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PloS One 2021To investigate salivary gland ultrasonography (SGUS) findings in primary Sjögren's syndrome (pSS) patients positive for the anti-centromere antibody (ACA) and compare...
PURPOSE
To investigate salivary gland ultrasonography (SGUS) findings in primary Sjögren's syndrome (pSS) patients positive for the anti-centromere antibody (ACA) and compare these with those in ACA-negative pSS patients.
METHODS
We analyzed demographic, clinical, laboratory, and SGUS data of pSS patients who fulfilled the 2002 American-European Consensus Group classification criteria for pSS. SGUS findings of four major salivary glands (bilateral parotid and submandibular glands) were scored in five categories and compared between ACA-positive and ACA-negative pSS patients. Linear regression analysis was performed to elucidate the factors associated with SGUS score.
RESULTS
In total, 121 pSS patients were enrolled (19, ACA-positive). The ACA-positive patients were older (67.0 vs 58.0 years, P = 0.028), whereas anti-Ro/SSA and anti-La/SSB positivity was more prevalent in the ACA-negative group (89.2% vs 21.1%, P < 0.001, and 47.1% vs 10.5%, P = 0.007, respectively). The total SGUS and hypoechoic area scores were lower in ACA-positive patients (16.0 vs 23.0, P = 0.027, and 4.0 vs 7.0, P = 0.004, respectively). In univariate regression analysis, being positive for unstimulated salivary flow rate (USFR < 1.5 ml/15 min), anti-Ro/SSA, and rheumatoid factor were positively associated whereas ACA positivity was negatively associated with the SGUS score. In multivariate regression analysis, being positive for USFR, anti-Ro/SSA, and rheumatoid factor showed significant association with the SGUS score.
CONCLUSIONS
ACA-positive pSS patients showed a lower SGUS score than ACA-negative patients, which was especially prominent in the hypoechoic area component.
Topics: Adult; Aged; Antibodies, Antinuclear; Female; Humans; Linear Models; Male; Middle Aged; Rheumatoid Factor; Salivary Glands; Sjogren's Syndrome; Submandibular Gland
PubMed: 34731207
DOI: 10.1371/journal.pone.0259519 -
Microbiology Spectrum Sep 2021Both the QuantiFERON-TB Gold Plus (QFT-Plus) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) tests are interferon gamma (IFN-γ) release assays (IGRAs) intended to detect...
Both the QuantiFERON-TB Gold Plus (QFT-Plus) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) tests are interferon gamma (IFN-γ) release assays (IGRAs) intended to detect cell-mediated immune responses to Mycobacterium tuberculosis antigens. In this study, we retrospectively analyzed performance data for both the QFT-GIT and QFT-Plus test systems from over 2 million samples. QFT-Plus and QFT-GIT testing was performed as specified in the respective package inserts at 23 Quest Diagnostics sites. Blood specimens were collected from individuals in all 50 states from November 2018 through December 2019. Retrospective analyses compared the proportion of positive, indeterminate, and conversion/reversion results. The overall proportion of QFT-positive results was 7% for both the QFT-Plus and QFT-GIT. The proportion of positive results was highest for QFT-GIT (7.5%) followed by the heparin 1-tube QFT-Plus (7.2%); a lower proportion of positives was observed with the 4-tube (all four QFT tubes were used in blood collection) QFT-Plus (6.0%). The proportions of indeterminate results for the 1-tube (heparin-only tube collection) and 4-tube QFT-Plus methods were less than 1% and 4%, respectively. This study indicates a higher proportion of positive results for M. tuberculosis than data from other studies. Additionally, the proportion of indeterminate QFT results were markedly lower when the sample was transported in one lithium-heparin tube instead of direct inoculation into 4 QFT-Plus tubes at the site of blood collection. In this study, we retrospectively analyzed results from both the QFT-GIT and QFT-Plus test systems from over 2 million blood specimens. The variables analyzed were (i) QFT positivity rates among various U.S. populations, (ii) indeterminate rates among various types of blood draws and how often an indeterminate result was resolved within 30 days after the initial draw, and (iii) the association of TB1 and TB2 antigen tubes with IGRA reversion and conversion events from serial QFT testing. This is, to our knowledge, the largest QFT study representing patients from an extensive geographic coverage across the United States and U.S. territories.
