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Existing guidelines on overviews of reviews and umbrella reviews recommend an assessment of the certainty of evidence but provide limited guidance on how to apply GRADE to such a complex evidence synthesis. We present one approach to applying GRADE to an overview of reviews developed using general principles derived from current GRADE guidelines.
Methods
The methods were developed in an iterative and exploratory fashion following discussion with 11 methodologists and health services researchers. Key principles were distilled on the five GRADE domains (risk of bias, inconsistency, imprecision, indirectness, and publication bias) from the relevant GRADE guidelines, particularly those on test accuracy.
Results
A ‘general principles’ approach of applying the five domains of GRADE to an overview of reviews and arriving at an overall summary judgment for outcomes was developed. These methods were successfully applied to an overview of reviews on 18F-prostate specific membrane antigen positron emission tomography and computed tomography in the staging of patients with high-risk or recurrent prostate cancer.
Conclusions
Our approach distilled key principles from relevant GRADE guidelines and allowed us to apply GRADE to a complex body of evidence. Such an approach may be of interest to other researchers working on overviews of reviews or umbrella reviews.
We evaluated whether universal chlorhexidine bathing (decolonization) with or without COVID-19 intensive training impacted COVID-19 rates in 63 nursing homes (NHs) during the 2020–2021 Fall/Winter surge. Decolonization was associated with a 43% lesser rise in staff case-rates (P < .001) and a 52% lesser rise in resident case-rates (P < .001) versus control.
In much of the Western world, collaborative research undertaken by settler archaeologists readily lends itself, at least in part, to a continuation of the colonial project. Yet, against this backdrop, Australia's First Nations’ peoples continue to work with researchers and to drive systemic change in research practice. Community-engaged archaeology, defined here as codeveloped studies of ancestral places (following Schaepe et al. 2017), is directed to improving relationships between Indigenous peoples and archaeologists. Even so, the practice of archaeology with and for nonsettler communities remains underdeveloped with regard to institutional priorities and funding agency bureaucracies. Here, we (Mirarr Traditional Owners, Mirarr employees, and settler archaeologist researchers) reflect on these issues as part of our ongoing research on the ochres and bim (rock art) of the well-known Madjedbebe rockshelter in the Alligator Rivers region, Northern Territory, Australia.
To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Design:
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Setting:
Community settings and care homes in 26 UK centers.
Participants:
People with probable or possible Alzheimer’s disease and agitation.
Measurements:
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
Results:
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
Conclusions:
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms.
Design:
Multicenter retrospective cohort study.
Setting:
The study included 43 hospitals using a common infection prevention surveillance system.
Methods:
A space–time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods.
Results:
We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals’ surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work.
Conclusions:
Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.
The extent to which indices of maternal physiological arousal (skin conductance augmentation) and regulation (vagal withdrawal) while parenting predict infant attachment disorganization and behavior problems directly or indirectly via maternal sensitivity was examined in a sample of 259 mothers and their infants. Two covariates, maternal self-reported emotional risk and Adult Attachment Interview attachment coherence were assessed prenatally. Mothers' physiological arousal and regulation were measured during parenting tasks when infants were 6 months old. Maternal sensitivity was observed during distress-eliciting tasks when infants were 6 and 14 months old, and an average sensitivity score was calculated. Attachment disorganization was observed during the Strange Situation when infants were 14 months old, and mothers reported on infants' behavior problems when infants were 27 months old. Over and above covariates, mothers' arousal and regulation while parenting interacted to predict infant attachment disorganization and behavior problems such that maternal arousal was associated with higher attachment disorganization and behavior problems when maternal regulation was low but not when maternal regulation was high. This effect was direct and not explained by maternal sensitivity. The results suggest that maternal physiological dysregulation while parenting places infants at risk for psychopathology.
This Summary for Policymakers presents key findings from the Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX). The SREX approaches the topic by assessing the scientific literature on issues that range from the relationship between climate change and extreme weather and climate events (‘climate extremes’) to the implications of these events for society and sustainable development. The assessment concerns the interaction of climatic, environmental, and human factors that can lead to impacts and disasters, options for managing the risks posed by impacts and disasters, and the important role that non-climatic factors play in determining impacts. Box SPM.1 defines concepts central to the SREX.
The character and severity of impacts from climate extremes depend not only on the extremes themselves but also on exposure and vulnerability. In this report, adverse impacts are considered disasters when they produce widespread damage and cause severe alterations in the normal functioning of communities or societies. Climate extremes, exposure, and vulnerability are influenced by a wide range of factors, including anthropogenic climate change, natural climate variability, and socioeconomic development (Figure SPM.1). Disaster risk management and adaptation to climate change focus on reducing exposure and vulnerability and increasing resilience to the potential adverse impacts of climate extremes, even though risks cannot fully be eliminated (Figure SPM.2). Although mitigation of climate change is not the focus of this report, adaptation and mitigation can complement each other and together can significantly reduce the risks of climate change. [SYR AR4, 5.3]
Hematologic malignancies were the first human cancers to be studied in depth at the molecular level, and recent years have seen important advances in treatment. This comprehensive reference book covers the full range of hematologic malignancies, including all subtypes of leukemias, lymphomas, and plasma cell dyscrasias. Authored by internationally known experts, each chapter emphasizes diagnostic work-up, staging, and therapeutic approaches. Up-to-date hematopathology, treatment, and outcomes data are presented in a way which is directly applicable to patient care. Highly illustrated with color images, graphs, flowcharts and treatment algorithms, the book is perfect for quick clinical reference as well as providing detailed reference lists for further study. With its authoritative and practical focus and visually stimulating presentation, this is a key text for hematology and oncology fellows, physicians, oncology nurses, physician assistants and other healthcare workers in the field of oncology.
By
Karen W. L. Yee, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada,
Susan M. O'Brien, Hematopathology and Oncology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults in the Western world, accounting for nearly 25% of all leukemias with an estimated annual age-adjusted incidence of 3 per 100,000 persons in the United States. The median age at diagnosis is approximately 70 years, with 81% of the patients diagnosed when aged ≥ 60 years. Under the World Health Organization (WHO) classification, CLL is a B-cell neoplasm and the entity T-cell CLL has been reclassified as T-cell prolymphocytic leukemia (PLL). Recent data from the Surveillance, Epidemiology, and End Results (SEER) cancer statistics indicate that 5-year survival of patients with CLL is 73%.
Significant changes in the understanding and management of CLL have occurred in the last two decades. With the advent of newer treatment modalities, such as purine analogs and monoclonal antibodies, substantial improvements have been made in achieving complete responses (CR), with a proportion achieving molecular remissions and durable responses. Despite the advances in the treatment of patients with CLL, the majority of patients will relapse after primary therapy.
Diagnosis
The current diagnosis of CLL is based on minor modifications of the criteria originally proposed by the National Cancer Institute (NCI) (Table 5.1). A bone marrow evaluation is no longer required for diagnosis but is useful to determine the extent and pattern of involvement and to clarify the etiology of cytopenias.
The morphology and immunophenotype are adequate for diagnosis and to distinguish CLL from other disorders (Table 5.2).
A developmental cascade model of early emotional and social competence predicting later peer acceptance was examined in a community sample of 440 children across the ages of 2 to 7. Children's externalizing behavior, emotion regulation, social skills within the classroom and peer acceptance were examined utilizing a multitrait–multimethod approach. A series of longitudinal cross-lag models that controlled for shared rater variance were fit using structural equation modeling. Results indicated there was considerable stability in children's externalizing behavior problems and classroom social skills over time. Contrary to expectations, there were no reciprocal influences between externalizing behavior problems and emotion regulation, although higher levels of emotion regulation were associated with decreases in subsequent levels of externalizing behaviors. Finally, children's early social skills also predicted later peer acceptance. Results underscore the complex associations among emotional and social functioning across early childhood.