A Historical Perspective on Presentations of Hypertensive Acute Heart Failure

BACKGROUND: The initial systolic blood pressure (SBP) in patients presenting to the hospital with acute heart failure (AHF) informs prognosis, diagnosis, and guides initial treatment. However, over time AHF presentations with elevated SBP appear to have declined. The present study examined whether the frequency of AHF presentations with systolic hypertension (SBP \u3e 160 mmHg) declined over a nearly two-decade time interval. METHODS: This study compares four historical, cross-sectional cohorts with AHF who were admitted to tertiary care medical centres in the North-eastern USA in 1995, 2000, 2006, and 2011-13. The main outcome was the proportion of AHF patients presenting with an initial SBP \u3e 160 mmHg. RESULTS: 2,366 patients comprised the study sample. The average age was 77 years, 55% were female, 94% white, and 75% had prior heart failure. In 1995, 34% of AHF patients presented with an initial SBP \u3e 160 mmHg compared to 20% in 2011-2013 (p \u3c 0.01). Multivariate logistic regression demonstrated reduced odds of presenting with a SBP \u3e 160 mmHg in 2006 (0.64, 95% CI 0.42-0.96) and 2011-13 (0.46, 95% CI 0.28-0.74) compared with patients in 1995. CONCLUSION: The proportion of patients with AHF and initial SBP \u3e 160 mmHg significantly declined over the study time period. There are several potential reasons for this observation and these findings highlight the need for ongoing surveillance of patients with AHF as changing clinical characteristics can impact early treatment decisions

Can global rainfall forecasts identify areas at flash flood risk? Proof of concept for Ecuador

Globally, flash floods are one of the costliest natural hazards for property damage and loss of life. The low accuracy of flash flood forecasts beyond a few hours limits their use in early warning systems. This study aims to compare the performance of ECMWF raw ensemble (ENS) and ecPoint rainfall forecasts. These two systems are profoundly different because the first provides forecasts at a grid-scale while the second provides forecasts at a point-scale that mirror point observations such as rain gauges. ecPoint rainfall forecasts have been shown to provide better guidance than ENS in predicting extreme (localized) rainfall up to 10 days ahead. Hence, this study assesses whether ecPoint also enhances ENS performance in identifying areas at risk of flash floods up to medium-range leads. A one-year objective verification was conducted for flash flood events in Ecuador. The country’s varied climate and the existence of a comprehensive database describing the occurrence of flash flood events made Ecuador an attractive site for the verification analysis. Knowing the magnitudes of flash-flood-triggering rainfall events is imperative to carry out the objective verification analysis. The authors did not have this information at their disposal, and suitable rainfall observations were not available to estimate the magnitudes of flash-flood-triggering rainfall events. This study proposes a methodology that uses short-term ecPoint rainfall forecasts as a proxy for point rainfall observations to define the magnitude of flash-flood triggering rainfall events when suitable rainfall observations are unavailable. Due to the probabilistic nature of the ecPoint output, this approach simulates a very high-density observational network in data-scarce regions. From a general comparison of the rainfall thresholds defined using short-range ecPoint rainfall forecast and those computed from a low-density observational network, overall, the flash-flood-triggering rainfall thresholds seem reasonable, but they might be slightly underestimated in the coastal region and overestimated in the Andean region. The verification results suggest that ecPoint generally provides better guidance than ENS in identifying areas at risk of flash floods when rainfall originates from small-scale convective systems. In these cases, ENS might completely miss the flash flood event, while ecPoint was able to anticipate it. When rainfall originates from large-scale convective systems, ecPoint and ENS performances are comparable, showing that ENS can predict areas at risk of flash floods around the globe up to medium-range leads under certain weather conditions. However, ecPoint provides better guidance on the magnitude of the flash-flood-triggering rainfall events. The findings of this study have the potential to significantly improve early warning systems, aid decision-makers, and enhance emergency preparedness worldwide against flash floods. This would ultimately contribute to better mitigation of the devastating impacts of flash floods on communities and infrastructure

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder

Purpose We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Methods Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. Results We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. Conclusion Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals

Kỳ quan thiên nhiên thế giới

209 tr.: minh hoạ ; 27 c

Kỳ quan thiên nhiên thế giới

209 tr.: minh hoạ ; 27 cm

Advocacy in Action: Leveraging the Power of Patient Voices to Impact Ovarian Cancer Outcomes in Canada

Prior to 1997, ovarian cancer (OC) was a ‘poor target’ for patient advocacy. At that time, there were only three OC researchers in Canada, little information available for women diagnosed, and no community of survivors existed. The Corinne Boyer Fund to advance OC was founded in 1997 (later renamed the National Ovarian Cancer Association (NOCA) and subsequently Ovarian Cancer Canada (OCC)), and a Blueprint for Action was established. NOCA developed training programs for public education, partnered with clinicians and scientists, established a Tissue Banking Network across Canada In 2015, the Ladyballs awareness campaign was launched nationally, giving the community a presence and voice. Strategic planning by the organization put advocacy for research funding as a top priority and, working with patients and researchers across the country, petitioned the government for C$10 million in research funding. In 2019, OCC received the funding. In 2020, the OvCAN project was launched with the aim to improve the outcomes of women diagnosed with OC. In the first three years of OvCAN, a pan-Canadian team of 25 Patient Partners was established, and 41 projects to date on research models, pre-clinical and clinical trials covering a wide spectrum of OC types have been funded

Understanding the Experience of Canadian Women Living with Ovarian Cancer through the Every Woman Study™

The EveryWoman Study™: Canadian Edition is the most comprehensive study to date exploring patient-reported experiences of ovarian cancer (OC) on a national scale. An online survey conducted in Fall 2020 included individuals diagnosed with OC in Canada, reporting responses from 557 women from 11 Canadian provinces/territories. Median age at diagnosis was 54 (11–80), 61% were diagnosed between 2016–2020, 59% were stage III/IV and all subtypes of OC were represented. Overall, 23% had a family history of OC, 75% had genetic testing and 19% reported having a BRCA1/2 mutation. Most (87%) had symptoms prior to diagnosis. A timely diagnosis of OC ( 3 months from first presentation with symptoms) was predicted by age (>50) or abdominal pain/persistent bloating as the primary symptom. Predictors of an acute diagnosis (<1 month) included region, ER/urgent care doctor as first healthcare provider or stage III/IV disease. Regional differences in genetic testing, treatments and clinical trial participation were also noted. Respondents cited substantial physical, emotional, practical and financial impacts of an OC diagnosis. Our national survey has revealed differences in the pathway to diagnosis and post-diagnostic care among Canadian women with OC, with region, initial healthcare provider, specific symptoms and age playing key roles. We have identified many opportunities to improve both clinical and supportive care of OC patients across the country.Medicine, Faculty ofNon UBCObstetrics and Gynaecology, Department ofReviewedFacultyResearche