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)

MRSA Infection in Vascular Surgical Patients: The HKL Experience

ABSTRAK Jangkitan Methicillin-resistant Staphylococcus aureus (MRSA) kerap berlaku di kalangan pesakit yang menjalani pembedahan vaskular. Ianya boleh mengakibatkan kehilangan anggota atau kematian. Kami melaksanakan analisa retrospektif terhadap nota pesakit pembedahan vaskular di Hospital Kuala Lumpur untuk tempoh 2 tahun mulai Januari 2005 hingga Disember 2007. Ianya bertujuan mengamati corak jangkitan dan faktor-faktor yang mengakibatkan jangkitan ini. Seramai 999 pesakit menjalani pembedahan vaskular dalam rangkuman jangkamasa kajian ini. Dari jumlah ini, seramai 24 pesakit (2.4%) dikesan terjangkit oleh MRSA. Jangkitan ini didapati terjurus kepada pesakit yang merokok, pesakit diabetes melitus dan mereka yang terdahulunya pernah menjalani pembedahan vaskular. Kebanyakan jangkitan bercorak kemusnahan terhadap luka pembedahan dan berlaku dalam kategori pembedahan kecemasan. Sebanyak 54% dari kes jangkitan berakhir dengan kehilangan anggota atau pengeluaran graf vaskular atau kematian. Jangkitan MRSA mengakibatkan kesan klinikal yang buruk terhadap pesakit yang menjalani pembedahan vaskular. Langkah pencegahan yang intensif diperlukan bagi mengelakkan kesan buruk yang tidak diingini ini. Kata kunci: jangkitan MRSA, pembedahan vaskular ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infection is important among vascular surgical patients. Its effect can be devastating resulting in limb amputation and mortality. We performed a retrospective patients record analysis to determine the pattern of MRSA infection among vascular surgical patients in Hospital Kuala Lumpur from January 2005 to December 2007. We also attempted to identify the factors associated with poor clinical outcome after such infection. There were 999 patients who underwent vascular surgeries in HKL within the analysis period. Of these 24 patients (2.4%) were detected to have MRSA surgical site infection. The infection was commoner among cigarette smokers, patients with diabetes melitus and those who & Health 2008; 3(2): 294-299 had previous vascular surgery. Most infections occurred in the emergency surgery category and manifested as wound breakdown. Fifty-four percent of the infected patients ended with graft removal, amputations or death. MRSA infection complicating vascular surgery resulted in poor clinical outcome. This serious threat requires intensified preventive measures

Dissecting mitosis by RNAi in Drosophila tissue culture cells

Here we describe a detailed methodology to study the function of genes whose products function during mitosis by dsRNA-mediated interference (RNAi) in cultured cells of Drosophila melanogaster. This procedure is particularly useful for the analysis of genes for which genetic mutations are not available or for the dissection of complicated phenotypes derived from the analysis of such mutants. With the advent of whole genome sequencing it is expected that RNAi-based screenings will be one method of choice for the identification and study of novel genes involved in particular cellular processes. In this paper we focused particularly on the procedures for the proper phenotypic analysis of cells after RNAi-mediated depletion of proteins required for mitosis, the process by which the genetic information is segregated equally between daughter cells. We use RNAi of the microtubule-associated protein MAST/Orbit as an example for the usefulness of the technique

Caspase Inhibition Blocks Cell Death and Enhances Mitophagy but Fails to Promote T-Cell Lymphoma

Caspase-9 is a component of the apoptosome that mediates cell death following release of cytochrome c from mitochondria. Inhibition of Caspase-9 with a dominant negative construct (Casp9DN) blocks apoptosome function, promotes viability and has been implicated in carcinogenesis. Inhibition of the apoptosome in vitro impairs mitochondrial function and promotes mitophagy. To examine whether inhibition of the apoptosome would enhance mitophagy and promote oncogenesis in vivo, transgenic mice were generated that express Casp9DN in the T cell lineage. The effects of Casp9DN on thymocyte viability, mitophagy and thymic tumor formation were examined. In primary thymocytes, Casp9DN delayed dexamethasone (Dex)-induced cell death, altered mitochondrial structure, and decreased oxidant production. Transmission electron microscopy (TEM) revealed that inhibition of the apoptosome resulted in structurally abnormal mitochondria that in some cases were engulfed by double-membrane structures resembling autophagosomes. Consistent with mitochondria being engulfed by autophagosomes (mitophagy), confocal microscopy showed colocalization of LC3-GFP and mitochondria. However, Casp9DN did not significantly accelerate T-cell lymphoma alone, or in combination with Lck-Bax38/1, or with Beclin 1+/− mice, two tumor-prone strains in which altered mitochondrial function has been implicated in promoting tumor development. In addition, heterozygous disruption of Beclin 1 had no effect on T-cell lymphoma formation in Lck-Bax38/1 mice. Further studies showed that Beclin 1 levels had no effect on Casp9DN-induced loss of mitochondrial function. These results demonstrate that neither inhibition of apoptosome function nor Beclin 1 haploinsufficiency accelerate T-cell lymphoma development in mice

Oncogene Activation Induces Metabolic Transformation Resulting in Insulin-Independence in Human Breast Cancer Cells

Normal breast epithelial cells require insulin and EGF for growth in serum-free media. We previously demonstrated that over expression of breast cancer oncogenes transforms MCF10A cells to an insulin-independent phenotype. Additionally, most breast cancer cell lines are insulin-independent for growth. In this study, we investigated the mechanism by which oncogene over expression transforms MCF10A cells to an insulin-independent phenotype. Analysis of the effects of various concentrations of insulin and/or IGF-I on proliferation of MCF10A cells demonstrated that some of the effects of insulin were independent from those of IGF-I, suggesting that oncogene over expression drives a true insulin-independent proliferative phenotype. To test this hypothesis, we examined metabolic functions of insulin signaling in insulin-dependent and insulin-independent cells. HER2 over expression in MCF10A cells resulted in glucose uptake in the absence of insulin at a rate equal to insulin-induced glucose uptake in non-transduced cells. We found that a diverse set of oncogenes induced the same result. To gain insight into how HER2 oncogene signaling affected increased insulin-independent glucose uptake we compared HER2-regulated gene expression signatures in MCF10A and HER2 over expressing MCF10A cells by differential analysis of time series gene expression data from cells treated with a HER2 inhibitor. This analysis identified genes specifically regulated by the HER2 oncogene, including VAMP8 and PHGDH, which have known functions in glucose uptake and processing of glycolytic intermediates, respectively. Moreover, these genes specifically implicated in HER2 oncogene-driven transformation are commonly altered in human breast cancer cells. These results highlight the diversity of oncogene effects on cell regulatory pathways and the importance of oncogene-driven metabolic transformation in breast cancer

Economic Impact of Dengue Illness and the Cost-Effectiveness of Future Vaccination Programs in Singapore

Dengue illness is a tropical disease transmitted by mosquitoes that threatens more than one third of the worldwide population. Dengue has important economic consequences because of the burden to hospitals, work absenteeism and risk of death of symptomatic cases. Governments attempt to reduce the disease burden using costly mosquito control strategies such as habitat reduction and spraying insecticide. Despite such efforts, the number of cases remains high. Dengue vaccines are expected to be available in the near future and there is an urgent need to evaluate their cost-effectiveness, i.e. whether their cost will be justified by the reduction in disease burden they bring. For such an evaluation, we estimated the economic impacts of dengue in Singapore and the expected vaccine costs for different prices. In this way we estimated price thresholds for which vaccination is not cost-effective. This research provides useful estimates that will contribute to informed decisions regarding the adoption of dengue vaccination programs

The Policy Dystopia Model:an interpretive analysis of tobacco industry political activity

BACKGROUND: Tobacco industry interference has been identified as the greatest obstacle to the implementation of evidence-based measures to reduce tobacco use. Understanding and addressing industry interference in public health policy-making is therefore crucial. Existing conceptualisations of corporate political activity (CPA) are embedded in a business perspective and do not attend to CPA's social and public health costs; most have not drawn on the unique resource represented by internal tobacco industry documents. Building on this literature, including systematic reviews, we develop a critically informed conceptual model of tobacco industry political activity. METHODS AND FINDINGS: We thematically analysed published papers included in two systematic reviews examining tobacco industry influence on taxation and marketing of tobacco; we included 45 of 46 papers in the former category and 20 of 48 papers in the latter (n = 65). We used a grounded theory approach to build taxonomies of "discursive" (argument-based) and "instrumental" (action-based) industry strategies and from these devised the Policy Dystopia Model, which shows that the industry, working through different constituencies, constructs a metanarrative to argue that proposed policies will lead to a dysfunctional future of policy failure and widely dispersed adverse social and economic consequences. Simultaneously, it uses diverse, interlocking insider and outsider instrumental strategies to disseminate this narrative and enhance its persuasiveness in order to secure its preferred policy outcomes. Limitations are that many papers were historical (some dating back to the 1970s) and focused on high-income regions. CONCLUSIONS: The model provides an evidence-based, accessible way of understanding diverse corporate political strategies. It should enable public health actors and officials to preempt these strategies and develop realistic assessments of the industry's claims

Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra

Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells