Cognitive bias modification to prevent depression (COPE): results of a randomised controlled trial.

BACKGROUND: Although efficacious treatments for major depression are available, efficacy is suboptimal and recurrence is common. Effective preventive strategies could reduce disability associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel and safe intervention that attenuates biases associated with depression. This study investigated whether the delivery of a CBM programme designed to attenuate negative cognitive biases over a period of 1 year would decrease the incidence of major depression among adults with subthreshold symptoms of depression. METHODS: Randomised double-blind controlled trial delivered an active CBM intervention or a control intervention over 52 weeks. Two hundred and two community-dwelling adults who reported subthreshold levels of depression were randomised (100 intervention, 102 control). The primary outcome of interest was the incidence of major depressive episode assessed at 11, 27 and 52 weeks. Secondary outcomes included onset of clinically significant symptoms of depression, change in severity of depression symptoms and change in cognitive biases. RESULTS: Adherence to the interventions was modest though did not differ between conditions. Incidence of major depressive episodes was low. Conditions did not differ in the incidence of major depressive episodes. Likewise, conditions did not differ in the incidence of clinically significant levels of depression, change in the severity of depression symptoms or change in cognitive biases. CONCLUSIONS: Active CBM intervention did not decrease the incidence of major depressive episodes as compared to a control intervention. However, adherence to the intervention programme was modest and the programme failed to modify the expected mechanism of action.

B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial.

BACKGROUND: Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration. AIMS: To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks. METHOD: Randomised, double-blind, placebo-controlled trial of citalopram (20-40 g) together with 0.5 mg of vitamin B12, 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12. Results In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12-5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12-0.94). CONCLUSIONS: B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults.

Antibiotic prescribing practices in paediatric septic shock in a tertiary care hospital in a resource limited setting: an audit.

INTRODUCTION: Early empiric broad spectrum antibiotic administration in children with septic shock improves outcome. Knowledge on possible bacterial aetiology, drug resistance pattern and rational choice of antibiotics is crucial in management of septic shock. METHODS: This was an audit carried out among 50 (0- 5 years age) children admitted with septic shock at the Kenyatta National Hospital between October to December 2016. A standard questionnaire was used for data collection as per the Surviving Sepsis Guideline. Data were stored in Excel and analyzed in Strata 12. RESULTS: Of the 50 admitted children with septic shock 86% were less than one-year age. Samples for blood cultures were removed from 12(24%) prior to administration of antibiotics. Blood culture bottles were unavailable in 80%. All children received antibiotics. Antibiotics were initiated in 44(88%) in the golden hour of diagnosis of septic shock. Monotherapy with cephalosporins 30 (60%) was the commonest choice of initial antibiotic. Antibiotics were changed in 7(22.6%) and 1(5.3%) at 24 and 48 hours respectively due to clinical deterioration. Over mortality at 72 hours was 35 (70%). All the 9 children initiated on meropenem monotherapy on admission died. CONCLUSION: The majority of patients with septic shock were under one-year age. All patients were initiated on antibiotics. Blood cultures were done in a quarter of the patients. Monotherapy with cephalosporin was the commonest choice of antibiotic. De-escalation was not well accomplished due to microbiological culture limitation. There was no standard antibiotic choice hence antibiotic use in septic shock needs to be included in the paediatric local guidelines.

Prevalence and Management of Septic Shock among Children Admitted at the Kenyatta National Hospital, Longitudinal Survey.

BACKGROUND: Paediatric septic shock is a subset of sepsis associated with high mortality. Implementing the existing international Surviving Sepsis Campaign Guidelines 2012 (SSCG) have contributed to reduction of mortality in many places but these have not been adopted in our setting. The current study aimed at documenting the practice at a national referral hospital. METHODS: A hospital based longitudinal survey carried out among 325 children from September to October 2016. Children aged 0 days (≥37 weeks gestation) to12 years were included. The aim was to determine the prevalence, audit the management and determine the outcome at 72 hours of septic shock among children admitted at the Kenyatta National Hospital (KNH). A standard questionnaire was used for data collection and Surviving Sepsis Guideline 2012 was used as a reference for auditing the management of septic shock. Data was stored in MS-EXCEL and analysed in STATA 12. RESULTS: The prevalence of septic shock was 50 (15.4%), with a median age of 4 months. Septic shock was recognized by the attending clinician in 28 (56%). The level of care to children with septic shock was not to the level recommended by the SSCG 2012. Odds of being diagnosed with septic shock reduced with age (odds ratio 4.38 (1.7-11.0), p = 0.002) and no child aged above 60 months age was diagnosed with septic shock. The mortality was 35 (70%) at 72 hours of admission, with a median of 14 hours. Infants had the highest case fatality of 82.6%. It was found that lack of mechanical ventilation, and presence of hypotension at admission were associated with greater mortality (p values of 0.03 and 0.01 respectively). CONCLUSION: The prevalence rate of septic shock is 15.4% among children admitted at the KNH and is associated with high mortality. The advanced degree of shock contributed to mortality. The level of care at KNH was not to the level of SSCG 2012, and hence the need to include septic shock management guidelines/protocols in our local Kenyan paediatric guideline.

Approach to childhood interstitial lung disease in resource limited setting.

Childhood interstitial lung disease (ChILD) is a rare disease and sensitization is needed in the recognition, diagnosis and treatment approaches. There is no formal approach to diagnosis or therapy in resource limited regions. We present a case of a 4-month infant who presented with all the criteria for diagnosis of ChILD. Lung biopsy being the gold standard is a challenge in our setting and diagnosis was based on clinical signs and imaging after ruling out of other similar respiratory conditions by way of individual trials of therapy. Monotherapy with prednisone showed clinical improvement within days of initiation.

Cognitive bias modification to prevent depression (COPE): study protocol for a randomised controlled trial.

BACKGROUND: Depression is a leading cause of disability worldwide and, although efficacious treatments are available, their efficacy is suboptimal and recurrence of symptoms is common. Effective preventive strategies could reduce disability and the long term social and health complications associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel, simple, and safe intervention that addresses attentional and interpretive biases associated with anxiety, dysphoria, and depression. The primary aim of this trial is to determine if CBM decreases the one-year onset of a major depressive episode among adults with subsyndromal depression. DESIGN AND METHODS: This randomised controlled trial will recruit 532 adults with subsyndromal symptoms of depression living in the Australian community (parallel design, 1:1 allocation ratio). Participants will be free of clinically significant symptoms of depression and of psychotic disorders, sensory and cognitive impairment, and risky alcohol use. The CBM intervention will target attentional and interpretive biases associated with depressive symptoms. The sessions will be delivered via the internet over a period of 52 weeks. The primary outcome of interest is the onset of a major depressive episode according the DSM-IV-TR criteria over a 12-month period. Secondary outcomes of interest include change in the severity of depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9), use of antidepressants or benzodiazepines, and changes in attention and interpretive biases. The assessment of outcomes will take place 3, 6, 9, and 12 months after randomisation and will occur via the internet. DISCUSSION: We propose to test the efficacy of an innovative intervention that is well grounded in theory and for which increasing empirical evidence for an effect on mood is available. The intervention is simple, inexpensive, easy to access, and could be easily rolled out into practice if our findings confirm a role for CBM in the prevention of depression. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12613001334796. Date: 5th December 2013.

Homocysteine, depression and cognitive function in older adults.

BACKGROUND: Depression and high total plasma homocysteine (tHcy) are independently associated with cognitive impairment in older adults. We designed this study to determine if high tHcy is a mediator of cognitive performance in older adults with major depression. METHODS: We recruited 358 community-dwelling older adults experiencing depressive symptoms, 236 (65.9%) of who met DSM-IV-TR criteria for major depression. Assessment included the Montgomery Asberg Depression Rating Scale (MADRS), fasting tHcy and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. RESULTS: Individuals with major depression and high tHcy had significantly worse immediate verbal and delayed visual recall. Non-depressed participants with high tHcy had lower MMSE, immediate and delayed recall scores than those with normal tHcy. The odds of cognitive inefficiency for those with high tHcy was nearly doubled for the MMSE (OR 1.9, 95%CI 1.1-3.3), immediate (OR 1.9, 95%CI 1.1-3.5) and delayed (OR 1.9, 95%CI 1.1-3.4) word recall after adjusting for age, gender, IHD and MADRS score. LIMITATIONS: The presence of sub-syndromal depressive symptoms in our non-depressed group and exclusion of participants with established cognitive impairment may limit the generalizability of this study. CONCLUSIONS: Elevated tHcy was associated with weaker performance in tests of immediate and delayed memory and global cognitive performance when compared to those with normal tHcy independent of the presence of major depression or the severity of depressive symptoms. Homocysteine lowering B-vitamin supplementation may offer a potential therapeutic target to try and mitigate the often-disabling impact of cognitive deficits found in this population.

The B-VITAGE trial: a randomized trial of homocysteine lowering treatment of depression in later life.

BACKGROUND: Depression is a leading cause of disability worldwide and depressive symptoms are common in later life. Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine (tHcy), but the results of randomized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6, B12 and folate benefits depressive symptoms. We designed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6, B12 and folate increases the efficacy of standard antidepressant treatment. METHODS/DESIGN: The B-VITAGE trial is a 12-month randomized, double-blind, placebo-controlled trial of daily citalopram (20 to 40 mg) plus B12(0.5 mg), B6 (25 mg) and folic acid (2 mg) or citalopram (20 to 40 mg) plus placebo for the treatment of depression in later life. The trial aims to recruit over 300 older adults with major depression (DSM-IV) and has been powered to detect the impact of an intervention associated with moderate effect size. Depressive symptoms will be rated with the Montgomery-Asberg Depression Rating Scale (MADRS). The trial has two main outcomes of interest: a reduction of 50% or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12, 26 and 52 according to DSM-IV criteria. We hypothesize that subjects randomly allocated to the vitamin arm of the study will be more likely to show a clinically significant improvement and achieve and maintain remission of symptoms at 12, 26 and 52 weeks. Secondary outcomes of interest include compliance with treatment, reduction in the severity of depressive symptoms, switching to different antidepressants, the use of non-pharmacological antidepressant treatments, response to treatment according to MTHFRC677T genotype, and changes in cognitive function over 52 weeks. CONCLUSIONS: The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to standard antidepressant treatment. We anticipate that our findings will have implications for clinical practice and health policy development. TRIAL REGISTRATION: The trial is registered with the Australian Clinical Trials Registry, trial number (())ACTRN12609000256279.