Socioeconomic and gender inequalities in mental disorders among adolescents and young adults.

BACKGROUND: Socioeconomic status (SES) and gender play a key role in mental health. The objective of this study was to assess socioeconomic and gender mental health inequalities in adolescents and young adults using a population-based registry. MATERIALS AND METHODS: We conducted a lifetime follow-up study of all residents in the Basque Country between 1 and 30 years old (n=609,381) as of 31 December 2018. Primary care, specialized outpatient, and hospital care records were searched for diagnoses. SES was assessed based on household income. We estimated disaggregated lifetime prevalence of substance use, behaviour, anxiety, depression, psychosis, and attention deficit hyperactivity disorder. The local Institute of Statistics validated the mortality data. The likelihood of risks was estimated using logistic regression. RESULTS: Overall, 96,671 individuals (15.9%) had a diagnosed mental disorder, with clear gradients by gender and SES. Females of medium-to-high SES had the lowest prevalence of all mental disorders, except anxiety and depression. This group was followed by males of the same SES and females of low SES, while the highest prevalence of mental disorders was observed in low-SES males. The lower income categories had higher risks of psychiatric admission (adjusted odds ratio [AOR]: 3.64 for females; 6.66 for males) and death (AOR: 5.42). People with a mental health diagnosis had higher mortality (AOR: 2.38). CONCLUSIONS: Our work evidenced important SES and gender inequalities in the mental health and premature mortality of adolescents and young adults, findings that should drive the development and implementation of early preventive interventions.

Comorbidity and household income as mediators of gender inequalities in dementia risk: a real-world data population study.

BACKGROUND: Low household income (HI), comorbidities and female sex are associated with an increased risk of dementia. The aim of this study was to measure the mediating effect of comorbidity and HI on the excess risk due to gender in relation to the incidence and prevalence of dementia in the general population. METHODS: A retrospective and observational study using real-world data analysed all people over 60 who were registered with the Basque Health Service in Gipuzkoa. The study measured HI level, the Charlson comorbidity index (CCI), age and sex. The prevalence and incidence of dementia were analysed using logistic regression and Poisson regression models, respectively, adjusted by HI, sex, comorbidity and age. We estimated the combined mediation effect of HI and comorbidity on the prevalence of dementia associated with gender. RESULTS: Of the 221,777 individuals, 3.85% (8,549) had a diagnosis of dementia as of 31 December 2021. Classification by the CCI showed a gradient with 2.90% in CCI 0-1, 10.60% in CCI 2-3 and 18.01% in CCI > 3. Both low HI and gender were associated with a higher crude prevalence of dementia. However, in the CCI-adjusted model, women had an increased risk of dementia, while HI was no longer statistically significant. The incidence analysis produced similar results, although HI was not significant in any model. The CCI was significantly higher for men and for people with low HI. The mediation was statistically significant, and the CCI and HI explained 79% of the gender effect. CONCLUSIONS: Comorbidity and low HI act as mediators in the increased risk of dementia associated with female sex. Given the difference in the prevalence of comorbidities by HI, individual interventions to control comorbidities could not only prevent dementia but also reduce inequalities, as the risk is greater in the most disadvantaged population.

Sex differences in clinical response to deep brain stimulation in resistant obsessive-compulsive disorder.

INTRODUCTION: Deep brain stimulation (DBS) is an effective alternative to treat severe refractory obsessive-compulsive disorder (OCD), although little is known on factors predicting response. The objective of this study was to explore potential sex differences in the pattern of response to DBS in OCD patients. METHODS: We conducted a prospective observational study in 25 patients with severe resistant OCD. Response to treatment was defined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. Logistic regression models were calculated to measure the likelihood of response at short and long-term follow-up by sex as measured by Y-BOCS score. Similar analyses were carried out to study changes in depressive symptomatology assessed with the Hamilton Depression Rating Scale (HDRS). Additionally, effect sizes were calculated to assess clinical significance. RESULTS: We did not observe significant clinical differences between men and women prior to DBS implantation, nor in the response after one year of stimulation. At long-term follow-up, 76.9% of men could be considered responders to DBS versus only 33.3% of women. The final response odds ratio in men was 10.05 with significant confidence intervals (88.90-1.14). No other predictors of response were identified. The sex difference in Y-BOCS reduction was clinically significant, with an effect size of 3.2. The main limitation was the small sample size. CONCLUSIONS: Our results suggest that gender could influence the long-term response to DBS in OCD, a finding that needs to be confirmed in new studies given the paucity of results on predictors of response to DBS.

Using Age-Specific Rates for Parametric Survival Function Estimation in Simulation Models.

PURPOSE: To describe a procedure for incorporating parametric functions into individual-level simulation models to sample time to event when age-specific rates are available but not the individual data. METHODS: Using age-specific event rates, regression analysis was used to parametrize parametric survival distributions (Weibull, Gompertz, log-normal, and log-logistic), select the best fit using the R2 statistic, and apply the corresponding formula to assign random times to events in simulation models. We used stroke rates in the Spanish population to illustrate our procedure. RESULTS: The 3 selected survival functions (Gompertz, Weibull, and log-normal) had a good fit to the data up to 85 y of age. We selected Gompertz distribution as the best-fitting distribution due to its goodness of fit. CONCLUSIONS: Our work provides a simple procedure for incorporating parametric risk functions into simulation models without individual-level data. HIGHLIGHTS: We describe the procedure for sampling times to event for individual-level simulation models as a function of age from parametric survival functions when age-specific rates are available but not the individual dataWe used linear regression to estimate age-specific hazard functions, obtaining estimates of parameter uncertainty.Our approach allows incorporating parameter (second-order) uncertainty in individual-level simulation models needed for probabilistic sensitivity analysis in the absence of individual-level survival data.

Cost-Effectiveness Analysis of Vaccines for COVID-19 According to Sex, Comorbidity and Socioeconomic Status: A Population Study.

BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccines are extremely effective in preventing severe disease, but their real-world cost effectiveness is still an open question. We present an analysis of the cost-effectiveness and economic impact of the initial phase of the COVID-19 vaccination rollout in the Basque Country, Spain. METHODS: To calculate costs and quality-adjusted life years for the entire population of the Basque Country, dynamic modelling and a real-world data analysis were combined. Data on COVID-19 infection outcomes (cases, hospitalisations, intensive care unit admissions and deaths) and population characteristics (age, sex, socioeconomic status and comorbidity) during the initial phase of the vaccination rollout, from January to June of 2021, were retrieved from the Basque Health Service database. The outcomes in the alternative scenario (without vaccination) were estimated with the dynamic model used to guide public health authority policies, from February to December 2020. Individual comorbidity-adjusted life expectancy and costs were estimated. RESULTS: By averting severe disease-related outcomes, COVID-19 vaccination resulted in monetary savings of €26.44 million for the first semester of 2021. The incremental cost-effectiveness ratio was €707/quality-adjusted life year considering official vaccine prices and dominant real prices. While the analysis by comorbidity showed that vaccines were considerably more cost effective in individuals with pre-existing health conditions, this benefit was lower in the low socioeconomic status group. CONCLUSIONS: The incremental cost-effectiveness ratio of the vaccination programme justified the policy of prioritising high-comorbidity patients. The initial phase of COVID-19 vaccination was dominant from the perspective of the healthcare payer.

First-episode psychosis intervention programme versus standard care for the clinical management of early phases of psychosis: cost analysis.

BACKGROUND: Early intervention programmes (EIPs) in psychosis have gained attention as specialised interventions to improve health-related and societal impacts for people with psychotic disorders. Previous studies have presented evidence in favour of EIPs over the first year of intervention, despite none considering the critical period before psychosis onset (5 years). AIMS: To compare the associated costs of the First Episode Psychosis Intervention Program (CRUPEP) and treatment as usual (TAU) in a real-world cohort in a non-specialised psychiatric community setting. METHOD: Direct and indirect mental health-related costs were calculated over 1 year and up to 7 years. Healthcare and societal costs were calculated from economic data related to the consumption of all healthcare resources, including emergency department attendances, hospital admissions, psychotropic medication prescriptions and societal costs. RESULTS: From a healthcare perspective, the intervention (CRUPEP) group initially showed a marginally higher cost per patient than the TAU group (€7621 TAU group v. €11 904 CRUPEP group) over the first year of follow-up. However, this difference was reversed between the groups on considering the entire follow-up, with the TAU group showing considerably higher associated costs per patient (€77 026 TAU v. €25 247 CRUPEP). CONCLUSIONS: The EIP (CRUPEP) showed clinical benefits and minimised the direct and indirect health-related costs of the management of psychosis. Although the CRUPEP intervention initially reported increased costs over 1 year, TAU surpassed the global costs over the entire follow-up.

Excess healthcare costs of mental disorders in children, adolescents and young adults in the Basque population registry adjusted for socioeconomic status and sex.

BACKGROUND: Mental illnesses account for a considerable proportion of the global burden of disease. Economic evaluation of public policies and interventions aimed at mental health is crucial to inform decisions and improve the provision of healthcare services, but experts highlight that nowadays the cost implications of mental illness are not properly quantified. The objective was to measure the costs of excess use of all healthcare services by 1- to 30-year-olds in the Basque population as a function of whether or not they had a mental disorder diagnosis. METHODS: A real-world data study was used to identify diagnoses of mental disorders and to measure resource use in the Basque Health Service Registry in 2018. Diagnoses were aggregated into eight diagnostic clusters: anxiety, attention deficit hyperactivity disorder, conduct disorders, mood disorders, substance use, psychosis and personality disorders, eating disorders, and self-harm. We calculated the costs incurred by each individual by multiplying the resource use by the unit costs. Annual costs for each cluster were compared with those for individuals with no diagnosed mental disorders through entropy balancing and two-part models which adjusted for socioeconomic status (SES). RESULTS: Of the 609,381 individuals included, 96,671 (15.9%) had ≥ 1 mental disorder diagnosis. The annual cost per person was two-fold higher in the group diagnosed with mental disorders (€699.7) than that with no diagnoses (€274.6). For all clusters, annual excess costs associated with mental disorders were significant. The adjustment also evidenced a social gradient in healthcare costs, individuals with lower SES consuming more resources than those with medium and higher SES across all clusters. Nonetheless, the effect of being diagnosed with a mental disorder had a greater impact on the mean and excess costs than SES. CONCLUSIONS: Results were consistent in showing that young people with mental disorders place a greater burden on healthcare services. Excess costs were higher for severe mental disorders like self-harm and psychoses, and lower SES individuals incurred, overall, more than twice the costs per person with no diagnoses. A socioeconomic gradient was notable, excess costs being higher in low SES individuals than those with a high-to-medium SES. Differences by sex were also statistically significant but their sizes were smaller than those related to SES.

Are all primary retinal detachments the same? Anatomic and functional differences between phakic and pseudophakic patients.

BACKGROUND: Given differences in the pathogenic mechanisms underlying primary retinal detachment (RD) as a function of the status of the lens, the objective was to explore differences between pseudophakic and phakic patients with primary RD. METHODS: A retrospective study including 821 patients who underwent surgery for RD [491 cases of phakic and 330 of pseudophakic RD (pRD and psRD, respectively)] in our hospital between 2012 and 2020. RESULTS: The mean age was 58.24 ± 12.76 years in the pRD group and 66.87 ± 11.18 years in the psRD group (p = 0.001). There were more men in both groups (70% and 64.23% of pseudophakic and phakic patients, respectively; p = 0.07). The most common location for the RD was superior in both groups (43.94% and 51.93% of pseudophakic and phakic patients, respectively), rates of inferior and total RD were somewhat higher in the psRD group (31.82% and 13.33% in pseudophakic vs 25.25% and 11.0% in phakic patients, p = 0.001). In pseudophakic and phakic patients respectively, macular involvement in 69.09% and 62.73% of cases (p = 0.067). Proliferative vitreoretinopathy was significantly more common in the psRD group (7.88% vs 3.6% in phakic patients, p = 0.01).The rate of final anatomic reattachment differed markedly between groups, with a higher rate in phakic (94.03%) than pseudophakic (87.27%) patients (p = 0.001). CONCLUSIONS: The specific pathogenic mechanism involved in psRD seems to be responsible for worse evolution characteristics which are associated with poorer final anatomic and functional outcomes in pseudophakic patients.

Cost-utility analysis of the UPRIGHT intervention promoting resilience in adolescents.

BACKGROUND: As mental health in adulthood is related to mental status during adolescence, school-based interventions have been proposed to improve resilience. The objective of this study was to build a simulation model representing the natural history of mental disorders in childhood, adolescence and youth to estimate the cost-effectiveness of the UPRIGHT school-based intervention in promoting resilience and mental health in adolescence. METHODS: We built a discrete event simulation model fed with real-world data (cumulative incidence disaggregated into eight clusters) from the Basque Health Service database (609,381 individuals) to calculate utilities (quality-adjusted life years [QALYs]) and costs for the general population in two scenarios (base case and intervention). The model translated changes in the wellbeing of adolescents into different risks of mental illnesses for a time horizon of 30 years. RESULTS: The number of cases of anxiety was estimated to fall by 5,125 or 9,592 and those of depression by 1,269 and 2,165 if the effect of the intervention lasted 2 or 5 years respectively. From a healthcare system perspective, the intervention was cost-effective for all cases considered with incremental cost-utility ratios always lower than €10,000/QALY and dominant for some subgroups. The intervention was always dominant when including indirect and non-medical costs (societal perspective). CONCLUSIONS: Although the primary analysis of the trial did not did not detect significant differences, the UPRIGHT intervention promoting positive mental health was dominant in the economic evaluation from the societal perspective. Promoting resilience was more cost-effective in the most deprived group. Despite a lack of information about the spillover effect in some sectors, the economic evaluation framework developed principally for pharmacoeconomics can be applied to interventions to promote resilience in adolescents. As prevention of mental health disorders is even more necessary in the post-coronavirus disease-19 era, such evaluation is essential to assess whether investment in mental health promotion would be good value for money by avoiding costs for healthcare providers and other stakeholders.

The effect of mixed vaccination rollout strategy: A modelling study.

Vaccines have measurable efficacy obtained first from vaccine trials. However, vaccine efficacy (VE) is not a static measure and long-term population studies are needed to evaluate its performance and impact. COVID-19 vaccines have been developed in record time and the currently licensed vaccines are extremely effective against severe disease with higher VE after the full immunization schedule. To assess the impact of the initial phase of the COVID-19 vaccination rollout programmes, we used an extended Susceptible - Hospitalized - Asymptomatic/mild - Recovered (SHAR) model. Vaccination models were proposed to evaluate different vaccine types: vaccine type 1 which protects against severe disease only but fails to block disease transmission, and vaccine type 2 which protects against both severe disease and infection. VE was assumed as reported by the vaccine trials incorporating the difference in efficacy between one and two doses of vaccine administration. We described the performance of the vaccine in reducing hospitalizations during a momentary scenario in the Basque Country, Spain. With a population in a mixed vaccination setting, our results have shown that reductions in hospitalized COVID-19 cases were observed five months after the vaccination rollout started, from May to June 2021. Specifically in June, a good agreement between modelling simulation and empirical data was well pronounced.

Incidence of mental disorders in the general population aged 1-30 years disaggregated by gender and socioeconomic status.

PURPOSE: The objective of this study was to estimate the incidence and age of onset of mental disorders diagnosed by gender and socioeconomic status (SES) in children, adolescents, and young adults up to 30 years of age in the whole population of the Basque Country (Spain). METHODS: All mental health diagnoses documented in Basque Health Service records from 1 January 2003 to 31 December 2018, were classified into eight clusters: anxiety, attention deficit hyperactivity disorder (ADHD), conduct disorders, depression, psychosis/personality disorders, substance use, eating disorders, and self-harm. We calculated incidence and cumulative incidence for each cluster, disaggregated by gender, and socioeconomic status (SES). Poisson regression analyses were performed. RESULTS: Overall, 9,486,853 person-years of observation were available for the 609,281 individuals included. ADHD and conduct disorders were diagnosed in the first decade, anxiety and depression disorders in the second and third decades, and psychosis/personality and substance use in the third. The cumulative incidence at 18 years of age for any type of disorder was 15.5%. The group with low SES had a statistically significantly higher incidence of all eight clusters. The incidence of ADHD, conduct disorders, depression, psychosis/personality disorders, and substance use was higher in males and that of anxiety, eating disorders and self-harm was higher in females. CONCLUSIONS: The incidence of mental disorders is high among children, adolescents, and young adults in the Basque Country underlining the need for preventive interventions. Marked differences by gender and SES highlight mental health inequalities, especially for depression and psychosis in low SES males.

Budget impact analysis of the use of Souvenaid in patients with prodromal Alzheimer's Disease in Spain.

INTRODUCTION: The effectiveness, safety, and cost-effectiveness of the use of Souvenaid for Alzheimer's disease (AD) have been previously evidenced. To complete the economic analysis, there is a need to assess whether society can afford it. The objective of this study was to carry out a budget impact analysis of the use of Souvenaid in Spain under the conditions of the LipiDidiet clinical trial from a societal perspective. METHODS: We built a population model that took into account all the cohorts of individuals with AD, their individual progression, and the potential impact of Souvenaid treatment on their trajectories. Patient progression data were obtained from mixed models. The target population was estimated based on the population forecast for 2020-2035 and the incidence of dementia. Individual progression to dementia measured by the Clinical Dementia Rating-Sum of Boxes was reproduced using mixed models. Besides the costs of treatment and diagnosis, direct costs of medical and non-medical care and indirect costs were included. RESULTS: The epidemiological indicators and the distribution of life expectancy by stages validated the model. From the third year (2022), the differences in the cost of dementia offset the incremental cost of diagnosis and treatment. The costs of dependency reached €500 million/year while those of the intervention were limited to €40 million. CONCLUSIONS: Souvenaid, with modest effectiveness in delaying dementia associated with AD, achieved a positive economic balance between costs and savings. Its use in the treatment of prodromal AD would imply an initial cost that would be ongoing, but this would be offset by savings in the care system for dependency associated with dementia from the third year. These results were based on adopting a societal perspective taking into account the effect of treatment on the use of health, social, and family resources.

Tear proteome profile in eyes with keratoconus after intracorneal ring segment implantation or corneal crosslinking.

Purpose: Keratoconus (KC) is a corneal ectasia characterized by structural changes, resulting in progressive thinning and biomechanical weakening that can lead to worsening visual acuity due to irregular astigmatism. Corneal collagen Crosslinking (CXL) and Intracorneal Ring Segment (ICRS) are widely used treatments in KC disease, but the alterations they cause in biomechanical mediators are still poorly understood. The aim of this study was to analyze the tear proteome profile before and after treatments to identify biomarkers altered by surgery. Materials and methods: An observational, prospective, case-control pilot study was conducted, analyzing tear samples from KC patients by nano-liquid chromatography-mass spectrometry (nLC-MS/MS). Data are available via ProteomeXchange with identifier PXD035655. Patients with KC who underwent ICRS surgery (n = 4), CXL (n = 4), and healthy subjects (Ctrl, n = 4) were included in this study. Clinical parameters were measured and tear samples were collected before and 18 months after surgery. Proteins with ≥2 expression change and p-value < 0.05 between groups and times were selected to study their role in post-operative corneal changes. Results: These analyses led to the identification of 447 tear proteins, some of which were dysregulated in KC patients. In comparisons between the two surgical groups and Ctrls, the biological processes that were altered in KC patients at baseline were those that were dysregulated as a consequence of the disease and not of the surgical intervention. Among the biological processes seen to be altered were: immune responses, cytoskeleton components, protein synthesis and metabolic reactions. When comparing the two treatment groups (ICRS and CXL), the process related to cytoskeleton components was the most altered, probably due to corneal thinning which was more pronounced in patients undergoing CXL. Conclusion: The changes observed in tears after 18 months post-operatively could be due to the treatments performed and the pathology. Among the deregulated proteins detected, A-kinase anchor protein 13 (AKAP-13) deserves special attention for its involvement in corneal thinning, and for its strong overexpression in the tears of patients with more active KC and faster disease progression. However, it should be kept in mind that this is a pilot study conducted in a small number of patients.

Changes in Social and Clinical Determinants of COVID-19 Outcomes Achieved by the Vaccination Program: A Nationwide Cohort Study.

BACKGROUND: The objective of this study was to assess changes in social and clinical determinants of COVID-19 outcomes associated with the first year of COVID-19 vaccination rollout in the Basque population. METHODS: A retrospective study was performed using the complete database of the Basque Health Service (n = 2,343,858). We analyzed data on age, sex, socioeconomic status, the Charlson comorbidity index (CCI), hospitalization and intensive care unit (ICU) admission, and COVID-19 infection by Cox regression models and Kaplan-Meier curves. RESULTS: Women had a higher hazard ratio (HR) of infection (1.1) and a much lower rate of hospitalization (0.7). With older age, the risk of infection fell, but the risks of hospitalization and ICU admission increased. The higher the CCI, the higher the risks of infection and hospitalization. The risk of infection was higher in high-income individuals in all periods (HR = 1.2-1.4) while their risk of hospitalization was lower in the post-vaccination period (HR = 0.451). CONCLUSION: Despite the lifting of many control measures during the second half of 2021, restoring human mobility patterns, the situation could not be defined as syndemic, clinical determinants seeming to have more influence than social ones on COVID-19 outcomes, both before and after vaccination program implementation.

Estimation of the epidemiology of dementia and associated neuropsychiatric symptoms by applying machine learning to real-world data.

INTRODUCTION: Incidence rates of dementia-related neuropsychiatric symptoms (NPS) are not known and this hampers the assessment of their population burden. The objective of this study was to obtain an approximate estimate of the population incidence and prevalence of both dementia and NPS. METHODS: Given the dynamic nature of the population with dementia, a retrospective study was conducted within the database of the Basque Health Service (real-world data) at the beginning and end of 2019. Validated random forest models were used to identify separately depressive and psychotic clusters according to their presence in the electronic health records of all patients diagnosed with dementia. RESULTS: Among the 631,949 individuals over 60 years registered, 28,563 were diagnosed with dementia, of whom 15,828 (55.4%) showed psychotic symptoms and 19,461 (68.1%) depressive symptoms. The incidence of dementia in 2019 was 6.8/1000 person-years. Most incident cases of depressive (72.3%) and psychotic (51.9%) NPS occurred in cases of incident dementia. The risk of depressive-type NPS grows with years since dementia diagnosis, living in a nursing home, and female sex, but falls with older age. In the psychotic cluster model, the effects of male sex, and older age are inverted, both increasing the probability of this type of symptoms. CONCLUSIONS: The stigmatization factor conditions the social and attitudinal environment, delaying the diagnosis of dementia, preventing patients from receiving adequate care and exacerbating families' suffering. This study evidences the synergy between big data and real-world data for psychiatric epidemiological research.

Long-term comparative effectiveness of deep brain stimulation in severe obsessive-compulsive disorder.

BACKGROUND: Twenty years after the first use of Deep Brain Stimulation (DBS) in obsessive-compulsive disorder (OCD), our knowledge of the long-term effects of this therapeutic option remains very limited. OBJECTIVE: Our study aims to assess the long-term effectiveness and tolerability of DBS in OCD patients and to look for possible predictors of long-term response to this treatment. METHODS: We studied the course of 25 patients with severe refractory OCD treated with DBS over an average follow-up period of 6.4 years (±3.2) and compared them with a control group of 25 patients with severe OCD who refused DBS and maintained their usual treatment. DBS was implanted at the ventral anterior limb of the internal capsule and nucleus accumbens (vALIC-Nacc) in the first six patients and later at the bed nucleus of stria terminalis (BNST) in the rest of patients. Main outcome was change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score between the two groups assessed using mixed models. Secondary effectiveness outcomes included Hamilton Depression Rating Scale (HDRS) and Global Assessment of Functioning (GAF) scores. RESULTS: Obsessive symptoms fell by 42.5% (Y-BOCS score) in patients treated with DBS and by 4.8% in the control group. Fifty-six per cent of DBS-treated patients could be considered responders at the end of follow-up and 28% partial responders. Two patients among those who rejected DBS were partial responders (8%), but none of the non-DBS group achieved criteria for complete response. HDRS and GAF scores improved significantly in 39.2% and 43.6% among DBS-treated patients, while did not significantly change in those who rejected DBS (improvement limited to 6.2% in HDRS and 4.2% in GAF scores). No statistically significant predictors of response were found. Mixed models presented very large comparative effect sizes for DBS (4.29 for Y-BOCS, 1.15 for HDRS and 2.54 for GAF). Few patients experienced adverse effects and most of these effects were mild and transitory. CONCLUSIONS: The long-term comparative effectiveness and safety of DBS confirm it as a valid option for the treatment of severe refractory OCD.

Modeling the initial phase of COVID-19 epidemic: The role of age and disease severity in the Basque Country, Spain.

Declared a pandemic by the World Health Organization (WHO), COVID-19 has spread rapidly around the globe. With eventually substantial global underestimation of infection, by the end of March 2022, more than 470 million cases were confirmed, counting more than 6.1 million deaths worldwide. COVID-19 symptoms range from mild (or no) symptoms to severe illness, with disease severity and death occurring according to a hierarchy of risks, with age and pre-existing health conditions enhancing risks of disease severity. In order to understand the dynamics of disease severity during the initial phase of the pandemic, we propose a modeling framework stratifying the studied population into two groups, older and younger, assuming different risks for severe disease manifestation. The deterministic and the stochastic models are parametrized using epidemiological data for the Basque Country population referring to confirmed cases, hospitalizations and deaths, from February to the end of March 2020. Using similar parameter values, both models were able to describe well the existing data. A detailed sensitivity analysis was performed to identify the key parameters influencing the transmission dynamics of COVID-19 in the population. We observed that the population younger than 60 years old of age would contribute more to the overall force of infection than the older population, as opposed to the already existing age-structured models, opening new ways to understand the effect of population age on disease severity during the COVID-19 pandemic. With mild/asymptomatic cases significantly influencing the disease spreading and control, our findings support the vaccination strategy prioritising the most vulnerable individuals to reduce hospitalization and deaths, as well as the non-pharmaceutical intervention measures to reduce disease transmission.

Dementia Risk Score for a Population in Southern Europe Calculated Using Competing Risk Models.

BACKGROUND: Dementia prevention can be addressed if the intervention is applied early. OBJECTIVE: The objective of this study was to develop and validate competing risk models to predict the late risk of dementia based on variables assessed in middle age in a southern European population. METHODS: We conducted a prospective observational study of the EPIC-Spain cohort that included 25,015 participants. Dementia cases were identified from electronic health records and validated by neurologists. Data were gathered on sociodemographic characteristics and cardiovascular risk factors. To stratify dementia risk, Fine and Gray competing risk prediction models were constructed for the entire sample and for over-55-year-olds. Risk scores were calculated for low (the 30% of the sample with the lowest risk), moderate (> 30% -60%), and high (> 60% -100%) risk. RESULTS: The 755 cases of dementia identified represented a cumulative incidence of 3.1% throughout the study period. The AUC of the model for over-55-year-olds was much higher (80.8%) than the overall AUC (68.5%) in the first 15 years of follow-up and remained that way in the subsequent follow-up. The weight of the competing risk of death was greater than that of dementia and especially when the entire population was included. CONCLUSION: This study presents the first dementia risk score calculated in a southern European population in mid-life and followed up for 20 years. The score makes it feasible to achieve the early identification of individuals in a southern European population who could be targeted for the prevention of dementia based on the intensive control of risk factors.

Potential Tear Biomarkers for the Diagnosis of Parkinson's Disease-A Pilot Study.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography-mass spectrometry (nLC-MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.

Health care costs of breast, prostate, colorectal and lung cancer care by clinical stage and cost component.

OBJECTIVE: To measure 3-year care costs of breast, prostate, colorectal and lung cancers disaggregated by site and clinical stage. METHOD: A retrospective observational design was employed to investigate care costs of cases recorded in the Registry of the Basque Country between 2010 and 2015. Data gathered included TNM stage and demographic, clinical and resource use variables. Total costs per patient with stage IV disease were calculated by combining generalized linear models with parametric survival analysis. Unit costs were obtained from the analytical accounting system of the Basque Health Service. RESULTS: The sample comprised 23,782 cancer cases (7801 colorectal, 5530 breast, 4802 prostate and 5649 lung cancer). The mean 3-year costs per patient with stage I to III disease were €11,323, €13,727, €8,651 and €12,023 for colorectal, breast, prostate and lung cancer, respectively. The most important cost components were surgery and chemotherapy. Total survival-adjusted costs until death for patients with stage IV disease (€27,568, €26,296, €16,151 and €15,931 for breast, colorectal, lung and prostate cancer, respectively) were higher than the 3-year costs for those with earlier-stage disease. CONCLUSIONS: This study quantitatively shows the pattern of changes in the economic burden of cancer throughout its natural history and the great magnitude of this burden for the health system. The use of indicators based on real-world data from each regional health service would allow cancer care in each region to be tailored to local population needs.