Protocol for a parallel cluster randomized trial of a participatory tailored approach to reduce overuse of antibiotics at hospital discharge: the ROAD home trial.

BACKGROUND: Antibiotic overuse at hospital discharge is common, costly, and harmful. While discharge-specific antibiotic stewardship interventions are effective, they are resource-intensive and often infeasible for hospitals with resource constraints. This weakness impacts generalizability of stewardship interventions and has health equity implications as not all patients have access to the benefits of stewardship based on where they receive care. There may be different pathways to improve discharge antibiotic prescribing that vary widely in feasibility. Supporting hospitals in selecting interventions tailored to their context may be an effective approach to feasibly reduce antibiotic overuse at discharge across diverse hospitals. The objective of this study is to evaluate the effectiveness of the Reducing Overuse of Antibiotics at Discharge Home multicomponent implementation strategy ("ROAD Home") on antibiotic overuse at discharge for community-acquired pneumonia and urinary tract infection. METHODS: This 4-year two-arm parallel cluster-randomized trial will include three phases: baseline (23 months), intervention (12 months), and postintervention (12 months). Forty hospitals recruited from the Michigan Hospital Medicine Safety Consortium will undergo covariate-constrained randomization with half randomized to the ROAD Home implementation strategy and half to a "stewardship as usual" control. ROAD Home is informed by the integrated-Promoting Action on Research Implementation in Health Services Framework and includes (1) a baseline needs assessment to create a tailored suite of potential stewardship interventions, (2) supported decision-making in selecting interventions to implement, and (3) external facilitation following an implementation blueprint. The primary outcome is baseline-adjusted days of antibiotic overuse at discharge. Secondary outcomes include 30-day patient outcomes and antibiotic-associated adverse events. A mixed-methods concurrent process evaluation will identify contextual factors influencing the implementation of tailored interventions, and assess implementation outcomes including acceptability, feasibility, fidelity, and sustainment. DISCUSSION: Reducing antibiotic overuse at discharge across hospitals with varied resources requires tailoring of interventions. This trial will assess whether a multicomponent implementation strategy that supports hospitals in selecting evidence-based stewardship interventions tailored to local context leads to reduced overuse of antibiotics at discharge. Knowledge gained during this study could inform future efforts to implement stewardship in diverse hospitals and promote equity in access to the benefits of quality improvement initiatives. TRIAL REGISTRATION: Clinicaltrials.gov NCT06106204 on 10/30/23.

Development of Patient Safety Measures to Identify Inappropriate Diagnosis of Common Infections.

BACKGROUND: Inappropriate diagnosis of infections results in antibiotic overuse and may delay diagnosis of underlying conditions. Here we describe the development and characteristics of 2 safety measures of inappropriate diagnosis of urinary tract infection (UTI) and community-acquired pneumonia (CAP), the most common inpatient infections on general medicine services. METHODS: Measures were developed from guidelines and literature and adapted based on data from patients hospitalized with UTI and CAP in 49 Michigan hospitals and feedback from end-users, a technical expert panel (TEP), and a patient focus group. Each measure was assessed for reliability, validity, feasibility, and usability. RESULTS: Two measures, now endorsed by the National Quality Forum (NQF), were developed. Measure reliability (derived from 24 483 patients) was excellent (0.90 for UTI; 0.91 for CAP). Both measures had strong validity demonstrated through (a) face validity by hospital users, the TEPs, and patient focus group, (b) implicit case review (ĸ 0.72 for UTI; ĸ 0.72 for CAP), and (c) rare case misclassification (4% for UTI; 0% for CAP) due to data errors (<2% for UTI; 6.3% for CAP). Measure implementation through hospital peer comparison in Michigan hospitals (2017 to 2020) demonstrated significant decreases in inappropriate diagnosis of UTI and CAP (37% and 32%, respectively, P < .001), supporting usability. CONCLUSIONS: We developed highly reliable, valid, and usable measures of inappropriate diagnosis of UTI and CAP for hospitalized patients. Hospitals seeking to improve diagnostic safety, antibiotic use, and patient care should consider using these measures to reduce inappropriate diagnosis of CAP and UTI.

Excellence in Antibiotic Stewardship: A mixed methods study comparing High, Medium, and Low Performing Hospitals.

