Benefits of using exchangeable copper and the ratio of exchangeable copper in a real-world cohort of patients with Wilson disease.

Wilson disease (WD) is a complex disease in which diagnosis and long-term metabolic copper control remains challenging. The absence of accurate biomarkers requires the combination of different parameters to ensure copper homeostasis. Exchangeable copper and its ratio (REC) have been suggested to be useful biomarkers in this setting. We aimed at introducing these measurements and evaluate their performance and accuracy in our real-world cohort of WD patients. Exchangeable copper and REC were measured in 48 WD patients and 56 control individuals by inductively coupled plasma-mass-spectrometry. Demographic and clinical characteristics were collected. REC was shown to be significantly higher among WD patients compared to controls and useful for WD identification by using the previously established cutoffs: 71.4% of WD patients with a recent diagnosis had REC ≥18.5% and 95.1% of long-term treated WD had REC ≥14%; only four patients of the cohort presented discordant levels. Moreover, REC values were below 15% in all the control individuals. Exchangeable copper was significantly higher in WD patients compared to controls and tended to be reduced among WD patients who were compliant to medication. This real-life study confirmed that exchangeable copper and REC are useful serum biomarkers that can be used as complementary tests to ensure WD diagnosis (REC) and copper homeostasis whithin time (exchangeable copper). The desirable target levels for this last objective still needs to be validated in prospective cohorts.

Transcriptomic study in explanted liver from a patient with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a rare disease caused by a deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme-synthesis pathway. Decreased enzymatic activity in the liver induces an overproduction of heme-precursors and acute neurological attacks. We report a 36-years-old female with AIP with a long-term history of severe, disabling, recurrent attacks, who underwent curative liver transplantation. Tissue samples from the explant were obtained for transcriptome analysis. Whole RNA was extracted and 16 gene-transcripts were selected and investigated by quantitative polymerase chain reaction. These included nine genes encoding enzymes that consecutively catalyze heme-synthesis and catabolism in the liver (ALAS1; ALAD; HMBS; UROS; UROD; CPOX; PPOX; FECH; HMOX1). Additionally, we studied genes related to inflammation (IL6; TNF) insulin signaling (PGC-1α; IGF-1; FOXO-1) and tryptophan metabolism (TDO2; IDO). Transcripts of eight house-keeping genes were co-measured for normalization. All transcripts were also measured in five control samples from healthy living liver donors. The transcriptome of the controls showed important differences between the various genes, with the first two genes of the heme-synthesis pathway, ALAS1 and ALAD showing strikingly high mRNA levels compared to the consecutive HMBS gene. Transcripts of several genes significantly differed in the AIP liver compared to controls. Transcripts of HMOX1 and UROS were increased in the AIP liver whereas transcripts of UROD; CPOX, PPOX, and TDO2 were decreased. ALAS1 expression was not increased, possibly due to hemin administered to the patient before transplantation. These results highlight several transcriptomic changes related to heme homeostasis in AIP.

Dried Blood Spot (DBS) as a useful tool to improve clozapine, aripiprazole and paliperidone treatment: From adherence to efficiency.

INTRODUCTION: Therapeutic Drug Monitoring (TDM) of antipsychotics in schizophrenia is a powerful tool that allows tailoring the treatment in an individualized approach. Our goals are to develop and validate a Dried Blood Spot (DBS) method for monitoring some commonly used antipsychotics (aripiprazole, clozapine, and paliperidone) and to evaluate its usefulness as a compliance biomarker, as well as in drug-dose adjustment to personalize the antipsychotic treatment to improve its efficacy and safety. METHODS: 31 first-psychotic episode (FEP) and schizophrenia patients were included; 5 refer to naïve FEP who started antipsychotic treatment; 26, to patients with more than one episode and under antipsychotic treatment: aripiprazole (7 cases), clozapine (17), paliperidone (11). For DBS sample collection, 25µl of capillary blood were placed in the spot of a FTA™DMPK-C-card. After completely dryness, antipsychotics were extracted and analyzed by a validated UHPLC-MS/MS-method. DBS antipsychotic results were compared with those obtained in venous blood/plasma. RESULTS: Aripiprazole, paliperidone and clozapine showed from good to excellent correlations between concentrations in venous blood and DBS capillary blood (r2, from 0.500 to 0.721). The correlation between conventional plasma and DBS concentrations for paliperidone, aripiprazole, clozapine, and their metabolites were moderate, suggesting that optimal drug target concentrations should be established for DBS. CONCLUSIONS: In this study, for aripiprazole, dehydroaripiprazole, paliperidone, clozapine and desmethylclozapine, DBS has provided good analytical performance for TDM. Thus, DBS sampling can offer a great alternative over conventional sampling for plasma measurement. The assay provides good analytical performances for TDM and clinical research applicability, suggesting that DBS is a promising clinical application in TDM in psychiatry.

Dried Blood Spot (DBS) as a useful tool to improve clozapine, aripiprazole and paliperidone treatment: From adherence to efficiency / Análisis de sangre seca (Dried Blood Spot [DBS]) como herramienta útil para mejorar el tratamiento con clozapina, aripiprazol y paliperidona: de la adherencia a la eficacia

Introduction: Therapeutic Drug Monitoring (TDM) of antipsychotics in schizophrenia is a powerful tool that allows tailoring the treatment in an individualized approach. Our goals are to develop and validate a Dried Blood Spot (DBS) method for monitoring some commonly used antipsychotics (aripiprazole, clozapine, and paliperidone) and to evaluate its usefulness as a compliance biomarker, as well as in drug-dose adjustment to personalize the antipsychotic treatment to improve its efficacy and safety. Methods: 31 first-psychotic episode (FEP) and schizophrenia patients were included; 5 refer to naïve FEP who started antipsychotic treatment; 26, to patients with more than one episode and under antipsychotic treatment: aripiprazole (7 cases), clozapine (17), paliperidone (11). For DBS sample collection, 25μl of capillary blood were placed in the spot of a FTA™DMPK-C-card. After completely dryness, antipsychotics were extracted and analyzed by a validated UHPLC-MS/MS-method. DBS antipsychotic results were compared with those obtained in venous blood/plasma. Results: Aripiprazole, paliperidone and clozapine showed from good to excellent correlations between concentrations in venous blood and DBS capillary blood (r2, from 0.500 to 0.721). The correlation between conventional plasma and DBS concentrations for paliperidone, aripiprazole, clozapine, and their metabolites were moderate, suggesting that optimal drug target concentrations should be established for DBS. (AU)

Introducción: La monitorización terapéutica de medicamentos (Therapeutic Drug Monitoring [TDM]) de los antipsicóticos en la esquizofrenia es una potente herramienta que permite adaptar el tratamiento de forma individualizada y personalizada. Los objetivos del presente estudio son desarrollar y validar un método de análisis en sangre seca (Dried Blood Spot [DBS]) para la monitorización de algunos antipsicóticos de uso común (aripiprazol, clozapina y paliperidona) y evaluar su utilidad como biomarcador de cumplimiento y adherencia terapéutica, así como en el ajuste de la dosis del fármaco para personalizar el tratamiento antipsicótico para mejorar su eficacia y su seguridad. Metodología: Se incluyeron 31 pacientes con un primer episodio psicótico (PEP) o un diagnóstico de esquizofrenia; 5 eran PEP que iniciaron tratamiento antipsicótico, y 26 eran pacientes con más de un episodio y que seguían tratamiento con antipsicóticos: aripiprazol (7 casos), clozapina (17), paliperidona (11). Para la recogida de muestras de DBS se colocaron 25μl de sangre capilar en el punto de una tarjeta FTATMDMPK-C. Tras secarse completamente, se extrajeron los antipsicóticos y se analizaron mediante un método UHPLC-MS/MS validado. Los resultados de los antipsicóticos según la DBS se compararon con los obtenidos en sangre venosa/plasma. Resultados: El aripiprazol, la paliperidona y la clozapina mostraron de buenas a excelentes correlaciones entre las concentraciones en sangre venosa y en sangre capilar del DBS (r2, de 0,500 a 0,721). La correlación entre las concentraciones plasmáticas convencionales y las del DBS para la paliperidona, el aripiprazol, la clozapina y sus metabolitos fue moderada, lo que sugiere que se deberían definir y establecer concentraciones óptimas del fármaco para el DBS. (AU)

Neonatal Feeding Trajectories in Mothers With Bipolar Disorder Taking Lithium: Pharmacokinetic Data.

Purpose: Women who take lithium during pregnancy and continue after delivery may choose to breastfeed, formula feed, or mix these options. The aim of the study was to evaluate the neonatal lithium serum concentrations based on these three feeding trajectories. Methods: We followed 24 women with bipolar disorder treated with lithium monotherapy during late pregnancy and postpartum (8 per trajectory). Lithium serum concentrations were determined by an AVL 9180 electrolyte analyser with a 0.10 mEq/L detection limit and a 0.20 mEq/L limit of quantification (LoQ). Results: There was complete lithium placental passage at delivery, with a mean ratio of lithium concentration in the umbilical cord to maternal serum of 1.12 ± 0.17. The median times to LoQ were 6-8, 7-8, and 53-60 days for formula, mixed, and exclusive breastfeeding respectively. The generalized log-rank testing indicated that the median times to LoQ differ according to feeding trajectory (p = 0.037). According to the multivariate analysis-adjusted lithium serum concentrations at birth, times to LoQ are, on average, longer under exclusive breastfeeding (formula, p = 0.015; mixed, p = 0.012). No lithium accumulation was observed in infants under either exclusive or mixed breastfeeding. During the lactation follow-up, there was no acute growth or developmental delays in any neonate or infant. Indeed, lithium concentrations in the three trajectories declined in all cases. However, the time needed to reach the LoQ was much longer for those breastfeeding exclusively. Conclusions: In breastfeed infant no sustained accumulation of lithium and no adverse effects on development or growth were observed.

Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series.

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice. Objectives: To present clinical and pharmacokinetic data of nine mother-infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006-2018). Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother-infant pairs at delivery, and at days 1-5, 7-11, 30, and 60 postpartum, and monthly until 6-months. Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02-1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum. Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair.

Wrist flexion and extension strength in patients with work-related chronic elbow pain: the isokinetic effort factor and its implications.

BACKGROUND: The validity of isokinetic strength findings relating to forearm muscles in patients with chronic elbow pain and/or epicondylitis is not well established. Furthermore, given the nature of this disorder, ensuring maximal effort in performing the tests is an essential prerequisite. The isokinetic-based DEC parameter (defined as the difference between high- and low-velocity eccentric-to-concentric ratios of a given muscle) has been shown to efficiently detect maximal effort. The purpose of this study was therefore to assess the validity of isokinetic strength tests in patients with chronic elbow pain and/or epicondylitis. METHODS: A cohort consisting of 44 male patients with chronic elbow pain (average evolution time, 262 ± 193.04 days) was recruited. The wrist extensor and flexor concentric and eccentric isokinetic strength of the involved and uninvolved sides was measured. The involved-uninvolved and flexor-extensor (F/E) ratios, as well as the DEC (eccentric-concentric difference), were computed based on peak moment values. Work disability and relapse within the first year were registered. In maximal performers, associations between deficits, F/E ratios, work disability, and symptom relapse were explored applying multiple comparisons. RESULTS: Of the patients, 68.2% met the maximal-effort criteria, with the involved-side muscles being significantly weaker than their uninvolved-side counterparts in most cases. Although the mean deficit in this group was not associated with either work disability or relapse, patients with a relapse of symptoms within the first year had a significantly higher F/E ratio than those without relapse. CONCLUSION: In patients presenting with chronic elbow pain who perform at the maximal level of effort, high wrist F/E strength ratios may predict symptom relapse.

Clinical Lactation Studies of Lithium: A Systematic Review.

Background: There is substantial evidence that postpartum prophylaxis with lithium lowers the rate of relapse in bipolar disorder. However, it is contraindicated during breastfeeding due to the high variability of the transfer into breast milk. Aims: We conducted a systematic review of the current evidence of studies assessing the transfer of lithium to lactating infants and short-term infant outcomes. Methods: An a priori protocol was designed based on PRISMA guidelines. Searches in PubMed and LactMed were conducted until September 2018. Studies assessing lithium pharmacokinetic parameters and short-term infant outcomes were included. Quality was assessed using a checklist based on international guidelines (i.e., FDA). Results: From 344 initial studies, 13 case reports/series with 39 mother-child dyads were included. Only 15% of studies complied with ≥50% of the items on the quality assessment checklist. Infants breastfeed a mean (SD) of 58.9 (83.3) days. Mean maternal lithium dose was 904 (293) mg/day, corresponding lithium plasma/serum concentration was 0.73(0.26) mEq/L, and breast milk concentration was 0.84(0.14) mEq/L. Mean infant lithium plasma/serum concentration was 0.23(0.26) mEq/L. Twenty-six (80%) infants had concentrations ≤0.30 mEq/L without adverse effects. Eight (20%) showed a transient adverse event (i.e., acute toxicity or thyroid alterations). All of them were also prenatally exposed to lithium monotherapy or polytherapy. Conclusion: The current evidence comes from studies with a degree of heterogeneity and of low-moderate quality. However, it identifies areas of improvement for future clinical lactation studies of lithium and provides support for some clinical recommendations.

Clozapine Use During Pregnancy and Lactation: A Case-Series Report.

The current prescription of clozapine in psychotic women of reproductive age makes it crucial to understand its pharmacokinetics during pregnancy and lactation as well as its risk profile for neonatal outcome. The aim of this case series was to provide new evidence on the pharmacokinetic features of clozapine that determine its passage through the placenta and amniotic fluid, as well as the neonatal clozapine elimination half-life (t1/2). This case series demonstrates for the first time that clozapine might show partial placental passage similar to other atypical antipsychotics. Clozapine levels decreased during the first few days in nursing infants. The half-life of clozapine in neonates was slightly higher than previously estimated. Clozapine use in pregnancy may be associated with diabetes mellitus, especially if there is a family history of this disease. Although no acute toxicological effects were observed in the intrauterine exposed newborn, close follow-up of pregnancy is recommended. However, these results must be taken with caution being a case series with small sample size.

Intuitive pharmacogenetic dosing of risperidone according to CYP2D6 phenotype extrapolated from genotype in a cohort of first episode psychosis patients.

Risperidone (R) is the most prescribed antipsychotic drug for patients with a first episode of psychosis (FEP). In a naturalistic cohort of chronic psychiatric inpatients, we demonstrated that clinicians adjust R dosage by CYP2D6 activity, despite being blinded to the genotype, which we described as an "intuitive pharmacogenetic" process. The aim of the present study is to replicate our previous findings of intuitive pharmacogenetic in a cohort of FEP patients using CYP2D6 phenotype extrapolated from genotypes. 70 FEP patients, under baseline treatment with R monotherapy were genotyped using the iPLEX® ADME PGx multiplex panel and TaqMan® Genotyping and Copy Number Assays. Plasma concentrations of R and its metabolite, 9-hydroxyrisperidone (9-OH), were determined. The predictive properties of those variables associated with R dosage were tested using a multiple linear regression model as well as regression trees. Significant differences in the mean daily dosage of R among CYP2D6 phenotypes were observed (Kruskal-Wallis test p=0.02): PM (4.00±2.3mg/mL), IM (4.56±2.44), EM (6.22±4.0mg/day) and UM (10.20±4.91mg/day). However, non-significant differences were observed in the R/9-OH ratio or in the Concentration/Dose ratio. Regression tree provided better estimations of R dosage than the multiple linear regression model (MAE=0.958 and R2=0.871). We confirm the "intuitive pharmacogenetic" dosing of R according to the CYP2D6 phenotype in a FEP cohort. The results presented provides a rationale for the clinical use of CYP2D6 genotyping in personalized medicine.

Antipsychotic Response Worsens With Postmenopausal Duration in Women With Schizophrenia.

BACKGROUND: The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia. METHODS: Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response. RESULTS: Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms. DISCUSSION: Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.

Respuesta antipsicótica en trastorno delirante y esquizofrenia: estudio prospectivo de cohortes / Antipsychotic response in delusional disorder and schizophrenia: a prospective cohort study

Introducción. La evidencia científica centrada en la respuesta terapéutica en pacientes con trastorno delirante (TD) es escasa, y los hallazgos contradictorios. Nuestro objetivo fue comparar la respuesta antipsicótica a las 12 semanas en pacientes con TD y esquizofrenia, e identificar potenciales dimensiones de respuesta. Metodología. Se llevó a cabo un estudio prospectivo, observacional, de cohortes de 12 semanas de seguimiento en pacientes con TD y esquizofrenia, apareados por sexo, edad y años de evolución. Se administraron las siguientes escalas: Escala de los Síndromes Positivo y Negativo (PANSS; 5-factores), Funcionamiento Social y Personal (PSP), Impresión Clínica Global (CGI) y Escala Columbia de Severidad Suicida (C-SSRS). La respuesta al tratamiento fue definida como una reducción en puntuación total de PANSS ≥30%. Se realizaron análisis de Regresión Lineal y Regresión Logística para investigar el valor predictivo de los dominios psicopatológicos sobre la respuesta antipsicótica. Resultados. Los porcentajes de respuesta en TD y esquizofrenia fueron 61,5% y 69,2% respectivamente. La duración de la psicosis no tratada, la dosis antipsicótica y el diagnóstico no predijeron la respuesta antipsicótica. En la muestra total, la reducción de síntomas positivos se asoció de forma significativa a una mejoría clínica global (p=0.006) dando cuenta de hasta un 20% de la varianza del modelo. En la submuestra de pacientes con TD, la mejoría en síntomas cognitivos se asoció a la mejoría en impresión clínica global llegando a explicar un 30% de su varianza (p=0.030) (AU). Conclusiones. Tanto los porcentajes de respuesta como las dosis antipsicóticas fueron similares en el TD y en la esquizofrenia. El cambio en síntomas positivos se asoció a mejoría clínica global en la muestra total, y el cambio en síntomas cognitivos se correlacionó con la impresión clínica global exclusivamente en el TD

Introduction. Scientific evidence focused on the treatment response in delusional disorder (DD) patients is scarce, and the findings are controversial. Our goal was to compare the antipsychotic response at the 12-week followup between patients diagnosed with DD and patients diagnosed with schizophrenia and to identify potential response dimensions. Methods. A prospective, observational, cohort study with 12-week follow-up was conducted with DD and schizophrenia patients matched for sex, age and cumulative years of disease. The following scales were assessed: Positive and Negative Syndrome Scale (PANSS; 5-factors), Personal and Social Performance Scale (PSP), Clinical Global Impression Scale (CGI), and Columbia-Suicide Severity Rating Scale (C-SSRS). Treatment response was defined as a ≥30% reduction in the total PANSS score. Linear and logistic regression models were used to investigate the potential predictive value of psychopathological variables for the antipsychotic response. Results. Response percentages in DD and schizophrenia were 61.5% and 69.2%, respectively. The duration of untreated psychosis, antipsychotic dosage, and diagnosis did not predict antipsychotic response. In the whole sample, improvement in positive symptoms was significantly associated with the clinical global improvement (p=0.006). explaining almost 20% of the variance in the model. Within the DD group, improvement in cognitive symptoms explained 30% of the variance in clinical global improvement. Conclusions. Both response percentages and required antipsychotic doses were similar between DD and schizophrenia. Changes in positive symptoms were associated with clinical global improvement in the entire sample, and improvement in cognitive symptoms was correlated with global improvement exclusively in DD (AU)

Antipsychotic response in delusional disorder and schizophrenia: a prospective cohort study.

INTRODUCTION: Scientific evidence focused on the treatment response in delusional disorder (DD) patients is scarce, and the findings are controversial. Our goal was to compare the antipsychotic response at the 12-week followup between patients diagnosed with DD and patients diagnosed with schizophrenia and to identify potential response dimensions. METHODS: A prospective, observational, cohort study with 12-week follow-up was conducted with DD and schizophrenia patients matched for sex, age and cumulative years of disease. The following scales were assessed: Positive and Negative Syndrome Scale (PANSS; 5-factors), Personal and Social Performance Scale (PSP), Clinical Global Impression Scale (CGI), and Columbia-Suicide Severity Rating Scale (C-SSRS). Treatment response was defined as a ≥30% reduction in the total PANSS score. Linear and logistic regression models were used to investigate the potential predictive value of psychopathological variables for the antipsychotic response. RESULTS: Response percentages in DD and schizophrenia were 61.5% and 69.2%, respectively. The duration of untreated psychosis, antipsychotic dosage, and diagnosis did not predict antipsychotic response. In the whole sample, improvement in positive symptoms was significantly associated with the clinical global improvement (p=0.006), explaining almost 20% of the variance in the model. Within the DD group, improvement in cognitive symptoms explained 30% of the variance in clinical global improvement. CONCLUSIONS: Both response percentages and required antipsychotic doses were similar between DD and schizophrenia. Changes in positive symptoms were associated with clinical global improvement in the entire sample, and improvement in cognitive symptoms was correlated with global improvement exclusively in DD.

Brote de saturnismo asociado a un tratamiento basado en la medicina ayurvédica / Outbreak of lead poisoning associated with ayurvedic medicine

Fundamento y objetivo: El saturnismo es una enfermedad de causa tóxica que es producida, habitualmente, por la inhalación repetida de plomo en un ámbito laboral. Pero este metal puede también ser absorbido por vía digestiva. En medicinas alternativas, como la ayurvédica, el plomo puede formar parte de algunos tratamientos y ser causa de intoxicación. Pacientes y método: Se recogen los casos de saturnismo atendidos y tratados en el Hospital Clínic de Barcelona en relación con un tratamiento ayurvédico. Resultados: Se han incluido 2 mujeres de 45 y 57 años que iniciaron un tratamiento ayurvédico que comprendía la ingesta de diversos medicamentos. El primer caso desarrolló anemia y dolor abdominal. La plumbemia fue de 74 μg/dl y la protoporfirina eritrocitaria de 163 μg/dl. Fue tratada con etilendiaminotetraacetato de calcio y disodio (CaNa2EDTA) intravenoso y posteriormente con ácido dimercaptosuccínico (DMSA) oral, con buena evolución. El segundo caso presentó dolor abdominal y un ribete de Burton. La plumbemia fue de 52 μg/dl y la protoporfirina eritrocitaria de 262 μg/dl. Fue tratada con DMSA oral, evolucionando favorablemente. Las concentraciones de plomo en algunas de las pastillas suministradas a las pacientes fueron de 2.003 y 19.650 μg/g de pastilla. Conclusiones: La intoxicación por plomo puede ser el resultado de un tratamiento basado en la medicina ayurvédica y puede llegar a adquirir características epidémicas. Es necesario un control sanitario de los medicamentos alternativos (AU)

Background and objective: Lead poisoning is normally caused by repeated occupational inhalation of lead. However, lead may also be absorbed through the digestive route. Some alternative medical treatments, such as Ayurvedic medicine, can also contain lead and may result in poisoning. Patients and method: We collected cases of lead poisoning related to Ayurvedic treatments attended at the Hospital Clinic of Barcelona. Results: Two female patients, aged 45 and 57 years, respectively, who initiated Ayurvedic treatments which involved the ingestion of various medicaments, were included. The first patient presented with anemia and abdominal pain. The lead level was 74 μg/dL and free erythrocyte protoporphyrin was 163 μg/dL. She was treated with intravenous calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) and later with oral dimercaptosuccinic acid (DMSA) with a good evolution. The second patient presented with abdominal pain and a Burton's line. The lead level was 52 μg/dL and free erythrocyte protoporphyrin was 262 μg/dL. She was treated with oral DMSA and evolved favorably. Lead concentrations in some of the tablets supplied to the patients reached 2,003 and 19,650 μg/g of tablet. Conclusions: Lead poisoning may result from treatments based on Ayurvedic medicine and may reach epidemic proportions. Health control of alternative medicines is necessary (AU)

[Outbreak of lead poisoning associated with Ayurvedic medicine]. / Brote de saturnismo asociado a un tratamiento basado en la medicina ayurvédica.

BACKGROUND AND OBJECTIVE: Lead poisoning is normally caused by repeated occupational inhalation of lead. However, lead may also be absorbed through the digestive route. Some alternative medical treatments, such as Ayurvedic medicine, can also contain lead and may result in poisoning. PATIENTS AND METHOD: We collected cases of lead poisoning related to Ayurvedic treatments attended at the Hospital Clinic of Barcelona. RESULTS: Two female patients, aged 45 and 57 years, respectively, who initiated Ayurvedic treatments which involved the ingestion of various medicaments, were included. The first patient presented with anemia and abdominal pain. The lead level was 74µg/dL and free erythrocyte protoporphyrin was 163µg/dL. She was treated with intravenous calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) and later with oral dimercaptosuccinic acid (DMSA) with a good evolution. The second patient presented with abdominal pain and a Burton's line. The lead level was 52µg/dL and free erythrocyte protoporphyrin was 262µg/dL. She was treated with oral DMSA and evolved favorably. Lead concentrations in some of the tablets supplied to the patients reached 2,003 and 19,650µg/g of tablet. CONCLUSIONS: Lead poisoning may result from treatments based on Ayurvedic medicine and may reach epidemic proportions. Health control of alternative medicines is necessary.

Plasma fluoxetine concentrations and clinical improvement in an adolescent sample diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder.

UNLABELLED: Fluoxetine (FLX) has been one of the most widely studied selective serotonin reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to 40% of patients do not respond to treatment. AIMS: The aim of this study was to evaluate whether clinical improvement or adverse events are related to the corrected dose of FLX at 8 and 12 weeks after starting treatment in a sample of adolescents diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder. METHODS: Seventy-four subjects aged between 10 and 17 years participated in the study. Clinical improvement was measured with the Clinical Global Impression-Improvement Scale, whereas the UKU (Udvalg for Klinske Undersogelser) scale was administered to assess adverse effects of treatment. RESULTS: Fluoxetine per kilograms of body weight was related to serum concentration of FLX, NORFLX (norfluoxetine), FLX + NORFLX, and FLX/NORFLX. No relationship was found between dose-corrected FLX levels and therapeutic or adverse effects. No differences in serum concentrations were found between responders and nonresponders to treatment. Sex differences were observed in relation to dose and FLX serum concentration. The analysis by diagnosis revealed differences in FLX dose between obsessive-compulsive disorder patients and both generalized anxiety disorder and major depressive disorder patients. CONCLUSIONS: Fluoxetine response seems to be influenced by factors such as sex, diagnosis, or certain genes that might be involved in the drug's pharmacokinetics and pharmacodynamics. Clinical and pharmacogenetic studies are needed to elucidate further the differences between treatment responders and nonresponders.

Association between symptomatic profile and remission following antidepressant treatment in unipolar major depression.

BACKGROUND: To evaluate, in patients affected by an acute major depressive episode, what predictive value certain baseline psychopathological characteristics have with regard to expected therapeutic remission following biological antidepressant treatment (pharmacological/electroconvulsive; non-psychological). METHODS: Six predefined psychopathological characteristics in acute major depressive episode were evaluated using a logistic regression model through a protocolised antidepressant treatment to assess their predictive value with regard to expected remission rate. RESULTS: The final study sample consisted of 129 subjects affected by an acute major depressive episode. From the baseline evaluation of the anguish/restlessness, reduced emotional reactivity, reduced attention, reduced motor response, feeling of worthlessness, and mood characteristics items, it was possible to correctly classify 88.1% of the sample as remitter/non-remitter with sensitivity of 0.77 and specificity of 0.96. Addition of the 17-item HRSD baseline variable to the regression model increased the capacity for correct classification of the baseline sample by only 0.09%. LIMITATIONS: Protocolised antidepressant treatment was used. The results of this study may not be generalisable to pharmacological treatments not included in this protocol. CONCLUSIONS: The results of this study suggest that certain baseline psychopathological characteristics (and perhaps other clinical variables too) of the acute major depressive episode may be of great use in establishing patient subgroups according to expected clinical remission to the administration of biological antidepressant treatment. This could have considerable consequences for individualised therapeutic decision-making and for future researches (clinical trials included).

Painful lateral knee condyle bone marrow edema after treatment with lateral wedged insole.

A 50-yr-old man arrived at our department for a rehabilitation prescription after a right knee medial collateral ligament sprain. Magnetic resonance imaging showed medial collateral ligament partial rupture and medial femoral condyle increased signal intensity indicating bone edema. After treatment, the patient still complained of weight-bearing knee medial compartment pain. A lateral wedged insole was prescribed to decrease medial compartment compression forces. Initial response to insole use was good, but soon after, the patient complained of severe worsening knee pain. On examination, the lateral joint line and condyle palpation were tender. Insole use discontinuation was recommended, and another magnetic resonance imaging scan was performed. It showed an high T2-weighted signal intensity, representing bone marrow edema comprising a volume of 5 x 5 x 4.5 cm of lateral femoral condyle. Discontinuation of orthosis use relieved the pain, and the edema disappeared. To our knowledge, lateral femoral condyle painful bone marrow edema after lateral wedged insole use has not been previously described. The findings of this case report indicate that lateral wedged insole prescription should be carefully evaluated.