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.

Effectiveness of Pilates compared with home-based exercises in individuals with chronic non-specific low back pain: Randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of a Pilates exercise program compared with home-based exercises in individuals with chronic non-specific low back pain. DESIGN: A randomised controlled trial with a six-month follow-up. SETTING: Rehabilitation clinic. PARTICIPANTS: One hundred and forty-five individuals (18-50 years of age) with low back pain for ≥ 12 consecutive weeks were enrolled and randomly allocated to either Pilates (n = 72) or home-based exercise groups (n = 73). INTERVENTIONS: Method Pilates (Mat Pilates exercises using accessories) versus home-based exercise (postural exercises, muscle stretching and strengthening, and spine stabilisation/mobilisation), twice a week, for 6 weeks. MAIN MEASURES: Assessments were performed at baseline, post-intervention, and six months follow-up. Outcomes were pain intensity, disability, and health-related quality of life. RESULTS: At post-intervention, the Pilates group had significantly lower pain intensity (mean difference = -1.14; 95% CI -2.05; -0.23), less disability (mean difference = -6.7; 95% CI -11.3; -2.0), and higher health-related quality of life (mean difference = 0.102; 95% CI 0.054; 0151) compared to the home-based exercise group. At follow-up, the Pilates group had a significantly higher health-related quality of life (mean difference = 0.055; 95% CI 0.003; 0.106) compared with the home-based exercise group but there were no significant differences in pain and disability. A significant overall effect of Pilates compared to home-based exercise was found for disability (mean difference = -4.4; 95% CI -7.6; -1.1), and health-related quality of life (mean difference = 0.049; 95% CI 0.022; 0.076), but not for pain. CONCLUSION: Although Pilates was significantly superior to home exercise for pain and disability, the differences were not considered clinically relevant. However, Pilates did provide significant and clinically relevant differences in utility.

Performance bonuses and the quality of primary health care delivered by family health teams in Brazil: A difference-in-differences analysis.

BACKGROUND: Pay-for-performance (P4P) programmes to incentivise health providers to improve quality of care have been widely implemented globally. Despite intuitive appeal, evidence on the effectiveness of P4P is mixed, potentially due to differences in how schemes are designed. We exploited municipality variation in the design features of Brazil's National Programme for Improving Primary Care Access and Quality (PMAQ) to examine whether performance bonuses given to family health team workers were associated with changes in the quality of care and whether the size of bonus mattered. METHODS AND FINDINGS: For this quasi-experimental study, we used a difference-in-differences approach combined with matching. We compared changes over time in the quality of care delivered by family health teams between (bonus) municipalities that chose to use some or all of the PMAQ money to provide performance-related bonuses to team workers with (nonbonus) municipalities that invested the funds using traditional input-based budgets. The primary outcome was the PMAQ score, a quality of care index on a scale of 0 to 100, based on several hundred indicators (ranging from 598 to 660) of health care delivery. We did one-to-one matching of bonus municipalities to nonbonus municipalities based on baseline demographic and economic characteristics. On the matched sample, we used ordinary least squares regression to estimate the association of any bonus and size of bonus with the prepost change over time (between November 2011 and October 2015) in the PMAQ score. We performed subgroup analyses with respect to the local area income of the family health team. The matched analytical sample comprised 2,346 municipalities (1,173 nonbonus municipalities; 1,173 bonus municipalities), containing 10,275 family health teams that participated in PMAQ from the outset. Bonus municipalities were associated with a 4.6 (95% CI: 2.7 to 6.4; p < 0.001) percentage point increase in the PMAQ score compared with nonbonus municipalities. The association with quality of care increased with the size of bonus: the largest bonus group saw an improvement of 8.2 percentage points (95% CI: 6.2 to 10.2; p < 0.001) compared with the control. The subgroup analysis showed that the observed improvement in performance was most pronounced in the poorest two-fifths of localities. The limitations of the study include the potential for bias from unmeasured time-varying confounding and the fact that the PMAQ score has not been validated as a measure of quality of care. CONCLUSIONS: Performance bonuses to family health team workers compared with traditional input-based budgets were associated with an improvement in the quality of care.

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.

Advances in the Asymmetric Synthesis of BINOL Derivatives.

BINOL derivatives have shown relevant biological activities and are important chiral ligands and catalysts. Due to these properties, their asymmetric synthesis has attracted the interest of the scientific community. In this work, we present an overview of the most efficient methods to obtain chiral BINOLs, highlighting the use of metal complexes and organocatalysts as well as kinetic resolution. Further derivatizations of BINOLs are also discussed.

Epidermoid cyst mimicking a thyroglossal duct cyst in a pediatric patient: a case report.

This article presents a case of an epidermoid cyst that mimicked a thyroglossal duct cyst in a pediatric patient. An 8-year-old boy was referred for evaluation of a volumetric increase in the median cervical region with an evolution of about 4 years. The skin in the submental region was healthy and normal colored. Palpation revealed a mobile, well-circumscribed nodular lesion of soft consistency. Computed tomography of the neck showed an expansive hypodense formation extending from the base of the tongue to the upper portion of the hyoid bone, suggesting a thyroglossal duct cyst. Considering the diagnostic hypothesis, cystic enucleation via the Sistrunk procedure was planned. However, no ductal structure was identified during the surgical procedure, and the lesion was only near, but not attached to, the hyoid bone. Simple excision of the lesion was therefore performed. At the most recent follow-up examination, about 3 months postoperatively, the patient demonstrated satisfactory clinical progress. The epidermoid cyst close to the hyoid bone presented diagnostic difficulty due to its similarity to a thyroglossal duct cyst. Computed tomography provides limited information for diagnosing this type of lesion, and ultrasonography is the preferred test. In view of the uncertain diagnosis in this case, the extent of the excision was determined during the surgery, and simple excision was a satisfactory treatment associated with a good prognosis.

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.

Ultrastructural changes caused by the combination of intravenous immunoglobulin with meropenem, amikacin and colistin in multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic pathogen associated with increased morbidity and mortality in Healthcare-associated infections (HAI). Combination antimicrobial therapy, meropenem, amikacin and colistin, has been used as an alternative in multidrug-resistant (MDR) A. baumannii infections due to reduced treatment options. However, these combinations are not always effective and exhibit high toxicity. Empiric therapy of intravenous immunoglobulin (IVIG) associated with antimicrobials has shown promising results in bacterial infections, considering the immunomodulatory action of IVIG. Thus, the aim of this study was to determine the combined antimicrobial action and to describe the ultrastructural changes caused in ten MDR A. baumannii isolates submitted to IVIG alone and in combination with colistin, meropenem and amikacin. Minimum Inhibitory Concentration (MIC) of antimicrobials and checkerboard were determined. Isolates were submitted to 4 mg/mL of IVIG alone and in combination with different synergistic sub-MIC of antimicrobials tested, and processed for scanning electron microscopy. Nine bacterial isolates showed meropenem-resistant, two isolates had colistin-intermediate, and four isolates were considered intermediate to amikacin. Synergism in five isolates for meropenem/amikacin and meropenem/colistin were observed. Bacterial cells submitted to IVIG and meropenem, amikacin and colistin presented several ultrastructural changes, such as cell elongation and rupture, membrane roughness, incomplete cell division, cell surface "bubbles" and "depression". A. baumannii isolates presented high resistance to meropenem and synergism among evaluated antimicrobials. In addition, it was possible to verify in vitro that IVIG associated with meropenem, amikacin and colistin is a promising alternative for MDR A. baumannii infections. Thus, these data support the continued empirical use and stimulate in vivo analyzes with IVIG to search for new therapeutic options for HAI.

Antimicrobial activity and biofilm inhibition of riparins I, II and III and ultrastructural changes in multidrug-resistant bacteria of medical importance.

Natural products have been used to treat various infections; however, the development of antimicrobials has made natural products in disuse. Riparin I, II and III are natural alkamide isolated from Aniba riparia (Ness) Mez (Lauraceae), that exhibit economic importance and it is used in traditional medicine, and popularly known as "louro". This study investigated the cytotoxicity, antimicrobial and antibiofilm activity, and ultrastructural changes in vitro by riparins I, II and III in Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. We analyzed the cytotoxicity by MTT assay in Vero cells and hemolytic action verified in human erythrocytes. The antimicrobial activity was determined by microdilution in broth against ATCC strains, identifying the susceptible species. Subsequently, only the MDR isolates of sensitive bacterial species were evaluated regarding its biofilm formation and ultrastructural changes. Riparin I presented low cytotoxicity and hemolytic percentage ranging from of 9.01%-12.97%. Only the riparin III that showed antimicrobial activity against MDR clinical isolates, and significant reduction in biofilm formation in S. aureus. Moreover, the riparin III promoted ultrastructural changes in bacterial cells, such as elongated cellular without bacterial septum, cells with a rugged appearance on the cell surface and cytoplasmic material extravasation. As has been noted riparin III has an inhibitory potential against biofilm formation in S. aureus, besides having antimicrobial activity and promoting ultrastructural changes in MDR clinical isolates. Thus, riparin III is an interesting alternative for further studies aiming to develop new therapeutic options.

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.

Accuracy of Orthognathic Surgical Outcomes Using 2- and 3-Dimensional Landmarks-The Case for Apples and Oranges?

PURPOSE: To verify predicted versus obtained surgical movements in 2-dimensional (2D) and 3-dimensional (3D) measurements and compare the equivalence between these methods. MATERIALS AND METHODS: A retrospective observational study of bimaxillary orthognathic surgeries was performed. Postoperative cone-beam computed tomographic (CBCT) scans were superimposed on preoperative scans and a lateral cephalometric radiograph was generated from each CBCT scan. After identification of the sella, nasion, and upper central incisor tip landmarks on 2D and 3D images, actual and planned movements were compared by cephalometric measurements. One-sample t test was used to statistically evaluate results, with expected mean discrepancy values ranging from 0 to 2 mm. Equivalence of 2D and 3D values was compared using paired t test. RESULTS: The final sample of 46 cases showed by 2D cephalometry that differences between actual and planned movements in the horizontal axis were statistically relevant for expected means of 0, 0.5, and 2 mm without relevance for expected means of 1 and 1.5 mm; vertical movements were statistically relevant for expected means of 0 and 0.5 mm without relevance for expected means of 1, 1.5, and 2 mm. For 3D cephalometry in the horizontal axis, there were statistically relevant differences for expected means of 0, 1.5, and 2 mm without relevance for expected means of 0.5 and 1 mm; vertical movements showed statistically relevant differences for expected means of 0, 0.5, 1.5 and 2 mm without relevance for the expected mean of 1 mm. Comparison of 2D and 3D values displayed statistical differences for the horizontal and vertical axes. CONCLUSIONS: Comparison of 2D and 3D surgical outcome assessments should be performed with caution because there seems to be a difference in acceptable levels of accuracy between these 2 methods of evaluation. Moreover, 3D accuracy studies should no longer rely on a 2-mm level of discrepancy but on a 1-mm level.

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.

Direct healthcare costs for people with cerebral palsy in the Brazilian unified health system between 2015 and 2019.

BACKGROUND: Estimate the costs of inpatient and outpatient care for people with Cerebral Palsy (CP) in Brazil. RESEARCH DESIGN AND METHODS: Health records of people with CP in the Hospital and Outpatient Information Systems of Brazil between 2015 and 2019 were analyzed. Variables analyzed were gender, age, ICD, Intensive Care Unit (ICU) use, total cost, and ICU cost. Costs were adjusted for inflation and converted to dollars. Linear regression analysis was performed to investigate the association between social and clinical variables and direct costs. RESULTS: A total direct cost of approximately $166 million to the National Health System was identified, with $7.08 million/year and $26.1 million/year of inpatient and outpatient costs, respectively. The healthcare was primarily for children up to 14 years of age. The ICD 'spastic quadriplegic CP' received the most attendance. Rehabilitation was responsible for 75% of the outpatient care, with physiotherapy standing out. Increased age, use of ICU, and the types of CP are related to increased cost. CONCLUSIONS: Healthcare for people with CP produced expressive costs for the Brazilian public health system, mainly with outpatient procedures and rehabilitation, with children being the most attended. Estimating these costs assist in better resource allocation for more effective healthcare provision.

Understanding the municipal-level design and adaptation of pay-for-performance schemes across two states of Brazil.

The design of complex health systems interventions, such as pay for performance (P4P), can be critical to determining such programmes' success. In P4P programmes, the design of financial incentives is crucial in shaping how these programmes work. However, the design of such schemes is usually homogenous across providers within a given scheme. Consequently, there is a limited understanding of the strengths and weaknesses of P4P design elements from the implementers' perspective. This study takes advantage of the unique context of Brazil, where municipalities adapted the federal incentive design, resulting in variations in incentive design across municipalities. The study aims to understand why municipalities in Brazil chose certain P4P design features, the associated challenges and the local adaptations made to address problems in scheme design. This study was a multiple case study design relying on qualitative data from 20 municipalities from two states in Northeastern Brazil. We conducted two key informant interviews with municipal-level stakeholders and focus group discussions with primary care providers. We also reviewed municipal Primary Care Access and Quality laws in each municipality. We found substantial variation in the design choices made by municipalities regarding 'who was incentivized', the 'payment size' and 'frequency'. Design choices affected relationships within municipalities and within teams. Challenges were chiefly associated with fairness relating to 'who received the incentive', 'what is incentivized' and the 'incentive size'. Adaptations were made to improve fairness, mostly in response to pressure from the healthcare workers. The significant variation in design choices across municipalities and providers' response to them highlights the importance of considering local context in the design and implementation of P4P schemes and ensuring flexibility to accommodate local preferences and emerging needs. Attention is needed to ensure that the choice of 'who is incentivized' and the 'size of incentives' are inclusive and fair and the allocation and 'use of funds' are transparent.

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.

Prevalence, risk factors, and impact of long COVID in a socially vulnerable community in Brazil: a prospective cohort study.

Background: Long COVID is an emerging global public health issue. Socially vulnerable communities in low- and-middle-income countries were severely impacted by the pandemic and are underrepresented in research. This prospective study aimed to determine the prevalence of long COVID, its impact on health, and associated risk factors in one such community in Rio de Janeiro, Brazil. Methods: A total of 710 individuals aged 18 and older, with confirmed SARS-CoV-2 infection at least three months prior, were enrolled between November 25, 2021, and May 5, 2022. Participants were assessed via telephone or in person using a standardized questionnaire to evaluate their perception of recovery, symptoms, quality of life, and functional status. Findings: Twenty percent of participants did not feel fully recovered, 22% experienced new or persistent symptoms, 26% had worsened functional status, 18% had increased dyspnoea, and 32% reported a worse quality of life. Persistent symptoms included headache, cough, fatigue, muscle pain, and shortness of breath. Dyspnoea during the acute phase was the strongest independent predictor of worsening outcomes. Females and individuals with comorbidities were more likely to report worse recovery, functioning, dyspnoea, and quality of life. Interpretation: Our findings reveal a high burden of severe and persistent physical and mental health sequelae in a socially vulnerable community following COVID-19. Funding: UK Foreign, Commonwealth and Development Office and Wellcome Trust Grant (222048/Z/20/Z), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and the Centers for Disease Control and Prevention (CDC).

Economic burden of depression in Brazil: a cost-of-illness study based on productivity losses and healthcare costs between 2010 to 2018.

BACKGROUND: Depression is disabling disorder and cause functional impairments, and high costs for the health and social security system. OBJECTIVE: The direct and indirect costs of depression from the societal perspective were estimated for the period 2010 to 2018. METHODS: This cost-of-illness study in adults is based on prevalence, with a top-down approach, from the societal perspective. Direct (hospital and outpatient) and indirect (absenteeism) costs were included. Data were extracted from the Hospital and Outpatient Information Systems and the National Social Security Institute. RESULTS: The cost of depression was Int$ 2,288,511,607.39 in the analyzed period, with an average annual cost of Int$ 254,279,067.49. From 2014 to 2018, had a sharp and persistent decrease in the cost of depression (-44.24%), mainly in indirect costs (-55.83%). In the period investigated, indirect costs represented 74.85% of the total cost. Over time, outpatient surpassed hospital cost. In 2017 and 2018, outpatient costs represented 43.22% and 39.57% of total costs. In all the years and cost components analyzed, women predominated. CONCLUSIONS: Depression is a disease with a high economic burden for the healthcare system. Investments are still needed, such as higher coverage of services, multidisciplinary teams, and training of health professionals for psychosocial care.