Debbie A Lawlor

Bio: Debbie A Lawlor is an academic researcher from University of Bristol. The author has contributed to research in topics: Population & Body mass index. The author has an hindex of 147, co-authored 1114 publications receiving 101123 citations. Previous affiliations of Debbie A Lawlor include Southampton General Hospital & University of Vermont.

Trajectories of child emotional and behavioural difficulties before and during the COVID-19 pandemic in a longitudinal UK cohort

Abstract: ImportanceCOVID-19 public health mitigation measures are likely to have detrimental effects on emotional and behavioural problems in children However, longitudinal studies with pre-pandemic data are scarce ObjectiveTo explore trajectories of childrens emotional and behavioural difficulties during the COVID-19 pandemic Design and settingData were from children from the third generation of a birth cohort study; the Avon Longitudinal Study of Parents and Children - Generation 2 (ALSPAC-G2) in the southwest of England ParticipantsThe study population comprised of 708 children (median age at COVID-19 data collection was 44 years, SD=29, IQR= [22 to 69]), whose parents provided previous pre-pandemic surveys and a survey between 26 May and 5 July 2020 that focused on information about the COVID-19 pandemic as restrictions from the first lockdown in the UK were eased ExposuresWe employed multi-level mixed effects modelling with random intercepts and slopes to examine whether childrens trajectories of emotional and behavioural difficulties (a combined total difficulties score) during the pandemic differ from expected pre-pandemic trajectories Main outcomesChildren had up to seven measurements of emotional and behavioural difficulties from infancy to late childhood, using developmentally appropriate scales such as the Emotionality Activity Sociability Temperament Survey in infancy and Strengths and Difficulties Questionnaire in childhood ResultsThe observed normative pattern of childrens emotional and behavioural difficulties pre-pandemic, was characterised by an increase in scores during infancy peaking around the age of 2, and then declining throughout the rest of childhood Pre-pandemic, the decline in difficulties scores after age 2 was 06 points per month; but was approximately one third of that in post-pandemic trajectories (there was a difference in mean rate of decline after age 2 of 02 points per month in pre vs during pandemic trajectories [95 % CI: 010 to 030, p <0001]) This lower decline in scores over the years translated to older children having pandemic difficulty scores higher than would be expected from pre-pandemic trajectories (for example, an estimated 100 point (equivalent of 08 standard deviations) higher score (95% CI: 50 to 150) by age 85 years) Results remained similar although somewhat attenuated after adjusting for maternal anxiety and age Conclusion and relevanceThe COVID-19 pandemic may be associated with greater persistence of emotional and behavioural difficulties after the age 2 Emotional difficulties in childhood predict later mental health problems Further evidence and monitoring of emotional and behavioural difficulties are required to fully understand the potential role of the pandemic on young children Key FindingsO_ST_ABSQuestionC_ST_ABSHow has the COVID-19 pandemic influenced emotional difficulties in young children? FindingsUsing repeated longitudinal data from before and during the pandemic we provide evidence that emotional difficulty scores of primary school aged children are higher by an estimated 100 points (08 standard deviations) (95% CI: 50 to 150) by age 85 years than would be expected based on pre pandemic data MeaningThe level of difference in emotional difficulties found in the current study has been linked to increased likelihood of mental health problems in adolescence and adulthood Therefore, this increase in difficulties needs careful monitoring and support

Adverse socioeconomic position across the lifecourse increases coronary heart disease risk cumulatively: findings from the British women’s heart and health study

Abstract: To examine the associations of childhood and adult measurements of socioeconomic position with coronary heart disease (CHD) risk. Cross sectional and prospective analysis of a cohort of 4286 British women who were aged 60–79 years at baseline. Among these women there were …

Geographical variation in cardiovascular incidence: results from the British Women's Heart and Health Study

Abstract: Prevalence of cardiovascular disease (CVD) in women shows regional variations not explained by common risk factors. Analysis of CVD incidence will provide insight into whether there is further divergence between regions with increasing age. Seven-year follow-up data on 2685 women aged 59-80 (mean 69) at baseline from 23 towns in the UK were available from the British Women's Heart and Health Study. Time to fatal or non-fatal CVD was analyzed using Cox regression with adjustment for risk factors, using multiple imputation for missing values. Compared to South England, CVD incidence is similar in North England (HR 1.05 (95% CI 0.84, 1.31)) and Scotland (0.93 (0.68, 1.27)), but lower in Midlands/Wales (0.85 (0.64, 1.12)). Event severity influenced regional variation, with South England showing lower fatal incident CVD than other regions, but higher non-fatal incident CVD. Kaplan-Meier plots suggested that regional divergence in CVD occurred before baseline (before mean baseline age of 69). In women, regional differences in CVD early in adult life do not further diverge in later life. This may be due to regional differences in early detection, survivorship of women entering the study, or event severity. Targeting health care resources for CVD by geographic variation may not be appropriate for older age-groups.

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women

Abstract: Anti-Mullerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in MCM8 has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10 -8 : the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 , and CDCA7 . The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (r g = 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the AMH gene and three other loci that may affect circulating AMH levels in women.

Bias from questionnaire invitation and response in COVID-19 research: an example using ALSPAC

Abstract: Background: Longitudinal studies are crucial for identifying potential risk factors for infection with, and consequences of, COVID-19, but relationships can be biased if they are associated with invitation and response to data collection. We describe factors relating to questionnaire invitation and response in COVID-19 questionnaire data collection in a multigenerational birth cohort (the Avon Longitudinal Study of Parents and Children, ALSPAC). Methods: We analysed online questionnaires completed between the beginning of the pandemic and easing of the first UK lockdown by participants with valid email addresses who had not actively disengaged from the study. We assessed associations of pre-pandemic sociodemographic, behavioural, anthropometric and health-related factors with: i) being sent a questionnaire; ii) returning a questionnaire; and iii) item response (for specific questions). Analyses were conducted in three cohorts: the index children born in the early 1990s (now young adults; 41 variables assessed), their mothers (35 variables) and the mothers’ partners (27 variables). Results: Of 14,849 young adults, 41% were sent a questionnaire, of whom 57% returned one. Item response was >95%. In this cohort, 78% of factors were associated with being sent a questionnaire, 56% with returning one, and, as an example of item response, 20% with keyworker status response. For instance, children from mothers educated to degree-level had greater odds of being sent a questionnaire (OR=5.59; 95% CI=4.87-6.41), returning one (OR=1.60; 95% CI=1.31-1.95), and responding to items (e.g., keyworker status OR=1.65; 95% CI=0.88-3.04), relative to children from mothers with fewer qualifications. Invitation and response rates and associations were similar in all cohorts. Conclusions: These results highlight the importance of considering potential biases due to non-response when using longitudinal studies in COVID-19 research and interpreting results. We recommend researchers report response rates and factors associated with invitation and response in all COVID-19 observational research studies, which can inform sensitivity analyses.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …