Pharmacological Treatment of Insomnia Symptoms in Individuals with Substance Use Disorders in Spain: A Quasi-Experimental Study.

INTRODUCTION: Pharmacological treatment of insomnia in patients with addictions has been hardly investigated and there are few researches about it in an inpatient detoxification. The aim of this study was to describe the outcomes of the pharmacological treatment of insomnia in SUD patients admitted to a detoxification unit in Spain, with a focus on the primary substance of abuse and co-occurring mental disorders. METHODS: A quasi-experimental study was conducted in 481 addicted in patients, who were admitted for substances detoxification in Vall d´Hebron University Hospital, Barcelona, Spain, from 2010 to 2015. The patients underwent systematic evaluation of axes I and II psychiatric disorders (SCID-I, SCID-II, and CAADID). Insomnia was evaluated using a night time sleep log. Substance-dependent patients, who had insomnia during hospital detoxification, received a psychotropic medication with hypnotic effect, keeping the regular clinical practice without randomization. RESULTS: At discharge, insomnia was considered to have been alleviated in 63.8% (n = 204) of patients while 36.2% (n = 116) of patients remained with insomnia disturbances. Comparing hypnotic treatments it was observed that mirtazapine and clotiapine were the treatment that corrected the insomnia more frequently. DISCUSSION: Since insomnia is not corrected in all patients, it should be further investigated in medications with hypnotic purpose. Based on the results of this work, randomized clinical trials might be proposed.

Higher severity of cocaine addiction is associated with tactile and somatic hallucinations.

BACKGROUND: The aim of this study is to describe the features of cocaine-dependent patients who have had cocaine-induced tactile/somatic hallucinations (CITSH), and to analyze the association with addiction-related variables and psychiatric comorbidity, comparing patients with CITSH, patients with cocaine psychotic symptoms (CIP) and no CITSH, and patients without any psychotic symptom. METHOD: A cross-sectional study was conducted in 767 cocaine-dependent patients in an outpatient treatment center for addictions. The following data were obtained: sociodemographic characteristics, CIP information, addiction-related variables and psychiatric comorbidity. A bivariate and multivariate analysis was performed. RESULTS: Of the whole sample, 6.6% reported CITSH at some point of their lives, 48.4% had suffered some CIP other than CITSH, and 45% had not experienced any psychotic symptom. According to multivariate analysis, risk of overdose increases by 12.1 (OR) times the probability of having had CITSH compared patients with CIP-no-CITSH. Other variables associated to patients with CITSH were: age of drug use onset, presence of episodes of overdose, prevalence of psychotic disorder induced by cocaine. In general, in all variables studied, patients with CITSH presented worse clinical features (addiction variables and psychiatric comorbidity) than patients with CIP without CITSH and non-CIP group. CONCLUSION: CITSH are usually associated with other psychotic symptoms induced by cocaine. The patients who experienced CITSH are more severe cases compared both with patients with CIP without CITSH and patients without CIP. Increased risk of overdose is an important issue in this type of patients.

Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence.

Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed after a 5 µM cocaine exposure, whereas no changes in gene expression or in neuronal activity took place at 1 µM cocaine. Changes in gene expression were identified in a total of 756 genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as mitogen-activeated protein kinase (MAPK), CREB, neurotrophin and neuregulin signaling pathways. Some genes displaying altered expression were subsequently targeted with predicted functional single-nucleotide polymorphisms (SNPs) in a case-control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3'-untranslated region of the NFAT5 gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with magnetic resonance imaging, did not correlate with NFAT5 variation. These results suggest that the NFAT5 gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence.

Gonococcal arthritis.

Disseminated gonococcal infection is the most common systemic complication of acute gonorrhea and occurs in 0.5% to 3.0% of patients with untreated mucosal infection. It is also the most common cause of septic arthritis in patients less than 30 years of age. Fortunately, the incidence of gonorrhea is decreasing dramatically in the United States and Western Europe, although it is still high in developing countries. Increasing resistance to antibiotics requires continuous surveillance of antimicrobial susceptibilities to determine the efficacy of current therapeutic measures.

IgA anticardiolipin and anti-beta2-glycoprotein I are the most prevalent isotypes in African American patients with systemic lupus erythematosus.

