McMaster University

Aims: Magnetic resonance imaging (MRI) studies have identified brain structural predictors of treatment response in individuals with alcohol use disorder (AUD), but with varying findings and primarily in male veterans. The present study investigated cortical surface area and thickness (CT) as predictors of brief intervention response in community-based adults with AUD. Methods: Sixty-five non-treatment-seeking adults with AUD (44.6% male, aged 33.2±10.3 years) underwent an MRI and received a brief intervention comprising personalized feedback and motivational interviewing, with follow-up approximately 6-8 weeks later to quantify changes in drinks/week (DPW), the primary outcome. Eighteen bilateral a priori regions of interest (ROIs) were used to predict DPW at follow-up, adjusting for baseline drinking. Significant predictors were examined with secondary outcomes, percent drinking and heavy drinking days, and in relation to out-of-scanner measures of impulsivity and comorbidities. Results: Participants exhibited expected significant decreases in alcohol consumption in response to the brief intervention. Eight bilateral CT ROIs in the frontal, temporal, and occipital lobes, most notably medial orbitofrontal, middle temporal, and lateral occipital gyri, predicted DPW; however, only three predicted the secondary outcomes. Significant associations were observed between CT in frontal and occipital regions with impulsivity (delay discounting, lack of premeditation), executive functioning, anxiety, and stress. Conclusions: Thinner frontal, temporal, and occipital ROIs predicted poorer brief intervention response, with notable overlap with brain regions previously implicated in AUD. Clarifying whether these regions reflect premorbid or acquired differences and, if the latter, the potential for recovery of cortical gray matter following drinking reductions are future priorities.

BACKGROUND AND OBJECTIVES The temporalis muscle flap has historically been used for repairing defects from orbital procedures and is commonly used in cranial, oral, and facial reconstructions. However, its application for reconstructing the skull base after a transorbital approach has not been explored. Reconstruction after a transorbital intradural approach is still object of preclinical and clinical investigation, with various techniques emerging recently. This study introduces a novel method suitable for extensive resections of the skull base, including intradural resections of the anterior, middle, and posterior cranial fossae. The study aimed to investigate the feasibility of rotating a vascularized myofascial flap from the anterior third of the temporalis muscle onto the skull base, exploring its extension into the middle cranial fossa after drilling the greater wing of the sphenoid. METHODS Six endoscopic dissections were performed on formalin-fixed heads to illustrate the feasibility of preparing a deep fascia flap from the temporalis muscle. Red silicone latex was injected into the external carotid artery to confirm the vascular integrity of the deep temporal branches of the maxillary artery. RESULTS The deep temporalis myofascial flap offers a large, well-vascularized tissue that can be easily rotated to cover skull base defects after transorbital approaches. Its coverage extends from the middle and anterior cranial fossae to the infratemporal fossa and the lateral wall of the cavernous sinus. It also effectively covers dural defects at the temporal pole. CONCLUSION With an appropriate temporal bony window and sufficient exposure, it is feasible to endoscopically prepare a rotation flap from the anterior third of the temporalis muscle, minimizing the need for resecting the lateral orbital margin. This approach is a favorable alternative to traditional reconstruction techniques, offering quick setup in a single operative procedure. Future studies are needed to confirm minimal donor site morbidity regarding masticatory function.

Importance Diffusion-weighted imaging (DWI) lesions have been demonstrated in patients with subacute intracerebral hemorrhage (ICH), suggesting ischemic injury, which may be related to blood pressure (BP) reduction. Objective To test the hypothesis that acute intensive BP lowering is associated with DWI lesions after ICH. Design, Setting, and Participants The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial 2 (ICHADAPT-2) was a multicenter, randomized, open-label, blinded–end point trial. Between November 2012 and August 2022, patients with ICH presenting within 6 hours of onset were randomized to a systolic BP (SBP) target of less than 140 mm Hg or less than 180 mm Hg. The trial was conducted at 3 comprehensive stroke centers in Canada and Australia, including 1 telestroke referral hub and 1 community stroke hospital. A total of 162 patients with acute ICH were randomized. The primary analysis population was restricted to those undergoing DWI at 48 hours. Intervention Patients were randomly assigned to an acute SBP target of less than 140 mm Hg or less than 180 mm Hg. Main Outcome and Measure The primary end point was the incidence of acute DWI lesions on brain magnetic resonance imaging obtained 48 ± 12 hours after randomization. Results DWI was obtained in 79 (48% female) patients with a mean (SD) age of 71 (13) years and median baseline ICH volume of 11.2 (range, 0.5-122.2) mL. The median times from onset to randomization and DWI were 3.17 (range, 0.7-14.6) hours and 51.6 (range, 17.0-121.4) hours, respectively. Mean (SD) baseline SBP was 183 (22) mm Hg in the less than 140 mm Hg target group and 181 (28) mm Hg in the less than 180 mm Hg target group. Mean SBP was lower over the 48-hour period after randomization in the less than 140 mm Hg group (mean difference, 18.9 mm Hg [95% CI, 17.6-20.2]; P < .001). DWI lesions were detected in 13 of 42 patients (31%) in the less than 140 mm Hg group and 14 of 37 patients (38%) in the less than 180 mm Hg group (odds ratio, 0.74 [95% CI, 0.12-4.64]; P = .32). The median number of DWI lesions (1 [95% CI, 1-10] vs 1.5 [95% CI, 1-10]; P = .26) and total DWI lesion volume (0.1 [95% CI, 0.01-41.3] mL vs 0.3 [95% CI, 0.02-2.03] mL; P = .17) were not different in the less than 140 mm Hg and less than 180 mm Hg groups. Conclusions and Relevance DWI lesion frequency and volume were unaffected by intensive antihypertensive therapy. These results support the safety of early BP reduction in acute ICH.

When is the best time to breed? This is an important question, especially for fishes that breed in the intertidal zone, a dynamic habitat where conditions change rapidly and cyclically. Many intertidal fishes reproduce during the spring tides (during the new and full moons when tidal fluctuations are strongest). However, we use long-term field data to present a counter example, the toadfish, Porichthys notatus, which spawns more often during the neap tides (during the quarter moons when tidal fluctuations are weakest). We hypothesize that if a species’ reproduction involves time-consuming tasks, such as courtship, mate selection, nest preparation, and prolonged egg-laying, and if these activities must occur underwater, then such species will align their reproduction with neap tides rather than spring tides. To examine the prevalence of neap tide spawning, we conducted a comprehensive literature review to explore the diversity of reproductive strategies and timings in intertidal fishes. Because some species must leave the intertidal zone or find refuge when the tides recede, whereas others exhibit amphibious lifestyles and can even breathe air, we paid specific attention to different species’ requirements for submersion to perform their reproductive behaviours. We gathered data on 131 fish species and ultimately highlight a scarcity in data on reproductive timing in intertidal fishes. Our literature survey provides preliminary support for our hypothesis, and we now call on researchers to directly examine lunar synchrony of reproduction in intertidal fishes to better understand how reproductive strategies are shaped by the tides.

Importance Masks reduce transmission of SARS-CoV2 and other respiratory pathogens. Comparative studies of the fitted filtration efficiency of different types of masks are scarce. Objective To describe the fitted filtration efficiency against small aerosols (0.02–1 µm) of medical and non-medical masks and respirators when worn, and how this is affected by user modifications (hacks) and by overmasking with a cloth mask. Design We tested a 2-layer woven-cotton cloth mask of a consensus design, ASTM-certified level 1 and level 3 masks, a non-certified mask, KF94s, KN95s, an N95 and a CaN99. Setting Closed rooms with ambient particles supplemented by salt particles. Participants 12 total participants; 21–55 years, 68% female, 77% white, NIOSH 1–10. Main Outcome and Measure Using standard methods and a PortaCount 8038, we counted 0.02–1 µm particles inside and outside masks and respirators, expressing results as the percentage filtered by each mask. We also studied level 1 and level 3 masks with earguards, scrub caps, the knot-and-tuck method, and the effects of braces or overmasking with a cloth mask. Results Filtration efficiency for the cloth mask was 47–55%, for level 1 masks 52–60%, for level 3 masks 60–77%. A non-certified KN95 look-alike, two KF94s, and three KN95s filtered 57–77%, and the N95 and CaN99 97–98% without fit testing. External braces and overmasking with a well-fitting cloth mask increased filtration, but earguards, scrub caps, and the knot-and-tuck method did not. Limitations Limited number of masks of each type sampled; no adjustment for multiple comparisons. Conclusions and Relevance Well-fitting 2-layer cotton masks filter in the same range as level 1 masks when worn: around 50%. Level 3 masks and KN95s/KF94s filter around 70%. Over a level 1 mask, external braces or overmasking with a cloth-mask-on-ties produced filtration around 90%. Only N95s and CaN99s, both of which have overhead elastic, performed close to the occupational health and safety standards for fit tested PPE (>99%), filtering at 97–99% when worn, without formal fit testing. These findings inform public health messaging about relative protection from aerosols afforded by different mask types and explain the effectiveness of cloth masks observed in numerous epidemiologic studies conducted in the first year of the pandemic. A plain language summary of these findings is available at https://maskevidence.org/masks-compared.

