Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies.

Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.

Half a century of research on Attention-Deficit/Hyperactivity Disorder: A scientometric study.

We performed a scientometric analysis of the scientific literature on ADHD to evaluate key themes and trends over the past decades, informing future lines of research. We conducted a systematic search in Web of Science Core Collection up to 15 November, 2021 for scientific publications on ADHD. We retrieved 28,381 publications. We identified four major research trends: 1) ADHD treatment, risks factors and evidence synthesis; 2) neurophysiology, neuropsychology and neuroimaging; 3) genetics; 4) comorbidity. In chronological order, identified clusters of themes included: tricyclic antidepressants, ADHD diagnosis/treatment, bipolar disorder, EEG, polymorphisms, sleep, executive functions, pharmacology, genetics, environmental risk factors, emotional dysregulation, neuroimaging, non-pharmacological interventions, default mode network, Tourette, polygenic risk score, sluggish cognitive tempo, evidence-synthesis, toxins/chemicals, psychoneuroimmunology, Covid-19, and physical exercise. In conclusion, research on ADHD over the past decades has been driven mainly by a medical model. Whereas the neurobiological correlates of ADHD are undeniable and crucial, we look forward to further research on relevant psychosocial aspects related to ADHD, such as societal pressure, the concept of neurodiversity, and stigma.

Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review.

BACKGROUND: The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS: We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS: We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION: Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING: None.

The need for holistic, longitudinal and comparable, real-time assessment of the emotional, behavioral and societal impact of the COVID-19 pandemic across nations.

As of the end of 2020, the COVID-19 pandemic has led to over 82 million verified infections and almost 1.8 million COVID-19-related deaths worldwide,1 resulting to an unprecedented public health response around the globe. The COVID-19 pandemic, together with the applied multi-level restrictive measures, has generated a unique combination of an unpredictable and stressful biomedical and socioeconomic environment (i.e., syndemic),2 introducing real-life threat, involuntary and drastic every-day life-style changes with uncertain financial and future prospects, alongside with minimized coping and stress management possibilities.3 This combination of so many different and vital stressors may lead to acute as well as long-term, direct, indirect and even transgenerational unfavourable effects on physical and mental health and functioning, which might even represent the most precarious and still unpredictable public-health-related part of the pandemic.4 Thereby, specific population groups could be at particular risk of poor health outcomes in relation to applied public health measures.4, 5 However, not every individual will experience the same level of negative impact on health and well-being during the pandemic, as several additional national, socioeconomic, environmental, behavioural, emotional and cognitive factors can moderate individual resilience and coping.6 Pandemic-related research should, thus, assess as many multidimensional risk and protective factors as possible in a longitudinal, large-scale and multi-national manner, enabling a profound and comprehensive understanding of the complex health and societal impact of the pandemic worldwide.7 Nevertheless, to date, most research findings are cross-sectional, report on small and non- representative samples from individual countries, or on specific population groups (e.g., health care workers, students, clinical populations) and usually assess only a very restricted set of outcomes and time-points. Thereby, only few studies assess coping strategies, medical history or detailed socioeconomic, demographic and environmental data. In addition, most studies leave behind linguistic differences, being available in one or at best two different languages. Such investigations of small outcome subsets within a narrow framework preclude a broader and clear understanding of the multifaceted pandemic impact on the general population and specific subgroups. Acknowledging these gaps in the existing literature, large- scale, collaborative research prospectively collecting and monitoring a broad range of real- time, multi-dimensional health-related, societal and behavioural outcome data from countries across the globe is currently explicitly needed. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH- FIT) envisions to fill this gap. Based on an easy-to-access webpage (www.coh-fit.com), COH- FIT is the currently largest-scale known international collaborative study of over 200 researchers around the globe, prospectively collecting the biggest set of multi-dimensional and multi-disciplinary data from 150 high, middle, and low-income countries in over 30 languages and in three different age groups (adults, adolescents, children) of the general population, focusing also on relevant at-risk subgroups. Albeit being a cross-sectional anonymous survey on an individual level, it is a longitudinal study on a population level, as data are collected continuously since April 2020 and until the WHO declares the end of the pandemic. In addition to snowball recruitment, this project also collects information from nationally representative samples. Furthermore, COH-FIT is the first study of this scale investigating pandemic effects on health and functioning measures between family members, while it also specifically assesses a large list of behavioral and coping factors (e.g., screen time, social media usage, physical activity, social interaction, religious practices, etc.) on outcomes of interest. COH-FIT also monitors changes in public health restrictive measures to enhance data harmonization across nations and time, and to better investigate their impact on physical and mental health, while it also collects information on changes in healthcare systems functioning. The COH-FIT project was worldwide first initiated in Greece after the ethics committee approval of the School of Medicine of the Aristotle University of Thessaloniki and is officially supported by the Hellenic Psychiatric Association, European Psychiatric Association, World Association of Social Psychiatry, ECNP Network on the Prevention of Mental Disorders and Mental Health Promotion, among many other national and international scientific associations. To date, COH-FIT has already collected >115,000 participations worldwide (>8,000 in Greece), but more participants are still needed, both during the second and third wave of the pandemic, as in the future, after the pandemic has ended. Currently, the COH-FIT survey actively collects the largest sample on multifactorial data on the impact of the COVD-19 pandemic on health and functioning not only in Greece, but around the globe. The elaborated design of COH-FIT and similar studies may allow a better identification of key parameters and population groups at increased risk during the pandemic, as well as potential targets for acute and long-term prevention or intervention strategies in the current as in possible future pandemics. A profound understanding of the health and societal impact of the pandemic could facilitate an optimized governmental, social and individual health preparedness during infection times8 and the bridging of individuals', societal and systemic needs and actions through multi-level guideline development with the aim to improve mental health outcomes globally.

