Association between depression and anxiety with skin and musculoskeletal clinical phenotypes in systemic lupus erythematosus.

OBJECTIVES: To study the clinical phenotypes, determined based on cumulative disease activity manifestations, and sociodemographic factors associated with depression and anxiety in SLE. METHODS: Patients attending a single centre were assessed for depression and anxiety. SLE clinical phenotypes were based on the organ systems of cumulative 10-year SLE Disease Activity Index 2000 (SLEDAI-2K), prior to visit. Multivariable logistic regression analyses for depression, anxiety, and coexisting anxiety and depression were performed to study associated SLE clinical phenotypes and other factors. RESULTS: Among 341 patients, the prevalence of anxiety and depression was 34% and 27%, respectively, while 21% had coexisting anxiety and depression. Patients with skin involvement had significantly higher likelihood of anxiety compared with patients with no skin involvement [adjusted odds ratio (aOR) = 1.8; 95% CI: 1.1, 3.0]. Patients with skin involvement also had higher likelihood of having coexisting anxiety and depression (aOR = 2.0, 95% CI: 1.2, 3.9). Patients with musculoskeletal (MSK) (aOR = 1.9; 95% CI: 1.1, 3.5) and skin system (aOR = 1.8; 95% CI: 1.04, 3.2) involvement had higher likelihood of depression compared with patients without skin or musculoskeletal involvement. Employment status and fibromyalgia at the time of the visit, and inception status were significantly associated with anxiety, depression, and coexisting anxiety and depression, respectively. CONCLUSION: SLE clinical phenotypes, specifically skin or MSK systems, along with fibromyalgia, employment and shorter disease duration were associated with anxiety or depression. Routine patient screening, especially among patients with shorter disease duration, for these associations may facilitate the diagnosis of these mental health disorders, and allow for more timely diagnosis.

Epigenetic markers of prostate cancer in plasma circulating DNA.

Epigenetic differences are a common feature of many diseases, including cancer, and disease-associated changes have even been detected in bodily fluids. DNA modification studies in circulating DNA (cirDNA) may lead to the development of specific non-invasive biomarkers. To test this hypothesis, we investigated cirDNA modifications in prostate cancer patients with locally confined disease (n = 19), in patients with benign prostate hyperplasias (n = 20) and in men without any known prostate disease (n = 20). This initial discovery screen identified 39 disease-associated changes in cirDNA modification, and seven of these were validated using the sodium bisulfite-based mapping of modified cytosines in both the discovery cohort and an independent 38-patient validation cohort. In particular, we showed that the DNA modification of regions adjacent to the gene encoding ring finger protein 219 distinguished prostate cancer from benign hyperplasias with good sensitivity (61%) and specificity (71%). We also showed that repetitive sequences detected in this study were meaningful, as they indicated a highly statistically significant loss of DNA at the pericentromeric region of chromosome 10 in prostate cancer patients (p = 1.8 × 10(-6)). Based on these strong univariate results, we applied machine-learning techniques to develop a multi-locus biomarker that correctly distinguished prostate cancer samples from unaffected controls with 72% accuracy. Lastly, we used systems biology techniques to integrate our data with publicly available DNA modification and transcriptomic data from primary prostate tumors, thereby prioritizing genes for further studies. These data suggest that cirDNA epigenomics are promising source for non-invasive biomarkers.

Herpes zoster in SLE: prevalence, incidence and risk factors.

OBJECTIVES: This study aimed to evaluate the prevalence and incidence of herpes zoster (HZ) events and describe its associated factors in a study of patients with SLE. METHODS: 491 consecutive SLE participants were screened for HZ events using a patient-reported questionnaire to capture outcomes on pain and other characteristics associated with HZ events. Sociodemographic, clinical and laboratory measures were also analysed, and time-dependent Cox regression survival analyses were performed to investigate factors associated with HZ events. RESULTS: Prevalence of HZ was 30.5%, incidence was 14.3 cases per 1000 person-years. Lymphopenia and glucocorticoid dosing were significantly associated with HZ events. CONCLUSIONS: HZ is highly prevalent in SLE, which may be linked to disease-related and treatment-related effects on cellular immunity. Our results suggest that the presence of certain risk factors may be useful to allow identification of patients at risk of HZ and improve its management in patients with SLE.