The stigma surrounding mental illnesses is widespread and informal caregivers of patients with mental illness face stigma because of their relationship with the patients they care for. Despite the key role played by these informal caregivers in the management of people with mental illness, few studies have assessed affiliate stigma and its factors associated among this population. This study aimed to investigate the prevalence of affiliate stigma and associated factors among caregivers of patients with mental illness in southwestern Uganda. We used a cross-sectional study design and enrolled 385 caregivers. We assessed affiliate stigma, depression, and social support using the affiliate stigma scale, patient health questionnaire-9 and social support using the social provision scale respectively. We ran multivariable logistic regression models to assess for the factors associated with affiliate stigma among caregivers. The prevalences of affiliate stigma and depression were 65.97% and 25.2% respectively. Factors associated with affiliate stigma included caregiving for one year or longer (AOR: 1.89; 95% CI: 01.07–03.35; p = 0.03), having more than one patient to care for (AOR: 3.40; 95% CI: 01.39–08.36; p = 0.01), being the only caregiver to the patient (AOR: 2.60; 95% CI: 1.27–5.33; p = 0.01), being depressed (AOR: 75.76; 95% CI: 10.03–572.26; p < 0.001), and social support (AOR: 0.14; 95% CI: 0.06–0.29; p = 0.04). This prevalence of affiliate stigma among caregivers of patients with mental illness is high in southwestern Uganda and depression is a key predictor. Considering the important role played by informal caregivers, more studies are necessary to inform interventions to address affiliate stigma, depression, and overall mental health of caregivers.

Introduction Shoulder pain is a debilitating musculoskeletal condition with functional, physical, and psychological impacts. Interventions for chronic shoulder pain should address the biopsychosocial model, with Cognitive Functional Therapy (CFT) emerging as a promising physiotherapy approach. CFT approaches the multidimensional nature of pain, integrating physical and cognitive aspects. To date, no study has assessed the effectiveness of CFT in individuals with chronic shoulder pain. Therefore, this randomized controlled trial aims to compare the effects of CFT to therapeutic exercises on pain intensity, disability, self-efficacy, sleep quality, biopsychosocial aspects, and central pain processing in individuals with chronic shoulder pain. Methods This will be a randomized controlled trial, single-blinded with two parallel groups. Seventy-two individuals with chronic shoulder pain will be randomly assigned to one of two groups: CFT or Therapeutic exercise. The interventions will last 8 weeks, with the CFT group receiving therapy once a week and the therapeutic exercise group receiving sessions twice a week. The primary outcomes will be pain intensity and disability, while the secondary outcomes will include function, self-efficacy, sleep quality, biopsychosocial factors, perception of improvement/deterioration, and central pain processing. The outcome measures will be assessed at baseline, 4th week, end of treatment (8th week), and 12th-week follow-up. Conclusion The results of this study will contribute to understanding the effectiveness of CFT in treating individuals with chronic shoulder pain. Trial registration number: NCT06542666

