Evaluation of the Behavioral Effect of Psychostimulants in Children with Autism Spectrum Disorder: A Cross-Sectional Study.

BACKGROUND: Autism spectrum disorder (ASD) is often accompanied by comorbid conditions such as attention deficit hyperactivity disorder and epilepsy. In this context, patients are often treated with psychostimulants in an attempt to control behavioral symptoms. This study aims to understand the behavioral effects of psychostimulants in children with ASD and investigate if interictal epileptiform discharges on electroencephalogram (EEG) can act as a modifying factor in this behavior. METHODS: Sixty-eight patients with ASD who were being accompanied in the Department of Child and Adolescent Psychiatry of the Centro Hospitalar Universitário de São João and had previously done an EEG assessment answered a questionnaire regarding their behavioral response to psychostimulants. RESULTS: In total, 47.4% of patients reported improved agitation, 56.1% enhanced concentration, and 8.8% improved sleep. Conversely, 28.1% experienced worsened agitation, 15.8% worsened concentration, and 17.5% worsened sleep. The remaining reported no alterations. The age of diagnosis correlated significantly with improved agitation, with a higher diagnosis age being associated with a higher probability of improvement. Extended-release methylphenidate and genetic variations were significantly associated with worsening of agitation. Regarding speech, 86% exhibited no changes, while 14% showed alterations, mostly, 87.5%, characterized as negative. For other behavioral alterations, 45.6% reported negative changes, 3.5% reported positive changes, and 50.9% reported no additional alterations. Female gender was significantly associated with other negative behavioral changes. A significant correlation was found between treatment duration and the probability of improvement in agitation, concentration, and other behavioral changes.

[Estimation of cancer incidence in Brazil and its regions in 2018: methodological aspects]. / Estimativa de incidência de câncer no Brasil e regiões em 2018: aspectos metodológicos.

The aim of this study was to develop a methodology for estimating cancer incidence in Brazil and its regions. Using data from population-based cancer registries (RCBP, acronym in Portuguese) and the Brazilian Mortality Information System (SIM, acronym in Portuguese), annual incidence/mortality (I/M) ratios were calculated by type of cancer, age group and sex in each RCBP. Poisson longitudinal multilevel models were applied to estimate the I/M ratios by region in 2018. The estimate of new cancer cases in 2018 was calculated by applying the estimated I/M ratios to the number of SIM-corrected deaths that occurred that year. North and Northeast concentrated the lowest I/M ratios. Pancreatic, lung, liver and esophageal cancers had the lowest I/M ratios, whereas the highest were estimated for thyroid, testicular, prostate and female breast cancers. For 2018, 506,462 new cancer cases were estimated in Brazil. Female breast and prostate were the two main types of cancer in all regions. In the North and Northeast, cervical and stomach cancers stood out. Differences in the I/M ratios between regions were observed and may be related to socioeconomic development and access to health services.

O objetivo deste estudo foi desenvolver metodologia para estimar a incidência de câncer no Brasil e regiões. A partir de dados dos registros de câncer de base populacional (RCBP) e do Sistema de Informações sobre Mortalidade (SIM) foram calculadas razões de incidência e mortalidade (I/M) anuais, tipo de câncer, faixa etária e sexo em cada RCBP. Para estimar as razões I/M por região em 2018, foram aplicados modelos multiníveis longitudinais de Poisson. A estimativa de casos novos de câncer, em 2018, foi calculada aplicando-se as razões I/M estimadas ao número de óbitos corrigidos do SIM ocorridos naquele ano. Norte e Nordeste concentraram as menores razões I/M. Os cânceres de pâncreas, pulmão, fígado e esôfago tiveram as menores razões I/M, enquanto as maiores razões I/M foram estimadas para câncer de tireoide, testículo, próstata e mama feminina. Para 2018, foram estimados 506.462 casos novos de câncer no Brasil. Mama feminina e próstata foram os dois principais tipos de câncer em todas as regiões. No Norte e no Nordeste, destacaram-se os cânceres do colo do útero e de estômago. Diferenças nas razões I/M entre as regiões foram observadas e podem estar relacionadas ao desenvolvimento socioeconômico e ao acesso a serviços de saúde.

El objetivo de este estudio fue desarrollar una metodología para estimar la incidencia de cáncer en Brasil y sus regiones. A partir de datos de los registros de cáncer de base poblacional (RCBP) y el Sistema de Informaciones de Mortalidad (SIM), se calcularon las tasas anuales de incidencia y mortalidad (I/M), tipo de cáncer, grupo de edad y sexo en cada RCBP. Para estimar las tasas de I/M por región en 2018, se aplicaron modelos multinivel longitudinales de Poisson. Los nuevos casos de cáncer en 2018 se estimaron mediante la aplicación de las tasas I/M que se esperan para el número de muertes corregidas de SIM que habían ocurrido ese año. Las regiones Norte y Nordeste concentraron las más bajas tasas de I/M. Los cánceres de páncreas, pulmón, hígado y esófago tuvieron las más bajas tasas de I/M, mientras que las más altas tasas de I/M se estimaron para los cánceres de tiroides, testículos, próstata y mama femenina. Para 2018, se estimaron 506.462 nuevos casos de cáncer en Brasil. La mama femenina y la próstata representaron técnicas de estimación y configuraron ser los tipos principales de cáncer en todas las regiones. En el Norte y el Nordeste se destacaron los cánceres de cuello uterino y estómago. Se observaron diferencias en las tasas de I/M entre regiones, las cuales pueden estar relacionadas con el desarrollo socioeconómico y el acceso a los servicios de salud.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

Current and Projected Mortality and Hospitalization Rates Associated With Conditional Cash Transfer, Social Pension, and Primary Health Care Programs in Brazil, 2000-2030.

Importance: The health outcomes of increased poverty and inequalities in low- and middle-income countries (LMICs) have been substantially amplified as a consequence of converging multiple crises. Brazil has some of the world's largest conditional cash transfer (Programa Bolsa Família [PBF]), social pension (Beneficio de Prestacão Continuada [BPC]), and primary health care (Estratégia de Saúde da Família [ESF]) programs that could act as mitigating interventions during the current polycrisis era of increasing poverty, slow or contracting economic growth, and conflicts. Objective: To evaluate the combined association of the Brazilian conditional cash transfer, social pension, and primary health care programs with the reduction of morbidity and mortality over the last 2 decades and forecast their potential mitigation of the current global polycrisis and beyond. Design, Setting, and Participants: This cohort study used a longitudinal ecological design with multivariable negative binomial regression models (adjusted for relevant socioeconomic, demographic, and health care variables) integrating the retrospective analysis from 2000 to 2019, with dynamic microsimulation models to forecast potential child mortality scenarios up to 2030. Participants included a cohort of 2548 Brazilian municipalities from 2004 to 2019, projected from 2020 to 2030. Data analysis was performed from September 2022 to February 2023. Exposure: PBF coverage of the target population (those who were poorest) was categorized into 4 levels: low (0%-29.9%), intermediate (30.0%-69.9%), high (70.0%-99.9%), and consolidated (≥100%). ESF coverage was categorized as null (0), low (0.1%-29.9%), intermediate (30.0%-69.9%), and consolidated (70.0%-100%). BPC coverage was categorized by terciles. Main outcomes and measures: Age-standardized, all-cause mortality and hospitalization rates calculated for the entire population and by age group (<5 years, 5-29 years, 30-69 years, and ≥70 years). Results: Among the 2548 Brazilian municipalities studied from 2004 to 2019, the mean (SD) age-standardized mortality rate decreased by 16.64% (from 6.73 [1.14] to 5.61 [0.94] deaths per 1000 population). Consolidated coverages of social welfare programs studied were all associated with reductions in overall mortality rates (PBF: rate ratio [RR], 0.95 [95% CI, 0.94-0.96]; ESF: RR, 0.93 [95% CI, 0.93-0.94]; BPC: RR, 0.91 [95% CI, 0.91-0.92]), having all together prevented an estimated 1 462 626 (95% CI, 1 332 128-1 596 924) deaths over the period 2004 to 2019. The results were higher on mortality for the group younger than age 5 years (PBF: RR, 0.87 [95% CI, 0.85-0.90]; ESF: RR, 0.89 [95% CI, 0.87-0.93]; BPC: RR, 0.84 [95% CI, 0.82-0.86]), on mortality for the group aged 70 years and older, and on hospitalizations. Considering a shorter scenario of economic crisis, a mitigation strategy that will increase the coverage of PBF, BPC, and ESF to proportionally cover the newly poor and at-risk individuals was projected to avert 1 305 359 (95% CI, 1 163 659-1 449 256) deaths and 6 593 224 (95% CI, 5 534 591-7 651 327) hospitalizations up to 2030, compared with fiscal austerity scenarios that would reduce the coverage of these interventions. Conclusions and relevance: This cohort study's results suggest that combined expansion of conditional cash transfers, social pensions, and primary health care should be considered a viable strategy to mitigate the adverse health outcomes of the current global polycrisis in LMICs, whereas the implementation of fiscal austerity measures could result in large numbers of preventable deaths.

Comparison of four different human papillomavirus genotyping methods in cervical samples: Addressing method-specific advantages and limitations.

Since human papillomavirus (HPV) is recognized as the causative agent of cervical cancer and associated with anogenital non-cervical and oropharyngeal cancers, the characterization of the HPV types circulating in different geographic regions is an important tool in screening and prevention. In this context, this study compared four methodologies for HPV detection and genotyping: real-time PCR (Cobas® HPV test), nested PCR followed by conventional Sanger sequencing, reverse hybridization (High + Low PapillomaStrip® kit) and next-generation sequencing (NGS) at an Illumina HiSeq2500 platform. Cervical samples from patients followed at the Family Health Strategy from Juiz de Fora, Minas Gerais, Brazil, were collected and subjected to the real-time PCR. Of those, 114 were included in this study according to the results obtained with the real-time PCR, considered herein as the gold standard method. For the 110 samples tested by at least one methodology in addition to real-time PCR, NGS showed the lowest concordance rates of HPV and high-risk HPV identification compared to the other three methods (67-75 %). Real-time PCR and Sanger sequencing showed the highest rates of concordance (97-100 %). All methods differed in their sensitivity and specificity. HPV genotyping contributes to individual risk stratification, therapeutic decisions, epidemiological studies and vaccine development, supporting approaches in prevention, healthcare and management of HPV infection.

Estimativa de incidência de câncer no Brasil e regiões em 2018: aspectos metodológicos / Estimation of cancer incidence in Brazil and its regions in 2018: methodological aspects / Estimación de la incidencia del cáncer en Brasil y regiones en 2018: aspectos metodológicos

Resumo: O objetivo deste estudo foi desenvolver metodologia para estimar a incidência de câncer no Brasil e regiões. A partir de dados dos registros de câncer de base populacional (RCBP) e do Sistema de Informações sobre Mortalidade (SIM) foram calculadas razões de incidência e mortalidade (I/M) anuais, tipo de câncer, faixa etária e sexo em cada RCBP. Para estimar as razões I/M por região em 2018, foram aplicados modelos multiníveis longitudinais de Poisson. A estimativa de casos novos de câncer, em 2018, foi calculada aplicando-se as razões I/M estimadas ao número de óbitos corrigidos do SIM ocorridos naquele ano. Norte e Nordeste concentraram as menores razões I/M. Os cânceres de pâncreas, pulmão, fígado e esôfago tiveram as menores razões I/M, enquanto as maiores razões I/M foram estimadas para câncer de tireoide, testículo, próstata e mama feminina. Para 2018, foram estimados 506.462 casos novos de câncer no Brasil. Mama feminina e próstata foram os dois principais tipos de câncer em todas as regiões. No Norte e no Nordeste, destacaram-se os cânceres do colo do útero e de estômago. Diferenças nas razões I/M entre as regiões foram observadas e podem estar relacionadas ao desenvolvimento socioeconômico e ao acesso a serviços de saúde.

Abstract: The aim of this study was to develop a methodology for estimating cancer incidence in Brazil and its regions. Using data from population-based cancer registries (RCBP, acronym in Portuguese) and the Brazilian Mortality Information System (SIM, acronym in Portuguese), annual incidence/mortality (I/M) ratios were calculated by type of cancer, age group and sex in each RCBP. Poisson longitudinal multilevel models were applied to estimate the I/M ratios by region in 2018. The estimate of new cancer cases in 2018 was calculated by applying the estimated I/M ratios to the number of SIM-corrected deaths that occurred that year. North and Northeast concentrated the lowest I/M ratios. Pancreatic, lung, liver and esophageal cancers had the lowest I/M ratios, whereas the highest were estimated for thyroid, testicular, prostate and female breast cancers. For 2018, 506,462 new cancer cases were estimated in Brazil. Female breast and prostate were the two main types of cancer in all regions. In the North and Northeast, cervical and stomach cancers stood out. Differences in the I/M ratios between regions were observed and may be related to socioeconomic development and access to health services.

Resumen: El objetivo de este estudio fue desarrollar una metodología para estimar la incidencia de cáncer en Brasil y sus regiones. A partir de datos de los registros de cáncer de base poblacional (RCBP) y el Sistema de Informaciones de Mortalidad (SIM), se calcularon las tasas anuales de incidencia y mortalidad (I/M), tipo de cáncer, grupo de edad y sexo en cada RCBP. Para estimar las tasas de I/M por región en 2018, se aplicaron modelos multinivel longitudinales de Poisson. Los nuevos casos de cáncer en 2018 se estimaron mediante la aplicación de las tasas I/M que se esperan para el número de muertes corregidas de SIM que habían ocurrido ese año. Las regiones Norte y Nordeste concentraron las más bajas tasas de I/M. Los cánceres de páncreas, pulmón, hígado y esófago tuvieron las más bajas tasas de I/M, mientras que las más altas tasas de I/M se estimaron para los cánceres de tiroides, testículos, próstata y mama femenina. Para 2018, se estimaron 506.462 nuevos casos de cáncer en Brasil. La mama femenina y la próstata representaron técnicas de estimación y configuraron ser los tipos principales de cáncer en todas las regiones. En el Norte y el Nordeste se destacaron los cánceres de cuello uterino y estómago. Se observaron diferencias en las tasas de I/M entre regiones, las cuales pueden estar relacionadas con el desarrollo socioeconómico y el acceso a los servicios de salud.

Viability of Collagen Matrix Grafts Associated with Nanohydroxyapatite and Elastin in Bone Repair in the Experimental Condition of Ovariectomy.

Bone lesions have the capacity for regeneration under normal conditions of the bone metabolism process. However, due to the increasing incidence of major traumas and diseases that cause bone-mineral deficiency, such as osteoporosis, scaffolds are needed that can assist in the bone regeneration process. Currently, natural polymeric scaffolds and bioactive nanoparticles stand out. Therefore, the objective of the study was to evaluate the osteoregenerative potential in tibiae of healthy and ovariectomized rats using mineralized collagen and nanohydroxyapatite (nHA) scaffolds associated with elastin. The in-vivo experimental study was performed with 60 20-week-old Wistar rats, distributed into non-ovariectomized (NO) and ovariectomized (O) groups, as follows: Controls (G1-NO-C and G4-O-C); Collagen with nHA scaffold (G2-NO-MSH and G5-O-MSH); and Collagen with nHA and elastin scaffold (G3-NO-MSHC and G6-O-MSHC). The animals were euthanized 6 weeks after surgery and the samples were analyzed by macroscopy, radiology, and histomorphometry. ANOVA and Tukey tests were performed with a 95% CI and a significance index of p < 0.05. In the histological analyses, it was possible to observe new bone formed with an organized and compact morphology that was rich in osteocytes and with maturity characteristics. This is compatible with osteoconductivity in both matrices (MSH and MSHC) in rats with normal conditions of bone metabolism and with gonadal deficiency. Furthermore, they demonstrated superior osteogenic potential when compared to control groups. There was no significant difference in the rate of new bone formation between the scaffolds. Ovariectomy did not exacerbate the immune response but negatively influenced the bone-defect repair process.

Papanicolaou test in Brazil: analysis of the National Health Survey of 2013 and 2019.

