Objective: Prior studies evaluating the impact of discontinuation of contact precautions (DcCP) on methicillin-resistant Staphylococcus aureus (MRSA) outcomes have characterized all healthcare-associated infections (HAIs) rather than those likely preventable by contact precautions. We aimed to analyze the impact of DcCP on the rate of MRSA HAI including transmission events identified through whole genome sequencing (WGS) surveillance. Design: Quasi experimental interrupted time series. Setting: Acute care medical center. Participants: Inpatients. Methods: The effect of DcCP (use of gowns and gloves) for encounters among patients with MRSA carriage was evaluated using time series analysis of MRSA HAI rates from January 2019 through December 2022, compared to WGS-defined attributable transmission events before and after DcCP in December 2020. Results: The MRSA HAI rate was 4.22/10,000 patient days before and 2.98/10,000 patient days after DcCP (incidence rate ratio [IRR] 0.71 [95% confidence interval 0.56-0.89]) with a significant immediate decrease (P = .001). There were 7 WGS-defined attributable transmission events before and 11 events after DcCP (incident rate ratio 0.90 [95% confidence interval 0.30-2.55]). Conclusions: DcCP did not result in an increase in MRSA HAI or, in WGS-defined attributable transmission events. Comprehensive analyses of the effect of transmission prevention measures should include outcomes specifically measuring transmission-associated HAI.
Current pharmacological therapeutic approaches targeting chronic inflammation exhibit transient efficacy, often with adverse effects, limiting their widespread use - especially in the context of neuroinflammation. Effective interventions require the consideration of homeostatic function, pathway dysregulation, and pleiotropic effects when evaluating therapeutic targets. Signalling molecules have multiple functions dependent on the immune context, and this complexity results in therapeutics targeting a single signalling molecule often failing in clinical translation. Additionally, the administration of non-physiologic levels of neurotrophic or anti-inflammatory factors can alter endogenous signalling, resulting in unanticipated effects. Exacerbating these challenges, the central nervous system (CNS) is isolated by the blood brain barrier (BBB), restricting the infiltration of many pharmaceutical compounds into the brain tissue. Consequently, there has been marked interest in therapeutic techniques capable of modulating the immune response in a pleiotropic manner; ultrasound remains on this frontier. While ultrasound has been used therapeutically in peripheral tissues - accelerating healing in wounds, bone fractures, and reducing inflammation - it is only recently that it has been applied to the CNS. The transcranial application of low intensity pulsed ultrasound (LIPUS) has successfully mitigated neuroinflammation in vivo, in models of neurodegenerative disease across a broad spectrum of ultrasound parameters. To date, the underlying biological effects and signalling pathways modulated by ultrasound are poorly understood, with a diverse array of reported molecules implicated. The distributed nature of the beneficial response to LIPUS implies the involvement of an, as yet, undetermined upstream signalling pathway, homologous to the protective effect of febrile range hyperthermia in chronic inflammation. As such, we review the heat shock response (HSR), a protective signalling pathway activated by thermal and mechanical stress, as the possible upstream regulator of the anti-inflammatory effects of ultrasound.
Heat-Shock Response , Neuroinflammatory Diseases , Humans , Animals , Neuroinflammatory Diseases/immunology , Ultrasonic Therapy/methods , Inflammation/immunology , Blood-Brain Barrier/metabolism
OBJECTIVES: Previous literature has consistently documented harassment and discrimination in surgery. These experiences may contribute to the continuing gender inequity in surgical fields. The objective of our study was to survey Canadian surgeons and surgical trainees to gain a greater understanding of the experience of harassment across genders, career stage, and specialty. METHODS: A cross-sectional, online survey was distributed to Canadian residents, fellows, and practicing surgeons in general surgery, plastic surgery, and neurosurgery through their national society email lists and via social media posts. RESULTS: There were 194 included survey respondents (60 residents, 11 fellows, and 123 staff) from general surgery (44.8%), plastic surgery (42.7%), and neurosurgery (12.5%). 59.8% of women reported having experienced harassment compared to only 26.0% of men. Women were significantly more likely to be harassed by colleagues and patients/families compared to men. Residents (62.5%) were two times more likely to report being harassed compared to fellows/staff (38.3%). Residents were significantly more likely to be harassed by patients/families while fellows/staff were more likely to be harassed by colleagues. There were no significant differences in self-reported harassment across the three surgical specialties. There was no significant difference in rates of reported harassment between current residents (62.5%), and fellow/staff recollections of their experiences of harassment during residency (59.2%). CONCLUSIONS: The prevalence of gender-based discrimination remains high and harassment prevalence remains largely unchanged from when current staff were in residency. Our findings highlight a need to implement systemic changes to support the increasing number of women entering surgery, and to improve surgical culture to continue to attract the best and brightest to the field.
BACKGROUND AND OBJECTIVES: Pain management in patients with cancer is a critical issue in oncology palliative care as clinicians aim to enhance quality of life and mitigate suffering. Most patients with cancer experience cancer-related pain, and 30%-40% of patients experience intractable pain despite maximal medical therapy. Intrathecal pain pumps (ITPs) have emerged as an option for achieving pain control in patients with cancer. Owing to the potential benefits of ITPs, we sought to study the long-term outcomes of this form of pain management at a cancer center. METHODS: We retrospectively reviewed medical records of all adult patients with cancer who underwent ITP placement at a tertiary comprehensive cancer center between 2013 and 2021. Baseline characteristics, preoperative and postoperative pain control, and postoperative complication rate data were collected. RESULTS: A total of 193 patients were included. We found that the average Numerical Rating Scale (NRS) score decreased significantly by 4.08 points (SD = 2.13, P < .01), from an average NRS of 7.38 (SD = 1.64) to an average NRS of 3.27 (SD = 1.66). Of 185 patients with preoperative and follow-up NRS pain scores, all but 9 experienced a decrease in NRS (95.1%). The median overall survival from time of pump placement was 3.62 months (95% CI: 2.73-4.54). A total of 42 adverse events in 33 patients were reported during the study period. The 1-year cumulative incidence of any complication was 15.6% (95% CI: 10.9%-21.1%) and for severe complication was 5.7% (95% CI: 3.0%-9.7%). Eleven patients required reoperation during the study period, with a 1-year cumulative incidence of 4.2% (95% CI: 2.0%-7.7%). CONCLUSION: Our study demonstrates that ITP implantation for the treatment of cancer-related pain is a safe and effective method of pain palliation with a low complication rate. Future prospective studies are required to determine the optimal timing of ITP implantation.
Background: Vancomycin-resistant enterococcal (VRE) infections pose significant challenges in healthcare. Transmission dynamics of VRE are complex, often involving patient colonization and subsequent transmission through various healthcare-associated vectors. We utilized a whole genome sequencing (WGS) surveillance program at our institution to better understand the contribution of clinical and colonizing isolates to VRE transmission. Methods: We performed whole genome sequencing on 352 VRE clinical isolates collected over 34 months and 891 rectal screening isolates collected over a 9-month nested period, and used single nucleotide polymorphisms to assess relatedness. We then performed a geo-temporal transmission analysis considering both clinical and rectal screening isolates compared with clinical isolates alone, and calculated 30-day outcomes of patients. Results: VRE rectal carriage constituted 87.3% of VRE acquisition, with an average monthly acquisition rate of 7.6 per 1000 patient days. We identified 185 genetically related clusters containing 2-42 isolates and encompassing 69.6% of all isolates in the dataset. The inclusion of rectal swab isolates increased the detection of clinical isolate clusters (from 53% to 67%, P<0.01). Geo-temporal analysis identified hotspot locations of VRE transmission. Patients with clinical VRE isolates that were closely related to previously sampled rectal swab isolates experienced 30-day ICU admission (17.5%), hospital readmission (9.2%), and death (13.3%). Conclusions: Our findings describe the high burden of VRE transmission at our hospital and shed light on the importance of using WGS surveillance of both clinical and rectal screening isolates to better understand the transmission of this pathogen. This study highlights the potential utility of incorporating WGS surveillance of VRE into routine hospital practice for improving infection prevention and patient safety.
BACKGROUND AND HYPOTHESIS: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient. METHODS: Using a dataset of 6666 deceased and living kidney donors from seven different European ancestry transplant cohorts, we investigated the role of polygenic burden for cerebrovascular traits (hypertension, stroke, and intracranial aneurysm (IA)) on donor age of death and recipient graft outcomes. RESULTS: We found that kidney donors who died of stroke had elevated intracranial aneurysm and hypertension polygenic risk scores, compared to healthy controls and living donors. This burden was associated with age of death among donors who died of stroke. Increased donor polygenic risk for hypertension was associated with reduced long term graft survival (HR: 1.44, 95% CI [1.07, 1.93]) and increased burden for hypertension, and intracranial aneurysm was associated with reduced recipient estimated glomerular filtration rate (eGFR) at 1 year. CONCLUSIONS: Collectively, the results presented here demonstrate the impact of inherited factors associated with donors' death on long-term graft function.
A central aim of genome-wide association studies (GWASs) is to estimate direct genetic effects: the causal effects on an individual's phenotype of the alleles that they carry. However, estimates of direct effects can be subject to genetic and environmental confounding and can also absorb the "indirect" genetic effects of relatives' genotypes. Recently, an important development in controlling for these confounds has been the use of within-family GWASs, which, because of the randomness of mendelian segregation within pedigrees, are often interpreted as producing unbiased estimates of direct effects. Here, we present a general theoretical analysis of the influence of confounding in standard population-based and within-family GWASs. We show that, contrary to common interpretation, family-based estimates of direct effects can be biased by genetic confounding. In humans, such biases will often be small per-locus, but can be compounded when effect-size estimates are used in polygenic scores (PGSs). We illustrate the influence of genetic confounding on population- and family-based estimates of direct effects using models of assortative mating, population stratification, and stabilizing selection on GWAS traits. We further show how family-based estimates of indirect genetic effects, based on comparisons of parentally transmitted and untransmitted alleles, can suffer substantial genetic confounding. We conclude that, while family-based studies have placed GWAS estimation on a more rigorous footing, they carry subtle issues of interpretation that arise from confounding.
Genome-Wide Association Study , Multifactorial Inheritance , Humans , Genotype , Phenotype , Multifactorial Inheritance/genetics , Alleles , Polymorphism, Single Nucleotide/genetics
"All or none" approaches to the use of contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) both fail to recognize that transmission risk varies. This qualitative study assessed healthcare personnel perspectives regarding the feasibility of a risk-tailored approach to use contact precautions for MRSA more strategically in the acute care setting.
Purpose: Bronchial thermoplasty (BT) is a bronchoscopic intervention for the treatment of severe asthma. Despite demonstrated symptomatic benefit, the underlying mechanisms by which this is achieved remain uncertain. We hypothesize that the effects of BT are driven by improvements in ventilation heterogeneity as assessed using functional respiratory imaging (FRI). Patient and Methods: Eighteen consecutive patients with severe asthma who underwent clinically indicated BT were recruited. Patients were assessed at baseline, 4-week after treatment of the left lung, and 12-month after treatment of the right lung. Data collected included short-acting beta-agonist (SABA) and oral prednisolone (OCS) use, asthma control questionnaire (ACQ-5) and exacerbation history. Patients also underwent lung function tests and chest computed tomography. Ventilation parameters including interquartile distance (IQD; measure of ventilation heterogeneity) were derived using FRI. Results: 12 months after BT, significant improvements were seen in SABA and OCS use, ACQ-5, and number of OCS-requiring exacerbations. Apart from pre-bronchodilator FEV1, no other significant changes were observed in lung function. Ventilation heterogeneity significantly improved after treatment of the left lung (0.18 ± 0.04 vs 0.20 ± 0.04, p=0.045), with treatment effect persisting up to 12 months later (0.18 ± 0.05 vs 0.20 ± 0.04, p=0.028). Ventilation heterogeneity also improved after treatment of the right lung, although this did not reach statistical significance (0.18 ± 0.05 vs 0.19 ± 0.04, p=0.06). Conclusion: Clinical benefits after BT are accompanied by improvements in ventilation heterogeneity, advancing our understanding of its mechanism of action. Beyond BT, FRI has the potential to be expanded into other clinical applications.
