Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil.

BACKGROUND AIMS: The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective. METHODS: A survey containing structured questions was conducted among research participants who work at companies that commercialize ATMPs. A descriptive analysis was performed. RESULTS: We invited 15 foreign pharmaceutical companies, of which 10 agreed to participate. Overall, participants assessed that Brazil has a well-established regulatory system, especially the sanitary registration by the National Health Surveillance Agency (Anvisa), which ensures the quality, safety, and efficacy of the products. The Agency's good interaction with the regulated sector, the harmonization of sanitary and ethical assessment systems with other countries, and the analysis time in the biosafety assessment of Genetically Modified Organisms (GMOs) stand out as positive in industry's evaluation. On the other hand, it is important to advance the pricing regulation for these products since Brazilian regulations do not establish specific criteria for ATMP. One of the biggest challenges is the difficulty for the SUS in reimbursing these very high-cost therapies, especially using current Health Technology Assessment (HTA) methods. CONCLUSIONS: Considering the increasing number of approvals of cell and gene therapies in Brazil in the coming years, a close dialogue between the industry and the public sector is recommended to advance regulatory improvements (pricing and HTA). Additionally, the construction of policies to promote the national Health Economic-Industrial Complex, based on a mission-oriented vision that encourages innovative models of financing, especially those that consider risk-sharing and co-financing technologies, will help provide the population with universal, equitable and sustainable access to ATMP in the SUS.

Landscape of Brazilian research and development public funding in advanced therapies: lessons learned and a roadmap for middle-income economies.

BACKGROUND AIMS: Advanced therapy medicinal products (ATMPs) have reached the forefront of biotechnological innovation, partly due to public funders' efforts in the early stages of research and development (R&D). Data on investment in R&D of ATMPs are recognized as scarce, particularly in developing countries. Because of the numerous peculiarities of the Brazilian health system and the science and technology (S&T) system, the country is a good example for the evaluation of public investments in R&D of ATMPs. The aim of this study is to analyze the evolution of investments made by the Ministry of Health (MoH) of Brazil and partners in the ATMP field between 2004 and 2020. METHODS: A descriptive analysis was performed based on secondary data. The analysis was based on S&T and innovation research and support for research infrastructure in the field. The database was stratified by year of funding, ATMP type, type of study or research infrastructure project, amount invested in the project, targeted disease for which clinical trials in ATMPs were developed and financing sector (health, education, S&T and economic). RESULTS: The investments coordinated by MoH (61.5%) in partnership with the S&T, education and economic sectors (38.5%) consisted of Int$137.35 million in 282 ATMP projects. Funding included S&T and innovation research (67% of the total amount) and projects to implement or maintain infrastructure in selected research centers (32.98%). With regard to global convergence, cell therapy was the type of ATMP that most benefited from public investment, totaling 82.23% of the total funding in the analyzed period. Cardiology (29%) and neurology (21%) were the main focus of clinical trials. Following the global trend of public sector R&D funding, the number of basic and pre-clinical research projects represented 78.06% of the total number of projects. CONCLUSIONS: Despite the need to implement improvements in ATMP R&D financing policy in Brazil, the country has made important steps in the field and can serve as a benchmark for other countries with socioeconomic similarities. Among the main lessons are the prioritization of research aligned with the health needs of the population, cross-sector articulation by the health policymaker to coordinate R&D efforts of the sector and formulation of a specific sector policy (Programa Genomas Brasil, the Brazilian National Program of Genomic and Precision Medicine) to promote knowledge translation.

Public engagement in health technology assessment in Brazil: the case of the public consultation on National Clinical Guidelines for Care in Normal Birth.

