丹红注射液的毒理学研究

目的 观察丹红（倍通）注射液的急慢性毒性，对其进行安全性评价。方法 小鼠连续7d静脉给药，测定药物的半数致死量（LD50）。大鼠连续给药90d后，处死大部动物，取血，做血常规、血液生化指标测定，取主要脏器称重进行病理学检查。余下大鼠在停药继续喂养2周后，处死进行病理组织学检查。结果 小鼠LD50为39．5ml／kg。各实验组大鼠在体质量增加、器官系数、血常规、血液生化指标上基本相似，与对照组比较差异无统计学意义（P〉0．05）。主要脏器的病理组织学检查未见明显异常。结论 急慢性毒性实验的结果表明该药安全可靠。     

Peer community health workers improve HIV testing and ART linkage among key populations in Zambia: retrospective observational results from the Z‐CHECK project, 2019–2020

IntroductionZambia has made tremendous progress towards HIV epidemic control; however, gaps remain among key populations (KPs), such as female sex workers (FSWs), men who have sex with men (MSM), people who inject drugs (PWID) and people in prisons and enclosed settings due to cultural, social and legal barriers. The University of Maryland, Baltimore Zambia Community HIV Epidemic Control for Key Populations (Z‐CHECK) project aimed to improve HIV case‐finding, linkage and treatment adherence at the community level for KPs in Zambia. We describe Z‐CHECK strategies and examine HIV positivity yield and antiretroviral therapy (ART) linkage among KPs to inform ongoing programme improvement.MethodsZ‐CHECK recruited, trained and deployed peer community health workers (CHWs) for KP groups, with ongoing mentorship in community engagement. CHWs offered HIV testing in safe spaces and escorted newly HIV‐diagnosed clients for same‐day ART initiation. Z‐CHECK also reached out to KP community leaders and gatekeepers for KP mobilization and trained healthcare workers (HCWs) on KP services and sensitivity. We conducted a retrospective observational review of routinely collected aggregate data for KPs aged ≥15 years at high risk for HIV transmission across five districts in Zambia from January 2019 to December 2020.ResultsZ‐CHECK provided HIV testing for 9211 KPs, of whom 2227 were HIV positive (positivity yield, 24%). Among these, 1901 (85%) were linked to ART; linkage for MSM, FSW, PWID and people in prisons and enclosed settings was 95%, 89%, 86% and 65%, respectively. Programme strategies that contributed to high positivity yield and linkage included the use of peer KP CHWs, social network testing strategies and opportunities for same‐day ART initiation. Challenges to programme implementation included stigma and discrimination among HCWs, as well as KP CHW attrition, which may be explained by high mobility.ConclusionsPeer CHWs were highly effective at reaching KP communities, identifying persons living with HIV and linking them to care. Engaging KP community gatekeepers resulted in high diffusion of health messages and increased access to health resources. The mobility of CHWs and HCWs is a challenge for programme implementation. Innovative interventions are needed to support PWID and people in prisons and enclosed settings.     

A Testing Campaign Intervention Consisting of Peer-Facilitated Engagement,Point-of-Care HCV RNA Testing,and Linkage to Nursing Support to Enhance Hepatitis C Treatment Uptake among People Who Inject Drugs: The ETHOS Engage Study

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018–September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.     

Does informing people who inject drugs of their hepatitis C status influence their injecting behaviour? Analysis of the Networks II study

BackgroundPeople who inject drugs (PWID) are at risk of hepatitis C virus (HCV). It is plausible that PWID who receive a diagnosis of HCV will reduce their injecting risk out of concern for their injecting partners, although evidence for this is currently limited. The aim of this study was to investigate whether informing PWID of their HCV diagnosis was associated with a change in injecting behaviour.MethodsProspective, longitudinal study of PWID recruited from street drug markets across Melbourne, Australia. Interviews and HCV testing were conducted at 3-monthly intervals. The association between receiving a diagnosis of HCV and (i) injecting frequency and (ii) injecting equipment borrowing, was examined using generalized estimating equations (GEE) analysis.ResultsThirty-five individuals received a diagnosis of HCV during the study period. Receiving a diagnosis of HCV was associated with a decrease of 0.35 injections per month (p = 0.046) but there was no change in injecting equipment borrowing (p = 0.750).ConclusionsA small reduction in injecting frequency was observed in PWID who received a diagnosis of HCV. This finding should be investigated further in larger studies examining a wider range of injecting risk behaviours.     

