Background Recent clinical practice guidelines have highlighted the importance of advance care planning (ACP) for improving end-of-life care for people with chronic kidney disease (CKD). Study Design ...We conducted a systematic integrative review of the literature to inform future ACP practice and research in CKD, searching electronic databases in April 2013. Synthesis used narrative methods. Setting & Population We focused on adults with a primary diagnosis of CKD in any setting. Selection Criteria for Studies We included studies of any design, quantitative or qualitative. Interventions ACP was defined as any formal means taken to ensure that health professionals and family members are aware of patients’ wishes for care in the event they become too unwell to speak for themselves. Outcomes Measures of all kinds were considered of interest. Results 55 articles met criteria reporting on 51 discrete samples. All patient samples included people with CKD stage 5; 2 also included patients with stage 4. Seven interventions were tested; all were narrowly focused and none was evaluated by comparing wishes for end-of-life care with care received. One intervention demonstrated effects on patient and family outcomes in the form of improved well-being and anxiety following sessions with a peer mentor. Insights from qualitative studies that have not been used to inform interventions include the importance of instilling patient confidence that their advance directives will be enacted and discussing decisions about (dis)continuing dialysis therapy separately from “aggressive” life-sustaining treatments (eg, ventilation). Limitations Although quantitative and qualitative findings were integrated according to best practice, methods for this are in their infancy. Conclusions Research on ACP in patients with CKD is limited, especially intervention studies. Interventions in CKD should attend to barriers and facilitators at the levels of patient, caregiver, health professional, and system. Intervention studies should measure impact on compliance with patient wishes for end-of-life care.
In 2007, the M-type binary Asteroid 22 Kalliope reached one of its annual equinoxes. As a consequence, the orbit plane of its small moon, Linus, was aligned closely to the Sun's line of sight, giving ...rise to a mutual eclipse season. A dedicated international campaign of photometric observations, based on amateur–professional collaboration, was organized and coordinated by the IMCCE in order to catch several of these events. The set of the compiled observations is released in this work. We developed a relevant model of these events, including a topographic shape model of Kalliope refined in the present work, the orbit solution of Linus as well as the photometric effect of the shadow of one component falling on the other. By fitting this model to the only two full recorded events, we derived a new estimation of the equivalent diameter of Kalliope of
166.2
±
2.8
km
, 8% smaller than its IRAS diameter. As to the diameter of Linus, considered as purely spherical, it is estimated to
28
±
2
km
. This substantial “shortening” of Kalliope, gives a bulk density of
3.35
±
0.33
g
/
cm
3
, significantly higher than past determinations but more consistent with its taxonomic type. Some constraints can be inferred on the composition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The fast-track registration policy of the South African National Department of Health allows for rapid registration of new medicines of public health importance and of all medicines on the Essential ...Medicines List, most of which are generics. No limit is placed on the number of generic brands of a medicine that can be submitted for fast-track registration. This, together with resource constraints at the regulator, may delay access to important new medicines, new fixed-dose combinations of critical medicines or affordable versions of biological medicines (biosimilars). One reason for not limiting the number of fast-track generic applications was to promote price competition among generic brands. We found this not to be valid, since market share correlated poorly with price. Generic brands with high market share were, mostly, those that were registered first. We propose that the number of generic brands accepted for fast-tracking be limited to not more than seven per medicine.
•People who had both type 2 diabetes and hypertension had larger volumes of perivascular spaces (PVS) in their white matter visible on MRI•In people with hypertension, PVS) mediated associations ...between type 2 diabetes and small vessel disease (SVD) markers, and SVD progression over 1 year•PVS may be a target to mitigate the impact of T2DM and hypertension on the small cerebral vessels
Type 2 diabetes mellitus (T2DM) and hypertension are established risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). Patients with neurodegenerative diseases were stratified by presence or absence of T2DM. MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, and PVS in the white matter (wmPVS) or basal ganglia (bgPVS). Patients with T2DM had greater wmPVS volume, but not other SVD volumes, and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Delivering uninterrupted cancer treatment to patients with musculoskeletal tumors has been essential during the rapidly evolving coronavirus 2019 (COVID-19) pandemic, as delays in management can be ...detrimental. Currently, the risk of contracting COVID-19 in hospitals when admitted for surgery and the susceptibility due to adjuvant therapies and associated mortality due to COVID-19 is unknown, but knowledge of these potential risks would help treating clinicians provide appropriate cancer care.
(1) What is the risk of hospital-acquired COVID-19 in patients with musculoskeletal tumors admitted for surgery during the initial period of the pandemic? (2) What is the associated mortality in patients with musculoskeletal tumors who have contracted COVID-19? (3) Are patients with musculoskeletal tumors who have had neoadjuvant therapy (chemotherapy or radiation) preoperatively at an increased risk of contracting COVID-19? (4) Is a higher American Society of Anesthesiologists (ASA) grade in patients with musculoskeletal tumors associated with an increased risk of contracting COVID-19 when admitted to the hospital for surgery?
