Evidence for public health on novel psychoactive substance use: a mixed-methods study

Background: Novel psychoactive substances (NPSs) contribute to the public health impact of substance misuse. This report provides research evidence addressing 11 research questions related to NPSs, covering types, patterns and settings of use; supply sources; and implications for policy and practice. Methods: The study used a conceptually linked three-phase mixed-methods design with a shared conceptual framework based on multiple-context risk and protective factors. Phase 1 was a quantitative phase involving secondary data analysis of the longitudinal Belfast Youth Development Study (BYDS), a latent class analysis using the 2039 BYDS participants. Phase 2 was an extensive qualitative analysis via narrative interviews with participants, sampled from BYDS, drug/alcohol services and prisons, to explore NPS use trajectories. Phase 3 was the final quantitative phase; generalisability of the shared risk factor part of the model was tested using the manual three-step approach to examine risk factors associated with latent class membership. The quantitative and qualitative analyses were integrated, thus allowing emerging findings to be further explored. Results: The data suggest that NPSs have a place within a range of polydrug use trajectories. Models showed no distinctive NPS class, with no clear evidence of differential risks for NPS use compared with the use of other substances. From the qualitative analysis, a taxonomy of groups was derived that explored how and where NPSs featured in a range of trajectories. This taxonomy was used to structure the analysis of factors linked to use within a risk and protective framework. Drivers for use were considered alongside knowledge, perceptions and experience of harms. Suggestions about how interventions could best respond to the various patterns of use – with special consideration of synthetic cannabinoids (SCs), including how they relate to the use of heroin and the potential for NPSs to operate as a ‘snare’ to more problem use – were also presented. Limitations: The study was conducted during 2016/17; generalisability beyond this sample and time point is limited. The level of missing data for some of the BYDS analysis was a limitation, as was the fact that the BYDS data were collected in 2011, so in a different context from the data collected during the narrative interviews. The Psychoactive Substances Act 2016 (Great Britain. Psychoactive Substances Act 2016. London: The Stationery Office; 2016) came into force during qualitative fieldwork and, although not particularly influential in this study, may be influential in future work. It is acknowledged that many of the data related to SCs and mephedrone. Although drug use was measured by self-report, the strength of rapport within interviews, reflective diaries and methodological acceptability checks helped to mitigate self-report bias. Conclusions: NPSs continue to present significant challenges for legislation and monitoring, researching and developing interventions. Understanding of usage patterns remains poor, with most information based on populations and settings where problems have already occurred. This research contributes to the evidence base by providing much needed further empirical data on the lived experiences of NPS users across a range of settings. In the light of these data, implications for policy and practice are discussed. Future work: Future research must generate improved epidemiological data on the extent, patterns and motivations for use longitudinally. The uniqueness of the information concerning SC use points to a specific set of findings not evidenced in other literature (e.g. intensity of SC withdrawal). Future research should focus on the symbiotic link between SC and heroin use

What is news? News values revisited (again)

The deceptively simple question “What is news?” remains pertinent even as we ponder the future of journalism in the digital age. This article examines news values within mainstream journalism and considers the extent to which news values may be changing since earlier landmark studies were undertaken. Its starting point is Harcup and O’Neill’s widely-cited 2001 updating of Galtung and Ruge’s influential 1965 taxonomy of news values. Just as that study put Galtung and Ruge’s criteria to the test with an empirical content analysis of published news, this new study explores the extent to which Harcup and O’Neill’s revised list of news values remain relevant given the challenges (and opportunities) faced by journalism today, including the emergence of social media. A review of recent literature contextualises the findings of a fresh content analysis of news values within a range of UK media 15 years on from the last study. The article concludes by suggesting a revised and updated set of contemporary news values, whilst acknowledging that no taxonomy can ever explain everything

Current state of Fusarium wilt of banana in the subtropics

The original publication is available at https://www.actahort.org/books/1272/1272_7.ht

A study protocol for a randomised controlled feasibility trial of an intervention to increase activity and reduce sedentary behaviour in people with severe mental illness: Walking fOR Health (WORtH) Study

