The surprise question is a validated tool for identifying patients with increased risk of death within one year who could, therefore, benefit from palliative care. However, its utility in surgery is ...unknown.
We sought to determine whether the surprise question predicted 12-month mortality in older emergency general surgery patients.
This was a prospective cohort study.
Emergency general surgery attendings and surgical residents in or beyond their third year of training at a single tertiary care academic hospital from January to July 2014.
Surgeons responded to the surprise question within 72 hours of evaluating patients, ≥65 years, hospitalized with an acute surgical condition. Patient data, including demographic and clinical characteristics, were extracted from the medical record. Mortality within 12 months of initial evaluation was determined by using Social Security death data.
Ten attending surgeons and 18 surgical residents provided 163 responses to the surprise question for 119 patients: 60% of responses were "No, I would not be surprised" and 40% were "Yes, I would be surprised." A "No" response was associated with increased odds of death within 12 months in binary logistic regression (OR 4.8 95% CI 2.1-11.1).
The surprise question is a valuable tool for identifying older patients with higher risk of death, and it may be a useful screening criterion for older emergency general surgery patients who would benefit from palliative care evaluation.
Although many factors have been proposed to trigger symptom exacerbations (flares) in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, ...few studies have investigated these factors empirically. Therefore, we embedded a case-crossover study in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain longitudinal study to evaluate a range of patient reported triggers.
We assessed exposure to proposed triggers, including diet, physical activities, sedentary behaviors, stress, sexual activities, infection-like symptoms and allergies, by questionnaire a maximum of 3 times when participants reported flares and at 3 randomly selected times. We compared participant preflare to nonflare exposures by conditional logistic regression.
In our full analytical sample of 292 participants only 2 factors, including recent sexual activity (OR 1.44, 95% CI 1.06–1.96) and urinary tract infection symptoms (OR 3.39, 95% CI 2.02–5.68), which may overlap with those of flares, were associated with flare onset. On subanalyses restricted to flares with specific suspected triggers additional positive associations were observed for some factors such as certain dietary factors, abdominal muscle exercises, and vaginal infection-like symptoms and fever, but not for other factors (eg stress).
Except for sexual activity our findings suggest that patient reported triggers may be individual or group specific, or they may not contribute to flares. These findings suggest caution in following rigid, global flare prevention strategies and support additional research to develop evidence-based strategies.
The aims of this study were to assess for changes in uninsured rates among trauma patients at age 64 versus 65 years and whether there are associated changes in post-discharge rehabilitation; ...determine whether changes are driven by rehabilitation provided at home, skilled nursing facilities (SNFs), or acute inpatient facilities; and determine whether changes vary among stratified subgroups of trauma-related "best-practice" factors.
Rehabilitation is an important component of high-quality trauma systems with access heavily influenced by insurance status. In the wake of policy changes affecting insurance coverage, it remains unknown the extent to which insurance changes associate with variations in rehabilitation access/use among otherwise similar patients.
Regression discontinuity models were used to assess for changes in insurance status and rehabilitation at age 64 versus 65 years among adults ages 54 to 75 years (±10 years age-related Medicare eligibility). Data were extracted from the 2007-2012 National Trauma Data Bank.
A total of 305,198 patients were included; 40.1% were discharged to rehabilitation. Medicare eligibility was associated with an abrupt 6.4 (95% confidence interval: 5.8-7.0) percentage-point decline in uninsured and a 9.6 (95% confidence interval: 6.5-12.6) percentage-point increase in rehabilitation at age 64 versus 65 years, enabling an additional 1-in-10 patients to access rehabilitation. Differences were driven by SNF use and were greatest among patients with less-severe clinical presentations. Restriction based on Medicare-payment eligibility to patients with length of stay ≥3days (SNF requirement) and ≥1 "presumptive diagnosis codes" (inpatient facilities' 60% rule) demonstrated abrupt gains in both SNF and inpatient care.
The results reveal the magnitude of changes in access to rehabilitation associated with changes in insurance coverage at age 65 years. Use of quasiexperimental models enabled meaningful consideration of health-policy change.
Body size is key to many life-history processes, including reproduction. Across species, climate change and other stressors have caused reductions in the body size to which animals can grow, called ...asymptotic size, with consequences for demography. A reduction in mean asymptotic length was documented for critically endangered North Atlantic right whales, in parallel with declines in health and vital rates resulting from human activities and environmental changes. Here, we tested whether smaller body size was associated with lower reproductive output, using a state-space model for individual health, survival and reproduction that quantifies the mechanistic links between these processes. Body size (as represented by the cube of length) was strongly associated with a female's calving probability at each reproductive opportunity. This relationship explained 62% of the variation in calving among reproductive females, along with their decreasing health (20%). The effects of decreasing mean body size on reproductive performance are another concerning indication of the worsening prospects for this species and many others affected by environmental change, requiring a focus of conservation and management interventions on improving conditions that affect reproduction as well as reducing mortality.
Trauma is the leading cause of death and disability among young adults, who are also among the most likely to be uninsured. Efforts to increase insurance coverage, including passage of the Patient ...Protection and Affordable Care Act (ACA), were intended to improve access to care and promote improvements in outcomes. However, despite reported gains in coverage, the ACA's success in promoting use of high-quality care and enacting changes in clinical end points remains unclear.
To assess for observed changes in insurance coverage and rehabilitation use among young adult trauma patients associated with the ACA, including the Dependent Coverage Provision (DCP) and Medicaid expansion/open enrollment, and to consider possible insurance and rehabilitation differences between DCP-eligible vs -ineligible patients and among stratified demographic and community subgroups.
A longitudinal assessment of DCP implementation and Medicaid expansion/open enrollment using risk-adjusted before-and-after, difference-in-difference, and interrupted time-series analyses was conducted. Eleven years (January 1, 2005, to September 31, 2015) of Maryland Health Services Cost Review Commission data, representing complete patient records from all payers within the state, were used to identify all hospitalized young adult (aged 18-34 years) trauma patients in Maryland during the study period.
Of the 69 507 hospitalized patients included, 50 548 (72.7%) were male, and the mean (SD) age was 25 (5) years. Before implementation of the DCP, 1 of 4 patients was uninsured. After ACA implementation, the number fell to less than 1 of 10, with similar patterns emerging in emergency department and outpatient settings. The change was primarily driven by Medicaid expansion/open enrollment, which corresponded to a 20.1 percentage-point increase in Medicaid (95% CI, 18.9-21.3) and an 18.2 percentage-point decrease in uninsured (95% CI, -19.3 to -17.2). No changes were detected among privately insured patients. Rehabilitation use increased by 5.4 percentage points (95% CI, 4.5-6.2)-a 60% relative increase from a baseline of 9%. Mortality (-0.5; 95% CI, -0.9 to -0.1) and failure-to-rescue rates (-4.5; 95% CI, -7.4 to -1.6) also significantly declined. Stratified changes point to significant differences in the percentage of uninsured patients and rehabilitation access across the board, mitigating or even eradicating disparities in certain cases.
For patients who are injured, young, and uninsured, Medicaid expansion/open enrollment in Maryland changed insurance coverage and altered patient outcomes in ways that the DCP alone was never intended to do. Implementation of Medicaid expansion/open enrollment transformed the landscape of trauma coverage, directly affecting the health of one of the country's most vulnerable at-risk groups.
Human induced pluripotent stem cells (iPSCs) are a valuable tool for studying the cardiac developmental process in vitro, and cardiomyocytes derived from iPSCs are a putative cell source for ...personalized medicine. Changes in mitochondrial morphology have been shown to occur during cellular reprogramming and pluripotent stem cell differentiation. However, the relationships between mitochondrial dynamics and cardiac mesoderm commitment of iPSCs remain unclear. Here we demonstrate that changes in mitochondrial morphology from a small granular fragmented phenotype in pluripotent stem cells to a filamentous reticular elongated network in differentiated cardiomyocytes are required for cardiac mesodermal differentiation. Genetic and pharmacological inhibition of the mitochondrial fission protein, Drp1, by either small interfering RNA or Mdivi-1, respectively, increased cardiac mesoderm gene expression in iPSCs. Treatment of iPSCs with Mdivi-1 during embryoid body formation significantly increased the percentage of beating embryoid bodies and expression of cardiac-specific genes. Furthermore, Drp1 gene silencing was accompanied by increased mitochondrial respiration and decreased aerobic glycolysis. Our findings demonstrate that shifting the balance of mitochondrial morphology toward fusion by inhibition of Drp1 promoted cardiac differentiation of human iPSCs with a metabolic shift from glycolysis towards oxidative phosphorylation. These findings suggest that Drp1 may represent a new molecular target for future development of strategies to promote the differentiation of human iPSCs into cardiac lineages for patient-specific cardiac regenerative medicine.
Although the role of ETS family transcriptional factor PU.1 is well established in macrophage maturation, its role in mature macrophages with reference to sepsis- related animal model has not been ...elucidated. Here, we report the in vivo function of PU.1 in mediating mature macrophage inflammatory phenotype by using bone marrow chimera mice with conditional PU.1 knockout. We observed that the expression of monocyte/macrophage-specific markers CD 11b, F4/80 in fetal liver cells, and bone marrow–derived macrophages were dependent on functional PU.1. Systemic inflammation as measured in terms of NF-κB reporter activity in lung, liver, and spleen tissues was significantly decreased in PU.1-deficient chimera mice compared with wild-type chimeras on lipopolysaccharide (LPS) challenge. Unlike wild-type chimera mice, LPS challenge in PU.1-deficient chimera mice resulted in decreased lung neu-trophilic inflammation and myeloperoxidase activity. Similarly, we found attenuated inflammatory gene expression (cyclooxygenase-2, inducible nitric-oxide synthase, and TLR4) and inflammatory cytokine secretion (IL-6, MCP-1, IL-1β, TNF-α, and neutrophilic chemokine keratinocyte-derived chemokine) in PU.1-deficient mice. Most importantly, this attenuated lung and systemic inflammatory phenotype was associated with survival benefit in LPS-challenged heterozygotic PU.1-deficient mice, establishing a novel protective mechanistic role for the lineage-specific transcription factor PU.1.
A substantial proportion of adverse intraoperative events are attributed to failures in nontechnical skills. To strengthen these skills and improve surgical safety, the Non-Technical Skills for ...Surgeons (NOTSS) taxonomy was developed as a common framework. The NOTSS taxonomy was adapted for low- and middle-income countries, where variable resources pose a significant challenge to safe surgery. The NOTSS for variable-resource contexts (VRC) curriculum was developed and implemented in Rwanda, with the aim of enhancing knowledge and attitudes about nontechnical skills and promoting surgical safety.
The NOTSS-VRC curriculum was developed through a rigorous process of integrating contextually appropriate values. It was implemented as a 1-day training course for surgical and anesthesia postgraduate trainees. The curriculum comprises lectures, videos, and group discussions. A pretraining and posttraining questionnaire was administered to compare knowledge and attitudes regarding nontechnical skills, and their potential to improve surgical safety.
The setting of this study was in the tertiary teaching hospital of Kigali, Rwanda.
Participants were residents of the University of Kigali. A total of 55 residents participated from general surgery (31.4%), obstetrics (25.5%), anesthesia (17.6%), and other surgical specialties (25.5%).
In a paired analysis, understanding of NOTSS improved significantly (55.6% precourse, 80.9% postcourse, p<0.01). All residents reported that the course would improve their ability to provide safer patient care, and 97.4% believed developing nontechnical skills would improve patient outcomes.
Nontechnical skills must be highlighted in surgical training in low- and middle-income countries. The NOTSS-VRC curriculum can be implemented without additional technology or significant financial cost. Its deliberate design for resource-constrained settings allows it to be used both as an educational course and a quality improvement strategy. Our research demonstrates it is feasible to improve knowledge and attitudes about NOTSS through a 1-day course, and represents a novel approach to improving global surgical safety.
Up to 40% of the world's population is at risk for Plasmodium vivax malaria, a disease that imposes a major public health and economic burden on endemic countries. Because P. vivax produces latent ...liver forms, eradication of P. vivax malaria is more challenging than it is for P. falciparum. Genetic analysis of P. vivax is exceptionally difficult due to limitations of in vitro culture. To overcome the barriers to traditional molecular biology in P. vivax, we examined parasite transcriptional changes in samples from infected patients and mosquitoes in order to characterize gene function, define regulatory sequences and reveal new potential vaccine candidate genes.
We observed dramatic changes in transcript levels for various genes at different lifecycle stages, indicating that development is partially regulated through modulation of mRNA levels. Our data show that genes involved in common biological processes or molecular machinery are co-expressed. We identified DNA sequence motifs upstream of co-expressed genes that are conserved across Plasmodium species that are likely binding sites of proteins that regulate stage-specific transcription. Despite their capacity to form hypnozoites we found that P. vivax sporozoites show stage-specific expression of the same genes needed for hepatocyte invasion and liver stage development in other Plasmodium species. We show that many of the predicted exported proteins and members of multigene families show highly coordinated transcription as well.
We conclude that high-quality gene expression data can be readily obtained directly from patient samples and that many of the same uncharacterized genes that are upregulated in different P. vivax lifecycle stages are also upregulated in similar stages in other Plasmodium species. We also provide numerous examples of how systems biology is a powerful method for determining the likely function of genes in pathogens that are neglected due to experimental intractability.
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