression, anxiety, and disability, affecting basic activities of daily living. Individuals with confirmed and suspected SIH had similar levels of head pain, depression, anxiety and suicidality in our cohort. Symptom-free individuals following successful treatment or spontaneous remission showed improved outcomes comparable to the general population. Improved identification and treatment of SIH are imperative to improving patients’ QoL. <b>Disclosure:</b> Mr. Liaw has nothing to disclose. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan/Abbvie. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Friedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Friedman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Impel. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Friedman has received personal compensation in the range of $0-$499 for serving as a Consultant for Teva. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zosano. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium Pharmaceuticals. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Impel. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Reviews. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology . The institution of Dr. Friedman has received research support from Zosano. The institution of Dr. Friedman has received research support from Allergan. The institution of Dr. Friedman has received research support from Spinal CSF Leak Foundation. Dr. Friedman has a non-compensated relationship as a Program Co-Chair, Scottsdale Headache Symposium with American Headache Society that is relevant to AAN interests or activities. Dr. Friedman has a non-compensated relationship as a Medical Advisor with Spinal CSF Leak Foundation that is relevant to AAN interests or activities. Mr. McCreary has nothing to disclose.

Current recommendation for isolation in COVID-19 infection: a perspective review article

Introduction: There have been multiple variants of Severe acute respiratory syndrome coronavirus 2 (SARS CoV- 2), a strain of coronavirus, that causes COVID-19, a respiratory illness responsible for the ongoing COVID-19 pandemic, since its first identified outbreak in Wuhan, China in November 2019. Since the pandemic began there have been various changes in the isolation period of the identified cases reducing from 2 to 3 weeks to the current recommendation of 5 days of isolation in symptom-free individuals in various countries. As of July 2022, only the Omicron variant has been identified as a variant of concern by the World Health Organization.&#x0D; &#x0D; Method: Articles were searched in Google scholar, PubMed, CDC guidelines, NHS guidelines (UK), Indian guidelines (Ministry of Health and Family Welfare), Nepal guidelines (Ministry of Health and Population), and WHO guidelines.&#x0D; &#x0D; Result: The guidelines recommend a self-isolation period of infected individuals ranging from 5 to 14 days after testing positive for the COVID-19 disease.&#x0D; &#x0D; Conclusion: COVID-19 is here to stay and showing no signs of slowing down though overall fatality rate have been on decline owing to vaccination and increased immunity against the virus, it is ideal to shorten the duration of isolation and focus on protection against the virus all the times and not letting the guard down.

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

Simple SummaryThere is an alarming increase of cardiovascular disease (CVD) and type 2 diabetes (T2D) in Mexican nationals and Mexican Americans. Studying adipose tissue (AT) dysfunction and early biomarkers of cardiovascular and immunometabolic risk in Mexican nationals may have a strong impact on future public health policies for US-born Mexican Americans and other populations of Mexican origin in the US. The goal of this study is to evaluate the early transition towards healthy/unhealthy adipose tissue expansion to identify AT dysfunction through systemic, molecular and OMICS measures in the fasting and fed states in symptom-free volunteers with no history of age-related chronic diseases in support of precision medicine and discovery.We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

Estimating asymptomatic SARS-CoV-2 infections in a geographic area of low disease incidence

BackgroundThe SARS-CoV-2 infection has emerged as a rapidly spreading infection. Today it is relatively easy to isolate Covid-19 symptomatic cases, while remains problematic to control the disease spread by infected but symptom-free individuals. The control of this possible path of contagion requires drastic measures of social distancing, which imply the suspension of most activities and generate economic and social issues. This study is aimed at estimating the percentage of asymptomatic SARS-CoV-2 infection in a geographic area with relatively low incidence of Covid-19.MethodsBlood serum samples from 388 healthy volunteers were analyzed for the presence of anti-SARS-CoV-2 IgG by using an ELISA assay based on recombinant viral nucleocapsid protein.ResultsWe found that 7 out of 388 healthy volunteers, who declared no symptoms of Covid-19, like fever, cough, fatigue etc., in the preceding 5 months, have bona fide serum anti-SARS-CoV-2 IgG, that is 1.8% of the asymptomatic population (95% confidence interval: 0.69–2.91%).ConclusionsThe estimated range of asymptomatic individuals with anti-SARS-CoV-2 IgG should be between 26,565 and 112, 350. In the same geographic area, there are 4665 symptomatic diagnosed cases.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) screening among symptom-free healthcare workers.

Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.

Diverse Adiposity and Atrio-Ventricular Dysfunction across Obesity Phenotypes: Implication of Epicardial Fat Analysis.

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions < 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement < 0.05) mainly in the NW phenotypes (p interaction < 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.

NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population.

To test the hypothesis that the prevalence and clinical effect of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been underestimated in Asian populations. The Taiwan Biobank, containing 1,517 Taiwanese genome sequences, was queried for pathogenic NOTCH3 cysteine-altering mutations. NOTCH3 mutations identified in the reference population were genotyped in 7,038 stroke- and dementia-free individuals and 800 patients with ischemic stroke. NOTCH3 genotyping, clinical manifestations, and the severity of white matter lesions on MRI were compared between the 2 groups. Three cysteine-altering NOTCH3 variants (p.R544C, p.C853Y, and p.C884Y) were identified from the Taiwan Biobank. We confirmed that the NOTCH3 p.R544C mutation was present in a significant number of individuals in Taiwan, including 60 of the 7,038 healthy controls (0.9%), 17 of the 800 patients with ischemic stroke (2.1%), and 16 of the 245 patients with small vessel occlusion (SVO) stroke (6.5%). The other 2 cysteine-altering mutations were rarely detected. After adjusting for vascular risk factors, harboring the p.R544C variant resulted in a 3.40-fold increased risk for overall stroke and an 11.05-fold increased risk for SVO stroke (p = 0.0001 and 3.9 × 10-10, respectively). Three symptom-free individuals carrying the p.R544C mutation had extensive leukoencephalopathy typical of CADASIL at age 59, 66, and 67, suggesting that p.R544C-related CADASIL could remain subclinical at advanced age. The NOTCH3 p.R544C variant is an important risk factor for SVO stroke in Taiwan. Phenotypic variation among individuals carrying a NOTCH3 mutation indicates the existence of disease-modifying factors in CADASIL.

Zwischen Präzisionsmedizin und symbolischer Bewältigung: Was Ärzte wünschen

IntroductionCaring for patients is inevitably fraught with uncertainties. These may result from clinicians not having or not using the available knowledge, from the incompleteness of the medical science base as a whole, or from the inevitable randomness of biological, psychological and social phenomena. Advances in science promise to reduce uncertainty by making ever more precise diagnosis and treatment possible. MethodsHere, we discuss two typical examples of scientific progress and on how they impact on clinical uncertainty: first, the stratification of chemotherapy for early breast cancer by a 70-gene signature, and second, the interpretation of knee MRI regarding meniscal damage. ResultsAccording to a large randomized trial, the 70-gene -signature successfully differentiates between strata for invasive treatments. The quantitative results and related trade-offs, however, pose considerable difficulties for patient information and shared decision-making, thus increasing uncertainty. Knee complaints are only weakly associated with MRI findings. Pathological findings are highly prevalent in symptom-free individuals. ConclusionRecent advances in diagnostic methods increase the cognitive demands on clinicians and thus their uncertainty. By uncritically using advanced technologies in their practice, physicians exploit their archetypical healing powers. In a paradoxical way, modern technologies reduce uncertainties felt by doctors and their patients in an archaic fashion.

Youth at-risk for serious mental illness: methods of the PROCAN study

BackgroundMost mental disorders begin in adolescence; however, there are gaps in our understanding of youth mental health. Clinical and policy gaps arise from our current inability to predict, from amongst all youth who experience mild behavioural disturbances, who will go on to develop a mental illness, what that illness will be, and what can be done to change its course and prevent its worsening to a serious mental illness (SMI). There are also gaps in our understanding of how known risk factors set off neurobiological changes that may play a role in determining who will develop a SMI. Project goals are (i) to identify youth at different stages of risk of SMI so that intervention can begin as soon as possible and (ii) to understand the triggers of these mental illnesses.MethodThis 2-site longitudinal study will recruit 240 youth, ages 12–25, who are at different stages of risk for developing a SMI. The sample includes (a) healthy individuals, (b) symptom-free individuals who have a first-degree relative with a SMI, (c) youth who are experiencing distress and may have mild symptoms of anxiety or depression, and (d) youth who are already demonstrating attenuated symptoms of SMI such as bipolar disorder or psychosis. We will assess, every 6 months for one year, a wide range of clinical and psychosocial factors to determine which factors can be used to predict key outcomes. We will also assess neuroimaging and peripheral markers. We will develop and validate a prediction algorithm that includes demographic, clinical and psychosocial predictors. We will also determine if adding biological markers to our algorithm improves prediction.DiscussionOutcomes from this study include an improved clinical staging model for SMI and prediction algorithms that can be used by health care providers as decision-support tools in their practices. Secondly, we may have a greater understanding of clinical, social and cognitive factors associated with the clinical stages of development of a SMI, as well as new insights from neuroimaging and later neurochemical biomarker studies regarding predisposition to SMI development and progression through the clinical stages of illness.

Are MRI-detected erosions specific for RA? A large explorative cross-sectional study

ObjectivesMRI is recommended in the diagnostic process of rheumatoid arthritis (RA) to detect joint damage early. MRI-detected erosions are also present in symptom-free controls, especially at older age. It is...

Effect of 8% lidocaine spray on the sensory and pain thresholds of the skin of the face and hands evaluated by quantitative sensory testing.

BackgroundRecently, we examined the effects of 2% lidocaine gel on the tactile sensory and pain thresholds of the face, tongue and hands of symptom-free individuals using quantitative sensory testing (QST); its effect was less on the skin of the face and hands than on the tongue. Consequently, instead of 2% lidocaine gel, we examined the effect of 8% lidocaine spray on the tactile sensory and pain thresholds of the skin of the face and hands of healthy volunteers.MethodsUsing Semmes-Weinstein monofilaments, QST of the skin of the cheek and palm (thenar skin) was performed in 20 healthy volunteers. In each participant, two topical sprays were applied. On one side, 0.2 mL of 8% lidocaine pump spray was applied, and on the other side, 0.2 mL of saline pump spray was applied as control. In each participant, QST was performed before and 15 min after each application. Pain intensity was measured using a numeric rating scale (NRS).ResultsBoth the tactile detection threshold and filament-prick pain detection threshold of the cheek and thenar skin increased significantly after lidocaine application. A significant difference between the effect of lidocaine and saline applications was found on the filament-prick pain detection threshold only. NRS of the cheek skin and thenar skin decreased after application of lidocaine, and not after application of saline.ConclusionThe significant effect of applying an 8% lidocaine spray on the sensory and pain thresholds of the skin of the face and hands can be objectively scored using QST.

The impact of choosing words carefully: an online investigation into imaging reporting strategies and best practice care for low back pain.

BackgroundLow back pain clinical practice guidelines consistently recommend against the routine ordering of spinal imaging; however, imaging is frequently requested in primary care, without evidence of benefit. Imaging reports frequently identify degenerative features which are likely to be interpreted as ‘abnormal’, despite their high prevalence in symptom-free individuals. The aim of this study was to investigate whether post-imaging back-related perceptions are influenced by providing prior information about normal findings, and to compare the effect of receiving imaging results with best practice care (without imaging). The impact of introducing novel, ‘enhanced’ reporting strategies was also explored.MethodsThis study was a simulated-patient, randomised, multiple-arm experiment. Patient scenarios were presented to volunteer healthy adult participants via an online survey. In the scenarios, ‘virtual’ patients with low back pain were randomised to one of three groups. Group 1 received imaging and was pre-informed about normal findings. Group 2 received imaging (without pre-information). Group 3 received best practice care: quality information without imaging. Group 1 was further divided to receive either a standard report, or an ‘enhanced’ report (containing altered terminology and epidemiological information). The primary outcome was back-related perceptions (BRP), a composite score derived from three numeric rating scale scores exploring perceptions of spinal condition, recovery concerns and planned activity. The secondary outcomes were satisfaction and kinesiophobia.ResultsFull data were available from 660 participants (68% female). Analysis of covariance revealed a significant effect of group after controlling for baseline BRP scores n}{}(F(2,74)=10.4,plt 0.001,{eta }_{p}^{2}=.04). Pairwise comparisons indicated that receiving best practice care resulted in more positive BRPs than receiving imaging results, and receiving prior information about normal findings had no impact. Enhanced reporting strategies also positively impacted BRPs n}{}(F(1,275)=13.06,plt 0.001,{eta }_{p}^{2}=.05). Significant relationships between group allocation and both satisfaction n}{}(F(2,553)=7.5,p=0.001,{eta }_{p}^{2}=.03) and kinaesiophobia n}{}(F(2,553)=3.0,p=0.050,{eta }_{p}^{2}=.01) were found, with statistically significant pairwise comparisions again in favour of best-practice care.ConclusionIntervention strategies such as enhanced reporting methods and the provision of quality information (without imaging) have the potential to improve the outcome of patients with recent-onset LBP and should be further considered by primary care providers.

