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1.
Am J Disaster Med ; 19(2): 91-100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698507

RESUMO

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the first of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee workgroup conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product exploring disaster healthcare disparities seen in disaster. Many solutions for disaster healthcare disparities during preparation were found. Some of these solutions have been successfully implemented, while others are still theoretical. Solutions for disaster healthcare disparities seen in disaster preparation are achievable, but there is still much work to do. There are a variety of solutions that can be easily advocated for by disaster and nondisaster specialists, leading to better care for our patients.


Assuntos
Planejamento em Desastres , Disparidades em Assistência à Saúde , Humanos , Planejamento em Desastres/organização & administração , Estados Unidos
2.
Am J Disaster Med ; 19(2): 109-117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698509

RESUMO

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the third of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product. Many solutions for disaster healthcare disparities seen during recovery and mitigation were found. Some of these solutions have been successfully implemented and some remain theoretical. Solutions for disaster healthcare disparities seen during recovery and mitigation are achievable but there is still much work to do. Many of these solutions can be advocated for by nondisaster specialists.


Assuntos
Planejamento em Desastres , Disparidades em Assistência à Saúde , Humanos , Planejamento em Desastres/organização & administração , Desastres , Estados Unidos
3.
Am J Disaster Med ; 19(2): 101-108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698508

RESUMO

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the second of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product. Many solutions for disaster healthcare disparities during disaster response were found. Some of these solutions have been successfully implemented and some are hypothetical. Solutions for disaster healthcare disparities seen during response are achievable but there is still much work to do. A variety of the proposed solutions can be advocated for by nondisaster specialists leading to better care for all our patients.


Assuntos
Planejamento em Desastres , Disparidades em Assistência à Saúde , Humanos , Planejamento em Desastres/organização & administração , Estados Unidos , Desastres
4.
Open Forum Infect Dis ; 11(4): ofae155, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651137

RESUMO

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

5.
J Infect Dis ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655824

RESUMO

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesised these differences may be due to virus-specific effects on mitochondrial function. METHODS: Seahorse technology was utilised to investigate effects of virus infection on mitochondrial function. Cell based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV expressing, HCV infected and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real time PCR and western blot. RESULTS: Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impairs glycolysis and reduces expression of genes regulating fatty acid oxidation, promoting lipid accumulation. HBV causes lactate accumulation by increasing expression of lactate dehydrogenase A, which converts pyruvate to lactate. In HBV expressing cells there was marked enrichment of pyruvate dehydrogenase kinase, inhibiting conversion of pyruvate to acetyl-CoA and thereby reducing its availability for mitochondrial oxidative phosphorylation. CONCLUSIONS: HCV and HBV impair mitochondrial function and reduce ATP production. HCV reduces acetyl-CoA availability for energy production by impairing fatty acid oxidation, causing lipid accumulation and hepatic steatosis. HBV has no effect on fatty oxidation but reduces acetyl-CoA availability by disrupting pyruvate metabolism. This promotes lactic acidosis and oxidative stress, increasing the risk of disease progression and liver cancer.

6.
J Infect Dis ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408366

RESUMO

Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all these viruses rely on secretion through the host endoplasmic reticulum-Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions and HBV subviral particles. Moreover, in a cohort of people with hepatitis B a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.

7.
Viruses ; 15(11)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38005851

RESUMO

Chronic hepatitis B affects >300 million people worldwide and is a major cause of liver disease, causing ~800,000 deaths each year [...].


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética
8.
EClinicalMedicine ; 64: 102203, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37719417

RESUMO

Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2-8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27-2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32-0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69-3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26-0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3-2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

9.
Life Sci Alliance ; 6(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37648284

RESUMO

Polo-like kinase 1 (PLK1) is a regulator of cell mitosis and cytoskeletal dynamics. PLK1 overexpression in liver cancer is associated with tumour progression, metastasis, and vascular invasion. Hepatitis C virus (HCV) NS5A protein stimulates PLK1-mediated phosphorylation of host proteins, so we hypothesised that HCV-PLK1 interactions might be a mechanism for HCV-induced liver cancer. We used a HCV cell-culture model (Jc1) to investigate the effects of virus infection on the cytoskeleton. In HCV-infected cells, a novel posttranslational modification in ß-actin was observed with phosphorylation at Ser239. Using in silico and in vitro approaches, we identified PLK1 as the mediating kinase. In functional experiments with a phosphomimetic mutant form of ß-actin, Ser239 phosphorylation influences ß-actin polymerization and distribution, resulting in increased cell motility. The changes were prevented by treating cells with the PLK1 inhibitor volasertib. In HCV-infected hepatocytes, increased cell motility contributes to cancer cell migration, invasion, and metastasis. PLK1 is an important mediator of these effects and early treatment with PLK1 inhibitors may prevent or reduce HCC progression, particularly in people with HCV-induced HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Hepacivirus , Actinas , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Movimento Celular/genética , Quinase 1 Polo-Like
11.
Int J Mol Sci ; 24(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37240132

RESUMO

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis.


Assuntos
Fígado Gorduroso , Hepatite C Crônica , Hepatite C , Humanos , Hepacivirus/genética , Hepacivirus/metabolismo , Transferases/metabolismo , Hepatite C/genética , Fígado Gorduroso/patologia , Replicação Viral , Genótipo , Colesterol/metabolismo , Fosfatidilcolinas/metabolismo , Fenótipo , Fosfatidiletanolamina N-Metiltransferase/genética
12.
Mil Med ; 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37042677

RESUMO

Syphilis is becoming an increasingly concerning sexually transmitted infection in the primary care setting with a precipitous rise in cases in the USA over the past decade according to the CDC surveillance data. This rise in cases is particularly relevant in military medicine as the greatest increase in cases is among adults in their 20s. Nodular syphilis is a rare presentation of the secondary stage of syphilis, and contrary to the well-known maculopapular rash seen with syphilis infection, little is known about effective treatment of nodular manifestations of the disease. We present a case of a 54-year-old HIV-positive man with nodular secondary syphilis effectively treated with an empiric 2-week course of oral doxycycline. Initial differential diagnosis included erythema nodosum, arthropod vector disease, skin infection, and erythema elevatum diutinum. Biopsy demonstrated granulomatous dermatitis, and serology revealed positive Treponema pallidum antibodies with a rapid plasma reagin of 1:256, confirming the diagnosis of secondary syphilis with granulomatous dermatitis. This case indicates that clinicians should consider this unusual cutaneous presentation of secondary syphilis when evaluating patients with nodular skin lesions, especially in high-risk individuals.

13.
EBioMedicine ; 90: 104545, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37002990

RESUMO

BACKGROUND: The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and the related sub-lineage BA.5. Following resolution of the global BA.5 wave, a diverse grouping of Omicron sub-lineages emerged derived from BA.2, BA.5 and recombinants thereof. Whilst emerging from distinct lineages, all shared similar changes in the Spike glycoprotein affording them an outgrowth advantage through evasion of neutralising antibodies. METHODS: Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants in the Australian community at three levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from stringently curated vaccine and convalescent cohorts. (iii) finally we determine the in vitro efficacy of clinically approved therapies Evusheld and Sotrovimab. FINDINGS: In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases, we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with isolates BQ.1.1, XBB.1, BR.2.1 and XBF the most evasive. Further, these emerging variants were resistant to Evusheld, whilst increasing neutralization resistance to Sotrovimab was restricted to BQ.1.1 and XBF. We conclude at this current point in time that dominant variants can evade antibodies at levels equivalent to their most evasive lineage counterparts but sustain an entry phenotype that continues to promote an additional outgrowth advantage. In Australia, BR.2.1 and XBF share this phenotype and, in contrast to global variants, are uniquely dominant in this region in the later months of 2022. INTERPRETATION: Whilst the appearance of a diverse range of omicron lineages has led to primary or partial resistance to clinically approved monoclonal antibodies, the maturation of the antibody response across both cohorts and a large donor pools importantly observes increasing breadth in the antibody neutralisation responses over time with a trajectory that covers both current and known emerging variants. FUNDING: This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (SGT, GM & WDR), Medical Research Future Fund Antiviral Development Call grant (WDR), the New South Wales Health COVID-19 Research Grants Round 2 (SGT & FB) and the NSW Vaccine Infection and Immunology Collaborative (VIIM) (ALC). Variant modeling was supported by funding from SciLifeLab's Pandemic Laboratory Preparedness program to B.M. (VC-2022-0028) and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb) to B.M.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias/prevenção & controle , COVID-19/prevenção & controle , Austrália/epidemiologia , Anticorpos Neutralizantes , Imunoglobulina G , Anticorpos Antivirais
15.
Am J Disaster Med ; 17(2): 171-184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36494888

RESUMO

OBJECTIVE: To review the literature on the effects seen after disaster on those with poor social determinants of health (SDOH) and individual social needs. DESIGN: The Disaster Preparedness and Response Committee of the American College of Emergency Physicians (ACEP) formed a work group to study healthcare disparities seen in disaster. This group was composed of six physicians on the committee, all of whom have extensive background in disaster medicine and the chair of the committee. A systematic literature review regarding past disasters and all the healthcare disparities seen was undertaken with the goal of organizing this information in one broad concise document looking at multiple disasters over history. The group reviewed multiple documents regarding SDOH and individual social needs for a complete understanding of these factors. Then, a topic list of healthcare disparities resulting from these factors was composed. This list was then filled out with subtopics falling under the header topics. Each member of the workgroup took one of these topics of healthcare disparity seen in disasters and completed a literature search. The databases reviewed include PubMed Central, Google Scholar, and Medline. The terms queried were disaster, healthcare disparities, disaster healthcare disparities, healthcare disparities associated with disasters, SDOH and disaster, special populations and disaster effects, and vulnerable populations and disaster effects. Each author chose articles they felt were most representative and demonstrative of the healthcare disparities seen in past disasters. These social determinant factors and individual social needs were then cross referenced in relation to past disasters for both their causes and the effect they had on various populations after disaster. This was presented to the ACEP board as a committee report. RESULTS: All the SDOH and individual social needs showed significant negative effects for the populations when combined with a disaster event. These SDOH cut across age, race, and gender affecting a wide swath of people. Previous disaster planning either did not plan or under planned for these marginalized populations during disaster events. CONCLUSIONS: Disparities in healthcare are a pervasive problem that effects many different groups. Disasters magnify and more fully expose these healthcare disparities. We have explored the healthcare disparities with past disasters. These disparities, although common, can be mitigated. The recognition of these poor determinants of health can lead to better and more comprehensive disaster planning for future disasters. Subsequent research is needed to explore these healthcare disparities exacerbated by disasters and to find methods for their mitigation.


Assuntos
Medicina de Desastres , Planejamento em Desastres , Desastres , Humanos , Inquéritos e Questionários , Atenção à Saúde
16.
JHEP Rep ; 4(9): 100514, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35898957

RESUMO

Background & Aims: The chronicity of HBV (and resultant liver disease) is determined by intrahepatic persistence of the HBV covalently closed circular DNA (cccDNA), an episomal form that encodes all viral transcripts. Therefore, cccDNA is a key target for new treatments, with the ultimate therapeutic aim being its complete elimination. Although established cccDNA molecules are known to be stable in resting hepatocytes, we aimed to understand their fate in dividing cells using in vitro models. Methods: We infected HepG2-NTCP and HepaRG-NTCP cells with HBV and induced mitosis by passaging cells. We measured cccDNA copy number (by precise PCR assays) and HBV-expressing cells (by immunofluorescence) with wild-type HBV. We used reporter viruses expressing luciferase or RFP to track number of HBV-expressing cells over time after mitosis induction using luciferase assays and live imaging, respectively. Results: In all cases, we observed dramatic reductions in cccDNA levels, HBV-positive cell numbers, and cccDNA-dependent protein expression after each round of cell mitosis. The rates of reduction were highly consistent with mathematical models of a complete cccDNA loss in (as opposed to dilution into) daughter cells. Conclusions: Our results are concordant with previous animal models of HBV infection and show that HBV persistence can be efficiently overcome by inducing cell mitosis. These results support therapeutic approaches that induce liver turnover (e.g. immune modulators) in addition to direct-acting antiviral therapies to achieve hepatitis B cure. Lay summary: Chronic hepatitis B affects 300 million people (killing 884,000 per year) and is incurable. To cure it, we need to clear the HBV genome from the liver. In this study, we looked at how the virus behaves after a cell divides. We found that it completely clears the virus, making 2 new uninfected cells. Our work informs new approaches to develop cures for chronic hepatitis B infections.

