Conventional press-and-breathe metered dose inhalers (MDIs) are widely prescribed but are often difficult for many patients to properly use. A total of 501 patients from different medical specialties were enrolled in this study, which evaluated how the patients used their MDIs. Using a conservative method (minimum number of errors) of determining errors, we found that 388 (77.5%) of the patients made at least one error when demonstrating how they use their MDI for two observers. Using a liberal (maximum number of errors) method of analysis, we found that 447 (89.2%) of the patients made at least one error. There was no difference in errors made stratified by patient gender, patient age, or the medical specialty that treated the patient's pulmonary disease. The two most common errors made by patients were failure to breathe out to functional residual capacity before actuation (225 by minimum method, 280 by maximum method) and not actuating the canister at the start of inhalation (207 by minimum method, 323 by maximum method). Of the patients with improper timing of actuation, the majority (121 patients by minimum method and 187 patients by maximum method) actuated the canister early. In this large patient sample, regardless of which medical specialty provided the treatment, the majority of the patients evaluated had less than optimal MDI technique. Routine assessment of MDI technique should be instituted as standard practice care.

Gentleness assessments favored the silicone tape compared to a paper tape and warrant further clinical investigation in the neonatal intensive care unit.

Background Prospective randomized controlled studies have demonstrated that addition of chlorhexidine (CHG) dressings reduces the rate of catheter (central venous and arterial)-associated bloodstream infections (CABSIs). However, studies confirming their impact in a real-world setting are lacking. Methods We conducted a real-world data study evaluating the impact of incrementally introducing chlorhexidine dressings (sponge or gel) in addition to an ongoing catheter bundle on the rates of CABSI, expressed as incidence density rates per 1000 catheter-days measured as part of a surveillance program. Poisson regression models were used to compare infection rates over time. Both dressings were used simultaneously during one of the five study periods. Results From 2006 to 2014, 18,286 patients were admitted (91,292 ICU-days and 155,242 catheter-days). We recorded 111 CABSIs. We observed a progressive but significant decrease of CABSI rates from 1.48 (95% CI 1.09–2.01) without CHG dressings to 0.69 (95% CI 0.43–1.09) and 0.23 (95% CI 0.11–0.48) episodes per 1000 catheter-days when CHG sponge and CHG gel dressings were used ( p = 0.0007; p < 0.001). A non-significant lower rate of infections occurred with CHG gel compared with CHG sponge dressings. An identical low rate of allergic skin reactions (0.3/1000 device-days) was observed with both types of CHX dressings. Post-study data until 2018 confirmed a sustained decrease of infection rates over 11 years. Conclusions The addition of chlorhexidine dressings to all CVC and arterial lines to an ongoing catheter bundle was associated with a sustained 11-year reduction of all catheter-associated bloodstream infections. This large real-world data study further supports the current recommendations for the systematic use of CHG dressings on all catheters of ICU patients. Electronic supplementary material The online version of this article (10.1007/s00134-019-05617-x) contains supplementary material, which is available to authorized users.

The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proventil-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconstriction, to validate this method and provide recommendations. The protective effects of 100-, 200-, and 400-micrograms doses of Proventil-HFA were compared with the same doses of Ventolin-CFC in 18 adult asthmatics (mean FEV1, 92% predicted; mean baseline PC20 methacholine, 1.8 mg/ml), in a dose-level blind, balanced, eight-period, crossover, placebo-controlled study. The log-transformed PC20 values after each dose of the drugs were compared by repeated-measures analysis of variance (ANOVA). A significant dose-effect was present (p < 0.0001). Using the Finney assay, the RP of Proventil-HFA compared with Ventolin-CFC was 1.08 (90% CI, 0.81-1.46) (80% power). This was also estimated using a nonlinear Emax model to validate the Finney method. The most precise estimate of RP was obtained with the comparison between 100- and 200-micrograms doses (RP, 1.00; 90% CI, 0.77-1.31). There were no adverse events resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection to methacholine is a valid method of demonstrating bioequivalence. By this method, 100- and 200-micrograms doses of salbutamol inhalations from an MDI will suffice.

We have compared the serum pharmacokinetics of the metabolites of beclomethasone dipropionate after inhalation from chlorofluorocarbon (CFC) and hydrofluoroalkane HFA-134a (HFA) formulations in asthmatic patients. Twenty-three patients completed this open-label, randomized, single-dose, three-period crossover study. Each patient received in separate periods 200 microg or 400 microg HFA-beclomethasone dipropionate, or 400 microg CFC-beclomethasone dipropionate. Venous blood samples were collected over 24 h for the determination of beclomethasone esters and beclomethasone in the serum. Significant differences in pharmacokinetics following HFA- and CFC-beclomethasone dipropionate were observed. Following a 400 microg beclomethasone dipropionate dose, the HFA formulation gave mean maximum concentrations (Cmax) and area under the curve (AUC) values of beclomethasone esters of 1153 pg mL(-1) and 4328 pg h mL(-1), respectively, and beclomethasone Cmax and AUC values of 69 pg mL(-1) and 682 pg h mL(-1), respectively. These values were approximately 2-3-fold those seen with the CFC formulation (beclomethasone esters Cmax and AUC of 380 pg mL(-1) and 1764 pg h mL(-1), respectively; beclomethasone Cmax and AUC of 41 pg ml(-1) and 366 pg h mL(-1), respectively). Beclomethasone esters, the major component of beclomethasone dipropionate in the serum, peaked significantly earlier for the HFA formulation (0.8 h) than for the CFC formulation (2 h). Tests for dose proportionality of beclomethasone esters pharmacokinetics following HFA-beclomethasone dipropionate showed that the two hydrofluoroalkane strengths were proportional. The more rapid and greater efficiency of systemic drug delivery of the HFA formulation compared with the CFC formulation can be explained if most of each inhalation from CFC-beclomethasone dipropionate is swallowed and absorbed orally, whereas most of each inhalation from HFA-beclomethasone dipropionate is absorbed through the lungs. There is a need for comprehensive dose-response efficacy trials, with the use of the steep portion of the dose-response relationship, to evaluate the significance of these pharmacokinetic differences.

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A new skin protectant was developed for use on conditions involving partial-thickness skin loss such as severe incontinence-associated dermatitis. This new formulation is based on a cyanoacrylate chemistry designed to polymerize in situ and create a breathable film able to protect the skin surface from external irritants. This film provides an environment favorable for healing to occur beneath the film. To evaluate the characteristics of the novel chemistry, we devised a preclinical testing strategy comprising three different animal models. The data from all three models was considered collectively to create an overall assessment of effectiveness. A guinea pig model was used to evaluate the barrier efficacy of the new product in protecting intact skin from irritation. A porcine partial-thickness wound model was used to evaluate the efficacy of the product in helping control minor bleeding and exudate. A similar model was also used to assess the process of reepithelialization in the continued presence of an irritant. In the first model, untreated sites had 8.5 times more irritation than sites covered with the new product (p < 0.001). In the second model, a single application of the new product successfully attached to intact peri-wound skin and to denuded, weepy skin. It significantly reduced the amount of fluid weeping from the wounds (p 0.001) and continued to perform throughout a 96 hours experiment. In the third model, the percent of reepithelialization was significantly greater for the wounds covered with the new product than for the control wounds (p 5 0.003; on average, 18.3% greater, with a 95% confidence interval of 9.2% to 27.5%). These results suggest that the new skin protectant protects intact and denuded skin from irritants and provides an environment favorable to healing, offering promise for the management of various conditions involving loss of epidermis. Wound healing is a complex biological process with several steps involved to restore skin integrity (hemostasis, inflammation, granulation tissue formation, and remodel-ing). The biological events involved and how they can be modulated using current knowledge and technology have been recently reviewed by Wong et al. 1 The context of the wound impacts the sequence of events that will follow and the successful resolution of the wound. A variety of products are available to manage wounds. Dressings are typically used for acute (surgical or traumatic) and chronic wounds (recently reviewed by Sood et al. 2); however, severe skin damage such as that seen in incontinence-associated dermatitis (IAD) requires a different approach due to the location on the body and the necessity for frequent cleaning caused by incontinence episodes. In mild cases of IAD (skin is red and macerated but epidermis is still present), barrier films can be used. These products are applied as liquids, either in a spray formulation, a wipe, or a wand applicator, and polymerize to form a film in situ and protect the skin. In severe cases of IAD, however , the epidermis is breached...

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