Implementation and Evaluation of a mHealth-Based Community Health Worker Feedback Loop for Hispanics with and at Risk for Diabetes.

BACKGROUND: Gaps in accessibility and communication hinder diabetes care in poor communities. Combining mobile health (mHealth) and community health workers (CHWs) into models to bridge these gaps has great potential but needs evaluation. OBJECTIVE: To evaluate a mHealth-based, Participant-CHW-Clinician feedback loop in a real-world setting. DESIGN: Quasi-experimental feasibility study with intervention and usual care (UC) groups. PARTICIPANTS: A total of 134 participants (n = 67/group) who were all low-income, uninsured Hispanics with or at-risk for type 2 diabetes. INTERVENTION: A 15-month study with a weekly to semimonthly mHealth Participant-CHW-Clinician feedback loop to identify participant issues and provide participants monthly diabetes education via YouTube. MAIN MEASURES: We used pre-defined feasibility measures to evaluate our intervention: (a) implementation, the execution of feedback loops to identify and resolve participant issues, and (b) efficacy, intended effects of the program on clinical outcomes (baseline to 15-month HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight changes) for each group and their subgroups (at-risk; with diabetes, including uncontrolled (HbA1c ≥ 7%)). KEY RESULTS: CHWs identified 433 participant issues (mean = 6.5 ± 5.3) and resolved 91.9% of these. Most issues were related to supplies, 26.3% (n = 114); physical health, 23.1% (n = 100); and medication access, 20.8% (n = 90). Intervention participants significantly improved HbA1c (- 0.51%, p = 0.03); UC did not (- 0.10%, p = 0.76). UC DBP worsened (1.91 mmHg, p < 0.01). Subgroup analyses revealed HbA1c improvements for uncontrolled diabetes (intervention: - 1.59%, p < 0.01; controlled: - 0.72, p = 0.03). Several variables for UC at-risk participants worsened: HbA1c (0.25%, p < 0.01), SBP (4.05 mmHg, p < 0.01), DBP (3.21 mmHg, p = 0.01). There were no other significant changes for either group. CONCLUSIONS: A novel mHealth-based, Participant-CHW-Clinician feedback loop was associated with improved HbA1c levels and identification and resolution of participant issues. UC individuals had several areas of clinical deterioration, particularly those at-risk for diabetes, which is concerning for progression to diabetes and disease-related complications. CLINICAL TRIAL: NCT03394456, accessed at https://clinicaltrials.gov/ct2/show/NCT03394456.

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

Determining call-to-entry rate and recruitment barriers in clinical studies for community clinics serving low-income populations: a cohort study.

BACKGROUND: Recruitment for clinical studies is challenging. To overcome barriers, investigators have previously established call-to-entry rates to assist in planning. However, rates specific to low-income minority populations are needed to account for additional barriers to enrolment these individuals face. OBJECTIVE: To obtain a call-to-entry rate in a low-income uninsured Hispanic population with chronic disease. METHODS: We used data from four of our randomised clinical studies to determine the call-to-entry rate for individuals (n=1075) with or at risk for type 2 diabetes: participants needed/potential participants contacted=recruitment rate (yield). Research staff contacted potential participants to enrol in a study that evaluated 6 month diabetes programmes at community clinics from 2015 to 2020. We recorded call-to-entry rates, reasons for declining the study, show rates, and attrition. RESULTS: The call-to-entry rate was 14.5%. Forty per cent of potential participants could not be contacted, and 30.6%, 19.1%, and 5.4% responded yes, no, and maybe, respectively. No show percentages were 54% for yes and 91.4% for maybe responders. The majority (61.6%) declined due to inability to attend; reasons to decline included work (43%), eligibility (18%), transportation (10%), out of town (9%), did not think they needed the programme (7%) and other/unknown (14%). Being a physician predicted inability to reach participants (adjusted OR 2.91, 95% CI 1.73 to 4.90). Attrition was 6.8%. CONCLUSIONS: We described a call-to-entry rate and detailed recruitment data, including reasons to decline the study. This valuable information can assist investigators in study planning and overcoming enrolment barriers in low-income populations. Telehealth-based or strategies that limit transportation needs may increase participant involvement. TRIAL REGISTRATION NUMBER: NCT03394456.

Intrapulmonary administration of purified NEIL2 abrogates NF-κB-mediated inflammation.

Aberrant or constitutive activation of nuclear factor kappa B (NF-κB) contributes to various human inflammatory diseases and malignancies via the upregulation of genes involved in cell proliferation, survival, angiogenesis, inflammation, and metastasis. Thus, inhibition of NF-κB signaling has potential for therapeutic applications in cancer and inflammatory diseases. We reported previously that Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase, is involved in the preferential repair of oxidized DNA bases from the transcriptionally active sequences via the transcription-coupled base excision repair pathway. We have further shown that Neil2-null mice are highly sensitive to tumor necrosis factor α (TNFα)- and lipopolysaccharide-induced inflammation. Both TNFα and lipopolysaccharide are potent activators of NF-κB. However, the underlying mechanism of NEIL2's role in the NF-κB-mediated inflammation remains elusive. Here, we have documented a noncanonical function of NEIL2 and demonstrated that the expression of genes, such as Cxcl1, Cxcl2, Cxcl10, Il6, and Tnfα, involved in inflammation and immune cell migration was significantly higher in both mock- and TNFα-treated Neil2-null mice compared with that in the WT mice. NEIL2 blocks NF-κB's binding to target gene promoters by directly interacting with the Rel homology region of RelA and represses proinflammatory gene expression as determined by co-immunoprecipitation, chromatin immunoprecipitation, and electrophoretic mobility-shift assays. Remarkably, intrapulmonary administration of purified NEIL2 via a noninvasive nasal route significantly abrogated binding of NF-κB to cognate DNA, leading to decreased expression of proinflammatory genes and neutrophil recruitment in Neil2-null as well as WT mouse lungs. Our findings thus highlight the potential of NEIL2 as a biologic for inflammation-associated human diseases.

Utilizing Telemedicine for Group Visit Provider Encounters: A Feasibility and Acceptability Study.

BACKGROUND: The value of telemedicine has been underscored during the coronavirus pandemic. Utilizing telemedicine could markedly enhance group visit scalability and sustainability. However, there are limited data demonstrating telemedicine use for group visits. OBJECTIVE: To evaluate the feasibility and acceptability of provider encounters conducted via telemedicine in group visits. MATERIALS AND METHODS: We conducted a 6-month diabetes group visit program and compared in-person (months 1-3) versus telemedicine (videoconferencing) (months 4-6) patient-provider encounters. Participants completed the Telehealth Usability Questionnaire (TUQ) at 6-months (primary outcome). To ensure telemedicine did not negatively affect clinical outcomes, we compared in-person versus telemedicine differences in HbA1c, blood pressure, body mass index (BMI), and attendance. RESULTS: The TUQ revealed that participants (N=19) found telemedicine useful and easy to use (4.9/5.0, 4.4/5.0, respectively) and with excellent interface (4.3/5.0), interaction (4.6/5.0), reliability (4.2/5.0), and satisfaction (4.4/5.0). There were no significant differences in clinical outcomes between arms: HbA1c (in-person: -0.60%, telemedicine: -0.52%, p=0.86), blood pressure (systolic: p=0.475, diastolic: p=0.683), weight (p=0.982), BMI (p=0.981), attendance (in-person: 75.44%, telemedicine: 70.12%, p=0.551). CONCLUSION: Provider telemedicine encounters in group visits are feasible and acceptable. This is a promising model to address provider limitations in group visits and increase access to care. Larger studies are needed to further evaluate these findings.

Evaluating the Impact of Telehealth-Based, Diabetes Medication Training for Community Health Workers on Glycemic Control.

BACKGROUND: Diabetes is a major contributor to morbidity and mortality. Community Health Workers (CHWs) have been instrumental in improving patient outcomes. However, CHW training largely focuses on general diabetes concepts rather than medications. Providing accessible, diabetes medication training for CHWs has the potential to increase patient understanding, personalized care, and adherence, thereby improving outcomes. OBJECTIVE: To evaluate the impact of a telehealth-based diabetes medication training for CHWs on patient outcomes as measured by HbA1c changes. METHODS: We provided a 12-month weekly, telehealth (videoconference) medication training for CHWs who led 6-month diabetes programs for low-income Latino(a)s in community clinics. We measured participant HbA1c (primary outcome), blood pressure, and body mass index (BMI) changes. We evaluated CHW knowledge via two pre/post-tests: medication adverse events/side effects (TEST-1, months 1-6) and dosing, titration, and emergencies (TEST-2, months 7-12). We assessed CHW training application by their ability to identify patient, provider, and healthcare system medication barriers. RESULTS: Participants' (n = 55) HbA1c improved (9.0% (75 mmol/mol) to 7.8% (62 mmol/mol) (p = 0.001)). Blood pressure and BMI changes were not significant. CHWs improved their knowledge: TEST-1: 10.5-18.2/20.0 (p = 0.002), TEST-2: 10.3-17.3/19.0 (p = 0.0019). CHWs identified 984 patients (n = 610), providers (n = 151), and healthcare systems (n = 223) medication barriers during the 12-month training. CONCLUSIONS: Providing a telehealth-based, diabetes medication training program for CHWs allowed a personalized approach to identify barriers to care at several levels, which was associated with significant participant HbA1c reductions and improved CHW knowledge. This is a promising cost-effective, culturally sensitive strategy to improve diabetes care. Larger longitudinal evaluations are needed to fully understand the impact of CHW medication training.

Metformin use and health care utilization in patients with coexisting chronic obstructive pulmonary disease and diabetes mellitus.

Background: Chronic obstructive pulmonary disease (COPD) is associated with persistent systemic inflammation. Anti-inflammatory therapies have been shown to decrease acute exacerbations of COPD. The antidiabetic medication metformin decreases oxidative stress and inflammation and may benefit patients with COPD. We aimed at investigating the effect of metformin on health care utilizations in patients with coexisting COPD and diabetes mellitus (DM). Methods: We studied 5% Medicare beneficiaries with coexisting COPD and DM prescribed metformin or other antidiabetics during the period 2007-2010. The primary outcome was COPD-specific emergency room (ER) visits and hospitalizations; the secondary outcome was all-cause ER visits and hospitalizations over the 2-year follow-up after the index antidiabetic prescription. The effects of metformin were examined by COPD complexity and compared with the effects of other antidiabetic medications. Results: Among 11,260 patients, 3,193 were metformin users and 8,067 were nonusers. Metformin users were younger, were less sick, were less likely to be on oxygen, and had fewer hospitalizations in the prior year compared with the nonusers. Over a 2-year period, metformin users had lower COPD-specific and all-cause ER visits and hospitalizations (7.11% vs 9.61%, p<0.0001; and 61.63% vs 71.27%, p<0.0001, respectively). In a stratified multivariable analysis, the odds of COPD-specific ER visits and hospitalizations were lower in patients with low-complexity COPD (adjusted odds ratio =0.66, 95% confidence interval =0.52-0.85). However, patients with all COPD complexities get benefits of metformin on all-cause ER visits and hospitalizations. Conclusion: The use of metformin in patients with coexisting COPD and DM was associated with fewer COPD-specific ER visits and hospitalizations, especially in low-complexity COPD.

Integrating CHWs as Part of the Team Leading Diabetes Group Visits: A Randomized Controlled Feasibility Study.

Purpose The purpose of the study was to evaluate the feasibility of integrating Community Health Workers (CHWs) as part of the team leading diabetes group visits. Methods This was a randomized controlled study that integrated CHWs as part of the team leading diabetes group visits for low-income Hispanic adults (n = 50). Group visits met for 3 hours each month for a 6-month duration. Main measures included baseline and 6-month clinical outcomes (ie, A1C, lipids), concordance with 8 standard of care guidelines (ie, screens for cervical, breast, and colon cancer) from the US Preventive Task Force and American Diabetes Association, and participant acceptability. Results Compared to control participants, the intervention group resulted in significantly better clinical outcomes or guideline concordance for the following areas: target A1C levels, retinal eye exams, diabetes foot exams, mammograms, and urine microalbumin. Significantly more individuals in the control group gained weight, whereas a greater number of participants in the intervention group lost weight. Intervention participants found the group visits highly acceptable. Conclusions Integrating CHWs as part a comprehensive diabetes group visit program is a feasible and effective system-level intervention to improve glycemic control and achieve guideline concordance.

Rapid response team in an academic institution: does it make a difference?

BACKGROUND: Although data remain contradictory, rapid response systems are implemented across US hospitals. We aimed to determine whether implementation of a rapid response team (RRT) in a tertiary academic hospital improved outcomes. METHODS: Our hospital is a tertiary academic medical center with 24-h in-house resident coverage. We conducted a retrospective cohort study comparing 27 months after implementation of the RRT (April 1, 2006, to June 31, 2008) and 9 months before (January 1, 2005, to September 31, 2005). Outcomes included incidence of codes (cardiac and/or respiratory arrests), outcome of the codes, and overall hospital mortality. RESULTS: We analyzed 16,244 nonobstetrics hospital admissions and 70,208 patient days in the control period and 45,145 nonobstetrics hospital admissions and 161,097 patient days after the RRT was implemented. The RRT was activated 1,206 times (7.7 calls per 1,000 patient days). There was no difference in the code rate (0.83 vs 0.98 per 1,000 patient days, P = .3). There was a modest but nonsustained improvement in nonobstetrics hospital mortality during the study period (2.40% vs 2.15%; P = .05), which could not be explained by the RRT effect on code rates. The mortality was 2.40% in the control group and 2.06%, 1.94%, and 2.46%, respectively, during the next three consecutive 9-month intervals. CONCLUSIONS: In our single-institution study involving an academic hospital with 24-h in-house coverage, we found that RRT implementation did not reduce code rates in the 27 months after intervention. Although there was a decrease in overall hospital mortality, this decrease was small, nonsustained, and not explained by the RRT effect on code rates.

Venovenous carbon dioxide removal in chronic obstructive pulmonary disease: experience in one patient.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Acute exacerbations of COPD account for up to 84% of the total economic cost of this disease. The altered mechanics of the COPD patient represent a unique challenge to the clinician instituting assisted ventilation in this population. We developed an alternative mode of limited extracorporeal support termed Venovenous carbon dioxide removal (VVCO2R). We report our first case using VVCO2R, a 42-year-old white woman with a history of COPD and asthma, who was a heavy smoker at the time of admission. We utilized a compact, low flow pediatric extracorporeal circuit interposed with a low resistance gas exchange device. Venovenous carbon dioxide removal allowed for a reduction in the patient's minute ventilation to 30% of baseline with improved arterial blood gases (ABGs), a reduction in peak airway pressures and improvement in her hyperinflation. Our experience demonstrates that this system can effectively remove CO2 safely in a single cannula venous configuration while maintaining minimal anticoagulation. We believe this system could potentially be utilized in any medical or surgical intensive care unit.

Comparison of POCT and central laboratory blood glucose results using arterial, capillary, and venous samples from MICU patients on a tight glycemic protocol.

BACKGROUND: Point of care (POC) glucose meters are routinely used to monitor glucose levels for patients on tight glycemic control therapy. We determined if glucose values were different for a POC glucose meter as compared to the main clinical laboratory for medical intensive care unit patients on a tight glycemic protocol and whether the site of blood sampling had a significant impact on glucose values. METHODS: Eighty-four patients (114 paired samples) who were on a tight glycemic protocol in the period November 2005 through August 2006 were enrolled. After simultaneous blood draws, we compared the glucose levels for the glucose meter (arterial/venous/capillary), blood gas (arterial/venous), and central clinical laboratory (serum/plasma from arterial/venous samples). RESULTS: The mean glucose levels of all arterial/venous/fingerstick samples using the glucose meter demonstrated a positive bias of 0.7-0.9 mmol/l (12.6-16.2 mg/dl) (p<0.001) relative to central laboratory venous plasma. There was also a smaller positive (0.1-0.3 mmol/l or 1.8-5.4 mg/dl, p<0.05) bias for arterial/venous blood gas samples and laboratory arterial serum/plasma glucose samples. Using Parkes error grid analysis we were able to show that the bias for arterial or venous POC glucose results would have not impacted clinical care. This was not the case, however, for fingerstick sampling where a high bias could have significantly impacted clinical care. Additionally, in 3 fingerstick samples a severe underestimation (<46% of the central laboratory plasma result) was found. CONCLUSION: Glucose meters using arterial/venous whole blood may be utilized in the MICU; however, due to the increased variability of results we do not recommend the routine use of capillary blood sampling for monitoring glucose levels in the MICU setting.

Percutaneous venovenous CO2 removal with regional anticoagulation in an ovine model.

Extracorporeal CO2 removal may reduce minute ventilation requirements and allow for better tolerance of low tidal volume ventilating strategies in patients with severe respiratory insufficiency. Conventional extracorporeal gas exchange is labor-intensive, expensive, and usually requires systemic anticoagulation. In this study, a simplified venovenous circuit was developed by using regional citrate anticoagulation to avoid potential complications associated with systemic heparin. Five healthy adult sheep underwent percutaneous placement of a double-lumen 18F catheter into the internal jugular vein. The extracorporeal circuit consisted of a hollow fiber oxygenator and a variable speed roller pump. Regional anticoagulation consisted of a continuous citrate infusion to the inflow limb of the circuit. Systemic calcium levels were maintained by calcium chloride infusion through a central line. CO2 transfer was measured at varying levels of blood and gas flow. CO2 transfer ranged from 31 ml/min (500 ml/min blood flow; 2 l/min gas flow) to 150 ml/min (1000 ml/min blood flow; 15 l/min gas flow) and was directly proportional to blood flow and gas flow (p < 0.05). Normocapnia was maintained despite a 75% reduction in minute ventilation. At 24 hours, there was no significant clot formation in the circuit.

High-frequency percussive ventilation with systemic heparin improves short-term survival in a LD100 sheep model of acute respiratory distress syndrome.

We undertook an assessment of high-frequency percussive ventilation (HFPV) and systemic heparin on survival in our LD100 sheep model of smoke/burn-induced acute respiratory distress syndrome (ARDS). This was a prospective controlled outcomes study in a large animal critical care laboratory. ARDS was induced in 13 sheep by a combination of 48 cotton smoke breaths and 40% full-thickness cutaneous burn (LD100) followed by mechanical ventilation (15 ml/kg tidal volume). After meeting ARDS criteria (PaO2/FiO2 < 200), the sheep were divided into high-frequency percussive ventilation (HFPV; n = 7) or volume-controlled mechanical ventilation (VCMV; n = 6) groups. Both groups received systemic heparin to achieve an ACT 180-300 seconds. HFPV was managed with the Volumetric Diffusive Respiration Ventilator (Percussionaire Corp., Sandpoint, ID). The VCMV group was managed with up to 10 ml/kg tidal volume. Arterial blood gases and ventilator settings were monitored every 6 hours after onset of ARDS. HFPV did not affect sheep hemodynamics. Survival 84 hours after smoke and burn injury was significantly greater in the HFPV (7/7, 100%) compared with the VCMV group (3/6, 50%, P < .05). PaCO2 was significantly greater in VCMV group at 36, 48, and 72 hours after smoke and burn injury. PaO2/FiO2 after 36 hours of smoke and burn injury in the HFPV group was improved compared with the VCMV group, but no statistical difference was found. In the VCMV group, peak airway pressure was decreased to 19.7 +/- 2.2 cm H2O at 36 hours from 29 +/- 2.8 at 24 hours as the tidal volume changed from 15 ml/kg to 10 ml/kg and then gradually increased to 39 +/- 5.6 cm H2O at 72 hours. In the HFPV group, peak inspiratory pressure kept constant at a level of 30 cmH2O. In our smoke/burn-induced LD100 sheep model of ARDS, volume-controlled mechanical ventilation with systemic heparin achieved a 50% survival whereas HFPV with systemic heparin achieved 100% survival at 60 hours after the onset of ARDS.

Mechanical ventilation and acute respiratory distress syndrome.

Acute respiratory distress syndrome continues to be a high-mortality condition. The role of mechanical ventilation remains primarily a supportive modality. Recent research has elucidated the adverse impact of traditional ventilation strategies on development of the disease and, ultimately, mortality. The institution of low tidal volume ventilation has been the only intervention that has resulted in definitive improvement in survival. Animal and human investigations that culminated in the Acute Respiratory Distress Syndrome Network low tidal volume study are reviewed. Current controversies in the application of mechanical ventilation including the use of positive end-expiratory pressure, recruitment maneuvers, and high frequency oscillatory ventilation are also addressed.

Diagnosis and management of pneumonia in the intensive care unit.

Ventilator-associated pneumonia is a significant contributor to excess morbidity and mortality in the ICU. Alteration of physical defenses, bacterial flora, and immune response contribute to the susceptibility of the critically ill ventilated patient. Controversies regarding its definition continue to complicate the understanding of the extent of the disease and evaluation of the outcome of therapies. Traditional parameters, such as clinical suspicion with standard tracheal aspirates, are associated with overuse of antibiotics, a prime risk factor for development of resistant organisms and increased mortality. Global emergence of resistance is also a major concern. Whether invasive methods have any substantial clinical benefit either through improved patient outcomes or lower rates of resistance remains to be proved. In patients who fail to respond to therapy, a search for nonpulmonary infections and noninfectious causes of pulmonary infiltrates is essential. Finally, preventative measures offer additional areas of investigation that could favorably impact on the incidence of infection.