Real-world glycaemic outcomes of automated insulin delivery in type 1 diabetes: A meta-analysis.

AIM: To evaluate the real-world effectiveness of automated insulin delivery (AID) systems in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for studies published up until 2 March 2024. We included pragmatic randomized controlled trials (RCTs), cohort studies, and before-after studies that compared AID systems with conventional insulin therapy in real-world settings and reported continuous glucose monitoring outcomes. Percent time in range (TIR; 3.9-10 mmol/L), time below range (TBR; <3.9 mmol/L), time above range (TAR; >10 mmol/L), and glycated haemoglobin (HbA1c) level were extracted. Data were summarized as mean differences (MDs) with 95% confidence interval. RESULTS: A total of 23 before-after studies (101 704 participants) were included in the meta-analysis. AID systems were associated with an increased percentage of TIR (11.61%, 10.47 to 12.76; p < 0.001). The favourable effect of AID systems was consistently observed when used continuously for 6 (11.76%) or 12 months (11.33%), and in both children (12.16%) and adults (11.04%). AID systems also showed favourable effects on TBR (-0.53%, -0.63 to -0.42), TAR (-9.65%, -10.63 to -8.67) and HbA1c level (-0.42%, -0.47 to -0.37) when compared with previous treatments. CONCLUSIONS: Similar improvements in glycaemic parameters were observed in real-world settings in RCTs using AID systems in T1D. AID systems benefit both children and adults by increasing TIR for both short- and long-term interventions.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis.

BACKGROUND: It was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC. METHODS: Published randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, Delta, or Omicron) were searched until 4 March 2022. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1-estimate). RESULTS: Eleven RCTs (161,388 participants), 20 cohort studies (52,782,321 participants), and 26 case-control studies (2,584,732 cases) were included. Eleven COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, BBIBP-CorV, SCB-2019, CVnCoV, and HB02) were included in this analysis. Full vaccination was effective against Alpha, Beta, Gamma, Delta, and Omicron variants, with VE of 88.0% (95% CI, 83.0-91.5), 73.0% (95% CI, 64.3-79.5), 63.0% (95% CI, 47.9-73.7), 77.8% (95% CI, 72.7-82.0), and 55.9% (95% CI, 40.9-67.0), respectively. Booster vaccination was more effective against Delta and Omicron variants, with VE of 95.5% (95% CI, 94.2-96.5) and 80.8% (95% CI, 58.6-91.1), respectively. mRNA vaccines (mRNA-1273/BNT162b2) seemed to have higher VE against VOC over others; significant interactions (pinteraction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. not mRNA vaccines). CONCLUSIONS: Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta, Gamma, and Delta variants. Booster vaccination is more effective against Delta and Omicron variants. mRNA vaccines seem to have higher VE against Alpha, Beta, Gamma, and Delta variants over others.

Dual-hormone artificial pancreas for glucose control in type 1 diabetes: A meta-analysis.

AIM: To evaluate the efficacy and safety of a dual-hormone artificial pancreas (DH) in type 1 diabetes. MATERIAL AND METHODS: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for studies published up to February 16, 2022. We included randomized controlled trials that compared DH with single-hormone artificial pancreas (SH), continuous subcutaneous insulin infusion (CSII) or sensor-augmented pumps (SAP), and predictive low glucose suspend systems (PLGS) in type 1 diabetes. The primary outcome was percent time in target (3.9-10 mmol/L [70-180 mg/dL]). Data were summarized as mean differences (MDs) or risk differences (RDs). RESULTS: A total of 17 randomized crossover trials (438 participants) were included. There were nine trials of DH versus SH, 13 trials of DH versus SAP/CSII, and two trials of DH versus PLGS. For time in target, DH showed no significant difference in time in target compared with SH (MD 2.69%, 95% confidence interval [CI] -0.38 to 5.76) but resulted in 16.05% (95% CI 12.06 to 20.05) and 6.89% (95% CI 2.63 to 11.14) more time in target range compared with SAP/CSII and PLGS, respectively. DH slightly reduced time in hypoglycaemia (MD -1.20%, 95% CI -1.85 to -0.56) but increased the risk of gastrointestinal symptoms (RD 0.18, 95% CI 0.08 to 0.27) compared with SH. CONCLUSIONS: The results of this study suggest that DH has a comparable effect on time in target compared with SH, but is associated with a longer time in target range compared with SAP/CSII and PLGS. The DH slightly reduced time in hypoglycaemia but may increase the risk of gastrointestinal symptoms compared with the SH. PROSPERO registration number: CRD42022314015.

Pharmacologic and Nutritional Interventions for Early Alzheimer's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). Objective: We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence. Results: Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments- ranging from low to high certainty- showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] -0.239, 95% confidence interval [CI] -0.343 to -0.134) and lecanemab (SMD -0.194, 95% CI -0.279 to -0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo. Conclusions: Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD.

Vitamin D supplementation for prevention of acute respiratory infections in older adults: A systematic review and meta-analysis.

BACKGROUND: Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults. METHODS: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17. RESULTS: Twelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97-1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration <50 nmol/L (OR, 0.90; 95% CI, 0.79-1.04, I2 = 14.7%). Additionally, vitamin D supplements might result in little to no difference in death due to any cause, any adverse event, hypercalcinemia, and kidney stones. CONCLUSIONS: Vitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries. TRIAL REGISTRATION: This study was registered on PROSPERO (CRD42023451265).

Efficacy and safety of vaccines to prevent respiratory syncytial virus infection in infants and older adults: A systematic review and meta-analysis.

OBJECTIVES: To determine the efficacy and safety of respiratory syncytial virus (RSV) vaccines in infants and older adults. METHODS: We performed a systematic review and meta-analysis of randomized control trials that evaluated the efficacy of maternal RSV immunization against infections in infants, as well as the efficacy of RSV vaccines in older adults. The primary outcome was the vaccine efficacy against RSV-related lower respiratory tract disease (LRTD). Grading of Recommendations Assessment, Development and Evaluation criteria was used to evaluate the level of evidence. RESULTS: Ten trials were included in the review. For maternal vaccination, the RSV vaccine showed favourable efficacy against RSV-related LRTD (vaccine efficacy 57.3%, 95% confidence interval [CI] 31.3-73.5; low certainty) and RSV-related severe LRTD (vaccine efficacy 81.9%, 95% CI 56.8-92.4; moderate certainty) in infants within 90 days after birth. For older adults, Meta-analysis showed that RSV vaccines could also reduce the risk of RSV-related LRTD (vaccine efficacy 78.3%, 95% CI 65.6-86.3; moderate certainty) and RSV-related severe LRTD (vaccine efficacy 86.5%, 95% CI 68.3-94.3; moderate certainty). There was no significant difference in serious adverse events between RSV vaccines and placebo. CONCLUSION: RSV vaccines have the potential to offer protection against RSV disease in both infants and older adults, without apparent safety concerns.

Association of statin use with risk of depression and anxiety: A prospective large cohort study.

OBJECTIVES: To examine associations between regular statin use and the incidence of depression and anxiety. METHODS: This cohort was based on UK Biobank participants without depression/anxiety recruited between 2006 and 2010. The self-reported regular statin use was collected at baseline. Depression and anxiety outcomes were assessed by diagnostic interviews (international classification of diseases codes) and nondiagnostic scales (mental well-being questionnaires). Cox proportional hazards models adjusted for a wide range of confounders were used to estimate associations of statins with incident depression/anxiety. RESULTS: Among 363,551 eligible participants, 55,838 reported regular statin use. During a 13-year follow-up, 14,765 cases of depression and 15,494 cases of anxiety were identified. Compared with non-statin users, statin use was associated with reduced risk of depression (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81, 0.94) and anxiety (HR: 0.90, 95% CI: 0.84, 0.97). Effects of statins on depression were consistent in sensitivity analyses and may be less influenced by unmeasured confounders. However, results of online survey data showed that statin use might not be associated with incident anxiety (HR: 0.96, 95% CI: 0.85, 1.09). CONCLUSION: Regular statin use was associated with a lower risk of depression. No clear associations between statin use and anxiety were found.

Circulating tumor DNA as prognostic markers of relapsed breast cancer: a systematic review and meta-analysis.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50-0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04-0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73-12.17; relapse outcome: RR = 7.11, 95% CI: 3.05-16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12-3.70; post-operative: HR = 6.03, 95% CI: 1.31-27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

The prognostic role of circulating tumor DNA across breast cancer molecular subtypes: A systematic review and meta-analysis.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

Efficacy and safety of immune checkpoint inhibitors and targeted therapies in resected melanoma: a systematic review and network meta-analysis.

Background: Multiple immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatments for high-risk resected melanoma, with unclear comparative efficacy and safety. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 6 June 2023. We included RCTs that assess adjuvant ICIs or targeted therapies in high-risk resected melanoma. Frequentist random-effect network meta-analyses (NMA) were performed. The primary outcome was recurrence-free survival (RFS). Results: Eleven trials including 10,712 patients and comparing 10 treatments (nivolumab [Nivo], ipilimumab 3 mg/kg [Ipi3], Ipi10, pembrolizumab [Pemb], vemurafenib [Vemu], bevacizumab [Beva], Nivo + Ipi1, Nivo + Ipi3, dabrafenib plus trametinib [Dab + Tram], and placebo/observation [Pla/Obs]) were included. NMA showed that all treatments showed RFS benefit over placebo/observation except Ipi3 (hazard ratio [HR], 0.78; 95% CI, 0.58-1.05). Combination therapy of Nivo + Ipi3 was the most effective treatment, which significantly improved RFS compared with other treatments. NMA also showed that all treatments were associated with an increased risk of grade 3-5 adverse events over placebo/observation except Nivo (HR, 1.25; 95% CI, 0.87-1.80). NMA suggested that Nivo and Pemb were the two safest treatments except for placebo/observation. Although three combination therapies ranked as the top three in terms of RFS, they did not show significant overall survival benefits compared to monotherapies including Pemb, Nivo, Ipi3, and Ipi10. Conclusion: In this NMA, adjuvant Nivo and Pemb are the preferred options in patients with resected melanoma considering the benefits and harms. Combination therapy of Nivo + Ipi3 may be a promising strategy, but more evidence from phase 3 trials is needed. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438667, PROSPERO (CRD42023438667).

Automated Insulin Delivery Systems in Children and Adolescents With Type 1 Diabetes: A Systematic Review and Meta-analysis of Outpatient Randomized Controlled Trials.

BACKGROUND: The glycemic control of automated insulin delivery (AID) systems in outpatient children and adolescents with type 1 diabetes (T1D) has not been systematically evaluated. PURPOSE: To evaluate the efficacy and safety of AID systems in children and adolescents in outpatient settings. DATA SOURCES: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched until 4 May 2023. This study was registered with PROSPERO (2023, CRD42023395252). STUDY SELECTION: Randomized controlled trials that compared AID systems with conventional insulin therapy in outpatient children and adolescents with T1D and reported continuous glucose monitoring outcomes were selected. DATA EXTRACTION: Percent time in range (TIR) (3.9-10 mmol/L), time below range (TBR) (<3.9 mmol/L), and time above range (TAR) (>10 mmol/L) were extracted. Data were summarized as mean differences (MDs) with 95% CIs. DATA SYNTHESIS: Twenty-five trials (1,345 participants) were included in the meta-analysis. AID systems were associated with an increased percentage of TIR (MD, 11.38% [95% CI 9.01-13.76], P < 0.001; high certainty). The favorable effect was consistent whether AID was used over 3 months (10.46% [8.71-12.20]) or 6 months (10.87% [7.11-14.63]). AID systems had a favorable effect on the proportion of TBR (-0.59% [-1.02 to -0.15], P = 0.008; low certainty) or TAR (-12.19% [-14.65 to -9.73], P < 0.001; high certainty) compared with control treatment. LIMITATIONS: Substantial heterogeneity was observed in most analyses. CONCLUSIONS: AID systems are more effective than conventional insulin therapy for children and adolescents with T1D in outpatient settings. The favorable effect is consistent both in the short term and long term.

Breast cancer screening using synthesized two-dimensional mammography: A systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to compare the screening performance of synthesized mammography (SM) plus digital breast tomosynthesis (DBT) with digital mammography (DM) plus DBT or DM alone. METHODS: Medline, Embase, Web of Science, and the Cochrane Library databases were searched from January 2010 to January 2021. Eligible population-based studies on breast cancer screening comparing SM/DBT with DM/DBT or DM in asymptomatic women were included. A random-effect model was used in this meta-analysis. Data were summarized as risk differences (RDs), with 95 % confidence intervals (CIs). RESULTS: Thirteen studies involving 1,370,670 participants were included. Compared with DM/DBT, screening using SM/DBT had similar breast cancer detection rate (CDR) (RD = -0.1/1000 screens, 95 % CI = -0.4 to 0.2, p = 0.557, I2 = 0 %), but lower recall rate (RD = -0.56 %, 95 % CI = -1.03 to -0.08, p = 0.022, I2 = 90 %) and lower biopsy rate (RD = -0.33 %, 95 % CI = -0.56 to -0.10, p = 0.005, I2 = 78 %). Compared with DM, SM/DBT improved CDR (RD = 2.0/1000 screens, 95 % CI = 1.4 to 2.6, p < 0.001, I2 = 63 %) and reduced recall rate (RD = -0.95 %, 95 % CI = -1.91 to -0.002, p = 0.049, I2 = 99 %). However, SM/DBT and DM had similar interval cancer rate (ICR) (RD = 0.1/1000 screens, 95 % CI = -0.6 to 0.8, p = 0.836, I2 = 71 %) and biopsy rate (RD = -0.05 %, 95 % CI = -0.35 to 0.24, p = 0.727, I2 = 93 %). CONCLUSIONS: Screening using SM/DBT has similar breast cancer detection but reduces recall and biopsy when compared with DM/DBT. SM/DBT improves CDR when compared with DM, but they have little difference in ICR. SM/DBT could replace DM/DBT in breast cancer screening to reduce radiation dose.