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AJPM Focus Jun 2024In the U.S., xylazine, the veterinary non-opioid sedative, has emerged as a major threat to people who use illicitly manufactured fentanyl and other drugs. The aim of...
INTRODUCTION
In the U.S., xylazine, the veterinary non-opioid sedative, has emerged as a major threat to people who use illicitly manufactured fentanyl and other drugs. The aim of this study was to compare wastewater detection of xylazine with other public health and safety surveillance data from 2019 to 2023 in Kentucky.
METHODS
Wastewater samples from 5 rest areas, 2 truck weigh stations, and 4 wastewater treatment plants were tested for xylazine. Wastewater xylazine positivity rates were compared with xylazine-positive submission rates from the National Forensic Laboratory Information System and Kentucky's fatal overdoses in 6-month periods (Period 1=January-June; Period 2=July-December).
RESULTS
Xylazine was detected in 61.6% (424 of 688) of daily wastewater samples from roadway sites/wastewater treatment plants. For roadways, detection increased from 55% (Period 1, 2021) to 94% (Period 1, 2023), and wastewater treatment plants had an overall detection of 25.8% (=66 samples, Periods 1 and 2, 2022). Increasing roadway positivity corresponded to trends in National Forensic Laboratory Information System xylazine-positive submission rates: from 0.19 per 1,000 submissions (Period 1, 2019) to 2.9 per 1,000 (Period 2, 2022, latest available). No deaths from xylazine were reported publicly in Kentucky, although this study's authors identified 1-4 deaths (true count suppressed) in the overdose surveillance system, which, in back-of-the-envelope comparisons with other states, is far fewer than expected.
CONCLUSIONS
Wastewater signals indicate broad geographic exposure to xylazine in Kentucky, yet health outcomes data suggest otherwise. These findings may inform regional, national, and international efforts to incorporate wastewater-based drug surveillance. Harm-reduction activities along roadways and other suitable locations may be needed.
PubMed: 38883693
DOI: 10.1016/j.focus.2024.100203 -
Journal of Clinical Immunology Aug 2023COVID-19 infection in immunodeficient individuals can result in chronically poor health, persistent or relapsing SARS-CoV-2 PCR positivity, and long-term infectious...
PURPOSE
COVID-19 infection in immunodeficient individuals can result in chronically poor health, persistent or relapsing SARS-CoV-2 PCR positivity, and long-term infectious potential. While clinical trials have demonstrated promising outcomes using anti-SARS-CoV-2 medicines in immunocompetent hosts, their ability to achieve sustained viral clearance in immunodeficient patients remains unknown. We therefore aimed to study long-term virological outcomes in patients treated at our centre.
METHODS
We followed up immunocompromised inpatients treated with casirivimab-imdevimab (Ronapreve) between September and December 2021, and immunocompromised patients who received sotrovimab, molnupiravir, nirmatrelvir/ritonavir (Paxlovid), or no treatment from December 2021 to March 2022. Nasopharyngeal swab and sputum samples were obtained either in hospital or in the community until sustained viral clearance, defined as 3 consecutive negative PCR samples, was achieved. Positive samples were sequenced and analysed for mutations of interest.
RESULTS
We observed sustained viral clearance in 71 of 103 patients, none of whom died. Of the 32/103 patients where sustained clearance was not confirmed, 6 died (between 2 and 34 days from treatment). Notably, we observed 25 cases of sputum positivity despite negative nasopharyngeal swab samples, as well as recurrence of SARS-CoV-2 positivity following a negative sample in 12 cases. Patients were then divided into those who cleared within 28 days and those with PCR positivity beyond 28 days. We noted lower B cell counts in the group with persistent PCR positivity (mean (SD) 0.06 (0.10) ×10/L vs 0.22 (0.28) ×10/L, p = 0.015) as well as lower IgA (median (IQR) 0.00 (0.00-0.15) g/L vs 0.40 (0.00-0.95) g/L, p = 0.001) and IgM (median (IQR) 0.05 (0.00-0.28) g/L vs 0.35 (0.10-1.10) g/L, p = 0.005). No differences were seen in CD4+ or CD8+ T cell counts. Antiviral treatment did not impact risk of persistent PCR positivity.
CONCLUSION
Persistent SARS-CoV-2 PCR positivity is common among immunodeficient individuals, especially those with antibody deficiencies, regardless of anti-viral treatment. Peripheral B cell count and serum IgA and IgM levels are predictors of viral persistence.
Topics: Humans; COVID-19; SARS-CoV-2; Antiviral Agents; Polymerase Chain Reaction; Immunologic Deficiency Syndromes; Immunoglobulin A; Immunoglobulin M; COVID-19 Testing
PubMed: 37148422
DOI: 10.1007/s10875-023-01504-9 -
Frontiers in Cellular and Infection... 2023Oral and/or tongue swabs have demonstrated ability to detect in adults with pulmonary tuberculosis (TB). Swabs provide useful alternative specimens for diagnosis of TB...
INTRODUCTION
Oral and/or tongue swabs have demonstrated ability to detect in adults with pulmonary tuberculosis (TB). Swabs provide useful alternative specimens for diagnosis of TB using molecular assays however, the diagnostic pickup by culture requires further improvement and development. Several studies identified the presence of differentially culturable tubercle bacilli (DCTB) populations in a variety of clinical specimens. These organisms do not grow in routine laboratory media and require growth factors in the form of culture filtrate (CF) from logarithmic phase cultures of H37Rv.
METHODS
Herein, we compared the diagnostic performance of sputum and tongue swabs using Mycobacterial Growth Indicator Tube (MGIT) assays, Auramine smear, GeneXpert and DCTB assays supplemented with or without CF.
RESULTS
From 89 eligible participants, 83 (93%), 66 (74%) and 79 (89%) were sputum positive by MGIT, smear and GeneXpert, respectively. The corresponding tongue swabs displayed a lower sensitivity with 39 (44%), 2 (2.0%) and 18 (20%) participants respectively for the same tests. We aimed to improve the diagnostic yield by utilizing DCTB assays. Sputum samples were associated with a higher positivity rate for CF-augmented DCTB at 82/89 (92%) relative to tongue swabs at 36/89 (40%). Similarly, sputum samples had a higher positivity rate for DCTB populations that were CF-independent at 64/89 (72%) relative to tongue swabs at 26/89 (29%). DCTB positivity increased significantly, relative to MGIT culture, for tongue swabs taken from HIV-positive participants. We next tested whether the use of an alternative smear stain, DMN-Trehalose, would improve diagnostic yield but noted no substantial increase.
DISCUSSION
Collectively, our data show that while tongue swabs yield lower bacterial numbers for diagnostic testing, the use of growth supplementation may improve detection of TB particularly in HIV-positive people but this requires further interrogation in larger studies.
Topics: Adult; Humans; Tuberculosis, Pulmonary; Bacillus; Firmicutes; Mycobacterium tuberculosis; Lacticaseibacillus casei; HIV Infections
PubMed: 37743867
DOI: 10.3389/fcimb.2023.1186191 -
Health Promotion and Chronic Disease... Jul 2023The broaden and build theory of positive emotions maintains that positive emotions serve to broaden individuals' thoughts and behaviours, resulting in the accrual of...
INTRODUCTION
The broaden and build theory of positive emotions maintains that positive emotions serve to broaden individuals' thoughts and behaviours, resulting in the accrual of resources (e.g. resilience) that catalyze upward spirals of well-being. However, there is a relative dearth of research examining the upward spiral hypothesis in the context of adolescence.
METHODS
Adolescents (n = 4064) in participating Canadian high schools were surveyed annually for three years as part of the COMPASS study. Reciprocal associations between positive emotions and resilience were examined as predictors of flourishing.
RESULTS
Adolescents who experienced positive emotions more frequently than usual reported higher levels of resilience one year later. Similarly, adolescents who had higher levels of resilience than usual reported more positive emotions the following year. Higher than usual levels of resilience and positive emotions positively predicted flourishing.
CONCLUSION
Positive emotions result in a cascade of beneficial outcomes including increased resilience and enhanced well-being, catalyzing an upward spiral towards flourishing. Opportunities to enhance positive emotions early on in adolescence may help build resources that can set students on the path towards increased well-being.
