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Oral Therapy (oral + therapy)
Selected AbstractsAdherence to Oral Therapy for Type 2 Diabetes: Opportunities for Enhancing Glycemic ControlJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 1 2004CDEArticle first published online: 24 MAY 200, David Bartels PharmD Purpose Although diet and exercise are important parts of type 2 diabetes treatment, most patients require pharmacological intervention with multiple agents to maintain adequate glycemic control. This article addresses the numerous patient-related, disease-related, and demographic variables affecting medication adherence in this patient population. Data Sources Extensive review of scientific literature, clinical practice guidelines, and Internet sources. Conclusions Studies have demonstrated that treatments including multiple medications or frequent dosing had a negative impact on adherence. Practitioners have used several approaches in an effort to improve adherence to oral antidiabetic medical therapy, including increased communication between health care providers and patients, implementation of multidisciplinary programs, and use of treatment regimens with easier dosing (i.e., reduced number of drugs or doses taken per day). Implications for Practice Options for type 2 diabetes treatments that combine effective medications into a simpler oral-dosage form may motivate and improve patient adherence. Ultimately, simplifying dosing may lead to better glycemic control, thereby reducing the risks associated with long-term consequences of the disease. [source] ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy of Erectile Dysfunction: A Phase III Clinical TrialTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Sidney Glina MD ABSTRACT Introduction., This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. Aim., Expanding information on LC efficacy and safety. Main Outcome Measures., International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). Methods., A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. Results., IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] ± standard deviation [SD]): placebo = 13.9 ± 5.2 and 14.8 ± 7.8; LC 40 mg = 13.6 ± 5.3 and 18.6 ± 8.0; LC 80 mg = 13.4 ± 4.9 and 20.6 ± 7.7 (analysis of variance [anova]P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M ± SD): placebo = 55.3 ± 43.2% and 52.1 ± 41.4%; LC 40 mg = 46.4 ± 44.3% and 63.5 ± 42.0%; LC 80 mg = 50.2 ± 40.9% and 80.8 ± 32.3% (anovaP < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 ± 32.3% and 29.7 ± 38.1%; LC 40 mg = 19.6 ± 34.3% and 50.8 ± 44.4%; LC 80 mg = 20.8 ± 33.2% and 66.0 ± 39.3% (anovaP < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. Conclusions., LC showed a satisfactory efficacy,safety profile for oral therapy of ED. Glina S, Fonseca GN, Bertero EB, Damićo R, Rocha LCA, Jardim CRF, Cairoli CE, Teloken C, Torres LO, Faria GE, da Silva MB, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: A phase III clinical trial. J Sex Med 2010;7:1928,1936. [source] Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical TrialTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009Sidney Glina MD ABSTRACT Introduction., Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. Aim., This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Main Outcome Measures., Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Methods., Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. Results., IIEF erectile domain scores before and after the use of medications were (mean ± standard deviation [SD]): placebo: 11.9 ± 3.4 and 12.6 ± 5.5; LC 20 mg: 15.8 ± 4.1 and 18.9 ± 6.6; LC 40 mg: 11.9 ± 4.4 and 15.4 ± 8.1; LC 80 mg: 14.2 ± 4.7 and 22.8 ± 6.0 (anovaP < 0.01). The SEP-2 scores before and after the use of medications were (Mean ± SD): placebo: 71.0 ± 33.1 and 51.2 ± 43.1; LC 20 mg 70.3 ± 34.2 and 75.5 ± 31.5; LC 40 mg: 48.4 ± 42.1 and 60.8 ± 42.5; LC 80 mg: 68.6 ± 33.5 and 89.6 ± 26.0. The SEP-3 scores were: placebo 23.3 ± 27.6 and 33.6 ± 42.3; LC 20 mg: 32.3 ± 38.9 and 51.2 ± 41.7; LC 40 mg: 39.7 ± 44.7 and 46.7 ± 41.1; LC 80 mg* 17.2 ± 29.5 and 74.3 ± 36.4 (*P < 0.05 for difference to placebo). Conclusions., The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Góes PM, Jśnior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553,557. [source] Oral therapy for migraine: Comparisons between rizatriptan and sumatriptan.PAIN PRACTICE, Issue 2 2001A review of 4 randomized, Denmark) Neurology 2000;55:S1, Glostrup, double-blinded clinical trials. (University of Copenhagen Four comparative, placebo-controlled, randomized clinical trials of oral rizatriptan versus oral sumatriptan including one Phase II trial and three Phase III trials were reported in this study. Forty mg rizatriptan was found to be more effective than 100 mg sumatriptan, but was associated with a high incidence of adverse effects. Five mg rizatriptan was comparable to 50 mg sumatriptan. In two trials, rizatriptan 10 mg, the recommended dose in most countries, had a more rapid onset of action than 50 mg and 100 mg of sumatriptan. In addition, 10 mg of rizatriptan resulted in more patients being pain-free after 2 h than 100 mg of sumatriptan, and resulted in fewer drug-related adverse events than sumatriptan. [source] Photosensitive psoriasis in a vitiligo patientTHE JOURNAL OF DERMATOLOGY, Issue 12 2006Daniele TORCHIA ABSTRACT We report a case of a 15-year-old Caucasian female, previously affected by non-segmental vitiligo and psoriasis vulgaris, who developed a psoriatic eruption on sun-exposed skin during the summer. Oral therapy with cyclosporine A achieved a rapid improvement of the clinical picture. The main features of photosensitive psoriasis and the association between psoriasis and vitiligo are discussed herein. [source] Effects of Oral L-Arginine on the Foetal Condition and Neonatal Outcome in Preeclampsia: A Preliminary ReportBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2006Krzysztof Rytlewski Randomized, placebo-controlled, double-blind, clinical trial. Oral therapy with 3 g of L-arginine daily or placebo as a supplement to standard therapy. Eighty-three preeclamptic women, randomly assigned to the L-arginine (n=42) or placebo (n=41) groups; [n=30 (L-arginine) and n=31 (placebo) ended the study, respectively]. Foetal gain chances due to ultrasound biometry, biophysical profile, Doppler velocimetry of pulsatility indices of