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Background: Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season., Methods: A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes., Results: A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], P<.001)., Conclusion: Risk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

While the differential for suicidal ideations is broad, it is known that pathologic brain issues are a cause. Here, a case is presented of a gentleman who had an unusual growth into his frontal lobe leading to the suicidal ideations. The fact that he is chronically immunosuppressed likely led to this unique situation.

One quarter of children and young people (CYP) experience anxiety and/or depression before adulthood, but treatment is sometimes unavailable or inadequate. Self-help interventions may have a role in augmenting treatment and this work aimed to systematically review the evidence for computerised anxiety and depression interventions in CYP aged 5-25 years old. Databases were searched for randomised controlled trials and 27 studies were identified. For young people (12-25 years) with risk of diagnosed anxiety disorders or depression, computerised CBT (cCBT) had positive effects for symptoms of anxiety (SMD -0.77, 95% CI -1.45 to -0.09, k = 6, N = 220) and depression (SMD -0.62, 95% CI -1.13 to -0.11, k = 7, N = 279). In a general population study of young people, there were small positive effects for anxiety (SMD -0.15, 95% CI -0.26 to -0.03; N = 1273) and depression (SMD -0.15, 95% CI -0.26 to -0.03; N = 1280). There was uncertainty around the effectiveness of cCBT in children (5-11 years). Evidence for other computerised interventions was sparse and inconclusive. Computerised CBT has potential for treating and preventing anxiety and depression in clinical and general populations of young people. Further program development and research is required to extend its use and establish its benefit in children., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The widespread availability of the Internet and mobile-device applications (apps) is changing the treatment of mental health problems. The aim of the present study was to review the research on the effectiveness of e-therapy for eating disorders, using the methodology employed by the UK's National Institute for Health and Care Excellence (NICE). Electronic databases were searched for published randomised controlled trials of e-therapies, designed to prevent or treat any eating disorder in all age groups. Studies were meta-analysed where possible, and effect sizes with confidence intervals were calculated. The GRADE approach was used to determine the confidence in the effect estimates. Twenty trials met the inclusion criteria. For prevention, a CBT-based e-intervention was associated with small reductions in eating disorder psychopathology, weight concern and drive for thinness, with moderate confidence in the effect estimates. For treatment and relapse prevention, various e-therapies showed some beneficial effects, but for most outcomes, evidence came from single studies and confidence in the effect estimates was low. Overall, although some positive findings were identified, the value of e-therapy for eating disorders must be viewed as uncertain. Further research, with improved methods, is needed to establish the effectiveness of e-therapy for people with eating disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Optimal human function and performance through diet strategies are critical for everyone but especially for those involved in collegiate or professional athletics. Currently, individualized medicine (IM) is emerging as a more efficacious approach to health with emphasis on personalized diet strategies for the public and is common practice for elite athletes. One method for directing patient-specific foods in the diet, while concomitantly impacting physical performance, may be via IgG food sensitivity and Candida albicans analysis from dried blood spot (DBS) collections., Methods: The authors designed a quasi-experimental, nonrandomized, pilot study without a control group. Twenty-three participants, 15 female, 8 male, from soccer/volleyball and football athletic teams, respectively, mean age 19.64+0.86 years, were recruited for the study, which examined preposttest 300-meter run times and questionnaire responses after a 14-day IgG DBS-directed food elimination diet based on IgG reactivity to 93 foods. DBS specimen collection, 300-meter run times, and Learning Difficulties Assessment (LDA) questionnaires were collected at the participants' university athletics building on campus. IgG, C albicans, and S cerevisiae analyses were conducted at the Great Plains Laboratory, Lenexa, Kansas., Results: Data indicated a change in 300-meter run time but not of statistical significance (run time baseline mean=50.41 sec, run time intervention mean=50.14 sec). Descriptive statistics for frequency of responses and chi-square analysis revealed that 4 of the 23 items selected from the LDA (Listening-Memory and Concentration subscale R=.8669; Listening-Information Processing subscale R=.8517; and General Concentration and Memory subscale R=.9019) were improved posttest., Conclusion: The study results did not indicate merit in eliminating foods based on IgG reactivity for affecting athletic performance (faster 300-meter run time) but did reveal potential for affecting academic qualities of listening, information processing, concentration, and memory. Further studies are warranted evaluating IgG-directed food elimination diets for improving run time, concentration, and memory among college athletes as well as among other populations.

