Initial Years Research Articles

A potential biomarker of radiosensitivity in metastatic hormone sensitive prostate cancer patients treated with combination external beam radiotherapy and radium-223

PurposeThe ADRRAD trial reported the safety and feasibility of the combination of external beam radiotherapy and radium-223 in the treatment of de novo bone metastatic prostate. This study aimed to determine if any biomarkers predictive of response to these treatments could be identified. Experimental design30 patients with newly diagnosed bone metastatic hormone sensitive prostate cancer were recruited to the ADRRAD trial. Blood samples were taken pre-treatment, before cycles 2 to 6 of radium-223, and 8 weeks and 6 months after treatment. Mononuclear cells were isolated and DNA damage was assessed at all timepoints. ResultsDNA damage was increased in all patients during treatment, with bigger increases in foci observed in patients who relapsed late compared to those who relapsed early. Increases in DNA damage during the radium-223 only cycles of treatment were specifically related to response in these patients. Analysis of hematology counts also showed bigger decreases in red blood cell and hemoglobin counts in patients who experienced later biochemical relapse. ConclusionsWhile some patients responded to this combination treatment, others relapsed within one year of treatment initiation. This study identifies a biomarker based approach that may be useful in predicting which patients will respond to treatment, by monitoring both increases in DNA damage above baseline levels in circulating lymphocytes and decreases in red blood cell and hemoglobin counts during treatment.

Wildlife Roadkill Driven by Hydrological Regime in a Subtropical Wetland

This study explored the role of the hydrological regime as a trigger factor for wildlife roadkill along a 22 km road crossing the Taim Wetland, a Ramsar site of international importance in South Brazil. The north–south crossing of BR-471, a federal highway, causes fatalities to numerous animals due to collisions with vehicles. An 11-year long-term time series study encompassing monthly roadkill incidents, water level, and rainfall was analyzed by considering three different periods related to a Wildlife Protection System (WPS): (i) 3 initial years before the WPS implementation (BWPS); (ii) 4 intermediate years after the WPS implementation (AWPS), which includes fences, fauna tunnels, cattle guard stocks, bumps, and speed control; (iii) 4 final years during partial destruction of the WPS (PDWPS). A pseudo-2D full hydrodynamic cell model was employed to fill missing water level data. The model had a good to very good performance (NSE: 0.73 to 0.87; R2: 0.79 to 0.90). The relationship between roadkill incidents and the WPS periods (BWPS, AWPS, and PDWPS) was modeled using Generalized Additive Models for Location, Scale, and Shape (GAMLSS), considering rainfall and water level as predictor variables. The analysis revealed a higher incidence of wildlife roadkill in BWPS compared to AWPS and PDWPS, suggesting the effectiveness of the implemented measures. Critical season and interplay between water levels, rainfall, and the roadkill were assessed. Mammals was the most common roadkill class identified (~92%), followed by reptiles (13%) and birds (2%), with no change in these percentual in the BWPS, AWPS, and PDWPS. Among mammals, capybara (Hydrochoerus hydrochaeris) and coypu (Myocastor coypu) were the most frequent victims (~93% of mammals). Winter, followed by autumn, recorded the highest number of roadkill incidents (>60%), and this pattern remained consistent during the three periods. While rainfall did not emerge as a determining variable for roadkill, water levels above certain thresholds (>3.3 m) drastically diminished the effectiveness of the WPS, mainly due to fauna tunnel submersion. These findings offer valuable insights for enhancing wildlife conservation strategies in this protected area by incorporating hydrological information providing a baseline for designing WPS in similar environments.

Societal costs of illness for infantile epileptic spasms syndrome and evolutionary cost prediction in the era of WHO’s IGAP

