The Joint Panel of the American Academy of Family Physicians and the American College of Physicians, in collaboration with the Johns Hopkins Evidence-based Practice Center, systematically reviewed ...the available evidence on the management of newly detected atrial fibrillation and developed recommendations for adult patients with first-detected atrial fibrillation. The recommendations do not apply to patients with postoperative or post-myocardial infarction atrial fibrillation, patients with class IV heart failure, patients already taking antiarrhythmic drugs, or patients with valvular disease. The target physician audience is internists and family physicians dedicated to primary care. The recommendations are as follows: RECOMMENDATION 1: Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation. Rhythm control has not been shown to be superior to rate control (with chronic anticoagulation) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control. Rhythm control is appropriate when based on other special considerations, such as patient symptoms, exercise tolerance, and patient preference. Grade: 2A. RECOMMENDATION 2: Patients with atrial fibrillation should receive chronic anticoagulation with adjusted-dose warfarin, unless they are at low risk of stroke or have a specific contraindication to the use of warfarin (thrombocytopenia, recent trauma or surgery, alcoholism). Grade: 1A. RECOMMENDATION 3: For patients with atrial fibrillation, the following drugs are recommended for their demonstrated efficacy in rate control during exercise and while at rest: atenolol, metoprolol, diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is only effective for rate control at rest and therefore should only be used as a second-line agent for rate control in atrial fibrillation. Grade: 1B. RECOMMENDATION 4: For those patients who elect to undergo acute cardioversion to achieve sinus rhythm in atrial fibrillation, both direct-current cardioversion (Grade: 1C+) and pharmacological conversion (Grade: 2A) are appropriate options. RECOMMENDATION 5: Both transesophageal echocardiography with short-term prior anticoagulation followed by early acute cardioversion (in the absence of intracardiac thrombus) with postcardioversion anticoagulation versus delayed cardioversion with pre- and postanticoagulation are appropriate management strategies for those patients who elect to undergo cardioversion. Grade: 2A. RECOMMENDATION 6: Most patients converted to sinus rhythm from atrial fibrillation should not be placed on rhythm maintenance therapy since the risks outweigh the benefits. In a selected group of patients whose quality of life is compromised by atrial fibrillation, the recommended pharmacologic agents for rhythm maintenance are amiodarone, disopyramide, propafenone, and sotalol (drugs listed in alphabetical order). The choice of agent predominantly depends on specific risk of side effects based on patient characteristics. Grade: 2A.
Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people ...living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22–49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK, VSZLJ
Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients.
...We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen.
analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI).
Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m
), 204 (33%) were overweight (25 kg/m
⩽ BMI < 30 kg/m
), and 213 (34%) were normal or underweight (BMI < 25 kg/m
). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (
= 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% 95% confidence interval, -19 to -6;
= 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% 95% confidence interval, -11 to -2;
= 0.006).
Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).
Spleen tyrosine kinase (SYK) signaling pathway regulates critical processes in innate immunity, but its role in parenchymal cells remains elusive in chronic liver diseases. We investigate the ...relative contribution of SYK and its substrate c-Abl Src homology 3 domain-binding protein-2 (3BP2) in both myeloid cells and hepatocytes in the onset of metabolic steatohepatitis.
Hepatic SYK-3BP2 pathway was evaluated in mouse models of metabolic-associated fatty liver diseases (MAFLD) and in obese patients with biopsy-proven MAFLD (n = 33). Its role in liver complications was evaluated in Sh3bp2 KO and myeloid-specific Syk KO mice challenged with methionine and choline deficient diet and in homozygous Sh3bp2KI/KI mice with and without SYK expression in myeloid cells.
Here we report that hepatic expression of 3BP2 and SYK correlated with metabolic steatohepatitis severity in mice. 3BP2 deficiency and SYK deletion in myeloid cells mediated the same protective effects on liver inflammation, injury, and fibrosis priming upon diet-induced steatohepatitis. In primary hepatocytes, the targeting of 3BP2 or SYK strongly decreased the lipopolysaccharide-mediated inflammatory mediator expression and 3BP2-regulated SYK expression. In homozygous Sh3bp2KI/KI mice, the chronic inflammation mediated by the proteasome-resistant 3BP2 mutant promoted severe hepatitis and liver fibrosis with augmented liver SYK expression. In these mice, the deletion of SYK in myeloid cells was sufficient to prevent these liver lesions. The hepatic expression of SYK is also up-regulated with metabolic steatohepatitis and correlates with liver macrophages in biopsy-proven MAFLD patients.
Collectively, these data suggest an important role for the SYK-3BP2 pathway in the pathogenesis of chronic liver inflammatory diseases and highlight its targeting in hepatocytes and myeloid cells as a potential strategy to treat metabolic steatohepatitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction and hypothesis
This study aims to evaluate clinical outcomes of concomitant suburethral sling with LeFort colpocleisis including its effect on postoperative voiding.
Methods
We performed ...a retrospective review of all LeFort colpocleisis procedures from our institution. We reviewed demographics, symptoms of stress urinary incontinence, incontinent events/day, pads usage/day, urodynamic parameters, and presence of voiding dysfunction.
Results
Two hundred ten patients underwent colpocleisis during the study period. Mean age was 82.2 ± 4.9 and median follow-up was 22 weeks (2–169). Preoperatively, 73 (35%) complained of stress urinary incontinence (SUI) symptoms, and an additional 105 (50%) were diagnosed with occult SUI. One hundred sixty-one (77%) patients underwent concurrent suburethral sling. Overall, sling placement resulted in a 92.5% subjective stress continent rate. Fifty-six patients presented with voiding dysfunction (VD). Postoperatively, VD resolved in 91%. De novo VD occurred in two patients (1.9%) and one (0.6%) required sling revision.
Conclusions
Sling placement at time of colpocleisis is associated with high continence rates with minimal risk of postoperative voiding dysfunction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The point prevalence survey of healthcare-associated infections (HAIs) and antimicrobial use organized by the European Centre for Disease Prevention and Control (ECDC-PPS) and the Global Point ...Prevalence Survey of antimicrobial consumption (Global-PPS) were simultaneously performed in Belgian acute care hospitals in 2017.
Belgian acute care hospitals were invited to participate in either the ECDC or Global-PPS. Hospital/ward/patient-level data were collected between September-December 2017. All patients present in the wards at 8 a.m. on the day of the PPS were included. The data of the ECDC and Global-PPS on antimicrobial consumption were pooled. Detailed data on HAIs were analysed for ECDC-PPS.
Overall, 110 Belgian acute care hospital sites participated in the ECDC and Global-PPS (countrywide participation rate: 81.4%, 28,007 patients). Overall, a crude prevalence of patients with at least one antimicrobial of 27.1% (95% confidence interval (CI) 26.5-27.6%) was found. The most frequently reported indications were pneumonia (23.2%), urinary tract infections (15.2%) and skin and soft tissue infections (11.9%). The reason for antimicrobial use was recorded for 81.9% of the prescriptions, a stop/review date for 40.8% and compliance with local antibiotic guidelines for 76.6%. In the ECDC-PPS, the crude prevalence of patients with at least one HAI was 7.3% (95%CI 6.8-7.7%). Most frequently reported HAIs were pneumonia (21.6%) and urinary tract infections (21.3%).
HAI and antimicrobial use prevalence remained stable in comparison with the previous PPS (7.1% and 27.4% in 2011 and 2015, respectively). Belgian hospitals should be further stimulated to set local targets to improve antibiotic prescribing and reduce HAI.
Both for cattle nutrition and biofuel production, the improvement in maize (Zea mays L.) cell wall degradability depends on understanding the genetic mechanisms involved in the biosynthesis of ...phenylpropanoids. Most of the genes involved in monolignol and p-hydroxycinnamate biosynthesis are known, but many belong to multigene families. A macro-array with cell wall gene specific tags was used to characterize the different gene expression profiles in maize ear internode at four stages from 7 d before silking to 15 d after silking. Gene expression profiles were related to biochemical variation observed for lignin content, lignin structure, and esterified and etherified ferulic acid content. Most of the significantly expressed genes had a maximum at the first stages of sampling with their expression decreasing rapidly thereafter. A few genes had a second later expression peak. In each multigene family, only a restricted number of genes were expressed during maize cell wall formation in the below-ear internode. Genes for three phenylalanine ammonia-lyases, two cinnamate 4-hydroxylases, two 4-coumarate:coenzyme A ligases, three caffeoyl-CoA O-methyltransferases, but only one cinnamoyl-CoA reductase, two cinnamyl alcohol dehydrogenases, one ferulate 5-hydroxylase, the only caffeic acid O-methyltransferase, and a ZRP4-like O-methyltransferase were significantly expressed. These genes are likely the most important ones in maize stem lignification, and hence are priority targets in maize breeding.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation ...respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone.
Methods
Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure.
Results
Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, − 11% 95% CI, − 25 to 2;
p
= 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, − 28% 95% CI, − 54 to − 6;
p
= 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (
p
= 0.21).
Conclusions
In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death.
Trial registration number
The trial was registered at
http://www.clinicaltrials.gov
with the registration number NCT03121482 the 20th April 2017.
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