17.
Vaccines (Basel) ; 10(6)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35746497

RESUMO

Background: In this study, we determined the impact of the COVID-19 pandemic on Western Sydney patients with substance use disorders (SUD) by comparing emergency department (ED) admission rates before and after the onset of the COVID-19 pandemic and before the rollout of COVID-19 vaccination. Methods: ED admission data for patients with SUD were retrieved from the local electronic medical record (eMR) on the hospital central database. ED data collected from 25 January to 25 July 2019 (before the COVID-19 pandemic) were compared with data from 25 January to 25 July 2020 (early pandemic). ED admission reasons were categorised based on the presenting complaints and ED diagnoses. Results: Despite an overall reduction in ED admissions during the early pandemic, compared to the pre-pandemic period, admissions for patients with SUD increased significantly (1.7% to 3.4%, p < 0.01). ED admission rates related to infection (0.05% to 0.12%, p < 0.01), local infection (0.02% to 0.05%, p < 0.01), trauma (0.06% to 0.12%, p < 0.01), alcohol (0.01% to 0.03%, p < 0.05), and other issues (0.06% to 0.10%, p < 0.05) increased significantly among Indigenous patients with SUD. ED admission rates related to drugs (0.12% to 0.39%, p < 0.01), infection (0.21% to 0.34%, p < 0.01), local infection (0.07% to 0.18%, p < 0.01), gastrointestinal (0.15% to 0.23%, p < 0.05), trauma (0.14% to 0.25%, p < 0.01), alcohol (0.36% to 0.74%, p < 0.01), and 'other' issues (0.47% to 0.91%, p < 0.01) increased significantly among non-Indigenous patients with SUD. Four cases of COVID-19 were reported among these patients. Conclusions: There was an increase in ED admissions for patients with SUD in the initial six months of the COVID-19 pandemic (before vaccine rollout), mainly for drugs, systemic infection, local infection, trauma, and alcohol-related reasons. Now that most people in New South Wales have been vaccinated against COVID-19, a further study is needed to quantify the effect of the pandemic on patients with SUD in the post-vaccine era.

18.
JHEP Rep ; 4(5): 100462, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35434589

RESUMO

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.

19.
Am J Public Health ; 112(3): 417-425, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35196039

RESUMO

Community-based organizations (CBOs) are integral to achieving the goal of Ending the HIV epidemic (EHE). Their familiarity with and proximity to communities position them to effectively implement strategies necessary to address determinants of health through their formal and informal medical and social services. However, structural inequities have contributed to the demise of many organizations that were instrumental in early responses to the HIV epidemic. We define structural inequities for HIV CBOs as systems in which policies, institutional practices, organizational (mis)representations, and other norms work to produce and maintain inequities that affect CBOs' ability to survive and thrive. In this discussion, we describe the organizational threats to grassroots HIV CBOs and the risks to livelihood and longevity, including examples. The invaluable role of HIV CBOs in EHE and their role in responding to existing and novel infectious diseases like COVID-19 should not be overlooked. Recommendations to promote structural equity are offered. (Am J Public Health. 2022;112(3):417-425. https://doi.org/10.2105/AJPH.2021.306688).


Assuntos
Redes Comunitárias/organização & administração , Infecções por HIV/epidemiologia , Organizações sem Fins Lucrativos/organização & administração , Epidemias , Humanos , Organizações sem Fins Lucrativos/economia
20.
Lancet Planet Health ; 6(1): e59-e65, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34998461

RESUMO

Sustainable and resilient food systems depend on sustainable and resilient water management. Resilience is characterised by overlapping decision spaces and scales and interdependencies among water users and competing sectors. Increasing water scarcity, due to climate change and other environmental and societal changes, makes putting caps on the consumption of water resources indispensable. Implementation requires an understanding of different domains, actors, and their objectives, and drivers and barriers to transformational change. We suggest a scale-specific approach, in which agricultural water use is embedded in a larger systems approach (including natural and human systems). This approach is the basis for policy coherence and the design of effective incentive schemes to change agricultural water use behaviour and, therefore, optimise the water we eat.


Assuntos
Agricultura , Água , Mudança Climática , Humanos , Políticas , Abastecimento de Água
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