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1.
Chem Sci ; 15(19): 7041-7050, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756811

RESUMO

Developing tunable materials which exhibit sustained drug release is a considerable challenge. Herein, we report the concept of Therapeutic Coordination Polymers (TCPs); non-porous coordination polymers constructed from biocompatible components which demonstrate tunable zero-order drug release kinetics upon degradation of metal-ligand bonds. TCPs were constructed from three principal components: (i) a cationic metal center (M = Mg2+, Mn2+, Zn2+, or Cu2+); (ii) an anionic drug (Diclofenac); and (iii) an alkyl bis-imidazole organic ligand which behaves as a "linker" between metal centers. Most drug-release materials, such as amorphous polymer dispersions, or metal-organic frameworks rely on a diffusion-based mechanism for drug release, but the degradation-controlled release of drugs from non-porous one-periodic coordination polymers has been largely unexplored. TCPs described herein exhibit a high wt% of pharmaceutical (>62%), tailorable zero-order drug release rate kinetics which span over three orders of magnitude, and stimuli-responsive drug release behavior making them well suited for extended drug-release applications.

2.
Cytotherapy ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613540

RESUMO

Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38502866

RESUMO

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: There are currently no consensus guidelines on establishing metrics for investigational drug services (IDS). Because of the complexity of research protocols, it remains difficult for sites to track pharmacy productivity and create a baseline for IDS growth within the institution, as well as to perform benchmarking with peer institutions. The goal of this study was to help establish practical guidance for IDS metrics and site utility as applicable. METHODS: This was a survey-based project conducted by the metrics subgroup of the Hematology/Oncology Pharmacy Association (HOPA) IDS special interest group (SIG), which was formed specifically for this analysis. Three surveys developed by the metrics subgroup were sent to members of the IDS HOPA SIG to gather metrics. The first survey included questions about what metrics IDS sites currently collect. The identified metrics were then condensed into categories. Through a consensus-based approach, standardized definitions were established and applied to future surveys. The 2 subsequent surveys sent to HOPA SIG members helped create a list of top recommended metrics that are recommended for every IDS site to track. RESULTS: A total of 3 surveys were sent to 75 recipients, with the response rate ranging from 24% to 38%. From these surveys and consensus with the metrics subgroup, 5 top recommended metrics were identified: (1) active protocols; (2) dispenses; (3) new clinical trials initiated; (4) patients treated; and (5) clinical interventions. CONCLUSION: These recommended metrics should serve as guidance and allow for standardization to help ensure adequate resources are available for IDS pharmacy staff. These recommendations should serve as a basis for standardization and benchmarking with peer institutions.

4.
J Pers Assess ; : 1-11, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478969

RESUMO

Alterations in interoception have been linked to psychopathology. Recent findings suggest that both the attention to and the accuracy of, interoceptive perceptions may be oppositely related to subclinical symptomatology. Thus, providing well-validated tools that tap into these interoceptive processes is crucial for understanding the relation between interoceptive processing and subclinical psychopathology. In the current study (N = 642), we aimed to (1) validate the German version of the Interoceptive Attention Scale (IATS; Gabriele et al., 2022), and (2) test the differential association of self-reported interoceptive attention and accuracy with subclinical symptomatology, including alexithymia, depressive, and anxious symptomatology. We observed that a one-factor solution is a well-fitting model for the IATS. Further, the IATS showed good internal consistency, convergent, and divergent validity, but poor test-retest reliability. Self-reported interoceptive attention and accuracy were unrelated to each other. However, IATS scores were positively related to all measures of psychopathology (except depressive symptomatology), whereas self-reported interoceptive accuracy scores showed negative or nonsignificant relations with these. Our data suggest that the IATS is a good instrument to measure self-report interoceptive attention in the German population. Further, we highlight the need to distinguish between constructs of interoception to better understand the relation between interoception and psychopathology.

5.
Neurology ; 102(6): e209161, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38447117

RESUMO

BACKGROUND AND OBJECTIVES: Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions. METHODS: We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution's neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses. RESULTS: Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, p < 0.001), and this disparity was similar after controlling for other demographic factors in multivariable analysis. Patients from the least wealthy quartile of zip codes were also less likely to be evaluated (OR 0.67, p < 0.001). Among patients who underwent evaluation, there were no disparities in the likelihood of completing genetic testing, nor in the likelihood of a diagnostic result after adjusting for age. Analyses restricted to specific indications for genetic testing supported these findings. DISCUSSION: We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.