OBJECTIVES: To compare the coverage of cervical cancer screening in Brazil in 2013 and 2019, investigating the factors associated with having the test performed and the reasons given for not doing it. Additionally, a comparison is made concerning the time taken to receive the test result in SUS (Sistema Único de Saúde) and in the private health services. METHODS: Using data from the National Health Survey (Pesquisa Nacional de Saúde - PNS), prevalence rates and corresponding confidence intervals were calculated to determine the frequency of recent cervical cancer screenings among women aged between 25 and 64 years old in Brazil, for both 2013 and 2019. Poisson regression models were employed to compare the prevalence of the outcome according to sociodemographic characteristics. The reasons for not having the test and the time between performing and receiving the result were also analyzed. RESULTS: The findings revealed an increase in the coverage of preventive cervical cancer exams in Brazil from 78.7% in 2013 to 81.3% in 2019. Additionally, there was a decline in the proportion of women who had never undergone the exam, from 9.7% to 6.1%. Prevalence of test uptake was higher among white women, those with higher levels of education and income, and those residing in the South and Southeast regions of the country. The most commonly cited reasons for not taking the test were the impression it was unnecessary (45% in both 2013 and 2019) and never having been asked to undergo the test (20.6% in 2013 and 14.8% in 2019). CONCLUSIONS: Despite the high coverage of screening achieved in the country, there is great inequality in access to the test, and a non-negligible number of women are at greater risk of dying from a preventable disease. Efforts must be made to structure an organized screening program that identifies and captures the most vulnerable women.

Development and Initial Assessment of [18F]OP-801: a Novel Hydroxyl Dendrimer PET Tracer for Preclinical Imaging of Innate Immune Activation in the Whole Body and Brain.

PURPOSE: Innate immune activation plays a critical role in the onset and progression of many diseases. While positron emission tomography (PET) imaging provides a non-invasive means to visualize and quantify such immune responses, most available tracers are not specific for innate immune cells. To address this need, we developed [18F]OP-801 by radiolabeling a novel hydroxyl dendrimer that is selectively taken up by reactive macrophages/microglia and evaluated its ability to detect innate immune activation in mice following lipopolysaccharide (LPS) challenge. PROCEDURES: OP-801 was radiolabeled in two steps: [18F]fluorination of a tosyl precursor to yield [18F]3-fluoropropylazide, followed by a copper-catalyzed click reaction. After purification and stability testing, [18F]OP-801 (150-250 µCi) was intravenously injected into female C57BL/6 mice 24 h after intraperitoneal administration of LPS (10 mg/kg, n=14) or saline (n=6). Upon completing dynamic PET/CT imaging, mice were perfused, and radioactivity was measured in tissues of interest via gamma counting or autoradiography. RESULTS: [18F]OP-801 was produced with >95% radiochemical purity, 12-52 µCi/µg specific activity, and 4.3±1.5% decay-corrected yield. Ex vivo metabolite analysis of plasma samples (n=4) demonstrated high stability in mice (97±3% intact tracer >120 min post-injection). PET/CT images of mice following LPS challenge revealed higher signal in organs known to be inflamed in this context, including the liver, lung, and spleen. Gamma counting confirmed PET findings, showing significantly elevated signal in the same tissues compared to saline-injected mice: the liver (p=0.009), lung (p=0.030), and spleen (p=0.004). Brain PET/CT images (summed 50-60 min) revealed linearly increasing [18F]OP-801 uptake in the whole brain that significantly correlated with murine sepsis score (r=0.85, p<0.0001). Specifically, tracer uptake was significantly higher in the brain stem, cortex, olfactory bulb, white matter, and ventricles of LPS-treated mice compared to saline-treated mice (p<0.05). CONCLUSION: [18F]OP-801 is a promising new PET tracer for sensitive and specific detection of activated macrophages and microglia that warrants further investigation.

Socioeconomic status and cancer survival in Brazil: Analysis of population data from the municipalities of Aracaju and Curitiba, 1996-2012.

INTRODUCTION: The association between socioeconomic status and cancer prognosis has been demonstrated in several countries. Despite the existence of indirect evidence of this phenomenon in Brazil, few studies in this regard are available. OBJECTIVES: The objective of the present study is to analyse socioeconomic related survival gaps for patients diagnosed with breast, cervical, lung, prostate, and colorectal cancer in the cities of Aracaju (SE) and Curitiba (PR). METHODS: Using population-based data, we estimated net survival by tumour site, year of diagnosis, socioeconomic status and local of residence. Net survival estimation was done with multilevel parametric model allowing flexible spline functions do estimate excess mortality hazards. RESULTS: 28,005 cases were included in survival analysis. Five-year net survival showed positive association with SES. Intermunicipal survival gaps favouring Aracaju where prominent for breast (reaching 16,1% in 5 years) OBJECTIVES: Study the impact of socioeconomic factors on cancer survival in two Brazilian capitals. METHODS: Survival analysis using population-based cancer data including patients diagnosed with breast, lung, prostate, cervical and colorectal cancer between 1996 and 2012 in Aracaju and Curitiba. Outcomes were excessive mortality hazard (EMH) and 5- and 8-years net survival (NS). The association of race/skin color and socioeconomic level (SES) with EMH and net survival were analyzed using a multilevel regression model with flexible splines. RESULTS: 28,005 cases were included, 6636 from Aracaju and 21,369 from Curitiba. NS for all diseases studied increased more prominently for Curitiba population. We observed NS gap between the populations of Aracaju and Curitiba that increased or remained stable during the study period, with emphasis on the growth of the difference in NS of lung and colon cancer (among men). Only for cervical cancer and prostate cancer there was a reduction in the intermunicipal gaps. 5-year NS for breast cancer in Aracaju ranged from 55.2% to 73.4% according to SES. In Curitiba this variation was from 66.5% to 83.8%. CONCLUSION: The results of the present study suggests widening of socioeconomic and regional inequalities in the survival of patients with colorectal, breast, cervical, lung and prostate cancers in Brazil during the 1990 s and 2000 s.

Post-traumatic osteoarthritis: the worst associated injuries and differences in patients' profile when compared with primary osteoarthritis.

BACKGROUND: The estimated prevalence of post-traumatic osteoarthritis (PTOA) is 10-12% and in this study 12.4%. Different knee and hip injuries have been identified as risk factors for PTOA, but there is no consensus regarding the most painful and disabling injuries. Identifying these injuries might help in the prevention of PTOA. Additionally, patients with PTOA have a higher risk for complications after arthroplasty than patients with primary OA, perhaps due to differences in the profile and comorbidity that might help to explain the difference. This work aims 1) to identify the most common past injuries associated with the most painful and disabling PTOA cases in non-athlete patients and 2) to compare the comorbidities and characteristics between PTOA and primary OA. METHODS: Retrospective hospital-based cohort study with 1290 participants with joint complaints or who received arthroplasty. Medical records included demographic information, diagnosis, medication, smoking, alcohol history and comorbidities. Data from January 2012 orthopaedic consults till December 2019 was reviewed and had the type and date of injury, pain score by the numerical rating scale and walking disability. Odds Ratio (OR) and 95% confidence intervals are presented. RESULTS: There were 641 cases with primary OA (65% females) and 104 with PTOA (61% males). Patients with PTOA were 7.5 years younger (P < 0.001), reported more alcohol consumption (P = 0.01) and had higher odds of osteoporotic fractures (OP) and psychosis than patients with primary OA (OR = 2.0, CI = 1.06-3.78 and OR = 2.90, CI = -0.91-9.18, respectively). Knee fractures were most common in males and hip fractures in females (31% and 37.5%, respectively, P < 0.005). The PTOA-associated injuries with the highest pain and disability scores were meniscal injuries and hip fractures. Besides, in the group with primary OA, there were more diabetes, hypertension and hypothyroidism cases than in PTOA. However, after adjustment, differences were only significant for diabetes (ORadj = 1.78, CI = 1.0-3.2). CONCLUSIONS: Past meniscal injuries and hip fractures were the most relevant PTOA-associated injuries regarding pain and walking disability. This, together with differences in their profile when compared with primary OA, might help to decide the orthopaedic management of these injuries to prevent complications such as PTOA and recurrence, with appropriate preoperative planning, surgery choice and comorbidity treatment.

Clinical Radiosynthesis and Translation of [18F]OP-801: A Novel Radiotracer for Imaging Reactive Microglia and Macrophages.

Positron emission tomography (PET) is a powerful tool for studying neuroinflammatory diseases; however, current PET biomarkers of neuroinflammation possess significant limitations. We recently reported a promising dendrimer PET tracer ([18F]OP-801), which is selectively taken up by reactive microglia and macrophages. Here, we describe further important characterization of [18F]OP-801 in addition to optimization and validation of a two-step clinical radiosynthesis. [18F]OP-801 was found to be stable in human plasma for 90 min post incubation, and human dose estimates were calculated for 24 organs of interest; kidneys and urinary bladder wall without bladder voiding were identified as receiving the highest absorbed dose. Following optimization detailed herein, automated radiosynthesis and quality control (QC) analyses of [18F]OP-801 were performed in triplicate in suitable radiochemical yield (6.89 ± 2.23% decay corrected), specific activity (37.49 ± 15.49 GBq/mg), and radiochemical purity for clinical imaging. Importantly, imaging mice with tracer (prepared using optimized methods) 24 h following the intraperitoneal injection of liposaccharide resulted in the robust brain PET signal. Cumulatively, these data enable clinical translation of [18F]OP-801 for imaging reactive microglia and macrophages in humans. Data from three validation runs of the clinical manufacturing and QC were submitted to the Food and Drug Administration (FDA) as part of a Drug Master File (DMF). Subsequent FDA approval to proceed was obtained, and a phase 1/2 clinical trial (NCT05395624) for first-in-human imaging in healthy controls and patients with amyotrophic lateral sclerosis is underway.

Percepão do enfermeiro na promoção de consulta de enfermagem de saúde familiar: Relatório Final de estágio / Relatório Final de estágio: Percepão do enfermeiro na promoção de consulta de enfermagem de saúde familiar / Nurse's perception in promoting family health nursing consultation: Final internship report

