Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial

Background & Aims: Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among histamine related symptoms, headache is one of the most recorded. Current clinical strategies for the treatment of the symptomatology related to this disorder are based on the exclusion of foods with histamine or other bioactive amines and/or exogenous DAO supplementation. The aim of this study was to assess the efficacy of a food supplement consisting of DAO enzyme as a preventive treatment of migraine in patients with DAO deficiency through a randomized double-blind trial. Methods: 100 patients with confirmed episodic migraine according to current International Headache Society (IHS) criteria and DAO deficiency (levels below 80 HDU/ml) were randomized in two groups. One group received DAO enzyme supplementation and the other received placebo for one month. Clinical outcomes assessed were duration and number of attacks, perception of pain intensity and adverse effects during treatment. The use of triptans was also recorded. Results: Great variability was found in the duration of migraine attacks reported by placebo and DAO groups. A significant reduction (p=0.0217) in hours of pain was achieved in patients treated with DAO supplement, with mean durations of 6.14 (±3.06) and 4.76 (±2.68) hours before and after treatment, respectively. A smaller reduction without statistical signification was also observed for this outcome in the placebo group, from 7.53 (±4.24) to 6.68 (±4.42) hours. Only in DAO group, a decrease in the percentage of patients taking triptans was observed. The number of attacks and the scores of pain intensity showed a similar reduction in both groups. No adverse effects were registered in patients treated with DAO enzyme. Conclusions: Migranous patients supplemented with DAO enzyme during one month significantly reduced the duration of their migraine attacks by 1.4 hours. No statistically significant reduction was found in placebo group before and after treatment. The reduction of pain hours observed in placebo group (0.9 hours) could explain the lack of significant differences between both study groups. One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation. Clinical trial registration number ISRCTN10091019; www.isrctn.org

Low serum diamine oxidase (DAO) activity levels in patients with migraine.

Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among the several multifaced symptoms associated with histamine intolerance, headache is one of the most recognised and disabling consequences. The aim of this study was to determine the prevalence of DAO deficiency in patients with a confirmed migraine diagnosis according to the current International Headache Society (IHS) and in non-migraine subjects. DAO activity was assessed in a total of 198 volunteers recruited at the Headache Unit of the Hospital General de Catalunya, 137 in the migraine group and 61 as a control group. DAO enzyme activity in blood samples was determined by ELISA test. Values below 80 HDU/ml (Histamine Degrading Unit/ml) were considered as DAO deficient. Mean value of DAO activity from migraine population (64.5 ±33.5 HDU/ml) was significantly lower (p<0.0001) than that obtained from healthy volunteers (91.9 ± 44.3 HDU/ml). DAO deficiency was more prevalent in migraine patients than in the control group. A high incidence rate of DAO deficiency (87%) was observed in the group of patients with migraine. On the other hand, 44% of non-migranous subjects had levels of DAO activity lower than 80 HDU/ml. Despite the multifactorial etiology of migraine, these results seem to indicate that this enzymatic deficit could be related to the onset of migraine

Antifibrinolytic therapy in complex spine surgery: a case-control study comparing aprotinin and tranexamic acid

Abstract: A case-control study was performed to determine the impact of aprotinin or tranexamic acid use on reducing intraoperative blood loss and transfusion needs in complex spine surgery. Sixty-nine patients undergoing complex spine surgery received aprotinin or tranexamic acid. The aprotinin group contained 30 patients (8 men and 22 women) and the tranexamic acid group 39 patients (11 men and 28 women). The following variables were recorded: duration of surgery, number of levels fused, intraoperative and total blood loss, and number of blood units transfused (autologous and allogenic). In addition, various parameters related to blood loss in this type of surgery were calculated. The groups differed with regard to duration of surgery (aprotinin 662 min vs tranexamic acid 448 min, P<.001) and number of levels fused (aprotinin 11.2 vs tranexamic acid 7.6, P=.004). There were no significant differences in intraoperative blood loss (aprotinin 2118 mL vs tranexamic acid 1608 mL, P=.066) or total blood loss (aprotinin 3312 mL vs tranexamic acid 2627 mL, P=.056). Statistical differences were found for the number of autologous blood units transfused (aprotinin 2.2 vs tranexamic acid 1.3 P=.047) and total units transfused (aprotinin 4.1 vs tranexamic acid 2.6, P=.008). Blood loss per hour of surgery, transfused units per level fused, and transfused units per hour of surgery were similar in the 2 groups. Significant differences were found for intraoperative blood loss per fusion level (aprotinin 228 mL vs tranexamic acid 428, P=.025) and total blood loss per fusion level (aprotinin 360 mL vs tranexamic acid 638 mL, P=.01). Analysis of the applied geometric mean showed that aprotinin reduced total blood loss by 16.4% and total number of blood units transfused by 12.4% as compared to tranexamic acid, although statistical significance was not reached. The type of antifibrinolytic used did not have a significant impact on the main outcome variables of the study

Les Coves de Santa Maira (Castell de Castells, La Marina Alta-Alacant):

Es presenta una descripció preliminar de la seqüència arqueològica de les Coves de Santa Maira (Castell de Castells). Els conjunts arqueològics i les datacions C 14 obtingudes indiquen que la cavitat registra ocupacions humanes estratificades entre el XIV i el VI mil·lenni BP, amb materials arqueològics que poden ser relacionats amb el magdalenià superior, epipaleolític sauvaterrià, mesolític i neolític II. Des d’aquest moment la cavitat es va fer servir, bàsicament, de corral per al tancament de ramat domèstic. Paraules clau: Cova. Magdalenià. Epipaleolític. Mesolític. Neolític. Marina Alta (Alacant).A preliminary description of the archaeological sequence of Les Coves de Santa Maira (Castell de Castells) is offered. Archaeological assemblies and obtained C 14 datings indicate that the cavity registers stratified human occupations between 14th and 6th millenium BP, with archaeological record that can be related to the Upper Magdalenian, Sauveterroid Epipaleolithic Period, Mesolithic and Neolithic II. Since this moment the cavity had a function, basically, of corral for the closing of domestic cattle. Key Words: Cave. Magdalenian. Epipaleolithic. Mesolithic. Neolithic. Marina Alta (province of Alicante).Se ofrece una descripción preliminar de la secuencia arqueológica de las Coves de Santa Maira (Castell de Castells). Los conjuntos arqueológicos y las dataciones C 14 obtenidas indican que la cavidad registra ocupaciones humanas estratificadas entre el XIVº y VIº milenio BP, con materiales arqueológicos que pueden ser relacionados con el Magdaleniense superior, Epipaleolítico sauveterroide, Mesolítico y Neolítico II. A partir de este momento la cavidad tuvo una función, básicamente, de corral para el cierre del ganado doméstico. Palabras Clave: Cueva. Magdaleniense. Epipaleolítico. Mesolítico. Neolítico. Marina Alta (Alicante)

Características del dolor neuropático crónico y su relación con el bienestar psicológico en pacientes con lesión medular

Objetivos. Determinar la prevalencia del dolor neuropático (DN) en una muestra de pacientes con lesión medular (LM), examinar la relación entre las características clínicas, demográficas y psicológicas con la prevalencia del DN después de una LM y a su vez con los diferentes tipos de DN, y estudiar el valor predictivo de los factores más significativos. Pacientes y métodos. Estudio transversal observacional de un total de 260 pacientes que acudieron a una revisión anual. Las principales medidas de resultados incluyeron presencia/ausencia de DN, índice de bienestar psicológico, historia detallada del dolor y escala de puntuación numérica de 0-10 para la media de intensidad del dolor. Resultados. 93 pacientes (36%) con LM tenían DN. De los pacientes que presentaron DN, un 35% mostró dolor a nivel de la lesión, mientras que un 65% presentó DN por debajo. La única variable con capacidad predictiva sobre la prevalencia del DN fue la edad en el momento de la LM. Se observaron diferencias estadísticamente significativas entre la prevalencia del DN y la percepción de bienestar psicológico; el grupo de pacientes con DN fue el que tuvo proporcionalmente un malestar psicológico mayor. En cuanto a los diferentes tipos de DN, las variables con capacidad predictiva sobre la clasificación del DN eran el inicio temprano del dolor en el DN a nivel y el hecho de que la lesión sea incompleta en el DN por debajo. Conclusión. El DN aparece con frecuencia después de la LM y se da de forma más común en aquellos pacientes que han sufrido la lesión a edades más avanzadas. El DN tiene un impacto negativo en la percepción de bienestar psicológicoAIMS. To determine the prevalence of neuropathic pain (NP) in a sample of patients with spinal cord injury (SCI), to examine the relation between clinical, demographic and psychological characteristics with the prevalence of NP after SCI and the different types of NP, and to study predictive factors. PATIENTS AND METHODS. Transversal observational study of 260 patients who attended their annual revision. Main outcome measures included presence/absence of NP, psychological well-being index, detailed pain history and 0-10 numerical rating scale of average pain intensity. RESULTS. 93 patients (36%) with SCI had NP. Of the patients with NP, 35% showed pain at level, while 65% showed NP below the level of injury. The only variable with a predictive value on the prevalence of NP was older age at the time of SCI. Statistically significant differences were observed between the prevalence of NP and the perception of psychological well-being; patients with NP were the ones with more psychological distress. As for the different types of NP, the variables with predictive value on the classification of NP were early onset of pain at level, and incompleteness of the lesion in the below level NP. CONCLUSION. The results of this study show that NP appears frequently after SCI being more prevalent in patients who suffered the injury at more advanced ages. NP has a negative impact on the perception of psychological well-bein

Incidence and characteristics of adverse drug reactions in a cohort of patients treated with PD-1/PD-L1 inhibitors in real-world practice

Adverse reaction; Immunotherapy; PharmacovigilanceReacción adversa; Inmunoterapia; FarmacovigilanciaReacció adversa; Immunoteràpia; FarmacovigilànciaBackground: Data related to adverse drug reactions (ADRs), specifically immune-related adverse events (irAEs), in long-term treatment with immunotherapy in real-world practice is scarce, as is general information regarding the management of ADRs. Objectives: To characterize and describe the incidence of ADRs in patients who began immunotherapy treatment in clinical practice. Methods: In a prospective observational study cancer patients ≥18 years of age who were treated with a monotherapy regime of PD-1/PD-L1 inhibitors were evaluated. The study period was from November 2017 to June 2019 and patients were followed up until June 2021. Patients were contacted monthly by telephone and their electronic health records were reviewed. Each ADR was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). Results: Out of 99 patients, 86 met the inclusion criteria. Most were male (67.4%), with a median age of 66 (interquartile range, IQR: 59–76). The most frequent cancer was non-small cellular lung cancer (46 cases, 53.5%), followed by melanoma (22, 25.6%). A total of 74 patients (86%) were treated with anti-PD-1 drugs and 12 (14%) were treated with anti-PD-L1 drugs. The median treatment durations were 4.9 (IQR: 1.9–17.0) and 5.9 months (IQR: 1.2–12.3), respectively. Sixty-three patients (73%) developed from a total of 156 (44% of the total number of ADR) irADRs, wherein the most frequent were skin disorders (50 cases, 32%, incidence = 30.5 irADRs/100 patients per year [p-y]), gastrointestinal disorders (29, 19%, 17.7 irADRs/100 p-y), musculoskeletal disorders (17, 11%, 10.4 irADRs/100 p-y), and endocrine disorders (14, 9%, 8.6 irADRs/100 p-y). A total of 22 irADRs (14%) had a latency period of ≥12 months. Twelve irADRs (7.7%) were categorized as grade 3–4, and while 2 (1.3%) were categorized as grade 5 (death). Sixty-one irADRs (39.1%) in 36 patients required pharmacological treatment and 47 irADRs (30.1%) in 22 patients required treatment with corticosteriods. Conclusion: The majority of patients treated with anti-PD1/PDL1-based immunotherapy experienced adverse reactions. Although most of these reactions were mild, 11.5% were categorized as grade 3 or above. A high percentage of the reactions were immune-related and occurred throughout the treatment, thereby indicating that early identification and close monitoring is essential

Combining fMRI and DISC1 gene haplotypes to understand working memory-related brain activity in schizophrenia

Altres ajuts: Ministerio de Ciencia e Innovación; Fondo Europeo de Desarrollo Regional (FEDER); European Social Fund ("Investing in your future"); Generalitat de Catalunya, Departament de Salut (SLT017/20/000233).The DISC1 gene is one of the most relevant susceptibility genes for psychosis. However, the complex genetic landscape of this locus, which includes protective and risk variants in interaction, may have hindered consistent conclusions on how DISC1 contributes to schizophrenia (SZ) liability. Analysis from haplotype approaches and brain-based phenotypes can contribute to understanding DISC1 role in the neurobiology of this disorder. We assessed the brain correlates of DISC1 haplotypes associated with SZ through a functional neuroimaging genetics approach. First, we tested the association of two DISC1 haplotypes, the HEP1 (rs6675281-1000731-rs999710) and the HEP3 (rs151229-rs3738401), with the risk for SZ in a sample of 138 healthy subjects (HS) and 238 patients. This approach allowed the identification of three haplotypes associated with SZ (HEP1-CTG, HEP3-GA and HEP3-AA). Second, we explored whether these haplotypes exerted differential effects on n-back associated brain activity in a subsample of 70 HS compared to 70 patients (diagnosis × haplotype interaction effect). These analyses evidenced that HEP3-GA and HEP3-AA modulated working memory functional response conditional to the health/disease status in the cuneus, precuneus, middle cingulate cortex and the ventrolateral and dorsolateral prefrontal cortices. Our results are the first to show a diagnosis-based effect of DISC1 haplotypes on working memory-related brain activity, emphasising its role in SZ

Telepsychiatry During the COVID-19 Pandemic: Development of a Protocol for Telemental Health Care

Background The rapid spread of the Coronavirus disease 2019 (COVID-19) has forced most countries to take drastic public health measures, including the closure of most mental health outpatient services and some inpatient units. This has suddenly created the need to adapt and expand telepsychiatry care across the world. However, not all health care services might be ready to cope with this public health demand. The present study was set to create a practical and clinically useful protocol for telemental health care to be applied in the context of the current COVID-19 pandemic. Methods A panel of psychiatrists from 15 different countries [covering all World Health Organization (WHO) regions] was convened. The panel used a combination of reactive Delphi technique and consensus development conference strategies to develop a protocol for the provision of telemental health care during the COVID-19 pandemic. Results The proposed protocol describes a semi-structured initial assessment and a series of potential interventions matching mild, moderate, or high-intensity needs of target populations. Conclusions Telemedicine has become a pivotal tool in the task of ensuring the continuous provision of mental health care for the population, and the outlined protocol can assist with this task. The strength of this protocol lies in its practicality, clinical usefulness, and wide transferability, resulting from the diversity of the consensus group that developed it. Developed by psychiatrists from around the globe, the proposed protocol may prove helpful for many clinical and cultural contexts, assisting mental health care providers worldwide