All-cause and cause-specific mortality among people with regular or problematic cocaine use:A systematic review and meta-analysis

Aims: To estimate pooled all-cause and cause-specific mortality risk for people with regular or problematic cocaine use.Methods: Systematic review and meta-analysis of prospective or retrospective cohort studies or clinical trials (n ≥30) of people with regular or problematic cocaine use with data on all-cause or cause-specific mortality. Of 2808 papers, 28 were eligible and reported on 21 cohorts, with a total 170 019 individuals. Cohorts identified based on acute care for drug poisoning or other severe health presentation were excluded. Title/abstract screening was conducted by one reviewer; a second reviewer independently checked 10% of excluded studies. Two reviewers conducted full-text screening. Data were extracted by one reviewer and checked by a second. A customized review-specific study reporting quality/risk of bias tool was used. Data on crude mortality rates (CMR) and standardized mortality ratios were extracted for both all-cause and cause-specific mortality. Standardized mortality ratios were imputed where not provided by the author using extracted data and information from the Global Burden of Disease Study 2017. Data were pooled using a random-effects model.Results: The pooled all-cause crude mortality rate was 1.24 per 100 person-years [95% confidence interval (CI) = 0.86, 1.78; n = 16 cohorts], but with considerable heterogeneity (I2 = 98.8%). The pooled all-cause standardized mortality ratio (SMR) was 6.13 (95% CI = 4.15, 9.05; n = 16 cohorts). Suicide (SMR = 6.26, 95% CI = 2.84, 13.80), accidental injury (SMR = 6.36, 95% CI = 4.18, 9.68), homicide (SMR = 9.38, 95% CI 3.45-25.48) and AIDS-related mortality (SMR = 23.12, 95% CI = 11.30, 47.31) were all elevated compared with age and sex peers in the general population.Conclusions: There are elevated rates of mortality among people with regular or problematic cocaine use for traumatic deaths and deaths attributable to infectious disease

Overseas Treatment of Latent Tuberculosis Infection in US-Bound Immigrants.

Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs:a systematic review and meta-analysis

BACKGROUND AND AIM: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID. METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95. CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade

Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries

Background: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course. Method/Design: This is a prospective multi-centre observational study aiming to enrol 7–8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. Discussion: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for “Integrated Management of Childhood Illness” used in dengue-endemic countries. Trial registration: NCT01550016. Registration Date: March 7, 201

Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis

Streptococcus suis causes disease in pigs worldwide and is increasingly implicated in zoonotic disease in East and South-East Asia. To understand the genetic basis of disease in S. suis, we study the genomes of 375 isolates with detailed clinical phenotypes from pigs and humans from the United Kingdom and Vietnam. Here, we show that isolates associated with disease contain substantially fewer genes than non-clinical isolates, but are more likely to encode virulence factors. Human disease isolates are limited to a single-virulent population, originating in the 1920 s when pig production was intensified, but no consistent genomic differences between pig and human isolates are observed. There is little geographical clustering of different S. suis subpopulations, and the bacterium undergoes high rates of recombination, implying that an increase in virulence anywhere in the world could have a global impact over a short timescale.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Mortality among people with regular or problematic use of amphetamines: a systematic review and meta‐analysis

Background and aims: Amphetamines are the second most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with regular or dependent use of amphetamines, with a focus upon all-cause mortality as well as specific causes of death. Design: Systematic review and meta-analysis of cohorts of people with problematic use or dependence on amphetamines with data on all-cause or cause-specific mortality. Setting and participants: Of 4240 papers, 30 were eligible, reporting on 25 cohorts that measured all-cause mortality, drug poisoning, suicide, accidental injuries, homicide and cardiovascular mortality. Cohorts (n\ua0=\ua035-74 139) were in North America, several Nordic countries and Asia Pacific. Measurement: Titles/abstracts were independently screened by one reviewer and excluded those reviewed by a second reviewer. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMR) per 100\ua0person-years (py), standardized mortality ratios (SMRs). We imputed SMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random-effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta-regressions. Findings: Twenty-three cohorts contributed data for the pooled all-cause CMR: 1.14 per 100\ua0py [95% confidence interval (CI)\ua0=\ua00.92-1.42]. Pooled cause-specific mortality rates were: drug poisoning, 0.14 per 100\ua0py (95% CI\ua0=\ua00.06-0.34); cardiovascular disease, 0.13 per 100\ua0py (95% CI\ua0=\ua00.06-0.29); suicide, 0.20 per 100\ua0py (95% CI\ua0=\ua00.07-0.55); accidental injury, 0.20 per 100\ua0py (95% CI\ua0=\ua00.08-0.47) and homicide, 0.03 per 100\ua0py (95% CI\ua0=\ua00.02-0.06). There was substantial heterogeneity for all pooled CMR estimates except homicide. The pooled all-cause SMR was 6.83 (95% CI\ua0=\ua05.27-8.84). Pooled cause-specific SMRS were: poisoning, 24.70 (95% CI\ua0=\ua016.67, 36.58); homicide, 11.90 (95% CI\ua0=\ua07.82-18.12); suicide, 12.20 (95% CI\ua0=\ua04.89-30.47); cardiovascular disease, 5.12 (95% CI\ua0=\ua03.74-7.00) and accidental injury, 5.12 (95% CI\ua0=\ua02.88-9.08). Conclusions: People with regular or dependent amphetamine use are at elevated risk of a range of causes of mortality compared with people without regular or dependent amphetamine use