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Obstetric complications (OCs) are associated with cognitive and brain abnormalities observed in patients with schizophrenia. Gyrification, a measure of cortical integrity sensitive to events occurring during the prenatal and perinatal periods, is also altered in first-episode psychosis (FEP). We examined the relationship between OCs and gyrification in FEP, as well as whether gyrification mediates the relationship between OCs and cognition.
Methods
We examined differences in the Local Gyrification Index (LGI) for the frontal, parietal, temporal, occipital, and cingulate cortices between 139 FEP patients and 125 healthy controls (HCs). Regression analyses explored whether OCs and diagnosis interact to explain LGI variation. Parametric mediation analyses were conducted to assess the effect of LGI on the relationship between OCs and cognition for FEP and HC.
Results
Significant LGI differences were observed between FEP patients and HC in the left parietal and bilateral cingulate and occipital cortices. There was a significant interaction between OCs and diagnosis on the left cingulate cortex (LCC) that was specific to males (p = 0.04) and was driven by gestational rather than intrauterine OCs.
In HCs, OCs had a direct effect on working memory (WM) (p = 0.048) in the mediation analysis, whereas in FEP, we observed no significant effect of OCs on either verbal or WM.
Conclusions
OCs interact with diagnosis to predict LCC gyrification, such that males with FEP exposed to OCs exhibit the lowest LGI. OCs influence WM, and LCC gyrification may mediate this relation only in HC, suggesting a differential neurodevelopmental process in psychosis.
While the literature has largely focused on legal challenges to public healthcare rationing decisions, claims against private insurance companies in voluntary health insurance (VHI) schemes have received less attention. This paper aims to fill this gap by analysing a representative sample of 1,547 court of appeal decisions related to treatment funding claims filed against private insurance companies in Brazil from 2018 to 2021. Courts decided 83.6% of cases in favour of patients, ordering VHI companies to fully fund the claimed treatment. Patients´ rate of success is even higher (96%) in the cases in which insurance companies denied coverage on the grounds that the claimed treatment was not listed in the benefits package mandated by regulation. Court decisions present additional challenges to setting priorities through health technology assessment and explicit packages in the VHI sector. This has broader implications for health care equality and access in Brazil.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
By constraining organic carbon (OC) turnover times and ages, radiocarbon (14C) analysis has become a crucial tool to study the global carbon cycle. However, commonly used “bulk” measurements yield average turnover times, masking age variability within complex OC mixtures. One method to unravel intra-sample age distributions is ramped oxidation, in which OC is oxidized with the aid of oxygen at increasing temperatures. The resulting CO2 is collected over prescribed temperature ranges (thermal fractions) and analyzed for 14C content by accelerator mass spectrometry (AMS). However, all ramped oxidation instruments developed to date are operated in an “offline” configuration and require several manual preparation steps, hindering sample throughput and reproducibility. Here we describe a compact, online ramped oxidation (ORO) setup, where CO2 fractions are directly collected and transferred for 14C content measurement using an AMS equipped with a gas ion source. Our setup comprises two modules: (i) an ORO unit containing two sequential furnaces, the first of which holds the sample and is ramped from room temperature to ∼900°C, the second of which is maintained at 900°C and holds catalysts (copper oxide and silver) to ensure complete oxidation of evolved products to CO2; and (ii) a dual-trap interface (DTI) collection unit containing two parallel molecular sieve traps, which alternately collect CO2 from a given fraction and handle its direct injection into the AMS. Initial results for well-characterized samples indicate that 14C content uncertainties and blank background values are like those obtained during routine gas measurements at ETH, demonstrating the utility of the ORO-DTI setup.
This paper reports the methods and preliminary findings of Germina, an ongoing cohort study to identify biomarkers and trajectories of executive functions and language development in the first 3 years of life. 557 mother-infant dyads (mean age of mothers 33.7 years, 65.2% white, 48.7% male infants) have undergone baseline and are currently collecting data for other timepoints. A linear regression was used to predict baseline Bayley-III using scores derived from data-driven sparse partial least squares utilizing a multiple holdout framework of 15 domains. Significant associations were found between socioeconomic/demographic characteristics (B = 0.29), epigenetics (B = 0.11), EEG theta (B = 0.14) and beta activity (B = 0.11), and microbiome functional pathways (B = 0.08) domains, and infant development measured by the Bayley-III at T1, suggesting potential interventions to prevent impairments.
Mosquitoes, particularly Aedes aegypti, pose significant public health risks by transmitting diseases like dengue, zika and chikungunya. Bacillus thuringiensis var. israelensis (BTI) is a crucial larvicide targeting mosquitoes while sparing other organisms and the environment. This study evaluated the effects of sublethal BTI doses on Ae. aegypti larvae regarding mortality, development, adult emergence and size, using a wide-area spray application in an urban neighbourhood. Laboratory experiments with four BTI concentrations (0, 0.008, 0.02 and 0.04 ppm) assessed compensatory and over compensatory responses. The spray achieved over 90% larval mortality within 48 h, but accumulating sublethal doses could trigger compensatory and over compensatory effects, enhancing the fitness of survivors. A dose–response relationship was evident, with higher BTI concentrations leading to increased mortality, reduced longevity and fewer pupae. BTI exposure also skewed the sex ratio towards males and altered adult sizes, potentially affecting population dynamics and vectorial capacity. These findings highlight the effectiveness of BTI in Ae. aegypti control and the importance of understanding compensation, overcompensation and density-dependent effects. While wide-area BTI applications can reach inaccessible breeding sites and offer potent mosquito control, careful consideration of ecological and evolutionary consequences is crucial.
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.
In the present study, we assessed the sponge fauna, sponge-associated, and planktonic prokaryotic communities residing in Burgers' Zoo Ocean aquarium, Arnhem, the Netherlands. The Ocean aquarium consisted of separate displays and life support systems, and included fish-only systems in addition to a large, 750,000 L tank containing a living, tropical coral reef ecosystem. Sponges were observed throughout the aquarium system and were identified as belonging to the genera Chalinula, Chondrilla, Chondrosia, Cinachyrella, Stylissa, Suberites and Tethya. There was a highly significant difference in composition between sponge-associated and planktonic prokaryotic communities. The tanks in which the sponges were sampled appeared to have a secondary structural effect on prokaryotic composition with sponges and water from the same tanks sharing several microorganisms. Both sponge-associated and planktonic prokaryotic communities housed prokaryotic taxa, which were highly similar to microorganisms previously recorded in sponges or coral reef environments, including taxa potentially involved in nitrification, denitrification, sulphur oxidation, and antibiotic biosynthesis. Several abundant microorganisms were only recorded in sponges and these may play a role in maintaining water quality in the aquarium system. Potential pathogens, e.g. related to Photobacterium damselae, and beneficial organisms, e.g. related to Pseudovibrio denitrificans, were also detected. The present study showed that Burgers' Zoo Ocean aquarium housed diverse free-living and host-associated prokaryotic communities. Future research should focus on identifying conditions and microbial communities conducive to a healthy aquarium environment.
This study aims to outline Clostridioides difficile infection (CDI) trends and outcomes in Mexican healthcare facilities during the COVID-19 pandemic.
Design:
Observational study of case series.
Setting:
Sixteen public hospitals and private academic healthcare institutions across eight states in Mexico from January 2016 to December 2022.
Patients:
CDI patients.
Methods:
Demographic, clinical, and laboratory data of CDI patients were obtained from clinical records. Cases were classified as community or healthcare-associated infections, with incidence rates calculated as cases per 10,000 patient days. Risk factors for 30-day all-cause mortality were analyzed by multivariate logistic regression.
Results:
We identified 2,356 CDI cases: 2,118 (90%) were healthcare-associated, and 232 (10%) were community-associated. Common comorbidities included hypertension, diabetes, and cancer. Previous high use of proton-pump inhibitors, steroids, and antibiotics was observed. Recurrent infection occurred in 112 (5%) patients, and 30-day mortality in 371 (16%). Risk factors associated with death were a high Charlson score, prior use of steroids, concomitant use of antibiotics, leukopenia, leukocytosis, elevated serum creatine, hypoalbuminemia, septic shock or abdominal sepsis, and SARS-CoV-2 coinfection. The healthcare-associated CDI incidence remained stable at 4.78 cases per 10,000 patient days during the pre-and pandemic periods. However, the incidence was higher in public hospitals.
Conclusions:
Our study underscores the need for routine epidemiology surveillance and standardized CDI classification protocols in Mexican institutions. Though CDI rates in our country align with those in some European countries, disparities between public and private healthcare sectors emphasize the importance of targeted interventions.
This position paper by the international IMMERSE consortium reviews the evidence of a digital mental health solution based on Experience Sampling Methodology (ESM) for advancing person-centered mental health care and outlines a research agenda for implementing innovative digital mental health tools into routine clinical practice. ESM is a structured diary technique recording real-time self-report data about the current mental state using a mobile application. We will review how ESM may contribute to (1) service user engagement and empowerment, (2) self-management and recovery, (3) goal direction in clinical assessment and management of care, and (4) shared decision-making. However, despite the evidence demonstrating the value of ESM-based approaches in enhancing person-centered mental health care, it is hardly integrated into clinical practice. Therefore, we propose a global research agenda for implementing ESM in routine mental health care addressing six key challenges: (1) the motivation and ability of service users to adhere to the ESM monitoring, reporting and feedback, (2) the motivation and competence of clinicians in routine healthcare delivery settings to integrate ESM in the workflow, (3) the technical requirements and (4) governance requirements for integrating these data in the clinical workflow, (5) the financial and competence related resources related to IT-infrastructure and clinician time, and (6) implementation studies that build the evidence-base. While focused on ESM, the research agenda holds broader implications for implementing digital innovations in mental health. This paper calls for a shift in focus from developing new digital interventions to overcoming implementation barriers, essential for achieving a true transformation toward person-centered care in mental health.
Like other animals, fish have unique personalities that can affect their cognition and responses to environmental stressors. These individual personality differences are often referred to as “behavioural syndromes” or “stress coping styles” and can include personality traits such as boldness, shyness, aggression, exploration, locomotor activity, and sociability. For example, bolder or proactive fish may be more likely to take risks and present lower hypothalamo–pituitary–adrenal/interrenal axis reactivity as compared to shy or reactive individuals. Likewise, learning and memory differ between fish personalities. Reactive or shy individuals tend to have faster learning and better association recall with aversive stimuli, while proactive or bold individuals tend to learn more quickly when presented with appetitive incentives. However, the influence of personality on cognitive processes other than cognitive achievement in fish has been scarcely explored. Cognitive bias tests have been employed to investigate the interplay between emotion and cognition in both humans and animals. Fish present cognitive bias processes (CBP) in which fish’s interpretation of stimuli could be influenced by its current emotional state and open to environmental modulation. However, no study in fish has explored whether CBP, like in other species, can be interpreted as long-lasting traits and whether other individual characteristics may explain its variation. We hold the perspective that CBP could serve as a vulnerability factor for the onset, persistence, and recurrence of stress-related disorders. Therefore, studying fish’s CBP as a state or trait and its interactions with individual variations may be valuable in future efforts to enhance our understanding of anxiety and stress neurobiology in animal models and humans.
This collectively authored article argues for a regional turn in the historical study of transnational activism. By considering not only pan-regional movements but also examples of borderland contexts, transregional connections and diasporic understandings of ‘region’, our discussion identifies fresh possibilities for investigating the evolution and functioning of transnational activism. Based on a Royal Historical Society-funded workshop held at and supported by Northumbria University, the article brings together insights from diverse locations and arenas of contestation. The first part considers literatures on three macro-regional settings – South Asia, Western Europe and Latin America – to illustrate the importance of distinctive regional contexts and constructs in shaping transnational activism and its goals. The second part turns to case studies of transnational activism in and beyond Eastern Europe, West Africa, the Caribbean and East Asia. In doing so, it explores very different notions of the regional to identify how transnational activism has both shaped and been shaped by these ideas. Taken together, the two parts highlight the role of regional identities and projects in challenging inequalities and external domination. Our analysis and examples indicate the possibilities of a regionally rooted approach for writing histories of transnational activism.
Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction are yet to be explored. This study assessed the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP.
Methods
A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study summary results, PRSEA were constructed for each individual. Two mediation models were performed. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms. The serial mediation model tested a causal chain of the three mediators: CR, NS, and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22.
Results
A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β = −0.35, 95%CI [−0.85, −0.04], p < 0.05). The model fit the data satisfactorily (CFI = 1.00; RMSEA = 0.00; SRMR = 7.2 × 10−7). Conversely, no parallel mediation was found between the three mediators, PRSEA and functionality and the model poorly fit the data (CFI = 0.30; RMSEA = 0.25; SRMR = 0.11).
Conclusions
Both CR and NS mediate the relationship between PRSEA and functionality at one-year follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients.
To identify urinary catheter (UC)–associated urinary tract infection (CAUTI) incidence and risk factors.
Design:
A prospective cohort study.
Setting:
The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries.
Participants:
The study included 169,036 patients, hospitalized for 1,166,593 patient days.
Methods:
Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression.
Results:
Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower–middle-income countries (3.05); and with patients in public hospitals (5.89).
The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P < .0001), female sex (aOR, 1.39; P < .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P < .0001), UC DU ratio (aOR, 1.09; P < .0001), public facilities (aOR, 2.24; P < .0001), and neurologic ICUs (aOR, 11.49; P < .0001).
Conclusions:
CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.
Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.
One of the largest remnants of tropical dry forest is the South American Gran Chaco. A quarter of this biome is in Paraguay, but there have been few studies in the Paraguayan Chaco. The Gran Chaco flora is diverse in structure, function, composition and phenology. Fundamental ecological questions remain in this biome, such as what bioclimatic factors shape the Chaco’s composition, structure and phenology. In this study, we integrated forest inventories from permanent plots with monthly high-resolution NDVI from PlanetScope and historical climate data from WorldClim to identify bioclimatic predictors of forest structure, composition and phenology. We found that bioclimatic variables related to precipitation were correlated with stem density and Pielou evenness index, while temperature-related variables correlated with basal area. The best predictor of forest phenology (NDVI variation) was precipitation lagged by 1 month followed by temperature lagged by 2 months. In the period with most water stress, the phenological response correlates with diversity, height and basal area, showing links with dominance and tree size. Our results indicate that even if the ecology and function of Dry Chaco Forest is characterised by water limitation, temperature has a moderating effect by limiting growth and influencing leaf flush and deciduousness.