The transition to Schizophrenia spectrum disorder from a first psychotic episode that did or did not appear to be induced by substance use.

The first years following a first-episode psychosis (FEP) are crucial. This retrospective cohort study investigates the evolution of first-episode psychosis (FEP), including substance-induced psychosis (SIP), and explores factors influencing the diagnostic conversion to Schizophrenia or Schizophrenia Spectrum Disorders (SSD). Diagnoses of patients discharged from Basurto University Hospital's inpatient psychiatry unit between January 2002 and December 2016 were reviewed. Sociodemographic, clinical, and substance use data, including cannabinoids, opioids, amphetamines, cocaine, and alcohol, were collected. The analysis utilized descriptive statistics, Kaplan-Meier survival curves, and Cox regression. Among 341 patients, 64.8% were male, with a mean age of 33.8 years. Psychiatric family history was present in 33.4% of cases, and cannabis was the most commonly used substance (78.9%). Of the patients, 52.8% received subsequent diagnoses of Schizophrenia or SSD, with 86.9% of these cases occurring within the first five years. No significant differences were observed between patients diagnosed with SIP and other diagnoses in terms of sociodemographic, clinical characteristics, or progression to Schizophrenia or SSD. However, use of cannabis (compared to use of another substance or polysubstance use) was associated with a higher risk to conversion (HR 1.96; p = 0.001). These findings underscore the importance of addressing substance use and treatment adherence in FEP.

Diagnostic stability in substance-induced psychosis.

INTRODUCTION: Substance-induced psychosis (SIP) is the name given to a psychosis that starts in the context of substance abuse but persists for days and weeks with no substance use. There is as yet little knowledge about the longitudinal course of this psychosis, which suggests that significant numbers go on to be diagnosed with a severe mental disorder (SMD). The objective of this study was to analyse the progression of SIP to SMD in our environment and the possible factors that may be involved in that conversion. MATERIAL AND METHODS: We used a retrospective cohort follow-up design. We reviewed all diagnoses of patients discharged from the psychiatric hospitalisation unit of the University Hospital of Basurto from January 2002 to December 2015 inclusively. In addition to sociodemographic and clinical data, information was collected on the consumption of cannabinoids, opioids, amphetamines, cocaine and alcohol. The data were analysed using descriptive analysis, Kaplan-Meier survival curves and Cox regression. RESULTS: Of the 116 patients, 78.4% were male, had an average age of 33.0 (SD = 8.9) years and 44.0% were single; 31.0% had a psychiatric family history; the most commonly used substance was cannabis (60.3%), followed by cocaine (40.5%). The cumulative risk of diagnostic conversion to an SMD in 16 years was 41.6% (95%CI: 32.2-52.2) over a mean 36.43 months. CONCLUSIONS: In interventions in episodes of SIP we must bear in mind that a significant proportion will progress to an SMD in the first three years.

Cost-Effectiveness of Therapeutic Drug Monitoring-Guided Adalimumab Therapy in Rheumatic Diseases: A Prospective, Pragmatic Trial.

INTRODUCTION: To assess the clinical and cost-effectiveness of therapeutic drug monitoring (TDM) based on serum adalimumab levels compared to standard of care in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. METHODS: This was a non-inferiority, multicentric, non-randomized, pragmatic trial including adult patients diagnosed with moderate-to-severe, clinically stable rheumatic diseases treated with adalimumab. Consecutive patients were assigned 1:2 to the control (CG) or the intervention group (IG), based on the site of inclusion, and followed up for 18 months. Adalimumab serum levels were measured at each study visit and released to the IG only to modify dosing strategy. Data on disease activity, healthcare resource utilization and health-related quality of life (HRQoL) measured through the EQ-5D-5L were collected. Number of persistent and overall flares, time to first flare, days experiencing high disease activity, total direct costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Of the 169 recruited patients, 150 were included in the analysis (52 and 98 patients in the CG and IG, respectively). The primary endpoint was not met as persistent flares were not significantly lower in the IG, although mean (SD) number of flares was numerically lower in the IG (0.67 [0.70] versus 0.90 [0.82], P = 0.073), respectively. Based on EQ-5D-5L utilities, HRQoL was significantly higher in the IG at 3 (P = 0.001) and 6 months (P = 0.035), which overall translated into 0.075 QALYs gained per patient for the IG at month 18. Overall, direct costs were significantly lower for the IG patients (€15,311.59 [4,870.04] versus €17,378.46 [6,556.51], P = 0.030), resulting in the intervention being dominant, leading to increased QALY at a lower overall cost CONCLUSION: Adalimumab dose tapering based on TDM for rheumatic patients led to an increased quality of life and QALY gain and entailed lower costs, being a more cost-effective alternative than clinically guided management.

Treatment With Tofacitinib in Refractory Psoriatic Arthritis: A National Multicenter Study of the First 87 Patients in Clinical Practice.

OBJECTIVE: Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti-tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice. METHODS: This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed. RESULTS: There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1-5.4) to 3.7 (IQR 2.8-4.7, P < 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4-34.1) to 15.5 (IQR 10.1-25.7, P < 0.01), and C-reactive protein from median 1.9 (IQR 0.3-5.0) to 0.5 (IQR 0.1-2.2) mg/dL (P < 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2-86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial. CONCLUSION: Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.

Cost-of-illness studies in rare diseases: a scoping review.

OBJECTIVE: The aim of this scoping review was to overview the cost-of-illness studies conducted in rare diseases. METHODS: We searched papers published in English in PubMed from January 2007 to December 2018. We selected cost-of-illness studies on rare diseases defined as those with prevalence lower than 5 per 10,000 cases. Studies were selected by one researcher and verified by a second researcher. Methodological characteristics were extracted to develop a narrative synthesis. RESULTS: We included 63 cost-of-illness studies on 42 rare diseases conducted in 25 countries, and 9 systematic reviews. Most studies (94%) adopted a prevalence-based estimation, where the predominant design was cross-sectional with a bottom-up approach. Only four studies adopted an incidence-based estimation. Most studies used questionnaires to patients or caregivers to collect resource utilisation data (67%) although an important number of studies used databases or registries as a source of data (48%). Costs of lost productivity, non-medical costs and informal care costs were included in 68%, 60% and 43% of studies, respectively. CONCLUSION: This review found a paucity of cost-of-illness studies in rare diseases. However, the analysis shows that the cost-of-illness studies of rare diseases are feasible, although the main issue is the lack of primary and/or aggregated data that often prevents a reliable estimation of the economic burden.

Diagnostic stability in substance-induced psychosis. / Estabilidad diagnóstica en la psicosis inducida por sustancias.

INTRODUCTION: Substance-induced psychosis (SIP) is the name given to a psychosis that starts in the context of substance abuse but persists for days and weeks with no substance use. There is as yet little knowledge about the longitudinal course of this psychosis, which suggests that significant numbers go on to be diagnosed with a severe mental disorder (SMD). The objective of this study was to analyse the progression of SIP to SMD in our environment and the possible factors that may be involved in that conversion. MATERIAL AND METHODS: We used a retrospective cohort follow-up design. We reviewed all diagnoses of patients discharged from the psychiatric hospitalisation unit of the University Hospital of Basurto from January 2002 to December 2015 inclusively. In addition to sociodemographic and clinical data, information was collected on the consumption of cannabinoids, opioids, amphetamines, cocaine and alcohol. The data were analysed using descriptive analysis, Kaplan-Meier survival curves and Cox regression. RESULTS: Of the 116 patients, 78.4% were male, had an average age of 33.0 (SD: 8.9) years and 44.0% were single; 31.0% had a psychiatric family history; the most commonly used substance was cannabis (60.3%), followed by cocaine (40.5%). The cumulative risk of diagnostic conversion to an SMD in 16years was 41.6% (95%CI: 32.2-52.2) over a mean 36.43months. CONCLUSIONS: In interventions in episodes of SIP we must bear in mind that a significant proportion will progress to an SMD in the first three years.

Feasibility, Validity and Differences in Adolescent and Adult EQ-5D-Y Health State Valuation in Australia and Spain: An Application of Best-Worst Scaling.

BACKGROUND: The measurement and valuation of health-related quality of life for and by young people are increasingly important, yet research on the impact of study perspective and validity of preferences obtained from young populations remains limited. OBJECTIVE: The objective of this study was to evaluate the feasibility and validity of collecting EQ-5D Youth version (EQ-5D-Y) preferences from adolescents, adults, and adults from a child perspective. METHODS: A profile case best-worst scaling (BWS) online survey was administered to representative Australian and Spanish adult (age ≥ 18 years) and child (age 11-17 years) samples. Adults were told to either answer from their own perspective or for a hypothetical 10-year-old child. Marginal best- and worst-choice frequencies, analysis of dominant choices, self-reported difficulty completing the tasks, and time to complete tasks were used to determine the validity of responses. RESULTS: In Australia, 2134 adults and 1010 adolescents completed the survey. In Spain, 2007 adults and 1000 adolescents completed it. Analysis of marginal choice frequencies and dominant choices indicated that the pattern of responses between adolescents and adults was similar. For Australian respondents, having no mobility problems was rated as best by adolescents, while adults rated having no pain and discomfort as 'best'. In Spain, both adults and adolescents rated no pain or discomfort as 'best'. Australian adolescents rated very worried, sad or unhappy as 'worst', while Spanish adolescents, Spanish adults and Australian adults rated a lot of pain and discomfort as 'worst'. CONCLUSIONS: Results suggest preferences from adolescents using direct BWS are valid. Our descriptive analysis also suggest that there are age-related and country-specific differences in elicitation values for the EQ-5D-Y.

The utility of clinical ultrasonography in identifying distal forearm fractures in the pediatric emergency department.

OBJECTIVE: The aim of this study is to evaluate the utility of Point-Of-Care Ultrasound (POCUS) for diagnosing distal forearm fractures in pediatric emergency departments (ED). PATIENTS AND METHODS: A prospective observational study was carried out in children aged younger than 15 years attended in an ED with an indication of radiography because of a suspected distal forearm fracture. The POCUS was performed considering cortical irregularity or disruption compatible with fracture. Then, the radiography was requested and the patient was evaluated by an ED traumatologist. Both tests were blinded to each other. The radiograph was considered to be the reference diagnostic test. Diagnostic validation tests were performed. RESULTS: A total of 115 patients [mean age: 9.1 (SD: 3.1) years; 50.4% males] were included, with 57 of these presenting fractures: 42 (73.7%) single bone fractures and 15 (26.3%) combined fractures of the radius and ulna. As such, 72 fractures were detected (prevalence 31.3%). The sensitivity and specificity of POCUS for detecting fractures were 94.4% [95% confidence interval (CI): 86.4-98.5] and 96.8% (95% CI: 92.8-99.0), respectively. The positive and negative predictive values were 93.2% (95% CI: 84.7-97.7) and 97.5% (95% CI: 93.6-99.3), respectively. CONCLUSION: POCUS enables the clinical diagnosis of distal forearm fractures in ED. In addition, this is a highly accurate technique that can be applied easily by the ED pediatrician. As such, its inclusion as part of the physical examination could improve the accuracy of the clinical diagnosis and the global management of the patient.

Validity of the EQ-5D-5L and reference norms for the Spanish population.

BACKGROUND AND OBJECTIVE: The EuroQol 5 dimensions 5 levels (EQ-5D-5L) is the new version of EQ-5D, developed to improve its discriminatory capacity. This study aims to evaluate the construct validity of the Spanish version and provide index and dimension population-based reference norms for the new EQ-5D-5L. METHODS: Data were obtained from the 2011/2012 Spanish National Health Survey, with a representative sample (n = 20,587) of non-institutionalized Spanish adults (≥ 18 years). The EQ-5D-5L index was calculated by using the Spanish value set. Construct validity was evaluated by comparing known groups with estimators obtained through regression models, adjusted by age and gender. Sampling weights were applied to restore the representativeness of the sample and to calculate the norms stratified by gender and age groups. We calculated the percentages and standard errors of dimensions, and the deciles, percentiles 5 and 95, means, and 95% confidence intervals of the health index. RESULTS: All the hypotheses established a priori for known groups were confirmed (P < 0.001). The EQ-5D-5L index indicated worse health in groups with lower education level (from 0.94 to 0.87), higher number of chronic conditions (0.96-0.79), probable psychiatric disorder (0.94 vs 0.80), strong limitations (0.96-0.46), higher number of days of restriction (0.93-0.64) or confinement to bed (0.92-0.49), and hospitalized in the previous 12 months (0.92 vs 0.81). CONCLUSIONS: The EQ-5D-5L is a valid instrument to measure perceived health in the Spanish-speaking population. The representative population-based norms provided here will help improve the interpretation of results obtained with the new EQ-5D-5L.

Prospective evaluation of clinical lung ultrasonography in the diagnosis of community-acquired pneumonia in a pediatric emergency department.

OBJECTIVES: To evaluate the applicability and utility of point-of-care lung ultrasonography (POCLUS) for the diagnosis of community-acquired pneumonia (CAP) in a pediatric emergency department. METHODS: A prospective observational study on children with suspected CAP was carried out in a pediatric emergency department from August to December 2014. The evaluation of the chest radiography (CR) by two independent radiologists was considered as a reference standard. POCLUS was performed by pediatricians who were blinded to CR results. Following the WHO criteria, typical CAP was defined as an alveolar consolidation or infiltrate in CR and a visualization of lung consolidation with sonographic air bronchograms in POCLUS. The diagnostic accuracy of POCLUS (sensitivity, specificity, positive, and negative predictive values) was established using CR as a gold standard. RESULTS: We enrolled 200 children with a median age of 29.5 months (interquartile range, 18.5-52.5); 58.1% were males and 42.0% had focal decreased breath sounds and/or crackles. The prevalence of typical CAP according to the radiologist's evaluation was 42.5% (end-point consolidation and/or pleural effusion 56.5%, alveolar infiltrate 43.5%). The sensitivity and specificity of POCLUS were 87.1% [95% confidence interval (CI) 78.0-93.4] and 94.8% (95% CI 89.0-98.1), respectively. The positive and negative predictive values were 92.5% (95% CI 84.4-97.2) and 90.8% (95% CI 84.2-95.3), respectively. CONCLUSION: POCLUS performed by an emergency pediatrician with a limited experience in ultrasonography enables the diagnosis of pneumonia with high accuracy. POCLUS could become a feasible and promising alternative to CR in the diagnosis of suspected CAP, leading to a relevant decrease in children's exposure to ionizing radiations. Further studies specifically carried out in the pediatric outpatient setting are needed.

Cost-of-Illness in Rare Diseases.

Cost-of-illness (COI) studies quantify the economic burden of a disease, including direct healthcare and non-healthcare costs and productivity losses. Different approaches can be adopted to evaluate the resources associated to a disease and to calculate the total costs. Prevalence-based studies estimate the total costs of a disease during a given period, while incidence-based studies measure lifetime costs from onset until death. Data can be collected from individuals, using a bottom-up approach, or from population statistics, using a top-down approach. Different perspectives are possible, but the broadest and also mostly used is the societal one. Appropriate discounting should be applied for future costs and a sensitivity analyses of main parameters should be performed. The main limitation of COI studies is that they don't account the outcomes or benefits of possible treatments.There is a lack of COI studies in the field of rare diseases. A multinational COI study (BURQOL-RD) evaluated recently the burden of 10 rare diseases in Europe, using a prevalence-based method with a bottom-up approach to quantify resources from a societal perspective, which is the mostly used methodology for COI studies in rare diseases; however, several other studies illustrate different approaches to conduct COI analysis in this field, such as incidence-based methods or narrower perspectives.COI studies are useful to inform policy-makers about the magnitude of a disease. To support correctly the decision-making process, it is necessary to identify the cost-drivers through COI studies with robust design and standardized methodology.

Novel evidence that attributing affectively salient signal to random noise is associated with psychosis.

We wished to replicate evidence that an experimental paradigm of speech illusions is associated with psychotic experiences. Fifty-four patients with a first episode of psychosis (FEP) and 150 healthy subjects were examined in an experimental paradigm assessing the presence of speech illusion in neutral white noise. Socio-demographic, cognitive function and family history data were collected. The Positive and Negative Syndrome Scale (PANSS) was administered in the patient group and the Structured Interview for Schizotypy-Revised (SIS-R), and the Community Assessment of Psychic Experiences (CAPE) in the control group. Patients had a much higher rate of speech illusions (33.3% versus 8.7%, ORadjusted: 5.1, 95% CI: 2.3-11.5), which was only partly explained by differences in IQ (ORadjusted: 3.4, 95% CI: 1.4-8.3). Differences were particularly marked for signals in random noise that were perceived as affectively salient (ORadjusted: 9.7, 95% CI: 1.8-53.9). Speech illusion tended to be associated with positive symptoms in patients (ORadjusted: 3.3, 95% CI: 0.9-11.6), particularly affectively salient illusions (ORadjusted: 8.3, 95% CI: 0.7-100.3). In controls, speech illusions were not associated with positive schizotypy (ORadjusted: 1.1, 95% CI: 0.3-3.4) or self-reported psychotic experiences (ORadjusted: 1.4, 95% CI: 0.4-4.6). Experimental paradigms indexing the tendency to detect affectively salient signals in noise may be used to identify liability to psychosis.

[HIV/AIDS screening program in community pharmacies in the Basque Country (Spain)]. / Programa de cribado de VIH/sida en las oficinas de farmacia en la Comunidad Autónoma del País Vasco.

OBJECTIVES: To describe the outcomes of the pilot program of a rapid HIV antibody screening test offered at Basque pharmacies, the socio-demographic characteristics of users and their acceptance of the test. METHODS: Users of a rapid HIV antibody screening test (20 pharmacies) were surveyed. A random sample of 3514 tests (N = 806) performed in 1 year was taken. Statistical analyses included exact tests. RESULTS: There were 806 valid questionnaires. Seven tests were positive (0.85%; 95% confidence interval: 0.34-1.75); five of the users with positive tests were men. The mean age was 36.2 years (standard deviation = 11.0; range: 16-82 years; 70.7% men). Users' risk behavior was predominantly heterosexual and half of the users (58.6%) had no previous HIV tests. The main reasons for choosing this test were its speed, and the convenience and accessibility of community pharmacies. CONCLUSIONS: This new rapid HIV antibody screening test in community pharmacies could supplement other HIV screening programs currently in operation.