Stroke, Ahead of Print. BACKGROUND:The PASSIoN study (Perinatal Arterial Stroke Treated With Stromal Cells Intranasally) demonstrated the feasibility and short-term safety of single-dose allogeneic mesenchymal stromal cells (MSCs) administered intranasally to neonates with perinatal arterial ischemic stroke between February 2020 and April 2021. In this study, we assessed long-term safety and neurodevelopmental outcomes and explored outcome differences with a non–MSC-treated cohort.METHODS:In this post hoc analysis, we evaluated the safety of MSC administration by assessing brain tissue loss, adverse events, and neurodevelopmental outcomes of PASSIoN participants (n=10). The tissue loss ratio was calculated using semi-automatic segmentation based on neonatal and 3-month magnetic resonance imaging. At the age of 2 years, we assessed the occurrence of cerebral palsy, motor and cognitive delays (Zscore
Search Results for: GPG: Versione 5.7.5 (Novembre 2021)
Here's what we've found for you
[Articles] Variability in trends of opioid-related hospital utilization among U.S. Adults, 2016–2021 check
The significant variability in opioid-related hospital utilization trends among U.S. adults underscores the need for careful consideration in the design of future policies, especially during crises. Management strategies should be tailored to specific subpopulations, opioid categories, and OUD-related clinical events to maximize success rates.
PREACT-digital: study protocol for a longitudinal, observational multicentre study on digital phenotypes of non-response to cognitive behavioural therapy for internalising disorders
Introduction
Cognitive behavioural therapy (CBT) serves as a first-line treatment for internalising disorders (ID), encompassing depressive, anxiety or obsessive-compulsive disorders. Nonetheless, a substantial proportion of patients do not experience sufficient symptom relief. Recent advances in wearable technology and smartphone integration enable new, ecologically valid approaches to capture dynamic processes in real time. By combining ecological momentary assessment (EMA) with passive sensing of behavioural and physiological information, this project seeks to track daily fluctuations in symptom-associated constructs like affect, emotion regulation (ER) and physical activity. Our central goal is to determine whether dynamic, multimodal markers derived from EMA and passive sensing can predict treatment non-response and illuminate key factors that drive or hinder therapeutic change.
Methods and analysis
PREACT-digital is a subproject of the Research Unit FOR 5187 (PREACT), a large multicentre observational study in four outpatient clinics. PREACT channels state-of-the-art machine learning techniques identify predictors of non-response to CBT in ID. The study is currently running and will end in June 2026. Patients seeking CBT at one of four participating outpatient clinics are invited to join PREACT-digital. They can take part in (1) a short version with a 14-day EMA and passive sensing phase prior to therapy, or (2) a long version in which the short version’s assessments are extended throughout the therapy. It is estimated that 468 patients take part in PREACT-digital, of which 350 opt for the long version of the study. Participants are provided with a smartwatch and a customised study app. We collect passive data on heart rate, physical activity, sleep and location patterns. EMA assessments cover affect, ER strategies, context and therapeutic agency. Primary outcomes on (non)-response are assessed after 20 therapy sessions and therapy end. We employ predictive and exploratory analyses. Predictive analyses focus on classification of non-response using basic algorithms (ie, logistic regression and gradient boosting) for straightforward interpretability and advanced methods (LSTM, DSEM) to capture complex temporal and hierarchical patterns. Exploratory analyses investigate mechanistic links, examine the interplay of variables over time and analyse change trajectories. Study findings will inform more personalised and ecologically valid approaches to CBT for ID.
Ethics and dissemination
The study has received ethical approval from the Institutional Ethics Committee of the Department of Psychology at Humboldt Universität zu Berlin (Approval No. 2021–01) and the Ethics Committee of Charité-Universitätsmedizin Berlin (Approval No. EA1/186/22). Written informed consent will be obtained from all participants prior to enrolment. Results will be disseminated through peer-reviewed journals and presentations at national and international conferences.
Trial registration number
DRKS00030915; OSF PREACT: http://osf.io/bcgax; OSF PREACT-digital: https://osf.io/253nb.
Association of Statin Treatment and Dose With the Clinical Course of Small Abdominal Aortic Aneurysms in Men: A 5-Year Prospective Cohort Study From 2 Population-Based Screening Trials
Circulation, Ahead of Print. BACKGROUND:Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death.METHODS:The study population included all men with screening-detected AAAs (30–55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008–2011) and the Danish Cardiovascular Screening trial (inclusion, 2014–2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021.RESULTS:A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67–72] years; median AAA diameter, 35.4 [IQR, 32–41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of −0.22 mm/year [95% CI, −0.39 to −0.06];P=0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70–0.97];P=0.023), which was significant after 2.5 years. Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner, with an adjusted HR of 0.83 ([95% CI, 0.73–0.94];P=0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses.CONCLUSIONS:High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.
Volumetric choice experiment to estimate the impact of e-cigarette and heated tobacco product characteristics on substitution and complementary use among adults who smoke cigarettes and recently initiated e-cigarette use
Background
This study addresses the limited evidence of the impact of product characteristics on demand for and the substitutability of electronic cigarettes (e-cigarettes) or heated tobacco products for combusted cigarettes among people who smoke and have newly begun to use e-cigarettes.
Methods
A sample of 318 adults who smoke and recently initiated/reinitiated e-cigarette use participated in an online volumetric choice experiment in 2020–2021 to assess stated preferences for consumption and own and cross-price elasticities of three e-cigarette options (cig-a-like, vape pen or tank, closed pod system), heated tobacco product (IQOS) and their usual brand of cigarettes. Product attributes manipulated were price, flavour, level of harm, how well the product reduces cravings to smoke, and how discretely the product can be used. Multilevel zero-inflated negative binomial models were used to model the purchased quantities.
Results
Cigarettes were preferred over all alternatives. However, demand for cig-a-likes, but not IQOS, increased when cigarette prices were higher. Higher prices for e-cigarettes and IQOS did not increase demand for cigarettes. The odds of buying e-cigarettes/IQOS were higher when their harm was stated as low or unknown versus being similar to cigarettes (ie, very high). Other attributes (including various flavour options) were not significantly associated with demand for e-cigarettes or IQOS.
Conclusions
People who smoke and recently began using e-cigarettes might substitute cig-a-likes for cigarettes when cigarette prices are higher. Policies to increase the cost of combusted cigarettes as well as communicate lower relative harm and low absolute harm of e-cigarettes may facilitate switching behaviour.
Association between loneliness and depression, anxiety and anger during the COVID-19 pandemic: a nationwide population-based survey
Objectives
This study aims to determine the association between loneliness and depression, anxiety and anger with a representative sample of the general population in Korea, which are the most prevalent mental health problems during the pandemic.
Design
Cross-sectional study.
Setting
National survey across all 17 provinces in South Korea between December 2021 and January 2022.
Participants
We conducted a national survey on 2699 participants aged 19–84 years using proportional stratified sampling. Using the UCLA Loneliness Scale and standardised questionnaires for depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and anger (Patient-Reported Outcomes Measurement Information System-Anger), we explored the prevalence and association of loneliness with these mental health outcomes.
Primary and secondary outcome measures
Primary outcomes included the prevalence and co-occurrence of depression, anxiety and anger across different levels of loneliness.
Results
Of total, 20.7% and 2.1% experienced moderately high and high levels of loneliness, respectively. Among participants with high levels of loneliness, 11.8%, 5.9% and 11.8% had depression, anxiety and anger, respectively, and 28.7% of them had depression, anxiety and anger together. The adjusted prevalence of depression was 0.2 (95% CI 0.0 to 0.5), 8.2 (95% CI 6.7 to 9.7), 31.3 (95% CI 27.4 to 35.3) and 63.5 (95% CI 50.1 to 76.8) for low, moderate, moderately high and high levels of loneliness, respectively. Similarly, increased adjusted prevalence of anxiety and anger was observed ㅈwith higher levels of loneliness.
Conclusions
Lonely people have a higher risk of depression, anxiety and anger. Identifying individuals who may be vulnerable to loneliness is important for early intervention.
Association Between Statin Use and Risk of Subarachnoid Hemorrhage: A Case-Control Study Using Large-Scale Claims Data
Stroke, Ahead of Print. BACKGROUND:While the efficacy of statins, which are cholesterol-lowering agents, in preventing subarachnoid hemorrhage (SAH) has been examined in experimental animal models and some clinical studies, findings remain inconclusive. This study aimed to investigate the association between statin use and the risk of SAH.METHODS:We conducted a large population-based case-control study using data from the Japanese Health Insurance Claims Database from January 2005 to August 2021. This nationwide database includes the data of individuals aged 0 to 74 years. Cases were defined as patients hospitalized with a first diagnosis of SAH (International Classification of Diseases, Tenth Revisioncode I60) during this period. Four controls per case were randomly selected and matched by age, sex, and follow-up period using incidence density sampling. Statin exposure (use, recency, and duration) was evaluated before the incidence of SAH. Conditional logistic regression, adjusted for patient characteristics, was used to assess the association between statin use and SAH risk. We also investigated whether this association varies with a history of hypertension, diabetes, cerebrovascular disease, unruptured intracranial aneurysms, and the use of antihypertensive medications.RESULTS:The study identified 3498 cases and 13 992 matched controls. Statin use was reported in 12.2% of SAH cases and 12.7% of the controls. After adjusting for patient characteristics, statin use was associated with a significantly reduced risk of SAH (adjusted odds ratio, 0.81 [95% CI, 0.69–0.95]). The association was significantly influenced by a history of hypertension or cerebrovascular disease (Pinteraction=0.042 and 0.042, respectively).CONCLUSIONS:Statin use was significantly associated with a reduced risk of SAH. These findings suggest that statins may play a role in the prevention of SAH, particularly in patients with a history of hypertension or cerebrovascular disease.
Platinum and etoposide chemotherapy, durvalumab with thoracic radiotherapy in the first-line treatment of patients with extensive-stage small-cell lung cancer: CHEST-RT (TROG 20.01) Trial – protocol for a phase II study
Background
Trans Tasman Radiation Oncology Group 20.01 CHEST-RT (Chemotherapy and Immunotherapy in Extensive Stage Small cell with Thoracic Radiotherapy) is a single-arm, open-label, prospective, multicentre phase II trial study that aims to establish the safety, feasibility and describe the efficacy of incorporating thoracic radiotherapy (TRT) (concurrent or sequential) to chemotherapy and immunotherapy in patients with extensive-stage small-cell lung cancer.
Methods
A single arm of up to 30 evaluable participants given TRT concurrent or sequentially with chemoimmunotherapy will be enrolled. Participants should commence radiotherapy with cycle 3 or cycle 4 of chemotherapy. Those not suitable for concurrent radiotherapy due to large tumour volumes may receive sequential radiotherapy. Accounting for a 15% non-evaluable rate, up to 35 participants will be enrolled. An independent data and safety monitoring committee will review the data and assess safety and feasibility. Progression to a phase III trial would be considered feasible if ≤20% of participants experienced ≥grade 3 oesophageal toxicity and ≤10% experienced ≥grade 3 pneumonitis. This approach would be considered feasible if there is ≤20% treatment discontinuation of systemic therapy secondary to radiation toxicities and ≥75% of participants have tumour volumes that can be safely treated to a dose of 30 Gy in 10 fractions. The primary outcome of the trial is safety and feasibility, and survival and responses will be assessed as secondary endpoints. A predefined subgroup analysis of toxicity will be performed on group 1 (concurrent TRT) versus group 2 participants (consolidation TRT).
Ethics and dissemination
This study was approved by the Peter MacCallum Human Research Ethics Committee (HREC/73189/PMCC-2021). The protocol, technical and clinical data will be disseminated by conference presentations and publications. Any modifications to the protocol will be formally documented by administrative letters and will be submitted to the approving HREC for review and approval.
Trial registration numbers
Australian New Zealand Clinical Trials Registry (ACTRN12621000586819) and ClinicalTrials.gov identifier (NCT05796089).
Implementation of an intervention to scale up coverage of pneumonia management in children younger than 5 years in a north Indian district: protocol for a quasi-experimental, mixed-methods, pre-post implementation study
Introduction
The National Family Health Survey-5 has reported an under-five mortality rate of 41.9 per 1000 live births in India. Pneumonia, one of the leading causes of under-five mortality, contributes substantially to this figure. The Indian government has made efforts through multiple national programmes, but pneumonia-specific mortality remains high. The Government of India revised their Childhood Pneumonia Management Guidelines in 2019 to improve under-five pneumonia prevention and management. This implementation study aims to achieve a high population-based coverage of pneumonia treatment for under 5 yearold children in the Palwal district of India.
Method and analysis
This implementation study uses a quasi-experimental pre-post design and a mixed-methods approach, conducted in three phases: (i) formative research, (ii) model optimisation through iterative testing in a learning block and (iii) scale-up and concurrent evaluation. The study is set in Palwal district, Haryana, and the primary catchment/study area will be the Health and Wellness Centres, the most accessible public health facilities for the community. Approximately 4167 households will be surveyed to capture ~2400 under-five children, among whom about 120 pneumonia cases (based on an estimated 5% prevalence) will be included in the analysis of treatment coverage and outcomes. Quantitative data will be analysed using descriptive statistics and generalised linear models, while qualitative data from focus group discussions and in-depth interviews will be thematically analysed using NVivo software.
Ethics and dissemination
Ethical approval was granted by the ethical committees of the Society for Applied Studies (ERC/IR Pneumonia/2021), the Regional Ethics Committee of Western Norway (2022/531608) and the WHO(ERC.0003652). Additionally, this study has obtained the Government of Haryana state (Memo no. HSHRC/2022/505) and Health Ministry steering committee (approval date: 19 Dec 2022, proposal id 2022–17596) approvals. Informed consent will be obtained from all participants, including caregivers and healthcare workers, prior to data collection. Dissemination meetings in the study country will share results with stakeholders, including Ministry of Health officials, health managers, families of under-five children, community leaders and academia, to discuss national health programme implications. Results will also be shared regionally and globally, with publications and presentations encouraged in national and international forums.
Study registration
Clinical Trials Registry – India, CTRI/2021/03/031622.
High-risk human papillomavirus infection (HPV 16/18) and its determinants among women in East Gojjam Zone, Northwest Ethiopia: a population-based cross-sectional study, 2021
Objective
This study aimed to assess high-risk human papillomavirus (HPV) infection (HPV 16/18) and its determinants among women in East Gojjam Zone, Northwest Ethiopia.
Design
An institutional-based cross-sectional study.
Setting and participants
The study was conducted among 337 women screened for cervical cancer in two hospitals in East Gojjam Zone from February to April 2021 gregoriean calander.
Results
The prevalence of HPV infection was 14.2% (95% CI: 10.7% to 18.1%). The mean age of the respondents was 36.7±9.1 years. Women in the age group of 55–65 years (adjusted OR (AOR)=7.91, 95% CI: 1.95 to 32.09), early initiation of sexual intercourse (AOR=5.36, 95% CI: 1.58 to 18.13), history of sexually transmitted infection (STI) (AOR=3.52, 95% CI: 1.27 to 9.72), HIV positive status (AOR=6.8, 95% CI: 1.99 to 23.54) and number of lifetime sexual partners (AOR=4.37, 95% CI: 1.15 to 17.3) were important independent factors associated with the presence of oncogenic HPV infection.
Conclusion and recommendation
We found a relatively low prevalence of high-risk HPV infection. Age, early initiation of sexual intercourse at less than 18 years, history of STI, being HIV seropositive and multiple sexual partners were important factors for high-risk HPV infection. Women aged >46 years, women with early initiation of sex, a history of STI, being HIV positive and a history of multiple sexual partners should be encouraged to be screened and vaccinated for HPV infection. Wider-ranging studies are also needed in HPV-infected women in association with the cervical lesion.
Associations between optimism and mental health in postradiotherapy cancer survivors: a cross-sectional survey study
Objectives
Cancer patients often experience psychological distress, while optimism has been identified as a protective factor. However, the mental health of postradiotherapy cancer survivors and its association with optimism remain largely unexplored. This study assesses the mental health status and optimism levels of postradiotherapy cancer survivors and evaluates their associations.
Design
Cross-sectional survey study.
Participants
114 Hong Kong cancer survivors who (1) were aged 18 years or above and (2) had received radiotherapy for their cancer treatment and finished the radiotherapy within the previous 3 years (2021–2024).
Outcome measures
Mental health was assessed using the Chinese Depression, Anxiety and Stress Scale, and optimism was measured using the Revised Life Orientation Test. Correlation and regression analyses were used to examine the associations between these measures.
Results
Participants reported overall low optimism with mild to moderate depression, anxiety and stress. Strong negative correlations were identified between optimism and depression (r=–0.833, p
Incidence and disability-adjusted life-years of infective endocarditis in China from 1990 to 2021: comparison with G20 based on the Global Burden of Disease Study 2021
Objectives
Infective endocarditis (IE) is a global public health challenge, and our understanding of its temporal evolution in China compared with the Group of Twenty (G20) countries remains limited. This study aims to analyse the disease burden of IE in China from 1990 to 2021, forecast trends for the next 15 years and compare the findings with those in G20 countries.
Design
Observational study.
Setting
The data of 20 countries and regions in G20 were obtained from the Global Burden of Disease (GBD) Study 2021.
Participants
Data were publicly available and individuals were not involved.
Main outcome measures
Using data from the GBD 2021, we collected incidence, disability-adjusted life-years (DALYs) and age-standardised rates for both China and G20 countries. Temporal trends were assessed using the estimated annual percentage change (EAPC) and a joinpoint regression analysis was conducted to pinpoint periods of significant change. Additionally, a decomposition analysis was performed to identify the factors driving changes. Finally, the Bayesian age-period-cohort model was used to forecast trends for the next 15 years.
Results
In 2021, there were 264 282 (95% UI: 216 083 to 315 405) incident cases of IE in China, resulting in 49 925 (95% UI: 38 779 to 69 119) DALYs. The age-standardised incidence rate (ASIR) and age-standardised DALY rate (ASDR) were 14.38 (95% UI: 12.03 to 16.92) and 3.46 (95% UI: 2.65 to 5.01) per 100 000 population, respectively, with both rates being higher in males than in females. Notably, both ASIR and ASDR showed a pattern of first decreasing and then increasing with age, with the highest values observed in the age group of 95 years and above. From 1990 to 2021, the ASIR of IE in China showed a slow upward trend (EAPC: 0.49, 95% CI: 0.44 to 0.55), which was lower than the average level among G20 countries. In contrast, the ASDR exhibited a significant downward trend (EAPC: –6.26, 95% CI: –6.8 to –5.71), representing the largest decline among the G20 countries. The most notable increase in ASIR occurred from 1995 to 2005 in both China and the G20. The greatest decrease in ASDR was observed in China between 2001 and 2004 and in the G20 between 2018 and 2021. Projections suggest that over the next 15 years, the ASIR for both males and females in China will continue to rise, while the ASDR will show a declining trend.
Conclusions
In China, the incidence of IE-related diseases has steadily increased across both genders, despite a declining trend in DALYs. Compared with G20 countries, China’s age-standardised burden of IE is relatively low, yet the large increasing number of cases should not be underestimated. Therefore, establishing effective prevention and treatment strategies is crucial to alleviating the future burden of IE.
Evaluation of optical sensor technology for the early detection of peripheral intravenous infiltration in neonates: a retrospective cohort study
Objective
This study aimed to evaluate the utility of optical sensor-based technology in mitigating the frequency and severity of peripheral intravenous infiltration and/or extravasation (PIVIE) in neonates.
Design
Single-centre, retrospective, observational cohort study.
Setting
Tertiary-level neonatal intensive care unit (NICU) (112 cots) at the Women’s Wellness and Research Centre (WWRC), Hamad Medical Corporation (HMC), Doha, Qatar, January 2019–December 2022.
Participants
All neonates admitted to the NICU requiring intravenous therapy via a neonatal short peripheral intravenous catheter (n-SPC) were included. Participants were excluded if the insertion was unsuccessful, if they had incomplete data, or if they received intravenous therapy exclusively through alternative vascular access devices.
Interventions
The study analysed two cohorts representing different clinical practices over two distinct periods. In the conventional cohort (Phase 1, 2019–2020), PIVIE detection relied solely on periodic ‘Touch Look Compare (TLC)’ assessments. In the ivWatch cohort (Phase 2, 2021–2022), continuous optical sensor-based monitoring using the ivWatch system was implemented alongside TLC assessments. This sequential design allowed for a comparison of outcomes between the two phases.
Outcome measurements
The primary outcomes were the occurrence and severity of PIVIE. Secondary outcomes included the influence of patient demographics, vascular access characteristics, and management details on PIVIE incidence and severity.
Results
Over the 4-year data collection period, 32 713 peripheral intravenous catheters were analysed across two cohorts. PIVIE was the most common reason for unplanned device removal. In the conventional cohort (Phase 1, 2019–2020), 4941 infiltration events were reported (29.9%), compared with 4872 events (30.1%) in the ivWatch cohort (Phase 2, 2021–2022). However, severity measures using the Intravenous Extravasation Grading Scale (IEGS) revealed a marked reduction in severe PIVIE cases, with severe events decreasing from 243 (4.9%) in the conventional cohort to 54 (1.1%) in the ivWatch cohort (p
Trends in educational inequality in healthy life expectancy in Denmark between 2010 and 2021: a population-based study
Objectives
For several decades, mortality has decreased more rapidly among individuals with a higher socioeconomic position than among those with a lower position. This widening social inequality gap has increasingly been recognised as an important aspect of public health research and policies. The objective of this study was to examine trends in educational inequality in healthy life expectancy (HLE) in Denmark between 2010 and 2021 at the age of 30 years.
Design
The study is a population-based study based on register data on longest attained education, standard life tables and self-reported health information from nationwide health surveys.
Setting
The study is conducted among the general adult population in Denmark.
Participants
Participants include respondents from the Danish National Health Survey and the Danish Health and Morbidity Survey in 2010, 2013, 2017 and 2021 aged ≥30 years.
Primary and secondary outcome measures
Expected lifetime in good self-rated health, with no long-standing illness and with no activity limitations was estimated by Sullivan’s method, and educational inequality was expressed by the Slope Index of Inequality.
Results
Between 2010 and 2021, educational inequality in HLE increased among both men and women for long-standing illness (5-year trend: +1.1 and +1.2 years) and activity limitations (+2.4 and +2.6 years) but remained stable among men (+0.1 year) and decreased among women (–0.3 year) for self-rated health. For the latter two indicators, the inequality gap narrowed after 2017.
Conclusion
Trends in educational inequality in HLE in Denmark 2010–2021 vary by health indicator. Steadily widening gaps were demonstrated for long-standing illness, while narrowing gaps were seen after 2017 for activity limitations and self-rated health. Future studies are encouraged to explore potential health risk behaviours that may explain or modify these inequality trends.
Private Equity Among US Psychiatric Hospitals
This study describes trends in private equity ownership of psychiatric hospitals from 2013 through 2021 and the cross-sectional association between private equity ownership and hospital staffing and quality.
Burden of Skin Cancer in Older Adults From 1990 to 2021 and Modelled Projection to 2050
This study using data from the Global Burden of Diseases database investigates the most updated trends in skin cancer burden across subgroups of age cohorts, sexes, geographical regions, and sociodemographic index levels and further models a predicted burden by 2050.