A study of efficacy of subcision, micro-needling and carbon dioxide fractional laser for treatment of acne scars

Background: Acne vulgaris is one of the most common skin problem encountered in adolescents. Complication of acne may lead to scar formation. Types of acne scars are atrophic scars (ice pick, rolling scars and box scar), hypertrophic scar and keloidal scar. Multiple modalities for treating acne scars are chemical peeling, derma roller, subcision, punch excision, cryoroller, CROSS (chemical reconstruction of skin scars), fractional lasers, etc. This study is to study the efficacy of derma roller, subcision and CO2 fractional laser in acne scar and complications associated with them.Methods: Total 45 patients with grade 2, 3 and 4 atrophic acne scar (Goodman and Baron grading system) were enrolled in the study and randomly assigned in three groups of 15 patients each. Group A: Derma roller, Group B: Subcision, Group C: CO2 fractional laser. 3 sittings at 28 days interval were done in each group. Evaluation was done by standardized digital photography pre-procedure and at each sitting. Physician’s evaluation was done in terms of excellent, good, fair, poor improvement or worsening. Patient’s self-evaluates as excellent, good, fair, poor improvement or worsening.Results: According to physicians evaluation at the end of 3 sittings excellent response was seen in 20% (n=3), 13.33% (n=2), 6.67% (n=1) in group B, group C, group A respectively. According to self-evaluation by patient at the end of 3 sittings, overall, 44.44% (n=20) patients showed an excellent response (score of 8-10).Conclusions: Time tested procedures; like subcision if done adequately and properly have excellent response and is comparable to newer and costly treatment like CO2 fractional laser.

Estimation of serum 25 hydroxy vitamin D level and its correlation with metabolic and endocrine dysregulation in women with PCOS

Background: Polycystic ovarian syndrome is the most common hormonal disturbance in the reproductive age women, with prevalence of 5-10%. Vitamin D deficiency is common in women with or without PCOS. The aim of this study was to assess association of serum vitamin D level with metabolic and endocrine dysregulation in women with PCOS.Methods: This cross-sectional study was done over a period of one year. 100 women of age group 20-40 years were divided in group A 30 (BMI >30 mg/m2) with PCOS, group B 20 (BMI <25 mg/m2) with PCOS, group C 50 controls and were investigated for serum FSH, LH, LH/FSH ratio, S. total testosterone, S. postprandial insulin level, glucose insulin ratio, 25 hydroxy vitamin D level.Results: LH/FSH ratio >2 (33.33% in obese and 50% in non-obese), serum total testosterone level >0.8ng/ml (80% in obese and 75% in non-obese) (p value was significant between study group as well as between study and control group). Serum fasting, postprandial blood glucose, postprandial serum insulin level was elevated in obese than non-obese PCOS. 25 (OH) vitamin D deficiency <20 ng/ml (56.675% in obese and 45% in non-obese). So, vitamin D deficiency was more common in obese PCOS.Conclusions: PCOS is more common in age group of 20-40 years. There is more Insulin resistance in obese PCOS as compared to non-obese PCOS. Vitamin D deficiency is comparatively more common in obese PCOS population than in non-obese PCOS.

Incidence of colonization of preterm neonates’ gastric aspirate and its correlation with neonatal, maternal and environmental risk factors

Background: Infants born with Very Low Birth Weight (< 1500 grams) and Extremely Low Birth Weight (< 1000 grams) are at a high risk of pre-discharge morbidities. Aim of our study was to know the incidence of colonization of the preterm neonates’ gastric aspirate and to co-relate it with the various neonatal, maternal and environmental risk factors. Material and Methods: This was a prospective, observational study in 100 neonates conducted over a period of two years at Pediatrics Department of a teaching hospital of Western Gujarat region. All pre-term newborns who did not have any clinical features for sepsis were included in the study. Results: In our study, most common organisms isolated were enterococcus (41%) followed by bacteroids (26%) and staphylococcus (14%) in 24 hours & 72 hours of gastric aspirate sample. Lower gestation age and low birth weight were significantly associated with colonization of the preterm neonatal gut (p<0.05). The positive colonization was also significantly correlated to low APGAR score. Highest incidence of neonatal sepsis was seen with enterococci organism (14.6%), where six newborns with enterococci isolates in gastric aspirate had developed neonatal sepsis, followed by E. coli isolates (12.5%). Conclusions: We found a high incidence of colonization of the preterm neonates’ gut, with enterococcus being the most common isolate. A significant association was observed between gut colonization and development of neonatal sepsis. Significant factors for development of gut colonization were: lower gestation age, multiple per-vaginal examinations and low birth weight of the newborns

A comparative study of the effect of dexmedetomidine and lignocaine on hemodynamic responses and recovery following tracheal extubation in patients undergoing intracranial surgery

Background: Recovery from general anesthesia and extubation is a period of intense physiological stress for patients. The most feared complications after intracranial surgery are development of an intracranial hematoma and major cerebral edema. Both may result in cerebral hypoperfusion and brain injury. Thus, the anesthetic emergence of a neurosurgical patient should include maintenance of stable respiratory and cardiovascular parameters. Minimal reaction to the endotracheal tube removal prevents sympathetic stimulation and increases in venous pressure. In our study, we compared dexmedetomidine HCl, lignocaine HCl and placebo to blunt stress response and providing a smooth transition from extubation phase.Methods: 75 ASA Grade I and II patients aged 18-60 years scheduled for elective intracranial surgery for intracranial space occupying lesions were randomly divided into three groups of 25 each. Balanced general anesthesia was given. Inhalation anesthetic was discontinued and after return of spontaneous respiration patient in Group D received injection dexmedetomidine 0.5 µg/kg intravenous (IV), Group X received injection lignocaine 1.5 mg/kg IV and Group P received 10 ml normal saline IV over 60 sec. Heart rate (HR), mean arterial pressure (MAP), quality of extubation were measured at 1, 3, 5, 10, 15 mins interval after extubation. Emergence time and extubation time were noted and quality of extubation was evaluated on cough grading.Results: There was a significant decrease in MAPs and HR in Group D as compared to Group L and Group P (p<0.05) at all-time interval after extubation. Extubation quality score of the majority of patients was 1 in Group D, 2 in Group X, and 3 in Group P (p<0.001). The duration of emergence and extubation were comparable in all three groups. Sedation score of the most patient was 3 (44%) in Group D and 2 (56%) in Group X. Six patients in Group D and 1 patient in Group X had bradycardia.Conclusion: Single bolus dose of IV dexmedetomidine HCl 0.5 mg/kg given before tracheal extubation effectively attenuates hemodynamic response to extubation as compared to 1.5 mg/kg lignocaine HCl

Consequence and Prevention of Haemodynamic Stress Response during Laryngoscopy and Endotracheal Intubation with Oral Ivabradine- A Multicentric Randomised Controlled Study

Introduction: Laryngoscopy and intubation cause lots of haemodynamic changes which adversely affects the patient during the perioperative period. Various methods have been applied to reduce stress response in high risk patients. Ivabradine is a unique cardiotonic drug which reduces the heart rate without compromising blood pressure, specially in debilitating and severely ill patients. Aim: To evaluate role of oral ivabradine in attenuating the haemodynamic stress response to laryngoscopy, intubation and extubation in patients undergoing surgical procedure under General Anaesthesia (GA) and to note the side-effects and its complications, if any. Materials and Methods: A randomised controlled multicentric study was conducted in 200 American Society of Anaesthesiologists’ (ASA)-I and II patients undergoing various surgery under general anaesthesia. The patients were randomly divided into two groups: group A (Test group, n=100) received 5 mg oral ivabradine one hour before intubation, group B (Control group, n=100) received placebo. The pulse rate, Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) were recorded at intubation and 10 minutes postintubation along with at extubation and postintubation period till 10 minutes. Patients were monitored for haemodynamic changes as per the protocol. Statistics analysis was done using Statistical Package of Social Science (SPSS) software version 21.0. Results: Demographic findings were comparable in both groups. Heart rate (84.36±4.11 versus 114.19±12.4), SBP (120±10.5 versus 150±17.5), DBP (76.08±4.29 versus 113.2±10.6), MAP (91.3±6.7 versus 124.4±12.8) at 10 minutes postintubation decreased more in test group as compared to control group from baseline (p-value <0.005). Similarly, heart rate (84.13±2.06 versus 110.58±8.92), SBP (123.4±10.06 versus 150.8±13.1), DBP (84.08±2.02 versus 107±10.2), MAP (97.8±6.47 versus 122.06±9.7) at 10 minutes postintubation decreased significantly in test group as compared to control group from baseline (p-value <0.005). Conclusion: Oral ivabradine is a very useful cardiotonic drug which facilitates the fluctuation in heart rate during laryngoscopy and endotracheal intubation

A comparison of the effects of physical and chemical mutagens in sesame (Sesamum indicum L.)

Three sesame genotypes (Rama, SI 1666 and IC 21706) were treated with physical (γ-rays: 200 Gy, 400 Gy or 600 Gy) or chemical (ethyl methane sulphonate, EMS: 0.5%, 1.0%, 1.5% or 2.0%) mutagens and their mutagenic effectiveness and efficiency were estimated in the M 2 generation. The M 3 generation was used to identify the most effective mutagen and dose for induction of mutations. The average effectiveness of EMS was much higher than γ-rays. The lowest dose of γ-rays (200 Gy) and the lowest concentration of EMS (0.5%) showed the highest mutagenic efficiency in all genotypes. Analysis of the M 3 generation data based on parameters such as the variance ratio and the difference in residual variances derived from the model of Montalván and Ando indicated that 0.5% concentration of EMS was the most effective treatment for inducing mutations

Fine mapping and sequence analysis reveal a promising candidate gene encoding a novel NB-ARC domain derived from wild rice (Oryza officinalis) that confers bacterial blight resistance

Bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious constraints in rice production. The most sustainable strategy to combat the disease is the deployment of host plant resistance. Earlier, we identified an introgression line, IR 75084-15-3-B-B, derived from Oryza officinalis possessing broad-spectrum resistance against Xoo. In order to understand the inheritance of resistance in the O. officinalis accession and identify genomic region(s) associated with resistance, a recombinant inbred line (RIL) mapping population was developed from the cross Samba Mahsuri (susceptible to bacterial blight) × IR 75084-15-3-B-B (resistant to bacterial blight). The F2 population derived from the cross segregated in a phenotypic ratio of 3: 1 (resistant susceptible) implying that resistance in IR 75084-15-3-B-B is controlled by a single dominant gene/quantitative trait locus (QTL). In the F7 generation, a set of 47 homozygous resistant lines and 47 homozygous susceptible lines was used to study the association between phenotypic data obtained through screening with Xoo and genotypic data obtained through analysis of 7K rice single-nucleotide polymorphism (SNP) chip. Through composite interval mapping, a major locus was detected in the midst of two flanking SNP markers, viz., Chr11.27817978 and Chr11.27994133, on chromosome 11L with a logarithm of the odds (LOD) score of 10.21 and 35.93% of phenotypic variation, and the locus has been named Xa48t. In silico search in the genomic region between the two markers flanking Xa48t identified 10 putatively expressed genes located in the region of interest. The quantitative expression and DNA sequence analysis of these genes from contrasting parents identified the Os11g0687900 encoding an NB-ARC domain-containing protein as the most promising gene associated with resistance. Interestingly, a 16-bp insertion was noticed in the untranslated region (UTR) of the gene in the resistant parent, IR 75084-15-3-B-B, which was absent in Samba Mahsuri. The association of Os11g0687900 with resistance phenotype was further established by sequence-based DNA marker analysis in the RIL population. A co-segregating PCR-based INDEL marker, Marker_Xa48, has been developed for use in the marker-assisted breeding of Xa48t

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions