Prioritising Infectious Disease Mapping.

BACKGROUND: Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. METHODOLOGY/PRINCIPAL FINDINGS: Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. CONCLUSIONS/SIGNIFICANCE: A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited

Prioritising Infectious Disease Mapping.

BACKGROUND: Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. METHODOLOGY/PRINCIPAL FINDINGS: Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. CONCLUSIONS/SIGNIFICANCE: A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited

Establishing a library of resources to help people understand key concepts in assessing treatment claims—The “Critical thinking and Appraisal Resource Library” (CARL)

Background People are frequently confronted with untrustworthy claims about the effects of treatments. Uncritical acceptance of these claims can lead to poor, and sometimes dangerous, treatment decisions, and wasted time and money. Resources to help people learn to think critically about treatment claims are scarce, and they are widely scattered. Furthermore, very few learning-resources have been assessed to see if they improve knowledge and behavior. Objectives Our objectives were to develop the Critical thinking and Appraisal Resource Library (CARL). This library was to be in the form of a database containing learning resources for those who are responsible for encouraging critical thinking about treatment claims, and was to be made available online. We wished to include resources for groups we identified as ‘intermediaries’ of knowledge, i.e. teachers of schoolchildren, undergraduates and graduates, for example those teaching evidence-based medicine, or those communicating treatment claims to the public. In selecting resources, we wished to draw particular attention to those resources that had been formally evaluated, for example, by the creators of the resource or independent research groups. Methods CARL was populated with learning-resources identified from a variety of sources—two previously developed but unmaintained inventories; systematic reviews of learning-interventions; online and database searches; and recommendations by members of the project group and its advisors. The learning-resources in CARL were organised by ‘Key Concepts’ needed to judge the trustworthiness of treatment claims, and were made available online by the James Lind Initiative in Testing Treatments interactive (TTi) English (www.testingtreatments.org/category/learning-resources).TTi English also incorporated the database of Key Concepts and the Claim Evaluation Tools developed through the Informed Healthcare Choices (IHC) project (informedhealthchoices.org). Results We have created a database of resources called CARL, which currently contains over 500 open-access learning-resources in a variety of formats: text, audio, video, webpages, cartoons, and lesson materials. These are aimed primarily at ‘Intermediaries’, that is, ‘teachers’, ‘communicators’, ‘advisors’, ‘researchers’, as well as for independent ‘learners’. The resources included in CARL are currently accessible at www.testingtreatments.org/category/learning-resources Conclusions We hope that ready access to CARL will help to promote the critical thinking about treatment claims, needed to help improve healthcare choices

The cost effectiveness of NHS physiotherapy support for occupational health (OH) services

Background: Musculoskeletal pain is detrimental to quality of life (QOL) and disruptive to activities of daily living. It also places a major economic burden on healthcare systems and wider society. In 2006, the Welsh Assembly Government (WAG) established a three tiered self-referral Occupational Health Physiotherapy Pilot Project (OHPPP) comprising: 1.) telephone advice and triage, 2.) face-to-face physiotherapy assessment and treatment if required, and 3.) workplace assessment and a return-to-work facilitation package as appropriate. This study aimed to evaluate the feasibility and cost-effectiveness of the pilot service. Methods: A pragmatic cohort study was undertaken, with all OHPPP service users between September 2008 and February 2009 being invited to participate. Participants were assessed on clinical status, yellow flags, sickness absence and work performance at baseline, after treatment and at 3 month follow up. Cost-effectiveness was evaluated from both top-down and bottom-up perspectives and cost per Quality Adjusted Life Year (cost/QALY) was calculated. The cost-effectiveness analysis assessed the increase in service cost that would be necessary before the cost-effectiveness of the service was compromised. Results A total of 515 patients completed questionnaires at baseline. Of these, 486 were referred for face to face assessment with a physiotherapist and were included in the analysis for the current study. 264 (54.3%) and 199 (40.9%) were retained at end of treatment and 3 month follow up respectively. An improvement was observed at follow up in all the clinical outcomes assessed, as well as a reduction in healthcare resource usage and sickness absence, and improvement in self-reported work performance. Multivariate regression indicated that baseline and current physical health were associated with work-related outcomes at follow up. The costs of the service were £194-£360 per service user depending on the method used, and the health gains contributed to a cost/QALY of £1386-£7760, which would represent value for money according to current UK thresholds. Sensitivity analyses demonstrated that the service would remain cost effective until the service costs were increased to 160% per user. Conclusions: This pragmatic evaluation of the OHPPP indicated that it was likely to be feasible in terms of service usage and could potentially be cost effective in terms of QALYs. Further, the study confirmed that improving physical health status for musculoskeletal pain patients is important in reducing problems with work capacity and related costs. This study suggests that this type of service could be potentially be useful in reducing the burden of pain and should be further investigated, ideally via randomised controlled trials assessing effectiveness and cost-effectiveness

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial?

Background Low back pain (LBP) is common in the population and multifactorial in nature, often involving negative consequences. Reassuring information to improve coping is recommended for reducing the negative consequences of LBP. Adding a simple non-threatening explanation for the pain (temporary muscular dysfunction) has been successful at altering beliefs and behavior when delivered with other intervention elements. This study investigates the isolated effect of this specific information on future occupational behavior outcomes when delivered to the workforce. Design A cluster-randomized controlled trial. Methods Publically employed workers (n=505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non-threatening explanation for LBP - the ‘functional-disturbance’-model. Data collections took place monthly over a 1-year period using text message tracking (SMS). Primary outcomes were self-reported days of cutting down usual activities and work participation. Secondary outcomes were self-reported back beliefs, work ability, number of healthcare visits, bothersomeness, restricted activity, use of pain medication, and sadness/depression. Results There was no between-group difference in the development of LBP during follow-up. Cumulative logistic regression analyses showed no between-group difference on days of cutting down activities, but increased odds for more days of work participation in the intervention group (OR=1.83 95% CI: 1.08-3.12). Furthermore, the intervention group was more likely to report: higher work ability, reduced visits to healthcare professionals, lower bothersomeness, lower levels of sadness/depression, and positive back beliefs. Conclusion Reassuring information involving a simple non-threatening explanation for LBP significantly increased the odds for days of work participation and higher work ability among workers who went on to experience LBP during the 12-month follow-up. Our results confirm the potential for public-health education for LBP, and add to the discussion of simple versus multidisciplinary interventions

Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi

Impact of COVID-19-related disruptions to measles, meningococcal A, and yellow fever vaccination in 10 countries

Background:: Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. Methods:: We used two to three models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption). Results:: Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (SIAs) planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people per year until the campaigns are implemented. For meningococcal A vaccination, short-term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1- to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns. Conclusions:: The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination. Funding:: Bill and Melinda Gates Foundation and Gavi, the Vaccine Alliance

Dairying, diseases and the evolution of lactase persistence in Europe

Update notice Author Correction: Dairying, diseases and the evolution of lactase persistence in Europe (Nature, (2022), 608, 7922, (336-345), 10.1038/s41586-022-05010-7) Nature, Volume 609, Issue 7927, Pages E9, 15 September 2022In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years(1). Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions(2,3). Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectoriesthan uniform selection since the Neolithic period. In the UK Biobank(4,5) cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.Peer reviewe

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group

Microduplications of 16p11.2 are associated with schizophrenia

Recurrent microdeletions and microduplications of a 600 kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1-3. Here we report the strong association of 16p11.2 microduplications with schizophrenia in two large cohorts. In the primary sample, the microduplication was detected in 12/1906 (0.63%) cases and 1/3971 (0.03%) controls (P=1.2×10-5, OR=25.8). In the replication sample, the microduplication was detected in 9/2645 (0.34%) cases and 1/2420 (0.04%) controls (P=0.022, OR=8.3). For the series combined, microduplication of 16p11.2 was associated with 14.5-fold increased risk of schizophrenia (95% C.I. [3.3, 62]). A meta-analysis of multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. The reciprocal microdeletion was associated only with autism and developmental disorders. Analysis of patient clinical data showed that head circumference was significantly larger in patients with the microdeletion compared with patients with the microduplication (P = 0.0007). Our results suggest that the microduplication of 16p11.2 confers substantial risk for schizophrenia and other psychiatric disorders, whereas the reciprocal microdeletion is associated with contrasting clinical features