A Quality Improvement Project to Decrease CLABSIs in Non-ICU Settings.

BACKGROUND AND OBJECTIVES: Central line-associated bloodstream infections (CLABSIs) are a common, preventable healthcare-associated infection. In our 3-hospital health system, CLABSI rates in non-intensive care unit (ICU) settings were above the internal target rate of zero. A robust quality improvement (QI) project to reduce non-ICU CLABSIs was undertaken by a team of Doctor of Nursing Practice (DNP)-prepared nurse leaders enrolled in a post-DNP Quality Implementation Scholars program and 2 QI experts. Based on a review of the literature and local root cause analyses, the QI team implemented the evidence-based practice of using 2% chlorhexidine gluconate (CHG) cloths for daily bathing for non-ICU patients with a central line. METHODS: A pre-post-design was used for this QI study. CHG bathing was implemented using multifaceted educational strategies that included an e-learning module, printed educational materials, educational outreach, engagement of unit-based CLABSI champions, and an electronic reminder in the electronic health record. Generalized linear mixed-effects models were used to assess the change in CLABSI rates before and after implementation of CHG bathing. CLABSI rates were also tracked using statistical process control (SPC) charts to monitor stability over time. CHG bathing documentation compliance was audited as a process measure. These audit data were provided to unit-based leadership (nurse managers and clinical team leaders) on a monthly basis. A Qualtrics survey was also disseminated to nursing leadership to evaluate their satisfaction with the CHG bathing implementation processes. RESULTS: Thirty-four non-ICU settings participated in the QI study, including general medical/surgical units and specialty areas (oncology, neurosciences, cardiac, orthopedic, and pediatrics). While the change in CLABSI rates after the intervention was not statistically significant ( b = -0.35, P = .15), there was a clinically significant CLABSI rate reduction of 22.8%. Monitoring the SPC charts demonstrated that CLABSI rates remained stable after the intervention at all 3 hospitals as well as the health system. CHG bathing documentation compliance increased system-wide from 77% (January 2020) to 94% (February 2021). Overall, nurse leaders were satisfied with the CHG bathing implementation process. CONCLUSIONS: To sustain this practice change in non-ICU settings, booster sessions will be completed at least on an annual basis. This study provides further support for using CHG cloths for daily patient bathing in the non-ICU setting.

Using statistical process control charts to measure changes from a nurse-driven protocol to remove urinary catheters.

BACKGROUND: Implementing a nurse-driven protocol (NDP) to remove indwelling urinary catheters is a strategy to reduce catheter-associated urinary tract infections (CAUTI). The purpose of this project was to implement a comprehensive NDP to reduce indwelling urinary catheter utilization and CAUTI rates at a large academic health system. METHODS: Statistical process control charts, a quality improvement method, was used to identify special cause variation. A formal protocol was developed to provide guidance for nurses to remove indwelling urinary catheters when no longer indicated. Changes were also made within the electronic health record. RESULTS: Signals of improvement were not noted on the Statistical process control charts for urinary catheter utilization or CAUTI rates. The frequency with which the NDP was documented (process measure) was assessed, showing it is used approximately 600 times each month. Of those catheters removed by the NDP, an average of 6% were reinserted within 48 hours (balancing measure). DISCUSSION: Our findings differed from other literature as we did not see a reduction in urinary catheter utilization after implementing a NDP. However, our project adds to the literature as we also evaluated process and balancing measures. CONCLUSIONS: A NDP for urinary catheter removal provides nurses with the autonomy to remove catheters when no longer indicated; however, other interventions should be added to a comprehensive CAUTI-prevention program.

Enhancement of infection prevention case review process to optimize learning from defects.

Hospitals continue to struggle with preventable healthcare-associated infections. Whereas the focus is generally on proactive prevention processes, performing retrospective case reviews of infections can identify opportunities for quality improvement and maximize learning from defects. This brief article provides practical information for structuring the case review process using readily available health system platforms. Using a structured approach for case reviews can help identify trends and opportunities for improvement.

Design and synthesis of novel tetrahydronaphthyl azoles and related cyclohexyl azoles as antileishmanial agents.