BACKGROUND: There is a growing body of literature that recognizes the importance of public engagement in health technology assessment. However, there is still uncertainty regarding how the results should be recorded, analyzed, and used by decision makers. OBJECTIVE: Synthesize the contributions of the Brazilian public (women, health professionals, managers, educational institutions, and companies) about the implementation of the National Clinical Guidelines for Care in Normal Birth from the public consultation carried out in Brazil. METHOD: IRaMuTeQ software was used to organize and summarize the corpus based on three types of analysis: descriptive statistics; descending hierarchical classification; and specificities analysis. The public consultation was conducted in 2016 by the National Committee for Health Technology Incorporation (CONITEC) in the Brazilian public health system as part of the guideline development process. RESULTS: The corpus consisted of 303 texts, separated into 1233 text segments, 1081 of which were used, corresponding to retention of 87.67%. Five classes emerged from our analyses: mandatory presence of an obstetrician during labor and delivery in hospital settings; barriers and facilitators for guideline implementation; use of evidence-based practices by health professionals; progression of labor and delivery and women's rights; and mobilization to promote the guideline For each class, the most frequent words and sentences with the highest chi-squared scores were presented. Barriers were associated with lack of financial resources, training and professional motivation, and facilitators with training to change the practices of health professionals. Obstetric nurses emerged as an alternative for supervising normal births as well as the mandatory presence of an obstetrician during childbirth in hospital settings. CONCLUSION: Our findings summarize the contributions provided by the Brazilian public and shed some light on the barriers and facilitators of clinical guidelines for care in normal birth. These topics are not typically explored by quantitative studies. Including this information in the decision-making process would not only increase public engagement, but provide greater evidence for implementing the clinical guidelines nationwide.

Direct from the COVID-19 crisis: research and innovation sparks in Brazil.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has spread throughout more than 160 countries, infecting millions of people worldwide. To address this health emergency, countries have organized the flow of production and innovation to reduce the impact on health. This article shows the response of the Brazilian scientific community to meet the urgent needs of the public unified health system [SUS], aiming to guarantee universal access to an estimated population of 211 million. By December 2020, Brazil had recorded more than six million cases and approximately 175,000 deaths. METHODS: We collected data on research, development and innovation projects carried out by 114 public universities (plus Oswaldo Cruz Foundation [Fiocruz] and Butantan Institute), as reported on their websites. Additionally, we examined the studies on COVID-19 approved by the National Comission for Research Ethics, as well as those reported on the Ministry of Education website as of May 15, 2020. RESULTS: The 789 identified projects were classified according to research categories as follows: development and innovation (n = 280), other types of projects (n = 226), epidemiologic research (n = 211), and basic research on disease mechanisms (n = 72). Most proposals focused on the development and innovation of personal protective equipment, medical devices, diagnostic tests, medicines and vaccines, which were rapidly identified as research priorities by the scientific community. Some promising results have been observed from phase III vaccine trials, one of which is conducted in partnership with Oxford University and another of which is performed with Sinovac Biotech. Both trials involve thousands of volunteers in their Brazilian arms and include technology transfer agreements with Fiocruz and the Butantan Institute, respectively. These vaccines proved to be safe and effective and were immediately licensed for emergency use. The provision of doses for the public health system, and vaccination, started on January 17, 2021. CONCLUSIONS: The mobilized Brazilian scientific community has generated comprehensive research, development and innovation proposals to meet the most urgent needs. It is important to emphasize that this response was only possible due to decades of investment in research, development and innovation in Brazil. We need to reinforce and protect the Brazilian science, technology and innovation system from austerity policies that disregard health and knowledge as crucial investments for Brazilian society, in line with the constitutional right of universal health access and universal health coverage.

Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review.

