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Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: The mental disorders included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were depressive disorders, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, eating disorders, idiopathic developmental intellectual disability, and a residual category of other mental disorders. We aimed to measure the global, regional, and national prevalence, disability-adjusted life-years (DALYS), years lived with disability (YLDs), and years of life lost (YLLs) for mental disorders from 1990 to 2019. Methods: In this study, we assessed prevalence and burden estimates from GBD 2019 for 12 mental disorders, males and females, 23 age groups, 204 countries and territories, between 1990 and 2019. DALYs were estimated as the sum of YLDs and YLLs to premature mortality. We systematically reviewed PsycINFO, Embase, PubMed, and the Global Health Data Exchange to obtain data on prevalence, incidence, remission, duration, severity, and excess mortality for each mental disorder. These data informed a Bayesian meta-regression analysis to estimate prevalence by disorder, age, sex, year, and location. Prevalence was multiplied by corresponding disability weights to estimate YLDs. Cause-specific deaths were compiled from mortality surveillance databases. The Cause of Death Ensemble modelling strategy was used to estimate death rate by age, sex, year, and location. The death rates were multiplied by the years of life expected to be remaining at death based on a normative life expectancy to estimate YLLs. Deaths and YLLs could be calculated only for anorexia nervosa and bulimia nervosa, since these were the only mental disorders identified as underlying causes of death in GBD 2019. Findings: Between 1990 and 2019, the global number of DALYs due to mental disorders increased from 80·8 million (95% uncertainty interval [UI] 59·5-105·9) to 125·3 million (93·0-163·2), and the proportion of global DALYs attributed to mental disorders increased from 3·1% (95% UI 2·4-3·9) to 4·9% (3·9-6·1). Age-standardised DALY rates remained largely consistent between 1990 (1581·2 DALYs [1170·9-2061·4] per 100 000 people) and 2019 (1566·2 DALYs [1160·1-2042·8] per 100 000 people). YLDs contributed to most of the mental disorder burden, with 125·3 million YLDs (95% UI 93·0-163·2; 14·6% [12·2-16·8] of global YLDs) in 2019 attributable to mental disorders. Eating disorders accounted for 17 361·5 YLLs (95% UI 15 518·5-21 459·8). Globally, the age-standardised DALY rate for mental disorders was 1426·5 (95% UI 1056·4-1869·5) per 100 000 population among males and 1703·3 (1261·5-2237·8) per 100 000 population among females. Age-standardised DALY rates were highest in Australasia, Tropical Latin America, and high-income North America. Interpretation: GBD 2019 showed that mental disorders remained among the top ten leading causes of burden worldwide, with no evidence of global reduction in the burden since 1990. The estimated YLLs for mental disorders were extremely low and do not reflect premature mortality in individuals with mental disorders. Research to establish causal pathways between mental disorders and other fatal health outcomes is recommended so that this may be addressed within the GBD study. To reduce the burden of mental disorders, coordinated delivery of effective prevention and treatment programmes by governments and the global health community is imperative. Funding: Bill & Melinda Gates Foundation, Australian National Health and Medical Research Council, Queensland Department of Health, Australia.

The lancet. Psychiatry · systematic review · 4002 citationsread the source →

Comparisons of ultrafine and fine particles in their associations with biomarkers reflecting physiological pathways.

Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics compared to before and after the Olympics, we conducted the current study to compare ultrafine particles (UFPs) and fine particles (PM2.5) in their associations with biomarkers reflecting multiple pathophysiological pathways linking exposure and cardiorespiratory events. Number concentrations of particles (13.0-764.7 nm) and mass concentrations of PM2.5 were measured at two locations within 9 km from the residence and workplace of 125 participating Beijing residents. Each participant was measured 6 times for biomarkers of autonomic function (heart rate, systolic and diastolic blood pressures), hemostasis (von Willebrand factor, soluble CD40 ligand, and P-selectin), pulmonary inflammation and oxidative stress (exhaled nitric oxide and exhaled breath condensate pH, malondialdehyde, and nitrite), and systemic inflammation and oxidative stress (urinary malondialdehyde and 8-hydroxy-2'-deoxyguanosine, plasma fibrinogen, and white blood cells). Linear mixed models were used to estimate associations of biomarkers with UFPs and PM2.5 measured 1-7 days prior to biomarker measurements (lags). We found that the correlation coefficient for UFPs at two locations (∼ 9 km apart) was 0.45, and at the same location, the correlation coefficient for PM2.5 vs UFPs was -0.18. Changes in biomarker levels associated with increases in UFPs and PM2.5 were comparable in magnitude. However, associations of certain biomarkers with UFPs had different lag patterns compared to those with PM2.5, suggesting that the ultrafine size fraction (≤ 100 nm) and the fine size fraction (∼ 100 nm to 2.5 μm) of PM2.5 are likely to affect PM-induced pathophysiological pathways independently.

Environmental science & technology · cohort or longitudinal · 75 citationsread the source →

Lipid-Based Nutrient Supplementation Reduces Child Anemia and Increases Micronutrient Status in Madagascar: A Multiarm Cluster-Randomized Controlled Trial.

Background: Iron deficiency anemia affects hundreds of millions of women and children worldwide and is associated with impaired infant outcomes. Small-quantity lipid-based nutrient supplement (LNS) have been found to reduce the prevalence of anemia and iron deficiency in some trials. Objectives: We evaluated the effectiveness of daily LNS supplementation on child anemia and micronutrient status in Madagascar within the context of an existing, scaled-up nutrition program. Methods: We cluster-randomized 125 communities to (T0) a routine program with monthly growth monitoring and nutrition education; (T1) T0 + home visits for intensive nutrition counselling; (T2) T1 + LNS for children aged 6-18 mo; (T3) T2 + LNS for pregnant/lactating women; or (T4) T1 + parenting messages. Pregnant women and infants aged <12 mo were enrolled in 2014 and followed for 2 y. Child outcome measures included hemoglobin and anemia assessed using the HemoCue 301 system (n = 3561), and serum ferritin and soluble transferrin receptor as markers of iron status, retinol-binding protein as a marker of vitamin A status, and C-reactive protein and α-1 acid glycoprotein from a finger stick blood draw among a subsample (n = 387). We estimated mean difference using linear regression and prevalence ratios using modified Poisson regression accounting for the clustered design. All analyses were intention-to-treat. Results: Children in the LNS groups (T2 and T3) had ∼40% lower prevalence of anemia and iron deficiency anemia and 25% lower prevalence of iron deficiency than children in the control group (T0) (P < 0.05 for all). There were no differences in any of the biomarkers when comparing children in the T4 group with those in T0; nor were there differences between T3 and T2. Conclusions: Our findings suggest the provision of LNS in the context of a large-scale program offers significant benefits on anemia and iron status in young children. This trial was registered at www.isrctn.com as ISRCTN14393738.

The Journal of nutrition · randomised controlled trial · 20 citationsread the source →

Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.

Background: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. Methods: EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). Findings: From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). Interpretation: In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Funding: Karuna Therapeutics.

Lancet (London, England) · randomised controlled trial · 144 citationsread the source →

Effectiveness of a brief lay counsellor-delivered, problem-solving intervention for adolescent mental health problems in urban, low-income schools in India: a randomised controlled trial.

Background: Mental health problems are a leading cause of disability in adolescents worldwide. Problem solving is a well-tested mental health intervention in many populations. We aimed to investigate the effectiveness of a brief, transdiagnostic problem-solving intervention for common adolescent mental health problems when delivered by non-specialist school counsellors in New Delhi, India. Methods: This randomised trial was done in six government-run schools (three all-boys schools, two all-girls schools, and one co-educational school) that serve low-income communities. We recruited participants from grades 9 to 12 (ages 12-20 years) by selecting students with persistently elevated mental health symptoms accompanied by distress or functional impairment. Clinical eligibility criteria were assessed by research assistants using the Hindi-language version of the Strengths and Difficulties Questionnaire (SDQ), with reference to locally validated borderline cutoff scores of 19 or greater for boys and 20 or greater for girls on the SDQ Total Difficulties scale, an abnormal score of 2 or more on the SDQ Impact scale, and persistence of more than 1 month on the SDQ Chronicity index. Participants were randomly allocated (1:1) to problem solving delivered through a brief (2-3 week) counsellor-led intervention with supporting printed materials (intervention group), or problem solving delivered via printed booklets alone (control group). Primary outcomes were adolescent-reported mental health symptoms (SDQ Total Difficulties scale) and idiographic psychosocial problems (Youth Top Problems [YTP]) at 6 weeks. Primary analyses were done on an intention-to-treat basis at the 6-week endpoint. The trial is registered with ClinicalTrials.gov, NCT03630471. Findings: Participants were enrolled between Aug 20, and Dec 4, 2018. 283 eligible adolescents were referred to the trial, and 251 (89%) of these were enrolled (mean age 15·61 years; 174 [69%] boys). 125 participants were allocated to each group (after accounting for one participant in the intervention group who withdrew consent after randomisation). Primary outcome data were available for 245 (98%) participants. At 6 weeks, the mean YTP scores were 3·52 (SD 2·66) in the intervention group and 4·60 (2·75) in the control group (adjusted mean difference -1·01, 95% CI -1·63 to -0·38; adjusted effect size 0·36, 95% CI 0·11 to 0·61; p=0·0015). The mean SDQ Total Difficulties scores were 17·48 (5·45) in the intervention group and 18·33 (5·45) in the control group (-0·86, -2·14 to 0·41; 0·16, -0·09 to 0·41; p=0·18). We observed no adverse events. Interpretation: A brief lay counsellor-delivered problem-solving intervention combined with printed booklets seemed to have a modest effect on psychosocial outcomes among adolescents with diverse mental health problems compared with problem-solving booklets alone. This counsellor-delivered intervention might be a suitable first-line intervention in a stepped care approach, which is being evaluated in ongoing studies. Funding: Wellcome Trust.

The Lancet. Child & adolescent health · randomised controlled trial · 69 citationsread the source →

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population. Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405. Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen's d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment. Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders. Funding: Multidisciplinary Association for Psychedelic Studies.

The lancet. Psychiatry · randomised controlled trial · 258 citationsread the source →

Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial.

Importance: Serotonin reuptake inhibitors (SRIs) are efficacious treatments for premenstrual dysphoric disorder (PMDD) when given daily or for half of the menstrual cycle during the luteal phase. Preliminary studies suggest that SRI treatment can be shortened to the interval from symptom onset through the beginning of menses. Objective: To determine the efficacy of symptom-onset dosing with the SRI sertraline hydrochloride for treatment of PMDD. Design, setting, and participants: A double-blind, placebo-controlled, multisite, parallel-group randomized clinical trial conducted September 1, 2007, to February 29, 2012, at 3 university medical centers. In all, 252 women with PMDD started treatment at symptom onset and continued until the first few days of menses for 6 menstrual cycles. Intent-to-treat analyses were performed February 28, 2014, through April 21, 2015. Interventions: Placebo or sertraline hydrochloride, 50 to 100 mg/d, during the symptomatic interval. Main outcomes and measures: Premenstrual Tension Scale (PMTS) score was the primary outcome measure (score range, 0-36; 36 indicates most severe score). Secondary outcome measures included the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) (score range, 0-84; 84 indicates most severe score), Daily Record of Severity of Problems (DRSP) (total and subscale scores; higher scores indicate most severe problems), Clinical Global Impression (CGI) scales (score range, 1-7; 7 indicates most severe symptoms and least improvement), and Michelson SSRI (Selective SRI) Withdrawal Symptoms Scale scores (range, 0-51; higher scores indicate more severe withdrawal symptoms). Results: Among the participants, 125 with PMDD were randomized to sertraline, and 127 to placebo. At baseline the mean (SD) PMTS scores for sertaline and placebo were 22.3 (4.8) and 21.4 (4.5), respectively, which declined to 11.7 (6.8) and 12.0 (6.9), respectively; group mean difference, 1.88 (95% CI, 0.01-3.75; P = .06). The mean (SD) estimated difference in IDS-C scores between baseline (35.4 [10.7] for sertraline; 32.8 [10.4] for placebo) and the end point (15.3 [10.7] for sertraline; 17.8 [11.0] for placebo) favored the sertraline group by 5.14 (95% CI, 1.97-8.31) points (P = .02). Compared with the placebo group, those assigned to sertraline showed greater improvement on the total DRSP score (estimated mean difference, 1.09 [95% CI, 0.96-1.25] points; P = .02) and Anger/Irritability DRSP subscale score (1.22 [95% CI, 1.05-1.41] points; P < .01) and were more likely to respond to treatment (77 of 115 patients [67.0%] for sertraline and 65 of 124 [52.4%] for placebo; χ21 = 5.23; P = .02). The mean (SD) number of symptomatic days before treatment diminished over time (sertraline, -0.7 [3.4] days; placebo, -1.0 [3.2] days), with no group differences in symptomatic days or the Michelson SSRI Withdrawal Symptoms Scale. Conclusions and relevance: Depending on the symptom scale, women with PMDD may or may not benefit from SRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses. Abrupt treatment cessation was not associated with discontinuation symptoms. Trial registration: clinicaltrials.gov Identifier: NCT00536198.

JAMA psychiatry · randomised controlled trial · 51 citationsread the source →

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial.

Background: Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development. Methods: CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens. Results: 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: -36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: -9; 72, p=0.08. Conclusion: The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation.

Vaccine · randomised controlled trial · 190 citationsread the source →

Cognitive-behavioral therapy, behavioral weight loss, and sequential treatment for obese patients with binge-eating disorder: a randomized controlled trial.

Objective: Cognitive-behavioral therapy (CBT) is the best established treatment for binge-eating disorder (BED) but does not produce weight loss. The efficacy of behavioral weight loss (BWL) in obese patients with BED is uncertain. This study compared CBT, BWL, and a sequential approach in which CBT is delivered first, followed by BWL (CBT + BWL). Method: 125 obese patients with BED were randomly assigned to 1 of the 3 manualized treatments delivered in groups. Independent assessments were performed posttreatment and at 6- and 12-month follow-ups. Results: At 12-month follow-up, intent-to-treat binge-eating remission rates were 51% (CBT), 36% (BWL), and 40% (CBT + BWL), and mean percent BMI losses were -0.9, -2.1, and 1.5, respectively. Mixed-models analyses revealed that CBT produced significantly greater reductions in binge eating than BWL through 12-month follow-up and that BWL produced significantly greater percent BMI loss during treatment. The overall significant percent BMI loss in CBT + BWL was attributable to the significant effects during the BWL component. Binge-eating remission at major assessment points was associated significantly with greater percent BMI loss cross-sectionally and prospectively (i.e., at subsequent follow-ups). Conclusions: CBT was superior to BWL for producing reductions in binge eating through 12-month follow-up, while BWL produced statistically greater, albeit modest, weight losses during treatment. Results do not support the utility of the sequential approach of providing BWL following CBT. Remission from binge eating was associated with significantly greater percent BMI loss. Findings support BWL as an alternative treatment option to CBT for BED.

Journal of consulting and clinical psychology · randomised controlled trial · 207 citationsread the source →

Preoperative biofeedback assisted behavioral training to decrease post-prostatectomy incontinence: a randomized, controlled trial.

Purpose: We tested the effectiveness of preoperative biofeedback assisted behavioral training for decreasing the duration and severity of incontinence, and improving quality of life in the 6 months following radical prostatectomy. Materials and methods: We performed a prospective, randomized, controlled trial comparing preoperative behavioral training to usual care. The volunteer sample included 125 men 53 to 68 years old who elected radical prostatectomy for prostate cancer. Patients were stratified according to age and tumor differentiation, and randomized to 1 preoperative session of biofeedback assisted behavioral training plus daily home exercise or a usual care control condition, consisting of simple postoperative instructions to interrupt the urinary stream. The main outcome measurements were duration of incontinence (time to continence), as derived from bladder diaries, incontinence severity (the proportion with severe/continual leakage), pad use, Incontinence Impact Questionnaire, psychological distress (Hopkins Symptom Checklist) and health related quality of life (Medical Outcomes Study Short Form Health Survey). Results: Preoperative behavioral training significantly decreased time to continence (p = 0.03) and the proportion of patients with severe/continual leakage at the 6-month end point (5.9% vs 19.6%, p = 0.04). There were also significant differences between the groups for self-reported urine loss with coughing (22.0% vs 51.1%, p = 0.003), sneezing (26.0% vs 48.9%, p = 0.02) and getting up from lying down (14.0% vs 31.9%, p = 0.04). No differences were found on return to work and usual activities or quality of life measures. Conclusions: Preoperative behavioral training can hasten the recovery of urine control and decrease the severity of incontinence following radical prostatectomy.

The Journal of urology · randomised controlled trial · 117 citationsread the source →

Caregiver outcomes of partners in dementia care: effect of a care coordination program for veterans with dementia and their family members and friends.

The objective is to test the effectiveness of Partners in Dementia Care (PDC), a care-coordination program that integrates and improves access to medical and nonmedical services, while strengthening the informal care network and providing information, coaching, and emotional support. PDC was delivered via a partnership between Veterans Affairs (VA) Medical Centers (VAMCs) and Alzheimer's Association chapters, for caregivers of veterans with dementia living in the community and receiving primary care from the VA. The initial sample was 486 caregivers of 508 veterans with diagnosed dementia. Outcomes were evaluated for 394 and 324 caregivers who completed 6- and 12- month follow-up, respectively. PDC had a standardized protocol that included assessment and reassessment, action planning, and ongoing monitoring. It was delivered by telephone and e-mail for cost efficiency and the ability to handle caseloads of 100 to 125. Care coordinators from VAMCs and Alzheimer's Association chapters worked as a team using a shared computerized record. A variety of caregiver outcomes was measured after 6 and 12 months. Intervention group caregivers had significant improvements in outcomes representing unmet needs, three types of caregiver strains, depression, and two support resources. Most improvements were evident after 6 months, with more-limited improvements from Months 6 to 12. Some outcomes improved for all caregivers, whereas some improved for caregivers experiencing more initial difficulties or caring for veterans with more-severe impairments. PDC is a promising model that improves linkages between healthcare services and community services, which is a goal of several new national initiatives such as the National Plan to Address Alzheimer's Disease and a proposed amendment to the Older Americans Act.

Journal of the American Geriatrics Society · randomised controlled trial · 72 citationsread the source →

Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study.

Background: Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety. Methods: In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 microg/kg (n=40), 30 microg/kg (n=43), 100 microg/kg (n=39), or 250 microg/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806. Findings: In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 microg/kg per day group, 42 in the relaxin 30 microg/kg per day group, 37 in the relaxin 100 microg/kg per day group, and 49 in the relaxin 250 microg/kg per day group. Dyspnoea improved with relaxin 30 microg/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale through day 14 (8214 mm x h [SD 8712] vs 4622 mm x h [9003]; p=0.053). Length of stay was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2.6% [95% CI 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of serious adverse events was similar between groups. Interpretation: When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety.

Lancet (London, England) · randomised controlled trial · 314 citationsread the source →

Telemedicine for Anger Management Therapy in a Rural Population of Combat Veterans With Posttraumatic Stress Disorder

Article AbstractObjective: To demonstrate the noninferiority of a telemedicine modality, videoteleconferencing, compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder (PTSD).Method: A randomized controlled noninferiority trial of 125 male veterans with PTSD (according to DSM criteria on the Clinician-Administered PTSD Scale) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics. Participants were randomly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person (n†‰=†‰64) or via videoteleconferencing (n†‰=†‰61). Participants were assessed at baseline, midtreatment (3 weeks), posttreatment (6 weeks), and 3 and 6 months posttreatment. The primary clinical outcome was reduction of anger difficulties, as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 (STAXI-2) and by the Novaco Anger Scale total score (NAS-T). Data were collected from August 2005 to October 2008.Results: Participants in both groups showed significant and clinically meaningful reductions in anger symptoms, with posttreatment and 3 and 6 months posttreatment effect sizes ranging from .12 to .63. Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes, participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ("non-inferior") to symptom reductions in the in-person groups. Additionally, no significant between-group differences were found on process variables, including attrition, adherence, satisfaction, and treatment expectancy. Participants in the in-person condition reported significantly higher group therapy alliance. Conclusions: Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence-based care for veterans residing in rural or remote locations. Trial Registration: clinicaltrials.gov Identifier: NCT00122109J Clin Psychiatry 2010;71(7):855-863Submitted: August 11, 2009; accepted September 28, 2009.Online ahead of print: January 26, 2010 (doi:10.4088/JCP.09m05604blu).Corresponding author: Leslie A. Morland, PsyD, National Center for PTSD-Pacific Islands Division, Department of Veterans Affairs Pacific Islands Healthcare System, 3375 Koapaka St, Suite I-560, Honolulu, HI 96819 (Leslie. Morland@va.gov).

The Journal of Clinical Psychiatry · randomised controlled trial · 279 citationsread the source →

AIDS as a chronic illness: psychosocial implications

Introduction Early in the epidemic, the public perception of AIDS as a highly fatal acute illness with a rapid downward trajectory was crystallized. Nevertheless, as early as 1991 in the nursing and medical sociology literature, a few investigators were already discussing HIV/AIDS as a chronic illness (for example [1,2]). Shortly thereafter, a number of psychosocial investigations of small groups of long-term AIDS survivors appeared in the literature, although these cases were still seen as infrequent exceptions (see [3] for a review). It was not until the advent of protease inhibitors in 1996, which ushered in the era of highly active antiretroviral therapy (HAART), that the view of AIDS as a chronic illness became widely accepted. These medications were touted in the mass media as ‘miraculous’ because they reduced the risk of opportunistic infections and extended survival by suppressing viral replication and increasing CD4 cell counts. Their availability was said to have “reinserted the word ‘hope’ into the discussion about AIDS for the first time in a decade of treatment trials” [4] (p. 161), and to have offered infected individuals the opportunity for a “second life” [5]. Among those at advanced stages of the disease, recoveries have often been so dramatic that the phenomenon has been dubbed the ‘Lazarus Syndrome’, referring to the seeming rising from the dead made possible by these new medications [6]. While in the United States recent treatment advances have had a profound impact on the illness trajectory and thus life expectancy of many infected individuals [7], AIDS-related mortality continues to rise unabated in parts of the world where access to the new therapies is limited. The prohibitively high prices of antiretrovirals coupled with inadequate and inefficient health delivery systems have allowed AIDS to reach catastrophic levels in many developing countries [8]. Even in the United States, however, not all infected persons have access to or choose to adopt the new treatments. Some physicians are less likely to offer HAART to patients they assume to be at risk for poor adherence, such as those with a history of drug use, the homeless, and the mentally ill [9–11], although the evidence supporting their actions remains inconclusive [12, 13]. Other research indicates that women, African-Americans, and those with low levels of education are less likely to have ever used the new therapies [14–17]. These findings have been attributed not only to a lack of access to these medications among these socio-economically disadvantaged groups, but also to their own reluctance to use them due to such factors as fear of medication side-effects and distrust of physicians. Similar issues were identified as barriers to antiretroviral use and medication adherence before HAART became available [18,19]. Chronic illness and AIDS Chronic illnesses are typically incurable, and thus the goals of medical care are usually containment, slowing disease progression and symptom management rather than cure. Beyond this, chronic diseases tend to share a variety of characteristics [20–23]. Frequently, they have an uncertain course or disease trajectory often characterized by alternating periods of remission and recurrence, or stable periods interrupted by episodic exacerbations of symptoms. Most require adherence to a treatment regimen, although these differ significantly across diseases in complexity and efficacy. Chronic disease also typically requires considerable self-care (including self-monitoring of symptoms) on the patient's part, since most of the day-to-day management of the illness takes place outside formal health institutions or facilities. As illness is a form of deviance and thus an undesirable state, chronic conditions also carry some degree of stigma. However, this varies greatly across diseases and depends on a variety of factors, such as whether the individual is perceived as being responsible for having acquired the illness, whether the illness is contagious and whether there is visible disfigurement. In addition, changes in roles and relationships are common. Illness almost always necessitates some degree of dependency, at least at the more advanced stages of a disease. Roles and responsibilities in relationships and families typically must be re-negotiated in light of the patient's limitations or disabilities. Finally, chronic diseases often bring about identity changes as the patient attempts to integrate the illness into his/her life and self-perception over the long haul. Psychological distress is a prevalent concomitant of living with chronic conditions, because of the uncertainty inherent in many of these illness characteristics. Each of these aspects of chronic disease posses an adaptive task or challenge (e.g., tolerating uncertainty, managing stigma, adhering to treatment) that is stressful for the individual to confront. How well the chronically ill individual will adapt to one's disease will depend in large part on his/her ability to master, or at least successfully manage, these tasks. Today, AIDS meets the criteria for a chronic illness [24]. While available treatments can render a viral load undetectable, they cannot fully eradicate it from the body and, left untreated, the viral load will rebound. Consequently, there is still no cure for the disease. Furthermore, while the natural history of the disease has been delineated, the course of HIV disease progression varies considerably among individuals [25]. Current multi-drug regimens remain complex, often requiring that many pills be taken on a rigid schedule while following strict dietary guidelines. Yet, similar to many other chronic illnesses, the regimens for HIV infection are not equally effective for all patients [26]. It is also well recognized that HIV/AIDS has a profound impact on intimate and social relationships. The fact that the disease can be transmitted through sexual behaviors renders intimate relationships fraught with anxiety and ambivalence. Moreover, infected adults often feel that others are unwilling to enter into long-term relationships with them for fear of having to assume care-giving responsibilities when the disease progresses. Additionally, self-care is a component of living with HIV. Many patients engage in self-initiated strategies (e.g., diet, relaxation exercises, stress avoidance) aimed at managing illness or treatment-related symptoms, boosting their immune system, or alleviating stress. In the present paper, we discuss several of the principal characteristics of chronic illnesses, reviewing in each case the relevant available literature. In each section, we attempt to highlight continuities and discontinuities between the pre-HAART and the HAART eras. In addition, we discuss prevention in the context of AIDS as a chronic illness. We conclude with some suggestions for future research in the field of HIV/AIDS and chronic illness. Emotional distress From the outset of the AIDS epidemic, there has been considerable documentation of the adverse psychological consequences of knowing one is infected. When AIDS was viewed as a highly fatal illness with an inexorable downhill course, much of this work focused on assessing depression (depressive symptomatology or clinical depression) and suicidal ideation or acts. While the findings of studies sometimes differed, the preponderance of evidence from the pre-HAART era suggested that depression was prevalent and that suicidal ideation and risk were elevated [27–30]. Infected individuals seemed particularly emotionally vulnerable shortly after diagnosis, when HIV-related symptoms first appeared, in the later stages of the disease, and after suffering multiple AIDS-related losses in their social network. It is a widely held, although largely unexamined, assumption that the experience of living with HIV infection in the HAART era is significantly less distressing compared with the past because of the prospects for extended survival and enhanced quality of life offered by the new treatments. Only recently, however, has this issue begun to be empirically investigated. Rabkin et al. [31] followed a sample of gay and bisexual men with symptomatic illness over a period that included the time before and after the availability of protease inhibitors. On all measures of psychological distress employed, the sample as a whole showed a statistically significant, although clinically modest, decline over time (when CD4 cell count, HIV symptoms, physical limitations, and social support were included as co-variates). However, when they further compared subjects whose status on medical markers had improved and had not improved, no significant differences in decline in hopelessness or improvement in quality of life were observed. In another study [32], changes in depressive symptomatology were investigated among 456 HIV-infected individuals (433 men) receiving antiretroviral treatment who were asked to complete a self-administered questionnaire annually. All study participants had completed at least one survey before and one after using protease inhibitors. The investigators found that, between assessment points, the percentage of individuals with a score indicative of probable clinical depression declined from 52 to 46%. While this change was not statistically significant, there were improvements in the total score of the Center for Epidemiological Studies—Depression scale, as well as on the depressive mood, positive affect and somatic symptom subscales. Similarly, in another study [33], changes in depressive symptomatology among 125 HIV-infected adults (most homosexual/bisexual males) assessed at 6-month intervals over a 2-year period were examined. The investigators found a pattern of declining scores on the Beck Depression Inventory over time, especially after the third assessment (12 months after baseline), when 51% of study participants were receiving HAART. There was, however, substantial drop-out before the 6-month assessment, and the number of cases included at each assessment point varied. It thus seems that the evidence on whether living with HIV infection is less psychologically distressing since the availability of HAART remains inconclusive. If ultimately it is shown to be so, this could have implications for needed mental health services. Catalan et al. [34], for example, suggest that as AIDS becomes a more manageable disease there will be a diminished need for acute mental health services (e.g., psychiatric hospitalization, crisis intervention), and a greater need for interventions assisting individuals in adjusting long-term to chronic-illness-related psychosocial stressors. While this may be true among gay and bisexual men and drug users who can recall infected individuals’ bleaker prospects in the pre-HAART era, the need for acute psychiatric services may grow among more recently impacted populations, such as infected adults living in rural America, adolescents, and heterosexual women without a history of drug use. Members of these populations often do not recognize that they were at risk for infection, making diagnosis a more psychologically disruptive event. Uncertainty Individuals living with HIV/AIDS have always confronted uncertainty. Early in the epidemic, this uncertainty revolved around issues such as when one had become infected, where one was in the disease trajectory, how long one was likely to survive, and whether any effective treatments for slowing or halting progression of one's disease would be developed. With the advent of zidovudine and other drugs of the pre-HAART era, uncertainty centered on issues such as whether to get tested, when to initiate treatment, and whether one would have a positive response to treatment. With the availability of HAART, new uncertainties have emerged [35] while old ones persist. For example, many infected individuals who realize extended survival as a result of new treatment regimens may confront emerging opportunistic infections that, in the past, patients did not live long enough to experience. Also, because these medications are new, there is uncertainty about their long-term safety. There is also a lack of clarity about how functional a restored immune system is likely to be [36,37]. The meaning of an improved CD4 cell count, a fundamental disease marker, is also ambiguous. For instance, is an individual who was diagnosed earlier as having AIDS solely on the basis of a CD4 cell count below 200 and who now has a count above that threshold still considered as having AIDS [35]? Those with advanced disease who had expected to die, but have now experienced a ‘reprieve’ on protease inhibitors, may feel insecure about their new-found well-being. While no longer imminently facing death, and possibly they recognize that they could experience a at any time, and The of many is by the fact that they have been to significant in their Finally, as in the pre-HAART era, and uncertainty to the of the time to initiate medication use Those who have not HAART recognize that not or can the Furthermore, those who have experienced recognize that they may be over an extended period of time adherence to the [26]. another of uncertainty is the risk of developing drug with Roles and relationships health has allowed infected individuals to the assumption of new social roles or the to old ones (e.g., For example, the in that zidovudine treatment could significantly of the from an infected to allowed infected women to more With the advent of HAART, more may now as a significant in viral load further the risk of survival and improved health due to HAART may also earlier about not being to or long enough to a However, the adverse of on their health to be of HIV-infected women the and of in the HAART Many infected individuals from HAART are also to work to their to become more to feel more and to however, uncertainty the impact of the stress of work their their after a long period of and their ability to their their health decline Many also about and in the Moreover, not all those using the new treatments feel to but may feel to do so the public perception of the new therapies as infected persons may that others view them as The of extended survival has also many infected individuals to the they have made their relationships Those a many of the confronted before HAART, the anxiety of one's HIV one's and Moreover, in an era of viral the of and may a considerable in relationships. The of living longer and may those who have in relationships because of about health and to the of these relationships Furthermore, the of of and sexual relationships may be anxiety when infected individuals do not feel for these changes The diagnosis of a chronic illness typically necessitates identity work Infected individuals differ in how they integrate their illness in their one are those who their life around their illness. These individuals may work or for AIDS are in or social on of infected and largely their social to other infected the other are those who have to and their illness while as much as possible with their to the illness from a in their In the era, many living with HIV/AIDS now have the opportunity to as living with a chronic illness rather than from a disease. Furthermore, new treatments have patients to feel and to their for longer periods of time, thus the and of the illness and the of the patient However, patients may feel their medication regimens are a of their patient From the outset of the epidemic, infected individuals have been and by have been to and social among physicians and in the United States to care for HIV-infected individuals has been well since early in the reluctance to care for these patients between 1991 and in HIV-related in the United States some but also some of stigma, support for (e.g., had significantly in almost of the that those with AIDS were responsible for the illness. Furthermore, significant they would be or having their with a with AIDS or having an with AIDS or at a where the had AIDS substantial also in that HIV could be transmitted through with AIDS on the a with them and using public all likely to be with to and HIV-infected has also that AIDS is on the it may be and at infected groups and of infected individuals may be greater in developing countries where there has been public education about the disease study of HIV-infected women in rural their that the to them at the time of delivery because of their infected that the medical were infected patients to the were also by study and so was their fear that their would or them Many infected individuals and the and feel and however, the and the and to public patients to remain for longer periods of time, the new treatments have made it possible for them to their illness longer and to as Their social identity as is thus and the many infected individuals experience with their distressing consequences are Yet, they may the psychological of having to a identity and possibly needed adherence The by of the of protease inhibitors was by the that adherence to these and regimens was often a task has been attributed to the to medication fear of the high that medication use will to of illness, and the of For these many individuals treatment or have been unwilling to use protease inhibitors from their physicians to do so While the of the recently regimens for treatment are being the impact of these of treatment on adherence remains to be While the of intervals may adherence because patients can to these treatment they also may adherence by patients to initiate their own who are to adherence to treatment regimens may engage in and have a of Those adhering to but not the dramatic health that early media with the ‘miraculous’ new medications may experience a of anxiety and fear and have also that, before HAART, all infected individuals a from the illness. However, now that some from treatment while others do of and has been by one of as becomes more that can be by and individual but also the to and (p. Finally, because many will not from HAART, those who do may experience a of similar to that in gay men who and to AIDS earlier in the care an part of the management of most chronic Many individuals living with HIV/AIDS engage in a variety of self-care to their immune system, to disease to stress and to symptoms. may be as as that their in a that for periods of so as to manage, for instance, remains a although we have an study infected individuals’ self-initiated for managing symptoms that they to the illness or to antiretroviral The research has focused on the use of and the of the new treatment use by HIV-infected persons has not diminished in the HAART era and and and or are used by infected adults in an to their immune system, to symptoms or medication and to stress. However, as most research has been on gay men with high levels of these findings may not be to other more disadvantaged populations, such as and In own we have found that infected adults often to when they cannot the side-effects of antiretrovirals or they Furthermore, most as than treatments. to these therapies is also by since the of many of are not by health in the era of HAART There is a that the of the new HAART and the availability of may to an in for a variety of the that AIDS is a chronic illness may significantly the of infection that has the of risk with considerably extended for may be a task for especially they feel well and become in relationships. some that having an viral load the of the to a on the impact of the new therapies on infected and although that the new treatments are about the of and sometimes also behaviors In a study of women and of heterosexual were asked about their and sexual behaviors the of viral and the new treatments. While many study that they were not as about being HIV positive because of the improved and they viewed AIDS as a less illness in the protease inhibitors era, they also that viral load and the new therapies (including have not them from Other however, evidence that the new treatments are in of sexual especially among gay and bisexual In one investigators found that, among active gay and bisexual those having sexual were more likely to the that having a who protease inhibitors or whose viral load is is less Additionally, a study of and heterosexual found that gay and bisexual men were more likely to sexual with or status in the HAART era while the sexual of heterosexual Finally, in a study of men and women who were and in more since the new therapies became available for future research for future research are suggested by the present that in survival and quality of life made possible by HAART can only be by those to these we must the treatment are the characteristics and of infected individuals who choose to remain antiretroviral to to their disease through or some other form or The phenomenon of long-term survivors be a one as treatments to the life expectancy of infected How is the of of later impacted by this illness. How HIV/AIDS or In the United States, HIV/AIDS has been a health in rural however, the of research on the disease has been on where health and social are more available and infected individuals may be more research whether the of living with HIV/AIDS in rural the rapid into rural among adolescents, heterosexual women, and future prevention and studies need to these more recently of risk behaviors and interventions behaviors were from work with gay and often these and interventions are in and long-term adherence to among the more recently populations be investigated. The of the epidemic, extended and new of AIDS as a manageable chronic illness may the of new prevention of the consequences that the new of AIDS as a manageable disease will have on and active of HIV-infected individuals is also As the treatment advances the and the health of will the fear and with the disease and, will social of those infected The issue of also be examined. HIV-infected individuals feel less about their illness, and are they more to their HIV status to in light of recent treatment advances and their consequences for those living with the As the present there are many continuities as well as discontinuities in the experience of living with HIV/AIDS over the past There is to feel by the that has been made since the of the in the diagnosis, treatment and clinical management of this disease. however, are still many of the psychosocial as in the pre-HAART era, in While we AIDS as a chronic illness, we to and we have about to with the illness, since many of the issues remain as the

AIDS · review · 178 citationsread the source →

Sleep maintains excitatory synapse diversity in the cortex and hippocampus.

Insufficient sleep is a global problem with serious consequences for cognition and mental health.1 Synapses play a central role in many aspects of cognition, including the crucial function of memory consolidation during sleep.2 Interference with the normal expression or function of synapse proteins is a cause of cognitive, mood, and other behavioral problems in over 130 brain disorders.3 Sleep deprivation (SD) has also been reported to alter synapse protein composition and synapse number, although with conflicting results.4,5,6,7 In our study, we conducted synaptome mapping of excitatory synapses in 125 regions of the mouse brain and found that sleep deprivation selectively reduces synapse diversity in the cortex and in the CA1 region of the hippocampus. Sleep deprivation targeted specific types and subtypes of excitatory synapses while maintaining total synapse density (synapse number/area). Synapse subtypes with longer protein lifetimes exhibited resilience to sleep deprivation, similar to observations in aging and genetic perturbations. Moreover, the altered synaptome architecture affected the responses to neural oscillations, suggesting that sleep plays a vital role in preserving cognitive function by maintaining the brain's synaptome architecture.

Current biology : CB · 14 citationsread the source →

Group Mindfulness-Integrated Cognitive Behavior Therapy (MiCBT) Reduces Depression and Anxiety and Improves Flourishing in a Transdiagnostic Primary Care Sample Compared to Treatment-as-Usual: A Randomized Controlled Trial.

Objectives: This study investigated the effectiveness of a group-based 8-week intervention, Mindfulness-integrated Cognitive Behavior Therapy (MiCBT), to decrease psychological distress and increase wellbeing in a heterogeneous population in primary health care. MiCBT focuses on the importance of interoception and its interaction with cognition in emotional experience. These interactions are represented in the co-emergence model of reinforcement, in which non-reactivity (equanimity) to interoceptive signals facilitates adaptive behavior. Methods: Participants (n = 125, aged 20-72) were randomized to two groups (MiCBT), and treatment-as-usual (TAU). Outcomes were assessed at pre-, mid-, and post-intervention and at 6-month follow-up. The primary outcome was psychological distress, measured by the Depression, Anxiety and Stress Scale (DASS-21). Secondary outcome measures were the Kessler Psychological Distress Scale-10 (K10), Satisfaction with Life Scale (SWLS), and Flourishing Scale (FS). Mediator or process measures of interoceptive awareness, metacognitive awareness (decentering), equanimity, and social functioning were included to investigate putative mediators. Results: The MiCBT intervention significantly reduced DASS-21 scores at mid and post-treatment and the gains were maintained at 6-month follow-up (p < 0.0001, d = 0.38). Flourishing scores also showed significant improvement post-treatment and at 6-month follow-up (d = 0.24, p < 0.0001). All measures selected showed a similar pattern of positive change, with the exception of the SWLS, which failed to reach significance. Mediation analysis suggested equanimity to be the most influential mediator of the primary outcome. Conclusions: The results support the effectiveness of MiCBT in creating rapid and sustainable reduction of psychological distress and improvement in flourishing in a primary mental health care setting with heterogenous groups. These promising results support the scaled-up implementation of this intervention. Clinical trial registration: This trial is registered with the Australian and New Zealand Clinical Trial Registry: https://www.anzctr.org.au/ACTRN12617000061336.

Frontiers in psychiatry · 20 citationsread the source →

Association between Precarious Employment and Chronic Stress: Effect of Gender, Stress Measurement and Precariousness Dimensions-A Cross-Sectional Study.

Precarious employment has been highlighted as a social determinant of health, given, among others, to its alleged association with chronic stress. However, few studies have been conducted analyzing such association, using both perceived stress indicators and biological markers. Accordingly, the present study analyzed the association of multidimensional (6 dimensions) precarious employment scale with perceived stress and 23 markers of adrenal and gonadal hormone production, including cortisol. The sample consisted of 255 salaried workers from Barcelona (125 men, 130 women) aged 25-60. OLS regression models stratified by sex were conducted. Results demonstrated that precarious employment increased the probabilities of having perceived stress in both sexes. In addition, the production of adrenal hormones among men is associated with precarious wages and among women with precarious contracts ("Temporariness", "Disempowerment", and "Rights" dimensions). Therefore, precarious employment could be embodied by workers, altering their perceived well-being and physiological characteristics. Differences between men and women in the physiological effect of precarious employment could express not just the biochemical differences inherent to biological sex, but also the social construction of gender identities, positions and roles in society and family, as well as gender inequalities in the labour market.

International journal of environmental research and public health · 21 citationsread the source →

Comparison of Racial, Ethnic, and Geographic Location Diversity of Participants Enrolled in Clinic-Based vs 2 Remote COVID-19 Clinical Trials.

Importance: Racial and ethnic diversity among study participants is associated with improved generalizability of clinical trial results and may address inequities in evidence that informs public health strategies. Novel strategies are needed for equitable access and recruitment of diverse clinical trial populations. Objective: To investigate demographic and geographical location data for participants in 2 remote COVID-19 clinical trials with online recruitment and compare with those of a contemporaneous clinic-based COVID-19 study. Design, setting, and participants: This cohort study was conducted using data from 3 completed, prospective randomized clinical trials conducted at the same time: 2 remotely conducted studies (the Early Treatment Study and Hydroxychloroquine COVID-19 Postexposure Prophylaxis [PEP] Study) and 1 clinic-based study of convalescent plasma (the Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study). Data were collected from March to August 2020 with 1 to 28 days of participant follow-up. All studies had clinical sites in Seattle, Washington; the 2 remote trials also had collaborating sites in New York, New York; Syracuse, New York; Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; New Orleans, Louisiana; and Los Angeles, California. Two remote trials with inclusive social media strategies enrolled 929 participants with recent SARS-CoV-2 exposure (Hydroxychloroquine COVID-19 PEP Trial) and 231 participants with COVID-19 infection (Early Treatment Study); the clinic-based Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study enrolled 250 participants with recent COVID-19 infection. Data were analyzed from April to August 2021. Interventions: Remote trials used inclusive social media strategies and clinician referral for recruitment and telehealth, courier deliveries, and self-collected nasal swabs for remotely conducted study visits. For the clinic-based study, participants were recruited via clinician referral and attended in-person visits. Main outcomes and measures: Google Analytics data were used to measure online participant engagement and recruitment. Participant demographics and geographical location data from remote trials were pooled and compared with those of the clinic-based study. Statistical comparison of demographic data was limited to participants with COVID infections (ie, those in the remotely conducted Early Treatment Study vs those in the clinic-based study) to improve accuracy of comparison given that the Hydroxychloroquine COVID-19 PEP Trial enrolled participants with COVID-19 exposures and thus had different enrollment criteria. Results: A total of 1410 participants were included. Among 1160 participants in remote trials and 250 participants in the clinic-based trial, the mean (range) age of participants was 39 (18-80) years vs 50 (19-79) years and 676 individuals (58.3%) vs 131 individuals (52.4%) reported female sex. The Early Treatment Study with inclusive social media strategies enrolled 231 participants in 41 US states with increased rates of racial, ethnic, and geographic diversity compared with participants in the clinic-based study. Among 228 participants in the remotely conducted Early Treatment Study with race data vs participants in the clinic-based study, 39 individuals (17.1%) vs 1 individual (0.4%) identified as Alaska Native or American Indian, 11 individuals (4.8%) vs 22 individuals (8.8%) identified as Asian, 26 individuals (11.4%) vs 4 individuals (1.6%) identified as Black, 3 individuals (1.3%) vs 1 individual identified as Native Hawaiian or Pacific Islander, 117 individuals (51.3%) vs 214 individuals (85.6%) identified as White, and 32 individuals (14.0%) vs 8 individuals (3.2%) identified as other race (P < .001). Among 230 individuals in the Early Treatment Study vs 236 individuals in the clinic-based trial with ethnicity data, 71 individuals (30.9%) vs 11 individuals (4.7%) identified as Hispanic or Latinx (P<.001). There were 29 individuals in the Early Treatment Study with nonurban residences (ie, rural, small town, or peri-urban; 12.6%) vs 6 of 248 individuals in the clinic-based trial with residence data (2.4%) (P < .001). In remote trial online recruitment, the highest engagement was with advertisements on social media platforms; among 125 147 unique users with age demographics who clicked on online recruitment advertisements, 84 188 individuals (67.3%) engaged via Facebook. Conclusions and relevance: These findings suggest that remote clinical trials with online advertising may be considered as a strategy to improve diversity among clinical trial participants.

JAMA network open · 48 citationsread the source →

The relationship of self-compassion and depression: Cross-lagged panel analyses in depressed patients after outpatient therapy.

Background: Previous cross-sectional studies suggest that self-compassion and depressive symptoms are consistently negatively associated. Although it is often implicitly assumed that (a lack of) self-compassion precedes depressive symptoms, so far no study has tested whether (lack of) self-compassion is a cause or a consequence of depressive symptoms, or both. Method: To examine such reciprocal effects, we used data of 125 depressed outpatients after a time limited cognitive-behavioral psychotherapy. We assessed self-compassion and depressive symptoms via self-report measures and the presence of a major depressive episode directly after therapy, as well as 6 and 12 months later. Results: Cross-lagged panel analyses indicated that (lack of) self-compassion significantly predicted subsequent depressive symptoms while controlling for autoregressive effects, whereas depressive symptoms did not predict subsequent levels of self-compassion. This was also the case for the relationship between self-compassion and the presence of a major depressive episode. The same patterns also occurred when we separately tested the reciprocal effects for two composite sub-measures of either positive or negative facets of self-compassion. Limitations: Causality cannot be inferred from our results. Depressive symptoms and self-compassion could still be causally unrelated, and a third variable could account for their negative association. Conclusions: These findings support the notions that (a lack of) self-compassion could serve as a vulnerability factor for depression and that cultivating self-compassion may deserve a focus in depression prevention programs or treatments.

Journal of affective disorders · 48 citationsread the source →

Health at the borders: Bayesian multilevel analysis of women's malnutrition determinants in Ethiopia.

Background: Women's malnutrition, particularly undernutrition, remains an important public health challenge in Ethiopia. Although various studies examined the levels and determinants of women's nutritional status, the influence of living close to an international border on women's nutrition has not been investigated. Yet, Ethiopian borders are regularly affected by conflict and refugee flows, which might ultimately impact health. Objective: To investigate the impact of living close to borders in the nutritional status of women in Ethiopia, while considering other important covariates. Design: Our analysis was based on the body mass index (BMI) of 6,334 adult women aged 20-49 years, obtained from the 2011 Ethiopian Demographic and Health Survey (EDHS). A Bayesian multilevel multinomial logistic regression analysis was used to capture the clustered structure of the data and the possible correlation that may exist within and between clusters. Results: After controlling for potential confounders, women living close to borders (i.e. ≤100 km) in Ethiopia were 59% more likely to be underweight (posterior odds ratio [OR]=1.59; 95% credible interval [CrI]: 1.32-1.90) than their counterparts living far from the borders. This result was robust to different choices of border delineation (i.e. ≤50, ≤75, ≤125, and ≤150 km). Women from poor families, those who have no access to improved toilets, reside in lowland areas, and are Muslim, were independently associated with underweight. In contrast, more wealth, higher education, older age, access to improved toilets, being married, and living in urban or lowlands were independently associated with overweight. Conclusions: The problem of undernutrition among women in Ethiopia is most worrisome in the border areas. Targeted interventions to improve nutritional status in these areas, such as improved access to sanitation, economic and livelihood support, are recommended.

