ORCID Profile
0000-0002-6784-8319
Current Organisations
Gustave Roussy
,
University of Oxford
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Publisher: Elsevier BV
Date: 02-2021
Publisher: Public Library of Science (PLoS)
Date: 12-01-2021
DOI: 10.1371/JOURNAL.PMED.1003487
Abstract: Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD. We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013–2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose–response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51) for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46) and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies. In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.
Publisher: Oxford University Press (OUP)
Date: 05-07-2019
DOI: 10.1093/IJE/DYZ148
Publisher: BMJ
Date: 20-01-2022
DOI: 10.1136/HEARTJNL-2021-320171
Abstract: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics. We conducted an in idual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists’ Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up. There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was −11.1 (−11.3 to −10.8)/−5.6 (−5.7 to −5.4) mm Hg between active treatment and placebo was −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mm Hg and between active and control arms for drug comparison trials was −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use. These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.
Publisher: Public Library of Science (PLoS)
Date: 06-2021
DOI: 10.1371/JOURNAL.PMED.1003599
Abstract: Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), in which in idual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in in iduals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.
Publisher: SAGE Publications
Date: 2021
DOI: 10.1177/17455065211019717
Abstract: It is important to evaluate sequalae for complex chronic health conditions such as endometriosis and mental health disorders. Endometriosis impacts 1 in 10 women. Mental health outcomes can be a primary determinant in many physical health conditions although this is an area not well researched particularly in women’s health. This has been problematic for endometriosis patients in particular, who report mental health issues as well as other key comorbidities such as chronic pelvic pain and infertility. This could be partly due to the complexities associated with comprehensively exploring overlaps between physical and mental health disorders in the presence of multiple comorbidities and their potential mechanistic relationship. In this evidence synthesis, a systematic methodology and mixed-methods approaches were used to synthesize both qualitative and quantitative data to examine the prevalence of the overlapping sequalae between endometriosis and psychiatric symptoms and disorders. As part of this, an evidence synthesis protocol was developed which included a systematic review protocol that was published on PROSPERO (CRD42020181495). The aim was to identify and evaluate mental health reported outcomes and prevalence of symptoms and psychiatric disorders associated with endometriosis. A total of 34 papers were included in the systematic review and 15 were included in the meta-analysis. Anxiety and depression symptoms were the most commonly reported mental health outcomes while a pooled analysis also revealed high prevalence of chronic pelvic pain and dyspareunia. It is evident that small-scale cross-sectional studies have been conducted in a variety of settings to determine mental health outcomes among endometriosis patients. Further research is required to comprehensively evaluate the mental health sequalae with endometriosis.
Publisher: BMJ
Date: 06-09-2021
DOI: 10.1136/BJSPORTS-2021-104050
Abstract: To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults. Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence. In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen’s kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average in idual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk. Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.
Publisher: Oxford University Press (OUP)
Date: 27-10-2021
DOI: 10.1093/IJE/DYAB228
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JCLINEPI.2012.05.001
Abstract: For systematic reviews, no guidance exists for what review methods support valid conclusions of equivalence (EQ) and noninferiority (NI). To provide such guidance, we convened a workgroup of 13 experienced systematic reviewers from seven evidence-based practice centers (EPCs) and the Agency for Healthcare Research and Quality (AHRQ). The Lead EPC first performed two methods projects intended to assist the workgroup in clarifying the context, prioritizing the issues, targeting the scope, and summarizing the state of the art. Based on expert opinion, we devised guidance in four areas: 1) Unique risk of bias issues for trials self-identifying as EQ-NI trials 2) Setting the reviewer's minimum important difference 3) Analytic foundations for concluding EQ or NI and 4) Language considerations when concluding EQ or NI. This article summarizes the main recommendations, and the full guidance chapter appears on the AHRQ Web site.
Publisher: MDPI AG
Date: 06-06-2022
Abstract: We aimed to examine the associations between cord blood lipids and childhood adiposity and to investigate whether these associations vary across birth weight categories (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) in 1306 infants in the Born in Guangzhou Cohort Study, China. Adiposity outcomes at the age of three years included z-scores of weight-for-length/height (WFLZ), body mass index (BMIZ), subscapular (SSTZ) and triceps skinfold thickness (TSTZ), and the sum of skinfold thicknesses (SSFTZ). Cord blood triglycerides (TG) levels were negatively associated with WFLZ and BMIZ, whereas high density lipoprotein (HDL) levels were positively associated with WFLZ, BMIZ, TSTZ and SSFTZ. These associations were attenuated after adjustment for birth weight. Stratified analyses revealed that total cholesterol (TC) and low-density lipoprotein (LDL) levels were positively associated with childhood adiposity indicators among AGA infants but tended to be negatively associated with the adiposity indicators among LGA infants (p values for interaction .05). Furthermore, TG levels appeared to be positively associated with adiposity indicators among SGA infants but negatively associated with the outcomes among LGA infants (p values for interaction .05). Cord blood lipids levels might be associated with childhood adiposity, and these associations appear to differ across different birth weight categories. If confirmed in future studies, our findings suggest that in idualized management plans might be warranted in preventing obesity.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.JSAMS.2018.10.008
Abstract: To describe the cross-sectional association between musculoskeletal pain at multiple sites and physical work capacity (PWC) and objectively measured physical activity (PA). Observational study. Data from a subs le of the UK Biobank were utilised (n=9856 mean age 58.5 years, mean body mass index 30.2kg/m Increase in number of painful sites was associated with lower PWC, moderate and vigorous PA and increased low intensity PA in a dose-response relationship (all p-values for trend ≤0.001) before and after adjustment for confounders. In site specific analyses, hip pain was associated with an increased low intensity PA (β 52.8min/week, 95% CI 2.3-103.2) and reduced moderate PA (β -50.1min/week, 95% CI -98.5 to -1.8). Knee pain was only associated with vigorous PA (β -5.7min/week, 95% CI -10.0 to -1.3). Pain at neck/shoulder pain and back were not independently associated with PWC and PA. Greater number of painful sites is consistently associated with poorer PWC, increased low intensity PA and reduced moderate to vigorous PA. Clinicians should address the critical role of being physically active in managing chronic musculoskeletal pain and interventions targeting musculoskeletal pain may be needed to increase PA levels.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Oxford University Press (OUP)
Date: 14-09-2021
DOI: 10.1093/IJE/DYAB199
Abstract: Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data. Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL) secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models. Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10–2.58)] and subtypes ALL [1.49 (0.87–2.56)] and AML [2.70 ([0.93–7.86)], but not with any cancer [1.13 (0.85–1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06–2.34)], ALL [1.43 (0.94–2.19)], AML [2.37 (1.10–5.12)] and any cancer [1.33 (1.09–1.63)] influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes. Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-01-2023
DOI: 10.1200/JCO.22.00393
Abstract: Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with RET fusion–positive non–small-cell lung cancer (NSCLC). We provide a registrational data set update in more than double (n = 316) of the original reported population (n = 144) and better characterization of long-term efficacy and safety. Patients were enrolled to LIBRETTO-001, a phase I/II, single-arm, open-label study of selpercatinib in patients with RET-altered cancers. An analysis of patients with RET fusion–positive NSCLC, including 69 treatment-naive and 247 with prior platinum-based chemotherapy, was performed. The primary end point was objective response rate (ORR RECIST v1.1, independent review committee). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival, and safety. In treatment-naive patients, the ORR was 84% (95% CI, 73 to 92) 6% achieved complete responses (CRs). The median DoR was 20.2 months (95% CI, 13.0 to could not be evaluated) 40% of responses were ongoing at the data cutoff (median follow-up of 20.3 months). The median PFS was 22.0 months 35% of patients were alive and progression-free at the data cutoff (median follow-up of 21.9 months). In platinum-based chemotherapy pretreated patients, the ORR was 61% (95% CI, 55 to 67) 7% achieved CRs. The median DoR was 28.6 months (95% CI, 20.4 to could not be evaluated) 49% of responses were ongoing (median follow-up of 21.2 months). The median PFS was 24.9 months 38% of patients were alive and progression-free (median follow-up of 24.7 months). Of 26 patients with measurable baseline CNS metastasis by the independent review committee, the intracranial ORR was 85% (95% CI, 65 to 96) 27% were CRs. In the full safety population (n = 796), the median treatment duration was 36.1 months. The safety profile of selpercatinib was consistent with previous reports. In a large cohort with extended follow-up, selpercatinib continued to demonstrate durable and robust responses, including intracranial activity, in previously treated and treatment-naive patients with RET fusion–positive NSCLC.
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2021
DOI: 10.1101/2021.02.19.21252066
Abstract: Evidence from randomised trials on long-term blood pressure (BP) reduction from pharmacologic treatment is limited. To investigate the effects of antihypertensive drugs on long-term BP change and examine its variation over time and among people with different clinical characteristics In idual participant-level data meta-analysis The Blood Pressure Lowering Treatment Trialists’ Collaboration involving 51 large-scale long-term randomised clinical trials 352,744 people (42% women) with mean age of 65 years and mean baseline systolic/diastolic BP of 152/87 mmHg, of whom 18% were current smokers, 50% had cardiovascular disease, 29% had diabetes, and 72% were taking antihypertensive treatment at baseline Pharmacological BP-lowering treatment Difference in longitudinal changes in systolic and diastolic BP between randomised treatment arms over an average follow-up of four years Drugs were effective in lowering BP, with the maximum effect becoming apparent after 12-month follow-up and with gradual attenuation towards later years. Based on measures taken ≥12 months post-randomisation, more intense BP-lowering treatment reduced systolic/diastolic BP (95% confidence interval) by −11.2 (−11.4 to −11.0)/−5.6 (−5.8 to −5.5) mmHg than less intense treatment active treatment by −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mmHg lower than placebo, and active arm by −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mmHg lower than the control arm for drug class comparison trials. BP reductions were consistently observed across a wide range of baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes, and prior antihypertensive treatment use. Pharmacological agents were effective in lowering long-term BP among in iduals with a wide range of characteristics, but the net between-group reductions were modest, which is partly attributable to the intended trial goals.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-09-2023
DOI: 10.1200/JCO.23.01476
Publisher: Elsevier BV
Date: 04-2021
Publisher: Oxford University Press (OUP)
Date: 05-02-2019
DOI: 10.1093/IJE/DYY294
Abstract: Physical inactivity is associated with an increased risk of major chronic diseases, although uncertainty exists about which chronic diseases, themselves, might contribute to physical inactivity. The objective of this study was to compare the physical activity of those with chronic diseases to healthy in iduals using an objective measure of physical activity. We conducted a cross-sectional analysis of data from 96 706 participants aged 40 years or older from the UK Biobank prospective cohort study (2006–10). Diagnoses were identified through ICD 9 and 10 coding within hospital admission records and a cancer registry linked to UK Biobank participants. We extracted summary physical activity information from participants who wore a wrist-worn triaxial accelerometer for 7 days. Statistical analyses included computation of adjusted geometric means and means using general linear models. Participants with chronic disease undertook 9% or 61 minutes (95% confidence interval: 57.8–64.8) less moderate activity and 11% or 3 minutes (95% confidence interval: 2.7–3.3) less vigorous activity per week than in iduals without chronic disease. Participants in every chronic-disease subgroup undertook less physical activity than those without chronic disease. Sixty-seven diagnoses within these subgroups were associated with lower moderate activity. The cross-sectional association of physical activity with chronic disease is broad. Given the substantial health benefits of being physically active, clinicians and policymakers should be aware that their patients with any chronic disease are at greater health risk from other diseases than anticipated because of their physical inactivity.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Rema Ramakrishnan.