Patient perspectives on incretin-based weight loss medications and relationship with demographic factors.

Objective: Treatment of obesity has been transformed by the recent approval of incretin-based therapies for weight loss (e.g., glucagon-like peptide 1 agonist semaglutide), but little is known about patient perspectives on these medications. Methods: Between December 2023 and March 2024, healthcare patients from an academic medical center in the Southeast United States with Body Mass Index ≥30 kg/m2 completed a cross-sectional online survey on attitudes toward incretin-based medications. Results: Compared to patients with a bachelor's degree, those without a degree were less likely to be aware of incretin-based pharmacotherapies (96% vs. 78%) and to have discussed pharmacotherapies with a doctor (43% vs. 27%) but had greater interest in using these pharmacotherapies (4.3 vs. 4.7). These pharmacotherapy-related variables did not differ significantly according to gender, race, or financial security. Concerns about side effects, long-term health risks, and potential for weight regain were highly endorsed and were associated with lower interest in using incretin-based therapies and with some demographic factors. Patients reported high interest in lifestyle programs designed for individuals taking anti-obesity medications. Conclusion: Demographic considerations, notably education level, should be factored into the strategy to promote equitable utilization of incretin-based therapies, particularly as their accessibility expands.

The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89-11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41-0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50-0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53-0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.

Emerging therapies for overactive bladder: preclinical, phase I and phase II studies.

INTRODUCTION: Overactive bladder syndrome is a common chronic condition with a significant impact on quality of life and economic burden. Persistence with pharmacologic therapy has been limited by efficacy and side effects. A greater understanding of the pathophysiology of overactive bladder has led to the initial evaluation of several drugs affecting ion channels, the autonomic nervous system, and enzymes which may provide useful alternatives for the management of overactive bladder. AREAS COVERED: A comprehensive review was performed using PubMed and Cochrane databases as well as reviewing clinical trials in the United States. The current standard of care for overactive bladder will be discussed, but this paper focuses on investigational drugs currently in preclinical studies and phase I and II clinical trials. EXPERT OPINION: Current therapies for overactive bladder have limitations in efficacy and side effects. A greater understanding of the pathophysiology of overactive bladder has identified the role(s) of other pathways in the overactive bladder syndrome. Targeting alternative pathways including ion channels and enzymes may provide alternative therapies of overactive bladder and a more tailored approach to the management of overactive bladder.

Efficacy of Amblyopia Treatments in Children Up to Seven Years Old: A Systematic Review.

Amblyopia is a neurodevelopmental disorder of the visual system that impairs the vision of millions of children worldwide. Amblyopia is best treated within the sensitive period of visual development when a child is up to seven years of age. Currently, the gold standard for early treatment of childhood amblyopia is patching, with new treatments emerging in recent years. We aim to evaluate the effectiveness of these newly developed treatments for amblyopia in children aged seven years and younger while comparing them to the current industry standard of patching. We searched online databases including PubMed, Google Scholar, and Cochrane Library for randomized controlled trials (RCTs), systematic reviews, meta-analyses, and narrative reviews relating to amblyopia treatment in children aged seven and younger. We only included articles and studies completed within the last five years and those written in the English language. After compiling a list of 297 articles, we removed duplicates, articles without an available full text, and those not relevant to our topic. Of the remaining 51 articles, we were left with 22 after reading abstracts and removing further irrelevant articles. We did a quality assessment on the remaining 22 articles and were left with 14 articles for our systematic review after removing eight low-quality articles. Of the 14 articles, we had eight RCTs, two systematic reviews, one comparative interventional study, and three narrative reviews. Seven of the articles contained data reinforcing the effectiveness of patching while comparing it to other treatment modalities. Three of the articles had data supporting spectacle correction, including a novel form called alternative flicker glass which delivers occlusion therapy via a spectacle frame with unique lenses, and ultimately deemed it at least as effective or more than patching. Data from three articles supported the use of surgery to successfully correct the angle of strabismus. Findings from five articles backed the use of pharmacologic therapy, specifically atropine when used alongside patching as a more effective alternative to patching solely. However, levodopa plus patching had no advantage over patching alone. Additionally, seven articles addressed the use of virtual reality (VR) and dichoptic therapy as prospective treatments for childhood amblyopia. VR therapy proved beneficial when used within one week after strabismus surgery. Dichoptic training was also effective in improving amblyopic-eye visual acuity when used on its own or in conjunction with spectacles. Furthermore, dichoptic movie therapy was found to be more effective than patching. Thus, we found multiple highly effective treatments for childhood amblyopia that are as effective or more than patching. Future studies should consider prescribing these treatments to larger cohorts while also performing a cost-benefit analysis for each treatment. In addition, more needs to be learned about the potential adverse side effects of these treatments, especially for pharmaceutical therapy.

Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases.

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets.

The differentiation of the competitive athlete with physiologic cardiac remodeling from the athlete with cardiomyopathy.

There are currently 5 million active high school, collegiate, professional, and master athletes in the United States. Regular intense exercise by these athletes can promote structural, electrical and functional remodeling of the heart, which is termed the "athlete's heart." In addition, regular intense exercise can lead to pathological adaptions that promote or worsen cardiac disease. Many of the athletes in the United States seek medical care. Consequently, physicians must be aware of the normal cardiac anatomy and physiology of the athlete, the differentiation of the normal athlete heart from the athlete with cardiomyopathy, and the contemporary care of the athlete with a cardiomyopathy. In athletes with persistent cardiovascular symptoms, investigations should include a detailed history and physical examination, an ECG, a transthoracic echocardiogram, and in athletes in whom the diagnosis is uncertain, a maximal exercise stress test or a continuous ECG recording, and cardiac magnetic resonance imaging or cardiac computed tomography angiography when definition of the coronary anatomy or characterization of the aorta and the aortic great vessels is indicated. This article discusses the differentiation of the normal athlete with physiologic cardiac remodeling from the athlete with hypertrophic, dilated or arrhythmogenic ventricular cardiomyopathy (ACM). The ECG changes in trained athletes that are considered normal, borderline, or abnormal are listed. In addition, the normal echocardiographic measurements for athletes who consistently participate in endurance, power, combined or heterogeneous sports are enumerated and discussed. Algorithms are listed that are useful in the diagnosis of trained athletes with borderline or abnormal echocardiographic measurements suggestive of cardiomyopathies along with the major and minor criteria for the diagnosis of ACM in athletes. Thereafter, the treatment of athletes with hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies are reviewed. The distinction between physiologic changes and pathologic changes in the hearts of athletes has important therapeutic and prognostic implications. Failure by the physician to correctly diagnose an athlete with hypertrophic cardiomyopathy, dilated cardiomyopathy, or ACM, can lead to the sudden cardiac arrest and death of the athlete during training or sports competition. Conversely, an incorrect diagnosis by a physician of cardiac pathology in a normal athlete can lead to an unnecessary restriction of athlete training and competition with resultant significant emotional, psychological, financial, and long-term health consequences in the athlete.

Research progress of pharmacologic therapy in obstructive sleep apnea / 中国临床药理学与治疗学

Obstructive sleep apnea (OSA) is a common sleep disordered breathing disorder. As a major global public health problem, untreated OSA can lead to a variety of adverse health outcomes, including various cardiovascular and cerebrovascular diseases, metabolic disorders, and psychiatric disorders such as anxiety and depression. Traditional OSA therapies such as positive airway pressure (PAP), weight loss, oral appliance, upper airway surgery, and postural therapy focus on the anatomical factors of OSA. However, the pathogenesis of OSA is heterogeneous, and non-anatomical factors also play an important role in most patients. Although there is no drug with exact efficacy for the treatment of OSA, with the deepening understanding of the pathophysiological mechanism of OSA, more and more clinical studies are devoted to the study of drug treatment of OSA and its complications, and a series of results have been achieved. The following is a review of the relevant studies on drug treatment of OSA in recent years, hoping to provide literature support and theoretical basis for future research on drug treatment of OSA.

The patient journey in Chronic Obstructive Pulmonary Disease (COPD): a human factors qualitative international study to understand the needs of people living with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common condition that causes irreversible airway obstruction. Fatigue and exertional dyspnoea, for example, have a detrimental impact on the patient's daily life. Current research has revealed the need to empower the patient, which can result in not only educated and effective decision-making, but also a considerable improvement in patient satisfaction and treatment compliance. The current study aimed to investigate the perspectives and requirements of people living with COPD to possibly explore new ways to manage their disease. METHODS: Adults with COPD from 8 European countries were interviewed by human factor experts to evaluate their disease journey through the gathering of information on the age, performance, length, and impact of diagnosis, symptoms progression, and family and friends' reactions. The assessment of present symptoms, services, and challenges was performed through a 90-min semi-structured interview. To identify possible unmet needs of participants, a generic thematic method was used to explore patterns, themes, linkages, and sequences within the data collected. Flow charts and diagrams were created to communicate the primary findings. Following analysis, the data was consolidated into cohesive insights and conversation themes relevant to determining the patient's unmet needs. RESULTS: The 62, who voluntarily accepted to be interviewed, were patients (61% females, aged 32-70 years) with a COPD diagnosis for at least 6 months with stable symptoms of different severity. The main challenges expressed by the patients were the impact on their lifestyle, reduced physical activity, and issues with their mobility. About one-fourth had challenges with their symptoms or medication including difficulty in breathing. Beyond finding a cure for COPD was the primary goal for patients, their main needs were to receive adequate information on the disease and treatments, and to have adequate support to improve physical activity and mobility, helpful both for patients and their families. CONCLUSIONS: These results could aid in the creation of new ideas and concepts to improve our patient's quality of life, encouraging a holistic approach to people living with COPD and reinforcing the commitment to understanding their needs.

Management of non-pharmacologic therapy for chronic refractory cough: Mechanism, composition, applicable population, and assessment.

Chronic cough is common in the clinic and can seriously affect the quality of life of patients. Following the existing guidelines for treatment, refractory chronic cough is defined as a clinical condition in which the cause of the cough remains unclear after comprehensive examination and treatment, or the cause is clear but symptomatic treatment is ineffective. It has been found that non-pharmacologic therapy can effectively improve the quality of life and reduce the frequency of coughing for some patients with refractory chronic cough. Compared with pharmacological therapy, non-pharmacologic therapy has no obvious adverse effects; therefore, non-pharmacologic therapy has good application prospects in the diagnosis and treatment of refractory chronic cough. This paper summarizes the composition, indication, action and mechanism of non-pharmacologic therapy in the diagnosis and treatment of refractory chronic cough and prospects for research on non-pharmacologic therapy.

The Pathophysiology and New Advancements in the Pharmacologic and Exercise-Based Management of Heart Failure With Reduced Ejection Fraction: A Narrative Review.

Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome whose management has significantly evolved based on the pathophysiology and disease process. It is widely prevalent, has a relatively high mortality rate, and is comparatively more common in men than women. In HFrEF, the series of maladaptive processes that occur lead to an inability of the muscle of the left ventricle to pump blood efficiently and effectively, causing cardiac dysfunction. The neurohormonal and hemodynamic adaptations play a significant role in the advancement of the disease and are critical to guiding the treatment and management of HFrEF. The first-line therapy, which includes loop diuretics, ß-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, hydralazine/isosorbide-dinitrate, and mineralocorticoid receptor antagonists (MRAs), has been proven to provide symptomatic relief and decrease mortality and complications. The newly recommended drugs for guideline-based therapy, angiotensin receptor/neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors, soluble guanylate cyclase, and myosin activators and modulators have also been shown to improve cardiac function, reverse cardiac remodeling, and reduce mortality rates. Recent studies have demonstrated that exercise-based therapy has resulted in an improved quality of life, exercise capacity, cardiac function, and decreased hospital readmission rates, but it has not had a considerable reduction in mortality rates. Combining multiple therapies alongside holistic advances such as exercise therapy may provide synergistic benefits, ultimately leading to improved outcomes for patients with HFrEF. Although first-line treatment, novel pharmacologic management, and exercise-based therapy have been shown to improve prognosis, the existing literature suggests a need for further studies evaluating the long-term effects of MRA and ARNI.

Environmental scan of current strategies to decrease sedative-hypnotic drug use and promote sleep in hospital patients.

BACKGROUND: Sedative-hypnotic drugs are often initiated in hospital to manage insomnia and anxiety. Guidelines discourage their use, particularly in older adults, due to risks of falls, fractures, and delirium. AIM: To identify publicly available resources to decrease the use of sedative-hypnotic drugs and promote sleep in hospital. METHOD: An advanced Google search with 6 search strategies was conducted. Key websites were also identified and searched. Hospital- or community-based resources using non-pharmacologic measures to reduce sedative-hypnotic drug use and/or to promote sleep were included if they were publicly available in English within the past 5 years. Full text screening and data extraction was performed independently by 2 reviewers; a third reviewer resolved disagreements by consensus. RESULTS: A total of 79 resources met inclusion criteria, with 65 (82.3%) providing education and 31 (39.2%) describing sleep hygiene strategies. Other resources included deprescribing (17, 21.5%), relaxation training (13, 16.5%), cognitive behavioural therapy for insomnia (9, 11.4%), and policies (7, 8.9%). The resources primarily targeted patients (59, 74.7%) followed by healthcare providers (9, 11.4%). There were 9 resources (11.4%) that applied to both community and hospital settings, and another 2 (2.5%) designed specifically for hospital. CONCLUSION: Many resources were available to patients and healthcare providers to reduce inappropriate or ineffective use of sedative-hypnotic drugs and promote better sleep. Specific resources for the hospital setting were infrequent and recommended that clinicians stop hospital-initiated sedatives when patients are discharged. Identified resources can be adapted by healthcare organizations to develop sedative-hypnotic prescribing programs and policies.

Efficacy and safety of pharmacologic therapies for prevention of osteoporotic vertebral fractures in postmenopausal women.

Background: There are many pharmaceutical interventions available to prevent osteoporotic vertebral fractures in postmenopausal women, but the efficacy and safety of these drugs are unknown. This study aimed to investigate the efficacy and safety of drugs in the prevention of osteoporotic vertebral fractures. Methods: PubMed, Embase, and the Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15, 2020, including postmenopausal women with osteoporosis. Network meta-analysis was conducted based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The relative risk (RR) and 95% confidence interval (CI) were used to report the results. This study was registered with PROSPERO, number CRD42020201167. Main Outcomes were incidences of new vertebral fracture and serious adverse events. Results: Fifty-five RCTs (n = 104 580) evaluating vertebral fractures of sixteen kinds of pharmacologic therapies were included in the network meta-analysis. Abaloparatide (RR, 0.21; [95% CI, 0.09 to 0.51]), alendronate (RR, 0.55; [95% CI, 0.38 to 0.81]), calcitonin (RR, 0.44; [95% CI, 0.25 to 0.78]), denosumab (RR, 0.33; [95% CI, 0.14 to 0.61]), parathyroid hormone (PTH) (RR, 0.32; [95% CI, 0.10 to 0.97]), risedronate (RR, 0.65; [95% CI, 0.42 to 1.00]), romosozumab (RR, 0.31; [95% CI, 0.16 to 0.61]), strontium ranelate (RR, 0.62; [95% CI, 0.42 to 0.93]), teriparatide (RR, 0.27; [95% CI, 0.17 to 0.43]), and zoledronate (RR, 0.41; [95% CI, 0.93]) were associated with lower vertebral fracture risk compared to placebo. PTH was associated with more adverse event rates. For any two drug treatments, the RR of serious adverse events was not statistically significant. Hormone replacement therapy (HRT) and calcitonin may be slower to work because they have only been shown to reduce the risk of vertebral fractures in long-term (>18 months) follow-up. Conclusions: A variety of drugs are safe and effective in preventing osteoporotic vertebral fractures. HRT and calcitonin only reduced the risk of vertebral fractures during a follow-up of 21-72 months.

Pharmacologic Therapy to Mitigate Acute Agitation in the Emergency Department: Case Reports of Diverse Patient Presentations.

Nurses in the emergency department often encounter patients exhibiting signs of aggressive behavior. Nurses need to know the pharmacologic treatment appropriate for the patient scenario to ensure safety for the patient and the emergency department team. This case review examines 4 common scenarios where a patient exhibits aggressive behavior. After each case review is a discussion about the appropriate pharmacologic therapy for that patient. The cases portrayed are fictional but based on experience and previous observations.

Potential pharmacological target of tight junctions to improve the BBB permeability in neonatal Hypoxic-Ischemic encephalopathy Diseases.

Neonatal encephalopathy (NE) is a pathological condition that describes a neurocognitive malfunction in the newborn that arises from fetal, peripartum, or intrapartum events of multifactorial nature, having a poor prognosis and accounting for an incidence of 5-8 per 1000 live births. Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most studied paradigms of NE, caused by a scarce cerebral perfusion and oxygen supply during perinatal life. The cerebral hypoxic-ischemic insult promotes a loss of permeability of the blood-brain barrier (BBB), an essential structural intermediary of blood-brain communication. This permeability disruption is associated with an increase in inflammatory cytokines, an increase of adhesion molecules, and oxidative stress which disturb the tight junction (TJ) performance and enable transcytosis and paracellular leakage, ultimately leading to death from brain cells. In this context, TJs proteins are essential to preserving the barrier mechanical stability and signaling that modulates the brain-blood vessel multicellular domains, known as neurovascular units (NVU). Recent studies have proposed different strategies with neuroprotective effects that allow for maintaining or restoring the integrity and permeability of the BBB. This review identifies and discusses regulator mechanisms and novel aspects of TJs in the BBB disruption induced by cerebral hypoxic insults during the perinatal period, evaluating potential pharmacological strategies to safeguard BBB integrity.

Use of Levosimendan in Patients with Advanced Heart Failure: An Update.

Levosimendan is an inodilator drug that, given its unique pharmacological actions and safety profile, represents a viable therapeutic option in patients with heart failure with reduced ejection fraction in the advanced stage of the disease (advHFrEF). Pulsed levosimendan infusion in patients with advHFrEF improves symptoms and clinical and hemodynamic status, prevents recurrent hospitalizations, and enables optimization of guidelines-directed medical therapy. Furthermore, considering its proprieties on right ventricular function and pulmonary circulation, levosimendan could be helpful for the prevention and treatment of the right ventricular dysfunction post-implanting a left ventricular assist device. However, to date, evidence on this issue is scarce and has yielded mixed results. Finally, preliminary experiences indicate that treatment with levosimendan at scheduled intervals may serve as a "bridge to transplant" strategy in patients with advHFrEF. In this review, we summarized the clinical pharmacology of levosimendan, the available evidence in the treatment of patients with advHFrEF, as well as a hypothesis for its use in patients with advanced heart failure with preserved ejection fraction.

Pharmacologic Therapy for Heart Failure with Preserved Ejection Fraction.

The management of heart failure with preserved ejection fraction (HFpEF) is rapidly evolving. The pharmacologic treatment of patients with HFpEF includes symptom management with diuretics and optimization of comorbidities, including hypertension, obesity, diabetes mellitus, and atrial fibrillation. Specific therapies, including angiotensin II receptor blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors, are well tolerated and can reduce the risk of HF hospitalization, particularly in those on the lower end of the HFpEF left ventricular ejection fraction spectrum. Ongoing trials should continue to inform optimal therapy in this evolving field.

Allergic Rhinitis: Pathophysiology and Treatment Focusing on Mast Cells.

Allergic rhinitis (AR) is a common rhinopathy that affects up to 30% of the adult population. It is defined as an inflammation of the nasal mucosa, develops in allergic individuals, and is detected mostly by a positive skin-prick test. AR is characterized by a triad of nasal congestion, rhinorrhea, and sneezing. Mast cells (MCs) are innate immune system effector cells that play a pivotal role in innate immunity and modulating adaptive immunity, rendering them as key cells of allergic inflammation and thus of allergic diseases. MCs are typically located in body surfaces exposed to the external environment such as the nasal mucosa. Due to their location in the nasal mucosa, they are in the first line of defense against inhaled substances such as allergens. IgE-dependent activation of MCs in the nasal mucosa following exposure to allergens in a sensitized individual is a cardinal mechanism in the pathophysiology of AR. This review is a comprehensive summary of MCs' involvement in the development of AR symptoms and how classical AR medications, as well as emerging AR therapies, modulate MCs and MC-derived mediators involved in the development of AR.