Demographic associations for autoantibodies in disease-free individuals of a European population

The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto)immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.

Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The Multiethnic Study of Atherosclerosis (MESA).

The association between subclinical cardiovascular disease and subsequent development of erectile dysfunction (ED) remains poorly described. Among multiple subclinical atherosclerosis and vascular dysfunction measurements, coronary artery calcium (CAC) score best predicts ED. After excluding participants taking ED medications at baseline, we studied 1862 men age 45 to 84 years free of known cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) with comprehensive baseline subclinical vascular disease phenotyping and ED status assessed at MESA visit 5 (9.4 ± 0.5 years after baseline) using a standardized question on ED symptoms. Multivariable logistic regression was used to assess the associations between baseline measures of vascular disease (atherosclerosis domain: CAC, carotid intima-media thickness, carotid plaque, ankle-brachial index; vascular stiffness/function domain: aortic stiffness, carotid stiffness, brachial flow-mediated dilation) and ED symptoms at follow-up. Mean baseline age was 59.5 ± 9 years, and 839 participants (45%) reported ED symptoms at follow-up. Compared with symptom-free individuals, participants with ED had higher baseline prevalence of CAC score >100 (36.4% vs 17.2%), carotid intima-media thickness Z score >75th percentile (35.3% vs 16.6%), carotid plaque score ≥2 (39% vs 21.1%), carotid distensibility <25th percentile (34.6% vs 17.1%), aortic distensibility <25th percentile (34.2% vs 18.7%), and brachial flow-mediated dilation <25th percentile (28.4% vs 21.3%); all P < 0.01. Only CAC >100 (odds ratio: 1.43, 95% confidence interval: 1.09-1.88) and carotid plaque score ≥2 (odds ratio: 1.33, 95% confidence interval: 1.02-1.73) were significantly associated with ED. Subclinical vascular disease is common in men who later self-report ED. Early detection of subclinical atherosclerosis, particularly advanced CAC and carotid plaque, may provide opportunities for predicting the onset of subsequent vascular ED.

Signal changes of the alar ligament in a healthy population: a dispositional or degenerative consequence?

OBJECT The alar ligaments (ALs) are vital for stabilizing the craniocervical junction. In terms of morphology, their appearance varies and is visible on MRI. Dark signal of the AL on proton-density (PD)-weighted images is generally considered the norm, but the etiology of frequently observed signal hyperintensities is poorly understood. Using spectral fat suppression, signal hyperintensities can be differentiated into fat- and nonfat-related hyperintensities (NFH). Although signal hyperintensities have no evident association with whiplash-associated disorder, age-related degeneration has often been theorized. Therefore, this study investigates the signal intensities of the ALs on 3.0-T MRI with special reference to age. Expanding thereon, the authors investigated the relationship between signal hyperintensities and patient characteristics, such as height, weight, and sex. METHODS Sixty-six healthy volunteers were scanned using 3.0-T PD-weighted MRI, including spectral fat suppression of the craniocervical junction. The study population was separated into 2 groups (old vs young) using 2 approaches: dichotomization at the median age (40.0 years) and the calculated threshold (28.5 years) using receiver operating characteristics (ROC). The AL was independently characterized with respect to continuity, course, shape, signal intensity, and graduation of homogeneity by 2 experienced neuroradiologists. Signal intensity was differentiated into fat-related hyperintensity and NFH. Univariate and multivariate logistic regression models were employed to investigate the relationship between patient characteristics and signal intensities. RESULTS Two different AL patterns were observed: inhomogeneous (33.3%) and homogeneous (66.7%). The latter pattern was mostly surrounded by a small dark rim (56.8%). Fat could be identified in 15.9% of all ALs (21 of 132 patients), and NFH was identified in 17.4% of all ALs (23 of 132 patients). Here, 28.5 years was the preferred threshold, demonstrating a relatively high sensitivity for dichotomizing the population based on the ROC of NFH. The most relevant factor for having NFH was being older than the calculated threshold (odds ratio [OR] 3.420, p = 0.051). Fat-related hyperintensities occurred significantly more frequently in men than women (OR 0.110 and p = 0.007 for women; OR 9.075 and p = 0.007 for men). Height was the second most significant factor: for every 1-cm increase, the odds of having fat lesions increased by approximately 10% (OR 1.102; p = 0.017). CONCLUSIONS This study shows that AL signal hyperintensities are substantially influenced by age, sex, and height in healthy individuals. Regarding fat-related hyperintensities, the most relevant factors proved to be sex and height. The odds of detecting NFH increased almost significantly after a relatively young age (> 28.5 years) and were remarkably more frequent in individuals older than 28.5 years. The authors caution presumptions equating signal alterations with age-related deterioration. Instead, they suggest that dispositional factors such as sex and height are more relevant in the AL constitution. Signal alterations in ALs naturally occur in healthy symptom-free individuals, underscoring the importance of cautiously interpreting such lesions on posttraumatic MRI scans.

Confiabilidade da avaliação da orientação e posição de repouso da escápula de indivíduos saudáveis e sedentários com o sistema eletromagnético de aquisição de dados

Electromagnetic systems for motion analysis are claimed as a precise technique for tracking position and orientation of human body segments. To date, reliability electromagnetic tracking was described only for the dynamic assessment of the scapula motion, and no reliability studies on its resting posture or positioning were found. The aim of this study was to analyze intra- and inter-session reliabilities and absolute errors of the scapular orientation and position at habitual resting posture in healthy individuals. Twenty-two shoulder symptom-free individuals non participants in professional or recreational sports activities involving upper extremities were volunteers in this study. The equipment used was 3SPACE Liberty system (Polhemus Inc.). The same examiner collected the kinematic data from subjects in two different sessions, with an interval from seven to ten days. Intraclass Correlation Coefficient (ICC2,1 and ICC2, k) and Standard Error of Measurement (SEM) were calculated. Inter-session reliability ranged from good to excellent (ICC from 0.66 to 0.96) and intra-session reliability was excellent (ICC ≥ 0.97). SEM values found for linear distances were smaller than 0.02 cm and scapular rotations ranged from 0.72° to 5.48°. Results of this study demonstrated that electromagnetic data acquisition of scapula habitual posture is a reliable tool for defining scapular position and orientation in sedentary shoulder symptom-free individuals.

Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: a model-based analysis.

Tuberculosis (TB) control is especially difficult in settings of high HIV prevalence; HIV co-infection erodes host immunity and increases risk of progression to active TB. Studies have demonstrated that a 6-month (or longer) course of monotherapy with isoniazid [isoniazid preventive therapy (IPT)] can reduce this risk. The World Health Organization endorses IPT for symptom-free individuals with HIV/TB co-infection and has recommended expanding IPT to entire communities (community-wide IPT). Although previous reviews have not found a statistically significant elevated risk of isoniazid-resistant TB among individuals previously treated with IPT, community-wide IPT programs may nonetheless generate substantial selective pressure and increase the burden of drug-resistant TB (DRTB). We developed mathematical models to identify the conditions under which community-wide IPT interventions could increase the burden of isoniazid-resistant Mycobacterium tuberculosis, even when we assumed that IPT does not select for resistance among those treated with IPT. We found that in models that included any mechanism of interstrain competition (such as partial immunity conferred by a previous M. tuberculosis infection), community-wide IPT interventions conferred an indirect benefit to drug-resistant strains through selective suppression of drug-sensitive infections. This result suggests that the absence of an observed elevation in the risk of DRTB among those receiving IPT in small-scale studies of limited duration does not imply that the selective pressure imposed by community-wide IPT will not be substantial. Community-wide IPT may play an important role in TB control in these settings, and its rollout should be accompanied by interventions to detect and treat drug-resistant disease.