As famílias em Portugal foram confrontadas com desafios pessoais, sociais e de saúde para os quais não estavam preparadas. A sociedade na atualidade, em rápida transformação e evolução, constrangida por acontecimentos como a pandemia COVID-19, a guerra na Ucrânia e outros acontecimentos, colocam enormes desafios às famílias e à profissão de enfermagem. Os dados demográficos em Portugal, fornecidos pelos Censos 2021, descrevem uma população envelhecida, mais vulnerável e com mais necessidade de cuidados (INE, 2021). O enfermeiro especialista em enfermagem de saúde familiar desenvolve a consulta, efetua a avaliação da família, identifica e implementa as intervenções de enfermagem adequadas, numa visão sistémica, de modo a desempenhar cuidados de excelência. As unidades funcionais dos cuidados de saúde primários, têm a responsabilidade de assegurar recursos humanos, condições físicas e disponibilidade de tempo que permitam o desenvolvimento da consulta de enfermagem de saúde familiar. Partindo desta premissa considerou-se pertinente conhecer a percepção dos enfermeiros de família na promoção da consulta de enfermagem de saúde familiar, que motivou a realização do presente estudo de investigação e contribuiu para a consecução dos objetivos do estágio, desenvolvido na Unidade de Saúde Familiar Rafael Bordalo Pinheiro (USF RBP). Após a caracterização do contexto da prática clínica de enfermagem de família, referente ao estágio na USF RBP, é apresentada a fundamentação teórica, a reflexão crítica das actividades para a aquisição de competências do enfermeiro especialista nesta área, terminando com o trabalho de investigação, seguido da sua discussão e implicações para a prática clínica. Objetivo: Conhecer a percepção do enfermeiro de família acerca da promoção da consulta de enfermagem de saúde familiar. Estratégia de pesquisa: Revisão Integrativa da Literatura. Mnemónica PICo: População (P) - enfermeiro de família; Intervenção (I) - percepção dos enfermeiros sobre a consulta de enfermagem; Contexto (Co) - cuidados de saúde primários. A extração de dados foi realizada por dois revisores independentes, assim como a sua análise e síntese. Foram considerados diferentes estudos quanto à sua metodologia, de 2017 a 2022, escritos em português, inglês, francês e espanhol. A pesquisa foi realizada através do portal EBSCO, de modo a aceder às bases de dados CINAHL Complete, MEDLINE Complete, Nursing & Allied Health Collection e Mediclatina. As pesquisas na biblioteca virtual da SciELO não obtiveram artigos de acordo com os critérios de inclusão e com os descritores utilizados. Apresentação e interpretação dos resultados: Identificaram-se 241 artigos, tendo sido excluídos 57 por serem duplicados. Permaneceram 184. Após a leitura dos títulos foram excluídos 144. Procedeu-se então à leitura reflexiva dos títulos e resumos dos quais foram excluídos 33 por não responderem aos critérios de inclusão. Ficaram 7 artigos para a elegibilidade, sendo que após a leitura integral dos mesmos, 5 não responderam à questão PICo formulada. Após este processo restaram 2 artigos para avaliação metodológica. Conclusão: Os enfermeiros descrevem fatores facilitadores e obstáculos na promoção da consulta de enfermagem. Como facilitadores: Enfermeiro como elemento estratégico na equipa de saúde para a capacitação das famílias; Adequadas condições físicas das instalações e suficientes recursos humanos; Enfermeiro ser detentor e confiante no desempenho de competências específicas; Reconhecimento pelos pares e pela comunidade, pela aquisição de resultados positivos no desempenho dos enfermeiros especialistas. Como obstáculos: Dificuldade do enfermeiro em manter o foco de cuidados na família; Sistemas informáticos com inadequada parametrização de dados mínimos; Sobrecarga de horário de trabalho; Burocracias atribuídas ao enfermeiro que não pertencem à sua esfera de competências. Implicações na prática clínica: Incentivar as unidades funcionais a investir na formação contínua no âmbito da intervenção à família; Recursos humanos e físicos adequados; Sistemas de informação padronizados; Criação de protocolos de consulta baseados num modelo conceptual de enfermagem; Elaboração de indicadores de resultados sensíveis aos cuidados de enfermagem à família; Mais Investigação na área de enfermagem de saúde familiar.

Families in Portugal were faced with personal, social and health challenges for which they were not prepared. Today's society, in rapid transformation and evolution, constrained by events such as the COVID-19 pandemic, the war in Ukraine and other events, poses enormous challenges to families and the nursing profession. Demographic data in Portugal, provided by the 2021 Census, describe an aging population, more vulnerable and in greater need of care (INE, 2021). The nurse specialist in family health nursing develops the consultation, carries out the family assessment, identifies and implements appropriate nursing interventions, from a systemic perspective, in order to provide excellent care. The functional units of primary health care are responsible for ensuring human resources, physical conditions and time availability that allow the development of family health nursing consultations. Based on this premise, it was considered pertinent to know the perception of family nurses in promoting family health nursing consultations, which motivated the carrying out of this research study and contributed to achieving the objectives of the internship, developed at the Rafael Family Health Unit. Bordalo Pinheiro (USF RBP). After characterizing the context of family nursing clinical practice, referring to the internship at USF RBP, the theoretical foundation is presented, as well as critical reflection on the activities for the acquisition of specialist nurse skills in this area, ending with research work, followed by its discussion and implications for clinical practice. Objective: To understand the perception of family nurses regarding the promotion of family health nursing consultations. Research strategy: Integrative Literature Review. PICo Mnemonic: Population (P) - family nurse; Intervention (I) - nurses' perception of the nursing consultation; Context (Co) - primary health care. Data extraction was carried out by two independent reviewers, as well as analysis and synthesis. Different studies were considered regarding their methodology, from 2017 to 2022, written in Portuguese, English, French and Spanish. The search was carried out through the EBSCO portal, in order to access the CINAHL Complete, MEDLINE Complete, Nursing & Allied Health Collection and Mediclatina databases. Searches in the SciELO virtual library did not obtain articles in accordance with the inclusion criteria and the descriptors used. Presentation and interpretation of results: 241 articles were identified, 57 of which were excluded for being duplicates. 184 remained. After reading the titles, 144 were excluded. We then proceeded to a reflective reading of the titles and abstracts, of which 33 were excluded because they did not meet the inclusion criteria. There were 7 articles left for eligibility, and after reading them in full, 5 did not answer the PICo question asked. After this process, 2 articles remained for methodological evaluation. Conclusion: Nurses describe facilitating factors and obstacles in promoting nursing consultation. As facilitators: Nurse as a strategic element in the health team to empower families; Adequate physical conditions of the facilities and sufficient human resources; Nurses have and are confident in performing specific skills; Recognition by peers and the community, for the acquisition of positive results in the performance of specialist nurses. Obstacles include: Difficulty for nurses to maintain the focus of care on the family; Computer systems with inadequate minimum data parameterization; Overload of working hours; Bureaucracies attributed to nurses that do not belong to their sphere of competence. Implications for clinical practice: Encourage functional units to invest in ongoing training within the scope of family intervention; Adequate human and physical resources; Standardized information systems; Creation of consultation protocols based on a conceptual nursing model; Development of results indicators sensitive to family nursing care; More Research in the area of family health nursing.

