Van Hooff J.,Maastricht University |
Van Der Walt I.,Jacaranda Hospital |
Kallmeyer J.,St Augustines Hospital |
Miller D.,Christiaan Barnard Memorial Hospital |
And 5 more authors.
Therapeutic Drug Monitoring | Year: 2012
Background: A prolonged-release formulation of tacrolimus for once-daily administration (Tacrolimus QD) has been developed to offer potential improvements in patient adherence. This study compared the pharmacokinetics (PK) of tacrolimus in stable kidney transplant recipients before and after conversion from twice-daily tacrolimus (Tacrolimus BID) to Tacrolimus QD. Methods: This was an open-label, multicenter replicate design study in stable adult kidney transplant recipients (≥6 months posttransplantation) maintained on Tacrolimus BID. Patients underwent four sequential 14-day treatment periods of alternating Tacrolimus BID and QD (mg:mg conversion). Four 24-hour PK profiles were collected, one on the last day of each treatment period. Adverse events were also reported. Results: A total of 60 of 69 patients completed all 4 PK profiles. Steady-state tacrolimus area under the curve from 0 to 24 hours and Cmin were comparable for both formulations, with treatment ratio means (90% confidence intervals) of 92.9% (89.8%-96.0%) and 90.9% (87.3%-94.6%), respectively (acceptance interval: 80%-125%). Both formulations were well tolerated, with renal function remaining stable over the 8-week period. There was a good correlation between area under the curve from 0 to 24 hours and Cmin for Tacrolimus QD and BID (r = 0.88 and 0.82, respectively). The relationship between these two parameters was also similar. Conclusions: The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring. Copyright © 2012 by LippincottWilliams & Wilkins.
Koegelenberg C.F.N.,Stellenbosch University |
Noor F.,Stellenbosch University |
Bateman E.D.,University of Cape Town |
Van Zyl-Smit R.N.,University of Cape Town |
And 7 more authors.
JAMA - Journal of the American Medical Association | Year: 2014
IMPORTANCE: Behavioral approaches and pharmacotherapy are of proven benefit in assisting smokers to quit, but it is unclear whether combining nicotine replacement therapy (NRT) with varenicline to improve abstinence is effective and safe. OBJECTIVE: To evaluate the efficacy and safety of combining varenicline and a nicotine patch vs varenicline alone in smoking cessation. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and a further 12-week follow-up conducted in 7 centers in South Africa from April 2011 to October 2012. Four hundred forty-six generally healthy smokers were randomized (1:1); 435 were included in the efficacy and safety analyses. INTERVENTIONS: Nicotine or placebo patch treatment began 2 weeks before a target quit date (TQD) and continued for a further 12 weeks. Varenicline was begun 1 week prior to TQD, continued for a further 12 weeks, and tapered off during week 13. MAIN OUTCOMES AND MEASURES: Tobacco abstinence was established and confirmed by exhaled carbon monoxide measurements at TQD and at intervals thereafter up to 24 weeks. The primary end point was the 4-week exhaled carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 of treatment, ie, the proportion of participants able to maintain complete abstinence from smoking for the last 4 weeks of treatment, as assessed using multiple imputation analysis. Secondary end points included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9 through 24, and adverse events. Multiple imputation also was used to address loss to follow-up. RESULTS: The combination treatment was associated with a higher continuous abstinence rate at 12 weeks (55.4% vs 40.9%; odds ratio [OR], 1.85; 95% CI, 1.19-2.89; P = .007) and 24 weeks (49.0% vs 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) and point prevalence abstinence rate at 6 months (65.1% vs 46.7%; OR, 2.13; 95% CI, 1.32-3.43; P = .002). In the combination treatment group, there was a numerically greater incidence of nausea, sleep disturbance, skin reactions, constipation, and depression, with only skin reactions reaching statistical significance (14.4% vs 7.8%; P = .03); the varenicline-alone group experienced more abnormal dreams and headaches. CONCLUSIONS AND RELEVANCE: Varenicline in combination with NRT was more effective than varenicline alone at achieving tobacco abstinence at 12 weeks (end of treatment) and at 6 months. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01444131. Copyright 2014 American Medical Association. All rights reserved.
Bai R.,The Texas Institute |
Di Biase L.,The Texas Institute |
Valderrabano M.,Methodist key Heart and Vascular Center |
Lorgat F.,Christiaan Barnard Memorial Hospital |
And 15 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2012
Worldwide Survey on Robotic AF Ablation. Introduction: The Hansen Robotic system has been utilized in ablation procedures for atrial fibrillation (AF). However, because of the lack of tactile feedback and the rigidity of the robotic sheath, this approach could result in higher risk of complications. This worldwide survey reports a multicenter experience on the methodology, efficacy, and safety of the Hansen system in AF ablations. Methods and Results: A questionnaire addressing questions on patient's demographics, procedural parameters, ablation success rate and safety information was sent to all centers where more than 50 robotic AF ablation cases have been performed. From June 2007 to December 2009, 1,728 procedures were performed at 12 centers utilizing the Hansen robotic navigation technology. The overall complication rate was 4.7% and the success rate was 67.1% after 18 ± 4 months of follow-up. In 5 low volume centers there appeared to be a learning curve of about 50 cases (complication rate 11.2% for the first 50 cases vs 3.7% for the 51-100 cases; P = 0.044) and a trend showing a decrease of complication rate with increasing case volume. However, in the remaining 7 centers no learning curve was present and the complication rate was stable over time (3.7% for the first 50 cases vs 3.6% for the 51st case thereafter; P = 0.942). Conclusion: The Hansen robotic system can be used for AF ablation safely. In low volume centers, there appeared to be a learning curve of the first 50 cases after which the complication rate decreased. With a higher case volume, the success rate increased. © 2012 Wiley Periodicals, Inc.
Wlodarczyk Z.,Collegium Medicum |
Ostrowski M.,General and Transplantology Surgery |
Mourad M.,Cliniques Universitaires Saint Luc |
Kramer B.K.,University of Mannheim |
And 6 more authors.
Therapeutic Drug Monitoring | Year: 2012
Background: Tacrolimus is a well-established immunosuppressive agent for the treatment and prevention of solid organ graft rejection. It is available as an immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged-release, once-daily formulation (Tacrolimus QD). In a previous study of the pharmacokinetics (PK) of these formulations, mean systemic exposure [area under the curve from 0 to 24 hours (AUC0-24)] of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure was similar; however, the mean dose of Tacrolimus QD was higher to achieve similar systemic exposure as Tacrolimus BID. Methods: To further compare the PK of the tacrolimus formulations during the first 2 weeks posttransplant, a substudy was performed in a subset of patients enrolled into a phase III trial in de novo kidney transplant recipients comparing Tacrolimus QD and Tacrolimus BID. To minimize the difference in exposure observed in the earlier study, tacrolimus therapy was initiated before transplant. The PK analysis set comprised 34 patients (17 patients per treatment group) who had 4 complete PK profiles and no major PK-related protocol violations. Results: Mean AUC 0-24 of tacrolimus on day 1 was approximately 16% lower for Tacrolimus QD than for Tacrolimus BID, although by day 3 onward, the exposure was similar between treatment groups. Analysis of dose-normalized AUC0-24 (dose normalized to 0.1 mg/kg) showed a similar pattern. There was a good correlation between AUC0-24 and concentration of tacrolimus at 24 hours postdose for both formulations (Tacrolimus QD, r = 0.87; Tacrolimus BID, r = 0.92), and the slope of the line of best fit was similar. Conclusions: These results suggest that initiating tacrolimus therapy before transplant reduces the difference in exposure between Tacrolimus QD and Tacrolimus BID. © 2012 Lippincott Williams & Wilkins.
Chetty S.,University of Witwatersrand |
Baalbergen E.,Life Vincent Pallotti Rehabilitation Unit |
I Bhigjee A.,University of KwaZulu - Natal |
Kamerman P.,University of Witwatersrand |
And 4 more authors.
South African Medical Journal | Year: 2012
Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for diagnosis and management of NeuP in South Africa. Following accurate diagnosis of NeuP, pregabalin, gabapentin, low-dose tricyclic antidepressants (e.g. amitriptyline) and serotonin norepinephrine reuptake inhibitors (duloxetine and venlafaxine) are all recommended as first-line options for the treatment of peripheral NeuP. If the response is insufficient after 2 - 4 weeks, the recommended next step is to switch to a different class, or combine different classes of agent. Opioids should be reserved for use later in the treatment pathway, if switching drugs and combination therapy fails. For central NeuP, pregabalin or amitriptyline are recommended as first-line agents. Companion treatments (cognitive behavioural therapy and physical therapy) should be administered as part of a multidisciplinary approach. Dorsal root entry zone rhizotomy (DREZ) is not recommended to treat NeuP. Given the large population of HIV/AIDS patients in South Africa, and the paucity of positive efficacy data for its management, research in the form of randomised controlled trials in painful HIV-associated sensory neuropathy (HIV-SN) must be prioritised in this country.
Kritzinger F.E.,Hospital for Sick Children |
Kritzinger F.E.,University of Toronto |
Kritzinger F.E.,Christiaan Barnard Memorial Hospital |
Al-Saleh S.,Hospital for Sick Children |
And 4 more authors.
Pediatric Pulmonology | Year: 2011
Data on central sleep apnea (CSA) and its significance in children are limited. Our objectives were to describe the polysomnogram (PSG) characteristics and clinical features of children with significant CSA at a single pediatric sleep center. Study Design and Methods A retrospective chart review of children diagnosed with CSA on a PSG, from January 2007 to December 2008, was performed. All the PSG's were performed in the pediatric sleep laboratory at The Hospital for Sick Children in Toronto, Canada. All children diagnosed with significant CSA with a PSG was eligible for inclusion. Each PSG was conducted and scored according to the American Academy of Sleep Medicine standard. Significant CSA was defined as a central apnea index (CAI) of >5events/hr. Outcome for each patient was defined by the percentage change in the CAI at follow up. Results 52/969 (5.4%) patients had a CAI>5/hr on a baseline PSG. Of the 25/52 (13 males) patients who met inclusion criteria, the median age was 19 months (range 3-156 months) and their median BMI z score was +0.27 (range -2.95 to 3.02). The median CAI was 11events/hr (range 6-198/hr). The mean oxygen saturations ranged from 92.8% to 98.5%, with a median of 97%. Six (24%) patients had associated sleep-related hypoventilation and none of the patients had periodic breathing. The commonest identifiable risk factor for CSA in the study population was a neurological disorder. Conclusions This study confirms that CSA is an important finding in a significant number of young children referred for an evaluation for suspected sleep related disordered breathing. Any child diagnosed with CSA warrants full clinical assessment, including neuro-imaging. Future research should aim to evaluate the long term outcome of significant CSA. Copyright © 2011 Wiley-Liss, Inc.
EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: A randomised, double-blind, placebo-controlled phase 2 clinical trial
Rice A.S.C.,Imperial College London |
Dworkin R.H.,University of Rochester |
McCarthy T.D.,Spinifex Pharmaceuticals |
Anand P.,Imperial College London |
And 8 more authors.
The Lancet | Year: 2014
Background: Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 receptor (AT2R) is a new target for neuropathic pain. EMA401, a highly selective AT2R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia. Methods: In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22-89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22-28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987. Findings: 92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores -2·29 [SD 1·75] vs -1·60 [1·66]; difference of adjusted least square means -0·69 [SE 0·25]; 95% CI -1·19 to -0·20; p=0·0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo. Interpretation: EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients.
Steyn E.,Christiaan Barnard Memorial Hospital |
Mohamed Z.,CNR Institute of Neuroscience |
Husselman C.,Netcare Kuilsriver Hospital
International Journal of Emergency Medicine | Year: 2013
A prospective multicentre clinical study was initiated to evaluate the safety and potential clinical benefit of noninvasive vagus nerve stimulation (nVNS) for the treatment of bronchoconstriction exacerbations in asthmatics. Due to slow enrolment and design changes of the device, the study was prematurely terminated after enrolment of four eligible patients. Three of the four patients were considered treatment successes based on improvement in FEV1, improvement in VAS dyspnoea scoring, and the absence of device-related adverse events. ©2013 Steyn et al.
Hugo-Hamman C.,Christiaan Barnard Memorial Hospital |
Jacobs J.P.,All Childrens Hospital
Cardiology in the Young | Year: 2012
The first World Congress of Paediatric Cardiology was held in London, United Kingdom, in 1980, organised by Dr Jane Somerville and Prof. Fergus Macartney. The idea was that of Jane Somerville, who worked with enormous energy and enthusiasm to bring together paediatric cardiologists and surgeons from around the world. The 2nd World Congress of Paediatric Cardiology took place in New York in 1985, organised by Bill Rashkind, Mary Ellen Engle, and Eugene Doyle. The 3rd World Congress of Paediatric Cardiology was held in Bangkok, Thailand, in 1989, organised by Chompol Vongraprateep. Although cardiac surgeons were heavily involved in these early meetings, a separate World Congress of Paediatric Cardiac Surgery was held in Bergamo, Italy, in 1988, organised by Lucio Parenzan. Thereafter, it was recognised that surgeons and cardiologists working on the same problems and driven by a desire to help children should really rather meet together. A momentous decision was taken to initiate a Joint World Congress of Paediatric Cardiology and Cardiac Surgery. A steering committee was established with membership comprising the main organisers of the four separate previous Congresses, and additional members were recruited in an effort to achieve numerical equality of cardiologists and surgeons and a broad geographical representation. The historic 1st World Congress of Paediatric Cardiology and Cardiac Surgery took place in Paris in June, 1993, organised by Jean Kachaner. The next was to be held in Japan, but the catastrophic Kobe earthquake in 1995 forced relocation to Hawaii in 1997. Then followed Toronto, Canada (2001, organised by Bill Williams and Lee Benson), Buenos Aires, Argentina (2005, organised by Horatio Capelli and Guillermo Kreutzer), and most recently Cairns, Australia (2009, organised by Jim Wilkinson). Having visited Europe (1993), Asia-Pacific (1997), North America (2001), South America (2005), and Australia (2009), and reflecting the African Renaissance, the World Congress is coming to Africa. The 6th World Congress of Paediatric Cardiology and Cardiac Surgery will be held in Cape Town, South Africa, from 17 to 22 February, 2013. Cape Town is a sublime and compelling African destination with irresistible appeal. The South African Heart Association is the host. Information about The 6th World Congress of Paediatric Cardiology and Cardiac Surgery can be found at http://www.pccs2013.co.za. © 2012 Cambridge University Press.
Lorgat F.,Christiaan Barnard Memorial Hospital |
Pudney E.,Christiaan Barnard Memorial Hospital |
Van Deventer H.,Christiaan Barnard Memorial Hospital
Cardiovascular Journal of Africa | Year: 2013
Catheter ablation of ventricular tachycardia (VT) is demanding and time consuming. Robotically controlled catheter ablation reduces operator fatigue and exposure to X-rays, and provides greater precision and stability of the catheter. A new flexible, integrated robotic sheath and ablation catheter has recently been introduced (Lynx™) and used in atrial ablation procedures. We describe the first VT substrate modification ablation in the world with the Lynx™ robotic radio frequency ablation catheter.