Aggressive Contact Investigation of In-Hospital Exposure to Active Pulmonary Tuberculosis.

BACKGROUND: In-hospital detection of newly diagnosed active pulmonary tuberculosis (TB) is important for prevention of potential outbreaks. Here, we report our experience of the aggressive contact investigation strategy in a university hospital in the Republic of Korea after healthcare workers (HCWs), patients, and visitors experience an in-hospital exposure to active pulmonary TB. METHODS: A contact investigation after the unexpected detection of newly diagnosed active pulmonary TB (index patients) was performed in a university hospital from August 2016 to April 2017. Initial and 3-month-post-exposure chest radiographs were advised for all patients, visitors, and HCWs in close contact with the index patients. An additional tuberculous skin test or interferon gamma releasing assay was performed at the time of exposure and 3 months post-exposure in HCWs in close contact with the index patients. RESULTS: Twenty-four index patients were unexpectedly diagnosed with active pulmonary TB after admission to the hospital with unassociated diseases. The median time from admission to TB diagnosis was 5 days (range, 1-22 days). In total, 1,057 people were investigated because of contact with the index patients, 528 of which had close contact (206 events in 157 HCWs, 322 patients or visitors). Three months post exposure, 9 (9.2%) among 98 TB-naïve close contact HCWs developed latent tuberculosis infections (LTBIs). Among the 65 close contact patients or visitors, there was no radiological or clinical evidence of active pulmonary TB. CONCLUSION: An aggressive contact investigation after an unexpected in-hospital diagnosis of active pulmonary TB revealed a high incidence of LTBI among TB-naïve HCWs who had contact with the index patients.

Steady amelioration of institutional hand hygiene behavior among health care personnel after 12-year consistent intervention.

BACKGROUND: Institutional hand hygiene (HH) behavior is difficult to monitor and improve consistently, especially over long periods. This study aimed to investigate the long-term effects of HH promotion activities. METHOD: We launched the HH promotion team in 2010 and conducted interventions including goal setting, observation and feedback, education, reward incentives, and accountability. Optimal HH compliance rates were calculated based on adherence to all 6-step HH technique and appropriate time recommended by the World Health Organization. HH and optimal HH compliance were calculated over 12 years. Poisson regression analysis was used to determine the trend in HH compliance according to year. RESULTS: In 2010, HH and optimal HH compliance were 59.7% and 15.6%, respectively. HH compliance increased by 83.9% in 2013 and remained over 75%. HH compliance increased significantly, with a relative risk (RR) of 1.014 (95% CI 1.002-1.025, P = .018). Optimal HH compliance increased by 67.8% in 2013 and remained over 60%, except in 2016 (58.8%) and 2019 (59.8%). Optimal HH compliance increased with RR 1.033 (95% CI 0.991-1.076, P = .123). DISCUSSION: HH and optimal HH compliance increased significantly over the 12 years when subgroup analysis was performed by job category. CONCLUSIONS: HH promotion team activities improved and maintained optimal HH compliance among HCWs.

Ventilation strategies based on an aerodynamic analysis during a large-scale SARS-CoV-2 outbreak in an acute-care hospital.

BACKGROUND: This study aimed to investigate ventilation strategies to prevent nosocomial transmission of coronavirus disease 2019 (COVID-19). METHODS: We conducted a retrospective epidemiological investigation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a teaching hospital (February-March 2021). The largest outbreak ward was studied, and measurements were taken to determine the pressure difference and air change per hour (ACH) of the rooms. Airflow dynamics were assessed using an oil droplet generator, indoor air quality sensor, and particle image velocimetry in the index patient's room, corridor, and opposite rooms, by varying the opening and closing of windows and doors. RESULTS: During the outbreak, 283 COVID-19 cases were identified. The SARS-CoV-2 spread occurred sequentially from the index room to the nearest room, especially the opposite. The aerodynamic study demonstrated that droplet-like particles in the index room diffused through the corridor and the opposite room through the opening door. The mean ACH of the rooms was 1.44; the air supply volume was 15.9% larger than the exhaust volume, forming a positive pressure. Closing the door prevented diffusion between adjacent rooms facing each other, and natural ventilation reduced the concentration of particles within the ward and minimised their spread to adjacent rooms. CONCLUSIONS: Spread of droplet-like particles between rooms could be attributed to the pressure difference between the rooms and corridor. To prevent spread of SARS-CoV-2 between rooms, increasing the ACH in the room by maximising ventilation and minimising the positive pressure through supply/exhaust control and closing the room door are essential.

Hand hygiene knowledge, attitude, barriers and improvement measures among healthcare workers in the Republic of Korea: a cross-sectional survey exploring interprofessional differences.

BACKGROUND: Hand hygiene (HH) is a fundamental component of infection prevention and control in healthcare settings. This study aimed to identify knowledge, attitude, and barriers to HH according to occupational groups and strategies to increase the rate of HH compliance among healthcare workers (HCWs). METHODS: This cross-sectional survey was conducted in July 2018 at four university-affiliated hospitals. The survey comprised seven parts with 49 items, including self-reported HH compliance, knowledge, attitudes, behaviours, barriers to HH, and improvement strategies. RESULTS: A total of 1046 HCWs participated in the survey. The nursing group's self-reported HH compliance rate was the highest, followed by other HCWs and physicians. The scores regarding knowledge, attitudes, and behaviours regarding HH were the highest in the nursing group. The nursing group also had higher internal and emotional motivation scores. Physicians and nurses found HH the most challenging in emergencies, while other HCWs considered skin problems caused by HH products the most significant barrier. Among 12 improvement measures, approximately 20% of the respondents ranked "diversify types of hand sanitisers," "install soap and paper towels in each hospital room," and "change perception through various HH campaigns" as the top three priorities. The physician group deemed the timely reminder of HH compliance as the second most critical improvement measure. CONCLUSION: Differences in knowledge, attitude and barriers hindering HH compliance and improvement plans were identified for each group. The findings suggest that targeted interventions tailored to the specific needs of different occupational groups may effectively improve HH compliance in healthcare settings.

A SARS-CoV-2 outbreak associated with vaccine breakthrough in an acute care hospital.

BACKGROUND: We aimed to analyze an outbreak caused by a vaccine breakthrough infection in a hospital with an active infection control program where 91.9% of health care workers were vaccinated. METHODS: We investigated a SARS-CoV-2 outbreak between September 9 and October 2, 2021, in a referral teaching hospital in Korea. We retrospectively collected data on demographics, vaccination history, transmission, and clinical features of confirmed coronavirus disease 2019 (COVID-19) in patients, health care workers, and caregivers. RESULTS: During the outbreak, 94 individuals tested positive for SARS-CoV-2 using reverse transcription-polymerase chain reaction testing. There were infections in 61 health care workers, 18 patients, and 15 caregivers; 74.5% (70/94) were vaccine breakthrough infections. Most transmissions appeared to be caused by three index cases, which accounted for 86.2% (81/94) of transmissions. Forty-seven (58.0%, 47/81) cases were associated with the hospital staff cafeteria and offices located in the basement. Among health care workers and caregivers, only one required oxygen supplementation. In contrast, among patients, there were four fatal cases (22.2%, 4/18), 3 of which were unvaccinated. CONCLUSIONS: Superspreading infection among fully vaccinated individuals occurred in an acute care hospital while the delta variant was dominant. Given the potential for severe complications, as this outbreak demonstrated, preventive measures including adequate ventilation should be emphasized to minimize transmission in hospitals.

Silicon switch approach in TRPV1 antagonist MK-056 and its analogues.

In searching for opportunities to exploit the benefits of silicon in TRPV1 research, we tried to investigate the pharmacological effects of sila-substitution (C/Si exchange) of tert-butyl group in the MK-056 series. Compound 13a, with a 4-positioned trimethylsilanyl group on the B ring in place of tert-butyl group, exhibited the most potent antagonist activity with IC(50) values of 0.15 microM, which is almost equipotent with that of MK-056. This is the first example that tert-butyl group on MK-056 series can be replaced to the other substituent without loss of activity.

Scope of a weekly infection control team rounding in an acute-care teaching hospital: a pilot study.

Regular and well-organized inspection of infection control is an essential element of an infection control program. The aim of this study was to identify the functional scope of weekly infection control team rounding (ICTR) in an acute care hospital. We conducted weekly ICTR between January 18 and December 26, 2018 to improve the compliance to infection control and prevention measures at a 734-bed academic hospital in the Republic of Korea and analyzed the results retrospectively. We categorized the results into five groups: "well maintained," "improvement needed," "long-term support, such as space or manpower, needed," "not applicable," or "could not be observed". A total of nine categories and 85 sub-elements of infection control and prevention practices were evaluated. The median number of infection control team (ICT) visits per department was 7 (interquartile range [IQR]: 6-7). The ICT assessed a median of 16 elements (IQR: 12-22), and a total of 7452 results were obtained. Of those, 75% were monitored properly, 22% were "not applicable", and 4% were difficult to observe. The most common practices that were difficult to observe were strategies to prevent catheter-related surgical site infections, pneumonia, and occupationally acquired infections as well as injection safety practices. Although the ICTR was able to maintain regular visits to each department, further strategies beyond regular ICTR are needed to reduce category of "could not observed". This pilot study may provide an important reference for institutional infection prevention practices as it is the first study to investigate the functional coverage of ICTR.

Design, synthesis, and biological evaluation of novel diarylalkyl amides as TRPV1 antagonists.

We have developed a new class of diarylalkyl amides as novel TRPV1 antagonists. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron. In particular, the amide 59 was identified as a potent antagonist with IC(50) of 57 nM. The synthesis and structure-activity relationship of the diarylalkyl amides are also described.

Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists.

Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron with IC(50)s of 25, 32 and 28 nM, respectively.

Design, synthesis, and biological evaluation of phenylpropanamides as novel transient receptor potential vanilloid 1 antagonists.

Synthesis and structure-activity relationship of N-benzyl-3-phenylpropanamides as transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of substituents such as halide, ester, nitro, and alkyl groups at 2 or 3-position of 4-(methylsulfonylamino) benzyl unit were examined. These compounds exhibited potent 45Ca2+ uptake inhibition in rat DRG neuron via TRPV1 blockade. Especially compound 28c, has been identified as a potent antagonist with IC50 of 38 nM.

Identifying the time to cure for patients with classic scabies after infection control intervention in acute care hospital settings.

Scabies is a re-emerging parasitic disease, particularly in hospitalized patients. This is a retrospective study analyzing adult patients with scabies admitted to a referral university hospital between 2008 and 2018. All patients were treated an average of 3times using scabicides; the median isolation period and time to cure were 14 and 15days, respectively.

Does Physician Leadership Influence Followers' Hand Hygiene Compliance?

The aim of this study was to determine factors influencing the hand hygiene compliance of a physician. We found a strong correlation between a leader's (staff member's or fellow's) and a follower's (resident's) hand hygiene compliance. Followers' appropriate hand hygiene compliance was significantly associated with the compliance of the leader (P = .01).

Antimelanogenic activity of a novel adamantyl benzylbenzamide derivative, AP736: a randomized, double-blind, vehicle-controlled comparative clinical trial performed in patients with hyperpigmentation during the summer.

BACKGROUND/PURPOSE: AP736 is a novel compound with an adamantyl benzylbenzamide moiety that has shown antimelanogenic activity in melanocytes in vitro and in artificial skin equivalent through the inhibition of key melanogenic enzymes and suppression of the cAMP-phosphokinase A-cAMP response element-binding protein signaling pathway. To estimate the clinical effectiveness of AP736 for the treatment of facial hyperpigmentation, we examined the efficacy and safety of a topical formulation containing AP736 compared with a vehicle formulation in human facial skin. To evaluate the degree of whitening when used in a real-life situation, subjects with hyperpigmentation conditions were selected and the trial was performed from mid-May to the end of June, when there are strong UV rays in Korea. MATERIALS AND METHODS: Forty-eight healthy Korean women aged 20-60 years were enrolled in this study for 6 weeks. Women who were pregnant or undergoing any concurrent therapy were excluded. Subjects were instructed to apply a randomly assigned formulation containing 0.5% AP736 (test formulation; n = 24) or vehicle (vehicle control; n = 24) in addition to an assigned sunscreen with a twice-daily application protocol. The degree of facial pigmentation was measured objectively using a Mexameter MX18 and Chromameter CM700, in addition to assessment by physicians using clinical photographs. RESULTS: The AP736 formulation was significantly (P < 0.05) more effective than the vehicle control formation in reducing the appearance of pigmentation at 3- and 6-week follow-up visits. CONCLUSION: A formulation containing a novel skin whitening ingredient, AP736, effectively reduced pigmentation and was well tolerated by study subjects in summer season.

