Exposure to potent synthetic opioids such as illicitly manufactured fentanyl (IMF) has fueled the escalating overdose crisis in the USA, particularly in the east coast. Drug checking services, which ...allow people who use drugs (PWUD) to learn about the contents of their drugs, remain limited and even criminalized in many states. Further, there is a persistent belief that PWUD are not willing or able to change their behaviors despite being aware of their potential exposure to fentanyl through drug use.
We conducted a multi-site cross-sectional study among PWUD to assess what behaviors, if any, were employed in the case of suspected fentanyl exposure, and the correlates of engaging in harm reduction behaviors (HRB). PWUD (N = 334) were recruited in Boston (n = 80), Providence (n = 79), and in Baltimore (n = 175). At the time of the survey, no legal drug checking services were available in these cities.
The majority of PWUD (84%) expressed concern about fentanyl. Among those who suspected fentanyl exposure prior to using their drugs (n = 196), 39% reported employing HRB including using less of the drug (12%) or abstaining altogether (10%), using more slowly (5%), and doing a tester shot (5%). In adjusted logistic regression models, the odds (aOR) of practicing HRB after suspecting fentanyl exposure were increased among PWUD who were non-White (aOR 2.1; p = 0.004) and older (aOR 1.52 per decade of age; p < 0.001). Daily injection (aOR 0.50; p < 0.001), using drugs in public (aOR 0.58; p = 0.001), using drugs alone (aOR 0.68; p < 0.001), and experiencing multiple recent overdoses (aOR 0.55; p < 0.001) were associated with decreased odds of practicing HRB.
These data illustrate that PWUD employ a number of practices to reduce overdose risk in a context of unknown drug purity and content. Results may also guide efforts to identify early adopters of drug checking services and engage them in peer-outreach to target the most socially and structurally vulnerable PWUD, who are not reporting behavior change, with harm reduction messaging.
Subcutaneous (s.c.) administration of monoclonal antibodies (mAbs) can reduce treatment burden for patients and healthcare systems compared with intravenous (i.v.) infusion through shorter ...administration times, made possible by convenient, patient‐centric devices. A deeper understanding of clinical pharmacology principles related to efficacy and safety of s.c.‐administered mAbs over the past decade has streamlined s.c. product development. This review presents learnings from key constituents of the s.c. mAb development pathway, including pharmacology, administration variables, immunogenicity, and delivery devices. Restricted mAb transportation through the hypodermis explains their incomplete absorption at a relatively slow rate (pharmacokinetic (PK)) and may impact mAb‐cellular interactions and/or onset and magnitude of physiological responses (pharmacodynamic). Injection volumes, formulation, rate and site of injection, and needle attributes may affect PKs and the occurrence/severity of adverse events like injection‐site reactions or pain, with important consequences for treatment adherence. A review of immunogenicity data for numerous compounds reveals that incidence of anti‐drug antibodies (ADAs) is generally comparable across i.v. and s.c. routes, and complementary factors including response magnitude (ADA titer), persistence over time, and neutralizing antibody presence are needed to assess clinical impact. Finally, four case studies showcase how s.c. biologics have been clinically developed: (i) by implementation of i.v./s.c. bridging strategies to streamline PD‐1/PD‐L1 inhibitor development, (ii) through co‐development with i.v. presentations for anti‐severe acute respiratory syndrome‐coronavirus 2 antibodies to support rapid deployment of both formulations, (iii) as the lead route for bispecific T cell engagers (BTCEs) to mitigate BTCE‐mediated cytokine release syndrome, and (iv) for pediatric patients in the case of dupilumab.
Observation and feedback are core strategies of hand hygiene (HH) improvement. Direct overt observation is currently the gold standard method. Observation bias, also known as the Hawthorne effect, is ...a major disadvantage of this method. Our aim was to examine the variation of the Hawthorne effect on HH observation in different healthcare groups and settings.
A prospective cohort study was performed in a tertiary teaching hospital during a 15-month period. Up to 38 overt observers (82% nurses) and 93 covert observers (81% medical students) participated in HH observation. The HH events observed overtly were matched for occupation, department, observation time, and location with those observed covertly. The data of matched pairs were then analysed to detect possible Hawthorne effects on different variables.
A total of 31,522 HH opportunities were observed (4581 overtly, 26,941 covertly). There were 3047 matched pairs after 1:1 matching of overt and covert observations. The overall HH compliance was higher with overt observation than with covert observation (78% vs. 55%, p < 0.001). The Hawthorne effect was nearly three times larger in nurses (30 percentage points) than in physicians (11 percentage points) and was significantly greater in outpatient clinics (41 percentage points) than in intensive care units (11 percentage points). The magnitude of the Hawthorne effect varied among healthcare worker occupations and observation locations (p values both < 0.001) but not among departments, observation times, or HH indications.
Heterogeneity in the Hawthorne effect may influence the interpretation of overt observations and prevent the correct identification of target populations with poor HH compliance. Therefore, directly observed HH compliance may not be an adequate performance indicator for infection control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Changes in whole body energy levels are closely linked to alterations in body weight and bone mass. Here, we show that hypothalamic signals contribute to the regulation of bone mass in a manner ...consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY), a well-known orexigenic factor whose hypothalamic expression is increased in fasting, have significantly increased bone mass in association with enhanced osteoblast activity and elevated expression of bone osteogenic transcription factors, Runx2 and Osterix. In contrast, wild type and NPY knockout (NPY (-/-)) mice in which NPY is specifically over expressed in the hypothalamus (AAV-NPY+) show a significant reduction in bone mass despite developing an obese phenotype. The AAV-NPY+ induced loss of bone mass is consistent with models known to mimic the central effects of fasting, which also show increased hypothalamic NPY levels. Thus these data indicate that, in addition to well characterized responses to body mass, skeletal tissue also responds to the perception of nutritional status by the hypothalamus independently of body weight. In addition, the reduction in bone mass by AAV NPY+ administration does not completely correct the high bone mass phenotype of NPY (-/-) mice, indicating the possibility that peripheral NPY may also be an important regulator of bone mass. Indeed, we demonstrate the expression of NPY specifically in osteoblasts. In conclusion, these data identifies NPY as a critical integrator of bone homeostatic signals; increasing bone mass during times of obesity when hypothalamic NPY expression levels are low and reducing bone formation to conserve energy under 'starving' conditions, when hypothalamic NPY expression levels are high.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Crack Deep Network (CrackDN) is proposed in this research with the purpose of detecting sealed and unsealed cracks with complex road backgrounds. CrackDN is based on Faster Region Convolutional ...Neural Network (Fast-RCNN) architecture by embedding a sensitivity detection network parallel to the feature extraction Convolutional Neural Network (CNN), both of which are then connected to the Region Proposal Refinement Network (RPRN) for classification and regression. The state-of-the-art aspect of this research lies in the fusion of sensitivity detection network, which facilitated the CrackDN of being able to detect sealed and unsealed cracks with sever complex background. Four kinds of background conditions are considered for both sealed and unsealed crack analysis: normal and unbalanced illuminations, with markings and shadings. The raw pavement images are first processed simultaneously by the sensitivity extraction network, which is formed by a batch of line filters that each differ in angles for sensitive region extraction, and the CNN, which utilized ZF-Net. Then the extracted sensitive maps and feature maps are applied as the input of RPRN, thereby the prediction scores together with the bounding box can be obtained. The performance of CrackDN is compared with Faster-RCNN and SSD300 architectures for sealed and unsealed crack detection. Results demonstrate that CrackDN can achieve the detection mean average precision of higher than 0.90, which outperforms both Faster-RCNN and SSD300. The detection speed of CrackDN (around 6 fps) are slightly lower than SSD300 but significantly higher than Faster-RCNN. Meanwhile, the performance of sealed crack detection is better than unsealed crack detection for most background conditions. Moreover, sealed and unsealed cracks on the markings are the most difficult conditions for detection. However, CrackDN still can obtain the detection accuracy of above 0.85.
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•Sensitivity detection is necessary for analyzing complex images.•IOU threshold and anchors significantly influence the crack detection.•CrackDN can detect both cracks and sealed pavement cracks.•Road marking impacts the accuracy of sealed and unsealed cracks detections.•Sealed cracks are easier to detect than unsealed cracks.
Acute promyelocytic leukemia (APL) is commonly complicated by a complex coagulopathy. Uncertainty remains as to which markers of bleeding risk are independent predictors. Drawing from 5 large ...clinical trials that included all-trans retinoic acid (ATRA) as part of induction, we assessed known determinants of bleeding at baseline and evaluated them as potential predictors of hemorrhagic death (HD) in the first 30 days of treatment. The studies included were ALLG APML3 (single arm of ATRA + idarubicin ± prednisone), ALLG APML4 (single arm of ATRA + idarubicin + arsenic trioxide + prednisone), CALGB C9710 (single arm of ATRA + cytarabine + daunorubicin), Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2491 (intergroup I0129, consisting of daunorubicin + cytarabine vs ATRA), and SWOG S0521 (single-arm induction of ATRA + cytarabine + daunorubicin). A total of 1009 patients were included in the original trials, of which 995 had sufficient data to be included in our multivariate analysis. In this final cohort, there were 37 HD cases during the first 30 days following induction, for an estimated cumulative incidence of 3.7% (95% confidence interval CI, 2.6% to 5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio of HD in the first 30 days was 2.17 (95% CI, 0.84-5.62) for an ECOG performance status of 3-4 vs 0-2 and 5.20 (95% CI, 2.70-10.02) for a white blood cell count of ≥20 000/μL vs <20 000/μL. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor of early HD.
•High WBC is an independent predictor of early HD in APL.
•Only one quarter of people who inject drugs (PWID) had heard of PrEP, but most were interested in taking it.•Most PWID thought taking PrEP everyday would be easy.•PWID who are at higher risk for HIV ...were more likely to be interested in PrEP.
Limited research has examined pre-exposure prophylaxis (PrEP) interest among people who inject drugs (PWID). To date, few studies have examined the relationship between PrEP eligibility and PrEP interest among PWID.
Data were from an anonymous, cross-sectional survey of Baltimore Syringe Services Program (SSP) clients and non-client peers, restricted to HIV-uninfected participants (N = 265). Participants were classified as PrEP eligible/ineligible based on injection related criteria outlined in the CDC’s PrEP guidelines. Participants were asked if they were previously aware of PrEP, would be interested in taking PrEP, and the ease of taking PrEP daily. Participants self-reported their sociodemographic characteristics, health diagnoses, and recent drug use, overdose, and drug treatment history. We estimated bivariate and multivariate logistic regression models to test for significant predictors of interest in PrEP.
One-quarter of PWID had previously heard of PrEP and 63% of the sample was interested in taking PrEP. Only two respondents were currently taking PrEP. The majority (89%) thought taking PrEP every day would be easy. In the presence of other variables, PrEP interest was associated with PrEP eligibility (adjusted odds ratio aOR = 2.46; 95% Confidence Interval CI:1.34,4.50) and the number of medical diagnoses (aOR = 1.16; 95% CI:1.01,1.33)
Most PWID were unaware of PrEP but interested in taking it. PWID who were eligible for PrEP are more likely to be interested in taking it. Having co-morbid conditions was an important correlate of PrEP interest. These results underscore the importance of providers across the healthcare sector engaging PWID in discussions about PrEP.
Growth differentiation factor-15 (GDF-15) is a member of the TGF-
cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a ...novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of
mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal
transcript levels (
=0.54,
=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45;
=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50;
=0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of
and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal
-related signaling pathways associated with CKD and CKD progression.
Fentanyl has caused rapid increases in US and Canadian overdose deaths, yet its presence in illicit drugs is often unknown to consumers. This study examined the validity in identifying the presence ...of fentanyl of three portable devices that could be used in providing drug checking services and drug supply surveillance: fentanyl test strips, a hand-held Raman Spectrometer, and a desktop Fourier-Transform Infrared Spectrometer.
In Fall 2017, we first undertook an assessment of the limits of detection for fentanyl, then tested the three devices’ sensitivity and specificity in distinguishing fentanyl in street-acquired drug samples. Utilizing test replicates of standard fentanyl reference material over a range of increasingly lower concentrations, we determined the lowest concentration reliably detected. To establish the sensitivity and specificity for fentanyl, 210 samples (106 fentanyl-positive, 104 fentanyl-negative) previously submitted by law enforcement entities to forensic laboratories in Baltimore, Maryland, and Providence, Rhode Island, were tested using the devices. All sample testing followed parallel and standardized protocols in the two labs.
The lowest limit of detection (0.100 mcg/mL), false negative (3.7%), and false positive rate (9.6%) was found for fentanyl test strips, which also correctly detected two fentanyl analogs (acetyl fentanyl and furanyl fentanyl) alone or in the presence of another drug, in both powder and pill forms. While less sensitive and specific for fentanyl, the other devices conveyed additional relevant information including the percentage of fentanyl and presence of cutting agents and other drugs.
Devices for fentanyl drug checking are available and valid. Drug checking services and drug supply surveillance should be considered and researched as part of public health responses to the opioid overdose crisis.
Criminal justice system costs in the United States have exponentially increased over the last decades, and providing health care to individuals released from incarceration is costly. To better ...understand how to manage costs to state budgets for those who have been incarcerated, we aimed to assess state-level costs of an enhanced primary care program, Transitions Clinic Network (TCN), for chronically-ill and older individuals recently released from prison.
We linked administrative data from Connecticut Department of Correction, Medicaid, and Department of Mental Health and Addiction Services to identify a propensity matched comparison group and estimate costs of a primary care program serving chronically-ill and older individuals released from incarceration between 2013 and 2016. We matched 94 people released from incarceration who received care at a TCN program to 94 people released from incarceration who did not receive care at TCN program on numerous characteristics. People eligible for TCN program participation were released from incarceration within the prior 6 months and had a chronic health condition or were over the age of 50. We estimated 1) costs associated with the TCN program and 2) costs accrued by Medicaid and the criminal justice system. We evaluated associations between program participation and Medicaid and criminal justice system costs over a 12-month period using bivariate analyses with nonparametric bootstrapping method.
The 12-month TCN program operating cost was estimated at $54,394 ($146 per participant per month). Average monthly Medicaid costs per participant were not statistically different between the TCN ($1737 ± $3449) and comparison ($1356 ± $2530) groups. Average monthly criminal justice system costs per participant were significantly lower among TCN group ($733 ± $1130) compared with the matched group ($1276 ± $1738, p < 0.05). We estimate every dollar invested in the TCN program yielded a 12-month return of $2.55 to the state.
Medicaid investments in an enhanced primary care program for individuals returning from incarceration are cost neutral and positively impact state budgets by reducing criminal justice system costs.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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