Pharmacodynamic monitoring by residual gene expression of the nuclear factor of activated T cell-regulated genes in lung transplant recipients and its correlation with tacrolimus blood levels.

Introduction: Trough blood levels (C0) of tacrolimus are used to adjust drug dosage, but they do not consistently correlate with clinical outcomes. Measurement of residual gene expression of nuclear factor of activated T cell (NFAT)-regulated genes (NFAT-RGE) has been proposed as a pharmacodynamic biomarker to assess the degree of immunosuppression in certain solid organ transplantations, but little is known regarding lung transplant recipients (LTR). Our primary objective is to correlate tacrolimus blood levels with NFAT-RGE. Methods: NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were determined in 42 patients at three, six and 12 months post-transplantation. Results: Tacrolimus C0 did not exhibit a correlation with NFAT-RGE, whereas C1.5 did. Besides, over 20% of measurements indicated high levels of immunosuppression based on the below 30% NFAT-RGE threshold observed in many studies. Among those measurements within the therapeutic range, 19% had an NFAT-RGE<30%. Conclusion: Consequently, a subset of patients within the tacrolimus therapeutic range may be more susceptible to infection or cancer, potentially benefiting from NFAT-RGE and tacrolimus peak level monitoring to tailor their dosage. Further quantitative risk assessment studies are needed to elucidate the relationship between NFAT-RGE and the risk of infection, cancer, or rejection.

Corrigendum: Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

[This corrects the article DOI: 10.3389/fmed.2023.1039223.].

Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

Introduction: The link between anxiety disorders and joint hypermobility syndrome (now under hypermobility spectrum disorders, which include hypermobile Ehlers-Danlos syndrome) has been widely replicated over the past 30 years and has grown beyond the initial nosological limits. To integrate clinical and research progress in this field, a new neuroconnective endophenotype (NE) and its corresponding instrument, the Neuroconnective Endophenotype Questionnaire (NEQ), have been developed. This new clinical construct, created with the active participation of patients, includes both somatic and psychological dimensions and symptoms and resilience items. Methods: The NE includes five dimensions: (1) sensorial sensitivity, (2) body signs and symptoms, (3) somatic conditions, (4) polar behavioral strategies, and (5) psychological and psychopathological dimensions. The NEQ information is collected through four self-administered questionnaires (sensorial sensitivity, body signs and symptoms, polar behavioral strategies, and psychological characteristics) and a structured diagnostic part that should be completed by a trained observer. This hetero-administered part incorporates (a) psychiatric diagnoses (using structured criteria, e.g., MINI), (b) somatic disorders diagnosis, using structured criteria, and (c) assessment of joint hypermobility criteria. Results: In a sample of 36 anxiety cases with 36 matched controls, the NEQ obtained high scores for test-retest, inter-rater reliability, and internal consistency. As for predictive validity, cases and controls significantly differed in all five dimensions and hypermobility measurements. Discussion: We can conclude that the NEQ has achieved acceptable reliability and validity values and, therefore, is ready to be used and tested in different samples. This original and consistent construct including somatic and mental items may improve clinical specificity, the search for more comprehensive therapies, and their genetic and neuroimaging bases.

Artificial intelligence: An eye cast towards the mental health nursing horizon.

There has been an international surge towards online, digital, and telehealth mental health services, further amplified during COVID-19. Implementation and integration of technological innovations, including artificial intelligence (AI), have increased with the intention to improve clinical, governance, and administrative decision-making. Mental health nurses (MHN) should consider the ramifications of these changes and reflect on their engagement with AI. It is time for mental health nurses to demonstrate leadership in the AI mental health discourse and to meaningfully advocate that safety and inclusion of end users' of mental health service interests are prioritized. To date, very little literature exists about this topic, revealing limited engagement by MHNs overall. The aim of this article is to provide an overview of AI in the mental health context and to stimulate discussion about the rapidity and trustworthiness of AI related to the MHN profession. Despite the pace of progress, and personal life experiences with AI, a lack of MHN leadership about AI exists. MHNs have a professional obligation to advocate for access and equity in health service distribution and provision, and this applies to digital and physical domains. Trustworthiness of AI supports access and equity, and for this reason, it is of concern to MHNs. MHN advocacy and leadership are required to ensure that misogynist, racist, discriminatory biases are not favoured in the development of decisional support systems and training sets that strengthens AI algorithms. The absence of MHNs in designing technological innovation is a risk related to the adequacy of the generation of services that are beneficial for vulnerable people such as tailored, precise, and streamlined mental healthcare provision. AI developers are interested to focus on person-like solutions; however, collaborations with MHNs are required to ensure a person-centred approach for future mental healthcare is not overlooked.

In vitro radiosensitization by eribulin in human cancer cell lines.

Background: The objective was to to determine the radiosensitizing properties of eribulin and the potential mechanisms of radiosensitization in cervical (HeLa) and pharyngeal (FaDu) cancer cell lines. Materials and methods: Cytotoxicity was evaluated by the crystal violet method. The 10% and 50% inhibitory concentration (IC10, IC50) for 24-hour drug exposure were determined. The surviving fraction at 2 Gy (SF2) and the sensitizer enhancement ratio (SER) were calculated from radiation cell survival curves in the presence or absence of eribulin. Combination index (CI) was calculated to determine if there is a true synergistic interaction between eribulin and irradiation. Cell cycle changes were assessed by propidium iodide staining and flow cytometry. Apoptotic cells were detected by annexin V and TUNEL-assay. Results: Mean IC50s and IC10s were 1.58 nM and 0.7 nM and 0.7 nM and 0.27 nM for HeLa and FaDu cells, respectively. Radiosensitization was observed in both lines with a SER up to 2.71 and 2.32 for HeLa and FaDu cells, respectively. A true synergistic effect was showed with a CI of 0.82 and 0.76 for HeLa and FaDu cells, respectively. Eribulin induced significant G2/M cell arrest and marked apoptosis. Irradiation combined with 3 nM eribulin increased the apoptotic response to radiation in Hela cells. Conclusion: Eribulin shows a true in vitro radiosensitizing effect in HeLa and FaDu cells by inducing significant G2/M phase arrest. In HeLa, the enhancement radiation-induced apoptosis could be an additional mechanism of radiosensitization. Further studies are needed to evaluate the clinical benefits of concurrent eribulin and radiotherapy as a novel therapeutic strategy for cancer.

Usefulness of the hemogram as a measure of clinical and serological activity in systemic lupus erythematosus.

Background and objectives: Systemic Lupus Erythematosus (SLE) follow-up is based on clinical, and analytical parameters. We aimed to determine the differences between the Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and Red blood cell distribution width (RDW) between SLE patients and healthy controls and to assess their association with anemia status, classical inflammatory biomarkers and cytokines, disease activity, SLE related factors and treatment received for SLE. Methods: Seventy-seven patients with SLE according to 2012 SLICC criteria and 80 healthy controls were included. Patients with SLE were classified in SLE with anemia (SLE-a) and SLE without anemia (SLE-na). Statistical analysis between SLE patients and controls and the association of serological and clinical activity markers with proposed hematological indices among SLE patients were performed. Results: RDW, NLR and PLR, were significantly higher in SLE patients than in healthy control group (p < 0.001), in SLE-a patients as compared to SLE-na (p < 0.0001) and were significantly associated with hypocomplementemia (p < 0.05). PLR was higher in active patients measured by SLEDAI-2K score and with longer disease duration (p < 0.05). RDW was associated with serological activity of the patients (p < 0.05) and was correlated with SLEDAI-2K and SLICC/ACR scores, hsCRP, D-dimer, fibrinogen, IL-6 and TNF as well as with corticosteroids intake (p = 0.05). A logistic regression analysis confirmed that after adjustment by age and hemoglobin values, RDW presented linear correlation with IL-6 levels (Beta-coefficient = 0.369, p = 0.003). Conclusion: NLR, PLR and RDW values suggest SLE serological and clinical activity. Given their availability, these markers not only could be useful tools to identify and monitor active SLE patients but whose application should be considered in inflammatory pathologies orchestrated by IL-6 and TNF.

Red blood cell distribution width as a marker of hyperinflammation and mortality in COVID-19.

BACKGROUND: Red blood cell distribution width (RDW) could reflect interleukin-6 (IL-6) systemic activity since anisocytosis represents the inhibition of erythropoiesis, leaded by the hyperinflammatory background. Our objective was to analyze RDW performance to predict outcome in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). METHODS: Retrospective observational study including 173 patients with COVID-19-associated ARDS. Data was analyzed at hospital admission, inclusion in the TOCICOV Study (day 0), days 1, 3, 7 and 15 post-inclusion. RESULTS: Overall, 57% patients received tocilizumab. Overall mortality was 20.8%. RDW was higher in non-survivors compared to survivors at admission (13.53% vs. 14.35, P=0.0016), day 0 (13.60% vs. 14.42, P=0.026), day 3 (13.43% vs. 14.36, P<0.001) and day 7 (13.41% vs. 14.31, P=0.046), presenting better discrimination ability for mortality than other prognostic markers [area under the curve-receiver operating characteristic (AUC-ROC) =0.668 for admission RDW, 0.680 for day 0 RDW, 0.695 for day 3 RDW and 0.666 for day 7 RDW]. RDW values did not vary significantly according to tocilizumab treatment. When adjusted by hemoglobin and tocilizumab treatment, only RDW at admission, day 0, day 3 and C reactive protein (CRP) at day 0 and day 1 were associated with mortality (P<0.05). Only in non-tocilizumab treated patients, IL-6 levels at day 0 were correlated with day 3 RDW (r=0.733, P=0.004) and with day 3 CRP (r=0.727, P=0.022). Both parameters showed significant statistical correlation (r=0.255 for day 1 RDW and CRP in the overall cohort and r=0.358 for day 3 RDW and CRP in patients not treated with tocilizumab, P<0.015). CONCLUSIONS: RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab treatment.

Serum cytokines to predict systemic lupus erythematosus clinical and serological activity.

We aimed to explore the role of interleukin (IL)-6, interferon-gamma (IFNγ), IL-10, and tumor necrosis factor (TNF) as predictors of systemic lupus erythematosus (SLE) clinical and serological activity, and their correlation with the treatment received. We performed a retrospective analysis of 77 patients with SLE according to the 2012 Systemic Lupus International Collaborative Clinics (SLICC) criteria. The outcomes were serological activity (SA), active disease (AD), complete remission (CR), the low-disease activity state (LDAS), and immunosuppressive treatment. SA was present in 17.1%, AD in 17.3%, CR in 13%, and LDAS in 64.9% of patients. IL-6 values were higher in patients in SA, in AD, in those receiving steroids alone, and in patients without CR or LDAS (p < 0.05). IFNγ was associated with anti-double stranded DNA (dsDNA) antibodies positivity and immunosuppression, whereas IL-10 values were higher in patients with CR (p < 0.05). The IL6-IFN product was able to predict anti-double stranded DNA (anti-dsDNA) antibodies positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.705, 95% confidence interval [CI] 0.563-0.847), SA (AUC-ROC = 0.720, 95% CI 0.542-0.899), AD (AUC-ROC = 0.701, 95% CI 0.520-0.882), steroid treatment (AUC-ROC = 0.751, 95% CI 0.622-0.879), and the absence of LDAS (AUC-ROC = 0.700, 95% CI 0.558-0.834). The IL6-IFN/IL10 ratio predicted AD (AUC-ROC = 0.742, 955 CI 0.540-0.944), steroid treatment (AUC-ROC = 0.721, 95% CI 0.572-0.870), and the absence of LDAS (AUC-ROC = 0.694, 95% CI 0.536-0.853). In conclusion, IL-6, IL-10, and IFNγ might help to assess SLE serological and clinical activity. Their combination in the IL-6-IFN product and the IL-6xIFN to IL-10 ratio results in novel tools to determine and predict SA, AD, and LDAS. Prompt detection of SLE activity might allow a rapid intervention to avoid established or chronic damage.

Trends in Hospital Admissions and Death Causes in Patients with Systemic Lupus Erythematosus: Spanish National Registry.

BACKGROUND: the admission and death causes of SLE patients might have changed over the last years. METHODS: Analysis of the Spanish National Hospital Discharge database. All individuals admitted with SLE, according to ICD-9, were selected. The following five admission categories were considered: SLE, cardiovascular disease (CVD), neoplasm, infection, and venous-thromboembolic disease (VTED), along four periods of time (1997-2000, 2001-2005, 2006-2010, and 2011-2015). RESULTS: The admissions (99,859) from 43.432 patients with SLE were included. The absolute number of admissions increased from 15,807 in 1997-2000 to 31,977 in 2011-2015. SLE decreased as a cause of admission (from 47.1% to 20.8%, p < 0.001), while other categories increased over the time, as follows: 5% to 8.6% for CVD, 8.2% to 13% for infection, and 1.4% to 5.5% for neoplasm (p < 0.001 for all). The admission mortality rate rose from 2.22% to 3.06% (p < 0.001) and the causes of death evolved in parallel with the admission categories. A significant trend to older age was observed over time in the overall population and deceased patients (p < 0.001). CONCLUSIONS: Better control of SLE over the past two decades has led to a decrease in early admissions, and disease chronification. As a counterpart, CVD, infections, and neoplasm have become the main causes of admissions and mortality.

Urolithiasis Develops Endothelial Dysfunction as a Clinical Feature.

An increased risk of cardiovascular morbidity has been reported in lithiasic patients. In this context, endothelial dysfunction (ED), an earlier status of atherogenesis, has been identified in hyperoxaluria rat models of urolithiasis. OBJECTIVE: The purpose of this study was to determine the endothelial vascular function in patients with urolithiasis in relation to systemic inflammatory, oxidative stress, and vascular function serum markers. METHODS: A cross-sectional study was performed between 27 urolithiasic patients, matched for age and sex, with 27 healthy patients. Endothelial function was assessed by measuring flow-mediated dilation (Celermajer method). Fasting blood was collected to determine metabolic parameters (glucose and lipid profile), along with serum CRP, IL-6, MDA, ADMA, and VCAM-1. RESULTS: Both the control and urolithiasis groups were homogenous in anthropometric, exploration, and general laboratory measures. Flow-mediated dilation (%FMD) was 11.85% (SE: 2.78) lower in the lithiasis group (p < 0.001). No significant differences were achieved between groups when CRP, IL-6, MDA, ADMA, and VCAM-1 were compared, although slightly higher values of CRP, ADMA, and VCAM-1 were detected in the lithiasic group. A correlation was not reached in any of the serum markers when they were related to flow-mediated values, although a slight negative correlation trend was observed in MDA, VCAM-1, and IL-6 values. CONCLUSIONS: Endothelial dysfunction constitutes an important disorder related to urolithiasis patients. It must be considered as an early feature responsible for future cardiovascular events. Our study did not find a significant association between inflammatory, oxidative stress, endothelial serum markers, and flow-mediated dilation.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Inflammatory-Related Clinical and Metabolic Outcomes in COVID-19 Patients.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection elicits inflammatory manifestations that relate with a "cytokine storm." OBJECTIVE: The aim of this research was to assess the role of circulating interleukin 6 (IL-6) levels and other inflammatory markers in patients with coronavirus disease 2019 (COVID-19) on metabolic functions and accompanying clinical complications. Patients and Methods. A total of 165 patients diagnosed with COVID-19 pneumonia were examined for medical features and inflammatory markers such as blood IL-6, CRP, ferritin, LDH, neutrophil/lymphocyte index (NLI), D-Dimer, and Red Cell Distribution Width (RDW). Regression analyses concerning electronically collected medical data were adjusted by appropriate factors and confounding variables. Results. Plasma IL-6 determinations evidenced a consistent association with hospital stay days, Intensive Care Unit (ICU) admission, and mortality rates. Similar trends were found for other proinflammatory variables, where ferritin and NLI showed a remarkable value as surrogates. Hyperglycaemia and the Charlson Comorbidity Index Score were positively associated with the inflammatory response induced by the SARS-COV-2 infection. An unhealthy lifestyle such as smoking and alcoholic drinks consumption as well as excessive body adiposity influenced inflammatory-related outcomes in the screened patients. CONCLUSION: IL-6 together with other inflammatory biomarkers accompanied poor clinical and metabolic outcomes in COVID-19-infected patients. IL-6 may result in a suitable proxy to individually categorise patients in order to manage this infectious pandemic.

Calcium and vitamin D supplement intake may increase arterial stiffness in systemic lupus erythematosus patients.

OBJECTIVES: Low serum levels of 25-hydroxyvitamin D (25(OH)D) have been associated with a higher frequency of risk factors and cardiovascular disease. The aim of this study is to evaluate the association of 25(OH)D, cardiovascular risk factors, and subclinical atherosclerosis in systemic lupus erythematosus (SLE) patients. METHOD: Forty-seven female SLE patients were studied. Data collected included demographics, SLE activity, disease damage, cardiovascular risk factors, and markers of subclinical atherosclerosis. Patient treatments and vitamin D and calcium supplementation (VitD-Ca) were recorded. Vitamin D deficiency was defined as serum 25(OH)D < 50 nmol/l measured by ultra-high-performance liquid chromatography. Atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry and intima-media thickness (IMT) by B-mode ultrasound scanning. RESULTS: 61.7% of patients were vitamin D deficient with a mean level of 31.91 ± 10.21 nmol/l. Serum vitamin D concentration was significantly higher in the 23 patients taking VitD-Ca supplements than that in patients not supplemented (p = 0.004). No significant association was found between 25(OH)D serum levels and cardiovascular risk factors, disease activity, or different treatments for SLE. A significant positive correlation was found between 25(OH)D levels, PWV (p = 0.02), and IMT (p = 0.01); moreover, patients taking VitD-Ca supplements presented an increased arterial stiffness. CONCLUSION: Patients with arterial stiffness showed higher levels of serum vitamin D and most of them were on VitD-Ca supplements. Although prospective studies with a larger number of patients and follow-up are needed, our findings suggest that VitD-Ca supplementation may have effects on SLE patients' arterial stiffness.

Psychometric Properties of the Spanish Version of the Panic Disorder Severity Scale.

The Panic Disorder Severity Scale (PDSS) is a well-established measure of panic symptoms but few data exist on this instrument in non north-American samples. Our main goal was to assess the psychometric properties (internal consistency, test re-test reliability, inter-rater reliability, convergent and divergent validity) and the factor structure of the Spanish version. Ninety-four patients with a main diagnosis of panic disorder were assessed with the Spanish version of PDSS, the Anxiety Sensitivity Index-3 (ASI-3), the Panic and Agoraphobia Scale (PAS), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory-II (BDI-II) the PDSS self-rating form and the Clinical Global Impression-Severity scale (CGI). The Spanish PDSS showed acceptable internal consistency (α = .74), excellent test-retest (total score and items 1-6: α > .58, p .90) and medium to large convergent validity (r = .68, 95% CI [.54, .79], p < .01; r = .80, 95% CI [.70, .87], p < .01; r = .48, 95% CI [.28, .67], p < .01; BAI, PAS and ASI-3 total scores respectively). Data on divergent validity (BDI-II total score: r = .52, 95% CI [.34, .67], p < .01) suggest some need for refinement of the PDSS. The confirmatory factor analysis suggested a two-factor modified model for the scale (nested χ2 = 14.01, df = 12, p < .001). The Spanish PDSS has similar psychometric properties as the previous versions and is a useful instrument to assess panic symptoms in clinical settings in Spanish-speaking populations.

Both anxiety and joint laxity determine the olfactory features in panic disorder.

Previous research showed a high sensitivity in sensorial modalities in panic disorder (PD). This disorder has been consistently associated to the joint hypermobility syndrome (JHS). In non-clinical samples, this collagen alteration has been also related to an enhanced sensitivity in some sensorial modalities. The main aim of this study is to explore the olfactory functioning in PD in relation to JHS. Sixty patients with PD and sixty healthy controls performed the Sniffin' Sticks Test (SST) (threshold subtest), and completed the Affective Impact of Odors scale (AIO), the Relational Scale of Olfaction (EROL), and the Odor Awareness Scale (OAS). Clinical symptom rating scales and JHS assessment were also obtained. PD patients showed enhanced odor acuity, greater reactivity to smells and also increased odor awareness compared to the healthy controls. Within the patients group, those suffering from JHS displayed higher functioning in all olfactory domains compared to the non-JHS ones. The JHS and anxiety measures emerged as predictor variables of the olfactory function. The present findings highlight the importance of the olfactory function in PD and underline that both, JHS and anxiety, determine the olfactory characteristics in this disorder.

Sudden gains in exposure-focused cognitive-behavioral group therapy for panic disorder.

In the context of psychological treatment, a sudden gain is a large and enduring improvement in symptom severity that occurs between two single therapy sessions. The influence of sudden gains on long-term outcomes and functional impairment in anxiety disorders is not well understood, and little is known with regard to panic disorder in particular. In addition, previous research on patients with anxiety disorders has produced inconsistent results regarding the relationship between sudden gains and cognitive change. We examined the incidence of sudden gains in a large sample (n = 116) of panic disorder patients undergoing exposure-focused cognitive-behavioral group therapy, and compared panic severity, functional impairment, and cognitive change in patients with and without sudden gains at posttreatment and 6-month follow-up. Participants who experienced sudden gains displayed lower levels of panic severity and functional impairment at posttreatment and 6-month follow-up than those who did not experience sudden gains. However, we observed no difference in cognitive changes between groups, either at posttreatment or at follow-up. Our results demonstrate that the beneficial effects of sudden gains on therapeutic outcomes not only extend to long-term and functional outcome measures but are also evident in less cognitive (i.e., exposure-focused) forms of psychological treatment. KEY PRACTITIONER MESSAGE: Sudden gains are common in panic disorder patients undergoing exposure-based cognitive-behavioral group therapy. Sudden gains during exposure-focused therapy are linked to greater improvement in panic disorder severity and functional impairment. The positive impact of sudden gains on panic disorder severity and functional impairment is maintained in the long term.

[Detecting and measuring functional and organic disease in general population: Development and validation of TOPYPS clinical scale]. / Detección y medición de la enfermedad funcional y orgánica en población general: desarrollo y validación de la escala clínica TOPYPS.

OBJECTIVE: To develop and validate the TOPYPS scale, an instrument designed to: (i)detect with a high degree of suspicion the most frequent functional pathologies according to standard diagnostic criteria, and (ii)to assess the physical health in the general population quickly, comprehensive and reliable. DESIGN: Validation of a scale. LOCATION: Primary Care Centre, Barcelona. PARTICIPANTS: The scale was administered to 67 randomly selected adults. MEASUREMENTS: TOPYPS scale was administered to 67 adults randomly selected from a primary care setting in Barcelona, Spain. TOPYPS has six sections based on body systems, each one scored according to the degree of interference in daily activity, type of treatment received, and prognostic of the reported illnesses in each section. Test-retest reliability completions were on two separate occasions one week apart. Validity was then tested by comparing the results with the clinical examination conducted by two different specialists in general practice (gold standard). RESULTS: Repeatability (test-retest) and inter-rater agreement for each of the six sections and for the total score were satisfactory. Validity was acceptable both for content and construct, according to their correlation with the gold standard. CONCLUSIONS: TOPYPS displayed good psychometrical properties. It is a suitable tool to detect and measure functional and organic diseases in general population.