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PURPOSE: Governance models are a defining characteristic of health-care systems, yet little research is available about the governance of health-care delivered in correctional facilities. This study aims to explore the perspectives of correctional services leaders in British Columbia, Canada, on the motivations for transferring responsibility for health-care services in provincial correctional facilities to the Ministry of Health, as well as key lessons learned. DESIGN/METHODOLOGY/APPROACH: Eight correctional services leaders participated in one-on-one interviews between September 2019 and February 2020. The authors used inductive thematic analysis to explore key themes. To triangulate early effects of the transfer identified by participants the authors used complaints data from Prisoners' Legal Services to examine changes over time. FINDINGS: The authors identified four major themes related to the rationale for this transfer: 1) quality and equivalence of care, 2) integration and throughcare, 3) values and expertise and 4) funding and resources. Facilitators included changes in the external environment, having the right people in the right places, a strong sense of alignment and shared goals and a changing culture in corrections. Participants also highlighted challenges, including ongoing human resourcing issues, having to navigate and define shared responsibilities and adapting a large bureaucracy to the environment in corrections. Consistent with outcomes described by participants, data showed that a lower proportion of complaints received after the transfer were related to health-care. ORIGINALITY/VALUE: The perspectives of correctional leaders on the transfer of governance for health-care services in custody to the community health-care system provide novel insights into the processes and potential of this change.
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Atenção à Saúde , Humanos , Colúmbia Britânica , Atenção à Saúde/organização & administração , Entrevistas como Assunto , Prisões/organização & administração , Estabelecimentos Correcionais , Liderança , Pesquisa QualitativaRESUMO
BACKGROUND: The grey garden slug (Deroceras reticulatum) is considered the most damaging slug pest in global agriculture. Control methods primarily rely on chemical pesticides, which pose environmental risks and potential hazards to human health. There is a need for sustainable management alternatives such as biologically-based slug control options. However, the efficacy of nonchemical measures for controlling pest slug populations remains limited, particularly in the context of variable outdoor conditions. Neuropeptides and their corresponding receptors have been proposed as promising biological targets for the development of new pest management strategies. RESULTS: A total of 23 bioactive peptides belonging to the PRX family, previously identified from the grey garden slug, D. reticulatum, were injected into or fed to this species. The detrimental effects of these peptides, including a reduction in body weight and an inhibition of feeding activity, were evaluated in feeding choice tests with D. reticulatum. Furthermore, the bioactive peptide formulated with a lipid particle demonstrated a feeding deterrent effect. One of the myomodulin (MM) peptides, APPLPRY, demonstrated a significant reduction in feeding activity, resulting in a reduction in slug weight or mortality in just 30 min. CONCLUSION: The results represent the first evidence of a bioactive peptide having detrimental effects on D. reticulatum including causing feeding deterrent for this slug pest. The in vivo results provide insights into the potential development of active ingredients for managing slugs in the field. © 2024 Society of Chemical Industry.
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BACKGROUND: In many jurisdictions, policies restrict access to Opioid Agonist Treatment (OAT) in correctional facilities. Receipt of OAT during incarceration is associated with reduced risk of fatal overdose after release but little is known about the effect on nonfatal overdose. This study aimed to examine the association between OAT use during incarceration and nonfatal overdose in the 30 days following release. METHODS AND FINDINGS: Using linked administrative healthcare and corrections data for a random sample of 20% of residents of British Columbia, Canada we examined releases from provincial correctional facilities between January 1, 2015 -December 1, 2018, among adults (aged 18 or older at the time of release) with Opioid Use Disorder. We fit Andersen-Gill models to examine the association between receipt of OAT in custody and the hazard of nonfatal following release. We conducted secondary analyses to examine the association among people continuing treatment initiated prior to their arrest and people who initiated a new episode of OAT in custody separately. We also conducted sex-based subgroup analyses. In this study there were 4,738 releases of 1,535 people with Opioid Use Disorder. In adjusted analysis, receipt of OAT in custody was associated with a reduced hazard of nonfatal overdose (aHR 0.55, 95% CI 0.41, 0.74). This was found for prescriptions continued from community (aHR 0.49, 95%CI 0.36, 0.67) and for episodes of OAT initiated in custody (aHR 0.58, 95%CI 0.41, 0.82). The effect was greater among women than men. CONCLUSIONS: OAT receipt during incarceration is associated with a reduced hazard of nonfatal overdose after release. Policies to expand access to OAT in correctional facilities, including initiating treatment, may help reduce harms related to nonfatal overdose in the weeks following release. Differences in the effect seen among women and men indicate a need for gender-responsive policies and programming.
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Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Humanos , Masculino , Feminino , Colúmbia Britânica/epidemiologia , Adulto , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Analgésicos Opioides/uso terapêutico , Prisões/estatística & dados numéricos , Adolescente , Tratamento de Substituição de Opiáceos/métodos , Prisioneiros/estatística & dados numéricos , Overdose de Opiáceos/tratamento farmacológico , Overdose de Opiáceos/epidemiologiaRESUMO
Performance testing of gamma cameras and single photon computed tomography/computed tomography (SPECT/CT) systems is not subject to regulatory requirements across states and territories in Australia. Internationally recognised testing standards from organisations such as the National Electrical Manufacturers Association (NEMA) describe methodologies for recommended tests. However, variations exist in suggested quality control (QC) schedules from professional bodies such as the Australia and New Zealand Society of Nuclear Medicine (ANZSNM). In this study, a survey was conducted to benchmark current QC programs across a selected sample of eight standalone and networked Australian public hospitals. Vendor-specific flood-field uniformity (intrinsic or extrinsic/system) verification without photomultiplier (PMT) tuning and CT QC were performed at all sites. Weekly and monthly PMT tuning followed by intrinsic flood-field verifications were performed at most sites. At least half of the sites performed monthly centre of rotation (COR) offset verifications. SPECT/CT alignment calibrations and verifications were undertaken by service engineers at all sites, and periodic verifications were performed by local staff at varying frequencies. Variations were observed for other periodic QC tests such as spatial resolution and planar sensitivity. Similarly, variations were observed for tests specific to whole-body systems and SPECT systems. Most sites checked daily and periodic QC results against pass/fail criteria set by vendors. Additional analyses of the QC results, including trend analysis and periodic reviews, were not common practice. The lack of regulatory requirements is likely to have led to variations in QC tests that are generally either harder to perform or are more labour intensive.
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BACKGROUND: The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations. METHODS: This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts. RESULTS: Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)]. CONCLUSIONS: Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk). IMPACT: These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.
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Detecção Precoce de Câncer , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Estudos Longitudinais , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Adulto , Detecção Precoce de Câncer/métodos , Pessoa de Meia-Idade , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Colúmbia Britânica/epidemiologia , Esfregaço Vaginal/métodos , Lesões Pré-Cancerosas/virologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Papillomaviridae/isolamento & purificação , CitologiaRESUMO
The grey garden slug (Deroceras reticulatum), a common terrestrial slug native to Europe with a global distribution including North America, is commonly considered the most severe slug pest in agriculture. The nematode Phasmarhabditis hermaphrodita, which has been used in the U.K. and Europe as a commercial biocontrol agent since 1994, has also recently been collected in Oregon and California and has long been considered a candidate biocontrol agent for slug management in the U.S. In this study, we report differential gene expressions in nematode-infected slugs using RNA-seq to identify slug immune-related genes against nematodes. Comparison of gene expression levels between the whole bodies of a nematode-infected slug (N-S) and an uninfected control slug (C-S) revealed that there were a total of 39,380 regulated unigenes, of which 3084 (3%) were upregulated and 6761 (6%) were downregulated at greater than 2-fold change (FC > 2) in the nematode-infected slug. To further investigate the biological functions of differentially expressed genes (DEGs), gene ontology (GO) and functional enrichment analysis were performed to map the DEGs to terms in the GO, eukaryotic ortholog groups of proteins (KOG) and Kyoto Encyclopedia of Genes and Genome Pathway (KEGG) databases. Among these DEGs, approximately 228 genes associated with immunity or immune-related pathways were upregulated 2-fold or more in the N-S compared to C-S. These genes include toll, Imd, JNK, scavenger receptors (SCRs), C-type lectins (CTLs), immunoglobulin-like domains, and JAK/STAT63 signaling pathways. From the RNA-seq results, we selected 18 genes and confirmed their expression levels by qRT-PCR. Our findings provide insights into the immune response of slugs during nematode infection. These studies provide fundamental information that will be valuable for the development of new methods of pest slug control using pathogenic nematodes in the field.
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This study aimed to assess the self-reported frequency and severity of gastrointestinal symptoms (GIS) at rest and around rugby training and match play in male and female rugby union players. An online questionnaire was sent to registered rugby union players (sevens or fifteens). Thirteen GIS were assessed alongside perceptions of appetite around rugby and rest using Likert and visual analog scales. Questions investigating a range of medical and dietary factors were included. Three hundred and twenty-five players (male n=271, female n=54) participated in the study. More frequent GIS (at least one GIS experienced weekly/more often) was reported by players at rest (n=203; 62%) compared to around rugby (n=154; 47%). The overall severity of GIS was low (mild discomfort), but a portion of players (33%) did report symptoms of moderate severity around rugby. Female players reported more frequent and severe symptoms compared to male counterparts (p<0.001). Self-reported appetite was significantly lower after matches compared to training. There were no dietary or medical factors associated with GIS severity scores. This study describes GIS characteristics in male and female rugby union players. Half of the players assessed experienced some form of GIS that may affect nutrition, training, or performance, and should thus be a consideration for practitioners supporting this cohort.
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Futebol Americano , Humanos , Masculino , Feminino , Rugby , Estado NutricionalRESUMO
BACKGROUND: Eating disorder diagnoses and disordered eating behaviours are more prevalent in people living with Type 1 Diabetes Mellitus, in particular in adolescents. The role of the dietitian in this setting is not clearly outlined in the literature. AIM: This scoping review aims to outline the available information for the role of the dietitian in identifying and managing eating disorders in adolescents and adults with co-occurring Type 1 Diabetes Mellitus (T1DM) in a clinical setting. METHODS: The Johanna Briggs Institute was utilised to guide this scoping review and to develop a search strategy for relevant databases. Relevant organisations and societies websites and professional magazines were reviewed as part of the grey literature search. RESULTS: 38 peer reviewed journal articles, 5 professional articles, 5 book chapters and 11 clinical guidelines were included in this scoping review. Roles for the dietitian in identification, prevention and screening for eating disorders in Type 1 Diabetes Mellitus were identified and outlined in a visual workflow. The role of the dietitian in the management of eating disorder in both the outpatient/community and inpatient setting and as core member of the multidisciplinary team was detailed in the literature. CONCLUSION: This scoping review mapped the available information in the current literature on the role of the dietitian in the identification and management of eating disorders and disordered eating in adolescents and adults with a dual diagnosis of T1DM. The reviewed literature suggests there is a strong reliance on expert opinion and practice to inform the role of the dietitian. Further research is required in order to ensure more robust evidence-based practice in this area.
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Diabetes Mellitus Tipo 1 , Transtornos da Alimentação e da Ingestão de Alimentos , Nutricionistas , Adulto , Humanos , Adolescente , Diabetes Mellitus Tipo 1/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Pacientes AmbulatoriaisRESUMO
Vitiligo is a complex disease with a multifactorial nature and a high impact on the quality of life of patients. Although there are multiple therapeutic alternatives, there is currently no fully effective treatment for this disease. In the current era, multiple drugs are being developed for the treatment of autoimmune diseases. This review assesses the available evidence on the pathogenesis of vitiligo, and a comprehensive review of treatments available for vitiligo now and in the near future is provided. This qualitative analysis spans 116 articles. We reviewed the mechanism of action, efficacy and safety data of phototherapy, afamelanotide, cyclosporine, phosphodiesterase 4 inhibitors, trichloroacetic acid, basic fibroblast growth factor, tumor necrosis factor (TNF) inhibitors, secukinumab, pseudocatalase and janus kinase (JAK) inhibitors. At the moment, there is no clearly outstanding option or fully satisfactory treatment for vitiligo, so it is necessary to keep up the development of new drugs as well as the publication of long-term effectiveness and safety data for existing treatments.
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Inibidores de Janus Quinases , Vitiligo , Humanos , Vitiligo/tratamento farmacológico , Qualidade de Vida , Inibidores de Janus Quinases/uso terapêutico , Fototerapia , Resultado do TratamentoRESUMO
In 2017, British Columbia (BC) transferred responsibility for healthcare services in provincial correctional facilities from the Ministry of Public Safety and Solicitor General to the Ministry of Health. This study explored how healthcare leadership perceived the impact of the transfer on services, work-life, and job satisfaction. We conducted one-on-one interviews (n = 8) with healthcare managers and medical and administrative leadership within Correctional Health Services. Using the Two-Factor theory of job satisfaction as a framework, we applied Interpretive Description methodology to analyse interview data. Participants identified changes to four areas of the working environment: (1) staffing, equipment, and resources (2) systems of supervision and support (3) standards, policies, and quality improvement and (4) culture and orientation. These changes predominantly affected motivational factors of job satisfaction and were described as enriching the roles of managers and staff. Participants described improved autonomy and recognition of providers, increased quality of services delivered, and a shift toward patient-centred care. The perspectives of healthcare leaders provide new insight into the potential impact of transferring healthcare services in custody to a public healthcare system. Discussion of changes and their affects also provide practical learning for jurisdictions seeking to improve healthcare under a variety of governance and service-delivery models.
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Background: Shifting from cytology to human papillomavirus (HPV)-based cervical cancer screening will initially increase colposcopy referrals. The anticipated impact on health systems has been raised as a concern for implementation. It is unclear if the higher rate of colposcopy referrals is sustained after initial HPV-based screens or reverts to new lower baselines due to earlier detection and treatment of precancer. This study aimed to investigate long-term rates of colposcopy referrals after participation in HPV-based screening. Methods: Participants of HPV for Cervical Cancer Screening trial (HPV FOCAL) received one (HPV1, N = 6204) or two (HPV2, N = 9540) HPV-based screens. After exit, they returned to British Columbia's (BC) cytology screening program. A comparison cohort from the BC screening population (BCS, N = 1,140,745) was identified, mirroring trial inclusion criteria. All participants were followed for 10-14 years through the provincial screening registry. Colposcopy referral rates per 1000 screens were calculated for each group. Trial colposcopy referrals for HPV1 and HPV2 were calculated under two referral scenarios: (1) all HPV positive referred to colposcopy; (2) cytology triage with ASCUS or greater referred to colposcopy. Colposcopy referrals from post-trial screens in HPV1 an HPV2 and all screens in BCS were based on actual recommendations from the screening program. A multivariable flexible survival regression model compared hazard ratios (HR) throughout follow-up. Findings: Scenario 2 referral rates were higher during initial HPV screen(s) vs cytology screen (HPV1: 28 per 1000 screens (95% CI: 24, 33), HPV2: 32 per 1000 screens (95% CI: 29, 36), BCS: 8 per 1000 screens (95% CI: 8.9)). However, post-trial rates in HPV1 and HPV2 were significantly lower than in BCS. Cumulative rates in HPV1 and HPV2 approached the cumulative rate in BCS 11-12 years after HPV-based screening (HPV1: 11 per 1000 screens (95% CI: 10, 12), HPV2: 16 per 1000 screens (95% CI: 15-17), BCS: 11 per 1000 screens (95% CI: 10, 11)). Adjusted models demonstrated reductions in referral rates in HPV1 (HR = 0.6, 95% CI: 0.5, 0.7) and HPV2 (HR = 0.7, 95% CI: 0.6, 0.8) relative to BCS by 54 and 72 months post-final HPV screen respectively. Interpretation: Reduced colposcopy referral rates were observed after initial rounds of HPV-based screening. After initial HPV screening, referral rates to colposcopy after cytology triage were below the current rates seen in a centralized cytology program after approximately four years. Any expected increase in referrals at initiation of HPV-based screening could be countered by staged program implementation. Funding: This work was supported by the National Institutes of Health (R01 CA221918), Michael Smith Health Research BC (RT-2021-1595), and the Canadian Institutes of Health Research (MCT82072).
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BACKGROUND: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902). METHODS: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines. The ability of ABBV-467 to induce tumor growth inhibition was investigated in xenograft models of human multiple myeloma and acute myelogenous leukemia. The first-in-human study was a multicenter, open-label, dose-escalation study assessing safety, pharmacokinetics, and efficacy of ABBV-467 monotherapy. RESULTS: Here we show that administration of ABBV-467 to MCL-1-dependent tumor cell lines triggers rapid and mechanism-based apoptosis. In vivo, intermittent dosing of ABBV-467 as monotherapy or in combination with venetoclax inhibits the growth of xenografts from human hematologic cancers. Results from a clinical trial evaluating ABBV-467 in patients with multiple myeloma based on these preclinical data indicate that treatment with ABBV-467 can result in disease control (seen in 1 patient), but may also cause increases in cardiac troponin levels in the plasma in some patients (seen in 4 of 8 patients), without other corresponding cardiac findings. CONCLUSIONS: The selectivity of ABBV-467 suggests that treatment-induced troponin release is a consequence of MCL-1 inhibition and therefore may represent a class effect of MCL-1 inhibitors in human patients.
Apoptosis is a type of cell death that removes abnormal cells from the body. Cancer cells can have increased levels of MCL-1, a protein that helps cells survive and prevents apoptosis. ABBV-467 is a new drug that blocks the action of MCL-1 (an MCL-1 inhibitor) and could promote apoptosis. In animal models, ABBV-467 led to cancer cell death and delayed tumor growth. ABBV-467 was also studied in a clinical trial in 8 patients with multiple myeloma, a blood cancer. In 1 patient, ABBV-467 treatment prevented the cancer from getting any worse for 8 months. However, in 4 out of 8 patients ABBV-467 increased the levels of troponin, a protein associated with damage to the heart. This concerning side effect may impact the future development of MCL-1 inhibitors as anticancer drugs.
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To explore the transition from correctional facilities to community among women living with HIV in Vancouver, Canada, we interviewed 19 recently incarcerated women and 6 service providers. Findings highlighted heightened risk of violence at release, a lack of immediate supports, challenges accessing safe housing and addictions treatment, and interruptions in HIV treatment and care. In the face of structural barriers, women blamed themselves for not being able to break the cycle of incarceration. There is a critical need for enhanced pre-release planning with a priority on housing and substance use services, alongside supports that are trauma-and violence-informed and culturally safe.
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Intravenous (IV) administration of poorly water-soluble small molecule therapeutics can lead to precipitation during mixing with blood. This can limit characterization of pharmacological and safety endpoints in preclinical models. Most often, tests of kinetic and thermodynamic solubility are used to optimize the formulation for solubility prior to infusion in animals, but these do not capture the dynamic precipitation processes that take place during in-vivo administration. To better capture the fluid dynamic processes that occur during IV administration, we developed the Optical Spatial PREcipitation analYzer (OSPREY) as a method to quantify the amount and size of compound precipitates in whole blood using a flow-through system that mimics IV administration. Here, we describe the OSPREY device and its underlying imaging processing methods. We then validate the ability to accurately segment particles according to their size using monodisperse suspensions of microspheres (diameter 50 to 425 µm). Next, we use a tool compound, ABT-737, to study the effects of compound concentration, vessel flow rate, compound infusion rate and vessel diameter on precipitation. Finally, we use the physiological diameter and flow rate of rat femoral vein and dog saphenous vein to demonstrate the potential of OSPREY to model in-vivo precipitation in a controlled, dynamic in-vitro assay.
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Água , Ratos , Animais , Cães , Injeções , Solubilidade , Precipitação QuímicaRESUMO
ABSTRACT: Women living with HIV are increasingly incarcerated and experience suboptimal HIV health outcomes post release from incarceration. Drawing on cohort data with cisgender and trans women living with HIV (Sexual Health and HIV/AIDS: Women's Longitudinal Needs Assessment), we used path analysis to investigate pathways from recent incarceration to optimal antiretroviral therapy (ART) adherence. We tested direct effects between recent incarceration, mediating variables, and ART adherence, along with indirect effects between incarceration and ART adherence through each mediator. We assessed model fit using chi-square, root-mean-square error of approximation (RMSEA), and comparative fit index (CFI). Our hypothesized model fit well to the data (χ2(1)=1.100; p=.2943; CFI = 1.000; RMSEA = 0.007). Recent experiences of homelessness, criminalized substance use, and gender-based violence each fully mediated the pathway between recent incarceration and optimal ART adherence. Findings highlight the need for safe and supportive housing, supports for criminalized substance use, and trauma and violence-informed care and practice post release from incarceration.
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Infecções por HIV , Prisioneiros , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Adesão à Medicação , Estabelecimentos CorrecionaisRESUMO
Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.
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Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controleRESUMO
The voltage-gated sodium channel Nav1.7 is an attractive target for the treatment of pain based on the high level of target validation with genetic evidence linking Nav1.7 to pain in humans. Our effort to identify selective, CNS-penetrant Nav1.7 blockers with oral activity, improved selectivity, good drug-like properties, and safety led to the discovery of 2-substituted quinolines and quinolones as potent small molecule Nav1.7 blockers. The design of these molecules focused on maintaining potency at Nav1.7, improving selectivity over the hERG channel, and overcoming phospholipidosis observed with the initial leads. The structure-activity relationship (SAR) studies leading to the discovery of (R)-(3-fluoropyrrolidin-1-yl)(6-((5-(trifluoromethyl)pyridin-2-yl)oxy)quinolin-2-yl)methanone (ABBV-318) are described herein. ABBV-318 displayed robust in vivo efficacy in both inflammatory and neuropathic rodent models of pain. ABBV-318 also inhibited Nav1.8, another sodium channel isoform that is an active target for the development of new pain treatments.
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Dor , Canais de Sódio , Humanos , Dor/tratamento farmacológico , Manejo da Dor , Isoformas de Proteínas , Canais de Sódio/metabolismo , Relação Estrutura-AtividadeRESUMO
While cervix screening using cytology is recommended at 2- to 3-year intervals, given the increased sensitivity of human papillomavirus (HPV)-based screening to detect precancer, HPV-based screening is recommended every 4- to 5-years. As organized cervix screening programs transition from cytology to HPV-based screening with extended intervals, there is some concern that cancers will be missed between screens. Participants in HPV FOr CervicAL Cancer (HPV FOCAL) trial received cytology (Cytology Arm) at 24-month intervals or HPV-based screening (HPV Arm) at 48-month intervals; both arms received co-testing (cytology and HPV testing) at exit. We investigated the results of the co-test to identify participants with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) who would not have had their precancer detected if they had only their arm's respective primary screen. In the Cytology Arm, 25/62 (40.3%) identified CIN2+s were missed by primary screen (ie, normal cytology/positive HPV test) and all 25 had normal cytology at the prior 24-month screen. In the HPV arm, three CIN2+s (3/49, 6.1%) were missed by primary screen (ie, negative HPV test/abnormal cytology). One of these three misses had low-grade cytology findings and would also not have been referred to colposcopy outside of the trial. Multiple rounds of cytology did not detect some precancerous lesions detected with one round of HPV-based screening. In our population, cytology missed more CIN2+, even at shorter screening intervals, than HPV-based screening. This assuages concerns about missed detection postimplementation of an extended interval HPV-based screening program. We recommend that policymakers consider a shift from cytology to HPV-based cervix screening.
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Alphapapillomavirus , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Colposcopia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Gravidez , Esfregaço VaginalRESUMO
Given sub-optimal HIV care outcomes for people living with HIV (PLWH) post-release from incarceration, we systematically searched peer-reviewed literature (2010-2021) describing controlled trial interventions aimed at improving Antiretroviral Therapy (ART) adherence and care linkage following release from correctional facilities for PLWH. Of 392 studies, 16 (4%) met the inclusion criteria. All studies were conducted in the United States and involved some form of intensive case management. Trials that scored highest in terms of study quality provided cell phones for engagement, reported sustained viral load suppression as a measurable outcome to infer ART adherence, and measured longitudinal data collected for at least 3-to-6 months following release. The two trials that demonstrated improved HIV viral load suppression involved Peer Navigators, and incentivized undetectable viral load, respectively. Facilitating support for addictions and addressing other social and structural barriers to achieving optimal health is also of vital importance in bridging care gaps for PLWH.
RESUMEN: Debido a los resultados suboptimos en los cuidados de las personas que viven con VIH después de su liberación del encarcelamiento, nosotros realizamos una revisión sistemática de la literatura (20102021) que describe ensayos control de intervenciones para mejorar la adherencia a la terapia antiretrovirales (TAR) y el vinculo con la atención medica después de la liberación del encarcelamiento de las personas que viven con VIH. De los 392 estudios, 16 (4%) cumplieron con los criterios de inclusión. Todos los estudios fueron realizados en los Estados Unidos e incluyen alguna forma de cuidados con manejo intensivo. Los ensayos que tenían los puntajes mas altos en términos de calidad proveían teléfonos celulares para la vinculación, reportaban supresión de la carga viral sostenida como medida indirecta de adherencia al TAR, y han medido datos longitudinales por lo menos de tres a seis meses después de la liberación carcelaria. Los dos ensayos que demostraron mejora en la supresión de la carga viral del VIH involucraban a los pares navegadores e incentivaban la carga viral no detectable, respectivamente. Facilitando el soporte para la adicción y el entendimiento de otras barreras sociales y estructurales para alcanzar una salud optima, es de vital importancia para superar las brechas en la atención de las personas que viven con VIH.