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First Choice (first + choice)
Terms modified by First Choice Selected AbstractsThe UK air inclusive-tour industry: a reassessment of the competitive positioning of the ,independent' sectorINTERNATIONAL JOURNAL OF TOURISM RESEARCH, Issue 6 2001Nigel G. Evans Abstract This paper investigates the increasing concentration in the UK air inclusive-tour (AIT) market and the behaviour of the dominant companies (Thomson, Airtours, First Choice and Thomas Cook) operating in the sector. Arguments relating to the theoretical organisational structure of the industry are explored and regulatory investigations that have taken place are discussed. Research evidence as to the competitive position of independent tour operators in the overall UK AIT market is provided. The research indicates that a key area of difficulty for the independent sector relates to the provision of charter airline capacity although access to distribution channels and the ability to contract accommodation are viewed as further concerns. The paper concludes that regulatory authorities are faced with trying to ensure that diversity is maintained while at the same time ensuring any economies of scale derived from consolidation of the sector are passed on to consumers. In order to properly understand the true effects of industrial concentration the assembled package must be dissembled into its component parts and an increasingly a pan-European perspective is necessary. Copyright © 2001 John Wiley & Sons, Ltd. [source] Analysis of micrometastatic disease in histologically negative lymph nodes of patients with adenocarcinoma of the distal esophagus or gastric cardiaDISEASES OF THE ESOPHAGUS, Issue 6 2008C. J. Buskens SUMMARY., Lymphatic dissemination is the most important prognostic factor in patients with esophageal carcinoma. However, the clinical significance of lymph node micrometastases is still debated due to contradictory results. The aim of the present study was to identify the incidence of potentially relevant micrometastatic disease in patients with histologically node-negative esophageal adenocarcinoma and to analyze the sensitivity and specificity of three different immunohistochemical assays. From a consecutive series of 79 patients who underwent a transthoracic resection with extended 2-field lymphadenectomy, all 20 patients with pN0 esophageal adenocarcinoma were included in this study. A total of 578 lymph nodes were examined for the presence of micrometastases by immunohistochemical analysis with the antibodies Ber-EP4, AE1/AE3 and CAM 5.2. Lymph node micrometastases were detected in five of the 20 patients (25%). They were identified in 16 of the 578 lymph nodes examined (2.8%) and most frequently detected with the Ber-EP4 and AE1/AE3 antibody (sensitivity 95% and 79% respectively). In 114 of the 559 negative lymph nodes (20.4%), positive single cells were found that did not demonstrate malignant characteristics. These false-positive cells were more frequently found with the AE1/AE3 staining (specificity of the Ber-Ep4 and AE1/AE3 antibody 94% and 84% respectively). The presence of nodal micrometastases was associated with the development of locoregional recurrences (P=0.01), distant metastases (P=0.01), and a reduced overall survival (log rank test, P=0.009). For the detection of clinically relevant micrometastatic disease in patients operated upon for adenocarcinoma of the distal esophagus or gastric cardia, Ber-EP4 is the antibody of first choice because of its high sensitivity and specificity. Immunohistochemically detected micrometastases in histologically negative lymph nodes have potential prognostic significance and are associated with a high incidence of both locoregional and systemic recurrence. Therefore, this technique has the potential to refine the staging system for esophageal cancer and to help identify patients who will not be cured by surgery alone. [source] Stability of medication in early psychosis: a comparison between second-generation and low-dose first-generation antipsychoticsEARLY INTERVENTION IN PSYCHIATRY, Issue 1 2009Stein Opjordsmoen Abstract Aim: This naturalistic study aims to compare discontinuation rates for low-dose first-generation versus second-generation antipsychotics in first-episode psychotic patients. Methods: The prescription of antipsychotic medication in 301 consecutively admitted patients with first-episode psychosis from four catchment areas is described. For the first year of inclusion a first-generation antipsychotic in low dose was recommended as the first medication. From the second year a second-generation antipsychotic was recommended as first choice. Switching was allowed when any drug was judged to be ineffective or to have serious side-effects. Switching during the first 2 years after inclusion is described. Results: Switching from a low-dose first-generation antipsychotic was more frequent than from a second-generation antipsychotic (90.7 vs. 58.4%). Lack of therapeutic effect and side-effects were the more frequently recorded reasons for changing in the first-generation group. Akathisia, parkinsonism, dyskinesias, dystonia and dysphoria were more often reported in patients on first-generation drugs. Weight gain and sedation were more often reported in patients on second-generation drugs. Conclusion: The findings suggest a better adherence to and tolerability for second-generation antipsychotics than for low-dose first-generation antipsychotics in first-episode psychosis. [source] AN INVESTIGATION OF HOME BIAS IN SUPERANNUATION INVESTMENT CHOICESECONOMIC PAPERS: A JOURNAL OF APPLIED ECONOMICS AND POLICY, Issue 1 2006PAUL GERRANS Australian superannuation funds have increased investment choices available for their members. Fund members can typically choose from a range of ready-made options or select their own asset allocations. Evidence suggests that individuals may display a home bias in these allocations by favouring domestic assets at the expense of international assets. Such a bias may produce a sub-optimal investment. This paper investigates the asset allocations of members of the Government Employees Superannuation Board (GESB), the superannuation fund for Western Australian public sector employees. Asset allocations appear to be in line with a normal allocation to international equity, especially at the time of their first choice. Subsequent choices however appear to be driven more by historical performance of the asset classes offered, rather than by a home bias. [source] The impact of diazepam's discovery on the treatment and understanding of status epilepticusEPILEPSIA, Issue 9 2009Howard P. Goodkin Summary The fortuitous discovery of the benzodiazepines and the subsequent application of these agents to the treatment of status epilepticus (SE) heralds in the modern age of treating this neurologic emergency. More than 50 years after their discovery, the benzodiazepines remain the drugs of first choice in the treatment of SE. However, the benzodiazepines can be ineffective, especially in those patients whose seizures are the most prolonged. The benzodiazepines act by increasing the affinity of ,-aminobutyric acid (GABA) for GABAA receptors. A receptor's subunit composition affects its functional and pharmacologic properties, trafficking, and cellular localization. The GABAA receptors that mediate synaptic inhibition typically contain a ,2 subunit and are diazepam-sensitive. Among the GABAA receptors that mediate tonic inhibition are the benzodiazepine-insensitive , subunit,containing receptors. The initial studies investigating the pathogenesis of SE demonstrated that a reduction in GABA-mediated inhibition within the hippocampus was important in maintenance of SE, and this reduction correlated with a rapid modification in the postsynaptic GABAA receptor population expressed on the surface of the hippocampal principal neurons. Subsequent studies found that this rapid modification is, in part, mediated by an activity-dependent, subunit-specific trafficking of the receptors that resulted in the reduction in the surface expression of the benzodiazepine-sensitive ,2 subunit,containing receptors and the preserved surface expression of the benzodiazepine-insensitive , subunit-containing receptors. This improved understanding of the changes in the trafficking of GABAA receptors during SE partially accounts for the development of benzodiazepine-pharmacoresistance and has implications for the current and future treatment of benzodiazepine-refractory SE. [source] Nucleic Acid Diagnostic FRET Particles Based on Layer-by-Layer TechnologyADVANCED MATERIALS, Issue 32 2010Jing Kang An advanced system based on layer-by-layer (LbL) technology and fluorescence resonance energy transfer (FRET) for the detection of small amounts of DNA has been developed. Several advantages over conventional particle systems due to nanoroughness, flexibility and specific surface properties of LbL films were determined, making LbL-oligonucleotide particles a first choice for homogeneous diagnostic assays. [source] Current antiviral therapies for chronic hepatitis BHEPATOLOGY RESEARCH, Issue 6 2008Mari Inada Among current treatment options for chronic hepatitis B, nucleoside/nucleotide analog therapy has better tolerability and most patients respond to the therapy, while interferon (IFN) therapy has rather severe side-effects and a lower response rate. However, nucleoside/nucleotide analog therapies have problems of the emergence of drug resistance and poor sustainability of response after discontinuation. After the first nucleoside/nucleotide analog lamivudine, adefovir and entecavir are now utilized in many countries. Adefovir has efficacy for lamivudine resistant patients and current data suggests that adding adefovir to ongoing lamivudine is better than switching to adefovir in terms of viral suppression and the occurrence of resistance. Entecavir can be the first choice for naïve patients, although cross-resistance has been known for lamivudine resistant patients and mutational screening should take place before using entecavir with such patients. Many other new nucleoside/nucleotide analogs are being developed such as telbivudine, clevudine and tenofovir; the details of each drug will be disclosed in near future. [source] Guidelines for palliative surgery of cholangiocarcinomaHPB, Issue 3 2008H. Witzigmann Abstract The aims of the guidelines are to help assess the evidence for palliation surgery in patients with cholangiocarcinoma (CCA). The guidelines are classified in accordance with the location of the primary lesion, i.e. intrahepatic, hilar, and distal. They are based on comprehensive literature surveys, including results from randomized controlled trials, systematic reviews and meta-analysis, and cohort, prospective, and retrospective studies. Intrahepatic CCA, i.e. resection of lymph-node-positive tumors and R1/R2 resections have not been shown to provide survival benefit: Evidence levels: 2b, 4; Recommendation grade C. Hilar CCA: R1 resection is justified as a very efficient palliation. Non-surgical biliary stenting is the first choice of palliative biliary drainage. Distal CCA: Resection of lymph-node-positive tumours and R1/R2 resections should be performed. Non-surgical stenting is regarded as the first choice of palliation for patients with short life expectancy. For patients with longer projected survival, surgical bypass should be considered. Palliative resections have a relevant beneficial impact on the outcome of patients with distal and hilar CCA. Non-surgical stenting is the first choice of palliative biliary drainage for patients with hilar CCA and for those with distal CCA and short life expectancy. For patients with distal CCA and longer projected survival, surgical bypass should be considered. [source] Hepatectomy for pyogenic liver abscessHPB, Issue 2 2003RW Strong Background Commensurate with the advances in diagnostic and therapeutic radiology in the past two decades, percutaneous needle aspiration and catheter drainage have replaced open operation as the first choice of treatment for both single and multiple pyogenic liver abscesses. There has been little written on the place of surgical resection in the treatment of pyogenic liver abscess due to underlying hepatobiliary pathology or after failure of non-operative management. Methods The medical records of patients who underwent resection for pyogenic liver abscess over a 15-year period were retrospectively reviewed. The demographics, time from onset of symptoms to medical treatment and operation, site of abscess, organisms cultured, aetiology, reason for operation, type of resection and outcome were analysed. There were 49 patients in whom the abscesses were either single (19), single but multiloculated (11) or multiple (19). The median time from onset of symptoms to medical treatment was 21 days and from treatment to operation was 12 days. The indications for operation were underlying hepatobiliary pathology in 20% and failed non-operative treatment in 76%. Two patients presented with peritonitis from a ruptured abscess. Results The resections performed were anatomic (44) and non-anatomic (5). No patient suffered a recurrent abscess or required surgical or radiological intervention for any abdominal collection. Antibiotics were ceased within 5 days of operation in all but one patient. The median postoperative stay was 10 days. There were two deaths (4%), both following rupture of the abscess. Discussion Except for an initial presentation with intraperitoneal rupture and, possibly, cases of hepatobiliary pathology causing multiple abscesses above an obstructed duct system that cannot be negotiated non-operatively, primary surgical treatment of pyogenic liver abscess is not indicated. Non-operative management with antibiotics and percutaneous aspiration/drainage will be successful in most patients. If non-operative treatment fails, different physical characteristics of the abscesses are likely to be present and partial hepatectomy of the involved portion of liver is good treatment when performed by an experienced surgeon. [source] Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2002JENS SØNKSEN Summary The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCI. Furthermore, it is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCI. Home insemination with semen obtained by penile vibratory and introduced intravaginally in order to achieve successful pregnancies may be an option for some spinal cord injured men and their partners. The majority of men will further enhance their fertility potential when using either penile vibratory or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in-vitro fertilization with or without intracytoplasmic sperm injection. [source] Update on medical treatment of ejaculatory disorders,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2002A. KAMISCHKE Summary Among the treatment modalities for ejaculatory disorders pharmacological treatment is the least invasive option. In this review, medical treatments for retrograde ejaculation (RE) and anejaculation (AE) are discussed systematically. Thirty-six studies dealing with patients with RE and 40 with AE evaluated the use of medical treatment and were included in this review. In addition four articles dealing with prostatic massage in anejaculatory patients were considered. Sperm quality in patients with retrograde and AE is often impaired. In patients with RE no differences in response to medical treatment could be detected between the different underlying diagnoses. Compared with ephedrine, imipramine and chlorpheniramine + phenylpropanalamine showed significantly higher reversal rates, while differences between the other treatments were not significant. Regarding the reversal of AE, the alpha agonistic drugs were significantly inferior to treatment with parasympathetic drugs. Of the different alpha agonistic medical treatments for the reversal of AE, milodrin showed significantly better rates than imipramine (p = 0.008), pseudoephidrine (p = 0.02) and ephedrine (p = 0.044), while all other treatments were not significantly different (p = 0.4). In conclusion, medical treatment for reversal of RE offers a realistic chance of conceiving offspring naturally and should be the treatment modality of first choice. In contrast, in AE, medical treatment cannot be recommended generally as treatment of first choice as it shows low overall success rates compared with electrovibration stimulation and electroejaculation. Under consideration of the mostly uncontrolled design of the majority of studies published, controlled clinical trials comparing different treatment options appear urgently warranted. [source] Adjuvant hydrodistension under epidural anesthesia for interstitial cystitisINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2003TETSUO YAMADA ABSTRACT Background: Hydrodistension is the first choice of treatment for interstitial cystitis because it allows for diagnosis, bladder biopsy and treatment. However, the method and efficacy of hydrodistension are variable. We performed adjuvant hydrodistension and examined the efficacy and factors that influence prognosis. Methods: Fifty-two patients participated in the present study as subjects; they satisfied the diagnostic inclusion and exclusion criteria established by the National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) in 1987, USA. Under epidural anesthesia, the bladder was repeatedly distended up to the maximal bladder capacity for treatment, diagnosis and biopsy. Hydrodistension was performed again on the following day for approximately 30 min under epidural anesthesia in a ward until macroscopic hematuria disappeared. Results: Five patients were classified into the good, 30 into the moderate and 17 into the poor response group. In the good response group, three patients had type I allergy and one patient did not fulfil all of the positive factors in the NIDDK criteria. The poor response group included one patient with collagen disease. The poor response group was further divided into two subgroups based on bladder capacity. One subgroup included eight patients with a bladder capacity of less than 100 mL and vesicoureteral reflux (VUR). The other subgroup included nine patients with a bladder capacity of more than 100 mL. Among these nine patients there were five patients who lacked one or two positive factors in the NIDDK criteria. Conclusion: Adjuvant hydrodistension under epidural anesthesia is effective for about 70% of patients for more than 3 months. It can be performed in a ward without any serious complications. It was observed that patients lacking one or two positive factors were included in the good and poor response groups. [source] Antimicrobial therapy in DermatologyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2006Cord Sunderkötter Antiseptika; Antibiotika; ,-Laktam-Resistenz; Weichteilinfektion Summary The extensive and sometimes indiscriminate use of antibiotics sometimes without strict indications has led to increases in both bacterial resistance and sensitization of patients. Systemic antibiotics in skin infections are indicated when a severe local infection occurs which spreads into the surrounding tissue or when there are signs of systemic infection. There are special indications in patients with peripheral arterial occlusive disease,diabetes or immunosuppression. Topical use of antibiotics should be abandoned and replaced by antiseptics. The ,-lactam antibiotics are the antibiotics of first choice for many skin infections. They are usually effective, have a well-defined profile of adverse events and most are affordable. Penicillin G or V are the first line treatment for erysipelas. Infections with Staphylococcus aureus are usually treated with isoxazolyl penicillins or second generation cephalosporins. In mixed infections in patients with diabetes or peripheral arterial occlusive disease,the treatment of choice is metronidazole plus ,-lactam-/,-lactamase inhibitor antibiotics, but quinolones or second generation cephalosporins can also be used, once again with metronidazole. The aim of this review is to define the indications for antibiotics in dermatology, to highlight their modes of action and adverse effects and to make suggestions for rational antibiotic therapy in cutaneous infections frequently encountered in the practice of dermatology. Zusammenfassung Der bisweilen unkritische Einsatz von Antibiotika hat die Resistenzentwicklung beschleunigt und die Sensibilisierungsrate bei Patienten erhöht. Systemische Antibiotika sind bei kutanen Superinfektionen in der Regel dann indiziert, wenn eine schwere lokale Infektion mit Ausbreitung in das umgebende Gewebe vorliegt oder wenn sich gleichzeitig Zeichen einer systemischen Infektion einstellen. Bei peripherer arterieller Verschlusskrankheit, Diabetes mellitus oder Immunsuppression kann die Indikation auch früher gestellt werden. Lokale Antibiotika sollten in der Regel gemieden und durch moderne Antiseptika ersetzt werden. ,-Laktam-Antibiotika stellen für viele bakterielle Infektionserkrankungen in der ambulanten und klinischen Dermatologie die Antibiotika der ersten Wahl dar. Sie sind häufig ausreichend wirksam, besitzen ein gut definiertes Nebenwir-kungsprofil und sind zumeist preisgünstig. So wird das klassische Streptokokken-Erysipel mit Penicillin G oder V therapiert, bei Infektionen durch S. aureus kommen primär Isoxazolyl-Penicilline oder Zweit-Generations-Cephalosporine zum Einsatz. Im Falle von Mischinfektionen bei Diabetes mellitus oder pAVK sind ,-Laktam/,-Laktamaseinhibitoren indiziert, alternativ auch Chinolone oder Zweitgenerations-Cephalosporine, jeweils in Kombination mit Metronidazol. Diese Übersicht möchte die Indikationen für Antibiotika in der Dermatologie aufzeigen, das Wichtigste zu deren Wirkungsweise und Nebenwirkungen aufzählen und Therapievorschläge für häufige Infektionen der Haut in der dermatologischen Praxis geben. [source] Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine,zinc): a case of decompensated liver cirrhosis in Wilson's diseaseJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2007C. C. Ping MPharm Summary Objectives:, To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. Case summary:, A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. Discussion:, Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20,30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. Conclusion:, In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned. [source] Oral pemphigus: long term behaviour and clinical response to treatment with deflazacort in sixteen casesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2000Michele D. Mignogna Abstract: Systemic corticosteroids remain the mainstay of therapy for pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. Unfortunately, the high doses and prolonged administration of corticosteroids that are often needed to control the disease result in numerous side effects, many of which are serious or even life-threatening. Sixteen patients affected by oral pemphigus vulgaris were retrospectively examined to illustrate the natural course of the disease and to describe the efficacy of the treatment we utilised. Deflazacort, used with azathioprine, is the steroid of first choice in our therapeutic protocols, while cyclophosphamide and methylprednisolone "pulse therapy" are reserved for cases unresponsive to high doses of oral corticosteroids. In addition, the literature on oral pemphigus vulgaris was reviewed with respect to clinical history, signs and symptoms, management, and treatment outcome. [source] Classifying degenerative joint disease by the RDC/TMD and by panoramic imaging: a retrospective analysisJOURNAL OF ORAL REHABILITATION, Issue 3 2010E. WINOCUR Summary, The purposes of the study were to evaluate the utility of diagnosing degenerative joint disease (DJD) by the clinical finding of coarse crepitus alone, without supporting imaging studies, as defined by the RDC/TMD, and to evaluate the contribution of panoramic radiography as an aid in the diagnosis of DJD. A retrospective analysis of 372 consecutive patients with TMD was conducted. Their panoramic radiographs were evaluated for the extent of their contribution to the final diagnosis. Panoramic radiography was of no diagnostic value in 94·4% of the cases when the group was considered as a whole. When patients diagnosed with DJD were considered separately, panoramic radiography was completely sufficient for reaching the final diagnosis in 20·0% of the cases. In almost 90% of these patients, however, the clinical examination did not support the diagnosis of DJD (no coarse crepitus was found). This raises some doubts about the effectiveness of the clinical examination according to the RDC/TMD and about the utility of panoramic radiography in the definitive diagnosis of DJD, because both techniques have low accuracy (11·1% and 20%, respectively). The present study supports the current recommendations that panoramic radiography should not be ordered routinely to assess DJD, but still it is first choice when any dental problem is suspected. Further additional imaging (computerized tomography, magnetic resonance imaging) should be considered only if there is reason to expect that the findings might affect diagnosis and management. This study adds to recent criticisms of the clinical validity of the RDC/TMD, with regard to DJD. [source] Microwave-assisted solid-phase peptide synthesis at 60 °C: alternative conditions with low enantiomerization,JOURNAL OF PEPTIDE SCIENCE, Issue 12 2009Carina Loffredo Abstract Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS-ET), but we have elected the following as our first choice: 2.5-fold molar excess of 0.04,0.08 M Boc or Fmoc-amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 °C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave-SPPS, peptides containing L -Ser, L -His, L -Cys and/or L -Met were manually synthesized traditionally, at 60 °C using conventional heating and at 60 °C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave-assisted coupling of L -Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 °C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave-assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS-ET and suggests alternative conditions for microwave-assisted SPPS. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Opposed bilateral transposition flap: a simple and effective way to close large defects, especially of the limbsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2008R Verdolini Abstract Background, Excision of large tumours, particularly of the limbs, can be challenging because of problems related to wound repair. This is especially true of the lower legs, where skin is often tight and difficult to mobilize. Closure by flap, which would represent the first choice for defects usually between 12,15 mm to 38,40 mm diameter, is at risk of developing complications, such as end-flap necrosis or dehiscence due to skin tension. For larger defects, usually more than 40 to 45 mm diameter, grafting still remains the only realistic option in the majority of cases, with all the various problems associated with this procedure, such as lengthy healing times and the risk of developing leg ulcers, above all in elderly patients with impaired blood circulation. Second intention healing implies extraordinarily long healing times with often unacceptable delays in normal ambulation and activity. Objective, To find an alternative to the usual repair techniques and to try to reduce the risk of complications. Conclusions, We developed a relatively simple but effective technique for the closure of large wounds resulting from the excision of tumours. Our technique consists of two longitudinal, parallel, transposition flaps obtained from two opposite sides of the wound, with major axes orientated in the cephalic-caudal direction. The two flaps are then rotated around two fulcra placed at two extremes of the wound by approximately 90°. This relatively simple technique has never caused any of the ordinarily associated problems in terms of necrosis or ulcer development. In addition, dehiscence of sutures never occurred, given the fact that suture tension is minimal. Quick healing has resulted in the majority of cases, avoiding all the problems associated with grafting or other traditional flap techniques. [source] Dermoscopy is a suitable method for the observation of the pregnancy-related changes in melanocytic neviJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2007AS Aktürk Summary Background, It is a common opinion that expansion and darkening in melanocytic nevi may occur during pregnancy. The main problem is that whether it is a usual finding, or it is a condition that requires suspicion about melanoma. Objectives, It was aimed to find the changes that might occur in the sizes and structures of melanocytic nevi during pregnancy. Methods, Ninety-seven nevi of the 56 pregnant women in the first trimester were evaluated in the study. The localization and size of the nevi were recorded on a standard body diagram. After clinical examination, dermoscopic analyses were applied. Pattern analyses were done, and total dermoscopy scores (TDS) were calculated by applying ABCD scoring system. All subjects were seen again during the third trimester. Results, There was a statistically significant difference between the mean diameters of nevi in the first and third trimester (P = 0.001). Of nevi whose diameters increased, 10 (50.00%) were localized on the front of body, 6 (30.00%) on the face and neck, 3 (15.00%) on the legs, and 1 (5.00%) on the back. The enlargement in diameters was more significant on the front of the body, but there was no statistically significant difference. Compared according to the pattern analysis, new dot formation was observed only on the structure of six nevi during the last trimester. Four of them were localized on the front of the body. There was statistically significant increase in mean TDS in comparison between the first and third trimesters (P = 0008). Conclusions, During the pregnancy, widening in diameters and structure changes of nevi may be seen especially on the front of the body. We also think that these findings might be connected with expansion of the skin during pregnancy. Dermoscopic controls are the first choice of method to analyse the nevi since the patient may not recognize these changes. [source] Position paper on diagnosis and treatment of atopic dermatitisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2005U Darsow ABSTRACT The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti-inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti-inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti-inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress-induced exacerbations may make psychosomatic counselling recommendable. ,Eczema school' educational programmes have proved to be helpful. [source] The management of severe Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001M. Parkes The treatment of severe and active Crohn's disease is currently based on immunosuppression, but also involves the management of nutrition, appropriate selection of patients for surgery, and maintenance of remission in the long term. Corticosteroids remain the drug of the first choice, particularly in the acute setting. However, there is evolving understanding of the role of other immunosuppressants and immune modifiers, as major concerns regarding side-effects and efficacy of steroids in the medium to long-term drive the search for alternatives. [source] Repair of buccal defects with anterolateral thigh flapsMICROSURGERY, Issue 3 2006Ömer Özkan M.D. The ideal reconstructive method for the buccal mucosa should provide durable, stable coverage and a natural contour, while simultaneously minimizing morbidity of both the defect and donor sites. Since the first report of the anterolateral thigh flap in 1984, it has become one of the most commonly used flaps for the reconstruction of various soft-tissue defects. From March 2004,April 2005, 24 free anterolateral thigh flaps were used to reconstruct buccal defects, including the retromolar trigone and as far as the oral commissure, and in some cases with extension to the neighboring palatal region and tongue. The study comprised 1 female and 23 male patients, with ages ranging from 26,63 years (mean age, 45.8 years). Two flaps required reoperation due to vascular compromise, and both were salvaged with arterial and venous anastomosis revisions, giving an overall success rate of 100%. Primary thinning of the flap was performed in 10 cases. In 2 cases, additional vastus lateralis muscle was included in the flap to fill the large defect. In 2 cases, marginal necrosis with dehiscence of the flap was observed, one of these patients having a history of atherosclerosis and diabetes mellitus (marginal skin necrosis and infection of the donor area were also observed in this patient). In 2 patients, seroma collection was observed in the neck at the dissection site. Chart reviews showed that most patients had a history of betel-nut chewing (95.8%) or a combination of smoking and betel-nut chewing (79.2%). During the follow-up period of 4,12 months, a sufficient level of mouth-opening with interincisal distances of 34 mm, 44 mm, and 48 mm was achieved in all 3 cases reconstructed after release of the trismus. Although it has some variations in the vascular pedicle, irregularity in derivation from the main vessels, and minimal morbidity of the donor site, the anterolateral thigh flap, with its evident functional, structural, and cosmetic advantages, can be considered an excellent and ideal flap option, and a first choice for most buccal defects. © 2006 Wiley-Liss, Inc. Microsurgery, 2006. [source] Hemispheric brain volume replacement with free latissimus dorsi flap as first step in skull reconstructionMICROSURGERY, Issue 4 2005Anton H. Schwabegger M.D. Large skull defects lead to progressive depression deformities, with resulting neurological deficits. Thus, cranioplasty with various materials is considered the first choice in therapy to restore cerebral function. A 31-year-old female presented with a massive left-sided hemispheric substance defect involving bone and brain tissue. Computed tomography showed a substantial convex defect involving the absence of calvarial bone as well as more than half of the left hemisphere of the brain, with a profound midline shift and a compression of the ventricular system. There was a severe problem due to multiple deep-skin ulcerations at the depression margin, prone to skin perforation with a probability of intracranial infection. In a first step, a free myocutaneous latissimus dorsi flap was transplanted for volume replacement of the hemispheric brain defect, and 4 months later, artificial bone substitute was implanted in order to prevent progressive vault depression deformity. Healing was uneventful, and the patient showed definite neurological improvement postoperatively. Free tissue transfer can be a valuable option in addition to cranioplasty in the treatment of large bony defects of the skull. Besides providing stable coverage for the reconstructed bone or its substitute, it can also serve as a volume replacement. © 2005 Wiley-Liss, Inc. Microsurgery 25:325,328, 2005. [source] Inflammation and Sleep Disordered Breathing in Children: A State-of-the-Art Review,PEDIATRIC PULMONOLOGY, Issue 12 2008Aviv D. Goldbart MD Abstract Sleep disordered breathing (SDB) represents a spectrum of breathing disorders, ranging from snoring to obstructive sleep apnea syndrome (OSAS), that disrupt nocturnal respiration and sleep architecture. OSAS is a common disorder in children, with a prevalence of 2,3%. It is associated with neurobehavioral, cognitive, and cardiovascular morbidities. In children, adenotonsillectomy is the first choice for treatment and is reserved for moderate to severe OSAS, as defined by an overnight polysomnography. In adults, OSAS is the result of mechanical dysfunction of the upper airway, manifesting as severity-dependent nasal, oropharyngeal, and systemic inflammation that decrease after continuous positive airway pressure therapy. Inflammatory changes have been reported in upper airway samples from children with OSAS, and systemic inflammation, as indicated by high-sensitivity C-reactive protein (hsCRP) levels, has been shown to decrease in children with OSAS after adenotonsillectomy. Anti-inflammatory treatments for children with mild OSAS are associated with major improvements in symptoms, polysomnographic respiratory values, and radiologic measures of adenoid size. Inflammation is correlated to some extent with OSAS-related neurocognitive morbidity, but the role of inflammatory markers in the diagnosis and management of OSAS, and the role of anti-inflammatory treatments, remains to be clarified. This review examines the role of inflammation in the pathophysiology of sleep-disordered breathing in pediatric patients and the potential therapeutic implications. Pediatr. Pulmonol. 2008; 43:1151,1160. © 2008 Wiley-Liss, Inc. [source] How pediatricians manage asthma in ThailandPEDIATRIC PULMONOLOGY, Issue 2 2001Pakit Vichyanond MD Abstract Currently, there is no existing information regarding prescribing practices for the management of childhood asthma among pediatricians in Thailand. In order to evaluate the management standards for childhood asthma in Thailand, 400 self-administered questionnaires were randomly mailed to nonacademic pediatricians throughout Thailand, asking questions about their preferences in the treatment of childhood asthma. One hundred and seventy-four of these 400 questionnaires were returned (a response rate of 43.5%). Data were analyzed using the descriptive module of the Epi-info 6 program. For acute asthma, 17% of the respondents used objective measures such as peak flow meters in assessing asthma severity and severity of acute asthma attacks. The drug of first choice for treating acute attacks was a nebulized beta-agonist q 20 min (81.8%). Although 93% indicated that they had used theophylline for treating acute attacks, most would reserve the drug for patients with severe symptoms. Corticosteroids were reserved for those with severe attacks (91.7% both for clinic and for in-hospital settings). Hydrocortisone was the most preferred corticosteroid preparation (59.8%). Ninety-seven percent used antibiotics in treating acute asthma, but only with appropriate indications. For chronic asthma, a strong preference was observed for oral beta-agonists as the bronchodilator of choice (88%). For moderately severe asthmatics, theophylline was still preferred by 41% of the responders. Among prophylactic agents, ketotifen was the most favored drug (90.4%), whereas inhaled steroids and cromolyn were chosen by 9.6% and 2.4%, respectively. Eighty-five percent indicated that they would prescribe prophylactic agents for 1 year or less. Forty-two percent never considered allergy evaluation as a part of a workup for childhood asthma. Certain prescribing practices of childhood asthma management in Thailand were observed among pediatricians, i.e., 1) low frequency of using objective measures in assessing asthma severity among pediatricians; 2) frequent use of theophylline and antibiotics in the treatment of acute asthma; 3) late introduction of corticosteroids in treating acute asthma; 4) preference for oral bronchodilators; and 5) preference of ketotifen as the prophylactic drug of choice. This survey provides baseline data and will aid in the evaluation of management guidelines for childhood asthma in Thailand. Pediatr Pulmonol. 2001; 32:109,114. © 2001 Wiley-Liss, Inc. [source] Pediatric renal transplantation: Single center experiencePEDIATRIC TRANSPLANTATION, Issue 1 2005Sevgi Mir Abstract:, Although renal transplantation (RTx) is actually the first choice of treatment for children with end-stage renal disease, the number of transplanted children remains low in comparison with adults. The experience of the individual pediatric transplant center is very important in the outcome of pediatric transplant recipients. In this study, our pediatric renal transplantation experience is presented. We retrospectively analyzed the results of 72 pediatric renal transplants performed at Ege University Pediatric Nephrology Transplantation Center between June 1989 and May 2003. They were 40 girls, 32 boys and their mean RTx age was 13.27±3.73 yr (range 3,20 yr). Thirty-eight (52.8%) of the transplanted kidneys came from a living related donor, and 34 (47.2%) from a cadaveric donor. Preemptive RTx was performed in one patient and a second RTx was performed in one patient after two-period hemodialysis. Hypertension (31.9%), acute rejection (27.8%) and chronic rejection (13.9%) were the most common complications. Cytomegalovirus (CMV) infection occurred in 15 children (20.8%), none of whom died or lost their graft as a result of the infection. Pretransplant acquired hepatitis C virus (HCV) infection was detected in 12 patients (16.7%). Urinary tract infections (UTIs) were seen in 31 (43.1%) recipients. The 1, 5 and 10 yr graft survival rates were 91, 84 and 77%, respectively, and corresponding patient survival rates were 97, 84 and 77%, respectively by Kaplan,Meier method. The graft and overall survival was not correlated with sex, donor type, treatment modality, acute rejection episodes, hypertension, UTIs, CMV and HCV infection. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2008Article first published online: 2 DEC 200 Osteoporosis guideline A new guideline on the management of osteoporosis in men over 50 and post-menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies. The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10-year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients. Efalizumab efficacy A multicentred postapproval trial has demonstrated long-term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis. The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non-blinded study, 68 per cent of participants achieved the primary efficacy end-point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment. Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections. New oral anticoagulant Rivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo-embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar. At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63. New products UCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial-onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100-200mg twice daily costs approximately £73-£140. A new non-nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV-1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment-experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily. Voltarol Pain-Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99. Atypicals and EPS risk Atypical antipsychotics are not associated with a significantly lower risk of extra-pyramidal symptoms than first-generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279,88). CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first-generation agent (Am J Psychiatry 2006;163:611,22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel). Mental health website A new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo-phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE). www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication. [source] Latest news and product developmentsPRESCRIBER, Issue 20 2007Article first published online: 26 NOV 200 GPs and pharmacists to work more closely Closer working between GPs and community and primary-care pharmacists ,could further improve prescribing quality and therapeutic outcomes for patients', according to a report by the London School of Pharmacy and Alliance Boots. The report suggests that the expansion of primary-care centres and the increasing complexity of care they offer mean that community pharmacists will increasingly need to take on some GP roles. It foresees an increase in shared premises and calls for closer interdisciplinary working between GPs, pharmacists and nurses. Variation in PCT commissioning of enhanced services from pharmacies has resulted in ,a fragmented system of postcode pharmaceutical care rationing'. Full read-write access to patients' records will be essential if the benefits of electronic prescribing are to be realised. How pharmacists can support commissioners The NHS Alliance and Primary Care Pharmacists' Association have published a guide for practice-based commissioners on making the most of primary-care pharmacists. Prescribing Support and Prescribing Advice for Practice Based Commissioners , A Guide for Commissioning Groups and GPs illustrates how pharmacists can support commissioners at all levels of medicines use. Copies are free to NHS Alliance members and cost £10 for others. Directory website aids diabetes management The National Diabetes Support Team is developing a website that brings together different datasets and tools for diabetes management. The Diabetes Data Directory (www.yhpho.org.uk/diabetesdatadirectory/introddd.asp) summarises what other online databases can provide and lists the tools that can be used to answer specific questions. The first edition is now online, providing direct links to the appropriate sites. Flu vaccine efficacy in older people challenged US reviewers have questioned the effectiveness of flu vaccine in older people (Lancet Infect Dis online: 24 September; doi: 10.1016/ S1473-3099(07)70236-0). They were unable to confirm a reduction in flu mortality since 1980, concluding that biased patient selection and nonspecific end-points such as all-cause mortality may have exaggerated the benefits of vaccination in clinical trials. The Department of Health is encouraging younger people in at-risk groups to be vaccinated against flu this winter; last year, 58 per cent of under-65s at risk were not vaccinated. OC cervical cancer risk probably overestimated Recent evidence that oral contraceptives may be associated with a small increase in the incidence of cervical cancer probably overestimates the risk, says the Clinical Effectiveness Unit of the Faculty of Family Planning and Reproductive Health Care (www.ffprhc.org.uk). A recent study in the BMJ reported a 12 per cent reduced overall risk of cancer associated with oral contraceptives but an increased risk of cervical cancer of 38 per 100 000 woman-years after at least eight years' use. The FFPRHC says this study was conducted before the UK cervical screening programme was established, and at a time when the average Inhaled insulin ,unlikely to be cost effective' Inhaled insulin (Exubera) is safe and effective but costs so much more than injected insulin that it is unlikely to be cost effective, according to a new Health Technology Assessment (2007;11:No.33.www.hta.nhsweb.nhs.uk). The review included nine trials (seven of Exubera), in which the only significant difference between inhaled and injected soluble insulin was in patient preference. However, most of the trials used syringes for insulin injection rather than pens. The extra cost of inhaled insulin is put at between £600 and £1000 per year. New topics for NICE The Secretary of State for Health has referred the novel antihypertensive aliskiren (Rasilez) for appraisal by NICE; aliskiren is the first direct renin inhibitor to be introduced. Other referrals to NICE include five clinical guidelines (multiple pregnancy, transient loss of consciousness, lower UTI in men, post-ITU rehabilitation and colorectal and anal cancer). Topics for technology appraisals include cetuximab (Erbitux) for colorectal and head and neck cancers. QOF statistics for 06/07 GPs in England averaged 96.3 per cent of the maximum points available for the clinical domain of the Quality and Outcomes Framework in 2006/07 compared with 97.1 per cent previously, official statistics show. Mean practice scores for most clinical areas were in the mid-90 per cent range, but highest for obesity (100 per cent) and lowest for depression (81 per cent), palliative care (90 per cent), mental health and epilepsy (<95 per cent). NICE consulting on type 2 diabetes guideline NICE is consulting on its draft clinical guideline for the management of type 2 diabetes. Comments should be submitted online by 22 November; publication is scheduled for April 2008. The drug of first choice for glycaemic control is metformin, which should be considered even for patients who are not overweight; a sulphonylurea is an alternative or adjunctive agent if glycaemic control is not achieved with metformin alone. If these regimens fail, a glitazone may be added. Exenatide (Byetta) is recommended only for obese patients for whom other oral treatments have failed. The guidance will update and replace clinical guidelines E, F, G and H, and technology appraisals 53, 60 and 63. Glitazones increase risk of HF but not CV death A new meta-analysis , this time of seven trials involving a total of 20 191 patients with type 2 diabetes or impaired glucose tolerance treated with a glitazone , has concluded that these agents are associated with an increased risk of heart failure but not cardiovascular death (Lancet 2007;370:1129,36). Compared with comparator drugs, glitazones were associated with an increased risk of congestive heart failure (2.3 vs 1.4 per cent; relative risk, RR, 1.72; number needed to harm over 30 months, 107). There was no heterogeneity between studies, showing that this is a class effect. However, the risk of cardiovascular death was not increased for either rosiglitazone (Avandia) or pioglitazone (Actos). Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 12 2007Article first published online: 4 OCT 200 NAO: GPs still not prescribing efficiently The National Audit Office (NAO) says NHS funds are being wasted through inefficient GP prescribing and patients not taking their medicines. The NAO's long-awaited report, Prescribing Costs in Primary Care (www.nao.org.uk), found large variations between PCTs in generic prescribing of statins, ACE inhibitors and angiotensin-II antagonists, and protonpump inhibitors; PCTs were also paying widely differing prices for these products. There was a five-fold variation in prescribing volume for clopidogrel between PCTs. These four drugs accounted for only 19 per cent of total spending but, if all practices matched the performance of the best 25 per cent, the NHS would save £200 million annually. PCTs should do more to rationalise prescribing and support their GPs, the NAO concludes. The NAO says that the cost of medicines dispensed for but not taken by patients lies somewhere in the range £100-£800 million annually. Strategies to reduce waste include public awareness campaigns and restricting supplies to four weeks (or two weeks for new medicines). Rosiglitazone may increase CV death risk A meta-analysis of 42 clinical trials has suggested that rosiglitazone is associated with increased risks of myocardial infarction (MI) and cardiovascular death (N Engl J Med 2007; published online 21 May: doi 10.1056/ NEJMoa072761). Like the COX-2 inhibitors, rosiglitazone was licensed without determining its possible effects on long-term cardiovascular outcomes, and interpretation of the latest findings is complicated by the multiple comparisons involved. For risk of MI, there was no significant difference between rosiglitazone and placebo (though this was of borderline statistical signifi-cance , p=0.07), metformin, sulphonylureas or insulin. Rosiglitazone was associated with a statistically significant 43 per cent increased risk compared with all comparators combined but the absolute increase in risk was very small (0.02 per cent). The trends were similar for risk of cardiovascular death, though rosiglitazone was associated with a 64 per cent increased risk compared with all comparators combined that was of borderline statistical significance (p=0.06). The authors acknowledge that their analysis pooled short-term studies that excluded patients at risk of heart disease and was not designed to determine cardiovascular outcomes, and they had no access to patientlevel data; as a result, there is uncertainty about their findings. Nevertheless, they say there is now an urgent need to clarify the risk associated with rosiglitazone. GlaxoSmithKline has rebutted the findings, stating that the cardiovascular risk profile of rosiglitazone is comparable with that of other oral antidiabetic drugs. The MHRA says warnings in the current SPCs for Avandia and Avandamet already reflect most of the data in the latest US review. The possible effects of rosiglitazone on cardiovascular events is currently being evaluated in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes (RECORD) study. Good management tool The Department of Health has published a disease management tool to enable PCTs to model local interventions that could reduce emergency admissions. The web-based ,voluntary good practice tool' will demonstrate how interventions in primary care and social care settings can improve the management of long-term conditions including cardiovascular disease, asthma and COPD, and dementia and depression. Counterfeit medicines The MHRA has issued an unprecedented three alerts about fake medicines in the legitimate supply chain, recalling all affected lot numbers. Three batches of Zyprexa 10mg tablets (olanzapine) were withdrawn after a company printing labels became suspicious and alerted Eli Lilly. Two of the batches, which contained 60 per cent of the stated active ingredient, had reached patients but no adverse events were reported. Two lots of parallel-imported Plavix 75mg tablets (clopidogrel) have been withdrawn after counterfeit packs were identified. The lots were in French original packaging but will have been overlabelled for the UK market. The counterfeits were mixed with genuine packs from Sanofi-Aventis. Fake Casodex 50mg tablets (bicalutamide) have been identified in a parallel import from France. The Royal Pharmaceutical Society reports that the fake contains 75 per cent of the stated dose of bicalutamide. Alcohol-free mometasone Schering-plough has introduced an alcohol-free formulation of mometasone furoate nasal spray (Nasonex) for hay fever. The company says that an alcohol vehicle causes nasal irritation and leaves an unpleasant aftertaste, adding that over 40 per cent of patients cite this as the main reason for stopping treatment, and over 50 per cent state a preference for an alcohol-free product. Aid to improve statin adherence Adherence to statin therapy can be improved if patients use a decision aid when they are offered treatment,US investigators say (Arch Intern Med 2007;167:1076-82). The decision aid estimated the individual's 10-year cardiovascular risk and the risk reduction from treatment, and summarised the disadvantages of statins.Patients with diabetes who used the aid knew more about their risk and were less indecisive about treatment than those who did not. The odds of having missed a dose over three months were three times higher for patients who had not used the aid. Online tool calculates switch savings A new online tool can help GPs estimate the savings achievable from switching patients to cheaper medicines. The Switch Saving Calculator, developed by the Prescribing Analysis & Support Team at the NHS Regional Drug and Therapeutics Centre in Newcastle, calculates potential savings based on past, current or projected use of the target drug. It can be applied to individual prescribers or scaled up to practice, commissioning group, PCT, health authority or even national level. Separate calculators are available for primary and secondary care. The current version calculates potential savings by switching from atorvastatin to simvastatin. The Newcastle team says other drugs will be added and they will update prices regularly. The calculator is at www.nyrdtc.nhs.uk:80/Services/presc_supp/ switch_saving_calculator/switch_saving_calculator.html. No improvement in drug information for patients leaving hospital The information given to patients discharged from hospital is not improving, according to the Healthcare Commission's annual patient survey (www.healthcare commission.org.uk). The 2006 survey found that the commonest reason patients were kept waiting for at least four hours to leave hospital was the delay in providing discharge medicines. Provision of written information increased from 62 per cent of patients in 2005 to 65 per cent in 2006. However, only 76 per cent said they had been told about their medicines in a way they could ,completely' understand (79 per cent in 2002). The proportion of patients reporting complete information about sideeffects also fell (from 40 per cent in 2005 to 37 per cent). Aspirin in preeclampsia A new meta-analysis has found that primary prevention with low-dose aspirin modestly but consistently reduces the risk of preeclampsia (Lancet 2007; published online 18 May). The study of 31 trials involving 32 217 women at low to moderate risk found that antiplatelet agents (mostly aspirin) reduced the risk of pre-eclampsia and preterm birth by 10 per cent without an increased risk of bleeding. The benefit was similar across subgroups. There were also nonsignificant reductions in the risk of small for age, stillborn and death before discharge. New from NICE NICE approves varenicline for NHS NICE has endorsed the use of varenicline (Champix) as an aid to smoking cessation within the NHS for England and Wales; it has already been approved for use in Scotland by the Scottish Medicines Consortium. Varenicline is a partial agonist at the ,4,2 nicotinic receptor. It alleviates craving and withdrawal symptoms, and reduces the rewarding and reinforcing effects of smoking. The commonest adverse effect is mild to moderate nausea, which improves with time.1 Varenicline is licensed for smoking cessation in adults; NICE says it should be offered as an option for smokers who say they want to quit as part of a programme of behavioural support. However, treatment should not be withheld if counselling and support are not available. NICE was critical of manufacturer Pfizer's economic arguments in favour of varenicline, which inappropriately included US data, assumed a single quit attempt and may have overestimated its efficacy. It nonetheless concluded that varenicline is more effective than nicotine replacement therapy (NRT) or bupropion (Zyban) in achieving continuous abstinence. NICE estimated that, compared with NRT, the odds of abstinence at one year with varenicline were 54 per cent greater. A Cochrane review1 concluded that abstinence was 66 per cent more likely with varenicline than with bupropion, and three times more likely than with placebo. There was also a benefit from offering smokers a wider choice of treatments. A 12-week course of varenicline costs £163.80; it is also licensed for an additional 12-week course and dose tapering may be considered for those at high risk of relapse. The final appraisal determination does not state which is the treatment of first choice for smoking cessation. NICE is currently preparing guidance on smoking cessation in pri-mary care, pharmacies and workplaces. Copyright © 2007 Wiley Interface Ltd [source] Routine use of operational diagnostic criteria affects the pharmacotherapy of dysthymia: National questionnaire survey of experienced psychiatrists in JapanPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2006TARO ENDO md Abstract, The purpose of the present paper was to evaluate, with the use of a questionnaire, how Japanese psychiatrists diagnose and treat a typical adult dysthymia case. Clinicians who routinely use operational diagnostic criteria (ODC) had more correct diagnoses than those who did not. Approximately 70% of psychiatrists who routinely use ODC chose selective serotonin re-uptake inhibitors (SSRI) as the first choice of treatment, while of those psychiatrists who do not use these criteria, only half prescribed SSRI. This difference was statistically significant (P = 0.01). The results of the present study suggest that psychiatrists who are familiar with ODC tend to treat dysthymia according to evidence-based pharmacotherapy. [source] | ||||||||||||||||||||||||||||||||||