INTRODUCTION: Mucopolysaccharidosis VI is a rare disease characterized by the arylsulfatase B enzyme deficiency, which is responsible for different clinical manifestations. The treatment consists of enzyme replacement therapy with intravenous administration of galsulfase. OBJECTIVE: Evaluate the effectiveness of the enzyme replacement therapy with galsulfase for the mucopolysaccharidosis VI treatment. METHOD: Systematic review of observational studies. The databases of PubMed, Cochrane Library, Lilacs, and Journal of Inherited Metabolic Disease were reviewed. The selection of studies, data mining, and methodological quality assessment were independently conducted by two authors. RESULTS: Eighteen studies fulfilled the inclusion criteria. Two studies were cohorts, one was longitudinal study, one was cross-sectional, one was a case-control, eight were case series, and five were case reports. A total of 362 participants with mucopolysaccharidosis type VI were evaluated, and 14 different outcomes related to the treatment effect were identified. Seven outcomes showed positive results, characterized by the patient survival, quality of life, respiratory function, joint mobility, physical resistance, reduction of urinary glycosaminoglycans, and growth. The hearing function and the cognitive development were stable after the treatment. Other outcomes related to the cardiac function, visual acuity, sleep apnea, and the size of the liver and spleen presented inconclusive outcomes. Concerning safety, light adverse reactions of hypersensitivity were reported. CONCLUSION: This review provided a broader panoramic view of the outcomes related to mucopolysaccharidosis type VI. Regardless of the inherent limitations of observational studies, the outcomes indicate that the enzyme replacement therapy has a positive effect on most of the outcomes associated to the disease.

Health conditions and occupational risks in a novel group: waste pickers in the largest open garbage dump in Latin America.

BACKGROUND: The inadequate management of solid waste impacts populations' health and quality of life, and disproportionately affects developing countries. This study aims to describe a protocol for epidemiological diagnosis, the purpose being to estimate the prevalence of chronic and communicable and non communicable diseases in waste pickers, and the occupational and environmental risk factors to which these are exposed. METHODS: This is a cross-sectional study, based on survey design in an area of extreme social vulnerability - the largest garbage dump in Latin America. Using a multidimensional research protocol, divided in three stages: 1- The identification of the subjects, and the scheduling of tests; 2- Situational diagnosis through interviews, anthropometric evaluation, measuring blood pressure, collecting hair and nail samples to detect exposure to heavy metals and undertaking laboratory tests; 3- The return of the waste pickers to receive the test results, followed by referral to the health team and to report occupational accidents. RESULTS: One thousand twenty-five waste pickers undertook tests and interviews. The majority were women (67.0%), with 36-45 years old (45.7%), and 96.0% had children. In total, 27.3% of the participants did not attend to any school and 47.7% were educated only up to primary level. The majority of waste pickers (68.70%) reported accidents and most of them (89.69%) were related to sharp objects. The mean time working in this open dump was 15 years. According the anthropometric measure, 32.6% were overweight and 21.1% were obese. The most common reported diseases were: osteomuscular disorders (78.7%); arboviruses (28.6%); episodic diarrhea (24.9%); hypertension (24.2%); bronchitis (14.3%); intestinal worms (12.6%) and diabetes (10.1%). According to the blood tests, the values outside the reference limits were: Uric acid (23.89%); creatinine (54.06%); GGT range (16.04%); SGOT - Serum Glutamic Oxaloacetic Transaminase (5.29%); SGPT - serum Glutamic-Pyruvic Transaminase (35.52%). CONCLUSIONS: This study is the first to evaluate multiple risks and diseases in the majority of waste pickers working in the largest garbage dump of a continent. These findings highlight the importance to address urgently the environmental, social and health impacts related to the management of solid waste in developmental countries to protect these workers and their families.

Public engagement in health technology assessment in Brazil: the case of the Trastuzumab public consultation.

BACKGROUND: Public engagement in health technology assessment (HTA) is increasing worldwide. There are several forms of public engagement and it is not always possible to determine which stakeholders participate in the HTA process and how they contribute. Our objective was to investigate which types of social representatives contributed to the public consultation on the incorporation of Trastuzumab for early-stage breast cancer treatment within the public health system in Brazil, held in 2012 by the National Committee for Health Technology Incorporation (CONITEC). METHODS: A mixed methods approach was used to analyze social representativeness and the composition of the corpus from the public consultation, which consisted of 127 contributions. Three types of analysis were performed using IRaMuTeQ software: classic lexical analysis, descending hierarchical classification and specificities analysis. The contributions were clustered according to the main categories of discourse observed, into four social representation categories: 1) patient representation/advocacy; 2) pharmaceutical industry/advocacy; 3) healthcare professionals; and 4) individual contributions. RESULTS: Category 1 contained words related to increased survival due to use of the drug and a low score for words pertaining to studies on Trastuzumab. The word "safety" obtained a positive score only in category 2, which was also the only category that exhibited a negative score for the word "risk". Category 3 displayed the lowest scores for "diagnosis" and "safety". The word "efficacy" had a negative score only in category 4. CONCLUSIONS: Each category exhibited different results for words related to health systems and to key concepts linked to HTA. Our analysis enabled the identification of the most prominent contributions for each category. Despite the promising results obtained, further research is needed to validate this software for use in analyzing public contributions.

Cost of providing doctors in remote and vulnerable areas: Programa Mais Médicos in Brazil.

OBJECTIVE: To evaluate the Programa Mais Médicos (More Doctors Program; PMM) in Brazil by estimating the proportional increase in the number of doctors in participating muni-cipalities and the program costs, stratified by cost component and funding source. METHODS: Official data from the 2013 edition of Demografia Médica no Brasil (Medical Demography in Brazil) was used to estimate the number of doctors prior to PMM. The number of doctors at the end of the fourth PMM recruiting cycle (July 2014) was obtained from the Ministry of Health. Cost components were identified and estimated based on PMM legislation and guidelines. The participating municipalities were chosen based on four criteria, all related to vulnerability. RESULTS: The PMM provided an additional 14 462 physicians to highly vulnerable, remote areas in 3 785 municipalities (68% of the total) and 34 Special Indigenous Sanitary Districts. There was a greater increase of physicians in the poorest regions (North and Northeast). The estimated annual cost of US$ 1.1 billion covered medical provision, continuing education, and supervision/mentoring. Funding was largely centralized at the federal level (92.6%). CONCLUSION: The cost of PMM is considered relatively moderate in comparison to its potential benefits for population health. The greater increase of doctors for the poorest and most vulnerable met the target of correcting imbalances in health worker distribution. The PMM experience in Brazil can contribute to the debate on reducing physician shortages.

Does pay-for-performance design matter? Evidence from Brazil.

Pay-for-performance (P4P) schemes have been shown to have mixed effects on health care outcomes. A challenge in interpreting this evidence is that P4P is often considered a homogenous intervention, when in practice schemes vary widely in their design. Our study contributes to this literature by providing a detailed depiction of incentive design across municipalities within a national P4P scheme in Brazil [Primary Care Access and Quality (PMAQ)] and exploring the association of alternative design typologies with the performance of primary health care providers. We carried out a nation-wide survey of municipal health managers to characterize the scheme design, based on the size of the bonus, the providers incentivized and the frequency of payment. Using OLS regressions and controlling for municipality characteristics, we examined whether each design feature was associated with better family health team (FHT) performance. To capture potential interactions between design features, we used cluster analysis to group municipalities into five design typologies and then examined associations with quality of care. A majority of the municipalities included in our study used some of the PMAQ funds to provide bonuses to FHT workers, while the remaining municipalities spent the funds in the traditional way using input-based budgets. Frequent bonus payments (monthly) and higher size bonus allocations (share of 20-80%) were strongly associated with better team performance, while who within a team was eligible to receive bonuses did not in isolation appear to influence performance. The cluster analysis showed what combinations of design features were associated with better performance. The PMAQ score in the 'large bonus/many workers/high-frequency' cluster was 8.44 points higher than the 'no bonus' cluster, equivalent to a difference of 21.7% in the mean PMAQ score. Evidence from our study shows how design features can potentially influence health provider performance, informing the design of more effective P4P schemes.

The care pathway of individuals with spinal disorders in a Health Care Network in the Federal District, Brazil: a retrospective study.

BACKGROUND: Understanding the care pathway is essential to identify how to effectively treat spinal disorders. However, there is no specific data on the pathway of these individuals in the Health Care Networks (HCN) in Brazil. OBJECTIVE: To investigate the pathway of individuals with non-specific spinal disorders (NSD) in the HCN in the Federal District, Brazil, and verify the interventions adopted, and to test whether sociodemographic and clinical variables predict the number of imaging tests, prescribed medication, and the first HCN access. METHODS: Retrospective study that analysed electronic records of 327 individuals with NSD between 2012 and 2018. Generalized linear models estimated the association between sociodemographic and clinical data and number of drugs prescribed and imaging tests requested. Multinomial logistic regression estimated the association between clinical and demographic variables and setting of first access. RESULTS: The median age was 57 years, and 75.5% were women. Emergency Department (ED) was the most accessed setting (43.7%), and back pain was the most prevalent condition (84.5%). Most individuals underwent imaging tests (60%) and drug prescriptions (86%). Physical exercises were prescribed to 13%, and 55% were referred to physical therapy. Women were more likely to first access the ED. CONCLUSION: The ED was the most used setting by people with NSD. Few participants received exercise prescriptions and half were referred to physical therapists. Individuals who used outpatient clinics and primary care received less drug prescriptions, and women were more likely to first access the ED. Increasing age was associated with greater chance of first accessing Outpatient Clinics.

Pay-for-performance for primary health care in Brazil: A comparison with England's Quality Outcomes Framework and lessons for the future.

Pay-for-performance (P4P) has been widely applied in OECD countries to improve the quality of both primary and secondary care, and is increasingly being implemented in low- and middle-income countries. In 2011, Brazil introduced one of the largest P4P schemes in the world, the National Programme for Improving Primary Care Access and Quality (PMAQ). We critically assess the design of PMAQ, drawing on a comparison with England's quality and outcome framework which, like PMAQ, was implemented at scale relatively rapidly within a nationalised health system. A key feature of PMAQ was that payment was based on the performance of primary care teams but rewards were given to municipalities, who had autonomy in how the funds could be used. This meant the incentives felt by family health teams were contingent on municipality decisions on whether to pass the funds on as bonuses and the basis upon which they allocated the funds between and within teams. Compared with England's P4P scheme, performance measurement under PMAQ focused more on structural rather than process quality of care, relied on many more indicators, and was less regular. While PMAQ represented an important new funding stream for primary health care, our review suggests that theoretical incentives generated were unclear and could have been better structured to direct health providers towards improvements in quality of care.

Association of the new zero-tolerance drinking and driving law with hospitalization rate due to road traffic injuries in Brazil.

We investigated the association of the new zero-tolerance drinking and driving law (Law 12,760, Dec. 2012) with hospital admissions due to road traffic injuries in Brazil by using interrupted time series from 2008 to 2019. We used linear regression designed to adjust for autocorrelation and Cumby-Huizinga test for residual autocorrelation. Newey-West standard errors was used to handle heteroscedasticity. We used ICD-10 codes for land transport accidents (V01-V89). The hospitalization rate was calculated per 100,000 inhabitants. The sources were the Hospital Information System and the Brazilian Institute for Geography and Statistics. Pre- and postintervention consist of 59 and 85 months, respectively. For Brazil, the hospitalization rate was associated with a reduction of 0.34 (p = 0.097; 95% CI - 0.74 to 0.06) in the first month of the intervention (Dec. 2012), followed by a significant change in the hospitalization trend. Compared to the period prior to the intervention, the monthly trend was associated with a reduction of 0.05 (p < 0.01; 95% CI - 0.06 to - 0.04) in the post period. These results stand in agreement with subgroup analyses for the Brazilian regions, although North and Northeast regions did not immediately reduce hospitalization rates (level change). Our results suggested that 440,599 hospitalizations for land transport accidents would be averted by the new zero-tolerance drinking and driving law from Dec. 2012 to Dec. 2019 in Brazil. Even using a quasi-experimental approach, our findings must be interpreted with caution due to observational design and registration flaws surrounding our data.

Analysis of the Financial Costs of a Health Promotion Program for Sexually Exploited Adolescents and Youngsters: The Case of the Vira Vida Program in Brazil.

The Vira Vida program promotes the health of adolescents and young adults, ages 16 to 24, who have been sexually exploited. It has served more than 3000 individuals in 18 Brazilian states. The objective of this research was to estimate the costs of Vira Vida and compare them with the costs of detention policies for juveniles under 18. This program cost study considers two periods: 2008 to 2012 (Cycle 1) and 2013 to 2014 (Cycle 2). The System S perspective and time horizon for one year were adopted. Direct costs incurred by the National Council of Industry Social Services, which coordinates Vira Vida, and by the Regional Departments (RD), responsible for the direct execution of Vira Vida, were analyzed. The cost of detention measures for adolescents and youngsters under the age of 18 was obtained from the literature. The annual cost per student enrolled in Vira Vida varied between US$ 3754.93 and US$27,244.48, depending on the cycle and the state. Most of the costs of the program were lower than those reported for detention measures for adolescents in Brazilian states. Evidence indicates that health promotion interventions targeting sexually exploited children and adolescents can help their recovery; on the other hand, studies indicate that detention measures do not help adolescents recover.

The cost of oral cancer: A systematic review.

Although clinical and epidemiological aspects of oral cancers (OC) are well-documented in the literature, there is a lack of evidence on the economic burden of OC. This study aims to provide a comprehensive systematic assessment on the economic burden of OC based on available evidence worldwide. A systematic review was conducted. The population was any individual, who were exposed to OC, considered here as lip (LC), oral cavity (OCC), or oropharynx (OPC) cancer. The outcome was information on direct (medical and non-medical) and indirect (productivity loss and early death) costs. The data sources included Scopus, Web of Science, Cochrane, BVS, and NHS EED. A search of grey literature (ISPOR and INAHTA proceedings) and a manual search in the reference lists of the included publications were performed (PROSPERO no. CRD42020172471). We identified 24 studies from 2001 to 2021, distributed by 15 countries, in 4 continents. In some developed western countries, the costs of LC, OCC, and OPC reached an average of Gross Domestic Product per capita of 18%, 75%, and 127%, respectively. Inpatient costs for OC and LC were 968% and 384% higher than those for outpatients, respectively. Advanced cancer staging was more costly (from ~22% to 373%) than the early cancer staging. The economic burden of oral cancer is substantial, though underestimated.

The disruption of elective procedures due to COVID-19 in Brazil in 2020.

Elective procedures were temporarily suspended several times over the course of the pandemic of COVID-19. Monthly data from the Unified Health System (SUS) were used for the period between January 2008 and December 2020 and the interrupted time series method was used to estimate the effect of the pandemic on the number of elective surgeries and elective procedures that were not performed. Considering a 9-month period, a reduction of 46% in the number of elective procedures carried out in the SUS could be attributed to COVID-19, corresponding to about 828,429 elective procedures cancelled, ranging from 549,921 to 1,106,936. To a full recovery of pre-pandemic performance, SUS would need to increase about 21,362 hospital beds, ranging from 12,370 to 36,392 hospital beds during a 6 month-period. This effort would represent an increase of 8.48% (ranging from 4.91 to 14.45%) in relation to the total number of SUS's hospital beds in 2019. As a result, the pandemic will leave a large number of elective procedures to be carried out, which will require efforts by health agencies to meet this demand.

Impact of COVID-19 on the mental health of public university hospital workers in Brazil: A cohort-based analysis of 32,691 workers.