Topics: Adolescent; Adult; Aged; Antigens, Bacterial; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Interferon-gamma Release Tests; Male; Middle Aged; Mycobacterium tuberculosis; Retrospective Studies; Tuberculosis; United States; Young Adult
PubMed: 34319139
DOI: 10.1128/Spectrum.00096-21 -
Journal of the National Cancer Institute Jul 2020Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal...
BACKGROUND
Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants.
METHODS
Using the Carolina Breast Cancer Study (phase I: 1993-1996; 2: 1996-2001; 3: 2008-2013), a population-based study that oversampled black women, we compared ER-borderline (n = 217) to ER-positive (n = 1885) and ER-negative (n = 757) tumors. PAM50 subtype and risk of recurrence score (ROR-PT, incorporates subtype, proliferation, tumor size) were measured. Relative frequency differences (RFD) were estimated using multivariable linear regression. Disease-free interval (DFI) was evaluated by ER category and endocrine therapy receipt, overall and by race, using Kaplan Meier and Cox models. Statistical tests were two-sided.
RESULTS
ER-borderlines were more frequently basal-like (RFD = +37.7%, 95% confidence interval [CI] = 27.1% to 48.4%) and high ROR-PT (RFD = +52.4%, 95% CI = 36.8% to 68.0%) relative to ER-positives. Having a high ROR-PT ER-borderline tumor was statistically significantly associated with black race (RFD = +26.2%, 95% CI = 9.0% to 43.3%). Compared to ER-positives, DFI of ER-borderlines treated with endocrine therapy was poorer but not statistically significantly different (hazard ratio [HR] = 2.03, 95% CI = 0.89% to 4.65%), whereas DFI was statistically significantly worse for ER-borderlines without endocrine therapy (HR = 3.33, 95% CI = 1.84% to 6.02%). However, black women with ER-borderline had worse DFI compared to ER-positives, even when treated with endocrine therapy (HR = 2.77, 95% CI = 1.09% to 7.04%).
CONCLUSIONS
ER-borderline tumors were genomically heterogeneous, with survival outcomes that differed by endocrine therapy receipt and race. Black race predicted high-risk ER-borderlines and may be associated with poorer endocrine therapy response.
Topics: Adult; Aged; Black People; Breast Neoplasms; Female; Humans; Immunohistochemistry; Middle Aged; Neoplasm Staging; North Carolina; Receptors, Estrogen; Transcriptome; White People; Young Adult
PubMed: 31742342
DOI: 10.1093/jnci/djz206 -
Journal of the International AIDS... Apr 2021Misclassification errors have been reported in rapid diagnostic HIV tests (RDTs) in sub-Saharan African countries. These errors can lead to missed opportunities for...
INTRODUCTION
Misclassification errors have been reported in rapid diagnostic HIV tests (RDTs) in sub-Saharan African countries. These errors can lead to missed opportunities for prevention-of-mother-to-child-transmission (PMTCT), early infant diagnosis and adult HIV-prevention, unnecessary lifelong antiretroviral treatment (ART) and wasted resources. Few national estimates or systematic quantifications of sources of errors have been produced. We conducted a comprehensive assessment of possible sources of misclassification errors in routine HIV testing in Zimbabwe.
METHODS
RDT-based HIV test results were extracted from routine PMTCT programme records at 62 sites during national antenatal HIV surveillance in 2017. Positive- (PPA) and negative-percent agreement (NPA) for HIV RDT results and the false-HIV-positivity rate for people with previous HIV-positive results ("known-positives") were calculated using results from external quality assurance testing done for HIV surveillance purposes. Data on indicators of quality management systems, RDT kit performance under local climatic conditions and user/clerical errors were collected using HIV surveillance forms, data-loggers and a Smartphone camera application (7 sites). Proportions of cases with errors were compared for tests done in the presence/absence of potential sources of errors.
RESULTS
NPA was 99.9% for both pregnant women (N = 17224) and male partners (N = 2173). PPA was 90.0% (N = 1187) and 93.4% (N = 136) for women and men respectively. 3.5% (N = 1921) of known-positive individuals on ART were HIV negative. Humidity and temperature exceeding manufacturers' recommendations, particularly in storerooms (88.6% and 97.3% respectively), and premature readings of RDT output (56.0%) were common. False-HIV-negative cases, including interpretation errors, occurred despite staff training and good algorithm compliance, and were not reduced by existing external or internal quality assurance procedures. PPA was lower when testing room humidity exceeded 60% (88.0% vs. 93.3%; p = 0.007).
