GRADE guidance 39: using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

BACKGROUND AND OBJECTIVE: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.

Telehealth for Substance Use Disorders: A Rapid Review for the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Substance Use Disorders.

BACKGROUND: Approximately 20.4 million Americans met criteria for a substance use disorder (SUD) in 2019; however, only about 12.2% of persons with an SUD receive specialty care. Telehealth offers alternatives to traditional forms of substance use treatment. PURPOSE: To synthesize recent findings on the efficacy of telehealth for SUDs. DATA SOURCES: MEDLINE, Embase, PubMed, and the Cochrane Library from January 2015 through August 2021 (English language only). STUDY SELECTION: Randomized controlled trials (RCTs) of adults with a diagnosis of SUD based on the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases. DATA EXTRACTION: One investigator abstracted data and assessed study quality, and a second checked for accuracy. DATA SYNTHESIS: This rapid review synthesized evidence from 17 RCTs. Evidence is very uncertain that telehealth provided as videoconference therapy (1 RCT) or web-based cognitive behavioral therapy (CBT) (3 RCTs) has similar effects to in-person therapy for improving abstinence from alcohol or cannabis. Low-strength evidence suggests that web-based CBT has similar effects for improving abstinence in multiple SUDs (2 RCTs). Low-strength evidence suggests that adding supportive text messaging to follow-up care improves abstinence and amount of alcohol per day (2 RCTs) but does not improve emergency department visits or frequency of consumption (2 RCTs). Enhanced telephone monitoring likely reduces readmissions for SUD detoxification compared with usual follow-up alone (1 RCT) but does not reduce days of substance use (low-strength evidence). LIMITATION: Narrative synthesis, heterogeneity of telehealth interventions, no assessment of publication bias, and study methodology. CONCLUSION: Evidence is very uncertain that telehealth is similar to in-person care for SUD outcomes. Limited evidence suggests some benefit of adding telehealth to usual SUD care. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Veterans Health Administration.

Effect of Intensive Blood Pressure Lowering on Cardiovascular Outcomes: A Systematic Review Prepared for the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Guidelines.

BACKGROUND: Recent clinical trials suggest that treating patients with hypertension to lower blood pressure (BP) targets improves cardiovascular outcomes. PURPOSE: To summarize the effects of intensive (or targeted) systolic BP (SBP) and diastolic BP (DBP) lowering with pharmacologic treatment on cardiovascular outcomes and harms in adults with hypertension. DATA SOURCES: Multiple databases, including MEDLINE and EMBASE, were searched for relevant systematic reviews (SRs) published in English from 15 December 2013 through 25 March 2019, with updated targeted searches through 8 January 2020. STUDY SELECTION: 8 SRs of randomized controlled trials examining either a standardized SBP target of -10 mm Hg (1 SR) or BP lowering below a target threshold (7 SRs). DATA EXTRACTION: One investigator abstracted data, assessed study quality, and performed GRADE assessments; a second investigator checked abstractions and assessments. DATA SYNTHESIS: The main outcome of interest was reduction in composite cardiovascular outcomes. High-strength evidence showed benefit of a 10-mm Hg reduction in SBP for cardiovascular outcomes among patients with hypertension in the general population, patients with chronic kidney disease, and patients with heart failure. Evidence on reducing SBP for cardiovascular outcomes in patients with a history of cardiovascular disease (moderate strength) or diabetes mellitus (high strength) to a lower SBP target was mixed. Low-strength evidence supported intensive lowering to a 10-mm Hg reduction in SBP for cardiovascular outcomes in patients with a history of stroke. All reported harms were considered, including general adverse events, serious adverse events, cognitive impairment, fractures, falls, syncope, hypotension, withdrawals due to adverse events, and acute kidney injury. Safety results were mixed or inconclusive. LIMITATIONS: This was a qualitative synthesis of new evidence with existing meta-analyses. Data were sparse for outcomes related to treating DBP to a lower target or for patients older than 60 years. CONCLUSION: Overall, current clinical literature supports intensive BP lowering in patients with hypertension for improving cardiovascular outcomes. In most subpopulations, intensive lowering was favored over less-intensive lowering, but the data were less clear for patients with diabetes mellitus or cardiovascular disease. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation.

Background: Early rehabilitation after stroke is essential to help reduce disability. Purpose: To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke. Data Sources: English-language searches of multiple electronic databases from April 2009 through July 2018; targeted searches to December 2018 for studies of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors. Study Selection: 19 systematic reviews and 37 randomized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke. Data Extraction: One investigator abstracted the data, and quality and GRADE assessment were checked by a second investigator. Data Synthesis: Most interventions (for example, SSRIs, mental practice, mirror therapy) did not improve motor function. High-quality evidence did not support use of fluoxetine to improve motor function. Moderate-quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living (ADLs). Low-quality evidence supported use of robotic arm training to improve ADLs. Low-quality evidence indicated that antidepressants may reduce depression, whereas the frequency and severity of antidepressant-related adverse effects was unclear. Low-quality evidence suggested that cognitive behavioral therapy and exercise, including mind-body exercise, may reduce symptoms of depression and anxiety. Limitation: Studies were of poor quality, interventions and comparators were heterogeneous, and evidence on harms was scarce. Conclusion: Cardiorespiratory training, repetitive task training, and transcranial direct current stimulation may improve ADLs in adults with stroke. Cognitive behavioral therapy, exercise, and SSRIs may reduce symptoms of poststroke depression, but use of SSRIs to prevent depression or improve motor function was not supported. Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.

Treatments for the Prevention and Management of Suicide: A Systematic Review.

Background: Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016. Purpose: To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults. Data Sources: MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018. Study Selection: Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide. Data Extraction: One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. Data Synthesis: Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or crisis planning. The evidence for pharmacologic treatments suggests that ketamine reduces suicidal ideation with minimal adverse events compared with placebo or midazolam. Lithium reduces rates of suicide among patients with unipolar or bipolar mood disorders compared with placebo. However, no differences were observed between lithium and other medications in reducing suicide. Limitation: Qualitative synthesis of new evidence with existing meta-analyses, methodological shortcomings of studies, heterogeneity of nonpharmacologic interventions, and limited evidence for pharmacologic treatments and harms. Conclusion: Both CBT and DBT showed modest benefit in reducing suicidal ideation compared with TAU or wait-list control, and CBT also reduced suicide attempts compared with TAU. Ketamine and lithium reduced the rate of suicide compared with placebo, but there was limited information on harms. Limited data are available to support the efficacy of other nonpharmacologic or pharmacologic interventions. Primary Funding Source: U.S. Department of Veterans Affairs Veterans Health Administration. (PROSPERO: CRD42018104978).

Hypobaric hypoxia exposure in rats differentially alters antidepressant efficacy of the selective serotonin reuptake inhibitors fluoxetine, paroxetine, escitalopram and sertraline.

Treatment-resistant depression, a chronic condition that affects 30% of depressed patients on antidepressants, is highly linked to suicidal behavior. Chronic hypoxia exposure via living at altitude (hypobaric hypoxia) or with chronic hypoxic diseases is demographically linked to increased risk for depression and suicide. We previously demonstrated that housing rats at altitude for a week incrementally increases depression-like behavior in the forced swim test (FST) in females, but not males. In animal models, high altitude exposure reduces brain serotonin, and selective serotonin reuptake inhibitors (SSRIs) can lose efficacy when brain serotonin levels are low. To address whether residence at moderate altitude is detrimental to SSRI function, we examined SSRI efficacy in the FST after a week of housing rats at altitudes of 4500 ft. or 10,000 ft. as compared to at sea level. In females, the tricyclic antidepressant desipramine (positive control) functioned well in all groups, increasing latency to immobility and decreasing immobility, by increasing climbing. However, the SSRIs fluoxetine, paroxetine and escitalopram were ineffective in females in all groups: only paroxetine improved swimming in the FST as expected of a SSRI, while all three unexpectedly reduced climbing. Fluoxetine was also ineffective in male rats. Sertraline was the only SSRI with antidepressant efficacy at altitude in both females and males, increasing swimming, climbing and latency to immobility, and reducing immobility. Hypobaric hypoxia thus appears to be detrimental to efficacy of the SSRIs fluoxetine, paroxetine and escitalopram, but not of sertraline. Unlike the other SSRIs, sertraline can improve both serotonergic and dopaminergic transmission, and may be less impacted by a hypoxia-induced serotonin deficit. A targeted approach may thus be necessary for successful antidepressant treatment in patients with depression who live at altitude or with chronic hypoxic diseases, and that sertraline may be the SSRI of choice for prescription for this population.

Effectiveness of indoor allergen reduction in asthma management: A systematic review.

