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To identify preventable factors that contribute to the cross transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to patients in healthcare facilities.
Design:
A case–control study was conducted among inpatients on a coronavirus disease 2019 (COVID-19) outbreak unit.
Setting:
This study was conducted in a medical-surgical unit of a tertiary-care hospital in Nova Scotia in May 2021.
Patients:
Patients hospitalized on the unit for at least 12 hours and healthcare workers (HCW) working on the unit within 2 weeks of outbreak declaration were included.
Methods:
Risk factors for SARS-CoV-2 infection were analyzed using simple and multiple logistic regression. Whole-genome sequencing (WGS) was performed to identify SARS-CoV-2 strain relatedness. Network analysis was used to describe patient accommodation.
Results:
SARS-CoV-2 infections were identified in 21 patients (29.6%) and 11 HCWs (6.6%). WGS data revealed 4 distinct clades of related sequences. Several factors likely contributed to the outbreak, including failure to identify SARS-CoV-2, a largely incomplete or unvaccinated population, and patient wandering behaviors. The most significant risk factor for SARS-CoV-2 infection was room sharing with an infectious patient, which was the only factor that remained statistically significant following multivariate analysis (odds ratio [OR], 9.2l; 95% confidence interval [CI], 2.04–41.67; P = .004).
Conclusions:
This outbreak likely resulted from admission of 2 patients with COVID-19, with subsequent transmissions to 17 patients and 11 staff. WGS and bioinformatics analyses were critical to identifying previously unrecognized nosocomial transmissions of SARS-CoV-2. This study supports strategies to reduce nosocomial transmissions of SARS-CoV-2, such as single-patient rooms, promotion of COVID-19 vaccination, and infection prevention and control measures including management of wandering behaviors.
Policies that promote conversion of antibiotics from intravenous to oral route administration are considered “low hanging fruit” for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.
Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.
U.S. veterans report high rates of traumatic experiences and mental health symptomology [e.g. posttraumatic stress disorder (PTSD)]. The stress sensitization hypothesis posits experiences of adversity sensitize individuals to stress reactions which can lead to greater psychiatric problems. We extend this hypothesis by exploring how multiple adversities such as early childhood adversity, combat-related trauma, and military sexual trauma related to heterogeneity in stress over time and, subsequently, greater risk for PTSD.
Methods
1230 veterans were recruited for an observational, longitudinal study. Veterans responded to questionnaires on PTSD, stress, and traumatic experiences five times over an 18-month study period. We used latent transition analysis to understand how heterogeneity in adverse experiences is related to transition into stress trajectory classes. We also explored how transition patterns related to PTSD symptomology.
Results
Across all models, we found support for stress sensitization. In general, combat trauma in combinations with other types of adverse experiences, namely early childhood adversity and military sexual trauma, imposed a greater probability of transitioning into higher risk stress profiles. We also showed differential effects of early childhood and military-specific adversity on PTSD symptomology.
Conclusion
The present study rigorously integrates both military-specific and early life adversity into analysis on stress sensitivity, and is the first to examine how sensitivity might affect trajectories of stress over time. Our study provides a nuanced, and specific, look at who is risk for sensitization to stress based on previous traumatic experiences as well as what transition patterns are associated with greater PTSD symptomology.
OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.
Research among non-industrial societies suggests that body kinematics adopted during running vary between groups according to the cultural importance of running. Among groups in which running is common and an important part of cultural identity, runners tend to adopt what exercise scientists and coaches consider to be good technique for avoiding injury and maximising performance. In contrast, among groups in which running is not particularly culturally important, people tend to adopt suboptimal technique. This paper begins by describing key elements of good running technique, including landing with a forefoot or midfoot strike pattern and leg oriented roughly vertically. Next, we review evidence from non-industrial societies that cultural attitudes about running associate with variation in running techniques. Then, we present new data from Tsimane forager–horticulturalists in Bolivia. Our findings suggest that running is neither a common activity among the Tsimane nor is it considered an important part of cultural identity. We also demonstrate that when Tsimane do run, they tend to use suboptimal technique, specifically landing with a rearfoot strike pattern and leg protracted ahead of the knee (called overstriding). Finally, we discuss processes by which culture might influence variation in running techniques among non-industrial societies, including self-optimisation and social learning.
Social distancing to limit COVID-19 transmission has led to extensive lifestyle changes, including for people with dementia (PWD). The aim of this study, therefore, was to assess the impact of lockdown on the mental health of PWD and their carers.
Methods:
Forty-five carers of PWD completed a telephone interview during the baseline assessment of the SOLITUDE study to gather information on life conditions and changes in symptoms of PWD during lockdown. Associations between changes in symptoms of PWD and carers’ concerns and mental health were investigated.
Results:
About 44% of carers experienced anxiety and irritability and reported changes in behavioural and cognitive symptoms in PWD. These changes were associated with worse carers’ mental health and concerns about faster disease progression (χ2 = 13.542, p < 0.001).
Conclusion:
COVID-19-related social isolation has had a negative impact on patients’ and carers’ mental health. Potential long-term neurocognitive consequences require further investigation.
Portable oxygen concentrators (POCs) are medical devices that use physical means to separate oxygen from the atmosphere to produce concentrated, medical-grade gas. Providing oxygen to low-resources environments, such as austere locations, military combat zones, rural Emergency Medical Services (EMS), and during disasters, becomes expensive and logistically intensive. Recent advances in separation technology have promoted the development of POC systems ruggedized for austere use. This review provides a comprehensive summary of the available data regarding POCs in these challenge environments.
Methods:
PubMed, Google Scholar, and the Defense Technical Information Center were searched from inception to November 2021. Articles addressing the use of POCs in low-resource settings were selected. Three authors were independently involved in the search, review, and synthesis of the articles. Evidence was graded using Oxford Centre for Evidence-Based Medicine guidelines.
Results:
The initial search identified 349 articles, of which 40 articles were included in the review. A total of 724 study subjects were associated with the included articles. There were no Level I systematic reviews or randomized controlled trials.
Discussion:
Generally, POCs are a low-cost, light-weight tool that may fill gaps in austere, military, veterinary, EMS, and disaster medicine. They are cost-effective in low-resource areas, such as rural and high-altitude hospitals in developing nations, despite relatively high capital costs associated with initial equipment purchase. Implementation of POC in low-resource locations is limited primarily on access to electricity but can otherwise operate for thousands of hours without maintenance. They provide a unique advantage in combat operations as there is no risk of explosive if oxygen tanks are struck by high-velocity projectiles. Despite their deployment throughout the battlespace, there were no manuscripts identified during the review involving the efficacy of POCs for combat casualties or clinical outcomes in combat. Veterinary medicine and animal studies have provided the most robust data on the physiological effectiveness of POCs. The success of POCs during the coronavirus disease 2019 (COVID-19) pandemic highlights the potential for POCs during future mass-casualty events. There is emerging technology available that combines a larger oxygen concentrator with a compressor system capable of refilling small oxygen cylinders, which could transform the delivery of oxygen in austere environments if ruggedized and miniaturized. Future clinical research is needed to quantify the clinical efficacy of POCs in low-resource settings.
The developmental origins of psychopathology begin before birth and perhaps even prior to conception. Understanding the intergenerational transmission of psychopathological risk is critical to identify sensitive windows for prevention and early intervention. Prior research demonstrates that maternal trauma history, typically assessed retrospectively, has adverse consequences for child socioemotional development. However, very few prospective studies of preconception trauma exist, and the role of preconception symptoms of posttraumatic stress disorder (PTSD) remains unknown. The current study prospectively evaluates whether maternal preconception PTSD symptoms predict early childhood negative affectivity, a key dimension of temperament and predictor of later psychopathology. One hundred and eighteen women were recruited following a birth and prior to conception of the study child and were followed until the study child was 3–5 years old. Higher maternal PTSD symptoms prior to conception predicted greater child negative affectivity, adjusting for concurrent maternal depressive symptoms and sociodemographic covariates. In exploratory analyses, we found that neither maternal prenatal nor postpartum depressive symptoms or perceived stress mediated this association. These findings add to a limited prospective literature, highlighting the importance of assessing the mental health of women prior to conception and providing interventions that can disrupt the intergenerational sequelae of trauma.
Children exposed to prenatal maternal psychological distress are at elevated risk for a range of adverse outcomes; however, it remains poorly understood whether postnatal influences can ameliorate impairments related to prenatal distress. The current study evaluated if sensitivematernal care during the first postnatal year could mitigate child cognitive and emotional impairments associated with prenatal psychological distress. Prenatal maternal psychological distress was assessed via self-reports of anxiety, depression, and perceived stress for 136 mothers at five prenatal and four postpartum time points. Quality of maternal care (sensitivity to nondistress, positive regard, and intrusiveness reverse-scored) were assessed during a mother–child play interaction at 6 and 12 months. Child cognitive function and negative emotionality were assessed at 2 years, using The Bayley Scales and the Early Childhood Behavior Questionnaire. Elevated prenatal distress was associated with poorer child cognitive function and elevated negative emotionality. Children exposed to elevated prenatal maternal distress did not, however, display these outcomes if they received high-quality caregiving. Specifically, maternal care moderated the relation between prenatal psychological distress and child cognitive function and negative emotionality. This association remained after consideration of postnatal maternal psychological distress and relevant covariates. Sensitive maternal care was associated with altered offspring developmental trajectories, supporting child resilience following prenatal distress exposure.
Maimonides makes extensive use of metaphysics in the Guide, but he does not discuss the discipline’s nature or many of the basic issues it addresses. Instead, the Guide’s readers would need to be familiar with the tradition of metaphysical inquiry that Maimonides draws on, which is that of the peripatetic philosophers. Aristotle’s Metaphysics stands at its head, and Maimonides received it mediated through Greek and Arabic commentaries. Among the major Arabic commentators, Al-Farabi is known as “the second teacher,” after Aristotle; the titles are accorded them by Avicenna, who credits Al-Farabi with enabling him to understand the Metaphysics.
Carbamazepine, an anticonvulsant also used as a mood stabilizer and for trigeminal neuralgia, is associated with serious, sometimes fatal cutaneous adverse drug reactions, including Stevens Johnson Syndrome and toxic epidermal necrolysis1. Current literature demonstrates a genetic predisposition linked to specific class I and II human leukocyte antigen (HLA) types in various ethnic populations2. HLA-A*31:01 is one such HLA type, and is routinely identified by the tag SNP rs1061235. However, rs1061235 has poor specificity for HLA*31:01 due to interference of HLA-A*33 types3. We investigated the false positive rate in our population and developed a novel real-time PCR assay that distinguishes HLA-A*31:01 from other HLA-A types including HLA-A*33.
Methods
120 unique samples were tested in triplicate during the validation of this assay and were sent to a reference lab for HLA next generation sequencing (NGS) typing, including 89 in-house samples and 31 Coriell samples with documented HLA typing results. The results from our real-time PCR assay were compared to the HLA typing results. HLA typing results were also compared to the tag SNP rs1061235 results to calculate the false positive rate.
Results
There was 100% concordance between our real-time PCR results and expected results based on HLA typing. 89 sample results for tag SNP rs1061235 were compared to HLA typing results. 75/89 samples had a rs1061235 variant, but 31/75 (41%) samples did not have the HLA-A*31:01 type, thus defining the false positive rate of the tag SNP for our population. We theorized there would be a small subset of rare HLA-A types that would interfere with the assay and we tested the three types available to us. We confirmed that 3 of the HLA types (HLA-A*31:04, 31:12, and 31:16) result falsely positive due to sequence homology with 31:01. There is no known literature indicating whether these rare HLA-A*31 subtypes are associated with cutaneous adverse reactions. These 3 HLA types and the other suspected interfering HLA types have limited frequency data sets and are expected to occur rarely in our patient population; we expect these HLA types make up less than 0.003% of the our population. Our assay specificity for the validation is >99%.
Conclusions
Our custom real-time PCR assay for detection of HLA-A*31:01 is significantly more specific than the commonly used tag SNP rs1061235. Clinicians considering carbamazepine therapy for their patients will have a better understanding of cutaneous adverse reaction risk and can make improved personalized treatment decisions. This quick, cost effective assay allows more patients in need of carbamazepine treatment to benefit from its use.
Subglacial sediments have the potential to reveal information about the controls on glacier flow, changes in ice-sheet history and characterise life in those environments. Retrieving sediments from beneath the ice, through hot water drilled access holes at remote field locations, present many challenges. Motivated by the need to minimise weight, corer diameter and simplify assembly and operation, British Antarctic Survey, in collaboration with UWITEC, developed a simple mechanical percussion corer. At depths over 1000 m however, manual operation of the percussion hammer is compromised by the lack of clear operator feedback at the surface. To address this, we present a new auto-release-recovery percussion hammer mechanism that makes coring operations depth independent and improves hammer efficiency. Using a single rope tether for both the corer and hammer operation, this modified percussion corer is relatively simple to operate, easy to maintain, and has successfully operated at a depth of >2130 m.
Sink drains in healthcare facilities may provide an environment for antimicrobial-resistant microorganisms, including carbapenemase-producing Klebsiella pneumoniae (CPKP).
Methods:
We investigated the colonization of a biofilm consortia by CPKP in a model system simulating a sink-drain P-trap. Centers for Disease Control (CDC) biofilm reactors (CBRs) were inoculated with microbial consortia originally recovered from 2 P-traps collected from separate patient rooms (designated rooms A and B) in a hospital. Biofilms were grown on stainless steel (SS) or polyvinyl chloride (PVC) coupons in autoclaved municipal drinking water (ATW) for 7 or 28 days.
Results:
Microbial communities in model systems (designated CBR-A or CBR-B) were less diverse than communities in respective P-traps A and B, and they were primarily composed of β and γ Proteobacteria, as determined using 16S rRNA community analysis. Following biofilm development CBRs were inoculated with either K. pneumoniae ST45 (ie, strain CAV1016) or K. pneumoniae ST258 KPC+ (ie, strain 258), and samples were collected over 21 days. Under most conditions tested (CBR-A: SS, 7-day biofilm; CBR-A: PVC, 28-day biofilm; CBR-B: SS, 7-day and 28-day biofilm; CBR-B: PVC, 28-day biofilm) significantly higher numbers of CAV1016 were observed compared to 258. CAV1016 showed no significant difference in quantity or persistence based on biofilm age (7 days vs 28 days) or substratum type (SS vs PVC). However, counts of 258 were significantly higher on 28-day biofilms and on SS.
Conclusions:
These results suggest that CPKP persistence in P-trap biofilms may be strain specific or may be related to the type of P-trap material or age of the biofilm.
Research shows that healthy ageing is defined differently by older adults and researchers, who may put more or less weight on the physiological, psychological, societal and personal aspects of ageing. Although there is growing interest in the research literature on lay models of healthy ageing in socio-cultural context, little work has been done to determine how important or feasible the various components of healthy ageing are viewed to be by older adults. This study asked a convenience sample of 54 older adults in the circumpolar North to rate the importance and feasibility of 36 previously identified components of healthy ageing in their community. Results indicate that seniors in the sample place the most importance on aspects of the social and physical environment, while least important concepts included psychological and individual behaviours. However, most feasible aspects were individual behaviours and least feasible were aspects of the social and physical environment. Although older adults are able to construct a model of what healthy ageing should look like in their community, they do not always view the most important aspects of healthy ageing to be the most feasible to achieve, providing ample opportunity for public and social policy change.
Background: Central-line–associated bloodstream infection (CLABSI) rates have steadily decreased as evidence-based prevention bundles were implemented. Bone marrow transplant (BMT) patients are at increased risk for CLABSI due to immunosuppression, prolonged central-line utilization, and frequent central-line accesses. We assessed the impact of an enhanced prevention bundle on BMT nonmucosal barrier injury CLABSI rates. Methods: The University of Iowa Hospitals & Clinics is an 811-bed academic medical center that houses the only BMT program in Iowa. During October 2018, we added 3 interventions to the ongoing CLABSI prevention bundle in our BMT inpatient unit: (1) a standardized 2-person dressing change team, (2) enhanced quality daily chlorhexidine treatments, and (3) staff and patient line-care stewardship. The bundle included training of nurse champions to execute a team approach to changing central-line dressings. Standard process description and supplies are contained in a cart. In addition, 2 sets of sterile hands and a second person to monitor for breaches in sterile procedure are available. Site disinfection with chlorhexidine scrub and dry time are monitored. Training on quality chlorhexidine bathing includes evaluation of preferred product, application per product instructions for use and protection of the central-line site with a waterproof shoulder length glove. In addition to routine BMT education, staff and patients are instructed on device stewardship during dressing changes. CLABSIs are monitored using NHSN definitions. We performed an interrupted time-series analysis to determine the impact of our enhanced prevention bundle on CLABSI rates in the BMT unit. We used monthly CLABSI rates since January 2017 until the intervention (October 2018) as baseline. Because the BMT changed locations in December 2018, we included both time points in our analysis. For a sensitivity analysis, we assessed the impact of the enhanced prevention bundle in a hematology-oncology unit (March 2019) that did not change locations. Results: During the period preceding bundle implementation, the CLABSI rate was 2.2 per 1,000 central-line days. After the intervention, the rate decreased to 0.6 CLABSI per 1,000 central-line days (P = .03). The move in unit location did not have a significant impact on CLABSI rates (P = .85). CLABSI rates also decreased from 1.6 per 1,000 central-line days to 0 per 1,000 central-line days (P < .01) in the hematology-oncology unit. Conclusions: An enhanced CLABSI prevention bundle was associated with significant decreases in CLABSI rates in 2 high-risk units. Novel infection prevention bundle elements should be considered for special populations when all other evidence-based recommendations have been implemented.
Background: Antibiotic time outs (ABTOs), formal reassessments of all new antimicrobial regimens by the care team, can optimize antimicrobial regimens, reducing antimicrobial overuse and potentially improving outcomes. Implementation of ABTOs is a substantial challenge. We used quality improvement methods to implement robust, meaningful, team-driven ABTOs in general medicine ward services. Methods: We identified and engaged stakeholders to serve as champions for the quality improvement initiative. On October 1, 2018, 2 internal medicine teaching services (services A and B), began conducting ABTOs on all patients admitted to their services receiving systemic antimicrobials for at least 36 hours. Eligible patients were usually identified by the team pharmacist. ABTOs were completed within 72 hours of antibiotic initiation and were documented in the electronic medical record (EMR) by providers using a template. The process was modified as necessary in response to feedback from frontline clinicians using plan-do-study-act (PDSA) methods. We subsequently spread the project to 2 additional internal medicine services (services C and D); 2 family medicine teams (services E and F); and 1 general pediatric service (service G). The project is ongoing. We collected data for the following metrics: (1) proportion of ABTO-eligible patients with an ABTO; (2) proportion of ABTOs conducted within the recommended time frame; (3) documented plan changes as a result of ABTO (eg, change IV antibiotics to PO); (4) proportion of documented plan changes actually completed within 24 hours. Results: Within 12 weeks, services A and B were successfully completing time outs in >80% of their patients. This target was consistently reached by services C, D, E, F, and G almost immediately following launch on those services. As of June 29, 2019, >80% of eligible patients across all participating services have had a time out conducted for 16 consecutive weeks. ABTOs have resulted in a change in management in 35% of cases, including IV-to-PO change in 19% of cases and discontinuation in 5%. Overall, 77% of time outs occurred during the 36–72-hour window. Ultimately, 95% of documented plan changes were completed within 24 hours. Conclusions: ABTOs are effective but implementation is challenging. We achieved high compliance with ABTOs without using electronic reminders. Our results suggest that ABTOs were impactful in the non–critical-care general medicine setting. Next steps include (1) development of EMR-based tools to facilitate identifying eligible patients and ABTO documentation; (2) continued spread through our health care system; and (3) analysis of ABTO impact using ABTO-unexposed patients as a control group.