Psychometric Evaluation of the Multidimensional Scale-Uremic Pruritus in Dialysis Patients (UP-Dial): Comparison in Hemodialysis and Peritoneal Dialysis Patients with Chronic Pruritus.

BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uremic Pruritus in Dialysis (UP-Dial) 14-item, by comparing hemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uremic Pruritus, a prospective, multicenter, longitudinal study. Data for this study were collected from February 1, 2019, to May 31, 2022. The adult sample of 226 hemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across hemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73 to 0.74) with global itching, a positively moderate correlation (0.33 to 0.58) with DLQI, PSQI, global fatigue, SSS-8, and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation: 0.84 to 0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-items in hemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

Effect of Curcuminoids on Contrast-Induced Acute Kidney Injury after Elective Coronary Angiography or Intervention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: The role of curcuminoids, a striking antioxidant, in prevention of contrast-induced acute kidney injury (CI-AKI) remains unknown. We aimed to evaluate the efficacy and safety of curcuminoids in preventing CI-AKI in patients undergoing elective coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). METHODS: We randomized 114 patients who were undergoing elective CAG and/or PCI to receive curcuminoids, 4 g/day (1 day before and 1 day after the procedure, n = 56), or placebo (n = 58). Serum creatinine was assessed at baseline, 12, 24, and 48 h after contrast exposure. The primary endpoint was development of CI-AKI defined as serum creatinine increase ≥0.3 mg/dL within 48 h after contrast exposure. The secondary endpoint was the occurrence of kidney injury defined by >30% increase in urine neutrophil gelatinase-associated lipocalin (NGAL). RESULTS: Baseline characteristics were comparable between the two groups. Seven (12.7%) in curcuminoids group and eight (14.0%) in placebo group developed CI-AKI (p = 0.84). The incidence of increased urine NGAL was comparable in the placebo and curcuminoids group (39.6% vs. 50%, respectively; p = 0.34). None in both groups had drug-related adverse events. CONCLUSION: This is a pilot study to demonstrate the safety and tolerability of curcuminoids in patients undergoing elective CAG and/or PCI. Curcuminoids have no protective effects against kidney injury after elective CAG and/or PCI.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

Mortality Rates and a Clinical Predictive Model for the Elderly on Maintenance Hemodialysis: A Large Observational Cohort Study of 17,354 Asian Patients.

INTRODUCTION: Mortality following hemodialysis initiation may influence the decision to initiate hemodialysis in elderly patients. Our objective is to demonstrate mortality following hemodialysis initiation in elderly patients (≥70 years) and to derive a prediction risk score based on clinical and laboratory indicators to determine risk of all-cause mortality in patients aged ≥80 years. METHODS: We identified elderly patients (≥70 years) who initiated maintenance hemodialysis between January 2005 and December 2016 using data from the Thai Renal Replacement Therapy (TRT) registry. The mortality rate was determined based on age categories. A predictive risk score for all-cause mortality was created for 4,451 patients aged ≥80 years by using demographics, laboratory values, and interview-based parameters. Using a flexible parametric survival analysis, we predicted mortality 3 months, 6 months, 1 year, 5 years, and 10 years after hemodialysis initiation. RESULTS: 17,354 patients (≥70 years) were included, mean age 76.9 ± 5.1 years, 46.5% male, and 6,309 (36.4%) died. Patients aged <80 years had a median survival time of 110.6 months. A 9-point risk score was developed to predict mortality in patients aged ≥80 years: age >85 years, male, body mass index <18.5 kg/m2, hemoglobin <10.0 g/dL, albumin <3.5 g/dL, substantial assistance required in daily living (1 point each), and Karnofsky Performance Status (KPS) score <50 (3 points). C-statistic of 0.797 indicated high model discrimination. Internal validation demonstrated good agreement between observed and anticipated mortalities. CONCLUSIONS: Hemodialysis is appropriate for patients aged 70-80 years. A risk score for mortality in patients aged ≥80 years has been developed. The score is based on seven readily obtainable and evaluable clinical characteristics.

Randomized Trial on the Effects of Dialysate Potassium Concentration on Intradialytic Hypertension.

Introduction: Intradialytic hypertension is not an uncommon condition during chronic hemodialysis. It is associated with unfavorable cardiovascular outcomes, including hospitalization and mortality. Several small studies have demonstrated the contradictory effects of different dialysate potassium concentrations on intradialytic blood pressure. This study is a randomized crossover trial aiming to evaluate the effects of different dialysate potassium concentrations on intradialytic hypertension. Methods: A 24-week, 2-treatment, 4-sequence, multicenter, double-blinded, randomized, crossover study was conducted at Maharaj Nakorn Chiang Mai Hospital and Lampang Hospital in Thailand among stable patients receiving chronic hemodialysis who experienced intradialytic hypertension >30% of their sessions over the past 3 months. Each participant was randomly assigned to 1 of 4 treatment sequences. During each intervention period, patients were dialyzed with dialysate potassium of either 2 mmol/l (D-K2) or 3 mmol/l (D-K3) for 4 weeks according to their preassigned sequence, separated by a 2-week washout period. The primary outcome was the incidence of intradialytic hypertension. Results: Forty eligible patients were recruited. The mean age was 61.4 ± 14.2 years and the mean systolic blood pressure (SBP) was 146.6 ± 11.2 mm Hg. Of the 40 patients, 95.5% had hypertension and their average number of antihypertensive drugs was 2.8 ± 1.9. A total of 1380 dialysis sessions were included in the analysis (695 sessions for D-K2 and 685 sessions for D-K3). The incidence of intradialytic hypertension was not significantly different between different dialysate potassium concentrations (D-K2 54.7% vs. D-K3 53.1%, P = 0.788). The changes in SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) were not different between the 2 dialysate potassium groups. Conclusion: Dialysate potassium concentration of 2 or 3 mmol/l did not affect the incidence of intradialytic hypertension in patients receiving chronic hemodialysis who frequently developed intradialytic hypertension.

Comparative Safety Profiles of Individual Second-Generation H1-Antihistamines for the Treatment of Chronic Urticaria: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The comparative safety and/or dosing regimens of individual second-generation H1-antihistamines (sgAHs) in patients with chronic urticaria (CU) remain poorly elucidated. OBJECTIVE: To compare the safety profiles of individual sgAHs and/or dosing regimens in adolescents or adult patients with CU using a systematic review and network meta-analysis of all available evidence. METHODS: With limited English publications, electronic databases and gray literature were searched for randomized clinical trials from inception, with searches last updated on January 20, 2023. Relevant safety outcomes included treatment unacceptability (all-cause discontinuation), tolerability (discontinuation due to any adverse events), adverse events, serious adverse events, central nervous system (CNS) side effects, and anticholinergic side effects. Regarding the network estimates, the probability of being associated with the highest adverse outcome risk was estimated for each treatment comparison. RESULTS: Fifty-one randomized clinical trials with 14 individual sgAHs and different dosing regimens, involving 7502 participants, were included. On the basis of the findings from network meta-analyses, variations in sgAH treatment comparisons were observed regarding the unacceptability of treatment, tolerability, adverse events, and CNS side effects. There were no statistically significant differences between the results of sgAH treatment for serious adverse events and those for anticholinergic side effects. On the basis of the ranking of safety profiles, emedastine 4 mg, mizolastine 10 mg, and cetirizine 10 mg were the top 3 ranked treatments with unfavorable safety profiles associated with CNS side effects and any adverse events. CONCLUSIONS: These findings suggest evidence of variations in safety profiles among sgAHs for CU treatment, particularly in terms of adverse events and CNS side effects.

Efficacy and safety of metformin for melasma treatment: a systematic review and meta-analysis.

Objective: Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking. The objective of this study was to assess the efficacy and safety of metformin in the treatment of melasma. Methods: MEDLINE, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, CINAHL, and grey literature databases were searched to 4 October 2022 and updated on 26 February 2023. Randomized controlled trials (RCTs), quasi-RCTs, observational studies, case series, and case reports investigating the efficacy and safety of metformin for melasma were included. The Melasma Area Severity Index (MASI) scores that changed from baseline were pooled using fixed-effects model and expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Three RCTs including 140 patients with melasma were included. The results demonstrated that after 8 weeks, 15% topical metformin significantly reduced the Melasma Area Severity Index (MASI) score compared to placebo (1 trial; n = 60; MD, -0.56; 95% CI, -1.07 to -0.04; p = 0.034). Furthermore, when compared to triple combination cream (TCC), 30% topical metformin demonstrated similar efficacy in reducing the MASI score after 8 weeks (2 trials; n = 80; MD, 0.19, 95% CI, -0.25 to 0.63; p = 0.390). Patients using 30% topical metformin had fewer adverse events compared to TCC users, although no statistical difference was found. Conclusion: Topical metformin was as effective as triple combination cream (TCC) in decreasing changes in the MASI score in patients with melasma, with minimum adverse events. Further studies with larger sample sizes, longer follow-up times, and well-designed trials are required. Systematic Review Registration: Identifier PROSPERO (CRD42022351966).

Transcultural adaptation and psychometric validation of the Thai-Brief Resilient Coping Scale: a cross-sectional study during the coronavirus disease 2019 pandemic in Thailand.

This study aimed to examine the transcultural adaptation, construct validity, and psychometric properties of the Thai-Brief Resilient Coping Scale (BRCS) among the general population and college students through the coronavirus disease 2019 (COVID-19) pandemic in Thailand. We invited the 4004 participants to complete sets of anchor-based measurement tools, including depressive symptoms, anxiety symptoms, perceived stress, well-being, and perceived social support. The scale factor structure of the Thai-BRCS was assessed using factor analysis, and nonparametric item response theory (IRT) analysis. The psychometric properties of the Thai-BRCS for validity (convergent and discriminant) and reliability (internal consistency and reproducibility) were assessed. Based on the construct validity testing, factor analysis, and nonparametric IRT analysis reaffirmed the unidimensionality with a one-factor structure of the Thai-BRCS version. For convergent validity, the scale was significantly correlated with all sets of anchor-based measurement tools (all P < 0.001). The discriminant validity was satisfactory with a group of medium and low resilience and the risk of adverse mental outcomes. For scale reliability, it revealed excellent internal consistency (alpha = 0.84, omega = 0.85) and reproducibility (intraclass correlation = 0.91). The Thai-BRCS version fulfills transcultural adaptation with satisfactory psychometric properties to measure psychological resilience in the Thai population during the COVID-19 pandemic.

Association Between Pretransplant Dialysis Modality and Kidney Transplant Outcomes: A Systematic Review and Meta-analysis.

Importance: The benefits and disadvantages of different pretransplant dialysis modalities and their posttransplant outcomes remain unclear in contemporary kidney transplant care. Objective: To summarize the available evidence of the association of different pretransplant dialysis modalities, including hemodialysis and peritoneal dialysis (PD), with posttransplant outcomes. Data Sources: MEDLINE, Embase, PubMed, Cochrane Library, Scopus, CINAHL, and gray literature were searched from inception to March 18, 2022 (updated to April 1, 2022), for relevant studies and with no language restrictions. Study Selection: Randomized clinical trials and nonrandomized observational (case-control and cohort) studies that investigated the association between pretransplant dialysis modality and posttransplant outcomes regardless of age or donor sources (living or deceased) were abstracted independently by 2 reviewers. Data Extraction and Synthesis: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines, 2 reviewers independently extracted relevant information using a standardized approach. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratio (HR) or odds ratio and 95% CI. Main Outcomes and Measures: Primary outcomes included all-cause mortality, overall graft failure, death-censored graft failure, and delayed graft function. Secondary outcomes included acute rejection, graft vessel thrombosis, oliguria, de novo heart failure, and new-onset diabetes after transplant. Results: The study analyzed 26 nonrandomized studies (1 case-control and 25 cohort), including 269 715 patients (mean recipient age range, 14.5-67.0 years; reported proportions of female individuals, 29.4%-66.9%) whose outcomes associated with pretransplant hemodialysis vs pretransplant PD were compared. No significant difference, with very low certainty of evidence, was observed between pretransplant PD and all-cause mortality (13 studies; n = 221 815; HR, 0.92 [95% CI, 0.84-1.01]; P = .08) as well as death-censored graft failure (5 studies; n = 96 439; HR, 0.98 [95% CI, 0.85-1.14]; P = .81). However, pretransplant PD was associated with a lower risk for overall graft failure (10 studies; n = 209 287; HR, 0.96 [95% CI, 0.92-0.99]; P = .02; very low certainty of evidence) and delayed graft function (6 studies; n = 47 118; odds ratio, 0.73 [95% CI, 0.70-0.76]; P < .001; low certainty of evidence). Secondary outcomes were inconclusive due to few studies with available data. Conclusions and Relevance: Results of the study suggest that pretransplant PD is a preferred dialysis modality option during the transition to kidney transplant. Future studies are warranted to address shared decision-making between health care professionals, patients, and caregivers as well as patient preferences.

Evidence Gaps in Clinical Trials of Pharmacologic Treatment for H1-Antihistamine-Refractory Chronic Spontaneous Urticaria: A Systematic Review and Future Perspectives.

No data addressing issues concerning disparities in participant and trial characteristics and trial outcome reporting have been established in clinical trials for H1-antihistamine-refractory chronic spontaneous urticaria (CSU). To better harmonize and compare the different treatment interventions, we systematically evaluated the overall landscape of pharmacological treatments for H1-antihistamine-refractory CSU clinical trials published between 2000 and 2021. This systematic review included 23 randomized clinical trials involving 2480 participants from 22 countries. We found significant increases in the number of globally published and newly tested drugs, especially biologic drugs. Regarding relatively small trials, we found that people living with H1-antihistamine-refractory CSU who were identified as members of minority groups (non-white population), populations of regions other than North America/Europe, and populations of low- to lower/upper-middle-income countries are underrepresented. Most trials were designed to evaluate treatment efficacy and safety profiles; however, less than half of the included trials reported the patient's perspective in terms of patient-reported outcomes. Disparities in outcome reporting, including clinimetric tools for assessing treatment response and outcome sets, were observed. To close the evidence gap in H1-antihistamine-refractory CSU trials, strategies for improving trial and participant enrollment and standardizing core outcome sets for trial reporting are needed.

Psychological Resilience and Adverse Mental Health Issues in the Thai Population during the Coronavirus Disease 2019 Pandemic.

In light of the coronavirus disease 2019 (COVID-19) pandemic and the enormous amount of uncertainty caused by it, mental health issues have become a great concern. Evidence regarding the effects of psychological resilience on the Thai population is scarce. We evaluated psychological resilience during the first wave of the COVID-19 pandemic and its association with the risk of mental health outcomes, such as depression, anxiety, stress, and health-related well-being. This cross-sectional study was a part of the HOME-COVID-19 project, which conducted an online survey of 4004 members of the general population in Thailand using the Brief Resilience Coping Scale. Logistic regression was performed to identify the association between psychological resilience and mental health issues and well-being. Groups with prevalence rates of 43.9%, 39.2%, and 16.9% were classified as low, moderate, and high resilient copers, respectively. Using high resilient copers as a reference group, the low resilient copers had a higher chance of having mental health adversities. The adjusted odds ratio (OR) was 1.89 (95% confidence interval [CI], 1.39-2.56; p < 0.001) for depression, 2.13 (95% CI, 1.45-3.14; p < 0.001) for anxiety, 4.61 (95% CI, 3.30-6.45; p < 0.001) for perceived stress, and 3.18 (95% CI, 2.31-4.38; p < 0.001) for low well-being. For the medium resilient copers, only low well-being was found to be statistically significant (OR, 1.60; 95% CI, 1.16-2.20; p = 0.004). It is important that resilience be considered in the development of strategies for managing the COVID-19 pandemic to prevent or reduce adverse mental health outcomes.

Disparities and Factors Associated with Coronavirus Disease-2019-Related Public Stigma: A Cross-Sectional Study in Thailand.

Coronavirus disease 2019 (COVID-19)-related public stigma is a major challenge, with scarce available evidence. This study aimed to determine the disparities and factors associated with COVID-19-related public stigma in the Thai population. We conducted a cross-sectional study involving a voluntary online survey in Thailand from 21 April 2020 to 4 May 2020. We invited 4004 participants to complete a series of questionnaires, including the validated COVID-19 public stigma scale and questions on relevant COVID-19-related psychosocial issues. Multinomial logistic regression was performed to investigate the factors associated with COVID-19-related public stigma. The prevalence of COVID-19-related public stigma was 24.2% (95% confidence interval [CI], 22.2-26.2) for no/minimal, 35.5% (95% CI, 33.4-37.6) for moderate, and 40.3% (95% CI, 38.2-42.4) for high. We observed disparities in the prevalence of COVID-19-related public stigma according to participant characteristics and psychosocial factors. Using the no/minimal group as a reference group, the six predominant risk factors significantly associated with a moderate and high degree of COVID-19-related public stigma were middle-aged or older adults, male, divorced/widowed/separated, current quarantine status, moderate/severe fear of COVID-19, and medium/high perceived risk of COVID-19. Additional risk factors significantly related to a high degree of COVID-19-related public stigma were religion (Buddhist), region of residence (non-capital city), and exposure to COVID-19-related information. Disparities in COVID-19-related public stigma due to sociodemographic and psychosocial issues are frequent in the Thai population. To reduce public stigmatization, early identification of vulnerable groups and the development of tailored mitigation strategies should be implemented during the pandemic.

Use of Thiazide Diuretics and Risk of All Types of Skin Cancers: An Updated Systematic Review and Meta-Analysis.

Background: The use of thiazide diuretics is associated with skin cancer risk; however, whether this applies to all skin cancer types is unclear. Methods: In this meta-analysis, we searched multiple electronic databases and gray literature up to 10 April 2022, with no language restrictions, to identify relevant randomized controlled trials (RCTs) and non-randomized studies (cohort, case-control) that investigated the association between thiazide diuretics and skin cancer. The primary outcomes of interest were malignant melanoma and non-melanoma skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]). Secondary outcomes included other skin cancers (lip cancer, Merkel cell carcinoma, malignant adnexal skin tumors, oral cavity cancer, and precursors of skin cancer). We used a random-effects meta-analysis to estimate pooled adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirty non-randomized studies (17 case-control, 13 cohort, no RCTs) were included. Thiazide diuretic users had a higher risk of malignant melanoma (17 studies; n = 10,129,196; pooled adjusted OR, 1.10; 95% CI, 1.04−1.15; p < 0.001; strength of evidence, very low; very small harmful effect), BCC (14 studies; n = 19,780,476; pooled adjusted OR, 1.05; 95% CI, 1.02−1.09; p = 0.003; strength of evidence, very low; very small harmful effect), and SCC (16 studies; n = 16,387,862; pooled adjusted OR, 1.35; 95% CI, 1.22−1.48; p < 0.001; strength of evidence, very low; very small harmful effect) than non-users. Thiazide diuretic use was also associated with a higher risk of lip cancer (5 studies; n = 161,491; pooled adjusted OR, 1.92; 95% CI, 1.52−2.42; p < 0.001; strength of evidence, very low; small harmful effect), whereas other secondary outcomes were inconclusive. Conclusions: Thiazide diuretics are associated with the risk of all skin cancer types, including malignant melanoma; thus, they should be used with caution in clinical practice.

Benefits and Harms of Treatment and Preventive Interventions for Hereditary Angioedema: Protocol for a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease that can lead to potentially life-threatening airway attacks. Although novel therapies for HAE treatment have become available over the past decades, a comparison of all available treatments has not yet been conducted. As such, we will perform a systematic review and network meta-analysis to identify the best evidence-based treatments for the management of acute attacks and prophylaxis of HAE. METHODS: This study will include both parallel and crossover randomized controlled trials that have investigated prevention or treatment strategies for HAE attacks. We will search electronic databases, including Medline, Embase, PubMed, Cochrane Library, Scopus, and CINAHL, from inception with no language restrictions. Potential trials will be supplemented through a gray literature search. The process of study screening, selection, data extraction, risk-of-bias assessment, certainty assessment and classification of treatments will be performed independently by a pair of reviewers. Any discrepancy will be addressed through team discussion. A two-step approach of pairwise and network meta-analysis will be performed. The summarized effect estimates of direct and indirect treatment comparisons will be pooled using DerSimonion-Laird random-effects models. The incoherence assumption, in terms of the consistency of direct and indirect effects, will be assessed. An evidence-based synthesis will be performed, based on the magnitudes of effect size, evidence certainty, and ranking of treatment effects, with respect to treatment benefits and harms. DISCUSSION: This systematic review and network meta-analysis will summarize evidence-based conclusions with respect to the ratio of benefits and harms arising from interventions for the treatment of acute attacks and prophylaxis of HAE. Evidence from this network estimate could promote the rational use of interventions among people living with HAE in clinical practice settings. PROSPERO registration number: CRD42021251367.

Fear of COVID-19 and Perceived Stress: The Mediating Roles of Neuroticism and Perceived Social Support.

Background: Fear of COVID-19 leads to stress and may result in various kinds of mental health problems. Many factors are associated with an individual's perception of stress, including neuroticism and perceived social support. This study aimed to examine the role of neuroticism and perceived social support as mediators of fear of COVID-19 on perceived stress. Methods: Data from 3299 participants aged ≥18 years from the HOME-COVID-19 survey in 2020 were used for analysis. Measurements used included the Fear of COVID-19 and Impact on Quality of Life Scale, the Perceived Stress Scale-10, the Neuroticism inventory and the Multidimensional Scale of Perceived Social Support-12. A parallel mediation model within a structural equation modeling framework with 5000 bootstrapping sampling was used to test the mediating effect. Results: Fear of COVID-19 had a direct effect on perceived stress (B = 0.100, 95% CI = 0.080−0.121, p < 0.001), whereas neuroticism, but not perceived social support, partially mediated the relationship between fear of COVID-19 and perceived stress (B = 0.018, 95% CI = 0.000−0.036). Among all types of social support, only perceived support from friends was a significant mediator (B = 0.016, 95% CI = 0.006−0.025). Conclusions: Neuroticism and perceived support from friends are critical factors in the relationship between fear of COVID-19 and perceived stress.

Prevalence of chronic kidney disease stages 3-5 in low- and middle-income countries in Asia: A systematic review and meta-analysis.

Chronic kidney disease (CKD) is a major public health problem in low- and middle-income countries (LMICs). Although CKD prevalence has been rapidly increasing in LMICs, particularly in Asia, quantitative studies on the current epidemiology of CKD in this region are limited. This study aimed to identify the prevalence of CKD stages 3-5 in LMICs in Asia, by subregion, country economy classification, identification of CKD, traditional and non-traditional risk factors. A systematic review and meta-analysis of observational studies was conducted through a literature search of seven electronic databases and grey literature search published until November 2021. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the risk of bias of each study. A random-effects model was used to estimate pooled prevalence. The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42019120519). Of 4,548 potentially relevant records, 110 studies with moderate and high quality were included with 4,760,147 subjects. The average prevalence (95% CI) of CKD stages 3-5 in 14 LMICs in Asia was 11.2% (9.3-13.2%). The prevalence of CKD stages 3-5 was varied among subregions and country economic classification. CKD prevalence was 8.6% (7.2-10.2%) in east Asia, 12.0% (7.7-17.0%) in south-east Asia, 13.1% (8.7-18.2%) in western Asia, and 13.5% (9.5-18.0%) in south Asia. CKD prevalence was 9.8% (8.3-11.5%) in upper-middle-income countries and 13.8% (9.9-18.3%) in lower-middle-income countries. Prevalence of CKD stage 3-5 in LMICs in Asia is comparable to global prevalence. High level of heterogeneity was observed. Study of factors and interventions that lead to the delay of CKD progression is needed.

Impact of Pharmacological Treatments for Chronic Spontaneous Urticaria with an Inadequate Response to H1-Antihistamines on Health-Related Quality of Life: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Recently, pharmacological treatment options for H1-antihistamine-refractory chronic spontaneous urticaria have increased dramatically; however, their effects on patient-reported outcomes, including health-related quality of life (HRQOL), remain unclear. OBJECTIVE: To compare the impact of these treatments on HRQOL among H1-antihistamine-refractory patients with chronic spontaneous urticaria. METHODS: We completed a comprehensive search of the available literature in the electronic databases, gray literature, and preprint reports up to April 19, 2021, with no language restrictions. The primary outcome for evaluation was a change in HRQOL from the baseline, and secondary outcomes included patient unacceptability and other patient-reported outcomes. We used a random-effects network meta-analysis and estimated differences in standardized mean differences (SMDs) and odds ratios with 95% CIs. Evidence-based synthesis was based on magnitudes of effect size, evidence certainty, ranking of treatment effects, and clinically meaningful improvement. RESULTS: Twelve randomized controlled trials encompassing 1866 adolescent and adult patients were included. Our evidence synthesis analyses revealed that hydroxychloroquine (SMD, -1.00 [-1.61 to -0.39]), 72 mg ligelizumab (SMD, -0.66 [-0.96 to -0.35]), 240 mg ligelizumab (SMD, -0.67 [-0.98 to -0.37]), and 300 mg omalizumab (SMD, -0.53 [-0.67 to -0.39]) significantly improved HRQOL with a moderate beneficial effect. However, the use of hydroxychloroquine seems to be limited by a higher risk of patient unacceptability of treatment. Other secondary outcomes remain inconclusive based on the available evidence. CONCLUSIONS: Both ligelizumab (72 or 240 mg) and 300 mg omalizumab appeared to be effective treatments for H1-antihistamine-refractory chronic spontaneous urticaria, because they were closely associated with improved HRQOL.

Cost-effectiveness analysis of pharmacist interventions in patients with heart failure in Thailand.

INTRODUCTION: Patients with heart failure (HF) are likely to have multiple diseases with complex therapy regimens. Pharmacist intervention in HF treatment can reduce all-cause mortality and hospitalization, but the economic outcome is not known. OBJECTIVE: This study aimed to assess the cost-effectiveness of pharmacist contribution in HF setting compared with usual care. METHODS: A decision analytical model was developed to estimate the cost and outcome from a health care system perspective in Thailand. Clinical inputs were obtained from literature review. Pharmacist costs, hospitalization cost for HF, risk of hospitalization death, risk of nonhospitalization death, and readmission rate were based on data from Thailand. The cost and outcome were discounted at 3% annually. OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER) was calculated and presented for the year 2020. A series of sensitivity analysis was also performed. RESULTS: Pharmacist intervention incurred higher total costs than usual care, because total cost of pharmacists was 186,040 THB (5936 USD) whereas usual care cost was 151,654 THB (4839 USD). It also provided more quality-adjusted life years (QALYs) than usual care, from 2.4 to 2.8. In addition, patient life years (LY) were increasing from 3.3-3.8. This yielded an ICER of 77,398 THB/LY (2467 USD/LY) or 103,037 THB/QALYs (3288 USD/QALYs). This ICER is considered to be cost-effective at the willingness-to-pay level of 160,000 THB/QALY (5191.87 USD). CONCLUSION: At this current situation in Thailand, pharmacists may represent good value for the nation's limited health care resources. The information should be used in national policies to plan for pharmacist work force implementation and production line in the near future.

Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: a systematic review and meta-analysis.

BACKGROUND: Serotonin reuptake inhibitor (SRI) antidepressants are implicated in increasing the risk of bleeding among users; however, the comparative increase in bleeding risk with concurrent antithrombotic therapy (anticoagulant or antiplatelet) remains unclear. As such, we performed a systematic review and meta-analysis of all available evidence to evaluate the effects of SRI and the risk of bleeding complications among patients receiving antithrombotic therapy. METHODS: We searched Medline, Embase, PubMed, PsycINFO, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature (Google Scholar and preprint reports) up to 26 November, 2020, with no language restrictions (updated on 31 July 2021). The primary outcome of interest was major bleeding. Secondary outcomes included intracranial haemorrhage, gastrointestinal bleeding, and any bleeding events. We used a random-effects model meta-analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We did not identify any randomised studies but found 32 non-randomized studies (cohort or case-control) with 1,848,285 patients that fulfilled the study selection criteria and were included in the meta-analysis. Among individuals receiving anticoagulants (13 studies), SRI users experienced a statistically higher risk of major bleeding compared to non-SRI users: pooled OR was 1.39 (95% CI, 1.23-1.58; p < .001; moderate heterogeneity). Among individuals receiving antiplatelet therapy (2 studies), SRI users were associated with an increased risk of major bleeding: pooled OR was 1.45 (95% CI, 1.17-1.80; p = .001; low heterogeneity). For secondary outcomes, the use of SRI among individuals treated with antithrombotic therapy revealed a higher risk of gastrointestinal bleeding or any bleeding events, whereas only anticoagulant use was illustrated an increased risk of intracranial haemorrhage. CONCLUSIONS: The use of SRI antidepressants among patients treated with antithrombotic therapy (either anticoagulant or antiplatelet) is associated with a higher risk of bleeding complications, suggesting that caution is warranted in co-prescription. PROSPERO REGISTRATION: CRD42018083917KEY MESSAGESIn this meta-analysis of 32 non-randomized studies, SRI users were associated with the risk of bleeding complications compared to non-SRI users, with concurrent antithrombotic use (either anticoagulant or antiplatelet).The risk was consistently elevated across types of bleeding events (major bleeding, gastrointestinal bleeding, or any bleeding events), whereas only anticoagulant use was associated with intracranial haemorrhage.To promote the rational use of medicines, our findings suggest that the risk-benefit ratio must account for the clear efficacy of SRI against safety concerns in terms of bleeding risks.