Topics: Humans; Adolescent; Emotions; Canada; Schools; Students; Surveys and Questionnaires
PubMed: 37466396
DOI: 10.24095/hpcdp.43.7.01 -
Frontiers in Immunology 2023Idiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual...
BACKGROUND
Idiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies. There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear.
METHODS
Immunohistochemical staining of PLA2R, THSD7A, and NELL-1 was conducted on kidney tissue samples obtained from patients diagnosed with IMN. Simultaneously, the presence of corresponding serum antibodies was determined. Patients exhibiting positivity for dual antigens were included in the study, identified either through tissue staining or serum antibody detection. We retrospectively collected their clinical, pathological, and follow-up data and measured their serum antibody levels at multiple time points. Additionally, the same type of dual antigen-positive IMN cases reported in the literature were reviewed to extract clinical, pathological, and prognostic information. We compared the data for all of the above dual antigen-positive and PLA2R single-positive IMN cases at our center.
RESULTS
We identified 6 IMN patients with dual antigen positivity at our center, approximately 0.7% of whole MN series; the previous literature reports 43 IMN patients with dual antigen positivity, the proportion ranged from 0.2% to 2.8%. The IgG1 positivity rate in the renal tissue of the dual antigen-positive patients at our center was significantly lower than that of dual antigen-positive patients previously reported (16.7% vs. 100.0%, p=0.015), but there was no significant difference in clinical or prognostic aspects. Patients with dual antigen positivity reported at our center and in the literature were combined and compared with PLA2R single-positive IMN reported at our center. Compared with PLA2R single-positive IMN patients, dual antigen-positive IMN patients had a higher renal tissue IgG1 positivity rate (58.3% vs. 22.3%, p=0.016), and the time required to achieve remission was longer [13.5 (3.3,35.0) vs. 3.0 (1.0,8.0), p=0.052]. Overall, The changes in urine protein were consistent with the changes in serum PLA2R antibody levels in dual antigen-positive IMN patients.
CONCLUSIONS
For patients with primary membranous nephropathy who did not attain remission following prolonged treatment, multiple target antigen staining should still be actively performed, even with positivity for the PLA2R target antigen.
Topics: Adult; Humans; Prognosis; Glomerulonephritis, Membranous; Retrospective Studies; Immunoglobulin G; Nephrotic Syndrome
PubMed: 38250076
DOI: 10.3389/fimmu.2023.1297107 -
Acta Biochimica Polonica Dec 2023This study is an exploration of the relationship between chemical industrial environment and allergic skin diseases.
OBJECTIVE
This study is an exploration of the relationship between chemical industrial environment and allergic skin diseases.
METHODS
In this retrospective analysis, 200 patients with allergic skin diseases who worked or lived in a chemical industrial zone and were admitted in our hospital between January 2018 and January 2020 were enrolled as Group A. Besides, 500 patients with allergic skin disease who lived in Zhenhai New District, five kilometers away from the chemical radiation zone, were selected as Group B. The specific immunoglobulin E (IgE) levels were determined by Western blotting. The allergen positivity, as well as allergen positivity between different age, sex and body mass index (BMI) were compared between the two groups. The positive food-specific allergen IgE antibody (sIgE) and positive inhalational sIgE were compared between the two groups.
RESULTS
The positive rate of total IgE and inhalational sIgE in Group A was higher than that in Group B (P<0.05), while there was no significant difference in positive rate in food sIgE between the two groups (P>0.05). In Group A, the differences in positive rates of total IgE, food-induced sIgE and inhalational sIgE were not significant between patients with different ages, sexes and BMI (P>0.05). There was no significant difference between the two groups in sIgE positive rates of wheat, mango, soybean/peanut/cashew nut combination, limb/beef combination, crab/shrimp/fish combination, milk and egg white (P>0.05). The positive rates of inhalational sIgE in tree combination and dust mites/household dust mites combination in Group A were higher than those in Group B (P<0.05), but had no significant difference between the two groups in the positive rates of inhalational sIgE in Humulus japonicus, mold combination 1, cockroach, cat/dog hair combination, and ragweed/artemisia combination (P>0.05).
CONCLUSION
Chemical industrial environment is closely associated with allergic dermatosis, and the positive rate of total IgE and inhalational sIgE increases significantly in patients living there.
