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Selected AbstractsIntracellular and plasma steady-state pharmacokinetics of raltegravir, darunavir, etravirine and ritonavir in heavily pre-treated HIV-infected patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2010Rob Ter Heine WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The combination of raltegravir, etravirine and ritonavir boosted darunavir is a potent antiretroviral regimen for patients who have been heavily pre-treated for HIV-infection. All these agents have to exert their action intracellularly. However, only little is known about the cellular pharmacology of these agents. WHAT THIS STUDY ADDS , We investigated the steady-state plasma and cellular pharmacokinetics of raltegravir, etravirine, darunavir and ritonavir and the observed distinct intracellular accumulation ratios indicated that these antiretroviral drugs have different affinity for the cellular compartment. AIM To study the steady-state plasma and intracellular pharmacokinetics of raltegravir, etravirine, darunavir and ritonavir in heavily pre-treated patients. METHODS Patients on a salvage regimen containing raltegravir, etravirine, darunavir and ritonavir were eligible for inclusion. During a 12 h dosing interval plasma and peripheral blood mononuclear cells were collected. Drug concentrations were measured using a validated LC-MS/MS assay and pharmacokinetic analysis was performed using non-linear mixed effect modelling. RESULTS Irregular absorption was observed with raltegravir and darunavir, which may be caused by enterohepatic cycling. Relative bioavailability of ritonavir was low, when compared with other ritonavir regimens. Raltegravir plasma pharmacokinetics showed wide interpatient variability, while intracellular raltegravir concentrations could not be detected (<0.001 mg l,1 in cell lysate). The intracellular to plasma ratios for etravirine, darunavir and ritonavir were 12.9, 1.32 and 7.72, respectively, and the relative standard error of these estimates were 16.3%, 12.3% and 13.0%. CONCLUSIONS The observed distinct intracellular accumulation indicated that these drugs have different affinity for the cellular compartment. The relatively high intracellular accumulation of etravirine may explain its efficacy and its previously described absence of PK,PD relationships in the therapeutic concentration range, when compared with other non-nucleoside reverse transcriptase inhibitors. Lastly, the intracellular concentrations of ritonavir seem sufficient for inhibition of viral replication in the cellular compartment in PI-naive patients, but not in patients with HIV harbouring PI resistance. [source] Long-term efficacy and safety of insulin detemir compared to Neutral Protamine Hagedorn insulin in patients with Type 1 diabetes using a treat-to-target basal,bolus regimen with insulin aspart at meals: a 2-year, randomized, controlled trialDIABETIC MEDICINE, Issue 4 2008P. C. Bartley Abstract Aims This 24-month, multi-national, open-label, parallel group trial investigated the long-term efficacy and safety of insulin detemir and Neutral Protamine Hagedorn insulin in combination with mealtime insulin aspart in patients with Type 1 diabetes using a treat-to-target concept. Methods Patients were randomized 2 : 1 to detemir (n = 331) or NPH (n = 166) groups. Basal insulin was initiated once daily (evening) and titrated individually based on self-measured plasma glucose (PG) levels, aiming for pre-breakfast and pre-dinner targets , 6.0 mmol/l. A second basal morning dose could be added according to pre-defined criteria. Results After 24 months, superiority of glycated haemoglobin (HbA1c) was achieved with detemir compared to NPH (detemir 7.36%, NPH 7.58%, mean difference ,0.22% points) [95% confidence interval (CI) ,0.41 to ,0.03%], with reductions of 0.94% and 0.72% points, respectively. Fasting PG (FPGlab) was also lower with detemir (detemir 8.35 mmol/l, NPH 9.43 mmol/l; P = 0.019). Twenty-two per cent of patients treated with detemir reached an HbA1c , 7.0% in the absence of confirmed hypoglycaemia during the last month of treatment vs. 13% on NPH (P = 0.019). Risk of major and nocturnal hypoglycaemia was 69% and 46% lower with detemir than with NPH (P < 0.001), respectively; patients treated with detemir gained less weight (detemir 1.7 kg, NPH 2.7 kg; P = 0.024). The overall safety profile was similar in the two groups and treatment with detemir did not result in any unexpected findings. Conclusions Long-term treatment with the insulin analogues detemir + aspart was superior to NPH + aspart in reducing HbA1c, with added benefits of less major and nocturnal hypoglycaemia and less weight gain. [source] Low-risk HLA genotype in Type 1 diabetes is associated with less destruction of pancreatic B-cells 12 months after diagnosisDIABETIC MEDICINE, Issue 12 2007M. Spoletini Abstract Aims The role of human leukocyte antigen (HLA) genes in the susceptibility to Type 1 diabetes (T1DM) is well known. However, we do not know whether the degree of pancreatic B-cell destruction depends on different HLA genetic risk. The aim of this study was to analyse the influence of DRB1* and DQB1* genes on the rate of pancreatic B-cell loss in a prospective series of 120 consecutive newly diagnosed T1DM subjects in the first 12 months after diagnosis. Methods Patients were typed for HLA-DRB1* and DQB1* loci by a reverse line blot assay using an array of immobilized sequence-specific oligonucleotide probes. C-peptide, insulin requirement and glycated haemoglobin (HbA1c) were determined at diagnosis and every 3 months for 12 months. The variance of C-peptide as evidence of B-cell loss during follow-up was analysed using the general linear model for repeated-measures procedure. Results Fasting C-peptide in T1DM subjects with low HLA genetic risk was significantly higher when compared with subjects with moderate or high HLA genetic risk from time of diagnosis up to 12 months (P = 0.007 and P = 0.0002, respectively). Nonetheless, the changes in C-peptide levels over a 12-month period did not differ significantly between T1DM subjects with different HLA genetic risks. Conclusions Low-risk HLA genotype in T1DM is associated with less destruction of pancreatic B-cells up to 12 months after diagnosis. These results are useful when designing trials for therapies aimed to prevent the progression of B-cell destruction in recent-onset T1DM. [source] A qualitative investigation of the views and health beliefs of patients with Type 2 diabetes following the introduction of a diabetes shared care serviceDIABETIC MEDICINE, Issue 10 2003S. M. Smith Abstract Aims A qualitative research approach was adopted in order to explore the views and health beliefs of patients with Type 2 diabetes who had experienced a new structured diabetes shared care service. Methods Patients from 15 general practices were randomly selected and invited to attend three focus groups. Two independent researchers adopted the ,Framework' technique to analyse the transcribed data and identify key themes expressed by patients. Results Themes relating to diabetes included frustration, victimization and powerlessness in relation to living with diabetes, controlling blood sugar, medication and economic barriers to care. Differences in emphases between patients and healthcare providers emerged. Patients were generally positive about shared care and largely identified it with the nurses involved. Conclusion This research highlights the importance of an in-depth exploration of patients' views during changes in diabetes care delivery to identify service delivery failures and gaps in patient knowledge such as lack of awareness of the extent of macrovascular risk. [source] Moderators and mediators of two brief interventions for alcohol in the emergency departmentADDICTION, Issue 3 2010Nancy P. Barnett ABSTRACT Objective To evaluate moderators and mediators of brief alcohol interventions conducted in the emergency department. Methods Patients (18,24 years; n = 172) in an emergency department received a motivational interview with personalized feedback (MI) or feedback only (FO), with 1- and 3-month booster sessions and 6- and 12-month follow-ups. Gender, alcohol status/severity group [ALC+ only, Alcohol Use Disorders Identification Test (AUDIT+) only, ALC+/AUDIT+], attribution of alcohol in the medical event, aversiveness of the event, perceived seriousness of the event and baseline readiness to change alcohol use were evaluated as moderators of intervention efficacy. Readiness to change also was evaluated as a mediator of intervention efficacy, as were perceived risks/benefits of alcohol use, self-efficacy and alcohol treatment seeking. Results Alcohol status, attribution and readiness moderated intervention effects such that patients who had not been drinking prior to their medical event, those who had low or medium attribution for alcohol in the event and those who had low or medium readiness to change showed lower alcohol use 12 months after receiving MI compared to FO. In the AUDIT+ only group those who received MI showed lower rates of alcohol-related injury at follow-up than those who received FO. Patients who had been drinking prior to their precipitating event did not show different outcomes in the two interventions, regardless of AUDIT status. Gender did not moderate intervention efficacy and no significant mediation was found. Conclusions Findings may help practitioners target patients for whom brief interventions will be most effective. More research is needed to understand how brief interventions transmit their effects. [source] The outcome of a rapid hepatitis B vaccination programme in a methadone treatment clinicADDICTION, Issue 2 2010Parameswaran Ramasamy ABSTRACT Aim Injecting drug users are a high-risk population for hepatitis B (HBV), but are difficult to engage in vaccination programmes. This study examines the completion rates of a HBV vaccination schedule and seroconversion in a group of patients in methadone maintenance treatment. Methods Patients at a public methadone maintenance programme in Sydney, Australia, were screened for viral hepatitis (hepatitis A, B and C) and offered a rapid HBV vaccination schedule (0, 1 and 2 months). Hepatitis B surface antibody (antiHBs) was retested on completion of the vaccination schedule. Results A total of 143 patients [71.3% male, mean age 33.1 (standard deviation ± 8.3)] enrolled in the project. Forty-nine per cent of patients were HAV antibody (Ab) positive, 81.1% hepatitis C virus (HCV) antibody (Ab) positive and 38.9% antiHBs positive. Exposure to multiple hepatitis viruses was common, with 24.5% testing positive for all three viruses. Seventy-three (83%) of the 88 antiHBs negative patients completed the vaccination schedule. Post-vaccination serology indicated a seroconversion rate of 75.4% (55 of 73) of completors, or 62.5% of eligible participants (55 of 88). Conclusion While there was a high rate of completion of the rapid vaccination schedule in this population, a moderate seroconversion rate was achieved. Further work is required to identify an optimal vaccination schedule in opioid substitution patients. [source] The European NEAT Program: An Integrated Approach Using Acamprosate and Psychosocial Support for the Prevention of Relapse in Alcohol-Dependent Patients With a Statistical Modeling of Therapy Success PredictionALCOHOLISM, Issue 10 2002Isidore Pelc Background A multicenter, prospective study was conducted in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques, within the setting of standard patient care. Methods Patients diagnosed as alcohol dependent using DSM-III-R criteria were treated, for 24 weeks, with acamprosate and appropriate psychosocial support. Potential predictor variables were recorded at inclusion. Drinking behavior was monitored throughout; the proportion of cumulative abstinence days was the principal outcome measure. The influence of baseline clinical and demographic variables on outcome was assessed using multiple regression analysis. Adverse events were recorded systematically. Results A total of 1289 patients were recruited; 1230 took at least one dose of the drug and provided at least one set of follow-up data; 543 (42.1%)patients were observed for the full 24-week period. The overall proportion of cumulative abstinence days was 0.48. Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome, as were, to a lesser extent, multiple previous episodes of detoxification, unemployment, and living alone. Older age and stable employment were positively associated with outcome. The difference in the unadjusted proportion of cumulative abstinence days between countries was significant (p < 0.001) but less so when adjusted for the predictive factors identified in the multivariate model (p < 0.019). Overall, outcome was not influenced by the nature of the psychosocial support provided. Adverse events were generally mild, with gastrointestinal disorders, which occurred in 21.5% of patients, being the most frequent. Conclusions This open-label study confirms the efficacy and safety of acamprosate in the treatment of alcohol dependence in the setting of standard patient care. Treatment benefit was observed irrespective of the nature of the psychosocial support provided. Predictors of the response to treatment were identified; their heterogeneous distribution within the study population explained, at least in part, the differences in outcome between countries. [source] Toenail abnormalities and onychomycosis in chronic venous insufficiency of the legs: should we treat?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2008A Shemer Abstract Background Toenail manifestations of chronic venous insufficiency (CVI) may often mimic the nail changes of onychomycosis. The current study aims to determine the frequency of toenails deformations in patients with CVI, onychomycosis prevalence among deformed toenails and the outcome of itraconazole treatment. Methods Patients with clinical evidence of (CVI) were enrolled. All patients with toenails deformations and proven onychomycosis were treated by itraconazole pulse therapy for 4 months and then followed-up for additional 5 to 6 months. Results Forty-four patients with CVI entered the study. Thirty-seven patients (84%) had nail deformations; 28 of 37 patients (75%) had onychomycosis; and 24 patients completed the follow-up period. Total cure was achieved in 6 of 24 patients (25%), and 14 patients (58%) had no improvement. Patients' age and CVI duration were significantly correlated to onychomycosis cure rate. Conclusions Nail deformations are more prevalent in CVI patients (84%) then in the general elderly population, and 75% of affected nails had also onychomycosis. In these patients, itraconazole achieved only 25% total cure rate compared with the 60% to 70% cure rate commonly cited in the literature, probably due to irreversible nail deformity caused by the CVI and due to the thickened nail that prevented penetrance of itraconazole into the nail plate. Therefore, before antifungal treatment is started for onychomycosis in patients with CVI, especially in older patients, the caregiver must stress out that the final outcome might not be as desirable as in pure onychomycosis patients. [source] Long-term follow-up of patients with mild to moderate drug-induced liver injuryALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2007E. BJÖRNSSON Summary Aim To evaluate the long-term prognosis of patients diagnosed with drug-induced liver injury, and the nature of the liver injury. Methods Patients with a diagnosis of drug-induced liver injury between 1994 and 2005 were identified in a university hospital clinic. Patients surviving drug-induced liver injury-associated liver failure were excluded. Results Seventy-seven cases were identified and those who were alive (69) were invited to attend follow-up. Of those patients who had died, none had died of liver disease. Of those patients who had survived, 59 were reviewed in the clinic. Patients had a median follow-up of 48 months. Before the diagnosis of drug-induced liver injury, nine had a chronic liver disease, four with autoimmune hepatitis, two with non-alcoholic liver disease, one each with non-alcoholic fatty liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. There was no evidence of progression of their liver disease during follow-up. Among 50 patients without a known liver disease prior to the drug-induced liver injury, 10 had abnormal liver tests. Diagnostic work-up revealed alternative cause of liver disease in all except three patients (6%), who had asymptomatic abnormal liver tests (but normal bilirubin in all). Conclusions Chronic abnormalities in liver tests, not explained by an identified liver disease, are very rare in patients previously diagnosed with drug-induced liver injury. This group of patients did not seem to have a clinically significant liver injury at long-term follow-up. [source] Staging of Obstructive Sleep Apnea/Hypopnea Syndrome: A Guide to Appropriate Treatment,THE LARYNGOSCOPE, Issue 3 2004Michael Friedman MD Abstract Objective Early studies by Friedman et al. have demonstrated the value of staging obstructive sleep apnea/hypopnea syndrome (OSAHS) patients for the prediction of success for uvulopalatopharyngoplasty (UPPP) on the basis of short-term follow up. The goal of this study is to test the value of this staging system in a prospective study. Study Design This is a prospective study of two cohorts of patients: one was treated with the benefit of a clinical staging system and the other without. Methods Patients with symptoms of OSAHS were assessed by polysomnography and were staged according to a previously described staging system. The staging system is based on palate position, tonsil size, and body mass index (BMI). The control group was treated without the benefit of staging. All patients in the control group were treated with UPPP only. Patients in the experimental group were treated based on their clinical stage. Patients with stage I disease, regardless of the severity of disease, were treated with UPPP only. Selected patients with stage II and stage III disease were treated with UPPP in addition to a staged tongue-base reduction using a radiofrequency technique (TBRF). Results Follow-up at 6 months showed significant improvement compared with a group of patients treated without the benefit of a staging system. Successful treatment of patients with stage II disease improved from 37.9% to 74.0%. The overall success rate improved from 40% to 59.1%. Conclusion Clearly, patients with stage I disease had the best success rate, but a selective protocol based on clinical staging improves the overall success rate. In addition, it can eliminate as surgical candidates those patients with whom the procedure is likely to fail. [source] Hypothermia During Head and Neck Surgery,THE LARYNGOSCOPE, Issue 8 2003Nishant Agrawal MD Abstract Objective To determine the predictors and incidence of hypothermia in patients undergoing head and neck surgery. Study Design Retrospective analysis. Methods Patients were either not warmed (n = 43) or actively warmed with forced-air warming (n = 25). Clinical variables that were assessed as predictors of core body temperature included age, body mass, duration of procedure, estimated blood loss, amount of intravenous fluids administered, and the use of forced-air warming. The incidence of severe intraoperative hypothermia and potential hypothermia-related complications was also examined. Results The study demonstrated that advanced age is a risk factor for hypothermia and decreased body mass is associated with lower final body temperatures in the groups of patients that was not warmed. After adjusting for differences in the ages and weights between the two groups, the mean core body temperature was found to be 0.4°C lower in the patients who were not warmed. Severe intraoperative hypothermia occurred in 5 of 38 patients (11.6%) who were not warmed and 2 of 23 patients (8.0%) who were warmed. The complications associated with hypothermia included delayed time to extubation, the development of neck seromas, and flap dehiscence. Conclusions Patients undergoing head and neck surgery are at risk for the development of intraoperative hypothermia and require careful temperature monitoring. Elderly patients and patients with low body mass are more prone to develop low intraoperative core body temperatures. Active warming with forced-air warmers should be considered for patients at risk for intraoperative hypothermia and for patients who develop hypothermia intraoperatively, to avoid hypothermia-related complications. [source] Pulmonary Function After Pectoralis Major Myocutaneous Flap HarvestTHE LARYNGOSCOPE, Issue 3 2002FACS, Yoav P. Talmi MD Abstract Objective The pectoralis major myocutaneous flap is widely used in the reconstruction of surgical defects in the head and neck region. Pulmonary atelectasis has been reported in patients undergoing these procedures, and many of these patients are heavy smokers and drinkers and have associated cardiopulmonary disorders. Flap harvest and donor site closure may lead to impairment of pulmonary function before and after the use of pectoralis major myocutaneous (PMC) in surgical reconstruction in patients with cancer of the head and neck. Methods Patients undergoing extirpation of head and neck tumors with PMC reconstruction were prospectively evaluated. Patient age, smoking history (pack-years), anesthesia duration, percentage predicted pre- and postoperative FEV1, percentage-predicted pre- and postoperative FVC (forced vital capacity), and preoperative SaO2 (oxygen saturation) were evaluated. Preoperative FEV1/FVC ratio was calculated. Chest x-rays were reviewed. Results Only 11 patients, 5 of whom smoked, could be evaluated postoperatively. Preoperative FEV1/FVC was more than 70 and FEV1 more than 75% predicted in all patients. A decrease in FVC was observed in 7 of the 11 patients, which ranged between 2% and 27% without any clinically obvious respiratory manifestations. A baseline SaO2 of more than 96% was noted in all patients. Four of 9 postoperative chest x-rays demonstrated atelectasis. Conclusions PMC harvest and donor site closure may lead to the recorded decrease in FVC measurements. These changes did not manifest clinically. Nevertheless, alternative methods of surgical defect closure should be considered in patients with severe preexisting pulmonary disorders. [source] Preoperative versus Postoperative Role of Vestibular-Evoked Myogenic Potentials in Cerebellopontine Angle Tumor,THE LARYNGOSCOPE, Issue 2 2002Cheng-Wei Chen MD Abstract Objective/Hypothesis Vestibular-evoked myogenic potential (VEMP) examination was performed on patients with a cerebellopontine angle (CPA) tumor to evaluate its clinical role. Methods Patients with a CPA tumor were subjected to caloric test and VEMP examination. Follow-up study was performed 1 year after the surgery. Results Six (69%) of the 9 tumors did not exhibit either caloric response or VEMP on the lesioned side. Three patients received tumor excision and all tumors involved both the superior and inferior vestibular nerves. Two (22%) of the 9 tumors had normal caloric responses but no VEMP. One underwent surgical excision, and the tumor originated from the inferior vestibular nerve. In the follow-up study, only 1 patient with epidermoid cyst presented complete recovery of caloric response and VEMP, whereas in the other 3 patients with vestibular schwannoma, the responses were all absent persistently. Conclusion Before surgery, VEMP test can be used to predict the nerve of origin and to formulate the best surgical approach. After surgery, VEMP test can be used to define the nature of the tumor (compressing or infiltrating the nerve) and disclose the residual function of the inferior vestibular nerve. [source] Autoimmune Sensorineural Hearing Loss in Young Patients: An Exploratory StudyTHE LARYNGOSCOPE, Issue 11 2001Jean-Paul Tomasi MD Abstract Objectives P0 protein is expressed exclusively in myelinating Schwann cells of the peripheral nervous system. In a previous study from our laboratory, 27% of patients with sensorineural hearing loss (SNHL) had antibodies to P0 protein in their serum. The purpose of the present exploratory study was to examine the relationship between the clinical presentation of SNHL among children and young adults (age range, 5,30 y) and the presence of serum anti-P0 antibodies. Study Design The data were collected by retrospective questionnaires from Belgian otolaryngologists. Methods Patients were divided for comparison into two groups according to the presence or absence of anti-P0 antibodies. Results Analyses of clinical data and audiometric results indicated that a progressive hearing loss was more frequently recorded in the patients in the anti-P0 antibody,positive group (82% [14 of 17]) than in those in the anti-P0 antibody,negative group (35% [6 of 17]) (P <.005). Conclusions Thus, in the age group in the present study, autoimmune SNHL (as measured in the present study by the presence of anti-P0 antibodies) is more frequently associated with progressive than with sudden hearing loss. The implications of this finding for preventive screening of hearing loss in children and young adults are discussed. [source] Pseudotumor of Infancy and Congenital Muscular Torticollis: 170 Cases,THE LARYNGOSCOPE, Issue 4 2001Julie L. Wei MD Abstract Objectives To review pseudotumor of infancy (POI) and congenital muscular torticollis (CMT) and to suggest an algorithm for treatment. Study Design Retrospective review of cases from 1962 to 1998 at a tertiary care center. Methods Patients included in this study were 81 boys and 89 girls who had a diagnosis of POI (n = 38) or CMT (n = 132) before 24 months of age. Results For all patients, the mean age at diagnosis was 4 months; 54.1% had the left side of the neck affected, over 90% had a head tilt, and 2.4% had feeding difficulty as a result of the disorder. Plagiocephaly was present in 39.5% of patients with POI and 63.6% of patients with CMT; a neck mass, in 63.2% and 18.2%, respectively; and facial asymmetry, in 7.9% and 15.9%, respectively. All patients had a complete physical examination; 54.1% had plain cervical radiography, 4.1%, computed tomography, and 2.9%, ultrasonography. Passive range of motion was the initial treatment recommended for 65.3% of patients. Conservative treatment failed for 16 patients; subsequently, they had surgical treatment. Follow-up data were available for 159 patients; 85.5% experienced total resolution and 14.5% experienced subtotal resolution or long-term abnormality. Conclusions Children diagnosed with POI or CMT should be treated and observed for at least 12 months or until symptoms resolve. If symptoms persist 1 year after diagnosis despite conservative therapy, surgical treatment should be considered. The majority of children with POI or CMT experience total resolution of symptoms. [source] Early Oral Feeding Following Total Laryngectomy,,THE LARYNGOSCOPE, Issue 3 2001Jesus E. Medina MD Abstract Objectives The time to begin oral feeding after total laryngectomy remains a subject of debate among head and neck surgeons. The prevailing assumption is that early initiation of oral feeding may cause pharyngocutaneous fistula; thus, the common practice of initiating oral feeding after a period of 7 to 10 days. The objective of the study was to demonstrate the feasibility and safety of oral feeding 48 hours after total laryngectomy. Study Design Two-part study includes, first, a sequential study and, second, a prospective analysis of our practice. Methods Patients undergoing total laryngectomy without partial pharyngectomy or radiation treatment (except irradiation through small ports for a T1 or T2 glottic carcinoma) were included. In the first, sequential part of the study (part I), a group of 18 patients who were fed 7 to 10 days after total laryngectomy (control group) was compared with a group of 20 patients who received oral feeding within 48 hours. To confirm the results of part I, a prospective analysis of this practice was conducted (part II) in which 35 additional patients who met the above criteria were fed within 48 hours after surgery. Results In part I, pharyngocutaneous fistula occurred in one patient (5%) in the early feeding group and in two patients (11%) in the control group. In part II, pharyngocutaneous fistula occurred in one patient (2.8%). Overall, fistula occurred in two patients in the combined early feeding group (3.6%). This rate of pharyngocutaneous fistula compares favorably with the fistula rate in the control group of 18 patients. Pharyngeal stricture that required dilation occurred in three of our patients in the study group and two in the control group (5.5% vs. 11%, respectively). The length of hospital stay was significantly shortened from 12 to 7 days. Conclusion Our results indicate that in this patient population initiation of oral feeding 48 hours after total laryngectomy is a safe clinical practice. [source] Efficacy of Concomitant Chemoradiation and Surgical Salvage for N3 Nodal Disease Associated With Upper Aerodigestive Tract Carcinoma,THE LARYNGOSCOPE, Issue 11 2000Khwaja A. Ahmed MD Abstract Objectives/Hypothesis To determine whether an aggressive approach using trimodality therapy would improve the outcome in head and neck cancer patients with advanced (N3) nodal disease. Study Design In this retrospective, nonrandomized review, we analyzed a subset of patients who were treated in a targeted chemoradiation therapy protocol, consisting of 31 patients who received treatment between June 1993 and June 1997. Methods Patients received selective intra-arterial infusions of cisplatin (150 mg/m2/wk for 4 weeks) and concomitant radiation therapy (2 Gy/fraction × 35 daily fractions over a 7-wk period) to the primary and clinically positive nodal disease. The patients were re-evaluated 2 months later and underwent salvage neck dissections if there was any residual disease. Results Classification of disease in the primary site was as follows: T1 in 2 patients, T2 in 6 patients, T3 in 14 patients, and T4 in 9 patients. Among the 31 patients who were assessed for response at the nodal site, 4 of 31 (13%) had a complete response, 21 of 31 (68%) had a partial response, and 1 of 31 (3%) had no response. Excluding the 5 patients who could not be evaluated, 4 of 26 patients (15%) had a complete response, 21 of 26 (81%) had a partial response, and 1 of 26 (4%) had no response. Nineteen patients subsequently underwent neck dissection, and five patients had histological evidence of residual disease. The remaining seven patients included four who had a complete response in their necks and three who died of intercurrent disease before re-staging. Among the 23 patients who were rendered disease free, there were no recurrences within the neck, whereas 1 patient had recurrence at the primary site and 11 patients had recurrence at distant sites. With a median follow-up of 15 months (range, 4,41 mo), the 3-year overall survival and disease-specific survival were 41% and 43%, respectively. Conclusions Targeted chemoradiation therapy followed by surgical salvage is a highly effective approach for regional control of patients with N3 nodal disease, whereas additional strategies are required to address the problem of distant metastases. [source] Bed rest versus free mobilisation following embryo transfer: a prospective randomised studyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2004Zouhair O. Amarin Objective To evaluate the efficacy of two clinical methods of post-embryo transfer protocols in patients undergoing in vitro fertilisation. Design Prospective, randomised clinical trial. Setting Hospital-based clinic for reproductive medicine. Sample Women under 40 years of age who were undergoing in vitro fertilisation with GnRH pituitary down-regulation and controlled ovarian hyperstimulation. Methods Patients were randomised to rest for either 1 or 24 hours after embryo transfer. Main outcome measure Clinical pregnancy per cycle rate (the percentage of cycles started that demonstrated a live fetus on ultrasound examination performed at six or seven weeks of gestation). Results The clinical pregnancy rates were 21.5% for the 1-hour and 18.2% for the 24-hour post-embryo transfer groups. The implantation rate per embryo was significantly higher in the 1-hour group (14.4%) than in the 24-hour group (9%). Conclusion One-hour and 24-hour rest post-embryo transfer result in comparable rates of clinical pregnancy. However, 24-hour rest results in reduced implantation rate per embryo. [source] Randomised controlled trial of total compared with subtotal hysterectomy with one-year follow up resultsBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2003Helga Gimbel Objective To compare total abdominal hysterectomy and subtotal abdominal hysterectomy performed for benign uterine diseases. Design Randomised, controlled, unblinded trial with central, computer-generated randomisation. Setting Danish trial performed in 11 departments of gynaecology. Population Women referred for benign uterine diseases were randomised to total abdominal hysterectomy (n= 158) or subtotal abdominal hysterectomy (n= 161). One-year follow up questionnaires had a response rate of 87%. Methods Patients were followed by strict data collection procedures, including postal questionnaires. The results after one year of follow up were analysed by intention-to-treat analyses. Main outcome measures (1) Primary: urinary incontinence and (2) secondary: post-operative complications, quality of life (SF-36), constipation, prolapse of the vaginal vault/cervical stump, satisfaction with sexual life, pelvic pain and vaginal bleeding. Results A significantly (P= 0.043) smaller proportion of women had urinary incontinence one year after total abdominal hysterectomy compared with subtotal abdominal hysterectomy [9%vs 18% (OR 2.08, 95% CI 1.01,4.29)]. The lower proportion of incontinent women in the total abdominal hysterectomy group was a result of a higher proportion of symptom relief (total abdominal hysterectomy: 20/140, subtotal abdominal hysterectomy: 14/136) as well as a lower proportion of women with new symptoms (total abdominal hysterectomy: 3/140, subtotal abdominal hysterectomy: 10/137). Twenty-seven women (20%) from the subtotal abdominal hysterectomy group had vaginal bleeding and two of them had to have their cervix removed. No other clinically important differences were found between the two hysterectomy methods. Conclusions A smaller proportion of women suffered from urinary incontinence after total abdominal hysterectomy than after subtotal abdominal hysterectomy one year post-operatively. [source] Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2003Anne Flem Jacobsen Objective To evaluate the effect and dose of dalteparin given to pregnant women with acute venous thromboembolism. Design An observational study of pregnant women in Norway. Setting Delivery and haematological departments in Norway. Population Twenty women, aged 22,41 years, with acute venous thromboembolism verified by objective means. Methods Patients were treated with dalteparin from diagnosis until delivery. Treatment was monitored with anti-activated factor Xa (anti-Xa) activity, and the dose was adjusted to achieve target 0.5,1.0 U/mL 2,3 hours post-injection. Main outcome measure Anti-Xa activity and side effects. Result None of the patients suffered recurrent venous thromboembolism or major bleeding complications. In 9 of 13 women starting with conventional dose of dalteparin (100 iu/kg bd), dose escalation was necessary to reach target anti-Xa activity. None of the six women who started with 105,118 iu/kg bd required dose escalation. One woman who started with 133 iu/kg bd required dose reduction. Bioaccumulation of dalteparin was not observed. Conclusion Our study suggests that dalteparin may be used for the treatment of acute venous thromboembolism in pregnancy. Approximately 10,20% higher doses of dalteparin may be needed as compared with non-pregnant individuals. [source] The frequency of fragrance allergy in patch-tested patients increases with their ageBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2003D.A. Buckley Summary Background The most likely age of sensitization to fragrance chemicals is unknown. Objectives To investigate the frequency of allergy to the 8% fragrance mix (FM) in each decade of life in patients undergoing patch testing for the investigation of skin symptoms. Methods Patients (n = 23 846; 14 104 female and 9742 male) underwent patch testing to a standard series between 1 January 1984 and 31 December 1998. All data were recorded on a computerized database. Results We found that 8·4% of females and 6·4% of males were allergic to the FM. The frequency of fragrance allergy was low in the first two decades of life (2·5,3·4%). It gradually increased in females after the age of 20 years to peak in the 60s at 14·4% of those tested, with a decline to 11·6% in the 80s. The prevalence in males rose more slowly and peaked at 13·7% in the 70s, declining to 10·8% in the 80s. The youngest patients sensitized were aged 2 years. Conclusions These findings support the hypothesis that allergy to fragrance results from a combination of repeated environmental exposure and age-related susceptibility factors. [source] An evaluation of the usefulness of mycophenolate mofetil in pemphigusBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003A.M. Powell SummaryBackground Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. Objectives The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. Methods Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. Results Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. Conclusions We found that MMF permitted a reduction in prednisolone dosage without disease relapse. [source] The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trialBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003E.M.G.J. De Jong SummaryBackground A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. Objectives To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. Methods Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. Results The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3·4 mg week,1 (phase (II) and 2·6 mg week,1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). Conclusions The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased. [source] 2263: Analysis of the utility of QuantiFERON-TB GoldTM in tube and measurement of IFN, release by peripheral mononuclear cells in response to different mycobacterium antigen in the work-up of patients with uveitisACTA OPHTHALMOLOGICA, Issue 2010D MAKHOUL Purpose Tuberculosis remains an important cause of infectious uveitis and immune reaction against mycobacteria may contribute to the development of certain forms of autoimmune uveitis. Moreover, many non-infectious uveitis patients are treated with immunomodulatory treatment. The evaluation of tuberculosis immunity is thus an important aspect in the work-up of patients with uveitis. In this work, we would like to investigate the usefulness of different methods of tuberculosis immunity testing in a series of patients with intraocular inflammation. Methods Patients with uveitis will undergo a standard diagnosis procedure, including a chest Xray. Quantiferon TB Gold in Tube (QFT) and tuberculin skin test (TST) will be performed. IFN, production by mononuclear cells in response to PPD and to HBHA will be measured by ELISA. Results Thirty-two patients have already been recruited. Sixteen had a negative QFT and a negative TST. In two of them, mononuclear cells produce IFN, in response to PPD (but not to HBHA) and in 1 in response to HBHA (but not to PPD). In 11 patients QFT and TST were positive. In this group, IFN, response to PPD was observed in 82% but only in 50% in response to HBHA. Discordant results between QFT and TST were observed in 5 patients. One had a positive QFT and a negative TST and 4 had a positive TST and a negative QFT. In this group IFN, response to PPD or HBHA was not observed. Conclusion Discordant results between QuantiFERON-TB Gold and TST were observed in 15 % of uveitis patients. Analysis of the IFN, production in response to PPD and to HBHA seems to add important information in both concordant and discordant group. [source] 4243: Capsular peeling in premium IOLs to improve visual outcomeACTA OPHTHALMOLOGICA, Issue 2010MJ TASSIGNON Purpose To demonstrate that capsular peeling may improve quality of vision of patients who experienced reduced vision in the short postoperative period after premium IOL implantation due to decentration of the IOL secondary to PCO. Methods Patients who were refered to our centre because of unsatisfactory quality of vision after premium IOL implantation (more specifically after multifocal IOLs) were scheduled for surgery aiming at peeling the capsular bag. The conditions which the patient needed to meet were: increased higher order aberrations, evidence of tilt or decentration of the IOL, important fibrotic proliferation in the capsular bag, no YAG laser capsulotomy performed. Results After capsular peeling, it was possible to demonstrate that the quality of vision of the patient improved, the higher order aberrations reduced and it was often unnecessary to explant the premium IOL. Although there was an obvious improvement of the quality of vision, this improvement still did not reached the high standard of vision as measured after monofcal IOLs. Conclusion This paper shows how important the role is of PCO on quality of vision. Because contrast sensitivity is already reduced after premium IOL implantation, patients will be very sensitive to an additional reduction as it appears after PCO. [source] 2123: Transferrin and transthyretin in vitreoretinal surgeryACTA OPHTHALMOLOGICA, Issue 2010C ARNDT Purpose The concentration of transferrin in the vitreous is known to be higher than in plasma or aqueous humor. This has been related to a local synthesis of transferrin by the ciliary body. Increased levels have been found in vitro-retinal proliferation. A relationship between the level of transthyretin and the functional outcome has been previously reported. The purpose of the study was to look for a relation between transferrin and transthyretin. Methods Patients with epiretinal membrane and rhegmatogenous retinal detachment were prospectively enrolled. The vitreous samples were obtained without intraocular infusion. The levels of transferrine and transthyretin (prealbumin) were determined in all cases. Results In the group of patients with retinal detachment (n=18), two groups could be identified: the transferrin levels were either low between 40 and 70 mg/l with low transthyretin (<17,8 mg/l)(n=6) or high (>400 mg/l) with transthyretin levels between 200 and 400 mg/l (n=12). No relationship to any clinical parameters (extension of the detachment, onset of symptoms or degre of vitreo-retinal proliferation) could be demonstrated. In patients with epiretinal membranes (n=6), the transferrin levels <40 mg/l, transthyretin < 17,8 mg/l. Conclusion Increased transferrin seems to correlate with increased transthyretin levels in the vitreous. The clinical signification of this relationship remains to be demonstrated and probably requires a larger patient sample. [source] Does delayed treatment shorten the life of patients with fatal choroidal melanoma?ACTA OPHTHALMOLOGICA, Issue 2009B DAMATO Purpose Metastatic death from uveal melanoma occurs in about 50% of patients many of whom experience a delay in treatment, either intentionally or accidentally. The aim of this study was to determine whether treatment delay shortens survival in patients with choroidal melanoma whose disease apparently proved fatal. Methods Patients with choroidal melanoma were included in the study if resident in mainland Britain and if deceased. Survival was analysed according to basal tumour diameter by Kaplan-Meier and Log rank analysis. Results A total of 696 patients with choroidal melanoma died. The patients had a median age of 65 years and a median basal tumour diameter of 15.0 mm. The basal tumour diameter was <10mm in 41 patients; 10-11mm in 88; 12-13mm in 108; 14-15mm in 165; 16-17mm in 123; and >17mm in 171 patients. Log-rank analysis showed no correlation between survival and basal tumour diameter in these patients (Log rank analysis, p = 0.5537). There was perhaps a trend towards longer survival in patients with a basal tumour diameter less than 10mm. Conclusion In patients with fatal uveal melanoma, there is no significant correlation between basal tumour diameter and survival time. Delay in treatment does not seem to worsen prognosis for survival significantly, except perhaps in patients with small tumours. This finding adds further support to the concept that the main objective of ocular treatment is to conserve the eye with as much useful vision as possible. Since ocular treatment can itself cause significant visual loss, the benefit of treating asymptomatic uveal melanomas is uncertain. There is scope for randomized, prospective studies of treatment versus non-treatment of patients with asymptomatic choroidal melanoma. [source] An audit of eccentrically-positioned ruthenium plaque radiotherapy of choroidal melanoma in LiverpoolACTA OPHTHALMOLOGICA, Issue 2009A RUSSO Purpose Brachytherapy is usually administered with the plaque overlapping the entire tumour margin by at least 1-2mm. With posterior tumours, our practice is to position the plaque with its posterior edge aligned with the posterior tumour margin. We audited ocular outcomes after eccentrically-placed ruthenium plaque radiotherapy of choroidal melanoma. Methods Patients were included if receiving primary ruthenium brachytherapy for choroidal melanoma during the three years up to the 31st July 2007. A perforated template was used to facilitate plaque positioning. For posterior tumors, the template was positioned so that trans-illumination produced a glow at the posterior tumour margin (,sunset sign'). Minimum doses of 300-350 Gy and 80-90 Gy were prescribed to the sclera and apex, respectively. Results The cohort comprised 162 patients (93 female and 69 male). The time to the last known visual acuity had a median of 23 months. The initial visual acuity was 20/40 or better in 94.6%, 20/60 to 20/200 in 13.0% and worse than 20/200 in 1.9% of patients. The tumours had a mean basal diameter of 11.7mm. Ten tumours exceeded 5.4 mm in height. Tumour extension to within 5mm of optic disc, fovea or both occurred in 18 (11.1%), 28 (17.3%) and 27 (16.7%) cases respectively. Risk factors for visual loss were proximity to optic disc or fovea, initial visual acuity worse than 20/40 and tumour height exceeding 5.4 mm. In 66 patients with none of these risk factors, 92% retained 20/40 or better and 5 had vision of 20/60 , 20/200. In 72 with one risk factor, 74.3% retained 20/16 , 20/40 and 95.7% had vision of 20/200 or better. In 12 patients with 2 risk factors, these percentages were 25.0% and 91.7%. Only 3 patients had 3 risk factors and one retained vision of 20/200 or better. Tumours distanced < 5 mm to fovea were divided in 3 groups, and visual acuity analysed. Three patients had local tumour recurrence and were treated respectively by proton beam radiotherapy, plaque radiotherapy and enucleation (the only eye lost in this series). Conclusion Eccentric plaque radiotherapy of choroidal melanoma achieves good rates of local tumour control, ocular retention and preservation of vision. [source] Primary photodynamic therapy of choroidal melanomaACTA OPHTHALMOLOGICA, Issue 2009H HEIMANN Purpose To review our initial experience with photodynamic therapy of choroidal melanoma at the Ocular Oncology Service in Liverpool. Methods Patients were included in the study if they underwent primary photodynamic therapy for choroidal melanoma. The treatment was administered using the same protocol as for choroidal neovascularization. Results The patients (12 male and 5 female) had a mean age of 62.2 years. The melanomas were located in the right eye in 11 patients and the left eye in 6 patients. The tumour margin extended anteriorly to pre-equatorial choroid in one patient and posteriorly to include optic disc in 7 patients. The melanomas had a mean diameter of 7.6 mm and a mean thickness of 2.0mm. The initial visual acuity was 6/12 or better in 13 patients and 6/18-6/60 in 4 patients. Biopsy showed the tumour to be of spindle cell type in two patients and to contain epithelioid cells in three patients. One patient was found to have monosomy 3 so that the tumour was treated with proton beam radiotherapy. The follow-up ranged to 622 days with a median of 101 days. Four patients subsequently underwent proton beam radiotherapy and one patient was treated by endoresection. The last known visual acuity was 6/12 or better in 11 patients, 6/18 to 6/60 in 4 patients and 3/60 to Counting Fingers in 2 patients. Conclusion Photodynamic therapy may be worth attempting in patients with a small choroidal melanoma when other methods are likely to cause visual loss. Many patients subsequently require more aggressive treatment to achieve local tumour control. [source] Study of the immune response in patients with uveitis and latent tuberculosisACTA OPHTHALMOLOGICA, Issue 2009D MAKHOUL Purpose Mycobacterium tuberculosis infects up to 30 % of the population worldwide. In the majority of the cases a lifelong immune response, based on the production of IFN, by CD4+ lymphocytes, restricts the infection into lung granulomas. A dysregulation of T regulatory cell function has also been implicated. It has been postulated that this constant immune response might contribute to certain forms of tuberculosis associated uveitis (hypersensitivity uveitis). The aim of this work is to analyse the lymphocyte production of IFN, and the percentage of regulatory T cells in sight threatening uveitis patients with or without latent tuberculosis. Methods Patients with sight threatening uveitis suspected to be related to tuberculosis or to autoimmune disease will be recruited at the CHU St-Pierre. Patients will be included if the work-up is compatible with the diagnosis of tuberculosis related uveitis or autoimmune uveitis used as a control. Signed informed consent will be obtained and blood samples will be taken. Results IFN, production in response to different mycobacterial peptides will be measured by QuantiFERONÔ-TB Gold in-tube and by ELISA. IL-17 will be quantified by ELISA and the percentage of T regulatory cells analysed by flow cytometry (CD3+CD4+ CD25high, CD127low, FOXP3+). Conclusion The diagnosis of tuberculosis uveitis is a clinical challenge. The disease is probably mediated through infectious and immune mechanisms. By studying the CD4 + and regulatory T lymphocytes function in patients with uveitis and latent tuberculosis, we hope that we will better understand this pathology. In addition, this study will evaluate the usefulness of QuantiFERONÔ-TB Gold in-tube in the evaluation of patient with uveitis. [source] | ||||||||||