Global health action · 21 citationsread the source →

Understanding nutrition, depression and mental illnesses

INTRODUCTION Few people are aware of the connection between nutrition and depression while they easily understand the connection between nutritional deficiencies and physical illness. Depression is more typically thought of as strictly biochemical-based or emotionally-rooted. On the contrary, nutrition can play a key role in the onset as well as severity and duration of depression. Many of the easily noticeable food patterns that precede depression are the same as those that occur during depression. These may include poor appetite, skipping meals, and a dominant desire for sweet foods.[1] Nutritional neuroscience is an emerging discipline shedding light on the fact that nutritional factors are intertwined with human cognition, behavior, and emotions. The most common mental disorders that are currently prevalent in numerous countries are depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder (OCD).[2] The dietary intake pattern of the general population in many Asian and American countries reflects that they are often deficient in many nutrients, especially essential vitamins, minerals, and omega-3 fatty acids.[3] A notable feature of the diets of patients suffering from mental disorders is the severity of deficiency in these nutrients.[3] Studies have indicated that daily supplements of vital nutrients are often effective in reducing patients' symptoms.[4] Supplements containing amino acids have also been found to reduce symptoms, as they are converted to neurotransmitters which in turn alleviate depression and other mental health problems.[4] On the basis of accumulating scientific evidence, an effective therapeutic intervention is emerging, namely nutritional supplement/treatment. These may be appropriate for controlling and to some extent, preventing depression, bipolar disorder, schizophrenia, eating disorders and anxiety disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), autism, and addiction.[4] Most prescription drugs, including the common antidepressants lead to side effects.[4] This usually causes the patients to skip taking their medications. Such noncompliance is a common occurrence encountered by psychiatrists. An important point to remember here is that, such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. In some cases, chronic use or higher doses may lead to drug toxicity, which may become life threatening to the patient.[4] An alternate and effective way for psychiatrists to overcome this noncompliance is to familiarize themselves about alternative or complementary nutritional therapies. Although further research needs to be carried out to determine the best recommended doses of most nutritional supplements in the cases of certain nutrients, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained by closely observing the changes in the patient.[4] When we take a close look at the diet of depressed people, an interesting observation is that their nutrition is far from adequate. They make poor food choices and selecting foods that might actually contribute to depression. Recent evidence suggests a link between low levels of serotonin and suicide.[5] It is implicated that lower levels of this neurotransmitter can, in part, lead to an overall insensitivity to future consequences, triggering risky, impulsive and aggressive behaviors which may culminate in suicide, the ultimate act of inwardly directed impulsive aggression. Depression is a disorder associated with major symptoms such as increased sadness and anxiety, loss of appetite, depressed mood, and a loss of interest in pleasurable activities. If there is no timely therapeutic intervention, this disorder can lead to varied consequences. Patients who are suffering from depression exhibit suicidal tendency to a larger degree and hence are usually treated with antidepressants and/or psychotherapy.[6] Deficiencies in neurotransmitters such as serotonin, dopamine, noradrenaline, and γ-aminobutyric acid (GABA) are often associated with depression.[6–11] As reported in several studies, the amino acids tryptophan, tyrosine, phenylalanine, and methionine are often helpful in treating many mood disorders including depression.[12–17] When consumed alone on an empty stomach, tryptophan, a precursor of serotonin, is usually converted to serotonin. Hence, tryptophan can induce sleep and tranquility. This implies restoring serotonin levels lead to diminished depression precipitated by serotonin deficiencies.[8] Tyrosine and sometimes its precursor phenylalanine are converted into dopamine and norepinephrine.[18] Dietary supplements containing phenyl alanine and/or tyrosine cause alertness and arousal. Methionine combines with adenosine triphosphate (ATP) to produce S-adenosylmethionine (SAM), which facilitates the production of neurotransmitters in the brain.[19–22] The need of the present paradigm is, more studies shedding light on the daily supplemental doses of these neurochemicals that should be consumed to achieve antidepressant effects. Researchers attribute the decline in the consumption of omega-3 fatty acids from fish and other sources in most populations to an increasing trend in the incidence of major depression.[23] The two omega-3 fatty acids, eicosapentaenoic acid (EPA) which the body converts into docosahexanoic acid (DHA), found in fish oil, have been found to elicit antidepressant effects in human. Many of the proposed mechanisms of this conversion involve neurotransmitters. For instance, antidepressant effects may be due to bioconversion of EPA to leukotrienes, prostaglandins, and other chemicals required by the brain. Others hypothesize that both EPA and DHA influence neuronal signal transduction by activating peroxisomal proliferator-activated receptors (PPARs), inhibiting G-proteins and protein kinase C, in addition to calcium, sodium, and potassium ion channels. Whichever may be the case, epidemiological data and clinical studies have clearly shown that omega-3 fatty acids can effectively treat depression.[24] In depressed patients, daily consumption of dietary supplements of omega-3 fatty acid that contain 1.5-2 g of EPA has been shown to stimulate mood elevation. Nevertheless, doses of omega-3 higher than 3 g do not show better effects than placebos and may be contraindicative in cases, such as those taking anticlotting drugs.[25] In addition to omega–3 fatty acids, vitamin B (e.g., folate) and magnesium deficiencies have been linked to depression.[26–28] Randomized, controlled trials that involve folate and vitamin B12 suggest that patients treated with 0.8 mg of folic acid/day or 0.4 mg of vitamin B12/day will exhibit decreased depression symptoms.[27] In addition, the results of several case studies where patients were treated with 125-300 mg of magnesium (as glycinate or taurinate) with each meal and at bedtime led to rapid recovery from major depression in < 7 days for most of the patients. Previous research has revealed the link between nutritional deficiencies and some mental disorders.[232529–32] The most common nutritional deficiencies seen in patients with mental disorders are of omega–3 fatty acids, B vitamins, minerals, and amino acids that are precursors to neurotransmitters.[20232427283033] Accumulating evidence from demographic studies indicates a link between high fish consumption and low incidence of mental disorders; this lower incidence rate being the direct result of omega–3 fatty acid intake.[233132] One to two grams of omega-3 fatty acids taken daily is the generally accepted dose for healthy individuals, but for patients with mental disorders, up to 9.6 g has been shown to be safe and effective.[34–36] Majority of Asian diets are usually also lacking in fruits and vegetables, which further lead to mineral and vitamin deficiencies. The significance of various nutrients in mental health, with special relevance to depression has been discussed below. CARBOHYDRATES Carbohydrates are naturally occurring polysaccharides and play an important role in structure and function of an organism. In higher organisms (human), they have been found to affect mood and behavior. Eating a meal which is rich in carbohydrates triggers the release of insulin in the body. Insulin helps let blood sugar into cells where it can be used for energy and simultaneously it triggers the entry of tryptophan to brain. Tryptophan in the brain affects the neurotransmitters levels. Consumption of diets low in carbohydrate tends to precipitate depression, since the production of brain chemicals serotonin and tryptophan that promote the feeling of well being, is triggered by carbohydrate rich foods. It is suggested that low glycemic index (GI) foods such as some fruits and vegetables, whole grains, pasta, etc. are more likely to provide a moderate but lasting effect on brain chemistry, mood, and energy level than the high GI foods - primarily sweets - that tend to provide immediate but temporary relief. PROTEINS Proteins are made up of amino acids and are important building blocks of life. As many as 12 amino acids are manufactured in the body itself and remaining 8 (essential amino acids) have to be supplied through diet. A high quality protein diet contains all essential amino acids. Foods rich in high quality protein include meats, milk and other dairy products, and eggs. Plant proteins such as beans, peas, and grains may be low in one or two essential amino acids. Protein intake and in turn the individual amino acids can affect the brain functioning and mental health. Many of the neurotransmitters in the brain are made from amino acids. The neurotransmitter dopamine is made from the amino acid tyrosine and the neurotransmitter serotonin is made from the tryptophan.[5] If there is a lack of any of these two amino acids, there will not be enough synthesis of the respective neurotransmitters, which is associated with low mood and aggression in the patients. The excessive buildup of amino acids may also lead to brain damage and mental retardation. For example, excessive buildup of phenylalanine in the individuals with disease called phenylketonuria can cause brain damage and mental retardation. ESSENTIAL FATTY ACIDS Omega-3 fatty acids The brain is one of the organs with the highest level of lipids (fats). Brain lipids, composed of fatty acids, are structural constituents of membranes. It has been estimated that gray matter contains 50% fatty acids that are polyunsaturated in nature (about 33% belong to the omega-3 family), and hence are supplied through diet. In one of the first experimental demonstrations of the effect of dietary substances (nutrients) on the structure and function of the brain, the omega-3 fatty acids (specially alpha-linolenic acid, ALA) were the member to take part. An important trend has been observed from the findings of some recent studies that lowering plasma cholesterol by diet and medications increases depression. Among the significant factors involved are the quantity and ratio of omega-6 and omega-3 polyunsaturated fatty acids (PUFA) that affect serum lipids and alter the biochemical and biophysical properties of cell membranes. It has been hypothesized that sufficient long chain PUFAs, especially DHA, may decrease the development of depression.[37] The structural and functional components of membrane in cells of brain which is a lipid-rich organ, include polar phospholipids, spingolipids, and cholesterol. The glycerophospholipids in brain consist of high proportion of PUFA derived from the essential fatty acids (EFAs), linoleic acid and α-linolenic acid. The main PUFA in the brain are DHA, derived from the omega-3 fatty acid α-linolenic acid, arachidonic acid (AA) and docosa tetraenoic acid, both derived from omega-6 fatty acid linoleic acid. Experimental studies have revealed that diets lacking omega-3 PUFA lead to considerable disturbance in neural function.[38] Studies by Marszalek and Lodish indicate that despite their abundance in the nervous system, DHA and AA cannot be synthesized by mammals de novo and hence they or their precursors have to be supplied through the diet and transported to the brain. During late gestation and the early postnatal period, neurodevelopment occurs at significantly rapid rates which make the supply of adequate quantity of PUFAs, particularly DHA, imperative to ensure neurite outgrowth in addition to appropriate development of brain and retina.[39] Bruinsma and Taren of University of Arizona College of Public Health, Tucson, USA explored the involvement of dieting-related psychological factors as potential confounders.[40] They discussed studies that have both supported and contested the proposition that lowering plasma cholesterol by diet and medications contributes to depression. Research findings point out that an imbalance in the ratio of the EFAs, namely the omega-6 and omega-3 fatty acids, and/or a deficiency in omega-3 fatty acids, may be responsible for the heightened depressive symptoms associated with low plasma cholesterol. These relationships may explain the inconsistency in the results of trials on cholesterol-lowering interventions and depression. On similar lines, dieting behaviors have been associated with alterations in moods.[41] Dietary omega-3 fatty acids play a role in the prevention of some disorders including depression. Their deficiency can accelerate cerebral aging by preventing the renewal of membranes. However, the respective roles of the vascular component on one hand (where the omega-3s are active) and the cerebral parenchyma itself on the other, have not yet been clearly resolved. The role of omega–3 in certain diseases such as dyslexia and autism is suggested. It was omega–3 fatty acids that participated in the first coherent experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out on x-vivo cultured brain cells (1), then on in vivo brain cells (2), finally on physicochemical, biochemical, physiological, neurosensory, and behavioral parameters (3). These findings indicated that the nature of polyunsaturated fatty acids (in particular omega–3) present in formula milks for infants (both premature and term) determines the visual, cerebral, and intellectual abilities.[16] VITAMINS B-complex vitamins Nutrition and depression are intricately and undeniably linked, as suggested by the mounting evidence by researchers in neuropsychiatry. According to a study reported in Neuropsychobiology,[42] supplementation of nine vitamins, 10 times in excess of normal recommended dietary allowance (RDA) for 1 year improved mood in both men and women. The interesting part was that these changes in mood after a year occurred even though the blood status of nine vitamins reached a plateau after 3 months. This mood improvement was particularly associated with improved vitamin B2 and B6 status. In women, baseline vitamin B1 status was linked with poor mood and an improvement in the same after 3 months was associated with improved mood. Thiamine is known to modulate cognitive performance particularly in the geriatric population.[43] Vitamin B12 (Cynocobalamin) Clinical trials have indicated that Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), if it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin enhances cerebral and cognitive functions in the elderly; it frequently promotes the functioning of factors related to the frontal lobe, in addition to the language function of people with cognitive disorders. Adolescents who have a borderline level of vitamin B12 deficiency develop signs of cognitive changes.[43] Folate It has been observed that patients with depression have blood folate levels, which are, on an average, 25% lower than healthy controls.[44] Low levels of folate have also been identified as a strong predisposing factor of poor outcome with antidepressant therapy. A controlled study has been reported to have shown that 500 mcg of folic acid enhanced the effectiveness of antidepressant medication.[45] Folate's critical role in brain metabolic pathways has been well recognized by various researchers who have noted that depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency.[46] It is not clear yet whether poor nutrition, as a symptom of depression, causes folate deficiency or primary folate deficiency produces depression and its symptoms. MINERALS Calcium A recent study showed that selective serotonin uptake inhibitors (SSRIs) inhibit absorption of calcium into bones. In addition to this, the SSRIs can also lower blood pressure in people, resulting in falls which may lead to broken bones. Indiscriminate prescription of SSRIs by doctors and ingestion by patients at risk of depression or other mental health problems may put them at increased risk of fractures. Compounded by the fact that they may be aging and already taking other medications, may also predispose them to osteoporosis.[47] Chromium Many studies on the association of chromium in humans depression have been recorded[4849] which indicate the significance of this micronutrient in mental health. Iodine Iodine plays an important role in mental health. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells. During pregnancy, the dietary reduction of iodine induces severe cerebral dysfunction, eventually leading to cretinism. Iron Iron is necessary for oxygenation and to produce energy in the cerebral parenchyma (through cytochrome oxidase), and for the synthesis of neurotransmitters and myelin. Iron deficiency is found in children with attention-deficit/hyperactivity Iron in the are critical during the development of the and in with the in the with its associated deficiency is associated with disturbance in the development of cognitive Research findings out that as many as men are This in and more with of more depression than during other times in their These indicate the of in the of depression since its deficiency is known to cause and depression. Iron deficiency is for instance, with depression, and rapid a was first and by in while an of the mineral The role of has been well known in a into its its for bipolar disorder with and The therapeutic use of also its as an in depression, disorder, disorder, eating disorders, and in certain of adequate has to be taken while the mood in the can be used in patients with and The use of during and in and geriatric population needs observation about its In a of the of identified at studies, which indicate that low intake is associated with mood studies with with other populations that mood and in the of studies have shown that levels are lower in those with clinical intervention research that can influence the effectiveness of antidepressant also the brain cells the potential damage by studies have revealed the potential of the for physical development and mental development may be due to deficiency of When children and with poor nutritional status are to alterations of mental and behavioral they can be by dietary but to certain It has been observed that, of diet and meal pattern can have or immediate or effects. Dietary deficiencies of and nutrients vitamins, and such as during aging may precipitate brain which may be due to for of diet and depression which is a of to a factor that is often linked to increased and premature of aging may play an important role in this, by reducing food intake or reducing food intake in to such factors as in and poor use of prescription drugs, and and occurring in the in both and due to to They suggest changes associated with mental disorders such as dementia and depression, and and as to the of depression, people are the alternative and complementary are by the for and as a of and health and that are not currently to be a part of health need to be aware that it is likely that a of their patients with bipolar disorder might use these interventions to be and safe or to research in and brain indicates the of pathways that can provide a of the association between nutritional nervous system, and function an psychological health status. These findings may lead to of the therapeutic of dietary intervention health and health depression and other psychological disorders.

Indian Journal of Psychiatry · editorial or comment · 409 citationsread the source →

Maternal depression is associated with mother-infant interaction in preterm infants.

Aim: The purpose of this study was to assess the prevalence and the background factors of maternal depressive symptoms and their relation to the quality of mother-infant interaction in a group of preterm infants and their mothers. Methods: The signs of maternal depression were evaluated in 125 mothers of very preterm infants (birth weight < or = 1500 g or < 32 gestational weeks) at 6 months of infant's corrected age using Edinburgh Postnatal Depression Scale (EPDS). The association between maternal depressive symptoms and the quality of mother-infant interaction as assessed by the parent child early relational assessment method (PCERA) method was studied at 6 and 12 months of corrected age in 32 preterm infants who were their mothers' firstborn infants and singletons. Results: The prevalence of depression assessed by EPDS in mothers of very preterm infants was 12.6%. Most interestingly, the number of postnatal signs of depression associated negatively with the quality of the maternal interaction behaviour with their preterm infants. Conclusions: This study suggests that maternal depression may be a risk factor in the development of the mother-infant relationship between preterm infants and their mothers. Therefore, it would be important to identify signs of depression in mothers of preterm infants to offer early support.

Acta paediatrica (Oslo, Norway : 1992) · 99 citationsread the source →

The development of regulatory functions from birth to 5 years: insights from premature infants.

This study examined physiological, emotional, and attentional regulatory functions as predictors of self-regulation in 125 infants followed 7 times from birth to 5 years. Physiological regulation was assessed by neonatal vagal tone and sleep-wake cyclicity; emotion regulation by response to stress at 3, 6, and 12 months; and attention regulation by focused attention and delayed response in the 2nd year. Executive functions, behavior adaptation, and self-restraint were measured at 5 years. Regulatory functions showed stability across time, measures, and levels. Structural modeling demonstrated both mediated paths from physiological to self-regulation through emotional and attentional processes and direct continuity between vagal tone and each level of regulation. Results support the coherence of the regulation construct and are consistent with neurobiological models on self and consciousness.

Child development · 163 citationsread the source →

Pharmacological characterization of a highly selective and potent partial agonist of the MT₂ melatonin receptor.

Background/aims: The MT₂ melatonin receptor is a potential target for treating circadian rhythm sleep disorders. This study aims to characterize the recently identified MT₂ melatonin receptor agonist. Methods: The pharmacological properties of the MT₂ melatonin receptor-selective agonist as exemplified by compound 1 [N-(2-[7-benzyl-1,6-dihydro-2H-indeno(5,4-b)furan-8-yl]ethyl)acetamide] were evaluated by use of cell-free binding and cell-based functional assays. Results: Competition binding assays using 2-[(125)I]iodomelatonin revealed rapid, reversible, and high-affinity binding of compound 1 to human, mouse, and rat MT₂ melatonin receptors. cAMP, ERK1/2, and PathHunter β-arrestin recruitment assays revealed partial agonist activities. However, compound 1 induced a more intense internalization of human MT₂ melatonin receptor than melatonin. Based on studies using structurally related analogs of compound 1, we further demonstrated that the extent of internalization is independent of the intrinsic efficacy of agonists. Conclusion: These findings provide novel insights into the relationship between intrinsic agonist efficacy and agonist-induced internalization and demonstrate that compound 1 could serve as a pharmacological tool for future studies to elucidate the detailed molecular mechanism of MT₂ receptor internalization.

Pharmacology · 6 citationsread the source →

The Mediterranean diet is associated with a reduction in premature mortality among middle-aged adults.

The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death was 0.72 (95% CI: 0.58, 0.91; P = 0.006). Among highly educated, middle-aged adults, adherence to the traditional Mediterranean diet was associated with reduced risk of death.

The Journal of nutrition · 58 citationsread the source →

Asthma symptom burden: relationship to asthma severity and anxiety and depression symptoms.

Objective: The purpose of this work was to examine the relationship between youth-reported asthma symptoms, presence of anxiety or depressive disorders, and objective measures of asthma severity among a population-based sample of youth with asthma. Methods: We conducted a telephone survey of 767 youth with asthma (aged 11-17 years) enrolled in a staff model health maintenance organization. The Diagnostic Interview Schedule for Children was used to diagnose Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, anxiety and depressive disorders; the Child Health Status-Asthma questionnaire (modified) was used to assess asthma symptoms; and automated administrative data were used to measure asthma treatment intensity and severity. Analyses of covariance were performed to determine whether the number of anxiety and depressive symptoms was related to the number of asthma symptoms. Logistic regression analyses were used to evaluate the strength of association between individual symptoms of asthma and the presence of an anxiety or depressive disorder and objective measures of asthma severity. Results: After adjusting for demographic characteristics, objective measures of asthma severity, medical comorbidity, and asthma treatment intensity, youth with > or = 1 anxiety or depressive disorder (N = 125) reported significantly more days of asthma symptoms over the previous 2 weeks than youth with no anxiety or depressive disorders. The overall number of reported asthma symptoms was significantly associated with the number of anxiety and depressive symptoms endorsed by youth. In logistic regression analyses, having an anxiety or depressive disorder was also strongly associated with each of the 6 asthma-specific symptoms, as well as the 5 related nonspecific somatic symptoms contained in the Child Health Status-Asthma questionnaire. Conclusions: The presence of an anxiety or depressive disorder is highly associated with increased asthma symptom burden for youth with asthma.

Pediatrics · 145 citationsread the source →

“Let Me See If I Have This Right …”: Words That Help Build Empathy

Medical Writings7 August 2001"Let Me See If I Have This Right …": Words That Help Build EmpathyJohn L. Coulehan, MD, Frederic W. Platt, MD, Barry Egener, MD, Richard Frankel, PhD, Chen-Tan Lin, MD, Beth Lown, MD, and William H. Salazar, MDJohn L. Coulehan, MDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902, Frederic W. Platt, MDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902, Barry Egener, MDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902, Richard Frankel, PhDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902, Chen-Tan Lin, MDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902, Beth Lown, MDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902, and William H. Salazar, MDDr. Coulehan: State University of New York at Stony Brook; Stony Brook, NY 11794-8036Dr. Platt: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Egener: American Academy on Physician and Patient; Portland, OR 97210Dr. Frankel: Highland Hospital; Rochester, NY 14620Dr. Lin: University of Colorado Health Sciences Center; Denver, CO 80222Dr. Lown: Mount Auburn Hospital; Cambridge, MA 02238Dr. Salazar: Medical College of Georgia; Augusta, GA 30902Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-3-200108070-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Consider these two physician–patient dialogues:1. Patient: You know, when you discover a lump in your breast, you kind of feel—well, kind of—(her speech tapers off; she looks down; tears form in her eyes).Dr. A: When did you actually discover the lump?Patient: (absently) I don't know. It's been a while.2. Patient: (same as above)Dr. B: That sounds frightening. Patient: Well, yeah, sort of. Dr. B: Sort of frightening?Patient: Yeah … and I guess I'm feeling like my life is over. Dr. B: I see. Worried and sad too. Patient: That's it, Doctor. Dr. A's patient ...References1. Konrad TR, Williams ES, Linzer M, McMurray J, Pathman DE, Gerrity M, et al . Measuring physician job satisfaction in a changing workplace and a challenging environment. SGIM Career Satisfaction Study Group. Society of General Internal Medicine. Med Care. 1999;37:1174-82. [PMID: 10549620] CrossrefMedlineGoogle Scholar2. Donelan K, Blendon RJ, Lundberg GD, Calkins DR, Newhouse JP, Leape LL, et al . The new medical marketplace: physicians' views. Health Aff Millwood. 1997;16:139-48. [PMID: 9314685] CrossrefMedlineGoogle Scholar3. Bates AS, Harris LE, Tierney WM, Wolinsky FD. Dimensions and correlates of physician work satisfaction in a midwestern city. Med Care. 1998;36:610-7. 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Coulehan, MD, Department of Preventive Medicine, HSC L3-086, State University of New York at Stony Brook, Stony Brook, NY 11794-8036; e-mail, [email protected]sunysb.edu. Current Author Addresses: Dr. Coulehan: Department of Preventive Medicine, HSC L3-086, State University of New York at Stony Brook, Stony Brook, NY 11794-8036.Drs. Platt and Lin: University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80222.Dr. Egener: American Academy on Physician and Patient, Legacy Clinic Northwest, 1130 NW 22nd Avenue, Suite 220, Portland, OR 97210.Dr. Frankel: Highland Hospital, 1000 South Avenue, Rochester, NY 14620.Dr. Lown: Mount Auburn Hospital, 300 Mt. Auburn Street, Cambridge, MA 02238.Dr. Salazar: Medical College of Georgia, 1120 15th Street, HS2010, Augusta, GA 30902. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHow does narrative medicine impact medical trainees' learning of professionalism? 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PhD, M. MD, and and role in education about care in Competencies in Care for and Communication in patients with in the Care of Cancer in of and of Empathic during When Being Not empathy learning for be and for effective the role of care in with and in the of the medicine and outcomes of physician empathy in A structural focus study of and perceptions of the of of Medical Student role of empathy in in the a new and in the a of the An or Do You to to Patients Do Not or with Challenges and a of of the of a for children with Care. A to in care: The role of perceptions in Older in Clinical during Health and H. or Not to Is That the Right empathy and sympathy: responses to troubles on a health care with to make the patient the Communication and With Patients in Your as a of The of Medicine, and How to and A Patient-Centered Communication Illness Using to Communication Care and Social in the office approach to the Words That in to and MD, M. 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