BACKGROUND: This study aimed to synthesize and quantitatively examine Health State Utility Values (HSUVs) for Type 2 Diabetes Mellitus (T2DM) and its complications, providing a robust meta-regression framework for selecting appropriate HSUV estimates.
METHODS: We conducted a systematic review to extract HSUVs for T2DM and its complications, encompassing various influencing factors. Relevant literature was sourced from a review spanning 2000-2020, supplemented by literature from PubMed, Embase, and the Web of Science (up to March 2024). Multivariate meta-regression was performed to evaluate the impact of measurement tools, tariffs, health status, and clinical and demographic variables on HSUVs.
RESULTS: Our search yielded 118 studies, contributing 1044 HSUVs. The HSUVs for T2DM with complications varied, from 0.65 for cerebrovascular disease to 0.77 for neuropathy. The EQ-5D-3L emerged as the most frequently employed valuation method. HSUV differences across instruments were observed; 15-D had the highest (0.89), while HUI-3 had the lowest (0.70) values. Regression analysis elucidated the significant effects of instrument and tariff choice on HSUVs. Complication-related utility decrement, especially in diabetic foot, was quantified. Age <70 was linked to increased HSUVs, while longer illness duration, hypertension, overweight and obesity correlated with reduced HSUVs.
CONCLUSIONS: Accurate HSUVs are vital for the optimization of T2DM management strategies. This study provided a comprehensive data pool for HSUVs selection, and quantified the influence of various factors on HSUVs, informing analysts and policymakers in understanding the utility variations associated with T2DM and its complications.

OBJECTIVE: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine.
METHODS: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria.
RESULTS: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95%CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95% CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95% CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as \"low risk\", two were rated as \"high risk\", and the others were rated as \"unclear risk\". The reporting quality of RCTs of acupuncture for migraine remain suboptimal.
CONCLUSIONS: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months.
BACKGROUND: This meta-analysis has been registered on PROSPERO (CRD42023400493).

UNASSIGNED: The present study aimed to investigate the effectiveness of dietary β-mannanase supplementation on growth performance, intestinal morphology, digesta viscosity, and dietary nutrient utilization in broiler chickens through a meta-analysis. The effects were further examined by a meta-regression analysis with activity levels of β-mannanase in broiler diets.
UNASSIGNED: A total of 23 studies, which conducted in 11 countries and completed between December 2003 and August 2023, were finally selected for this meta-analysis. The standardized mean difference (SMD) and its 95% confidence interval (CI) were calculated as the effect size metrics using random effect model, with I2 value being utilized to measure heterogeneity. Investigated measurements included body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), villus height (VH), crypt depth (CD), VH:CD ratio, digesta viscosity, nitrogen-corrected metabolizable energy (AMEn), apparent ileal digestibility (AID), and apparent total tract retention (ATTR) of dry matter (DM), gross energy (GE), and nitrogen (N). All statistical analyses were performed using R version 4.3.3.
UNASSIGNED: Results revealed significant positive effects of dietary β-mannanase supplementation on BWG (P = 0.005), FCR (P < 0.001), VH (P < 0.001), VH:CD (P < 0.001), digesta viscosity (P < 0.001), AMEn (P = 0.011), AID of GE (P = 0.002) and N (P = 0.003), and ATTR of DM (P = 0.019), GE (P = 0.002), and N (P = 0.005) in broiler chickens. In the meta-regression analysis, increasing activity levels of β-mannanase in broiler diets increased VH:CD (P < 0.001, R2 = 79.2%) and AID of N (P = 0.038, R2 = 67.4%).
UNASSIGNED: the current meta-analysis indicates that dietary β-mannanase supplementation improves energy and nutrient utilization in broiler diets possibly by decreasing digesta viscosity and enhancing intestinal morphology in broiler chickens. These beneficial effects can contribute to improved growth performance in broiler chickens.

OBJECTIVE: Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA.
METHODS: We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity.
RESULTS: We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naïve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naïve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naïve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe.
CONCLUSIONS: Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naïve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.

UNASSIGNED: Air pollution is speculated to increase the risk of Coronavirus disease-2019 (COVID-19). Nevertheless, the results remain inconsistent and inconclusive. This study aimed to explore the association between ambient air pollution (AAP) and COVID-19 risks using a meta-analysis with meta-regression modelling.
UNASSIGNED: The inclusion criteria were: original studies quantifying the association using effect sizes and 95 % confidence intervals (CIs); time-series, cohort, ecological or case-crossover peer-reviewed studies in English. Exclusion criteria encompassed non-original studies, animal studies, and data with common errors. PubMed, Web of Science, Embase and Google Scholar electronic databases were systemically searched for eligible literature, up to 31, March 2023. The risk of bias (ROB) was assessed following the Agency for Healthcare Research and Quality parameters. A random-effects model was used to calculate pooled risk ratios (RRs) and their 95 % CIs.
UNASSIGNED: A total of 58 studies, between 2020 and 2023, met the inclusion criteria. The global representation was skewed, with major contributions from the USA (24.1 %) and China (22.4 %). The distribution included studies on short-term (43.1 %) and long-term (56.9 %) air pollution exposure. Ecological studies constituted 51.7 %, time-series-27.6 %, cohorts-17.2 %, and case crossover-3.4 %. ROB assessment showed low (86.2 %) and moderate (13.8 %) risk. The COVID-19 incidences increased with a 10 μg/m3 increase in PM2.5 [RR = 4.9045; 95 % CI (4.1548-5.7895)], PM10 [RR = 2.9427: (2.2290-3.8850)], NO2 [RR = 3.2750: (3.1420-3.4136)], SO2 [RR = 3.3400: (2.7931-3.9940)], CO [RR = 2.6244: (2.5208-2.7322)] and O3 [RR = 2.4008: (2.1859-2.6368)] concentrations. A 10 μg/m3 increase in concentrations of PM2.5 [RR = 3.0418: (2.7344-3.3838)], PM10 [RR = 2.6202: (2.1602-3.1781)], NO2 [RR = 3.2226: (2.1411-4.8504)], CO [RR = 1.8021 (0.8045-4.0370)] and O3 [RR = 2.3270 (1.5906-3.4045)] was significantly associated with COVID-19 mortality. Stratified analysis showed that study design, exposure period, and country influenced exposure-response associations. Meta-regression model indicated significant predictors for air pollution-COVID-19 incidence associations.
UNASSIGNED: The study, while robust, lacks causality demonstration and focuses only on the USA and China, limiting its generalizability. Regardless, the study provides a strong evidence base for air pollution-COVID-19-risks associations, offering valuable insights for intervention measures for COVID-19.

UNASSIGNED: Chronic inflammation is recognised as an important component of Alzheimer\'s disease (AD), yet its relationship with cognitive decline, sex-differences, and age is not well understood. This study investigated the relationship between inflammatory markers, cognition, sex, and age in individuals with mild cognitive impairment (MCI) and AD.
UNASSIGNED: A systematic review was performed to identify case-control studies which measured cognitive function and inflammatory markers in serum, plasma, and cerebrospinal fluid in individuals with MCI or AD compared with healthy control (HC) participants. Meta-analysis was performed with Hedges\' g calculated in a random effects model. Meta-regression was conducted using age, sex, and mini-mental status exam (MMSE) values.
UNASSIGNED: A total of 106 studies without a high risk of bias were included in the meta-analysis including 18,145 individuals: 5625 AD participants, 3907 MCI participants, and 8613 HC participants. Combined serum and plasma meta-analysis found that IL1β, IL6, IL8, IL18, CRP, and hsCRP were significantly raised in individuals with AD compared to HC. In CSF, YKL40, and MCP-1 were raised in AD compared to HC. YKL40 was also raised in MCI compared to HC. Meta-regression analysis highlighted several novel findings: MMSE was negatively correlated with IL6 and positively correlated with IL1α in AD, while in MCI studies, MMSE was negatively correlated with IL8 and TNFα. Meta-regression also revealed sex-specific differences in levels of IL1α, IL4, IL6, IL18, hsCRP, MCP-1, and YKL-40 across AD and MCI studies, and age was found to account for heterogeneity of CRP, MCP-1, and IL4 in MCI and AD.
UNASSIGNED: Elevated levels of IL6 and YKL40 may reflect microglial inflammatory activity in both MCI and AD. Systemic inflammation may interact with the central nervous system, as poor cognitive function in individuals with AD and MCI was associated with higher levels of serum and plasma proinflammatory cytokines IL6 and TNFα. Moreover, variations of systemic inflammation between males and females may be modulated by sex-specific hormonal changes, such as declining oestrogen levels in females throughout the menopause transition. Longitudinal studies sampling a range of biospecimen types are needed to elucidate the nuances of the relationship between inflammation and cognition in individuals with MCI and AD, and understand how systemic and central inflammation differentially impact cognitive function.

UNASSIGNED: Virtual reality exposure therapy offers a unique opportunity to treat social anxiety disorder. This meta-analysis aims to evaluate the effectiveness of virtual reality exposure therapy compared to waitlist comparators or other interventions for individuals with social anxiety disorder in alleviating anxiety symptoms.
UNASSIGNED: A three-step comprehensive search for the randomized controlled trials of virtual reality exposure therapy was conducted from inception to 7 December 2023. The overall effect was measured using Hedges\' g and determined using t-statistics at a significance level of p < 0.05. Sensitivity, subgroup, and meta-regression analyses were carried out.
UNASSIGNED: A total of 17 randomized control trials were retrieved from nine electronic databases. Virtual reality exposure therapy has greater efficacy than waitlist comparators in reducing anxiety symptoms at post-intervention and follow-up assessment. Virtual reality exposure therapy demonstrates a similar effect to other interventions at post-intervention and follow-up assessment. We observed a greater effect for participants with symptomatic social anxiety when we combined the intervention with cognitive behavioral therapy compared to its counterpart. Meta-regression analyses found no significant covariate.
UNASSIGNED: Overall, virtual reality exposure therapy can provide supplementary therapy for improving anxiety symptoms. Additional high-quality and large-scale trials with long-term follow-up are needed.

BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study.
METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses.
RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95% CI: 0.51-0.73), 0.77 points (95% CI: 0.60-0.94), 0.83 points (95% CI: 0.55-1.10), and 1.09 points (95% CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health.
CONCLUSIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations.
CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

OBJECTIVE: To provide an updated summary of published anchor-based Minimally Important Difference (MID) estimates for the EQ-5D index and EQ visual analog scale (EQ VAS) scores and identify factors influencing those estimates.
METHODS: We systematically searched eight electronic databases from January 1990 to March 2023. We examined the association of baseline score, type of score change (improvement/worsening), data source, value set, disease/condition, treatment type (surgical/non-surgical), and type of anchor (clinical vs. self-rated) with MID estimates for the EQ-5D-3L and EQ-5D-5L indices, and EQ VAS. Significant variables were used to develop prediction formulas for MID by testing both linear and nonlinear regression models.
RESULTS: Of 6786 records reviewed, 47 articles were included for analysis. MID ranges for improved scores were -0.13 to 0.68 (EQ-5D-3L), 0.01-0.41 (EQ-5D-5L), and 0.42-23.0 (EQ VAS). Surgical intervention and lower baseline scores were associated with higher MIDs for both the EQ indices but not for EQ VAS. The nonlinear polynomial model outperformed the linear model in predicting the MIDs. MIDs based on deteriorated scores were insufficient for quantitative synthesis (mean: -0.02 for EQ-5D-3L; -0.04 for EQ-5D-5L; and -6.5 for EQ VAS).
CONCLUSIONS: This review revealed that the MID of EQ-5D index scores varies with baseline score and treatment type, indicating that use of a uniform MID may not be appropriate. We recommend using baseline score-adjusted and treatment type-specific EQ-5D MIDs, and call for more MID research, particularly in the context of assessing deterioration in health using this widely used generic health-status instrument.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for the viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement but for its use adapted to the peculiarities of the disease manifestation and of the patients. A \"broad\" comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation therapy and its main challenger of clinical interest, the platelet-rich plasma treatment. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using algorithms implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, we adhere in a documented way to the opinion that HA-based products, currently under circumspection, are still clinically useful.