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

Effect of Herbal and Fluoride Mouth Rinses on Streptococcus mutans and Dental Caries among 12–15-Year-Old School Children: A Randomized Controlled Trial

To assess and compare the effect of herbal and fluoride mouth rinses on Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries, a parallel group placebo controlled randomized trial was conducted among 240 schoolchildren (12–15 years old). Participants were randomly divided and allocated into Group I (0.2% fluoride group), Group II (herbal group), and Group III (placebo group). All received 10 ml of respective mouth rinses every fortnight for a period of one year. Intergroup and intragroup comparison were done for Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries. Streptococcus mutans count showed a statistically significant difference between Group I and Group III (p=0.035) and also between Group II and Group III (p=0.039). Glucan concentration levels showed a statistically significant difference (p=0.024) between Group II and Group III at 12th month. Mean DMF scores showed no statistical difference between the three groups (p=0.139). No difference in the level of significance was seen in the intention-to-treat and per-protocol analysis. The present study showed that both herbal and fluoride mouth rinses, when used fortnightly, were equally effective and could be recommended for use in school-based health education program to control dental caries. Trial registration number is CTRI/2015/08/006070

Clinical Study Effect of Herbal and Fluoride Mouth Rinses on Streptococcus mutans and Dental Caries among 12-15-Year-Old School Children: A Randomized Controlled Trial

To assess and compare the effect of herbal and fluoride mouth rinses on Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries, a parallel group placebo controlled randomized trial was conducted among 240 schoolchildren (12-15 years old). Participants were randomly divided and allocated into Group I (0.2% fluoride group), Group II (herbal group), and Group III (placebo group). All received 10 ml of respective mouth rinses every fortnight for a period of one year. Intergroup and intragroup comparison were done for Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries. Streptococcus mutans count showed a statistically significant difference between Group I and Group III ( = 0.035) and also between Group II and Group III ( = 0.039). Glucan concentration levels showed a statistically significant difference ( = 0.024) between Group II and Group III at 12th month. Mean DMF scores showed no statistical difference between the three groups ( = 0.139). No difference in the level of significance was seen in the intention-to-treat and per-protocol analysis. The present study showed that both herbal and fluoride mouth rinses, when used fortnightly, were equally effective and could be recommended for use in school-based health education program to control dental caries. Trial registration number is CTRI/2015/08/006070

Experimental investigation of torsional vibration isolation using Magneto Rheological Elastomer

Rotating systems suffer from lateral and torsional vibrations which have detrimental effect on the roto-dynamic performance. Many available technologies such as vibration isolators and vibration absorbers deal with the torsional vibrations to a certain extent, however passive isolators and absorbers find less application when the input conditions are dynamic. The present work discusses use of a smart material called as Magneto Rheological Elastomer (MRE), whose properties can be changed based on magnetic field input, as a potential isolator for torsional vibrations under dynamic loading conditions. Carbonyl Iron Particles (CIP) of average size 5 μm were mixed with RTV Silicone rubber to form the MRE. The effect of magnetic field on the system parameters was comprehended under impulse loading conditions using a custom built in-house system. Series arrangement of accelerometers were used to differentiate between the torsional and the bending modes of vibration of the system. Impact hammer tests were carried out on the torsional system to study its response, in the presence and absence of magnetic field. The tests revealed a shift in torsional frequency in the presence of magnetic field which elucidates the ability of MRE to work as a potential vibration isolator for torsional systems

Experimental investigation of torsional vibration isolation using Magneto Rheological Elastomer

Rotating systems suffer from lateral and torsional vibrations which have detrimental effect on the roto-dynamic performance. Many available technologies such as vibration isolators and vibration absorbers deal with the torsional vibrations to a certain extent, however passive isolators and absorbers find less application when the input conditions are dynamic. The present work discusses use of a smart material called as Magneto Rheological Elastomer (MRE), whose properties can be changed based on magnetic field input, as a potential isolator for torsional vibrations under dynamic loading conditions. Carbonyl Iron Particles (CIP) of average size 5 μm were mixed with RTV Silicone rubber to form the MRE. The effect of magnetic field on the system parameters was comprehended under impulse loading conditions using a custom built in-house system. Series arrangement of accelerometers were used to differentiate between the torsional and the bending modes of vibration of the system. Impact hammer tests were carried out on the torsional system to study its response, in the presence and absence of magnetic field. The tests revealed a shift in torsional frequency in the presence of magnetic field which elucidates the ability of MRE to work as a potential vibration isolator for torsional systems

The Spectrum of Histomorphological Changes and Pathological Tumor Response following Preoperative Oral Metronomic Chemotherapy in Oral Squamous Cell Carcinoma

Abstract Sithara Aravind Background Oral metronomic chemotherapy (OMCT) represents an emerging concept in cancer treatment involving frequent administration of chemotherapeutic drugs at doses below maximum tolerated doses and with no prolonged drug-free break. OMCT is being tried preoperatively in developing nations with constrained resources to prevent disease progression during the waiting period from diagnosis to surgery (bridge OMCT). The aim of the present study was to assess the spectrum of histomorphological changes and pathological tumor response following bridge OMCT in oral squamous cell carcinoma (OSCC) and to propose a new pathological response scoring system. Materials and Methods A retrospective single-center study comprised of tissue sections of tumor proper and metastatic lymph nodes of 50, locally advanced OSCC patients treated with bridge OMCT, and had completed definitive surgery were analyzed. The present study evaluated the histomorphological features and proposed a new scoring system for pathologic tumor response. The pathologic tumor response was categorized as complete response (pCR), no response (pNR), and partial response (pPR). Results Of the total 50 patients, 2 patients had pCR, 3 had pNR, and 45 patients had pPR as per the new proposed scoring system. Note that 96% of the cases showed no disease progression. Conclusion Bridge OMCT is a novel treatment method that can be used to tide over the waiting period between the diagnosis and surgery in resource-constrained institutions with heavy patient load. This mode of treatment in locally advanced OSCC seems to provide promising results in this setting. Large multicentric trials are warranted to confirm these results

Etiological profile, targeted levothyroxine dosing and impact of partial newborn screening in congenital hypothyroidism—A single centre experience

Background: Congenital hypothyroidism (CH) is the most common cause of preventable intellectual disability. Newborn screening (NBS) for CH has been in vogue in many parts of the world since 1970, but despite its well-known benefits, many developing countries including India have not been able to establish universal NBS for CH till date. Objective: The aim of this study was to review the clinical aspects of congenital hypothyroidism in a tertiary care university referral teaching hospital, focusing on aetiology of CH, predictors of permanence, optimal targeted dose strategies based on aetiology and the effect of newborn screening on the time to diagnosis. Material and Methods: The electronic medical records of 233 children with CH referred to our centre between January 2009 and December 2019 were analysed. A partial NBS was established in the state in 2012. Results: Dyshormonogenesis (57.5%) was the most common aetiology of CH. The incidence of transient CH in children with a gland in situ (GIS) was 35%. Levothyroxine (LT-4) dose of >2.75 μg/kg/day (sensitivity 76.5, specificity 72), >2.15 μg/kg/day (sensitivity 82.4, specificity 61.9) and >1.85 μg/kg/day (sensitivity 76.5, specificity 61.9) at years 1, 2 and 3, respectively, were predictors of permanent CH. An initial LT-4 dose ≥8 μg/kg was sufficient and very seldom led to undertreatment in children with dyshormonogenesis. On the contrary, even doses ≥13 mcg/kg/day led to frequent undertreatment in children with thyroid dysgenesis. After the introduction of newborn screening, the median age at diagnosis came down from 45 days (IQR 14–180 days) to ten days (IQR 3–12 days). Conclusion: Targeted dosing based on aetiology of CH may be more appropriate to optimise outcomes. The time to diagnosis of CH reduced significantly after the adoption of even a partial NBS program highlighting the urgent need for implementation of the same in resource poor settings