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Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505.

*Kemeriz, Funda ( Aksaray, Yazar ) *Ordu, Melike ( Aksaray, Yazar ), Dear Editor Omalizumab is a humanized monoclonal antibody against human immunoglobulin E that is mainly indicated in asthma, allergic rhinitis, chronic spontaneous urticaria and is being increasingly used for other dermatological diseases, including atopic dermatitis, mastocytosis, hyper-IgE syndrome, and bullous pemphigoid.1,2 Rare cutaneous side effects, such as itching, skin rash, urticaria, and photosensitivity, have been reported to be associated with omalizumab use.

Acute generalized exanthematous pustulosis (AGEP) is a toxic cutaneous reaction pattern that is mostly caused by drug intake and rarely associated with spider bites. We report a case of a female patient, 47 years old, with febrile pustular lesions on an erythematous base at the abdominal region. She had three violaceous erythematous and edematous plaques on the interscapular region, one of which had a necrotic crust at its center. The lesions were compatible with spider bites. By considering histopathological and clinical findings, the patient was diagnosed with AGEP. Since she had no history of drug intake, viral infection or other triggers, a spider bite was thought to have caused the AGEP. © Copyright 2020 by Turkish Society of Dermatology and Venereology Turkderm - Turkish Archives of Dermatology and Venereology published by Galenos Yayınevi., The authors declared that this study has received no financial support.

The objective of the study is to analyze the factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis. The methodology used is based on a cross-sectional study in patients receiving hemodialysis at the Centro Nacional de Salud Renal. Severe pruritus was defined as a score on the visual analogue scale greater than or equal to 7, and the strength of association with the possible risk factors was assessed by calculating prevalence ratios. Regarding the results, 264 patients were included, 59.9% were male, with a mean time on hemodialysis of 10.26 ± 7.14 years. 75% experienced pruritus, of this group, 1 in 3 presented severe pruritus. Hyperphosphatemia and the use of antihistamines were associated with a higher prevalence of severe pruritus (RP 1.71, 95% CI 1.09-267 and RP 2.39, 95% CI 1.51-3.75, respectively). The positive serology for Hepatitis C Virus was described as a protective factor for presenting severe pruritus (RP 0.55, 95% CI 0.33 - 0.89). In conclusion, severe uremic pruritus is a frequent problem in patients with chronic terminal kidney disease who have hyperphosphatemia and treatment with antihistamines independently of the time they have been on hemodialysis. Revisión por pares

Background The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases. Methods ARIA serves to improve the care of patients with allergies and chronic respiratory diseases. In collaboration with other international initiatives, national associations and patient organizations in the field of allergies and respiratory diseases, real-life integrated care pathways have been developed for a digitally assisted, integrative, individualized treatment of allergic rhinitis (AR) with comorbid asthma. In the present work, these integrated care pathways have been adapted to the German situation and health system. Results The present ICP (integrated care pathways) guideline covers key areas of the care of AR patients with and without asthma. It includes the views of patients and other healthcare providers. Discussion A comprehensive ICP guideline can reflect real-life care better than traditional guideline models.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of interventions for pruritus of unknown cause in adults and children. © 2018 The Cochrane Collaboration.

OBJECTIVE: Antibiotic drugs are frequently used for viral infections in children. It is probable that health beliefs and parental concern have great influence on the use of drugs in children. This study, performed in The Netherlands, investigates whether the use of antibiotics in children is associated with the use of medicines by parents. DESIGN: Observational cohort study, using a prescription database. METHODS: We selected 6,731 children from the prescription database IADB.nl, who did not receive antibiotics until their fifth birthday, and 1,479 children who received at least one antibiotic prescription in every year. The parents for each group of children were identified and we compared the use of antibiotics and other medicines between the two groups of parents. RESULTS: Parents of children who received antibiotics recurrently were found to use more antibiotics themselves than parents of children who did not receive antibiotics. Moreover, this group showed a higher percentage of chronic medication use: 11.3% versus 6.2% (mothers) and 13.1% versus 9.5% (fathers). Mothers more often used antacids, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anxiolytics, hypnotics, antidepressants, asthma drugs and antihistamines. Fathers used more antacids, cardiovascular drugs, NSAIDs and asthma drugs. CONCLUSIONS: The parents of children who receive antibiotic drugs regularly use more medicines than the parents of children who use no antibiotic drugs. Parents' medicine use may influence that of children and is a factor physicians and pharmacists should take into account.

Objectives: This study describes the occurrence of angioedema among patients initiating ACEI therapy and evaluates the association of this outcome with demographic factors, co-medication and chronic comorbidities. Methods: A nested case-control study was conducted in a cohort of patients newly treated with ACEIs from 2007 to 2014 in the CPRD. Cases who had angioedema only during ACEI treatment were identified using medical codes and were matched on the duration of ACEI treatment at the angioedema date (index date) with up to 20 controls who never had angioedema recorded. The use of co-medication (anti-diabetics, antihistamines, anti-asthmatics, non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, calcium channel blockers and statins), was acquired from CPRD prescription records within a three months' time window before the index date. The history of comorbidities (asthma, allergy, chronic obstructive pulmonary disease (COPD), diabetes mellitus and rheumatoid arthritis) was retrieved from medical records any time before the index date. Odds ratios (ORs) and p-values were estimated using univariate logistic regression analysis. Results: The cohort included 276,977 patients aged ≥ 45 years initiating ACEI therapy. The study population included 416 cases of angioedema during ACEI therapy matched with 4,335 controls. Age over 65 years was associated with angioedema. The proportions of asthma, allergy, COPD and rheumatoid arthritis were significantly higher in ACEI consumers who developed angioedema during ACEI therapy (ORs 1.83, 2.03, 2.08 and 2.83 respectively; p

Background: Previous studies have shown that elosulfase alfa has a favorable efficacy/safety profile in Morquio A patients aged ≥5 y. This study evaluated safety and impact on urine keratan sulfate (uKS) levels and growth velocity in younger patients. Methods: Fifteen Morquio A patients aged

Objective: To describe the frequency, nature, determinants and clinical relevance of prescription modifications in a Dutch community pharmacy. Design: A descriptive, retrospective study of the documented prescription modifications during dispensing in 2007. Methods: The frequency and nature of prescription modifications and their patient, drug and prescriber related determinants were assessed. To examine the clinical value of pharmacists' interventions, each prescription modification was rated from A to D (A is clinically irrelevant, D is clinically relevant with possible fatal consequences for the patient). Results: In 2007, on average, one intervention was documented per workday. Almost 50% of all interventions concerned dose corrections. Prescriptions for incidental medications, children (0-20 year) and patients with less than four other medications, had a higher chance of modification. A higher chance of prescription modifications was found in anti-infective agents for systemic use, in treatments for the central nervous system and the sensory organs. Verification and attentiveness to the prescriptions of these risk groups can reduce (serious) clinical consequences. Of all prescription modifications 86% were clinically relevant (groups B, C and D) and every ten days at least one harmful clinical incident was prevented by prescription modifications. Conclusions: Modifications of prescriptions by pharmacists vary in nature from clinically irrelevant to potentially fatal. Analysis of documented interventions in one community pharmacy allows identification of patients who are at risk and need more attention from prescribing physicians. It also shows that pharmacists' interventions have a positive impact on patients' health.

Objective: To analyze prescribing patterns of chronic psychiatric patients living in sheltered housing facilities, to identify the extent of polypharmacy and to estimate associated risks in this patient group. Methods: In a retrospective cross-sectional study the prescription data of 323 chronic psychiatric patients (average age 48.5 years) living in sheltered housing facilities in Rotterdam, The Netherlands, were analyzed. Prescription data were obtained from pharmacy-dispensing records. Results: Patients received on average 4.6 drugs (95% CI, 4.3-4.9). The most frequently prescribed drugs were as expected antipsychotics, benzodiazepines and antimuscarinic drugs. Overall 25% (n = 81) of patients received two or more antipsychotic drugs. A high proportion of patients (38%, n = 124) received one benzodiazepine, and 15% (n = 50) received two or more benzodiazepines. Conclusion: Patients in our study received a worryingly high number of drugs, and a quarter of the population was subject to antipsychotic polypharmacy. This increases the risk that drug-drug interactions, adverse drug reactions and noncompliance occur. Our study indicates potentially low quality of prescribing and shows the need for reviewing and special monitoring of pharmacotherapy in this patient group. © 2008 Dustri-Verlag Dr. K. Feistle.

BACKGROUND: Childhood allergic diseases have a major impact on a child's quality of life, as well as that of their parents. We studied the coexistence of reported allergies in children who use asthma medication. Additionally, we tested the hypothesis that asthma severity is greater among children with certain combinations of co-morbid allergic conditions. METHODS: For this cross-sectional study, 703 children (ages 4 to 12 years) from the PACMAN cohort study were selected. All of the children were regular users of asthma medication. The study population was divided into nine subgroups according to parental-reported allergies of the child (hay fever, eczema, food allergy or combinations of these). In order to assess whether these subgroups differed clinically, the groups were compared for child characteristics (age, gender, family history of asthma), asthma exacerbations in the past year (oral corticosteroids (OCS) use; asthma-related emergency department (ED) visits), asthma control, fractional exhaled nitric oxide level (FeNO), and antihistaminic usage. RESULTS: In our study, 79.0 % of the parents reported that their child suffered from at least one atopic condition (hay fever, food allergy and eczema), and one quarter of the parents (25.6 %) reported that their child suffered from all three atopic conditions. Having more than one atopic condition was associated with an increased risk of OCS use (OR = 3.3, 95 % CI = 1.6 - 6.6), ED visits (OR = 2.3, 95 % CI = 1.2 - 4.6) in the past year and inadequate short term asthma control (OR = 1.9, 95 % CI = 1.3 - 2.8). CONCLUSIONS: Children who use asthma medication often also have other allergic conditions. Parental reported allergies were associated with a higher risk of more severe asthma (more asthma complaints and more asthma exacerbations).

Background: Since all antihistamines are capable of crossing the blood-brain barrier, they may also cause sedation which may impair daily activities such as driving a car. The purpose of this review was to examine the effects of antihistamines on driving ability. Method: A literature search revealed 18 double-blind placebo-controlled clinical trials that applied the on-road highway driving test. In this test, subjects are instructed to drive 100-km on a public highway with a steady lateral position and a constant speed (95 km/h). Primary outcome measure is the Standard Deviation of Lateral Position (SDLP, cm), i.e. the weaving of the car. Results: The literature search yielded 18 clinical trials. At therapeutic doses, a single dose of diphenhydramine, emedastine and hydroxizine impaired driving comparable or greater than the effects of BAC 0.08%. Clemastine, triprolidine, mizolastine, acrivastine, dexchlorpheniramine CR and mequitazine impaired driving performance to the same extent as BAC 0.05%. For mizolastine significant impairment was only seen after higher than therapeutic doses. Results for cetirizine were mixed, illustrating the drug has the potential to impair driving performance, especially in sensitive subjects. Terfenadine, loratadine, levocetirizine, desloratadine, ebastine, bilastine fexofenadine and rupatadine showed no driving impairment in the standard driving test after acute administration of their recommended dose. Several studies examined subchronic effects of antihistamines on driving performance. After 4 days of daily treatment significant driving impairment was found for emedastine (2 and 4 mg bid), diphenhydramine (50 mg), clemastine (2 mg bid), triprolidine (5 mg bid), after 5 days of ebastine (30 mg), and after 8 days of hydroxyzine (50 mg). Mixed results were found for cetirizine (10 mg), terfenadine (120 mg) and loratadine (20 mg). No significant differences from placebo were observed after 4 days of subchronic treatment with triprolidine (10 mg), levocetirizine (5 mg), fexofenadine (up to 120 mg), and after 8 days of daily treatment with dexchlorpheniramine (6 mg), bilastine (20 and 40 mg), and mequitazine (10 mg). Conclusion: First- and second-generation antihistamines may significantly impair driving performance. The newer antihistamines such as levocetirizine and fexofenadine that cross to blood brain barrier to a much lesser degree do not show clinically relevant sedation or driving impairment.

Background: Allergic rhinitis was recently classified by the ARIA guidelines as persistent or intermittent. Levocetivizine was shown to improve symptoms and health-related quality of life of patients with persistent allergic rhinitis in the XPERT™ study, a 6-month randomized double blind placebo-controlled trial. Objective: To assess the total costs of persistent allergic rhinitis, and the effect of long-term treatment with levocetirizine on these costs from several perspectives (societal, social security system, and employers). Methods: Direct medical cost parameters (medications, physician visits and hospitalizations) and time lost parameters (workdays and Usual Daily Activities (UDA) lost) related to persistent allergic rhinitis and its comorbidities (asthma, sinusitis, otitis and upper respiratory infection) were measured. A cost analysis was performed using 2002 French costing data. Results: From a societal perspective, the total cost of persistent allergic rhinitis without long-term treatment was estimated at €355.06/patient/month. From a social security perspective, levocetirizine treatment yielded an additional cost of €2.78/patient/month, compared to no-treatment. However, levocetirizine reduced the total cost of persistent allergic rhinitis and its comorbidities by €152.93/patient/month from a societal perspective and by €64.70/patient/month from an employer perspective. Most gains resulted from a decrease in the lost workdays and UDA in the levocetirizine group. Conclusion: The cost of persistent allergic rhinitis is substantial. Treatment with levocetirizine reduces the cost of persistent allergic rhinitis and its comorbidities to the society by €152.93/patient/month while improving symptoms and health-related quality of life. Copyright © Blackwell Munksgaard 2005. Chemicals / CAS: cromoglycate disodium, 15826-37-6, 16110-51-3, 93356-79-7, 93356-84-4; levocetirizine, 130018-77-8; prednisolone, 50-24-8; Cetirizine, 83881-51-0; Histamine H1 Antagonists, Non-Sedating; levocetirizine, 130018-77-8; Piperazines

The authors present a global overview on the issue of drugs and driving covering four major areas: (1) Epidemiology and Prevalence-which reviews epidemiological research, summarizes available information, discusses the methodological shortcomings of extant studies, and makes recommendations for future research to better define prevalence and epidemiology; (2) Effects of Medicinal and Illegal Drugs on Driving Performance-focuses on the six classes of drugs most often found in impaired and injured drivers, draws conclusions regarding the risk of these drugs to traffic safety and discusses the need for additional research; (3) Toxicological Issues-discusses ways to identify drug users via behavioral testing and analytical techniques, reviews the approaches used by different countries, screening and confirmation techniques, alternative specimens (e.g., urine, oral fluid, sweat), and how rapid roadside testing could be coupled with behavioral and laboratory testing in an effective approach to identifying and prosecuting drugged drivers; (4) Driving Under the Influence of Drugs [DUID] Laws-provides an overview of DUID laws in the United States and Europe, discusses the basic tenets of these laws, the various types of DUID statutes, the reasons why many existing laws hinder the prosecution of drugged drivers and the rationale for developing per se legislation as a strategy to more effectively manage the drugged driver problem.

The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague–Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3–H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

OBJECTIVE: Antibiotic drugs are frequently used for viral infections in children. It is probable that health beliefs and parental concern have great influence on the use of drugs in children. This study, performed in The Netherlands, investigates whether the use of antibiotics in children is associated with the use of medicines by parents. DESIGN: Observational cohort study, using a prescription database. METHODS: We selected 6,731 children from the prescription database IADB.nl, who did not receive antibiotics until their fifth birthday, and 1,479 children who received at least one antibiotic prescription in every year. The parents for each group of children were identified and we compared the use of antibiotics and other medicines between the two groups of parents. RESULTS: Parents of children who received antibiotics recurrently were found to use more antibiotics themselves than parents of children who did not receive antibiotics. Moreover, this group showed a higher percentage of chronic medication use: 11.3% versus 6.2% (mothers) and 13.1% versus 9.5% (fathers). Mothers more often used antacids, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anxiolytics, hypnotics, antidepressants, asthma drugs and antihistamines. Fathers used more antacids, cardiovascular drugs, NSAIDs and asthma drugs. CONCLUSIONS: The parents of children who receive antibiotic drugs regularly use more medicines than the parents of children who use no antibiotic drugs. Parents' medicine use may influence that of children and is a factor physicians and pharmacists should take into account.

Recently, two importance articles about St. John's wort (Hypericum perforatum) appeared in the medical literature: a randomised clinical trial comparing St. John's wort with placebo and imipramine and a commentary about interactions between St. John's wort and registered medicines. These publications are discussed in the broader perspective of a benefit-risk assessment.

BACKGROUND: In chronic inpatients polypharmacy is common and sometimes the combinations of psychotropics are irrational from a theoretical point of view. AIMS Registration of polypharmacy and irrational combinations in clinical practice. METHODS: In this descriptive study of 127 longstay patients in a psychiatric hospital we registrated the frequency of polypharmacy, the number of irrational combinations of psycho tropics and the reasons to describe these combinations. We tried to find a relation with the type of housing (an indirect measure for the intensity of care) and to the DSM-IV diagnosis. RESULTS: We found the use of four or five psychotropics in 24% of the population, in these cases we found irrational combinations in 89%. This group mainly consisted of patients with (partial) therapy-resistant schizophrenia of the undifferentiated and disorganised subtype and with schizo-affective disorder. In the total group of users of four and five psychotropics we found relatively more premorbid personality disorders and mild mental retardation. The percentage of users of four and five psychotropics increased with the intensity of care. Irrational combinations were mainly the result of long-lasting treatment of complex symptomatology. Following literature, a list of possible treatments in case of therapy resistance and conduct disorders is given. The authors give recommendations for further research on addition with a second high-potency antipsychotic drug in the case of therapy resistance for clozapine, and for fostering the quality of prescribing low-potency antipsychotic drugs and benzodiazepines for addition in the case of conduct disorders. CONCLUSIONS: Polypharmacy and irrational combinations occur frequently in chronic inpatients and seem inevitable.

Objective Antibiotic drugs are frequently used for viral infections in children. It is probable that health beliefs and parental concern have great influence on the use of drugs in children. This study, performed in The Netherlands, investigates whether the use of antibiotics in children is associated with the use of medicines by parents.Patients and methods In this observational cohort study, the authors selected 6731 children from the prescription database IADB.nl who did not receive antibiotics until their fifth birthday and 1479 children who received at least one antibiotic prescription every year. The authors then selected parents for each group of children (5790 mothers and 4250 fathers for the children who did not receive antibiotics and 1234 mothers and 1032 fathers for the children who regularly received antibiotics). The authors compared the use of antibiotics and other medicines between the two groups of parents.Results Parents of children who received antibiotics recurrently were found to use more antibiotics themselves compared with parents of children who did not receive antibiotics. Moreover, this group also showed a higher percentage of chronic medication use: (11.3 vs 6.2% (mothers) and 13.1% vs 9.5% (fathers)). Mothers more often use antacids, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anxiolytics, hypnotics, antidepressants, drugs for treatment of asthma and antihistamines. Fathers use more antacids, cardiovascular drugs, NSAIDs and asthma drugs.Conclusions The parents of children who receive antibiotic drugs regularly use more medicines compared with the parents of children who use no antibiotic drugs. Parents' medicine use may influence that of children and is a factor physicians and pharmacists should take into account.