Topics: Animals; Dogs; Cattle; Humans; Retrospective Studies; Skin Tests; Allergens; Dermatitis, Atopic; Immunoglobulin E; Dust
PubMed: 38043082
DOI: 10.18388/abp.2020_6797 -
Scientific Reports Nov 2023Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC)...
Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC) remains challenging. The prognostic significance of HER2-low positivity in these patients is not fully understood. In our retrospective study, we analyzed 647 patients with HR-positive, HER2-negative, node-positive EBC, stratifying them into three cohorts based on axillary lymph node involvement, tumor size, and characteristics. Cohort 1 included patients with either ≥ 4 positive axillary lymph nodes or 1-3 positive nodes with histological grade 3 or tumor size ≥ 5 cm. Cohort 2 consisted of patients with 1-3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 ≥ 20%. Cohort 3 comprised patients with 1-3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 < 20%. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) between HER2-low (IHC1+ or IHC2+/FISH-) and HER2-zero (IHC0) groups in each cohort. In cohort 1, HER2-low patients exhibited significantly better 5-year IDFS (84.2% vs. 73.6%, p = 0.0213) and DRFS (88.2% vs. 79.8%, p = 0.0154). However, no significant differences were observed in cohorts 2 and 3. Our findings suggest HER2-low positivity as a prognostic factor in HR-positive, HER2-negative, and node-positive EBC.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Ki-67 Antigen; Retrospective Studies; Neoplasm Recurrence, Local; Receptor, ErbB-2
PubMed: 37952045
DOI: 10.1038/s41598-023-47033-8 -
Brazilian Journal of Physical Therapy 2023The validity of the ULTT is unclear, due to heterogeneity of test procedures and variability in the definition of a positive test OBJECTIVE: To evaluate test procedures... (Review)
Review
BACKGROUND
The validity of the ULTT is unclear, due to heterogeneity of test procedures and variability in the definition of a positive test OBJECTIVE: To evaluate test procedures and positive diagnostic criteria for the upper limb tension test (ULTT) in diagnostic test accuracy studies.
METHODS
A systematic review of diagnostic accuracy studies was performed. We conducted a search of the DiTA (Diagnostic Test Accuracy) database and selected primary studies evaluating the diagnostic accuracy of the ULTT. We assessed risk of bias, performed data extraction on study characteristics, test procedures, and positive diagnostic criteria, and performed a descriptive analysis.
RESULTS
We included nine studies (681 participants), four diagnosing people with cervical radiculopathy (CR), four diagnosing people with carpal tunnel syndrome (CTS), and one included both CR and CTS. The risk of bias varied between 2 and 6 out of 6 positive items. Eight studies reported on the ULTT1 (median nerve). Overall, all studies clearly described their test procedures and positive diagnostic criteria although the order of movements and the diagnostic criteria between studies varied. We suggest a more standardised test procedure for the ULTT1 to consist of: 1) stabilising the shoulder in abduction, 2) extending the wrist/fingers, 3) supinating the forearm, 4) externally rotating the shoulder, 5) extending the elbow, and finally 6) performed structural differentiation by side bending (lateral flexion) of the neck. This proposed test procedure should reproduce the symptoms and enables the clinician to evaluate whether symptoms increase/decrease when stressing or relaxing the nerves.
CONCLUSION
Based on our findings we proposed a more standardised test procedure for the ULTT1 with accompanying positive diagnostic criteria to facilitate homogeneity in future diagnostic accuracy studies of the ULTT.
Topics: Humans; Physical Examination; Upper Extremity; Wrist; Carpal Tunnel Syndrome; Fingers
PubMed: 37967500
DOI: 10.1016/j.bjpt.2023.100558 -
Kidney International Nov 2023Systematic screening for BKPyV-DNAemia has been advocated to aid prevention and treatment of polyomavirus associated nephropathy (PyVAN), an important cause of kidney...
