Symptomatic Population Research Articles

Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer.

To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with a novel noninvasive ocular surface analyzer. Limbal and bulbar redness classification, lipid layer thickness, tear meniscus height, and first and mean noninvasive break-up time (FNIBUT and MNIBUT) were performed before and 30 and 45 min after liposome-crosslinked hyaluronic acid (LCHA) and standard hyaluronic acid (HA) eye drop instillations. LCHA had a higher lipid layer thickness than HA (grades 2.00 ± 0.83 and 1.17 ± 0.63 on the Guillon pattern, respectively). LCHA achieved a better tear meniscus height than HA (0.23 ± 0.02 and 0.21 ± 0.02 mm, respectively). LCHA improved FNIBUT and MNIBUT more than HA (for FNIBUT, 6.30 ± 0.94 and 4.77 ± 0.89 s, respectively. For MNIBUT, 17.23 ± 5.11 and 12.41 ± 4.18 s, respectively). Crosslinking hyaluronic acid with liposomes and crocin significantly increases the permanence and stability of the lipid, aqueous, and mucin tear film layers. In a short-term period, liposome and crosslinked hyaluronic acid achieved better first and mean noninvasive break-up times than standard hyaluronic acid.

Detection of macular findings in highly myopic eyes with OCT and to correlate it to various visual parameters

: High myopia is when axial length is more than >26 mm and refractive error of atleast 6.00 diopters (D). The definition of pathologic myopia in early studies was not consistent. It revolved around a combination of refractive error and axial length, which simply suggests high myopia. To study the pathological findings in subjects with high axial myopia and their relationship with other visual parameters. In this crosssectional analytical study, 200 eyes from 100 patients were studied. Fundus was evaluated with indirect ophthalmoscope. After pupillary dilatation, multiple OCT scans were performed across the macula area centering the fovea with the help of SD-OCT SD OCT revealed that 46% had normal appearance. Among pathological findings, most common was CNV (10%). Other findings were lamellar macular hole (7%), full thickness macu lar hole (7%), retinal detachment (3%), epiretinal membrane (3%), traction maculopathy (4%), PVD (8%), dome shaped macula (8%)and posterior staphyloma (4%). Fifty four percent eyes had one or more fundus changes observed by bio-microscopy. Most common findings were lattice degeneration (33.33%) and WWP & WWOP (25%). Other findings were posterior staphyloma (7.41%), retinal detachment (5.51%), Chorioretinal degeneration (11.11%), macular hole (8.3%), PVD (3.70%), Retinal hole (0.92%), maculopathy (0.97%) and CNV (3.70%). : OCT can be done in a healthy high myopic population and in symptomatic myopic population who complains of worsening of visual function to look for epiretinal and/or vitreoretinal traction and related macular damage.

Performance of the TaqMan COVID-19 Pooling Kit for detection of SARS-CoV-2 in asymptomatic and symptomatic populations.

Clinical evidence for asymptomatic cases of coronavirus disease (COVID-19) has reinforced the significance of effective surveillance testing programs. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assays are considered the ‘gold standard’ for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. However, the labor and resource requirements can be prohibitive with respect to large testing volumes associated with the pandemic. Pooled testing algorithms may serve to increase testing capacity with more efficient resource utilization. Due to the lack of carefully curated cohorts, there is limited evidence for the applicability of RT-PCR pooling in asymptomatic COVID-19 cases. In this study, we compared the analytical sensitivity of the TaqMan™ SARS-CoV-2 Pooling Assay to detect one positive sample in a pool of five anterior nares swabs in symptomatic and asymptomatic cohorts at an institute of higher education. Positive pools were deconvoluted and each individual sample was retested using the TaqPath™ COVID-19 Combo Kit. Both assays target the open reading frame (ORF) 1ab, nucleocapsid (N), and spike (S) gene of the strain that originated in Wuhan, Hubei, China. Qualitative results demonstrated absolute agreement between pooled and deconvoluted samples in both cohorts. Independent t-test performed on Ct shifts supported an insignificant difference between cohorts with p-values of 0.306 (Orf1ab), 0.147 (N), and 0.052 (S). All negative pools were correctly reported as negative. Pooled PCR testing up to five samples is a valid method for surveillance testing of students and staff in a university setting, especially when the prevalence is expected to be low.

Risk-stratified FIT for urgent colonoscopy in Lynch syndrome: A clinical service throughout the COVID-19 pandemic.