A novel series of trans-2-aryloxy-1,2,3,4,-tetrahydronaphthyl azoles and related cyclohexyl azoles were synthesized and evaluated in vitro against Leishmania donovani. Compound 9 identified as most active analog with IC(50) value of 0.64 µg/mL and SI value of 34.78 against amastigotes, and is several folds more potent than the reference drugs sodium stilbogluconate and paromomycin. It also exhibited significant in vivo inhibition of 83.33%, and provided a new structural scaffold for antileishmanials.

Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents.

A series of aryloxy alkyl/aryl alkyl imidazoles were synthesized and evaluated in vitro as antileishmanials against Leishmania donovani. All the 19 compounds exhibited 94-100% inhibition at 10microg/mL against promastigotes and 12 compounds exhibited high inhibition with an IC(50) in the range of 0.47-4.85microg/mL against amastigotes. Promising compounds were tested further in vivo. Among all, compounds 4 and 23 with 4-CF(3) aryloxy moiety exhibited medium in vivo inhibition of 58-60%, thus providing new structural lead for antileishmanials.

Aryloxy cyclohexyl imidazoles: a novel class of antileishmanial agents.

Thirteen novel aryloxy cyclohexane-based mono and bis imidazoles were synthesized and evaluated in vitro as antileishmanials against Leishmania donovani and cytotoxicity assessed. These compounds were better than the existing drugs, sodium stibogluconate and pentamidine in respect to IC(50) and SI values. Promising compounds were tested further in vivo. Among all, the bis methylimidazole with 2-fluoro, 4-nitro aryloxy group (9) exhibited significant in vivo inhibition of 77.9%, thus providing new structural lead for antileishmanials.

Gender equity in mass drug administration for neglected tropical diseases: data from 16 countries.

BACKGROUND: Gender equity in global health is a target of the Sustainable Development Goals and a requirement of just societies. Substantial progress has been made towards control and elimination of neglected tropical diseases (NTDs) via mass drug administration (MDA). However, little is known about whether MDA coverage is equitable. This study assesses the availability of gender-disaggregated data and whether systematic gender differences in MDA coverage exist. METHODS: Coverage data were analyzed for 4784 district-years in 16 countries from 2012 through 2016. The percentage of districts reporting gender-disaggregated data was calculated and male-female coverage compared. RESULTS: Reporting of gender-disaggregated coverage data improved from 32% of districts in 2012 to 90% in 2016. In 2016, median female coverage was 85.5% compared with 79.3% for males. Female coverage was higher than male coverage for all diseases. However, within-country differences exist, with 64 (3.3%) districts reporting male coverage >10 percentage points higher than female coverage. CONCLUSIONS: Reporting of gender-disaggregated data is feasible. And NTD programs consistently achieve at least equal levels of coverage for women. Understanding gendered barriers to MDA for men and women remains a priority.

Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success.

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for NTD control but also are poised to help solve two of the most important future NTD challenges-how to maintain control of STH infections after the community-based LF "treatment platform" ceases and how to ensure appropriate morbidity management for patients currently suffering from lymphatic filarial disease.

Synthesis and evaluation of new furanyl and thiophenyl azoles as antileishmanial agents.

A series of benzyloxy furanyl and benzyloxy thiophenyl azoles were synthesized and screened for their in vitro antileishmanial activity against Leishmania donovani. Among all, 16 compounds have shown more than 90% inhibition against promastigotes at 20 µM while 11 compounds exhibited IC50 in the range of 3.04-9.39 µM against amastigotes. Compound 4, a 3-chlorobenzyloxy furanyl imidazole emerged as the most active compound in the series with IC50 value of 3.04 µM and SI value of 19.80, and was several folds more potent than the reference drugs miltefosine and miconazole.

Novel aryloxy azolyl chalcones with potent activity against Mycobacterium tuberculosis H37Rv.

