Shoulder pain, health-related quality of life and physical function in community-dwelling older adults.

The impact of shoulder pain on health-related quality of life and physical function among community-dwelling older adults (>60 years) not seeking medical care is not well understood. Forty-four community-dwelling older adult volunteers with low comorbidity were stratified into two groups by the presence (n = 18) or absence (n = 26) of shoulder pain. Participants completed the 36-Item Short Form and American Shoulder and Elbow Surgeon surveys and received shoulder range of motion and magnetic resonance imaging testing. Participants with shoulder pain perceived more difficulty accomplishing usual tasks secondary to their physical and emotion health and displayed inferior shoulder function, relative to participants without shoulder pain. This study suggests that shoulder pain reduces quality of life and physical function in the population of community-dwelling older adults not seeking medical evaluation for their symptoms.

Effect of Doxycycline on Progression of Arterial Calcification in the Noninvasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT).

BACKGROUND: Doxycycline has been shown to prevent arterial calcification via attenuation of matrix metalloproteinases (MMP) in preclinical models. We assessed the effects of doxycycline on progression of arterial calcification in patients enrolled in the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT). METHODS: Two hundred and sixty-one patients were randomized to 100 mg doxycycline twice daily or placebo. Arterial calcification was measured in abdominal vessels on noncontrast computed tomography scans. Patients with baseline computed tomography scan and 1 or more follow-up scans within the 2-year study were included for analysis. For individual arteries, mean change in iliofemoral artery calcification over time was calculated via linear regression. Serum MMP-3 and MMP-9 levels were measured at baseline and 6 months. RESULTS: Sixty-five patients in the doxycycline and 66 in the placebo arm were included in this analysis. Baseline characteristics between the groups were similar. The unadjusted mean change in iliofemoral calcium score per year trended toward higher values in patients treated with doxycycline compared with placebo (322 ± 399 units/year vs. 217 ± 307 units/year, P = 0.09). After 6 months, changes in serum MMP-3 and MMP-9 levels were not significantly different between study arms. CONCLUSIONS: In patients with small aortic aneurysm, treatment with doxycycline 100 mg twice daily did not decrease circulating levels of the matrix degrading enzymes MMP-3 and 9 or alter the progression of arterial calcification.

Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes for survivors of critical illness-The ExPrES study.

BACKGROUND: Neuromuscular electrical stimulation (NMES) with high protein supplementation (HPRO) to preserve muscle mass and function has not been assessed in ICU patients. We compared the effects of combining NMES and HPRO with mobility and strength rehabilitation (NMES+HPRO+PT) to standardized ICU care. OBJECTIVES: To assess the effectiveness of combined NMES+HPRO+PT in mitigating sarcopenia as evidenced by CT volume and cross-sectional area when compared to usual ICU care. Additionally, we assessed the effects of the combined therapy on select clinical outcomes, including nutritional status, nitrogen balance, delirium and days on mechanical ventilation. METHODS: Participants were randomized by computer generated assignments to receive either NMES+HPRO+PT or standard care. Over 14 days the standardized ICU care group (N = 23) received usual critical care and rehabilitation while the NMES+HPRO+PT group (N = 16) received 30 min neuromuscular electrical stimulation of quadriceps and dorsiflexors twice-daily for 10 days and mean 1.3 ± 0.4 g/kg body weight of high protein supplementation in addition to standard care. Nonresponsive participants received passive exercises and, once responsive, were encouraged to exercise actively. Primary outcome measures were muscle volume and cross-sectional area measured using CT-imaging. Secondary outcomes included nutritional status, nitrogen balance, delirium and days on mechanical ventilation. RESULTS: The NMES+HPRO+PT group (N = 16) lost less lower extremity muscle volume compared to the standard care group (N = 23) and had larger mean combined thigh cross-sectional area. The nitrogen balance remained negative in the standard care group, while positive on days 5, 9, and 14 in the NMES+HPRO+PT group. Standard care group participants experienced more delirium than the NMES+HPRO+PT group. No differences between groups when comparing length of stay or mechanical ventilation days. CONCLUSIONS: The combination of neuromuscular electrical stimulation, high protein supplementation and mobility and strength rehabilitation resulted in mitigation of lower extremity muscle loss and less delirium in mechanically ventilated ICU patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02509520. Registered July 28, 2015.

Predicting the likelihood of lower respiratory tract Ureaplasma infection in preterms.

OBJECTIVE: To develop predictive models of Ureaplasma spp lower airway tract infection in preterm infants. METHODS: A dataset was assembled from five cohorts of infants born <33 weeks gestational age (GA) enrolled over 17 years (1999-2016) with culture and/or PCR-confirmed tracheal aspirate Ureaplasma status in the first week of life (n=415). Seventeen demographic, obstetric and neonatal factors were analysed including admission white blood cell (WBC) counts. Best subset regression was used to develop three risk scores for lower airway Ureaplasma infection: (1) including admission laboratory values, (2) excluding admission laboratory values and (3) using only data known prenatally. RESULTS: GA and rupture of membranes >72 hours were significant predictors in all 3 models. When all variables including admission laboratory values were included in the regression, WBC count was also predictive in the resulting model. When laboratory values were excluded, delivery route was found to be an additional predictive factor. The area under the curve for the receiver operating characteristic indicated high predictive ability of each model to identify infants with lower airway Ureaplasma infection (range 0.73-0.77). CONCLUSION: We developed predictive models based on clinical and limited laboratory information available in the perinatal period that can distinguish between low risk (<10%) and high risk (>40%) of lower airway Ureaplasma infection. These may be useful in the design of phase III trials of therapeutic interventions to prevent Ureaplasma-mediated lung disease in preterm infants and in clinical management of at-risk infants.

Identification of Community-Dwelling Older Adults With Shoulder Dysfunction: A Pilot Study to Evaluate the Disabilities of the Arm, Shoulder and Hand Survey.

Introduction: The Disabilities of the Arm, Shoulder and Hand (DASH) survey estimates the upper limbs' dysfunction in one score, but limited evidence exists to justify use of DASH to screen older adults for shoulder dysfunction at routine health maintenance primary care visits. We sought (1) to determine if the DASH, American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) surveys are related to one another and (2) to determine the relationship of DASH, ASES and SST scores with 36-Item Short Form (SF-36) subscales, shoulder forward flexion range of motion (FF-ROM) and abduction (ABD-ROM) in older adults. Methods: Prospective pilot study of 23 community-dwelling adult volunteers [mean age (± standard deviation), 69.3 ± 6.7 years; range, 61-84 years, with no rotator cuff repair or joint replacement. Shoulder MRI, ROM testing, DASH, ASES, SST, SF-36, Katz activities of daily living (ADLs), and Lawton-Brody instrumental ADLs (IADLs) were completed at one time point. Descriptive and correlation analyses were performed. Results: Means: DASH, 17.4 ± 19.5; ASES, 81.3 ± 19.7; SST, 71.7 ± 28.5; Katz ADLs, 5.9 ± .3; Lawton-Brody IADLs, 8.0 ± .0; FF-ROM, 140.2° ± 31.5°; and ABD-ROM, 128.3° ± 31.9°. Nearly 48% had supraspinatus tendon tear. Correlation among DASH, ASES, and SST was strong (|rho ≥.88|; P < .001). DASH, ASES, and SST had strong correlation (|rho ≥.71|;P < .001) with shoulder FF-ROM and ABD-ROM. DASH had near equivalent or slightly stronger correlation for all SF-36 subscales relative to ASES and SST. DASH showed strong or moderate correlation (P < .05) to most SF-36 subscales. Conclusion: DASH, ASES and SST strongly correlated with one another. DASH, relative to ASES and SST, has similar correlation to shoulder FF-ROM, ABD-ROM and SF-36 subscales in older adults. Our pilot study suggests that the DASH survey has potential utility to identify occult shoulder dysfunction in community-dwelling older adults who have normal Katz ADLs and Lawton-Brody IADLs if administered during routine health maintenance primary care visits.

Role of volume in small abdominal aortic aneurysm surveillance.

OBJECTIVE: Current management of small abdominal aortic aneurysms (AAAs) primarily involves serial imaging surveillance of maximum transverse diameter (MTD) to estimate rupture risk. Other measurements, such as volume and tortuosity, are less well-studied and may help characterize and predict AAA progression. This study evaluated predictors of AAA volume growth and discusses the role of volume in clinical practice. METHODS: Subjects from the Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (baseline AAA MTD, 3.5-5.0 cm) with ≥2 computed tomography scans were included in this study (n = 250). Computed tomography scans were conducted approximately every 6 months over 2 years. MTD, volume, and tortuosity were used to model growth. Univariable and multivariable backwards elimination least squares regressions assessed associations with volume growth. RESULTS: Baseline MTD accounted for 43% of baseline volume variance (P < .0001). Mean volume growth rate was 10.4 cm3/year (standard deviation, 8.8 cm3/year) (mean volume change +10.4%). Baseline volume accounted for 30% of volume growth variance; MTD accounted for 13% of volume growth variance. More tortuous aneurysms at baseline had significantly larger volume growth rates (difference, 32.8 cm3/year; P < .0001). Univariable analysis identified angiotensin II receptor blocker use (difference, -3.4 cm3/year; P = .02) and history of diabetes mellitus (difference, -2.8 cm3/year; P = .04) to be associated with lower rates of volume growth. Baseline volume, tortuosity index, current tobacco use, and absence of diabetes mellitus remained significantly associated with volume growth in multivariable analysis. AAAs that reached the MTD threshold for repair had a wide range of volumes: 102 cm3 to 142 cm3 in female patients (n = 5) and 105 cm3 to 229 cm3 in male patients (n = 20). CONCLUSIONS: Baseline AAA volume and MTD were found to be moderately correlated. On average, AAA volume grows about 10% annually. Baseline volume, tortuosity, MTD, current tobacco use, angiotensin II receptor blocker use, and history of diabetes mellitus were predictive of volume growth over time.

Randomized trial of azithromycin to eradicate Ureaplasma respiratory colonization in preterm infants: 2-year outcomes.

BACKGROUND: To assess the potential impact of azithromycin treatment in the first week following birth on 2-year outcomes in preterm infants with and without Ureaplasma respiratory colonization who participated in a double-blind, placebo-controlled randomized controlled trial. METHODS: Respiratory morbidity was assessed at NICU discharge and at 6, 12, and 22-26 months corrected age using pulmonary questionnaires. Comprehensive neurodevelopmental assessments were completed between 22 and 26 months corrected age. The primary and secondary composite outcomes were death or severe respiratory morbidity and death or moderate-severe neurodevelopmental impairment, respectively, at 22-26 months corrected age. RESULTS: One hundred and twenty-one randomized participants (azithromycin, N = 60; placebo, N = 61) were included in the intent-to-treat analysis. There were no significant differences in death or serious respiratory morbidity (34.8 vs 30.4%, p = 0.67) or death or moderate-severe neurodevelopmental impairment (47 vs 33%, p = 0.11) between the azithromycin and placebo groups. Among all trial participants, tracheal aspirate Ureaplasma-positive infants experienced a higher frequency of death or serious respiratory morbidity at 22-26 months corrected age (58%) than tracheal aspirate Ureaplasma-negative infants (34%) or non-intubated infants (21%) (p = 0.028). CONCLUSIONS: We did not observe strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes in preterm infants treated with azithromycin in the first week of life compared to placebo. IMPACT: No strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes was identified at 22-26 months corrected age in infants treated with azithromycin in the first week of life compared to placebo. The RCT is the first study of 2-year pulmonary and neurodevelopmental outcomes of azithromycin treatment in ELGANs. Provides evidence that ELGANs with lower respiratory tract Ureaplasma have the most frequent serious respiratory morbidity in the first 2 years of life, suggesting that a Phase III trial of azithromycin to prevent BPD targeting this population is warranted.

Evaluating Growth Patterns of Abdominal Aortic Aneurysm Diameter With Serial Computed Tomography Surveillance.

Importance: Small abdominal aortic aneurysms (AAAs) are common in the elderly population. Their growth rates and patterns, which drive clinical surveillance, are widely disputed. Objective: To assess the growth patterns and rates of AAAs as documented on serial computed tomography (CT) scans. Design, Setting, and Participants: Cohort study and secondary analysis of the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT), a randomized, double-blind placebo-controlled clinical trial conducted from 2013 to 2018, with CT imaging every 6 months for 2 years. The trial was a multicenter, observational secondary analysis, not related to treatment hypotheses of data collected in the N-TA3CT. Participants included 254 patients with baseline AAA diameter between 3.5 and 5.0 cm. Exposures: Patients received serial CT scan measurements, analyzed for maximum transverse diameter, at 6-month intervals. Main Outcomes and Measures: The primary study outcome was AAA annual growth rate. Secondary analyses included characterizing AAA growth patterns, assessing likelihood of AAA diameter to exceed sex-specific intervention thresholds over 2 years. Results: A total of 254 patients, 35 women with baseline AAA diameter 3.5 to 4.5 cm and 219 men with baseline diameter 3.5 to 5.0 cm, were included. Yearly growth rates of AAA diameters were a median of 0.17 cm/y (interquartile range [IQR], 0.16) and a mean (SD), 0.19 (0.14) cm/y. Ten percent of AAAs displayed minimal to no growth (<0.05 cm/y), 62% displayed low growth (0.05-0.25 cm/y), and 28% displayed high growth (>0.25 cm/y). Baseline AAA diameter accounted for 5.4% of variance of growth rate (P < .001; R2, 0.054). Most AAAs displayed linear growth (70%); large variations in interval growth rates occurred infrequently (3% staccato growth and 4% exponential growth); and some patients' growth patterns were not clearly classifiable (23% indeterminate). No patients with a maximum transverse diameter less than 4.25 cm exceeded sex-specific repair thresholds at 2 years (men, 0 of 92; 95% CI, 0.00-0.055; women, 0 of 25 ; 95% CI, 0.00-0.247). Twenty-six percent of patients with a maximum transverse diameter of at least 4.25 cm exceeded sex-specific repair thresholds at 2 years (n = 12 of 83 men with diameter ranging from 4.25 to <4.75 cm; 95% CI, 0.091-0.264; n = 21 of 44 men with diameter ranging from 4.75-5.0 cm; 95% CI, 0.362-0.669; n = 3 of 10 women with diameter ≥4.25 cm; 95% CI, 0.093-0.726). Conclusions and Relevance: Most small AAAs showed linear growth; large intrapatient variations in interval growth rates were infrequently observed over 2 years. Linear growth modeling of AAAs in individual patients suggests smaller AAAs (<4.25 cm) can be followed up with a CT scan in at least 2 years with little chance of exceeding interventional thresholds. Trial Registration: ClinicalTrials.gov Identifier: NCT01756833.

Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants.

OBJECTIVE: To test whether azithromycin eradicates Ureaplasma from the respiratory tract in preterm infants. DESIGN: Prospective, phase IIb randomised, double-blind, placebo-controlled trial. SETTING: Seven level III-IV US, academic, neonatal intensive care units (NICUs). PATIENTS: Infants 240-286 weeks' gestation (stratified 240-266; 270-286 weeks) randomly assigned within 4 days following birth from July 2013 to August 2016. INTERVENTIONS: Intravenous azithromycin 20 mg/kg or an equal volume of D5W (placebo) every 24 hours for 3 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was Ureaplasma-free survival. Secondary outcomes were all-cause mortality, Ureaplasma clearance, physiological bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age, comorbidities of prematurity and duration of respiratory support. RESULTS: One hundred and twenty-one randomised participants (azithromycin: n=60; placebo: n=61) were included in the intent-to-treat analysis (mean gestational age 26.2±1.4 weeks). Forty-four of 121 participants (36%) were Ureaplasma positive (azithromycin: n=19; placebo: n=25). Ureaplasma-free survival was 55/60 (92% (95% CI 82% to 97%)) for azithromycin compared with 37/61 (61% (95% CI 48% to 73%)) for placebo. Mortality was similar comparing the two treatment groups (5/60 (8%) vs 6/61 (10%)). Azithromycin effectively eradicated Ureaplasma in all azithromycin-assigned colonised infants, but 21/25 (84%) Ureaplasma-colonised participants receiving placebo were culture positive at one or more follow-up timepoints. Most of the neonatal mortality and morbidity was concentrated in 21 infants with lower respiratory tract Ureaplasma colonisation. In a subgroup analysis, physiological BPD-free survival was 5/10 (50%) (95% CI 19% to 81%) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonisation versus 2/11 (18%) (95% CI 2% to 52%) in placebo-treated infants. CONCLUSION: A 3-day azithromycin regimen effectively eradicated respiratory tract Ureaplasma colonisation in this study. TRIAL REGISTRATION NUMBER: NCT01778634.

A Survey of Academic Intensivists' Use of Neuromuscular Blockade in Subjects With ARDS.

BACKGROUND: Our Cooling to Help Injured Lungs (CHILL) trial of therapeutic hypothermia in ARDS includes neuromuscular blockade (NMB) as an inclusion criterion to avoid shivering. NMB has been used to facilitate mechanical ventilation in ARDS and was shown to reduce mortality in the ACURASYS trial. To assess the feasibility of a multi-center CHILL trial, we conducted a survey of academic intensivists about their NMB use in patients with ARDS. METHODS: We distributed via email a 16-question survey about NMB use in patients with ARDS including frequency, indications, and dosing strategy. RESULTS: 212 (24.3%) of 871 respondents completed the survey: 94.7% were board-certified in internal medicine, 88% in pulmonary and critical care; 90.3% practiced in academic medical centers, with 87% working in medical ICUs; 96.6% of respondents who treat ARDS use NMB, and 39.7% use NMB in ≥ 50% of these patients. Of 4 listed indications for initiating NMB in ARDS, allowing adherence with lung-protective ventilator strategies and patient-ventilator synchrony were cited as the most important reasons, followed by the results of the ACURASYS trial and facilitating prone positioning. CONCLUSIONS: We conclude that NMB is frequently used by academic intensivists to facilitate mechanical ventilation in patients with moderate to severe ARDS.

Asymptomatic carotid stenosis is associated with mobility and cognitive dysfunction and heightens falls in older adults.

BACKGROUND: Atherosclerosis of the carotid bifurcation with plaque formation causes asymptomatic carotid artery stenosis (ACAS), which may also be associated with cerebral hypoperfusion. Cerebral hypoperfusion adversely affects multiple aspects of mobility and cognition. This study tests the hypothesis that community-dwelling older adults with a 50% or greater diameter-reducing ACAS will have mobility and cognitive impairments that heighten their risk for falls. METHODS: Eighty community-dwelling adults completed a mobility assessment (Short Physical Performance Battery, Berg Balance Scale, Four Square Step Test, Dynamic Gait Index, Timed Up and Go, and gait speed), self-reported physical function (Activities-Specific Balance Confidence, SF-12 Physical Function Component), and cognitive tests (Mini-Mental State Examination). Falls were recorded for the past 6 months. Standardized carotid ultrasound examination classified participants into no stenosis (<50% diameter reduction) (n = 54), moderate stenosis (50%-69%) (n = 17), and high-grade stenosis (70%-99%) (n = 9) groups. Linear and logistic regression analyses determined the associations between these measures and the degree of stenosis (three groups). RESULTS: Logistic regression analysis showed their degree of stenosis was associated with reductions in mobility (Short Physical Performance Battery [P = .008], Berg Balance Scale [P = .0008], Four Square Step Test [P = .005], DGI [P = .0001], TUG [P = .0004], gait speed [P = .02]), perceived physical function (ABC [P < .0001], SF-12 Physical Function Component [P < .0001]), and cognition (MMSE [P = .003]). Adults with moderate- and high-grade stenosis had a greater incidence of falls compared with those without stenosis (relative risk, 2.86; P = .01). Results remained unchanged after adjustment for age, sex and cardiovascular risk factors. CONCLUSIONS: ACAS is associated with impaired mobility and cognition that are accompanied with increased fall risk. These impairments increased with worsening severity.

An mHealth Diabetes Intervention for Glucose Control: Health Care Utilization Analysis.

BACKGROUND: Type 2 diabetes (T2D) is a major chronic condition requiring management through lifestyle changes and recommended health service visits. Mobile health (mHealth) is a promising tool to encourage self-management, but few studies have investigated the impact of mHealth on health care utilization. OBJECTIVE: The objective of this analysis was to determine the change in 2-year health service utilization and whether utilization explained a 1.9% absolute decrease in glycated hemoglobin (HbA1c) over 1-year in the Mobile Diabetes Intervention Study (MDIS). METHODS: We used commercial claims data from 2006 to 2010 linked to enrolled patients' medical chart data in 26 primary care practices in Maryland, USA. Secondary claims data analyses were available for 56% (92/163) of participants. In the primary MDIS study, physician practices were recruited and randomized to usual care and 1 of 3 increasingly complex interventions. Patients followed physician randomization assignment. The main variables in the analysis included health service utilization by type of service and change in HbA1c. The claims data was aggregated into 12 categories of utilization to assess change in 2-year health service usage, comparing rates of usage pre- and posttrial. We also examined whether utilization explained the 1.9% decrease in HbA1c over 1 year in the MDIS cluster randomized clinical trial. RESULTS: A significant group by time effect was observed in physician office visits, general practitioner visits, other outpatient services, prescription medications, and podiatrist visits. Physician office visits (P=.01) and general practitioner visits (P=.02) both decreased for all intervention groups during the study period, whereas prescription claims (P<.001) increased. The frequency of other outpatient services (P=.001) and podiatrist visits (P=.04) decreased for the control group and least complex intervention group but increased for the 2 most complex intervention groups. No significant effects of utilization were observed to explain the clinically significant change in HbA1c. CONCLUSIONS: Claims data analyses identified patterns of utilization relevant to mHealth interventions. Findings may encourage patients and health providers to discuss the utilization of treatment-recommended services, lab tests, and prescribed medications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01107015; https://clinicaltrials.gov/ct2/show/NCT01107015 (Archived by Webcite at http://www.webcitation.org/72XgTaxIj).

A multimodal rehabilitation program for patients with ICU acquired weakness improves ventilator weaning and discharge home.

PURPOSE: To compare the effects of adding a progressive multimodal rehabilitation program to usual care (MRP + UC) versus UC alone on 1) functional mobility, strength, endurance and 2) ventilator weaning and discharge status of patients with ICU-acquired weakness (ICUAW) receiving prolonged mechanical ventilation (PMV). METHODS: Randomized pilot trial of an individualized MRP + UC versus UC in middle-aged and older ICU survivors with ICUAW receiving PMV. Outcomes compare changes in strength, mobility, weaning success and discharge home from a long-term acute care hospital (LTACH) between the groups. RESULTS: Eighteen males and 14 females (age 60.3 ±â€¯11.9 years) who received PMV for ≥14 days were enrolled. Despite no significant differences between groups in the changes in handgrip, gait speed, short physical performance battery or 6-min walk distance after treatment, the MRP + UC group had greater weaning success (87% vs. 41%, p < 0.01), and more patients discharged home than UC (53 vs. 12%, p = 0.05). Post hoc analyses, combining patients based on successful weaning or discharge home, demonstrated significant improvements in strength, ambulation and mobility. CONCLUSION: The addition of an MRP that improves strength, physical function and mobility to usual physical therapy in LTACH patients with ICUAW is associated with greater weaning success and discharge home than UC alone.

The Impact of a Mobile Diabetes Health Intervention on Diabetes Distress and Depression Among Adults: Secondary Analysis of a Cluster Randomized Controlled Trial.

BACKGROUND: Diabetes is a complex, demanding disease that requires the constant attention of patients. The burden of self-management, including different medication regimens, routine self-care activities, and provider visits, has an impact on patients' emotional well-being. Diabetes distress and depression are two important components of emotional well-being that may negatively affect diabetes outcomes. OBJECTIVE: The aim was to determine the impact of the 1-year Mobile Diabetes Intervention Study cluster randomized clinical trial on emotional well-being measured by diabetes distress and depression among adults with type 2 diabetes (T2D). METHODS: A total of 163 adults with not-well-managed T2D were enrolled from community primary care practices. Primary care practices were cluster randomized into either a usual care control group or intervention group. Intervention participants were given a mobile phone with coaching software including a Web portal to communicate with providers. A priori established secondary outcomes included distress measured by the Diabetes Distress Scale (DDS), with subscales measuring emotional burden, interpersonal distress, physician-related distress, and regimen-related distress, as well as depression measured by the Patient Health Questionnaire (PHQ-9). Linear mixed models were used to calculate the effect of the intervention on diabetes distress levels over time, both overall and separately by sex, and to determine if the intervention affected distress or depression. The impact of total DDS on changes in HbA1c was also studied. RESULTS: There were no significant treatment group effects for DDS total (baseline: P=.07; differences over time: P=.38) or for depression (P=.06 over time). Significant declines in total DDS were observed over the 12-month intervention period (P=.01). Regimen-related distress significantly decreased for all study participants (P<.001), but no significant change over time was observed for emotional burden (P=.83), interpersonal distress (P=.64), or physician-related distress (P=.73). Women in both the usual care and intervention groups were more likely to have higher overall DDS, emotional burden, physician-related distress, and regimen-related distress, but not interpersonal distress. Women also reported higher baseline depression compared to men (P=.006). Overall, depression decreased over the treatment period (P=.007), but remained unaffected by group assignment (P=.06) or by sex (P=.97). Diabetes distress had no effect on the change in HbA1c (P=.91) over the treatment period. CONCLUSIONS: Although we found no definitive overall or sex-specific effect of the intervention on diabetes distress or depression, this study makes an important contribution to the understanding of mobile health interventions and the impact on emotional health. Our study verified previous work that although diabetes distress and depression are highly correlated, these measures are not evaluating the same construct. Design of future mobile technology provides an opportunity to personalize, contextualize, and intervene in the emotional well-being of persons with diabetes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01107015; https://clinicaltrials.gov/ct2/show/NCT01107015 (Archived by WebCite at http://www.webcitation.org/6vVgRCLAF).

Pilot Feasibility Study of Therapeutic Hypothermia for Moderate to Severe Acute Respiratory Distress Syndrome.

OBJECTIVES: Prior studies suggest hypothermia may be beneficial in acute respiratory distress syndrome, but cooling causes shivering and increases metabolism. The objective of this study was to assess the feasibility of performing a randomized clinical trial of hypothermia in patients with acute respiratory distress syndrome receiving treatment with neuromuscular blockade because they cannot shiver. DESIGN: Retrospective study and pilot, prospective, open-label, feasibility study. SETTING: Medical ICU. PATIENTS: Retrospective review of 58 patients with acute respiratory distress syndrome based on Berlin criteria and PaO2/FIO2 less than 150 who received neuromuscular blockade. Prospective hypothermia treatment in eight acute respiratory distress syndrome patients with PaO2/FIO2 less than 150 receiving neuromuscular blockade. INTERVENTION: Cooling to 34-36°C for 48 hours. MEASUREMENTS AND MAIN RESULTS: Core temperature, hemodynamics, serum glucose and electrolytes, and P/F were sequentially measured, and medians (interquartile ranges) presented, 28-day ventilator-free days, and hospital mortality were calculated in historical controls and eight cooled patients. Average patient core temperature was 36.7°C (36-37.3°C), and fever occurred during neuromuscular blockade in 30 of 58 retrospective patients. In the prospectively cooled patients, core temperature reached target range less than or equal to 4 hours of initiating cooling, remained less than 36°C for 92% of the 48 hours cooling period without adverse events, and was lower than the controls (34.35°C [34-34.8°C]; p < 0.0001). Compared with historical controls, the cooled patients tended to have lower hospital mortality (75% vs 53.4%; p = 0.26), more ventilator-free days (9 [0-21.5] vs 0 [0-12]; p = 0.16), and higher day 3 P/F (255 [160-270] vs 171 [120-214]; p = 0.024). CONCLUSIONS: Neuromuscular blockade alone does not cause hypothermia but allowed acute respiratory distress syndrome patients to be effectively cooled. Results support conducting a randomized clinical trial of hypothermia in acute respiratory distress syndrome and the feasibility of studying acute respiratory distress syndrome patients receiving neuromuscular blockade.

Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT): Design of a Phase IIb, placebo-controlled, double-blind, randomized clinical trial of doxycycline for the reduction of growth of small abdominal aortic aneurysm.

OBJECTIVES: The Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT) is a Phase IIb randomized, placebo-controlled clinical trial, testing doxycycline (100mg bid) for inhibition of growth in the greatest transverse, orthogonal diameter of small abdominal aortic aneurysms (AAA). METHODS: We will enroll 258 patients, ≥55years of age who have AAA, men: 3.5-5.0cm and women: 3.5-4.5cm on CT scans confirmed centrally. The primary outcome is growth in maximal transverse, orthogonal diameter from baseline to 24-month follow-up. Secondary analyses address doxycycline effects on clinical events, aneurysm volume, and biomarkers. Primary analysis will be performed according to the principle of intention-to-treat accounting for death and ruptures by use of normal scores in analysis of covariance. At the time of the data file reported, 200 subjects have been randomized. We started enrollment in mid-2013 and will complete enrollment by mid-2016. RESULTS: Participant average age=70.9years, (SD=7.6years) and maximum transverse diameter=4.3cm for men (SD=0.4) and 4.0cm for women (SD=0.3). CONCLUSION: N-TA(3)CT is a critical experiment to determine whether doxycycline reduces growth of small AAA and systemic markers of inflammation previously seen in bench experiments and observational human studies to be associated with AAA growth. Our patient population baseline measurements agree with the design assumptions supporting our expectation of 90% power or greater to reject a null hypothesis in favor of an alternative hypothesis when growth is reduced by at least 40%. REGISTRATION: clinicaltrials.gov #NCT01756833.

Mobile Diabetes Intervention for Glycemic Control in 45- to 64-Year-Old Persons With Type 2 Diabetes.

The purpose of this study was to assess effects of a mobile coaching system on glycated hemoglobin (HbA1c) levels in younger versus older patients over 1 year. Participants (n = 118) included adult patients with Type 2 diabetes cared for by community physicians. Intervention patients received mobile phone coaching and individualized web portal. Control patients received usual care. Patients were stratified into two age groups: younger (<55 years) and older (≥ 55 years). The intervention resulted in greater 12-month declines in HbA1c, compared with usual care, for patients in both age groups (p < .0001). Among older patients, HbA1c changed by -1.8% (95% confidence interval [CI] = [-2.4, -1.1]) in the intervention group and -0.3% (95% CI = [-0.9, +0.3]) in the control group. Among younger patients, HbA1c changed by -2.0% (95% CI = [-2.5, -1.5]) in the intervention group and -1.0% (95% CI = [-1.6, -0.4]) in the control group. The mobile health intervention was as effective at managing Type 2 diabetes in older adults as younger persons.

Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization.

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg(0.75), 1.88 liters · kg, 1.79 liters/h · kg(0.75), and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼ 4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating Ureaplasma spp. from the preterm respiratory tract.