A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.

Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their extensive mutations complicate phylogenetic inference, and as a result, we know relatively little about their within-host evolutionary origins and dynamics. Using >1400 longitudinal single-genome-amplified HIV sequences isolated from six women over a median of 18 years of follow-up-including plasma HIV RNA sequences collected over a median of 9 years between seroconversion and ART initiation, and >500 proviruses isolated over a median of 9 years on ART-we evaluated three approaches for masking hypermutation in nucleotide alignments.

Examining the association between fentanyl use and perceived adequacy of methadone dose: A retrospective cohort study.

Background: People exposed to fentanyl may report that the dose of methadone in the commonly accepted therapeutic range feels too low. We examined self-reported methadone dose adequacy.

Methods: We conducted a retrospective cohort study of individuals prescribed methadone at a dose of at least 60mg daily using data from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through March 2020.

Polygenic Risk Score Implementation into Clinical Practice for Primary Prevention of Cardiometabolic Disease.

: Cardiovascular disease is a leading cause of mortality globally and a major contributor to disability. Traditional risk factors, as initially established in the FRAMINGHAM study, have helped to stratify populations and identify patients for early intervention. Incorporating genetic factors enhances risk stratification tools, enabling the earlier identification of individuals at increased risk and facilitating more targeted and effective risk factor modifications.

Putative biomarkers of hepatic dysfunction in critically ill sepsis patients.

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach.

An anesthesiology-led perioperative outreach service: experience from a Canadian centre and a focused narrative literature review.

Approximately 320 million surgeries occur annually worldwide, increasingly performed on an ageing, comorbid population in whom postoperative complications contribute significantly to mortality. While anesthesiologists have led advances in perioperative care, the optimal structure of the provision of postoperative care has lacked discourse. In this article, we describe the implementation, structure, role, and benefits of an Anesthesiology Perioperative Outreach Service (APOS) at a Canadian tertiary hospital, providing proactive daily review and management of high-risk surgical patients.

Real-world experience and long-term outcomes of a mandatory non-medical switch of adalimumab originator to biosimilars in inflammatory bowel disease.

Background: Over the last decade, the treatment options for inflammatory bowel disease (IBD) have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation. Adalimumab (ADA) is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD. In April 2021, the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira to ADA biosimilars.

Adverse changes in close social ties in aging women and men: A population-based longitudinal study of the CLSA (2011-2021).

Close social ties are important for health but these can decline as people age. Moreover, losses of close social ties may be worse for women, older age and low socioeconomic groups. We characterized alterations in both marital status or living arrangement over 6 years by gender, and assessed patterns by age, country of origin, geographic location, education, wealth, and household income.

"There was no services that I could access so I just stayed on the street…using until I went into labour.": A qualitative study of accessibility and cultural safety of services for perinatal substance use in British Columbia, Canada.

Background: Perinatal substance use is a critical public health challenge, impacting both mother and fetus. Its prevalence has increased in British Columbia, Canada, disproportionately impacting First Nations people. For specialized perinatal substance use services to be effective, they must be accessible and safe.

Oncologic safety and technical feasibility of completion transanal total mesorectal excision after local excision; a cohort study from the International TaTME Registry.

Background: As part of an organ sparing strategy, a surgical local excision may be performed in patients with early-stage rectal cancer or following neoadjuvant (chemo)radiotherapy. In selected cases, a completion total mesorectal excision may be recommended which can be more complex because of the preceding local excision. A transanal approach to perform completion total mesorectal excision may offer an advantage through the better visualization of the surgical field in the distal rectum and less forceful retraction for exposure.

Coxsackievirus B3-Induced mA Modification of RNA Enhances Viral Replication via Suppression of YTHDF-Mediated Stress Granule Formation.

N6-methyladenosine (mA) is the most prevalent internal RNA modification. Here, we demonstrate that coxsackievirus B3 (CVB3), a common causative agent of viral myocarditis, induces mA modification primarily at the stop codon and 3' untranslated regions of its genome. As a positive-sense single-stranded RNA virus, CVB3 replicates exclusively in the cytoplasm through a cap-independent translation initiation mechanism.

From fixing to connecting: parents' experiences supporting adult children with eating disorders.

Background: Unlike evidence-based guidelines that exist for families of youth with eating disorders, little is known about the optimal role for families of adult patients. Given issues of patient autonomy and confidentiality, it is common for family members to report high levels of distress, confusion about how to offer support, and feelings of exclusion. Nevertheless, interactions with parents play a critical role in the recovery process.

The BNT162b2 mRNA vaccine demonstrates reduced age-associated T1 support and .

mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex.

Gaps in health coverage for racialized im/migrant sex workers in metro Vancouver: Findings of a community-based cohort study (2014-2021).

Background: Sex workers face substantial health inequities related to sexual health and gender-based violence, many of which are amplified for the large proportion of workers who are racialized im/migrants. While criminalization and stigma are known barriers to health care for this population, we know little about health insurance coverage, and in particular how this relates to im/migration experience and racialization. We examined associations between im/migration status, duration, and racialization on gaps in health insurance coverage in a cohort of women sex workers.

Clinicians' Perspectives and an Ethical Analysis of Safer Supply Opioid Prescribing.

In British Columbia, Canada, many physicians providing care to individuals with high-risk opioid use disorder adopted safer supply (SS) opioid prescribing in the spring of 2020 with the goal of facilitating public health measures for COVID-19. This prescribing practice continued after measures were lifted. This study aimed to explore prescribers' perspectives following several years of local experience in prescribing SS opioids, primarily in the form of hydromorphone tablets, and to apply ethical concepts to explore current challenges and ongoing sources of provider distress.

Indications and Techniques for Surgical Lead Extraction and Device Reimplantation.

Cardiac implantable electronic devices (CIEDs) can be lifesaving but complications associated with CIEDs can lead to significant morbidity and mortality. Effective techniques to remove these devices are critical to reducing complications and improving quality of life. Percutaneous extraction techniques are effective for removing the majority of CIEDs but surgical lead extraction is still required in certain situations.

Impactful Cardiac CT and MRI Articles from 2023.

Cardiac imaging is important in diagnosing, treating, and predicting prognosis in patients with cardiovascular disease. Imaging protocols and analysis are consistently evolving, and the implementation of artificial intelligence-based applications is of increasing interest. This review presents recent advancements in noninvasive cardiac imaging, specifically focusing on cardiac CT and MRI, from notable publications across multidisciplinary journals in 2023 of interest to both radiologists and referring clinicians in the field.

Supporting young people through the COVID-19 pandemic and beyond: a multi-site qualitative longitudinal study.

Background: Throughout the COVID-19 pandemic, youth have experienced substantial stress due to abrupt changes in education, finances, and social life, compounding pre-existing stressors. With youth (ages 15-26) often at critical points in development, they are vulnerable to long-term mental health challenges brought on by pandemic trauma.

Methods: To identify youth experiences throughout the pandemic and examine changes over time, we conducted semi-structured interviews among n = 141 youth in two Canadian provinces (Ontario and British Columbia) and across the country of Ireland at three time points over the course of more than one year (August 2020-October 2021).

Changes in hepatic steatosis before and after direct acting antiviral treatment in people living with HIV and Hepatitis C coinfection.

Background: Both HIV and hepatitis C virus (HCV) infection increase the risk of hepatic steatosis (HS), which in turn contributes to the severity and progression of liver disease. Direct acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear.

Methods: HS was assessed using the controlled attenuation parameter (CAP) and the hepatic steatosis index (HSI) in participants coinfected with HIV-HCV from the Canadian Coinfection Cohort.

Population perinatal substance use and an environmental scan of health services in British Columbia, Canada.

Background: Substance use during pregnancy is underreported globally and there is limited data on its prevalence and the availability of supportive services. This study determined population perinatal substance use in British Columbia (BC) by region and examined the availability of clinical and community-based programs.

Methods: Using linked provincial health administrative data, we conducted a population-based retrospective cohort study including all BC residents accessing care for substance use (alcohol, opioids, stimulants, sedatives, and cannabis) within 12 months of first perinatal care record to delivery during 2016-2021.