The IMBG Test for Evaluating the Pharmacodynamic Response to Immunosuppressive Therapy in Kidney Transplant Patients: Current Evidence and Future Applications.

Immunosuppressive drugs are widely used to prevent rejection after kidney transplantation. However, the pharmacological response to a given immunosuppressant can vary markedly between individuals, with some showing poor treatment responses and/or experiencing serious side effects. There is an unmet need for diagnostic tools that allow clinicians to individually tailor immunosuppressive therapy to a patient's immunological profile. The Immunobiogram (IMBG) is a novel blood-based in vitro diagnostic test that provides a pharmacodynamic readout of the immune response of individual patients to a range of immunosuppressants commonly used in kidney transplant recipients. Here, we discuss the current approaches used to measure the pharmacodynamic responses of individual patients to specific immunosuppressive drugs in vitro, which can then be correlated with patient's clinical outcomes. We also describe the procedure of the IMBG assay, and summarize the results obtained using the IMBG in different kidney transplant populations. Finally, we outline future directions and other novel applications of the IMBG, both in kidney transplant patients and other autoimmune diseases.

The Immunobiogram, a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients.

BACKGROUND: Diagnostic tools to measure the response to individual immunosuppressive drugs for transplant patients are currently lacking. We previously developed the blood-based Immunobiogram bioassay for in-vitro characterization of the pharmacodynamic response of patients' own immune cells to a range of immunosuppressants. We used Immunobiogram to examine the association between patients' sensitivity to their prescribed immunosuppressants and clinical outcome. METHODS: We conducted an international, multicenter, observational study in a kidney transplant population undergoing maintenance immunosuppressive therapy. Patients were selected by clinical course poor [PCC] N = 53 (with renal dysfunction, and rejection signs in biopsy or/and an increase in DSA strength in last 12 months) versus good [GCC] N = 50 (with stable renal function and treatment, no rejection and no DSA titers). Immunobiogram dose-response curve parameters were compared between both subgroups in patients treated with mycophenolate, tacrolimus, corticosteroids, cyclosporine A or everolimus. Parameters for which significant inter-group differences were observed were further analyzed by univariate and subsequent multivariate logistic regression. RESULTS: Clinical outcome was associated with following parameters: area over the curve (AOC) and 25% (ID25) and 50% (ID50) inhibitory response in mycophenolate, tacrolimus, and corticosteroid-treated subgroups, respectively. These statistically significant associations persisted in mycophenolate (OR 0.003, CI95% <0.001-0.258; p = 0.01) and tacrolimus (OR < 0.0001, CI95% <0.00001-0.202; p = 0.016) subgroups after adjusting for concomitant corticosteroid treatment, and in corticosteroid subgroup after adjusting for concomitant mycophenolate or tacrolimus treatment (OR 0.003; CI95% <0.0001-0.499; p = 0.026). CONCLUSIONS: Our results highlight the potential of Immunobiogram as a tool to test the pharmacodynamic response to individual immunosuppressive drugs.

Dynamic profiles and predictive values of some biochemical and haematological quantities in COVID-19 inpatients.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in some hospitalized patients has shown some important alterations in laboratory tests. The aim of this study was to establish the most relevant quantities associated with the worst prognosis related to COVID-19. MATERIALS AND METHODS: This was a descriptive, longitudinal, observational and retrospective study, in a cohort of 845 adult inpatients from Bellvitge University Hospital (L'Hospitalet de Llobregat, Barcelona, Spain). A multivariate regression analysis was carried out in demographic, clinical and laboratory data, comparing survivors (SURV) and non-survivors (no-SURV). A receiver operating characteristic analysis was also carried out to establish the cut-off point for poor prognostic with better specificity and sensibility. Dynamic changes in clinical laboratory measurements were tracked from day 1 to day 28 after the onset of symptoms. RESULTS: During their hospital stay, 18% of the patients died. Age, kidney disease, creatinine (CREA), lactate-dehydrogenase (LD), C-reactive-protein (CRP) and lymphocyte (LYM) concentration showed the strongest independent associations with the risk of death in the multivariate regression analysis. Established cut-off values for poor prognosis for CREA, LD, CRP and LYM concentrations were 75.0 µmol /L, 320 U/L, 80.9 mg/L and 0.69 x109/L. Dynamic profile of laboratory findings, were in agreement with the consequences of organ damage and tissue destruction. CONCLUSIONS: Age, kidney disease, CREA, LD, CRP and LYM concentrations in COVID-19 patients from the southern region of Catalonia provide important information for their prognosis. Measurement of LD has demonstrated to be very good indicator of poor prognosis at initial evaluation because of its stability over time.

The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy.

Immunosuppressive drugs are widely used to treat several autoimmune disorders and prevent rejection after organ transplantation. However, intra-individual variations in the pharmacological response to immunosuppressive therapy critically influence its efficacy, often resulting in poor treatment responses and serious side effects. Effective diagnostic tools that help clinicians to tailor immunosuppressive therapy to the needs and immunological profile of the individual patient thus constitute a major unmet clinical need. In vitro assays that measure immune cell responses to immunosuppressive drugs constitute a promising approach to individualized immunosuppressive therapy. Here, we present the Immunobiogram, a functional pharmacodynamic immune cell-based assay for simultaneous quantitative measurement of a patient's immune response to a battery of immunosuppressive drugs. Peripheral blood mononuclear cells collected from patients are immunologically stimulated to induce activation and proliferation and embedded in a hydrogel mixture in which they are exposed to a concentration gradient of the immunosuppressants of interest. Analysis of samples from kidney transplant patients using this procedure revealed an association between the sensitivity of individual patients to the immunosuppressive regimen and their immunological risk of transplant rejection. Incorporation of the Immunobiogram assay into clinical settings could greatly facilitate personalized optimization and monitoring of immunosuppressive therapy, and study of the mechanisms underlying resistance to immunosuppressants.

A Case of Velocardiofacial Syndrome With Bilateral Inferior Punctum and Canalicular Agenesis.

A 16-year-old girl diagnosed with velocardiofacial syndrome complained of occasional bilateral ocular discharge. Examination revealed an agenesia of the inferior puncti and canaliculi, while the irrigation through the superior puncta was patent on both sides. Dacryocystorhinostomy with insertion of Lester Jones tubes is not considered for the time being because of the absence of epiphora. To the best of the authors' knowledge, this is the second reported case of lacrimal system agenesia in velocardiofacial syndrome.

Iris-claw intraocular lens for aphakia: Can location influence the final outcomes?

PURPOSE: To describe the demographic data, evaluate the long-term refractive and anatomical outcomes, and report the incidence of complications of anterior iris (prepupillary) and posterior iris (retropupillary) fixation of the Artisan aphakia iris-claw intraocular lens (IOL). SETTING: Complejo Hospitalario Universitario de Santiago de Compostela, Spain. DESIGN: Retrospective case series. METHODS: Patients who had iris-claw IOL implantation were divided into 2 groups: Group 1 (prepupillary) and Group 2 (retropupillary). The corrected distance visual acuity (CDVA), anatomical changes, endothelial cell count (ECC), presence of cystoid macular edema (CME), and operative and postoperative complications were determined. RESULTS: The study comprised 95 eyes of 95 patients. Fifty-seven patients had prepupillary implantation and 38 patients had retropupillary implantation. Indications for surgery were IOL luxation or subluxation (n = 24), lens luxation or subluxation (n = 17), trauma (n = 15), aphakia (n = 30), and other (n = 9). The CDVA improved significantly in both groups and there were no differences between them. A significant ECC reduction was observed in both groups, with no differences between them. The incidence of CME was 16.1% (21.8% in the prepupillary group and 7.9% in the retropupillary group at 3 months and 8 months, respectively), although the difference was not statistically significant. Other postoperative complications were rare and no differences were found between groups. CONCLUSIONS: Irrespective of location, the iris-claw IOL provided good visual outcomes with few complications. However, prepupillary IOL implantation seemed to contribute to greater endothelial cell loss and earlier onset of CME.

Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review.

BACKGROUND: Nonadherence to medication is a recognized problem and may be the most challenging aspect of treatment. METHODS: We performed a systematic review of factors that influence adherence and the consequences of nonadherence to the patient, healthcare system and society, in patients with schizophrenia. Particular attention was given to the effect of nonadherence on hospitalization rates, as a key driver of increased costs of care. A qualitative systematic literature review was conducted using a broad search strategy using disease and adherence terms. Due to the large number of abstracts identified, article selection was based on studies with larger sample sizes published after 2001. Thirty-seven full papers were included: 15 studies on drivers and 22 on consequences, of which 12 assessed the link between nonadherence and hospitalization. RESULTS: Key drivers of nonadherence included lack of insight, medication beliefs and substance abuse. Key consequences of nonadherence included greater risk of relapse, hospitalization and suicide. Factors positively related to adherence were a good therapeutic relationship with physician and perception of benefits of medication. The most frequently reported driver and consequence were lack of insight and greater risk of hospitalization respectively. CONCLUSIONS: Improving adherence in schizophrenia may have a considerable positive impact on patients and society. This can be achieved by focusing on the identified multitude of factors driving nonadherence.

Dosing frequency and adherence in chronic psychiatric disease: systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to investigate the impact of dosing frequency on adherence in severe chronic psychiatric and neurological diseases. METHODS: A systematic literature review was conducted for articles in English from medical databases. Diseases were schizophrenia, psychosis, epilepsy, bipolar disorder, and major depressive disorder. RESULTS: Of 1420 abstracts screened, 12 studies were included. Adherence measures included Medication Event Monitoring System (MEMS(®)), medication possession ratio, medication persistence, and refill adherence. Three schizophrenia and one epilepsy study used MEMS, and all showed a trend towards higher adherence rates with less frequent dosing regimens. Three depression and one schizophrenia study used the medication possession ratio; the pooled odds ratio of being adherent was 89% higher (ie, 1.89, 95% credibility limits 1.71-2.09) on once-daily versus twice-daily dosing. Two studies in depression and one in all bupropion patients assessed medication persistence and refill adherence. The pooled odds ratio for the two depression studies using medication persistence was 2.10 (95% credibility limits 1.86-2.37) for once-daily versus twice-daily dosing. For refill adherence after 9 months, 65%-75% of patients on once-daily versus 56% on twice-daily dosing had at least one refill. In all but one of the studies using other measures of adherence, adherence rates were higher with once-daily dosing compared with more frequent dosing regimens. No relevant studies were identified for bipolar disorder or psychosis. CONCLUSION: Differences in study design and adherence measures used across the studies were too large to allow pooling of all results. Despite these differences, there was a consistent trend of better adherence with less frequent dosing.

The reptile type specimens preserved in the Museo Nacional de Ciencias Naturales (CSIC) of Madrid, Spain.

A first complete list of the reptile type specimens preserved in the Museo Nacional de Ciencias Naturales (CSIC) of Madrid (updated until 15 July 2012) is provided. The collection houses a total of 319 type specimens representing 24 taxa belonging to 6 families and 12 genera. There are 22 taxa represented by primary types (19 holotypes, 2 neotypes and 1lectotype) and at least one paratype, and only two taxa are exclusively represented by one secondary type (paratype). The collection is specially rich in Spanish endemisms. Special attention is deserved by the type series of many subspecies of Podarcis lilfordi described by A. Salvador and V. Pdéez-Mellado. All type specimens are housed in the Herpetological collection except Blanus mariae and Psaimodroims occidentalis type series and Psammodroims hispanicus (neotype) which are preserved in the DNA/Tissues Collection.

Validación de la versión en castellano de la Escala del Bienestar Subjetivo con Neurolépticos (SWN-K) en pacientes con esquizofrenia / Validation of the Spanish version of the Subjective Well-being under Neuroleptic Scale (SWN-K) in patients with schizophrenia

Fundamento y objetivo: La experiencia subjetiva de los pacientes psicóticos con el tratamiento neuroléptico es un factor clave en la adherencia terapéutica, calidad de vida y pronóstico. El objetivo de este trabajo fue realizar la adaptación cultural al castellano de la Escala del Bienestar Subjetivo con Neurolépticos (SWN-K) y analizar sus propiedades psicométricas en pacientes con esquizofrenia. Pacientes y método: Se realizó un estudio transversal en dos fases (adaptación cultural y validación psicométrica) en el que se incluyó a 97 pacientes mayores de 18 años en tratamiento antipsicótico. Se valoraron la factibilidad, fiabilidad y validez de la escala. Resultados:Se demostró una buena aceptabilidad de la escala SWN-K. El coeficiente α de Cronbach de la puntuación total de la escala SWN-K fue de 0,86. La fiabilidad test-retest fue de 0,88 (intervalo de confianza del 95% [IC 95%] 0,84 y 0,93). La SWN-K discriminó entre los niveles de gravedad de la ICG-G (p < 0,01 ANOVA unilateral) y se observó una tendencia lineal (p<0,001).Conclusiones: La versión adaptada al castellano de la SWN-K muestra propiedades psicométricas adecuadas como instrumento autoadministrado de evaluación del bienestar subjetivo en esquizofrenia (AU)

Background and objective: The subjective experience of patients with psychoses towards neuroleptic treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim was to achieve a linguistic adaptation and psychometric validation into Spanish of the Subjective Well-being under Neuroleptic Scale (SWN-K) among patients with schizophrenia.Material and method: Cross-sectional validation study conducted in two phases (cultural adaptation into Spanish and psychometric validation) in clinically stable patients under antipsychotic treatment. Feasibility and reliability were explored.Results: A total of 97 patients were included. Most patients were male (72%), with mean age of 35 years (SD=10). The SWN-K showed a good acceptability. SWN-K total score Cronbach's α was 0.86. The SWN-K total score test-retest reliability was 0.88 (95% CI=0.84 to 0.93). The SWN-K discriminated among CGI-S levels (one-way ANOVAS P<0.01), showing a linear trend (P<0.001). Conclusions: The Spanish version of the SWN-K is feasible, reliable, and appropriated as a patient-reported outcome to evaluate patients’ subjective well being under treatment (AU)

Prevalence of depression and its relationship with other clinical characteristics in a sample of patients with stable schizophrenia.

AIM: To evaluate the prevalence of depression using the Calgary Depression Scale for Schizophrenia (CDSS) in a sample of Spanish patients with stable schizophrenia and without a diagnosis of depression. METHODS: We included stable outpatients of 18 to 50 years of age, with a diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder who had not been diagnosed with depression. In this cross-sectional study, we administered the CDSS, the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale to Assess Unawareness of Mental Disorder (SUMD), the Simpson Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). RESULTS: A total of 95 patients were recruited, 90 of them were included in the statistical analysis. Twenty-eight patients had a total score of 5 or more points on the CDSS, making the prevalence of depression 31% (95% confidence interval, 22-41). The CDSS had a high correlation with the depressive factor of the PANSS and a moderate correlation with the general psychopathology subscale of the PANSS. The correlation of the CDSS total score with negative symptoms was moderate using the SANS and low with the PANSS-negative. There was no correlation between depressive symptoms and positive symptoms, insight, and extrapyramidal symptoms; and the correlation with akathisia was low. CONCLUSION: Our results suggest that patients with stable schizophrenia who have not been diagnosed with depression frequently have clinically relevant symptoms of depression, and that these symptoms, with the possible exception of a contribution from negative symptoms, are not secondary to other symptoms of their disorder or to extrapyramidal adverse effects of medications.

[Validation of the Spanish version of the Subjective Well-being under Neuroleptic Scale (SWN-K) in patients with schizophrenia]. / Validación de la versión en castellano de la Escala del Bienestar Subjetivo con Neurolépticos (SWN-K) en pacientes con esquizofrenia.

BACKGROUND AND OBJECTIVE: The subjective experience of patients with psychoses towards neuroleptic treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim was to achieve a linguistic adaptation and psychometric validation into Spanish of the Subjective Well-being under Neuroleptic Scale (SWN-K) among patients with schizophrenia. MATERIAL AND METHOD: Cross-sectional validation study conducted in two phases (cultural adaptation into Spanish and psychometric validation) in clinically stable patients under antipsychotic treatment. Feasibility and reliability were explored. RESULTS: A total of 97 patients were included. Most patients were male (72%), with mean age of 35 years (SD=10). The SWN-K showed a good acceptability. SWN-K total score Cronbach's α was 0.86. The SWN-K total score test-retest reliability was 0.88 (95% CI=0.84 to 0.93). The SWN-K discriminated among CGI-S levels (one-way ANOVAS P<0.01), showing a linear trend (P<0.001). CONCLUSIONS: The Spanish version of the SWN-K is feasible, reliable, and appropriated as a patient-reported outcome to evaluate patients' subjective well being under treatment.

Impact of depressive symptoms on subjective well-being: the importance of patient-reported outcomes in schizophrenia.

OBJECTIVE: The subjective experience of psychotic patients toward treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim of this study was to assess the subjective well-being in patients with schizophrenia and to examine its relationship with the presence and severity of depressive symptoms. METHODS: A multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. The Subjective Well-Being under Neuroleptic Scale - short version (SWN-K) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to gather information on well-being and the presence and severity of depressive symptoms, respectively. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the CDSS total score. Discriminative validity was evaluated against that criterion by analysing the area under the curve (AUC). RESULTS: Ninety-seven patients were included in the study. Mean age was 35 years (standard deviation = 10) and 72% were male. Both the total SWN-K scale and its five subscales correlated inversely and significantly with the CDSS total score (P < 0.0001). The highest correlation was observed for the total SWN-K (Spearman's rank order correlation [rho] = -0.59), being the other correlations: mental functioning (-0.47), social integration (-0.46), emotional regulation (-0.51), physical functioning (-0.48), and self-control (-0.41). A total of 33 patients (34%) were classified as depressed. Total SWN-K showed the highest AUC when discriminating between depressive severity levels (0.84), followed by emotional regulation (0.80), social integration (0.78), physical functioning and self-control (0.77), and mental functioning (0.73). Total SWN-K and its five subscales showed a significant linear trend against CDSS severity levels (P < 0.001). CONCLUSION: The presence of moderate to severe depressive symptoms was relatively high, and correlated inversely with patients' subjective well-being. Routine assessment of patient-reported measures in patients with schizophrenia might reduce potential discrepancy between patient and physician assessment, increase therapeutic alliance, and improve outcome.

Factors associated with the effectiveness of a telephone-based nursing strategy for enhancing medication adherence in schizophrenia.

A post hoc analysis was made to identify factors associated with success following a 4-month telephone-based strategy for enhancing adherence to antipsychotic treatment in schizophrenia. A total of 928 stable outpatients were randomized to receive a monthly telephone call provided by a nurse or routine clinical care. Logistic regression with a backward stepwise procedure was used. A higher percentage of patients in the intervention group (25.7%, n=109) improved adherence at the end of the study compared with the control group (16.8%, n=74) (p=0.0013). The intervention was significantly associated with adherence improvement in those patients with a previous negative attitude towards medication (OR=4.7, 95% CI =2.4-9.0, p<0.0001). A slight concordance was obtained between adherence improvement and improvement in patient perception of treatment (kappa=0.21; 95% CI=0.15-0.27). The identification of factors related to the effectiveness of a specific intervention would offer clinicians the opportunity to more adequately select patients who are eligible for such intervention.

Estimation of a multiattribute utility function for the Spanish version of the TooL questionnaire.

OBJECTIVES: To estimate and assess the psychometric properties of a multiattribute utility function (MAUF) for the Spanish version of the Tolerability and Quality of Life (TooL questionnaire). METHODS: Balanced data on 243 patients diagnosed with schizophrenia or bipolar disorder were gathered. In addition to the demographic and clinical variables and the usual generic health-related quality of life (HRQoL) questionnaires (EuroQol-5D [EQ-5D] and Short Form-6D [SF-6D]), instruments considered included the Spanish versions of the Positive and Negative Symptoms of Schizophrenia Scale (PANSS), Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), Udvalg for Kliniske Undersogelser (UKU), and Clinical Global Impression Severity (CGIS) scale. MAUF parameters estimation involved a number of visual analogue scale (VAS) and time trade-off (TTO) ratings that proved difficult to be performed by the patients. After checking for inconsistencies in patient responses, the original sample was reduced to a still balanced subsample of 70 individuals. A multiplicative-form MAUF was estimated following the standard methodology. RESULTS: Good convergent validity was demonstrated because utility estimates from the MAUF presented strong correlations with utilities from the generic HRQoL instruments included: SF-6D (0.66, P < 0.01), EQ-5D (0.69, P < 0.01), and moderate correlations with the rest of instruments considered: PANSS (-0.27, P = 0.10), YMRS (-0.30, P = 0.08), MADRS (-0.48, P < 0.01), UKU (-0.35, P < 0.01). Criterion validity was also met because differences in mean utilities by clinical severity were found (P < 0.01). Utilities from the MAUF covered a wider range of health states [0.04,1.00] than those from the SF-6D [0.53,1.00] and EQ-5D [0.23,0.96]. CONCLUSIONS: Utilities from the MAUF showed good psychometric properties, serving as a complement to generic health utilities. If misapplied, however, utilities from this instrument might favor the positive evaluation of drugs showing fewer associated side effects.

Validation of a specific measure to assess health-related quality of life in patients with schizophrenia and bipolar disorder: the 'Tolerability and quality of life' (TOOL) questionnaire.

BACKGROUND: Perception of quality of life may differ depending on the perspective. The aim of the study was to assess the psychometric properties of the Spanish version of the 'TOlerability and quality Of Life' (TOOL) questionnaire, a specific self-rated instrument to evaluate the impact of side effects of antipsychotic drugs on health-related quality of life (HRQoL). The questionnaire consists of eight items answered on a four-point Likert scale. METHODS: A psychometric study was conducted with clinically stable outpatients with schizophrenia and bipolar disorder under antipsychotic treatment. The translation and cultural adaptation of the questionnaire was performed according to international standards. Internal consistency using the Cronbach α coefficient and test-retest reliability using the intraclass correlation coefficient (ICC) was used to assess the reliability of the instrument. Patients completed generic and specific measures of quality of life and clinical severity. RESULTS: A total of 238 patients were analysed, with a mean age of 42 years (SD 10.9). The mean completion time was 4.9 min (SD 4.4). Internal consistency and intraclass correlation coefficient were adequate (Cronbach α = 0.757 and ICC = 0.90). Factorial analysis showed a unidimensional structure (a single eigenvalue >1, accounting for 39.1% of variance). Significant Spearman's rank correlations between the TOOL and both generic and specific measures were found. The questionnaire was able to discriminate among the Clinical Global Impression - Severity scores (Mann-Whitney U test, P < 0.001). CONCLUSIONS: The TOOL questionnaire shows appropriate feasibility, reliability, and discriminative performance as a patient-reported outcome. TOOL constitutes a valuable addition to measure the impact of adverse events of antipsychotic drugs from the patient perspective.

Pattern of healthcare resource utilization and direct costs associated with manic episodes in Spain.

BACKGROUND: Although some studies indicate that bipolar disorder causes high health care resources consumption, no study is available addressing a cost estimation of bipolar disorder in Spain. The aim of this observational study was to evaluate healthcare resource utilization and the associated direct cost in patients with manic episodes in the Spanish setting. METHODS: Retrospective descriptive study was carried out in a consecutive sample of patients with a DSM-IV diagnosis of bipolar type I disorder with or without psychotic symptoms, aged 18 years or older, and who were having an active manic episode at the time of inclusion. Information regarding the current manic episode was collected retrospectively from the medical record and patient interview. RESULTS: Seven hundred and eighty-four evaluable patients, recruited by 182 psychiatrists, were included in the study. The direct cost associated with healthcare resource utilization during the manic episode was high, with a mean cost of nearly 4,500 euros per patient, of which approximately 55% corresponded to the cost of hospitalization, 30% to the cost of psychopharmacological treatment and 10% to the cost of specialized care. CONCLUSIONS: Our results show the high cost of management of the patient with a manic episode, which is mainly due to hospitalizations. In this regard, any intervention on the management of the manic patient that could reduce the need for hospitalization would have a significant impact on the costs of the disease.

Telephone-based nursing strategy to improve adherence to antipsychotic treatment in schizophrenia: A controlled trial.

Abstract Objective. Adherence to prescribed antipsychotic medication is a major factor in achieving optimal long-term clinical outcomes. The aim of this study was to evaluate the impact of a telephone-based strategy provided by a nurse on adherence to antipsychotic treatment among patients with schizophrenia. Methods. A total of 928 clinically stable outpatients with schizophrenia were randomized to receive a monthly telephone call by a nurse or routine clinical care. Telephone calls were performed at weeks 4, 8, and 12, consisting of a standardized interview to detect and assess therapeutic adherence and subjective attitude towards medication. Patients were followed for 4 months. A cut-point of ≥ 60% of prescribed dose was used to classify patients as being adherent. Results. At week 16, a significantly higher percentage of patients who received a telephone-based follow-up (96.7%, n = 410) were classified as adherent compared to the control group (91.2%, n = 402) (P = 0.0007). Patients in the intervention group were significantly more likely to be adherent than control group (adjusted OR = 3.3 95% CI 1.6-6.6, P = 0.0001). Conclusions. Telephone-based nursing strategy showed a significant improvement in adherence to antipsychotic drugs. Further studies are necessary to confirm if this kind of intervention could be a complementary strategy to optimize adherence in patients with schizophrenia.

Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926).

Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine. Further modifications of the A-ring system generated three series of analogues with improved potency and/or solubility. Lead compounds from each series were characterized in vitro and evaluated in vivo for biological activity and pharmacokinetic properties. These studies led to the discovery of IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and compound 2. As a result, complete tumor regression was observed in a Hh-dependent medulloblastoma allograft model after daily oral administration of 40 mg/kg of compound 28.