Opioid substitution therapy in manipur and nagaland, north-east india: operational research in action

<p>Abstract</p> <p>Background</p> <p>There is good evidence for the effectiveness of opioid substitution therapy (OST) for injecting drug users (IDUs) in middle and high-income countries but little evidence regarding the provision of OST by non-government organisations (NGOs) in resource-poor settings. This paper reports on outcomes of an NGO-based OST program providing sub-lingual buprenorphine to opiate dependent IDUs in two north-east Indian states (Manipur and Nagaland), a region where conflict, under-development and injecting of heroin and Spasmoproxyvon (SP) are ongoing problems. The objectives of the study were: 1) to calculate OST treatment retention, 2) to assess the impact on HIV risk behaviours and quality of life, and 3) to identify client characteristics associated with cessation of treatment due to relapse.</p> <p>Methods</p> <p>This study involves analysis of data that were routinely and prospectively collected from all clients enrolled in an OST program in Manipur and Nagaland between May 2006 and December 2007 (n = 2569, 1853 in Manipur and 716 in Nagaland) using standardised questionnaires, and is best classified as operational research. The data were recorded at intake into the program, after three months, and at cessation. Outcome measures included HIV risk behaviours and quality of life indicators. Predictors of relapse were modelled using binary logistic regression.</p> <p>Results</p> <p>Of all clients enrolled in OST during the month of May 2006 (n = 713), 72.8% remained on treatment after three months, and 63.3% after six months. Statistically significant (p = 0.05) improvements were observed in relation to needle sharing, unsafe sex, incidents of detention, and a range of quality of life measures. Greater spending on drugs at intake (OR 1.20), frequently missing doses (OR 8.82), and having heroin rather than SP as the most problematic drug (OR 1.95) were factors that increased the likelihood of relapse, and longer duration in treatment (OR 0.76) and regular family involvement in treatment (OR 0.20) reduced the likelihood of relapse.</p> <p>Conclusion</p> <p>The findings from this operational research indicate that the provision of OST by NGOs in the severely constrained context of Manipur and Nagaland achieved outcomes that are internationally comparable, and highlights strategies for strengthening similar programs in this and other resource-poor settings.</p

My first time: initiation into injecting drug use in Manipur and Nagaland, north-east India

<p>Abstract</p> <p>Background</p> <p>The north-east Indian states of Manipur and Nagaland are two of the six high HIV prevalence states in the country, and the main route of HIV transmission is injecting drug use. Understanding the pathways to injecting drug use can facilitate early intervention with HIV prevention programs. While several studies of initiation into injecting drug use have been conducted in developed countries, little is known about the situation in developing country settings. The aim of this study was to increase understanding of the contextual factors associated with initiation into injecting drug use in north-east India, and the influence of these factors on subsequent initiation of others.</p> <p>Method</p> <p>In mid 2006 a cross-sectional survey among 200 injecting drug users (IDUs) was undertaken in partnership with local NGOs that provide HIV prevention and care services and advocacy for IDUs in Imphal, Manipur and Dimapur, Nagaland. The questionnaire elicited detailed information about the circumstances of the first injection and the contexts of participants' lives. Demographic information, self-reported HIV status, and details about initiation of others were also recorded.</p> <p>Results</p> <p>Initiation into injecting drug use occurred at 20 years of age. The drugs most commonly injected were Spasmo-proxyvon (65.5%) and heroin (30.5%). In 53.5% cases, a needle belonging to someone else was used. Two-thirds (66.7%) had used the drug previously, and 91.0% had known other IDUs prior to initiation (mean = 7.5 others). The first injection was usually administered by another person (94.5%), mostly a friend (84.1%). Initiation is a social event; 98% had others present (mean = 2.7 others). Almost 70% of participants had initiated at least one other (mean = 5 others). Initiation of others was independently associated with being male and unemployed; having IDU friends and using alcohol around the time of initiation; and having been taught to inject and not paid for the drug at the time of initiation.</p> <p>Conclusion</p> <p>Targeting harm reduction messages to (non-injecting) drug users and capitalising on existing IDU social networks to promote safe injecting and deter initiation of others are possible strategies for reducing the impact of injecting drug use and the HIV epidemic in north-east India.</p

Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population

SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited. Here we studied ~45,000 reinfections from the UK’s national COVID-19 Infection Survey and quantified the risk of reinfection in multiple waves, including those driven by BA.1, BA.2, BA.4/5, and BQ.1/CH.1.1/XBB.1.5 variants. Reinfections were associated with lower viral load and lower percentages of self-reporting symptoms compared with first infections. Across multiple Omicron waves, estimated protection against reinfection was significantly higher in those previously infected with more recent than earlier variants, even at the same time from previous infection. Estimated protection against Omicron reinfections decreased over time from the most recent infection if this was the previous or penultimate variant (generally within the preceding year). Those 14–180 days after receiving their most recent vaccination had a lower risk of reinfection than those &gt;180 days from their most recent vaccination. Reinfection risk was independently higher in those aged 30–45 years, and with either low or high viral load in their most recent previous infection. Overall, the risk of Omicron reinfection is high, but with lower severity than first infections; both viral evolution and waning immunity are independently associated with reinfection

Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection

The BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) is being utilised internationally for mass COVID-19 vaccination. Evidence of single-dose protection against symptomatic disease has encouraged some countries to opt for delayed booster doses of BNT162b2, but the effect of this strategy on rates of asymptomatic SARS-CoV-2 infection remains unknown. We previously demonstrated frequent pauci- and asymptomatic SARS-CoV-2 infection amongst healthcare workers (HCWs) during the UK’s first wave of the COVID-19 pandemic, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020). Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and find a fourfold reduction in asymptomatic infection amongst HCWs ≥12 days post-vaccination. These data provide real-world evidence of short-term protection against asymptomatic SARS-CoV-2 infection following a single dose of BNT162b2 vaccine, suggesting that mass first-dose vaccination will reduce SARS-CoV-2 transmission, as well as the burden of COVID-19 disease

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio