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1.  Simultaneous Population Pharmacokinetic Modelling of Atazanavir and Ritonavir in HIV-Infected Adults and Assessment of Different Dose Reduction Strategies 
Objectives
The objective of this study was to develop a simultaneous population pharmacokinetic (PK) model to describe atazanavir/ritonavir (ATV/RTV) PK (300/100 mg) and to assess the effect of RTV dose reduction on ATV PK. Simulations of ATV concentration-time profiles were performed at doses of ATV/RTV 300/50 mg, 200/50 mg, and 200/100 mg once daily.
Methods
A total of 288 ATV and 312 RTV plasma concentrations from 30 patients were included to build a population PK model using the stochastic approximation expectation maximization algorithm implemented in MONOLIX 3.2 software.
Results
A one-compartment model with first-order absorption and lag-time best described the data for both drugs in the final simultaneous model. A maximum-effect model in which RTV inhibited the elimination of ATV was used to describe the relationship between RTV concentrations and ATV clearance (CL/F). An RTV concentration of 0.22 mg/L was associated with 50% maximum inhibition of ATV CL/F. The population prediction of ATV CL/F in the absence of RTV was 16.6 L/h (relative standard error, 7.0%), and the apparent volume of distribution and absorption rate constant were 106 L (relative standard error, 8%) and 0.87 per hour (fixed), respectively. Simulated average ATV trough concentrations at ATV/RTV 300/50 mg, 200/50 mg, and 200/100 mg once daily were 45%, 63%, and 33% lower, respectively, than that of the standard dose.
Conclusion
Although simulated median ATV trough concentrations after dose reductions were still more than the ATV minimum effective concentration (2.9-, 1.9-, and 3.6-fold for ATV/RTV 300/50 mg, 200/50 mg, and 200/100 mg, respectively); our modeling predicted a high proportion of individuals with subtherapeutic trough concentrations on the 200/50 mg dose. This suggests that 300/50 mg and 200/100 mg dosing are preferred candidate regimens in future clinical studies.
doi:10.1097/QAI.0b013e3182737231
PMCID: PMC3594700  PMID: 23011396
population PK; nonlinear mixed effect; atazanavir; ritonavir; dose reduction
2.  Biologically Based Restorative Management of Tooth Wear 
The prevalence and severity of tooth wear is increasing in industrialised nations. Yet, there is no high-level evidence to support or refute any therapeutic intervention. In the absence of such evidence, many currently prevailing management strategies for tooth wear may be failing in their duty of care to first and foremost improve the oral health of patients with this disease. This paper promotes biologically sound approaches to the management of tooth wear on the basis of current best evidence of the aetiology and clinical features of this disease. The relative risks and benefits of the varying approaches to managing tooth wear are discussed with reference to long-term follow-up studies. Using reference to ethical standards such as “The Daughter Test”, this paper presents case reports of patients with moderate-to-severe levels of tooth wear managed in line with these biologically sound principles.
doi:10.1155/2012/742509
PMCID: PMC3272350  PMID: 22315608
3.  Use of the out-of-hours emergency dental service at two south-east London hospitals 
BMC Oral Health  2009;9:19.
Background
Prior to the introduction of the 2006 NHS dental contract in England and Wales, general dental practitioners (GDPs) were responsible for the provision of out-of-hours (OOH) emergency dental services (EDS); however there was great national variation in service provision. Under the contractual arrangements introduced 1st April 2006, local commissioning agencies became formally responsible for the provision of out-of-hours emergency dental services. This study aimed to examine patients' use of an out-of-hours emergency dental service and to determine whether the introduction of the 2006 national NHS dental contract had resulted in a change in service use, with a view to informing future planning and commissioning of care.
Methods
A questionnaire was administered to people attending the out-of-hours emergency dental service at two inner city London hospitals over two time periods; four weeks before and six months after the introduction of the dental contract in April 2006. The questionnaire explored: reasons for attending; dental registration status and attendance; method of access; knowledge and use of NHS Direct; satisfaction with the service; future preferences for access and use of out-of-hours dental services. Data were compared to determine any impact of the new contract on how and why people accessed the emergency dental service.
Results
The response rate was 73% of attendees with 981 respondents for the first time period and 546 for the second. There were no significant differences between the two time periods in the gender, age, ethnic distribution or main language of service users accessing the service. Overall, the main dental problem was toothache (72%) and the main reason for choosing this service was due to the inability to access another emergency dental service (42%). Significantly fewer service users attended the out-of-hours emergency dental service during the second period because they could not get an appointment with their own dentist (p = 0.002 from 28% to 20%) and significantly more service users in the second period felt the emergency dental service was easier to get to than their own dentist (P = 0.003 from 8% to 14%). Service users found out about the service from multiple sources, of which family and friends were the most common source (30%). In the second period fewer service users were obtaining information about the service from dental receptionists (P = 0.002 from 14% to 9%) and increased use of NHS Direct for a dental problem was reported (P = 0.002 from 16% to 22%) along with more service users being referred to the service by NHS Direct (P = 0.02 from 19% to 24%). The most common preference for future emergency dental care was face-to-face with a dentist (79%).
Conclusion
This study has provided an insight into how and why people use an out-of-hours emergency dental service and has helped to guide future commissioning of these services. Overall, the service was being used in much the same way both before and after the 2006 dental contract. Significantly more use was being made of NHS Direct after April 2006; however, informal information networks such as friends and family remain an important source of information about accessing emergency dental services.
doi:10.1186/1472-6831-9-19
PMCID: PMC2729730  PMID: 19630986
4.  Contemporary management of tooth replacement in the traumatized dentition 
Dental Traumatology  2012;28(3):183-192.
Dental trauma can result in tooth loss despite best efforts at retaining and maintaining compromised teeth (Dent Traumatol, 24, 2008, 379). Upper anterior teeth are more likely to suffer from trauma, and their loss can result in significant aesthetic and functional problems that can be difficult to manage (Endod Dent Traumatol, 9, 1993, 61; Int Dent J 59, 2009, 127). Indeed, teeth of poor prognosis may not only present with compromised structure but trauma may also result in damage to the support tissues. Injury to the periodontium and alveolus can have repercussions on subsequent restorative procedures (Fig. 19). Where teeth are identified as having a hopeless prognosis either soon after the incident or at delayed presentation; planning for eventual tooth loss and replacement can begin at the early stages. With advances in both adhesive and osseointegration technologies, there are now a variety of options for the restoration of edentate spaces subsequent to dental trauma. This review aims to identify key challenges in the provision of tooth replacement in the traumatized dentition and outline contemporary methods in treatment delivery.
doi:10.1111/j.1600-9657.2012.01122.x
PMCID: PMC3430882  PMID: 22494549
diagnosis; permanent tooth; prognosis; tooth injury; treatment

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