To manage defoliation from insect outbreaks, about half of the forested land in New Brunswick, Canada, was treated with dichlorodiphenyltrichloroethane (DDT) between 1952 and 1968. Aerial applications of DDT have thus likely increased the risk of chronic effects in aquatic ecosystems from this legacy insecticide given its high persistence in soil and sediments and its bioaccumulation potential within the food web. We investigated DDT and its metabolites (total ΣDDTs = ∑ DDT + ∑ DDD + ∑ DDE) in Brook Trout (Salvelinus fontinalis) associated with geospatial data of historical applications to lake watersheds and sedimentary measures of DDT and its metabolites from five “impact” and two “reference” study lakes. Total ΣDDTs in recent lake sediments were significantly correlated with cumulative DDT applied aerially to the lake’s watershed. Brook Trout muscle tissue showed total ΣDDTs that were significantly higher from impact lakes than reference lakes. On average, total ΣDDTs in Brook Trout from impact lakes exceeded ecological guidelines for consumers of aquatic biota by about ten times. Most legacy DDT in Brook Trout and lake sediments were the metabolites ΣDDE and ΣDDD, which suggests the importance of environmental conditions and transport of weathered sources of this organochlorine insecticide to biota. Stable isotopes from fish and common invertebrate prey also suggested that Brook Trout were at a similar trophic position among all study lakes and thus storage pools of legacy DDT likely explain contamination levels within biota. Our findings clearly demonstrate that chronic effects of historical DDT applications likely persist throughout aquatic environments in north-central New Brunswick.

While the aging population is well documented and understood, as is the fact that avoiding premature death is important in being able to age well, the concept of aging well is a more elusive idea. In general, the idea of successful aging in health terms means compression of the period of morbidity experienced by an individual (Fries et al. J Aging Res, 2011). Comments in the literature noting that there is not yet a consensus definition of aging well reflects the very individual and subjective nature of expectations, adaptation, and satisfaction with life that relate to this. A systematic analysis by Kim et al. of “successful aging” includes domains such as avoiding disease and disability, having high cognitive, mental, and physical function, being actively engaged in life, and being psychologically well adapted in later life (Kim and Park, Res Aging 39(5):657–677, 2017). Similarly, in the model of “Aging well” by Fernandez-Ballesteros et al., successful aging is defined by the domains of health and activities of daily living (ADL), physical and cognitive functioning, social participation and engagement, and also positive affect and control (Fernández-Ballesteros et al. J Am Geriatr Soc 56(5):950–952, 2008). For every individual a life worth living on their terms may be very different, as eloquently expressed by Sir Theodore Fox, an Editor of the Lancet for many years. “Not least do people differ in their attitude to life. Some cling to it as a miser to his money, and to as little purpose. Others wear it lightly—ready to risk it for a cause, a hope, a song, the wind on their face. When so many people think of it as a means, the doctor, surely, would be wrong to insist that it is always the first of ends. Life is not really the most important thing in life.” (Fox Lancet 286(7417):801–805, 1965)

The initial microbial colonization of the infant gut during birth plays a critical role in shaping both immediate and long-term health outcomes. While mode of delivery is a known determinant of this colonization process, the potential impacts of infant sex and birth order remain underexplored. This study investigates the influence of delivery mode, infant sex, and birth order (maternal parity) on the microbial communities in first-pass meconium samples from neonates, using 16S rRNA gene sequencing. We found that delivery mode impacted the presence of detectable microbial communities. Specifically, only 17% of samples from neonates delivered by elective Cesarean section showed any microbial presence, compared to approximately two-thirds of samples from neonates exposed to maternal vaginal microbes (emergency C-section or vaginal delivery). Among vaginally delivered neonates without antibiotic exposure, birth order was associated with taxonomic shifts. Neonates born to primiparous mothers had a lower abundance of Bifidobacterium, a keystone species in the infant gut microbiome. Unexpectedly, the gut microbiota differed by infant sex, with males having lower alpha diversity and shifts in microbial community composition (PERMANOVA p = 0.008), characterized by elevated levels of Enterobacteriales, which was both less prevalent and less abundant in female neonates. These findings highlight the intricate interplay between delivery mode, infant sex, and birth order in shaping the early gut microbiome.

Atrial fibrillation is a frequent cardiac arrhythmia and is associated with an increased risk of cardioembolic stroke. The left atrial appendage is a finger-like extension originating from the main body of the left atrium and the main location of thrombus formation in patients with atrial fibrillation. Surgical or percutaneous left atrial appendage occlusion (LAAO) aims at preventing clot formation in the left atrial appendage. Here, we describe available surgical and percutaneous approaches to achieve LAAO and discuss the available evidence for LAAO in patients with atrial fibrillation. We discuss the role of LAAO and its role in stroke prevention in frequent scenarios in cerebrovascular medicine: LAAO as a potential alternative to oral anticoagulation in patients with a history of intracranial hemorrhage, and LAAO as a promising add-on therapy to direct oral anticoagulant therapy in patients with breakthrough stroke despite anticoagulation. Finally, we provide an outlook on currently ongoing trials that will provide further evidence in the next years.

Background: Since the beginning of the COVID-19 pandemic, moral distress among healthcare workers in the Intensive Care Unit (ICU) has garnered both media and academic attention. Moral distress has been theorized as occurring when individuals are constrained from doing what they perceive as morally right. This study sought to empirically examine the lived experiences of moral distress among clinical and administrative healthcare professionals in a sample of Canadian ICUs during the COVID-19 pandemic. Methods: Qualitative case study methodology was used as the overarching approach, collecting and comparing data from two distinct cases: one ICU in Ontario and one in Alberta. Data collection involved two primary sources: semi-structured interviews with staff and document review of institutional and government directives to provide contextual data. Data analysis commenced concurrently with data collection, and generated within- and across-case themes, as well as allowed descriptive accounts of moral distress. Results: Thirty-six healthcare workers across two sites were interviewed. Participants described three primary categories of constraints leading to moral distress. These were: 1) The rapidity and opaqueness of policy development, specifically pertaining to 2) the implementation of family visitation and treatment triage decisions, and 3) resource shortages, which reduced patient interactions, shifted professional responsibilities. Each of these constraints yielded circumstances and forced decisions that were perceived as morally wrong because they compromised care quality and outcomes. Conclusions: While sharing similarities with the growing literature on moral distress in the context of the COVID-19 pandemic, this study reveals new insights on how provincial and institutional policy has direct bearing on experiences of moral distress. Policies and circumstances forced ICU staff to choose between actions they considered the most right and the least wrong. Understanding these specific policy-driven constraints highlights the need for healthcare systems and processes that mitigate moral distress and sustain our health workforce.

Background Clinical practice guidelines provide important evidence-based recommendations to optimize patient care, but their development is labor-intensive and time-consuming. Large language models have shown promise in supporting academic writing and the development of systematic reviews, but their ability to assist with guideline development has not been explored. In this study, we tested the capacity of LLMs to support each stage of guideline development, using the latest SAGES guideline on the surgical management of appendicitis as a comparison. Methods Prompts were engineered to trigger LLMs to perform each task of guideline development, using key questions and PICOs derived from the SAGES guideline. ChatGPT-4, Google Gemini, Consensus, and Perplexity were queried on February 21, 2024. LLM performance was evaluated qualitatively, with narrative descriptions of each task’s output. The Appraisal of Guidelines for Research and Evaluation in Surgery (AGREE-S) instrument was used to quantitatively assess the quality of the LLM-derived guideline compared to the existing SAGES guideline. Results Popular LLMs were able to generate a search syntax, perform data analysis, and follow the GRADE approach and Evidence-to-Decision framework to produce guideline recommendations. These LLMs were unable to independently perform a systematic literature search or reliably perform screening, data extraction, or risk of bias assessment at the time of testing. AGREE-S appraisal produced a total score of 119 for the LLM-derived guideline and 156 for the SAGES guideline. In 19 of the 24 domains, the two guidelines scored within two points of each other. Conclusions LLMs demonstrate potential to assist with certain steps of guideline development, which may reduce time and resource burden associated with these tasks. As new models are developed, the role for LLMs in guideline development will continue to evolve. Ongoing research and multidisciplinary collaboration are needed to support the safe and effective integration of LLMs in each step of guideline development.