Systematic screening for BKPyV-DNAemia has been advocated to aid prevention and treatment of polyomavirus associated nephropathy (PyVAN), an important cause of kidney graft failure. The added value of performing a biopsy at time of BKPyV-DNAemia, to distinguish presumptive PyVAN (negative SV40 immunohistochemistry) and proven PyVAN (positive SV40) has not been established. Therefore, we studied an unselected cohort of 950 transplantations, performed between 2008-2017. BKPyV-DNAemia was detected in 250 (26.3%) transplant recipients, and positive SV40 in 91 cases (9.6%). Among 209 patients with a concurrent biopsy at time of first BKPyV-DNAemia, 60 (28.7%) biopsies were SV40 positive. Plasma viral load showed high diagnostic value for concurrent SV40 positivity (ROC-AUC 0.950, 95% confidence interval 0.916-0.978) and the semiquantitatively scored percentage of tubules with evidence of polyomavirus replication (pvl score) (0.979, 0.968-0.988). SV40 positivity was highly unlikely when plasma viral load is below 4 log copies/ml (negative predictive value 0.989, 0.979-0.994). In SV40 positive patients, higher plasma BKPyV-DNA load and higher pvl scores were associated with slower viral clearance from the blood (hazard ratio 0.712, 95% confidence interval 0.604-0.839, and 0.327, 0.161-0.668, respectively), whereas the dichotomy positivity/negativity of SV40 immunohistochemistry did not predict viral clearance. Although the pvl score offers some prognostic value for viral clearance on top of plasma viral load, the latter provided good guidance for when a biopsy was unnecessary to exclude PyVAN. Thus, the distinction between presumptive and proven PyVAN, based on SV40 immunohistochemistry, has limited clinical value. Hence, management of BKPyV-DNAemia and immunosuppression reduction should be weighed against the risk of occurrence of rejection, or exacerbation of rejection observed concomitantly.
PubMed: 37598855
DOI: 10.1016/j.kint.2023.07.025 -
Alzheimer's & Dementia (New York, N. Y.) 2023Alzheimer's disease (AD) is characterized by the presence of both amyloid and tau pathology. In vivo diagnosis can be made with amyloid and tau positron emission...
INTRODUCTION
Alzheimer's disease (AD) is characterized by the presence of both amyloid and tau pathology. In vivo diagnosis can be made with amyloid and tau positron emission tomography (PET) imaging. Emergent evidence supports that amyloid and tau accumulation are associated and that amyloid accumulation may precede that of tau. This report further investigates the relationship between amyloid and tau to assess whether elevated cortical tau can predict elevated amyloid in participants with early symptomatic AD.
METHODS
Florbetapir F18 and flortaucipir F18 uptake were evaluated from baseline PET scans collected in three multi-center studies with cognitively impaired participants, including A05 ( = 306; NCT02016560), TB ( = 310; TRAILBLAZER-ALZ; NCT03367403), and TB2 ( = 1165; TRAILBLAZER-ALZ 2; NCT04437511). Images were assessed using visual and quantitative approaches to establish amyloid (A+) and tau (T+) positivity, as well as a combination method (tauVQ) to establish T+. Associations between global amyloid and tau were evaluated with positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-). Predictive values within subgroups according to ethnicity, race, cognitive score, age, and sex were also evaluated. The relationship between regional tau (four target and two reference regions were tested) and global amyloid was investigated in A05 participant scans using receiver-operating characteristic (ROC) curves.
RESULTS
PPV for amyloid positivity was ≥93% for all three trials using various A+ and T+ definitions, including visual, quantitative, and combination methods. Population characteristics did not have an impact on A+ predictability. Regional analyses (early tau (Eτ) volume of interest (VOI), temporal, parietal, frontal) revealed significant area under the ROC curve in Eτ VOI compared to frontal region, regardless of reference region and consistent among visual and quantitative A+ definitions ( < 0.001).
DISCUSSION
These findings suggest that a positive tau PET scan is associated (≥93%) with amyloid positivity in individuals with early symptomatic AD, with the potential benefits of reducing clinical trial and health care expenses, radiation exposure, and participant time.
HIGHLIGHTS
Positron emission tomography (PET) evaluates candidates for Alzheimer's disease (AD) research. A positive tau PET scan is associated (≥93%) with amyloid positivity.A positive amyloid PET is not necessarily associated with tau positivity.Tau PET could be the sole diagnostic tool to confirm candidates for AD trials.
PubMed: 37600216
DOI: 10.1002/trc2.12415