Immune Response Dynamics and Biomarkers in COVID-19 Patients.

BACKGROUND: The immune response dynamics in COVID-19 patients remain a subject of intense investigation due to their implications for disease severity and treatment outcomes. We examined changes in leukocyte levels, eosinophil activity, and cytokine profiles in patients hospitalized with COVID-19. METHODS: Serum samples were collected within the first 10 days of hospitalization/confirmed infection and analyzed for eosinophil granule proteins (EGP) and cytokines. Information from medical records including comorbidities, clinical symptoms, medications, and complete blood counts were collected at the time of admission, during hospitalization and at follow up approximately 3 months later. RESULTS: Serum levels of eotaxin, type 1 and type 2 cytokines, and alarmin cytokines were elevated in COVID-19 patients, highlighting the heightened immune response (p < 0.05). However, COVID-19 patients exhibited lower levels of eosinophils and eosinophil degranulation products compared to hospitalized controls (p < 0.05). Leukocyte counts increased consistently from admission to follow-up, indicative of recovery. CONCLUSION: Attenuated eosinophil activity alongside elevated chemokine and cytokine levels during active infection, highlights the complex interplay of immune mediators in the pathogenesis COVID-19 and underscores the need for further investigation into immune biomarkers and treatment strategies.

Reliability, Concurrent Validity, and Minimal Detectable Change of Timed Up and Go Obstacle Test in People With Stroke.

OBJECTIVE: The aims of this study were to investigate the psychometric property of the timed Up and Go Obstacle (TUGO) test in people with stroke. DESIGN: Cross-sectional design. SETTING: University based neurorehabilitation laboratory. PARTICIPANTS: Twenty-eight people with stroke and 30 healthy older adults. INTERVENTION: Not Applicable. OUTCOME MEASURES: The TUGO (obstacle heights: 0, 5, 17 cm) test completion times, Fugl-Meyer Assessment (FMA) score, ankle dorsiflexor and plantarflexor muscle strength, Berg Balance Scale (BBS) score, Narrow Corridor Walking Test (NCWT) completion time, timed Up and Go (TUG) test completion time, and Community Integrated Measure. RESULTS: Excellent inter-rater (intraclass correlation coefficient [ICC]=0.999-1.000) and test-retest reliabilities (ICC=0.917-0.975) were found for TUGO test completion times for all obstacle heights. The TUGO test completion times for all obstacle heights were significantly correlated with NCWT and TUG test completion times (r=0.817-0.912). Only TUGO test completion times for 0 and 5 cm obstacle heights showed significant correlations with BBS scores (r=-0.518 to -0.534), while the TUGO test completion time for the 17 cm obstacle height correlated significantly with FMA scores. The minimal detectable change and optimal cut-off values for TUGO test completion times for the 0, 5, and 17 cm obstacle heights were 2.54, 3.60, and 3.07 s, and 14.69, 14.76, and 16.10 s, respectively. CONCLUSION: The TUGO test is a reliable, valid, and easy-to-administer clinical measure to discriminate between people with stroke and healthy older adults.

Comparative Effectiveness of Carotid Stenting to Medical Therapy Among Patients With Asymptomatic Carotid Stenosis.

BACKGROUND: No completed trials have compared carotid artery stenting (CAS) to medical therapy (MT). We examined the effectiveness of CAS compared with MT in patients with asymptomatic carotid stenosis. METHODS: We conducted a retrospective cohort study of 219 979 Veterans ≥65 years who received carotid imaging for asymptomatic carotid stenosis between 2005 and 2009 in the US Veterans Health Administration. We constructed a sample of patients who received MT (n=2509) and comparable patients who received CAS (n=551) and followed them for 5 years. Using target trial methodology, we computed weighted Kaplan-Meier curves and estimated the risk of fatal and nonfatal stroke in each group over 5 years of follow-up. We also estimated the cumulative incidence functions for fatal and nonfatal stroke accounting for nonstroke deaths as competing risks. RESULTS: Five hundred fifty-one patients received CAS, and 2509 patients received MT. The observed rate of stroke or death (perioperative complications) within 30 days in the CAS arm was 2.2%. Using the target trial methodology, the 5-year risk of fatal and nonfatal stroke was similar among patients assigned to CAS (6.9%) compared with patients assigned to MT (7.1%; risk difference, -0.1% [95% CI, -2.6% to 2.7%]). In an analysis that incorporated the competing risk of death, the risk difference between the two arms remained nonsignificant (risk difference, -1.5% [95% CI, -3.0% to 0.3%]). CONCLUSIONS: In this sample of older male adults, we found no difference between MT and CAS in the treatment of asymptomatic carotid stenosis. Future studies in other settings are needed to confirm these findings.

Implementation fidelity of a nurse-led RCT-tested complex intervention, care coordination for health promotion and activities in Parkinson's disease (CHAPS) in meeting challenges in care management.

BACKGROUND: Parkinson's disease (PD) complexity poses challenges for individuals with Parkinson's, providers, and researchers. A recent multisite randomized trial of a proactive, telephone-based, nurse-led care management intervention - Care Coordination for Health Promotion and Activities in Parkinson's Disease (CHAPS) - demonstrated improved PD care quality. Implementation details and supportive stakeholder feedback were subsequently published. To inform decisions on dissemination, CHAPS Model components require evaluations of their fidelity to the Chronic Care Model and to their implementation. Additionally, assessment is needed on whether CHAPS addresses care challenges cited in recent literature. METHODS: These analyses are based on data from a subset of 140 intervention arm participants and other CHAPS data. To examine CHAPS Model fidelity, we identified CHAPS components corresponding to the Chronic Care Model's six essential elements. To assess implementation fidelity of these components, we examined data corresponding to Hasson's modified implementation fidelity framework. Finally, we identified challenges cited in current Parkinson's care management literature, grouped these into themes using open card sorting techniques, and examined CHAPS data for evidence that CHAPS met these challenges. RESULTS: All Chronic Care Model essential elements were addressed by 17 CHAPS components, thus achieving CHAPS Model fidelity. CHAPS implementation fidelity was demonstrated by adherence to content, frequency, and duration with partial fidelity to telephone encounter frequency. We identified potential fidelity moderators for all six of Hasson's moderator types. Through card sorting, four Parkinson's care management challenge themes emerged: unmet needs and suggestions for providers (by patient and/or care partner), patient characteristics needing consideration, and standardizing models for Parkinson's care management. CHAPS activities and stakeholder perceptions addressed all these themes. CONCLUSIONS: CHAPS, a supportive nurse-led proactive Parkinson's care management program, improved care quality and is designed to be reproducible and supportive to clinicians. Findings indicated CHAPS Model fidelity occurred to the Chronic Care Model and fidelity to implementation of the CHAPS components was demonstrated. Current Parkinson's care management challenges were met through CHAPS activities. Thus, dissemination of CHAPS merits consideration by those responsible for implementing changes in clinical practice and reaching people in need. TRIAL REGISTRATION: ClinicalTrials.gov as NCT01532986 , registered on January 13, 2012.

Feasibility of bubble non-invasive positive pressure ventilation, a first-in-human study.

PURPOSE: Infant respiratory distress is  a significant cause of mortality globally. Bubble continuous positive airway pressure (CPAP) is a simple and effective therapy, but sicker infants may require additional support such as non-invasive positive-pressure ventilation (NIPPV). We investigated the feasibility of a simple, low-cost, non-electric bubble NIPPV device. METHODS: In this cross-over feasibility study, seven newborns with moderate respiratory distress (Downes score ≥ 3), weight > 1500 g and gestational age > 32 weeks were randomized to  4 h of treatment with bubble CPAP (5-8 cm H2O) vs. bubble NIPPV (Phigh 8-10 cm H2O/Plow 5-8 cm H2O) followed by 4 h of the alternate treatment. Treatment order (CPAP vs. NIPPV) was randomized. Outcome measures included hourly vital signs, Downes score and O2 saturation. Adverse events including pneumothorax, nasal septal necrosis, necrotizing enterocolitis and death before discharge were also recorded. RESULTS: It took nurses 39 (7.3) s to assemble the bubble NIPPV device. Patients had similar vital signs and Downes scores on both treatments; median (IQR) values on bubble CPAP vs. bubble NIPPV were: heart rate 140 (134.5, 144), 140 (134.5, 144); respiratory rate 70 (56, 80), 65 (58, 82), Downes score 4 (3, 5.75), 4 (3, 5), O2 96 (94, 98), 97 (96, 98). All newborns survived to discharge and there were no adverse events. . CONCLUSIONS: A simple, low-cost, non-electric method of providing NIPPV for newborns with respiratory distress is feasible in limited resource settings. Randomized-controlled trials comparing bubble CPAP and bubble NIPPV are justified.

An overview of the intraoral features and craniofacial morphology of growing and adult Japanese cleidocranial dysplasia subjects.

BACKGROUND: Orthodontic treatment for cleidocranial dysplasia (CCD) requires an understanding of the nature of the retained deciduous teeth, supernumerary teeth, delayed eruption of the permanent teeth, and craniofacial morphology from childhood to adulthood. This study aimed to provide an overview of the intraoral and craniofacial characteristics of growing and adult Japanese CCD subjects. METHODS: We assessed cross-sectionally the intraoral features of 28 CCD subjects (males, 15.3 ± 7.0 years; females, 15.2 ± 5.1 years) using orthopantomograms and photographs. Mean facial diagrams (profilograms) of 3 age groups (5-10 years, 11-14 years, over 15 years: adult) were constructed, and linear and angular measurements of 2 age groups (under 15 years, adult) were performed by using cephalograms. The data were compared with Japanese standards. RESULTS: A mean of 11.7 and 8.4 retained deciduous teeth, 10.4 and 15.8 erupted permanent teeth were observed in the adult males and females, and a mean of 6.8 and 5.3 supernumerary teeth were observed in all males and females, respectively. A positive correlation was found between the number of supernumerary teeth and the age at initial visit. Cephalometric analysis showed an average to anteriorly positioned maxilla, a tendency for counter-clockwise rotation of the ramus, and a prognathic mandible in all groups. CONCLUSIONS: The number of supernumerary teeth increased with age. The maxilla was average to anteriorly positioned, and the mandible was counter-clockwise rotated and prognathic for all groups. These characteristic craniofacial morphologies and changes of intraoral conditions at different ages in CCD patients should be considered when proposing rational orthodontic treatment plans.

Derivation and Application of a Tool to Estimate Benefits From Multiple Therapies That Reduce Recurrent Stroke Risk.

Background and Purpose- Lowering blood pressure and cholesterol, antiplatelet/antithrombotic use, and smoking cessation reduce risk of recurrent stroke. However, gaps in risk factor control among stroke survivors warrant development and evaluation of alternative care delivery models that aim to simultaneously improve multiple risk factors. Randomized trials of care delivery models are rarely of sufficient duration or size to be powered for low-frequency outcomes such as observed recurrent stroke. This creates a need for tools to estimate how changes across multiple stroke risk factors reduce risk of recurrent stroke. Methods- We reviewed existing evidence of the efficacy of interventions addressing blood pressure reduction, cholesterol lowering, antiplatelet/antithrombotic use, and smoking cessation and extracted relative risks for each intervention. From this, we developed a tool to estimate reductions in recurrent stroke risk, using bootstrapping and simulation methods. We also calculated a modified Global Outcome Score representing the proportion of potential benefit (relative risk reduction) achieved if all 4 individual risk factors were optimally controlled. We applied the tool to estimate stroke risk reduction among 275 participants with complete 12-month follow-up data from a recently published randomized trial of a healthcare delivery model that targeted multiple stroke risk factors. Results- The recurrent stroke risk tool was feasible to apply, yielding an estimated reduction in the relative risk of ischemic stroke of 0.36 in both the experimental and usual care trial arms. Global Outcome Score results suggest that participants in both arms likely averted, on average, 45% of recurrent stroke events that could possibly have been prevented through maximal implementation of interventions for all 4 individual risk factors. Conclusions- A stroke risk reduction tool facilitates estimation of the combined impact on vascular risk of improvements in multiple stroke risk factors and provides a summary outcome for studies testing alternative care models to prevent recurrent stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00861081.

Factors Associated With Participation in the Chronic Disease Self-Management Program: Findings From the SUCCEED Trial.

BACKGROUND AND PURPOSE: Self-management programs may improve quality of life and self-efficacy for stroke survivors, but participation is low. In a randomized controlled trial of a complex, multidisciplinary, team-based secondary stroke prevention intervention, we offered participants Chronic Disease Self-Management Program (CDSMP) workshops in addition to clinic visits and home visits. To enhance participation, workshops were facilitated by community health workers who were culturally and linguistically concordant with most participants and scheduled CDSMP sessions at convenient venues and times. Over time, we implemented additional strategies such as free transportation and financial incentives. In this study, we aimed to determine factors associated with CDSMP participation and attendance. METHODS: From 2014 to 2018, 18 CDSMP workshop series were offered to 241 English and Spanish-speaking individuals (age ≥40 years) with recent stroke or transient ischemic attack. Zero-inflated Poisson regression was used to identify factors associated with participation and attendance (ie, number of sessions attended) in CDSMP. Missing values were imputed using multiple imputation methods. RESULTS: Nearly one-third (29%) of intervention subjects participated in CDSMP. Moderate disability and more clinic/home visits were associated with participation. Participants with higher numbers of clinic and home visits (incidence rate ratio [IRR], 1.06 [95% CI, 1.01-1.12]), severe (IRR, 2.34 [95% CI, 1.65-3.31]), and moderately severe disability (IRR, 1.55 [95% CI, 1.07-2.23]), and who enrolled later in the study (IRR, 1.12 [95% CI, 1.08-1.16]) attended more sessions. Individuals with higher chaos scores attended fewer sessions (IRR, 0.97 [95% CI, 0.95-0.99]). CONCLUSIONS: Less than one-third of subjects enrolled in the SUCCEED (Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities) intervention participated in CDSMP; however, participation improved as transportation and financial barriers were addressed. Strategies to address social determinants of health contributing to chaos and engage individuals in healthcare may facilitate attendance. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01763203.

Stakeholder perceptions of components of a Parkinson disease care management intervention, care coordination for health promotion and activities in Parkinson's disease (CHAPS).

BACKGROUND: A recent nurse-led proactive care management intervention, Care Coordination for Health Promotion and Activities in Parkinson Disease (CHAPS), improved care quality when compared to usual care in a randomized controlled trial. Therefore, stakeholder (patient participants, nurse care managers, and Parkinson disease (PD) specialists) perceptions of key intervention components merit evaluation to inform decisions about dissemination. METHODS: This multi-site study occurred in five southwest United States Veterans Health Administration medical centers. Stakeholders were surveyed on their perceptions of CHAPS including the CHAPS Assessment, CHAPS nurse care managers, the Siebens Domain Management Model™ (a practical clinical model), and the Siebens Health Care Notebook (Notebook) (self-care tool). Participants' electronic medical records were abstracted for perceptions of the Notebook. Statistical analysis software was used to provide summary statistics; open card sorting methodology was used to identify themes and attributes in qualitative data including usability of some components. RESULTS: Participants, overall, highly rated their medication self-management, acknowledged some challenges with the CHAPS self-care tools, reported knowledge of PD specialist follow-up and PD red flags, and rated CHAPS nurse care managers as helpful. Nurse care manager responses indicated the CHAPS Assessment and Program highly facilitated care of their patients. Most all PD specialists would refer other patients to CHAPS. Nurse care manager and PD specialist responses indicated improved participant management of their PD. Three themes emerged in participant perceptions of the Notebook: Notebook Assets (e.g., benefits and features-liked); Deferring Notebook Review (e.g., no time to review); and Reasons for Not Using (e.g., participant preference). Shared attributes regarding the Siebens Domain Management Model and Notebook usability, reported by nurse care managers, were user-friendly, person/patient-centered, and organized. Some challenges to their use were also reported. CONCLUSIONS: Overall, stakeholder perceptions of the proactive nurse-led CHAPS intervention indicated its value in the care of individuals with PD. Responses about the CHAPS Assessment, Siebens Domain Management Model, and Notebook self-care tool signified their usefulness. Stakeholders' constructive suggestions indicated their engagement in CHAPS. These findings support CHAPS dissemination and contribute to research in care management. TRIAL REGISTRATION: ClinicalTrials.gov as NCT01532986 , registered on January 13, 2012.

Quality and extent of implementation of a nurse-led care management intervention: care coordination for health promotion and activities in Parkinson's disease (CHAPS).

BACKGROUND: A recent nurse-led, telephone-administered 18-month intervention, Care Coordination for Health Promotion and Activities in Parkinson's Disease (CHAPS), was tested in a randomized controlled trial and improved care quality. Therefore, intervention details on nurse care manager activity (types and frequencies) and participant actions are needed to support potential dissemination. Activities include nurse care manager use of a holistic organizing framework, identification of Parkinson's disease (PD)-related problems/topics, communication with PD specialists and care coordination, participant coaching, and participant self-care actions including use of a notebook self-care tool. METHODS: This article reports descriptive data on the CHAPS intervention. The study setting was five sites in the Veterans Affairs Healthcare System. Sociodemographic data were gathered from surveys of study participants (community-dwelling veterans with PD). Nurse care manager intervention activities were abstracted from electronic medical records and logbooks. Statistical analysis software was used to provide summary statistics; closed card sorting was used to group some data. RESULTS: Intervention participants (n = 140) were primarily men, mean age 69.4 years (standard deviation 10.3) and community-dwelling. All received the CHAPS Initial Assessment, which had algorithms designed to identify 31 unique CHAPS standard problems/topics. These were frequently documented (n = 4938), and 98.6% were grouped by assigned domain from the Organizing Framework (Siebens Domain Management Model™). Nurse care managers performed 27 unique activity types to address identified problems, collaborating with participants and PD specialists. The two most frequent unique activities were counseling/emotional support (n = 387) and medication management (n = 349). Both were among 2749 total performed activities in the category Implementing Interventions (coaching). Participants reported unique self-care action types (n = 23) including use of a new notebook self-care tool. CONCLUSIONS: CHAPS nurse care managers implemented multiple activities including participant coaching and care coordination per the CHAPS protocol. Participants reported various self-care actions including use of a personalized notebook. These findings indicate good quality and extent of implementation, contribute to ensuring reproducibility, and support CHAPS dissemination as a real-world approach to improve care quality. TRIAL REGISTRATION: ClinicalTrials.gov as NCT01532986 , registered on January 13, 2012.