Clinician's Approach to Advanced Statistical Methods: Win Ratios, Restricted Mean Survival Time, Responder Analyses, and Standardized Mean Differences.

Novel statistical methods have emerged in recent medical literature, which clinicians must understand to properly appraise and integrate evidence into their practice. Some of these key concepts include win ratios, restricted mean survival time, responder analyses, and standardized mean difference. This article offers guidance to busy clinicians on the comprehension and practical applicability of the results to patients. Win ratios provide an alternative method to analyze composite outcomes by prioritizing individual components of the composite; prioritization of the outcomes should be evidence-based, pre-specified, and patient-centered. Restricted mean survival time presents a method to analyze Kaplan-Meier curves when assumptions required for Cox proportional hazards analysis are not met. As it only considers outcomes that occur within a specific timeframe, the duration of follow-up must be appropriately defined and based on prior epidemiologic and mechanistic evidence. Researchers can analyze continuous outcomes with responder analyses, in which participants are dichotomized into "responders" or "non-responders." While clinicians and patients may more easily grasp outcomes analyzed in this way, they should be aware of the loss of information and resulting imprecision, as well as potential to manipulate data presentation. When meta-analyzing continuous outcomes, point estimates can be converted to standardized mean differences to facilitate the combination of data utilizing various outcome measures. However, clinicians may find it challenging to grasp the clinical meaningfulness of a standardized mean difference, and may benefit from converting it to well-known outcomes. By providing the background knowledge of these statistical methods, along with practical applicability, benefits, and inevitable limitations, this article aims to provide clinicians with an approach to appraise the literature and apply the results in clinical practice.

Association between ultra-processed foods and recurrence of depressive symptoms: the Whitehall II cohort study.

OBJECTIVES: To examine the association between high intakes of ultra-processed foods (UPF) and recurrence of depressive symptoms (DepS) in a Western non-Mediterranean country and its contribution to the overall diet-depression relationship. METHODS: Analyses were carried out on British participants from the Whitehall II cohort. Present analyses were restricted to white participants N = 4554 (74% men, mean age = 61; SD = 5.9). UPF consumption was estimated from a 127-item food frequency questionnaire using the NOVA classification, and cumulative average of UPF intakes (g/day) over 11 years of exposure (1991/1994-2002/2004) was computed. Recurrent DepS after measurement of UPF was defined as having two or more episodes of DepS (the Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 or antidepressants use) during four phases of follow-up (2002/2004-2015/2016). RESULTS: Over the follow-up, 588 (12.9%) cases of recurrent DepS were observed. After adjusting for socio-demographic factors, health behaviours and health status, participants in top quintile of UPF intakes [mean 33% of total daily intakes in grams] had 31% higher odds of recurrent DepS (odds ratio 1.31; 95% CI 1.04-1.64) compared to participants in the four lowest quintiles of UPF [mean 18.1% of total daily intakes in grams]. Additional analyses showed that associations between adherence to several diet quality measures and recurrent DepS were partially attenuated (17-27%) by UPF intakes. CONCLUSION: In this British population, high intakes of ultra-processed foods were associated with increased odds of recurrent depressive symptoms and contributed to the overall diet quality-depressive symptoms association.

Brain derived neurotrophic factor in perioperative neurocognitive disorders: Current evidence and future directions.

An increase in the age of surgical patients as well as the volume of surgeries is associated with a rise in perioperative neurocognitive disorders. These disorders encompass acute delirium and longer-term cognitive dysfunctions. Brain derived neurotrophic factor (BDNF) is a neurotrophin that plays a dynamic role in a series of neurological functions including neuroplasticity, neurogenesis and synaptic regulation. Given the possible alterations to brain physiology in response to surgery, this review aims to explore the relationship between changes in central and peripheral BDNF concentrations and perioperative neurocognitive disorders. Higher levels of Brain tissue and blood BDNF have been associated with better cognitive function; however, the nature of the association between BDNF and delirium is uncertain. Preclinical models point to a significant depletion in BDNF expression and signalling within the brain post-operatively, while preliminary human studies demonstrate depletions in serum BDNF concentration after surgery. These findings suggest that the reduced BDNF concentrations may be associated with post-operative cognitive dysfunction. Thus, understanding the BDNF expression/signalling pathways may present a promising avenue for managing perioperative neurocognitive disorders symptoms. Nonetheless, given that results were primarily derived from preclinical models, it is critical for these findings to be validated in humans to confirm the relevance of this promising target.

The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies.

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

Diet and depression: exploring the biological mechanisms of action.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.

The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials.

Neurosteroid and immunological actions of vitamin D may regulate depression-linked physiology. Meta-analyses investigating the effect of vitamin D on depression have been inconsistent. This meta-analysis investigated the efficacy of vitamin D in reducing depressive symptoms among adults in randomized placebo-controlled trials (RCT). General and clinical populations, and studies of ill individuals with systemic diseases were included. Light therapy, co-supplementation (except calcium) and bipolar disorder were exclusionary. Databases Medline, PsycINFO, CINAHL and The Cochrane Library were searched to identify relevant articles in English published before April 2022. Cochrane risk-of-bias tool (RoB 2) and GRADE were used to appraise studies. Forty-one RCTs (n = 53,235) were included. Analyses based on random-effects models were performed with the Comprehensive Meta-analysis Software. Results for main outcome (n = 53,235) revealed a positive effect of vitamin D on depressive symptoms (Hedges' g = -0.317, 95% CI [-0.405, -0.230], p < 0.001, I2 = 88.16%; GRADE: very low certainty). RoB assessment was concerning in most studies. Notwithstanding high heterogeneity, vitamin D supplementation ≥ 2,000 IU/day appears to reduce depressive symptoms. Future research should investigate possible benefits of augmenting standard treatments with vitamin D in clinical depression. PROSPERO registration number: CRD42020149760. Funding: Finnish Medical Foundation, grant 4120 and Juho Vainio Foundation, grant 202100353.

Adherence to the ultra-processed dietary pattern and risk of depressive outcomes: Findings from the NutriNet Brasil cohort study and an updated systematic review and meta-analysis.

BACKGROUND & AIMS: We aimed to analyze the prospective association between adherence to the ultra-processed dietary pattern and risk of depressive outcomes using original data from the NutriNet Brasil cohort and via a systematic review and meta-analysis of observational studies that have investigated the same association. METHODS: In our original research analysis, we used data from 15,960 adults (≥18 y) participating in the NutriNet Brasil cohort study, free of depression or depressive symptoms during the baseline (77.5% women, 45.8 ± 13.0 y). The mean dietary share of ultra-processed foods (%Kcal/d), calculated from two baseline 24-h dietary recalls, was used to measure the adherence to the ultra-processed dietary pattern. New cases of depressive symptoms were assessed using the Patient Health Questionnaire-9 over the follow-up period (mean: 18.3 months). Cox proportional hazards models were used for the main analyses. In our systematic review and meta-analysis, we incorporated effect estimates from six prospective cohort studies that have examined the same association, including ours. RESULTS: In the adjusted model, each 10% increase in the dietary share of ultra-processed foods was associated with a 10% increase in the hazard of incident cases of depressive symptoms (HR:1.10; 95%CI: 1.07-1.14). This association was slightly attenuated in the models including potential mediators. In our meta-analysis of six prospective studies, high versus low exposure to ultra-processed foods was associated with a summary hazard ratio of depressive outcomes of 1.32; 95%CI: 1.19-1.46; I2: 71%. CONCLUSION: A higher adherence to the ultra-processed dietary pattern was associated with a higher risk of developing depressive outcomes in the NutriNet Brasil cohort and in the meta-analysis.

Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses.

OBJECTIVE: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. DESIGN: Systematic umbrella review of existing meta-analyses. DATA SOURCES: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality. RESULTS: The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality. CONCLUSIONS: Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023412732.

Ultra-Processed Food Consumption and Depressive Symptoms in a Mediterranean Cohort.

Excess consumption of ultra-processed foods (UPFs) is currently under investigation for its potentially detrimental impact on human health. Current evidence demonstrates a substantial association with an increased risk of metabolic disorders, but data on mental health outcomes are just emerging. The aim of this study was to investigate the relationship between the consumption of UPFs and depressive symptoms in a sample of younger Italian adults. A cross-sectional study was conducted on 596 individuals (age 18-35 y) recruited in southern Italy. Food frequency questionnaires and the NOVA classification were used to assess dietary factors; the Center for the Epidemiological Studies of Depression Short Form (CES-D-10) was used to assess presence of depressive symptoms. Individuals in the highest quartile of UPF consumption had higher odds of having depressive symptoms in the energy-adjusted model (odds ratio (OR) = 1.89, 95% confidence interval (CI): 1.06, 3.28); the association remained significant after adjusting for potential confounding factors (OR = 2.04, 95% CI: 1.04, 4.01) and became even stronger after further adjustment for adherence to the Mediterranean diet as a proxy of diet quality (OR = 2.70, 95% CI: 1.32, 5.51). In conclusion, a positive association between UPF consumption and likelihood of having depressive symptoms was found in younger Italian individuals. Given the consistency of the findings after adjustment for diet quality, further studies are needed to understand whether non-nutritional factors may play a role in human neurobiology.

Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research.

Numerous animal and human studies have assessed the relationship between polyphenols and outcomes related to depression. However, no comprehensive synthesis of the main findings has been conducted. The aim of this manuscript was to systematically review the available evidence from animal and human studies on the association and the effects of dietary polyphenols on depression and provide recommendations for future research. We based our review on 163 preclinical animal, 16 observational and 44 intervention articles assessing the relationship between polyphenols and outcomes related to depression. Most animal studies demonstrated that exposure to polyphenols alleviated behaviours reported to be associated with depression. However, human studies are less clear, with some studies reporting an inverse relationship between the intake of some polyphenols, and polyphenol rich foods and depression risk and symptoms, while others reporting no association or effect. Hence, while there has been extensive research conducted in animals and there is some supporting evidence in humans, further human studies are required, particularly in younger and clinical populations.

The effects of anodal tDCS on pain reduction in people with knee osteoarthritis: A systematic review and meta-analysis.

OBJECTIVES: To synthesise the literature on the efficacy of primary motor cortex anodal transcranial direct current stimulation (M1-a-tDCS), as a standalone or priming technique, for pain reduction in people with knee osteoarthritis (KOA). METHODS: The systematic literature search was conducted in MEDLINE, CINAHL, Embase and CENTRAL according to PRISMA statement. RESULTS: Fourteen studies involving 740 people with KOA were included. In the meta-analysis, six studies compared a-tDCS alone with sham stimulation, and five studies compared a-tDCS combined with other methods with sham stimulation. We found positive effect of a-tDCS alone on pain in KOA (standard mean difference (SMD) -0.52; 95% CI, -0.78 to -0.25; P=0.001; I2 = 69%). Further, a-tDCS with other treatments showed positive effect (SMD -1.23; 95% CI, -1.59 to -0.88; P<0.001; I2 = 48%) on pain in people with KOA. This evidence showed low certainty due to a high risk of bias and imprecision. DISCUSSION AND CONCLUSION: A-tDCS could be considered as standalone and an adjunct treatment for pain reduction in people with KOA. Future randomised studies should address quality issues, including small sample size, to enhance the overall certainty of the findings. SIGNIFICANCE: A-tDCS can be used as a standalone and adjunct treatment for KOA. STUDY REGISTRATION: PROSPERO number CRD42021255114.

Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies.

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended.

High ultra-processed food consumption is associated with elevated psychological distress as an indicator of depression in adults from the Melbourne Collaborative Cohort Study.

