Hospital Consultation From Outpatient Clinicians for Medically Complex Children: A Randomized Clinical Trial.

Importance: Children with medical complexity (CMC) frequently experience fragmented care. We have demonstrated that outpatient comprehensive care (CC) reduces serious illnesses, hospitalizations, and costs for high-risk CMC. Yet continuity of care for CMC is often disrupted with emergency department (ED) visits and hospitalizations. Objective: To evaluate a hospital consultation (HC) service for CMC from their outpatient CC clinicians. Design, Setting, and Participants: Randomized quality improvement trial at the University of Texas Health Science Center at Houston with an outpatient CC clinic and tertiary pediatric hospital (Children's Memorial Hermann Hospital). Participants included high-risk CMC (≥2 hospitalizations or ≥1 pediatric intensive care unit [PICU] admission in the year before enrolling in our clinic) receiving CC. Data were analyzed between January 11, 2018, and December 20, 2019. Interventions: The HC included serial discussions between CC clinicians, ED physicians, and hospitalists addressing need for admission, inpatient treatment, and transition back to outpatient care. Usual hospital care (UHC) involved routine pediatric hospitalist care. Main Outcomes and Measures: Total hospital days (primary outcome), PICU days, hospitalizations, and health system costs in skeptical bayesian analyses (using a prior probability assuming no benefit). Results: From October 3, 2016, through October 2, 2017, 342 CMC were randomized to either HC (n = 167) or UHC (n = 175) before meeting the predefined bayesian stopping guideline (>80% probability of reduced hospital days). In intention-to-treat analyses, the probability that HC reduced total hospital days was 91% (2.72 vs 6.01 per child-year; bayesian rate ratio [RR], 0.61; 95% credible interval [CrI], 0.30-1.26). The probability of a reduction with HC vs UHC was 98% for hospitalizations (0.60 vs 0.93 per child-year; RR, 0.68; 95% CrI, 0.48-0.97), 89% for PICU days (0.77 vs 1.89 per child-year; RR, 0.59; 95% CrI, 0.26-1.38), and 94% for mean total health system costs ($24 928 vs $42 276 per child-year; cost ratio, 0.67; 95% CrI, 0.41-1.10). In secondary analysis using a bayesian prior centered at RR of 0.78, reflecting the opinion of 7 experts knowledgeable about CMC, the probability that HC reduced hospital days was 96%. Conclusions and Relevance: Among CMC receiving comprehensive outpatient care, an HC service from outpatient clinicians likely reduced total hospital days, hospitalizations, PICU days, other outcomes, and health system costs. Additional trials of an HC service from outpatient CC clinicians are needed for CMC in other centers. Trial Registration: ClinicalTrials.gov Identifier: NCT02870387.

Unexpected results of a randomized quality improvement program for children with severe asthma.

Objective: To assess whether an asthma intervention program reduces treatment days outside the home among children with severe asthma receiving comprehensive care (CC) in our center.Methods: Between October 21, 2014 and September 28, 2016, children with severe asthma were randomized to receive CC alone (n = 29) or CC plus the asthma intervention program (n = 34) which involved collaboration with pharmacists and school nurses, motivational interviewing, and tracking the one-second forced expiratory volume at home. All patients were followed through March 31, 2017. Frequentist and Bayesian intent-to-treat analyses were performed.Results: The asthma intervention program doubled the telephone calls between the staff and families (753 vs 356 per 100 child years for the intervention group vs. control group; Rate Ratio [RR], 2.11 [95% confidence interval, 1.29-3.45]). Yet, we found no evidence that it reduced the composite number of days of healthcare outside home which includes: clinic visits, ED visits, and hospital admissions (1179 vs 958 per 100 child-years in the intervention group vs. control group; [RR], 1.23 [95% CI, 0.82-1.84]) or secondary outcomes which are individual components (clinic visits, ED visits, hospitalizations, PICU admissions and school absences; RR 1.15 - 2.30; p > 0.05). Bayesian analysis indicated a 67% probability that the intervention program increases total treatment days outside the home and only a 14% probability of a true decrease of >20% as originally hypothesized.Conclusion: A multi-component intervention program provided to children with severe asthma failed to reduce and may have increased days of healthcare outside home and school absenteeism.

Post-Trial Sustainability and Scalability of the Benefits of a Medical Home for High-Risk Children with Medical Complexity.

OBJECTIVE: To assess the sustainability of the benefits relative to usual care of a medical home providing comprehensive care for high-risk children with medical complexity (≥2 hospitalizations or ≥1 pediatric intensive care unit [PICU] admission in the year before enrollment) after we made comprehensive care our standard practice and expanded the program. STUDY DESIGN: We conducted pre-post comparisons of the rate of children with serious illness (death, PICU admission, or >7-day hospitalization) and health-system costs observed after program expansion (March 2014-June 2015) to those during the clinical trial (March 2011-August 2013) for each of the trial's treatment groups (usual care, n = 96, and comprehensive care, n = 105; primary analyses), and among all children given comprehensive care (nPost-trial = 233, including trial usual care children who transitioned to comprehensive care post-trial and newly enrolled medically complex children, and nTrial = 105; secondary analyses). We also analyzed the findings for the trial patients as a 2-phase stepped-wedge study. RESULTS: In intent-to-treat analyses, rates of children with serious illness and costs were reduced or unchanged post-trial vs trial for the trial's usual care group (rate ratio [RR], 0.36; 95% CI, 0.20-0.64; cost ratio [CR], 0.68; 95% CI, 0.28-1.68), the trial's comprehensive care group (RR, 0.74; 95% CI, 0.39-1.41; CR, 0.67; 95% CI, 0.51-0.89), and among all children given comprehensive care (RR, 0.97; 95% CI, 0.61-1.52; CR, 0.75; 95% CI, 0.61-0.93). Conservative stepped-wedge analyses identified overall benefits with comprehensive care across both study periods (RR, 0.46; 95% CI, 0.30-0.72; CR, 0.64; 95% CI, 0.43-0.99). CONCLUSIONS: Major benefits of comprehensive care did not diminish with post-trial program expansion.

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of morbidity and mortality in vulnerable populations. Macrolides have received considerable attention for their anti-inflammatory actions beyond their antibacterial effect. We hypothesize that prophylactic azithromycin will be effective in reducing the severity of RSV infection in a mouse model. METHODS: Four groups of BALB/c mice were studied for 8 days: Control (C), RSV-infected (R), early prophylaxis with daily azithromycin from days 1 to 8, (E), and late prophylaxis with daily azithromycin from days 4 to 8 (L). Mice were infected with RSV on day 4, except for the control group. All groups were followed for a total of 8 days when bronchoalveolar lavage cell count and cytokines levels were measured. Mouse weight, histopathology, and mortality data were obtained. RESULTS: Prophylactic azithromycin significantly attenuated post-viral weight loss between group R and both groups E and L (P = 0.0236, 0.0179, respectively). IL-6, IL-5, and Interferon-Gamma were significantly lower in group L (P = 0.0294, 0.0131, and 0.0056, respectively) compared with group R. The total cell count was significantly lower for group L as compared with group R (P < 0.05). Mortality was only observed in group R (8%). Lung histology in the prophylactic groups showed diminished inflammatory infiltrates and cellularity when compared with group R. CONCLUSION: Prophylactic azithromycin effectively reduced weight loss, airway inflammation, cytokine levels and mortality in RSV-infected mice. These results support the rationale for future clinical trials to evaluate the effects of prophylactic azithromycin for RSV infection.

Use of Nasal Non-Invasive Ventilation with a RAM Cannula in the Outpatient Home Setting.

BACKGROUND: Nasal non-invasive-ventilation (Nasal NIV) is a mode of ventilatory support providing positive pressure to patients via a nasal interface. The RAM Cannula is an oxygen delivery device that can be used as an alternative approach to deliver positive pressure. Together they have been successfully used to provide respiratory support in neonatal in-patient settings. OBJECTIVE: To describe the outpatient use of Nasal NIV/RAM Cannula as a feasible alternative for home respiratory support in children with chronic respiratory failure. METHODS: We performed a retrospective case series of 18 children (4 months to 19 years old) using the Nasal NIV/RAM Cannula in the Pediatric Pulmonary Clinic at the McGovern Medical School, UTHealth (2014-16). Consideration for Nasal NIV/RAM Cannula utilization included: inability to wean-off in-patient respiratory support, comfort for dyspnea, intolerability of conventional mask interfaces and tracheostomy avoidance. RESULTS: Average age was 7 years. 50% were Caucasian, 38% African-American and 11% Hispanics. Pulmonary disorders included: chest wall weakness (38%), central control abnormalities (33%), obstructive lung disease (16%) and restrictive lung disease (11%). Indications for Nasal NIV/RAM Cannula initiation included: CPAP/BPAP masks intolerability (11%), dyspnea secondary to chest wall weakness (38%) and tracheostomy avoidance (50%). Average length of use of Nasal NIV/RAM Cannula was 8.4 months. Successful implementation of Nasal NIV/Ram Cannula was 94%. One patient required a tracheostomy following the use of Nasal NIV/RAM Cannula. Significant decrease in arterial PaCO2 pre and post Nasal NIV/RAM cannula initiation was notable (p=0.001). CONCLUSION: Outpatient use of Nasal NIV/RAM Cannula may prove to be a feasible and save treatment alternative for children with chronic respiratory failure, chest wall weakness, dyspnea and traditional nasal/face mask intolerance to avoid tracheostomy.

Effect of an enhanced medical home on serious illness and cost of care among high-risk children with chronic illness: a randomized clinical trial.

IMPORTANCE: Patient-centered medical homes have not been shown to reduce adverse outcomes or costs in adults or children with chronic illness. OBJECTIVE: To assess whether an enhanced medical home providing comprehensive care prevents serious illness (death, intensive care unit [ICU] admission, or hospital stay >7 days) and/or reduces costs among children with chronic illness. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of high-risk children with chronic illness (≥3 emergency department visits, ≥2 hospitalizations, or ≥1 pediatric ICU admissions during previous year, and >50% estimated risk for hospitalization) treated at a high-risk clinic at the University of Texas, Houston, and randomized to comprehensive care (n = 105) or usual care (n = 96). Enrollment was between March 2011 and February 2013 (when predefined stopping rules for benefit were met) and outcome evaluations continued through August 31, 2013. INTERVENTIONS: Comprehensive care included treatment from primary care clinicians and specialists in the same clinic with multiple features to promote prompt effective care. Usual care was provided locally in private offices or faculty-supervised clinics without modification. MAIN OUTCOMES AND MEASURES: Primary outcome: children with a serious illness (death, ICU admission, or hospital stay >7 days), costs (health system perspective). Secondary outcomes: individual serious illnesses, medical services, Medicaid payments, and medical school revenues and costs. RESULTS: In an intent-to-treat analysis, comprehensive care decreased both the rate of children with a serious illness (10 per 100 child-years vs 22 for usual care; rate ratio [RR], 0.45 [95% CI, 0.28-0.73]), and total hospital and clinic costs ($16,523 vs $26,781 per child-year, respectively; cost ratio, 0.58 [95% CI, 0.38-0.88]). In analyses of net monetary benefit, the probability that comprehensive care was cost neutral or cost saving was 97%. Comprehensive care reduced (per 100 child-years) serious illnesses (16 vs 44 for usual care; RR, 0.33 [95% CI, 0.17-0.66]), emergency department visits (90 vs 190; RR, 0.48 [95% CI, 0.34-0.67]), hospitalizations (69 vs 131; RR, 0.51 [95% CI, 0.33-0.77]), pediatric ICU admissions (9 vs 26; RR, 0.35 [95% CI, 0.18-0.70]), and number of days in a hospital (276 vs 635; RR, 0.36 [95% CI, 0.19-0.67]). Medicaid payments were reduced by $6243 (95% CI, $1302-$11,678) per child-year. Medical school losses (costs minus revenues) increased by $6018 (95% CI, $5506-$6629) per child-year. CONCLUSIONS AND RELEVANCE: Among high-risk children with chronic illness, an enhanced medical home that provided comprehensive care to promote prompt effective care vs usual care reduced serious illnesses and costs. These findings from a single site of selected patients with a limited number of clinicians require study in larger, broader populations before conclusions about generalizability to other settings can be reached. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02128776.

Functional and immune response to respiratory syncytial virus infection in aged BALB/c mice: a search for genes determining disease severity.

BACKGROUND: Recent studies have demonstrated that respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in the elderly. The cellular mechanisms that determine the host's susceptibility and severity of the disease are not well understood. In this study, we sought a mouse model of human respiratory disease by studying the functional and cellular response to RSV in aged animals. METHODS: Aged BALB/c mice (>10 months of age) were infected with human RSV (strain A2) and compared with sham-infected mice. Clinical progress of the illness was monitored by daily assessment of weight changes and mortality. The animals were sacrificed four days postinfection. Lung pathology was obtained and viral titers were measured by plaque assay. Gene expression profiles were studied from lung tissue RNA using gene array. RESULTS: RSV produced significant clinical illness in aged mice as evidenced by a 15% weight loss and a 10% mortality rate. Lung pathology revealed inflammatory changes with a predominance of neutrophils and diffuse alveolar damage. Microarray analysis revealed variable profiles of gene activation/downregulation at day 4 postinfection. RSV infection resulted in a proinflammatory response. Surprisingly, some of the genes involved in antigen-processing pathway were downregulated, specifically, genes implicated in the major histocompatibility complex (MHC) class II pathway. CONCLUSIONS: Our findings indicate that RSV infection produces profound functional and cellular changes in aged mice thus resembling the human disease described in the elderly. Further studies will be needed to understand the cellular mechanisms involved in the host response to RSV in aged mice.

Decreased exhaled nitric oxide levels in patients with mitochondrial disorders.

BACKGROUND: Nitric oxide (NO) deficiency may occur in mitochondrial disorders (MD) and can contribute to the pathogenesis of the disease. It is difficult and invasive to measure systemic nitric oxide. NO is formed in the lungs and can be detected in expired air. Currently, hand-held fractional exhaled nitric oxide (FeNO) measurement devices are available enabling a fast in-office analysis of this non-invasive test. It was postulated that FeNO levels might be reduced in MD. METHODS: Sixteen subjects with definite MD by modified Walker criteria (4 to 30 years of age) and sixteen healthy control subjects of similar age, race and body mass index (BMI) underwent measurement of FeNO in accordance with the American Thoracic Society guidelines. RESULTS: Sixteen patient-control pairs were recruited. The median FeNO level was 6.5 ppm (IQR: 4-9.5) and 10.5 ppm (IQR: 8-20.5) in the MD and control groups, respectively. In 13 pairs (81%), the FeNO levels were lower in the MD cases than in the matched controls (p=0.021). Eleven (69%) cases had very low FeNO levels (≤7ppm) compared to only 1 control (p=0.001). All cases with enzymatic deficiencies in complex I had FeNO ≤7ppm. CONCLUSIONS: Single-breath exhaled nitric oxide recordings were decreased in patients with MD. This pilot study suggests that hand-held FeNO measurements could be an attractive non-invasive indicator of MD. In addition, measurement of FeNO could be used as a parameter to monitor therapeutic response in this population.