Home Oxygen Evaluation by Respiratory Therapists in Patients Hospitalized for COPD Exacerbations: The RIsOTTO Study.

BACKGROUND: The majority of prescriptions for supplemental oxygen are written when patients are discharged to home from the hospital and the evaluation of these patients is inconsistent. Respiratory Therapists receive training in the evaluation and management of patients needing oxygen. The primary goal of the study was to estimate the frequency with which respiratory therapists (RTs) evaluate the need for home oxygen in patients hospitalized for COPD exacerbations before discharge. METHODS: An online questionnaire was distributed to RTs in the United States by the American Association for Respiratory Care. RTs were asked to indicate how frequently they evaluate the need for home oxygen on an ordinal scale: Never, Rarely/occasionally, Sometimes, Most of the time, Almost every time, or Every time. Consistent evaluation for home oxygen was defined as performing an evaluation for home oxygen therapy Almost every time or Every time (ie, > 75% of the time). Bivariate and multivariable analyses were assessed using the Fisher exact test and logistic regression models. RESULTS: Of 611 respondents, 490 were eligible for analysis. Fifty-eight percent of RTs reported consistently evaluating patients for home oxygen at rest, whereas 43% reported doing so during activity and 14% during sleep. Consistent evaluation for home oxygen requirements at rest was significantly associated with more years of practice (P = .03; highest among RTs with ≥ 30 y of practice at 40%), region of practice (P = .001; highest in the Midwest at 44%), and greater familiarity with criteria for home oxygen (P < .001; highest among RTs who selected Very familiar with guidelines from the Centers for Medicare and Medicaid Services at 58%). Practice in the Midwest and greater familiarity with criteria for home oxygen was associated with consistent evaluation for home oxygen during activity. Practice in the Midwest (vs Northeast; adjusted odds ratio 2.56, P < .001) and being very familiar with home oxygen criteria (vs not at all familiar; adjusted odds ratio 5.66, P < .001) were independently associated with a higher odds of evaluating for home oxygen at rest and with activity. Only 25% of RTs were involved in making decisions about home oxygen equipment. CONCLUSIONS: RTs do not consistently evaluate patients hospitalized for COPD exacerbations for home oxygen prior to discharge, and only a minority of RTs are involved in selecting home oxygen equipment.

Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.

Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane.

The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease1 and antipsychotic drugs2. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine3, leading to stimulation of Gi and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-Gi complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular Gi-binding site. The DRD2-Gi structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders.

Home Oxygen Therapy for Patients With COPD: Time for a Reboot.

Just over 100 years ago, John Scott Haldane published a seminal report about the therapeutic potential of supplemental oxygen to treat hypoxemia. In the 1980s, a pair of clinical trials confirmed the benefit of long-term oxygen therapy in improving survival in patients with COPD associated with severe resting hypoxemia. This review provides a summary of evidence supporting long-term and short-term oxygen therapy, as well as the various types of oxygen equipment commonly used in homes to deliver supplemental oxygen. Because the majority of orders for home oxygen occur at hospital discharge following acute illness, a typical conversation between a patient and their pulmonologist following a COPD exacerbation is presented. The SHERLOCK Consortium, a multi-stakeholder group established following the publication of the COPD National Action Plan in 2017 is also detailed. Interim results of the SHERLOCK Consortium, which suggest a chain of care involving 9 steps to ensure that patients are successfully initiated on home oxygen therapy during transitions from hospital to home, are presented. Recommendations to support evidence-based policies in this high-risk population are provided.

Daily Physical Activity in Patients With COPD After Hospital Discharge in a Minority Population.

BACKGROUND: Low physical activity in patients with chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality. To inform the design of a home-based physical activity promotion program for patients with COPD recently discharged from a minority-serving hospital, we conducted a cohort study to evaluate objectively measured daily physical activity and patient-reported outcomes. METHODS: This was a 12-week prospective cohort study of patients with a physician diagnosis of COPD recently hospitalized (≤ 12 weeks) for respiratory symptoms. Daily physical activity was recorded using wrist-based and "clip-on" pedometers, and analyzed as mean daily step counts averaged over 7 days. RESULTS: Twenty-two patients were enrolled a median (interquartile range, [IQR]) of 14 (7 to 29) days after hospital discharge. The median daily step count (IQR) in the first week after enrollment (week 1) was 3710 (1565 to 5129) steps. The median within-person change in daily step count (IQR) from week 1 to week 12 was 314 (-30 to 858) steps (p=0.28). Within-person correlation of week-to-week daily step counts was high (r ≥ 0.75). Time from hospital discharge to enrollment was not correlated with mean daily step counts on week 1 (r= -0.13) and only weakly correlated with change in mean daily step counts from week 1 to week 12 (r=0.37). CONCLUSIONS: Daily physical activity was variable in this cohort of recently hospitalized patients with COPD, but with little within-person change over a 12-week period. These observations highlight the need for flexible physical activity promotion programs addressing the needs of a heterogeneous patient population.

Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial.

RATIONALE: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. OBJECTIVES: To identify patient characteristics at the time of oxygen initiation associated with its adherence. METHODS: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0-10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0-30 days), medium-term (months 9-12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. RESULTS: Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05-1.40) and 94% (OR 1.94, 95% CI 1.45-2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90-31.79; intermittent, OR 38.08, 95% CI 6.96-208.20). CONCLUSIONS: Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.

Home Oxygen in Chronic Obstructive Pulmonary Disease.

Two landmark trials conducted more than 35 years ago provided scientific evidence that, under very specific circumstances, long-term oxygen therapy (LTOT) may prolong life. These two trials enrolled 290 patients with chronic obstructive pulmonary disease and severe daytime hypoxemia documented by direct arterial blood gas measurement. From that time, LTOT became a standard of care, and the indications for oxygen therapy expanded to include nocturnal oxygen therapy for isolated nocturnal oxygen desaturation, ambulatory oxygen to correct exercise-induced desaturation, and short-burst oxygen to relieve dyspnea. In most cases, the rationale for broadening the indications for oxygen therapy is that, if hypoxemia exists, correcting it by increasing the FiO2 should help. However, with the exception of LTOT in severely hypoxemic patients with chronic obstructive pulmonary disease, randomized controlled trials of oxygen therapy have failed to demonstrate clinically significant benefits. Also, adherence to LTOT is usually suboptimal. Important areas for future research include improving understanding of the mechanisms of action of supplemental oxygen, the clinical and biochemical predictors of responsiveness to LTOT, the methods for measuring and enhancing adherence to LTOT, and the cost-effectiveness of oxygen therapy. A standardization of terminology to describe the use of supplemental oxygen at home is provided.

Computational design of ligand-binding membrane receptors with high selectivity.

Accurate modeling and design of protein-ligand interactions have broad applications in cell biology, synthetic biology and drug discovery but remain challenging without experimental protein structures. Here we developed an integrated protein-homology-modeling, ligand-docking protein-design approach that reconstructs protein-ligand binding sites from homolog protein structures in the presence of protein-bound ligand poses to capture conformational selection and induced-fit modes of ligand binding. In structure modeling tests, we blindly predicted, with near-atomic accuracy, ligand conformations bound to G-protein-coupled receptors (GPCRs) that have rarely been identified using traditional approaches. We also quantitatively predicted the binding selectivity of diverse ligands to structurally uncharacterized GPCRs. We then applied this technique to design functional human dopamine receptors with novel ligand-binding selectivity. Most blindly predicted ligand-binding specificities closely agreed with experimental validations. Our method should prove useful in ligand discovery approaches and in reprogramming the ligand-binding profile of membrane receptors that remain difficult to crystallize.

Computed diffusion-weighted MRI for prostate cancer detection: the influence of the combinations of b-values.

OBJECTIVE: To evaluate the influence of the combinations of b-values on computed diffusion-weighted images (cDWIs) for prostate cancer (PCa) detection at b = 2000 s mm(-2). METHODS: Diffusion-weighted imaging (DWIs) for 31 patients with PCa (65.2 ± 7.1 years) were obtained pre-operatively at different b-values (0, 100, 500, 1000 and 2000 s mm(-2)) on a 3-T MRI. cDWIs at b = 2000 were generated by using six b-value combinations: 0-100 s mm(-2) (cDWI0-100); 0-500 s mm(-2) (cDWI0-500); 100-500 s mm(-2) (cDWI100-500); 0-1000 s mm(-2) (cDWI0-1000); 100-1000 s mm(-2) (cDWI100-1000); and 500-1000 s mm(-2) (cDWI500-1000). These cDWIs and measured DWIs with b = 2000 s mm(-2) (mDWI2000) were evaluated in this setting. To assess image quality for each DWI, contrast ratios (CRs) of cancerous and non-cancerous lesions were evaluated. To compare the detectability of PCa for each DWI, receiver operating characteristic analysis was used. RESULTS: CRs of all cDWIs were significantly higher than those of mDWI2000 (p < 0.05). Areas under the curve of cDWI0-100 (0.62) and cDWI0-500 (0.65) were significantly smaller (p < 0.05) than those of others (cDWI100-500, 0.72; cDWI0-1000, 0.73; cDWI100-1000, 0.71; cDWI500-1000, 0.74; mDWI2000, 0.72). CONCLUSION: The combinations of b-values influenced image quality and diagnostic ability of cDWIs for PCa detection. The combinations of b ≥ 100 and b ≥ 500 s mm(-2), as well as b = 0 and b = 1000 s mm(-2), were optimal in this study. ADVANCES IN KNOWLEDGE: For generating the useful cDWI for PCa detection, radiologists should take care of the combination of b-values when including low b-values.

A prospective study of the incidence and outcomes of incidental dural tears in microendoscopic lumbar decompressive surgery.

Little information is available about the incidence and outcome of incidental dural tears associated with microendoscopic lumbar decompressive surgery. We prospectively examined the incidence of dural tears and their influence on the outcome six months post-operatively in 555 consecutive patients (mean age 47.4 years (13 to 89)) who underwent this form of surgery. The incidence of dural tears was 5.05% (28/555). The risk factors were the age of the patient and the procedure of bilateral decompression via a unilateral approach. The rate of recovery of the Japanese Orthopaedic Association score in patients with dural tears was significantly lower than that in those without a tear (77.7% vs. 87.6%; p < 0.02), although there were no significant differences in the improvement of the Oswestry Disability Index between the two groups. Most dural tears were small, managed by taking adequate care of symptoms of low cerebrospinal fluid pressure, and did not require direct dural repair. Routine MRI scans were undertaken six months post-operatively; four patients with a dural tear had recurrent or residual disc herniation and two had further stenosis, possibly because the dural tear prevented adequate decompression and removal of the fragments of disc during surgery; as yet, none of these patients have undergone further surgery.

High-resolution modeling of transmembrane helical protein structures from distant homologues.

Eukaryotic transmembrane helical (TMH) proteins perform a wide diversity of critical cellular functions, but remain structurally largely uncharacterized and their high-resolution structure prediction is currently hindered by the lack of close structural homologues. To address this problem, we present a novel and generic method for accurately modeling large TMH protein structures from distant homologues exhibiting distinct loop and TMH conformations. Models of the adenosine A2AR and chemokine CXCR4 receptors were first ranked in GPCR-DOCK blind prediction contests in the receptor structure accuracy category. In a benchmark of 50 TMH protein homolog pairs of diverse topology (from 5 to 12 TMHs), size (from 183 to 420 residues) and sequence identity (from 15% to 70%), the method improves most starting templates, and achieves near-atomic accuracy prediction of membrane-embedded regions. Unlike starting templates, the models are of suitable quality for computer-based protein engineering: redesigned models and redesigned X-ray structures exhibit very similar native interactions. The method should prove useful for the atom-level modeling and design of a large fraction of structurally uncharacterized TMH proteins from a wide range of structural homologues.

The natural history of asymptomatic lumbar canal stenosis in patients undergoing surgery for cervical myelopathy.

We retrospectively examined the prevalence and natural history of asymptomatic lumbar canal stenosis in patients treated surgically for cervical compressive myelopathy in order to assess the influence of latent lumbar canal stenosis on the recovery after surgery. Of 214 patients who had undergone cervical laminoplasty for cervical myelopathy, we identified 69 (32%) with myelographically documented lumbar canal stenosis. Of these, 28 (13%) patients with symptomatic lumbar canal stenosis underwent simultaneous cervical and lumbar decompression. Of the remaining 41 (19%) patients with asymptomatic lumbar canal stenosis who underwent only cervical surgery, 39 were followed up for ≥ 1 year (mean 4.9 years (1 to 12)) and were included in the analysis (study group). Patients without myelographic evidence of lumbar canal stenosis, who had been followed up for ≥ 1 year after the cervical surgery, served as controls (135 patients; mean follow-up period 6.5 years (1 to 17)). Among the 39 patients with asymptomatic lumbar canal stenosis, seven had lumbar-related leg symptoms after the cervical surgery. Kaplan-Meier analysis showed that 89.6% (95% confidence interval (CI) 75.3 to 96.0) and 76.7% (95% CI 53.7 to 90.3) of the patients with asymptomatic lumbar canal stenosis were free from leg symptoms for three and five years, respectively. There were no significant differences between the study and control groups in the recovery rate measured by the Japanese Orthopaedic Association score or improvement in the Nurick score at one year after surgery or at the final follow-up. These results suggest that latent lumbar canal stenosis does not influence recovery following surgery for cervical myelopathy; moreover, prophylactic lumbar decompression does not appear to be warranted as a routine procedure for coexistent asymptomatic lumbar canal stenosis in patients with cervical myelopathy, when planning cervical surgery.

Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: Human bocavirus (HBoV) is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). METHODS: We retrospectively tested 212 COPD patients, 141 (66.5%) with AE-COPD and 71 (33.5%) with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA). The specificity of positive polymerase chain reaction results was confirmed by sequencing. RESULTS: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%). Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8%) and stable COPD (2.9%). HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain. CONCLUSION: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely.

[Scimitar syndrome; report of a case].

A 17-year-old woman with scimitar syndrome without an atrial septal defect was operated by intra-cardiac conduit repair. Computed tomography (CT) and magnetic resonance imaging (MRI) showed resolution images of anatomical findings of scimitar vein. Surgical procedures for the scimitar syndrome have varied according to the anatomic features presented in each case. The detection of precise anatomy of scimitar syndrome is important for determining the appropriate surgical procedure. Images of 3-dimensional (3-D) CT and MRI of scimitar syndrome were demonstrated.

Experimental and modeling studies on sorption and diffusion of radium in bentonite.

The sorption and desorption behavior of radium on bentonite and purified smectite was investigated as a function of pH, ionic strength and liquid to solid ratio by batch experiments. The distribution coefficients (Kd) were in the range of 10(2) to > 10(4) ml g-1 and depended on ionic strength and pH. Most of sorbed Ra was desorbed by 1 M KCl. The results for purified smectite indicated that Ra sorption is dominated by ion exchange at layer sites of smectite, and surface complexation at edge sites may increase Ra sorption at higher pH region. Reaction parameters between Ra and smectite were determined based on an interaction model between smectite and groundwater. The reaction parameters were then used to explain the results of bentonite by considering dissolution and precipitation of minerals and soluble impurities. The dependencies of experimental Kd values on pH, ionic strength and liquid to solid ratio were qualitatively explained by the model. The modeling result for bentonite indicated that sorption of Ra on bentonite is dominated by ion exchange with smectite. The observed pH dependency was caused by changes of Ca concentration arising from dissolution and precipitation of calcite. Diffusion behavior of Ra in bentonite was also investigated as a function of dry density and ionic strength. The apparent diffusion coefficients (Da) obtained in compacted bentonite were in the range of 1.1 x 10(-11) to 2.2 x 10(-12) m2 s-1 and decreased with increasing in dry density and ionic strength. The Kd values obtained by measured effective diffusion coefficient (De) and modeled De were consistent with those by the sorption model in a deviation within one order of magnitude.

An integrated sorption-diffusion model for the calculation of consistent distribution and diffusion coefficients in compacted bentonite.

A thermodynamic sorption model and a diffusion model based on electric double layer (EDL) theory are integrated to yield a surface chemical model that treats porewater chemistry, surface reactions, and the influence of charged pore walls on diffusing ions in a consistent fashion. The relative contribution of Stern and diffuse layer to the compensation of the permanent surface charge represents a key parameter; it is optimized for the diffusion of Cs in Kunipia-F bentonite, at a dry density of 400 kg/m3. The model is then directly used to predict apparent diffusivities (Da) of Cs, Sr, Cl-, I- and TcO4- and corresponding distribution coefficients (Kd) of Cs and Sr in different bentonites as a function of dry density, without any further adjustment of surface chemical and EDL parameters. Effective diffusivities (De) for Cs, HTO, and TcO4- are also calculated. All calculated values (Da, De, Kd) are fully consistent with each other. A comparison with published, measured data shows that the present model allows a good prediction and consistent explanation of (i) apparent and effective diffusivities for cations, anions, and neutral species in compacted bentonite, and of (ii) Kd values in batch and compacted systems.

A new regulatory region of the IL-2 locus that confers position-independent transgene expression.

Although the promoter/enhancer of the IL-2 gene mediates inducible reporter gene expression in vitro, it cannot drive consistent expression in transgenic mice. The location and existence of any regulatory elements that could open the IL-2 locus in vivo have remained unknown, preventing analysis of IL-2 regulation in developmental contexts. In this study, we report the identification of such a regulatory region, marked by novel DNase-hypersensitive sites upstream of the murine IL-2 promoter in unstimulated and stimulated T cells. Inclusion of most of these sites in an 8.4-kb IL-2 promoter green fluorescent protein transgene gives locus control region-like activity. Expression is efficient, tissue specific, and position independent. This transgene is expressed not only in peripheral T cells, but also in immature thymocytes and thymocytes undergoing positive selection, in agreement with endogenous IL-2 expression. In contrast, a 2-kb promoter green fluorescent protein transgene, lacking the new hypersensitive sites, is expressed in only a few founder lines, and expression is dysregulated in CD8(+) cells. Thus, the 6.4 kb of additional upstream IL-2 sequence contains regulatory elements that provide integration site independence and differential regulation of transgene expression in CD8 vs CD4 cells.

Speed congenics: a classic technique in the fast lane (relatively speaking).

Marker-assisted selection protocol (MASP)-based strategies produce congenic strains with the target gene contained on clearly defined donor-derived genomic intervals in less than half the member of generations required by the classic protocol. Thus, the quality and speed of congenic strain construction are enhanced by this methodology. Here, Edward Wakeland and colleagues compare various MASP-based strategies and discuss their advantages with reference to immunological traits.