BACKGROUND: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. METHODS: We conducted an explanatory, sequential mixed methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. RESULTS: Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (p=0.001), considered valuable team members (p=0.001), comfortable recommending antibiotic changes (p=0.02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had four distinguishing characteristics: a) robust knowledge of and access to antibiotic stewardship guidance, b) high quality clinical pharmacist-physician relationships, c) tools and infrastructure to support stewardship, and d) highly engaged Infectious Diseases physicians who advocated stewardship principles. CONCLUSION: This mixed-method study demonstrates the importance of organizational context for high performance in stewardship and suggests improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions.

Gender differences in COVID-19-related manuscript authorship by hospitalists during the pandemic: A bibliometric analysis.

BACKGROUND: Hospital medicine (HM) has a well-described gender disparity related to academic work and promotion. During the COVID-19 pandemic, female authorship across medicine fell further behind historical averages. OBJECTIVE: Examine how COVID-19 affected the publication gender gap for hospitalists. DESIGN, SETTINGS, AND PARTICIPANTS: Bibliometric analysis to determine gender and specialty of US-based physician first and last authors of COVID-19 articles published March 1, 2020 to February 28, 2021 in the four highest impact general medical journals and two highest impact HM-specific journals. MAIN OUTCOME AND MEASURES: We characterized the percentage of all physician authors that were women, the percentage of physician authors that were hospitalists, and the percentage of HM authors that were women. We compared author gender between general medical and HM-specific journals. RESULTS: During the study period, 853 manuscripts with US-based first or last authors were published in eligible journals. Included manuscripts contained 1124 US-based physician first or last author credits, of which 34.2% (384) were women and 8.8% (99) were hospitalists. Among hospitalist author credits, 43.4% (n = 43/99) were occupied by women. The relative gender equity for hospitalist authors was driven by the two HM journals where, compared to the four general medical journals, hospitalist authors (54.1% [33/61] vs. 26.3% [10/38] women, respectively, p = .002) and hospitalist last authors (51.9% [14/27] vs. 20% [4/20], p = .03) were more likely to be women. CONCLUSIONS: Across COVID-19-related manuscripts, disparities by gender were driven by the high-impact general medical journals. HM-specific journals had more equitable inclusion of women authors, demonstrating the potential impact of proactive editorial policies on diversity.

Antibiotic Stewardship Strategies and Their Association With Antibiotic Overuse After Hospital Discharge: An Analysis of the Reducing Overuse of Antibiotics at Discharge (Road) Home Framework.

BACKGROUND: Strategies to optimize antibiotic prescribing at discharge are not well understood. METHODS: In fall 2019, we surveyed 39 Michigan hospitals on their antibiotic stewardship strategies. The association of reported strategies with discharge antibiotic overuse (unnecessary, excess, suboptimal fluoroquinolones) for community-acquired pneumonia (CAP) and urinary tract infection (UTI) was evaluated in 2 ways: (1) all strategies assumed equal weight and (2) strategies were weighted based on the ROAD (Reducing Overuse of Antibiotics at Discharge) Home Framework (ie, Tier 1-Critical infrastructure, Tier 2-Broad inpatient interventions, Tier 3-Discharge-specific strategies) with Tier 3 strategies receiving the highest weight. RESULTS: Between 1 July 2017 and 30 July 2019, 39 hospitals with 20 444 patients (56.5% CAP; 43.5% UTI) were included. Survey response was 100%. Hospitals reported a median (interquartile range [IQR]) 12 (9-14) of 34 possible stewardship strategies. On analyses of individual stewardship strategies, the Tier 3 intervention, review of antibiotics prior to discharge, was the only strategy consistently associated with lower antibiotic overuse at discharge (adjusted incident rate ratio [aIRR] 0.543, 95% confidence interval [CI]: .335-.878). On multivariable analysis, weighting by ROAD Home tier predicted antibiotic overuse at discharge for both CAP and UTI. For diseases combined, having more weighted strategies was associated with lower antibiotic overuse at discharge (aIRR 0.957, 95% CI: .927-.987, per weighted intervention); discharge-specific stewardship strategies were associated with a 12.4% relative decrease in antibiotic overuse days at discharge. CONCLUSIONS: The more stewardship strategies a hospital reported, the lower its antibiotic overuse at discharge. However, Tier 3, or discharge-specific strategies, appeared to have the largest effect on antibiotic prescribing at discharge.

Propofol for Treatment-Resistant Depression: A Pilot Study.

Background: We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Methods: Ten participants with moderate-to-severe medication-resistant depression (age 18-45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Results: Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0-45 points), corresponding to a mean 58% improvement from baseline (range 0-100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. Conclusions: These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol's antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.

Correction: Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression.

[This corrects the article DOI: 10.1371/journal.pone.0069809.].

Gene Expression Factor Analysis to Differentiate Pathways Linked to Fibromyalgia, Chronic Fatigue Syndrome, and Depression in a Diverse Patient Sample.

OBJECTIVE: To determine if independent candidate genes can be grouped into meaningful biologic factors, and whether these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS), while controlling for comorbid depression, sex, and age. METHODS: We included leukocyte messenger RNA gene expression from a total of 261 individuals, including healthy controls (n = 61), patients with FMS only (n = 15), with CFS only (n = 33), with comorbid CFS and FMS (n = 79), and with medication-resistant (n = 42) or medication-responsive (n = 31) depression. We used exploratory factor analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine whether these factors were associated with specific diagnoses. RESULTS: EFA resulted in 4 independent factors with minimal overlap of genes between factors, explaining 51% of the variance. We labeled these factors by function as 1) purinergic and cellular modulators, 2) neuronal growth and immune function, 3) nociception and stress mediators, and 4) energy and mitochondrial function. Regression analysis predicting these biologic factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (Quick Inventory for Depression Symptomatology score), but not associated with FMS. CONCLUSION: Expression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters, but in opposite directions, when controlling for comorbid FMS. Given high comorbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression.

Fatigue sensation and gene expression in trained cyclists following a 40 km time trial in the heat.

PURPOSE: We examined the effect of race-effort cycling exercise with and without heat stress on post-exercise perceptions of fatigue and pain, as well as mRNA expression in genes related to exercise responses. METHODS: Trained cyclists (n = 20) completed 40 km time trials during temperate (TC, 21 °C) and hot (HC, 35 °C) conditions. Blood lactates were measured 1 and 5 min post-exercise. Venous blood samples and ratings of fatigue and pain perceptions were obtained at baseline and at 0.5, 8, 24, and 48 h post-exercise. Leukocyte mRNA expression was performed for metabolite detecting, adrenergic, monoamine, and immune receptors using qPCR. RESULTS: Significantly lower mean power (157 ± 32.3 vs 187 ± 40 W) and lactates (6.4 ± 1.7 vs 8.8 ± 3.2 and 4.2 ± 1.5 vs 6.6 ± 2.7 mmol L(-1) at 1- and 5-min post-exercise) were observed for HC versus TC, respectively (p < 0.05). Increases (p < 0.05) in physical fatigue and pain perception during TTs did not differ between TC and HC (p > 0.30). Both trials resulted in significant post-exercise decreases in metabolite detecting receptors ASIC3, P2X4, TRPV1, and TRPV4; increases in adrenergic receptors α2a, α2c, and ß1; decreases in adrenergic ß2, the immune receptor TLR4, and dopamine (DRD4); and increases in serotonin (HTR1D) and IL-10 (p < 0.05). Post-exercise IL-6 differed between TC and HC, with significantly greater increases observed following HC (p < 0.05). CONCLUSIONS: Both TT performances appeared to be regulated around a specific sensory perception of fatigue and pain. Heat stress may have compensated for lower lactate during HC, thereby matching changes in metabolite detecting and other mRNAs across conditions.

Does Dopamine Replacement Medication Affect Postural Sequence Learning in Parkinson's Disease?

Deficits in sequence-specific learning (SSL) may be a product of Parkinson's disease (PD) but this deficit could also be related to dopamine replacement. The purpose of this study was to determine whether dopamine replacement affected acquisition and retention of a standing Continuous Tracking Task in individuals with PD. SSL (difference between random/repeated Root Mean Square Error across trials) was calculated over 2 days of practice and 1 day of retention for 4 groups; 10 healthy young (HY), 10 healthy elders, 10 individuals with PD on, 9 individuals with PD off their usual dosage of dopamine replacement. Improvements in acquisition were observed for all groups; however, only the HY demonstrated retention. Therefore, age appeared to have the largest effect on SSL with no significant effect of medication. Additional research is needed to understand the influence of factors such as practice amount, task difficulty, and dopamine replacement status on SSL deficits during postural tasks.