This retrospective, observational study analyzed patients with musculoskeletal tumors who underwent surgery in one of eight specialist centers in the United Kingdom, which included the five designated cancer centers in England, one specialist soft tissue sarcoma center, and two centers from Scotland between March 12, 2020 and May 20, 2020. A total of 347 patients were included, with a median (range) age of 53 years (10 to 94); 60% (207 of 347) were men, and the median ASA grade was II (I to IV). These patients had a median hospital stay of 8 days (0 to 53). Eighteen percent (61 of 347) of patients had received neoadjuvant therapy (8% 27 chemotherapy, 8% 28 radiation, 2% 6 chemotherapy and radiation) preoperatively. The decision to undergo surgery was made in adherence with United Kingdom National Health Service and national orthopaedic oncology guidelines, but specific data with regard to the number of patients within each category are not known. Fifty-nine percent (204 of 347) were negative in PCR testing done 48 hours before the surgical procedure; the remaining 41% (143 of 347) were treated before preoperative PCR testing was made mandatory, but these patients were asymptomatic. All patients were followed for 30 days postoperatively, and none were lost to follow-up during that period. The primary outcome of the study was contracting COVID-19 in the hospital after admission. The secondary outcome was associated mortality after contracting COVID-19 within 30 days of the surgical procedure. In addition, we assessed whether there is any association between ASA grade or neoadjuvant treatment and the chances of contracting COVID-19 in the hospital. Electronic patient record system and simple descriptive statistics were used to analyze both outcomes.
Four percent (12 of 347) of patients contracted COVID-19 in the hospital, and 1% (4 of 347) of patients died because of COVID-19-related complications. Patients with musculoskeletal tumors who contracted COVID-19 had increased mortality compared with patients who were asymptomatic or tested negative (odds ratio 55.33 95% CI 10.60 to 289.01; p < 0.001).With the numbers we had, we could not show that adjuvant therapy had any association with contracting COVID-19 while in the hospital (OR 0.94 95% CI 0.20 to 4.38; p = 0.93). Increased ASA grade was associated with an increased likelihood of contracting COVID-19 (OR 58 95% CI 5 to 626; p < 0.001).
Our results show that surgeons must be mindful and inform patients that those with musculoskeletal tumors are at risk of contracting COVID-19 while admitted to the hospital and some may succumb to it. Hospital administrators and governmental agencies should be aware that operations on patients with lower ASA grade appear to have lower risk and should consider restructuring service delivery to ensure that procedures are performed in designated COVID-19-restricted sites. These measures may reduce the likelihood of patients contracting the virus in the hospital, although we cannot confirm a benefit from this study. Future studies should seek to identify factors influencing these outcomes and also compare surgical complications in those patients with and without COVID-19.
Level III, therapeutic study.
ATP Binding Cassette (ABC) transporters play prominent roles in numerous cellular processes and many have been implicated in human diseases. Unfortunately, detailed mechanistic information on the ...majority of ABC transporters has not yet been elucidated. The slow rate of progress of molecular and high resolution structural studies may be attributed to the difficulty in the investigation of integral membrane proteins. These difficulties include the expression of functional, non-aggregated protein in heterologous systems. Furthermore, the extraction of membrane proteins from source material remains a major bottle-neck in the process since there are relatively few guidelines for selection of an appropriate detergent to achieve optimal extraction. Whilst affinity tag strategies have simplified the purification of membrane proteins; many challenges remain. For example, the chromatographic process and associated steps can rapidly lead to functional inactivation, random aggregation, or even precipitation of the target protein. Furthermore, optimisation of high yield and purity, does not guarantee successful structure determination. Based on this series of potential issues, any investigation into structure–function of membrane proteins requires a systematic evaluation of preparation quality. In particular, the evaluation should focus on function, homogeneity and mono-dispersity. The present investigation provides a detailed assessment of the quality of purified ATP Binding Cassette (ABC) transporters; namely ABCB1 (P-gp) and ABCA4 (ABCR). A number of suggestions are provided to facilitate the production of functional, homogeneous and mono-disperse preparations using the insect cell expression system. Finally, the ABCA4 samples have been used to provide structural insights into this essential photo-receptor cell protein.
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•ABCB1 and ABCA4 could be isolated to high purity; however, the proteins exhibited heterogeneity.•Removal of imidazole generates greater homogeneity of both proteins.•A cholesterol derivative ensures retention of function and improved homogeneity of ABCB1.•Low resolution structural data for ABCA4 were generated using electron microscopy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A range of commercially important powders (hydrated alumina, a silica aerogel, limestone, titania and zeolite) was attached to atomic force microscopy (AFM) cantilevers, and force–distance curves ...were studied for particle–particle and particle–wall contacts as a function of relative humidity (10–90%RH). The single-particle behaviour was compared with observations from bulk cohesion testers. Topographic images of particles were also acquired to compare surface morphology and roughness. The particle–particle pull-off forces with weak cantilevers (spring constant 0.032–0.064 N/m) were reproducible for a given material and rather similar (5–15 nN) for all materials in dry air. Alumina and limestone showed simple force curves with no significant RH dependence. No particle size effects were apparent in alumina (6 and 60 μm), in contrast to the behaviour in cohesion testers. The other materials showed more complex force curve behaviour. Zeolite showed adhesion increasing strongly with RH and evidence for stable liquid bridges, possibly associated with this material's special pore structure. Coated silica aerogel showed long-range charging effects. Most materials showed much larger particle–wall (steel) adhesion than particle–particle adhesion, with the exception of titania. This behaviour may be linked with particle size and wall roughness and is relevant to cohesion testers. The adhesion studies, together with parallel work on friction described elsewhere, form the basis of an ongoing study linking the single-particle and bulk behaviour.
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