Intersecting epidemics of HIV,HCV, and syphilis among soon-to-be released prisoners in Kyrgyzstan: Implications for prevention and treatment

BackgroundCentral Asia is afflicted with increasing HIV incidence, low antiretroviral therapy (ART) coverage and increasing AIDS mortality, driven primarily by people who inject drugs (PWID). Reliable data about HIV, other infectious diseases, and substance use disorders in prisoners in this region is lacking and could provide important insights into how to improve HIV prevention and treatment efforts in the region.MethodsA randomly sampled, nationwide biobehavioural health survey was conducted in 8 prisons in Kyrgyzstan among all soon-to-be-released prisoners; women were oversampled. Consented participants underwent computer-assisted, standardized behavioural health assessment surveys and testing for HIV, HCV, HBV, and syphilis. Prevalence and means were computed, and generalized linear modelling was conducted, with all analyses using weights to account for disproportionate sampling by strata.ResultsAmong 381 prisoners who underwent consent procedures, 368 (96.6%) were enrolled in the study. Women were significantly older than men (40.6 vs. 36.5; p = 0.004). Weighted prevalence (%), with confidence interval (CI), for each infection was high: HCV (49.7%; CI: 44.8–54.6%), syphilis (19.2%; CI: 15.1–23.5%), HIV (10.3%; CI: 6.9–13.8%), and HBV (6.2%; CI: 3.6–8.9%). Among the 31 people with HIV, 46.5% were aware of being HIV-infected. Men, compared to women, were significantly more likely to have injected drugs (38.3% vs.16.0%; p = 0.001). Pre-incarceration and within-prison drug injection, primarily of opioids, was 35.4% and 30.8%, respectively. Independent correlates of HIV infection included lifetime drug injection (adjusted odds ratio [AOR] = 38.75; p = 0.001), mean number of years injecting (AOR = 0.93; p = 0.018), mean number of days experiencing drug problems (AOR = 1.09; p = 0.025), increasing duration of imprisonment (AOR = 1.08; p = 0.02 for each year) and having syphilis (AOR = 3.51; p = 0.003), while being female (AOR = 3.06; p = 0.004) and being a recidivist offender (AOR = 2.67; p = 0.008) were independently correlated with syphilis infection.ConclusionDrug injection, syphilis co-infection, and exposure to increased risk during incarceration are likely to be important contributors to HIV transmission among prisoners in Kyrgyzstan. Compared to the community, HIV is concentrated 34-fold higher in prisoners. A high proportion of undiagnosed syphilis and HIV infections presents a significant gap in the HIV care continuum. Findings highlight the critical importance of evidence-based responses within prison, including enhanced testing for HIV and sexually transmitted infections, to stem the evolving HIV epidemic in the region.     

Lower life expectancy among people with an HCV notification: a population‐based linkage study

Among people with hepatitis C virus (HCV) infection, liver disease‐related deaths have risen over the last 20 years. Life expectancy has not been estimated in this population. HCV notifications (mandatory notification of anti‐HCV‐positive serology since 1991) reported to the New South Wales Health Department from 1992 to 2006 were linked to cause of death data. Abridged life tables were constructed from age‐specific mortality rates. Life expectancy from ages 18–70 years for non‐drug‐related mortality causes was estimated using competing risk methods and compared to the general population of Australia. The cohort comprised 81 644 individuals with an HCV notification, with median follow‐up of 7.6 years. Median age at notification was 34 years [interquartile range (IQR) 28–42] and 63% were male. Between 1992 and 2006, 4607 deaths occurred. Median age at liver‐ and drug‐related death among males was 51 (IQR 45–66) and 36 (IQR 31–42) years, respectively, and among females was 63 (IQR 49–74) and 36 (IQR 30–41) years, respectively. In each year of follow‐up before 2000, 15–21% of deaths were liver‐ and 30–39% were drug‐related. After 2000, liver‐related deaths increased to 20–26% of deaths in each year and drug‐related deaths decreased to 13–19%. Excluding drug‐related causes of death, life expectancy was lowered by an average of 4.2 (SD ± 1.0) and 5.4 (SD ± 0.7) years for males and females, respectively. Among people with an HCV notification, an increasing proportion of deaths are liver‐related. Following removal of drug‐related mortality, life expectancy in this population remained considerably lower, compared with the general population.     

Need of structural interventions for linking people who inject drugs with antiretroviral treatment: A qualitative study

Objective: People who inject drugs (PWIDs) are highly vulnerable to acquiring HIV infection. Existing interventions have not succeeded in linking PWIDs to antiretroviral treatment (ART). Structural interventions (SIs) or public health interventions that alter the structural context need investigation for a suitable linking to care (LIC) strategy.

Methods: We conducted in-depth interviews with 31 HIV-infected PWIDs. Using a thematic approach, interviews were stopped on reaching saturation of themes.

Results: Personal barriers like denial of HIV status, fatalistic attitude, inability to find time because of earning livelihood, or money for their drugs, transportation difficulties and hospital level barriers like time required for registration, crowd at the hospital, and difficulty traversing departments dissuaded LTC. Using social networks, drug peddlers or provision through mobile health units were accepted as feasible alternatives.

Conclusion: PWIDs face various barriers to LTC. SIs are required for LTC of PWIDs. Storytelling for educational campaign, mobile health units at hot spots to provide HIV test and ART, and using social networks and drug peddlers to assist with education and LTC are suggested.

Practice implications: Existing interventions have not succeeded in reducing HIV prevalence as well as linking to ART care. New SI interventions need to be experimented for LTC.

Abbreviations: AIDS: autoimmune deficiency syndrome; ART: antiretroviral treatment; HIV: human immunodeficiency virus; LTC: linking to care; PWID: people who inject drugs; SI: structural Interventions; TB: htuberculosis Bacillus infection     

Prospective Cohort Study of Infective Endocarditis in People Who Inject Drugs

BackgroundInfective endocarditis (IE) in people who inject drugs (PWID) is an emergent public health problem.ObjectivesThe purpose of this study was to investigate IE in PWID and compare it with IE in non-PWID patients.MethodsTwo prospective cohort studies (ICE-PCS and ICE-Plus databases, encompassing 8,112 IE episodes from 2000 to 2006 and 2008 to 2012, with 64 and 34 sites and 28 and 18 countries, respectively). Outcomes were compared between PWID and non-PWID patients with IE. Logistic regression analyses were performed to investigate risk factors for 6-month mortality and relapses amongst PWID.ResultsA total of 7,616 patients (591 PWID and 7,025 non-PWID) were included. PWID patients were significantly younger (median 37.0 years [interquartile range: 29.5 to 44.2 years] vs. 63.3 years [interquartile range: 49.3 to 74.0 years]; p < 0.001), male (72.5% vs. 67.4%; p = 0.007), and presented lower rates of comorbidities except for human immunodeficiency virus, liver disease, and higher rates of prior IE. Amongst IE cases in PWID, 313 (53%) episodes involved left-side valves and 204 (34.5%) were purely left-sided IE. PWID presented a larger proportion of native IE (90.2% vs. 64.4%; p < 0.001), whereas prosthetic-IE and cardiovascular implantable electronic device-IE were more frequent in non-PWID (9.3% vs. 27.0% and 0.5% vs. 8.6%; both p < 0.001). Staphylococcus aureus caused 65.9% and 26.8% of cases in PWID and non-PWID, respectively (p < 0.001). PWID presented higher rates of systemic emboli (51.1% vs. 22.5%; p < 0.001) and persistent bacteremia (14.7% vs. 9.3%; p < 0.001). Cardiac surgery was less frequently performed (39.5% vs. 47.8%; p < 0.001), and in-hospital and 6-month mortality were lower in PWID (10.8% vs. 18.2% and 14.4% vs. 22.2%; both p < 0.001), whereas relapses were more frequent in PWID (9.5% vs. 2.8%; p < 0.001). Prior IE, left-sided IE, polymicrobial etiology, intracardiac complications, and stroke were risk factors for 6-month mortality, whereas cardiac surgery was associated with lower mortality in the PWID population.ConclusionsA notable proportion of cases in PWID involve left-sided valves, prosthetic valves, or are caused by microorganisms other than S. aureus.