Improvement of the rapid response system at an acute rehabilitation hospital in New Mexico.

Aim: Enhance the Rapid Response System (RRS) in a free-standing acute rehabilitation hospital (ARH) by improving announcements, crash cart standardization and role assignments. Materials & methods: Pre-intervention (PreIQ) and post-intervention questionnaires (PostIQ), conducted in English and utilizing a Likert scale, were distributed in-person to clinical staff, yielding a 100% response rate. The questionnaire underwent no prior testing. The PreIQ were disseminated in February 2021, and PostIQ in December 2022. Results: PostIQ illustrated the improvement of audibility and improved the clarity of roles. The training positively impacted the RRS in the ARH. Conclusion: This study highlights the value of continuous RRS improvement in ARHs. Interventions led to notable enhancements, emphasizing the need for sustained efforts and future research on broader implementation.

Cross-Reactive Polyclonal Antibodies Raised Against GalNAc-Conjugated siRNA Recognize Mostly the GalNAc Moiety.

Small interfering RNA (siRNA) is gaining momentum as a therapeutic modality with six approved products. Since siRNA has the potential to elicit undesired immune responses in patients, immunogenicity assessment is required during clinical development by regulatory authorities. In this study, anti-siRNA polyclonal antibodies were generated through animal immunization. These cross-reactive polyclonal antibodies recognized mostly the N-acetylgalactosamine (GalNAc) moiety with a small fraction against sequence-independent epitopes. We demonstrate that the polyclonal antibodies can be utilized as immunogenicity assay positive controls for the same class of GalNAc-conjugated siRNAs. In addition, anti-GalNAc mAbs showed desired sensitivity and drug tolerance, supporting their use as alternative surrogate positive controls. These findings can guide positive control selection and immunogenicity assay development for GalNAc-conjugated siRNAs and other oligonucleotide therapeutics.

The Association of Anticoagulation Intensity with Outcomes in Hospitalized COVID-19 Patients.

Venous thromboembolism (VTE) risk is increased in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A key question was whether increased intensity of anticoagulation would help prevent VTE and improve patient outcomes, including transfer to the intensive care unit (ICU) and mortality. At the start of the coronavirus disease-19 (COVID-19) pandemic, our institution, Boston Medical Center, instituted a VTE risk stratification protocol based on patients' initial D-dimer levels, medical history, and presence of thrombosis to determine whether they should receive standard-dose prophylaxis, high-dose prophylaxis, or therapeutic anticoagulation. We performed a retrospective observational cohort study examining the association of degree of anticoagulation with outcomes in 915 hospitalized COVID-19 patients hospitalized initially on the general inpatient wards between March 1,, 2020, and June 1, 2020. Patients directly hospitalized in the ICU were excluded. Most, 813 patients (89%), in our cohort were on standard-dose prophylaxis; 32 patients (3.5%) received high-dose prophylaxis; 70 patients (7.7%), were treated with therapeutic anticoagulation. VTE occurred in 45 patients (4.9%), and the overall in-hospital mortality rate was 5.4% (49 deaths). On multivariable analysis of clinical outcomes in relation to type of anticoagulation, in the high-dose prophylaxis group, there was a trend towards increased in-hospital mortality (odds ratio 2.4 (0.8-7.5, 95% CI)) and increased ICU transfer (odds ratio 2.2 (0.9-5.7, 95% CI)). Our results suggest that patients receiving high-dose prophylaxis had more severe disease that was not mitigated by intermediate-dose anticoagulation.

Prevalence and correlates of self-reported access to a gun among students at 24 postsecondary institutions by sex and gender identity.

OBJECTIVE: Estimate prevalence and identify correlates of self-reported access to a gun among college students. PARTICIPANTS: Degree seeking students never serving in the military at 24 postsecondary institutions participating in ACHA-NCHA III during spring of 2020 and 2021 (N = 17,293) stratified by ciswomen, cismen, and transgender/gender nonconforming. METHODS: Independent variables included measures of individual-level risk behaviors and experiences including interpersonal violence, mental health issues, and current and lifetime substance use. Individual-level demographics, indicators of institutional affiliation, and institutional characteristics used as controls. Descriptive statistics, chi-square tests of independence, and adjusted odds ratios are reported. RESULTS: About 14% (n = 2,349) of sample self-reported access. Students' involvement with multiple different risk behaviors and experiences increased the odds of access. CONCLUSIONS: Access is a prerequisite to firearm use and resulting on-campus assaults, suicides, and homicides. Additional research on access prevalence, location and type of firearm being accessed, and the correlates of access is needed.

Multiplexed Capillary-Flow Driven Immunoassay for Respiratory Illnesses.

Multiplexed analysis in medical diagnostics is widely accepted as a more thorough and complete method compared to single-analyte detection. While analytical methods like polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) exist for multiplexed detection of biomarkers, they remain time-consuming and expensive. Lateral flow assays (LFAs) are an attractive option for point-of-care testing, and examples of multiplexed LFAs exist. However, these devices are limited by spatial resolution of test lines, large sample volume requirements, cross-reactivity, and poor sensitivity. Recent work has developed capillary-flow microfluidic ELISA platforms as a more sensitive alternative to LFAs; however, multiplexed detection on these types of devices has yet to be demonstrated. In the aftermath of the initial SARS-CoV-2 pandemic, the need for rapid, sensitive point-of-care devices has become ever clearer. Moving forward, devices that can distinguish between diseases with similar presenting symptoms would be the ideal home diagnostic. Here, the first example of a multiplexed capillary-flow immunoassay device for the simultaneous detection of multiple biomarkers is reported. From a single sample addition step, the reagents and washing steps required for two simultaneous ELISAs are delivered to spatially separated test strips. Visual results can be obtained in <15 min, and images captured with a smartphone can be analyzed for quantitative data. This device was used to distinguish between and quantify H1N1 hemagglutinin (HA) and SARS-CoV-2 nucleocapsid protein (N-protein). Using this device, analytical detection limits of 840 and 133 pg/mL were obtained for hemagglutinin and nucleocapsid protein, respectively. The presence of one target in the device did not increase the signal on the other test line, indicating no cross-reactivity between the assays. Additionally, simultaneous detection of both N-protein and HA was performed as well as simultaneous detection of N-protein and human C-reactive protein (CRP). Elevated levels of CRP in a patient infected with SARS-CoV-2 have been shown to correlate with more severe outcomes and a greater risk of death as well. To further expand on the simultaneous detection of two biomarkers, CRP and N-protein were detected simultaneously, and the presence of SARS-CoV-2 N-protein did not interfere with the detection of CRP when both targets were present in the sample.

Safety and Efficacy of Propylene Glycol-Free Melphalan in Patients with AL Amyloidosis Undergoing Autologous Stem Cell Transplantation: Results of a Phase II Study.

Patients with systemic light chain (AL) amyloidosis undergoing treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) may develop renal and cardiac toxicities potentially exacerbated by the co-solvent propylene glycol in conventional melphalan formulations. We investigated the safety and efficacy of propylene glycol-free melphalan (PGF-Mel) during HDM/SCT in patients with AL amyloidosis (ClinicalTrials.gov identifier NCT02994784). The primary objective of this phase II, open-label study was evaluation for renal dysfunction, new cardiac arrhythmias, and postural hypotension related to autonomic dysfunction. Secondary objectives included time to neutrophil and platelet engraftment, treatment-related mortality (TRM), overall hematologic response, organ response, and number of peritransplantation hospitalizations. Twenty-eight patients with AL amyloidosis enrolled, of whom 27 underwent HDM/SCT. PGF-Mel at 140 to 200 mg/m2 was administered i.v. in 2 equally divided doses. Patients were monitored for up to 30 days after the last administration of PGF-Mel to assess for treatment-related toxicity. Patients were followed for 12 months from the time of treatment with HDM/SCT for evaluation of hematologic and organ responses. Kaplan-Meier analysis was used to estimate progression-free survival. Two patients (7%) developed renal dysfunction, 5 (19%) experienced new cardiac arrhythmias, and 3 (11%) developed orthostatic hypotension. All patients achieved neutrophil and platelet engraftment, at a median of 10 days and 17 days post-HDM/SCT, respectively. TRM on day +100 was 0%. Peritransplantation hospitalization was required for 23 patients (85%). The most common nonhematologic adverse events were diarrhea (93%), fatigue (82%), and nausea (74%). At 6 months post-HDM/SCT, hematologic complete response or very good partial response occurred in 66% of the patients. At 12 months post-HDM/SCT, renal response occurred in 12 of 23 (52%) patients with renal involvement, and cardiac response occurred in 3 of 11 (27%) patients with evaluable cardiac involvement. Our data indicate that PGF-Mel is safe and efficacious as a high-dose conditioning regimen for autologous SCT in patients with AL amyloidosis.

Capillary flow-driven immunoassay platform for COVID-19 antigen diagnostics.

Over the last few years, the SARS-CoV-2 pandemic has made the need for rapid, affordable diagnostics more compelling than ever. While traditional laboratory diagnostics like PCR and well-plate ELISA are sensitive and specific, they can be costly and take hours to complete. Diagnostic tests that can be used at the point-of-care or at home, like lateral flow assays (LFAs) are a simple, rapid alternative, but many commercially available LFAs have been criticized for their lack of sensitivity compared to laboratory methods like well-plate ELISAs. The Capillary-Driven Immunoassay (CaDI) device described in this work uses microfluidic channels and capillary action to passively automate the steps of a traditional well-plate ELISA for visual read out. This work builds on prior capillary-flow devices by further simplifying operation and use of colorimetric detection. Upon adding sample, an enzyme-conjugated secondary antibody, wash steps, and substrate are sequentially delivered to test and control lines on a nitrocellulose strip generating a colorimetric response. The end user can visually detect SARS-CoV-2 antigen in 15-20 min by naked eye, or results can be quantified using a smartphone and software such as ImageJ. An analytical detection limit of 83 PFU/mL for SARS-CoV-2 was determined for virus in buffer, and 222 PFU/mL for virus spiked into nasal swabs using image analysis, similar to the LODs determined by traditional well-plate ELISA. Additionally, a visual detection limit of 100 PFU/mL was determined in contrived nasal swab samples by polling 20 untrained end-users. While the CaDI device was used for detecting clinically relevant levels of SARS-CoV-2 in this study, the CaDI device can be easily adapted to other immunoassay applications by changing the reagents and antibodies.

Successful dasatinib therapy in newly diagnosed chronic myeloid leukemia in the setting of short bowel syndrome.

INTRODUCTION: There is limited guidance on the selection of tyrosine kinase inhibitors (TKIs) in patients with short bowel syndrome (SBS). Concerns regarding absorption, toxicity profiles, and drug interactions should be considered when selecting optimal TKI therapy. CASE REPORT: A 57-year-old male with SBS was newly diagnosed with chronic myeloid leukemia (CML). A careful review of his surgical history, comorbidities, and concurrent medications led to a treatment decision to initiate dasatinib at 100 mg once daily. MANAGEMENT AND OUTCOME: After initiation of therapy, the patient achieved a complete hematological response after two weeks and an early major molecular response on a three-month assessment. The therapy was tolerated well with no identified adverse effects. DISCUSSION: Clinical rationale for selecting dasatinib in patients with SBS includes supporting literature regarding its pharmacokinetic absorption characteristics, its efficacy with lower doses in newly diagnosed patients with CML, and its side effect profile in comparison to other second-generation TKIs. The case discussed provides an example of successful therapy in a patient with SBS undergoing treatment for CML.

Usability Evaluation of a Noninvasive Neutropenia Screening Device (PointCheck) for Patients Undergoing Cancer Chemotherapy: Mixed Methods Observational Study.

BACKGROUND: Patients with cancer undergoing cytotoxic chemotherapy face an elevated risk of developing serious infection as a consequence of their treatment, which lowers their white blood cell count and, more specifically, their absolute neutrophil count. This condition is known as neutropenia. Neutropenia accompanied by a fever is referred to as febrile neutropenia, a common side effect of chemotherapy with a high mortality rate. The timely detection of severe neutropenia (<500 absolute neutrophil count/µL) is critical in detecting and managing febrile neutropenia. Current methods rely on blood draws, which limit them to clinical settings and do not allow frequent or portable monitoring. In this study, we demonstrated the usability of PointCheck, a noninvasive device for neutropenia screening, in a simulated home environment without clinical supervision. PointCheck automatically performs microscopy through the skin of the finger to image the blood flowing through superficial microcapillaries and enables the remote monitoring of neutropenia status, without requiring venipuncture. OBJECTIVE: This study aimed to evaluate the usability of PointCheck, a noninvasive optical technology for screening severe neutropenia, with the goal of identifying potential user interface, functionality, and design issues from the perspective of untrained users. METHODS: We conducted a multicenter study using quantitative and qualitative approaches to evaluate the usability of PointCheck across 154 untrained participants. We used a mixed method approach to gather usability data through user testing observations, a short-answer qualitative questionnaire, and a standardized quantitative System Usability Scale (SUS) survey to assess perceived usability and satisfaction. RESULTS: Of the 154 participants, we found that 108 (70.1%) scored above 80.8 on the SUS across all sites, with a mean SUS score of 86.1 across all sites. Furthermore, the SUS results indicated that, out of the 151 users who completed the SUS survey, 145 (96%) found that they learned how to use PointCheck very quickly, and 141 (93.4%) felt very confident when using the device. CONCLUSIONS: We have shown that PointCheck, a novel technology for noninvasive, home-based neutropenia detection, can be safely and effectively operated by first-time users. In a simulated home environment, these users found it easy to use, with a mean SUS score of 86.1, indicating an excellent perception of usability and placing this device within the top tenth percentile of systems evaluated for usability by the SUS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04448314; https://clinicaltrials.gov/ct2/show/NCT04448314 (Hospital Universitario 12 de Octubre registration) and NCT04448301; https://clinicaltrials.gov/ct2/show/NCT04448301 (Boston Medical Center registration).

Impact of Human T Cell Lymphotropic Virus Type 1 and 2 Infection on Survival Following Stem Cell Transplantation.

Human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) are delta retroviruses. HTLV-1 may lead to complications, including adult T cell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy. Immunosuppression may result in progression from an asymptomatic carrier state to ATLL. Data on the safety of stem cell transplantation (SCT) in patients with HTLV-1/2 infection are lacking. The Center for International Blood and Marrow Transplant Research database was queried for patients who tested positive for HTLV infection in the pretransplantation workup and underwent either autologous SCT (autoSCT) or allogeneic SCT (alloSCT). Patients were excluded if they underwent SCT for ATLL. The primary outcome was overall survival (OS) at 3 years and 4 years post-SCT. In those who underwent autoSCT, 54 patients were HTLV-positive and 9836 were HTLV-negative. In those who underwent alloSCT, 105 patients were HTLV-positive and 18,077 were HTLV-negative. No difference in OS was noted between the HTLV-positive and HTLV-negative patients at 3 years post-autoSCT (76% versus 77%; P = .916). Inferior OS (32% versus 46%; P = .017) and nonrelapse mortality (35% versus 27%; P = .030) were observed in HTLV-positive patients at 4 years post-alloSCT. Future work should examine the mechanism by which HTLV-1/2 impact survival in alloSCT recipients.

Primary pulmonary marginal zone lymphoma: an unusual cause of pulmonary infiltrates.

Primary pulmonary extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), also known as bronchus-associated lymphoid tissue (BALT lymphoma), is the most common primary pulmonary lymphoma but is rare (<1%) among all non-Hodgkin lymphomas and among pulmonary neoplasms in general. We herein report the case of a 59-year-old male who presented with stable exertional dyspnoea and persistent lung infiltrates who was referred to our hospital for further assessment. A computed tomography (CT)-guided core biopsy was performed showing a dense lymphoid infiltrate, with further testing revealing the diagnosis of pulmonary MALT lymphoma. This uncommon lung tumour is usually seen in older adults and typically associated with a relatively indolent course. Rituximab, an anti-CD20 antibody, has been shown to be effective in up to 70% of cases.

Novel methodology comparing two assay formats for the assessment of immunogenicity from clinical trial samples.

Aim: We present a novel methodology to compare results between distinct immunogenicity assays, performed by two laboratories, for the same biotherapeutic. Materials & methods: Human serum pools from clinical trials were generated to provide representative immunogenicity titers. Pools were evaluated at two laboratories in a blinded fashion to assess the effect of assay format and laboratory change on clinical interpretation of immunogenicity results. Results: The laboratories validated two different assay formats and demonstrated comparable sensitivity and drug tolerance. Overall, the comparisons in assay format and laboratory ensured a comparable ability to detect treatment-emergent antidrug antibodies for a biotherapeutic. Conclusion: We have established an approach, using pooling of patient samples, that allows for the interlaboratory comparisons without creating duplicative results.

Lay abstract Measuring immunogenicity, an immune response to a drug, is important in understanding the benefits and risks associated with a drug. Immunogenicity is measured by specific tests within a laboratory; however, these tests and laboratories may change over time. This paper proposes a method to determine if a change in test and laboratory will impact the interpretation of immunogenicity for a drug. Blood samples from clinical trial patients were combined in order to provide representative samples for the immunogenicity tests. The samples were tested at two laboratories with two tests to measure if any interpretation of immunogenicity results would change due to the different tests and laboratories. Laboratories and tests demonstrated similar and reliable results of the samples. This study has established a method which allows for the comparison of immunogenicity results when tests and/or laboratories are changed.

Development and validation of a novel immunogenicity assay to detect anti-drug and anti-PEG antibodies simultaneously with high sensitivity.

Polyethylene glycol (PEG) represents an effective strategy to improve the pharmacokinetic profile of a molecule as it extends the biotherapeutic's half-life, masks immunogenic epitopes or modifies its distribution. The addition of one or multiple PEG moieties, in either linear or branched form, is known to carry the risk of potentially inducing an immunogenic response against PEG. The importance of accurately quantifying anti-PEG antibodies during a clinical study is well recognized and stems from the fact that anti-PEG antibodies have been shown to negatively impact the efficacy of the biotherapeutic that the PEG is coupled to. As a consequence, sponsors are encouraged to develop immunogenicity assays to assess appropriately the presence of anti-drug antibodies (ADA) against the protein component as well as the PEG. However, detection of anti-PEG antibodies is complicated by a number of technical challenges, including the availability of appropriate positive control material. In addition, the fact that some anti-PEG antibodies are known to circulate as low-affinity IgM, drives the need for an assay able to detect low affinity anti-PEG ADA even in the presence of high concentrations of the biotherapeutic. To address this need, we developed and validated an Affinity Capture Elution (ACE)-AGL assay to detect anti-drug and anti-PEG antibodies. In this assay, which we call ACE-AGL, ADA are captured by biotin-PEG-drug, acid eluted and re-captured on a second plate coated with protein AGL. ADA are then detected using Ruthenium-PEG-drug. The new assay format described is highly sensitive to both anti-drug and anti-PEG antibodies and very drug-tolerant. The ACE-AGL assay is easy to perform and has been successfully validated at two separate CROs. We propose the ACE-AGL format as a valid and effective alternative to the currently available assay methods.

Free-standing acute inpatient rehabilitation hospital enhanced practices and policies in response to the COVID-19 outbreak.

This special report was developed to communicate policy and procedures for free-standing acute inpatient rehabilitation hospitals (AIRHs) to protect patients and healthcare personnel and to prevent further spread of severe acute respiratory syndrome coronavirus 2. The recommended policies were developed in conjunction with the New Mexico Department of Health and hospital leadership. As we attain additional knowledge and experience during this pandemic, suggestions of best practice will continue to evolve for AIRHs. The authors encourage readers to work with local regulatory officials to ensure regulatory compliance as well as respect of the availability of local resources.

Acute promyelocytic leukaemia presenting as necrotising fasciitis of the perineum (Fournier gangrene).

We present a case of an unusual presentation of acute promyelocytic leukaemia (APML), which presented with Fournier gangrene (FG). A 38-year-old man presented with malaise, groin swelling, anal bleeding, fever and was found to have FG. Initial workup revealed pancytopaenia, borderline low fibrinogen, prolonged international normalized ratio (INR), which raised the suspicion for leukaemia. The peripheral blood differential revealed leucopaenia with absolute neutropaenia and a 5% abnormal promyelocytes but no blasts, suspicious for APML. Bone marrow biopsy was performed and fluorescence in situ hydridization (FISH), karyotype and PCR confirmed a t(15;17) translocation, establishing a diagnosis of APML. After 1 month of therapy for intermediate risk APML with All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), repeat chromosomal analysis and repeat bone marrow biopsy revealed no evidence of residual APML. After the consolidation phase was started with ATRA and ATO regimen, the wound healed after 2 months and the patient achieved complete remission.

A before-after study of hospital use in two frail populations receiving different home-based services over the same time in Vancouver, Canada.

BACKGROUND: As individuals age, they are more likely to experience increasing frailty and more frequent use of hospital services. First, we explored whether initiating home-based primary care in a frail homebound cohort, influenced hospital use. Second, we explored whether initiating regular home care support for personal care with usual primary care, in a second somewhat less frail cohort, influenced hospital use. METHODS: This was a before-after retrospective cohort study of two frail populations in Vancouver, Canada using administrative data to assess the influence of two different services started in two different cohorts over the same time period. The participants were 246 recipients of integrated home-based primary care and 492 recipients of home care followed between July 1st, 2008 and June 30th, 2013 before and after starting their respective services. Individuals in each group were linked to their hospital emergency department visit and discharge abstract records. The main outcome measures were mean emergency department visit and hospital admission rates per 1000 patient days for 21 months before versus the period after receipt of services, and the adjusted incidence rate ratios (IRRs) on these outcomes post receipt of service. RESULTS: Before versus after starting integrated home-based primary care, emergency department visit rates per 1000 patient days (95% confidence intervals) were 4.1 (3.8, 4.4) versus 3.7 (3.3, 4.1), and hospital admissions rates were 2.3 (2.1, 2.5) versus 2.2 (1.9, 2.5). Before versus after starting home care, emergency department visit rates per 1000 patient days (95% confidence intervals) were 3.0 (2.8, 3.2) versus 4.0 (3.7, 4.3) visits and hospital admissions rates were 1.3 (1.2, 1.4) versus 1.9 (1.7, 2.1). Home-based primary care IRRs were 0.91 (0.72, 1.15) and 0.99 (0.76, 1.27) and home care IRRs were 1.34 (1.15, 1.56) and 1.46 (1.22, 1.74) for emergency department visits and hospital admissions respectively. CONCLUSIONS: After enrollment in integrated home-based primary care, emergency department visit and hospital admission rates stabilized. After starting home care with usual primary care, emergency department visit and hospital admission rates continued to rise.

High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. MATERIALS AND METHODS: Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. RESULTS: At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group. CONCLUSION: In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.

Home-based Physical Activity Coaching, Physical Activity, and Health Care Utilization in Chronic Obstructive Pulmonary Disease. Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial Secondary Outcomes.

RATIONALE: Physical inactivity among patients with chronic obstructive pulmonary disease is associated with exacerbations requiring high-cost health care utilization including urgent, emergent, and hospital care. OBJECTIVES: To examine the effectiveness of a behavioral lifestyle physical activity intervention combined with chronic obstructive pulmonary disease self-management education to prevent high-cost health care utilization. METHODS: This was an analysis of secondary outcomes of the Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial, a two-arm randomized trial of stable adult outpatients with chronic obstructive pulmonary disease recruited from primary care and pulmonary clinics. Following a 6-week self-management education run-in period, participants were randomized to usual care or to a telephone-delivered home-based health coaching intervention over 20 weeks. Secondary outcomes of physical activity and health care utilization were determined by self-report 6, 12, and 18 months after randomization. Associations between treatment allocation arm and these secondary outcomes were examined using log-binomial and Poisson regression models. RESULTS: A total of 325 outpatients with stable chronic obstructive pulmonary disease were enrolled in the trial. Their average age was 70.3 years (standard deviation, 9.5), and 50.5% were female; 156 were randomized to usual care and 149 to the intervention. A greater proportion of participants reported being persistently active over the 18-month follow-up period in the intervention group (73.6%) compared with the usual care group (57.8%) (mean difference, 15.8%; 95% confidence interval, 4.0-27.7%). This association varied by severity of forced expiratory volume in 1 second impairment (P for interaction = 0.09). Those in the intervention group with moderate impairment (forced expiratory volume in 1 second, 50-70% predicted), more frequently reported being persistently active compared with the usual care (86.0 vs. 65.1%; mean difference, 20.9%; 95% confidence interval, 5.7-36.1%). Patients with severe and very severe forced expiratory volume in 1 second impairment (forced expiratory volume in 1 second < 50% predicted) in the intervention group also reported being persistently active more frequently compared with usual care (63.3 vs. 50.8%; mean difference, 12.6%; 95% confidence interval, -4.7 to 29.8). The intervention was associated with a lower rate of lung-related utilization (adjusted rate ratio, 0.38; 95% confidence interval, 0.23-0.63) only among participants with severe spirometric impairment. CONCLUSIONS: Our results demonstrate that a feasible and generalizable home-based coaching intervention may decrease sedentary behavior and increase physical activity levels. In those with severe chronic obstructive pulmonary disease, this intervention may reduce lung disease-related health care utilization. Clinical trial registered with www.clinicaltrials.gov (NCT01108991).