BackgroundTo achieve the goal of improving the quality of life for persons with epilepsy within the framework of the WHO’s Intersectoral Global Action Plan (IGAP), our study aimed to assess the societal financial burden linked to infantile epileptic spasms syndrome (IESS), ensuring that children afflicted with IESS receive high-quality healthcare without enduring substantial financial constraints. MethodsBetween August 2022 and March 2023, 92 children with IESS (male: female: 2:1), recently diagnosed or previously followed-up, were recruited. We gathered costs for drugs, tests, and medical services, along with legal guardians’ monthly income. Total expenditure was determined by multiplying unit costs by the yearly service usage commencing from the onset. Time series analysis was utilised to forecast the financial burden from 2022 to 2032. ResultsClinicians' first choice of treatment was ACTH (n = 60, 65·2%), prednisolone (n = 25, 27·2%), and vigabatrin (n = 7, 7·6%) and the median cost of treatment during the initial year was INR 39,010 [USD 479·2]. The median direct medical, direct non-medical, and indirect cost were INR 31,650 [USD 388·4], INR 6581 [USD 80·8], and INR 10,100 [USD 124·07], respectively. Families lost a median of 12 days of work annually. Drug costs and loss of wages were the key factors in the financial burden. The projected and adjusted figures exhibited an incremental growth rate of 2·6% tri-annually. InterpretationThis pioneering study in developing countries, the first of its kind, evaluates the societal cost, financial hardship, and trajectory of incremental cost in IESS. The primary drivers of the financial burden were pharmacological treatment and family work adjustments. The government shoulders 62% of the financial burden, and projected a triannual growth of 2·6% from 2022 to 2032. Our results rationalize policymakers' focus on incorporating IESS into social security programs, particularly in developing countries.

The 16th century Carrera del Pacífico: its sailor-merchants and their trade goods

This article focuses on the sailors who served during the initial years of the Carrera del Pacífico, one of the globalizing projects of the Spanish Monarchy. In particular, the paper aims to examine the sailors who took advantage of the Pacific trade circuits by actively participating in various income-generating activities created by the Carrera. Using the sailors’ economic endeavors, especially as sailor-merchants, as a lens can elucidate how early global trade was conducted and demonstrate the dynamics of the early Pacific trade. The paper argues that by seizing the opportunities presented by the Carrera, primarily by assuming the dual roles of sailors and merchants, these laborers helped consolidate the Spanish-Pacific region and reshape the consumption pattern of its local population. The sailors engaged in the transportation, sale, and purchase of global commodities during the early modern period, including textiles and chinaware, which catered to the demands of the broader consumer base in Spanish America. The sources draw data from the Royal Treasury of Acapulco registers during its first decade (1590-1600), where 1,574 sailors were identified. It belongs to Archivo General de Indias’ Contaduría (Account) records, which contain the duties of commodities entering and leaving the port of Acapulco.

A Performance based Ranking of Initial Public Offerings (IPOs) in India

In recent times, Indian Stock Market (ISM) has been witnessing a surge in the number of IPOs listed in stock exchanges. However, in many occasions it has been noticed that post-listing performance of several IPOs are below par to the expectations of the investors. IPO performance has been one of the major concerns. In this context, the present paper endeavours to carry out a comparative performance assessment of a list of IPOs. We consider a period of three years after listing. Our sample consists of a list of IPOs having heterogeneous nature of business operations and introduced in 2018. We consider two aspects of the performance such as market-based indicators and fundamental efficiency in terms of profitability, liquidity and risk. For comparison, LOgarithmic Percentage Change-driven Objective Weighting (LOPCOW) is used. The study period is considered as Fy 2020-21. The results reflect that for IPOs, market performance does not necessarily because of the fundamental efficiency. Further, we notice that the nature of equity ownership does not influence the market performance significantly. We surmise that during initial years, the performance of the IPOs at the marketplace is more driven by speculations and short-term goals of the investors. The result of validation test indicates that the ranking using LOPCOW method is comparable and consistent with a widely used model like Entropy.

The Socio-Economic Situation in An Uzbek Village in the 20-30s of the Xx Century: from Reforms to Collectivization

Objectives: The primary objectives of this article center on analyzing the socio-economic situation in an Uzbek village during the 20-30s of the XX century. The study aims to understand the impact of Soviet power on rural areas, specifically focusing on the presence and influence of the government during the initial years. Additionally, the objectives include examining the period of reforms in the 20s that led to significant improvements in the economic indicators of the agricultural sector.
 
 Methods: The research methodology involves a historical analysis of the socio-economic conditions in the Uzbek village during the specified time frame. It includes a detailed examination of archival documents, historical records, and relevant literature to trace the changes in the rural landscape. The methods also entail a closer look at the policies implemented during the 20s, such as reforms and their effects, leading up to the initiation of collectivization and dispossession in 1929.
 
 Results: The findings of the study highlight the initially unfelt presence of Soviet power in rural areas during the first years. The 20s, marked by reforms, saw significant economic improvements in the agricultural sector. However, the results underscore the detrimental impact of the subsequent policies of collectivization and dispossession in 1929. These policies transformed the role of the Uzbek farmer from an owner to a worker, leading to the destruction of the institution of private property and causing a tragic disruption in the once peaceful social life of the village.
 
 Conclusion: In conclusion, the study reveals the dual nature of the Soviet influence on the Uzbek village during the 20-30s. While the initial years brought about positive economic changes through reforms, the subsequent policies had severe consequences, destroying the institution of private property and disrupting the social fabric of the village. The conclusion emphasizes the profound impact of governmental policies on local farmers and the transformation of their socio-economic status during this crucial period.

Transmission of natural disasters to the banking sector: Evidence from thirty years of tropical storms in the Caribbean

Banks can play a vital role in helping affected communities to cope with natural disasters. Using data on 92 damaging tropical storms, this paper explores the channels through which 111 individual banks from 20 Caribbean and Central American jurisdictions have been affected. Our results suggest that damaging tropical storms are associated with immediate and long-lasting adverse funding shocks. Banks from the small island economies face withdrawals of deposits, while banks from the continental countries are affected by adverse shocks to short-term funding. In both regions bank lending to the private sector drops in the initial years. The natural disaster shock is associated with persistent loan defaults and bank losses in the continental countries, whereas in the small island economies losses only start materializing after four years. In the two regions, the tropical storm recovery is thus credit-less.

The Decision Dilemma: Disinvestment or Turnaround?

The case describes the journey of one of the most ambitious public sector undertakings, Heavy Engineering Corporation Limited (HECL), in the earlier unified state of Bihar, India. Despite being a leading manufacturer and supplier of capital equipment and experiencing growth in the initial years, the company incurred losses for over 17 consecutive years. In the year 2006–2007, the company briefly bounced back to profits, but those revival hopes faded within five years, leaving the company in dire need of an immediate strategic rethink and a complete overhaul. This case specifically focuses on the problems and challenges faced by the cash-strapped public sector enterprise, HECL. It addresses issues such as its negative net worth, the rising wage and incentive bills of its employees, declining product competitiveness at the global level and other persistent financial difficulties and bureaucratic hurdles that created inflexibilities in decision-making. The need for agile and lean management approaches that could increase overall organizational performance, efficiency and value deliverables was also explored.

Optimizing vertical ground heat exchanger modelling through GPU-accelerated computation strategies

Enhancing Vertical Ground Heat Exchanger (VGHE) modelling for efficient Vertical Ground-Coupled Heat Pump (VGCHP) systems, renowned for their eco-friendly operation, has garnered significant attention. Optimally designing and sustaining the long-term efficiency of VGCHP systems necessitates rigorous, protracted VGHE modelling, a process fraught with computational intensity. To surmount this challenge, this contribution introduces an accelerated VGHE modelling paradigm grounded in Graphics Processing Unit (GPU) processing. This entails employing the Finite Line Source (FLS) model based on Fast Fourier Transform (FFT). To ameliorate computational demands, the processing capabilities of both Central Processing Units (CPUs) and GPUs are harnessed, leveraging CPU- and GPU-based FFT and inverse FFT (IFFT). Hybrid and non-hybrid processing modes are explored, differentiating between CPU- and GPU-based FFT in non-hybrid scenarios, while hybrid approaches combine both for distinct simulation periods. By scrutinizing two processing systems with varying specifications, diverse CPU- and GPU-based FFT combinations are assessed. Findings unequivocally underscore the superiority of CPU-based FFT for initial years, succeeded by GPU-based FFT for ensuing years, in terms of computational efficiency. The efficacy of the hybrid computation approach is demonstrated through a reduction of total computational time in 20-year VGCHP operation simulations by up to 33.5 % compared to conventional CPU-based FFT methods.

Socio-demographic, economic and behavioral determinants of loss to follow-up status among human immunodeficiency virus-infected patients in southern Benin in 2020

Background: The recurrence of cases lost to follow-up constitutes a major concern for human immunodeficiency virus (HIV) care programs, particularly in Africa. The present study was carried out to determine the economic and socio-behavioral factors associated with the status of loss to follow-up among HIV-infected patients followed at the Suru Lere Zonal Teaching Hospital Center in Benin. Methods: This was a case-control study carried out with 41 cases selected for convenience and 82 controls retained according to a reasoned choice. Matching was done on the variables age (±5 years), sex and year of initiation of treatment. The data collected using questionnaires and counting sheets then entered using the Epi data 3.1 software were analyzed using the STATA 11 software. A multiple conditional logistic regression model at the 5% threshold was used to determine factors associated with “lost to follow-up” status. Results: In the sample, the average age of the people surveyed was 41±9 years for both cases and controls and women were predominantly represented (63.41%). The factors associated with the status of loss to follow-up were the non-existence of a means of transport (p=0.008), the lack of nutritional support (p=0.01), incorrect knowledge about antiretroviral treatment such as “ARVs cure HIV/AIDS” (p=0.002) or “treatment can be stopped when you feel better” (p=0.014). Conclusions: This study revealed the significant association of “lost to follow-up” status with socio-demographic, economic and behavioral factors among people on ARV treatment. These results will lead to better guide the care of these patients and improve the performance of the AIDS control program.

Physiotherapy case reports on three people with progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative brain disease that affects patient's functionality and quality of life. Physiotherapy should be recommended at the time of diagnosis to slow the progression of disability and enhance the quality of life of these patients. Here, we describe three cases of patients with PSP, outlining their motor and non-motor symptoms and examining their clinical progression with physiotherapy intervention. During the initial intervention years, a reduction in the number of falls was achieved, along with improvements in gait and balance. Exercise and physiotherapy appear to be beneficial for patients with PSP by enhancing their functionality and quality of life. Controlling or reducing the number of falls should be the primary goal of any intervention for patients with PSP.

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Association Between Excessive Screen Time and Language Delay in Preschool Children

Background: Language is a fundamental medium for expression and comprehension of complex ideas and is acquired from early childhood through both receptive and expressive forms, such as spoken words or sign language. The initial years of life are critical for language development, and the rise of digital device usage during this period prompts an investigation into its potential impact. Objective: This study aims to explore the connection between excessive screen time and language delay in preschool children, a subject of increasing relevance in the digital age. Methods: A cross-sectional approach was taken, gathering data from the caregivers of 318 preschool children in Lahore, using the Ages and Stages Questionnaires-3 (ASQ-3) to measure developmental milestones. SPSS version 23 was employed for statistical analysis. Results: The study included 318 participants, with a gender distribution of 218 females (68.6%) and 100 males (31.4%). In terms of device usage, 209 children (65.7%) used mobile phones, while 91 (28.6%) watched television, and 18 (5.7%) played video games. Regarding screen time duration, 65 children (20.4%) used devices for 1-3 hours, 105 (33.0%) for 3-6 hours, 113 (35.5%) for 6-9 hours, and 35 (11.0%) for more than 9 hours. Notably, for children with over 9 hours of screen time, only 27% met their language developmental milestones at 33 months, which reduced with age, culminating in just 20.1% meeting milestones by 60 months. Conclusion: The study's findings suggest a significant negative correlation between excessive screen time and language development in preschool children, with a clear trend of decreasing milestone achievement with increased screen time. This highlights the need for strategic interventions to manage screen time in early childhood.

Досвід фінансування військових витрат під час Першої світової війни

Continuation of the Russian-Ukrainian war increases the risks of growing financial and economic dependence of the country on the political will and economic capabilities of our allies, underscoring the importance of studying the experience in developing and implementing measures to transform the country's economic and financial policies in wartime conditions. The features of using emission, tax and credit instruments to ensure the financial capacity to cover the growing military needs of the Russian Empire and its allies during the First World War have been analyzed. The specifics of the financial policy of the imperial government during the initial years of the war, reflecting contemporary ideas about state intervention in economic life, are characterized. On the one hand, there was extensive issuance of credit notes to fund war needs, leading to the spread of inflationary processes. On the other hand, the authorities sought, through coercion, to curb price increases. It is argued that the absence of a long-term transformation program in the financial sphere after the onset of the war forced the government to resort to excessive expansion of the emission activities of the State Bank, gradually reducing the gold backing of the ruble, resulting in the proliferation of inflationary processes and negatively impacting economic development. The policy in the field of state credit, actively applied to finance war expenditures, is characterized. Three components of internal state credit are distinguished: obligations of the state treasury, essentially interest-bearing money; treasury notes that were essentially interest-bearing money; and bond loans that dominated in covering war expenditures.