Assuntos
Doenças do Sistema Nervoso , Neurologia , Adulto , Humanos , Estudos Retrospectivos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Instituições de Assistência Ambulatorial , Testes Genéticos
6.
Sci Total Environ ; 926: 171838, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38518820

RESUMO

Safe and hygienic management of human waste is essential in humanitarian settings. Urine-diverting dry toilets (UDDTs) can enable this management in some humanitarian emergency settings. A seeded, longitudinal environmental study was conducted in Hiloweyn refugee camp, Dollo Ado, Ethiopia, to measure Escherichia coli and Ascaris suum ova inactivation within closed UDDT vaults and to document environmental conditions (temperature, moisture content, and pH) that could influence inactivation. Hiloweyn camp represented an optimal location for a desiccation-based sanitation technology such as the UDDT. E. coli and Ascaris ova inactivation was observed in UDDTs under warm, dry, alkaline conditions at 6, 9, and 12 months of storage; UDDTs with samples containing <1000 E. coli/g total solids increased from 30 % to 95 % over 12 months, and a >2.8-log10 reduction in Ascaris ova viability was observed after 6 months. Additional laboratory-based studies were conducted to provide insights into the field study findings and study the impact of hydrated lime on E. coli and Ascaris ova inactivation. Results suggest that adding hydrated lime to elevate pH > 12 may increase inactivation and decrease storage time. Overall, UDDTs could contribute to the safe and hygienic management of human waste in comparable warm and dry humanitarian settings.


Assuntos
Aparelho Sanitário , Escherichia coli , Óxidos , Animais , Humanos , Etiópia , Compostos de Cálcio/química , Ascaris/fisiologia
7.
Trials ; 25(1): 143, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395922

RESUMO

BACKGROUND: Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the 'Building Resilience through Socioemotional Training' (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology. METHODS: A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12-14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention. DISCUSSION: This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people's emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence. TRIAL REGISTRATION: ISRCTN88585916. Trial registration date: 20/04/2023.


Assuntos
Transtornos Mentais , Resiliência Psicológica , Humanos , Adolescente , Emoções , Instituições Acadêmicas , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Biol Psychol ; 186: 108761, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309512

RESUMO

Previous research suggests that the processing of internal body sensations (interoception) affects how we experience pain. Some evidence suggests that people with fibromyalgia syndrome (FMS) - a condition characterised by chronic pain and fatigue - may have altered interoceptive processing. However, extant findings are inconclusive, and some tasks previously used to measure interoception are of questionable validity. Here, we used an alternative measure - the Phase Adjustment Task (PAT) - to examine cardiac interoceptive accuracy in adults with FMS. We examined: (i) the tolerability of the PAT in an FMS sample (N = 154); (ii) if there are differences in facets of interoception (PAT performance, PAT-related confidence, and scores on the Private Body Consciousness Scale) between an FMS sample and an age- and gender-matched pain-free sample (N = 94); and (iii) if subgroups of participants with FMS are identifiable according to interoceptive accuracy levels. We found the PAT was tolerable in the FMS sample, with additional task breaks and a recommended hand posture. The FMS sample were more likely to be classified as 'interoceptive' on the PAT, and had significantly higher self-reported interoception compared to the pain-free sample. Within the FMS sample, we identified a subgroup who demonstrated very strong evidence of being interoceptive, and concurrently had lower fibromyalgia symptom impact (although the effect size was small). Conversely, self-reported interoception was positively correlated with FMS symptom severity and impact. Overall, interoception may be an important factor to consider in understanding and managing FMS symptoms. We recommend future longitudinal work to better understand associations between fluctuating FMS symptoms and interoception.


Assuntos
Fibromialgia , Interocepção , Adulto , Humanos , Fibromialgia/complicações , Fibromialgia/diagnóstico , Conscientização , Dor , Fadiga , Frequência Cardíaca
10.
Q J Exp Psychol (Hove) ; 77(2): 223-229, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37082986

RESUMO

In recent years, there has been a significant rise in interest in interoception, the processing of internal bodily signals. This interest has been coupled by increased concerns regarding the measurement and conceptualisation of interoception. Focusing on cardiac interoceptive accuracy, I outline what I believe to be the most pressing issues in the field of interoception-specifically the continued reliance on the heartbeat counting task. I then provide an overview of what I believe to be more general limitations concerning how we measure and conceptualise individual differences in interoception and suggestions for a way forward. Specifically, I believe that by moving beyond single measurements, establishing optimal levels of interoceptive accuracy, and refocusing from accuracy to propensity, we may be able to uncover the real-life relevance of interoceptive abilities.


Assuntos
Interocepção , Humanos , Conscientização , Coração , Frequência Cardíaca , Individualidade
11.
Skeletal Radiol ; 53(6): 1219-1224, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37934213

RESUMO

Chondroblastoma is a rare benign tumor, typically presenting in the first two decades. Systemic metastases in chondroblastoma are extremely rare and it is the rarity of these metastases which lead the World Health Organisation to re-classify this lesion from "intermediate" to "benign" in its updated classification of bone tumors in 2020. We present an unusual case of a 55 year-old male patient who presented with multiple FDG-avid bone lesions on a background of conventional chondroblastoma of the rib excised at another institution 11-years previously. Two of these lesions were also histologically-proven as conventional chondroblastoma at biopsy. This case highlights that, although rare, metastases can be seen in patients with chondroblastoma. To our knowledge, this is the only case with an unusual pattern of metastases limited to bone.


Assuntos
Neoplasias Ósseas , Condroblastoma , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , Condroblastoma/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Biópsia
12.
Brain Behav Immun ; 116: 259-266, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38081435

RESUMO

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 'Pre-Pandemic', 28 'Pandemic') using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 ('Pre-Pandemic' cLBP) or between August 2020 and May 2022 ('Pandemic' cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = -0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.


Assuntos
COVID-19 , Dor Crônica , Adulto , Humanos , Pandemias , Dor Crônica/metabolismo , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Envelhecimento , Receptores de GABA/metabolismo
13.
Skeletal Radiol ; 53(5): 917-922, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37957342

RESUMO

OBJECTIVE: To evaluate a range of pathologically proven malignant bone tumours, including primary bone sarcoma and metastatic bone lesions, referred to a tertiary referral centre for the presence of the flow-void sign on MR imaging. MATERIALS AND METHODS: A retrospective search was performed using the radiology information system and oncology database in our institution to identify patients over the age of 40 years referred with a solitary bone lesion. Patients with a range of pathologically proven malignant bone tumours, including primary bone tumours and metastatic bone lesions, were included in the study. MRI images were reviewed for the presence of the flow-void sign. The presence and type of the flow-void sign were correlated with lesion size. RESULTS: Two hundred and sixty-six cases were included in the study. Overall, the flow-void sign was identified in 40.9% of cases. The flow-void sign was most frequently seen in renal cell carcinoma metastasis (90.0%). The sign is highly sensitive (90%) for renal cell carcinoma metastases with a high negative predictive value (98.09%). When the flow-void sign is identified, the lesion is almost three times more likely to represent a renal cell carcinoma metastasis than any other malignant tumour in patients over the age of 40 years with a solitary bone lesion. CONCLUSION: The flow-void sign is highly sensitive for renal cell carcinoma bone metastases and could negate the need for biopsy in patients with a known history of renal cell carcinoma or in whom an occult renal cell carcinoma is subsequently identified.


Assuntos
Neoplasias Ósseas , Carcinoma de Células Renais , Doenças das Cartilagens , Neoplasias Renais , Humanos , Adulto , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Neoplasias Ósseas/secundário , Imageamento por Ressonância Magnética/métodos , Neoplasias Renais/patologia
14.
Mil Med ; 189(3-4): e502-e508, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-37464930

RESUMO

INTRODUCTION: Since the start of the Global War on Terrorism, exponential demands have been put on military personnel, their families, and the military health care system. In response to a Department of Defense Task Force on Mental Health, the U.S. military began developing and fielding programs to promote the psychological health of its personnel. As part of these initiatives, the Navy and Marine Corps developed the Stress Continuum model. The Stress Continuum is a stress classification system ("ready," "reacting," "injured," and "ill") that provides a common language for identifying, engaging, and intervening when stress reactions or stress injuries are present in military personnel. It is the foundation for resilience and prevention efforts across the Navy and Marine Corps. Although the Stress Continuum has strong face validity, is consistent with current theory, and has been agreed up by expert consensus, it has yet to be empirically validated. The goal of the current article is to begin to empirically validate the Stress Continuum using validated measures of psychological stress. MATERIALS AND METHODS: We conducted a retrospective analysis of Stress Continuum data (n = 2,049) collected as part of a program evaluation of two Navy operational stress control programs. Receiver operating characteristic (ROC) curves and analyses were conducted to determine the classification quality of the Stress Continuum using a validated measure of stress (a brief version of the Perceived Stress Scale [PSS-4]). RESULTS: For the first ROC curve, we used the "ill" category (vs. the other three categories) to identify the cut point on the PSS-4. PSS-4 cut point values of 9 and 10, respectively, maximized sensitivity and 1-specificity values. Using the chi-square test, we further found that a more accurate prediction for those in the "ill" category was using the cut point of 9 (79%) relative to 10 (71.8%). For the second and the third ROC curves, we used the "ill" and "injured" categories (vs. the other two categories) and "ill," "injured," and "reacting" categories (vs. the "ready" category), respectively. No optimal cut points on the PSS-4 were identified for these models, indicating that the PSS-4 could not reliably differentiate true-positive and false-positive rates. CONCLUSIONS: We found that the "ill" category of the Stress Continuum was predictive of higher levels of stress on the validated measure of perceived stress. Thus, our findings strongly suggest that the individuals in the "ill" zone likely warrant some type of intervention by a trained professional. FUTURE RESEARCH: The Navy has recently leveraged the Stress Continuum to create the Stress-o-Meter to support the fundamental principles of early recognition, peer intervention, and connection to services at the unit level. The Stress-o-Meter serves as a prevention tool that has the capability to collect information about stress levels throughout the entire unit at any time. Continued work on validating the Stress Continuum model and making it easily accessible to military units will ensure service members get the support they need and leaders are able to address the psychological health of their units.


Assuntos
Militares , Testes Psicológicos , Autorrelato , Estresse Psicológico , Humanos , Estudos Retrospectivos , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Militares/psicologia , Saúde Mental
15.
J Neurol ; 271(2): 733-747, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37891417

RESUMO

The role of genetic testing in neurologic clinical practice has increased dramatically in recent years, driven by research on genetic causes of neurologic disease and increased availability of genetic sequencing technology. Genetic testing is now indicated for adults with a wide range of common neurologic conditions. The potential clinical impacts of a genetic diagnosis are also rapidly expanding, with a growing list of gene-specific treatments and clinical trials, in addition to important implications for prognosis, surveillance, family planning, and diagnostic closure. The goals of this review are to provide practical guidance for clinicians about the role of genetics in their practice and to provide the neuroscience research community with a broad survey of current progress in this field. We aim to answer three questions for the neurologist in practice: Which of my patients need genetic testing? What testing should I order? And how will genetic testing help my patient? We focus on common neurologic disorders and presentations to the neurology clinic. For each condition, we review the most current guidelines and evidence regarding indications for genetic testing, expected diagnostic yield, and recommended testing approach. We also focus on clinical impacts of genetic diagnoses, highlighting a number of gene-specific therapies recently approved for clinical use, and a rapidly expanding landscape of gene-specific clinical trials, many using novel nucleotide-based therapeutic modalities like antisense oligonucleotides and gene transfer. We anticipate that more widespread use of genetic testing will help advance therapeutic development and improve the care, and outcomes, of patients with neurologic conditions.


Assuntos
Doenças do Sistema Nervoso , Neurociências , Adulto , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/terapia , Testes Genéticos , Neurologistas , Instituições de Assistência Ambulatorial
17.
J Subst Use Addict Treat ; 159: 209270, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38103831

RESUMO

BACKGROUND: Despite significant efforts to improve access to medications for opioid use disorder (MOUD), uptake remains low relative to the scope of the problem in the United States. A growing body of quantitative and qualitative research has documented consistent barriers to MOUD treatment access and retention, at the level of individuals, institutions, and society at large. Stigma - surrounding both people who use opioids (PWUO) and treatment using MOUD - is among the most-cited barriers by patients and providers alike, yet few studies have examined provider-based stigma specifically, or considered its interaction with other impediments to OUD care. METHODS: This paper employs a qualitative approach to the analysis of provider-based stigma among professionals involved in the treatment or supervision of individuals with OUD. We conducted and analyzed interviews with 19 professionals as part of a larger mixed methods study on stigma among substance use treatment providers and court personnel in Pennsylvania. Beyond capturing providers' perceptions of PWUO and MOUD, the authors asked participants to describe barriers to recovery, and the effective delivery of care within this population. RESULTS: Interviewees enumerated multiple entrenched barriers that sometimes operated at different levels, such as criminal-legal involvement, which weakened PWUO's social networks and employment prospects, while undermining providers' attempts at continuity of care; moreover, participants cited the "War on Drugs" as an overarching impediment to effective substance use treatment, not least for its role in perpetuating stigma against PWUO. CONCLUSIONS: Interestingly, while an overwhelming majority of participants named stigma as a barrier to treatment at every level, most also articulated stigmatizing beliefs around PWUO. Namely, providers evoked one element of stigma - blameworthiness - in their contention that many PWUO are inadequately motivated to recover. In addition to adding further complexity to MOUD barriers research, this study troubles the notion that professional training and education on the disease model of addiction serve to eradicate stigma.


