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The Nasrid emirate of southern Iberia emanated power through architecture; this project aims to better understand how this was made possible, via an interdisciplinary exploration of the Alhambra monument and other Al-Andalus constructions. Initial results of archaeological campaigns, structure chronologies and communication plans undertaken in 2021 and 2022 are presented.
Brazil’s public health system serves most of the population, but 25 percent of citizens rely on private health insurance. The National Regulatory Agency for Private Health Insurance and Plans (ANS) regulates private medicine reimbursements, which diverge from the public sector threshold. In 2022, the National Committee for Health Technology Incorporation (CONITEC) set a willingness-to-pay benchmark of BRL40,000 (USD8,215) per quality-adjusted life-year. The ANS has no such benchmark, highlighting a pivotal gap in economic evaluations for private health care.
Methods
This quantitative study investigated the Incremental cost-effectiveness ratios (ICER) for reimbursed medicines in Brazil’s private health sector, comparing them with CONITEC’s benchmarks and international thresholds. Data were extracted from industry reimbursement submissions to the ANS and analyzed for statistical disparity and policy implications.
Results
Preliminary findings found an ICER peak of BRL619,900 (USD127,220) per quality-adjusted life-year for talazoparib, which is used to treat certain advanced breast cancers. This contrasted sharply with CONITEC’s established threshold, indicating a critical need to evaluate ANS policies.
Conclusions
Early results indicate that the ICERs for some medicines surpass CONITEC’s willingness-to-pay limit, suggesting that the ANS should consider establishing a defined cost-effectiveness threshold. This is imperative to harmonize with global standards and maintain sustainable health financing.
Despite medical advancements, endocarditis still results in high mortality rates. Surgery, while often essential, elevates the risk of hyperinflammation, sepsis, and cytokine release. The use of a cytokine filter to prevent this remains controversial. This study reviewed existing literature to assess the efficacy of cytokine filters and to support its integration into supplementary health services.
Methods
An exhaustive search of the MEDLINE, Cochrane Library, Embase, LILACS, and CytoSorbents Corporation databases was conducted to identify relevant meta-analyses and systematic reviews. The study focused on randomized controlled trials and case series studies assessing the efficacy of cytokine filtration. Key variables considered were the duration of antibiotic treatment, severity of endocarditis, and surgical treatment rationale. These factors were crucial for evaluating clinical outcomes and patient survival after surgery.
Results
The systematic reviews yielded mixed outcomes. Two found no benefits for hemoadsorption, while one found that it reduced mortality rates and intensive care unit stays based on observational studies. Randomized controlled trials, however, showed no significant impact for cytokine filters on mortality rates or postoperative hemodynamic parameters. In contrast, case series studies reported potential benefits, but these results were confounded by biases in patient allocation and failure to account for critical variables like antibiotic treatment duration, case severity, and surgical rationale. These discrepancies highlight the complexity of evaluating the effectiveness of cytokine filtration in surgical settings.
Conclusions
Randomized and non-randomized controlled trials on the role of cytokine filters in cardiac surgery for endocarditis reported contradictory findings. Only case series studies suggested benefits from cytokine filters, necessitating further high quality research before recommending their widespread use. Understanding the implications of these results is essential, underscoring the need for more rigorous studies to resolve these inconsistencies.
Informed healthcare policies in Brazil rely on robust health technology assessment (HTA), especially for conditions like non-small cell lung cancer (NSCLC). We present an efficiency frontier analysis to evaluate NSCLC treatments that correlates annual treatment costs with clinical outcomes, offering a systematic approach to enhance decision-making in the Brazilian healthcare context.
Methods
This quantitative study analyzed NSCLC drug costs within the Brazilian healthcare system and the clinical efficacy data of pivotal studies. The data were analyzed using Python and R software. The dataset comprised drug costs and hazard ratios for overall survival. After data preparation, which involved normalization and outlier management, we constructed an efficiency frontier by ranking drugs based on cost and effectiveness. A linear regression model was then developed to extrapolate this frontier, deriving a formula that predicts treatment costs for specified improvements in overall survival.
Results
The analysis delineated an efficiency frontier and revealed cost-effective NSCLC treatments in Brazil. The following linear regression equation was derived: overall survival = (1.033551 − 0.000003) × treatment cost (USD). This allows for the estimation of appropriate treatment costs for new therapies based on their expected clinical outcomes. This initial model provides a foundation for estimating the economic impact of new treatments.
Conclusions
This preliminary efficiency frontier analysis offers a novel perspective for evaluating NSCLC treatment strategies in Brazil to support sustainable healthcare policy decisions. The model is subject to limitations due to the absence of a systematic literature review. However, it represents an initial step towards a more comprehensive HTA framework. Further research should refine the model by including systematic data collection and analysis.
In Brazil, equitable access to medications is critical. There are significant pricing disparities between the National Health System and private health care, which are influenced by the National Committee for Health Technology Incorporation (CONITEC) and Law 14.307. This study investigated these disparities, with aim of proposing strategies for equitable access and sustainability in health care.
Methods
This analysis compared prices between the public and private sectors for trastuzumab and adalimumab. Public sector prices were obtained from the Health Prices Database (HPD) and private sector prices were obtained from the Unimed National Table of Materials and Medications (TNUMM), as of May 2023. The study evaluated the extent of pricing discrepancies, considering Drug Market Regulation Chamber ceiling prices and industry discounts.
Results
The cost of the trastuzumab biosimilar, KANJINTI® (Amgen Inc.), was BRL15.79 (USD3.24) per mg in the private sector, compared with BRL4.50 (USD0.92) per mg in the public sector (a 250% difference). The original version of adalimumab, HUMIRA® (AbbVie), was priced at BRL5,450.38 (USD1,120.53) in the TNUMM versus BRL2,445.46 (USD502.33) in the HPD (a 123% difference). The adalimumab biosimilar, HYRIMOZ® (Sandoz Inc.), was priced at BRL7,723.99 (USD1,586.87) in the TNUMM compared with BRL2,449.19 (USD503.05) in the HPD (a 215% price discrepancy).
Conclusions
The study highlights significant disparities in drug pricing between Brazil’s public and private healthcare sectors. These disparities affect the financial sustainability of private health entities and elevate costs for consumers, potentially increasing reliance on the National Health System. Policy revisions, price parity strategies, and further studies are vital for a sustainable healthcare system.
Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not ‘excessive’ relative to the context. We carried out the first large-scale, cross-national study to explore the implications of removing this excessiveness requirement.
Methods
Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 criteria for GAD were compared to respondents meeting all criteria for GAD, and to respondents without GAD, on clinically-relevant correlates.
Results
Removing the excessiveness requirement increases the global lifetime prevalence of GAD from 2.6% to 4.0%, with larger increases in LMICs than HICs. Non-excessive and excessive GAD cases worry about many of the same things, although non-excessive cases worry more about health/welfare of loved ones, and less about personal or non-specific concerns, than excessive cases. Non-excessive cases closely resemble excessive cases in socio-demographic characteristics, family history of GAD, and risk of temporally secondary comorbidity and suicidality. Although non-excessive cases are less severe on average, they report impairment comparable to excessive cases and often seek treatment for GAD symptoms.
Conclusions
Individuals with non-excessive worry who meet all other DSM-5 criteria for GAD are clinically significant cases. Eliminating the excessiveness requirement would lead to a more defensible GAD diagnosis.
The studies about the negative effect of epiphytes on their phorophytes show contradictory results and are based on limited variables (e.g., shoot survival). On branches of Bursera copallifera, we experimented with the transplantation/removal of Tillandsia recurvata and artificial tussocks, measuring shoot survival, growth, generation of new shoots, and production of inflorescences and fruits. Most single traits did not differ between treatments. The generation of new shoots was lower in the treatments where T. recurvata was present and increased in the branches where it was removed. The lowest shoot survival was in the treatments where T. recurvata was present or was removed. Removing T. recurvata increased plant relative fitness, and it was 43% lower in branches with T. recurvata. Tillandsia recurvata is a structural parasite of B. copallifera. A negative effect of epiphytes on their phorophytes appears counterintuitive since it would not be evolutionarily stable for an epiphyte to shorten the lifespan of its support. Tillandsia recurvata populations are concentrated on B. copallifera branches between 2-4 cm in diameter, while smaller branches are mostly empty, so it is possible that the negative effect of T. recurvata occurs in the smallest branches, explaining why T. recurvata populations are biased to larger branches.
Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor.
Methods
This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury).
Results
The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt.
Conclusion
Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.
This study aims to develop a framework for establishing priorities in the regional health service of Murcia, Spain, to facilitate the creation of a comprehensive multiple criteria decision analysis (MCDA) framework. This framework will aid in decision-making processes related to the assessment, reimbursement, and utilization of high-impact health technologies.
Method
Based on the results of a review of existing frameworks for MCDA of health technologies, a set of criteria was proposed to be used in the context of evaluating high-impact health technologies. Key stakeholders within regional healthcare services, including clinical leaders and management personnel, participated in a focus group (n = 11) to discuss the proposed criteria and select the final fifteen. To elicit the weights of the criteria, two surveys were administered, one to a small sample of healthcare professionals (n = 35) and another to a larger representative sample of the general population (n = 494).
Results
The responses obtained from health professionals in the weighting procedure exhibited greater consistency compared to those provided by the general public. The criteria more highly weighted were “Need for intervention” and “Intervention outcomes.” The weights finally assigned to each item in the multicriteria framework were derived as the equal-weighted sum of the mean weights from the two samples.
Conclusions
A multi-attribute function capable of generating a composite measure (multicriteria) to assess the value of high-impact health interventions has been developed. Furthermore, it is recommended to pilot this procedure in a specific decision context to evaluate the efficacy, feasibility, usefulness, and reliability of the proposed tool.
We aimed to explore the reciprocal effects of social participation, loneliness, and physical inactivity over a period of 6 years in a representative sample of European adults over 50 years old.
Design:
A longitudinal study with a six-year follow-up period was conducted.
Setting:
Four waves of the Survey of Health, Ageing and Retirement in Europe project were used.
Participants:
This study includes 64,887 participants from Europe and Israel, who were aged 50 or older at the first time.
Measurements:
The relationship between participation in social activities, loneliness and physical inactivity was analyzed, controlling for age, gender, and disability. A series of cross-lagged panel models (CLPMs) were applied to analyze the relationships among these variables.
Results:
A CLPM with equal autoregressive cross-lagged effects across waves was the best fit to the data (χ2 = 7137.8, CFI = .972, RMSEA = .049, SRMR = .036). The autoregressive effects for the three variables showed high stability across waves, and all the cross-lagged effects in the model were statistically significant. Social activity and physical inactivity maintained a strong negative cross-lagged effect, while their cross-lagged effects on loneliness were comparatively smaller. Social activity had a positive cross-lagged effect on loneliness, while physical inactivity had a negative cross-lagged effect on loneliness.
Conclusions:
These findings highlight the importance of promoting physical activity and social participation and addressing loneliness through targeted interventions in older adults.
Refluxing chromium (III) acetate with a Na+-montmorillonite suspension gives rise to the intercalation of linear Cr(III) polyhydroxo-acetate oligomers. Thermally stable chromia pillared mont-morillonite materials are obtained upon calcination under ammonia up to 625°C, and basal expansions up to 6 Å are maintained. The porous materials retain high surface areas (366–464 m2 g−1), a micropore volume of 0.1 cm3 g−1 and narrow pore size distributions centered between 7.5 and 12 Å. The most thermally stable materials in air were those prepared under ammonia at 625°C, containing NH4+ as the exchangeable ion.
There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research.
Aims
This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery–Åsberg Depression Rating Scale (MADRS-6).
Method
A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation.
Results
The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set.
Conclusions
The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.
Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6–44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6–88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8–53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0–54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0–41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0–46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9–35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0–48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0–43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (β = 0.836, p < 0.001), older publication year (β = 0.404, p = 0.038) and higher proportion of non-White FEP patients (β = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8–28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.
Pulmonary regurgitation is the most common complication in repaired tetralogy of Fallot patients. Severe chronic pulmonary regurgitation can be tolerated for decades, but if not treated, it can progress to symptomatic, irreversible right ventricular dilatation and dysfunction. We investigated clinical associations with pulmonary valve replacement among patients with significative pulmonary regurgitation and how interventional developments can change their management.
Methods:
All adult patients with repaired tetralogy of Fallot who were followed at an adult CHD Clinic at a single centre from 1980 to 2022 were included on their first outpatient visit. Follow-up was estimated from the time of correction surgery until one of the following events occurred first: pulmonary valve replacement, death, loss to follow-up or conclusion of the study.
Results:
We included 221 patients (116 males) with a median age of 19 (18–25). At a median age of 33 (10) years old, 114 (51%) patients presented significant pulmonary regurgitation. Among patients with significant pulmonary regurgitation, pulmonary valve replacement was associated with male gender, older age at surgical repair, and longer QRS duration in adulthood. Pulmonary valve replacement was performed in 50 patients, including four transcatheter pulmonary valve implantations, at a median age of 34 (14) years.
Conclusion:
Pulmonary regurgitation affects a large percentage of tetralogy of Fallot adult patients, requiring a long-term clinical and imaging follow-up. Sex, age at surgical repair and longer QRS are associated with the need of PVR among patients with significative pulmonary regurgitation. Clinical practice and current literature support TPVI as the future gold standard intervention.
Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation.
Methods
Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months.
Results
10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation.
Conclusion
Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.
Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) play a pivotal role in stimulating motivational behavior toward food and energy metabolism. Aberrant functioning of the endocannabinoid system has been observed in extreme weight conditions (EWCs), suggesting it may influence pathophysiology. Then, we aimed to analyze fasting AEA and 2-AG plasma concentrations among individuals with EWC (i.e., anorexia nervosa [AN] and obesity with and without eating disorders [EDs]) compared with healthy controls (HCs), and its association with clinical variables and body mass index (BMI).
Methods
The sample included 113 adult women. Fifty-seven belonged to the obesity group, 37 without EDs (OB-ED) and 20 with ED (OB+ED classified within the binge spectrum disorders), 27 individuals from the AN group, and 29 from the HC group. Peripheral blood samples, several clinical variables, and BMI were evaluated.
Results
Unlike 2-AG, AEA concentrations showed significant differences between groups (p < 0.001). Increased AEA was observed in the OB-ED and OB+ED compared with both HC and AN group, respectively. Likewise, AEA was differentially associated with emotional dysregulation, general psychopathology, food addiction, and BMI in all clinical groups.
Conclusions
These results support the interaction between biological and clinical factors contributing to delineating vulnerability pathways in EWC that could help fit personalized therapeutic approaches.
Frontline healthcare workers (FHCWs) exposed to COVID-19 patients are at an increased risk of developing psychological burden. This study aims to determine the prevalence of mental health symptoms and associated factors among Mexican FHCWs attending COVID-19 patients.
Methods:
FHCWs, including attending physicians, residents/fellows, and nurses providing care to COVID-19 patients at a private hospital in Monterrey, Mexico, were invited to answer an online survey between August 28, and November 30, 2020. Symptoms of depression, anxiety, post-traumatic stress, and insomnia were evaluated with the Patient Health Questionnaire (PHQ)-9, Generalized Anxiety Disorder (GAD)-7, Impact of Event Scale-Revised (IES-R), and Insomnia Severity Index (ISI). Multivariate analysis was performed to identify variables associated with each outcome.
Results:
131 FHCWs, 43.5% attending physicians, 19.8% residents/fellows, and 36.6% nurses were included. The overall prevalence of depression, anxiety, post-traumatic stress, and insomnia was 36%, 21%, 23%, and 24% respectively. Multivariate analysis revealed that residents/fellows and nurses reported more depression and insomnia than attending physicians. Although not significant, residents/fellows were more likely to experience all symptoms than nurses.
Conclusions:
Mexican FHCWs, especially nurses and residents/fellows, experienced a significant psychological burden while attending to COVID-19 patients. Tailored interventions providing support to FHCWs during future outbreaks are required.
To describe the importance of community engagement from research projects and research centers in times of disasters or emergencies, using the case of Puerto Rico in recent years (2017 - 2022) as an example.
Methods:
First, research participants and stakeholders from local community and health organizations were contacted via email and phone calls after each emergency to assess their immediate needs. Second, needs were classified in categories (materials, educational resources, service referrals, and collaborations). Finally, delivery of support was coordinated in a timely manner whether in person or online.
Results:
Activities were conducted such as handing out materials, providing educational resources, contacting participants, and stakeholders, as well as coordinating collaboration with community and organizations.
Conclusion:
Several lessons were learned from our experiences related to Puerto Rico’s recent emergencies as well as some relevant recommendations for future disasters. The efforts presented illustrate the importance of community engagement from academic institutions in disasters. Research centers and research projects, particularly those with community engagement components, should consider providing support in the preparedness phase as well as the recovery phase if necessary. Community engagement in emergencies is crucial to recovery efforts as well as fostering empowerment and making an impact on individual and societal levels.