Worldwide economic losses from extreme weather events (EWE) have increased over recent decades, with significant geographic heterogeneity in damages. The IPCC defines the risk from EWE as a function ...of the climate hazard, socioeconomic exposure, and vulnerability. Although these three drivers vary at fine spatial scales, spatial variability largely has been overlooked in assessments of the drivers of economic loss from EWE. Using cluster analysis, we developed a novel socio-climate hazard typology (SCT) that integrates locally defined climate hazard and socioeconomic exposure and social vulnerability typologies. The results identified 838 unique SCT types impacted by EWE across the Gulf Coastal United States during 1981-2010. We regressed the SCT types and their constituent hazard and socioeconomic components against the cumulative economic loss (1981-2010) from EWE for each SCT type. Across the landscape, economic damages of SCT types were determined by unique, spatially explicit combinations of different risk factors, even in explaining the same level of economic loss. For example, multi-billion-dollar damages in the central Gulf Coast and peninsular Florida were explained by different drivers of risk, with damages in the former explained by additive interaction between climate hazard and multiplicative interaction between climate hazard and socioeconomic exposure and vulnerability, and in the latter explained by socioeconomic exposure and vulnerability. These results highlight the need to diagnose additive and multiplicative interactions among drivers of EWE risk in a spatially explicit context.
Critically ill patients can develop acute respiratory failure requiring endotracheal intubation. Swallowing dysfunction after liberation from mechanical ventilation, also known as post-extubation ...dysphagia, is common and deleterious among patients without neurologic disease. However, the risk factors associated with the development of post-extubation dysphagia and its effect on hospital lengthofstay in critically ill patients with neurologic disorders remains relatively unexplored.
We conducted a retrospective, observational cohort study from 2008 to 2010 of patients with neurologic impairment who required mechanical ventilation and subsequently received a bedside swallow evaluation (BSE) by a speech-language pathologist.
A BSE was performed after mechanical ventilation in 25% (630/2,484) of all patients. In the 184 patients with neurologic impairment, post-extubation dysphagia was present in 93% (171/184), and was classified as mild, moderate, or severe in 34% (62/184), 26% (48/184), and 33% (61/184), respectively. In univariate analyses, statistically significant risk factors for moderate/severe dysphagia included longer durations of mechanical ventilation and the presence of a tracheostomy. In multivariate analysis, adjusting for age, tracheostomy, cerebrovascular disease, and severity of illness, mechanical ventilation for >7 days remained independently associated with moderate/severe dysphagia (adjusted odds ratio=4.48 (95%confidence interval=2.14 to 9.81), P<0.01). The presence of moderate/severe dysphagia was also significantly associated with prolonged hospital lengthofstay, discharge status, and surgical placement of feeding tubes. When adjusting for age, severity of illness, and tracheostomy, patients with moderate/severe dysphagia stayed in the hospital 4.32 days longer after their initial BSE than patients with none/mild dysphagia (95% confidence interval=3.04 to 5.60 days, P<0.01).
In a cohort of critically ill patients with neurologic impairment, longer duration of mechanical ventilation is independently associated with post-extubation dysphagia, and the development of post-extubation dysphagia is independently associated with a longer hospital length of stay after the initial BSE.
Patient-reported outcomes (PROs) play an increasingly important role in clinical practice and research. Modern psychometric methods such as item response theory (IRT) enable the creation of item ...banks that support fixed-length forms as well as computerized adaptive testing (CAT), often resulting in improved measurement precision and responsiveness. Here we describe and discuss the case for developing an international core set of PROs building from the US PROMIS® network.PROMIS is a U.S.-based cooperative group of research sites and centers of excellence convened to develop and standardize PRO measures across studies and settings. If extended to a global collaboration, PROMIS has the potential to transform PRO measurement by creating a shared, unifying terminology and metric for reporting of common symptoms and functional life domains. Extending a common set of standardized PRO measures to the international community offers great potential for improving patient-centered research, clinical trials reporting, population monitoring, and health care worldwide. Benefits of such standardization include the possibility of: international syntheses (such as meta-analyses) of research findings; international population monitoring and policy development; health services administrators and planners access to relevant information on the populations they serve; better assessment and monitoring of patients by providers; and improved shared decision making.The goal of the current PROMIS International initiative is to ensure that item banks are translated and culturally adapted for use in adults and children in as many countries as possible. The process includes 3 key steps: translation/cultural adaptation, calibration, and validation. A universal translation, an approach focusing on commonalities, rather than differences across versions developed in regions or countries speaking the same language, is proposed to ensure conceptual equivalence for all items. International item calibration using nationally representative samples of adults and children within countries is essential to demonstrate that all items possess expected strong measurement properties. Finally, it is important to demonstrate that the PROMIS measures are valid, reliable and responsive to change when used in an international context.IRT item banking will allow for tailoring within countries and facilitate growth and evolution of PROs through contributions from the international measurement community. A number of opportunities and challenges of international development of PROs item banks are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE: To assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would ...suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. RESEARCH DESIGN AND METHODS: Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for ≥50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA₁c, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. RESULTS: A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. CONCLUSIONS: The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.
In a prior report, we showed that extended-release guanfacine (GEXR) is safe and effective for children with autism spectrum disorder (ASD) accompanied by ADHD symptoms. Here, we examine the impact ...of GEXR on oppositional behavior, anxiety, repetitive behavior, and sleep disturbance. Sixty-two subjects with ASD (53 boys, 9 girls; ages 5-14 years) were randomly assigned to GEXR (n = 30) or placebo (n = 32) for 8 weeks. Outcomes include the Home Situation Questionnaire-Modified for ASD (HSQ-ASD), Anxiety scale of the Child and Adolescent Symptom Inventory (CASI), Children's Yale-Brown Obsessive-Compulsive Scale-Modified for ASD (CYBOCS-ASD), and Children's Sleep Habits Questionnaire (CSHQ). A repeated measures linear mixed model was used to determine the effects of treatment group and time on HSQ scores. For other measures, change from baseline was evaluated with Analysis of Covariance (ANCOVA).After 8 weeks of treatment, parent ratings of oppositional behavior on the HSQ declined by 44% (per item mean from 3.4 to 1.9) in the GEXR group compared to 12% (from 3.3 to 2.9) for placebo (p = 0.004). Repetitive behavior on the CYBOCS-ASD showed a significantly greater decline in GEXR-treated participants compared to placebo (24% vs. <1%, p = 0.01). No group differences were observed on CASI Anxiety or CSHQ (p = 0.64 and 0.75, respectively). GEXR was effective in reducing oppositional behavior and, more modestly, repetitive behavior. GEXR was not superior to placebo for anxiety, though baseline anxiety ratings were low. GEXR did not significantly improve sleep habits. Future studies could focus on repetitive behavior or anxiety, symptoms with limited treatment options.
Doxorubicin (DOXO) induces significant, but transient, increases in apoptosis in the stem cell zone of the jejunum, followed by mucosal damage involving a decrease in crypt proliferation, crypt ...number, and villus height. The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated a symbiotic relationship between intestinal bacteria and intestinal epithelial cells (IEC) in maintaining homeostatic functions of the intestine. However, whether enteric bacteria play a role in DOXO-induced damage is not well understood. We hypothesized that enteric bacteria are necessary for induction of apoptosis and damage associated with DOXO treatment. Conventionally raised (CONV) and germ free (GF) mice were given a single injection of DOXO, and intestinal tissue was collected at 6, 72, and 120 h after treatment and from no treatment (0 h) controls. Histology and morphometric analyses quantified apoptosis, mitosis, crypt depth, villus height, and crypt density. Immunostaining for muc2 and lysozyme evaluated Paneth cells, goblet cells or dual stained intermediate cells. DOXO administration induced significant increases in apoptosis in jejunal epithelium regardless of the presence of enteric bacteria; however, the resulting injury, as demonstrated by statistically significant changes in crypt depth, crypt number, and proliferative cell number, was dependent upon the presence of enteric bacteria. Furthermore, we observed expansion of Paneth and goblet cells and presence of intermediate cells only in CONV and not GF mice. These findings provide evidence that manipulation and/or depletion of the enteric microbiota may have clinical significance in limiting chemotherapy-induced mucositis.
Africa is inferred to be the continent of origin for all modern human populations, but the details of human prehistory and evolution in Africa remain largely obscure owing to the complex histories of ...hundreds of distinct populations. We present data for more than 580,000 SNPs for several hunter-gatherer populations: the Hadza and Sandawe of Tanzania, and the not equalKhomani Bushmen of South Africa, including speakers of the nearly extinct N
Background
Recent research suggests that latent phase of labor may terminate at 6 rather than 4 centimeters of cervical dilation. The objectives of this study were to: (a) characterize duration of ...the latent phase of labor among term, low‐risk, United States women in spontaneous labor using the women's self‐identified onset; and (b) quantify associations between demographic and maternal/newborn health characteristics and the duration of the latent phase.
Methods
This prospective study (n = 1281) described the duration of the latent phase of labor in hours, stratified by parity at the mean, median, and 80th, 90th, and 95th percentiles. The duration of the latent phase was compared for each characteristic using t tests or Wilcoxon rank‐sum tests and regression models that controlled for confounders.
Results
In this sample of predominantly white, healthy women, duration of the latent phase of labor was longer than described in previous studies: The median duration was 9.0 hours and mean duration was 11.8 hours in nulliparous women. The median duration was 6.8 hours and mean duration was 9.3 hours in multiparous women. Among nulliparous women, longer duration was seen in women whose fetus was in a malposition. Among multiparous women, longer durations were noted in women with chorioamnionitis and those who gave birth between 41 and 41 + 6 weeks’ gestation (vs between 40 and 40 + 6 weeks’ gestation).
Conclusions
The latent phase of labor may be longer than previously estimated. Contemporary estimates of latent phase of labor duration will help women and providers accurately anticipate, prepare, and cope during spontaneous labor.
Abstract Objective Native aortic valve calcium and transcatheter aortic valve oversize have been reported to predict pacemaker implantation after transcatheter aortic valve insertion. We reviewed our ...experience to better understand the association. Methods We retrospectively reviewed the records of 300 patients with no prior permanent pacemaker implantation who underwent transcatheter aortic valve insertion from November 2008 to February 2015. Valve oversize was calculated using area. The end point of the study was 30-day postoperative pacemaker implantation. Results Patient data included age of 81.1 ± 8.4 years, female sex in 135 patients (45%), atrial fibrillation in 74 patients (24.7%), Society of Thoracic Surgeons predicted risk of mortality of 7.6% (interquartile range IQR, 5.3-10.6), aortic valve calcium score of 2568 (IQR, 1775-3526) Agatston units, and annulus area of 471 ± 82 mm2 . Balloon-expandable valves were inserted in 244 patients (81.3%). Transcatheter aortic valve oversize was 12.8% (IQR, 3.9-23.3). Pacemaker implantation was performed in 59 patients (19.7%). Aortic valve calcium score (adjusted P = .275) and transcatheter valve oversize (adjusted P = .833) were not independent risk factors for pacemaker implantation when controlling for preoperative right bundle branch block (adjusted odds ratio, 3.49; 95% confidence interval, 1.61-8.55; P = .002), implantation of self-expanding valve (adjusted odds ratio, 4.09; 95% confidence interval, 1.53-10.96; P = .005), left bundle branch block (adjusted P = .331), previous percutaneous coronary intervention (adjusted P = .053), or valve surgery (adjusted P = .111), and PR interval (adjusted P = .350). Conclusions Right bundle branch block and implantation of a self-expanding prosthesis were predictive of pacemaker implantation, but not native aortic valve score or transcatheter valve oversize.
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. Here, The HD Consortium ...reports the generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls. Microarray profiling revealed CAG-repeat-expansion-associated gene expression patterns that distinguish patient lines from controls, and early onset versus late onset HD. Differentiated HD neural cells showed disease-associated changes in electrophysiology, metabolism, cell adhesion, and ultimately cell death for lines with both medium and longer CAG repeat expansions. The longer repeat lines were however the most vulnerable to cellular stressors and BDNF withdrawal, as assessed using a range of assays across consortium laboratories. The HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a human stem cell platform for screening new candidate therapeutics.
► Induced pluripotent cell lines with a range of CAG repeats generated from HD patients ► Genomic profiles of HD-iPSC-derived neurons show disease-specific expression patterns ► HD lines with long CAGs were most susceptible to stress and BDNF withdrawal ► The HD lines are a valuable resource for mechanistic studies and drug screens
The Huntington's Disease iPSC Consortium generated 14 iPSC lines from HD patients and controls and characterized degenerative phenotypes in iPSC-derived neural cells. This resource reveals CAG-expansion-associated gene expression patterns unique to patient lines and opens new opportunities to understand the disease process and develop novel therapeutic drug compounds.
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