The Assessment of Anxiety and Depression and its Associated Factors in SLE.

BACKGROUND: Depression and anxiety are common neuropsychiatric complaints in patients with Systemic Lupus Erythematosus (SLE). While numerous studies have been performed to investigate the prevalence, impact, and associated factors of depression and anxiety, current literature presents mixed results. In particular, the prevalence of anxiety and depression varies substantially between studies due to methodological limitations, and heterogeneity in defining anxiety and depression, patient selection, and metrics used. Moreover, there is a lack of studies evaluating the validity, reliability, and interpretability of commonly used screening tools for depression and anxiety in SLE patients. RESULT AND CONCLUSION: Further investigations should aim to reach a consensus surrounding the role of controversial associated factors in depression and anxiety of SLE patients, while also focusing on the identification of novel factors that have not yet been highlighted in the literature.

Assessment of the psychometric properties of patient-reported outcomes of depression and anxiety in systemic lupus erythematosus.

OBJECTIVES: This study aimed to: 1) determine the prevalence of depression and anxiety in SLE patients using the Center for Epidemiological Studies-Depression Scale [CES-D], Hospital Anxiety and Depression Scale [HADS], and Beck Anxiety Inventory [BAI] questionnaires; 2) study the criterion validity, interpretability, and test-retest reliability of CES-D, HADS and BAI; and 3) evaluate their diagnostic accuracy when compared to the assessment of an independent psychiatric assessment using the Mini-International Neuropsychiatric Interview (MINI). METHODS: 159 consecutive SLE participants were screened for depression and anxiety using the CES-D, HADS, and BAI, and underwent the MINI. Sensitivity and specificity were evaluated against the MINI. Test-retest reliability was studied. Receiver operator characteristic (ROC) curves were utilized to determine the cut-off scores for CES-D, HADS and BAI. RESULTS: The prevalence of depression ranged from 29% (HADS-D) to 52% (CES-D) and the prevalence of anxiety ranged from 45% (BAI) to 50% (HADS-A). ROC showed similar performance for CES-D and HADS-D. The diagnostic accuracy of HADS-A outperformed BAI. Furthermore, these self-reported questionnaires demonstrated good to excellent test-retest reliability. Analyses exhibited optimal cut-offs for CES-D (26), BAI (19), HADS-A (6), and HADS-D (8) that optimized their sensitivity and specificity as screening metrics for depression and anxiety in SLE patients. CONCLUSIONS: Anxiety and depression are highly prevalent in patients with SLE. Patient-reported outcome questionnaires such as the CES-D, HADS, and BAI may be useful tools to screen for depression and anxiety in SLE. Our results suggest that SLE-specific cut-offs may improve diagnostic accuracy of current screening metrics in patients with lupus.

Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients.

Purpose: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance.Experimental Design: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients.Results: Thirty cytosines showed significant modification differences (FDR Q < 0.05) between AA-sensitive and AA-resistant patients during the treatment, of which 21 cytosines were differentially modified prior to treatment. In addition, AA-sensitive patients, but not AA-resistant patients, lost interindividual variation of cfDNA modification shortly after starting AA treatment, but such variation returned to initial levels in the later phases of treatment.Conclusions: Our findings provide a list of potential biomarkers for predicting AA-treatment response, highlight the prognostic value of using cytosine modification variance as biomarkers, and shed new insights into the mechanisms of prostate cancer relapse in AA-sensitive patients. Clin Cancer Res; 24(14); 3317-24. ©2018 AACR.

What is the prevalence of cognitive impairment in lupus and which instruments are used to measure it? A systematic review and meta-analysis.

OBJECTIVES: To systematically review the literature on the prevalence of Cognitive Dysfunction (CD) in SLE patients in studies that used a specified neuropsychological instrument. METHODS: This review was prepared with a protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocols statement. Literature search in Ovid Medline, Embase, and Psyc INFO for articles on CD in adult SLE patients was conducted. Included studies were critically appraised (Newcastle-Ottawa Evaluation Scale) and the Pooled Prevalence (PP) of CD was studied for all instruments. The association between demographics and CD, the risk of CD in SLE compared to healthy subjects and patients with RA, and the course of CD over time were studied narratively whenever sufficient information was available. RESULT: Of 8054 references, 670 were selected for detailed review and 78 were included in the final analysis. Comprehensive Battery (CB) was utilized in 35 studies in 2463 SLE patients and PP was 38% (95%; CI: 33-43%). The CD prevalence was higher in NPSLE [PP 39% (95% CI: 24-55%]. Automated Neuropsychological Assessment Metric (ANAM) was utilized in 7 studies in 438 patients (PP of CD 26% (95% CI: 12-42%). Other less frequently utilized tools were the Modified Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), Controlled Oral Word Association Test (COWAT) and The Hopkins Verbal Learning Test-Revised (HVLT-R) and subjective tools and others. The relative risk for CD in SLE was greater when compared to RA and to healthy individuals; RR being 1.80 and 2.80, respectively. Information on demographics and its association with CD was very heterogeneous among studies. CONCLUSION: Patients with lupus have a high prevalence of CD. The delay in diagnosis of CD is complex; although caregivers and patients express concerns about cognitive function, testing for CD often imposes administrative and cost burdens. There is an unmet need to identify the best screening, diagnostic metrics of CD. The assessment of cognitive function over time, and the association of demographics with CD, will require further research.

Improving the quality of randomized controlled trials in Chinese herbal medicine, part I: clinical trial design and methodology.

OBJECTIVE: To discuss the quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) with respect to design and methodology, and provide suggestions for further improvement in future clinical trials. METHODS: A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005. Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement, with 2 items specific to CHM (i.e. herb preparation form and quality control of herbs). RESULTS: The search yielded 167 RCTs that were selected for assessment. All trials included statements about the interventions, objectives, primary outcome design, statistical methods, and herb preparation form. Although 163 (97.6%) trials reported inclusion criteria, exclusion criteria were only reported in 26 (15.6%) trials. Fewer than 10% of trials clearly stated the random allocation sequence generation methods, and only 2.4% mentioned allocation concealment. The vast majority (86.8%) of trials were open-label, while only 13.2% used blinding. Almost half (45.5%) administered the CHM intervention as a tea or decoction. Only one trial (0.6%) reported a sample size calculation, and a single trial (0.6%) discussed quality control of the CHM intervention. CONCLUSION: The overall methodologic quality of RCTs in CHM was poor. It is essential to improve the design of future RCTs in this clinical area. RECOMMENDATIONS: (1) Investigator conducting RCTs should have formal training about clinical trial design; (2) A flow chart is recommended to ensure that all essential steps of clinical trial design are included. (3) Conducting pilot studies prior to RCTs may help improve their design; (4) Registration of clinical trials and publishing their protocols prior to enrollment may reduce publication bias and solicit peer reviews of the proposed design; (5) Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM.

Electroacupuncture for older adults with mild cognitive impairment: study protocol for a randomized controlled trial.

BACKGROUND: Mild cognitive impairment is an intermediary state between normal aging and clinical Alzheimer's disease. Early intervention of mild cognitive impairment may be an important strategy in the management of Alzheimer's disease. The proposal aims to evaluate if electroacupuncture would optimize cognitive function in subjects with mild cognitive impairment and understand the role of electroacupuncture in the treatment of Alzheimer's disease. METHODS/DESIGN: A randomised patient- and assessor-blind sham-controlled trial is designed to assess whether electroacupuncture intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment. One hundred and fifty subjects aged 65 years of age or over with a diagnosis of mild cognitive impairment are recruited from the community and elderly centre in Hong Kong. All subjects are randomly allocated into two groups (75 subjects each group): the electroacupuncture group and sham control. Participants in the electroacupuncture group receive electroacupuncture stimulation by sterile, disposable acupuncture needles inserted to the acupoints with a depth of 1 to 3 cm. The acupuncture needles are subjected to 2 Hz electroacupuncture with an intensity of 5 to 10 mA. Each participant receives electroacupuncture for 8 weeks (once a day, 3 days a week) and the treatment lasts for 30 minutes each time. For sham electroacupuncture, needles are inserted to a depth of 1 to 2 mm, and connected to the electroacupuncture device without any current passing through. Outcome measures (including primary and secondary outcome measures) are collected at baseline, at the end day of intervention, and months 4 and 6 after intervention. The primary outcome is measured by the Alzheimer Disease Assessment Scale-Cognitive subscale. Secondary outcomes are measured by the mini-mental state examination, category fluency text and the Short Form 12. DISCUSSION: The study will provide evidence for evaluating and understanding the role of electroacupuncture in the treatment of Alzheimer's disease. TRIAL REGISTRATION: This trial is registered with chictr.org (registration number: ChiCTR-TRC-12002414 . Registration date: 11 August 2012.

DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.

BACKGROUND: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. METHODS: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. RESULTS: In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. CONCLUSIONS: Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.

Measuring body constitution: validation of the Body Constitution Questionnaire (BCQ) in Hong Kong.

BACKGROUND: The Body Constitution Questionnaire (BCQ) was developed in Taiwan to classify people into body constitution (BC) types based on Traditional Chinese Medicine (TCM) theories. Since the culture of Hong Kong is different from Taiwan, the BCQ must be validated before a wider application can be preceded. AIM AND OBJECTIVES: To adapt and validate the Hong Kong version of BCQ in Hong Kong Chinese population. METHODS: The content validity of BCQ was investigated by the cognitive debriefing with 10 patients and 10 Chinese Medicine Practitioners (CMP). A cross-sectional study of 1084 Chinese patients recruited from TCM and Western Medicine (WM) outpatient clinics to confirm the construct validity, reliability, sensitivity and responsiveness of BCQ. 225 of the patients were assessed after 2 weeks for the test-retest reliability. 404 subjects were followed up to evaluate the responsiveness after 3-6 months. RESULTS: Cognitive debriefing confirmed the content validity of the BCQ (HK version) with content validity index of all items ranged from 70 to 100%. 1084 out of 2128 patients (51%) completed the cross-sectional study. The construct validity was confirmed with scaling success rates that ranged from 87.5 to 89.5%, moderate correlations between with SF-12v2 scores, and 3-factors structure with confirmatory factor analysis. The reliability was confirmed by the Cronbach's alphas >0.8 and test-retest reliability (intra-class correlation coefficients >0.8). CONCLUSION: BCQ was adapted and validated on Hong Kong Chinese population. Patients with imbalanced BC types had lower health-related quality of life (HRQOL) than those with balanced BC types, which supported the validity and importance of the body constitution under the concept of TCM.

Validation of the constitution in chinese medicine questionnaire: does the traditional chinese medicine concept of body constitution exist?

The study aims to adapt and validate the Constitution in Chinese Medicine Questionnaire (CCMQ) in Hong Kong Chinese people. 10 patients and 10 Chinese medicine practitioners (CMP) confirmed the content validity (CVI: 50%-100%) of CCMQ. 1084 HK subjects completed a cross-sectional study with 98.6% who could be classified into one or more BC types. Scaling success rates were 85.7%-100% for the 9 BC scales. Construct validity was supported by moderate correlations between CCMQ and SF-12v2 scores. The confirmatory factor analysis showed a reproducible structure as hypothesized. People with gentleness BC type had better health-related quality of life, HRQOL, than those with other (imbalanced) BC types. Internal consistency (reliability) (Cronbach's alpha > 0.6) and test-retest reliability were also satisfactory (ICC > 0.6) for all scales. However, the sensitivity and specificity in predicting the BC types diagnosed by CMP were only fair, ranging from 42.7% to 82.7%. 27.6% of subjects had a change from the imbalanced BC types to gentleness BC type after 6 months. The CCMQ was adapted for HK Chinese people and proved to be valid, reliable, and responsive. People classified to have imbalanced BC types had significantly lower HRQOL than gentleness BC type, which supported the validity and importance of the TCM concept of the physiological BC type.