Jaime Fernández-Bravo-Rodrigo

Context: Omega-3 polyunsaturated fatty acids (PUFAs) have demonstrated metabolic benefits in several populations; however, their efficacy in type 1 diabetes mellitus (T1D) is not well established. Objective: The aim of this systematic review and meta-analysis was to assess the efficacy of omega-3 PUFAs supplementation on the lipid and glycemic profile in T1D. Data sources: A systematic search was conducted in Medline, Scopus, Web of Science, and the Cochrane Library, from inception to June 2026. Data extraction: Studies evaluating the effect of omega-3 PUFA supplementation on total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), triglycerides, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were included. Random-effects meta-analyses of randomized clinical trials (RCTs) and of the pre-post effect of a single intervention arm were performed separately. Heterogeneity was assessed using the I2 statistic. Data analysis: Eighteen studies were included. In the RCTs, omega-3 PUFA supplementation increased HDL-C by 4.47 mg/dL (95% CI, 0.07 to 8.86) with an I2 of 64.87%, and decreased triglycerides by 9.49 mg/dL (95% CI, 16.60 to −2.38) with an I2 of 29.83%. There was no effect on the other outcomes, including TC, LDL-C, FPG, and HbA1c. Finally, the effect on the meta-analyses of pre-post studies was similar to that found in the RCTs. Conclusions: Although omega-3 supplementation has been associated with modest improvements in lipid levels in people with T1D, the results are statistically fragile. No glycemic benefits were observed. Future RCTs focusing on hard cardiovascular outcomes and standardized protocols are necessary to determine the clinical efficacy of omega-3 supplementation beyond surrogate metabolic markers. Systematic Review Registration: PROSPERO registration No. [CRD420261297164].

Introduction: Prostate cancer (PC) is a highly prevalent malignant tumour associated with significant morbidity and mortality. While physical activity has been linked to a lower risk of PC and exercise has been shown to reduce mortality, the evidence for the association between physical activity and mortality is limited. Objective: This study aimed to assess the association between physical activity and mortality risk in men with or at risk of PC. Methods: A systematic search was conducted in Medline, Scopus and Web of Science from inception until April 2026. Observational studies analysing physical activity and all-cause and PC-specific mortality were included. The data were synthesised and interpreted using a synthesis without meta-analysis (SWiM) approach. The quality of the studies was assessed using the NHLBI tool. The certainty of the evidence was assessed using the GRADE framework. Results: Fifteen observational studies were included. The hazard ratio (HR) was the predominant effect measure. Physical activity was associated with a reduction in all-cause mortality (HRs: 0.40–0.88; highest versus lowest categories), and a dose–response gradient was observed within two cohorts. Associations with PC-specific mortality were less consistent, with significant inverse findings concentrated in post-diagnosis assessments. The quality of the studies was generally poor, and the certainty of the evidence was very low for both outcomes. Conclusions: Physical activity was associated with lower all-cause mortality risk in men with or at risk of PC, and the most consistent inverse estimates were observed in post-diagnostic assessments. These findings are observational and should not be interpreted as a clinical recommendation. A dose–response pattern was noted within individual studies, although the certainty of evidence was very low for this outcome. Additionally, evidence for PC-specific mortality was inconsistent and of very low certainty. Prospective studies with standardised, objective measures of physical activity are required.

Objective: This study aimed to summarize and pool real‐world evidence on the clinical effectiveness and safety of galcanezumab. Background: Migraine is a disabling primary headache disorder. Several drugs that target calcitonin gene‐related peptide, such as galcanezumab, have recently been developed. However, real‐world effects have not been well studied. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted from inception to February 2025. Studies that estimated the real‐world effects of galcanezumab on monthly migraine days (MMDs), monthly headache days (MHDs), Headache Impact Test, Migraine Disability Assessment Scale, number of days in medication, acute monthly intake (AMI), pain intensity, and safety outcomes were included. Meta‐analyses of proportions or mean differences were performed. Results: Thirty‐six studies were included, with an agreement of 0.93 [95% confidence interval (CI): 0.90, 0.96]. One month after the first injection, the reduction effects were −6.93 days (95% CI: −7.88, −5.99) for MMD, −8.55 days (95% CI: −11.32, −5.78) for MHD, and −7.96 points (95% CI: −8.93, −6.99) for Headache Impact Test. Over 60% of patients achieved a reduction in MMD/MHD of at least 50% within 3 months. The effect increased gradually and slightly up to 12 months. The adverse event rates were 0.25 (95% CI: 0.14, 0.38) and 0.35 (95% CI: 0.27, 0.45) at 6 and 12 months, respectively, with constipation being the most common. Conclusion: Galcanezumab appears to be associated with clinically meaningful improvements in migraine and favorable safety outcomes, although the evidence certainty is limited by heterogeneity.

Background/Objectives: Dietary advanced glycation end products (dAGEs) have a pro-inflammatory effect and increase oxidative stress, potentially leading to cancer. The aim of this study was to estimate the association between dAGEs consumption and risk and mortality from overall cancer and according to its site. Methods: A systematic search was conducted in Medline, Scopus, Web of Science, and the Cochrane Library from inception to April 2025. The search strategy was conducted according to the PECO structure adapted to this study, as well as the inclusion criteria, in which the population (P) was the adult population, the exposure (E) was the highest level of dAGEs intake, the comparator (C) was the lowest level of dAGEs intake, and the outcomes (O) were the overall cancer risk, cancer risk by site, and cancer mortality. Results across studies were summarised using random effects and fixed effects. Results: Fourteen studies were included in the systematic review. In the random-effects meta-analysis, high dAGEs intake was associated with Hazard Ratio (HR) = 0.99 [95% Confidence Interval (95% CI): 0.98, 1.00] for overall cancer risk. However, although there was no association with breast cancer (BC), there was an association with invasive BC, with HR = 1.14 (95% CI: 1.05, 1.23). In contrast, in other tumours, there were opposite results depending on the site of the cancer. Conclusions: The reduction in cancer risk is not clinically significant. However, high consumption of dAGEs may increase the risk of BC, particularly the invasive BC, which is a challenge for cancer prevention and subsequent mortality. Due to the limited evidence, further studies are needed to confirm the potential impact of dAGEs, as well as other dietary factors that may play a larger role in cancer development.

Background: Dystrophinopathies are associated with neuropsychiatric disorders due to alterations in dystrophin/DMD expression. Objective: The objective was to estimate the association of developmental disorders, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and obsessive-compulsive disorder with the dystrophin/DMD genotype in population with dystrophinopathies. Methods: Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were performed from inception to September 2022. We included observational studies in the population with Becker or Duchenne muscular dystrophies (BMD, DMD) that estimated the prevalence of these disorders according to Dp140 and/or Dp71 genotype. Meta-analysis of the prevalence ratio (PR) of genotype comparisons was conducted for each disorder. Results: Ten studies were included in the systematic review. In BMD, Dp140+ vs. Dp140– and Dp71+ vs. Dp71– were associated with developmental disorders with a PR of 0.11 (0.04, 0.34) and 0.22 (0.07, 0.67), respectively. In DMD, Dp140+/Dp71+ vs. Dp140– /Dp71– had a PR of 0.40 (0.28, 0.57), and Dp71+ vs. Dp71– had a PR of 0.47 (0.36, 0.63) for ADHD. However, there was no association of genotype with ASD, only a trend was observed for Dp71+ vs. Dp71–, with a PR of 0.61 (0.35, 1.06). Moreover, the data showed no association of these isoforms with emotional-related disorders. Conclusions: In BMD, Dp140 and Dp71 could be associated with developmental disorders, while ADHD might be associated with the Dp71 genotype in DMD. Further research is needed regarding Dp140 and Dp71, especially in DMD for ASD.

Dystrophin alterations in the brain have been associated with an increased risk of epilepsy in Becker and Duchenne muscular dystrophies (BMD and DMD). Moreover, an association between the mutation site and the risk of epilepsy is not ruled out. The aim of this systematic review and meta-analysis was to estimate the prevalence of epilepsy in BMD and DMD populations and to establish a possible association between the site of mutation in the dystrophin gene and the risk of epilepsy. Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were conducted to identify relevant studies published from inception to January 2022. Observational studies of participants with BMD/DMD estimating the prevalence of epilepsy were included. The main outcome was the prevalence of epilepsy, and the secondary outcome was the prevalence ratio considering genotype. A random effects meta-analysis was performed for the prevalence of epilepsy. Eight studies were included in the systematic review and meta-analysis. The prevalence of epilepsy was 7% (95% CI 3–11%) in BMD, 5% (95% CI 2–8%) in DMD, and 5% (95% CI 3–7%) in the overall estimate. No association was observed between mutation site and the prevalence of epilepsy. BMD/DMD is strongly associated with the prevalence of epilepsy, with a higher prevalence in BMD/DMD populations than in the general population, probably owing to alterations in Dp427. The current evidence does not support the hypothesis that Dp140 or Dp71 affect epilepsy risk.

Background: Migraine is a common and disabling primary headache disorder, associated with many medical comorbidities, highly prevalent, with complex treatment and management. Currently, monoclonal antibodies targeting the trigeminal sensory neuropeptide, calcitonin gene-related peptide (CGRP), are available. The aim of this protocol is to provide a review comparing the effects and safety profile of different monoclonal antibodies in migraine patients. Methods: The literature search will be performed through the MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), Web of Science and Scopus databases, following the PICO strategy. Real World studies and randomized clinical trials assessing the effect of monoclonal antibodies against CGRP interventions (erenumab, eptinezumab, fremanezumab and galcanezumab) on monthly migraine days (MMD), monthly headache days (MHD), headache impact test (HIT-6) and triptan days of use (TriD) will be included. In Real World studies, the DerSimonian and Laird method will be used to calculate pooled estimates of the mean change difference and in randomized clinical trials, a network meta-analysis will be performed to estimate the comparative effects of different monoclonal antibodies against CGRP. Results: The findings of this study will be reported in a peer-reviewed journal. Conclusions: This study will provide evidence to health professionals on the efficacy and safety of different monoclonal antibodies against CGRP on the outcomes studied.