Effectiveness of transcranial direct current stimulation (tDCS) as adjunctive treatment for chronic headache in adults with clinically stable systemic lupus erythematosus (SHADE): a randomised double-blind multiarm sham controlled clinical trial.

BACKGROUND: Chronic headache is a 'silent' neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches. METHODS AND ANALYSIS: SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement. ETHICS AND DISSEMINATION: Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05613582.

Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial.

Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult systemic lupus erythematosus (SLE) patients. Subjects were randomized to receive either synbiotics or a placebo. Fecal microbiota, hs-CRP, IL-6, and IL-17 were measured at baseline and after 60 days. Patients who fulfilled the inclusion criteria were randomized into synbiotic (n = 23) and placebo groups (n = 23). In the synbiotic group, hs-CRP was not significantly increased (1.8 [0.9; 4.85] vs. 2.1 [0.9; 4.25] mg/L; pre vs. post; p = 0.23), whereas in the placebo group hs-CRP was increased significantly (1.75 [0.4; 4.45] vs. 3.75 [0.58; 7.05] mg/L; pre vs. post; p = 0.005). In the synbiotic group, IL-6 decreased significantly (8.76 [6.62; 11.39] vs. 6.59 [4.96; 8.01]; pre vs. post; p = 0.02), while there was no significant change in IL-17 level. In the placebo group, there was no significant change in IL-6 and IL-17. Synbiotic supplementation increased the Firmicutes:Bacteroidetes ratio (0.05 ± 0.60 vs. -0.08 ± 0.63, synbiotic vs. placebo p = 0.48) and butyrate metabolism (p = 0.037) and decreased amino sugar and nucleotide sugar metabolism (p = 0.040). There was improvement in the SLE disease activity index 2K (SLEDAI-2K) score in the synbiotic group (14 [9; 16] vs. 8 [2; 12]; pre vs. post; p < 0.001), while no change in the placebo group (9 [8; 18.25] vs. 9 [5.5; 15]; pre vs. post; p = 0.31). Synbiotic supplementation could reduce systemic inflammation and SLE disease activity and alter the composition and functions of gut microbiota.

Ramadan fasting reduces high-sensitivity C-reactive protein among HIV-infected patients receiving antiretroviral therapy.

Background: Inflammatory conditions and oxidative stress increase in HIV infection, and inflammation increases the risk of cardiovascular disease. Ramadan fasting is known to reduce inflammation and oxidative stress in diabetic patients. This study examined the effects of Ramadan fasting on high-sensitivity C-reactive protein (hs-CRP) levels and total antioxidant status (TAOS) in HIV patients on antiretroviral therapy (ART). Methods: This was a prospective cohort study comparing HIV-infected patients on stable ART who fasted throughout Ramadan to HIV-infected patients who did not fast during Ramadan. Inclusion criteria were men aged 20-40 years, taking first-line ART for at least 6 months, Muslims intent to fast for Ramadan, no current hospitalization because of acute conditions and not being treated for opportunistic infections. Results: After 2 weeks, hs-CRP had decreased significantly in the fasting group (-0.41 mg/L [IQR = -1; 0.10]) compared to the non-fasting group (0.20 mg/L [IQR = -0.30; 1.50]) (p = 0.004). The linear regression analysis has shown that Ramadan fasting contributed to 10.10% of the variance in hs-CRP value (R 2 = 0.101) and decreased its value by 0.317 points (B = -0.317). Changes in TAOS did not significantly different (p = 0.405) between the fasting group (0.05 mmol/L [IQR = -0.03; 0.12]) and the non-fasting group (0.04 mmol/L [IQR = -0.13; 0.36]). In the fasting group, there were significant changes in polyunsaturated fatty acid consumption (p = 0.029), body weight (p = 0.001), cigarette smoking (p = 0.001), and sleeping duration (p = 0.001). Conclusion: Ramadan fasting reduces hs-CRP concentrations among HIV patients on ART.

Impact of sofosbuvir and daclastavir on health-related quality of life in patients co-infected with hepatitis C and human immunodeficiency virus.

BACKGROUND: We conducted a real-life study of health-related quality of life (HRQoL) transformation before and 12 weeks after sofosbuvir and daclatasvir therapy in HCV/HIV co-infected patients. Factors related to the significant changes of each HRQoL domain/item were also evaluated. METHODS: A prospective study was performed in the HIV integrated clinic at Cipto Mangunkusumo Hospital, Jakarta. HCV/HIV co-infected patients who started sofosbuvir and daclatasvir from government free DAA program in 2017-2019. WHOQoL-HIV BREF and RAND SF-36 questionnaires were recorded at baseline and post-treatment week 12. RESULTS: 145 patients with mean age of 37.8 years (SD = 4.2) were included in the analysis. Most of patients were male (89%), previous IVDU (89%), active smoker (50.4%) and non-cirrhosis (80%). SVR12 was achieved in 95.5% of patients. Sofosbuvir and daclatasvir treatments showed positive impacts on 2 domains and 2 other items of WHOQoL-HIV BREF and 2 domains and 1 item of SF-36. Predicting factors of significant increase in each domain/item were: male and normal body mass index (BMI) for level of independence (RR 4.01,95% CI 1.09-14.74 and 4.80,95% CI 1.79-12.81); higher HCV-RNA for overall perception of QoL (RR 0.42,95% CI 0.18-0.94); non-smoking status for overall perception of health (RR 0.32,95% CI 0.15-0.66); male and fibrosis stage 0-1 for general health (RR 6.21,95% CI 1.69-22.88 and 2.86,95% CI 1.16-7.00); and the use of NNRTI-based ART (RR 5.23, 95% CI 1.16-23.65). Spiritual/personal belief decline was predicted by non-smoking status (RR 0.46, 95% CI 0.23-0.95). Treatment success was not associated with any changes of HR-QoL domain/item. CONCLUSIONS: HCV/HIV co-infected patients were successfully treated with sofosbuvir and daclatasvir and experienced improvement of HRQoL 12 weeks after treatment completion.

Diagnostic performance of APRI and FIB-4 for confirming cirrhosis in Indonesian HIV/HCV co-infected patients.

BACKGROUND: After successful of antiretroviral therapy, highly effective direct acting antiviral (DAA) make HCV elimination reasonable in HIV/HCV co-infected patients. However, in achieving this target, there are still barriers to start DAA treatment, particularly in the area of liver fibrosis assessment that determine the duration of therapy. We aimed to assess the diagnostic performance of APRI and FIB-4 for diagnosing cirrhosis in HIV/HCV co-infected patients using hepatic transient elastography (TE) as gold standard. METHOD: This is a retrospective study on HIV/HCV co-infected patients who concomitantly performed hepatic TE measurement, APRI, and FIB-4 evaluation before HCV treatment initiation at a tertiary hospital in Jakarta from 2014 to 2019. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) ≥ 12.5 kPa was determined by receiver operator characteristics curves. RESULTS: 223 HIV/HCV co-infected patients on stable antiretroviral therapy were included, of whom 91.5% were male with mean age of 37 (SD 5) years. Only 28.7% of patients were classified as cirrhosis (F4). Using TE as gold standard (≥12.5 kPa), the low threshold of APRI (1) had specificity 95%, sensitivity 48.4%, correctly classified 81.6% of patients, with moderate performance, AUC at 0.72 (95% CI 0.63-0.80). The optimal cut-off of FIB-4 was 1.66 [specificity 92.5%, sensitivity 53.1%, AUC at 0.73 (95% CI 0.65-0.81)] and correctly classified 81.1% of the patients. CONCLUSION: APRI score ≥ 1 and FIB-4 score ≥ 1.66 had moderate performance with high specificity in diagnosing cirrhosis. These biochemical markers could be used while TE is not available.