Background: Lithium is the established standard in the long-term treatment of bipolar disorder, but several new drugs have been assessed for this indication. We did a network meta-analysis to investigate the comparative efficacy and tolerability of available pharmacological treatment strategies for bipolar disorder., Methods: We systematically searched Embase, Medline, PreMedline, PsycINFO, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before June 28, 2013, that compared active treatments for bipolar disorder (or placebo), either as monotherapy or as add-on treatment, for at least 12 weeks. The primary outcomes were the number of participants with recurrence of any mood episode, and the number of participants who discontinued the trial because of adverse events. We assessed efficacy and tolerability of bipolar treatments using a random-effects network meta-analysis within a Bayesian framework., Findings: We screened 114 potentially eligible studies and identified 33 randomised controlled trials, published between 1970 and 2012, that examined 17 treatments for bipolar disorder (or placebo) in 6846 participants. Participants assigned to all assessed treatments had a significantly lower risk of any mood relapse or recurrence compared with placebo, except for those assigned to aripiprazole (risk ratio [RR] 0·62, 95% credible interval [CrI] 0·38-1·03), carbamazepine (RR 0·68, 0·44-1·06), imipramine (RR 0·95, 0·66-1·36), and paliperidone (RR 0·84, 0·56-1·24). Lamotrigine and placebo were significantly better tolerated than carbamazepine (lamotrigine, RR 5·24, 1·07-26·32; placebo, RR 3·60, 1·04-12·94), lithium (RR 3·76, 1·13-12·66; RR 2·58, 1·33-5·39), or lithium plus valproate (RR 5·95, 1·02-33·33; RR 4·09, 1·01-16·96)., Interpretation: Although most of the drugs analysed were more efficacious than placebo and generally well tolerated, differences in the quality of evidence and the side-effect profiles should be taken into consideration by clinicians and patients. In view of the efficacy in prevention of both manic episode and depressive episode relapse or recurrence and the better quality of the supporting evidence, lithium should remain the first-line treatment when prescribing a relapse-prevention drug in patients with bipolar disorder, notwithstanding its tolerability profile., Funding: None., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to quantify the unique useful yield from the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database to National Institute for Health and Clinical Excellence (NICE) clinical guidelines. A secondary objective is to investigate the relationship between this yield and different clinical question types. It is hypothesized that the unique useful yield from CINAHL is low, and this database can therefore be relegated to selective rather than routine searching., Study Design and Setting: A retrospective sample of 15 NICE guidelines published between 2005 and 2009 was taken. Information on clinical review question type, number of references, and reference source was extracted., Results: Only 0.33% (95% confidence interval: 0.01-0.64%) of references per guideline were unique to CINAHL. Nursing- or allied health (AH)-related questions were nearly three times as likely to have references unique to CINAHL as non-nursing- or AH-related questions (14.89% vs. 5.11%), and this relationship was found to be significant (P<0.05). No significant relationship was found between question type and unique CINAHL yield for drug-related questions., Conclusions: The very low proportion of references unique to CINAHL strongly suggests that this database can be safely relegated to selective rather than routine searching. Nursing- and AH-related questions would benefit from selective searching of CINAHL., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium., Methods: We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity., Findings: We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders., Interpretation: Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment., Funding: National Institute for Health Research Programme Grant for Applied Research., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Conventional meta-analyses have shown inconsistent results for efficacy of pharmacological treatments for acute mania. We did a multiple-treatments meta-analysis, which accounted for both direct and indirect comparisons, to assess the effects of all antimanic drugs., Methods: We systematically reviewed 68 randomised controlled trials (16,073 participants) from Jan 1, 1980, to Nov 25, 2010, which compared any of the following pharmacological drugs at therapeutic dose range for the treatment of acute mania in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, quetiapine, risperidone, topiramate, and ziprasidone. The main outcomes were the mean change on mania rating scales and the number of patients who dropped out of the allocated treatment at 3 weeks. Analysis was done by intention to treat., Findings: Haloperidol (standardised mean difference [SMD] -0·56 [95% CI -0·69 to -0·43]), risperidone (-0·50 [-0·63 to -0·38), olanzapine (-0·43 [-0·54 to -0·32], lithium (-0·37 [-0·63 to -0·11]), quetiapine (-0·37 [-0·51 to -0·23]), aripiprazole (-0·37 [-0·51 to -0·23]), carbamazepine (-0·36 [-0·60 to -0·11], asenapine (-0·30 [-0·53 to -0·07]), valproate (-0·20 [-0·37 to -0·04]), and ziprasidone (-0·20 [-0·37 to -0·03]) were significantly more effective than placebo, whereas gabapentin, lamotrigine, and topiramate were not. Haloperidol had the highest number of significant differences and was significantly more effective than lithium (SMD -0·19 [95% CI -0·36 to -0·01]), quetiapine (-0·19 [-0·37 to 0·01]), aripiprazole (-0·19 [-0·36 to -0·02]), carbamazepine (-0·20 [-0·36 to -0·01]), asenapine (-0·26 [-0·52 to 0·01]), valproate (-0·36 [-0·56 to -0·15]), ziprasidone -0·36 [-0·56 to -0·15]), lamotrigine (-0·48 [-0·77 to -0·19]), topiramate (-0·63 [-0·84 to -0·43]), and gabapentin (-0·88 [-1·40 to -0·36]). Risperidone and olanzapine had a very similar profile of comparative efficacy, being more effective than valproate, ziprasidone, lamotrigine, topiramate, and gabapentin. Olanzapine, risperidone, and quetiapine led to significantly fewer discontinuations than did lithium, lamotrigine, placebo, topiramate, and gabapentin., Interpretation: Overall, antipsychotic drugs were significantly more effective than mood stabilisers. Risperidone, olanzapine, and haloperidol should be considered as among the best of the available options for the treatment of manic episodes. These results should be considered in the development of clinical practice guidelines., Funding: None., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Long duration of untreated psychosis (DUP) is common and associated with poor outcomes. Strategies to enhance early detection of first-episode psychosis have been advocated., Aims: To evaluate initiatives for early detection of psychosis., Method: Systematic review of available evidence on the effectiveness of early detection initiatives to reduce the DUP., Results: The review included 11 studies which evaluated 8 early detection initiatives. Evidence suggests that general practitioner education campaigns and dedicated early intervention services do not by themselves reduce DUP or generate more treated cases. Evidence for multifocus initiatives is mixed: intensive campaigns targeting the general public as well as relevant professionals may be needed. No studies evaluated initiatives targeting young people or professionals from non-health organisations., Conclusions: How early detection can be achieved is not clear. Evidence is most promising for intensive public awareness campaigns: these require organisation and resourcing at a regional or national level. More good-quality studies are needed to address gaps in knowledge.

In the primate prefrontal cortex (PFC), the functional maturation of the synaptic connections of certain classes of gamma-aminobutyric acid (GABA) neurons is very complex. For example, the levels of both pre- and postsynaptic proteins that regulate GABA neurotransmission from the chandelier class of cortical interneurons to the axon initial segment (AIS) of pyramidal neurons undergo marked changes during both the perinatal period and adolescence in the monkey PFC. In order to understand the potential molecular mechanisms associated with these developmental refinements, we quantified the relative densities, laminar distributions, and lengths of pyramidal neuron AIS immunoreactive for ankyrin-G, betaIV spectrin, or gephyrin, three proteins involved in regulating synapse structure and receptor localization, in the PFC of rhesus monkeys ranging in age from birth through adulthood. Ankyrin-G- and betaIV spectrin-labeled AIS declined in density and length during the first 6 postnatal months, but then remained stable through adolescence and into adulthood. In contrast, the density of gephyrin-labeled AIS was stable until approximately 15 months of age and then markedly declined during adolescence. Thus, molecular determinants of the structural features that define GABA inputs to pyramidal neuron AIS in monkey PFC undergo distinct developmental trajectories with different types of changes occurring during the perinatal period and adolescence. In concert with previous data, these findings reveal a two-phase developmental process of GABAergic synaptic stability and GABA neurotransmission at chandelier cell inputs to pyramidal neurons that likely contributes to the protracted maturation of behaviors mediated by primate PFC circuitry.