Attention-deficit hyperactivity disorder diagnoses and prescriptions in UK primary care, 2000–2018: population-based cohort study

Background Rates of diagnosed attention-deficit hyperactivity disorder (ADHD) may be increasing in the UK. Aims Estimate incidence and prevalence of ADHD diagnoses and ADHD prescriptions in UK adults and children in primary care. Method We conducted a cohort study using IQVIA Medical Research Data, a UK primary care database. Rates of ADHD diagnoses and ADHD prescriptions were calculated between 2000 and 2018 for individuals aged 3–99 years, analysed by age, gender, social deprivation status and calendar year. Results Of 7 655 931 individuals, 35 877 (0.5%) had ADHD diagnoses; 18 518 (0.2%) received ADHD medication prescriptions. Diagnoses and prescription rates were greater in men versus women, children versus adults, and deprivation status (nearly double in most deprived versus least deprived quintile). By 2018, the proportion of ADHD diagnoses was 255 per 10 000 (95% CI 247–263) in boys and 67.7 per 10 000 (95% CI 63.5–71.9) in girls; for adults, it was 74.3 per 10 000 (95% CI 72.3–76.2) in men and 20 per 10 000 (95%CI 19.0–21.0) in women. Corresponding figures for prescriptions were 156 per 10 000 (95% CI 150–163) in boys, 36.8 per 10 000 (95% CI 33.8–40.0) in girls, 13.3 per 10 000 (95% CI 12.5–14.1) in men and 4.5 per 10 000 (95% CI 4.1–5.0) in women. Except among 3- to 5-year-olds, the incidence and prevalence of ADHD diagnoses and prescriptions have increased from 2000 to 2018 in all age groups. The absolute increase was highest in children, but the relative increase was largest among adults (e.g. among men aged 18–29 years, approximately 20-fold and nearly 50-fold increases in diagnoses and prescriptions, respectively). Conclusions The incidence and prevalence of both ADHD diagnoses and medication are highest among children. Proportionally, rates increased most among adults during 2000–2018. ADHD diagnoses and prescriptions are associated with socioeconomic deprivation

General practice and the Medical Licensing Assessment

From 2024/2025, all UK medical students will sit the Medical Licensing Assessment (MLA),1 a mandated national exam comprising: a written applied knowledge test (AKT) in single best answer (SBA) format; and a clinical and professional skills assessment (CPSA). Here we consider the implications for primary care, and for those involved in teaching primary care to medical undergraduates, including GPs and other primary care professionals

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Technology as an Enabler of the Global Branding of Retail Financial Services

The author argues that, though there is little doubt that technology has transformed the delivery of retail financial services in the past decade, this transformation also has implications for the global branding of financial services. The article presents a conceptual framework that illustrates how new distribution and processing technologies on the supply-side and changes in consumer attitudes to banking on the demand-side have driven the global branding of retail financial services. On the supply side, the change process has occurred through the removal of geographic and cost barriers to global distribution, which have enabled insurance companies, supermarkets, utilities, Internet-only banks, and other new players to enter traditional banking markets. Technology has created globally accessible internal information management systems, reduced the need for physical branch networks, stimulated greater brand awareness through interactive Web sites, fuelled the expansion of multinational banks and consolidation through mergers, and ultimately has eroded product differentiation and distribution channels as sources of competitive advantage. The combination of these supply-side elements increases the need for, and the effectiveness of, global brands. On the demand side, the change process has been driven by global convergence in key benefits sought by banking consumers in developed countries. The move to electronic delivery of retail financial services has increased competition and consumer sophistication, and consumers have become less loyal, more informed, and more willing to switch providers and use multiple providers in order to maximize the value of the unique mix of savings, loan, and transactions services they seek. Yet, at the same time, the ongoing need for security and reliability when performing financial transactions means consumers place value on brands that have established images as trusted parties. The result is an increased consumer preference for globally recognized brands and a willingness to purchase financial services from firms other than traditional financial institutions, provided the brand name is a trusted one. The author concludes that for managers of firms providing retail financial services, the major implication of these technology-induced changes in supply and demand is the need for customer-focused marketing strategies