In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor α (anti-TNFα) therapy are unknown.
At Kaiser Permanente Northern ...California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000-2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure.
Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02).
Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.
Objective
Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown ...whether time‐averaged disease activity in RA correlates with CV events.
Methods
We studied patients with RA whose cases were followed in a longitudinal US‐based registry. Time‐averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes.
Results
A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person‐years (95% confidence interval 95% CI 6.7–8.9). In models adjusted for variables noted above, a 10‐point reduction in the time‐averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13–29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable.
Conclusion
Our findings showed that reduced time‐averaged disease activity in RA is associated with fewer CV events.
The prediction of a supersonic solar wind
was first confirmed by spacecraft near Earth
and later by spacecraft at heliocentric distances as small as 62 solar radii
. These missions showed that plasma ...accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy
. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams
. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii
, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age
.
Summary
Prior national cost estimates of osteoporosis and fractures in the USA have been based on diverse sets of provider data or selected commercial insurance claims. Based on a random ...population-based sample of older adults, the US medical cost of osteoporosis and fractures is estimated at $22 billion in 2008.
Introduction
National cost estimates of osteoporosis and fractures in the USA have been based on diverse sets of provider data or selected commercial insurance claims. We sought to characterize prevalence and costs for osteoporosis using a random population-based sample of older adults.
Methods
A cross-sectional estimate of medical cost was made with 2002 data from the Medicare Current Beneficiary Survey (MCBS). MCBS combines health interviews with claims information from all payers to profile a random sample of 12,700 Medicare recipients. Three cohorts aged 65 or over were defined: (1) patients experiencing a fracture-related claim in 2002; (2) patients with a diagnosis, medication, or self-report for osteoporosis or past hip fracture; and (3) non-case controls. The total cost of patient claims was compared to that of controls using multiple regression.
Results
Of 30.2 million elderly Medicare recipients in 2002, 1.6 million (5%) were treated for a fracture that year, and an additional 7.2 million (24%) have osteoporosis without a fracture. The estimated mean impact of fractures on annual medical cost was $8,600 (95% confidence interval, $6,400 to $10,800), implying a US cost of $14 billion ($10 to $17 billion). Half of the non-fracture osteoporosis patients received drug treatment, averaging $500 per treated patient, or $2 billion nationwide.
Conclusions
The annual cost of osteoporosis and fractures in the US elderly was estimated at $16 billion, using a national 2002 population-based sample. This amount corroborates previous estimates based on substantially different methodologies. Projected to 2008, the national cost of osteoporosis and fractures was $22 billion.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. For many patients, maximal therapy for COPD produces only modest or incomplete relief of ...disabling symptoms and these symptoms result in a significantly reduced quality of life. Despite the high morbidity and mortality associated with severe COPD, many patients receive inadequate palliative care. There are several reasons for this. First, patient-physician communication about palliative and end-of-life care is infrequent and often of poor quality. Secondly, the uncertainty in predicting prognosis for patients with COPD makes communication about end-of-life care more difficult. Consequently, patients and their families frequently do not understand that severe COPD is often a progressive and terminal illness. The purpose of the present review is to summarise recent research regarding palliative and end-of-life care for patients with COPD. Recent studies provide insight and guidance into ways to improve communication about end-of-life care and thereby improve the quality of palliative and end-of-life care the patients receive. Two areas that may influence the quality of care are also highlighted: 1) the role of anxiety and depression, common problems for patients with COPD; and 2) the importance of advance care planning. Improving communication represents an important opportunity for the improvement of the quality of palliative and end-of-life care received by these patients.
We present a new determination of the ultraviolet (UV) galaxy luminosity function (LF) at redshift z 7 and 8, and a first estimate at z 9. An accurate determination of the form and evolution of the ...galaxy LF during this era is of key importance for improving our knowledge of the earliest phases of galaxy evolution and the process of cosmic reionization. Our analysis exploits to the full the new, deepest Wide Field Camera 3/infrared imaging from our Hubble Space Telescope (HST) Ultra-Deep Field 2012 (UDF12) campaign, with dynamic range provided by including a new and consistent analysis of all appropriate, shallower/wider area HST survey data. Our new measurement of the evolving LF at z 7 to 8 is based on a final catalogue of 600 galaxies, and involves a step-wise maximum-likelihood determination based on the photometric redshift probability distribution for each object; this approach makes full use of the 11-band imaging now available in the Hubble Ultra-Deep Field (HUDF), including the new UDF12 F140W data, and the latest Spitzer IRAC imaging. The final result is a determination of the z 7 LF extending down to UV absolute magnitudes M
1500 = −16.75 (AB mag) and the z 8 LF down to M
1500 = −17.00. Fitting a Schechter function, we find M1500
* = −19.90+0.23
−0.28, log φ* = −2.96+0.18
−0.23 and a faint-end slope α = −1.90+0.14
−0.15 at z 7, and M1500* = −20.12+0.37
−0.48, log φ* = −3.35+0.28
−0.47 and α = −2.02+0.22
+0.23 at z 8. These results strengthen previous suggestions that the evolution at z > 7 appears more akin to 'density evolution' than the apparent 'luminosity evolution' seen at z 5 − 7. We also provide the first meaningful information on the LF at z 9, explore alternative extrapolations to higher redshifts, and consider the implications for the early evolution of UV luminosity density. Finally, we provide catalogues (including derived z
phot, M
1500 and photometry) for the most robust z ∼ 6.5-11.9 galaxies used in this analysis. We briefly discuss our results in the context of earlier work and the results derived from an independent analysis of the UDF12 data based on colour-colour selection.
Summary
An analysis of United States (US) Medicare claims data from 2002 to 2015 for women aged ≥ 65 years found that age-adjusted hip fracture rates for 2013, 2014, and 2015 were higher than ...projected, resulting in an estimated increase of more than 11,000 hip fractures.
Introduction
Hip fractures are a major public health concern due to high morbidity, mortality, and healthcare expenses. Previous studies have reported a decrease in the annual incidence of hip fractures in the US beginning in 1995, coincident with the introduction of modern diagnostic tools and therapeutic agents for osteoporosis. In recent years, there has been less bone density testing and fewer prescriptions for osteoporosis treatments. The large osteoporosis treatment gap raises concern of possible adverse effects on hip fracture rates.
Methods
We assessed hip fracture incidence in the US to determine if the previous decline in hip fracture incidence continued. Using 2002 to 2015 Medicare Part A and Part B claims for women ≥ 65 years old, we calculated age-adjusted hip fracture rates, weighting to the 2014 population.
Results
We found that hip fracture rates declined each year from 2002 to 2012 and then plateaued at levels higher than projected for years 2013, 2014, and 2015.
Conclusions
The plateau in age-adjusted hip fracture incidence rate resulted in more than 11,000 additional estimated hip fractures over the time periods 2013, 2014, and 2015. We recommend further study to assess all factors contributing to this remarkable change in hip fracture rate and to develop strategies to reduce the osteoporosis treatment gap.
Purpose
Prior studies identified high variability in prevalence of withdrawal of life-sustaining treatment in the ICU. Variability in end-of-life decision-making has been reported at many levels: ...between countries, ICUs, and individual intensivists. We performed a systematic review examining regional, national, inter-hospital, and inter-physician variability in withdrawal of life-sustaining treatment in the ICU.
Methods
Using a predefined search strategy, we queried three electronic databases for peer-reviewed articles addressing withdrawal of life-sustaining treatment in adult patients in the ICU. Data were analyzed for variability in prevalence of withdrawal of life-sustaining treatment. Withholding of life-sustaining treatment was also examined where information was provided. An assessment tool was developed to quantify the risk of bias in the included articles.
Results
We identified 1284 studies, with 56 included after review. Most studies had unclear or high risk of bias, primarily due to unclear case definitions or potential confounding. The mean prevalence of withdrawal of life-sustaining treatment for patients who died varied from 0 to 84.1 % between studies, with standard deviation of 23.7 %. Sensitivity analysis of general ICU patients yielded similar results. Withholding also varied between 5.3 and 67.3 % (mean 27.3, SD 18.5 %). Substantial variability was found between world regions, countries, individual ICUs within a country, and individual intensivists within one ICU.
Conclusions
We identified substantial variability in the withdrawal of life-sustaining treatment across world regions and countries. Similar variability existed between ICUs within countries and even between providers within the same ICU. Further study is necessary, and could lead to interventions to improve end-of-life care in the ICU.
Switchbacks (rotations of the magnetic field) are observed on the Parker Solar Probe. Their evolution, content, and plasma effects are studied in this paper. The solar wind does not receive a net ...acceleration from switchbacks that it encountered upstream of the observation point. The typical switchback rotation angle increased with radial distance. Significant Poynting fluxes existed inside, but not outside, switchbacks, and the dependence of the Poynting flux amplitude on the switchback radial location and rotation angle is explained quantitatively as being proportional to (B sin(θ))2. The solar wind flow inside switchbacks was faster than that outside due to the frozen-in ions moving with the magnetic structure at the Alfvén speed. This energy gain results from the divergence of the Poynting flux from outside to inside the switchback, which produces a loss of electromagnetic energy on switchback entry and recovery of that energy on exit, with the lost energy appearing in the plasma flow. Switchbacks contain 0.3-10 Hz waves that may result from currents and the Kelvin-Helmholtz instability that occurs at the switchback boundaries. These waves may combine with lower frequency magnetohydrodynamic waves to heat the plasma.
We use the new ultra-deep, near-infrared imaging of the Hubble Ultra-Deep Field (HUDF) provided by our UDF12 Hubble Space Telescope (HST) Wide Field Camera 3/IR campaign to explore the rest-frame ...ultraviolet (UV) properties of galaxies at redshifts z > 6.5. We present the first unbiased measurement of the average UV power-law index, 〈β〉, (f
λ ∝ λβ) for faint galaxies at z 7, the first meaningful measurements of 〈β〉 at z 8, and tentative estimates for a new sample of galaxies at z 9. Utilizing galaxy selection in the new F140W (J
140) imaging to minimize colour bias, and applying both colour and power-law estimators of β, we find 〈β〉 = −2.1 ± 0.2 at z 7 for galaxies with M
UV −18. This means that the faintest galaxies uncovered at this epoch have, on average, UV colours no more extreme than those displayed by the bluest star-forming galaxies at low redshift. At z 8 we find a similar value, 〈β〉 = −1.9 ± 0.3. At z 9, we find 〈β〉 = −1.8 ± 0.6, essentially unchanged from z 6 to 7 (albeit highly uncertain). Finally, we show that there is as yet no evidence for a significant intrinsic scatter in β within our new, robust z 7 galaxy sample. Our results are most easily explained by a population of steadily star-forming galaxies with either solar metallicity and zero dust, or moderately sub-solar ( 10-20 per cent) metallicity with modest dust obscuration (A
V
0.1-0.2). This latter interpretation is consistent with the predictions of a state-of-the-art galaxy-formation simulation, which also suggests that a significant population of very-low metallicity, dust-free galaxies with β −2.5 may not emerge until M
UV > −16, a regime likely to remain inaccessible until the James Webb Space Telescope.
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