Radial artery access site complications during cardiac procedures, clinical implications and potential solutions : the role of nitric oxide

Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme.Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery, as this is safer than the femoral approach. However, despite improvements in technology and techniques, complications can occur. The most common complication, arterial spasm, can cause intense pain and, in some cases, procedural failure. The incidence of spasm is dependent on several variables, including operator experience, artery size, and equipment used. An anti-spasmolytic cocktail can be applied to reduce spasm, which usually includes an exogenous nitric oxide (NO) donor (glyceryl trinitrate). NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention. However, systemic administration can result in unwanted side-effects, such as hypotension. A method that adopts local delivery of NO might be advantageous. This review article describes the mechanisms involved in radial artery spasm, discusses the advantages and disadvantages of current strategies to reduce spasm, and highlight the potential of NO-loaded nanoporous materials for use in this setting.Publisher PDFPeer reviewe

Associations between prenatal exposure to antipsychotics and attention-deficit/hyperactivity disorder, autism spectrum disorder, preterm birth and small for gestational age: a population-based cohort study

Importance: The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear. / Objective: To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems. / Design, Setting, Participants: This population-based cohort study included children born between 2001–2015 with follow-up to 2019, identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestational-exposed and gestational non-exposed with propensity score fine-stratification. Additional analyses included gestational-exposed versus past-exposed and sibling-matched analysis to evaluate the effect of confounding by indication. / Exposures: Prenatal antipsychotic exposure. Main outcomes and measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. / Results: The cohorts included 333,749 mother-child pairs for ADHD and 411,251 pairs for ASD/preterm birth/small for gestational age analyses. There were 13,196 children (3.95%) diagnosed with ADHD, 8,715 (2.12%) with ASD, 33,891 (8.24%) preterm, and 7,009 (1.70%) small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% confidence interval [CI]=0.83-1.61) for ADHD and 1.06 (95%CI=0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95%CI=1.13-1.75) for preterm birth and 1.36 (95%CI=0.86-2.14) for small for gestational age, when comparing gestational-exposed to gestational non-exposed. Additional analyses showed no association when comparing gestational-exposed to past-exposed (ADHD: wHR=0.99, 95%CI=0.60-1.61); ASD: wHR=1.10, 95%CI=0.58-2.08; preterm birth: wOR=0.93, 95%CI=0.70-1.24; small for gestational age: wOR=1.21, 95%CI=0.66-2.20), and in sibling-matched analysis (ADHD: wHR=0.41, 95%CI=0.04-4.93; ASD: wHR=0.90, 95%CI=0.40-2.01; preterm birth: wOR=1.25, 95%CI=0.85-1.82; small for gestational age: wOR=0.86, 95%CI=0.32-2.31). / Conclusions and Relevance: We found no evidence that prenatal antipsychotics exposure increased the risk of ADHD, ASD or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestational-exposed to past-exposed and comparing gestational exposed to gestational non-exposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to stop their regular antipsychotic treatment during pregnancy

Health-related quality of life of children with attention-deficit/hyperactivity disorder versus children with diabetes and healthy controls

The impact of attention-deficit/hyperactivity disorder (ADHD) on health-related quality of life (HRQoL) is reported to be similar to that of other mental health and physical disorders. In this cross-sectional study, we hypothesized that children with ADHD and children with type 1 diabetes mellitus (T1DM) would have significantly worse HRQoL compared with healthy children, and that better clinical status in ADHD and T1DM would be associated with better HRQoL. Children were recruited from three outpatient services in Scotland. Responses to two frequently used validated HRQoL instruments, the Paediatric Quality of Life Inventory (PedsQL) and Child Health and Illness Profile-child edition (CHIP-CE), were obtained from parents/carers and children (6–16 years) with/without ADHD or T1DM. Child and parent/carer-completed HRQoL measurements were evaluated for 213 children with ADHD, 58 children with T1DM and 117 healthy children (control group). Significantly lower self and parent/carer ratings were observed across most PedsQL (P < 0.001) and CHIP-CE (P < 0.05) domains (indicating reduced HRQoL) for the ADHD group compared with the T1DM and control groups. Parent/carer and child ratings were significantly correlated for both measures of HRQoL (PedsQL total score: P < 0.001; CHIP-CE all domains: P < 0.001), but only with low-to-moderate strength. Correlation between ADHD severity and HRQoL was significant with both PedsQL and CHIP-CE for all parent/carer (P < 0.01) and most child (P < 0.05) ratings; more ADHD symptoms were associated with poorer HRQoL. These data demonstrate that ADHD has a significant impact on HRQoL (as observed in both parent/carer and child ratings), which seems to be greater than that for children with T1DM

Attention-Deficit/Hyperactivity Disorder medication consumption in 64 countries and regions from 2015 to 2019: a longitudinal study

Background: Timely recognition and appropriate treatment of attention-deficit/hyperactivity disorder (ADHD) are essential to enhance long-term outcomes of individuals with ADHD. This study aimed to evaluate the multinational trends and patterns of ADHD medication consumption. Methods: In this longitudinal trend study, we used pharmaceutical sales data of ADHD medication from the IQVIA-Multinational Integrated Data Analysis System between 2015 and 2019, covering 64 countries across the world. Consumption rates of ADHD medication were expressed as defined daily dose per 1000 child and adolescent inhabitants (aged 5–19) per day (DDD/TID). Linear mixed models were used to estimate the multinational, regional, and income level trend changes. Findings: The results showed that multinational ADHD medication consumption increased by +9.72% (95% confidence interval [CI], +6.25%, +13.31%) per year, from 1.19 DDD/TID in 2015 to 1.43 DDD/TID in 2019 across the 64 countries with marked differences between geographical locations. When stratified by countries’ income levels, increases in ADHD medication consumption were observed in high-income countries but not in middle-income countries. In 2019, the pooled consumption rates of ADHD medication were 6.39 DDD/TID (95% CI, 4.63, 8.84) in high-income countries, 0.37 DDD/TID (95% CI, 0.23, 0.58) in upper-middle-income countries and 0.02 DDD/TID (95% CI, 0.01, 0.05) in lower-middle-income countries. Interpretation: Current ADHD prevalence estimates and rates of ADHD medication consumption in most middle-income countries are lower than the global epidemiological prevalence. It is therefore imperative to evaluate the potential barriers to diagnosis and treatment in these countries to minimise the risk of negative outcomes from undiagnosed and untreated ADHD. Funding: This project was funded by a grant from the Hong Kong Research Grants Council Collaborative Research Fund (project number C7009-19G)

Changes in Clinical Context for Kaposi's Sarcoma and Non-Hodgkin Lymphoma Among People With HIV Infection in the United States

The biology of HIV-associated cancers may differ depending on immunologic and virologic context during development. Therefore, an understanding of the burden of Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL) relative to antiretroviral therapy (ART), virologic suppression, and CD4 count is important

Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis

Background: The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults. Methods: We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976. Findings: 133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD −1·02, 95% CI −1·19 to −0·85 for amphetamines, −0·78, −0·93 to −0·62 for methylphenidate, −0·56, −0·66 to −0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD −0·82, 95% CI −1·16 to −0·48) and modafinil (−0·76, −1·15 to −0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD −0·79, 95% CI −0·99 to −0·58), methylphenidate (−0·49, −0·64 to −0·35), bupropion (−0·46, −0·85 to −0·07), and atomoxetine (−0·45, −0·58 to −0·32), but not modafinil (0·16, −0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults (3·26, 1·54–6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20–5·81); and atomoxetine (2·33, 1·28–4·25), methylphenidate (2·39, 1·40–4·08), and modafinil (4·01, 1·42–11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs −0·46 to −0·24) and adults (−0·94 to −0·29). We did not find sufficient data for the 26-week and 52-week timepoints. Interpretation: Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. Funding: Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre

Comparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents: Protocol for a network meta-analysis

Introduction Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. Methods and analysis We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. Dissemination This NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication. Protocol registration PROSPERO CRD42015020841

Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis

Background Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. Methods We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. Findings We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference −0·51, 95% credible interval [CrI] −0·99 to −0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I2 values were 33·21% for efficacy and 0% for tolerability. Interpretation When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. Funding National Basic Research Program of China (973 Program)

Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis

Background: Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings: From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (–0·78, 95% CrI −1·55 to −0·01) and psychodynamic therapy (–1·14, −2·20 to −0·08), but not more effective than fluoxetine alone (–0·22, −0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from −1·73 to −0·51); and only interpersonal therapy was more effective than all psychological controls (–1·37 to −0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as “low” to “very low” in terms of confidence of evidence according to Confidence In Network Meta-Analysis. Interpretation: Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. Funding: National Key Research and Development Program of China

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas