Pilgaardhinrichsen4671

Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment.

To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment.

During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease-inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF).

A total of 866 samples was analysed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (-30 ng/mL at 4/7, P = 0.003). Significant lower plasma concentrations were observed for OFF vs ON except for ETR (n = 5, P = 0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100% and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6% and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable.

Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.

Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.Accumulating evidence has highlighted the essential roles of cytokines in itch processing. Although IL-23 and Th17 cytokines are elevated in inflammatory skin disorders, their role in itch is unknown. Here, we investigated the role of IL-23 and IL-17A in itch response using an in vitro calcium imaging of mouse dorsal root ganglion (DRG) neurons and an in vivo behaviour test. Calcium imaging studies revealed that a few DRG neurons (~5%) responded to either IL-23 or IL-17A. Pretreatment cells with IL-23 significantly reduced calcium responses to histamine and capsaicin but not chloroquine. Behaviour experiments showed neither IL-23 nor IL-17A evoked scratching. IL-23 significantly decreased histamine-evoked scratching without affecting chloroquine-evoked scratching. There was no difference in scratching between IL-17A- and vehicle-treated groups. These results indicate that IL-23 might play a role in regulating histaminergic itch via modulation of TRPV1 activity.

To assess obesity as a risk factor for tooth loss over 5years in an urban sample of Brazilian adults.

A total of 1586 individuals were surveyed using a multistage probabilistic approach. Five years later, 635 individuals 14-64years old were re-examined. An incident case of tooth loss was determined for a participant that had lost at least one tooth over time. Obesity was evaluated by calculating body mass index at baseline and by the change in obesity status over time.

Incident cases of tooth loss were significantly more frequent among obese (47.1%) than normal-weight individuals (32.4%) (p=.004). Obese individuals had 31% higher risk [relative risk (RR) =1.31; 95% confidence interval (95%CI) 1.04-1.65] for tooth loss than normal-weight individuals adjusting for age, socio-economic status, smoking, dental care and periodontitis. This association was significant for females (RR=1.47, 95%CI 1.08-2.01), but not for males. The risk for tooth loss was also modified by presence of periodontitis at baseline and lifetime smoking exposure. There was an increased risk for tooth loss for those that remained obese than those that remained normal weight.

Obesity is associated with higher risk for tooth loss. This association was modified by sex, periodontal status and smoking.

Obesity is associated with higher risk for tooth loss. This association was modified by sex, periodontal status and smoking.

A high prevalence of protein-energy wasting and malnutrition among uremic patients is associated with an increase in morbidity and mortality. We aimed to investigate the modulating effect of daily dietary protein intake (DPI) evaluated by normalised protein catabolic rate (nPCR) on mortality in long-term haemodialysis (HD) patient from a nationwide population-based study.

By Taiwan Renal Registry Data System between 2005 and 2012, we divided the long-term HD patients into average nPCR<1.2 and nPCR≥1.2 groups according to the current guideline. The relation of nPCR with three-year all-cause and cardiovascular (CV) mortality were evaluated. The cox regression method for predicted mortality by nPCR was used.

Among 88330 HD patients, 58122 (65.8%) patients were in average nPCR<1.2 group and 30208 (34.2%) in average nPCR≥1.2 group. Both all-cause and cardiovascular (CV) mortality risks were increased in nPCR<1.2 group after adjusting for demographics and laboratories cofactors in our multivariate cos presented by nPCR) independently correlated with all-cause and CV mortality among HD patients. Mortality risks were higher in low DPI patients even with normoalbuminaemia and non-hypocholesterolaemia. Further investigations on the importance of increasing DPI in HD patients is warranted.Ten cases of ertapenem neurotoxicity, mainly confusional states, are described, some of them with fatal outcomes. The majority of patients (90%) had a creatinine clearance (CrCl) less then 50 mL/min/1.73m2 at some point during treatment and hypoalbuminaemia was always present when ertapenem treatment was started. The pharmacokinetic and pharmacodynamic properties of this carbapenem could favour a different profile, and approved doses can be excessive in some patients with moderate renal failure (CrCl 31-59 mL/min/1.73 m2 ). It may be necessary to re-evaluate renal function during treatment and adjust doses or reconsider the adequacy of treatment based on clinical judgement, especially if relevant changes in the CrCl occur (i.e. KD025 a reduction to ≤30 mL/min/1.73 m2 ) or unexplained behavioural disorders are detected. The onset of the symptoms of ertapenem neurotoxicity can be insidious and go unnoticed, and so a knowledge and early suspicion of confusional states are important to improve the patient prognosis.