10606 Background: Lynch syndrome (LS) is an inherited disorder characterized by pathogenic variants within mismatch repair genes resulting in an increased risk of colorectal cancer (CRC). In England, the fecal immunochemical test for Haemoglobin (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy. Herein, we report results from a national emergency clinical service implemented during the COVID-19 pandemic which used FIT to prioritize colonoscopy in LS patients while endoscopy services were limited. Methods: Regional genetic and endoscopy services across England were invited to participate. Patient eligibility was determined by 1) Diagnosis of Lynch Syndrome 2) Planned colonoscopic surveillance between 1 March 2020 and 31 March 2021. Requests for FIT testing from participating NHS Trusts were sent to the NHS Bowel Cancer Screening South of England Hub’s Research Laboratory in Surrey. The Hub sent patients a FIT kit (OC-Sensor™ (Eiken, Japan)), instructions for use, a questionnaire, and a pre-paid return envelope. Lab reports with feecal haemoglobin (f-Hb) results were returned electronically for clinical action. LS patients were risk-stratified for colonoscopy based upon the following f-Hb thresholds: (1) f-Hb ≥10µg of Haemoglobin (Hb)/g (µg/g) faeces: triaged for colonoscopy via an urgent two-week wait (2WW) pathway, (2) f-Hb ≤10µg/g: schedule patients for colonoscopy within 6-12 weeks, where local endoscopy service availability permits. Results: Fifteen centers across England participated in the clinical service from 9th June 2020 to 31st March 2021. An uptake rate of 64% was observed from this cohort (375/588 invites), though 21 cases were removed from analysis due to repeat FITs, insufficient sample, missing clinical data, or FIT completed after colonoscopy. Of the remaining 354 patients analyzed, 269 patients (76%) had a f-Hb of <6µg/g. 6% (n=23) of patients had a f-Hb that was at or between greater than the limit of detection of the assay (≥6µg/g) yet below 10µg/g.18% (n=62) had FIT results of ≥10µg/g and met criteria for urgent colonoscopy triage via the 2WW pathway. Of the 62 urgently triaged patients, 22 had detectable adenomas, 6 had advanced adenomas (AAs), and 4 were diagnosed with CRC (table). Conclusions: The utility of FIT during the pandemic has demonstrated clinical value for LS patients requiring CRC surveillance. Further longitudinal investigation on the efficacy of FIT in people with LS is warranted and will be examined as part of the multi-center prospective research study “FIT for Lynch Syndrome” (ISRCTN15740250) which is presently recruiting patients in the UK. [Table: see text]

Effects of Asymptomatic Infections on the Spatial Spread of Infectious Diseases

Asymptomatic infection and transmission are common for quite a few directly or indirectly transmitted diseases such as COVID-19, cholera, and Zika fever. In this paper, we propose a susceptible-infective-asymptomatic-recovered patch model to address the influence of asymptomatic infections on the spatial spread of infectious diseases. The multipatch basic reproduction number ${\mathcal{R}}_0$ of the model is defined and shown to be a threshold quantity for disease eradication and persistence. Namely, the disease disappears if ${\mathcal{R}}_0\le1$ whereas it spreads otherwise. The monotonicity of ${\mathcal{R}}_0$ with respect to the dispersal rates of the symptomatic and asymptomatic populations is investigated. In particular, for the two-patch case, ${\mathcal{R}}_0$ is either strictly decreasing or strictly increasing or constant in terms of dispersal rates. However, nonmonotonic dependence can occur with movement between three or more patches. The asymptotic profiles of the endemic equilibrium (when it exists) as one or all dispersal rates approach zero or infinity are studied. Interestingly, an increase in infectious dispersal may decrease ${\mathcal{R}}_0$ but increase the number of nonsusceptible individuals. Analytical and numerical results confirm that ignoring asymptomatic carriers not only significantly underestimates the infection risk but also impairs the efficacy of travel restrictions.

0625 Characterization of Obstructive Sleep Apnea in Active-Duty US Military Personnel Receiving Interdisciplinary Care at the National Intrepid Center of Excellence

Abstract Introduction Among active-duty service members (ADSMs), obstructive sleep apnea (OSA) is associated with decreased quality of life and military readiness/retention. Limited evidence suggests mild traumatic brain injury (mTBI) patients have increased OSA incidence, but little is known about the underlying physiology. This study aims to characterize OSA in treatment-seeking ADSMs with a history of remote mTBI and/or persistent neurobehavioral symptoms to improve detection and early intervention. Methods This is a retrospective analysis of data collected from ADSMs attending the National Intrepid Center of Excellence Intensive Outpatient Program for persistent symptoms associated with mTBI. Sleep assessment included overnight polysomnography and self-report assessments of sleep quality, somatic and mood symptoms. OSA severity was determined by apnea-hypopnea index (negative: <5, mild: 5-15, moderate/severe: ≥15). Group differences were assessed using analysis of covariance and pairwise least squares regression, controlling for age and body mass index, and corrected for multiple comparisons. Results Analyses included 574 ADSMs, mostly male (99%), with a mean age of 39.7. The majority (n=288; 50.2%) were OSA negative (OSA-neg); a third had mild OSA (m-OSA) (n=216; 38%); and a tenth were diagnosed with moderate/severe OSA (mod/s-OSA) (n=70; 12%). Mod/s-OSA patients had increased arousal index (p<0.01), hypoxia time (p<0.001), reduced total sleep time (p<0.01) and sleep efficiency (p<0.001) compared to m-OSA and OSA-neg patients. M-OSA patients had an increased arousal index compared to OSA-neg patients (p<0.01). Patient groups did not significantly differ on subjective measures of sleep (i.e., quality, sleepiness), post-concussive, or behavioral health symptoms (anxiety, depression, post-traumatic stress symptoms, alcohol misuse). Conclusion In our sample of treatment-seeking ADSMs, nearly half presented with OSA according to cut-scores derived for AHI, greater than that expected in the general population. As reported in civilian populations, mod/s-OSA patients demonstrated worse objective sleep measures compared to m-OSA and OSA-neg patients, yet in our sample their self-reported symptom severity did not differ. These findings suggest a low threshold for OSA screening is needed in the symptomatic mTBI population and that multiple factors other than OSA likely contribute to perceived sleep disturbances and neurobehavioral symptoms. Support (If Any) None.

Normative Values of the Nasal Obstruction Symptom Evaluation Scale.

Background: The Nasal Obstruction Symptom Evaluation (NOSE) scale is widely used by clinicians in evaluation of nasal airway obstruction (NAO). Objective: To determine normative values for the NOSE scale among both symptomatic and asymptomatic members of the general U.S. population. Methods: A survey of NAO symptoms in adults of age 18 years and older was performed. The distribution of NOSE scores among the general population was estimated. Influence of features including age, gender, race, location, and symptomatology on NOSE scores was evaluated. Results: Surveys were completed by 2333 participants. Mean NOSE score was 11 (standard deviation [SD] 11) in the asymptomatic, and 28 (SD 22) in the symptomatic population (p < 0.0001). Increasing age was associated with an increase in scores until 45 years, after which it was associated with decreasing scores. No significant differences were found related to other investigated demographics. Conclusions: Normative ranges for the NOSE scale are established, and are largely consistent with values in the existing literature. NOSE scores do not appear to be influenced by gender, race, or geography, although age should be considered in their interpretation.

Saliva versus Upper Respiratory Swabs: Equivalent for Severe Acute Respiratory Syndrome Coronavirus 2 University Screening while Saliva Positivity Is Prolonged After Symptom Onset in Coronavirus Disease 2019 Hospitalized Patients

Reopening of schools and workplaces during the ongoing coronavirus disease 2019 (COVID-19) pandemic requires affordable and convenient population-wide screening methods. Although upper respiratory swab is considered the preferable specimen for testing, saliva offers several advantages, such as easier collection and lower cost. In this study, we compared the performance of saliva with upper respiratory swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. Paired saliva and anterior nares specimens were collected from a largely asymptomatic cohort of students, faculty, and staff from the University of Pennsylvania. Paired saliva and combined nasopharyngeal/oropharyngeal (NP/OP) specimens were also collected from hospitalized patients with symptomatic COVID-19 following confirmatory testing. All study samples were tested by real-time PCR in the Hospital of the University of Pennsylvania. In the university cohort, positivity rates were 37 of 2500 for saliva (sensitivity, 86.1%) and 36 of 2500 for anterior nares (sensitivity, 83.7%), with an overall agreement of 99.6%. In the hospital study cohort, positivity rates were 35 of 49 for saliva (sensitivity, 89.3%) and 28 of 49 for NP/OP (sensitivity, 75.8%), with an overall agreement of 75.6%. A larger proportion of saliva than NP/OP samples tested positive after 4 days of symptom onset in hospitalized patients. Our results show that saliva has an acceptable sensitivity and is comparable to upper respiratory swab, supporting the use of saliva for SARS-CoV-2 detection in both symptomatic and asymptomatic populations.

Tuberculosis in Greenland - Time from first contact to diagnosis and treatment

ABSTRACT Tuberculosis (TB) is a persistent health issue in Greenland. While rapid diagnosis is crucial to reducing transmission of the disease, remote settlements have limited access to healthcare services. We aimed to assess and compare the time intervals from first contact to diagnosis and treatment for patients with active TB in the cities and settlements of Greenland. A total of 153 cases were included and divided according to place of residence and whether the diagnosis was based on symptomatic presentation or contact tracing. The median time from first contact to diagnosis was 19 days for the total population. The symptomatic settlement population waited longer (median = 88.5 days) than the symptomatic city population (median = 19 days) (p = 0.018). The system interval was longer for the symptomatic settlement population than for the symptomatic city population with a median of 49.5 days vs. 3 days for chest imaging (p < 0.001) and 66.5 days vs. 10 days for expectorate sample (p = 0.008). The diagnostic, system, and total intervals were significantly longer for symptomatic patients in settlements than in cities. This may explain a higher TB incidence in the settlements and calls for the development of better diagnostic pathways.

Large-Scale SARS-CoV-2 Antigen Testing With Real-World Specimens.

Real-world data are needed to establish SARS-CoV-2 rapid antigen testing (RAT) as an effective and reliable approach for SARS-CoV-2 screening. This study included 1,952,931 individuals who provided upper respiratory specimens during SARS-CoV-2 screening at CityMD urgent care locations in the New York metropolitan area from October 2020 to March 2021. Positive and negative results, as determined by the BD Veritor™ System for Rapid Detection of SARS-CoV-2 antigen (Veritor), were obtained for all individuals, with reflex reverse transcriptase-polymerase chain reaction (RT-PCR) testing performed on a case-by-case basis, per standard of care. Using verification bias adjustment, two alternative model assumptions were utilized for RAT results with missing reflex RT-PCR results. The worst antigen diagnostic performance estimates asserted that missing RT-PCR results would show a distribution similar to those RT-PCR results actually obtained, based on symptom category. The best antigen diagnostic performance estimates asserted that individuals without RT-PCR results had a clinical presentation consistent with RAT results, and, therefore, missing RT-PCR results would agree with RAT results. For patients with symptoms or high-risk exposure, 25.3% (n = 86,811/343,253) of RAT results were positive; vs. 3.4% (n = 53,046/1,559,733) positive for asymptomatic individuals without high-risk exposure. Reflex RT-PCR results were obtained from 46.3% (n = 158,836/343,253) and 13.8% (n = 215,708/1,559,733) of symptomatic and asymptomatic individuals, respectively. RT-PCR confirmed 94.4% (4,265/4,518) of positive and 90.6% (139,759/154,318) of negative RAT results in symptomatic individuals; and confirmed 83.4% (6,693/8,024) of positive and 95.3% (197,955/207,684) of negative RAT results in asymptomatic individuals. Applied assumptions for missing reflex RT-PCR results led to worst performance sensitivity estimates of 77.2 and 38.5% in the symptomatic and asymptomatic populations, respectively; assumptions for best performance estimates led to sensitivity values of 85.6 and 84.2%, respectively. Specificity values, regardless of assumptions or symptom category, ranged from 97.9–99.9%. At 10% SARS-CoV-2 prevalence, RAT positive predictive value was 86.9 and 99.0% for worst and best performance estimates across the total population, respectively; negative predictive values were >95% regardless of the applied assumption. Veritor test performance was consistent with that listed in the manufacturer instructions for use for symptomatic individuals. Real-world evidence should be gathered on RATs to support their efficacy as SARS-CoV-2 persists.

WHAT DOES GRIP STRENGTH REFLECT IN HAND OSTEOARTHRITIS? RESULTS FROM THE DIGICOD COHORT

Purpose: Among the general population over 60 years-old, the decrease in grip strength is a marker of morbidity and mortality. However, hand osteoarthritis (HOA), which can modulate grip strength and which is also associated with comorbidities, is never taken into account. The objectives of this study are to describe grip strength in a symptomatic HOA population, to investigate painful osteoarthritic joints associated with decreased grip strength, and to determine whether decreased grip strength is independently associated with comorbidities in this population.

