Selective serotonin reuptake inhibitors in pediatric depression: is the balance between benefits and risks favorable?

Recent controversies surrounding the use of selective serotonin reuptake inhibitors (SSRIs) have highlighted the need to reassess potential benefits, as well as potential risks of this class of medications in the treatment of pediatric depression. The recent availability of data from meta-analyses of published and unpublished antidepressant trials, epidemiological studies, and the Treatment for Adolescents with Depression Study (TADS) has facilitated a reanalysis of this risk/benefit relationship. Despite reviewing similar data, various regulatory agencies have arrived at rather disparate conclusions regarding the data, resulting in continued controversy. Although all groups appear to agree that careful assessment, education regarding risks, and closer monitoring are essential for SSRIs, only the U.S. Food and Drug Administration (FDA) and the U.K. Medicine and Health Care Products Regulatory Agency maintain that an acceptable risk/benefit relationship exists for fluoxetine. The European Medicines Agency concluded that the SSRIs should not be used in the treatment of depression in children and adolescents. The authors of this review have taken into consideration many of these same data and offer a critical discussion of the pros and cons of SSRIs in pediatric depression. The authors have concluded that SSRIs -- in particular, fluoxetine -- do have a role in the treatment of pediatric depression

Remission and recovery in the Treatment for Adolescents with Depression Study (TADS): acute and long-term outcomes.

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS). METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission. RESULTS: At week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive-behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36. CONCLUSIONS: Most depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment

Direct observation of the energy release site in a solar flare by SDO/AIA, Hinode/EIS and RHESSI

We present direct evidence for the detection of the main energy release site in a non-eruptive solar flare, SOL2013-11-09T06:38UT. This GOES C2.7 event was characterised by two flaring ribbons and a compact, bright coronal source located between them, which is the focus of our study. We use imaging from SDO/AIA, and imaging spectroscopy from RHESSI to characterise the thermal and non-thermal emission from the coronal source, and EUV spectroscopy from the Hinode/EIS, which scanned the coronal source during the impulsive peak, to analyse Doppler shifts in Fe XII and Fe XXIV emission lines, and determine the source density. The coronal source exhibited an impulsive emission lightcurve in all AIA filters during the impulsive phase. RHESSI hard X-ray images indicate both thermal and non-thermal emission at the coronal source, and its plasma temperature derived from RHESSI imaging spectroscopy shows an impulsive rise, reaching a maximum at 12-13 MK about 10 seconds prior to the hard X-ray peak. High redshifts associated with this bright source indicate downflows of 40-250 km/s at a broad range of temperatures, interpreted as loop shrinkage and/or outflows along the magnetic field. Outflows from the coronal source towards each ribbon are also observed by AIA images at 171, 193, 211, 304 and 1600 A. The electron density of the source obtained from a Fe XIV line pair is $10^{11.50}$ which is collisionally thick to electrons with energy up to 45-65 keV, responsible for the source's non-thermal X-ray emission. We conclude that the bright coronal source is the location of the main release of magnetic energy in this flare, with a geometry consistent with component reconnection between crossing, current-carrying loops. We argue that the energy that can be released via reconnection, based on observational estimates, can plausibly account for the non-thermal energetics of the flare.Comment: 10 pages, 7 figure

The Concise Health Risk Tracking - Self-Report (CHRT-SR)—A measure of suicidal risk: Performance in adolescent outpatients

Article describes how the Concise Health Risk Tracking Self-Report (CHRT-SR) assesses the risk of suicidal behavior. The authors report its psychometric properties in a representative sample of adolescent outpatients

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)

Treatment for Adolescents with Depression Study (TADS): safety results.

OBJECTIVE: To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO). METHOD: Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic measures for specific physical and psychiatric symptoms. Suicidal ideation and suicidal behavior were systematically assessed by self- and clinician reports. Suicidal events were also reanalyzed by the Columbia Group and expert raters using the Columbia-Classification Algorithm for Suicidal Assessment used in the U.S. Food and Drug Administration reclassification effort. RESULTS: Depressed adolescents reported high rates of physical symptoms at baseline, which improved as depression improved. Sedation, insomnia, vomiting, and upper abdominal pain occurred in at least 2% of those treated with FLX and/or COMB and at twice the rate of placebo. The rate of psychiatric AEs was 11% in FLX, 5.6% in COMB, 4.5% in PBO, and 0.9% in CBT. Suicidal ideation improved overall, with greatest improvement in COMB. Twenty-four suicide-related events occurred during the 12-week period: 5 patients (4.7%) in COMB, 10 (9.2%) in FLX, 5 (4.5%) in CBT, and 3 (2.7%) in placebo. Statistically, only FLX had more suicide-related events than PBO (p =.0402, odds ratio (OR) = 3.7, 95% CI 1.00-63.7). Only five actual attempts occurred (2 COMB, 2 FLX, 1 CBT, 0 PBO). There were no suicide completions. CONCLUSIONS: Different methods for eliciting AEs produce different results. In general, as depression improves, physical complaints and suicidal ideation decrease in proportion to treatment benefit. In this study, psychiatric AEs and suicide-related events are more common in FLX-treated patients. COMB treatment may offer a more favorable safety profile than medication alone in adolescent depression

Extreme Ultra-Violet Spectroscopy of the Lower Solar Atmosphere During Solar Flares

The extreme ultraviolet portion of the solar spectrum contains a wealth of diagnostic tools for probing the lower solar atmosphere in response to an injection of energy, particularly during the impulsive phase of solar flares. These include temperature and density sensitive line ratios, Doppler shifted emission lines and nonthermal broadening, abundance measurements, differential emission measure profiles, and continuum temperatures and energetics, among others. In this paper I shall review some of the advances made in recent years using these techniques, focusing primarily on studies that have utilized data from Hinode/EIS and SDO/EVE, while also providing some historical background and a summary of future spectroscopic instrumentation.Comment: 34 pages, 8 figures. Submitted to Solar Physics as part of the Topical Issue on Solar and Stellar Flare

Degree of urbanization and gender differences in substance use among Slovak adolescents

Substance use among adolescents varies with gender and between countries. Urbanization may contribute to this. The aim of our study is to explore the association between the degree of urbanization and gender differences in adolescent smoking, binge drinking, and cannabis use. A cross-sectional questionnaire survey of Slovak adolescents was used (N = 3,493; mean age = 14.33), stratified by degree of urbanization. The effects of gender and urbanization of the area and their interaction on substance use (smoking, binge drinking, and cannabis) were analyzed using a logistic regression model adjusted for age. Gender and area and their interaction had statistically significant (p <0.01) associations with substance use. The lower the urbanization of the area, the less riskily females behaved. An exception was found in the case of binge drinking where the results of the interaction of gender and degree of urbanization were not significant for the second least urbanized area. Prevalence rate of substance use among girls increased along with an increasing degree of urbanization, while the prevalence rate of substance use among boys remained constant

Risk of acute kidney injury and survival in patients treated with Metformin:an observational cohort study

Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI