Аналіз публічних закупівель лікарських засобів для лікування хворих на епілепсію

Aim. To analyze public procurement of medicines for the treatment of patients with epilepsy using methods of clinical and economic analysis.Materials and methods. For the study, the official data of the Ministry of Health of Ukraine for 2014-2018 concerning public procurement of antiepileptic drugs were used. The total amount of public procurement of medicines for all trade names was determined, and the sums of purchases were grouped by international nonproprietary names. To conduct the analysis of public procurement of antiepileptic drugs, ABC and VEN analyses were performed. Based on the results of the integrated ABC / VEN analysis the volumes of procurement costs were ranked taking into account the requirements of the regulatory framework providing medical and pharmaceutical care for patients with epilepsy.Results. According to the results of the study it was found that during 2014-2018 the average growth rate of public procurement of antiepileptic drugs in UAH equivalent was 136 %, and in dollar equivalent – 110 %. It was determined that in 2018 the volume of expenditures per patient for the purchase of antiepileptic drugs in UAH equivalent increased by 305 % compared to 2014. However, the volume of expenditures in terms of US dollars in 2018 increased only by 22 % compared to 2014. It is due to the fact that in 2014 there were crisis processes at the financial market of Ukraine, which led to an increase in the price of medicines and had a direct impact on the volume of expenses for the purchase of medicines. It has been proven that during 2014-2018 in the volume of public procurement there is a negative trend of prevalence of antiepileptic drugs of foreign manufacture. Thus, the ratio of the volume of costs for the purchase of foreign drugs to domestic ones amounted to 87 % to 13 %, respectively. The analysis of public procurement by the lines of therapy determined that the main share of the expenses belonged to the first-line pharmacotherapy drugs. The ABC analysis showed that the total government spending on the purchase of antiepileptic drugs had uneven dynamics. The results of the VEN analysis indicated that any antiepileptic drugs for INN were not assigned to the category “N”. According to the results of the integrated ABC / VEN analysis it was found that the share of expenses from group A / V in the total amount of the antiepileptic drugs purchased ranged from 70.1 % (2014) to 72.8 % (2018).Conclusions. The results of the study can be used in the development of scientific and applied approaches to the organization of effective financing of pharmaceutical care in Ukraine.Цель: анализ публичных закупок лекарственных средств для лечения больных эпилепсией с использованием методов клинико-экономического анализа.Материалы и методы. Для проведения исследования были использованы официальные данные МОЗ Украины за 2014-2018 гг. по объемам публичных закупок противоэпилептических препаратов. Определена общая сумма публичных закупок лекарственных препаратов по всем торговым наименованиям и проведено группирование сумм закупок по международным непатентованным названиям. Публичные закупки противоэпилептических препаратов нами проанализированы с помощью АВС- и VEN-анализа. По результатам интегрированного ABC / VEN-анализа проведено ранжирование объемов затрат на закупки с учетом требований нормативно-правовой базы, регулирующей предоставление медицинской и фармацевтической помощи больным эпилепсией.Результаты. По результатам исследования установлено, что в течение 2014-2018 гг. средний темп роста объемов публичных закупок ПЭП в гривневом эквиваленте имел значение 136 %, а в долларовом – 110 %. Определено, что в 2018 г. объемы расходов на одного больного на закупку противоэпилептических препаратов в гривневом эквиваленте выросли на 305 % по сравнению с 2014 г. Вместе с тем объем расходов в пересчете на дол. США в 2018 г. увеличился только на 22 % по сравнению с 2014 г. Это обусловлено тем, что в 2014 г. произошли кризисные процессы на финансовом рынке Украины, которые привели к росту цен на лекарственные средства и оказывали непосредственное влияние на объемы расходов на закупку лекарств. Доказано, что в течение 2014-2018 гг. в объемах публичных закупок наблюдается негативная тенденция превалирования противоэпилептических препаратов иностранного производства. Так, соотношение объемов затрат на закупки иностранных и отечественных препаратов составило 87 и 13 % соответственно. Анализ публичных закупок по линиям терапии определил, что основная доля расходов принадлежала препаратам первой линии фармакотерапии. Проведенный АВС-анализ показал, что общие объемы государственных расходов на закупку противоэпилептических препаратов имели неравномерную динамику. Результаты VEN-анализа свидетельствуют, что к категории «N» не было отнесено ни одного ПЭП по МНН. По итогам интегрированного АВС / VEN анализа установлено, что доля расходов из группы А/V в общей сумме закупленных ПЭП колебались от 70,1 % (2014) до 72,8 % (2018).Выводы. Результаты исследования могут быть использованы в разработке научно-прикладных подходов к организации эффективного финансирования предоставления фармацевтической помощи в Украине.Мета: аналіз публічних закупівель лікарських засобів для лікування хворих на епілепсію з використанням методів клініко-економічного аналізу.Матеріали та методи. Для проведення дослідження були використані офіційні дані МОЗ України за 2014-2018 рр. щодо обсягів публічних закупівель протиепілептичних препаратів. Визначена загальна сума публічних закупівель лікарських препаратів за всіма торговими назвами та проведено групування сум закупівель за міжнародними непатентованими назвами. Публічні закупівлі протиепілептичних препаратів були проаналізовані за допомогою АВС- та VEN-аналізу. За результатами інтегрованого ABC/VEN-аналізу проведено ранжування обсягів витрат на закупівлі з урахуванням вимог нормативно-правової бази, що регулює надання медичної та фармацевтичної допомоги хворим на епілепсію.Результати. За результатами дослідження встановлено, що протягом 2014-2018 рр. середній темп росту обсягів публічних закупівель ПЕП у гривневому еквіваленті мав значення 136 %, а у доларовому – 110 %. Визначено, що у 2018 р. обсяги витрат на одного хворого на закупівлю протиепілептичних препаратів у гривневому еквіваленті зросли на 305 % порівняно з 2014 р. Разом з тим обсяг витрат у перерахунку на дол. США у 2018 р. збільшився тільки на 22 % порівняно з 2014 р. Це обумовлено тим, що у 2014 р. відбулися кризові процеси на фінансовому ринку України, що призвели до зростання цін на лікарські засоби та чинили безпосередній вплив на обсяги витрат на закупівлю ліків. Доведено, що протягом 2014-2018 рр. в обсягах публічних закупівель спостерігається негативна тенденція превалювання протиепілептичних препаратів іноземного виробництва. Так, співвідношення обсягів витрат на закупівлі іноземних і вітчизняних препаратів склало 87 та 13 % відповідно. Аналіз публічних закупівель за лініями терапії визначив, що основна частка витрат припадала на препарати першої лінії фармакотерапії. Проведений АВС-аналіз показав, що задинаміку. Результати VEN-аналізу свідчать, що до категорії «N» не було віднесено жодного ПЕП за МНН. За підсумками інтегрованого АВС/VEN аналізу встановлено, що частка витрат з групи А/V у загальній сумі закуплених ПЕП коливались від 70,1 % (2014 р.) до 72,8 % (2018 р.).Висновки. Результати дослідження можуть бути використанні у розробці науково-прикладних підходів до організації ефективного фінансування надання фармацевтичної допомоги в Україні

Дослідження показників захворюваності населення на епілепсію в Україні на державному та регіональному рівнях

Aim. To analyze the dynamics of the epileptic population morbidity rate in Ukraine in its administrative and territorial regions.Materials and methods. The study was conducted within 2013-2017 according to the official data of the State Institution “Center for Medical Statistics of the Ministry of Health of Ukraine”. The logical, mathematical and statistical, system-analytical, retrospective and comparative methods of analysis were used.Results. The study has found that the minimum number of epileptic patients among the population of Ukraine for 2013-2017 was recorded in 2014. This fact is due to a significant decrease in the population of the country against the background of separation of the Crimea and the introduction of military regime in the east of the country. The analysis of the incidence of epilepsy among people of the working age has determined that an increase in patients is observed in such administrative and territorial regions as Odessa, Sumy, Lviv and Ternopil region. It has been proven that the western regions of Ukraine lead the way in quantitative indicators of morbidity. By the average value of the population morbidity rate for epilepsy (2013-2017) the administrative and territorial regions have been groupped, and three groups of regions have been formed (high, medium and low level). It has been determined that the most threatening epidemiological situation is observed in 8 regions of Ukraine. The calculation of the indicator of the overall morbidity rate of epileptic patients of the working age has shown that the highest values of the incidence are observed in Volyn (2.75 %), Transcarpathian (2.25 %) and Lviv (1.55 %) regions.Conclusions. The results of the study can be used in the development of scientific and applied approaches to the organization of effective financing of the provision of effective medical and pharmaceutical care in Ukraine taking into account the dynamic and territorial features of the development of the epidemiological process.Цель: анализ динамики показателей заболеваемости населения эпилепсией в Украине и в ее административно-территориальных объединениях (областях).Материалы и методы. Исследование проведено за период 2013-2017 pp. согласно официальным данным ГУ «Центр медицинской статистики Министерства здравоохранения Украины». Использовались логический, математико-статистический, системно-аналитический, ретроспективный и сравнительный методы анализа.Результаты исследования. По результатам исследования установлено, что минимальное количество больных эпилепсией среди населения Украины за 2013-2017 гг. отмечалось именно в 2014 г. Это обусловлено значительным снижением количества населения страны вследствие отделения АР Крым и введения военного режима на востоке страны. Анализ заболеваемости эпилепсией среди лиц трудоспособного возраста определил, что увеличение больных наблюдается в таких административно-территориальных объединениях, как Одесская, Сумская, Львовская и Тернопольская области. Доказано, что именно западные области Украины лидируют по количественным показателям заболеваемости. По среднему значению показателей заболеваемости населения эпилепсией (2013-2017 гг.) сгруппированы административно-территориальные объединения и сформированы три группы областей (с высоким, средним и низким уровнем заболеваемости). Установлено, что наиболее угрожающая эпидемиологическая ситуация наблюдается в 8 областях Украины. Расчет показателя уровня общей заболеваемости больных эпилепсией трудоспособного возраста показал, что максимальные значения заболеваемости наблюдаются в Волынской (2,75 %), Закарпатской (2,25 %) и Львовской (1,55 %) областях.Выводы. Результаты исследования могут быть использованы в разработке научно-прикладных подходов к организации эффективного финансирования оказания эффективной медицинской и фармацевтической помощи в Украине с учетом динамических и территориальных особенностей развития эпидемиологического процесса.Мета: аналіз динаміки показників захворюваності населення на епілепсію в Україні та в її адміністративно-територіальних об’єднаннях (областях).Матеріали і методи. Дослідження проведено за 2013-2017 pp. відповідно до офіційних даних ДЗ «Центр медичної статистики Міністерства охорони здоров’я України». Використовувались логічний, математико-статистичний, системно-аналітичний, ретроспективний та порівняльний методи аналізу.Результати дослідження. За результатами дослідження установлено, що мінімальна кількість хворих на епілепсію серед населення України за 2013-2017 рр. відмічалась саме у 2014 р. Це обумовлено значним зниженням кількості населення країни внаслідок відокремлення АР Крим та уведення військового режиму на сході країни. Аналіз показників захворюваності на епілепсію серед осіб працездатного віку визначив, що збільшення кількості хворих спостерігається у таких адміністративно-територіальних об’єднаннях, як Одеська, Сумська, Львівська і Тернопільська області. Доведено, що саме західні області України лідирують за кількісними показниками захворюваності. За середнім значенням показників захворюваності населення на епілепсію (2013-2017 рр.) проведено розподіл адміністративно-територіальних об’єднань та сформовано три групи областей (із високим, середнім та низьким рівнем захворюваності). Установлено, що найбільш загрозлива епідеміологічна ситуація спостерігається у 8 областях України. Визначення показника рівня загальної захворюваності хворих на епілепсію працездатного віку показало, що максимальні значення захворюваності спостерігаються у Волинській (2,75 %), Закарпатській (2,25 %) та Львівській (1,55 %) областях.Висновки. Результати дослідження можуть бути використанні у розробці науково-прикладних підходів до організації ефективного фінансування надання ефективної медичної та фармацевтичної допомоги в Україні з урахуванням динамічних і територіальних особливостей розвитку епідеміологічного процесу

Дослідження напівпровідникового твердого розчину V1-xTixFeSb. I. Особливості електрокінетичних характеристик

The peculiarities of the temperature and concentration characteristics of resistivity and thermopower of V1-xTixFeSb semiconductor solid solution were investigated in the temperature and concentration ranges of T = 4.2 -400 K and Ті  ≈ 9.5·1019–3.6·1021 см-3 (х = 0.005 - 0.20), respectively. The existence of previously unknown mechanism for the generation of structural defects with donor nature which determined the conduction of n-VFeSb and V1-xTixFeSb was established. The acceptor type of structural defects generated in V1-xTixFeSb by substitution of V atoms by Ti ones was confirmed.Досліджено особливості температурних та концентраційних характеристик питомого електроопору та коефіцієнта термо-ерс напівпровідникового твердого розчину V1-xTixFeSb у діапазонах температур та концентрацій: Т = 4,2 – 400 К та Ті  ≈ 9.5·1019–3,6·1021 см-3 (х = 0,005–0,20). Встановлено існування невідомого раніше механізму генерування структурних дефектів донорної природи, які визначають провідність n-VFeSb та V1-xTixFeSb. Підтверджено акцепторну природу структурних дефектів, генерованих у V1-xTixFeSb, при заміщенні V атомами Ті

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

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 incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill &amp; Melinda Gates Foundation

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

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