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Pilonidal disease (PD) is a common and debilitating inflammatory condition with significant impact on quality of life. Minimally invasive techniques (MIT) have shown promising results comparing to traditional excision. Herein we present a comparison of two MIT techniques -sinusectomy (SE) and pit-picking plus laser ablation (PPL).All cases of paediatric PD treated by PPL and SE at our center between August 2018 and August 2020 were retrospectively reviewed.One-hundred and six patients were included, with a median age of 16 years (IQR 15-16). PPL was the procedure of choice in 36 patients (34%) and the remaining underwent SE (66%). Median healing time was significantly lower in SE group (20 days), comparing to PPL (30 days) (p = 0.002). Early healing failure occurred more frequently in the PPL group (p = 0.003). Recurrence rate was similar between groups - PPL 17% versus SE 16% (p = 0.89). Overall complication rate was 9% and was significantly higher in PPL (p = 0.03).MIT techniques are promising solutions in PD treatment. Although similarly easy and fast to perform, SE technique showed better healing profile and lower complication rate but no significant difference on recurrence rates was observed.

To identify barriers and facilitators to adoption of a new surgical procedure via an implementation science framework to characterize associated socioemotional, clinical, and decision-making processes.Qualitative study with a semistructured interview approach.Large tertiary care referral center.Academic otolaryngologists with at least 2 years of practice were identified and interviewed. Transcripts were thematically coded and separated into steps in the clinical pathway. Synthesis of major themes characterized facilitators and barriers to uptake of a new surgical technique.Of 22 otolaryngologists, 19 were interviewed (85% male). They had a median 18 years of practice (interquartile range, 7.8-26.3), and 65% were subspecialty trained. In the decision to implement a new procedure, improving patient outcomes and addressing unmet clinical needs facilitated adoption, whereas costs and adopting profit-driven technologies without improved outcomes were barriers. In patient consults, establishing trust facilitated implementation of new techniques; barriers included participants' hesitation to communicate about the unknowns of a new procedure. Intraoperatively, little change to existing workflow or improved efficiency facilitated adoption, while a substantial learning curve for the new procedure was a barrier. Achieving favorable outcomes and patient satisfaction sustained implementation of new procedures. Too few referrals or indications for the new procedure hindered implementation.Our study demonstrates that innovation in otolaryngology is often an individual iterative process that providers pursue to improve patients' outcomes. Although models for the oversight of surgical innovation emphasize the need for evidence, obtaining sufficient numbers of providers and patients to generate evidence remains a challenge in specialty surgical practice.

Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT‐prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J‐Tpeak and Tpeak‐Tend intervals. Concentration‐effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J‐Tpeakc. Levofloxacin had little effect on J‐Tpeakc. For moxifloxacin, the concentration‐effect modeling showed a greater effect for women on QTcF and J‐Tpeakc, whereas for levofloxacin the inverse was true: women had smaller QTcF and J‐Tpeakc effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined IKs and IKr inhibitory properties of moxifloxacin versus IKr suppression only of levofloxacin. The equipotent inhibition of IKs and IKr appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in IKr and IKs balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.

A thorough QT/QTc study in healthy white Caucasian subjects demonstrated that rupatadine has no proarrhythmic potential and raised no cardiac safety concerns. The present phase 1 study aimed to confirm the cardiac safety of rupatadine in healthy Japanese subjects. In this randomized, double-blind, placebo-controlled study, 27 healthy Japanese subjects were administered single and multiple escalating rupatadine doses of 10, 20, and 40 mg or placebo. Triplicate electrocardiogram (ECG) recordings were performed on days -1, 1, and 5 at several points, and time-matched pharmacokinetic samples were also collected. Concentration-effect analysis based on the change in the QT interval corrected using Fridericia's formula (QTcF) from average baseline was performed. Data from the formal TQT study in white Caucasian subjects was used for a comparison analysis. The ECG data for rupatadine at doses up to 40 mg did not show an effect on the QTc interval of regulatory concern. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a significant shortening of QTcF on days 1 and 5 four hours after a standardized meal. The data from this study exhibited no statistically significant differences in the QTc effect between Japanese and white Caucasian subjects.

Understanding the physiological fluctuations in the corrected QT (QTc) interval is important to accurately interpret the variations in drug-induced prolongation. The present study aimed to define the time course of the effect of moxifloxacin on the QT interval to understand the duration of the responses to moxifloxacin. This retrospective analysis was performed on data taken from a thorough QT 4-way crossover study with 40 subjects. Each period consisted of a baseline electrocardiogram (ECG) day (day -1) and a treatment day (day 1). On both days, ECGs were recorded simultaneously using 2 different systems operating in parallel: a bedside ECG and a continuous Holter recording. The subjects were randomized to 1 of 4 treatments: 5 mg and 40 mg of intravenous amisulpride, a single oral dose of moxifloxacin (400 mg), or placebo. Standardized meals, identical in all 4 periods, with similar nutritional value were served. Bedside ECG results confirmed that the moxifloxacin peak effect was delayed in the fed state and showed that the Fridericia corrected QT prolongation induced by moxifloxacin persisted until the end of the 24-hour measurement period. The use of continuous Holter monitoring provided further insight, as it revealed that the moxifloxacin effect on QTc was influenced by diurnal and nocturnal environmental factors, and hysteresis effects were noticeable. The findings suggested that moxifloxacin prolongs QTc beyond its elimination from the blood circulation. This is of relevance to current concentration-effect modeling approaches, which presume the absence of hysteresis effects.

Aim The D2/D3 antagonist amisulpride has shown promising efficacy against postoperative nausea and vomiting (PONV) at low doses. We investigated whether intravenous amisulpride has an effect on the QTc interval in a formal Thorough QT study (TQT). Methods This was a randomized, double-blind, placebo and positive-controlled, four-way crossover study. Forty healthy Caucasian and Japanese subjects were included to receive a single administration of 5 mg and 40 mg of i.v. amisulpride or a single oral dose of moxifloxacin or placebo per period. Results The therapeutic dose of 5 mg amisulpride was associated with a slight, transient increase in mean ΔΔQTcF, from 2.0 ms prior to dosing to a peak of 5 ms (90% CI: 2.8, 7.1 ms) at 8 min, decreasing to 2.1 ms at 30 min after dosing. The supra-therapeutic dose of 40 mg given at twice the infusion rate was associated with prolongation in ΔΔQTcF peaking at 23.4 ms (90% CI: 21.3, 25.5 ms) at the end of infusion (8 min), returning below 10 ms within 1.5 h. Assay sensitivity was confirmed; ΔΔQTcF had increased by 12.3 ms (90% CI 10.1, 14.6 ms) at 4 h post-dose. The PK-PD relationship revealed no differences between Caucasian and Japanese subjects (p-value > 0.5). Conclusions Amisulpride has a plasma concentration-dependent effect on the QTc interval. The proposed therapeutic dose for management of PONV does not lead to a prolongation of QTcF above the threshold of regulatory concern, while such effect could not be excluded for the supratherapeutic dose.

The efficiency of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (Tetra-Py(+)-Me) in the photodynamic inactivation of single-species biofilms of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans and mixed biofilms of S. aureus and C. albicans was evaluated. The effect on the extracellular matrix of P. aeruginosa was also assessed. Irradiation with white light up to an energy dose of 64.8 J cm(-2) in the presence of 20 mum of Tetra-Py(+)-Me caused significant inactivation in all single-species biofilms (3-6 log reductions), although the susceptibility was attenuated in relation to planktonic cells. In mixed biofilms, the inactivation of S. aureus was as efficient as in single-species biofilms but the susceptibility of C. albicans decreased. In P. aeruginosa biofilms, a reduction of 81% in the polysaccharide content of the matrix was observed after treatment with a 20 mum PS concentration and a total light dose of 64.8 J cm(-2). The results show that the Tetra-Py(+)-Me causes significant inactivation of the microorganisms, either in biofilms or in the planktonic form, and demonstrate that polysaccharides of the biofilm matrix may be a primary target of photodynamic damage.