BACKGROUND: Adverse outcomes from moderate aortic stenosis (AS) may be caused by progression to severe AS or by the effects of comorbidities. In the absence of randomized trial evidence favoring aortic valve replacement (AVR) in patients with moderate AS, phenotyping patients according to risk may assist decision making.
OBJECTIVE: This study sought to identify and validate clusters of moderate AS that may be used to guide patient management.
METHODS: Unsupervised clustering algorithms were applied to demographics, comorbidities, and echocardiographic parameters in a training data set in patients with moderate AS (n = 2,469). External validation was obtained by assigning the defined clusters to an independent group with moderate AS (n = 1,358). The primary outcome, a composite of cardiac death, heart failure hospitalization, or aortic valve (AV) intervention after 5 years, was assessed between clusters in both data sets.
RESULTS: Four distinct clusters-cardiovascular (CV)-comorbid, low-flow, calcified AV, and low-risk-with significant outcomes (log-rank P < 0.0001 in both data sets) were identified and replicated. The highest risk was in the CV-comorbid cluster (validation HR: 2.00 [95% CI: 1.54-2.59]; P < 0.001). The effect of AVR on cardiac death differed among the clusters. There was a significantly lower rate of outcomes after AVR in the calcified AV cluster (validation HR: 0.21 [95% CI: 0.08-0.57]; P = 0.002), but no significant effect on outcomes in the other 3 clusters. These analyses were limited by the low rate of AVR.
CONCLUSIONS: Moderate AS has several phenotypes, and multiple comorbidities are the key drivers of adverse outcomes in patients with moderate AS. Outcomes of patients with noncalcified moderate AS were not altered by AVR in these groups. Careful attention to subgroups of moderate AS may be important to define treatable risk.

Evidence-based treatment recommendations for psoriatic arthritis (PsA) suggest that treatment should be individualised but acknowledge the difficulty of correctly defining levels of activity (mild, moderate and severe). The aim of this study was to define the parameters or disease characteristics that should be included in a future definition of moderate PsA. Mixed. methods: (1) literature review to identify previous assessment tools used to classify patients into mild, moderate and severe forms, and (2) survey of rheumatologists, and experts in PsA, to obtain their opinion on the degree of validation and applicability of published definitions and tools, and on the parameters that should be included in a future definition of moderate PsA. We propose eight domains/items to be included in a definition of moderate PsA: number of active joints and inflamed entheses, physician global assessment (by visual analogue scale), dactylitis, body surface area (BSA) affected by psoriasis, psoriasis in special locations, and absence of hip involvement. The Disease Activity Index for Psoriatic Arthritis (DAPSA) score would be supported as part of this definition, as would the Psoriatic Arthritis Impact of Disease (PsAID) index. This study proposes a set of items/domains to be included in a definition of moderate PsA based on literature and expert opinion, which can be the starting point for further development and validation studies of the proposed items.

暂无摘要。

We report an extremely rare case of long-standing (> six months) minimal pericardial effusion attributed to dermatomyositis. The patient was inadvertently administered antitubercular drug therapy for three months after which the patient developed significant weight loss, extreme anorexia, nausea, and vomiting refractory to conventional management. The key message in the manuscript is that even indolent dermatomyositis can present solely as an unexplained pericardial effusion in an individual.

BACKGROUND: Psoriasis involvement in special areas (e.g., scalp or nails) is associated with a great disease burden yet it is often inadequately treated with topical treatments. The efficacy and tolerability of apremilast plus existing topical therapy in Japanese patients with mild to moderate plaque psoriasis were demonstrated in PROMINENT, a phase 3b, multicenter, open-label, single-arm study. We evaluated the efficacy of apremilast across disease severities and special areas involved in these patients.
METHODS: In PROMINENT, patients received apremilast 30 mg twice daily for 16 weeks in addition to their existing topical therapy, with the option of topical therapy reduction at the discretion of their physician while continuing apremilast treatment from Weeks 16 to 32. We performed a post hoc analysis, assessing apremilast efficacy and safety in Japanese patients stratified by baseline static Physician Global Assessment (sPGA) score (2 [mild] or 3 [moderate]) and special area involvement.
RESULTS: Of patients with baseline sPGA = 2 and sPGA = 3, 62.7% and 30.7%, respectively, achieved sPGA score 0 or 1 at Week 32. At Week 32, improvements in skin, nail, scalp, and quality of life assessments were observed regardless of baseline sPGA score. Improvements in these endpoints at Week 32 were also observed in patients with special area (scalp or nail) involvement (n = 134). Incidence of adverse events was similar between patients with baseline sPGA = 2 and sPGA = 3.
CONCLUSIONS: Apremilast in combination with topical therapy may be a beneficial treatment for Japanese patients, who have limited systemic treatment options for mild to moderate psoriasis or psoriasis in special areas.
BACKGROUND: NCT03930186.

Background: Hemophilia is a congenital disorder characterized by deficiency or absence of clotting factor VIII in hemophilia A (HA) or clotting factor IX in hemophilia B (HB), resulting in frequent, repeated, and prolonged spontaneous or traumatic bleeding into joints or soft tissue. Severity is classified by the patient\'s baseline level of clotting factor activity as mild (>5%-40%), moderate (1%-5%), or severe (<1%). In Spain, there is limited information on the societal economic burden of disease. Objective: To estimate the economic and humanistic burden of disease in adult patients with non-inhibitor moderate and severe HA and HB in Spain. Methods: Spanish data from the CHESS II study (2018-2020) on patients\' clinical characteristics, health-related quality of life (HRQoL) and hemophilia-related healthcare resource utilization were analyzed. Economic burden was determined by estimating condition-related annual per-patient direct (medical and nonmedical) and indirect costs, stratified according to hemophilia type and severity and presented as 2022 Euros. HRQoL was assessed via the EQ-5D-5L. Results: Of 341 patients in the Spanish CHESS II cohort, 288 patients met the inclusion criteria: 181 had HA (37% [n = 66] moderate and 63% [n=115] severe) and 107 had HB (26% [n = 28] moderate and 74% [n = 79] severe). Mean annual direct cost was higher in HB than in HA, and higher in severe than in moderate patients, resulting in an annual cost/patient of €17 251 (moderate HA), €17 796 (moderate HB), €116 767 (severe HA) and €206 996 (severe HB). The main direct cost component in all groups except moderate HA was factor replacement therapy. Mean per-patient indirect cost was €4089 (moderate HA), €797 (moderate HB), €8633 (severe HA) and €8049 (severe HB). Finally, the mean total cost (direct and indirect) for moderate and severe patients were €91 017 (HA) and €163 924 (HB). EQ-5D-5L [SD] scores were lower in patients with severe HA (0.77 [0.18]) and severe HB (0.70 [0.22]) compared with patients with moderate HA (0.81 [0.15]) and moderate HB (0.86 [0.17]). Conclusions: Independently of the type of hemophilia, greater condition severity was associated with increased costs and a decrease in HRQoL.

Many previous studies have found that disability leads to cognitive impairment, and in order to better understand the underlying mechanisms between disability and cognitive impairment, the present study aimed to investigate the moderating role of social relationships, including their role as mediators between disability and cognitive impairment in depressive symptoms.
This is a cross-sectional study.
A total of 5,699 Chinese older adults from the 2018 China Longitudinal Healthy Longevity Survey (CLHLS) were included in this study, and PROCESS macro was used to perform simple mediator and moderator mediator analyses, which were used to analyze the relationship between depressive symptoms and social relationships between disability and cognitive impairment.
The results of this study showed significant correlations between disability, cognitive impairment, depressive symptoms, and social relationships, and that depressive symptoms mediated the relationship between disability and cognitive functioning [B = -0.232; 95% CI: (-0.304, -0.164)], and that social relationships mediated disability and cognitive functioning through pathway a (Disability-Depressive Symptoms) [B = 0.190; 95% CI: (0.020, 0.036)], path b (depressive symptoms-cognitive impairment) [B = 0.029; 95% CI: (0.015, 0.042)], and path c\' (incapacitation-cognitive impairment) [B = 0.492; 95% CI: (0.298, 0.685)] to modulate the effect of incapacitation on cognitive impairment. In addition, social activities and social networks moderated the mediation model directly or indirectly, whereas social support moderated only the direct effect.
This study explains the intrinsic link between incapacitation and cognitive impairment in Chinese older adults, and that social relationships and depressive symptoms can directly or indirectly modulate the effects between them. This provides a basis for healthcare professionals to be able to better develop interventions that can be used to improve the level of cognitive functioning and mental health of older adults.

OBJECTIVE: To characterise non-severe haemophilia A (HA) patients enrolled on the Australian Bleeding Disorders Registry (ABDR) treated through a state-wide Haemophilia Treatment Centre (HTC) with respect to their mutational profile, inhibitor risk and health-care burden.
METHODS: We conducted a single-centre observational study of all non-severe HA patients treated at the Alfred Health HTC registered on the ABDR as of the 26th July 2023. Data were extracted from the ABDR and electronic medical record (EMR) regarding demographics, severity, genetic testing, treatment, inhibitors, bleeding events and procedures. Inhibitor risk was calculated as a function of exposure days (EDs) of FVIII replacement.
RESULTS: There were 289 non-severe HA patients treated at the Alfred HTC registered on the ABDR as of July 2023, all of whom were adult patients aged > 18 years old. Genotyping had been performed in 228/289 (78.9%). Of the inhibitor analysis population, 14/193 (7.3%) had an inhibitor. The cumulative incidence of inhibitor development at 75 EDs was 31% (95% CI 13%-46%). The median cost of bypassing agents per inhibitor patient was $57,087.50/year.
CONCLUSIONS: These results demonstrate a relatively high inhibitor prevalence and incidence risk in non-severe HA compared to previously published work, although this may partly reflect a smaller population size. High rates of genotyping have allowed representative mutational characterisation. The burden of care imposed by non-severe HA in terms of bleeding events, procedures and bypassing agent cost is larger than expected, particularly within the inhibitor population.

Peer victimization (PV) is a common and serious problem in school contexts, which hinders adolescents\' emotional development and social adaptation. The present study aimed to test the longitudinal relationship between PV and the increase of depressive symptoms (DSs) among Chinese mid-late adolescents using a two-wave longitudinal design and examine the buffering effects of self-compassion (SC) and parental autonomy support (PAS) on this relationship. A relatively large sample of Chinese high school students (N = 722, 52.1% boys; age at Time 2 = 16.23 years old, SD = 0.79) were surveyed annually at two time points. The results showed that PV at Time 1 positively predicted DSs at Time 2 after controlling for the DSs at Time 1. In addition, SC and PAS moderated the longitudinal relationship between PV and the development of DSs, while such moderating effects only existed in girls but not in boys. Specifically, the positive relationship between PV and DSs was non-significant among girls with higher levels of SC or PAS. Our findings highlighted that SC and PAS might be important protective factors buffering against DSs for victimized girls.

Neuroticism, an emotion-related personality trait, is often associated with a greater susceptibility to depression. On the other hand, self-compassion involves treating oneself in a peaceful, mindful, and friendly manner, particularly in the face of failure or frustration. The study investigated the relationship between neuroticism and depression in junior high school students, as well as the moderating role of self-compassion. A total of 757 junior high school students participated in the survey, which included the Children\'s Depression Inventory, the Eysenck Personality Questionnaire-Revised, Short Scale for Chinese, and the Chinese version of the Self-Compassion Scale. The results revealed that neuroticism positively predicted depression, while self-compassion had a significant moderating effect on the relationship between neuroticism and depression. Specifically, higher levels of self-compassion were associated with a weaker link between neuroticism and depression. These findings suggest that interventions promoting self-compassion may be beneficial for students exhibiting neurotic tendencies.