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Strategies for pandemic preparedness and response are urgently needed for all settings. We describe our experience using inverted classroom methodology (ICM) for COVID-19 pandemic preparedness in a small hospital with limited infection prevention staff. ICM for pandemic preparedness was feasible and contributed to an increase in COVID-19 knowledge and comfort.
Background:Staphylococcus aureus is the leading cause of joint infections. These infections may arise in native or prosthetic joints. Previous analysis of population-based surveillance has documented racial differences in incidence of invasive S. aureus bloodstream infections. We hypothesized that racial differences in incidence would not persist among of S. aureus joint infections. Methods: We utilized data from the Georgia Emerging Infections Program (GA EIP), which conducts CDC-funded active, population-based surveillance for iSA within the 8-county area of Atlanta. Cases were defined as residents of the surveillance area with S. aureus isolated during 2016–2018 from joint fluid or tissue, and cultures within a 30-day period after the initial culture date were considered a single case. Age- and race-specific incidence were calculated using US census data; incidence rate ratios (RR) and adjusted rate ratios (aRR) were calculated using the Mantel-Hanzel method. Results: Between 2016 and 2018, 500 iSA joint infections were identified (iMRSA, 28.2% and iMSSA, 71.8%): 34.4% occurred in black patients and 65.6% occurred in white patients. Also, 90 cases (18%) had a bloodstream infection (BSI) within 30 days of the joint infection. Incidence of iSA joint infections dropped 22% from 9.4 per 100,000 in 2016 to 7.5 per 100,000 in 2018 (RR, 0.79; 95% CI, 0.7–0.9). Adjusting for year, incidence was 40% lower among blacks than whites (RR, 0.6,; 95% CI, 0.5–0.7); this finding was attributed to blacks having 60% lower incidence of iMSSA joint infections compared to whites (aRR, 0.4; 95% CI, 0.3–0.5) but similar MRSA incidence (aRR, 1.2; 95% CI, 0.8–1.6). The highest incidence was observed among whites aged >65 years with iMSSA infections (30.2 per 100,000) (Fig. 1). Among cases with a full chart review (n = 138), surgery in the prior 90 days was uncommon (n = 42, 30.4%), and a preceding major orthopedic procedure was even more rare (n = 13, 9.4%). Antecedent therapeutic injections and arthroscopic procedures are under investigation. Conclusions: Unlike S. aureus bacteremia, where previous analysis demonstrates higher incidences among blacks predominantly due to MRSA, our data demonstrate that the incidence of S. aureus joint infections is higher in whites, predominantly due to MSSA. Investigations in differential practices regarding orthopedic illness and injury should be pursued.
Disclosures: Scott Fridkin reports that his spouse receives consulting fees from the vaccine industry.
Background: Due to reliance on hospital discharge data for case identification, the burden of noninvasive and community-acquired S. aureus disease is often underestimated. To determine the full burden of S. aureus infections, we utilized population-based surveillance in a large urban county. Methods: The Georgia Emerging Infections Program (GA EIP) conducted CDC-funded, population-based surveillance by finding cases of S. aureus infections in 8 counties around Atlanta in 2017. Cases were residents with S. aureus isolated from either a normally sterile site in a 30-day period (invasive cases) or another site in a 14-day period (noninvasive cases). Medical records (all invasive and 1:4 sample of noninvasive cases) among Fulton County residents were abstracted for clinical, treatment, and outcome data. Cases treated were mapped to standard therapeutic site codes. Noninvasive specimens were reviewed and attributed to an invasive case if both occurred within 2 weeks. Incidence rates were calculated using 2017 census population and using a weight-adjusted cohort to account for sampling. Results: In total, 1,186 noninvasive (1:4 sample) and 529 invasive cases of S. aureus in Fulton county were reviewed. Only 35 of 1,186 (2.9%) noninvasive cases were temporally linked to invasive cases, resulting in 5,133 cases after extrapolation (529 invasive, 4,604 noninvasive). All invasive cases and 3,776 of 4,604 noninvasive cases (82%) were treated (4,305 total). Treatment was highest in skin (90%) and abscess (97%), lowest in urine (62%) and sputum (60%), and consisted of antibacterial agents alone (65%) or in addition to drainage procedures (35%). Overall, 41% of all cases were hospitalized, 12% required ICU admission, and 2.7% died, almost exclusively with bloodstream and pulmonary infections. Attribution of noninvasive infection was most often outside healthcare settings (87%); only 341 (7.9%) were hospital-onset cases; however, 34% of cases had had healthcare exposure in the preceding year, most often inpatient hospitalization (75%) or recent surgery (35%). Estimated countywide incidence was 414 per 100,000 (130 for MRSA and 284 for MSSA), invasive infection was 50 per 100,000. Among treated cases, 57% were SSTI, and the proportion of cases caused by MRSA was ~33% but varied slightly by therapeutic site (Fig. 1). Conclusions: The incidence of treated S. aureus infection in our large urban county is estimated to be 414 per 100,000 persons, which exceeds previously estimated rates based on hospital discharge data. Only 12% of treated infections were invasive, and <1 in 10 were hospital onset. Also, two-thirds of treated disease cases were MSSA; most were SSTIs.
Funding: Proprietary Organization: Pfizer.
Disclosures: Scott Fridkin, consulting fee - vaccine industry (spouse).
Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.
Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.
More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.
Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
Presenteeism, or working while ill, by healthcare personnel (HCP) experiencing influenza-like illness (ILI) puts patients and coworkers at risk. However, hospital policies and practices may not consistently facilitate HCP staying home when ill.
Objective and methods:
We conducted a mixed-methods survey in March 2018 of Emerging Infections Network infectious diseases physicians, describing institutional experiences with and policies for HCP working with ILI.
Of 715 physicians, 367 (51%) responded. Of 367, 135 (37%) were unaware of institutional policies. Of the remaining 232 respondents, 206 (89%) reported institutional policies regarding work restrictions for HCP with influenza or ILI, but only 145 (63%) said these were communicated at least annually. More than half of respondents (124, 53%) reported that adherence to work restrictions was not monitored or enforced. Work restrictions were most often not perceived to be enforced for physicians-in-training and attending physicians. Nearly all (223, 96%) reported that their facility tracked laboratory-confirmed influenza (LCI) in patients; 85 (37%) reported tracking ILI. For employees, 109 (47%) reported tracking of LCI and 53 (23%) reported tracking ILI. For independent physicians, not employed by the facility, 30 (13%) reported tracking LCI and 11 (5%) ILI.
More than one-third of respondents were unaware of whether their institutions had policies to prevent HCP with ILI from working; among those with knowledge of institutional policies, dissemination, monitoring, and enforcement of these policies was highly variable. Improving communication about work-restriction policies, as well as monitoring and enforcement, may help prevent the spread of infections from HCP to patients.
To assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention.
A pre- and postintervention, quasi-experimental quality improvement study.
Setting and participants:
Adult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center.
We evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014–January 2015) and the intervention period (April 2015–October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated.
Among 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06–0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039).
The CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.
Neuropsychological assessment data from 121 participants in the Alzheimer’s Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.
A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.
LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
The Health Technology Assessment (HTA) Program at the Institute of Health Economics (IHE) has conducted rapid assessments (RAs) for 25 years. The presentation draws on this experience to chart the evolution of RAs over a 25-year relationship between a policy maker and an arms-length HTA agency to quantify the effects of this partnership on the RAs produced.
The number, types, and methodological attributes of RAs produced over a 25-year partnership with a single requestor were reviewed. The reasons for developmental changes in RA products over time were charted to document the push-pull tension between requestor needs and HTA best practice. The elements contributing to the relevance and impact, or not, of the RAs were also identified.
Results demonstrated the dynamic relationship required for HTA researchers to meet best practice and requestor needs. As literature search spans lengthened and data analyses became more complex, limitations were imposed on RAs to fulfill the requirements of timeliness, utility, and best practice. Adaptations were driven by requestor, researcher, and the external policy environment. Facilitators of RA utility for HTA requestors include: asking focused, well-articulated questions; specifying the request's purpose; providing detailed information about local context and other relevant issues; and understanding the risk of bias associated with RAs. Considerations for HTA doers include: assembling a team using a triage process; involving requestors throughout RA development; negotiating deliverables and timelines using a HTA product matrix; transparently reporting methods; narratively describing methodological issues; and internally reviewing the draft RAs.
RAs are a useful component of HTA programs. To keep these products relevant and useful, HTA agencies must allow RAs to evolve according to need, but with grounding in good practice. Negotiating the line between rigor and relevance is a key skill for HTA agencies. Having the right team is helpful.
Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating 13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of 2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMW β-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMW β-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) of β-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barley β-glucan. The pronounced TC reduction in G allele carriers of rs3808607 observed in the previous study may be due to enhanced bile acid synthesis in response to high-viscosity β-glucan consumption in those individuals.
Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13–2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11–5.29; p=.03). Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163–175)
Eastern hemlock [Tsuga canadensis (L.) Carrière] is a valuable component of Allegheny Plateau forests in northwestern Pennsylvania and western New York. Since the 1950s, hemlock forests throughout the Central Appalachians have been under threat from a nonnative forest insect pest, the hemlock woolly adelgid (Adelges tsugae Annand). In 2012, to address this threat at the most meaningful scale, the United States Forest Service and The Nature Conservancy organized a diverse partnership to develop a strategy for landscape-level conservation of hemlock on the High Allegheny Unglaciated Plateau. The main goal of the partnership was to locate hemlock across the landscape regardless of land ownership and prioritize the hemlock for monitoring and protection from the adelgid. The priority Hemlock Conservation Areas that were identified by this partnership provide a guide for focusing limited financial and personnel resources, with the goal of protecting at least a portion of these areas from the impacts of the adelgid until more long-term management techniques are identified. To protect the important hemlock forests identified in this prioritization, a partnership of private and public land managers are forming a Cooperative Pest Management Area to continue this important collaboration, allocate scarce resources across the area, and allow private partners access to public funding for protection of priority hemlock on their lands.