Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.     

Interventions for postoperative pain in children: An overview of systematic reviews

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti‐inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non‐Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children.     

Protective effects of polydatin against CCl4-induced injury to primarily cultured rat hepatocytes

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Prevalence of Dental Fluorosis Among Primary School Children in Rural Areas of Chidambaram Taluk, Cuddalore District, Tamil Nadu, India

Background:

Fluorosis is one of the common but major emerging areas of research in the tropics. It is considered endemic in 17 states of India. However, the Cuddalore district of Tamil Nadu is categorised as a fluorosis non-endemic area. But clinical cases of dental fluorosis were reported in the field practice area of Department of Community Medicine, Rajah Muthiah Medical College, Annamalai University, Chidambaram. Since dental fluorosis has been described as a biomarker of exposure to fluoride, we assessed the prevalence and severity of dental fluorosis among primary school children in the service area.

Materials and Methods:

Children studying in six primary schools of six villages in the field practice area of Rural Health Centre of Faculty of Medicine, Annamalai University, Chidambaram, were surveyed. Every child was clinically examined at the school by calibrated examiners with Dean''s fluorosis index recommended by WHO (1997). Chi-square test, Chi-square trend test and Spearman''s rank correlation coefficient test were used for statistical analysis.

Results:

Five hundred and twenty-five 5- to 12-year-old school children (255 boys and 270 girls) were surveyed. The overall dental fluorosis prevalence was found to be 31.4% in our study sample. Dental fluorosis increased with age P < 0.001, whereas gender difference was not statistically significant. Aesthetically objectionable dental fluorosis was found in 2.1% of the sample. Villages Senjicherry, Keezhaperambai and Kanagarapattu revealed a community fluorosis index (CFI) score of 0.43, 0.54 and 0.54 with 5.6%, 4.8% and 1.4% of objectionable dental fluorosis, respectively. Correlation between water fluoride content and CFI values in four villages was noted to be positively significant.

Conclusion:

Three out of six villages studied were in ‘borderline’ public health significance (CFI score 0.4-0.6). A well-designed epidemiological investigation can be undertaken to evaluate the risk factors associated with the condition in the study region.     

Speech perception scores in cochlear implant recipients: An analysis of ceiling effects in the CUNY sentence test (Quiet) in post-lingually deafened cochlear implant recipients

Objectives: To evaluate the clinical utility of the City University of New York sentence test in a cohort of post-lingually deafened cochlear implants recipients over time.

Methods: 117 post-lingually deafened, Australian English-speaking CI recipients aged between 23 and 98 years (M?=?66 years; SD?=?15.09) were recruited. CUNY sentence test scores in quiet were collated and analysed at two cut-offs, 95% and 100%, as ceiling scores.

Results: CUNY sentence scores ranged from 4% to 100% (M?=?86.75; SD?=?20.65), with 38.8% of participants scoring 95% and 16.5% of participants reaching the 100% scores. The percentage of participants reaching the 95% and 100% ceiling scores increased over time (6 and 12 months post-implantation).

The distribution of all post-operative CUNY test scores skewed to the right with 82% of test scores reaching above 90%.

Discussion: This study demonstrates that the CUNY test cannot be used as a valid tool to measure the speech perception skills of post-lingually deafened CI recipients over time. This may be overcome by using adaptive test protocols or linguistically, cognitively or contextually demanding test materials.

Conclusion: The high percentage of CI recipients achieving ceiling scores for the CUNY sentence test in quiet at 3 months post-implantation, questions the validity of using CUNY in CI assessment test battery and limits its application for use in longitudinal studies evaluating CI outcomes. Further studies are required to examine different methods to overcome this problem.     

Microbiological culture analysis of the tongue anaerobic microflora in subjects with and without halitosis

Objective:  Determination of the microflora present on the tongue dorsum of subjects with and without halitosis using conventional microbiological culture methods.
Methods:  Twenty-one halitosis and 20 control patients were recruited using a strict clinical protocol. Samples were collected from the posterior dorsum of the tongue using a sterile brush. Each sample was vortex mixed for 30 s and serial 10-fold dilutions to 10⁻⁷ were carried out. Samples were plated onto fastidious anaerobe agar (FAA) and FAA enriched with vancomycin. These were incubated under anaerobic conditions for 10 days at 37°C. Strict anaerobes were identified by metronidazole sensitivity and bacteria were identified to genus level by a combination of colony morphology, Gram staining and biochemical and enzymatic tests (rapid ID 32 A).
Results:  The predominant species in test and control groups were Veillonella sp. and Prevotella sp. Greater species diversity was found in the halitosis samples compared with controls. The halitosis samples contained an increased incidence of unidentifiable Gram-negative rods, Gram-positive rods and Gram-negative coccobacilli.
Conclusions:  There was no obvious association between halitosis and any specific bacterial genus. The increased species diversity found in halitosis samples suggests that halitosis may be the result of complex interactions between several bacterial species. The role of uncultivable bacteria may also be important in contributing to this process.