IntroductionHeart failure (HF) mortality rates continue to pose a significant challenge despite advancements in recent decades – in the UK, one-year mortality rates are approximately 20%, ranging up ...to 30% globally among HF patients.1, 2 Of note, elderly individuals, a substantial segment of the HF population, face particularly high one-year mortality rates.3Reduced left ventricular ejection fraction (EF) is a key prognostic element in HF, and so a target for intervention.4, 5 The strategic introduction and uptitration of evidence-based HF medications, encompassing angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor neprilysin inhibitor (ARNI), ß-blockers (BB), mineralocorticoid receptor antagonists (MRA), and SGLT-2 inhibitors (SLGT2i), constitutes an opportunity for treatment.6 Despite these interventions, difficulties persist in timely and efficient drug deployment. Previously, in a smaller cohort of 73 patients, we have shown that Consultant-supervised nurse-led HF clinics (CoNHFCs) offer a viable method of early initiation and uptitration of medications, leading to significant improvements in ejection fraction.7AimsTo assess the impact of early initiation and uptitration of evidence-based HF medications through CoNHFCs on one-year mortality rates in patients with heart failure with reduced (HFrEF) and mildly reduced ejection fraction (HFmREF).MethodsData was obtained from electronic patient records of HFrEF and HFmrEF patients who attended a minimum of two CoNHFCs between 21/2/2021 and 23/2/2023. Information collected included demographics, comorbidities, baseline and follow-up EFs, prescribed HF drugs and doses, as well as mortality within the first year after initial CoNHFC attendance.ResultsOne hundred and nine patients were included. The mean age was 61 years, 69.7% were male. The one-year mortality rate following initial CoNHFC attendance was 3.7%. For patients aged ≥70 years and ≥80 years, one-year mortality rates of 6.5% and 11.1% were recorded, respectively.Additionally, significant improvements were seen in pharmacotherapy and ejection fractions of this expanded cohort, consistent with our prior findings.7 Ejection fraction increased significantly from an average of 31.0% (+/-8.8) to 40.1% (+/-10.7) (p<0.05) before vs after attending CoNHFCs.Comparing HF pharmacotherapy at the initial visit to the last, the percentage of the cohort prescribed prognostic HF drugs – BB, ACE-I/ARB, MRA, ARNI, and SGLT2i – stood at 83.5% vs 92.7%, 70.6% vs 38.6%, 38.6% vs 61.5%, 9.2% vs 54.1%, and 16.5% vs 68.8%, respectively. Patients prescribed all four ’pillar’ HF drugs increased from 10.1% to 40.4%, the proportion prescribed three ’pillar’ drugs rose from 35.8% to 77.1%.ConclusionEarly introduction and uptitration of the four pillars of HF medications through consultant-supervised nurse-led clinics led to one-year mortality rates substantially lower than those previously reported in national and international studies.1, 2Abstract 167 Table 1Study population characteristics and one-year mortality Characteristic Figures Male (%) 69.7 Female (%) 30.3 Average age, years (range) 61 (22–89) IHD diagnosis (%) 26.6 One-year mortality (%) 3.7 One-year mortality age ≥70 yrs (%) 6.5 One-year mortality age ≥80 yrs (%) 11.1 Abstract 167 Table 2Change in mean EF and proportion of study population prescribed the different four ‘pillar’ HF drugs before and after two attendances at CoNHFC Drug class, EF Before After BB (%) 83.5 92.7 ACEI/ARB (%) 70.6 38.6 ARNI (%) 9.2 54.1 MRA (%) 38.6 61.5 SGLT2i (%) 16.5 68.8 Mean EF (%, +/- SD) 31.0 (+/- 8.8) 40.1 (+/- 10.7) Conflict of InterestNone
A return to cocaine use following abstinence frequently occurs in a social context, and the presence of other individuals using cocaine may contribute to the likelihood of use. Previous studies have ...reported that chronic d-amphetamine treatment decreases cocaine self-administration in laboratory animals and reduces a return to cocaine use following abstinence in humans.
The purpose of this study was to examine the effects of chronic d-amphetamine treatment on the reacquisition of cocaine use in rats self-administering cocaine in different social contexts.
Male and female rats were implanted with intravenous catheters and trained to self-administer cocaine during daily 6-hr sessions. After 14 days, cocaine self-administration was extinguished by substituting saline for the cocaine stimulus. At this time, rats were randomized to receive chronic treatment with either d-amphetamine or saline. After 9 days of extinction, cocaine was again made available during daily 6-hr sessions. At this time, rats were further randomized into three social conditions: (1) rats continued self-administering cocaine in isolation, (2) rats self-administered cocaine in the presence of a same-sex partner that also self-administered cocaine, or (3) rats self-administered cocaine in the presence of a same-sex partner that did not have access to cocaine. Daily treatment with d-amphetamine or saline continued for the duration of reacquisition testing.
Chronic treatment with d-amphetamine decreased cocaine intake during reacquisition, but these effects were not influenced by the social context. No sex differences were observed.
These data support previous studies reporting that d-amphetamine decreases cocaine intake and demonstrate its efficacy across social contexts.
•D-amphetamine and social context were examined on cocaine self-administration.•Cocaine self-administration was established prior to extinction and reacquisition.•Chronic d-amphetamine decreased the reacquisition of cocaine self-administration.•The effects of d-amphetamine were independent of social context.
Vascular dementia (VaD), characterized by cognitive decline attributable to cerebrovascular disease, is the second most common type of dementia after Alzheimer’s disease. This review aims to explore ...the prevalent risk factors, pharmacological interventions, and non-pharmacotherapeutic strategies associated with the condition. Recognized risk factors include advanced age, hypertension, diabetes mellitus, obesity, and hyperlipidemia with emerging evidence implicating additional lifestyle and genetic factors. Pharmacotherapy for VaD mainly focuses on managing these underlying risk factors, coupled with symptomatic treatments. Therapeutic agents commonly used include antihypertensives, statins, antiplatelet drugs, antidiabetic agents, and specific cognitive enhancers like cholinesterase inhibitors. However, the effectiveness of these treatments remains under continuous study, underscoring the need for comprehensive, individualized treatment plans. Non-pharmacotherapeutic strategies, encompassing lifestyle modifications such as diet and exercise have gained considerable attention. They have shown promise in improving cognitive function and enhancing the quality of life in patients with VaD. The application of a multi-domain intervention approach may provide a more holistic management strategy for VaD. Further research is needed to define the best practices in both pharmacotherapy and non-pharmacotherapy treatments, considering the multifactorial and heterogeneous nature of this condition.
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•The risk of cardiac failure is distinctly elevated in the diabetic heart.•Chronic diabetes produces cardiac muscle-specific microvascular complications, clinically termed as diabetic ...cardiomyopathy.•The cellular homeostasis process of autophagy is frequently impaired in the diabetic heart.•A precise assessment of autophagy, its adaptations, and molecular regulations in diabetic cardiomyopathy is crucial for efficient diagnosis and therapeutics.•AMPK, SIRT1/3, and FOXOs are promising targets to develop interventional strategies for autophagy in the diabetic heart.
Association of diabetes with an elevated risk of cardiac failure has been clinically evident. Diabetes potentiates diastolic and systolic cardiac failure following the myocardial infarction that produces the cardiac muscle-specific microvascular complication, clinically termed as diabetic cardiomyopathy. Elevated susceptibility of diabetic cardiomyopathy is primarily caused by the generation of free radicals in the hyperglycemic milieu, compromising the myocardial contractility and normal cardiac functions with increasing redox insult, impaired mitochondria, damaged organelles, apoptosis, and cardiomyocytes fibrosis. Autophagy is essentially involved in the recycling/clearing the damaged organelles, cytoplasmic contents, and aggregates, which are frequently produced in cardiomyocytes. Although autophagy plays a vital role in maintaining the cellular homeostasis in diligent cardiac tissues, this process is frequently impaired in the diabetic heart. Given its clinical significance, accumulating evidence largely showed the functional aspects of autophagy in diabetic cardiomyopathy, elucidating its intricate protective and pathogenic outcomes. However, etiology and molecular readouts of these contrary autophagy activities in diabetic cardiomyopathy are not yet comprehensively assessed and translated. In this review, we attempted to assess the role of autophagy and its adaptations in the diabetic heart. To delineate the molecular consequences of these events, we provided detailed insights into the autophagy regulation pieces of machinery including the mTOR/AMPK, TFEB/ZNSCAN3, FOXOs, SIRTs, PINK1/Parkin, Nrf2, miRNAs, and others in the diabetic cardiomyopathy. Given the clinical significance of autophagy in the diabetic heart, we further discussed the potential pharmacotherapeutic strategies towards targeting autophagy. Taken together, the present report meticulously assessed autophagy, its adaptations, and molecular regulations in diabetic cardiomyopathy and reviewed the current autophagy-targeting strategies.
Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and ...reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today.
To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.
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