CONCLUSIONS
False-HIV-negative results were still common in Zimbabwe in 2017 and could be reduced with HIV testing algorithms that use RDTs with higher sensitivity under real-world conditions and greater practicality under busy clinic conditions, and by strengthening proficiency testing procedures in external quality assurance systems. New false-HIV-positive RDT results were infrequent but earlier errors in testing may have resulted in large numbers of uninfected individuals being on ART.
Topics: Adult; Diagnostic Tests, Routine; Female; HIV Infections; HIV Testing; Humans; Infectious Disease Transmission, Vertical; Male; Mass Screening; Pregnancy; Pregnancy Complications, Infectious; Reproducibility of Results; Sensitivity and Specificity; Zimbabwe
PubMed: 33882190
DOI: 10.1002/jia2.25700 -
Preventive Medicine Aug 2022In 2009, visual inspection with acetic acid (VIA) followed by cryotherapy (VIA-and-cryotherapy), was introduced into the Eswatini cervical cancer prevention programme....
In 2009, visual inspection with acetic acid (VIA) followed by cryotherapy (VIA-and-cryotherapy), was introduced into the Eswatini cervical cancer prevention programme. We present screening results of 654 women attending VIA-and-cryotherapy who participated in a sexually transmitted infections prevalence study, at which samples for HPV DNA testing and liquid-based cytology (LBC) were also collected. VIA positives (VIA+) ineligible for cryotherapy, suspected cancers and women with high-grade squamous intraepithelial or worse lesions (HSIL+) on LBC were referred for diagnosis and treatment. Women with negative VIA who were HPV positive (HPV+) and those VIA+ treated with cryotherapy were recalled for another VIA one-year later. The positivity rates of VIA, HPV, atypical squamous cells of undetermined significance or worse cytology abnormalities (LBC ASCUS+) and low-grade squamous intraepithelial or worse lesions (LBC LSIL+) were 9.7%, 42.6%, 13.2% and 5.3%, respectively. HPV testing detected 29 of 31 LSIL+ (93.6%, 95%CI: 78.6-99.2) while VIA only detected 11 (35.6%, 95%CI: 19.2-54.6). The HIV prevalence was 43% (95%CI: 39.2-46.9). HIV positives were at increased risk of being VIA+ (age-adjusted odds ratio: 2.5, 95%CI: 1.5-4.3), HPV+ (3.7, 2.6-5.3) and having LSIL+ (16.3, 4.9-54.8). The ineligibility rates for cryotherapy were 38% (24 of 63 VIA+), and 46% among HIV positives (18 of 39 VIA+). HPV testing was substantially more sensitive than VIA, thus, HPV followed by ablative treatment may be more effective. However, the high ineligibility for cryotherapy highlights the need for improving the assessment of eligibility for ablative treatment and for strengthening colposcopy, particularly in populations with high HIV prevalence.
Topics: Acetic Acid; Carcinoma, Squamous Cell; Colposcopy; Early Detection of Cancer; Eswatini; Female; HIV Infections; Humans; Mass Screening; Papillomaviridae; Papillomavirus Infections; Pregnancy; Uterine Cervical Neoplasms; Vaginal Smears; Uterine Cervical Dysplasia
PubMed: 35810934
DOI: 10.1016/j.ypmed.2022.107144 -
Brain Communications 2022Early detection of Alzheimer's disease is required to identify patients suitable for disease-modifying medications and to improve access to non-pharmacological...