BACKGROUND: Few studies have tested longitudinal associations between ultra-processed food consumption and depressive outcomes. As such, further investigation and replication are necessary. The aim of this study is to examine associations of ultra-processed food intake with elevated psychological distress as an indicator of depression after 15 years. METHOD: Data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 23,299). We applied the NOVA food classification system to a food frequency questionnaire (FFQ) to determine ultra-processed food intake at baseline. We categorised energy-adjusted ultra-processed food consumption into quartiles by using the distribution of the dataset. Psychological distress was measured by the ten-item Kessler Psychological Distress Scale (K10). We fitted unadjusted and adjusted logistic regression models to assess the association of ultra-processed food consumption (exposure) with elevated psychological distress (outcome and defined as K10 ≥ 20). We fitted additional logistic regression models to determine whether these associations were modified by sex, age and body mass index. RESULTS: After adjusting for sociodemographic characteristics and lifestyle and health-related behaviours, participants with the highest relative intake of ultra-processed food were at increased odds of elevated psychological distress compared to participants with the lowest intake (aOR: 1.23; 95%CI: 1.10, 1.38, p for trend = 0.001). We found no evidence for an interaction of sex, age and body mass index with ultra-processed food intake. CONCLUSION: Higher ultra-processed food intake at baseline was associated with subsequent elevated psychological distress as an indicator of depression at follow-up. Further prospective and intervention studies are necessary to identify possible underlying pathways, specify the precise attributes of ultra-processed food that confer harm, and optimise nutrition-related and public health strategies for common mental disorders.

Higher Ultra-Processed Food Consumption Is Associated with Greater High-Sensitivity C-Reactive Protein Concentration in Adults: Cross-Sectional Results from the Melbourne Collaborative Cohort Study.

Background: Few studies have examined associations between ultra-processed food intake and biomarkers of inflammation, and inconsistent results have been reported in the small number of studies that do exist. As such, further investigation is required. Methods: Cross-sectional baseline data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 2018). We applied the NOVA food classification system to data from a food frequency questionnaire (FFQ) to determine ultra-processed food intake (g/day). The outcome was high-sensitivity C-reactive protein concentration (hsCRP; mg/L). We fitted unadjusted and adjusted linear regression analyses, with sociodemographic characteristics and lifestyle- and health-related behaviours as covariates. Supplementary analyses further adjusted for body mass index (kg/m2). Sex was assessed as a possible effect modifier. Ultra-processed food intake was modelled as 100 g increments and the magnitude of associations expressed as estimated relative change in hsCRP concentration with accompanying 95% confidence intervals (95%CIs). Results: After adjustment, every 100 g increase in ultra-processed food intake was associated with a 4.0% increase in hsCRP concentration (95%CIs: 2.1−5.9%, p < 0.001). Supplementary analyses showed that part of this association was independent of body mass index (estimated relative change in hsCRP: 2.5%; 95%CIs: 0.8−4.3%, p = 0.004). No interaction was observed between sex and ultra-processed food intake. Conclusion: Higher ultra-processed food intake was cross-sectionally associated with elevated hsCRP, which appeared to occur independent of body mass index. Future prospective and intervention studies are necessary to confirm directionality and whether the observed association is causal.

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders.

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.

Ultra-Processed Food Consumption and Mental Health: A Systematic Review and Meta-Analysis of Observational Studies.

Since previous meta-analyses, which were limited only to depression and by a small number of studies available for inclusion at the time of publication, several additional studies have been published assessing the link between ultra-processed food consumption and depression as well as other mental disorders. We aimed to build on previously conducted reviews to synthesise and meta-analyse the contemporary evidence base and clarify the associations between the consumption of ultra-processed food and mental disorders. A total of 17 observational studies were included (n = 385,541); 15 cross-sectional and 2 prospective. Greater ultra-processed food consumption was cross-sectionally associated with increased odds of depressive and anxiety symptoms, both when these outcomes were assessed together (common mental disorder symptoms odds ratio: 1.53, 95%CI 1.43 to 1.63) as well as separately (depressive symptoms odds ratio: 1.44, 95%CI 1.14 to 1.82; and, anxiety symptoms odds ratio: 1.48, 95%CI 1.37 to 1.59). Furthermore, a meta-analysis of prospective studies demonstrated that greater ultra-processed food intake was associated with increased risk of subsequent depression (hazard ratio: 1.22, 95%CI 1.16 to 1.28). While we found evidence for associations between ultra-processed food consumption and adverse mental health, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Major Depressive Disorder in Older Patients as an Inflammatory Disorder: Implications for the Pharmacological Management of Geriatric Depression.

Depression is a common and highly disabling condition in older adults. It is a heterogenous disorder and there is emerging evidence of a link between inflammation and depression in older patients, with a possible inflammatory subtype of depression. Persistent low-level inflammation, from several sources including psychological distress and chronic disease, can disrupt monoaminergic and glutaminergic systems to create dysfunctional brain networks. Despite the evidence for the role of inflammation in depression, there is insufficient evidence to recommend use of any putative anti-inflammatory agent in the treatment of depression in older adults at this stage. Further characterisation of markers of inflammation and stratification of participants with elevated rates of inflammatory markers in treatment trials is needed.

Ultra-Processed Food Consumption and Adult Diabetes Risk: A Systematic Review and Dose-Response Meta-Analysis.

(1) Background: Recent individual studies have demonstrated that consumption of ultra-processed food (UPF) may be related to type two diabetes mellitus (T2DM). We aimed to synthesize the results from these individual studies by conducting an updated systematic review and meta-analysis of observational studies evaluating the association between UPF consumption and the risk of T2DM. (2) Methods: A systematic search was conducted using ISI Web of Science, PubMed/MEDLINE and Scopus electronic databases from inception up to August 2021. Data were extracted from five studies (one cross-sectional study and four cohort studies, totaling 230,526 adults from four different countries). Risk ratios (RR) of pooled results were estimated using a random-effects model. (3) Results: Our results revealed that higher UPF consumption was significantly associated with an increased risk of T2DM (RR = 1.74; 95% CI: 1.36, 2.22; I2 = 68.9%; p < 0.001; n = 5). Linear dose-response analysis indicated that each 10% increase in UPF consumption (kcal/d) was associated with a 15% higher risk of T2DM (RR = 1.15; 95% CI: 1.06, 1.26; I2 = 86.0%; p < 0.001; n = 5) among adults. Non-linear dose-response analysis demonstrated a positive linear association between UPF consumption and T2DM (pnonlinearity = 0.13, pdose-response < 0.001; n = 5) among adults. (4) Conclusions: A higher intake of UPF was significantly associated with an increased risk of T2DM. However, underlying mechanisms remain unknown and future experimental studies are warranted.

Possible use of fermented foods in rehabilitation of anorexia nervosa: the gut microbiota as a modulator.

Anorexia nervosa is a serious psychiatric disorder with high morbidity and mortality rate. Evidence for the optimal psychopharmacological approach to managing the disorder remains limited, with nutritional treatment, focused on weight restoration through the consumption of high energy diet, regarded as one of the fundamental steps in treatment. The human gut microbiome is increasingly recognised for its proposed role in gastrointestinal, metabolic, immune and mental health, all of which may be compromised in individuals with anorexia nervosa. Dietary intake plays an important role in shaping gut microbiota composition, whilst the use of fermented foods, foods with potential psychobiotic properties that deliver live bacteria, bacterial metabolites, prebiotics and energy, have been discussed to a lesser extent. However, fermented foods are of increasing interest due to their potential capacity to affect gut microbiota composition, provide beneficial bacterial metabolites, and confer beneficial outcomes to host health. This review provides an overview of the role of the gut microbiota in relation to the disease pathology in anorexia nervosa and especially focuses on the therapeutic potential of fermented foods, proposed here as a recommended addition to the current nutritional treatment protocols warranting further investigation.