A series of twenty seven novel aryloxy azolyl chalcones were synthesized and evaluated in vitro for the growth inhibition of Mycobacterium tuberculosis H37Rv. Ten compounds from this series exhibited good activity with MIC in the range of 3.12-0.78 µg/mL and six of them were found non-toxic against VERO cells and MBMDMøs (mouse bone-marrow derived macrophages), were further evaluated ex-vivo for their potential to kill intracellular bacilli. Two compounds 4 and 19 showed 99% and 71% killing respectively, of intracellular bacilli in MBMDMøs infection model. Further, compound 19, an imidazolyl chalcone with a 2,4-difluorobenzyloxy moiety also exhibited moderate in vivo activity in mice against virulent M. tuberculosis, thus providing a new structural lead towards TB drug development.

Antileishmanial activity of benzocycloalkyl azole oximino ethers: the conformationally constraint analogues of oxiconazole.

Antileishmanial activities of 16 synthetic oximino benzocycloalkyl azoles against Leishmania donovani were evaluated in vitro against extracellular promastigotes and intracellular amastigotes. Based on SI (Selectivity Index), five compounds were tested further in vivo in hamster model. Out of these, three compounds have shown medium activity (53-58%) and one has shown significant inhibition of parasite multiplication (70%). Despite the fact that these compounds were better than the existing antileishmanials in respect to IC(50) and SI values, they were less active than miltefosine in vivo. The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent.

Tetrahydronaphthyl azole oxime ethers: the conformationally rigid analogues of oxiconazole as antibacterials.

A series of novel (Z)- and (E)-2-imidazolo-/triazolo-methyl tetrahydronaphthyl oxime ethers (7-28) were synthesized as conformationally constrained analogues of oxiconazole and evaluated for antifungal and antibacterial activities. Many of these derivatives exhibited potent antibacterial activity and surprisingly none of them was active against fungal strains. The SAR studies showed that imidazole oxime ethers were more active than the corresponding triazole oxime ethers. Imidazole derivatives 8, 11, 12, 15, 18, 19, 21 and 23 exhibited high inhibitory activity with 1.56-0.39 microg/mL MIC values against Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus. These compounds represent new structure scaffolds that can be further optimized to give new antibacterial agents with structures significantly different from those of existing classes of antibiotics.

Synthesis and appetite suppressant activity of 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes as conformationally rigid analogues of fluoxetine.

Several 1-aryloxy-2-substituted aminomethyltetrahydronaphthalenes (7-21) as conformationally rigid analogues of fluoxetine were synthesized and evaluated for their anorexigenic and antidepressant activities. For SAR studies the related acyclic analogues (22-27) were also prepared. Out of the 21 synthesized compounds, 10 compounds (9, 10, 11, 15, 16, 18, 21, 22, 23 and 27) exhibited significant anorexigenic activity (at 75 micromol/kg). Interestingly, all the compounds (7-20, 22-26) were devoid of antidepressant effect, except for compounds 21 and 27 in which the antidepressant activity was retained. Compound 16 emerged as the most active compound of the series with better anorexigenic activity (97.92%) compared to fluoxetine (76.25%) and even with a clinically used drug sibutramine, thus providing a new structural lead for appetite suppressants.

Substituted propanolamines and alkylamines derived from fluoxetine as potent appetite suppressants.

A series of propanolamine and alkylamine analogues of fluoxetine (7-26, 28-31) were synthesized and assessed for their anorexigenic and antidepressant activities. Effect of various substituents at C-4 aryl position of fluoxetine has also been studied. Most of the propanolamine analogues (7-13, 16-26) displayed significant anorexigenic activity but interestingly they were devoid of antidepressant activity whereas anorexigenic as well as antidepressant activity was retained in the alkylamine series (28-31). Compounds 10 and 26 emerged as the most active compound and anorexigenic activity was better (83.67% and 82.45%) compared to fluoxetine (81.25%).

Synthesis of tetrahydronaphthyl thioureas as potent appetite suppressants.

A series of thiourea derivatives (7-23, 25-27) of 1-aminotetrahydronaphthalene (4) and 1-amino-2-hydroxytetrahydronaphthalene (5) were synthesized in single pot in 48-90% yield and evaluated for their anorexigenic activity. Among them compounds 10, 14, 15, 16 and 22 exhibited significant anorexigenic activity without any antidepressant effect and provided a new structural lead for appetite suppressants.