BACKGROUND: In early 2020, the COVID-19 pandemic paralyzed the world and exposed the fragility of health systems in the face of mass illness. Health professionals became protagonists, fulfilling their mission at the risk of physical and mental illness. The study aimed to evaluate absenteeism indirectly related to SARS-CoV-2 infection in a large population of health care professionals. METHODS: An observational longitudinal repeated measures study was performed, including workers linked to 40 public university hospitals in Brazil. All causes of absenteeism were analyzed, focusing on those not directly attributed to COVID-19. Results for the same population were compared over two equivalent time intervals: prepandemic and during the pandemic. FINDINGS: A total of 32,691 workers were included in the study, with health professionals comprising 82.5% of the sample. Comparison of the periods before and during the pandemic showed a 26.6% reduction in work absence for all causes, except for COVID-19 and mental health-related absence. Concerning work absence related to mental health, the odds ratio was 39.0% higher during the pandemic. At the onset of the pandemic, there was an increase in absenteeism (all causes), followed by a progressive reduction until the end of the observation period. INTERPRETATION: Work absence related to mental illness among health care professionals increased during the COVID-19 pandemic, highlighting the need for health care managers to prioritize and implement support strategies to minimize absenteeism.

Dissemination interventions to improve healthcare workers' adherence with infection prevention and control guidelines: a systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has challenged health systems worldwide since 2020. At the frontline of the pandemic, healthcare workers are at high risk of exposure. Compliance with infection prevention and control (IPC) should be encouraged at the frontline. This systematic review aimed to assess the effects of dissemination interventions to improve healthcare workers' adherence with IPC guidelines for respiratory infectious diseases in the workplace. METHODS: We searched CENTRAL, MEDLINE, Embase, and the Cochrane COVID-19 Study Register. We included randomized controlled trials (RCTs) and cluster RCTs that assessed the effect of any dissemination strategy in any healthcare settings. Certainty of evidence was assessed using the GRADE approach. We synthesized data using random-effects model meta-analysis in Stata 14.2. RESULTS: We identified 14 RCTs conducted from 2004 to 2020 with over 65,370 healthcare workers. Adherence to IPC guidelines was assessed by influenza vaccination uptake, hand hygiene compliance, and knowledge on IPC. The most assessed intervention was educational material in combined strategies (plus educational meetings, local opinion leaders, audit and feedback, reminders, tailored interventions, monitoring the performance of the delivery of health care, educational games, and/or patient-mediated interventions). Combined dissemination strategies compared to usual routine improve vaccination uptake (risk ratio [RR] 1.59, 95% confidence interval [CI] 1.54 to 1.81, moderate-certainty evidence), and may improve hand hygiene compliance (RR 1.70; 95% CI 1.03 to 2.83, moderate-certainty). When compared to single strategies, combined dissemination strategies probably had no effect on vaccination uptake (RR 1.01, 95% CI 0.95 to 1.07, low-certainty), and hand hygiene compliance (RR 1.16, 95% CI 0.99 to 1.36, low-certainty). Knowledge of healthcare workers on IPC improved when combined dissemination strategies were compared with usual activities, and the effect was uncertain in comparison to single strategy (very low-certainty evidence). CONCLUSIONS: Combined dissemination strategies increased workers' vaccination uptake, hand hygiene compliance, and knowledge on IPC in comparison to usual activities. The effect was negligible when compared to single dissemination strategies. The adoption of dissemination strategies in a planned and targeted way for healthcare workers may increase adherence to IPC guidelines and thus prevent dissemination of infectious disease in the workplace. TRIAL REGISTRATION: Protocol available at http://osf.io/aqxnp .

Direct healthcare costs of lip, oral cavity and oropharyngeal cancer in Brazil.

The efficiency of public policies includes the measurement of the health resources used and their associated costs. There is a lack of studies evaluating the economic impact of oral cancer (OC). This study aims to estimate the healthcare costs of OC in Brazil from 2008 to 2016. This is a partial economic evaluation using the gross costing top-down method, considering the direct healthcare costs related to outpatients, inpatients, intensive care units, and the number of procedures, from the perspective of the public health sector. The data were extracted from the Outpatient and Inpatient Information System of the National Health System, by diagnosis according to the 10th Revision of the International Classification of Diseases, according to sites of interest: C00 to C06, C09 and C10. The values were adjusted for annual accumulated inflation and expressed in 2018 I$ (1 I$ = R$2,044). Expenditure on OC healthcare in Brazil was I$495.6 million, which was composed of 50.8% (I$251.6 million) outpatient and 49.2% (I$244.0 million) inpatient healthcare. About 177,317 admissions and 6,224,236 outpatient procedures were registered. Chemotherapy and radiotherapy comprised the largest number of procedures (88.8%) and costs (94.9%). Most of the costs were spent on people over 50 years old (72.9%) and on males (75.6%). Direct healthcare costs in Brazil for OC are substantial. Outpatient procedures were responsible for the highest total cost; however, inpatient procedures had a higher cost per procedure. Men over 50 years old consumed most of the cost and procedures for OC. The oropharynx and tongue were the sites with the highest expenditure. Further studies are needed to investigate the cost per individual, as well as direct non-medical and indirect costs of OC.

Direct cost of systemic arterial hypertension and its complications in the circulatory system from the perspective of the Brazilian public health system in 2019.

INTRODUCTION: Systemic arterial hypertension (SAH), a global public health problem and the primary risk factor for cardiovascular diseases, has a significant financial impact on health systems. In Brazil, the prevalence of SAH is 23.7%, which caused 203,000 deaths and 3.9 million DALYs in 2015. OBJECTIVE: To estimate the cost of SAH and circulatory system diseases attributable to SAH from the perspective of the Brazilian public health system in 2019. METHODS: A prevalence-based cost-of-illness was conducted using a top-down approach. The population attributable risk (PAR) was used to estimate the proportion of circulatory system diseases attributable to SAH. The direct medical costs were obtained from official Ministry of Health of Brazil records and literature parameters, including the three levels of care (primary, secondary, and tertiary). Deterministic univariate analyses were also conducted. RESULTS: The total cost of SAH and the proportion of circulatory system diseases attributable to SAH was Int$ 581,135,374.73, varying between Int$ 501,553,022.21 and Int$ 776,183,338.06. In terms only of SAH costs at all healthcare levels (Int$ 493,776,445.89), 97.3% were incurred in primary care, especially for antihypertensive drugs provided free of charge by the Brazilian public health system (Int$ 363,888,540.14). Stroke accounted for the highest cost attributable to SAH and the third highest PAR, representing 47% of the total cost of circulatory diseases attributable to SAH. Prevalence was the parameter that most affected sensitivity analyses, accounting for 36% of all the cost variation. CONCLUSION: Our results show that the main Brazilian strategy to combat SAH was implemented in primary care, namely access to free antihypertensive drugs and multiprofessional teams, acting jointly to promote care and prevent and control SAH.

COVID-19 as the leading cause of hospital deaths in the Brazilian public health system in 2020.

OBJECTIVES: To describe the profile of hospital deaths in Brazil according to cause of admission during the pre-pandemic (2019) and pandemic periods (2020). METHODS: Descriptive study based on individual-level records of all hospital admissions with death outcomes reimbursed by the Brazilian National Health System in 2019 and 2020. RESULTS: The number of hospital deaths increased by 16.7% in 2020 compared with 2019 (522,686 vs 609,755). Coronavirus disease 2019 (COVID-19) was associated with 19.5% (118,879) of all hospital deaths in 2020, surpassing diseases of the circulatory system (15.4%, 93,735) and diseases of the respiratory system (14.9%, 91,035). CONCLUSIONS: COVID-19 was the main cause of death in public hospitals in Brazil in 2020.