The impact of methylene blue in colorectal cancer: Systematic review and meta-analysis study.

PURPOSE: In patients with colorectal cancer (CRC), the most important factor to decide the need of adjuvant chemotherapy is the histological lymph node (LN) evaluation. Our work aimed to give a broad view over the use of methylene blue and its consequences in the number of lymph node harvest. METHODS: PUBMED, WEB OF SCIENCE and EMBASE databases were consulted, retrieving clinical trials, which mentioned the used of intra-arterial methylene blue in patients with colorectal cancer. RESULTS: Eighteen clinical trials analyzing the use of intra-arterial methylene blue in specimens of colorectal cancer were selected. The articles show a statistical difference between the use of methylene blue and the classical dissection in both variable at study. The results of the statistical analysis of the lymph node harvest variable demonstrate a significant statistical difference between the group that received methylene blue injection and the group that underwent conventional dissection. There is a significant statistical difference between the experimental and control groups for the ideal lymph node harvest (lymph node harvest count greater than 12). CONCLUSION: The use of intra-arterial methylene blue revealed a high potential for the quantification of lymph nodes, considering the increase of lymph node harvest and the higher percentage of cases with more than 12 lymph nodes count, albeit the high heterogeneity between the studies in terms of reported results. Future investigations with controlled double blinded studies obtaining better categorized results should be conducted in order to better evaluate this technique and compare it to the current paradigm.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

The effects of physical exercise on axial spondyloarthritis - a systematic review.

AIM: To collect and summarize the available scientific evidence that evaluates the effects of physical exercise interventions on axial spondyloarthritis (axSpA). METHODS: A systematic review was conducted in accordance to the guidance of Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) to collect randomized controlled trials on the PubMed, Embase and Web of Science Core Collection databases. The search strategy included terms regarding physical exercise interventions targeted to axSpA participants and all of its variants in multiple combinations adapted to each one of the databases regarding its own special requirements. Several outcomes were defined: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), ASDAS (Ankylosing Spondylitis Disease Activity Score), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), the 36-item short form health survey (SF-36) and the Ankylosing Spondylitis Quality of Life questionnaire (ASQoL). Two independent researchers screened the titles and abstracts followed by full-text analysis when suitable, using EndnoteTM online. Selected articles, according to exclusion/inclusion criteria defined, were submitted to data extraction and bias assessment was performed for each study's outcomes using the Cochrane risk-of-bias tool for randomized trials. RESULTS: A total of 2063 articles were identified through the electronic databases search. After removal of duplicates, 1435 were eligible for screening, of which 45 articles went through full text evaluation. Only 24 articles met the inclusion/exclusion criteria. Physical exercise contributes for a statistically significant improvement of BASDAI in 13 studies, BASFI in 10, BASMI in 6, ASDAS in 3, CRP in 2, ESR in 1, SF-36 in 2 and ASQoL in 3.No major adverse effects were reported and an overall benefit was noted with the implementation of physical exercise as a treatment modality for axSpA. CONCLUSION: Physical exercise seems to be an effective non-pharmacological therapy for axSpA, with positive effects in disease activity, physical function, and quality of life.

Corrigendum: Colloidal nanomaterials for water quality improvement and monitoring.

[This corrects the article DOI: 10.3389/fchem.2022.1011186.].

A suggestive approach for assessing item quality, usability and validity of Automatic Item Generation.

Automatic Item Generation (AIG) refers to the process of using cognitive models to generate test items using computer modules. It is a new but rapidly evolving research area where cognitive and psychometric theory are combined into digital framework. However, assessment of the item quality, usability and validity of AIG relative to traditional item development methods lacks clarification. This paper takes a top-down strong theory approach to evaluate AIG in medical education. Two studies were conducted: Study I-participants with different levels of clinical knowledge and item writing experience developed medical test items both manually and through AIG. Both item types were compared in terms of quality and usability (efficiency and learnability); Study II-Automatically generated items were included in a summative exam in the content area of surgery. A psychometric analysis based on Item Response Theory inspected the validity and quality of the AIG-items. Items generated by AIG presented quality, evidences of validity and were adequate for testing student's knowledge. The time spent developing the contents for item generation (cognitive models) and the number of items generated did not vary considering the participants' item writing experience or clinical knowledge. AIG produces numerous high-quality items in a fast, economical and easy to learn process, even for inexperienced and without clinical training item writers. Medical schools may benefit from a substantial improvement in cost-efficiency in developing test items by using AIG. Item writing flaws can be significantly reduced thanks to the application of AIG's models, thus generating test items capable of accurately gauging students' knowledge.

Prevalence of undiagnosed rheumatic and musculoskeletal diseases and its association with health-related quality of life and with physical function.

AIM: To estimate the disease specific prevalence of undiagnosed rheumatic and musculoskeletal diseases (RMDs) in Portugal and determine if people with undiagnosed RMDs have worse quality of life, physical function and higher health resources consumption, than people without RMDs. METHODS: A subgroup analysis of EpiReumaPt was made that included all participants≥18 years evaluated by a rheumatologist. Participants were stratified into three groups: undiagnosed RMDs; previously diagnosed RMDs; non-RMDs. A descriptive analysis of the three groups was performed. To estimate the prevalence of undiagnosed RMDs, weighted proportion were computed considering the sample design. The three groups were compared (Undiagnosed RMDs vs non-RMDs; Previously diagnosed RMDs vs non-RMDs) for health related quality of life (HRQoL) (EQ5D), physical function (HAQ), mental health (HADS) and health resources consumption. The effect of being undiagnosed for these outcomes was assessed in multivariable models adjusted for age, gender, geographical region and years of education (reference: non-RMD). RESULTS: A total of 3877 participants were included. The prevalence of undiagnosed RMDs was 29%. Compared to participants without RMDs, undiagnosed participants had lower HRQoL (EQ-5D: ß (95% CI)=-0.07 (-0.103,-0.043)) and physical function (HAQ: ß (95% CI)=0.10 (0.05, 0.15)), more anxiety (OR (95% CI)=2.3 (1.4, 3.7)) and depression symptoms (OR (95% CI)=1.4 (0.8, 2.4)). Undiagnosed RMDs participants were more likely to visit an orthopedist (OR (95% CI)=2.0 (1.1, 3.5)) and had a higher number of orthopedic appointments (IRR (95% CI)=2.5 (1.3, 4.9)) than participants without RMDs. CONCLUSION: Patients with undiagnosed RMDs are frequent in Portugal, have worse HRQoL, physical function and mental health than people without RMDs. Undiagnosed patients are nonetheless consumers of health resources and tend to seek help from specialties other than rheumatology. Increasing the awareness of RMDs might promote their early identification and treatment leading to both personal and societal benefits.

Surgical approaches to colonic and rectal anastomosis: systematic review and meta-analysis.

PURPOSE: Postoperative complications after a colonic and rectal surgery are of significant concern to the surgical community. Although there are different techniques to perform anastomosis (i.e., handsewn, stapled, or compression), there is still no consensus on which technique provides the least number of postoperative problems. The objective of this study is to compare the different anastomotic techniques regarding the occurrence or duration of postoperative outcomes such as anastomotic dehiscence, mortality, reoperation, bleeding and stricture (as primary outcomes), and wound infection, intra-abdominal abscess, duration of surgery, and hospital stay (as secondary outcomes). METHODS: Clinical trials published between January 1, 2010, and December 31, 2021, reporting anastomotic complications with any of the anastomotic technique were identified using the MEDLINE database. Only articles that clearly defined the anastomotic technique used, and report at least two of the outcomes defined were included. RESULTS: This meta-analysis included 16 studies whose differences were related to the need of reoperation (p < 0.01) and the duration of surgery (p = 0.02), while for the anastomotic dehiscence, mortality, bleeding, stricture, wound infection, intra-abdominal abscess, and hospital stay, no significant differences were found. Compression anastomosis reported the lowest reoperation rate (3.64%) and the handsewn anastomosis the highest (9.49%). Despite this, more time to perform the surgery was required in compression anastomosis (183.47 min), with the handsewn being the fastest technique (139.92 min). CONCLUSIONS: The evidence found was not sufficient to demonstrate which technique is most suitable to perform colonic and rectal anastomosis, since the postoperative complications were similar between the handsewn, stapled, or compression techniques.

Myocarditis as the Initial Presentation of a Refractory Adult-Onset Still's Disease.

We present a case of adult-onset Still's disease, a rare disease that presented with a rare complication, myocarditis. After initial therapy with prednisolone 1 mg/kg/day, the patient experienced dyspnea due to severe pleural effusion and palpitations on account of new-onset supraventricular tachycardia. Therapy with three consecutive pulses of 1000 mg of methylprednisolone and anakinra 100 mg/day proved to be effective, with a progressive resolution of all symptoms. However, at three months follow-up, oligoarthritis recurred along with high serum ferritin. Secondary failure to anakinra was assumed, and a switch to tocilizumab 162 mg was made. Nevertheless, arthralgia of the wrists and knees as well as high serum ferritin still persisted after two months of therapy. Chronic disease was assumed, and the patient switched to canakinumab 4 mg/kg/dose q4week, and a complete resolution of symptoms occurred with normalization of inflammation markers. Follow-up cardiac magnetic resonance showed a complete resolution of heart involvement.

Colloidal nanomaterials for water quality improvement and monitoring.

Water is the most important resource for all kind forms of live. It is a vital resource distributed unequally across different regions of the globe, with populations already living with water scarcity, a situation that is spreading due to the impact of climate change. The reversal of this tendency and the mitigation of its disastrous consequences is a global challenge posed to Humanity, with the scientific community assuming a major obligation for providing solutions based on scientific knowledge. This article reviews literature concerning the development of nanomaterials for water purification technologies, including collaborative scientific research carried out in our laboratory (nanoLAB@UA) framed by the general activities carried out at the CICECO-Aveiro Institute of Materials. Our research carried out in this specific context has been mainly focused on the synthesis and surface chemical modification of nanomaterials, typically of a colloidal nature, as well as on the evaluation of the relevant properties that arise from the envisaged applications of the materials. As such, the research reviewed here has been guided along three thematic lines: 1) magnetic nanosorbents for water treatment technologies, namely by using biocomposites and graphite-like nanoplatelets; 2) nanocomposites for photocatalysis (e.g., TiO2/Fe3O4 and POM supported graphene oxide photocatalysts; photoactive membranes) and 3) nanostructured substrates for contaminant detection using surface enhanced Raman scattering (SERS), namely polymers loaded with Ag/Au colloids and magneto-plasmonic nanostructures. This research is motivated by the firm believe that these nanomaterials have potential for contributing to the solution of environmental problems and, conversely, will not be part of the problem. Therefore, assessment of the impact of nanoengineered materials on eco-systems is important and research in this area has also been developed by collaborative projects involving experts in nanotoxicity. The above topics are reviewed here by presenting a brief conceptual framework together with illustrative case studies, in some cases with original research results, mainly focusing on the chemistry of the nanomaterials investigated for target applications. Finally, near-future developments in this research area are put in perspective, forecasting realistic solutions for the application of colloidal nanoparticles in water cleaning technologies.

Perceived stress modulates the activity between the amygdala and the cortex.

The significant link between stress and psychiatric disorders has prompted research on stress's impact on the brain. Interestingly, previous studies on healthy subjects have demonstrated an association between perceived stress and amygdala volume, although the mechanisms by which perceived stress can affect brain function remain unknown. To better understand what this association entails at a functional level, herein, we explore the association of perceived stress, measured by the PSS10 questionnaire, with disseminated functional connectivity between brain areas. Using resting-state fMRI from 252 healthy subjects spanning a broad age range, we performed both a seed-based amygdala connectivity analysis (static connectivity, with spatial resolution but no temporal definition) and a whole-brain data-driven approach to detect altered patterns of phase interactions between brain areas (dynamic connectivity with spatiotemporal information). Results show that increased perceived stress is directly associated with increased amygdala connectivity with frontal cortical regions, which is driven by a reduced occurrence of an activity pattern where the signals in the amygdala and the hippocampus evolve in opposite directions with respect to the rest of the brain. Overall, these results not only reinforce the pathological effect of in-phase synchronicity between subcortical and cortical brain areas but also demonstrate the protective effect of counterbalanced (i.e., phase-shifted) activity between brain subsystems, which are otherwise missed with correlation-based functional connectivity analysis.

A Teledentistry Pilot Study on Patient-Initiated Care.

COVID-19 has challenged the public dental workforce in their ability to continue providing routine oral health care services. To mitigate the risk of COVID-19 transmission to staff and patients, Teledentistry was implemented in many parts of the world, mainly to provide remote consultations, undertake triage, and offer preventive educational sessions. The aim of this paper is to describe Dental Health Services Victoria's (DHSV) patient-initiated Teledentistry model of care implemented during peak COVID transmission in Victoria. The Teledentistry model supported patient-centered care involving active collaboration and shared decision making between patients, families, and clinicians in designing and managing remote care plans. DHSV's eligible patient cohort includes disadvantaged population groups with greater oral health needs. Strong emphasis was placed on the simplicity and user friendliness of the Telehealth platform, as well as the support for patients with low technology literacy. Consumers and dental workforce were consulted and modifications to the use of language and services were undertaken before the launch. A total of 2492 patients accessed Telehealth services between May 2020 and April 2021. Approximately 39% of patients were born in a country other than Australia. A total of 489 patient-reported experience measures (PREMs) were received. Patients agreed or strongly agreed that the care they received met their needs (87%); they received answers to their questions (89%); they left their visit knowing what is next (87%); they felt they were taken care of during their visit (90%); and they felt involved in their treatment (89%). Teledentistry enabled patients to initiate access to care and consult with dental workforce remotely and safely during peak pandemic.

Unraveling the Pivotal Role of Atropisomerism for Cellular Internalization.

The intrinsic challenge of large molecules to cross the cell membrane and reach intracellular targets is a major obstacle for the development of new medicines. We report how rotation along a single C-C bond, between atropisomers of a drug in clinical trials, improves cell uptake and therapeutic efficacy. The atropisomers of redaporfin (a fluorinated sulfonamide bacteriochlorin photosensitizer of 1135 Da) are separable and display orders of magnitude differences in photodynamic efficacy that are directly related to their differential cellular uptake. We show that redaporfin atropisomer uptake is passive and only marginally affected by ATP depletion, plasma proteins, or formulation in micelles. The α4 atropisomer, where meso-phenyl sulfonamide substituents are on the same side of the tetrapyrrole macrocycle, exhibits the highest cellular uptake and phototoxicity. This is the most amphipathic atropisomer with a conformation that optimizes hydrogen bonding (H-bonding) with polar head groups of membrane phospholipids. Consequently, α4 binds to the phospholipids on the surface of the membrane, flips into the membrane to adopt the orientation of a surfactant, and eventually diffuses to the interior of the cell (bind-flip mechanism). We observed increased α4 internalization by cells of the tumor microenvironment in vivo and correlated this to the response of photodynamic therapy when tumor illumination was performed 24 h after α4 administration. These results show that properly orientated aryl sulfonamide groups can be incorporated into drug design as efficient cell-penetrating motifs in vivo and reveal the unexpected biological consequences of atropisomerism.

Association of amygdala size with stress perception: Findings of a transversal study across the lifespan.

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.

Clinical features and outcome of 1054 patients with Systemic Sclerosis: analysis of Reuma.pt/SSc registry.

BACKGROUND: Systemic sclerosis (SSc) is a rare connective tissue disorder with heterogeneous manifestations and outcomes. Besides differences in disease characteristics among distinct ethnic groups and geographical regions, several questions regarding the impact of the disease and the effectiveness of treatments remain unanswered. To address these questions, the Rheumatic Diseases Portuguese Register (Reuma.pt) launched a specific protocol for the prospective follow-up of SSc patients. OBJECTIVES: To describe the baseline characteristics, disease subsets, treatments used and survival of SSc patients registered in Reuma.pt/SSc. METHODS: Data from adult patients with SSc included in Reuma.pt up to November 2020 were analysed. Demographic features, SSc subsets, fulfilment of classification criteria, main clinical and immunological features, comorbidities, treatments used and survival data were described and compared between diffuse cutaneous (dc) and limited cutaneous (lc) disease subsets. Survival was calculated for patients included in Reuma.pt within the first two years of diagnosis. RESULTS: In total, 1054 patients were included, 87.5% female, with a mean age at diagnosis of 52.7 +/- 14.8 years. The most common subset was lcSSc (56.3%), followed by dcSSc (17.5%), preclinical SSc (13%), overlap syndrome (9.8%) and SSc sine scleroderma (3.3%). Raynaud's phenomenon (93.4%) and skin thickening (76.9%) were the most frequently observed clinical manifestations. Gastrointestinal (62.8% versus 47.8%), pulmonary (59.5% versus 23%) and cardiac (12.8% versus 6.9%) involvements were significantly more prevalent in dcSSc than lcSSc. Ninety per-cent of patients were Antinuclear antibody positive, 52.5% were Anti-centromere antibody positive and 21% anti-topoisomerase positive, with significant differences between lcSSc and dcSSc. One-third of patients were treated with immunomodulators, 53.6% with vasodilators, 23% with glucocorticoids and 2.3% with biologics. During follow-up, 83 deaths (7.9%) were reported. The overall 1-, 2- and 5-year survivals were 98.0%, 96.8% and 92.6%, respectively, without significant differences between lcSSc and dcSSc. CONCLUSION: Reuma.pt/SSc data highlights the importance of registries in improving knowledge about rare and complex diseases, such as SSc. Clinical features of Portuguese SSc patients are similar to those of other populations. In recently diagnosed patients, 5-year survival is over 92%. To the best of our knowledge, this is the first study showing that clinical features of Portuguese SSc are similar to those of other cohorts.

Natural solar activation of modified zinc oxides with rare earth elements (Ce, Yb) and Fe for the simultaneous disinfection and decontamination of urban wastewater.

This study investigates the capability of modified zinc oxides (ZnO) with Ce, Yb and Fe towards the simultaneous inactivation of pathogenic bacteria (Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa) and Contaminants of Emerging Concern (CECs, Diclofenac, Sulfamethoxazole and Trimethoprim) under natural sunlight. Several catalyst loads (from 0 to 500 mg/L) were assessed as proof-of principle in isotonic solution followed by the evaluation of organic matter effect in simulated and actual urban wastewater (UWW), using bare TiO2-P25 as reference. The order of photocatalysts efficiency for both bacterial and CECs removal was: ZnO-Ce â‰… TiO2-P25 > ZnO-Yb > ZnO-Fe > photolysis > darkness in all water matrices. The best photocatalytic performance for water disinfection and decontamination was obtained with 500 mg/L of ZnO-Ce: 80% of ∑CECs removal after 45 min (4.4 kJ/L of accumulated solar UV-A energy (QUV)) and the total inactivation of bacteria (Detection Limit of 2 CFU/mL) after 120 min (14 kJ/L of QUV) in UWW. The microbial and CECs abatement mechanism was described based on the generation of hydroxyl radicals, which was experimentally demonstrated for ZnO-Ce. Additionally, no significant release of Zn2+ and Ce was detected after the solar exposure. These results point out for the first time the capability of ZnO-Ce for the simultaneous UWW disinfection and decontamination under natural sunlight.

Attenuation of toxicity and occurrence of degradation products of the fungicide tebuconazole after combined vacuum UV and UVC treatment of drinking water.

Antifungal azoles are the most frequently used fungicides worldwide and occur as active ingredients in many antifungal pharmaceuticals, biocides, and pesticides. Azole fungicides are frequent environmental contaminants and can affect the quality of surface waters, groundwater, and drinking water. This study examined the potential of combined vacuum UV (185 nm) and UVC (254 nm) irradiation (VUV/UVC) of the azole fungicide tebuconazole and the transformation product 1,2,4-trizole on degradation and changes in ecotoxicity. In vivo ecotoxicity was examined before and after UV treatment using bioassays with test organisms from different trophic levels to integrate changes in biological effect of the parent compound and the degradation products. The test battery included the luminescent bacterium Aliivibrio fischeri, the Gram-positive bacterium Bacillus subtilis, the fungus Fusarium graminearum, the green microalga Raphidocelis subcapitata, and the crustacean Daphnia magna. The combined VUV/UVC treatment of tebuconazole in drinking water efficiently degraded the parent compound at the µg/L-mg/L level and resulted in transformation products with lower toxicity than the parent compound. A direct positive correlation was observed between the applied UV dose (fluence, J/cm2), the disappearance of tebuconazole, and the decrease in ecotoxicity. The combined VUV/UVC process does not require addition of supplementary oxidants or catalysts and our study suggests that VUV/UVC-mediated photolysis of azole fungicides in water can decrease the overall toxicity and represent a potentially environmentally friendly treatment method.

Design and development of a novel double-chamber syringe concept for venous catheterization.

This paper presents the optimization process for the development of an innovative double chamber syringe. Several aspects are involved such as design, functionality, fluid-structure interaction and friction between solids. To assist in the development of this medical device, a numerical based methodology was developed and validated in order to predict the syringe´s functionality, as well as its production by injection molding. The mechanical and flow behavior, during the filling and administration of medicine and washing solutions, were numerically modelled using the commercial software ABAQUS and FLUENT, respectively. The injection molding process was analyzed using the software MOLDFLOW. The aim was to evaluate the feasibility of the proposed concept in terms of mechanical design, fluid flow and production process behavior. By highlighting critical design issues in this way, it was possible to identify promising geometric changes and, consequently, optimize iteratively the syringe's design, until all the defined requirements are fulfilled. This iterative process based on numerical simulations proved to be a powerful tool for product development that generated fast and accurate results without the need to produce multiple prototypes.

Gender differences in clinical features and outcomes of a Portuguese systemic sclerosis cohort.

Evidence for the role of sex in the clinical manifestations of systemic sclerosis (SSc) patients is emerging. Some multicenter cohorts have shown that male SSc patients have more severe disease and worse survival. To assess the differences in clinical manifestations and survival in Portuguese SSc patients according to gender. Data from male and female adult SSc patients included in the Rheumatic Diseases Portuguese Register (Reuma.pt) were analysed and compared. Survival was calculated for patients included in Reuma.pt. within the first two years of diagnosis (inception cohort). In total, 1054 adult patients with SSc were included, 12.5% males. No differences in demographic features and comorbidities were found between the sexes, except for a higher rate of cigarette smokers among men. Diffuse cutaneous SSc and anti-topoisomerase antibodies were more prevalent in males than females. Additionally, male patients presented significantly more myositis, interstitial lung disease and gastric involvement. There were no differences in the patterns of drug use between the sexes. During follow-up, more deaths were reported in men than women (12.1% vs 7.3%, p = 0.04). The overall 1-, 3-, and 5-year survivals from diagnosis of the inception cohort (N = 469) for men vs women were 96.4% vs 98.2%, 93% vs 95.9%, and 75.8% vs 93.2%, respectively, with statistically significant differences (p < 0.01). This study confirms the existence of gender differences in clinical and immunological SSc features. Although SSc is less common in men than women, men have a more severe expression of skin and internal organ involvement and worse survival. Key Points • There are differences in SSc disease manifestations between sexes. • Males more commonly have diffuse cutaneous SSc, anti-topoisomerase antibodies, pulmonary and musculoskeletal involvement. • In the inception cohort, men had worse survival rates than women.