Estimating the number of people who inject drugs in Australia

Abstract Background Injecting drug use is associated with considerable morbidity and mortality. Estimates of the size of the population of people who inject drugs are critical to inform service planning and estimate disease burden due to injecting drug use. We aimed to estimate the size of the population of people who inject drugs in Australia. Methods We applied a multiplier method which used benchmark data (number of people in opioid substitution therapy (OST) on a snapshot day in 2014) and multiplied it by a factor derived from the prevalence of current OST among people who inject drugs participating in the Australian Needle and Syringe Program Survey in 2014. Estimates of the total population of people who inject drugs were calculated in each state and territory and summed to produce a national estimate. We used the sex and age group distribution seen in datasets relating to people who inject drugs to derive sex- and age-stratified estimates, and calculated prevalence per 1000 population. Results Between 68,000 and 118,000 people aged 15–64 years inject drugs in Australia. The population prevalence of injecting drug use was 6.0 (lower and upper uncertainty intervals of 4.3 and 7.6) per 1000 people aged 15–64 years. Injecting drug use was more common among men than women, and most common among those aged 35–44 years. Comparison of expected drug-related deaths based on these estimates to actual deaths suggest that these figures may be underestimates. Conclusions These are the first indirect prevalence estimates of injecting drug use in Australia in over a decade. This work has identified that there are limited data available to inform estimates of this population. These estimates can be used as a basis for further work estimating injecting drug use in Australia

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

The profile of psychiatric symptoms exacerbated by methamphetamine use

Background: Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. Methods: 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. Results: Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, χ2(df1) = 3.66, p = 0.056). Conclusion: Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome

SARS-CoV-2 neutralizing antibodies : longevity, breadth, and evasion by emerging viral variants

The Severe Acute Respiratory Syndrome Coronavirus 2 (SAU ARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

BACKGROUND: The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. METHODS: The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. RESULTS: Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. CONCLUSIONS: Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570