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 twenty 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 PMAQ laws in each municipality. We found substantial variation in the design choices made by municipalities regarding 'who was incentivised', 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 incentivised', 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 the choice of 'who is incentivised' and the 'size of incentives' are inclusive and fair, and the allocation and 'use of funds' are transparent.

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.

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 (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 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 family health team 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.

In vitro evaluation of human intravenous immunoglobulin in combination with antimicrobials and human serum against multidrug-resistant isolates of Acinetobacter baumannii.

The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii-infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4 mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG preparations for the treatment of A. baumannii MDR infections.

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.

Extensive tongue lymphangioma followed for eight years: Case report.

Lymphangiomas are benign hamartomatous tumours similar to lymphatic vessel neoplasms, originating from lymphatic tissue sequestration and may or may not communicate with the rest of the system. There are several treatment options for lymphangioma, such as surgery, sclerotherapy, cryotherapy, lasers, steroids and bleomycin. Although surgery is the most indicated treatment, it can result in severe sequelae and loss of function in patients. The present case shows a 5-year-old patient diagnosed with extensive tongue lymphangioma and, due to the mutilation that would be caused by its complete excision, the option was for more conservative treatments such as laser therapy and cryotherapy. After follow-up for 8 years, the patient presents with preserved functions and controlled lesion.

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.

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.

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.

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.

How long does it take to translate research findings into routine healthcare practice?-the case of biological drugs for rheumatoid arthritis in Brazil.

Background: The literature reports long time lags between the several processes involved in the translation of drug research and development into clinical application. To expedite these processes, translational research has emerged as a process that can be applied to reduce the lag between scientific discoveries and their practical application. Thus, the objective of this study was to estimate the time lag in translational research of biological drugs for the treatment of rheumatoid arthritis included in the Brazilian Unified Health System [Sistema Único de Saúde (SUS)]. Methods: A descriptive retrospective study was conducted based on secondary data loaded by SUS users in public sources and systems to estimate the time lag between the publication of phase I clinical trial results to drug use in clinical settings. The dates of translational research activities were identified from markers and steps. Structured searches were conducted in the literature and reports from the National Commission for the Incorporation of Technologies in the SUS (Conitec) as well as from health authorities, and analyzed. Results: Between 2012 and 2019, SUS included five biological agents for the treatment of rheumatoid arthritis. The mean time lag from clinical development to use of these agents was 11.13 years (range, 8.57 to 12.90 years). The mean time lag for the stages of translational research were 5.30 (T1-basic research to clinical research), 5.08 (T2-clinical research to research synthesis), and 0.75 (T3-research synthesis to evidence-based practice) years. A shorter time lag was observed in the Brazilian case when it was possible to compare with other studies. Conclusions: The estimated time lag of biological drugs used in the treatment of rheumatoid arthritis was determined based on the translational research steps model adapted to the Brazilian context. Brazil has instituted legal frameworks that set deadlines for sanitary registration, health technology assessment (HTA), and the availability of drugs in the SUS, thus, allowing for a reduced stage T2 time lag. Nevertheless, improvements are still required in stages T1 and T2, especially in publishing the results of clinical trials.

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.

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.

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.

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.

Adoption of new therapies in the treatment of Hepatitis: a verification of the accuracy of budget impact analysis to guide investment decisions.

OBJECTIVES: While there are good Budget Impact Analysis (BIA) guidelines, studies still register potential bias. To do this, we compared the results between theoretical and real-world evidence (RWE) expenditures for medicines for Hepatitis C: boceprevir (BOC) and telaprevir (TVR). While both are not currently recommended in treatment guidelines following recent developments, this is an emblematic case because for 4 years these medicines consumed considerable resources. METHODS: Theoretical results and RWE expenditures were compared regarding the incorporation of BOC and TVR in 2013-2014 into the Brazilian Public Health System. Theoretical values were extracted from Commission for Technology Incorporation Report and RWE expenditures were extracted from the administrative data records using deterministic-probabilistic linkage. RESULTS: The estimated number of patients treated (BOC+TVR) was 13,012 versus 7,641 (real). The estimated purchase price for BOC was US$6.20 versus US$11.07 (real) and for TVR was US$42.21 versus US$84.09 (average/real). The estimated budget impact was US$285.16 million versus US$128.58 million (real). CONCLUSION: This study demonstrates appreciable divergence (US$156.58 million) between the theoretical budget impact and RWE expenditures due to underestimated purchase prices and overestimated populations. The greater the degree of accuracy the more reliable and usable BIAs become for decision-making.

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.

Budget impact analysis of medicines: estimated values versus real-world evidence and the implications.

OBJECTIVES: Budget Impact Analyses (BIA) of medicines helps managers in promoting health systems' sustainability when assessing the role and value of new medicines. However, it is not clear whether BIAs typically underestimate or overestimate the impact on real-world budgets. This retroactive analysis seeks to compare estimated values obtained by a BIA and Real-World Evidence (RWE) to guide discussions. METHODS: The estimated values were obtained through a BIA concerning the incorporation of adalimumab for the treatment of Rheumatoid Arthritis into the Brazilian Unified Health System (SUS) carried out retroactively and per international guidelines. RWE data was extracted from SUS computerized systems. We subsequently compared the number of treatments, costs, and Incremental Budget Impact (IBI). RESULTS: - The total number of treatments was underestimated by 10% (6,243) and the total expenditure was overestimated by 463% (US$ 4.7 billion). In five years, the total difference between the estimated values and real IBI reached US$ 1.1 billion. A current expenditure of US$ 1.0 was observed for every US$ 5.60 of estimated expenditure. CONCLUSION: - The higher estimates from the BIA might cause decision makers to be more cautious with the introduction of a new medicine to reduce the opportunity costs for other interventions.

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.