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Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism.
Methods
To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression.
Results
Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism.
Conclusions
Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Using National Healthcare Safety Network data, an interrupted time series of intravenous antimicrobial starts (IVAS) among hemodialysis patients was performed. Annual adjusted rates decreased by 6.64% (January 2012–March 2020) and then further decreased by 8.91% until December 2021. IVAS incidence trends have decreased since 2012, including during the early COVID-19 pandemic.
We examined the association between influenza vaccination policies at acute care hospitals and influenza vaccination coverage among healthcare personnel for the 2021–22 influenza season. Mandatory vaccination and masking for unvaccinated personnel were associated with increased odds of vaccination. Hospital employees had higher vaccination coverage than licensed independent practitioners.
Resilience of the healthcare system has been described as the ability to absorb, adapt, and respond to stress while maintaining the provision of safe patient care. We quantified the impact that stressors associated with the COVID-19 pandemic had on patient safety, as measured by central line-associated bloodstream infections (CLABSIs) reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network.
Design:
Acute care hospitals were mandated to report markers of resource availability (staffing and hospital occupancy with COVID-19 inpatients) to the federal government between July 2020 and June 2021. These data were used with community levels of COVID-19 to develop a statistical model to assess factors influencing rates of CLABSIs among inpatients during the pandemic.
Results:
After risk adjustment for hospital characteristics, measured stressors were associated with increased CLABSIs. Staff shortages for more than 10% of days per month were associated with a statistically significant increase of 2 CLABSIs per 10,000 central line days versus hospitals reporting staff shortages of less than 10% of days per month. CLABSIs increased with a higher inpatient COVID-19 occupancy rate; when COVID-19 occupancy was 20% or more, there were 5 more CLABSIs per 10,000 central line days versus the referent (less than 5%).
Conclusions:
Reporting of data pertaining to hospital operations during the COVID-19 pandemic afforded an opportunity to evaluate resilience of US hospitals. We demonstrate how the stressors of staffing shortages and high numbers of patients with COVID-19 negatively impacted patient safety, demonstrating poor resilience. Understanding stress in hospitals may allow for the development of policies that support resilience and drive safe care.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
The field of healthcare epidemiology is increasingly focused on identifying, characterizing, and addressing social determinants of health (SDOH) to address inequities in healthcare quality. To identify evidence gaps, we examined recent systematic reviews examining the association of race, ethnicity, and SDOH with inpatient quality measures.
Methods:
We searched Medline via OVID for English language systematic reviews from 2010 to 2022 addressing race, ethnicity, or SDOH domains and inpatient quality measures in adults using specific topic questions. We imported all citations to Covidence (www.covidence.org, Veritas Health Innovation) and removed duplicates. Two blinded reviewers assessed all articles for inclusion in 2 phases: title/abstract, then full-text review. Discrepancies were resolved by a third reviewer.
Results:
Of 472 systematic reviews identified, 39 were included. Of these, 23 examined all-cause mortality; 6 examined 30-day readmission rates; 4 examined length of stay, 4 examined falls, 2 examined surgical site infections (SSIs) and one review examined risk of venous thromboembolism. The most evaluated SDOH measures were sex (n = 9), income and/or employment status (n = 9), age (n = 6), race and ethnicity (n = 6), and education (n = 5). No systematic reviews assessed medication use errors or healthcare-associated infections. We found very limited assessment of other SDOH measures such as economic stability, neighborhood, and health system access.
Conclusion:
A limited number of systematic reviews have examined the association of race, ethnicity and SDOH measures with inpatient quality measures, and existing reviews highlight wide variability in reporting. Future systematic evaluations of SDOH measures are needed to better understand the relationships with inpatient quality measures.
A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60 % high-fat diet for 3 months. Mice were then dosed hPNO for 24 d, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced body weight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice, but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4.
The IntCal family of radiocarbon (14C) calibration curves is based on research spanning more than three decades. The IntCal group have collated the 14C and calendar age data (mostly derived from primary publications with other types of data and meta-data) and, since 2010, made them available for other sorts of analysis through an open-access database. This has ensured transparency in terms of the data used in the construction of the ratified calibration curves. As the IntCal database expands, work is underway to facilitate best practice for new data submissions, make more of the associated metadata available in a structured form, and help those wishing to process the data with programming languages such as R, Python, and MATLAB. The data and metadata are complex because of the range of different types of archives. A restructured interface, based on the “IntChron” open-access data model, includes tools which allow the data to be plotted and compared without the need for export. The intention is to include complementary information which can be used alongside the main 14C series to provide new insights into the global carbon cycle, as well as facilitating access to the data for other research applications. Overall, this work aims to streamline the generation of new calibration curves.
To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data.
Methods:
We analyzed 9,134,276 admissions from 265 hospitals during 2015–2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates.
Results:
The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023–0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model.
Conclusions:
Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.
To examine temporal changes in coverage with a complete primary series of coronavirus disease 2019 (COVID-19) vaccination and staffing shortages among healthcare personnel (HCP) working in nursing homes in the United States before, during, and after the implementation of jurisdiction-based COVID-19 vaccination mandates for HCP.
Sample and setting:
HCP in nursing homes from 15 US jurisdictions.
Design:
We analyzed weekly COVID-19 vaccination data reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network from June 7, 2021, through January 2, 2022. We assessed 3 periods (preintervention, intervention, and postintervention) based on the announcement of vaccination mandates for HCP in 15 jurisdictions. We used interrupted time-series models to estimate the weekly percentage change in vaccination with complete primary series and the odds of reporting a staffing shortage for each period.
Results:
Complete primary series vaccination among HCP increased from 66.7% at baseline to 94.3% at the end of the study period and increased at the fastest rate during the intervention period for 12 of 15 jurisdictions. The odds of reporting a staffing shortage were lowest after the intervention.
Conclusions:
These findings demonstrate that COVID-19 vaccination mandates may be an effective strategy for improving HCP vaccination coverage in nursing homes without exacerbating staffing shortages. These data suggest that mandates can be considered to improve COVID-19 coverage among HCP in nursing homes to protect both HCP and vulnerable nursing home residents.
To evaluate the prevalence of hospital-onset bacteremia and fungemia (HOB), identify hospital-level predictors, and to evaluate the feasibility of an HOB metric.
Methods:
We analyzed 9,202,650 admissions from 267 hospitals during 2015–2020. An HOB event was defined as the first positive blood-culture pathogen on day 3 of admission or later. We used the generalized linear model method via negative binomial regression to identify variables and risk markers for HOB. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables plus additional measures of blood-culture testing practices. Performance of each model was compared against the unadjusted rate of HOB.
Results:
Overall median rate of HOB per 100 admissions was 0.124 (interquartile range, 0.00–0.22). Facility-level predictors included bed size, sex, ICU admissions, community-onset (CO) blood culture testing intensity, and hospital-onset (HO) testing intensity, and prevalence (all P < .001). In the complex model, CO bacteremia prevalence, HO testing intensity, and HO testing prevalence were the predictors most associated with HOB. The complex model demonstrated better model performance; 55% of hospitals that ranked in the highest quartile based on their raw rate shifted to a lower quartile when the SIR from the complex model was applied.
Conclusions:
Hospital descriptors, aggregate patient characteristics, community bacteremia and/or fungemia burden, and clinical blood-culture testing practices influence rates of HOB. Benchmarking an HOB metric is feasible and should endeavor to include both facility and clinical variables.
To evaluate hospital-level variation in using first-line antibiotics for Clostridioides difficile infection (CDI) based on the burden of laboratory-identified (LabID) CDI.
Methods:
Using data on hospital-level LabID CDI events and antimicrobial use (AU) for CDI (oral/rectal vancomycin or fidaxomicin) submitted to the National Healthcare Safety Network in 2019, we assessed the association between hospital-level CDI prevalence (per 100 patient admissions) and rate of CDI AU (days of therapy per 1,000 days present) to generate a predicted value of AU based on CDI prevalence and CDI test type using negative binomial regression. The ratio of the observed to predicted AU was then used to identify hospitals with extreme discordance between CDI prevalence and CDI AU, defined as hospitals with a ratio outside of the intervigintile range.
Results:
Among 963 acute-care hospitals, rate of CDI prevalence demonstrated a positive dose–response relationship with rate of CDI AU. Compared with hospitals without extreme discordance (n = 902), hospitals with lower-than-expected CDI AU (n = 31) had, on average, fewer beds (median, 106 vs 208), shorter length of stay (median, 3.8 vs 4.2 days), and higher proportion of undergraduate or nonteaching medical school affiliation (48% vs 39%). Hospitals with higher-than-expected CDI AU (n = 30) were similar overall to hospitals without extreme discordance.
Conclusions:
The prevalence rate of LabID CDI had a significant dose–response association with first-line antibiotics for treating CDI. We identified hospitals with extreme discordance between CDI prevalence and CDI AU, highlighting potential opportunities for data validation and improvements in diagnostic and treatment practices for CDI.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.
Technical summary
A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.
Social media summary
How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.
To determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infection (HAI) incidence in US hospitals, national- and state-level standardized infection ratios (SIRs) were calculated for each quarter in 2020 and compared to those from 2019.
Methods:
Central–line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), select surgical site infections, and Clostridioides difficile and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia laboratory-identified events reported to the National Healthcare Safety Network for 2019 and 2020 by acute-care hospitals were analyzed. SIRs were calculated for each HAI and quarter by dividing the number of reported infections by the number of predicted infections, calculated using 2015 national baseline data. Percentage changes between 2019 and 2020 SIRs were calculated. Supporting analyses, such as an assessment of device utilization in 2020 compared to 2019, were also performed.
Results:
Significant increases in the national SIRs for CLABSI, CAUTI, VAE, and MRSA bacteremia were observed in 2020. Changes in the SIR varied by quarter and state. The largest increase was observed for CLABSI, and significant increases in VAE incidence and ventilator utilization were seen across all 4 quarters of 2020.
Conclusions:
This report provides a national view of the increases in HAI incidence in 2020. These data highlight the need to return to conventional infection prevention and control practices and build resiliency in these programs to withstand future pandemics.
During March 27–July 14, 2020, the Centers for Disease Control and Prevention’s National Healthcare Safety Network extended its surveillance to hospital capacities responding to COVID-19 pandemic. The data showed wide variations across hospitals in case burden, bed occupancies, ventilator usage, and healthcare personnel and supply status. These data were used to inform emergency responses.
We analyzed 2017 healthcare facility-onset (HO) vancomycin-resistant Enterococcus (VRE) bacteremia data to identify hospital-level factors that were significant predictors of HO-VRE using the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) multidrug-resistant organism and Clostridioides difficile reporting module. A risk-adjusted model that can be used to calculate the number of predicted HO-VRE bacteremia events in a facility was developed, thus enabling the calculation of VRE standardized infection ratios (SIRs).
Methods:
Acute-care hospitals reporting at least 1 month of 2017 VRE bacteremia data were included in the analysis. Various hospital-level characteristics were assessed to develop a best-fit model and subsequently derive the 2018 national and state SIRs.
Results:
In 2017, 470 facilities in 35 states participated in VRE bacteremia surveillance. Inpatient VRE community-onset prevalence rate, average length of patient stay, outpatient VRE community-onset prevalence rate, and presence of an oncology unit were all significantly associated (all 95% likelihood ratio confidence limits excluded the nominal value of zero) with HO-VRE bacteremia. The 2018 national SIR was 1.01 (95% CI, 0.93–1.09) with 577 HO bacteremia events reported.
Conclusion:
The creation of an SIR enables national-, state-, and facility-level monitoring of VRE bacteremia while controlling for individual hospital-level factors. Hospitals can compare their VRE burden to a national benchmark to help them determine the effectiveness of infection prevention efforts over time.
Data reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network (CDC NHSN) were analyzed to understand the potential impact of the COVID-19 pandemic on central-line–associated bloodstream infections (CLABSIs) in acute-care hospitals. Descriptive analysis of the standardized infection ratio (SIR) was conducted by location, location type, geographic area, and bed size.