Pattern of Public Healthcare Expenditure and Preparedness for COVID-19 in India: An Interstate Analysis

The present study made an attempt to examine the changing pattern of public healthcare expenditure across Indian states for the period 1979–1980 to 2019–2020 and tried to relate this with the spread and mortality of COVID-19 infected cases. An attempt was also made to analyse the responsiveness of per capita public healthcare expenditure (PCPHE) with the change in per capita GSDP (PCGSDP) to a much-disaggregated level. The supply side composite index (SSCI), panel regression and panel generalised method of moments (GMM) was used for analytical purpose. The study found that the greater variation in PCPHE across Indian states start exhibiting since the early years of initiation of NRHM policy and continued till recent years. Unlike the PCPHE, the public healthcare expenditure to GSDP ratio declined for all states in the subsequent time periods. The value of SSCI for both revenue and capital expenditure was low in states having larger populations and geographical areas. The study argued that the average PCPHE across Indian states exhibited irregular pattern of association with the COVID-19 confirmed cases, positivity and death rate. The panel GMM estimate of PCPHE exhibited an inelastic relationship with PCGSDP implying public healthcare is a ‘necessity’ across the Indian states.

Smoker's paradox in transcatheter aortic valve replacement: A National Inpatient Sample analysis from 2015 to 2020

BackgroundWhile smoking is recognized as a risk factor for multiple cardiovascular conditions, prior research has identified a smoker paradox, wherein smokers had better post-procedural outcomes following transcatheter aortic valve replacement (TAVR) in the initial years of its introduction among high-risk patients only. In recent years, TAVR has expanded to significant larger groups of low-risk patients and became the dominate approach for aortic valve replacement. Consequently, the study cohort from the previous research can no longer represent the current patient populations undergoing TAVR. This study aimed to examine the impact of smoking on TAVR outcomes in the later post-TAVR era. MethodsPatients who underwent TAVR were identified in the National Inpatient Sample (NIS) database from the last quarter of 2015–2020 by ICD-10-PCS. Patients were stratified into two cohorts based on smoker status. Multivariable analysis was performed comparing in-hospital post-TAVR outcomes. Adjusted pre-procedural variables included sex, age, race, socioeconomic status, comorbidities, and hospital characteristics. ResultsA total number of 58,934 patients who underwent TAVR were identified including 23,683 smokers and 35,251 non-smokers. Compared to non-smokers, smokers had lower in-hospital mortality (aOR 0.589, p < 0.01), MACE (aOR 0.678, p < 0.01), MI (aOR 0.719, p < 0.01), stroke (aOR 0.599, p < 0.01), neurological complications (aOR 0.653, p < 0.01), pacemaker implantation (aOR 0.911, p < 0.01), cardiogenic shock (aOR 0.762, p < 0.01), respiratory complications (aOR 0.822, p < 0.01), mechanical ventilation (aOR 0.669, p < 0.01), AKI (aOR 0.745, p < 0.01), VTE (aOR 0.578, p < 0.01), hemorrhage/hematoma (aOR 0.921, p < 0.01), infection (aOR 0.625, p < 0.01), vascular complications (aOR 0.802, p < 0.01), reopen surgery (aOR 0.453), and transfer out to another facility (aOR 0.79, p < 0.01). In addition, cigarette smokers had shorter LOS (p < 0.01), and less hospital charge (p < 0.01). ConclusionThis study identified the smoker paradox in the later post-TAVR era with remarkably broad protection from many complications and lower mortality. The reasons underlying this apparent smoker paradox merit deeper investigation.

Integrated Management of Childhood Illness in Oman: 16 Years of Pre-service Initiatives for Education and Training.

Each year, approximately 10 million children worldwide die before reaching the age of five, yet two-thirds of these deaths could be prevented with effective, low-cost interventions. The Integrated Management of Childhood Illness (IMCI) strategy was adopted in 1996 by the World Health Organization and the United Nations Children's Fund to address the holistic well-being of children. The ultimate goals of IMCI are to develop a healthcare system that adheres to best practices and to improve the knowledge, attitudes, and skills of healthcare professionals. This paper describes the IMCI in pre-service education and training and the steps involved in integrating it into the nursing course on child health at Oman College of Health Sciences. The program aims to reduce the morbidity and mortality rate of children under five years of age, as well as the severity of their diseases. The Oman College of Health Sciences was the first healthcare academic institution in Oman to implement IMCI in nursing education to strengthen the nursing students' knowledge, skills, and clinical practice.

A Compatible Marketing Strategy for the Faculty of Distance Education Institution

As a prominent distance education institution, Universitas Terbuka (UT) plays a vital role in enhancing educational equity for Indonesian citizens by offering flexible and cost-effective learning opportunities. However, the exposure of UT, particularly the Faculty of Education and Teacher Training (FKIP), requires further enhancement. The phenomenon that occurs must be addressed by choosing a marketing strategy that targets various groups, particularly millennials. The purpose of this study is to investigate the most compatible marketing strategy for faculty in distance education institutions. In the initial year of this study, two key questions are explored: First, the optimal strategy for UT, specifically FKIP, to market its study program, and second, the most effective approach to diversify and promote UT’s study programs. Employing qualitative research, data was collected from 131 respondents and 80 students across four regional offices, supplemented by insights from marketing experts. The findings reveal the necessity for a balanced approach incorporating both conventional and digital marketing strategies. While the conventional strategy emerged as more effective based on the questionnaire and FGD results, the research highlighted the importance of developing a digital marketing strategy aligned with UT’s identity as a cyber university.

Aneurysm and Artery Dissection After Oral VEGFR-TKI Use in Adults With Cancer

The association of tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR-TKIs) with aneurysm and artery dissection (AAD) has been frequently reported in spontaneous reporting databases. To investigate the risk and incidence of AAD occurrence in patients with cancer treated with oral VEGFR-TKIs, with capecitabine as an active comparator. This national, historical cohort study was conducted using national claims data from the National Health Insurance Service in Korea from 2007 to 2020, with a 1-year follow-up. Patients with cancer aged 40 years or older prescribed oral VEGFR-TKIs or capecitabine were enrolled. Data were analyzed from September 2022 through April 2023. Oral VEGFR-TKIs (sorafenib, regorafenib, vandetanib, sunitinib, lenvatinib, axitinib, and pazopanib) or capecitabine as a comparator. Hazard ratios (HRs) were used to investigate the association between VEGFR-TKI use and AAD after propensity score matching. The primary outcome was AAD, and secondary outcomes were aortic aneurysm and dissection and AAD with rupture. Outcomes were defined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes. Among 127 710 patients with cancer eligible for the study (80 386 males [62.9%]; mean [SD] age, 62.6 [10.9] years), 37 308 patients received VEGFR-TKIs and 90 402 patients received capecitabine. Among 27 535 matched patients receiving VEGFR-TKIs, the incidence of AAD within 1 year of treatment initiation was 6.0 per 1000 person-years. The median (IQR) time to AAD onset in the matched AAD group was 114 (67-257) days after treatment initiation, with the highest incidence observed during the first 3 months (45 incidents vs 31, 17, and 16 incidents during 3- to 6-month, 6- to 9-month, and 9- to 12-month periods, respectively). Cox regression modeling showed that the risk of AAD occurrence was significantly higher among patients prescribed VEGFR-TKIs than those receiving capecitabine (HR, 1.48; 95% CI, 1.08-2.02); similar results were obtained among females (HR, 2.08; 95% CI, 1.26-3.42), older adults (aged ≥65 years; HR, 1.42; 95% CI, 1.01-1.99), and patients with dyslipidemia (HR, 1.58; 95% CI, 1.11-2.24). In this study, the use of oral VEGFR-TKIs was associated with an increased risk of AAD occurrence. These findings elucidate vascular toxic effects and may provide a substantial reference for reducing the socioeconomic burden of adverse events associated with VEGFR-TKI use.

Teaching statistics through investigation: a proposal for a textbook for the initial years of Elementary School

The research is of a quantitative nature applied in research teaching as a tool to encourage students in the early years of Elementary School to explore, develop strategies, raise hypotheses and conjectures, test, debate and apply mathematical ideas to problem situations. The aim is to reflect on pedagogical practices in teaching Statistics, based on the guidelines of the National Curricular Parameters and the National Common Curricular Base. As a theoretical reference, the research sought support from sociointeractionism, from the perspective of Vygotsky. A paradidactic book was created for the statistical teaching, which involves the student in investigative activities and directs the teacher with strategies that mediate the construction of statistical reasoning. The application of the educational product occurred through a didactic sequence, with 18 students in the 3rd year of Elementary School from a public school in the city of Gama/DF, Brazil.