umbilical and middle cerebral arteries, cerebro-placental ratio, as well as differences in duration of pregnancy and clinical data of newborn. L-arginine treatment transitory accelerated foetal gain and improved biophysical profile. Starting from 3rd week of therapy, the umbilical artery pulsatility indices values were significantly lower in L-arginine than in placebo group. Moreover, treatment with L-arginine caused significant increase of middle cerebral artery pulsatility indices and cerbro-placental ratio values. Latency was longer in L-arginine group. Neonates delivered in the L-arginine group revealed higher Apgar score. Supplementary treatment with oral L-arginine seems to be promising in improving foetal well-being and neonatal outcome as well as in prolonging pregnancy complicated with preeclampsia. However, these benefits require confirmation in more-powered, larger studies. [source] Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitusJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006AK Gupta Abstract Background, Oral terbinafine and oral itraconazole are two of the most common agents used for the treatment of toenail dermatophyte onychomycosis. Despite the fact that diabetic patients are more likely to have onychomycosis than normal individuals are, there is little research into the efficacy of standard oral regimens of terbinafine and itraconazole for onychomycosis in the diabetic population. Study design, We present a prospective, randomized, single-blind, parallel group, comparator-controlled, multi-centre study designed to assess the efficacy of the pulse itraconazole (200 mg twice daily, 1 week on, 3 weeks off, for 12 weeks) vs. continuous terbinafine (250 mg once daily for 12 weeks) oral therapies in the treatment of dermatophyte toenail distal and lateral subungual onychomycosis (DLSO) in the diabetic population. Efficacy parameters, Primary efficacy measures included mycological cure rate (negative KOH and culture) and effective cure (mycological cure plus nail plate involvement of 10% or less) at Week 48. Results, At Week 48, mycological cure was attained by 88.2% (30 of 34) and 79.3% (23 of 29) of patients in the itraconazole and terbinafine groups, respectively (P not significant). Effective cure (mycological cure with , 10% of nail plate involvement) was attained by 52.9% (18 of 34) of the itraconazole group and 51.7% (15 of 29) of the terbinafine group (P not significant). Three itraconazole patients experienced side effects in the form of gastrointestinal problems. There were no serious adverse events and no interactions with concomitant medications recorded. Discussion, Both continuous terbinafine and itraconazole pulse therapy are effective and safe in the management of dermatophyte toenail onychomycosis in people with diabetes. [source] Topical antifungal drugs for the treatment of onychomycosis: an overview of current strategies for monotherapy and combination therapyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2005R Baran ABSTRACT Background, Onychomycosis is a relatively common disease accounting for up to 50% of all nail disorders and its prevalence rises with age. As onychomycosis is an important medical disorder affecting both patient's health and quality of life, it requires prompt and effective treatment. Objective, Topical antifungal nail lacquers have been formulated to provide efficient delivery to the nail unit. As both amorolfine and ciclopirox have proved useful as monotherapy for onychomycosis that does not involve the nail matrix area, the purpose of this article is to check if, when combined with oral agents, the effectiveness and scope of treatment can be improved further. Methods, Combining data for mycological cure with clinical success (nail morphology) provides a more exacting efficacy measure. Results, Clinical investigations have shown that the combination of oral therapies with antifungal nail lacquer can confer considerable advantage over monotherapy with either drug type. Conclusion, The improved effectiveness and economic advantages of combined topical/oral therapies benefit both patients and health providers; these treatment regimens therefore have an important role to play in the modern management of onychomycosis. [source] Balancing Risk and Benefit with Oral Hypoglycemic DrugsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Clinicians are faced with an expansive array of treatment choices when caring for patients with type 2 diabetes. Because patient compliance may be affected when media sensationalism about controversial findings is misunderstood, we sought to clarify the recent controversy surrounding the cardiovascular and bone-health risks of thiazolidinediones, the risk of lactic acidosis with metformin, and the risk of hypoglycemia with oral therapies. The side effect profile of thiazolidinediones includes fluid retention, heart failure; and an increased risk of fracture. A recent controversial meta-analysis suggested that rosiglitazone increases the risk of myocardial infarction, which is possibly related to thiazolidinedione-induced lipid changes, weight gain, congestive heart failure, and anemia. Metformin is restricted to patients with normal renal function because of concerns that metformin may cause lactic acidosis. However, few cases of metformin-associated lactic acidosis have been reported, and most have occurred in patients with other reasons for developing lactic acidosis, such as sepsis or renal failure. Although the use of metformin continues to increase, observational studies have not been able to demonstrate an increased incidence of lactic acidosis in metformin-treated patients, even when it is used in populations with relative contraindications. Some oral hypoglycemic medications can cause hypoglycemia. Hypoglycemia is especially common in older patients, alcoholics, and patients with liver or renal disease. Patients on sulfonylureas and meglitinides have the highest incidence of hypoglycemia because of their pharmacological action of increasing insulin secretion. Of the sulfonylureas, glyburide presents the highest risk of hypoglycemia. Combination therapies, especially those regimens containing a sulfonylurea, increase the risk of hypoglycemia. Mt Sinai J Med 76:234,243, 2009. © 2009 Mount Sinai School of Medicine [source] Combined treatment with vitamin E and colchicine in the early stages of Peyronie's diseaseBJU INTERNATIONAL, Issue 6 2003R.M. Prieto Castro Objective To assess the effectiveness of the combination of colchicine and vitamin E (which has anti-fibrotic, anti-mitotic and anti-inflammatory effects) in modifying the early stages of Peyronie's disease, by evaluating pain relief, correction of deformities and plaque size. Patients and methods In all, 45 patients were divided into two groups and treated from January 1998 to November 2001. Their mean (range) age was 53.4 (40,62) years, the time from onset of the disease < 6 months and they had penile deformity of < 30°; no patient had erectile dysfunction. Twenty-two patients were given ibuprofen 400 mg/day for 6 months, whilst 23 received a combination of vitamin E 600 mg/day plus colchicine 1 mg every 12 h. Pain, plaque size and penile deformity were assessed at 6 months. Results There were no statistically significant differences between the groups at baseline in age, time from onset of the disease until the initial evaluation or plaque size. Although the proportion of patients reporting pain relief was higher amongst those receiving colchicine plus vitamin E (91% vs 68%) this was not significantly different, but differences in plaque size and penile curvature were significant. Conclusions The use of colchicine plus vitamin E during the early stages of Peyronie's disease (time from onset < 6 months) in patients with penile curvature of < 30° and no erectile dysfunction is an effective and well-tolerated way to stabilize the disease. A more extensive study is needed, comparing these results with other oral therapies. [source] Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosisBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004A.K. Gupta Summary Background Onychomycosis is a common nail disease that is often chronic, difficult to eradicate, and has a tendency to recur. The most common oral therapies for dermatophyte toenail onychomycosis include terbinafine, itraconazole and fluconazole. Objectives A cumulative meta-analysis of the randomized controlled trials (RCTs) for antimycotic agents was performed to determine whether the pooled estimate of the cure rates has remained consistent over the years. Furthermore, for each agent we compared the overall meta-analytical average of both mycological and clinical response rates of RCTs vs. open studies. Methods We searched MEDLINE (1966 to November 2002) for relevant studies evaluating the efficacy of the oral antifungal agents terbinafine, itraconazole (pulse or continuous), fluconazole and griseofulvin for treating dermatophyte toenail onychomycosis. Studies included in this meta-analysis required a standard accepted dosage regimen, treatment duration and follow-up period. To determine the cumulative meta-analytical average, studies were sequentially pooled by adding one study at a time according to the date of publication (i.e. earliest to the most recent). Results There were 36 studies included in the analyses. For RCTs the change in efficacy of mycological cure rates from the first trial to the overall cumulative meta-average for each drug comparator is as follows (with 95% confidence interval): terbinafine, 78 ± 6% (n = 2 studies, 79 patients) to 76 ± 3% (n = 18 studies, 993 patients) (P = 0·68); itraconazole pulse, 75 ± 10% (n = 1 study, 20 patients) to 63 ± 7% (n = 6 studies, 318 patients) (P = 0·25); itraconazole continuous, 63 ± 5% (n = 1 study, 84 patients) to 59 ± 5% (n = 7 studies, 1131 patients) (P = 0·47); fluconazole, 53 ± 6% (n = 1 study, 72 patients) to 48 ± 5% (n = 3 studies, 131 patients) (P = 0·50); and griseofulvin, 55 ± 8% (n = 2 studies, 109 patients) to 60 ± 6% (n = 3 studies, 167 patients) (P = 0·41). The cumulative meta-analytical average of mycological cure rates when comparing RCTs vs. open studies was: terbinafine, 76 ± 3% (n = 18 studies, 993 patients) vs. 83 ± 12% (n = 2 studies, 391 patients) (P = 0·0028); itraconazole pulse, 63 ± 7% (n = 6 studies, 318 patients) vs. 84 ± 9% (n = 3 studies, 194 patients) (P = 0·0001); and fluconazole, 48 ± 5% (n = 3 studies, 131 patients) vs. 79 ± 3% (n = 3 studies, 208 patients) (P = 0·0001). Conclusions The cumulative meta-analysis of cure rates for RCTs suggests that over time, as new RCTs have been conducted, the efficacy rates have remained consistent. The efficacy rates of open studies are substantially higher compared with RCTs and may therefore overestimate cure rates. [source] Addition of insulin lispro protamine suspension or insulin glargine to oral type 2 diabetes regimens: a randomized trialDIABETES OBESITY & METABOLISM, Issue 10 2010K. Strojek Aims: The addition of basal insulin to existing oral therapy can help patients with type 2 diabetes (T2D) achieve glycaemic targets. This study compares the efficacy and safety of insulin lispro protamine suspension (ILPS) and insulin glargine in insulin-naive patients with T2D and inadequate control on oral antihyperglycaemic medication (OAM). Materials and Methods: An open-label, randomized, multicentre, multinational 24-week study of 471 patients receiving ,2 OAMs for ,3 months with a body mass index between 25 and 45 kg/m2 and HbA1c 7.5,10.0% was conducted. ILPS was injected once or twice daily vs. glargine injected once daily plus prestudy OAMs. Primary objective compared the HbA1c change from baseline. Results: HbA1c change from baseline to endpoint was similar in both groups [,1.46% (ILPS) and ,1.41% (glargine)]. Least-squares mean difference (95% CI) for HbA1c (,0.05 [,0.21, 0.11]%), glycaemic variability (0.06 [,0.06, 0.19] mmol/l) and weight change (,0.01 [,0.61, 0.59] kg) showed non-inferiority (margins of 0.4%, 0.8 mmol/l and 1.5 kg, respectively). Percentages of patients achieving HbA1c <7.0% were 43.8% ILPS and 41.2% glargine. Mean daily insulin dose was 0.39 vs. 0.35 U/kg (p = 0.02) and weight gain was 1.04 vs. 1.07 kg for ILPS vs. glargine (p = 0.98). Overall hypoglycaemia (episodes/patient/year) was similar for ILPS and glargine (24.2 ± 28.8 vs. 23.0 ± 30.9); nocturnal (6.1 ± 10.6 vs. 4.1 ± 9.4, p < 0.001) rates were higher for ILPS. Severe hypoglycaemia was higher for ILPS vs. glargine (n = 9 vs. n = 2; p = 0.04). Conclusions: At endpoint, ILPS was non-inferior to glargine in HbA1c change from baseline, but associated with increased risk of hypoglycaemia. [source] Gemcitabine induced digital ischaemia and necrosisEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2010A. HOLSTEIN md HOLSTEIN A., BÄTGE R. & EGBERTS E.-H. (2010) European Journal of Cancer Care19, 408,409 Gemcitabine induced digital ischaemia and necrosis A 70-year-old woman presented with a 7-day history of severe pain, paresthesia, oedema, acrocyanosis and punctate haemorrhagic lesions on her fingertips. The complaints began 2 days after the second cycle of a first-line chemotherapy consisting of cisplatin or carboplatin, and gemcitabine due to advanced urothelial carcinoma. At the fingertips of both hands, haemorrhagic and partly ulcerative lesions were found; these were attributed to vascular toxicity of gemcitabine. Therapeutically sympathicolysis by bilateral blockade of the brachial plexus was performed, accompanied by intravenous administration of the prostacyclin analog iloprost, fractionated heparin subcutaneously and oral therapy with corticosteroids and aspirin. Digital amputation could be avoided. Acral ischemia is a rare but probably underreported adverse effect of gemcitabine therapy and a potential source of misdiagnosis. [source] RDP58 is a novel and potentially effective oral therapy for ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 8 2005Simon Travis FRCP Abstract Background: RDP58 is a novel anti-inflammatory d-amino acid decapeptide that inhibits synthesis of proinflammatory cytokines by disrupting cell signaling at the pre-MAPK MyD88-IRAK-TRAF6 protein complex. We therefore evaluated its efficacy and safety in parallel multicenter, double-blind, randomized concept studies in ulcerative colitis (UC). Methods: In the first trial, 34 patients with mild to moderate active UC were randomized (1:2) to placebo (n = 13) or RDP58 100 mg (n = 21). In the second trial, 93 similar patients were randomized (1:1:1) to placebo (n = 30) RDP58 200 mg (n = 31), or RDP 300 mg (n = 32). In both studies, treatment success was defined as a simple clinical colitis activity index score of no more than 3 at 28 days. Sigmoidoscopy and rectal biopsy (at baseline and 28 days) and safety measures (baseline and 28 and 56 days) were other endpoints. Results: Treatment success on RDP 100 mg was 29% versus 46% on placebo (P = 0.46). There were no significant differences in sigmoidoscopy or histology score. In the second study, treatment success on the higher doses of RDP58 (200 and 300 mg) was 71% and 72%, respectively, versus 43% on placebo (P = 0.016). Improvements in sigmoidoscopy scores (41% on 200 mg and 46% on 300 mg versus 32% on placebo) did not reach significance, but histology scores improved significantly (P = 0.002) versus placebo. Overall, adverse events were no different between placebo (3.3 ± 2.4) and RDP58 (2.7 ± 1.4, 300-mg group). Conclusions: RDP58 at a dose of 200 or 300 mg, but not 100 mg, was effective in mild-to-moderate UC. RDP58 was safe and well tolerated, and its novel action makes it an attractive potential therapy. [source] Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous administrationINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2001Shigeru Satoh Abstract Background: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy. Methods: The blood concentration,time curve was studied in 10 living-related kidney transplant recipients, aged 18,51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy. Results: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0,27.2% for preoperative and 6.4,22.0% for postoperative area under the curve, respectively. Conclusion: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment. [source] Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysisJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2009H. Fukuchi MS Summary Objective:, To evaluate the influence of obesity on pharmacokinetics of amiodarone (AMD) using Non-Linear Mixed Effects Modelling (nonmem) in Japanese patients treated with oral therapy. Method:, Serum concentrations of AMD were determined by high performance liquid chromatography. One hundred and fifty-one trough concentrations from 23 patients receiving repetitive oral AMD were collected. Body mass index (BMI) and body fat percentage were measured. Results:, Estimates generated using nonmem indicated that the clearance of AMD was influenced by BMI, age and daily dosage of AMD. The final pharmacokinetic model was CL (L/h) = 0·16 · TBW · 0·53AGE , 65 · 0·78BMI , 25 · DD0·51, Vd (L) = 10·2 · TBW, where CL is total body clearance, TBW is total body weight (kg), DD (mg/kg/day) is daily dosage of AMD, AGE (years) ,65 = 1 for patient was 65 years old or over and 0 otherwise, BMI (kg/m2) ,25 = 1 for patient was 25 kg/m2 or over and 0 otherwise and Vd is apparent volume of distribution. The clearance of AMD decreased significantly by 22·3% with a BMI higher than 25 kg/m2. The clearance of AMD also decreased significantly by 46·9% when patient age was more than 65 years. Conclusion:, Population pharmacokinetic analysis confirms that obesity affects the pharmacokinetics of AMD. [source] Management of perioperative hypertensive urgencies with parenteral medications,JOURNAL OF HOSPITAL MEDICINE, Issue 2 2010Kartikya Ahuja MD Abstract BACKGROUND: Hypertension is the major risk factor for cardiovascular (CV) disease such as myocardial infarction (MI) and stroke. This risk is well known to extend into the perioperative period. Although most perioperative hypertension can be managed with the patient's outpatient regimen, there are situations in which oral medications cannot be administered and parenteral medications become necessary. They include postoperative nil per os status, severe pancreatitis, and mechanical ventilation. This article reviews the management of perioperative hypertensive urgency with parenteral medications. METHODS: A PubMed search was conducted by cross-referencing the terms "perioperative hypertension," "hypertensive urgency," "hypertensive emergency," "parenteral anti-hypertensive," and "medication." The search was limited to English-language articles published between 1970 and 2008. Subsequent PubMed searches were performed to clarify data from the initial search. RESULTS: As patients with hypertensive urgency are not at great risk for target-organ damage (TOD), continuous infusions that require intensive care unit (ICU) monitoring and intraarterial catheters seem to be unnecessary and a possible misuse of resources. CONCLUSIONS: When oral therapy cannot be administered, patients with hypertensive urgency can have their blood pressure (BP) reduced with hydralazine, enalaprilat, metoprolol, or labetalol. Due to the scarcity of comparative trials looking at clinically significant outcomes, the medication should be chosen based on comorbidity, efficacy, toxicity, and cost. Journal of Hospital Medicine 2010;5:E11,E16. © 2010 Society of Hospital Medicine. [source] Cancer risks in thiazolidinedione users compared to other anti-diabetic agents,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2007Carol Koro PhD Abstract Purpose We conducted three nested case-control studies to evaluate the risk of breast, colon, and prostate cancers developing in patients exposed to thiazolidinediones (TZDs) compared with other anti-diabetic agents. Methods Cancer cases were matched to five controls by age, gender, calendar year, and time in the database from a cohort of 1,26,971 diabetic patients taking anti-diabetic medication in the US Integrated Healthcare Information Services database. Five hundred thirteen breast cancer cases were matched with 2557 controls, 408 cases of colon cancer were matched with 2027 controls and 643 cases of prostate cancer were matched with 3176 controls. Exposure to an anti-diabetic agent within 90 days preceding the index date was defined as recent exposure and at any time during the follow-up was defined as ever exposed. Results The adjusted odds ratios and 95%CI of cancer from ever exposure to TZDs compared to oral monotherapy, oral dual therapy, oral triple therapy, insulin monotherapy, insulin and oral therapy and all non-TZD anti-diabetic agents were, respectively for breast cancer: 0.91 (0.69,1.20), 0.80 (0.56,1.14), 0.87 (0.32,2.35), 1.27 (0.61,2.67), 0.71 (0.36,1.37), 0.89 (0.68,1.15); for colon cancer: 1.06 (0.80,1.40), 1.12 (0.77,1.63), 1.73 (0.39,7.78), 4.46 (1.05,19.00), 1.06 (0.50,2.26) 1.03 (0.80,1.32) and for prostate cancer: 1.08 (0.85,1.37), 0.89 (0.66,1.21); 0.82 (0.33,2.06); 1.80 (0.79,4.07), 1.10 (0.55,2.18), 1.04 (0.83,1.31). Results for exposure within 90 days of the date of the cancer were similar. Conclusions Our findings suggest that the effect of TZDs on the likelihood of development of the cancers studied (colon, prostate and breast) appears to be neutral and do not support a beneficial or deleterious effect of TZD on the cancers studied. Copyright © 2006 John Wiley & Sons, Ltd. [source] Life is sweet in Fiji: the availability of diabetes healthcare and health education, and diabetes awareness amongst diabetic patients in FijiPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 6 2002Jay Kuruvatti BSc, MB ChB Pre-registration House Officer Abstract During an elective visit to Fiji we assessed the knowledge of diabetes possessed by patients who attended the hospital Diabetic Clinic in Lautoka. All the patients interviewed had type 2 diabetes and 15.4% were treated with insulin, 80.8% with oral therapy and 3.8% with diet alone. Blindness was the commonest complication known to patients but almost a quarter could not describe any diabetic complication. All patients had seen a hospital doctor regarding their diabetes; 17.9% also saw a private general practitioner, 80.8% had seen the diabetes nurse, 60.8% a dietician, and 57.7% a chiropodist. When asked about causative factors 12.8% thought diabetes was caused by overeating, 12.8% thought it was due to too much sugar in the diet, and the remaining 60.3% did not know. The methods by which the ever-increasing financial burden of diabetes in Fiji can be reduced are discussed. We feel that the prevention of diabetes and the early detection of complications would be the most cost-effective methods to improve overall diabetes care in Fiji. However, the whole diabetes care service in Fiji is constrained by the poor economic state of the country and the low profile of diabetes in the healthcare plans of the country. Copyright © 2002 John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy of Erectile Dysfunction: A Phase III Clinical TrialTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Sidney Glina MD ABSTRACT Introduction., This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. Aim., Expanding information on LC efficacy and safety. Main Outcome Measures., International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). Methods., A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. Results., IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] ± standard deviation [SD]): placebo = 13.9 ± 5.2 and 14.8 ± 7.8; LC 40 mg = 13.6 ± 5.3 and 18.6 ± 8.0; LC 80 mg = 13.4 ± 4.9 and 20.6 ± 7.7 (analysis of variance [anova]P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M ± SD): placebo = 55.3 ± 43.2% and 52.1 ± 41.4%; LC 40 mg = 46.4 ± 44.3% and 63.5 ± 42.0%; LC 80 mg = 50.2 ± 40.9% and 80.8 ± 32.3% (anovaP < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 ± 32.3% and 29.7 ± 38.1%; LC 40 mg = 19.6 ± 34.3% and 50.8 ± 44.4%; LC 80 mg = 20.8 ± 33.2% and 66.0 ± 39.3% (anovaP < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. Conclusions., LC showed a satisfactory efficacy,safety profile for oral therapy of ED. Glina S, Fonseca GN, Bertero EB, Damićo R, Rocha LCA, Jardim CRF, Cairoli CE, Teloken C, Torres LO, Faria GE, da Silva MB, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: A phase III clinical trial. J Sex Med 2010;7:1928,1936. [source] Postoperative Orgasmic Function Increases over Time in Patients Undergoing Nerve-Sparing Radical ProstatectomyTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Andrew Salonia MD ABSTRACT Introduction., Postprostatectomy orgasmic function (OF) remains poorly defined. Aims., To assess OF over time in patients who underwent bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP) for organ-confined prostate cancer (PCa). Methods., Baseline data were obtained from 334 consecutive preoperatively sexually active PCa patients at hospital admission; data included a medical and sexual history, IIEF domain scores, and ICIQ-SF. Questionnaire were then completed every 12 months postoperatively, and patients participated in a semistructured interview at the 12-month (191/334 [57.2%] patients), 24-month (95/334 [28.4%] patients), 36-month (42/334 [12.6%] patients), and 48-month (19/334 [5.7%] patients) follow-up (FU). Main Outcome Measures., IIEF-OF domain values throughout the FU. Multivariate linear regression analysis (MVA) of the association between predictors (patient's age, IIEF-erectile function [EF], ICIQ-SF, and the use of postoperative proerectile pharmacological treatments) and the IIEF-OF at 12-month, 24-month, and 36-month FU. Results., Preoperative mean (median) IIEF-OF was 7.6 (10). The anova analysis showed an increase of the IIEF-OF values (P = 0.008; F = 4.009) throughout the FU (namely, IIEF-OF 12-month: 6.1 [6]; 24-month: 7.2 [8]; 36-month: 7.3 [8]; and 48-month: 7.7 [9.50]). The 12-month MVA showed that while proerectile oral therapy did not affect postoperative OF (P = 0.150; Beta 0.081), IIEF-OF linearly increased with IIEF-EF (P < 0.001; Beta 0.425). Conversely, IIEF-OF linearly decreased with patient's age (P < 0.001; Beta ,0.135) and with ICQ-SF scores (P < 0.001; Beta ,0.438). The 24-month and 36-month analyses showed that IIEF-OF still linearly increased with IIEF-EF (P < 0.001; Beta 0.540, and P < 0.001; Beta 0.536 respectively at the 24- and 36-month FU), whereas pharmacological therapy, rate of urinary continence, and patient's age did not significantly affect postoperative OF. Conclusions., Postoperative OF significantly ameliorates over time in patients undergoing BNSRRP. The higher the postoperative EF score, the higher the OF throughout the FU time frame. Salonia A, Gallina A, Briganti A, Colombo R, Bertini R, Da Pozzo LF, Zanni G, Sacca A, Rocchini L, Guazzoni G, Rigatti P, and Montorsi F. Postoperative Orgasmic Function Increases over Time in Patients Undergoing Nerve-Sparing Radical Prostatectomy. J Sex Med 2010;7:149,155. [source] Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical TrialTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009Sidney Glina MD ABSTRACT Introduction., Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. Aim., This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Main Outcome Measures., Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Methods., Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. Results., IIEF erectile domain scores before and after the use of medications were (mean ± standard deviation [SD]): placebo: 11.9 ± 3.4 and 12.6 ± 5.5; LC 20 mg: 15.8 ± 4.1 and 18.9 ± 6.6; LC 40 mg: 11.9 ± 4.4 and 15.4 ± 8.1; LC 80 mg: 14.2 ± 4.7 and 22.8 ± 6.0 (anovaP < 0.01). The SEP-2 scores before and after the use of medications were (Mean ± SD): placebo: 71.0 ± 33.1 and 51.2 ± 43.1; LC 20 mg 70.3 ± 34.2 and 75.5 ± 31.5; LC 40 mg: 48.4 ± 42.1 and 60.8 ± 42.5; LC 80 mg: 68.6 ± 33.5 and 89.6 ± 26.0. The SEP-3 scores were: placebo 23.3 ± 27.6 and 33.6 ± 42.3; LC 20 mg: 32.3 ± 38.9 and 51.2 ± 41.7; LC 40 mg: 39.7 ± 44.7 and 46.7 ± 41.1; LC 80 mg* 17.2 ± 29.5 and 74.3 ± 36.4 (*P < 0.05 for difference to placebo). Conclusions., The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Góes PM, Jśnior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553,557. [source] Osteonecrosis of the Mandible or Maxilla Associated with the use of New Generation BisphosphonatesTHE LARYNGOSCOPE, Issue 1 2006Matthew C. Farrugia DO Objective: The use of bisphosphonates is well established for the treatment of patients with metastatic bone disease, osteoporosis, and Paget's disease. Osteonecrosis of the mandible or maxilla associated with the use of bisphosphonates is a newly described entity never before discussed in the otolaryngology literature. In this paper, we review a series of patients diagnosed with osteonecrosis, all treated with new generation bisphosphonates. Our objective is to inform and educate others, particularly otolaryngologists/head and neck surgeons, about this drug induced entity, a condition that should be recognized early to avoid potential devastating consequences. Study Design: Retrospective chart review of a series of patients from a tertiary referral center. Methods: Pathology reports of specimens submitted from either the mandible or maxilla were reviewed from the previous 12 months. Any patient diagnosed with osteonecrosis without evidence of metastatic disease at that site was included; those with a previous history of radiation therapy were excluded. Each patient's medical history and profile were reviewed. Results: Twenty-three patients were identified with osteonecrosis of the mandible or maxilla. All of these were associated with the use of new generation bisphosphonates: zolendronate (Zometa, Novartis), pamidronate (Aredia, Novartis), and alendronate (Fosamax, Merck). Eighteen patients with known bone metastases had been treated with the intravenous form, whereas five patients with either osteoporosis or Paget's disease were using oral therapy. Patients typically presented with a nonhealing lesion, often times the result of previous dental intervention. Although the majority of these patients were treated with conservative surgical debridement, we present a case requiring a near total maxillectomy. Conclusions: Drug induced osteonecrosis of the mandible or maxilla has been recently recognized as a sequelae of treatment with the new generation of bisphosphonates. Most patients can be treated with conservative surgical debridement and cessation of bisphosphonate therapy, whereas a few may require radical surgical intervention. Other recommendations include regimented prophylactic care with an assessment of dental status before the administration of bisphosphonates, avoidance of dental procedures, and close monitoring of oral hygiene. [source] Randomized Study of Early Intravenous Esmolol Versus Oral Beta-Blockers in Preventing Post-CABG Atrial Fibrillation in High Risk Patients Identified by Signal-Averaged ECG: Results of a Pilot StudyANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2002Nomeda Balcetyte-Harris M.D. Background: Patients with prolonged signal-averaged ECG have four times higher risk for development of atrial fibrillation (AF) after coronary artery bypass surgery (CABG). Incidence of AF is reduced, but not eliminated by prophylaxis with beta-blockers. The limitations of prophylaxis with oral beta-blockers may be related to the delayed effect of oral therapy. We performed a pilot study of the efficacy of early intravenous esmolol and an oral beta-blocker regimen for prevention of postoperative AF. Methods: Fifty patients referred for CABG and considered to be at high risk for postoperative AF on the basis of prolonged signal-averaged ECG P wave duration > 140 ms were randomized to receive either a 24-hour infusion of esmolol 6,18 hours after CABG, at an average dose 67 ± 7 ,/kg/min, followed by oral beta-blockers versus oral beta-blockers only beginning on postoperative day 1. Results: Seven of 27 patients (26%) in the esmolol group and 6 of 23 patients (26%) in the oral beta-blocker group developed postoperative AF, P = NS. The mean time of onset of AF (2.7 ± 0.5 vs 2.7 ± 0.3 postoperative day, P = NS) and the median duration of AF (10 [2192] vs 7 [1.16] hours, P = NS) were similar between the two groups. Eleven (41%) patients treated with esmolol developed adverse events (hypotension: 8, bradycardia requiring temporary pacing: 2, left ventricular failure:1 patient) as compared to only one patient (4%) in the beta-blocker group who developed hypotension, P = 0.006. Conclusions: This randomized controlled pilot study suggests that intravenous esmolol is less well tolerated and offers no advantages to standard beta-blocker in preventing AF after CABG. A.N.E. 2002;7(2):86,91 [source] Protective role of Coenzyme Q10 in two models of rat lung injuryANZ JOURNAL OF SURGERY, Issue 4 2010Hou-Kiat Lim Abstract Background:, Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q10 (CoQ10) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q10 pretreatment in a model of mild and severe lung injury. Methods:, We evaluated the impact of CoQ10 in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ10 following oral therapy we administered high-dose oral CoQ10 to rats (n = 6). In the second stage we evaluated the impact of CoQ10 in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation. Results:, High-dose oral CoQ10 for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ10. In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ10 treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ10 did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ10 markedly reduced the increase in tumour necrosis factor-alpha in ischaemic compared with normoxic lung (P = 0.027). Conclusions:, The effect of CoQ10 pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ10 may have a protective role. [source] Oral versus Intravenous Opioid Dosing for the Initial Treatment of Acute Musculoskeletal Pain in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 12 2008James R. Miner MD Abstract Objectives:, The objective was to compare the time to medication administration, the side effects, and the analgesic effect at sequential time points after medication administration of an oral treatment strategy using oxycodone solution with an intravenous (IV) treatment strategy using morphine sulfate for the initial treatment of musculoskeletal pain in emergency department (ED) patients. Methods:, This was a prospective randomized clinical trial of patients >6 years old who were going to receive IV morphine sulfate for the treatment of musculoskeletal pain but did not yet have an IV. Consenting patients were randomized to have the treating physician order either 0.1 mg/kg morphine sulfate IV or 0.125 mg/kg oxycodone orally in a 5 mg/5 mL suspension as their initial treatment for pain. The time from the placement of the order to the administration of the medication was recorded. Pain was measured using a 100-mm visual analog scale (VAS) and recorded at 0, 10, 20, 30 and 40 minutes after drug administration. Results:, A total of 405 eligible patients were identified during the study period; 328 (81.0%) patients consented to be in the study. A total of 158 patients were randomized to the IV morphine sulfate treatment group, and 162 were randomized to the oral oxycodone treatment group. Of the patients who were randomized to IV therapy, 34 were withdrawn from the study prior to drug administration; leaving 125 patients in the IV group for analysis. Of the patients who randomized to oral therapy, 22 were withdrawn from the study prior to drug administration, leaving 140 patients for analysis. No serious adverse events were detected. There was a 12-minute difference between the median time of the order and the administration of oral oxycodone (8.5 minutes) and IV morphine (20.5 minutes). The mean percent change in VAS score was larger for patients in the IV therapy group than those in the oral therapy group at 10 and 20 minutes. At 30 and 40 minutes, the authors could no longer detect a difference. The satisfaction scale score was higher after treatment for the morphine group (median = 4; interquartile range [IQR] = 4 to 5) than for the oxycodone group (median = 4; IQR = 2 to 5; p = 0.008). Conclusions:, The oral loading strategy was associated with delayed onset of analgesia and decreased patient satisfaction, but a shorter time to administration. The oral loading strategy using an oxycodone solution provided similar pain relief to the IV strategy using morphine 30 minutes after administration of the drug. Oral 0.125 mg/kg oxycodone represents a feasible alternative to 0.1 mg/kg IV morphine in the treatment of severe acute musculoskeletal pain when difficult or delayed IV placement greater than 30 minutes presents a barrier to treatment. [source] Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2005D.J. Tuffnell Objective To establish the risk of serious complications from severe pre-eclampsia and eclampsia in a region using a common guideline for the management of these conditions. Design A five-year prospective study. Setting Sixteen maternity units in Yorkshire. Population All women managed with severe pre-eclampsia and eclampsia. Methods A common guideline was developed for the management of women with these conditions. A network of midwives prospectively collected outcome data. Main outcome measure Incidence of the conditions and serious complication rates. Results A total of 210,631 women delivered in the 16 units between 1 January 1999 and 31 December 2003. One thousand eighty-seven women were diagnosed with severe pre-eclampsia or eclampsia (5.2/1000). One hundred and fifty-one women had serious complications including 82 women (39/10,000) having eclamptic seizures and 49 women (23/10,000) requiring ICU admission. There were no maternal deaths but 54 out of 1145 babies died before discharge, giving a mortality rate of 47.2/1000. Of the 82 cases of eclampsia, 45 occurred antenatally (55%), 18 before admission to the maternity unit. Eleven cases occurred in labour (13%), including 1 during a caesarean section, and 26 cases occurred following delivery (32%). Twenty-five women developed pulmonary oedema (2.3% of cases) and six women required renal dialysis (0.55% of cases). One hundred and sixty-five (15%) required no antihypertensive therapy and 489 (53%) of the remainder required only oral therapy. Two hundred and one (18.5%) required more than one drug. Conclusion A regional guideline for severe pre-eclampsia and eclampsia can be developed and implemented. Its use may contribute to a low rate of serious complications. [source] Onychomycosis in clinical practice: factors contributing to recurrenceBRITISH JOURNAL OF DERMATOLOGY, Issue 2003R.K. Scher Summary The treatment of onychomycosis has improved in recent years and many patients can now expect a complete and lasting cure. However, for up to 25% of patients, persistent disease remains a problem, thus presenting a particular challenge to the clinician. For these patients, it is obviously important to ensure that a correct diagnosis of onychomycosis has been made, as misdiagnosis will inevitably jeopardize the perception of therapeutic effectiveness. Although onychomycosis accounts for about 50% of all nail diseases seen by physicians, nonfungal causes of similar symptoms include repeated trauma, psoriasis, lichen planus, local tumours vascular disorders and inflammatory diseases. Predisposing factors that contribute to a poor response to topical and/or oral therapy include the presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes. However, poor penetration of systemic agents to the centre of infection, or the inability of topical agents to diffuse between the surface of the nail plate and the active disease below, probably contributes to this. Other factors contributing to recurrence may be related to the patient's family history, occupation, lifestyle or underlying physiology. In addition, patients with concomitant disease (e.g. peripheral vascular disease, diabetes) or patients who are immunosuppressed (e.g. those with human immunodeficiency virus/acquired immunodeficiency syndrome) are more susceptible to onychomycosis. In the elderly, the prevalence of onychomycosis may be as high as 60%, and increases with age; in this population, physical trauma plays a major role in precipitating recurrence, especially in patients with faulty biomechanics due to underlying arthritis and bone abnormalities. It is also possible that recurrence in some cases is due to early termination of treatment or use of an inappropriate dose, and these possibilities should be eliminated before further investigations are undertaken. ,There is good evidence to suggest that a combination of oral and topical therapies, when given at the same time, yield excellent clinical outcomes, although there remains a need for more effective topical agents with greater nail penetration and more effective oral antifungal agents. [source] Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Javier Angulo We have evaluated the participation of endothelium-derived hyperpolarizing factor (EDHF) in the endothelium-dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium-dependent relaxation of these tissues was investigated. Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium-dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K+ (35 mM) or by blocking Ca2+ -activated K+ channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100 nM), suggesting the involvement of EDHF in these responses. Endothelium-dependent relaxation to ACh was markedly enhanced by DOBE (10 ,M) in HPRA but not in HCC. The potentiating effects of DOBE on ACh-induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high K+ or a combination of APA and CTX. In vivo, DOBE (10 mg kg,1 i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. EDHF plays an important role in the endothelium-dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium-dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED. British Journal of Pharmacology (2003) 139, 854,862. doi:10.1038/sj.bjp.0705293 [source] Systemic immunosuppressant therapy in childhoodCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2002David Atherton The indications for systemic immunosuppressant therapy are much the same in children as in adults. Perhaps the most important difference is the need in a child to consider more carefully the patient's likely future therapy requirements. This need reflects a justifiable anxiety concerning the longer-term toxicity associated with some of these drugs. It is obvious that special attention should be paid to the dosage regimens that are appropriate in children. However, otherwise the principles of treatment are essentially the same as in adults. This talk will focus on the use of azathioprine in atopic eczema, methotrexate in psoriasis and linear morphoea, and intravenous methylprednisolone in severe muco-cutancous erythema multiforme and toxic epidermal necrolysis. The value of azathioprine as a treatment for severe childhood eczema was greatly increased by the elucidation of the metabolic pathways for this drug, and by the development of an assay for thiopurine methyl transferase to allow detection of those at greatest risk of myelosuppression. We now treat children with normal TPMT levels with 3 mg/kg per day with gratifying therapeutic response and limited requirement for monitoring of blood counts and liver function. More recently we have successfully treated TPMTHL heterozygotes with doses of around 1.5 mg/kg per day. We now consider azathioprine as superior to cyclosporin as a systemic therapy for atopic eczema. The value of methotrexate in adults with plaque psoriasis and generalized pustular psoriasis is well established. It is equally useful in children with these disorders, and the most appropriate dosage appears to be in the region of 0.3,0.4 mg/kg as a single weekly dose. Children generally tolerate oral therapy well. Methotrexate also appears helpful in arresting the progression of linear morphoea, both in the case of coup de sabre lesions and progressive hemi-facial atrophy, and in limb lesions that are interfering with joint mobility or are causing profound lipoatrophy. Intravenous methylprednisolone appears to be of value in several acute dermatoses in childhood, but is most commonly used at Great Ormond Street Hospital in the hope of arresting progression of severe muco-cutaneous erythema multiforme and toxic epidermal necrolysis. Various dose regimens are used in children, but in our unit we use a dose of 20,30 mg/kg per day, up to a maximum of 500 mg, for 3 successive days. Each dose is given over period of 2 h with frequent monitoring of vital signs, particularly blood pressure. [source] | ||||||||||||||||||||||||||||