Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Predictive value of upper lip bite test and ratio of height to thyromental distance compared to other multivariate airway assessment tests for difficult laryngoscopy in apparently normal patients

Background: Various anatomical measurements and non-invasive clinical tests, singly or in various combinations can be performed to predict difficult intubation. Recently introduced "Upper lip bite test" (ULBT) and "Ratio of height to Thyromental distance" (RHTMD) are claimed to have high predictability. We conducted a study to compare the Predictive Value of ULBT and RHTMD with Mouth opening (Inter-Incisor gap) (IIG), Modified Mallampatti Test (MMT), Head and neck movement (HNM) and Thyromental Distance (TMD) for Difficult Laryngoscopy. Materials and Methods: In this prospective, single blinded observational study, 480 adult patients of either sex, ASA grade I and II were assessed and graded for ULBT, RHTMD, TMD, MMT, IIG, and HNM according to standard methods and correlated with the Cormack and Lehane grade. Results: ULBT and RHTMD had highest sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio, i.e., 74.63%, 91.53%, 58.82%, 95.7%, 31.765 and 71.64%, 92.01%, 59.26%, 95.24%, 8.96 respectively, compared to TMD, MMT, IIG and HNM. Conclusions: ULBT is the best predictive test for difficult laryngoscopy in apparently normal patients but RHTMD can also be used as an acceptable alternative

Dexmedetomidine with 0.375% bupivacaine for prolongation of postoperative analgesia in supraclavicular brachial plexus block

Background: Regional anesthesia is the recommended technique for upper-limb surgeries with better postoperative profile. Various agents have been used as adjuvants to prolong the duration of action and improve the efficacy of local anesthetic agents, α2-agonists being the most recent ones. We evaluated the effect of dexmedetomidine with bupivacaine for prolongation of the duration of analgesia in supraclavicular brachial plexus block. Materials and Methods: After Institutional Ethics and Scientific Committee approval and written informed consent, this prospective, observational study was carried out on 64 ASA Grade I and II patients of either sex, aged 18–60 years who underwent upper-limb surgery under brachial plexus block. Patients received either bupivacaine or bupivacaine with dexmedetomidine and were randomly divided into two groups. The primary outcome was duration of analgesia, and the secondary outcome was onset and duration of sensory and motor blockade, Ramsay sedation score, and side effects, if any observed at scheduled intervals. Results: Duration of analgesia in Group B was 391.46 ± 30.66 min and in Group BD was 810 ± 39.52 min (P < 0.0001), onset of sensory block in Group B was 7.9 ± 1.33 min and in Group BD was 5.65 ± 0.68 min (P < 0.0001), onset of motor block in Group B was 15.65 ± 1.66 min and in Group BD was 8.93 ± 0.788 min (P < 0.0001), duration of sensory block in Group B was 236.43 ± 17.52 min and in Group BD was 479.68 ± 40.50 min (P < 0.0001), duration of motor block in Group B was 206.09 ± 24.26 min and in Group BD was 447.81 ± 41.88 min, and slightly higher Ramsay sedation score was seen in Group BD as compared to Group B. The side effects were found to be insignificant and incidental. Only two cases of bradycardia(6.25%) and one case(3.12%) of hypotension were noticed in group BD. Conclusion: Addition of dexmedetomidine to bupivacaine was associated with prolonged analgesia, prolonged sensory and motor blockades with mild sedation

Intravenous dexmedetomidine versus propofol for intraoperative moderate sedation during spinal anesthesia: A comparative study

Background and Aims: There has been a paradigm shift of focus toward quality of spinal anesthesia with sedation being an integral aspect of this regional anesthesia technique. Thus, this study was designed to compare efficacy of intravenous dexmedetomidine and propofol for moderate sedation during spinal anesthesia. Material and Methods: A total of 120 patients of age group 18-60 years of American Society of Anesthesiologists grade I & II, posted for surgeries under spinal anesthesia were randomly divided in to three groups (n = 40 each); Group D received infusion of dexmedetomidine 1 μg/kg over 10 min followed by maintenance infusion of 0.5 μg/kg/h. Group P received infusion of propofol 6 mg/kg/h for 10 min followed by the infusion maintenance of 2.5 mg/kg/h. Group C (control group) received normal saline. Level of sedation (using observer′s assessment of alertness/sedation score), pain intensity (by visual analogue scale), onset and recovery from sedation, hemodynamic changes, and overall patient′s satisfaction were assessed. Results: The onset and recovery from sedation were significantly earlier with propofol (15.57 ± 1.89 min vs. 27.06 ± 2.26 min; P < 0.001) however intraoperative sedation (level 4), and overall patient′s satisfaction was significantly better with dexmedetomidine group (p < 0.05). Duration of postoperative analgesia was significantly prolonged with dexmedetomidine (225.53 ± 5.61 min vs. 139.60 ± 3.03 min; P = 0.0013). Mean heart rate and blood pressure were significantly lower in the propofol group (P < 0.05). Conclusion: Dexmedetomidine with its stable cardio-respiratory profile, better sedation, overall patient′s satisfaction, and analgesia could be a valuable adjunct for intraoperative sedation during spinal anesthesia

“Spinal intramedullary cavernous venous malformation”: A dormant volcano

Cavernous venous malformations are a well recognized major pathologic categories of vascular malformations of the nervous system usually an incidental finding on routine imaging. These lesions are relatively rare in spinal cord and whenever present can lead to severe neurological deterioration due to significant hemorrhage and consequent mass effect. We present two such cases of spinal cord involvement and in brief described their imaging feature. They need to be armed with the appropriate knowledge of how to recognize and timely intervene

“Anomalous right pulmonary artery left atrial fistula”: Growth in vain

We report a case of direct communication between the right pulmonary artery and the left atrium; a rare cause of central cyanosis in 10 year old boy, emphasizing the role of multislice computed tomography scanner in delineating the complex vascular abnormality over more invasive conventional angiography

Hemosiderotic synovitis: Highlighting the role of T2∗ weighted sequence in skeletal MRI

We report a rare case of spontaneous hemosiderotic synovitis of knee joint in an otherwise healthy young male player, with no associated findings of bleeding disorder, inflammatory arthritis or other systemic illness. The role of T2 weighted gradient recalled echo (GRE) (T2∗WI) MRI sequence in skeletal imaging sticks out from this report. Close differential diagnosis of pigmented villonodular synovitis (a benign neoplastic condition) should be excluded by histological examination. Treatment aimed to prevent articular degeneration by prompt intervention