Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction

OBJECTIVE: Recent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality. METHODS: From 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients. RESULTS: Of 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75–0.94, p = 0.002) for mortality and 0.85 (0.78–0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years. CONCLUSIONS: This study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12471-021-01591-6) contains supplementary material, which is available to authorized users

Neutrophil to Lymphocyte Ratio and Outcomes in Patients with New-Onset or Worsening Heart Failure with Reduced and Preserved Ejection Fraction

Inflammation is thought to play a role in heart failure (HF) pathophysiology. Neutrophil-to-lymphocyte ratio (NLR) is a simple, routinely available measure of inflammation. Its relationship with other inflammatory biomarkers and its association with clinical outcomes in addition to other risk markers have not been comprehensively evaluated in HF patients. Methods We evaluated patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available NLR at baseline. The primary outcome was time to all-cause mortality or HF hospitalization. Outcomes were validated in a separate HF population. Results 1622 patients were evaluated (including 523 ventricular ejection fraction [LVEF] < 40% and 662 LVEF ≥ 40%). NLR was significantly correlated with biomarkers related to inflammation as well as NT-proBNP. NLR was significantly associated with the primary outcome in patients irrespective of LVEF (hazard ratio [HR] 1.18 per standard deviation increase; 95% confidence interval [CI] 1.11–1.26, P < 0.001). Patients with NLR in the highest tertile had significantly worse outcome than those in the lowest independent of LVEF (<40%: HR 2.75; 95% CI 1.84–4.09, P < 0.001; LVEF ≥ 40%: HR 1.51; 95% CI 1.05–2.16, P = 0.026). When NLR was added to the BIOSTAT-CHF risk score, there were improvements in integrated discrimination index (IDI) and net reclassification index (NRI) for occurrence of the primary outcome (IDI + 0.009; 95% CI 0.00–0.019, P = 0.030; continuous NRI + 0.112, 95% CI 0.012–0.176, P = 0.040). Elevated NLR was similarly associated with adverse outcome in the validation cohort. Decrease in NLR at 6 months was associated with reduced incidence of the primary outcome (HR 0.75; 95% CI 0.57–0.98, P = 0.036). Conclusions Elevated NLR is significantly associated with elevated markers of inflammation in HF patients and is associated with worse outcome. Elevated NLR might potentially be useful in identifying high-risk HF patients and may represent a treatment target

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Contains fulltext : 53264.pdf (publisher's version ) (Open Access)BACKGROUND: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. METHODS/DESIGN: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. DISCUSSION: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40512715

Voluntary disclosure of corporate strategy: determinants and outcomes. An empirical study into the risks and payoffs of communicating corporate strategy.

Business leaders increasingly face pressure from stakeholders to be transparent. There appears however little consensus on the risks and payoffs of disclosing vital information such as corporate strategy. To fill this gap, this study analyzes firm-specific determinants and organisational outcomes of voluntary disclosure of corporate strategy. Stakeholder theory and agency theory help to understand whether companies serve their interest to engage with stakeholders and overcome information asymmetries. I connect these theories and propose a comprehensive approach to measure voluntary disclosure of corporate strategy. Hypotheses from the theoretical framework are empirically tested through panel regression of data on identified determinants and outcomes and of disclosed strategy through annual reports, corporate social responsibility reports, corporate websites and corporate press releases by the 70 largest publicly listed companies in the Netherlands from 2003 through 2008. I found that industry, profitability, dual-listing status, national ranking status and listing age have significant effects on voluntary disclosure of corporate strategy. No significant effects are found for size, leverage and ownership concentration. On outcomes, I found that liquidity of stock and corporate reputation are significantly influenced by voluntary disclosure of corporate strategy. No significant effect is found for volatility of stock. My contributions to theory, methodology and empirics offers a stepping-stone for further research into understanding how companies can use transparency to manage stakeholder relations

Shared Decision-Making in Cosmetic Medicine and Aesthetic Surgery

Shared decision-making (SDM) invokes the bidirectional communication between physicians and patients required to involve the patient's preference in the eventual treatment choice. This paper will explain what SDM is, why it is important, and how it is performed in clinical practice. It is an essential part of evidence-based medicine, as it helps determine whether the available evidence on the possible benefits and harms of treatment options match the patient's characteristics and preferences. Cosmetic medicine and aesthetic surgery seem to be obvious fields of medicine in which SDM should be applied to achieve high-quality car

Shared Decision-Making in Cosmetic Medicine and Aesthetic Surgery

Shared decision-making (SDM) invokes the bidirectional communication between physicians and patients required to involve the patient's preference in the eventual treatment choice. This paper will explain what SDM is, why it is important, and how it is performed in clinical practice. It is an essential part of evidence-based medicine, as it helps determine whether the available evidence on the possible benefits and harms of treatment options match the patient's characteristics and preferences. Cosmetic medicine and aesthetic surgery seem to be obvious fields of medicine in which SDM should be applied to achieve high-quality car

Skin grafting and tissue replacement for treating foot ulcers in people with diabetes

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the benefits and harms of skin grafting and tissue replacement for treating foot ulcers in people with diabetes

Systematic review and meta-analysis of skin substitutes in the treatment of diabetic foot ulcers: Highlights of a Cochrane systematic review

Skin substitutes are increasingly used in the treatment of various types of acute and chronic wounds. The aim of this study was to perform a systematic review and meta-analysis to evaluate the effectiveness of skin substitutes on ulcer healing and limb salvage in the treatment of diabetic foot ulcers. Randomized clinical trials were searched and assessed following the methodology of The Cochrane Collaboration. We included 17 trials, totaling 1655 randomized participants. Risk of bias was variable among included trials. Thirteen trials compared the skin substitutes with standard care. The pooled results showed that that skin substitutes can, in addition to standard care, increase the likelihood of achieving complete ulcer closure compared with standard care alone after 6-16 weeks (risk ratio 1.55, 95% confidence interval [CI] 1.30-1.85). Four of the included trials compared two types of skin substitutes but no particular product showed a superior effect over another. Two trials reported on total incidence of lower limb amputations. Pooling the results of these two trials yielded a statistically significantly lower amputation rate among patients treated with skin substitutes (risk ratio 0.43, 95% CI 0.23-0.81), although the absolute risk difference was small (20.06, 95% CI 20.10 to 20.01). This systematic review provides evidence that skin substitutes can, in addition to standard care, increase the likelihood of achieving complete ulcer closure compared with standard care alone in the treatment of diabetic foot ulcers. However, effectiveness on the long term, including lower limb salvage and recurrence, is currently lacking and cost-effectiveness is unclea

Systemic wound care: a meta-review of cochrane systematic reviews

Wound care is a classic example of a surgical realm with a great variation in care. The diversity in wounds and wound treatments, the limited amount of convincing evidence, and the diverging opinions among doctors and nurses involved in wound care contribute to this undesirable variation in care. For chronic wounds, such as arterial or venous ulcers, pressure sores, and diabetic foot ulcers, but also for acute wounds after surgery or trauma, international and national guidelines provide recommendations on diagnostic procedures and treatment options, but rely mostly on expert opinion. We present the available evidence from Cochrane systematic reviews for the systemic treatment (i.e., not prevention) of patients with wounds, as opposed to topical wound treatments. This evidence shows: - Venous ulcers: High-compression therapy is the classic and evidence-based treatment for treating venous ulcers. Oral pentoxifylline promotes ulcer healing with and without compression therapy. Oral zinc is not effective to heal venous ulcers. - Acute wounds: Recombinant human growth hormone accelerates healing of large burn wounds and donor sites, while high-carbohydrate feeding might reduce the risk of pneumonia. Linezolid is more effective than vancomycin for treating skin and soft tissue infections. Hyperbaric oxygen may help heal crush wounds and skin grafts. Therapeutic touch does not heal acute wounds. - Pressure sores: Air-fluidized and some low-tech devices appear effective for treating existing pressure ulcers. Oral zinc, protein, or vitamin C supplements seem ineffective. Also, evidence is lacking on the effectiveness of repositioning regimes as a treatment option. - Diabetic ulcers: Hyperbaric oxygen therapy and pressure-relieving devices may improve healing rates. - Arterial ulcers: Prostanoids and spinal cord stimulation may be effective in healing ischemic ulcers. Thus, fortunately, some high-level evidence exists for various local and systemic interventions in wound care. Caregivers should be aware of, and apply, the strongest evidence available. Only when all stakeholders (patients, physicians, wound care nurses, but also manufacturers and buyers) implement this available evidence will optimum quality of care for patients with wounds be ensure