BACKGROUND: This review will inform updated National Asthma Education and Prevention Program clinical practice guidelines. OBJECTIVE: We sought to evaluate the effectiveness of allergen reduction interventions on asthma outcomes. METHODS: We systematically searched the "gray literature" and 5 bibliographic databases. Eligible studies included systematic reviews, randomized controlled trials, and nonrandomized interventional studies. Risk of bias was assessed by using the Cochrane Risk of Bias instrument and the Newcastle-Ottawa scale. The evidence base was assessed by using the approach of the Agency for Healthcare Research and Quality's Evidence-based Practice Center program. RESULTS: Fifty-nine randomized and 8 nonrandomized trials addressed 8 interventions: acaricide, air purification, carpet removal, high-efficiency particulate air filtration (HEPA) vacuums, mattress covers, mold removal, pest control, and pet removal. Thirty-seven studies evaluated single-component interventions, and 30 studies assessed multicomponent interventions. Heterogeneity precluded meta-analysis. For most interventions and outcomes, the evidence base was inconclusive or showed no effect. No interventions were associated with improvement in validated asthma control measures or pulmonary physiology. Exacerbations were diminished in multicomponent studies that included HEPA vacuums or pest control (moderate strength of evidence [SOE] for both). Quality of life improved in studies of air purifiers (SOE: low) and in multicomponent studies that included HEPA vacuums (SOE: moderate) or pest control (SOE: low). CONCLUSIONS: Single interventions were generally not associated with improvement in asthma measures, with most strategies showing inconclusive results or no effect. Multicomponent interventions improved various outcomes, but no combination of specific interventions appears to be more effective. The evidence was often inconclusive because of a lack of studies. Further research is needed comparing the effect of indoor allergen reduction interventions on validated asthma measures, with sufficient population sizes to detect clinically meaningful differences.

Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not in males.

Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males.

Factors influencing behavior in the forced swim test.

The forced swim test (FST) is a behavioral test in rodents which was developed in 1978 by Porsolt and colleagues as a model for predicting the clinical efficacy of antidepressant drugs. A modified version of the FST added the classification of active behaviors into swimming and climbing, in order to facilitate the differentiation between serotonergic and noradrenergic classes of antidepressant drugs. The FST is now widely used in basic research and the pharmaceutical screening of potential antidepressant treatments. It is also one of the most commonly used tests to assess depressive-like behavior in animal models. Despite the simplicity and sensitivity of the FST procedure, important differences even in baseline immobility rates have been reported between different groups, which complicate the comparison of results across studies. In spite of several methodological papers and reviews published on the FST, the need still exists for clarification of factors which can influence the procedure. While most recent reviews have focused on antidepressant effects observed with the FST, this one considers the methodological aspects of the procedure, aiming to summarize issues beyond antidepressant action in the FST. The previously published literature is analyzed for factors which are known to influence animal behavior in the FST. These include biological factors, such as strain, age, body weight, gender and individual differences between animals; influence of preconditioning before the FST: handling, social isolation or enriched environment, food manipulations, various kinds of stress, endocrine manipulations and surgery; schedule and routes of treatment, dosage and type of the drugs as well as experimental design and laboratory environmental effects. Consideration of these factors in planning experiments may result in more consistent FST results.

Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats.

The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies.

Exercise promotes positive impression formation towards both men and women.

Exercise is endorsed for its physiological and psychological benefits, and has been proposed to have positive effects on impression formation. To test this proposal, 62 female and 44 male college students read one of three brief descriptions of either a fictitious male or female "target" student. The descriptions varied only in exercise level: no exercise; moderate exercise and intensive exercise. Participants then rated the fictitious student on 38 personality traits. Ratings of characteristics that are associated with exercise (e.g. athletic; energetic) increased, while ratings associated with the lack of exercise (e.g. lazy; weak) decreased as a function of the reported level of exercise. Exercise level also positively influenced ratings of characteristics not related to exercise. These data show that even minimal information about exercise is an important component of first impressions in both men and women.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT).

OBJECTIVE: Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment, and depression are all common in individuals with kidney disease, including kidney transplant recipients. Accordingly, we assessed the prevalence of cognitive impairment and depressive symptoms in transplant recipients and their association with kidney function, plasma total homocysteine, and B-vitamin concentrations. SETTING: Cross-sectional analysis of baseline data from the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) Ancillary Cognitive Trial (FACT), which included 183 participants in FAVORIT who underwent detailed neuropsychological assessment before the study intervention. RESULTS: The mean age was 54.0 ± 9.5 years (range: 7 to 386 months). Men comprised 55.2% of the cohort, and the mean time between the current transplant and cognitive testing was 7.0 ± 5.8 years. Twenty-four percent of participants reported neurological or psychiatric complaints, and 30% exhibited symptoms of mild to severe depression. Testing revealed evidence of significant and selective deficits in this population: 33% performed more than 1 standard deviation (SD) below normed means on a memory test, 58% fell lower than 1 SD below the norms on a test of attention and mental processing speed, and 33% to 42% fell lower than 1 SD below the norms on several tests of executive function. Lower estimated glomerular filtration rate and lower folate were associated with poorer performance on tests of memory and executive function. CONCLUSIONS: These observations confirm previous reports of mood and cognitive impairments in adult kidney transplant recipients. Further research is needed to determine the benefit of B-vitamin supplementation and other interventions in this patient population.

Foods that are perceived as healthy or unhealthy differentially alter young women's state body image.

Body image can be influenced by day-to-day events, including food intake. The present study investigated the effects of foods typically perceived as "healthy" or "unhealthy" on state body image and mood. College-aged women were told the experiment was designed to assess the effects of food on cognition. Using a between-subjects design, participants consumed isocaloric amounts of foods perceived to be healthy (banana) or unhealthy (donut) or ate nothing. Next, participants completed three cognitive tasks. Prior to eating and following the cognitive tests, participants completed the BISS, POMS, the Figure Rating Scale, and the Restraint Scale. Body satisfaction decreased following intake of a donut, but was not altered in the other conditions. Depression scores significantly decreased after intake of either a donut or banana, but did not decrease in the no-food condition. Tension scores decreased significantly after consumption of a banana and in the no-food condition, but did not decrease following consumption of a donut. These results indicate that intake of a food that is perceived as unhealthy negatively affects state body image.

A potential role for creatine in drug abuse?

Supplemental creatine has been promoted for its positive health effects and is best known for its use by athletes to increase muscle mass. In addition to its role in physical performance, creatine supplementation has protective effects on the brain in models of neuronal damage and also alters mood state and cognitive performance. Creatine is found in high protein foods, such as fish or meat, and is also produced endogenously from the biosynthesis of arginine, glycine, and methionine. Changes in brain creatine levels, as measured using magnetic resonance spectroscopy, are seen in individuals exposed to drugs of abuse and depressed individuals. These changes in brain creatine indicate that energy metabolism differs in these populations relative to healthy individuals. Recent work shows that creatine supplementation has the ability to function in a manner similar to antidepressant drugs and can offset negative consequences of stress. These observations are important in relation to addictive behaviors as addiction is influenced by psychological factors such as psychosocial stress and depression. The significance of altered brain levels of creatine in drug-exposed individuals and the role of creatine supplementation in models of drug abuse have yet to be explored and represent gaps in the current understanding of brain energetics and addiction.

Water, hydration, and health.

This review examines the current knowledge of water intake as it pertains to human health, including overall patterns of intake and some factors linked with intake, the complex mechanisms behind water homeostasis, and the effects of variation in water intake on health and energy intake, weight, and human performance and functioning. Water represents a critical nutrient, the absence of which will be lethal within days. Water's importance for the prevention of nutrition-related noncommunicable diseases has received more attention recently because of the shift toward consumption of large proportions of fluids as caloric beverages. Despite this focus, there are major gaps in knowledge related to the measurement of total fluid intake and hydration status at the population level; there are also few longer-term systematic interventions and no published randomized, controlled longer-term trials. This review provides suggestions for ways to examine water requirements and encourages more dialogue on this important topic.

Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner.

Impairments in bioenergetic function, cellular resiliency, and structural plasticity are associated with the pathogenesis of mood disorders. Preliminary evidence suggests that creatine, an ergogenic compound known to promote cell survival and influence the production and usage of energy in the brain, can improve mood in treatment-resistant patients. This study examined the effects of chronic creatine supplementation using the forced swim test (FST), an animal model selectively sensitive to antidepressants with clinical efficacy in human beings. Thirty male (experiment 1) and 36 female (experiment 2) Sprague-Dawley rats were maintained on either chow alone or chow blended with either 2% w/w creatine monohydrate or 4% w/w creatine monohydrate for 5 weeks before the FST. Open field exploration and wire suspension tests were used to rule out general psychostimulant effects. Male rats maintained on 4% creatine displayed increased immobility in the FST as compared with controls with no differences by diet in the open field test, whereas female rats maintained on 4% creatine displayed decreased immobility in the FST and less anxiety in the open field test compared with controls. Open field and wire suspension tests confirmed that creatine supplementation did not produce differences in physical ability or motor function. The present findings suggest that creatine supplementation alters depression-like behavior in the FST in a sex-dependent manner in rodents, with female rats displaying an antidepressant-like response. Although the mechanisms of action are unclear, sex differences in creatine metabolism and the hormonal milieu are likely involved.