The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease‐oriented guidelines often inadequate and complicates clinical decision making. To address ...this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow‐up: strategies in care planning, self‐management and medication‐related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self‐management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.
Content List – Read more articles from the symposium: “Multimorbidity research at the cross‐roads: developing the evidence for clinical practice and health policy”.
Abstract
Ki67 immunohistochemistry (IHC), commonly used as a proliferation marker in breast cancer, has limited value for treatment decisions due to questionable analytical validity. The ...International Ki67 in Breast Cancer Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 IHC analytical validity and clinical utility in breast cancer, including the series of scoring studies the IKWG conducted on centrally stained tissues. Consensus observations and recommendations are: 1) as for estrogen receptor and HER2 testing, preanalytical handling considerations are critical; 2) a standardized visual scoring method has been established and is recommended for adoption; 3) participation in and evaluation of quality assurance and quality control programs is recommended to maintain analytical validity; and 4) the IKWG accepted that Ki67 IHC as a prognostic marker in breast cancer has clinical validity but concluded that clinical utility is evident only for prognosis estimation in anatomically favorable estrogen receptor–positive and HER2-negative patients to identify those who do not need adjuvant chemotherapy. In this T1-2, N0-1 patient group, the IKWG consensus is that Ki67 5% or less, or 30% or more, can be used to estimate prognosis. In conclusion, analytical validity of Ki67 IHC can be reached with careful attention to preanalytical issues and calibrated standardized visual scoring. Currently, clinical utility of Ki67 IHC in breast cancer care remains limited to prognosis assessment in stage I or II breast cancer. Further development of automated scoring might help to overcome some current limitations.
Managing mining of the deep seabed Wedding, L M; Reiter, S M; Smith, C R ...
Science,
07/2015, Letnik:
349, Številka:
6244
Journal Article
Recenzirano
Odprti dostop
Contracts are being granted, but protections are lagging
Interest in mining the deep seabed is not new; however, recent technological advances and increasing global demand for metals and rare-earth ...elements may make it economically viable in the near future (
1
). Since 2001, the International Seabed Authority (ISA) has granted 26 contracts (18 in the last 4 years) to explore for minerals on the deep seabed, encompassing ∼1 million km
2
in the Pacific, Atlantic, and Indian Oceans in areas beyond national jurisdiction (
2
). However, as fragile habitat structures and extremely slow recovery rates leave diverse deep-sea communities vulnerable to physical disturbances such as those caused by mining (
3
), the current regulatory framework could be improved. We offer recommendations to support the application of a precautionary approach when the ISA meets later this July.
Early warning systems (EWSs) are used to assist clinical judgment in the detection of acute deterioration to avoid or reduce adverse events including unanticipated cardiopulmonary arrest, admission ...to the intensive care unit and death. Sometimes healthcare professionals (HCPs) do not trigger the alarm and escalate for help according to the EWS protocol and it is unclear why this is the case. The aim of this qualitative evidence synthesis was to answer the question 'why do HCPs fail to escalate care according to EWS protocols?' The findings will inform the update of the National Clinical Effectiveness Committee (NCEC) National Clinical Guideline No. 1 Irish National Early Warning System (INEWS).
A systematic search of the published and grey literature was conducted (until February 2018). Data extraction and quality appraisal were conducted by two reviewers independently using standardised data extraction forms and quality appraisal tools. A thematic synthesis was conducted by two reviewers of the qualitative studies included and categorised into the barriers and facilitators of escalation. GRADE CERQual was used to assess the certainty of the evidence.
Eighteen studies incorporating a variety of HCPs across seven countries were included. The barriers and facilitators to the escalation of care according to EWS protocols were developed into five overarching themes: Governance, Rapid Response Team (RRT) Response, Professional Boundaries, Clinical Experience, and EWS parameters. Barriers to escalation included: Lack of Standardisation, Resources, Lack of accountability, RRT behaviours, Fear, Hierarchy, Increased Conflict, Over confidence, Lack of confidence, and Patient variability. Facilitators included: Accountability, Standardisation, Resources, RRT behaviours, Expertise, Additional support, License to escalate, Bridge across boundaries, Clinical confidence, empowerment, Clinical judgment, and a tool for detecting deterioration. These are all individual yet inter-related barriers and facilitators to escalation.
The findings of this qualitative evidence synthesis provide insight into the real world experience of HCPs when using EWSs. This in turn has the potential to inform policy-makers and HCPs as well as hospital management about emergency response system-related issues in practice and the changes needed to address barriers and facilitators and improve patient safety and quality of care.
Lecture is prominent, but practices vary
A large body of evidence demonstrates that strategies that promote student interactions and cognitively engage students with content (
1
) lead to gains in ...learning and attitudinal outcomes for students in science, technology, engineering, and mathematics (STEM) courses (
1
,
2
). Many educational and governmental bodies have called for and supported adoption of these student-centered strategies throughout the undergraduate STEM curriculum. But to the extent that we have pictures of the STEM undergraduate instructional landscape, it has mostly been provided through self-report surveys of faculty members, within a particular STEM discipline e.g., (
3
–
6
). Such surveys are prone to reliability threats and can underestimate the complexity of classroom environments, and few are implemented nationally to provide valid and reliable data (
7
). Reflecting the limited state of these data, a report from the U.S. National Academies of Sciences, Engineering, and Medicine called for improved data collection to understand the use of evidence-based instructional practices (
8
). We report here a major step toward a characterization of STEM teaching practices in North American universities based on classroom observations from over 2000 classes taught by more than 500 STEM faculty members across 25 institutions.
The modification of star formation (SF) in galaxy interactions is a complex process, with SF observed to be both enhanced in major mergers and suppressed in minor pair interactions. Such changes ...likely to arise on short time-scales and be directly related to the galaxy–galaxy interaction time. Here we investigate the link between dynamical phase and direct measures of SF on different time-scales for pair galaxies, targeting numerous star- formation rate (SFR) indicators and comparing to pair separation, individual galaxy mass and pair mass ratio. We split our sample into the higher (primary) and lower (secondary) mass galaxies in each pair and find that SF is indeed enhanced in all primary galaxies but suppressed in secondaries of minor mergers. We find that changes in SF of primaries are consistent in both major and minor mergers, suggesting that SF in the more massive galaxy is agnostic to pair mass ratio. We also find that SF is enhanced/suppressed more strongly for short-duration SFR indicators (e.g. Hα), highlighting recent changes to SF in these galaxies, which are likely to be induced by the interaction. We propose a scenario where the lower mass galaxy has its SF suppressed by gas heating or stripping, while the higher mass galaxy has its SF enhanced, potentially by tidal gas turbulence and shocks. This is consistent with the seemingly contradictory observations for both SF suppression and enhancement in close pairs.
When asked to perform the same task, different individuals exhibit markedly different patterns of brain activity. This variability is often attributed to volatile factors, such as task strategy or ...compliance. We propose that individual differences in brain responses are, to a large degree, inherent to the brain and can be predicted from task-independent measurements collected at rest. Using a large set of task conditions, spanning several behavioral domains, we train a simple model that relates task-independent measurements to task activity and evaluate the model by predicting task activation maps for unseen subjects using magnetic resonance imaging. Our model can accurately predict individual differences in brain activity and highlights a coupling between brain connectivity and function that can be captured at the level of individual subjects.
Summary Background In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive ...care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. Methods This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2 O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov , number NCT01396759. Findings Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk RR 0·27, 99·7% CI 0·07–0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11–2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07–0·89; p=0·022). Interpretation Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. Funding International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.
We use the first data release from the SINGG Ha survey of H i-selected galaxies to study the quantitative behavior of the diffuse, warm ionized medium (WIM) across the range of properties represented ...by these 109 galaxies. The mean fraction fwim of diffuse ionized gas in this sample is 0.59 plus or minus 0. 19, slightly higher than found in previous samples. Since lower surface brightness galaxies tend to have higher fwim, we believe that most of this difference is due to selection effects favoring large, optically bright, nearby galaxies with high star formation rates. As found in previous studies, there is no appreciable correlation with Hubble type or total star formation rate. However, we find that starburst galaxies, defined here by an Ha surface brightness > 2.5 x 10 super(39) erg super(-) sub(8) super(1) kpe super(-2) within the H alpha half-light radius, do show much lower fractions of diffuse Ha emission. The cause apparently is not dominated by a lower fraction of field OB stars. However, it is qualitatively consistent with an expected escape of ionizing radiation above a threshold star formation rate, predicted from our model in which the ISM is shredded by pressure-driven supernova feedback. The H i gas fractions in the starburst galaxies are also lower, suggesting that the starbursts are consuming and ionizing all the gas, and thus promoting regions of density-bounded ionization. If true, these effects Imply that some amount of Lyman continuum radiation is escaping from most starburst galaxies, and that WIM properties and outflows from mechanical feedback are likely to be pressure-driven. However, in view of previous studies showing that the escape fraction of ionizing radiation Is generally low, it is likely that other factors also drive the low fractions of diffuse ionized gas in starbursts.
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