Early detection of Alzheimer's disease is required to identify patients suitable for disease-modifying medications and to improve access to non-pharmacological preventative interventions. Prior research shows detectable changes in speech in Alzheimer's dementia and its clinical precursors. The current study assesses whether a fully automated speech-based artificial intelligence system can detect cognitive impairment and amyloid beta positivity, which characterize early stages of Alzheimer's disease. Two hundred participants (age 54-85, mean 70.6; 114 female, 86 male) from sister studies in the UK (NCT04828122) and the USA (NCT04928976), completed the same assessments and were combined in the current analyses. Participants were recruited from prior clinical trials where amyloid beta status (97 amyloid positive, 103 amyloid negative, as established via PET or CSF test) and clinical diagnostic status was known (94 cognitively unimpaired, 106 with mild cognitive impairment or mild Alzheimer's disease). The automatic story recall task was administered during supervised in-person or telemedicine assessments, where participants were asked to recall stories immediately and after a brief delay. An artificial intelligence text-pair evaluation model produced vector-based outputs from the original story text and recorded and transcribed participant recalls, quantifying differences between them. Vector-based representations were fed into logistic regression models, trained with tournament leave-pair-out cross-validation analysis to predict amyloid beta status (primary endpoint), mild cognitive impairment and amyloid beta status in diagnostic subgroups (secondary endpoints). Predictions were assessed by the area under the receiver operating characteristic curve for the test result in comparison with reference standards (diagnostic and amyloid status). Simulation analysis evaluated two potential benefits of speech-based screening: (i) mild cognitive impairment screening in primary care compared with the Mini-Mental State Exam, and (ii) pre-screening prior to PET scanning when identifying an amyloid positive sample. Speech-based screening predicted amyloid beta positivity (area under the curve = 0.77) and mild cognitive impairment or mild Alzheimer's disease (area under the curve = 0.83) in the full sample, and predicted amyloid beta in subsamples (mild cognitive impairment or mild Alzheimer's disease: area under the curve = 0.82; cognitively unimpaired: area under the curve = 0.71). Simulation analyses indicated that in primary care, speech-based screening could modestly improve detection of mild cognitive impairment (+8.5%), while reducing false positives (-59.1%). Furthermore, speech-based amyloid pre-screening was estimated to reduce the number of PET scans required by 35.3% and 35.5% in individuals with mild cognitive impairment and cognitively unimpaired individuals, respectively. Speech-based assessment offers accessible and scalable screening for mild cognitive impairment and amyloid beta positivity.
PubMed: 36381988
DOI: 10.1093/braincomms/fcac231 -
Journal of Pathology Informatics 2022The Visiopharm automated estrogen receptor (ER) digital imaging analysis (DIA) algorithm assesses digitized ER immunohistochemistry (IHC) by segmenting tumor nuclei and...
BACKGROUND
The Visiopharm automated estrogen receptor (ER) digital imaging analysis (DIA) algorithm assesses digitized ER immunohistochemistry (IHC) by segmenting tumor nuclei and detecting stained nuclei automatically. We aimed to integrate and validate this algorithm in a digital pathology workflow for clinical use.
DESIGN
The study cohort consisted of a serial collection of 97 invasive breast carcinoma specimens including 73 biopsies and 24 resections. ER IHC slides were scanned into Philips Image Management System (IMS) during our routine digital workflow and digital images were directly streamed into Visiopharm platform and analyzed using automated ER algorithm to obtain the positively stained tumor nuclei and staining intensity. ER DIA scores were compared with pathologists' manual scores.
RESULTS
The overall concordance between pathologists' reads and DIA reads was excellent (91/97, 93.8%). Pearson Correlation Coefficient of the percentage of ER positive nuclei between the original reads and VIS reads was 0.72. Six cases (3 ER-negative and 3 ER-positive) had discordant results. All 3 false negative cases had very weak ER staining and no more than 10% positivity. The causes for false positive DIA were mainly pre-analytic/pre-imaging and included intermixed benign glands in tumor area, ductal carcinoma in-situ (DCIS) components, and tissue folding.
CONCLUSIONS
Automated ER DIA demonstrates excellent concordance with pathologists' scores and accurately discriminates ER positive from negative cases. Furthermore, integrating automated biomarker DIA into a busy clinical digital workflow is feasible and may save time and labor for pathologists.
PubMed: 36268080
DOI: 10.1016/j.jpi.2022.100122 -
Journal of Personality and Social... Nov 2022The Positivity Resonance Theory of coexperienced positive affect describes moments of interpersonal connection characterized by shared positive affect, caring nonverbal...
The Positivity Resonance Theory of coexperienced positive affect describes moments of interpersonal connection characterized by shared positive affect, caring nonverbal synchrony, and biological synchrony. The construct validity of positivity resonance and its longitudinal associations with health have not been tested. The current longitudinal study examined whether positivity resonance in conflict interactions between 154 married couples predicts health trajectories over 13 years and longevity over 30 years. We used couples' continuous ratings of affect during the interactions to capture coexperienced positive affect and continuous physiological responses to capture biological synchrony between spouses. Video recordings were behaviorally coded for coexpressed positive affect, synchronous nonverbal affiliation cues (SNAC), and behavioral indicators of positivity resonance (BIPR). To evaluate construct validity, we conducted a confirmatory factor analysis to test a latent factor of positivity resonance encompassing coexperienced positive affect, coexpressed positive affect, physiological linkage of interbeat heart intervals, SNAC, and BIPR. The model showed excellent fit. To evaluate associations with health and longevity, we used dyadic latent growth curve modeling and Cox proportional hazards modeling, respectively, and found that greater latent positivity resonance predicted less steep declines in health and increased longevity. Associations were robust when accounting for initial health symptoms, sociodemographic characteristics, health-related behaviors, and individually experienced positive affect. We repeated health and longevity analyses, replacing latent positivity resonance with BIPR, and found consistent results. Findings validate positivity resonance as a multimodal construct, support the utility of the BIPR measure, and provide initial evidence for the characterization of positivity resonance as a positive health behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Topics: Humans; Longevity; Longitudinal Studies; Spouses
PubMed: 35099204
DOI: 10.1037/pspi0000385 -
Maternal Psychological Resilience During Pregnancy and Newborn Telomere Length: A Prospective Study.The American Journal of Psychiatry Feb 2021In the context of the importance of elucidating the determinants of the initial, newborn setting of telomere length (TL), it is increasingly evident that maternal stress...
OBJECTIVE
In the context of the importance of elucidating the determinants of the initial, newborn setting of telomere length (TL), it is increasingly evident that maternal stress and stress-related processes during pregnancy play a major role. Although psychological resilience may function as a buffer, research in this area has not yet examined its potential role vis-à-vis that of stress. The authors examined the relationship between maternal psychological resilience during pregnancy and newborn TL.
METHODS
In a sample of 656 mother-child dyads from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction cohort, multiple serial assessments were conducted over the course of pregnancy to quantify maternal stress, negative and positive emotional responses to pregnancy events, positive affect, and perceived social support. Principal component analysis identified two latent factors: stress and positivity. A measure of resilience was computed by regressing the positivity factor on the stress factor, in order to quantify positivity after accounting for stress. TL was measured using quantitative polymerase chain reaction in leukocytes extracted from cord blood shortly after birth. Linear regression was used to predict newborn TL from maternal resilience during pregnancy, adjusting for other potential determinants.
RESULTS
Maternal stress significantly predicted shorter newborn TL (β=-0.079), and positivity significantly predicted longer TL (β=0.135). Maternal resilience (positivity accounting for stress) was significantly and positively associated with newborn TL (β=0.114, 95% CI=0.035, 0.189), with each standard deviation increase in resilience predicting 12% longer newborn TL.
CONCLUSIONS
The results indicate that maternal psychological resilience may exert a salubrious effect on offspring telomere biology and highlight the importance of enhancing maternal mental health and well-being during pregnancy.
Topics: Adult; Cohort Studies; Female; Fetal Blood; Humans; Infant, Newborn; Maternal Health; Pregnancy; Pregnancy Complications; Prospective Studies; Real-Time Polymerase Chain Reaction; Resilience, Psychological; Telomere Homeostasis
PubMed: 32911996
DOI: 10.1176/appi.ajp.2020.19101003 -
Rheumatology Advances in Practice 2023SSc is a CTD characterized by excessive fibrosis of the skin and internal organs, along with microvascular damage, and is often associated with typical autoantibodies....
OBJECTIVE
SSc is a CTD characterized by excessive fibrosis of the skin and internal organs, along with microvascular damage, and is often associated with typical autoantibodies. The aim of this study was to analyse the correlation between specific autoantibody profiles, clinical and paraclinical features in Moroccan patients with SSc.
METHODS
We analysed the presence of specific autoantibodies in 46 SSc patients using IIF on HEp-2 cells and immunodot. We then correlated the types of autoantibodies with clinical and laboratory manifestations.
RESULTS
Among our patients, 86.9% were females. The mean age of patients at diagnosis was 50.21 years, with an average delay to diagnosis of 5 years. The main clinical manifestations found were RP (89.2%), sclerodactyly (84.8%), proximal scleroderma (67.4%), gastrointestinal involvement (50%) and interstitial lung disease (30.4%). According to the specific autoantibody profile, 14 patients were anti-topo I positive (30.4%), 8 anti-RNP (68 kDa/A/C) positive (17.4%) and 6 anti-RNA polymerase III positive (13%). We found a significant association of anti-RNA polymerase III with sclerodactyly and pulmonary arterial hypertension (<0.05). We also found an association between anti-topo I and interstitial lung disease in 30.4% of patients. There was no significant association between the positivity for the autoantibodies and other diagnosed clinical manifestations.
CONCLUSION
Some clinical manifestations of SSc might be positively correlated with the presence of specific autoantibodies. Environmental factors, ethnicity and gene interaction might also influence this correlation.
PubMed: 37091295
DOI: 10.1093/rap/rkad036