Assuntos
Comportamento Aditivo , Criminosos , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/terapia , Transporte Biológico
18.
Chem Sci ; 14(47): 13825-13831, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38075671

RESUMO

Significant evidence suggests that the failure of clinically tested epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (e.g. erlotinib, lapatinib, gefitinib) in glioblastoma (GBM) patients is primarily attributed to insufficient brain penetration, resulting in inadequate exposure to the targeted cells. Molecular imaging tools can facilitate GBM drug development by visualizing drug biodistribution and confirming target expression and localization. To assess brain exposure via PET molecular imaging, we synthesized fluorine-18 isotopologues of two brain-penetrant EGFR tyrosine kinase inhibitors developed specifically for GBM. Adapting our recently reported radiofluorination of N-arylsydnones, we constructed an ortho-disubstituted [18F]fluoroarene as the key intermediate. The radiotracers were produced on an automated synthesis module in 7-8% activity yield with high molar activity. In vivo PET imaging revealed rapid brain uptake in rodents and tumor accumulation in an EGFR-driven orthotopic GBM xenograft model.

19.
Trop Med Int Health ; 28(12): 881-889, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37940633

RESUMO

OBJECTIVES: Innovations to improve public sanitation facilities, especially in healthcare facilities (HCFs) in low-income countries, are limited. SaTo pans represent novel, largely untested, modifications to reduce odour and flies and improve acceptability of HCF sanitation facilities. We conducted a pilot project to evaluate acceptability, cleanliness, flies and odour within latrines in 37 HCFs in Kisumu, Kenya, randomised into intervention (SaTo pan modifications) and control arms by sub-county and HCF level. METHODS: At baseline (pre-intervention) and endline (>3 months after completion of SaTo pan installations in latrines in intervention HCFs), we surveyed users, cleaners and in-charges, observed odour and cleanliness, and assessed flies using fly tape. Unadjusted difference-in-difference analysis compared changes from baseline to endline in patient-reported acceptability and observed latrine conditions between intervention and control HCFs. A secondary assessment compared patient-reported acceptability following use of SaTo pan versus non-SaTo pan latrines within intervention HCFs. RESULTS: Patient-reported acceptability of latrines was higher following the intervention (baseline: 87%, endline: 96%, p = 0.05). However, patient-reported acceptability was also high in the control arm (79%, 86%, p = 0.34), and the between-arm difference-in-difference was not significant. Enumerator-observed odour declined in intervention latrines (32%-14%) compared with controls (36%-51%, difference-in-difference ratio: 0.32, 95% confidence interval: 0.12-0.84), but changes in flies, puddling of urine and visible faeces did not differ between arms. In the secondary assessment, fewer intervention than control latrines had patient-reported flies (0% vs. 26%) and odour (18% vs. 50%), and reported satisfaction was greater. Most cleaners reported dropholes and floors were easier to clean in intervention versus controls; limited challenges with water for flushing were reported. CONCLUSIONS: Our results suggest SaTo pans may be acceptable by cleaners and users and reduce odour in HCF sanitation facilities, though challenges exist and further evaluation with larger sample sizes is needed.


Assuntos
Dípteros , Banheiros , Animais , Humanos , Atenção à Saúde , Quênia , Projetos Piloto , Saneamento , Tecnologia
20.
J Sports Sci ; 41(16): 1507-1517, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38018365

RESUMO

Two factors that decrease the replicability of studies in the scientific literature are publication bias and studies with underpowered desgins. One way to ensure that studies have adequate statistical power to detect the effect size of interest is by conducting a-priori power analyses. Yet, a previous editorial published in the Journal of Sports Sciences reported a median sample size of 19 and the scarce usage of a-priori power analyses. We meta-analysed 89 studies from the same journal to assess the presence and extent of publication bias, as well as the average statistical power, by conducting a z-curve analysis. In a larger sample of 174 studies, we also examined a) the usage, reporting practices and reproducibility of a-priori power analyses; and b) the prevalence of reporting practices of t-statistic or F-ratio, degrees of freedom, exact p-values, effect sizes and confidence intervals. Our results indicate that there was some indication of publication bias and the average observed power was low (53% for significant and non-significant findings and 61% for only significant findings). Finally, the usage and reporting practices of a-priori power analyses as well as statistical results including test statistics, effect sizes and confidence intervals were suboptimal.


Assuntos
Projetos de Pesquisa , Humanos , Viés de Publicação , Reprodutibilidade dos Testes , Tamanho da Amostra , Viés
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