Trends of a syndromic approached based respiratory PCR during the second wave of the COVID 19 pandemic in a tertiary care center in Mumbai

PurposeThe clinical presentation of COVID 19 disease caused by Severe Acute Respiratory Syndrome Related Coronavirus – 2 (SARS-CoV2) is similar to other causes of upper respiratory viral infections caused by influenza, epidemic corona viruses, Parainfluenza virus etc. This study was undertaken to study the presence of different pathogens in the nasopharyngeal samples of symptomatic patients visiting the COVID OPD or the Emergency services over six month duration.Methods & MaterialsThis was a prospective study from Dec 2020 to May 2021 conducted in a 220 bed tertiary care hospital in Mumbai. We are a designated COVID care hospital with 55 isolation beds including 16 beds in the COVID ICU, a dedicated OPD for symptomatic patients and Emergency services (EMS). The test was performed on a syndromic approach based respiratory PCR with 22 targets inclusive of SARS-CoV2. Nasal and a pharyngeal swab samples (NPS) were collected and the results of the test were available in 1.5 hours from sample receipt to the lab.ResultsA total of 335 patient samples were received during the study period for the syndromic approach based PCR. 133 (39.7%) of the symptomatic patients had a positive test result. 87(26%) SARS-CoV2 and 27(8.05%) Rhinovirus/Enterovirus (RhV/EV) were the two common viruses that were identified during the study duration. Other viruses, like Parainfluenza 3 (PIV3), Coronavirus 229E (229E), Coronavirus HKU1 (HKU1), Influenza AH3 (AH3), H1N1, Coronavirus OC43 (OC43) and Adenovirus were also identified. We observed co-infections 1 each of RhV/EV+AH3, RhV/EV + OC43, SARS-CoV2 +PIV3 and 2 cases of SARS-CoV2+HKU1. The trend indicated the appearance of the 2nd wave of SARS-CoV2 infection that Mumbai experienced between 1st March to 15th May 2021. Other pathogens were mostly seen in the symptomatic population especially before and after the 2nd wave.ConclusionOur study documented the appearance of the second wave in Mumbai between 1st March to 15th May 2021. Approximately,34.5% of patients has other respiratory pathogens detected in the syndromic PCR. This is the 1st study from Mumbai documenting the types of respiratory pathogens and co infections seen during the 2nd wave of the COVID 19 pandemic in Mumbai.

A Comparative Analysis of COVID-19 IgG Antibody Level and Socio-Demographic Status in Symptomatic and Asymptomatic Population of South Andaman, India.

Introduction: The serosurveillance of COVID-19 antibody levels and their difference between symptomatic and asymptomatic groups can help in understanding the immune status of the community and the factors affecting it. Hence, the study was undertaken to find the differences between these two groups with respect to antibodies level and other socio-demographic variables in the South Andaman district.Methods: A population-based serosurveillance study covering more than 4,000 samples was carried out in the South Andaman district. The participants were selected by multistage cluster sampling. The venous blood samples were tested for IgG COVID-19 antibodies by Erba Lisa Elisa kit.Results: 5.3% of total individuals (217) were symptomatic whereas 94.7% (3,872) were asymptomatic. The symptomatic individuals had lower antibodies (33.6%) as compared to asymptomatic individuals (40.1%) (p-value=0.059). In the age group of 31-45 years, antibody positivity in the asymptomatic group was significantly higher than in the symptomatic group (p-value 0.031). The antibody positivity was higher in moderate to severe cases who needed hospital admission. The antibody positivity was found similar in both the groups in front-line workers as well as in non-front-line workers (p-value=0.104, 0.274, respectively).Conclusion: The antibody positivity was higher in asymptomatic individuals as compared to symptomatic individuals, particularly in the age group of 31-45 years. The higher level of antibody positivity in asymptomatic individuals reflected a stronger immune response which led to no clinical manifestations. The antibody positivity was also found higher in moderate to severe cases undergoing hospital admission whereas antibodies positivity was found similar in front-line and non-front-line workers.

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy.

It was previously shown in three subpopulations that subjects not identified with colorectal cancer (CRC) at bowel endoscopy, but with increased serological cancer-associated protein biomarker levels had an increased risk of being diagnosed with subsequent malignant diseases. The aim of the present study was to perform a pooled analysis of subjects from the three subpopulations and subsequently validate the results in an independent study. The study population denoted the training set includes N = 4,076 subjects with symptoms attributable to CRC and the independent validation set N = 3,774 similar subjects. Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy. Follow-up of subjects not diagnosed with CRC at endoscopy, was ten years and identified subjects diagnosed with primary intra- or extra-colonic malignant diseases. The primary analysis was time to a newly diagnosed malignant disease and was analyzed with death as a competing risk in the training set. Subjects with HNPCC or FAP were excluded. The cumulated incidence was estimated for each biomarker and in a multivariate model. The resulting model was then validated on the second study population. In the training set primary malignancies were identified in 515 (12.6%) of the 4,076 subjects, who had a colorectal endoscopy with non-malignant findings. In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. Multivariate additive analysis of the dichotomized biomarkers demonstrated that CEA (HR = 1.50, 95% CI:1.21-1.86, p < 0.001), CA19-9 (HR = 1.41, 95% CI:1.10-1.81, p = 0.007) and TIMP-1 (HR = 1.25 95% CI: 1.01-1.54, p = 0.041) were significant predictors of subsequent malignancy. The cumulated incidence at 5 years landmark time was 17% for those subjects with elevated CEA, CA19-9 and TIMP-1 versus 6.7% for those with low levels of all. When the model was applied to the validation set the cumulated 5-year incidence was 10.5% for subjects with elevated CEA, CA19-9 and TIMP-1 and 5.6% for subjects with low levels of all biomarkers. Further analysis demonstrated a significant interaction between TIMP-1 and age in the training set. The age dependency of TIMP-1 indicated a greater risk of malignancy in younger subjects if the biomarker was elevated. This observation was validated in the second set. Elevated cancer-associated protein biomarker levels in subjects with non-malignant findings at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy. CEA, CA19-9 and TIMP-1 were significant predictors of malignant disease in this analysis. TIMP-1 was found dependent on age. The results were validated in an independent symptomatic population.

Epidemiology of Herpes Simplex Virus Type 2 in Canada, Australia, and New Zealand: Systematic Review, Meta-Analyses, and Meta-Regressions.

This study characterized the epidemiology of herpes simplex virus type 2 (HSV-2) infection in Canada, Australia, and New Zealand. Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2-related data up to January 21, 2021. Meta-analyses and meta-regressions were performed. In Canada, pooled mean seroprevalence was 10.0% (95% confidence interval [CI], 7.8-12.4%) among general populations, 44.5% (95% CI, 20.0-70.5%) among sexually transmitted infection clinic attendees and symptomatic populations, and 60.7% (95% CI, 49.8-71.1%) among human immunodeficiency virus (HIV)-positive individuals and individuals in HIV-discordant couples. In Australia and New Zealand, combined, pooled mean seroprevalence was 15.4% (95% CI, 9.6-22.2%) among general populations, 27.8% (95% CI, 12.0-47.2%) among men who have sex with men, and 37.2% (95% CI, 23.7-51.8%) among sexually transmitted infection clinic attendees and symptomatic populations. Men had 0.64-fold (95% CI, 0.47-0.86) lower seroprevalence compared with women. No evidence was found for a decline in seroprevalence over time. Pooled mean proportion of HSV-2 isolation in laboratory-confirmed genital herpes was 62.1% (95% CI, 53.8-70.1%) in Canada and 71.9% (95% CI, 64.2-78.9%) in Australia and New Zealand. Proportion of HSV-2 isolation in genital herpes declined by 0.98-fold (95% CI, 0.97-0.99) per year. Pooled mean proportion of HSV-2 isolation in genital ulcer disease was 17.4% (95% CI, 4.0-37.1%) in these countries. Over 10% of adults in these countries are infected, with no evidence for declining seroprevalence, unlike other global regions. Over 60% of genital herpes cases are caused by HSV-2 in these countries, yet HSV-2's role is declining by 2% per year.

Association of circulating nucleosomes levels with FIT performance for advanced adenomas in a symptomatic population.

170 Background: The effectiveness of screening using either fecal immunochemical testing (FIT) or colonoscopy in reducing colorectal cancer (CRC) mortality has been demonstrated in previous studies. Nevertheless, the single test sensitivity of FIT for relevant precursor lesions, especially high-risk neoplasms like invasive cancer or advanced adenomas (AA), is a concern. Improving the sensitivity for high-risk neoplasm is critical to improving the effectiveness of screening in reducing CRC incidence and mortality. Dysregulation of histone post-translational modifications (PTMs) has been linked with several cancers including CRC. We investigated the clinical performance of circulating nucleosome levels containing specific histone PTMs in blood, in combination with FIT from symptomatic subjects referred to colonoscopy to evaluate their discriminant power towards CRC and AA. Methods: 10mls whole blood was obtained prior to colonoscopy from 476 patients referred to colonoscopy in National Taiwan University Hospital for surveillance or secondary to bowel symptoms. Patients were classified into 5 groups based on their colonoscopy reports: (i) patient with CRC (n = 67), (ii) patients with AA (n = 60, including 22 with AA≥2cm); (iii) patients with non-AA (n = 123); (iv) patients with non-neoplastic polyps (n = 29); (vi) healthy controls with no endoscopic lesion (n = 197). Plasma samples were analyzed for nucleosome levels using 7 different quantitative immunoassays (Nu.Q assays; Belgian Volition SRL, Belgium) targeting H3.1-nucleosomes or different histone modifications (H3K27Me3-, H3K36Me3-, H3K9Me3-, H3K14Ac-, H3K27Ac- or H3R8Cit-nucleosomes). All study subjects were asked to collect a stool sample at home within 48-hours before the colonoscopy. The fecal samples were assayed with the OC-SENSOR FIT kit (Eiken Chemical Co., Ltd., Tokyo, Japan) for all subjects. Results: At a cut-off of 20µg/g feces, the FIT test showed a sensitivity of 83.5% at 82.1% specificity for CRC +AA vs. Controls. All the CRC patients were detected but 35% of AA were missed, and 7 of which were high-risk adenomas (AA≥2cm). A combination of 2 Nu.Q biomarkers: H3K36Me3 and H3K9Me3 with FIT in a decision tree model showed an improved sensitivity of 98.4% allowing the detection of all CRC patients and 97% of the patients with AA including all high-risk adenomas. The 2 missed AA were one AA below 1cm and one between 1 and 2cm. Unnecessary colonoscopies could be reduced by 28.9% of the control and 20.7% of the non-neoplastic polyps subgroups as both are found negative with this panel of assays. Conclusions: At present, all the symptomatic patients are sent to colonoscopy in clinical practice. Our results indicate that H3K36Me3- and H3K9Me3-nucleosome levels, in combination with FIT in a decision tree model, could detect all CRC patients and all high-risk adenomas and help reduce unnecessary colonoscopies.

Prevalence of Borderline Acetabular Dysplasia in Symptomatic and Asymptomatic Populations: A Systematic Review and Meta-analysis.

Background:Patients with borderline acetabular dysplasia are a controversial patient population in hip preservation, as some have primarily impingement-based symptoms and others have instability-based symptoms. Borderline dysplasia is most commonly defined as a lateral center-edge angle (LCEA) of 20° to 25°. However, its prevalence has not been well established in the literature.Purpose:To (1) define the prevalence of borderline hip dysplasia in the general population as well as in populations presenting with hip pain using a systematic review and meta-analysis of the literature and (2) describe differences between male and female patients as well as differences in prevalence from that of classic acetabular dysplasia.Study Design:Systematic review; Level of evidence, 3.Methods:A systematic review of the literature was performed using search terms to capture borderline dysplasia, or studies reporting prevalence by LCEA. The search yielded 1932 results, of which 11 articles met inclusion criteria and were included in the final systematic review. Studies were grouped by patient cohort as (1) asymptomatic general population, (2) asymptomatic targeted population (eg, athletes in a specific sport), and (3) symptomatic hip pain population. The reporting of prevalence rates by subject or by hip was recorded. In a study, the rates of borderline dysplasia were compared with those of classic acetabular dysplasia (LCEA, <20°).Results:The 11 studies included 19,648 hips (11,754 patients). In the asymptomatic general population, the pooled estimate of the prevalence of borderline dysplasia was 19.8% by subject and 23.3% by hip (range, 16.7%-46.0%). The targeted subpopulation group included 236 athletes with subgroups in ballet, football, hockey, volleyball, soccer, and track and field with prevalence ranging from 17.8% to 51.1%. The prevalence of borderline dysplasia in groups presenting with hip pain was 12.8% (range, 12.6%-16.0%). Borderline acetabular dysplasia was 3.5 times more common than classic acetabular dysplasia in the asymptomatic general population.Conclusion:This study demonstrated a prevalence of borderline dysplasia of 19.8% to 23.3% in the asymptomatic general population. Additionally, an estimated prevalence of 12.8% of hips in symptomatic patients highlights the common decision-making challenges in this population.

Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening.

Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population. Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy. The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66-0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin. The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

Doing More with the Same: Comparing Public and Private Hospital Palliative Care within California.

Background: Public and private hospitals treat different patient populations, which may impact resources to deliver palliative care (PC). Objectives: Compare public and private hospital PC service structures, processes, and treatment outcomes. Design: Retrospective data analysis of the Palliative Care Quality Network between 2018 and 2019. Settings/Subjects: Six public and 40 private California hospitals provided PC consultations to 4244 and 38,354 adults, respectively. Measurements: PC team and patient characteristics, care processes, and treatment outcomes. Results: Public and private hospital PC services had similar full-time equivalent/100 beds (1.2 vs. 1.4, p = 0.4). Public hospital patients were younger (65.2 vs. 73.5, p < 0.001), less likely to be non-Hispanic Caucasian (22.5% vs. 57.5%, p < 0.001), or English speaking (51.1% vs. 79.9%, p < 0.001). Public hospital patients had more moderate/severe pain (21.3% vs. 19.3, p < 0.03), anxiety (12.4% vs. 9.2%, p < 0.001), nausea (6.5% vs. 4.7%, p < 0.001), and dyspnea (11.0% vs. 8.6%, p < 0.001). Both hospitals equally improved pain (70.9% vs. 70.5%, p = 0.83) and nausea (82.0% vs. 87.6%, p = 0.09), but public hospitals were less effective at improving anxiety (67.3% vs. 78.4%, p = 0.002) and dyspnea (58.4% vs. 67.9%, p = 0.05). Although there was no difference in hospital length of stay (public = 10.2 days vs. private = 9.5 days, p = 0.07), public hospitals conducted more patient visits (2.6 vs. 1.8, p < 0.001). They also more often clarified code status (87.7% vs. 84.4%, p < 0.001) and surrogate decision maker (94.9% vs. 89.9%, p < 0.001). Conclusions: Public hospital PC teams treat a more diverse symptomatic population. Yet, they achieved comparable outcomes with similar staffing to private hospitals. These findings have important ramifications for policy makers and public institution leaders.

Secondary prevention of gastric cancer: An alternative strategy

Background: Early detection and treatment provide the only curative possibility for gastric cancer. A cost-effective strategy is imperative in developing countries with high mortality rates. The objective of this study is to analyse the results of an organized endoscopic screening in a symptomatic population 40 years and older. Methods: This was a prospective observational study of patients with gastrointestinal symptomology referred by primary care who had direct access to an endoscopy unit at the secondary referral centre. Physicians were trained, and an endoscopy request form and a flowchart for referral and patient management were designed. Endoscopic performance, early detection rates, resectability and survival, overall and disaggregated by sex, were evaluated. Findings: From July 1, 1996, to June 30, 2013, 25.304 endoscopies were performed, of which 14.521 were in individuals in risk groups (70% women). A total of 339 gastric cancers were detected, for a detection rate of 2.3%. The rate of early gastric cancer (EGC) among all cancers was 34% (f: 46.6%, m: 27.6%). The resectability for both sexes was 68.1% (f: 78.8%, m: 62.4%). The EGC rate in resected patients was 45% (f: 54.8%, m: 38.4%). The five-year survival rate for all cancers was 38.1% (f: 51.7%, m: 30.8%), and that for patients who underwent resection was 57.6% (f: 69.0%, m: 50.0%). The 10-year survival for all cancers was 27.5% (f: 40.5%, m: 20.5%), and that for patients who underwent resection was 43.1% (f: 55.0%, m: 35.0%). Interpretation: Organized screening in a symptomatic population aged 40 years and older by endoscopy has high performance, increases the rate of EGC and impacts survival. Women achieved results similar to those reported by countries with mass survey. For men to achieve these results, it is necessary to educate the population at risk, especially the most vulnerable. Keywords: gastric cancer; endoscopic screening; resectability; early detection; survival.