Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients

Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430–3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241– 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284–3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%.     

Spectrophotometric analysis of crown discoloration induced by MTA- and ZnOE-based sealers

Crown discoloration can be induced by root canal sealer remnants following root canal treatment.

Objective:

The aim of this study was to evaluate chromatic alterations in human tooth crowns induced by a Mineral Trioxide Aggregate-based sealer (MTA Fillapex^® and a commonly used ZnOE-based sealer (Roth-811). The tested null hypothesis was that the application of the materials did not induce clinically perceptible crown discoloration (Ho: CIE color difference ΔE<3.7).

Material and Methods:

Forty five fully developed, intact, mandibular third molars were sectioned 1 mm below the cemento-enamel junction. The pulp chambers were chemomechanically debrided via the cervical access. The specimens were randomly assigned into three groups Group 1: MTA Fillapex, Group 2: Roth 811, Group 3: Negative control (unfilled) and immersed in individually marked vials containing distilled water up to the cervix (37±1º C). The spectral reflectance lines were recorded by utilizing a UV-VIS spectrophotometer equipped with integration sphere in the visual spectrum at baseline, 1 week, 1 and 3 months after material placement. Data were transformed into values of the CIE L*a*b* color system and the corresponding ΔE values were calculated. Statistical analysis was performed using two-way mixed ANOVA models, at p=0.05 level of significance.

Results:

A statistically significant increase in a* and b* chromatic parameters of the MTA Fillapex Group was measured. However, ΔE values did not exceed the human eye perceptibility threshold (set at ΔE<3.7) during the experimental period (ΔEt3=2.88). In Roth-811 Group, a statistically significant decrease in L* and a statistically significant increase in a* and b* chromatic parameters was measured, during all observation periods. Resultant ΔE values exceeded the human eye perceptibility threshold after 1 week (ΔEt1=5.65).

Conclusions:

Application of MTA Fillapex in tooth crowns resulted in minimal color alterations, while Roth 811 induced severe discoloration, in vitro. It could be suggested that, in terms of aesthetics, the use of MTA Fillapex appears to be favorable.     

Biocompatibility Study Based on Differential Sequestration Kinetics of CD14+CD16+ Blood Monocyte Subsets with Different Dialyzers

The immune defect in hemodialysis (HD) patients is associated with a monocyte dysfunction, including an increase in the production of proinflammatory cytokines. Blood membrane contact leads to an increase in cellular activation and sequestration into the capillary bed of the lung. The influence of the sequestration on the number of mature monocytes was studied by analyzing the fate of monocytes, particularly, the CD14+CD16+ subpopulation, during HD treatment.

In thirty stable HD patients, the distinct cell populations were determined by differential blood counts and flow cytometry. Patients with diabetes or systemic vasculitis, those showing evidence of infectious complications or malignancy, or those taking immunosuppressive medications were excluded from the study. Cells from this study population were analyzed before the start, 30 min thereafter, and at the end of HD treatment, each time using a different dialyzer: hemophan, methylmethacrylate (PMMA), triacetate membrane, cuprophane/vitamin E, acrylonitrile, and sodium methallylsulfonate polymer (AN69).

The CD14+CD16+ subset decreased at 30 min and remained suppressed for the course of dialysis. To examine whether currently used biocompatible membranes differ in their effect on the sequestration of monocyte subpopulations, temporal monocytic changes were comparatively analyzed during HD with a different dialyzer. The drop in the first 30 min until the end of HD treatment was significant (p<0.05), very uniform, and sharp in all patients, and was independent upon membrane type.

The CD14+CD16+ monocyte subpopulation showed increased and longer margination from the blood circulation during HD. Given the fact that CD14+CD16+ monocytes represent a sensitive marker for inflammation or cellular activation, the depletion of these cells may offer an easily accessible parameter that is more sensitive than complement activation for biocompatibility studies on forthcoming, improved dialyzer membranes.     

Proximal opening wedge metatarsal osteotomy for correction of moderate to severe hallux valgus deformity using a locking plate

Purpose

Hallux valgus is a complex deformity of the first metatarsophalangeal joint, with varus angulation of the first metatarsal, valgus deviation of the great toe and lateral displacement of the sesamoids and the extensor tendons. The aim of the surgery is to achieve correction of the varus deviation of the 1st metatarsal which is considered by some as the primary intrinsic predisposing factor to hallux valgus deformity.

Methods

We retrospectively reviewed 85 patients (107 feet) who underwent an opening wedge osteotomy of the 1st metatarsal for correction of moderate to severe hallux valgus and metatarsus primus varus. A medially applied anatomic pre-contoured locking plate was used for fixation of the osteotomy.

Results

The mean IMA was decreased from 15.8 (range 12–22) degrees to 7.8 (range 0–12) degrees. The mean pre-operative HVA was 39 (range 21–52) degrees and the mean postoperative HVA was 11.8 (6–19) degrees. The pre-operative AOFAS score was 52 (SD 3.1) and the postoperative score was 85 (SD 5.2).

Conclusion

The proximal opening wedge metatarsal osteotomy is a safe, effective and reproducible technique for correction of moderate to severe hallux valgus deformity. The use of a locking plate provides enough control at the fragments, enhancing healing of osteotomy and maintenance of the correction even with a violated proximal lateral cortex.     

Early postoperative voiding dysfunction after insertion of retropubic midurethral tape

Introduction and hypothesis

A significant proportion of patients develop voiding dysfunction after midurethral tape (MUT) insertion, which reduces patient satisfaction. The study’s purpose was to identify predictive factors of voiding dysfunction after a retropubic MUT procedure.

Methods

This was a retrospective study of 100 patients who underwent only a retropubic MUT procedure between January 2010 and December 2011. Early voiding dysfunction was defined when patients required a Foley catheter within 48 h. Data including demographic information, urogenital symptoms, previous surgery, preoperative uroflowmetry and urodynamic parameters were analysed using SPSS v22. Univariate analysis of all demographic variables was performed; those significant at 10 % were entered into a multivariate logistic regression.

Results

Fourteen patients required Foley catheter insertion, with a median age of 58 years (26–83 years), median BMI 28 kg/m² (20–48 kg/m2), and median parity 2 (0–4). Univariate analysis revealed peak flow rate <15 ml/s (OR 3.79; 1.07, 13.4; p?=?0.046), bladder capacity (p?=?0.044), stress incontinence versus mixed or urge incontinence (p?=?0.064) and previous surgery (OR 4.39; 1.34, 14.41; p?=?0.015) to be associated with voiding dysfunction. Multivariate analysis showed only previous pelvic floor surgery to be independently associated (OR 3.76; 1.14, 12.23, p?=?0.029).

Conclusions

Only previous pelvic-floor surgery was found to be a strong predictive factor of voiding dysfunction. The rate of voiding dysfunction was similar to those of published data. Previous studies revealed different predictive factors. A larger cohort is needed to provide a definite answer. Those with previous surgery appear to be those most at risk and pre-surgical counselling for these women could be suggested.

     

Digital assessment and quantification of pelvic organ prolapse (DPOP-Q): a randomised cross-over diagnostic agreement trial

Introduction

Pelvic Organ Prolapse Quantification (POP-Q) system, measured in centimetres using a ruler (e.g. POPstix®), is recommended to quantify prolapse severity. POPstix® are costly (US $1/ruler). Home-made devices are used instead, but these have not been shown to be reproducible.

Hypothesis

Digitally assessed POP-Q (DPOP-Q) is as reliable, reproducible and acceptable as POP-Q assessed using POPstix®.

Methods

In this randomised crossover diagnostic agreement trial, each assessor measured the index finger of their dominant hand using a ruler. At visit one, patients were randomised to either POPstix® POP-Q assessment in a modified lithotomy position or DPOP-Q in both modified a lithotomy and a standing position. After the first clinician conducted this assessment, a second blinded clinician then carried out the remaining assessment on the same patient. For each examination, duration was recorded, along with a patient-completed discomfort score. Twenty-five women were invited for visit two, at which DPOP-Q was recorded by the same clinician who undertook DPOP-Q at the first visit. This allowed evaluation of inter- and intraobserver agreement together with examination acceptability.

Results

One hundred and nine women were recruited [median age 55 years, parity 2, body mass index (BMI) 27.1]. Of the 25 patients invited, 23 returned for visit two. DPOP-Q had high interobserver reliability [κ?=?0.94, 95 % confidence interval (CI) 0.878–0.996] and intraobserver reliability (α?=?0.96) with POPstix®. DPOP-Q was significantly quicker (p?=?0.02) and less uncomfortable (p?<?0.01) than POPstix® POP-Q.

Conclusion

DPOP-Q is reliable, acceptable and cost effective.

     

Management of Urinary Symptoms Associated with Fibroids

Uterine fibroids are the most common benign tumours in women of reproductive age. Fibroids are linked with a variety of lower urinary tract symptoms (LUTS). Direct pressure on the bladder, but also vascular, neurogenic and hormonal changes have been proposed as underlying pathophysiological mechanisms. There is conflicting evidence in the literature regarding the association between LUTS and fibroid volume and position. Conservative management with bladder retraining, supervised pelvic floor muscle training with or without drug therapy might be used as first line. In the presence of persistent symptoms, conventional urodynamics or ideally videourodynamics might be considered before more invasive treatment. Counselling of patients prior to uterine artery embolisation, myomectomy or hysterectomy could be challenging, as it is difficult to estimate the effect of fibroid reduction or removal on LUTS.