Illicit COVID-19 products online: A mixed-method approach for identifying and preventing online health risks.

AIMS: The COVID-19 pandemic triggered a demand for vaccines, cures, and the need of related documentation for travel, work and other purposes. Our project aimed to identify the illicit availability of such products across the Dark Web Markets (DWMs). METHODS: A retrospective search for COVID-19 related products was carried out across 118 DWMs since the start of the pandemic (March 2020-October 2021). Data on vendors as well as advertised goods such as asking price, marketplace, listed date were collected and further validated through additional searches on the open web to verify the information relating to specific marketplaces. Both quantitative and qualitative methods were used for data analysis. RESULTS: Forty-two listings of unlicenced COVID-19 cures and vaccination certificates were identified across 8 marketplaces sold by 25 vendors with significant variation in prices. The listings were found to be geographically specific and followed the progression of the pandemic in terms of availability. Correlations between vendor portfolios of COVID-19 products and variety of goods of other illicit nature such as illegal weaponry, medication/drugs of abuse also emerged from our analysis. CONCLUSION: This study is one of the first attempts to identify the availability of unlicenced COVID-19 products on DWMs. The easy accessibility to vaccines, fake test certificates and hypothetical/illegal cures poses serious health risks to (potential) buyers due to the uncontrolled nature of such products. It also exposes buyers to an unwanted contact with vendors selling a variety of other dangerous illicit goods. Further monitoring and regulatory responses should be implemented to protect the health and safety of citizens especially at times of global crisis.

Implementation of individualised polygenic risk score analysis: a test case of a family of four.

BACKGROUND: Polygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level. CASE PRESENTATION: We performed a systematic curation of PRS sources from established data repositories, selecting 15 phenotypes, comprising an excess of 37 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four related individuals. Individual risk scores were given percentile values based upon reference distributions among 1000 Genomes Iberians, Europeans, or all samples. Over 96 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here. CONCLUSIONS: Our results highlight the need for further standardisation in the way PRS are developed and shared, the importance of individual risk assessment rather than the assumption of inherited averages, and the challenges currently posed when translating PRS into risk metrics.

Addiction of High Dose of Benzodiazepine: Verona Detox Approach With Flumazenil.

Introduction: Since the 1990s there has been evidence of the significant role Flumazenil (FLU) has in benzodiazepines (BZD) detoxes. The Verona Detox approach has been developed for high dose BZD and Z-drug detoxification via continuous subcutaneous infusion of FLU, a selective BZD receptor antagonist acting on the BZD subunit of the GABA-A receptor. Flumazenil is licensed in the United Kingdom and other countries to treat only BZD overdose although numerous studies have demonstrated its effectiveness in rapidly resetting GABA-A receptors, quickly reducing tolerance and dependence from BZD, and providing a safe and rapid detox from benzodiazepines. Objective: The aim of this article is to provide all healthcare professional who are interested in BZD detoxification with an approach and clear practical information on how to administer FLU. Method: In this article we outline the approach in detail, describing all medical and nursing procedures day by day. This detox treatment is indicated for patients abusing from at least 5 Defined Daily Dose (DDD) of BZDs or Z-drugs. The process lasts 7 days, and is conducted under medical supervision (daily reviews) and continuous nursing (24/7). During this period, 7mg of FLU is administered (1 mg/24) through an elastomeric pump, via continuous subcutaneous infusion. Conclusion: To this day, the largest database of FLU detoxification was published by our group, showing how this treatment is safe, with very little side effects even in patients with significant medical comorbidities.

Whole Genome Interpretation for a Family of Five.

Although best practices have emerged on how to analyse and interpret personal genomes, the utility of whole genome screening remains underdeveloped. A large amount of information can be gathered from various types of analyses via whole genome sequencing including pathogenicity screening, genetic risk scoring, fitness, nutrition, and pharmacogenomic analysis. We recognize different levels of confidence when assessing the validity of genetic markers and apply rigorous standards for evaluation of phenotype associations. We illustrate the application of this approach on a family of five. By applying analyses of whole genomes from different methodological perspectives, we are able to build a more comprehensive picture to assist decision making in preventative healthcare and well-being management. Our interpretation and reporting outputs provide input for a clinician to develop a healthcare plan for the individual, based on genetic and other healthcare data.

Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report.

BACKGROUND: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19. PATIENTS & METHODS: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin. RESULTS: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 â€‹× â€‹109/l (SD â€‹= â€‹2.70) which constituted a significant drop from a baseline value of 5.2 â€‹× â€‹109/l (SD â€‹= â€‹2.24). The mean relative reduction in ANC was -0.2729 (SD â€‹= â€‹0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue â€‹= â€‹8.96 â€‹× â€‹10-8 and an adjusted R2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. CONCLUSIONS: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

Can Kratom (Mitragyna speciosa) Alleviate COVID-19 Pain? A Case Study.

Among the symptoms of COVID-19 fever, general malaise, pain and aches, myalgia, fatigue, and headache can affect the quality of life of patients, even after the end of the acute phase of the infection and can be long lasting. The current treatment of these symptoms, also because COVID-19 patients have been asked not to use non-steroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen are often unsatisfactory. Among the above mentioned symptoms malaise and fatigue seem the most difficult to treat. In this case report we describe the use of kratom (Mitragyna speciosa) by a patient with confirmed COVID-19 infection. What we observed was a fast and sustained relieve of the above mentioned symptoms.

Novel Psychoactive Substances in Custodial Settings: A Mixed Method Investigation on the Experiences of People in Prison and Professionals Working With Them.

INTRODUCTION: Novel Psychoactive Substances (NPS), especially Synthetic Cannabinoid Receptor Agonists (SCRAs), pose a substantial challenge to health and the security of the prison environment. This study analyses the phenomenon from the perspective of people in prison and that of professionals working with them. METHODS: A phenomenological qualitative approach was used to analyze self-reported experiences with 'Spice' (NPS) among users in prison. A semi-structured questionnaire was also disseminated among professionals working in these settings to better understand (a) the impact of NPS on their work; (b) perceived issues on safety in their working environment; (c) approaches used to tackle the phenomenon and best practices. RESULTS: Psychotic events resulting from the collected Spice accounts (5) were marked by hallucinations, depression, self-harm, and suicidal ideations. Other emerging elements included fear, paranoia, inability to be with others, mistrust, breakdown and other risky behaviors. Overall, 186 responses from prison staff were collected across the country. 67% claimed NPS to have had a deep impact on their work as they commonly witnessed espisodes involving outbursts of anger, slurred speech, hallucinations, psychosis, and significant mental deterioration among those in prison. Some 91% have witnessed aggression at least once, with 53% experiencing direct harm. Suggested interventions included enhanced training and education (84%), improved detection (92%) and treatment and support services (93%). CONCLUSIONS: Findings highlight the urgent need for joint multi-disciplinary efforts to tackle the exponential escalation of NPS in prisons as well as to facilitate the recovery and societal reintegration of those affected. Phenomenology can be recommended as a valuable methods to study drug induced experiences.

The effect of CYP2D6 variation on antipsychotic-induced hyperprolactinaemia: a systematic review and meta-analysis.

Hyperprolactinemia is a known adverse drug reaction to antipsychotic treatment. Antipsychotic blood levels are influenced by cytochrome P450 enzymes, primarily CYP2D6. Variation in CYP450 genes may affect the risk of antipsychotic-induced hyperprolactinemia. We undertook a systematic review and meta-analysis to assess whether CYP2D6 functional genetic variants are associated with antipsychotic-induced hyperprolactinemia. The systematic review identified 16 relevant papers, seven of which were suitable for the meta-analysis (n = 303 participants including 134 extreme metabolisers). Participants were classified into four phenotype groups as poor, intermediate, extensive, and ultra-rapid metabolisers. A random effects meta-analysis was used and Cohen's d calculated as the effect size for each primary study. We found no significant differences in prolactin levels between CYP2D6 metabolic groups. Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia. However, statistical power is limited. Future studies with larger samples and including a range of prolactin-elevating drugs are needed.

Synthetic Cannabinoid use in a Case Series of Patients with Psychosis Presenting to Acute Psychiatric Settings: Clinical Presentation and Management Issues.

BACKGROUND: Novel Psychoactive Substances (NPS) are a heterogeneous class of synthetic molecules including synthetic cannabinoid receptor agonists (SCRAs). Psychosis is associated with SCRAs use. There is limited knowledge regarding the structured assessment and psychometric evaluation of clinical presentations, analytical toxicology and clinical management plans of patients presenting with psychosis and SCRAs misuse. METHODS: We gathered information regarding the clinical presentations, toxicology and care plans of patients with psychosis and SCRAs misuse admitted to inpatients services. Clinical presentations were assessed using the PANSS scale. Vital signs data were collected using the National Early Warning Signs tool. Analytic chemistry data were collected using urine drug screening tests for traditional psychoactive substances and NPS. RESULTS: We described the clinical presentation and management plan of four patients with psychosis and misuse of SCRAs. CONCLUSION: The formulation of an informed clinical management plan requires a structured assessment, identification of the index NPS, pharmacological interventions, increases in nursing observations, changes to leave status and monitoring of the vital signs. The objective from using these interventions is to maintain stable physical health whilst rapidly improving the altered mental state.

Transitioning Bodies. The Case of Self-Prescribing Sexual Hormones in Gender Affirmation in Individuals Attending Psychiatric Services.

Self-prescribing of sexual hormones for gender affirmation is a potentially widespread and poorly studied phenomenon that many clinicians are unaware of. The uncontrolled use of hormones poses significant health hazards, which have not been previously reported in the literature. We have collected seven clinical cases in general adult psychiatry settings (both inpatient and outpatients), describing transgender and gender non-conforming individuals' (TGNC) self-prescribing and self-administering hormones bought from the Internet without any medical consultation. Among these cases, two were taking androgens, and the rest were taking oestrogens. The main reason for self-administration of hormones seems to be the lack of access to specialised care due to discrimination and long waiting lists. We advocate for clinicians to be aware of the phenomenon and proactively help TGNC individuals by enquiring about self-prescribing of hormones, providing information and referring to the most appropriate treatment centre as well as encourage a public debate on the discrimination and the stigma that TGNC population suffer from. Overall, there is an urgent need for the implementation of different and innovative health care services for TGNC individuals as well as more targeted prevention strategies on such underreported and highly risky behaviours. Furthermore, it is necessary for every clinician involved in the care for TGNC people to be aware of their special needs and be able to be an allied and an advocate to help in reducing stigma and discrimination that affect the access to care for this often underserved population.

Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence.

This corrects the article DOI: 10.1038/npp.2016.289.

Ethnic Minority Status, Age-at-Immigration and Psychosis Risk in Rural Environments: Evidence From the SEPEA Study.

Objective: Several ethnic minority groups experience elevated rates of first-episode psychosis (FEP), but most studies have been conducted in urban settings. We investigated whether incidence varied by ethnicity, generation status, and age-at-immigration in a diverse, mixed rural, and urban setting. Method: We identified 687 people, 16-35 years, with an ICD-10 diagnosis of FEP, presenting to Early Intervention Psychosis services in the East of England over 2 million person-years. We used multilevel Poisson regression to examine incidence variation by ethnicity, rural-urban setting, generation status, and age-at-immigration, adjusting for several confounders including age, sex, socioeconomic status, population density, and deprivation. Results: People of black African (incidence rate ratio: 4.06; 95% confidence interval [CI]: 2.63-6.25), black Caribbean (4.63; 95% CI: 2.38-8.98) and Pakistani (2.31; 95% CI: 1.35-3.94) origins were at greatest FEP risk relative to the white British population, after multivariable adjustment. Non-British white migrants were not at increased FEP risk (1.00; 95% CI: 0.77-1.32). These patterns were independently present in rural and urban settings. For first-generation migrants, migration during childhood conferred greatest risk of psychotic disorders (2.20; 95% CI: 1.33-3.62). Conclusions: Elevated psychosis risk in several visible minority groups could not be explained by differences in postmigratory socioeconomic disadvantage. These patterns were observed across rural and urban areas of our catchment, suggesting that elevated psychosis risk for some ethnic minority groups is not a result of selection processes influencing rural-urban living. Timing of exposure to migration during childhood, an important social and neurodevelopmental window, may also elevate risk.

Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence.

Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction.

The Epidemiology of First-Episode Psychosis in Early Intervention in Psychosis Services: Findings From the Social Epidemiology of Psychoses in East Anglia [SEPEA] Study.

OBJECTIVE: Few studies have characterized the epidemiology of first-episode psychoses in rural or urban settings since the introduction of early intervention psychosis services. To address this, the authors conducted a naturalistic cohort study in England, where such services are well established. METHOD: All new first-episode psychosis cases, 16-35 years old, presenting to early intervention psychosis services in the East of England were identified during 2 million person-years follow-up. Presence of ICD-10 F10-33 psychotic disorder was confirmed using OPCRIT [operational criteria for psychotic illness]. Incidence rate ratios were estimated following multivariable Poisson regression, adjusting for age, sex, ethnicity, socioeconomic status, neighborhood-level deprivation, and population density. RESULTS: Of 1,005 referrals, 687 participants (68.4%) fulfilled epidemiological and diagnostic criteria for first-episode psychosis (34.0 new cases per 100,000 person-years; 95% CI=31.5-36.6). Median age at referral was similar for men (22.5 years; interquartile range: 19.5-26.7) and women (23.4 years; interquartile range: 19.5-29.1); incidence rates were highest for men and women before 20 years of age. Rates increased for ethnic minority groups (incidence rate ratio: 1.4; 95% CI=1.1-1.6), as well as with lower socioeconomic status (incidence rate ratio: 1.3; 95% CI=1.2-1.4) and in more urban (incidence rate ratio: 1.4;95%CI=1.0-1.8) and deprived (incidence rate ratio: 2.1; 95% CI=1.3-3.3) neighborhoods, after adjustment for confounders. CONCLUSIONS: Pronounced variation in psychosis incidence, peaking before 20 years old, exists in populations served by early intervention psychosis services. Excess rates were restricted to urban and deprived communities, suggesting that a threshold of socioenvironmental adversity may be necessary to increase incidence. This robust epidemiology can inform service development in various settings about likely population-level need.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

Reduction in ventral striatal activity when anticipating a reward in depression and schizophrenia: a replicated cross-diagnostic finding.

In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.

The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.

Olanzapine as the ideal "trip terminator"? Analysis of online reports relating to antipsychotics' use and misuse following occurrence of novel psychoactive substance-related psychotic symptoms.

OBJECTIVE: The pharmacological self-management of novel psychoactive substance (NPS)-induced psychopathological consequences represents a fast growing phenomenon. This is facilitated by the frequent sharing of NPS intake experiences online and by the ease of access to a range of psychotropic medications from both the online and street market. Olanzapine is anecdotally reported by Web users to be the most frequent self-prescribed medication to cope with NPS-induced psychoses. Hence, we aimed here at better assessing olanzapine use/misuse for this purpose. METHODS: Exploratory qualitative searches of 163 discussion fora/specialized websites have been carried out in four languages (English, German, Spanish, and Italian) in the time frame November 2012-2013. RESULTS: Most NPS-users allegedly self administer with olanzapine to manage related psychotic crises/"bad trips". This may be typically taken only for a few days, at a dosage range of 5-50 mg/day. CONCLUSIONS: Only a few research studies have formally assessed the effectiveness of olanzapine and indeed of other second-generation antipsychotics to treat NPS-induced psychosis. Olanzapine was suggested here from a range of pro drug websites as being the "ideal" molecule to terminate "bad trips". Health professionals should be informed about the risks related to olanzapine misuse.

Brain structural signatures of negative symptoms in depression and schizophrenia.

Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n = 24), schizophrenia (n = 22), and healthy controls (n = 20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.