Evidence-based hand hygiene: Liquid or gel handrub, does it matter?

BACKGROUND: Recent studies put under scrutiny the prevailing hand hygiene guidelines, which incorporate quantitative parameters regarding handrub volume and hand size. Understanding the criticality of complete (i.e., efficient) hand hygiene in healthcare, objectivization of hand hygiene related parameters are paramount, including the formulation of the ABHR. Complete coverage can be achieved with optimal Alcohol-Based Hand Rub (ABHR) provided. The literature is limited regarding ABHR formulation variances to antimicrobial efficiency and healthcare workers' preference, while public data on clinically relevant typical application differences is not available. This study was designed and performed to compare gel and liquid format ABHRs (the two most popular types in Europe) by measuring several parameters, including application time, spillage and coverage. METHODOLOGY: Senior medical students were invited, and randomly assigned to receive pre-determined ABHR volumes (1.5 or 3 ml). All the 340 participants were given equal amounts of gel and liquid on two separate hand hygiene occasions, which occurred two weeks apart. During the hand hygiene events, by employing a digital, fully automated system paired with fluorescent-traced ABHRs, disinfectant hand coverage was objectively investigated. Furthermore, hand coverage in relation to the participants' hand sizes was also calculated. Additional data collection was performed regarding volume differences and their effect on application time, participants' volume awareness (consciousness) and disinfectant spillage during the hand hygiene events. RESULTS: The 1.5 ml ABHR volume (commonly applied in healthcare settings) is insufficient in either formulation, as the non-covered areas exceeded significant (5%+) of the total hand surface area. 3 ml, on the contrary, resulted in almost complete coverage (uncovered areas remained below 1.5%). Participants typically underestimated the volume which they needed to apply. While the liquid ABHR spreads better in the lower, 1.5 ml volume compared to the gel, the latter was easier handled at larger volume. Drying times were 30/32 s (gel and liquid formats, respectively) when 1.5 ml handrub was applied, and 40/42 s when 3 ml was used. As the evaporation rates of the ABHR used in the study are similar to those available on the market, one can presume that the results presented in the study apply for most WHO conform ABHRs. CONCLUSION: The results show that applying 1.5 ml volume was insufficient, as large part of the hand surface remained uncovered (7.0 ± 0.7% and 5.8 ± 1.0% of the hand surface in the case of gel and liquid, respectively) When 3 ml handrub was applied drying times were 40 and 42 s (gel and liquid, respectively), which is a very long time in daily clinical practice. It looks like we cannot find a volume that fits for everyone. Personalized, hand size based ABHR volumes may be the solution to find an optimal balance between maximize coverage and minimise spillage and drying time. 3 ml can be a good volume for those who have medium size hands. Large handed people should use more handrub to reach appropriate coverage, while small-handed ones may apply less to avoid massive spillage and not to take unrealistically long to dry.

A large-scale investigation of alcohol-based handrub (ABHR) volume: hand coverage correlations utilizing an innovative quantitative evaluation system.

BACKGROUND: Current hand hygiene guidelines do not provide recommendations on a specific volume for the clinical hand rubbing procedure. According to recent studies volume should be adjusted in order to achieve complete coverage. However, hand size is a parameter that highly influences the hand coverage quality when using alcohol-based handrubs (ABHR). The purpose of this study was to establish a quantitative correlation between applied ABHR volume and achieved hand coverage. METHOD: ABHR based hand hygiene events were evaluated utilizing a digital health device, the Semmelweis hand hygiene system with respect to coverage achieved on the skin surface. Medical students and surgical residents (N = 356) were randomly selected and given predetermined ABHR volumes. Additionally, hand sizes were calculated using specialized software developed for this purpose. Drying time, ABHR volume awareness, as well spillage awareness were documented for each hand hygiene event. RESULTS: Hand coverage achieved during a hand hygiene event strongly depends on the applied ABHR volume. At a 1 ml dose, the uncovered hand area was approximately 7.10%, at 2 ml it decreased to 1.68%, and at 3 ml it further decreased to 1.02%. The achieved coverage is strongly correlated to hand size, nevertheless, a 3 ml applied volume proved sufficient for most hand hygiene events (84%). When applying a lower amount of ABHR (1.5 ml), even people with smaller hands failed to cover their entire hand surface. Furthermore, a 3 ml volume requires more than the guideline prescribed 20-30 s to dry. In addition, results suggest that drying time is not only affected by hand size, but perhaps other factors may be involved as well (e.g., skin temperature and degree of hydration). ABHR volumes of 3.5 ml or more were inefficient, as the disinfectant spilled while the additional rubbing time did not improve hand coverage. CONCLUSIONS: Hand sizes differ a lot among HCWs. After objectively measuring participants, the surface of the smallest hand was just over half compared to the largest hand (259 cm2 and 498 cm2, respectively). While a 3 ml ABHR volume is reasonable for medium-size hands, the need for an optimized volume of handrub for each individual is critical, as it offers several advantages. Not only it can ensure adequate hand hygiene quality, but also prevent unnecessary costs. Bluntly increasing the volume also increases spillage and therefore waste of disinfectant in the case of smaller hands. In addition, adherence could potentially decrease due to the required longer drying time, therefore, adjusting the dosage according to hand size may also increase the overall hand hygiene compliance.

Critical Reliability Issues of Common Type Alcohol-Based Handrub Dispensers.

BACKGROUND: Hand hygiene can only be efficient if the whole hand surface is treated with sufficient alcohol-based handrub (ABHR); therefore, the volume of handrub applied is a critical factor in patient safety. The proper amount of ABHR should be provided by handrub dispensers. The aim of this study was to investigate the dispensing performance of wall-mounted ABHR dispensers commonly employed in hospital settings. METHOD: In a multicenter study, we tested 46 dispensers (22 in laboratory and 24 in clinical environments), measuring dispensed ABHR volume during continuous use and after a period of non-use. The influence of the pumping mechanism, liquid level, ABHR formats, handrub composition, temperature, and atmospheric pressure was investigated. RESULTS: A total of 7 out of the 22 investigated dispensers (32%) lost a significant amount of handrub; greater than 30% of the nominal volume after 8 h of non-use, thus frequently dispensing suboptimal volume, as measured in laboratory settings. Key influencing factors were found to be handrub format (gel or liquid), handrub level in the container and type of dispenser. When gel ABHR was used, after 4 h of non-use of the dispensers, the volume of the dispensed amount of ABHR insignificantly changed (97% of the original amount), while it technically decreased to zero in the case of liquid ABHR (1% of the original amount). The liquid level had a medium effect on the dispensed volume in each investigated case; the magnitude of this effect varied widely depending on the dispensing mechanism. When dispensers were in continuous use, they dispensed a cumulated 3 mL of ABHR from two consecutive pushes, while when they were not in use for 1 h, up to 4 consecutive pushes were necessary to provide a total of 3 mL ABHR. Design and production quality were also identified as important contributing factors with respect to the volume dispensed. Data collected in clinical settings confirmed these findings, for multiple types of dispensers. CONCLUSION: All ABHR dispensers should be regularly audited to control the reference volume distributed, with particular attention paid to regular mechanical pump units filled with liquid handrub.

IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer.

Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP3 receptors (IP3R) and the mitochondrial calcium uniporter, and are central to cell survival. It remains unclear whether IP3Rs also have a structural role in contact formation and whether the different IP3R isoforms have redundant functions. Using an IP3R-deficient cell model rescued with each of the three IP3R isoforms and an array of super-resolution and ultrastructural approaches we demonstrate that IP3Rs are required for maintaining ER-mitochondrial contacts. This role is independent of calcium fluxes. We also show that, while each isoform can support contacts, type 2 IP3R is the most effective in delivering calcium to the mitochondria. Thus, these studies reveal a non-canonical, structural role for the IP3Rs and direct attention towards the type 2 IP3R that was previously neglected in the context of ER-mitochondrial calcium signaling.

[Hand hygiene technique assessment using electronic equipment in 26 Hungarian healthcare institutions]. / A kézhigiénés technika vizsgálata elektronikus ellenorzo berendezés segítségével 26 magyarországi betegellátó intézményben.

INTRODUCTION: Hand hygiene is probably the most effective tool of nosocomial infection prevention, however, proper feedback and control is needed to develop the individual hand hygiene practice. AIM: Assessing the efficiency of modern education tools, and digital demonstration and verification equipment during their wide-range deployment. METHOD: 1269 healthcare workers took part in a training organized by our team. The training included the assessment of the participants' hand hygiene technique to identify the most often missed areas. The hand hygiene technique was examined by a digital device. RESULTS: 33% of the participants disinfected their hands incorrectly. The most often missed sites are the fingertips (33% on the left hand, 37% on the right hand) and the thumbs (42% on the left hand, 32% on the right hand). CONCLUSION: The feedback has a fundamental role in the development of the hand hygiene technique. With the usage of electronic devices feedback can be provided efficiently and simply. Orv Hetil. 2017; 158(29): 1143-1148.

Isoform- and species-specific control of inositol 1,4,5-trisphosphate (IP3) receptors by reactive oxygen species.

Reactive oxygen species (ROS) stimulate cytoplasmic [Ca(2+)] ([Ca(2+)]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2) on IP3R-mediated Ca(2+) signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca(2+)]c spikes and frequency-modulated oscillations evoked by a O2 donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. The [Ca(2+)]c signal was mediated by ER Ca(2+) mobilization. X+XO added to permeabilized cells promoted the [Ca(2+)]c rise evoked by submaximal doses of IP3, indicating that O2 directly sensitizes IP3R-mediated Ca(2+) release. In response to X+XO, DT40 cells lacking two of three IP3R isoforms (DKO) expressing either type 1 (DKO1) or type 2 IP3Rs (DKO2) showed a [Ca(2+)]c signal, whereas DKO expressing type 3 IP3R (DKO3) did not. By contrast, IgM that stimulates IP3 formation, elicited a [Ca(2+)]c signal in every DKO. X+XO also facilitated the Ca(2+) release evoked by submaximal IP3 in permeabilized DKO1 and DKO2 but was ineffective in DKO3 or in DT40 lacking every IP3R (TKO). However, X+XO could also facilitate the effect of suboptimal IP3 in TKO transfected with rat IP3R3. Although in silico studies failed to identify a thiol missing in the chicken IP3R3, an X+XO-induced redox change was documented only in the rat IP3R3. Thus, ROS seem to specifically sensitize IP3Rs through a thiol group(s) within the IP3R, which is probably inaccessible in the chicken IP3R3.

Inhibition of G protein-activated inwardly rectifying K+ channels by extracts of Polygonum persicaria and isolation of new flavonoids from the chloroform extract of the herb.

The G protein-activated inwardly rectifying K+ channel-modulatory activities of Polygonum persicaria extracts were investigated by using an automated patch-clamp method, with the aim of identifying natural sources of promising ion channel-blocking compounds. The chloroform extract of the whole plant at 0.1 mg/mL exhibited high G protein-activated inwardly rectifying K+ channel-inhibitory activity. Fractionation of this extract by vacuum liquid chromatography on RP-silica gel resulted in 6 fractions, which were evaluated for G protein-activated inwardly rectifying K+ channel-modulatory activity. RP-HPLC of the most active fractions afforded the main compounds 1-4 in pure form and a mixture containing the minor constituents. The structures were identified by means of UV, HRMS, and advanced NMR methods as 3-O-senecioyl-isorhamnetin (1), 3-O-angeloyl-isorhamnetin (2), 5,3',4',5'-tetramethoxy-6,7-methylenedioxyflavone (3), and 3,5,3',4',5'-pentamethoxy-6,7-methylenedioxyflavone (4). Compounds 1-4 are new natural products, though 4 was reported earlier as a synthetic compound. Neither the individual, nor the combined application of compounds 1-4 modified the G protein-activated inwardly rectifying K+ channel activity. However, a marked G protein-activated inwardly rectifying K+ current-inhibitory effect was detected on use of the HPLC eluates containing the minor compounds. These results indicate the presence of electrophysiologically active agents among the minor compounds.

Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and GIRK channel activities of some Aconitum alkaloids.

Diterpene alkaloids neoline (1), napelline (2), isotalatizidine (3), karakoline (4), senbusine A (5), senbusine C (6), aconitine (7) and taurenine (8) were identified from Aconitum napellus L. subsp. firmum, four (2-4, 6) of which are reported for the first time from this plant. The structures were determined by means of LC-MS, 1D and 2D NMR spectroscopy, including (1)H-(1)H COSY, NOESY, HSQC and HMBC experiments. Electrophysiological effects of the isolated compounds, together with nine diterpene alkaloids previously obtained from Aconitum toxicum and Consolida orientalis were investigated on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cell lines using automated patch clamp equipment. Significant blocking activity on GIRK channel was exerted by aconitine (7) (45% at 10 µM), but no blocking activities of the other investigated compounds were detected. The tested compounds were inactive on hERG channel in the tested concentration. The comparison of the previously reported metabolites of A. napellus subsp. firmum and compounds identified in our experiment reveals substantial variability of the alkaloid profile of this taxon.

ABCG2 modulates chlorothiazide permeability--in vitro-characterization of its interactions.

We are showing that chlorothiazide, a diuretic, is an ABCG2 substrate. It is a Biopharmaceutics Classification System/Biopharmaceutics Drug Distribution and Classification System (BCS/BDDCS) Class IV drug with low bioavailability. Therefore, we tested if chlorothiazide interacts with major apically located intestinal efflux transporters. Our data show that chlorothiazide is transported by ABCG2 with a Km value of 334.6 µM and does not interact with ABCB1 or ABCC2. The chlorothiazide-ABCG2 interaction results in a vectorial transport in MDCKII-BCRP and Caco-2 cells with efflux ratios of 36 and 8.1 respectively. Inhibition of ABCG2 in Caco-2 cells reduced the efflux ratio to 1.4, suggesting that ABCG2 plays a role in limiting chlorothiazide bioavailability in humans.

ABCG2 (breast cancer resistance protein/mitoxantrone resistance-associated protein) ATPase assay: a useful tool to detect drug-transporter interactions.

The ATPase assay using membrane preparations from recombinant baculovirus-infected Spodoptera frugiperda ovarian (Sf9) cells is widely used to detect the interaction of compounds with different ATP-binding cassette transporters. However, Sf9 membrane preparations containing the wild-type ABCG2 transporter show an elevated baseline vanadate-sensitive ATPase activity, which cannot be further stimulated by substrates of ABCG2. Therefore, this assay system cannot be used for the detection of ABCG2 substrates. To overcome this difficulty we 1) purified membranes from a selected human cell line expressing wild-type ABCG2, and 2) inhibited the baseline ATPase activity with different inhibitors. In our modified assay, ABCG2 substrates were able to stimulate the baseline ATPase activity of ABCG2 expressed in membranes of human cells. Furthermore, using the specific ABCG2 inhibitors Ko143 or Ko134 allowed us to suppress the baseline vanadate-sensitive ATPase activity. Substrates of ABCG2 could stimulate this suppressed baseline ATPase, resulting in a better signal-to-background ratio and a robust assay to detect substrates of the ABCG2 transporter. The ATPase assay and the direct vesicular transport measurements for estrone-3-sulfate were in good accordance.