Sociodemographic and clinical features of patients with bipolar I disorder in Turkey-HOME study Objective: The present study aimed to investigate the sociodemographic and clinical characteristics and compare the interregional differences in bipolar patients, who presented with manic episodes and were admitted to various psychiatry centers in 7 different regions of Turkey. Method: This observational study was conducted on 584 patients with manic episodes at 53 centers in 7 regions in Turkey during 2 years. Sociodemographic and clinical findings of patients with DSM-IV diagnosis of bipolar I disorder were collected to investigate the interregional differences. Results: The mean age, age at first hospital admission, and duration of bipolar disorder of 584 patients were 33.9 +/- 11.2, 26.1 +/- 8.6, and 8.6 +/- 8.2 years, respectively. In the psychiatric history the most frequently encountered episode was manic type and among manic episodes the most common type was mania with psychotic features. At baseline, the mean Clinical Global Impression and Young Mania Rating Scale scores were 4.87 +/- 0.9 and 33.2 +/- 9.3, respectively. While age at first hospital admission, the ratios of typical antipsychotic, lithium, anticonvulsant, and anticholinergic/antihistaminic uses at treatment history, duration and the dose of drugs used in the treatment of current episode demonstrated interregional differences, no significant difference was found among the patients in terms of sociodemographic features. Conclusion: The present study is the first and only large scale study up to date performed within this context in Turkey. We think that knowing regional variations will help to understand treatment needs of bipolar patients. Amaç: Bu çalışmada, Türkiye’nin farklı coğrafi bölgelerindeki çeşitli psikiyatri kliniklerine “manik atak” ile başvuranbipolar bozukluğu (BB) olan hastaların, başvuru sırasındakisosyodemografik ve klinik özelliklerinin araştırılması vebölgeler arası farklılıkların karşılaştırılması amaçlanmıştır.Yöntem: Bu gözlemsel çalışmaya 2 sene boyuncaTürkiye’nin 7 coğrafi bölgesindeki 53 merkezdeki 584manik atak hastası alınmış ve Mental Bozuklukların Tanısalve Sayımsal El Kitabı, Dördüncü Baskı ölçütlerine göre bipolar I bozukluk tanısı almış bu hastaların sosyodemografikve klinik bulguları bölgesel farklılıkları araştıracak şekildederlenmiştir.Bulgular: Yaş ortalaması 33.9±11.2 olan 584 hastanın doktora ilk başvuru yaşı ortalama 26.1±8.6 yıl ve BB ortalamasüresi 8.6±8.2 yıl idi. Hastaların psikiyatrik özgeçmişlerinde,en fazla manik tip atakların görüldüğü ve manik ataklarınçoğunun psikotik özellikli olduğu saptandı. BaşlangıçtakiKlinik Global İzlem ve Young Mani Değerlendirme Ölçekskorları sırasıyla 4.87±0.9 ve 33.2±9.3 idi. Doktora ilk başvuru yaşı, tedavi geçmişinde tipik antipsikotik, lityum,antikonvülzan ve antikolinerjik/antihistaminik kullanım sıklıkları, şimdiki atağın süresi ve tedavisinde kullanılan ilaçların dozları bölgeler arasında farklılık gösterirken, hastalarınsosyodemografik özellikleri açısından bölgeler arasındaistatistiksel olarak anlamlı bir fark bulunamamıştır.Sonuç: Çalışmamızın Türkiye’de bu çapta yapılan ilk ve tekçalışma olması ve bölgesel farklılıklara işaret etmesi nedeniyle ülkemiz özelinde bipolar hastaların tedavi ihtiyaçlarınıanlamaya yardımcı olacağı kanaatindeyiz.

Background Chronic ordinary urticaria (COU) can severely reduce quality of life and be difficult to control. Ultraviolet (UV) A and UVB phototherapy has been reported to decrease the release of histamine from either mast cells and/or basophils. Previous small studies have suggested that UVB phototherapy is a good alternative treatment for COU. Objectives The purpose of this study was to assess the efficacy of narrow-band UVB (NB-UVB) phototherapy for COU. Materials and methods Twenty-two patients (three male, 19 female) received NB-UVB phototherapy. These patients had not responded to at least two H1 antihistamines, and most had been treated with a variety of antihistamine combinations. Clinical responses were assessed according to an outcome scoring scale. During both visits, patients were administered the following: the visual analogue scale (VAS) on present pruritus and/or whealing; chronic urticaria impact on patients' quality of life according to the interference with daily activities, quality of sleep, and flare-up rates. Results The median number of treatments was 31.4 (9-44), and the mean top dose was 9.46 J/cm(2) (1.1-16.4 J/cm(2)). NB-UVB treatment led to clearance in 10 patients (45%), marked improvement in five (22%), and moderate improvement in seven (31%) patients according to an outcome scoring scale. Mild side effects were observed in two patients. Six patients who cleared or observed marked improvement remained clear at follow-up for a period of six months to one year, and other patients had a few recurrent lesions that did not need retreatment. For VAS scores and total chronic urticaria impact on patients' quality of life scores, the differences between baseline and after treatment scores were significantly lower (P < 0.001, P < 0.001, respectively). Conclusion Narrow-band UVB (NB-UVB) therapy is an effective, well-tolerated treatment option in second-line therapy for COU. This therapy can lead to subjective relief of pruritus and whealing and objective reduction of whealing. Further larger studies with longer follow-up periods are necessary to determine the proper clinical response and long-term complications of this therapy in COU.

In a multicentre trial of the EORTC ECTG we have treated 43 non-pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (Taxotere). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgery. They received 100 mg m-2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. Prophylactic steroids, antihistaminics or antiemetics were not routinely given. Two patients were not evaluable because they withdrew from the study because of a hypersensitivity reaction after the second cycle. The main toxicity was neutropenia (80% of cycles), although infections were rare (4%). One patient died from sepsis during neutropenia. Hypersensitivity reactions necessitating interruption of docetaxel (Taxotere) infusions were found in only 10% of cycles. The overall response rate was 23% with one complete response, and seven partial responses. Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxotere) is among the most active drugs for treatment of NSCLC. © Macmillan Press Ltd., 1994. 70 2 384 387

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: Liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma. © Macmillan Press Ltd., 1994. 70 2 376 379

SummaryBackground Anaphylaxis is a serious and potentially lethal systemic reaction affecting more than one organ or system. Objective We aimed to describe the demographic characteristics, clinical features, causes, settings, and administered therapy in Turkish children. Methods This retrospective, case note study included all children referred to the outpatient clinics of the Pediatric Allergy Departments of the participating study centres from 1 July 1999 to 30 June 2009 for investigation of anaphylaxis or who were seen by us at the moment of the reaction during the same period and who met the clinical criteria of anaphylaxis. Results Two hundred and twenty-four cases of anaphylaxis were reported in 137 children (88 boys, P = 0.0001). The mean ± SD age at the referral was 7.7 ± 4.2 years (range: 4 months–17 years). Ninety-eight episodes (43.8%) occurred at home. The symptoms were cutaneous in 222 (99.1%) episodes, respiratory in 217 (96.9%), neuro-psychiatric in 118 (52.7%), cardiovascular in 92 (41.1%), and gastrointestinal in 88 (39.3%). Biphasic reaction was reported in seven episodes (3.1%, 95% CI: 1.5–6.3). Death occurred in one case (0.4%, 95% CI: 0.08–2.4). Treatment was available in 158 episodes (70.5%). Of them, 148 (93.7%) received antihistamines, 132 (83.5%) corticosteroids, 51 (32.3%) epinephrine, and 17 (10.8%) beta-2-mimetics. The causative agents were foods in 86 (38.4%) episodes, hymenoptera venom in 84 (37.5%), drugs and medications in 47 (21.0%), and latex in 5 (2.2%). In two episodes (0.9%), the causative agent was unidentified. Allergy to the trigger was known prior to anaphylaxis in 116 (51.8%) episodes. An epinephrine auto-injector had been prescribed for 70 children (51.1%). Conclusions and Clinical Relevance Anaphylaxis was seen significantly more in boys. Most of the reactions occurred at home. Foods were the most frequent cause. Epinephrine, the first-line treatment of anaphylaxis, was administered in only a third of the children.

Fixed drug eruption (FDE) is characterized by solitary erythematous macules, edematous plaques and bullous lesions that occur at the same place with recurrent exposure to a drug. Though more than 100 drugs have been implicated in leading to FDE, this side effect is more commonly caused by tetracyclines, sulfonamides, sulfone, penicillins, pyrazolones, barbiturates, phenolphthalein, pirazones, aspirin, oral contraceptives and nonsteroidal anti-inflammatory drugs. FDE occurrence has been reported in association with cetrizine, hydroxyzine, loratadine and levocetirizine, which are widely used in the treatment of allergic diseases, such as allergic rhinitis, eczema, asthma, urticaria. Patch, intradermal skin, prick tests or oral challenge test can be performed to identify the agent responsible for FDE. A 43-year-old male patient attended our outpatient clinic with itchy and erythematous rashes with sporadic blisters, starting from dorsum of his feet and spreading to other parts of his body, following oral intake of cetirizine for allergic rhinitis. He described that his eruptions exacerbated with hydoxyzin. Patient's history revealed that he had slightly suffered from the same cutaneous reactions one year ago, after oral administration of cetirizine. On physical examination, multiple, round, erythematoviolaceous, well-defined macules and plaques, with central blisters localized on the trunk, arms and legs were observed. Four months after the lesions regressed, patch test was performed to eight different antihistamines. The test was positive for cetirizine, levocetirizine and hydroxyzine.

The aim of this prospective study was to evaluate the value of unenhanced (three-dimensional constructive interference in steady state (3D-CISS)) and contrast-enhanced MR cisternography (CE-MRC) in detecting the localisation of cerebrospinal fluid (CSF) leak in patients with rhinorrhoea. 17 patients with active or suspected CSF rhinorrhoea were included in the study. 3D-CISS sequences in coronal and sagittal planes and fat-suppressed T-1-weighted spin-echo sequences in three planes before and after intrathecal contrast media adminstration were obtained. Images were obtained of the cribriform plate and sphenoid sinus. In addition, high-resolution CT (HRCT) was performed in order to evaluate the bony elements. The leak was present in 9/17 patients with 3D-CISS and 10/17 patients with CE-MRC. The leak from the cribriform plate to the nasal cavity in six patients and from the sphenoid sinus in four patients was nicely shown by CE-MRC. Eight of those patients were surgically treated, but spontaneous regression of the symptoms in two precluded any intervention. The leak localisations shown with CE-MRC were fully compatible with surgical results. The sensitivities of HRCT, 3D-CISS and CE-MRC for showing CSF leakage were 88%, 76% and 100%, respectively. In conclusion, 3D-CISS is a non-invasive and reliable technique, and should be the first-choice method to localise CSF leak. CE-MRC is helpful in conditions when there is no leak or in complicated cases with a positive beta 2-transferrin measurement.

Hexahydro-1H-phenothiazine moieties can be synthesized by domino aziridine ring opening with o-halothiophenols followed by copper-catalyzed Goldberg coupling-cyclization with good to excellent yields. Less reactive o-chlorothiophenols are also successfully utilized for the domino reaction to synthesize phenothiazine derivatives. This methodology is successfully applied in the synthesis of phenothiazine skeletons containing biologically active molecules such as antihistamine agents. � 2009 The Royal Society of Chemistry.

Objective: To describe the frequency, nature, determinants and clinical relevance of prescription modifications in a Dutch community pharmacy. Design: A descriptive, retrospective study of the documented prescription modifications during dispensing in 2007. Methods: The frequency and nature of prescription modifications and their patient, drug and prescriber related determinants were assessed. To examine the clinical value of pharmacists' interventions, each prescription modification was rated from A to D (A is clinically irrelevant, D is clinically relevant with possible fatal consequences for the patient). Results: In 2007, on average, one intervention was documented per workday. Almost 50% of all interventions concerned dose corrections. Prescriptions for incidental medications, children (0-20 year) and patients with less than four other medications, had a higher chance of modification. A higher chance of prescription modifications was found in anti-infective agents for systemic use, in treatments for the central nervous system and the sensory organs. Verification and attentiveness to the prescriptions of these risk groups can reduce (serious) clinical consequences. Of all prescription modifications 86% were clinically relevant (groups B, C and D) and every ten days at least one harmful clinical incident was prevented by prescription modifications. Conclusions: Modifications of prescriptions by pharmacists vary in nature from clinically irrelevant to potentially fatal. Analysis of documented interventions in one community pharmacy allows identification of patients who are at risk and need more attention from prescribing physicians. It also shows that pharmacists' interventions have a positive impact on patients' health.

Objective: To analyze prescribing patterns of chronic psychiatric patients living in sheltered housing facilities, to identify the extent of polypharmacy and to estimate associated risks in this patient group. Methods: In a retrospective cross-sectional study the prescription data of 323 chronic psychiatric patients (average age 48.5 years) living in sheltered housing facilities in Rotterdam, The Netherlands, were analyzed. Prescription data were obtained from pharmacy-dispensing records. Results: Patients received on average 4.6 drugs (95% CI, 4.3-4.9). The most frequently prescribed drugs were as expected antipsychotics, benzodiazepines and antimuscarinic drugs. Overall 25% (n = 81) of patients received two or more antipsychotic drugs. A high proportion of patients (38%, n = 124) received one benzodiazepine, and 15% (n = 50) received two or more benzodiazepines. Conclusion: Patients in our study received a worryingly high number of drugs, and a quarter of the population was subject to antipsychotic polypharmacy. This increases the risk that drug-drug interactions, adverse drug reactions and noncompliance occur. Our study indicates potentially low quality of prescribing and shows the need for reviewing and special monitoring of pharmacotherapy in this patient group. © 2008 Dustri-Verlag Dr. K. Feistle.

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Background: Since all antihistamines are capable of crossing the blood-brain barrier, they may also cause sedation which may impair daily activities such as driving a car. The purpose of this review was to examine the effects of antihistamines on driving ability. Method: A literature search revealed 18 double-blind placebo-controlled clinical trials that applied the on-road highway driving test. In this test, subjects are instructed to drive 100-km on a public highway with a steady lateral position and a constant speed (95 km/h). Primary outcome measure is the Standard Deviation of Lateral Position (SDLP, cm), i.e. the weaving of the car. Results: The literature search yielded 18 clinical trials. At therapeutic doses, a single dose of diphenhydramine, emedastine and hydroxizine impaired driving comparable or greater than the effects of BAC 0.08%. Clemastine, triprolidine, mizolastine, acrivastine, dexchlorpheniramine CR and mequitazine impaired driving performance to the same extent as BAC 0.05%. For mizolastine significant impairment was only seen after higher than therapeutic doses. Results for cetirizine were mixed, illustrating the drug has the potential to impair driving performance, especially in sensitive subjects. Terfenadine, loratadine, levocetirizine, desloratadine, ebastine, bilastine fexofenadine and rupatadine showed no driving impairment in the standard driving test after acute administration of their recommended dose. Several studies examined subchronic effects of antihistamines on driving performance. After 4 days of daily treatment significant driving impairment was found for emedastine (2 and 4 mg bid), diphenhydramine (50 mg), clemastine (2 mg bid), triprolidine (5 mg bid), after 5 days of ebastine (30 mg), and after 8 days of hydroxyzine (50 mg). Mixed results were found for cetirizine (10 mg), terfenadine (120 mg) and loratadine (20 mg). No significant differences from placebo were observed after 4 days of subchronic treatment with triprolidine (10 mg), levocetirizine (5 mg), fexofenadine (up to 120 mg), and after 8 days of daily treatment with dexchlorpheniramine (6 mg), bilastine (20 and 40 mg), and mequitazine (10 mg). Conclusion: First- and second-generation antihistamines may significantly impair driving performance. The newer antihistamines such as levocetirizine and fexofenadine that cross to blood brain barrier to a much lesser degree do not show clinically relevant sedation or driving impairment.

OBJETIVO: Avaliar a presença de conservantes, corantes, adoçantes e aromatizantes em 73 apresentações farmacêuticas de 35 medicamentos para uso oral, e as informações da bula sobre excipientes. MÉTODOS: Selecionamos 35 medicamentos, de venda livre ou sob prescrição médica, comercializados no Brasil. A amostra incluiu: analgésicos/antitérmicos, antimicrobianos, mucolíticos, antitussígenos, descongestionantes, anti-histamínicos, broncodilatadores, corticosteróides, antiinflamatórios e suplementos vitamínicos. Foram analisadas 73 apresentações desses fármacos, anotando-se as informações da bula sobre conservantes, corantes, adoçantes e aromatizantes. RESULTADOS: A bula de um medicamento (1,3%) não mencionava os ingredientes inativos. Os conservantes mais encontrados nos medicamentos foram metilparabeno e propilparabeno (43% e 35,6% respectivamente). Os adoçantes mais usados foram: sacarose (açúcar) (53,4%), sacarina sódica (38,3%) e sorbitol (36,9%). Vinte e um produtos (28,7%) continham dois adoçantes. Predominaram os medicamentos sem corante (43,8%), seguidos pelos coloridos por amarelo crepúsculo (amarelo FD&C no. 6) (15%). Cinco produtos (6,8%) continham mais de um corante. A tartrazina (amarelo FD&C no. 5) foi encontrada em sete formulações (9,5%). Os aromatizantes mais usados foram os de frutas (83%). Constatamos a freqüente omissão das bulas sobre o teor exato de açúcar dos produtos (77%). Duas das quatro bulas de medicamentos contendo aspartame não mencionavam as precauções no uso por fenilcetonúricos. CONCLUSÕES: A omissão e a imprecisão das informações da bula sobre os excipientes farmacêuticos expõem os indivíduos suscetíveis ao risco de reações adversas dos conservantes e corantes. Também podem ocorrer complicações do uso inadvertido de medicamentos contendo açúcar pelos pacientes diabéticos, ou de fármacos adoçados com aspartame pelos fenilcetonúricos. AIM: to evaluate the presence of preservatives, dyes, sweeteners and flavouring substances in 73 pharmaceutical preparations of 35 medicines for oral administration, according to drug labeling information about the excipients. METHODS: 35 medications were selected, both over-the-counter and prescription durgs, marketed in Brazil. The sample included: analgesic/antipyretic, antimicrobial, mucoregulatory, cough and cold, decongestant, antihistamine, bronchodilator, corticosteroid, antiinflammatory and vitamin medications. We collected data on 73 preparations of these drugs, according to drug labeling information regarding preservatives, dyes, sweeteners and flavourings. RESULTS: Methylparaben and propylparaben were the most common preservatives found (43% and 35.6% respectively). The most common sweeteners were: sucrose (sugar) (53.4%), sodium saccharin (38.3%) and sorbitol (36.9%). Twenty-one medicines (28,7%) contained two sweeteners. Colourless medicines predominated (43.8%), followed by those with sunset yellow dye (FD&C yellow no. 6) (15%). Five products (6.8%) contained more than one colour agent. Tartrazine (FD&C yellow no. 5) was present in seven preparations (9.5%). Fruit was the most common flavouring found (83%). Labelings of drugs which contained sugar frequently omitted its exact concentration (77%). Of the four labelings of medicines which contained aspartame, two did not warn patients regarding phenylketonuria. CONCLUSION: Omission and inacuracy of drug labeling information on pharmaceutical excipients may expose susceptible individuals to adverse reactions caused by preservatives and dyes. Complications of inadvertent intake of sugar-containing medicines by diabetics, or aspartame intake by patients with phenylketonuria may also occur.