Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression.

Ovarian cancer (OC) patients develop ascites, an accumulation of ascitic fluid in the peritoneal cavity anda sign of tumour dissemination within the peritoneal cavity. This body fluid is under-researched, mainly regarding the ascites formed during tumour progression that have no diagnostic value and, therefore, are discarded. We performed a discovery proteomics study to identify new biomarkers in the ascites supernatant of OC patients. In this preliminary study, we analyzed a small amount of OC ascites to highlight the importance of not discarding such biological material during treatment, which could be valuable for OC management. Our findings reveal that OC malignant ascitic fluid (MAF) displays a proliferative environment that promotes the growth of OC cells that shift the metabolic pathway using alternative sources of nutrients, such as the cholesterol pathway. Also, OC ascites drained from patients during treatment showed an immunosuppressive environment, with up-regulation of proteins from the signaling pathways of IL-4 and IL-13 and down-regulation from the MHC-II. This preliminary study pinpointed a new protein (Transmembrane Protein 132A) in the OC context that deserves to be better explored in a more extensive cohort of patients' samples. The proteomic profile of MAF from OC patients provides a unique insight into the metabolic kinetics of cancer cells during disease progression, and this information can be used to develop more effective treatment strategies.

Silver-nanoparticle-modified nanocellulose synthesized by pyroligneous acid: cytotoxicity towards HaCat cells.

In the present study, pyroligneous acid, also known as wood vinegar, has been employed as reducing and stabilizing agent in the synthesis of silver nanoparticles (AgNPs) anchored on nanocellulose (NC). The idea is to confer the latter bactericidal properties for its typical uses such as in cosmetics and food-packing. It has been demonstrated that AgNPs can be directly produced onto NC in one-pot fashion while dramatically enhancing the kinetics of AgNPs synthesis (2 h for reaction completion) in comparison to the NC-less counterpart (10 days for reaction completion). Furthermore, NC allowed for a narrower size distribution of AgNPs. NC-supported and non-supported AgNPs had sizes of 5.1 ± 1.6 nm and 16.7 ± 4.62 nm, respectively. Immortalized human keratinocytes (HaCat) cells were then employed as model to evaluate the cytotoxicity of the AgNPs-NC compound. The latter was found not to impact cell proliferation at any formulation, while decreasing the viability by only 6.8% after 72 h. This study contributes to the development of more environmentally benign routes to produce nanomaterials and to the understanding of their impact on cells.

The ADnet Bayesian belief network for alder decline: Integrating empirical data and expert knowledge.

The globalization in plant material trading has caused the emergence of invasive pests in many ecosystems, such as the alder pathogen Phytophthora ×alni in European riparian forests. Due to the ecological importance of alder to the functioning of rivers and the increasing incidence of P. ×alni-induced alder decline, effective and accessible decision tools are required to help managers and stakeholders control the disease. This study proposes a Bayesian belief network methodology to integrate diverse information on the factors affecting the survival and infection ability of P. ×alni in riparian habitats to help predict and manage disease incidence. The resulting Alder Decline Network (ADnet) management tool integrates information about alder decline from scientific literature, expert knowledge and empirical data. Expert knowledge was gathered through elicitation techniques that included 19 experts from 12 institutions and 8 countries. An original dataset was created covering 1189 European locations, from which P. ×alni occurrence was modeled based on bioclimatic variables. ADnet uncertainty was evaluated through its sensitivity to changes in states and three scenario analyses. The ADnet tool indicated that mild temperatures and high precipitation are key factors favoring pathogen survival. Flood timing, water velocity, and soil type have the strongest influence on disease incidence. ADnet can support ecosystem management decisions and knowledge transfer to address P. ×alni-induced alder decline at local or regional levels across Europe. Management actions such as avoiding the planting of potentially infected trees or removing man-made structures that increase the flooding period in disease-affected sites could decrease the incidence of alder disease in riparian forests and limit its spread. The coverage of the ADnet tool can be expanded by updating data on the pathogen's occurrence, particularly from its distributional limits. Research on the role of genetic variability in alder susceptibility and pathogen virulence may also help improve future ADnet versions.

Effects of high-intensity interval training on depressive and anxiety symptoms in healthy individuals: A systematic review and meta-analysis of randomized clinical trials.

Although evidence regarding the effects of high-intensity interval training (HIIT) on mental health has increased in recent years, there is still no consensus regarding the effects of HIIT on the symptoms of depression and anxiety in a healthy population. Therefore, this systematic review aimed to investigate the effects of HIIT on depressive and/or anxiety symptoms in healthy individuals. The following four databases were searched: PubMed, Scopus, Embase, and PsycINFO. Only randomized clinical trials (RCTs) were included. We performed a random-effects meta-analysis based on standardized mean difference (SMD). The risk of bias was assessed using the RoB 2.0 tool, and the certainty of the evidence was evaluated based on recommendations GRADE. Eight RCTs evaluating 471 participants (81% female) were considered eligible for inclusion. The results of the meta-analysis showed that HIIT-based interventions had no significant effect on reducing anxiety (SMD = -0.17; 95% CI: -0.53, 0.19; p = 0.27) and depressive symptoms (SMD = -0.38; 95% CI: -1.06, 0.30; p = 0.17) compared with the passive control group. In conclusion, HIIT does not improve symptoms of depression and anxiety in healthy individuals. This finding is based on evidence of very low certainty. Therefore, the evidence is still not consistent enough to support HIIT as a viable strategy to reduce both outcomes because of the limited number of included studies and the overall quality of evidence.

Analysis of glomerular deposition of IgM and C3 in patients with podocytopathies.

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are the main causes of nephrotic syndrome in the world. The complement system appears to play an important role in the pathogenesis of these diseases. To evaluate the deposition of immunoglobulins and particles of the complement system in renal biopsies of patients with FSGS and MCD and relate to laboratory data, we selected 59 renal biopsies from patients with podocytopathies, 31 from patients with FSGS and 28 with MCD. Epidemiological, clinical, laboratory information and the prognosis of these patients were evaluated. Analysis of the deposition of IgM, IgG, C3, C1q and C4d in renal biopsies was performed. We related IgM and C3 deposition with laboratory parameters. Statistical analysis was performed using GraphPad Prism version 7.0. Glomerular deposition of IgM was significantly higher in the FSGS group, as was codeposition of IgM and C3. The clinical course of patients and laboratory data were also worse in cases of FSGS, with a higher percentage progressing to chronic kidney disease and death. Patients with C3 deposition had significantly higher mean serum creatinine and significantly lower eGFR, regardless of disease. Patients with FSGS had more IgM and C3 deposition in renal biopsies, worse laboratory data and prognosis than patients with MCD. C3 deposition, both in FSGS and MCD, appears to be related to worsening renal function.

Rehabilitation of tropical urban streams improves their structure and functioning.

Urban streams are affected by a complex combination of stressors, which modify physical habitat structure, flow regime, water quality, biological community composition, and ecosystem processes and services, thereby altering ecosystem structure and functioning. Rehabilitation projects have been undertaken in several countries to rehabilitate urban streams. However, stream rehabilitation is still rarely reported for neotropical regions. In addition, most studies focus on structural aspects, such as water quality, sediment control, and flood events, without considering ecosystem function indicators. Here, we evaluated the structure and functioning of three 15-y old rehabilitated urban stream sites in comparison with three stream sites in the best available ecological condition (reference), three sites with moderate habitat alteration, and three severely degraded sites. Compared to degraded streams, rehabilitated streams had higher habitat diversity, sensitive macroinvertebrate taxa richness, and biotic index scores, and lower biochemical oxygen demand, primary production, sediment deposition, and siltation. However, rehabilitated streams had higher primary production than moderate and reference streams, and lower canopy cover, habitat diversity, sensitive macroinvertebrate taxa richness, and biotic index scores than reference streams. These results indicate that rehabilitated streams have better structural and functional condition than degraded streams, but do not strongly differ from moderately altered streams, nor have they reached reference stream condition. Nonetheless, we conclude that rehabilitation is effective in removing streams from a degraded state by improving ecosystem structure and functioning. Furthermore, the combined use of functional and structural indicators facilitated an integrative assessment of stream ecological condition and distinguished stream conditions beyond those based on water quality indicators.

Dieback and Replacement of Riparian Trees May Impact Stream Ecosystem Functioning.

Alders are nitrogen (N)-fixing riparian trees that promote leaf litter decomposition in streams through their high-nutrient leaf litter inputs. While alders are widespread across Europe, their populations are at risk due to infection by the oomycete Phytophthora ×alni, which causes alder dieback. Moreover, alder death opens a space for the establishment of an aggressive N-fixing invasive species, the black locust (Robinia pseudoacacia). Shifts from riparian vegetation containing healthy to infected alder and, eventually, alder loss and replacement with black locust may alter the key process of leaf litter decomposition and associated microbial decomposer assemblages. We examined this question in a microcosm experiment comparing three types of leaf litter mixtures: one representing an original riparian forest composed of healthy alder (Alnus lusitanica), ash (Fraxinus angustifolia), and poplar (Populus nigra); one with the same species composition where alder had been infected by P. ×alni; and one where alder had been replaced with black locust. The experiment lasted six weeks, and every two weeks, microbially driven decomposition, fungal biomass, reproduction, and assemblage structure were measured. Decomposition was highest in mixtures with infected alder and lowest in mixtures with black locust, reflecting differences in leaf nutrient concentrations. Mixtures with alder showed distinct fungal assemblages and higher sporulation rates than mixtures with black locust. Our results indicate that alder loss and its replacement with black locust may alter key stream ecosystem processes and assemblages, with important changes already occurring during alder infection. This highlights the importance of maintaining heathy riparian forests to preserve proper stream ecosystem functioning.

Macroplastic litter colonization by stream macroinvertebrates relative to that of plant litter: A meta-analysis.

Environmental pollution by anthropogenic litter is a global concern, but studies specifically addressing the interaction between macroplastics and macroinvertebrates in streams are scarce. However, several studies on plant litter decomposition in streams have also used plastic strips as a methodological approach to assess if macroinvertebrates colonize plant litter mostly as a substrate or a food resource. Looking at these studies from the plastic strips perspective may provide useful information on the interaction between macroplastics and macroinvertebrates in streams. I carried out a meta-analysis of 18 studies that have compared macroinvertebrate colonization of macroplastic litter and plant litter in streams to estimate the overall macroinvertebrate colonization of macroplastic litter relative to plant litter, and identify moderators of this difference. Macroinvertebrate colonization of macroplastic litter was overall lower (by âˆ¼ 40%) compared with plant litter. However, differences in macroinvertebrate colonization between macroplastic litter and plant litter were observed when considering leaf litter but not wood litter, which may be a poorer substrate and food resource for macroinvertebrates. Also, differences in macroinvertebrate colonization between macroplastic litter and leaf litter were observed for shredders, collectors and predators, but not for grazers that may feed on the biofilm developed on macroplastics. Macroplastic litter supported lower macroinvertebrate density, biomass, abundance, and richness, but higher macroinvertebrate diversity than leaf litter. Higher macroinvertebrate diversity on macroplastic litter may have occurred when macroplastics represented more heterogeneous substrates (e.g., mixture of plastic types) than leaf litter (e.g., needles). Differences in macroinvertebrate abundance between macroplastic litter and leaf litter were not significantly affected by plastic type, mesh opening size, plant functional group or plant identity. By testing previously untested hypotheses, this meta-analysis guides future empirical studies. Future studies should also consider the geographical areas most affected by macroplastic pollution and the plastic types most often found in the streams.

Psychosocial impact at the time of a rare disease diagnosis.

Over half of all persons with rare diseases (RDs) in Spain experience diagnostic delay (DD) but little is known about its consequences. This study therefore aimed to analyze the psychological impact of obtaining a diagnosis of an RD, and to ascertain what social determinants are influenced and what the personal consequences are, according to whether or not patients experienced DD. Data were obtained from a purpose-designed form completed by persons registered at the Spanish Rare Diseases Patient Registry. The following were performed: a descriptive analysis; a principal component analysis (PCA); and logistic regressions. Results revealed that while searching for a diagnosis, people who experienced DD were more in need of psychological care than those diagnosed in less than one year (36.2% vs 23.2%; p = 0.002; n = 524). The PCA identified three principal components, i.e., psychological effects, social implications, and functional impact. Reducing DD would improve psychological effects, such as irritability (OR 3.6; 95%CI 1.5-8.5), frustration (OR 3.4; 95%CI 1.7-7.1) and concentration on everyday life (OR 3.3; 95%CI 1.4-7.7). The influence of the social implications and functional repercussions of the disease was greater in persons with DD (scores of 22.4 vs 20 and 10.6 vs 9.4, respectively) in terms of the difficulty in explaining symptoms to close friends and family (3.3 vs 2.9), and loss of independence (3.3 vs 2.9). In conclusion, this is the first study to analyze the psychosocial impact of diagnosis of RDs in Spain and one of few to assess it in the patients themselves, based on data drawn from a purpose-designed form from a national registry open to any RD. People affected by RDs who underwent DD experienced greater psychosocial impact than did those who were diagnosed within the space of one year.

In situ assessment of Mindin as a biomarker of podocyte lesions in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.

Familial Mediterranean Fever in Spain: Time Trend and Spatial Distribution of the Hospitalizations.

Familial Mediterranean Fever (FMF) is a rare, hereditary, auto-inflammatory disease. The aims of this study were to explore the time trend and geographical distribution of hospitalizations in Spain from 2008 to 2015. We identified hospitalizations of FMF from the Spanish Minimum Basic Data Set at hospital discharge, using ICD-9-CM code 277.31. Age-specific and age-adjusted hospitalization rates were calculated. The time trend and the average percentage change were analyzed using Joinpoint regression. Standardized morbidity ratios were calculated and mapped by province. A total of 960 FMF-related hospitalizations (52% men) were identified across the period 2008-2015, with an increase in hospitalizations of 4.9% per year being detected (p < 0.05). The risk of hospitalization was higher than expected for the national total (SMR > 1) in 13 provinces (5 in the Mediterranean area), and lower (SMR < 1) in 14 provinces (3 in the Mediterranean area). There was an increase in hospitalizations of patients with FMF in Spain throughout the study period, with a risk of hospitalization that was higher, though not exclusively so, in provinces along the Mediterranean coast. These findings contribute to the visibility of FMF and provide useful information for health planning. Further research should take into account new population-based information, in order to continue monitoring this disease.

Diagnostic delay in rare diseases: data from the Spanish rare diseases patient registry.

BACKGROUND: According to the International Rare Diseases Research Consortium (IRDiRC), a known rare disease (RD) should be diagnosable within a year. This study sought: firstly, to ascertain how long it takes to obtain the diagnosis of a RD in Spain, along with its associated time trend; and secondly, to identify and measure diagnostic delay (defined by the IRDiRC as any period exceeding a year) by reference to the characteristics of RDs and the persons affected by them. METHODS: Using data sourced from the Spanish Rare Diseases Patient Registry, we performed a descriptive analysis of the time elapsed between symptom onset and diagnosis of each RD, by sex, age and date of symptom onset, and type of RD. We analysed the time trend across the period 1960-2021 and possible change points, using a Joinpoint regression model and assuming a Poisson distribution. The multivariate analysis was completed with backward stepwise logistic regression. RESULTS: Detailed information was obtained on 3304 persons with RDs: 56.4% had experienced delay in diagnosis of their RDs, with the mean time taken being 6.18 years (median = 2; IQR 0.2-7.5). Both the percentage of patients with diagnostic delay and the average time to diagnosis underwent a significant reduction across the study period (p < 0.001). There was a higher percentage of diagnostic delays: in women (OR 1.25; 95% CI 1.07-1.45); in cases with symptom onset at age 30-44 years (OR 1.48; 95% CI 1.19-1.84): and when analysed by type of RD, in mental and behavioural disorders (OR 4.21; 95% CI 2.26-7.85), followed by RDs of the nervous system (OR 1.39; 95% CI 1.02-1.88). CONCLUSIONS: This is the first study to quantify time to diagnosis of RDs in Spain, based on data from a national registry open to any RD. Since over half of all persons affected by RDs experience delay in diagnosis, new studies are needed to ascertain the factors associated with this delay and the implications this has on the lives of patients and their families.

Litter quality and stream physicochemical properties drive global invertebrate effects on instream litter decomposition.

Plant litter is the major source of energy and nutrients in stream ecosystems and its decomposition is vital for ecosystem nutrient cycling and functioning. Invertebrates are key contributors to instream litter decomposition, yet quantification of their effects and drivers at the global scale remains lacking. Here, we systematically synthesized data comprising 2707 observations from 141 studies of stream litter decomposition to assess the contribution and drivers of invertebrates to the decomposition process across the globe. We found that (1) the presence of invertebrates enhanced instream litter decomposition globally by an average of 74%; (2) initial litter quality and stream water physicochemical properties were equal drivers of invertebrate effects on litter decomposition, while invertebrate effects on litter decomposition were not affected by climatic region, mesh size of coarse-mesh bags or mycorrhizal association of plants providing leaf litter; and (3) the contribution of invertebrates to litter decomposition was greatest during the early stages of litter mass loss (0-20%). Our results, besides quantitatively synthesizing the global pattern of invertebrate contribution to instream litter decomposition, highlight the most significant effects of invertebrates on litter decomposition at early rather than middle or late decomposition stages, providing support for the inclusion of invertebrates in global dynamic models of litter decomposition in streams to explore mechanisms and impacts of terrestrial, aquatic, and atmospheric carbon fluxes.

The impact of toxic oil syndrome on physical and psychological health status using the HAQ and the PHQ-9 questionnaires.

BACKGROUND: Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication. To evaluate physical and mental health of TOS patients, we used the Health Assessment Questionnaire (HAQ) and the Patient Health Questionnaire-9 (PHQ-9). Additionally, we correlated both questionnaires with the results of the Short Form-36v2 (SF-36v2) Health Survey obtained in the same patients' sample. METHODS: 895 TOS patients who participated in the prior SF-36v2 study were invited to participate. We described patients' demographic and clinical characteristics, HAQ and PHQ-9 results. HAQ and PHQ-9 scores were correlated to the standardised SF-36v2 results obtained in our previous study. RESULTS: In total, 828 (92.5%) TOS annual follow-up and HAQ and 810 (90.5%) PHQ-9 valid questionnaires were analysed. Participants' average age was 65.4 (Standard Deviation (SD): 13.4), 521 (62.9%) were women, 725 (87.6%) reported having at least other chronic disease and 789 (95.3%) an additional TOS-related health problem. Average scores were 0.91 (SD: 0.83) for HAQ, 35.8 (SD: 10.1) for PCS and 37.8 (SD: 11.6) for MCS. Overall, 467 (57.7%) participants had moderate/severe depression (PHQ-9 ≥ 10), but only 229 (49.6%) of them reported having a depression diagnosis. Correlation between questionnaires was very strong for HAQ and physical function SF-36v2 dimension and moderate/fair for the rest of combinations. CONCLUSIONS: TOS cohort presented low/very low health status measured with SF-36v2, moderate difficulties in performing daily activities according to HAQ, and a high prevalence of major depression measured with PHQ-9. High proportion of undiagnosed depression was detected, proving PHQ-9 useful in terms of detecting and promoting depression diagnosis in the cohort.

Diagnostic Process in Rare Diseases: Determinants Associated with Diagnostic Delay.

Many people living with rare disease (RD) report a difficult diagnostic process from the symptom onset until they obtain the definitive diagnosis. The aim of this study was thus to ascertain the diagnostic process in RDs, and explore the determinants related with having to wait for more than one year in this process (defined as "diagnostic delay"). We conducted a case-control study, using a purpose-designed form from the Spanish Rare Diseases Patient Registry for data-collection purposes. A descriptive analysis was performed and multivariate backward logistic regression models fitted. Based on data on 1216 patients living with RDs, we identified a series of determinants associated with experiencing diagnostic delay. These included: having to travel to see a specialist other than that usually consulted in the patient's home province (OR 2.1; 95%CI 1.6-2.9); visiting more than 10 specialists (OR 2.6; 95%CI 1.7-4.0); being diagnosed in a region other than that of the patient's residence at the date of symptom onset (OR 2.3; 95%CI 1.5-3.6); suffering from a RD of the nervous system (OR 1.4; 95%CI 1.0-1.8). In terms of time taken to see a specialist, waiting more than 6 months to be referred from the first medical visit was the period of time which most contributed to diagnostic delay (PAR 30.2%). In conclusion, this is the first paper to use a collaborative study based on a nationwide registry to address the diagnostic process of patients living with RDs. While the evidence shows that the diagnostic process experienced by these persons is complex, more studies are needed to determine the implications that this has for their lives and those of their families at a social, educational, occupational, psychological, and financial level.

A global synthesis of human impacts on the multifunctionality of streams and rivers.

Human impacts, particularly nutrient pollution and land-use change, have caused significant declines in the quality and quantity of freshwater resources. Most global assessments have concentrated on species diversity and composition, but effects on the multifunctionality of streams and rivers remain unclear. Here, we analyse the most comprehensive compilation of stream ecosystem functions to date to provide an overview of the responses of nutrient uptake, leaf litter decomposition, ecosystem productivity, and food web complexity to six globally pervasive human stressors. We show that human stressors inhibited ecosystem functioning for most stressor-function pairs. Nitrate uptake efficiency was most affected and was inhibited by 347% due to agriculture. However, concomitant negative and positive effects were common even within a given stressor-function pair. Some part of this variability in effect direction could be explained by the structural heterogeneity of the landscape and latitudinal position of the streams. Ranking human stressors by their absolute effects on ecosystem multifunctionality revealed significant effects for all studied stressors, with wastewater effluents (194%), agriculture (148%), and urban land use (137%) having the strongest effects. Our results demonstrate that we are at risk of losing the functional backbone of streams and rivers if human stressors persist in contemporary intensity, and that freshwaters are losing critical ecosystem services that humans rely on. We advocate for more studies on the effects of multiple stressors on ecosystem multifunctionality to improve the functional understanding of human impacts. Finally, freshwater management must shift its focus toward an ecological function-based approach and needs to develop strategies for maintaining or restoring ecosystem functioning of streams and rivers.

A population-based study of mortality due to muscular dystrophies across a 36-year period in Spain.

Muscular dystrophies (MD) are a group of rare hereditary degenerative diseases. Our aim was to analyze the mortality pattern in Spain from 1981 to 2016 to assess the temporal trend and discern possible geographic differences using population-based data. Annual deaths related to MD were obtained from the National Statistics Institute with codes 359.1 of the ICD-9 (1981-1998) and G71.0 of the ICD-10 (1999-2016). Age-adjusted mortality rates were calculated and changes in mortality trends were identified. The standardized mortality ratios (SMR) and their respective 95% confidence intervals were calculated by district for 1999-2016. Smoothed SMRs and posterior probability were also assessed and then mapped to look for patterns or geographic distribution. All rates were expressed per 1,000,000 inhabitants. A total of 2,512 deaths (73.8% men) were identified. The age-adjusted mortality rates varied from 0.63 (95% CI 0.40-0.95) in 1981 to 1.51 (95% CI 1.17-1.93) in 2016. MD mortality showed a significant increase of 8.81% per year (95% CI 5.0-12.7) from 1981 to 1990, remaining stable afterwards. Areas with risk of death higher than expected for Spain as a whole were identified, not showing a specific regional pattern. In conclusion, the rising trend in MD mortality might be attributable to advanced improvements in diagnostic techniques leading to a rise in prevalence. Further research on the districts with the highest mortality would be necessary.

[Diagnostic delay in rare diseases: systematic review.] / Retraso diagnóstico en enfermedades raras: revisión sistemática.

BACKGROUND: The aims of the International Consortium for Rare Diseases Research (IRDiRC) include that the diagnosis of a known rare disease (RD) must be made within a year. The objective of this systematic review was to identify the scientific evidence about the time to diagnosis in patients affected by RDs and also to know if there is a diagnostic delay (more than one year) according to the objective set by the IRDiRC. METHODS: A systematic review was carried out according to PRISMA criteria in the PubMed, Scopus and Web of Science (WoS) databases. The quality of the articles was assessed using the STROBE statement. RESULTS: 17 articles were included. They were devoted to specific RDs, most of them metabolic diseases, neurological and disorders that affect immunity. The study designs were mainly cross-sectional, and two retrospective cohorts were also included. Most articles showed that it takes more than a year to get a diagnosis for these RDs. CONCLUSIONS: Scientific literature quantifying the time to diagnosis is still scarce and no study addresses RDs as a whole. In most cases, it takes more than one year to obtain a diagnosis of a RD, so there is an obvious delay according to the objective set by the IRDiRC. Therefore, new advances in the RD field are necessary to reduce the time from the onset of symptoms to the accurate diagnosis.

OBJETIVO: Según el Consorcio Internacional para la Investigación de Enfermedades Raras (IRDiRC) el diagnóstico de una enfermedad rara (ER) conocida debería hacerse en el plazo de un año. El objetivo de esta revisión sistemática fue identificar las evidencias científicas sobre el tiempo que transcurre hasta obtener el diagnóstico en pacientes con ER y conocer si se produce retraso, conforme al objetivo del IRDiRC (más de un año). METODOS: Se realizó una revisión sistemática según criterios PRISMA en las bases de datos PubMed, Scopus y Web of Science (WoS). Se valoró la calidad de los estudios incluidos conforme a la declaración STROBE. RESULTADOS: Se incluyeron 17 artículos orientados a ER específicas, principalmente metabólicas, neurológicas y trastornos que afectan a la inmunidad. Los diseños fueron fundamentalmente transversales, aunque también se incluyeron dos de cohorte retrospectivos. La mayoría de los estudios reflejan que se emplea más de un año en obtener el diagnóstico de estas ER. CONCLUSIONES: La literatura científica que cuantifica el tiempo hasta el diagnóstico en ER es aún escasa y ningún estudio se orienta a estas enfermedades en su conjunto. Según el objetivo del IRDiRC, existe un evidente retraso en el diagnóstico de ER, ya que en la mayoría de los casos se requiere de un tiempo superior a un año. Por tanto, son necesarios nuevos avances en campo de las ER para contribuir a la reducción del tiempo desde la aparición de los síntomas hasta el diagnóstico adecuado.

Retraso diagnóstico en enfermedades raras: revisión sistemática / Diagnostic delay in rare diseases: systematic review

Fundamentos: Según el Consorcio Internacional para la Investigación de Enfermedades Raras (IRDiRC) el diagnóstico de una enfermedad rara (ER) conocida debería hacerse en el plazo de un año. El objetivo de esta revisión sistemática fue identificar las evidencias científicas sobre el tiempo que transcurre hasta obtener el diagnóstico en pacientes con ER y conocer si se produce retraso, conforme al objetivo del IRDiRC (más de un año). Métodos: Se realizó una revisión sistemática según criterios PRISMA en las bases de datos PubMed, Scopus y Web of Science (WoS). Se valoró la calidad de los estudios incluidos conforme a la declaración STROBE. Resultados: Se incluyeron 17 artículos orientados a ER específicas, principalmente metabólicas, neurológicas y trastornos que afectan a la inmunidad. Los diseños fueron fundamentalmente transversales, aunque también se incluyeron dos de cohorte retrospectivos. La mayoría de los estudios reflejan que se emplea más de un año en obtener el diagnóstico de estas ER. Conclusiones: La literatura científica que cuantifica el tiempo hasta el diagnóstico en ER es aún escasa y ningún estudio se orienta a estas enfermedades en su conjunto. Según el objetivo del IRDiRC, existe un evidente retraso en el diagnóstico de ER, ya que en la mayoría de los casos se requiere de un tiempo superior a un año. Por tanto, son necesarios nuevos avances en campo de las ER para contribuir a la reducción del tiempo desde la aparición de los síntomas hasta el diagnóstico adecuado.(AU)

Background: The aims of the International Consortium for Rare Diseases Research (IRDiRC) include that the diagnosis of a known rare disease (RD) must be made within a year. The objective of this systematic review was to identify the scientific evidence about the time to diagnosis in patients affected by RDs and also to know if there is a diagnostic delay (more than one year) according to the objective set by the IRDiRC. Methods: A systematic review was carried out according to PRISMA criteria in the PubMed, Scopus and Web of Science (WoS) databases. The quality of the articles was assessed using the STROBE statement. Results: 17 articles were included. They were devoted to specific RDs, most of them metabolic diseases, neurological and disorders that affect immunity. The study designs were mainly cross-sectional, and two retrospective cohorts were also included. Most articles showed that it takes more than a year to get a diagnosis for these RDs. Conclusions: Scientific literature quantifying the time to diagnosis is still scarce and no study addresses RDs as a whole. In most cases, it takes more than one year to obtain a diagnosis of a RD, so there is an obvious delay accordingto the objective set by the IRDiRC. Therefore, new advances in the RD field are necessary to reduce the time from the onset of symptoms to the accurate diagnosis.(AU)

Toxic oil syndrome: health-related quality-of-life assessment using the SF-36 Health Survey.

BACKGROUND: Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication that occurred in Spain in 1981 affecting >20 000 persons. This study aims to evaluate the quality of life of the survivors' cohort after 38 years of follow-up using the Short Form 36 (SF-36) Health Survey. METHODS: One thousand patients were selected among the 14 084 alive TOS cohort members in 2018 using a stratified random sampling method. Stratification was performed by the 2017 self-rated health status reported by patients. SF-36 results were compared directly and as standardized (T scores) with the Spanish-population reference values. Relationship between self-rated health status and SF-36 results was assessed. RESULTS: Overall, 900 cohort members participated and 895 valid responses were included in the study. Participants' average age was 65.2 (standard deviation: 13.8) years and 563 (62.9%) participants were women. Participants' distribution by self-rated health status was: 219 (24.5%) good/very good, 415 (46.4%) fair and 261 (29.1%) poor/very poor. Quality of life was below the Spanish-population reference in 84% of the TOS patients (87.2% for women and 78.6% for men) for the Physical Component Summary (PCS) and in 75.4% (81.7% for women and 64.8% for men) for the Mental Component Summary (MCS). PCS and MCS scores decreased similarly for both sexes with worse self-rated health. CONCLUSIONS: Very low quality of life and self-rated health, especially for women, were found in the total TOS participants that can be extrapolated to the TOS survivors' cohort. The TOS cohort still requires standardization of care with integral plans around the country.