BACKGROUND: Ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies in patients with systemic lupus erythematosus (SLE). Few studies have been done in the African American population. METHODS: Serum samples from 100 African American patients with SLE were tested for IgG, IgM, and IgA aCL and anti-beta2-GPI antibodies by enzyme-linked immunosorbent assay (ELISA). Computerized clinical data on these patients were reviewed with a specific focus on clinical manifestations of antiphospholipid syndrome (APS). RESULTS: Positivity for at least one isotype of aCL antibodies was found in 33% of the patients, whereas 28% were positive for at least one isotype of anti-beta2-GPI antibodies. IgA was the most prevalent isotype for both antibodies; 24% of the patients in the aCL ELISA and 19% in the anti-beta2-GPI ELISA were positive for IgA. Positivity for both aCL and anti-beta2-GPI in the same patient was seen more frequently with the IgA isotype. Fewer than half of the patients positive for aCL antibodies had medium-to-high levels of antibodies. A few patients had presented thrombotic manifestations, and these patients were positive for aCL (P = 0.01) and anti-beta2-GPI antibodies (P = 0.02). No other manifestations of APS could be significantly correlated with the presence of these antibodies. CONCLUSIONS: Our results show that IgA is the most prevalent isotype among the African American patients with SLE studied. The predominance of the IgA isotype and the low prevalence of medium-to-high levels of aCL antibodies may account for the low frequency of clinical manifestations of APS in these patients.

[Treatment of hypertrophic obstructive cardiomyopathy with dual chamber pacing. Use of isoproterenol in determining the optimal AV interval]. / Tratamiento de la miocardiopatía hipertrófica obstructiva mediante marcapasos bicameral. Empleo del isoproterenol para determinar el intervalo AV óptimo.

Dual chamber pacing may be used as an alternative in the treatment of selected patients who are refractory to conventional medical treatment of hypertrophic obstructive cardiomyopathy. When programming the pacemaker it is essential to know the value of the atrio-ventricular interval which is able to cause the greatest reduction in the left ventricle outflow tract pressure gradient. We have used isoproterenol to calculate the parameter mentioned above. This allowed us to know the optimum value, not only in non-active conditions, but also reproducing the changes in the pressure gradient in different physiological situations.

[Prosthesis-related thrombosis cleared with fibrinolysis. Usefulness of transesophageal echocardiography]. / Trombosis protésica resuelta con fibrinólisis. Utilidad de la ecocardiografía transesofágica.

Thrombosis is an infrequent complication in mechanical valve prostheses carrying a vital risk for the patient. The performance of transesophageal echocardiography (TEE) is high in differentiating the thrombosis from other causes of flow obstruction and is fundamental for establishing treatment. Fibrinolysis is an effective alternative treatment to surgery when the latter carries a high risk. In the case herein reported TEE provided a rapid and precise diagnosis and allowed to prove the resolution of the prosthetic thrombosis following fibrinolytic treatment.

[Pulmonary thromboendarterectomy in a patient with primary antiphospholipid syndrome]. / Tromboendarterectomía pulmonar en un paciente con síndrome antifosfolípido primario.

Pulmonary arterial hypertension (PAH) is an infrequent manifestation of the primary antiphospholipid syndrome (PAPS). It may appear due to different mechanisms although the most common cause is recurrent pulmonary embolisms. In some cases the thrombi do not dissolve and organize to form fibrous masses which occlude the pulmonary veins giving place to chronic thromboembolic pulmonary hypertension. When the thrombi are located in the proximal arteries, thromboendarterectomy may be curative. The first case of a patient with PAPS diagnosed with PAH secondary to chronic thrombosis of the proximal pulmonary arteries, in whom a successful pulmonary thromboendarterectomy was performed is herein reported.

[Acute pancreatitis due to antimonials in patients with visceral leishmaniasis and HIV infection]. / Pancreatitis aguda por antimoniales en pacientes con leishmaniasis visceral e infección por VIH.

Acute pancreatitis is an adverse effect of the treatment with antimonial drugs which is infrequently described in patients with HIV infection and visceral leishmaniasis (VL). Twenty-two percent of the patients having this treatment had acute pancreatitis (7 cases) in the authors' center. In all the cases, severe immunosuppression was present with pancreatitis appearing following the administration of 3,400 to 15,300 mg of stibogluconate. The pancreatitis was slight in the 7 cases with no complications of note and with no symptoms observed in three cases. The maximum values of amylasemia ranged from 976 to 2,568 U/l, from 1,055 to 5,860 U/l for lipasemia, and from 1,970 to 25,520 U/l for trypsinemia. These values returned to normal from 15 days to 2 months after suppression of the drug. Stibogluconate was readministered in three patients due to VL recurrence with a further acute pancreatitis being observed. The authors conclude that acute pancreatitis is a relatively infrequent complication of antimonial treatment for VL in patients with HIV infection and believe that a maximum dose of 850 mg/day should not be surpassed.

[Anti-beta 2 glycoprotein I antibodies. Relationship with antiphospholipid antibodies and thrombosis]. / Anticuerpos anti-beta 2-glucoproteína I. Relación con los anticuerpos antifosfolípido y trombosis.

BACKGROUND: Anti-beta 2-glycoprotein I antibodies (a beta 2GPI) were studied in patients with diseases or clinical symptoms related to antiphospholipid antibodies (aPl) with the aim of establishing a relationship between both antibodies and these clinical manifestations. METHODS: The a beta 2GPI antibodies were determined by enzymeimmunoassay in a group of 94 altruist blood donors and 135 patients (98 with systemic lupus erythematosus, 21 cases of primary antiphospholipid syndrome, 10 cases with idiopathic Sneddon syndrome and 6 with Q fever). The lupus anticoagulating-type aPl antibodies were determined in the same subjects by kaolin coagulation time and the Russell's viper venom time while anticardiolipin-type IgG, IgM and IgA isotypes were determined by enzymeimmunoassay. The a beta 2GPI antibodies were related with the aPl antibodies, fetal losses and history of thrombosis by a contingency table with Yates correction in the first two parameters and means comparison by the Students' t test for the history of thrombosis. RESULTS: The aPl and a beta 2GPI antibodies in the control group were negative. In the group of patients the latter antibodies were positive in 33.6% (33 cases) of the patients with lupus, 57% (12 cases) of the patients with primary antiphospholipid syndrome, in one of the patients with the Sneddon syndrome and in none of the patients with Q fever. The aPl antibodies were positive in 26.5% of the patients with lupus and in 100% of the cases with primary antiphospholipid syndrome or Q fever and negative in all the cases with idiopathic Sneddon syndrome. A significant relationship was found between the a beta 2GPI antibodies and thrombotic manifestations (p = 0.01) or obstetric complications (p < 0.04). A dependent relationship was observed in both autoantibodies (aPl and a beta 2GPI) (p < 0.01). CONCLUSIONS: There is a significant relationship between the antiphospholipid antibodies and the anti-beta 2-glycoprotein I antibodies in addition to a relationship with thrombotic symptoms or obstetric complications.

[Acceptance of generic prescribing in general practice: effect of patient education and reference prices]. / Aceptación de los fármacos genéricos en equipos de atención primaria: efecto de una intervención educativa y de los precios de referencia.

AIMS: To assess patient acceptance of the substitution of brand-name drugs for generic equivalents in the context of repeat prescriptions for chronic diseases. METHODS: A prospective multicenter study of drug use was performed. Of the 31 centers included in the study, 8 were randomized to the intervention group and 23 to the control group. For 1 year, patients in the intervention group who visited the center to collect repeat prescriptions received verbal and written information on the advantages and disadvantages of generic and brand name drugs. Data on the number of patients taking brand-name drugs for which generic equivalents were available, as well as the reasons and variables related to refusal of generic drugs (age, gender, education, primary care centre, general practitioner, type of drug and total number of repeat prescriptions) were collected. The percentage of generic drugs among the total number of drugs prescribed was calculated at 2-monthly intervals. RESULTS: A total of 98.9% of the 4620 patients in the intervention group agreed to change to a generic formulation. The percentage of patients accepting generic drugs was significantly associated with the primary care centre, the class of drug, doctors' influence, and patient satisfaction with the drug. Generic prescriptions represented 5.9% in the intervention practices compared with 2.8% in controls. After the intervention, and before the application of reference prices, the percentages were 6.7% and 3.9%, respectively. Immediately after application of the reference prices, the percentages were 8.6% and 6.3%, respectively. CONCLUSIONS: Direct patient education is an effective strategy in increasing the prescription of generic equivalents. General practitioners' motivation and knowledge of generic drugs influenced their use. The application of reference prices increased the use of generic equivalents.

Thalidomide in the treatment of cutaneous lupus refractory to conventional therapy.

OBJECTIVE: We describe a prospective treatment study of thalidomide in a series of 22 patients with cutaneous lupus refractory to other treatments. METHODS: From 1992 to 1998, 22 patients with cutaneous lupus (9 with discoid lupus erythematosus, 7 with subacute cutaneous lupus, 4 with profundus lupus, 2 with nonspecific rash) were treated with thalidomide. Initial treatment was started at 100 mg daily. If the cutaneous lesions vanished, the dose was lowered to 50-25 mg daily as a maintenance therapy and it was considered a complete remission. If the lesions improved but remained, this was considered a partial response and treatment was continued until the lesions were not further modified. Periodically, adverse effects were evaluated. RESULTS: Three patients discontinued treatment because of side effects such as vertigo, persistent drowsiness, or paresthesia. Rash improved in 16/19 patients (84%). Complete remission occurred in 12/16 (75%). In 9 (65%) the rash resolved, but recurred 4-16 weeks after withdrawal of thalidomide; when it was used again, they improved. Partial response was achieved in 4/16 (25%) patients. No response occurred in 3/19 (16%). Many patients noted improvement within 2 weeks after starting thalidomide and maximum benefit was achieved within 3 months. Five of the 14 women had amenorrhea during the treatment with thalidomide. CONCLUSION: Thalidomide is effective in the treatment of cutaneous lupus refractory to other treatments. However, only some patients had a remission; the remainder relapsed when treatment was withdrawn, or required low doses of thalidomide to preserve inactive lesions. Amenorrhea was observed as a new secondary effect of thalidomide.

[Visceral leishmaniasis in patients with HIV infection]. / Leishmaniasis visceral en pacientes con infección por HIV.

BACKGROUND: Visceral leishmaniasis (VL) is an endemic parasitosis in Spain with a frequency which is increasing, specially among those patients with HIV infection. METHODS: The clinical characteristics of 36 episodes of VL in 20 patients with HIV infection diagnosed in the authors' center from January 1988 to October 1993 are herein described. The appearance of recurrences and mortality rate were analyzed with survival curves. RESULTS: The most frequently observed findings were constitutional syndrome (92%), fever (67%), splenomegaly (86%), hepatomegaly (80%) and hematologic changes (100%) with the symptoms being of longer duration in the initial episodes than in the recurrences. In 97% of the patients the CD4+ lymphocyte count was lower than 200 x 10(6)/l, with greater immunosuppression observed during the recurrences. Serology (IFI) was positive in 25% of the patients. Microscopic examination of bone marrow aspirate demonstrated the presence of Leishmania amastigotes in 82% of the initial episodes and in all the recurrences. Neither the bone marrow biopsy nor the culture improved this performance. Less than 10% of the episodes were recurrence free at 12 months of evolution with allopurinol prophylaxis not being useful. Mortality directly attributable to VL was nul and the survival curve showed a worse prognosis for patients who had a diagnosis of AIDS previously or simultaneously to the presentation of VL. CONCLUSIONS: The clinical manifestations of visceral leishmaniasis in patients with HIV infection are similar to those presented by non immunosuppressed patients. The serology is little sensitive for diagnosis and the exploration of choice is the microscopic examination of the bone marrow aspirate. The prognosis of acute infection is good but the frequency of recurrence is high. The authors believe that visceral Leishmaniasis should be considered as a diagnostic criteria for AIDS.

Effect of antiphospholipid antibodies on beta(2) glycoprotein I-phospholipid Interaction.

PROBLEM: Beta(2)glycoprotein I (beta(2)GPI) physiologically binds to negatively charged phospholipids (PLs) and is a natural regulator of the coagulation cascade. Thrombotic clinical complications and recurrent fetal loss associated with autoimmune antiphospholipid (aPL) antibodies are thought to be related to their binding to Beta(2)GPI-PL complex and interference with the physiological function of Beta(2)GPI. METHOD OF STUDY: To investigate the effect of aPL on beta(2)GPI-PL interaction, we studied the binding of biotinylated Beta(2)GPI to cardiolipin (CL) by enzyme-linked immunosorbent assay (ELISA) in the presence and absence of purified aPL immunoglobulin G (IgG) antibodies. RESULTS: Adding five different aPL IgG antibodies with different levels of aPL activity isolated from the sera of five patients with aPL-associated recurrent fetal death greatly increased the binding of biotinylated beta(2)GPI to CL-coated plates. The optical densities (ODs) were 0.635, 0.890, and 1.265 in the presence of three aPL IgG antibodies, compared to 0.425 in the absence of aPL IgG. In contrast, normal human IgG had no enhancing effect. The OD was 0.480 and 0.425, respectively. The enhancement of beta(2)GPI binding to CL by aPL IgG correlated with the titers of aPL antibodies. The use of phosphate-buffered saline with increasing salt concentrations as a washing buffer for the ELISA resulted in more stable binding of beta(2)GPI to PL in the presence of aPL IgG. CONCLUSIONS: These findings suggest that the binding of autoimmune aPL antibodies to beta(2)GPI-PL complex results in abnormally tighter interaction between beta(2)GPI and PLs, which may lead to physiological dysfunction of beta(2)GPI as a regulator of coagulation.

Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides.

We previously induced pathogenic antibodies against anionic phospholipids (PL) in experimental animals by immunization with lipid-free purified human beta2glycoprotein I (beta2GPI). We hypothesized that antiphospholipid antibodies (aPL) are induced by in vivo binding of foreign beta2GPI to self-PL, thus forming an immunogenic complex against which aPL antibodies are produced. If this hypothesis is true, other PL-binding proteins that are products of ubiquitous viral/bacterial agents may also induce aPL. To test this hypothesis, groups of NIH/Swiss mice were immunized with synthetic peptides of viral and bacterial origin that share structural similarity with the putative PL-binding region of beta2GPI. Compared with the control groups, animals immunized with the peptides produced significantly higher levels of aPL and anti-beta2GPI antibodies. These findings demonstrate that some PL-binding viral and bacterial proteins function like beta2GPI in inducing aPL and anti-beta2GPI production, and are consistent with a role for such viral and bacterial proteins in inducing aPL antibody production in humans.

Anticardiolipin and anti-beta2glycoprotein-I antibodies in patients with systemic lupus erythematosus: comparison between Colombians and Spaniards.

We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-beta2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-beta2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and anti-beta2GPI ELISA was more specific than aCL in both populations.

Antiphospholipid (Hughes') syndrome in African-Americans: IgA aCL and abeta2 glycoprotein-I is the most frequent isotype.

Antiphospholipid (Hughes') syndrome (APS) has not been reported in African-Americans (A-A) as frequently as in other ethnic groups. We describe eight A-A female patients with APS, including two cases of primary APS (PAPS), four with APS secondary to systemic lupus erythematosus (SLE), one with Sjögren's syndrome, and one with overlap connective tissue disease (CTD). Their mean age was 34 y (range 24-47 y). Patients were followed for a mean of 6 y (range 0.3-11 y). During follow up, both anticardiolipin (aCL) and anti-beta2glycoprotein-I (abeta2GPI) antibodies were measured in stored sera by enzyme-linked immunosorbent assay (ELISA). IgA was the most frequent isotype of aCL and abeta2GPI, and co-occurred with the IgM isotype in three of four patients with neurologic manifestations.

[Survey on the needs expressed by primary care doctors for continuing education in drug therapy]. / Encuesta sobre las necesidades sentidas por médicos de atención primaria sobre la formación continuada en terapéutica farmacológica.

OBJECTIVE: To describe the aspects of continuing education in pharmacological therapeutics considered as most relevant by the primary health care physicians. DESIGN: Observational study.Setting. Physicians filled-up the questionnaires during 45 minutes at their primary health care centres. PARTICIPANTS: Primary health care physicians involved in the Fundation Institut Català de Farmacologia continuing education activities since 1997 were selected. MAIN MEASUREMENTS: A specific questionnaire was designed to collect the physicians' opinion on different topics regarding continuing education in pharmacological therapeutics. RESULTS: 180 physicians from 21 primary health care centres answered the questionnaire. 68% of the responding physicians considered that continuing education has to be useful to improve routine clinical practice. Regular seminars and methods stimulating active participation administered by primary health care professionels are preferred. Continuing education in pharmacological therapeutics should be focused to health problems rather than being drug-oriented. They referred being more interested in drug selection issues and in the role of new drug in comparison with the existing alternatives rather than in regulation and drug consumption issues. 66,3% of the responding physicians considered that continuing education in pharmacological therapeutics should be compulsory. Public health authorities and primary health care physicians should share the responsibility in setting-up continuing education in pharmacological therapeutics programs, according to the opinion of almost 70% of the physicians. CONCLUSIONS: Primary health care physicians are interested in continuing education in pharmacological therapeutics as far as it is practical and useful to solve problems of their routine clinical practice.