Lack of complete biochemical response in autoimmune hepatitis leads to adverse outcome: First report of the IAIHG retrospective registry.

BACKGROUND AND AIMS: The International Autoimmune Hepatitis Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of autoimmune hepatitis (AIH). As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort. METHODS: This retrospective, observational, multicenter study included all patients with a clinical diagnosis of AIH from the IAIHG-RR. The quality assessment consisted of external validation of completeness and consistency for 29 predefined variables. Cox regression was used to identify risk factors for liver-related death and liver transplantation (LT). RESULTS: This analysis included 2559 patients across 7 countries. In 1700 patients, follow-up was available, with a completeness of individual data of 90% (range: 30-100). During a median follow-up period of 10 (range: 0-49) years, there were 229 deaths, of which 116 were liver-related, and 143 patients underwent LT. Non-White ethnicity (HR 4.1 95% CI: 2.3-7.1), cirrhosis (HR 3.5 95% CI: 2.3-5.5), variant syndrome with primary sclerosing cholangitis (PSC) (HR 3.1 95% CI: 1.6-6.2), and lack of complete biochemical response within 6 months (HR 5.7 95% CI: 3.4-9.6) were independent prognostic factors. CONCLUSIONS: The IAIHG-RR represents the world's largest AIH cohort with moderate-to-good data quality and a relevant number of liver-related events. The registry is a suitable platform for patient selection in future studies. Lack of complete biochemical response to treatment, non-White ethnicity, cirrhosis, and PSC-AIH were associated with liver-related death and LT.

Topological chiral crystals with helicoid-arc quantum states.

The quantum behaviour of electrons in materials is the foundation of modern electronics and information technology1-11, and quantum materials with topological electronic and optical properties are essential for realizing quantized electronic responses that can be used for next generation technology. Here we report the first observation of topological quantum properties of chiral crystals6,7 in the RhSi family. We find that this material class hosts a quantum phase of matter that exhibits nearly ideal topological surface properties originating from the crystals' structural chirality. Electrons on the surface of these crystals show a highly unusual helicoid fermionic structure that spirals around two high-symmetry momenta, indicating electronic topological chirality. The existence of bulk multiply degenerate band fermions is guaranteed by the crystal symmetries; however, to determine the topological invariant or charge in these chiral crystals, it is essential to identify and study the helicoid topology of the arc states. The helicoid arcs that we observe on the surface characterize the topological charges of ±2, which arise from bulk higher-spin chiral fermions. These topological conductors exhibit giant Fermi arcs of maximum length (π), which are orders of magnitude larger than those found in known chiral Weyl fermion semimetals5,8-11. Our results demonstrate an electronic topological state of matter on structurally chiral crystals featuring helicoid-arc quantum states. Such exotic multifold chiral fermion semimetal states could be used to detect a quantized photogalvanic optical response, the chiral magnetic effect and other optoelectronic phenomena predicted for this class of materials6.

Evidence for moiré excitons in van der Waals heterostructures.

Recent advances in the isolation and stacking of monolayers of van der Waals materials have provided approaches for the preparation of quantum materials in the ultimate two-dimensional limit1,2. In van der Waals heterostructures formed by stacking two monolayer semiconductors, lattice mismatch or rotational misalignment introduces an in-plane moiré superlattice3. It is widely recognized that the moiré superlattice can modulate the electronic band structure of the material and lead to transport properties such as unconventional superconductivity4 and insulating behaviour driven by correlations5-7; however, the influence of the moiré superlattice on optical properties has not been investigated experimentally. Here we report the observation of multiple interlayer exciton resonances with either positive or negative circularly polarized emission in a molybdenum diselenide/tungsten diselenide (MoSe2/WSe2) heterobilayer with a small twist angle. We attribute these resonances to excitonic ground and excited states confined within the moiré potential. This interpretation is supported by recombination dynamics and by the dependence of these interlayer exciton resonances on twist angle and temperature. These results suggest the feasibility of engineering artificial excitonic crystals using van der Waals heterostructures for nanophotonics and quantum information applications.

Synaptic Involvement of the Human Amygdala in Parkinson's Disease.

α-Synuclein, a protein mostly present in presynaptic terminals, accumulates neuropathologically in Parkinson's disease in a 6-stage sequence and propagates in the nervous system in a prion-like manner through neurons and glia. In stage 3, the substantia nigra are affected, provoking motor symptoms and the amygdaloid complex, leading to different nonmotor symptoms; from here, synucleinopathy spreads to the temporal cortex and beyond. The expected increase in Parkinson's disease incidence accelerates the need for detection biomarkers; however, the heterogeneity of this disease, including pathological aggregates and pathophysiological pathways, poses a challenge in the search for new therapeutic targets and biomarkers. Proteomic analyses are lacking, and the literature regarding synucleinopathy, neural and glial involvement, and volume of the human amygdaloid complex is controversial. Therefore, the present study combines both proteomic and stereological probes. Data-independent acquisition-parallel accumulation of serial fragmentation proteomic analysis revealed a remarkable proteomic impact, especially at the synaptic level in the human amygdaloid complex in Parkinson's disease. Among the 199 differentially expressed proteins, guanine nucleotide-binding protein G(i) subunit alpha-1 (GNAI1), elongation factor 1-alpha 1 (EEF1A1), myelin proteolipid protein (PLP1), neuroplastin (NPTN), 14-3-3 protein eta (YWHAH), gene associated with retinoic and interferon-induced mortality 19 protein (GRIM19), and orosomucoid-2 (ORM2) stand out as potential biomarkers in Parkinson's disease. Stereological analysis, however, did not reveal alterations regarding synucleinopathy, neural or glial populations, or volume changes. To our knowledge, this is the first proteomic study of the human amygdaloid complex in Parkinson's disease, and it identified possible biomarkers of the disease. Lewy pathology could not be sufficient to cause neurodegeneration or alteration of microglial and astroglial populations in the human amygdaloid complex in Parkinson's disease. Nevertheless, damage at the proteomic level is manifest, showing up significant synaptic involvement.

Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network.

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112). METHODS: Following 2020 PRISMA guidelines, original research articles focusing on DILI which used in vitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified 'Toxicological Data Reliability Assessment Tool'. RESULTS: A total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations. CONCLUSIONS: Extensive analysis highlighted the lack of agreement on control compounds for in vitro DILI assessment. Following comprehensive in vitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of in vitro models of DILI is proposed. IMPACT AND IMPLICATIONS: Prediction of human toxicity early in the drug development process remains a major challenge, necessitating the development of more physiologically relevant liver models and careful selection of drug-induced liver injury (DILI)-positive and -negative control drugs to better predict the risk of DILI associated with new drug candidates. Thus, this systematic study has crucial implications for standardizing the validation of new in vitro models of DILI. By establishing a consensus-driven list of positive and negative control drugs, the study provides a scientifically justified framework for enhancing the consistency of preclinical testing, thereby addressing a significant challenge in early hepatotoxicity identification. Practically, these findings can guide researchers in evaluating safety profiles of new drugs, refining in vitro models, and informing regulatory agencies on potential improvements to regulatory guidelines, ensuring a more systematic and efficient approach to drug safety assessment.

Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors. METHODS: We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry. The assessed clinical outcomes were HCC development, liver transplantation, and death. Fine and Gray regression analysis stratified by centre was applied to determine the effects of individual covariates; the cumulative incidence of HCC was estimated using the competing risk method with death as a competing risk. RESULTS: A total of 1,428 patients diagnosed with AIH from 1980 to 2020 from 22 eligible centres across Europe and Canada were included, with a median follow-up of 11.1 years (interquartile range 5.2-15.9). Two hundred and ninety-three (20.5%) patients had cirrhosis at diagnosis. During follow-up, 24 patients developed HCC (1.7%), an incidence rate of 1.44 cases/1,000 patient-years; the cumulative incidence of HCC increased over time (0.6% at 5 years, 0.9% at 10 years, 2.7% at 20 years, and 6.6% at 30 years of follow-up). Patients who developed cirrhosis during follow-up had a significantly higher incidence of HCC. The cumulative incidence of HCC was 2.6%, 4.6%, 5.6% and 6.6% at 5, 10, 15, and 20 years after the development of cirrhosis, respectively. Obesity (hazard ratio [HR] 2.94, p = 0.04), cirrhosis (HR 3.17, p = 0.01), and AIH/PSC variant syndrome (HR 5.18, p = 0.007) at baseline were independent risk factors for HCC development. CONCLUSIONS: HCC incidence in AIH is low even after cirrhosis development and is associated with risk factors including obesity, cirrhosis, and AIH/PSC variant syndrome. IMPACT AND IMPLICATIONS: The risk of developing hepatocellular carcinoma (HCC) in individuals with autoimmune hepatitis (AIH) seems to be lower than for other aetiologies of chronic liver disease. Yet, solid data for this specific patient group remain elusive, given that most of the existing evidence comes from small, single-centre studies. In our study, we found that HCC incidence in patients with AIH is low even after the onset of cirrhosis. Additionally, factors such as advanced age, obesity, cirrhosis, alcohol consumption, and the presence of the AIH/PSC variant syndrome at the time of AIH diagnosis are linked to a higher risk of HCC. Based on these findings, there seems to be merit in adopting a specialized HCC monitoring programme for patients with AIH based on their individual risk factors.

Safety, Efficacy, and Cost-effectiveness of Outpatient Surgery for Uncomplicated Acute Appendicitis: The PENDI-CSI Randomized Clinical Trial.

OBJECTIVE: To evaluate the safety, efficacy, and cost-effectiveness of outpatient appendectomy in patients with uncomplicated acute appendicitis. BACKGROUND: Given that acute appendicitis is the most common cause of acute abdomen, the introduction of outpatient appendectomy protocols could significantly improve the effectiveness and sustainability of health care systems. METHODS: A total of 300 patients were enrolled from October 2018 to June 2021 in the PENDI-CSI randomized clinical trial: 149 were assigned to the outpatient surgery (OPS) group and 151 to the inpatient surgery (IPS) group, followed by 1 month postoperatively. All patients were aged older than 14 years and had uncomplicated acute appendicitis. Exclusion criteria were pregnancy, neoplasms, inflammatory bowel disease, and high anesthetic risk (ASA IV). The OPS group was discharged from the postanesthesia care unit while the IPS group was admitted. RESULTS: In total, 128 patients in the OPS group (85.9%) were discharged without admission. Predictors whether patients in the OPS group had to be admitted were aged over 31 years [relative risk (RR): 2.42 (1.04-5.65)], hypertension [RR: 6.21 (3.22-11.97)], anesthetic risk II-III [RR: 2.63 (1.17-5.94)], previous abdominal surgery [RR: 3.34 (1.55-7.20)], postoperative pain with visual analog scale >6 [RR: 4.28 (2.67-6.86)], and postoperative fear [RR: 2.2 (1.04-4.67)]. There were no differences in terms of complications, readmissions, and reinterventions, and the perceived quality was similar in both groups. The outpatient modality produced savings of €1 034.97 per patient ( P < 0.001). CONCLUSIONS: Outpatient appendectomy is safe and effective for uncomplicated acute appendicitis. Patient-perceived quality is similar to that of IPS, although it successfully reduces hospital costs compared with inpatient appendectomy.

What factors influence the rediscovery of lost tetrapod species?

We created a database of lost and rediscovered tetrapod species, identified patterns in their distribution and factors influencing rediscovery. Tetrapod species are being lost at a faster rate than they are being rediscovered, due to slowing rates of rediscovery for amphibians, birds and mammals, and rapid rates of loss for reptiles. Finding lost species and preventing future losses should therefore be a conservation priority. By comparing the taxonomic and spatial distribution of lost and rediscovered tetrapod species, we have identified regions and taxa with many lost species in comparison to those that have been rediscovered-our results may help to prioritise search effort to find them. By identifying factors that influence rediscovery, we have improved our ability to broadly distinguish the types of species that are likely to be found from those that are not (because they are likely to be extinct). Some lost species, particularly those that are small and perceived to be uncharismatic, may have been neglected in terms of conservation effort, and other lost species may be hard to find due to their intrinsic characteristics and the characteristics of the environments they occupy (e.g. nocturnal species, fossorial species and species occupying habitats that are more difficult to survey such as wetlands). These lost species may genuinely await rediscovery. However, other lost species that possess characteristics associated with rediscovery (e.g. large species) and that are also associated with factors that negatively influence rediscovery (e.g. those occupying small islands) are more likely to be extinct. Our results may foster pragmatic search protocols that prioritise lost species likely to still exist.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

Bit by bit toward the diversity of metopids: Description of the genus Pidimetopus n. gen. (Ciliophora: Armophorea).

While metopids (Armophorea: Metopida) represent the most species-rich group of free-living anaerobic ciliates thriving in hypoxic environments, our understanding of their true diversity remains incomplete. Most metopid species are still characterized only morphologically. Particularly, the so-called IAC clade (named in the past after some of the taxa included, Idiometopus, Atopospira, and Clevelandellida), comprising free-living members as well as the endosymbiotic ones (order Clevelandellida), is in serious need of revision. In our study, we establish a new free-living genus in the IAC clade, Pidimetopus n. gen., with descriptions of two new species, P. nanus n. sp., and P. permonicus n. sp., using up-to-date molecular and morphologic methods. The genus is characterized by small cells (up to 75 µm long), not more than 10 adoral membranelles and eight somatic kineties, and usually, four long caudal cilia that can stiffen. In addition to morphologic and molecular characterizations, we also conducted a statistical morphotype analysis of the polymorphic species P. nanus n. sp. We discuss the relevance of the earlier morphologically described species Metopus minor as a putative collective taxon for several small metopids less than 50 µm long.

Morphology, morphogenesis, and molecular characterization of Castula specialis sp. nov. (Ciliophora, Armophorea, Metopida).

The morphology, morphogenesis, and molecular phylogeny of a new metopid ciliate, Castula specialis sp. nov., comprising three strains from geographically distant (China, Mexico, Czech Republic) anoxic freshwater habitats, were studied based on microscopic observation of live and protargol-stained specimens as well as SSU rRNA gene sequence data. The new species is characterized as follows: size in vivo 105-220 × 25-70 µm, body oblong to elongated ellipsoidal and asymmetrical; preoral dome distinctly projecting beyond the body; 32-46 adoral membranelles; 31-52 somatic kineties; and 4-7 setae. This study brings the first morphogenetic investigation of a member of the genus Castula. The morphogenesis of the type population (China) of the new species proceeds as in Metopus spp. comprising drastic changes in body shape and a pleurotelokinetal stomatogenesis; however, the main difference is the origin of the opisthe's paroral membrane that derives from all perizonal rows and some adjacent dome kineties. Phylogenetically, the genus Castula is paraphyletic.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

Lettre to editor: Case report of an ictal asystole as debut in new onset epilepsy.

The case report describes a 65-year-old man with arterial hypertension and a metallic aortic valve who presented to the emergency room for a loss of consciousness event and memory impairment. The electroencephalographic recording showed right temporal epileptiform activity followed by a 9 s asystole with quick consciousness recovery. The patient was diagnosed with right temporal epilepsy with asystole and was prescribed levetiracetam to prevent new events. A pacemaker was indicated in the follow-up for the long duration of the asystole, preventing major morbidity. Ictal asystole (IA) is a rare phenomenon of epilepsy that leads to syncope. It is observed in focal epilepsy, especially in left temporal epilepsy. Underlying cardiac pathology may facilitate IA, especially when the onset of the epilepsy is new. Knowledge of focal temporal semiology is key, concerning our case report, the memory impairment points to temporal pathology, and ictal vomiting in the non-dominant hemisphere. Anti-seizures drugs must be initiated in all patients, and there is a recommendation to avoid those with negative inotropic and arrhythmogenic effects (such as phenytoin, carbamazepine, and lacosamide). There is a discussion about pacemaker indication, however, it is highly recommended in non-controlled epilepsy and in ictal asystoles that last for more than 6 s to reduce morbidity.

Utility of non-invasive monitoring of exhaled carbon dioxide and perfusion index in adult patients in the emergency department.

BACKGROUND: Several noninvasive solutions are available for the assessment of patients at risk of deterioration. Capnography, in the form of end-tidal exhaled CO2 (ETCO2) and perfusion index (PI), could provide relevant information about patient prognosis. The aim of the present project was to determine the association of ETCO2 and PI with mortality of patients admitted to the emergency department (ED). METHODS: Multicenter, prospective, cohort study of adult patients with acute disease who needed continuous monitoring in the ED. The study included two tertiary hospitals in Spain between October 2022 and June 2023. The primary outcome of the study was in-hospital mortality (all-cause). Demographics, vital signs, ETCO2 and PI were collected. RESULTS: A total of 687 patients were included in the study. The in-hospital mortality rate was 6.8%. The median age was 79 years (IQR: 69-86), and 63.3% were males. The median ETCO2 value was 30 mmHg (26-35) in survivors and 23 mmHg (16-30) in nonsurvivors (p = 0.001). For the PI, the medians were 4.7% (2.8-8.1) for survivors and 2.5% (0.98-4-4) for nonsurvivors (p < 0.001). The model that presented the best AUC was age (odds ratio (OR): 1.02 (1.00-1.05)), the respiratory rate (OR: 1.06 (1.02-1.11)), and the PI (OR: 0.83 (0.75-0.91)), with a result of 0.840 (95% CI: 0.795-0.886); the model with the respiratory rate (OR: 1.05 (1.01-1.10)), the PI (OR: 0.84 (0.76-0.93)), and the ETCO2 (no statistically significant OR), with an AUC of 0.838 (95% CI: 0.787-0.889). CONCLUSIONS: The present study showed that the PI and respiratory rate are independently associated with in-hospital mortality. Both the PI and ETCO2 are predictive parameters with improved prognostic performance compared with that of standard vital signs.

GCAT|Panel, a comprehensive structural variant haplotype map of the Iberian population from high-coverage whole-genome sequencing.

The combined analysis of haplotype panels with phenotype clinical cohorts is a common approach to explore the genetic architecture of human diseases. However, genetic studies are mainly based on single nucleotide variants (SNVs) and small insertions and deletions (indels). Here, we contribute to fill this gap by generating a dense haplotype map focused on the identification, characterization, and phasing of structural variants (SVs). By integrating multiple variant identification methods and Logistic Regression Models (LRMs), we present a catalogue of 35 431 441 variants, including 89 178 SVs (≥50 bp), 30 325 064 SNVs and 5 017 199 indels, across 785 Illumina high coverage (30x) whole-genomes from the Iberian GCAT Cohort, containing a median of 3.52M SNVs, 606 336 indels and 6393 SVs per individual. The haplotype panel is able to impute up to 14 360 728 SNVs/indels and 23 179 SVs, showing a 2.7-fold increase for SVs compared with available genetic variation panels. The value of this panel for SVs analysis is shown through an imputed rare Alu element located in a new locus associated with Mononeuritis of lower limb, a rare neuromuscular disease. This study represents the first deep characterization of genetic variation within the Iberian population and the first operational haplotype panel to systematically include the SVs into genome-wide genetic studies.

Modeling the Therapeutic Process of Patients with Cocaine Use Disorders: A Guide for Predicting Readmission.

INTRODUCTION: Patients with cocaine use disorders have very high readmission rates. Our aim was to model the relationships between attributes of patients with cocaine use disorder at the beginning of treatment, therapeutic process indicators of time in treatment or proportion of appointments attended, and treatment outcomes, including outcomes at discharge and non-readmissions posttreatment as indicators of therapeutic success. METHOD: A retrospective observational design was used with 10,298 cocaine use disorder patients. Electronic health records were used for statistical analysis of the data. Randomized subsample 1 (n = 5,150) was used for exploratory analysis and subsample 2 (n = 5,148) for modeling relationships between the variables. RESULTS: Patients attributes at intake (e.g., legal services as the source of referral) were of limited significance in explaining time in treatment, proportion of appointments attended, and treatment outcomes. Time in treatment and proportion of appointments attended emerged as significant factors in explaining outcomes at discharge. However, readmissions were primarily explained by time in treatment and outcomes at discharge, although referrals to addiction centers by health services also appeared to be relevant for explaining readmission. DISCUSSION/CONCLUSION: Our study has shown that maintaining a sufficient appointment attendance rate and remaining in treatment for a longer duration are critical therapeutic process indicators for explaining outcomes at the point of discharge and therapeutic success, as indicated by a reduced likelihood of readmissions. Patients who remained in treatment for an extended period were found to have a reduced risk of future readmissions. In addition, our study highlights the importance of maintaining a satisfactory appointment attendance rate to attain successful short- and medium-term therapeutic discharge outcomes. These guidelines could help to increase the efficiency of patient treatment and alleviate the suffering of both patients and their families.

Innovative wood use can enable carbon-beneficial forest management in California.

Responsible stewardship of temperate forests can address key challenges posed by climate change through sequestering carbon, producing low-carbon products, and mitigating climate risks. Forest thinning and fuel reduction can mitigate climate-related risks like catastrophic wildfire. These treatments are often cost prohibitive, though, in part because of low demand for low-value wood "residues." Where treatment occurs, this low-value wood is often burned or left to decay, releasing carbon. In this study, we demonstrate that innovative use of low-value wood, with improved potential revenues and carbon benefits, can support economical, carbon-beneficial forest management outcomes in California. With increased demand for wood residues, forest health-oriented thinning could produce up to 7.3 million (M) oven-dry tonnes of forest residues per year, an eightfold increase over current levels. Increased management and wood use could yield net climate benefits between 6.4 and 16.9 million tonnes of carbon dioxide equivalent (M tCO2e) per year when considering impacts from management, wildfire, carbon storage in products, and displacement of fossil carbon-intensive alternatives over a 40-y period. We find that products with durable carbon storage confer the greatest benefits, as well as products that reduce emissions in hard-to-decarbonize sectors like industrial heat. Concurrently, treatment could reduce wildfire hazard on 4.9 M ha (12.1 M ac), a quarter of which could experience stand-replacing effects without treatment. Our results suggest that innovative wood use can support widespread fire hazard mitigation and reduce net CO2 emissions in California.

Validation of the Collett-Lester fear of death scale in occupational therapy students: psychometric testing and implications for palliative care education.

BACKGROUND: The fear of death is a common experience among healthcare students and professionals that may impact the quality of care provided to patients, particularly those receiving palliative care. The Collett-Lester Fear of Death Scale is a widely used instrument to assess this fear, although its psychometric properties have not been extensively studied in Occupational Therapy students. The present study aimed to validate the Collett-Lester Fear of Death Scale (CL-FODS) in a sample of Occupational Therapy students and to explore its implications for palliative care education. METHOD: A cross-sectional study was conducted to perform psychometric testing of the CL-FODS in Occupational Therapy undergraduate students. Structural validity, internal consistency, and test-retest reliability were analysed. A total of 195 Occupational Therapy students were included in this study. Additionally, the participants completed a brief survey on their experiences and attitudes towards palliative care. RESULTS: The internal consistency was satisfactory (α = 0.888). The exploratory factor analysis to evaluate the internal structure yielded four factors. The model fit indices were: comparative fit index = 0.89, and root mean square error of approximation = 0.06). The test-retest reliability was satisfactory and demonstrated an intraclass correlation coefficient of 0.939. CONCLUSION: The Spanish version of the CL-FODS showed satisfactory psychometric properties; therefore, assessing fear of death in Occupational Therapy students is helpful. This study highlights the importance of addressing fear of death and palliative care education in Occupational Therapy undergraduates to improve future professional attitudes and, consequently, the quality of patient care at the end of life.

Examining Profiles and Treatment Outcomes in Dual Diagnosis: Comparison of Coordinated Treatment With Mental Health Services Versus Addiction Center Alone. A Real-World Data Analysis.

OBJECTIVE: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. METHODS: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. RESULTS: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. CONCLUSIONS: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.

A Smartphone App for Real-Time Assessment of Malaria Prophylaxis Adverse Events.

Background: Growth of international travel to malarial areas over the last decades has contributed to more travelers taking malaria prophylaxis. Travel-related symptoms may be wrongly attributed to malaria prophylaxis and hinder compliance. Here, we aimed to assess the frequency of real-time reporting of symptoms by travelers following malaria prophylaxis using a smartphone app. Method: Adult international travelers included in this single-center study (Barcelona, Spain) used the smartphone Trip Doctor® app developed by our group for real-time tracking of symptoms and adherence to prophylaxis. Results: Six hundred four (n = 604) international travelers were included in the study; 74.3% (449) used the app daily, and for one-quarter of travelers, malaria prophylaxis was prescribed. Participants from the prophylaxis group traveled more to Africa (86.7% vs. 4.3%; p < 0.01) and to high travel medical risk countries (60.8% vs. 18%; p < 0.01) and reported more immunosuppression (30.8% vs. 23.1% p < 0.01). Regarding symptoms, no significant intergroup differences were observed, and no relationship was found between the total number of malarial pills taken and reported symptoms. Conclusions: In our cohort, the number of symptoms due to malaria prophylaxis was not significantly higher than in participants for whom prophylaxis was not prescribed, and the overall proportion of symptoms is higher compared with other studies.