Abstract Background People with severe mental illness (SMI) are less physically active and more sedentary than healthy controls, contributing to poorer physical health outcomes in this population. There is a need to understand the feasibility and acceptability, and explore the effective components, of health behaviour change interventions targeting physical activity and sedentary behaviour in this population in rural and semi-rural settings. Methods This 13-week randomised controlled feasibility trial compares the Walking fOR Health (WORtH) multi-component behaviour change intervention, which includes education, goal-setting and self-monitoring, with a one-off education session. It aims to recruit 60 inactive adults with SMI via three community mental health teams in Ireland and Northern Ireland. Primary outcomes are related to feasibility and acceptability, including recruitment, retention and adherence rates, adverse events and qualitative feedback from participants and clinicians. Secondary outcome measures include self-reported and accelerometer-measured physical activity and sedentary behaviour, anthropometry measures, physical function and mental wellbeing. A mixed-methods process evaluation will be undertaken. This study protocol outlines changes to the study in response to the COVID-19 pandemic. Discussion This study will address the challenges and implications of remote delivery of the WORtH intervention due to the COVID-19 pandemic and inform the design of a future definitive randomised controlled trial if it is shown to be feasible. Trial registration The trial was registered on clinicaltrials.gov ( NCT04134871 ) on 22 October 2019

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

ObjectiveShortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation.MethodsHigh-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming.ResultsUninfected controls had increased neuronal synchronization in the 6–12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions.ConclusionsMEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health

Functional Brain Abnormalities During Finger-Tapping in HIV-Infected Older Adults: A Magnetoencephalography Study

Despite the availability of combination antiretroviral therapy, at least mild cognitive dysfunction is commonly observed in HIV-infected patients, with an estimated prevalence of 35-70%. Neuropsychological studies of these HIV-associated neurocognitive disorders (HAND) have documented aberrations across a broad range of functional domains, although the basic pathophysiology remains unresolved. Some of the most common findings have been deficits in fine motor control and reduced psychomotor speed, but to date no neuroimaging studies have evaluated basic motor control in HAND. In this study, we used magnetoencephalography (MEG) to evaluate the neurophysiological processes that underlie motor planning in older HIV-infected adults and a matched, uninfected control group. MEG is a noninvasive and direct measure of neural activity with good spatiotemporal precision. During the MEG recording, participants fixated on a central crosshair and performed a finger-tapping task with the dominant hand. All MEG data was corrected for head movements, preprocessed, and imaged in the time-frequency domain using beamforming methodology. All analyses focused on the pre-movement beta desynchronization, which is known to be an index of movement planning. Our results demonstrated that HIV-1-infected patients have deficient beta desynchronization relative to controls within the left/right precentral gyri, and the supplementary motor area. In contrast, HIV-infected persons showed abnormally strong beta responses compared to controls in the right dorsolateral prefrontal cortex and medial prefrontal areas. In addition, the amplitude of beta activity in the primary and supplementary motor areas correlated with scores on the Grooved Pegboard test in HIV-infected adults. These results demonstrate that primary motor and sensory regions may be particularly vulnerable to HIV-associated damage, and that prefrontal cortices may serve a compensatory role in maintaining motor performance levels in infected patients

Decreased MEG beta oscillations in HIV-infected older adults during the resting state

The introduction of combination antiretroviral therapy significantly reduced the prevalence of the most severe form of HIV-associated neurocognitive disorders (HAND). Despite this decline, 35–70% of HIV-infected patients continue to develop mild motor and cognitive impairments. Although neuropsychological studies have shown that HAND affects a wide array of cognitive functions, a formal diagnosis is still based on the exclusion of opportunistic infections and other common ailments, as no specific tests or biomarkers are currently available. In this study, we used magnetoencephalography (MEG) to measure neural activity during the resting-state in 15 HIV-infected older patients and a demographically-matched group of 15 uninfected controls. MEG is a noninvasive and direct measure of neural activity with excellent spatiotemporal resolution. All MEG data were coregistered to structural MRI, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to quantify population-level neural oscillatory activity. We found that HIV-infected persons exhibited decreased beta oscillations in the supplementary motor area bilaterally, paracentral lobule, posterior cingulate, and bilateral regions of the superior parietal lobule relative to healthy controls. Beta oscillations in the posterior cingulate, a critical component of the default mode network, were also positively correlated with patient scores on the memory recall aspect of the Hopkins Verbal Learning Test-Revised. These results demonstrate that chronic HIV infection does not uniformly disturb cortical function, and that neuronal populations in dorso-medial motor and parietal cortices are especially affected. These findings also suggest that resting-state MEG recordings may hold significant promise as a functional biomarker for identifying HAND and monitoring disease progression

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

A Multicenter, Randomized, Placebo‐Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. Methods: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations