An assessment of introducers used for airway management.

Different introducers are available to assist with tracheal intubation. Subtle differences in the design of introducers can have a marked effect on safety and performance. The Difficult Airway Society's Airway Device Evaluation Project Team proposal states that devices should only be purchased for which there is at least a case-control study on patients assessing airway devices. However, resources are not currently available to carry out a case-control study on all introducers available on the market. This study comprised a laboratory and manikin-based investigation to identify introducers that could be suitable for clinical investigation. We included six different introducers in laboratory-based assessments (design characteristics) and manikin-based assessments involving the participation of 30 anaesthetists. Each anaesthetist attempted placement in the manikin's trachea with each of the six introducers in a random order. Outcomes included first-time insertion success rate; insertion success rate; number of attempts; time to placement; and distance placed. Each anaesthetist also completed a questionnaire. First-time insertion success rate depended significantly on the introducer used (p = 0.0016) and varied from 47% (Armstrong and P3) to 77% (Intersurgical and Frova). Median time to placement (including oesophageal placement) varied from 10 s (Eschmann and Frova) to 20 s (P3) (p = 0.0025). Median time to successful placement in the trachea varied from 9 s (Frova) to 22 s (Armstrong) (p = 0.037). We found that the Armstrong and P3 devices were not as acceptable as other introducers and, without significant improvements to their design and characteristics, the use of these devices in studies on patients is questionable. The study protocol is suitable for differentiating between different introducers and could be used as a basis for assessing other types of devices.

Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Asymptomatic Infections in 2 Large Academic Health Systems in Wisconsin.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic infections may play a critical role in disease transmission. We aim to determine the prevalence of asymptomatic SARS-CoV-2 infection at 2 hospital systems in 2 counties in Wisconsin. The SARS-CoV-2 prevalence was 1% or lower at both systems despite the higher incidence of coronavirus disease 2019 (COVID-19) in Milwaukee County.

Transmission Dynamics of Clostridioides difficile in 2 High-Acuity Hospital Units.

BACKGROUND: The key epidemiological drivers of Clostridioides difficile transmission are not well understood. We estimated epidemiological parameters to characterize variation in C. difficile transmission, while accounting for the imperfect nature of surveillance tests. METHODS: We conducted a retrospective analysis of C. difficile surveillance tests for patients admitted to a bone marrow transplant (BMT) unit or a solid tumor unit (STU) in a 565-bed tertiary hospital. We constructed a transmission model for estimating key parameters, including admission prevalence, transmission rate, and duration of colonization to understand the potential variation in C. difficile dynamics between these 2 units. RESULTS: A combined 2425 patients had 5491 admissions into 1 of the 2 units. A total of 3559 surveillance tests were collected from 1394 patients, with 11% of the surveillance tests being positive for C. difficile. We estimate that the transmission rate in the BMT unit was nearly 3-fold higher at 0.29 acquisitions per percentage colonized per 1000 days, compared to our estimate in the STU (0.10). Our model suggests that 20% of individuals admitted into either the STU or BMT unit were colonized with C. difficile at the time of admission. In contrast, the percentage of surveillance tests that were positive within 1 day of admission to either unit for C. difficile was 13.4%, with 15.4% in the STU and 11.6% in the BMT unit. CONCLUSIONS: Although prevalence was similar between the units, there were important differences in the rates of transmission and clearance. Influential factors may include antimicrobial exposure or other patient-care factors.

Elastomeric Respirators for COVID-19 and the Next Respiratory Virus Pandemic: Essential Design Elements.

Respiratory viruses are transmitted via respiratory particles that are emitted when people breath, speak, cough, or sneeze. These particles span the size spectrum from visible droplets to airborne particles of hundreds of nanometers. Barrier face coverings ("cloth masks") and surgical masks are loose-fitting and provide limited protection from airborne particles since air passes around the edges of the mask as well as through the filtering material. Respirators, which fit tightly to the face, provide more effective respiratory protection. Although healthcare workers have relied primarily on disposable filtering facepiece respirators (such as N95) during the COVID-19 pandemic, reusable elastomeric respirators have significant potential advantages for the COVID-19 and future respiratory virus pandemics. However, currently available elastomeric respirators were not designed primarily for healthcare or pandemic use and require further development to improve their suitability for this application. The authors believe that the development, implementation, and stockpiling of improved elastomeric respirators should be an international public health priority.

Infection Prevention Precautions for Routine Anesthesia Care During the SARS-CoV-2 Pandemic.

Many health care systems around the world continue to struggle with large numbers of SARS-CoV-2-infected patients, while others have diminishing numbers of cases following an initial surge. There will most likely be significant oscillations in numbers of cases for the foreseeable future, based on the regional epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Less affected hospitals and facilities will attempt to progressively resume elective procedures and surgery. Ramping up elective care in hospitals that deliberately curtailed elective care to focus on SARS-CoV-2-infected patients will present unique and serious challenges. Among the challenges will be protecting patients and providers from recurrent outbreaks of disease while increasing procedure throughput. Anesthesia providers will inevitably be exposed to SARS-CoV-2 by patients who have not been diagnosed with infection. This is particularly concerning in consideration that aerosols produced during airway management may be infective. In this article, we recommend an approach to routine anesthesia care in the setting of persistent but variable prevalence of SARS-CoV-2 infection. We make specific recommendations for personal protective equipment and for the conduct of anesthesia procedures and workflow based on evidence and expert opinion. We propose practical, relatively inexpensive precautions that can be applied to all patients undergoing anesthesia. Because the SARS-CoV-2 virus is spread primarily by respiratory droplets and aerosols, effective masking of anesthesia providers is of paramount importance. Hospitals should follow the recommendations of the Centers for Disease Control and Prevention for universal masking of all providers and patients within their facilities. Anesthesia providers should perform anesthetic care in respirator masks (such as N-95 and FFP-2) whenever possible, even when the SARS-CoV-2 test status of patients is negative. Attempting to screen patients for infection with SARS-CoV-2, while valuable, is not a substitute for respiratory protection of providers, as false-negative tests are possible and infected persons can be asymptomatic or presymptomatic. Provision of adequate supplies of respirator masks and other respiratory protection equipment such as powered air purifying respirators (PAPRs) should be a high priority for health care facilities and for government agencies. Eye protection is also necessary because of the possibility of infection from virus coming into contact with the conjunctiva. Because SARS-CoV-2 persists on surfaces and may cause infection by contact with fomites, hand hygiene and surface cleaning are also of paramount importance.

Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk Factors, Treatment, and Prevention.

Clostridium difficile is a significant pathogen in healthcare today, impacting both hospitalized and community-based patients. Immunocompromised patients experience a high incidence of C. difficile infection, ranging from 6% to 33% in the hematology-oncology population and up to 23% among lung transplant recipients, and have a rate of 7.1-8.3 cases per 1000 patient-years in patients with human immunodeficiency virus (HIV). Recurrence of C. difficile infections among immunocompromised patients is also high, with rates up to 40% in both the hematology-oncology population and solid organ transplant recipients. This higher incidence of C. difficile infection and recurrence is believed to be secondary to frequent antimicrobial use, suppressed immune function, increased exposure to healthcare settings, and higher prevalence of C. difficile colonization. This review summarizes published data describing the epidemiology, risk factors for acquisition and infection, treatment, and prevention of C. difficile in hematology-oncology, solid organ transplant, and HIV-infected patients.

The Juncture Between Clostridioides difficile Infection and Inflammatory Bowel Diseases.

The detection of Clostridioides difficile in inflammatory bowel disease (IBD) patients is a common occurrence, in part due to the standard clinical practice of testing for the presence of C. difficile during acute IBD exacerbations. Given the clinical overlap between C. difficile infections and acute IBD exacerbations (ie, increased frequency of loose stools, abdominal pain), it is hard to differentiate C. difficile infections versus colonizations in patients with underlying IBD who test positive for C. difficile. Here, we review the epidemiology, clinical presentation, risk factors, diagnosis, treatment, and outcomes of IBD patients with positive C. difficile tests.

Patient-to-Patient Transmission of Klebsiella pneumoniae Carbapenemase Variants with Reduced Ceftazidime-Avibactam Susceptibility.

We report patient-to-patient transmission of Enterobacter hormaechei isolates with reduced susceptibility to ceftazidime-avibactam due to production of KPC-40, a variant of KPC-3 with a two-amino-acid insertion in the Ω-loop region (L167_E168dup). The index patient had received a prolonged course of ceftazidime-avibactam therapy, whereas the second patient had not received the agent and still became colonized with the KPC-40-producing strain. The complex dynamics of KPC (Klebsiella pneumoniae carbapenemase) described here highlight several key diagnostic and therapeutic considerations.

Clostridioides difficile in transplant patients: early diagnosis, treatment, and prevention.

PURPOSE OF REVIEW: Clostridioides difficile infection is common in solid organ transplant and hematopoietic stem-cell transplant recipients and is associated with significant morbidity and mortality. These populations are also underrepresented in clinical trials, making optimal management difficult. Because of this, management of these populations follows national guideline recommendations. This review aims to summarize the recent relevant literature pertaining to the clinical management of C. difficile infection in transplant patients, with a particular focus on diagnosis, treatment, and prevention. RECENT FINDINGS: Early diagnosis of C. difficile colonization may mitigate both horizontal and vertical transmission (progression from colonization to colitis) of infection. Once diagnosed, recent literature suggests antibiotic treatment should align with that recommended by national guidelines. Fecal microbiota transplant is an emerging therapy for recurrent C. difficile infection, and recent data have demonstrated safety and efficacy. Prevention strategies including antimicrobial stewardship, probiotic administration, antibiotic administration, and bezlotoxumab may be beneficial in transplant populations, but more data are needed to confirm recent findings. SUMMARY: Studies evaluating C. difficile infection in transplant patients are only recently starting to emerge. Further research is needed to identify optimal treatment and prevention strategies, and to examine novel strategies such as microbiome manipulation.

Early life adversity and telomere length: a meta-analysis.

Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

Pain and functional trajectories in symptomatic knee osteoarthritis over up to 12 weeks of exercise exposure.

OBJECTIVE: Exercise is the recommended treatment for knee osteoarthritis (OA). However, heterogeneous patterns in treatment response are poorly understood. Our purpose was to identify pain and functional trajectories from exercise interventions in knee OA, and to determine their association with baseline factors. METHODS: Prospective cohort of 171 participants (mean age 61 years; BMI 32 kg/m2, 71% female; 57% white) with symptomatic knee OA from a randomized trial comparing 12-week Tai Chi and Physical Therapy. We analyzed weekly Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain (0-500) and function (0-1700) scores using group-based trajectory models. Associations between baseline factors and trajectories were examined using multinomial logistic regression. RESULTS: We identified four pain trajectories: Lower-Early Improvement (43%), Moderate-Early Improvement (32%), Higher-Delayed Improvement (15%), and Higher-No Improvement (10%). We found similar trajectories for function, except that the lower function trajectories diverged into gradual (12%) or delayed-improvement (15%). Compared with the Lower-Early Improvement pain trajectory, moderate and higher trajectories were associated with poorer physical and psychosocial health. A similar pattern of associations were found among the function trajectories. CONCLUSIONS: We found four distinct trajectories for pain and function over up to 12-weeks of exercise interventions. While most participants experienced improvements over a short-term exposure, subgroups with greater baseline pain/physical disability had either gradual, delayed, or no improvements. These findings help disentangle the heterogeneity of treatment response and may advance patient-centered care in knee OA.

Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection.

The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004). The anti-CD154 dAb effectively blocked CD40-CD154 interactions but lacked crystallizable fragment (Fc) binding activity and resultant platelet activation. In a nonhuman primate kidney transplant model, anti-CD154 dAb was safe and efficacious, significantly prolonging allograft survival without evidence of thromboembolism (Median survival time 103 days). The combination of anti-CD154 dAb and conventional immunosuppression synergized to effectively control allograft rejection (Median survival time 397 days). Furthermore, anti-CD154 dAb treatment increased the frequency of CD4+ CD25+ Foxp3+ regulatory T cells. This study demonstrates that the use of a novel anti-CD154 dAb that lacks Fc binding activity is safe without evidence of thromboembolism and is equally as potent as previous anti-CD154 agents at prolonging renal allograft survival in a nonhuman primate preclinical model.

Mindfulness is associated with psychological health and moderates pain in knee osteoarthritis.

OBJECTIVE: Previous studies suggest that higher mindfulness is associated with less pain and depression. However, the role of mindfulness has never been studied in knee osteoarthritis (OA). We evaluate the relationships between mindfulness and pain, psychological symptoms, and quality of life in knee OA. METHOD: We performed a secondary analysis of baseline data from our randomized comparative trial in participants with knee OA. Mindfulness was assessed using the Five Facet Mindfulness Questionnaire (FFMQ). We measured pain, physical function, quality of life, depression, stress, and self-efficacy with commonly-used patient-reported measures. Simple and multivariable regression models were utilized to assess associations between mindfulness and health outcomes. We further tested whether mindfulness moderated the pain-psychological outcome associations. RESULTS: Eighty patients were enrolled (60.3 ± 10.3 years; 76.3% female, body mass index: 33.0 ± 7.1 kg/m2). Total mindfulness score was associated with mental (beta = 1.31, 95% CI: 0.68, 1.95) and physical (beta = 0.69, 95% CI:0.06, 1.31) component quality of life, self-efficacy (beta = 0.22, 95% CI:0.07, 0.37), depression (beta = -1.15, 95% CI:-1.77, -0.54), and stress (beta = -1.07, 95% CI:-1.53, -0.60). Of the five facets, the Describing, Acting-with-Awareness, and Non-judging mindfulness facets had the most associations with psychological health. No significant association was found between mindfulness and pain or function (P = 0.08-0.24). However, we found that mindfulness moderated the effect of pain on stress (P = 0.02). CONCLUSION: Mindfulness is associated with depression, stress, self-efficacy, and quality of life among knee OA patients. Mindfulness also moderates the influence of pain on stress, which suggests that mindfulness may alter the way one copes with pain. Future studies examining the benefits of mind-body therapy, designed to increase mindfulness, for patients with OA are warranted.

The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

Handling Time-dependent Variables: Antibiotics and Antibiotic Resistance.

Elucidating quantitative associations between antibiotic exposure and antibiotic resistance development is important. In the absence of randomized trials, observational studies are the next best alternative to derive such estimates. Yet, as antibiotics are prescribed for varying time periods, antibiotics constitute time-dependent exposures. Cox regression models are suited for determining such associations. After explaining the concepts of hazard, hazard ratio, and proportional hazards, the effects of treating antibiotic exposure as fixed or time-dependent variables are illustrated and discussed. Wider acceptance of these techniques will improve quantification of the effects of antibiotics on antibiotic resistance development and provide better evidence for guideline recommendations.

Evaluating the Impact of Antibiotic Exposures as Time-Dependent Variables on the Acquisition of Carbapenem-Resistant Acinetobacter baumannii.

OBJECTIVES: To determine the time-dependent effect of antibiotics on the initial acquisition of carbapenem-resistant Acinetobacter baumannii. DESIGN: Retrospective cohort study. SETTING: Forty-bed trauma ICU in Miami, FL. PATIENTS: All consecutive patients admitted to the unit from November 1, 2010, to November 30, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients underwent surveillance cultures at admission to the unit and weekly thereafter. The primary outcome was the acquisition of carbapenem-resistant A. baumannii on surveillance cultures. Daily antibiotic exposures during the time of observation were used to construct time-dependent variables, including cumulative exposures (in grams and daily observed doses [defined daily doses]). Among 360 patients, 45 (12.5%) became colonized with carbapenem-resistant A. baumannii. Adjusted Cox models showed that each additional point in the Acute Physiologic and Chronic Health Evaluation score increased the hazard by 4.8% (hazard ratio, 1.048; 95% CI, 1.010-1.087; p = 0.0124) and time-dependent exposure to carbapenems quadrupled the hazard (hazard ratio, 4.087; 95% CI, 1.873-8.920; p = 0.0004) of acquiring carbapenem-resistant A. baumannii. Additionally, adjusted Cox models determined that every additional carbapenem defined daily dose increased the hazard of acquiring carbapenem-resistant A. baumannii by 5.1% (hazard ratio, 1.051; 95% CI, 1.007-1.093; p = 0.0243). CONCLUSIONS: Carbapenem exposure quadrupled the hazards of acquiring A. baumannii even after controlling for severity of illness.

Histologic Lesions Induced by Murine Norovirus Infection in Laboratory Mice.

Murine noroviruses (MNVs) are highly prevalent in laboratory mice, can cause persistent infections, and have been shown to infect macrophages, dendritic cells, and B cells. To address the potential impact of MNV infection on research outcomes, numerous studies have been conducted with various mouse models of human disease and have generated mixed results, ranging from no impact to significant disease. Many of these studies included histologic evaluations after MNV infection, and these results have similarly been variable in terms of whether MNV induces lesions, despite the fact that localization of MNV by viral culture and molecular techniques have demonstrated systemic distribution regardless of mouse immune status. The aim of this review is to summarize the histologic findings that have been reported with MNV infection in several mouse models. The studies demonstrate that experimental infection of MNV in wild-type mice results in minimal to no histologic changes. In contrast, immunodeficient mice consistently have detectable MNV-induced lesions that are typically inflammatory and, in the most severe cases, accompanied by necrosis. In these, the liver is commonly affected, with more variable lesions reported in the lung, gastrointestinal tract, mesenteric lymph nodes, brain, and spleen. In specific disease models including atherosclerosis, MNV infection had a variable impact that was dependent on the mouse model, viral strain, timing of infection, or other experimental variables. It is important to recognize the reported MNV lesions to help discern the possible influence of MNV infection on data generated in mouse models.