Novel potent antagonists of transient receptor potential channel, vanilloid subfamily member 1: structure-activity relationship of 1,3-diarylalkyl thioureas possessing new vanilloid equivalents.

Recently, 1,3-diarylalkyl thioureas have merged as one of the promising nonvanilloid TRPV1 antagonists possessing excellent therapeutic potential in pain regulation. In this paper, the full structure-activity relationship for TRPV1 antagonism of a novel series of 1,3-diarylalky thioureas is reported. Exploration of the structure-activity relationship, by systemically modulating three essential pharmacophoric regions, led to six examples of 1,3-dibenzyl thioureas, which exhibit Ca(2+) uptake inhibition in rat DRG neuron with IC(50) between 10 and 100 nM.

In vitro structure-activity relationship and in vivo studies for a novel class of cyclooxygenase-2 inhibitors: 5-aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives.

5-Aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives were studied as a novel class of selective cyclooxygenase-2 inhibitors with regard to synthesis, in vitro SAR, antiinflammatory activities, pharmacokinetic considerations, and gastric safety. 1f, a representative compound for methyl sulfone derivatives, showed a COX-2 IC(50) comparable to that of rofecoxib. In case of 20b, a representative compound for sulfonamide derivatives, a potent antiinflammatory ED(50) of 0.1 mg kg(-1) day(-1) was observed against adjuvant-induced arthritis by a preventive model, positioning 20b as one of the most potent COX-2 inhibitors ever reported. Furthermore, 20b showed strong analgesic activity as indicated by its ED(50) of 0.25 mg/kg against carrageenan-induced thermal hyperalgesia in the Sprague-Dawley rat. 3(2H)Furanone derivatives showed due gastric safety profiles as selective COX-2 inhibitors upon 7-day repeat dosing. A highly potent COX-2 inhibitor of the 3(2H)furanone scaffold could be considered suitable for a future generation COX-2 selective arthritis medication with improved safety profiles.

Extract of the mycelium of T. matsutake inhibits elastase activity and TPA-induced MMP-1 expression in human fibroblasts.

Skin aging is induced through complex biological processes in human skin caused by proteolysis of collagen and elastin, two structural proteins of the dermal extracellular matrix (ECM). Collagen and elastin degradation can induce the expression of matrix metalloproteinases (MMPs), as well as that of a family of zinc-dependent endopeptidases that play critical roles in skin aging. Moreover, elastase is a metalloproteinase which acts on the degradation of elastin in skin aging, and is also involved in the inhibition or the repair of wrinkle formation. Extract of the mycelium of Tricholoma matsutake (T. matsutake), or pine mushroom, is widely distributed in Asian countries. The extract is from the natural biomaterial of the mushroom which is rich in polysaccharides, including ß-glucan. This extract has shown potent bioactive antioxidant, immunomodulatory and antitumoral properties. In the present study, we investigated whether the extract of the mycelium of T. matsutake has effects on elastase activity, as well as on the expression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and MMP-1 under basal conditions. Our results revealed that the extract of the mycelium of T. matsutake significantly decreased elastase activity in a dose-dependent manner and reduced the levels of MMP-1 and MMP-3. On the other hand, the expression of TIMP-1 and tropoelastin was increased in fibroblasts treated with the extract of the mycelium of T. matsutake. However, collagent expression was not affected. In addition, our results demonstrated that the extract of the mycelium of T. matsutake inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-1 expression and suppressed TPA-induced p38 activity. Therefore, the inhibitory effects of the extract of the mycelium of T. matsutake on MMP-1 induction are mediated by the inhibition of p38 in human fibroblasts. Our data suggest that the extract of the mycelium of T. matsutake may prove to be an effective biomaterial for anti-wrinkle treatment, as it can obstruct the degradation of the dermal ECM.

Topical valproic acid increases the hair count in male patients with androgenetic alopecia: a randomized, comparative, clinical feasibility study using phototrichogram analysis.

Valproic acid (VPA), a widely used anticonvulsant, inhibits glycogen synthase kinase 3ß and activates the Wnt/ß-catenin pathway, which is associated with hair growth cycle and anagen induction. To assess the efficacy of topical VPA for treating androgenetic alopecia (AGA), we performed a randomized, double-blind, placebo-controlled clinical trial. Male patients with moderate AGA underwent treatment with either VPA (sodium valproate, 8.3%) or placebo spray for 24 weeks. The primary end-point for efficacy was the change in hair count during treatment, which was assessed by phototrichogram analysis. Of the 40 patients enrolled in the study, 27 (n = 15, VPA group; n = 12, placebo group) completed the entire protocol with good compliance. No statistical differences in age, hair loss duration and total hair count at baseline were found between the groups. The mean change in total hair count was significantly higher in the VPA group than in the placebo group (P = 0.047). Both groups experienced mostly mild and self-limited adverse events, but their differences in prevalence rates were similar between the two groups (P = 0.72). A subject treated with topical VPA developed ventricular tachycardia, but it did not seem to be related to the VPA spray. Topical VPA increased the total hair counts of our patients; therefore, it is a potential treatment option for AGA.

Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: constraint-induced enhancement of in vitro and in vivo activities.

A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.

Evaluation of anti-platelet and anti-thrombotic effects of cilostazol with PFA-100® and Multiplate® whole blood aggregometer in vitro, ex vivo and FeCl3-induced thrombosis models in vivo.

We evaluate the anti-platelet and anti-thrombotic effects of cilostazol using Multiplate® and PFA-100® in vitro and ex vivo with freshly isolated rat whole blood and in vivo venous and arterial thrombosis models in the same species, in an effort to assess the sensitivity of the whole blood aggregometer assays without potential issues of species differences. In vitro assay of anti-platelet effects of cilostazol against collagen-induced aggregation using Multiplate® produced a graded dose-dependent inhibition curve with IC50 value of 75.4 ± 2.4 µM while it showed a highly sensitive and all-or-none type inhibition response from 25 µM in PFA-100®. Interestingly, cilostazol manifested anti-thrombotic effects in vivo at much lower plasma concentrations than the effective concentrations measured in ex vivo or in vitro aggregation tests using PFA-100® or Multiplate®. In addition, the tail bleeding time measurement demonstrated that rats have lower sensitivity to the anti-platelet effects of cilostazol than mice. These results suggest that the detailed comparative evaluation of whole blood aggregometer assays with anti-thrombotic effects in vivo should be preceded before the application of these methods for the pharmacodynamic studies of anti-thrombotic agents.

TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery.

BACKGROUND: Transient receptor potential vanilloid type 1 (TRPV1) is a cation channel activated by diverse obnoxious stimuli like capsaicin, low pH or heat. Recently, it was revealed that TRPV1 might be deeply associated with skin permeability barrier function, suggesting that modulation of TRPV1 might be beneficial for the skin disorders with barrier damages. OBJECTIVE: We aimed to investigate whether the blockade of TRPV1 activation might accelerate skin barrier recovery and alleviate atopic dermatitis (AD)-like symptoms, employing a novel TRPV1 antagonist, PAC-14028. METHODS: TRPV1 antagonistic effects of PAC-14028 in human keratinocytes and skin were confirmed through capsaicin-evoked calcium influx assay and capsaicin-induced blood perfusion increase. Effects of PAC-14028 on skin barrier recovery were examined in vivo tape-stripping-induced barrier disruption in hairless mice. To determine the effects of PAC-14028 on AD, Dermatophagoides farina (Df)- and oxazolone (OXZ)-induced AD models were employed. RESULTS: PAC-14028 could inhibit capsaicin-evoked calcium influx in keratinocytes at sub-micromolar concentrations. This potent TRPV1 antagonistic activity in keratinocytes was manifested in vivo as the blockade of capsaicin-induced blood perfusion increase, and the accelerated barrier recovery from tape-stripping-induced barrier damages in hairless mice. PAC-14028 could also attenuate dermatitis-associated barrier damages in Df and OXZ models as determined by lower TEWL (trans-epidermal water loss), reformation of neutral lipid layer and reversion of changes in loricrin and filaggrin expression. Importantly, along with accelerated recovery of skin barrier function, PAC-14028 alleviated the general AD-like symptoms, including serum IgE increase, mast cell degranulation, scratching behavior and clinical severity of dermatitis. CONCLUSIONS: These results reflect that the blockade of TRPV1 activation can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery.