We present new, deep observations of the Phoenix cluster from Chandra, the Hubble Space Telescope, and the Karl Jansky Very Large Array. These data provide an order-of-magnitude improvement in depth ...and/or angular resolution over previous observations at X-ray, optical, and radio wavelengths. We find that the one-dimensional temperature and entropy profiles are consistent with expectations for pure-cooling models. In particular, the entropy profile is well fit by a single power law at all radii, with no evidence for excess entropy in the core. In the inner ∼10 kpc, the cooling time is shorter than any other known cluster by an order of magnitude, while the ratio of the cooling time to freefall time (tcool/tff) approaches unity, signaling that the intracluster medium is unable to resist multiphase condensation on kpc scales. The bulk of the cooling in the inner ∼20 kpc is confined to a low-entropy filament extending northward from the central galaxy, with tcool/tff ∼ 1 over the length of the filament. In this filament, we find evidence for ∼1010 M in cool (∼104 K) gas (as traced by the O iiλλ3726,3729 doublet), which is coincident with the low-entropy filament and absorbing soft X-rays. The bulk of this cool gas is draped around and behind a pair of X-ray cavities, presumably bubbles that have been inflated by radio jets. These data support a picture in which active galactic nucleus feedback is promoting the formation of a multiphase medium via uplift of low-entropy gas, either via ordered or chaotic (turbulent) motions.
Abstract Purpose An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This ...article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC). Methods Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research. Results Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community. Conclusion Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life.
Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is ...associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI.
With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions.
The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC.
NCT03984396. Registered on 13 June 2019.
Background. Most recommended care for chronic diseases is based on the research of single conditions. There is limited information on ‘best’ processes of care for persons with multiple morbidities. ...Our objective was to explore processes of care desired by elderly patients who have multimorbidities that may present competing demands for patients and providers. Methods. Qualitative investigation using one-on-one interviews of 26 community-dwelling HMO members aged 65–84 (50% male) who had, at a minimum, the combined conditions of diabetes, depression and osteoarthritis. Participants were chosen from a stratified random sample to have a range of 4–16 chronic medical conditions. Results. Participants’ desired processes of care included: the need for convenient access to providers (telephone, internet or in person), clear communication of individualized care plans, support from a single coordinator of care who could help prioritize their competing demands and continuity of relationships. They also desired providers who would listen to and acknowledge their needs, appreciate that these’ needs were unique and fluctuating and have a caring attitude. Conclusions. These respondents describe an ideal process of care that is patient centered and individualized and that supports their unique constellations of problems, shifting priorities and multidimensional decision making. Individual and ongoing care coordination managed by a primary contact person may meet some of these needs. Achieving these goals will require developing efficient methods of assessing patient care needs and flexible care management support systems that can respond to patients’ needs for different levels of support at different times.
ABSTRACT
We present results from a 577 ks XMM–Newton observation of SPT-CL J0459–4947, the most distant cluster detected in the South Pole Telescope 2500 square degree (SPT-SZ) survey, and currently ...the most distant cluster discovered through its Sunyaev–Zel’dovich effect. The data confirm the cluster’s high redshift, z = 1.71 ± 0.02, in agreement with earlier, less precise optical/IR photometric estimates. From the gas density profile, we estimate a characteristic mass of $M_{500}=(1.8\pm 0.2)\times 10^{14}\, {\rm M}_{\odot }$; cluster emission is detected above the background to a radius of $\sim \!2.2\, r_{500}$, or approximately the virial radius. The intracluster gas is characterized by an emission-weighted average temperature of 7.2 ± 0.3 keV and metallicity with respect to Solar of $Z/\, Z_{\odot }=0.37\pm 0.08$. For the first time at such high redshift, this deep data set provides a measurement of metallicity outside the cluster centre; at radii $r\gt 0.3\, r_{500}$, we find $Z/\, Z_{\odot }=0.33\pm 0.17$ in good agreement with precise measurements at similar radii in the most nearby clusters, supporting an early enrichment scenario in which the bulk of the cluster gas is enriched to a universal metallicity prior to cluster formation, with little to no evolution thereafter. The leverage provided by the high redshift of this cluster tightens by a factor of 2 constraints on evolving metallicity models, when combined with previous measurements at lower redshifts.
Aims
To evaluate the effectiveness of automated symptom and side effect monitoring on quality of life among individuals with symptomatic diabetic peripheral neuropathy.
Methods
We conducted a ...pragmatic, cluster randomized controlled trial (July 2014 to July 2016) within a large healthcare system. We randomized 1834 primary care physicians and prospectively recruited from their lists 1270 individuals with neuropathy who were newly prescribed medications for their symptoms. Intervention participants received automated telephone‐based symptom and side effect monitoring with physician feedback over 6 months. The control group received usual care plus three non‐interactive diabetes educational calls. Our primary outcomes were quality of life (EQ‐5D) and select symptoms (e.g. pain) measured 4–8 weeks after starting medication and again 8 months after baseline. Process outcomes included receiving a clinically effective dose and communication between individuals with neuropathy and their primary care provider over 12 months. Interviewers collecting outcome data were blinded to intervention assignment.
Results
Some 1252 participants completed the baseline measures mean age (sd): 67 (11.7), 53% female, 57% white, 8% Asian, 13% black, 20% Hispanic. In total, 1179 participants (93%) completed follow‐up (619 control, 560 intervention). Quality of life scores (intervention: 0.658 ± 0.094; control: 0.653 ± 0.092) and symptom severity were similar at baseline. The intervention had no effect on primary EQ‐5D: −0.002 (95% CI −0.01, 0.01), P = 0.623; pain: 0.295 (−0.75, 1.34), P = 0.579; sleep disruption: 0.342 (−0.18, 0.86), P = 0.196; lower extremity functioning: −0.079 (−1.27, 1.11), P = 0.896; depression: −0.462 (−1.24, 0.32); P = 0.247 or process outcomes.
Conclusions
Automated telephone monitoring and feedback alone were not effective at improving quality of life or symptoms for people with symptomatic diabetic peripheral neuropathy.
Trial Registration: ClinicalTrials.gov (NCT02056431).
What's new?
Frequent communication between individuals with diabetic peripheral neuropathy and primary care providers about symptoms and medication side effects is critical to optimizing medication dosing to treat painful diabetic peripheral neuropathy. Yet, there are considerable barriers to effective communication.
This cluster randomized controlled trial found that a brief intervention to automatically monitor person‐reported data on symptoms and side effects, and provide the information to physicians via an electronic health record was not effective in improving the outcomes valued by individuals with neuropathy.
Alerts alone are unlikely to change provider behaviour related to treatment intensification. More intensive interventions focused on individual activation or provider education may be more effective in changing prescribing behaviour and improving outcomes.
ABSTRACT
We use imaging from the first three years of the Dark Energy Survey to characterize the dynamical state of 288 galaxy clusters at 0.1 ≲ z ≲ 0.9 detected in the South Pole Telescope (SPT) ...Sunyaev–Zeldovich (SZ) effect survey (SPT-SZ). We examine spatial offsets between the position of the brightest cluster galaxy (BCG) and the centre of the gas distribution as traced by the SPT-SZ centroid and by the X-ray centroid/peak position from Chandra and XMM data. We show that the radial distribution of offsets provides no evidence that SPT SZ-selected cluster samples include a higher fraction of mergers than X-ray-selected cluster samples. We use the offsets to classify the dynamical state of the clusters, selecting the 43 most disturbed clusters, with half of those at z ≳ 0.5, a region seldom explored previously. We find that Schechter function fits to the galaxy population in disturbed clusters and relaxed clusters differ at z > 0.55 but not at lower redshifts. Disturbed clusters at z > 0.55 have steeper faint-end slopes and brighter characteristic magnitudes. Within the same redshift range, we find that the BCGs in relaxed clusters tend to be brighter than the BCGs in disturbed samples, while in agreement in the lower redshift bin. Possible explanations includes a higher merger rate, and a more efficient dynamical friction at high redshift. The red-sequence population is less affected by the cluster dynamical state than the general galaxy population.
The pulmonary and hepatic expression and catalytic activities of phase I and II drug-metabolizing enzymes were compared using human lung and liver tissue, and lung parenchymal cells (LPCs) and ...cryopreserved hepatocytes. Cytochrome P450 gene expression was generally lower in lung than in liver and CYP3A4 expression in lung was negligible. Esterase gene expression was similar in lung and liver. Expression of all sulfotransferase isoforms in lung was similar to or higher than that in liver. Lung tissue expressed low levels of UGT. However, the expression of UGT2A1 in lung was higher than that in liver. There was a range of catalytic activities in LPCs, including cytochrome P450, esterase, and sulfation pathways. Phase I activities were generally less than 10% of those determined in hepatocytes. Rates of ester hydrolysis and sulfation in LPCs were similar to those in hepatocytes. When measurable, glucuronidation in LPCs was present at very low levels, reflecting the gene expression data. The metabolism of salbutamol, formoterol, and budesonide was also investigated. Production of salbutamol-4-O-sulfate and budesonide oleate was observed in LPCs from at least two of three donor preparations studied. Formoterol sulfate and low levels of formoterol glucuronide were detected in one of three donors. In general, drug-metabolizing capability of LPCs is low compared with liver, although some evidence for substantial sulfation and deesterification capacity was observed. Therefore, these data support the use of this cell-based system for the investigation of key routes of xenobiotic metabolism in human lung parenchyma.
ABSTRACT PURPOSE Lower continuity of care has been associated with higher rates of adverse outcomes for persons with multiple chronic medical conditions. It is unclear, however, whether this ...relationship also exists within integrated systems that offer high levels of informational continuity through shared electronic health records. METHODS We conducted a retrospective cohort study of 12,200 seniors with 3 or more chronic conditions within an integrated delivery system. Continuity of care was calculated using the Continuity of Care Index, which reflects visit concentration with individual clinicians. Using Cox proportional hazards regression permitting continuity to vary monthly until the outcome or censoring event, we separately assessed inpatient admissions and emergency department visits as a function of primary care continuity and specialty care continuity. RESULTS After adjusting for covariates (demographics; baseline, primary, and specialty care visits; baseline outcomes; and morbidity burden), greater primary care continuity and greater specialty care continuity were each associated with a lower risk of inpatient admission (respective hazard ratios (95% CIs) = 0.97 (0.96, 0.99) and 0.95 (0.93, 0.98)) and a lower risk of emergency department visits (respective hazard ratios = 0.97 (0.96, 0.98) and 0.98 (0.96, 1.00)). For the subgroup with 3 or more primary care and 3 or more specialty care visits, specialty care continuity (but not primary care continuity) was independently associated with a decreased risk of inpatient admissions (hazard ratio = 0.94 (0.92, 0.97)), and primary care continuity (but not specialty care continuity) was associated with a decreased risk of emergency department visits (hazard ratio = 0.98 (0.96, 1.00)). CONCLUSIONS In an integrated delivery system with high informational continuity, greater continuity of care is independently associated with lower hospital utilization for seniors with multiple chronic medical conditions. Different subgroups of patients will benefit from continuity with primary and specialty care clinicians depending on their care needs.
We present a multi-wavelength analysis of the four most relaxed clusters in the South Pole Telescope 2500 deg2 survey, which lie at 0.55 < z < 0.75. This study, which utilizes new, deep data from the ...Chandra X-ray Observatory and Hubble Space Telescope, along with ground-based spectroscopy from Gemini and Magellan, improves significantly on previous studies in both depth and angular resolution, allowing us to directly compare to clusters at z ∼ 0. We find that the temperature, density, and entropy profiles of the intracluster medium (ICM) are very similar among the four clusters, and share similar shapes to those of clusters at z ∼ 0. Specifically, we find no evidence for deviations from self-similarity in the temperature profile over the radial range 10 kpc < r < 1 Mpc, implying that the processes responsible for preventing runaway cooling over the past 6 Gyr are, at least roughly, preserving self-similarity. We find typical metallicities of ∼0.3 Z in the bulk of the ICM, rising to ∼0.5 Z in the inner ∼100 kpc, and reaching ∼1 Z at r < 10 kpc. This central excess is similar in magnitude to what is observed in the most relaxed clusters at z ∼ 0, suggesting that both the global metallicity and the central excess that we see in cool core clusters at z ∼ 0 were in place very early in the cluster's lifetime, and specifically that the central excess is not due to late-time enrichment by the central galaxy. Consistent with observations at z ∼ 0, we measure a diversity of stellar populations in the central brightest cluster galaxies of these four clusters, with star formation rates spanning a factor of ∼500, despite the similarities in cooling time, cooling rate, and central entropy. These data suggest that, while the details vary dramatically from system to system, runaway cooling has been broadly regulated in relaxed clusters over the past 6 Gyr.
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