Lessons from the COVID-19 pandemic for substance misuse services: findings from a peer-led study.

BACKGROUND: The measures implemented to contain the spread of the COVID-19 virus disrupted the provision of substance misuse treatment and support. However, little is known about the impact of this disruption on individuals seeking treatment for drug- and/or alcohol-related problems (henceforth service users). This study aimed to help substance misuse services learn lessons and identify ways of optimising delivery and minimising harm in the event of any future lockdowns or global crises. METHODS: The study was co-produced by a team of peer researchers, practitioners, policymakers and academics. Telephone interviews were conducted with 202 substance misuse service users over a 6-month period commencing June 2020. The interviews were conducted by a small group of seven peer researchers each with lived experience of substance use problems. The interview data were recorded by the peers in an anonymous online questionnaire survey and analysed using standard quantitative and qualitative methods. RESULTS: Service users responded to the COVID-19 pandemic in a variety of ways. Diverse responses were noted in relation to their substance use patterns, their personal lives and their substance misuse treatment experiences. For some, the pandemic acted as a new risk environment factor that increased their vulnerability to substance-related harm. For others, it facilitated aspects of the enabling environment, thereby reducing the risk of harm. CONCLUSIONS: Service users are not a homogenous group, and an individualised approach to treatment that recognises the potential for varied responses to the same stimuli is needed. The findings suggest that service users would benefit from having a choice in how they access treatment and from greater access to outreach programmes that take treatments and harm reduction tools such as naloxone into the community. The research also supports the involvement of people with lived experience in substance use research, policy and practice.

Blood product transfusion in emergency department patients: a case-control study of practice patterns and impact on outcome.

BACKGROUND: Blood product transfusion occurs in a significant percentage of intensive care unit (ICU) patients. Pulmonary complications, such as acute respiratory distress syndrome (ARDS), occurring in the setting of transfusion, are associated with increased morbidity and mortality. Contrary to the ICU setting, there is little evidence describing the epidemiology of transfusion in the emergency department (ED) or its potential impact on outcome. The objectives of this study were to: (1) characterize transfusion practices in the ED with respect to patient characteristics and pre-transfusion laboratory values; and (2) investigate the effect of ED blood product transfusion on the incidence of pulmonary complications after admission. We hypothesized that blood product transfusion would increase the event rate for pulmonary complications, and have a negative impact on other clinically significant outcomes. METHODS: This was a retrospective case-control study with one-one matching of 204 transfused ED patients to 204 non-transfused controls. The primary outcome was a composite pulmonary outcome that included: acute respiratory failure, new need for ICU admission, and ARDS. Multivariable logistic regression was used to evaluate the primary outcome as a function of transfusion. RESULTS: One-hundred twenty four (60.8%) patients were transfused packed red blood cells (PRBC) in the ED. The mean pre-transfusion hemoglobin level was 8.5 g/dl. There were 73 patients with a hemoglobin value ≥10 g/dl; 19 (26.0%) received a PRBC transfusion. A total of 54 (26.5%) patients were transfused platelets. The main indications were thrombocytopenia (27.8%) and neurologic injury (24.1%). Ten patients had a platelet level <10,000 (guideline recommended threshold for transfusion to prevent spontaneous hemorrhage). The mean platelet count for neurologic injury patients was 197,000 prior to transfusion. The primary outcome occurred in 26 control patients (12.7%), as compared with 28 cases (13.7%). In multivariable logistic regression analysis, ED transfusion was not associated with an increased odds of primary outcome [adjusted OR 0.91 (0.48-1.72), P = 0.77]. The mortality rate was 10.8% in the cases and 8.8% in the controls, P = 0.51. CONCLUSIONS: A significant percentage of ED blood product transfusions are discordant with guideline recommendations. However, there was no association with ED transfusion and worse clinical outcome.

Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation.

Advances in sequencing technology allow researchers to map genome-wide changes in DNA methylation in development and disease. However, there is a lack of experimental tools to site-specifically manipulate DNA methylation to discern the functional consequences. We developed a CRISPR/Cas9 DNA methyltransferase 3A (DNMT3A) fusion to induce DNA methylation at specific loci in the genome. We induced DNA methylation at up to 50% of alleles for targeted CpG dinucleotides. DNA methylation levels peaked within 50 bp of the short guide RNA (sgRNA) binding site and between pairs of sgRNAs. We used our approach to target methylation across the entire CpG island at the CDKN2A promoter, three CpG dinucleotides at the ARF promoter, and the CpG island within the Cdkn1a promoter to decrease expression of the target gene. These tools permit mechanistic studies of DNA methylation and its role in guiding molecular processes that determine cellular fate.