The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Obtuse marginal coronary artery aneurysm on CT coronary angiogram

Coronary artery aneurysms are rare. We present an unusual case of an isolated coronary artery aneurysm in the obtuse marginal artery detected on a computed tomographic coronary angiogram, which is unlikely to be significant for the patient. A Medline literature search did not find a similar case. Keywords: CT coronary angiogram, Coronary artery aneurysm, Obtuse marginal arter

Neurobiological evidence for thalamic, hippocampal and related glutamatergic abnormalities in bipolar disorder: A review and synthesis

10.1016/j.neubiorev.2008.10.001Neuroscience and Biobehavioral Reviews333336-354NBRE

Balanced steady-state free precession fMRI with intravascular susceptibility contrast agent

One major challenge in echo planar imaging-based functional MRI (fMRI) is the susceptibility-induced image distortion. In this study, a new cerebral blood volume-weighted fMRI technique using distortion-free balanced steady-state free precession (bSSFP) sequence was proposed and its feasibility was investigated in rat brain at 7 Tesla. After administration of intravascular susceptibility contrast agent (monocrystalline iron oxide nanoparticle [MION] at 15 mg/kg), unilateral visual stimulation was presented using a block-design paradigm. With repetition time/echo time = 3.8/1.9 ms and α = 18°, bSSFP fMRI was performed and compared with the conventional cerebral blood volume-weighted fMRI using post-MION gradient echo and spin echo echo planar imaging. The results showed that post-MION bSSFP fMRI provides comparable sensitivity but with no severe image distortion and signal dropout. Robust negative responses were observed during stimulation and activation patterns were in excellent agreement with known neuroanatomy. Furthermore, the post-MION bSSFP signal was observed to decrease significantly during hypercapnia challenge, indicating its sensitivity to cerebral blood volume changes. These findings demonstrated that post-MION bSSFP fMRI is a promising alternative to conventional cerebral blood volume-weighted fMRI. This technique is particularly suited for fMRI investigation of animal models at high field. © 2011 Wiley Periodicals, Inc

The African sharptooth catfish Clarias gariepinus can tolerate high levels of ammonia in its tissues and organs during four days of aerial exposure

10.1086/430691Physiological and Biochemical Zoology784630-640PBZO

BOLD responses in the superior colliculus and lateral geniculate nucleus of the rat viewing an apparent motion stimulus

In rats, the superior colliculus (SC) is a main destination for retinal ganglion cells and is an important subcortical structure for vision. Electrophysiology studies have observed that many SC neurons are highly sensitive to moving objects, but complementary non-invasive functional imaging studies with larger fields of view have been rarely conducted. In this study, BOLD fMRI is used to measure the SC and nearby lateral geniculate nucleus' (LGN) hemodynamic responses, in normal adult Sprague Dawley (SD) rats, during a dynamic visual stimulus similar to those used in long-range apparent motion studies. The stimulation paradigm consists of four light spots arranged in a linear array and turned on and off sequentially at different rates to create five effective speeds of motion (7, 14, 41, 82, and 164°/s across the visual field). Stationary periods (same light spot always on) are interleaved between the moving periods. The speed response function (SRF), the hemodynamic response amplitude at each speed tested, is measured. Significant responses are observed in the SC and LGN at all speeds. In the SC, the SRF increases monotonically from 7 to 82°/s. The minimum response amplitude occurs at 164°/s. The results suggest that the SC is sensitive to slow moving visual stimuli but the hemodynamic response is reduced at higher speeds. In the LGN, the SRF exhibits a similar trend to that of the SC, but response amplitude during 7°/s stimulation is comparable to that during 164°/s stimulation. These findings are in good agreement with previous electrophysiology studies conducted on albino rats like the SD strain. This work represents the first fMRI study of stimulus speed dependence in the SC and is also the first fMRI study of motion responsiveness in the rat. © 2011 Elsevier Inc

Functional magnetic resonance imaging of sound pressure level encoding in the rat central auditory system

Intensity is an important physical property of a sound wave and is customarily reported as sound pressure level (SPL). Invasive techniques such as electrical recordings, which typically examine one brain region at a time, have been used to study neuronal encoding of SPL throughout the central auditory system. Non-invasive functional magnetic resonance imaging (fMRI) with large field of view can simultaneously examine multiple auditory structures. We applied fMRI to measure the hemodynamic responses in the rat brain during sound stimulation at seven SPLs over a 72. dB range. This study used a sparse temporal sampling paradigm to reduce the adverse effects of scanner noise. Hemodynamic responses were measured from the central nucleus of the inferior colliculus (CIC), external cortex of the inferior colliculus (ECIC), lateral lemniscus (LL), medial geniculate body (MGB), and auditory cortex (AC). BOLD signal changes generally increase significantly (p < 0.001) with SPL and the dependence is monotonic in CIC, ECIC, and LL. The ECIC has higher BOLD signal change than CIC and LL at high SPLs. The difference between BOLD signal changes at high and low SPLs is less in the MGB and AC. This suggests that the SPL dependences of the LL and IC are different from those in the MGB and AC and the SPL dependence of the CIC is different from that of the ECIC. These observations are likely related to earlier observations that neurons with firing rates that increase monotonically with SPL are dominant in the CIC, ECIC, and LL while non-monotonic neurons are dominant in the MGB and AC. Further, the IC's SPL dependence measured in this study is very similar to that measured in our earlier study using the continuous imaging method. Therefore, sparse temporal sampling may not be a prerequisite in auditory fMRI studies of the IC. © 2012 Elsevier Inc.