Interventions for reducing loneliness: An umbrella review of intervention studies.

Loneliness is a common phenomenon associated with several negative health outcomes. Current knowledge regarding interventions for reducing loneliness in randomised controlled trials (RCTs) is conflicting. The aim of the present work is to provide an overview of interventions to reduce loneliness, using an umbrella review of previously published systematic reviews and meta-analyses. We searched major databases from database inception to 31 March 2020 for RCTs comparing active versus non-active interventions for reducing loneliness. For each intervention, random-effects summary effect size and 95% confidence intervals (CIs) were calculated. For significant outcomes (p-value < 0.05), the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool was used, grading the evidence from very low to high. From 211 studies initially evaluated, seven meta-analyses for seven different types of interventions were included (median number of RCTs: 8; median number of participants: 600). Three interventions were statistically significant for reducing loneliness, that is, meditation/mindfulness, social cognitive training and social support. When applying GRADE criteria, meditation/mindfulness (mean difference, MD = -6.03; 95% CI: -9.33 to -2.73; very low strength of the evidence), social cognitive training (8 RCTs; SMD = -0.49; 95% CI: -0.84 to -0.13; very low strength of the evidence) and social support (9 RCTs; SMD = -0.13; 95% CI: -0.25 to -0.01; low strength of the evidence) significantly decreased the perception of loneliness. In conclusion, three intervention types may be utilised for reducing loneliness, but they are supported by a low/very low certainty of evidence indicating the need for future large-scale RCTs to further investigate the efficacy of interventions for reducing loneliness.

Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies.

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on P value, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; P value < 10-6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.

Consumption of Fish and ω-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies.

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks.

Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies.

PURPOSE: To map and grade all health outcomes associated with magnesium (Mg) intake and supplementation using an umbrella review. METHODS: Umbrella review of systematic reviews with meta-analyses of observational studies and randomized controlled trials (RCTs) using placebo/no intervention as control group. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects and excess significance. For meta-analyses of RCTs, outcomes with a random-effect p value < 0.005 and a high-GRADE assessment were classified as strong evidence. RESULTS: From 2048 abstracts, 16 meta-analyses and 55 independent outcomes were included (36 in RCTs and 19 in observational studies). In RCTs of Mg versus placebo/no active treatment, 12 over 36 outcomes reported significant results (p < 0.05). A strong evidence for decreased need for hospitalization in pregnancy and for decreased risk of frequency and intensity of migraine relapses in people with migraine was observed using the GRADE assessment. In observational studies, 9/19 outcomes were significant (p < 0.05). However, only one outcome presented highly suggestive evidence (lower incidence of type 2 diabetes in people with higher Mg intake at baseline) and one suggestive (lower incidence of stroke associated with higher Mg intake at baseline). CONCLUSION: Strong evidence according to the GRADE suggests that Mg supplementation can decrease the risk of hospitalization in pregnant women and reduce the intensity/frequency of migraine. Higher Mg intake is associated with a decreased risk of type 2 diabetes and stroke with highly suggestive and suggestive evidence, respectively, in observational studies.

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.

The Relationship between Dietary Vitamin K and Depressive Symptoms in Late Adulthood: A Cross-Sectional Analysis from a Large Cohort Study.

Few studies assessed the associations between dietary vitamin K and depressive symptoms. We aimed to investigate the association between dietary vitamin K and depressive symptoms in a large cohort of North American People. In this cross-sectional analysis, 4,375 participants that were aged 45⁻79 years from the Osteoarthritis Initiative were included. Dietary vitamin K intake was collected through a semi-quantitative food frequency questionnaire and categorized in quartiles. Depressive symptoms were diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16. To investigate the associations between vitamin K intake and depressive symptoms, logistic regression analysis were run, which adjusted for potential confounders. Overall, 437 (=10%) subjects had depressive symptoms. After adjusting for 11 confounders, people with the highest dietary vitamin K intake had lower odds of having depressive symptoms (OR = 0.58; 95%CI: 0.43⁻0.80). This effect was only present in people not taking vitamin D supplementation. In conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders. Future longitudinal research is required to explore the directionality of the association.

The effectiveness of hypnosis for pain relief: A systematic review and meta-analysis of 85 controlled experimental trials.

The current meta-analysis aimed to quantify the effectiveness of hypnosis for reducing pain and identify factors that influence efficacy. Six major databases were systematically searched for trials comparing hypnotic inductions with no-intervention control conditions on pain ratings, threshold and tolerance using experimentally-evoked pain models in healthy participants. Eighty-five eligible studies (primarily crossover trials) were identified, consisting of 3632 participants (hypnosis nö=ö2892, control nö=ö2646). Random effects meta-analysis found analgesic effects of hypnosis for all pain outcomes (gö=ö0.54-0.76, p's<.001). Efficacy was strongly influenced by hypnotic suggestibility and use of direct analgesic suggestion. Specifically, optimal pain relief was obtained for hypnosis with direct analgesic suggestion administered to high and medium suggestibles, who respectively demonstrated 42% (pö<ö.001) and 29% (pö<ö.001) clinically meaningful reductions in pain. Minimal benefits were found for low suggestibles. These findings suggest that hypnotic intervention can deliver meaningful pain relief for most people and therefore may be an effective and safe alternative to pharmaceutical intervention. High quality clinical data is, however, needed to establish generalisability in chronic pain populations.

Role of out of hours primary care service in limiting inappropriate access to emergency department.

Out of hours (OOH) doctors can have an important gate-keeping role over the access to the emergency department (ED), but the outcome and the quality of their ED referrals have been poorly studied. We aimed to investigate the outcome of patients referred to ED from OOH service and the determinants of admission or short-stay dispositions. We collected retrospectively data about referrals to ED from a local OOH service in the north-east of Italy using the OOH paper register and the ED electronic database, over the period of 01/10/2012 to 31/03/2013. Out of 5217 patients accessing the OOH service, 408 referrals were included in our analysis. 45.3% (185) of the referrals were admitted to hospital or the short-stay unit, 26 patients (=6.4%) were discharged as non-urgent outgoing codes after no specialist consultation or test, suggesting inappropriate referrals, and, of the remaining 197 (=48%), only 10 did not undergo any investigation or consultation. Significant determinants of admission were: age ≥65 years (OR = 2.619; 95% CI 1.528-4.491, p < 0.0001), domiciliary examination (OR = 2.168; 95% CI 1.353-3.476, p = 0.001), nursing home/palliative care setting (OR = 2.563; 95% CI 1.228-5.351, p = 0.012) and OOH triage code, ranging from an OR of 7.47 (95% CI 3.028-18.433) for minor urgencies to an OR of 26.835 (95% CI 6.761-106.508, p < 0.0001) for emergencies, in comparison to no urgent codes. OOH service seems to play an effective gate-keeping role limiting ED access. Determinants of admission to hospital suggest some simple interventions that could improve the adequacy of ED referral from OOH service.

Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis.

OBJECTIVE: Deficiency of acetyl-L-carnitine (ALC) seems to play a role in the risk of developing depression, indicating a dysregulation of fatty acid transport across the inner membrane of mitochondria. However, data about ALC supplementation in humans are limited. We thus conducted a systematic review and meta-analysis investigating the effect of ALC on depressive symptoms across randomized controlled trials (RCTs). METHODS: A literature search in major databases, without language restriction, was undertaken from inception until 30 December 2016. Eligible studies were RCTs of ALC alone or in combination with antidepressant medications, with a control group taking placebo/no intervention or antidepressants. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for summarizing outcomes with a random-effect model. RESULTS: Twelve RCTs (11 of which were ALC monotherapy) with a total of 791 participants (mean age = 54 years, % female = 65%) were included. Pooled data across nine RCTs (231 treated with ALC versus 216 treated with placebo and 20 no intervention) showed that ALC significantly reduced depressive symptoms (SMD = -1.10, 95% CI = -1.65 to -0.56, I = 86%). In three RCTs comparing ALC versus antidepressants (162 for each group), ALC demonstrated similar effectiveness compared with established antidepressants in reducing depressive symptoms (SMD = 0.06, 95% CI = -0.22 to 0.34, I = 31%). In these latter RCTs, the incidence of adverse effects was significantly lower in the ALC group than in the antidepressant group. Subgroup analyses suggested that ALC was most efficacious in older adults. CONCLUSIONS: ALC supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects. Future large scale trials are required to confirm/refute these findings.

Fried potato consumption is associated with elevated mortality: an 8-y longitudinal cohort study.

Background: Few studies have assessed the association between potato consumption and mortality.Objective: We investigated whether potato consumption (including fried and unfried potatoes) is associated with increased premature mortality risk in a North American cohort.Design: A longitudinal analysis included 4440 participants aged 45-79 y at baseline with an 8-y follow-up from the Osteoarthritis Initiative cohort study. Potato consumption (including fried and unfried potatoes) was analyzed by using a Block Brief 2000 food-frequency questionnaire and categorized as ≤1 time/mo, 2-3 times/mo, 1 time/wk, 2 times/wk, or ≥3 times/wk. Mortality was ascertained through validated cases of death. To investigate the association between potato consumption and mortality, Cox regression models were constructed to estimate HRs with 95% CIs, with adjustment for potential confounders.Results: Of the 4400 participants, 2551 (57.9%) were women with a mean ± SD age of 61.3 ± 9.2 y. During the 8-y follow-up, 236 participants died. After adjustment for 14 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not show an increased risk of overall mortality (HR: 1.11; 95% CI: 0.65, 1.91). However, subgroup analyses indicated that participants who consumed fried potatoes 2-3 times/wk (HR: 1.95; 95% CI: 1.11, 3.41) and ≥3 times/wk (HR: 2.26; 95% CI: 1.15, 4.47) were at an increased risk of mortality. The consumption of unfried potatoes was not associated with an increased mortality risk.Conclusions: The frequent consumption of fried potatoes appears to be associated with an increased mortality risk. Additional studies in larger sample sizes should be performed to confirm if overall potato consumption is associated with higher mortality risk. This trial was registered at clinicaltrials.gov as NCT00080171.

Dietary magnesium intake and fracture risk: data from a large prospective study.

Research considering the relationship between dietary Mg and osteoporosis as well as fractures are sparse and conflicting. We therefore aimed to investigate Mg intake and the onset of fractures in a large cohort of American men and women involved in the Osteoarthritis Initiative over a follow-up period of 8 years. Dietary Mg intake (including that derived from supplementation) was evaluated through a FFQ at baseline and categorised using sex-specific quintiles (Q); osteoporotic fractures were evaluated through self-reported history. Overall, 3765 participants (1577 men; 2071 women) with a mean age of 60·6 (sd 9·1) years were included. During follow-up, 560 individuals (198 men and 368 women) developed a new fracture. After adjusting for fourteen potential confounders at baseline and taking those with lower Mg intake as reference (Q1), men (hazard ratio (HR) 0·47; 95 % CI 0·21, 1·00, P=0·05) and women (HR 0·38; 95 % CI 0·17, 0·82, P=0·01) in the highest quintile reported a significantly lower risk for fracture. Women meeting the recommended Mg intake were at a 27 % decreased risk for future fractures. In conclusion, higher dietary Mg intake has a protective effect on future osteoporotic fractures, especially in women with a high risk for knee osteoarthritis. Those women meeting the recommended Mg intake appear to be at a lower risk for fractures.

Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review.

BACKGROUND: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. METHODS: Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint. RESULTS: Eight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression. LIMITATIONS: A meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence. CONCLUSIONS: This systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear.

Hypovitaminosis D and orthostatic hypotension: a systematic review and meta-analysis.

OBJECTIVES: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). METHODS: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25-2.84; I = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13-3.68; I = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = -0.42; 95% CI: -0.72 to -0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. CONCLUSION: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.

Vitamin D status in anorexia nervosa: A meta-analysis.

OBJECTIVE: In anorexia nervosa (AN), osteoporosis and osteopenia are common, which have been associated with low circulating levels of vitamin D (VitD) in other settings. We aimed to meta-analyze cross-sectional studies reporting on VitD parameters in patients with AN and healthy controls (HCs). METHOD: Electronic PubMed search from database inception until December 31, 2013 and meta-analysis of cross-sectional studies comparing serum levels of 25-hydroxyvitamin D (25OH-D), 1,25-dihydroxyvitamin D (1,25OH-D) and dietary VitD between patients with AN and HCs, before or after VitD supplementation. We calculated random effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as effect size measures. RESULTS: Out of 1,739 initial hits, 15 studies with a total of 927 participants (AN = 408 and HCs = 519) were meta-analyzed. In the unsupplemented state, both serum 25OH-D (studies = 4; n = 168; SMD = -0.43; 95%CI: -0.83 to -0.03; p = .03) and 1,25OH-D levels (studies = 4; n = 113; SMD = -1.06; 95%CI: -1.47 to -0.66; p < .00001) were significantly lower in AN than HCs. In AN patients treated with cholecalciferol supplementation, serum 25OH-D levels were significantly higher than in HCs (studies = 5; n = 449; SMD = 0.66; 95%CI: 0.01-1.31; p = .05). Paradoxically, despite lower 25OH-D and 1,25OH-D levels, AN patients reported similar intake of VitD compared to HCs (studies = 6; n = 314; SMD = 0.33; 95%CI: -0.16, 0.81; p = .19). DISCUSSION: Although AN patients reported similar dietary VitD intake compared to HCs, AN patients had significantly lower 25OH-D and 1,25OH-D levels without supplementation. Conversely, supplementation with cholecalciferol fully normalized VitD serum levels. Future studies are needed to clarify the role of VitD supplementation in AN for improving bone health.