Recent changes in trends of mortality from cervical cancer in Southeastern Brazil.

OBJECTIVE: To analyze the trends of cervical cancer mortality in Brazilian Southeastern states, and to compare them to Brazil and other regions between 1980 and 2020. METHODS: Time series study based on data from the Sistema de Informações de Mortalidade (Brazilian Mortality Information System). Death data were corrected by proportional redistribution of deaths from ill-defined causes and cervical cancer of unspecified portion. Age-standardized and age-specific rates were calculated by screening target (25-39 years; 40-64 years) and non-target (65 years or older) age groups. Annual percentage changes (APC) were estimated by linear regression model with breakpoints. The coverage of Pap Smear exam in the Unified Health System (SUS) was evaluated between 2009 and 2020 according to age group and locality. RESULTS: There were increases in corrected mortality rates both in 1980 and in 2020 in all regions, with most evident increments at the beginning of the series. There was a decrease in mortality nationwide between 1980-2020; however, the state of São Paulo showed a discrete upward trend in 2014-2020 (APC=1.237; 95%CI 0.046-2.443). Noteworthy is the trend increment in the 25-39 year-old group in all study localities, being sharper in the Southeast region in 2013-2020 (APC=5.072; 95%CI 3.971-6.185). Screening coverage rates were highest in São Paulo and lowest in Rio de Janeiro, with a consistent decline from 2012 onwards at all ages. CONCLUSIONS: São Paulo is the first Brazilian state to show a reversal trend in mortality from cervical cancer. The changes in mortality patterns identified in this study point to the need for reorganization of the current screening program, which should be improved to ensure high coverage, quality, and adequate follow-up of all women with altered test results.

Frequency and factors associated with delay in breast cancer treatment in Brazil, according to data from the Oncology Panel, 2019-2020.

OBJECTIVE: to analyze treatment delay and the flow of care for women with breast cancer in Brazil in 2019 and 2020. METHOD: this was a follow-up study of breast cancer cases available from the Oncology Panel; a chi-square test and multilevel logistic regression were performed in order to analyze the explanatory variables associated with delay (greater than 60 days) in starting treatment. RESULTS: 22,956 cases (54.5%) with delay in treatment were identified in 2019 and 17,722 (48.7%) in 2020; the Southeast region (54.6%) had the greatest proportion of delay; delay was greater when treatment was provided outside the municipality of residence and lower in 2020 compared to 2019; most outward flows were to the capital cities in the same Federative Units of residence. CONCLUSION: strategies to reduce cancer treatment delay and optimize health care networks in the Federative Units should be prioritized.

Imaging CD19+ B Cells in an Experimental Autoimmune Encephalomyelitis Mouse Model using Positron Emission Tomography.

Multiple sclerosis (MS) is the most common demyelinating central nervous system (CNS) disease affecting young adults, often resulting in neurological deficits and disability as the disease progresses. B lymphocytes play a complex and critical role in MS pathology and are the target of several therapeutics in clinical trials. Currently, there is no way to accurately select patients for specific anti-B cell therapies or to non-invasively quantify the effects of these treatments on B cell load in the CNS and peripheral organs. Positron emission tomography (PET) imaging has enormous potential to provide highly specific, quantitative information regarding the in vivo spatiotemporal distribution and burden of B cells in living subjects. This paper reports methods to synthesize and employ a PET tracer specific for human CD19+ B cells in a well-established B cell-driven mouse model of MS, experimental autoimmune encephalomyelitis (EAE), which is induced with human recombinant myelin oligodendrocyte glycoprotein 1-125. Described here are optimized techniques to detect and quantify CD19+ B cells in the brain and spinal cord using in vivo PET imaging. Additionally, this paper reports streamlined methods for ex vivo gamma counting of disease-relevant organs, including bone marrow, spinal cord, and spleen, together with high-resolution autoradiography of CD19 tracer binding in CNS tissues.

Frequency and factors associated with delay in breast cancer treatment in Brazil according to data from the Oncology Panel, 2019 and 2020 / Frecuencia y factores asociados al retraso en el tratamiento del cáncer de mama en Brasil según datos del Panel de Oncología, 2019 y 2020 / Frequência e fatores associados ao atraso para o tratamento do câncer de mama no Brasil segundo dados do PAINEL-Oncologia, 2019-2020

Objective: To analyze the delay in treatment and the flow of care for women with breast cancer in Brazil in 2019 and 2020. Method: Follow-up study of breast cancer cases available in the Oncology Panel. To analyze the explanatory variables associated with the delay (greater than 60 days) to start treatment, a chi-square test and multilevel logistic regression were performed. Results: 22,956 cases (54.5%) were identified in 2019 and 17,722 (48.7%) in 2020 with delay in treatment. The Southeast region (54.6%) had a higher proportion of delay, which was higher when carried out outside the municipality of residence and lower in 2020 compared to 2019. residence. Conclusion: Strategies that reduce the time interval until the beginning of cancer treatment and optimize health care networks in the states should be prioritized.

Objetivo: Analizar la demora en el tratamiento y el flujo de atención de mujeres con cáncer de mama en Brasil en 2019 y 2020. Método: Estudio de seguimiento de los casos de cáncer de mama disponibles en el Panel de Oncología. Para analizar las variables explicativas asociadas al retraso (mayor de 60 días) en el inicio del tratamiento se realizó la prueba de chi-cuadrado y regresión logística multinivel. Resultados: se identificaron 22.956 casos (54,5%) en 2019 y 17.722 (48,7%) en 2020 con retraso en el tratamiento. La región Sudeste (54,6%) tuvo mayor proporción de atraso, siendo mayor cuando se realiza fuera del municipio de residencia y menor en 2020 en relación a 2019. de residencia. Conclusión: Se deben priorizar estrategias que reduzcan el intervalo de tiempo hasta el inicio del tratamiento del cáncer y optimicen las redes de atención de salud en los estados.

Objetivo: analisar o atraso para o tratamento e o fluxo assistencial de mulheres com câncer de mama no Brasil em 2019 e 2020. Métodos: estudo de seguimento de casos de câncer de mama disponibilizados no PAINEL-Oncologia; para analisar as variáveis explicativas associadas ao atraso (maior que 60 dias) no início do tratamento, realizou-se teste qui-quadrado e regressão logística multinível. Resultados: identificaram-se 22.956 casos (54,5%) em 2019 e 17.722 (48,7%) em 2020, com atraso para o tratamento; a região Sudeste (54,6%) teve maior proporção de atraso, que foi maior quando o tratamento foi realizado fora do município de residência, e menor em 2020, comparando-se a 2019; os fluxos externos, em sua maioria, ocorreram para as capitas das mesmas Unidades da Federação (UFs) de residência. Conclusão: estratégias que diminuam o intervalo de tempo até o início do tratamento oncológico e otimizem as redes de atenção em saúde nas UFs devem ser priorizadas.

Papanicolaou test in Brazil: analysis of the National Health Survey of 2013 and 2019 / Exame de Papanicolaou no Brasil: análise da Pesquisa Nacional de Saúde em 2013 e 2019

ABSTRACT OBJECTIVES To compare the coverage of cervical cancer screening in Brazil in 2013 and 2019, investigating the factors associated with having the test performed and the reasons given for not doing it. Additionally, a comparison is made concerning the time taken to receive the test result in SUS (Sistema Único de Saúde) and in the private health services. METHODS Using data from the National Health Survey (Pesquisa Nacional de Saúde - PNS), prevalence rates and corresponding confidence intervals were calculated to determine the frequency of recent cervical cancer screenings among women aged between 25 and 64 years old in Brazil, for both 2013 and 2019. Poisson regression models were employed to compare the prevalence of the outcome according to sociodemographic characteristics. The reasons for not having the test and the time between performing and receiving the result were also analyzed. RESULTS The findings revealed an increase in the coverage of preventive cervical cancer exams in Brazil from 78.7% in 2013 to 81.3% in 2019. Additionally, there was a decline in the proportion of women who had never undergone the exam, from 9.7% to 6.1%. Prevalence of test uptake was higher among white women, those with higher levels of education and income, and those residing in the South and Southeast regions of the country. The most commonly cited reasons for not taking the test were the impression it was unnecessary (45% in both 2013 and 2019) and never having been asked to undergo the test (20.6% in 2013 and 14.8% in 2019). CONCLUSIONS Despite the high coverage of screening achieved in the country, there is great inequality in access to the test, and a non-negligible number of women are at greater risk of dying from a preventable disease. Efforts must be made to structure an organized screening program that identifies and captures the most vulnerable women.

RESUMO OBJETIVOS Comparar a cobertura do rastreamento do câncer de colo do útero no Brasil em 2013 e 2019, investigar os fatores associados à realização do exame e os motivos informados para não ter realizado, além de comparar o tempo do recebimento do resultado do exame no SUS e na rede privada. MÉTODOS A partir de dados da Pesquisa Nacional de Saúde (PNS) foram calculadas as prevalências e os respectivos intervalos de confiança de realização do exame preventivo do câncer do colo do útero há menos de três anos, em mulheres de 25 a 64 anos, em 2013 e 2019. Modelos de regressão de Poisson foram utilizados para comparar as prevalências do desfecho segundo características sociodemográficas. Também foram analisados os motivos para não ter feito o exame e o tempo entre a realização e o recebimento do laudo. RESULTADOS Houve aumento na cobertura do exame preventivo no Brasil entre 2013 (78,7%) e 2019 (81,3%) e redução na proporção de mulheres que nunca fizeram o exame de 9,7% para 6,1%. A prevalência de realização do exame foi maior em mulheres brancas, melhor escolaridade e renda mais alta, residentes nas regiões Sul e Sudeste. Os motivos mais frequentes para não realizar o exame foram achar desnecessário (45% em 2013 e em 2019) e nunca ter sido orientada a fazê-lo (20,6% em 2013 e 14,8% em 2019). CONCLUSÕES Apesar das elevadas coberturas de rastreamento alcançadas pelo país, há grande desigualdade no acesso ao exame, e uma parcela não desprezível de mulheres está sob maior risco de morrer por uma doença que pode ser evitada. Esforços devem ser feitos para a estruturação de um programa de rastreamento organizado que identifique e capte as mulheres mais vulneráveis.