Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma.

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.

Point prevalence survey of antibiotic use and healthcare-associated infections in acute care hospitals: a comprehensive report from the Marche Region of Italy.

BACKGROUND: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are serious health challenges. Point prevalence surveys (PPSs) are valuable tools for monitoring HAIs and AMR. AIM: To describe results of the ECDC PPS 2022 dealing with the prevalence of HAIs, antimicrobial consumption, and associated factors, in acute care hospitals. METHODS: The survey was performed in November 2022 in 14 hospitals according to the protocol proposed by the European Centre for Disease Prevention and Control. Multilevel logistic regression was performed using geographical area/hospital type as cluster variable to evaluate the factors independently associated with HAIs and antibiotics. FINDINGS: The point prevalence of HAIs was 7.43%. Patients hospitalized for longer periods were more likely to have an HAI as well as those aged 15-44 years, with a rapidly fatal disease, intubated, and with one or two devices. Antibiotics prevalence was 47.30%. Males, unknown McCabe scores, minimally invasive/non-National Healthcare Safety Network (NHSN) surgery, patients with HAIs, hospitals with a higher alcohol hand-rub consumption, hospitals with a greater number of IPC personnel, geriatric wards, and hospitals with 300-600 beds were more likely to be under antimicrobial therapy. CONCLUSION: This PPS provided valuable information on the prevalence of HAIs and antimicrobial consumption and variables associated. The high prevalence of HAIs highlights the need for improved infection control measures.

Different local estrogen therapies for a tailored approach to GSM.

Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.

MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. METHODS: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/ß = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. DISCUSSION: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. TRIAL REGISTRATION: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, "Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)", NCT05027711.

Topical application of a desensitizing agent containing potassium nitrate before dental bleaching: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the risk and intensity of tooth sensitivity (TS) after topical application of desensitizers containing potassium nitrate before dental bleaching. METHODS: We searched PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and SIGLE. We also surveyed gray literature without restrictions. We meta-analyzed the data using the random-effects model to compare potassium nitrate and placebo in terms of risk and intensity of TS and color change (∆SGU or ∆E). The quality of the evidence was rated using the GRADE approach. The risk of bias (RoB) of the included studies was analyzed using the Cochrane RoB tool. RESULTS: After the database screening, 24 articles remained. A significant 12% lower risk for the groups where desensitizing agents were applied (p = 0.02), with a risk ratio of 0.88 (95% CI 0.78 to 0.98). About the intensity of TS, a significant average mean difference of - 0.77 units of VAS units (95%CI - 1.34 to - 0.19; p = 0.01) in favor of the desensitizer group. In the NRS scale, a significant average mean difference of - 0.36 (95% CI - 0.61 to - 0.12; p value = 0.004) in favor of the desensitizer group. No significant difference was observed in color change (p > 0.28) in ∆SGU and ∆E. CONCLUSIONS: Although a significant reduction in the risk and intensity of TS was observed in groups treated with a potassium nitrate at some point during the bleaching, the clinical significance of this reduction is subtle and clinically questionable. Color change is not affected by the use of agents. CLINICAL RELEVANCE: The reduction in the risk and intensity of TS with the topical application of potassium nitrate-based desensitizing agents in dental bleaching is subtle and maybe clinically questionable.

Perception of Time-Discrete Haptic Feedback on the Waist is Invariant With Gait Events.

The effectiveness of haptic feedback devices highly depends on the perception of tactile stimuli, which differs across body parts and can be affected by movement. In this study, a novel wearable sensory feedback apparatus made of a pair of pressure-sensitive insoles and a belt equipped with vibrotactile units is presented; the device provides time-discrete vibrations around the waist, synchronized with biomechanically-relevant gait events during walking. Experiments with fifteen healthy volunteers were carried out to investigate users' tactile perception on the waist. Stimuli of different intensities were provided at twelve locations, each time synchronously with one pre-defined gait event (i.e. heel strike, flat foot or toe off), following a pseudo-random stimulation sequence. Reaction time, detection rate and localization accuracy were analyzed as functions of the stimulation level and site and the effect of gait events on perception was investigated. Results revealed that above-threshold stimuli (i.e. vibrations characterized by acceleration amplitudes of 1.92g and 2.13g and frequencies of 100 Hz and 150 Hz, respectively) can be effectively perceived in all the sites and successfully localized when the intertactor spacing is set to 10 cm. Moreover, it was found that perception of time-discrete vibrations was not affected by phase-related gating mechanisms, suggesting that the waist could be considered as a preferred body region for delivering haptic feedback during walking.

Bleaching-induced tooth sensitivity with application of a desensitizing gel before and after in-office bleaching: a triple-blind randomized clinical trial.

OBJECTIVES: This randomized triple-blind clinical trial, split-mouth design, evaluated the application effect of the desensitizing gel before and after in-office bleaching on tooth sensitivity. MATERIALS AND METHODS: In one group, the desensitizing gel was applied for 10 min before the bleaching with 35% hydrogen peroxide, and then application of placebo gel after (n = 90). In the other group, the desensitizing gel was applied before and after the bleaching procedure for 10 min (n = 90). The primary outcome was pain intensity assessed with a numeric rating scale and a visual analog scale. Color was evaluated by means of a digital spectrophotometer and a shade guides. RESULTS: The proportion of patients that experienced pain in the side of before application was 90% (95% CI 82 to 94.6%), while the side of before and after was 93% (95% CI 86.2 to 96.9%), without significant difference between groups (OR = 0.25; 95% CI 0.005 to 2.52; p = 0.37). Pain was correlated in both groups, for the NRS scale (p < 0.0001) and the VAS scale (p < 0.0001) in all assessment periods. Significant whitening was detected, and no significant difference of color change was observed between groups (p > 0.45). CONCLUSIONS: The application of the desensitizing agent did not influence the effectiveness of bleaching, but it was not efficient in reducing the sensitivity, when applied before the procedure, or before and after. CLINICAL RELEVANCE: The use of a desensitizing gel before or after in-office bleaching does not reduce incidence or intensity of tooth sensitivity.

Sexuality in premature ovarian insufficiency.

Sexuality in women with spontaneous premature ovarian insufficiency (POI) deserves attention because of the young age and the distressing impact of such a life-changing diagnosis. Biomedical and psychosocial factors work in concert to determine significant changes of sexual function. Early hormonal deprivation gives origin to symptomatic vulvovaginal atrophy and contributes to hypoactive sexual desire disorder modulating central and peripheral circuitries, which regulate sexual response. Emotional and cognitive adjustment to the short-term and long-term consequences of POI may further determine negative attitudes toward sexuality. It is essential to counsel POI women on every aspect of their life, from menopausal symptoms to fertility concerns, from health risks to potential therapeutic solutions. The biopsychosocial perspective is the best approach to manage sexual symptoms, including tailored hormone therapy and focused counseling. Pharmacotherapies specifically investigated in spontaneous POI conditions are lacking and clinical judgment has to guide the choice of treatment, which must be continued at least until the average age at natural menopause according to the most recent guidelines. Further studies are needed to better characterize POI women and to understand the effective role of novel therapeutic strategies, including androgens and cognitive-behavioral and sexual interventions.

Effect of Different Protocols in Preconditioning With EDTA in Sclerotic Dentin and Enamel Before Universal Adhesives Applied in Self-etch Mode.

OBJECTIVES: The aim of this study was to investigate the effect of different protocols of 17% ethylene diamine tetra-acetic acid (EDTA) conditioning on the etching pattern and immediate bond strength of universal adhesives to enamel and sclerotic dentin. METHODS AND MATERIALS: Forty bovine teeth with sclerotic dentin and 20 human third molars were randomly divided into eight groups resulting from the combination of the main factors surface treatment (none, two-minute EDTA conditioning manual application, 30-second EDTA manual application, 30-second EDTA sonic application) and adhesives systems (Scotchbond Universal Adhesive [SBU] and Prime & Bond Elect [PBE]). Resin-dentin and enamel-dentin bond specimens were prepared and tested under the microtensile bond strength (µTBS) and microshear bond strength (µSBS) tests, respectively. The etching pattern produced on the unground enamel and the sclerotic dentin surfaces under the different protocols and adhesive systems was evaluated under scanning electron microscopy. RESULTS: For enamel, only the main factor adhesive was significant (p<0.0001), with SBU showing the highest µSBS. In sclerotic dentin, the lowest mean was observed for the group without EDTA application and the highest mean in the group with EDTA application with the sonic device for 30 seconds. Regardless of the EDTA protocol, the highest means of µTBS were observed for SBU (p<0.05). CONCLUSIONS: EDTA conditioning improves the bonding performance of universal adhesives in the self-etch mode on sclerotic dentin, mainly when applied for 30 seconds with the aid of a sonic device. EDTA pretreatment also improves the retentive etching pattern of enamel, but it does not result in higher enamel bond strength.

Checking rounds for isolation precautions in the control of multidrug-resistant organisms: reduction achieved.

The objective of this investigation was to analyze the effectiveness of a quality improvement initiative in limiting the spread of multidrug-resistant organisms (MDROs) in the hospital setting. During the period 2011-2013, a multimodal intervention was activated at a tertiary care center in Italy. The intervention included: laboratory-based surveillance, interdisciplinary training sessions, monitoring the adoption of isolation precautions and daily supervision provided by infection control nurses, and a monthly feedback. Time series analysis was used to evaluate the trends and correlations between the MDROs rate, intensity of checking rounds, and hospital-wide data (i.e., transfer of patients, patients' days, site of isolation, etc.). A total of 149,251 patients were included in the study. The proportion of patients undergoing transmission-based isolation precautions within 24 h from a positive laboratory finding increased from 83% in 2011 to 99% in 2013 (p < 0.05). The wards appropriately adopting the correct isolation precaution increased from 83% in 2011 to 97.6% in 2013 (p < 0.05). The frequency of controls was significantly reduced after the observation of compliance in the appropriate wards (p < 0.05). After three years, the incidence rate changed from 5.8/1000 days of stay [95% confidence interval (CI) 5.6-6.1] in 2011 to 4.7 (95% CI 4.4-4.9) in 2013 (p < 0.0001). Moreover, microorganisms isolated from different types of specimens showed variable potential for transmission (i.e., skin as the most potential and urine the least). The results demonstrate the efficacy of the multimodal intervention, with sustained reduction of MDROs rate, besides check reduction, and highlight the long-term efficacy of checking rounds in changing professionals' behaviors.

Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases : Plan comparison and early clinical evaluation.

BACKGROUND: Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. MATERIALS AND METHODS: Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 × 20 Gy or 1 × 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 × 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. RESULTS: FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6­month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). CONCLUSION: SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity.

Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

Metasurface transformation for surface wave control.

Metasurfaces (MTSs) constitute a class of thin metamaterials used for controlling plane waves and surface waves (SWs). At microwave frequencies, they are constituted by a metallic texture with elements of sub-wavelength size printed on thin grounded dielectric substrates. These structures support the propagation of SWs. By averaging the tangential fields, the MTSs can be characterized through homogenized isotropic or anisotropic boundary conditions, which can be described through a homogeneous equivalent impedance. This impedance can be spatially modulated by locally changing the size/orientation of the texture elements. This allows for a deformation of the SW wavefront which addresses the local wavevector along not-rectilinear paths. The effect of the MTS modulation can be analysed in the framework of transformation optics. This article reviews theory and implementation of this MTS transformation and shows some examples at microwave frequencies.

Albedo neutron dosimetry in Germany: regulations and performance.

Personal neutron dosimetry has been performed in Germany using albedo dosemeters for >20 y. This paper describes the main principles, the national standards, regulations and recommendations, the quality management and the overall performance, giving some examples.

In vivo comparative efficacy of three surgical hand preparation agents in reducing bacterial count.

BACKGROUND: Besides objective efficacy, the choice between an antiseptic-based liquid soap, or an alcohol-based hand rub for surgical hand preparation technique is based on personal preference. Glycerol is often added to the formulations in order to enhance tolerability; however, it has been recently reported as a factor reducing the sustained effect of surgical hand rubs. AIM: To compare the efficacies of three commercial products for hand decontamination. METHODS: The in vivo efficacy of an alcohol-based hand rub (isopropyl alcohol 40%; N-propyl alcohol 25%; glycerin 1.74%; triethanolamine salt of carbomer <1%) was compared with other widely used products in surgical hand antisepsis (chlorhexidine and povidone-iodine). All products were used according to the manufacturers' instructions. FINDINGS: The best results were achieved with the alcohol-based hand rub and these were sustained for a period of 3h. Some volunteers experienced skin peeling off the hands when using alcohol-based hand rub; in this group of participants, the bacterial count was reduced only by 0.91 ± 1.67 log10 compared with 2.86 ± 1.22 log10 in the group who did not show this phenomenon. CONCLUSION: Besides confirming the importance of alcohol-based hand rubs for surgical hand decontamination, the results suggest the value of assessing the characteristics, and response of healthcare workers' skin, that may contribute to the development of skin peeling, and the subsequent possibility of a paradoxical overcolonization of hands after surgical preparation with alcohol-based hand rub.

Vitamin D supplementation is required to normalize serum level of 25OH-vitamin D in older adults: an observational study of 974 hip fracture inpatients.

BACKGROUND: Vitamin D deficiency is highly prevalent in older adults in all continents. In this study we assessed the vitamin D status of hip fracture subjects across different hospitals in a real word situation using the data from a multicenter cohort study on outcomes in orthogeriatric units. METHODS: We performed a prospective cohort study on 974 consecutive patients 75 yr or older admitted with fragility hip fracture over a 12 months period at 4 general hospitals of different districts in Emilia Romagna Region, Italy. Data collected included comorbidity, cognitive impairment, prefracture functional status, walking ability, living arrangement along with the use of antiosteoporotic drugs, serum intact PTH and serum 25-hydroxyvitamin D [25(OH)D]. RESULTS: Mean 25(OH)D serum levels were 12.2±9.4 ng/ml and 84.2% of patients had levels below recommended values. Male had a higher probability to have values within the reference range [odds ratio (OR): 1.74 (1.13-2.67); p=0.012] while living in nursing resulted negatively related even if only close to statistical significance [OR: 0.24 (0.06-1.02); p=0.051]. Vitamin D supplementation appeared to be the strongest factor associated with adequate level of vitamin D levels [OR: 4.50 (2.57-7.88); p<0.001). CONCLUSION: This study confirmed the very high rate of severe vitamin D deficiency in Italian subjects admitted with hip fracture. Our study also showed that supplementation of vitamin D is the strongest determinant influencing serum 25(OH)D level of older persons with hip fracture and these results should be taken into account when planning treatment in older persons.

Influence of ring size on the cognition-enhancing activity of DM235 and MN19, two potent nootropic drugs.

A series of analogs of DM235 and MN19, characterized by rings with different size, have been prepared and evaluated for their nootropic activity in the mouse passive-avoidance test. It was found that the optimal ring size for the analogs of DM235, showing endocyclic both amidic groups, is 6 or 7 atoms. For the compounds structurally related to MN19, carrying an exocyclic amide group, the piperidine ring is the moiety which gives the most interesting compounds.

A whole-body dosimetry system for personal monitoring based on hot-pressed thin layer TLD.

We are introducing a new high-capacity thermoluminescent dosemeter (TLD) system to measure the whole body values of H(p)(10) and H(p)(0.07) from photons for use in individual monitoring services. Small and light-weight badges allow a convenient application in a wide variety of workplaces with photon radiation from 20 keV to at least 7 MeV. The main advantage of this system will be the large capacity of ∼ 100,000 dosemeters per month at costs equivalent to the current film monitoring. The hot-pressed thin-layer TL detector (LiF:Mg,Ti) is welded onto an aluminium substrate and provided with a data matrix code for automatic processing. The detector holder has been optimised, that no additional filter is necessary. The new designed TLD reader with readout times <10 s will allow a large throughput and a considerable degree of automation.

Perioperative antibiotic prophylaxis: improved compliance and impact on infection rates.

The aims of this study were to determine adherence to the perioperative antibiotic prophylaxis (PAP) protocol used at a large Italian teaching hospital during a 6-year period, to assess the variables associated with inappropriate administration, and to measure the impact on surgical site infection (SSI) rates. There were 28 621 patients surveyed of which 74·6% received PAP. An improvement in adherence to the PAP protocol was registered for 58·8% of patients. Significant risk factors were an American Society of Anesthesiologists (ASA) score ≥ 2 [odds ratios (OR) from 1·28 (95% confidence interval (CI) 1·19-1·37) to 1·87 (95% CI 1·43-2·44)], prolonged duration of surgery (OR 1·68, 95% CI 1·56-1·82) and urgent surgery (OR 2·16, 95% CI 1·96-2·37). During the study period, a significant reduction in SSIs rates was detected. We concluded that the global reduction of inadequate PAP administration signifies the efficacy of a multidisciplinary quality improvement initiative on antimicrobial utilization, and this is supported by the observed reduction of the SSI rate.