Objectives: Increasing numbers of women enter medical school annually. The number of female physicians in leadership positions has been much slower to equalize. There are also well-documented differences in the treatment of women as compared to men in professional settings. Female presenters are less likely to be introduced by their professional title ("Doctor") for grand rounds and conferences, especially with a man performing the introduction. This study reviewed the Canadian Society of Otolaryngology-Head and Neck Surgery (CSOHNS) meetings from 2017 to 2020 to determine the proportion of presenters introduced by their professional title and whether this varied by gender. Methods: Recordings from CSOHNS meetings were reviewed and coded for introducer and presenter demographics, including leadership positions and gender. Chi-squared tests of proportion and multivariate logistic regression was used to compare genders and identify factors associated with professional versus unprofessional forms of address. Results: No significant association was found between professional title use and introducer or presenter gender. Female presenters were introduced with professional title 69.6% of the time, while male presenters were introduced with professional title 67.6% of the time (P = 0.69). Residents were introduced with a professional title with the most frequency (75.8%), while attending staff were introduced with a professional title with the least frequency (63.0%) (P = 0.02). Conclusions: The lack of gender bias in speaker introductions at recent CSOHNS meetings demonstrates progress in achieving gender equity in medicine. Research efforts should continue to define additional forms of unconscious bias that may be contributing to gender inequity in leadership positions.
Background: Ankyloglossia (AG) diagnoses are increasingly common, and management is not standardized. Nonsurgical alternative therapies are frequently recommended in conjunction with or instead of frenotomy, with uncertain evidence. Objective: To evaluate the efficacy of nonsurgical alternative therapies (chiropractic care, myofunctional therapy, and osteopathy) in improving breastfeeding for infants diagnosed with AG. Methods: PubMed, Embase, CINAHL, Scopus, Web of Science, Clinicaltrials.gov, and Google Scholar were searched (September-October 2023). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A librarian-designed search included the terms "Ankyloglossia," "Non-surgical," "myofunctional therapy," "chiropractic," "osteopathy," and related therapies, with no date restrictions. English language studies of infants <24 months with AG and alternative therapy were included. Risk-of-bias evaluation used Newcastle-Ottawa Scale (NOS). Results: Of 1,304 identified articles, four studies (2016-2022) met inclusion criteria (two cross-sectional, one case report, and one case series). All studies reported frenotomy in combination with alternative therapy yielded favorable outcomes for maternal pain, weight gain, feeding duration, and maintenance of latch. The risk of bias was moderate for two studies, low for the case series, and not calculated for the case report, which has an inherent high risk of bias. All studies lacked control or comparator groups preventing definitive conclusions about the role of alternative therapies in AG. Conclusion: Although some studies suggest the potential benefits of combining alternative therapies with surgery for AG-related breastfeeding issues, the lack of control groups renders the evidence inconclusive. Nonsurgical approaches alone currently lack sufficient evidence. As these alternative therapies gain popularity, rigorous research is crucial to determine their cost-effectiveness and role in managing AG.
Obesity is a contributing factor to asthma severity; while it has long been understood that obesity is related to greater asthma burden, the mechanisms though which this occurs have not been fully elucidated. One common explanation is that obesity mechanically reduces lung volume through accumulation of adipose tissue external to the thoracic cavity. However, it has been recently demonstrated that there is substantial adipose tissue within the airway wall itself, and that the presence of adipose tissue within the airway wall is related to body mass index. This suggests the possibility of an additional mechanism by which obesity may worsen asthma, namely by altering the behaviour of the airways themselves. To this end, we modify Anafi & Wilson's classic model of the bistable terminal airway to incorporate adipose tissue within the airway wall in order to answer the question of how much adipose tissue would be required in order to drive substantive functional changes. This analysis suggests that adipose tissue within the airway wall on the order of 1%-2% of total airway cross-sectional area could be sufficient to drive meaningful changes, and further that these changes may interact with volume effects to magnify the overall burden.
Adipose Tissue , Asthma , Models, Biological , Obesity , Adipose Tissue/metabolism , Humans , Asthma/physiopathology , Obesity/physiopathology , Obesity/metabolism , Lung/physiology
Two experiments investigated the role of visual imagery in prospective memory (PM). In experiment 1, 140 participants completed a general knowledge quiz which included a PM task of writing a letter "X" next to any questions that referred to space. Participants either visualised themselves performing this task, verbalised an implementation intention about the task, did both, or did neither. Performance on the PM task was enhanced in both conditions involving visual imagery but not by implementation intentions alone. In experiment 2, 120 participants imagined themselves writing a letter "X" next to questions about space, or in a bizarre imagery condition imagined themselves drawing an alien next to those questions. Relative to the control condition, PM was significantly enhanced when participants imagined writing a letter "X" next to the target questions, but not by the bizarre imagery task. The findings indicate that the robust effects of imagery observed in retrospective memory also extend to PM.
Imagination , Memory, Episodic , Humans , Male , Female , Young Adult , Adult , Visual Perception/physiology , Adolescent
INTRODUCTION: Women in surgery face unique challenges, particularly as it relates to family planning, parental leave, infant feeding, and career advancement. This study highlights disparities in present day general surgery training to tackle longstanding gender inequities. METHODS: An open, anonymous online survey was distributed to Canadian residents, fellows, and practicing general surgeons through the Canadian Association of General Surgeons e-mail list from November 2021-March 2022. Data were analyzed descriptively and chi-square tests were performed to examine categorical outcomes across gender. RESULTS: A total of 89 general surgery respondents (13.8% response rate) completed the survey (22 cisgender men; 65 cisgender women). Twenty six percent of participants had accessed fertility services or used assistive reproductive technologies. Of the participants with children, 36.4% of men and 100.0% of women took at least one parental leave during residency or clinical practice. A greater proportion of women compared to men agreed that their training/practice influenced their decision to have children (P = 0.002) and when to have children (P < 0.001). Similarly, a greater proportion of women indicated they had concerns about future family planning (P = 0.008), future fertility (P = 0.002), and future parental leave (P = 0.026). Fifty nine percent of women and zero men agreed that taking parental leave impacted their career advancement (P = 0.04). CONCLUSIONS: Women surgeons and surgical trainees continue to face challenges with respect to family planning, parental leave, infant feeding, and career advancement. Further research is needed to explore the experiences of women surgeons. By providing surgeons with the support required to achieve their family planning goals, surgeons can accomplish their family and career goals with less conflict.
General Surgery , Internship and Residency , Male , Child , Infant , Humans , Female , Family Planning Services , Canada , Gender Identity , Surveys and Questionnaires , Perception , General Surgery/education , Career Choice
Objective: Infants with significant retrognathia often have difficulty forming a latch adequate to establish exclusive breastfeeding. This article describes the use of at-breast supplementers (ABSs) to facilitate extended breastfeeding relationships, even when supplementation is necessary for growth. Methods: Two cases are described where infants with severe retrognathia initially struggled with weight gain necessitating supplementation but were able to ultimately exclusively feed at-breast with the use of ABSs. Results: While the two cases differed in the form of supplemental milk used and duration of ABS use, both dyads breastfed for beyond 2 years. Conclusions: Feeding solely at the breast and subsequent extended breastfeeding may be possible even for infants who require supplementation, including those with anatomical or functional challenges such as retrognathia. The ABS is a relatively simple system that may be beneficial for difficulties such as poor latch and low milk supply. More awareness and education is needed so that clinicians consider supporting dyads with this approach.
Breast Feeding , Retrognathia , Infant , Female , Humans , Animals , Allergens , Milk
OBJECTIVES: New Delhi metallo-ß-lactamase (NDM) is an emergent mechanism of carbapenem resistance associated with high mortality and limited treatment options. Because the blaNDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks. METHODS: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance performed weekly. To resolve NDM-encoding plasmids, we performed long-read sequencing and constructed hybrid assemblies. WGS data for suspected outbreaks was shared with the IP&C team for assessment and intervention. RESULTS: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included 7 bacterial species encoding the same NDM-5 plasmid. WGS surveillance and epidemiologic investigation characterized 10 horizontal plasmid transfer events and 6 bacterial transmission events between patients in varying hospital units. CONCLUSIONS: Our investigation revealed a complex, multispecies outbreak of NDM involving multiple plasmid transfer and bacterial transmission events. We highlight the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks.
Gammaproteobacteria , beta-Lactamases , Humans , Prospective Studies , Plasmids/genetics , beta-Lactamases/genetics , Hospitals , Genomics , Klebsiella pneumoniae , Disease Outbreaks , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests
