Postgraduate medicine最新文献

Objectives: Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Methods: NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs.

Results: NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (-44 [95% CI -328; -21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue.

Conclusion: Daridorexant 50 mg and 25 mg have a favorable benefit-risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

Insulin serves multiple functions as a growth-promoting hormone in peripheral tissues. It manages glucose metabolism by promoting glucose uptake into cells and curbing the production of glucose in the liver. Beyond this, insulin fosters cell growth, drives differentiation, aids protein synthesis, and deters degradative processes like glycolysis, lipolysis, and proteolysis. Receptors for insulin and insulin-like growth factor-1 are widely expressed in the central nervous system. Their widespread presence in the brain underscores the varied and critical functions of insulin signaling there. Insulin aids in bolstering cognition, promoting neuron extension, adjusting the release and absorption of catecholamines, and controlling the expression and positioning of gamma-aminobutyric acid (GABA). Importantly, insulin can effortlessly traverse the blood-brain barrier. Furthermore, insulin resistance (IR)-induced alterations in insulin signaling might hasten brain aging, impacting its plasticity and potentially leading to neurodegeneration. Two primary pathways are responsible for insulin signal transmission: the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, which oversees metabolic responses, and the mitogen-activated protein kinase (MAPK) pathway, which guides cell growth, survival, and gene transcription. This review aimed to explore the potential shared metabolic traits between Alzheimer's disease (AD) and IR disorders. It delves into the relationship between AD and IR disorders, their overlapping genetic markers, and shared metabolic indicators. Additionally, it addresses existing therapeutic interventions targeting these intersecting pathways.

For decades, we have been treating patients presenting with angina and concerning electrocardiographic changes indicative of ischemia or injury, in whom no culprit epicardial coronary stenosis was found during diagnostic coronary angiography. Unfortunately, the clinical outcomes of these patients were not better than those with recognized obstructive coronary disease. Improvements in technology have allowed us to better characterize these patients. Consequently, an increasing number of patients with ischemia and no obstructive coronary artery disease (INOCA) or myocardial infarction in the absence of coronary artery disease (MINOCA) have now gained formal recognition and are more commonly encountered in clinical practice. Although both entities might share functional similarities at their core, they pose significant diagnostic and therapeutic challenges. Unless we become more proficient in identifying these patients, particularly those at higher risk, morbidity and mortality outcomes will not improve. Though this field remains in constant flux, data continue to become available. Therefore, we thought it would be useful to highlight important milestones that have been recognized so we can all learn about these clinical entities. Despite all the progress made regarding INOCA and MINOCA, many important knowledge gaps continue to exist. For the time being, prompt identification and early diagnosis remain crucial in managing these patients. Even though we are still not clear whether intensive medical therapy alters clinical outcomes, we remain vigilant and wait for more data.

Objectives: Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA.

Methods: In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up.

Results: The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009-0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96).

Conclusion: Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA.

Objective: This study aimed to assess physicians' approach to cardiac murmurs and their level of knowledge about this sign, which is a crucial finding in childhood cardiac anomalies.

Methods: The study intended to include all family physicians in the Adıyaman province of Turkey, but ultimately 150 out of 210 physicians participated and was completed with a percentage response rate of 71%. Participants were asked about their approach to cardiac murmurs, answered knowledge questions, and completed a questionnaire on demographic characteristics. Subsequently, eight heart sounds were played, and participants were asked to identify the nature of each sound.

Results: Family medicine specialists (all scores were p < 0.001) and physicians who completed a pediatric internship lasting over a month (knowledge score p = 0.012, behavioral score p = 0.021, recording score p = 0.01) demonstrated significantly higher knowledge, approach, and recording scores. Age and years in the profession showed a negative correlation with recording scores.

Conclusions: The study highlights the significant impact of various factors such as gender, specialization, internship duration, experience, and theoretical knowledge on the ability to recognize and approach cardiac murmurs. These findings underscore the importance of incorporating these factors into medical education and development programs, especially those aimed at improving cardiac examination skills.

Objective: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD).

Methods: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), β-I type collagen carboxy-terminal peptide (β-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed.

Results: Compared with the T2DM+non-HF group, β-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, β-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with β-CTx [β = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [β=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between β-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith β-CTx [β = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [β=-0.124; 95% CI (0.007,0.001) and β=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [β=-0.117; 95% CI (-0.007, -0.001) and β=-0.003; 95% CI (-0.013, -0.003)].

Conclusion: SF level was positively correlated with β-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

Background: The current point-of-care ultrasound (POCUS) assessment of gastric fluid volume primarily relies on the traditional linear approach, which often suffers from moderate accuracy. This study aimed to develop an advanced machine learning (ML) model to estimate gastric fluid volume more accurately.

Methods: We retrospectively analyzed the clinical data and POCUS data (D1: craniocaudal diameter, D2: anteroposterior diameter) of 1386 patients undergoing elective sedated gastrointestinal endoscopy (GIE) at Nanjing First Hospital to predict gastric fluid volume using ML techniques, including six different ML models and a stacking model. We evaluated the models using the adjusted Coefficient of Determination (R²), mean absolute error (MAE) and root mean square error (RMSE). The SHapley Additive exPlanations (SHAP) method was used to interpret the importance of the variables. Finally, a web calculator was constructed to facilitate its clinical application.

Results: The stacking model (Linear regression + Multilayer perceptron) performed best, with the highest adjusted R² of 0.718 (0.632 to 0.804). The mean prediction bias was 4 ml (MAE: 4.008 (3.68 to 4.336)), which is better than that of the linear model. D1 and D2 ranked high in the SHAP plot and performed better in the right lateral decubitus (RLD) than in the supine position. The web calculator can be accessed at https://cheason.shinyapps.io/Stacking_regressor/.

Conclusion: The stacking model and its web calculator can serve as practical tools for accurately estimating gastric fluid volume in patients undergoing elective sedated GIE. It is recommended that anesthesiologists measure D1 and D2 in the patient's RLD position.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. Primary care providers play a critical role in the screening, diagnosis, and management of MASLD and/or metabolic dysfunction-associated steatohepatitis (MASH), though they can face challenges in this setting, particularly where healthcare resources are limited and barriers to care exist. To address these challenges, several guidelines have been developed to provide evidence-based recommendations for the clinical assessment and management of patients with MASLD/MASH.

Aims: To provide a unified, simple-to-understand, practical guide for MASLD screening, diagnosis, and management based on current guideline recommendations, for use by primary care providers in daily practice.

Methods: Evidence-based recommendations from several international guidelines were summarized, focusing on the similarities and differences between them.

Results: Recommendations are broadly aligned across the guidelines, but several key differences are evident. Practical guidance is provided on screening, identifying target populations for risk stratification, initial evaluation of individuals with suspected MASLD, surveillance, risk stratification and referral, as well as approaches to the management of MASLD and associated comorbidities, with specific considerations for the primary care setting.

Conclusions: Primary care providers are ideally placed to identify at-risk individuals, implement evidence-based interventions to prevent the development of fibrosis and cirrhosis, and effectively manage comorbidities. Equipping primary care providers with the necessary knowledge and tools to effectively manage MASLD/MASH may help to improve patient outcomes and reduce the burden of liver disease.

Objective: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are autoinflammatory disorders typically characterized by recurrent fever attacks. These recurrent fever attacks can lead to depression and anxiety in mothers of these patients. This study aimed to compare the depression and anxiety levels in mothers of PFAPA and FMF patients.

Methods: This study is a cross-sectional observational study. 48 mothers of children with FMF and 70 mothers of children with PFAPA participated in the study. Mothers in these two groups were compared in terms of anxiety and depression by using the validated Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).

Results: Depression and anxiety scores of mothers were found to be similar in FMF and PFAPA groups. Moderate or high level of anxiety was seen in 32% of mothers of patients with PFAPA and 27% of mothers of patients with FMF. 23% of mothers of patients with PFAPA were evaluated as having moderate or severe depression, and 18% of mothers of patients with FMF were evaluated as having moderate depression. There was no statistically significant difference between the duration, frequency of attacks, recurrent hospitalizations, sociodemographic characteristics, and inventory scores.

Conclusion: Depression and anxiety scores of mothers with children diagnosed with FMF and PFAPA are similar. These two diseases affect families psychosocially at similar levels. It is important to provide psychosocial support to families.

Use of innovative technologies such as continuous glucose monitoring (CGM) and insulin delivery systems have been shown to be safe and effective in helping patients with diabetes achieve significantly improved glycemic outcomes compared to their previous therapies. However, these technologies are underutilized in many primary care practices. This narrative review discusses some of the clinical and economic benefits of tubeless insulin delivery devices and discusses how this technology can overcome the main obstacles inherent to use of conventional insulin delivery devices.