The implementation of a standardized optimal procedure for peripheral venous catheters' management: Results from a multi-dimensional assessment.

Peripheral Venous Catheter (PVC) is a widely used device in the hospital setting and is often associated with significant adverse events that may impair treatment administration and patient health. The aim of the present study is to define the incremental benefits related to the implementation and the standardized and simultaneous use of three disposable devices for skin antisepsis, infusion, and cleaning, assuming the hospital's point of view, from an effectiveness, efficiency, and organizational perspective. For the achievement of the above objective, real-life data were collected by means of an observational prospective study, involving two hospitals in the Liguria Region (Northern Italy). Consecutive cases were enrolled and placed into two different scenarios: 1) use of all the three disposable devices, thus representing the scenario related to the implementation of a standardized optimal procedure (Scenario 1); 2) use of only one or two disposable devices, representing the scenario related to not being in a standardized optimal procedure (Scenario 2). For the definition of effectiveness indicators, the reason for PVC removal and the PVC-related adverse events occurrence were collected for each patient enrolled. In addition, an activity-based costing analysis grounded on a process-mapping technique was conducted to define the overall economic absorption sustained by hospitals when taking in charge patients requiring a PVC. Among the 380 patients enrolled in the study, 18% were treated with the standardized optimal procedure (Scenario 1). The two Scenarios differed in terms of number of patients for whom the PCV was removed due to the end of therapy (86.8% versus 39.40%, p-value = 0.000), with a consequent decrease in the adverse events occurrence rate. The economic evaluation demonstrated the sustainability and feasibility of implementing the standardized optimal procedure specifically related to the need for lower economic resources for the hospital management of adverse events occurred (€19.60 versus €21.71, p-value = 0.0019). An organizational advantage also emerged concerning an overall lower time to execute all the PVC-related activities (4.39 versus 5.72 minutes, p-value = 0.00). Results demonstrate the feasibility in the adoption of the standardized optimal procedure for PVC management, with significant advantages not only from a clinical point of view, but also from an organizational and economic perspective, thus being able to increase the overall operational efficiency of the hospitals.

Introduction

The Peripheral Venous Catheter (PVC) is a wisely used device in the hospital setting [1], representing an essential element of modern medicine, used for the administration of fluids, nutrients, drugs, and blood products, as well as in the collection of blood for examinations [2-4]. Up to 70% of patients require a PVC during their hospital stay, and conservative estimates suggest that PVC days account for 15%-20% of total patient days in acute care hospitals [5].

Although such devices are frequently used and often considered to present a low risk for the patient, PVCs are associated with significant adverse events that may impair treatment administration and patient health [6-8]. In optimal conditions, the mean dwell time of PVCs is 3–4 days, with a median dwell time of 2 days [9-11]. The short dwell time, which approaches the recommendation of the US Centers for Disease Control and Prevention (CDC) for catheter replacement, is usually the result of short operating times and short hospital stay [10, 12]. In contrast, PVCs often fail before the therapy is completed: this can occur because the device is not adequately attached to the skin, allowing the PVC to fall out, thus leading to complications such as phlebitis, infiltration, or occlusion, with the consequent increase in patient morbidity and length of stay [13]. The development of any of the above complications would lead to the PVC’s removal before the end of its intended dwell time [14, 15].

According to the above, recent studies show that, although scheduled cannula needle removal is common practice in many hospitals, regular catheter replacement does not reduce the occurrence of complications such as phlebitis, thrombophlebitis, infiltration, extravasation, occlusion, venous spasm, and catheter-related infections [15, 16]. Furthermore, it has been shown that the insertion and maintenance of PVCs conducted by untrained or inexperienced healthcare workers increases the risk of thrombophlebitis [17]. Infection and phlebitis are of primary concern [11], so registered nurses must ensure that their knowledge and skills related to the management of PVCs are up to date and evidence-based [18, 19] to reduce complications associated with these devices.

In this regard, both the choice of the appropriate medical device and appropriate knowledge of its use throughout the entire process of PVC management -from skin antisepsis to washing up -could represent independent factors for successful patient care.

According to the above, literature on the topic suggested the simultaneous use of three specific disposable medical devices, such as ChloraPrep (disposable device used for skin antisepsis), Nexiva (PVC, to be inserted), and Posiflush (disposable device to be used for staying “in situ” and for washing up the patients after the catheter removal). On the one hand, the use of ChloraPrep is implemented for skin preparation to rapidly kill micro-organisms; it also continues the antimicrobial activity for at least 48 hours [20, 21], thereby leading to a decrease in PVC-related infections [22-24]. ChloraPrep is composed of 2% chlorhexidine gluconate and 70% isopropyl alcohol in a single-dose applicator and sterile solution. On the other hand, the PVC Nexiva, in comparison to traditional cannula, incorporates a stabilization platform, an extension set and a needle-less access site, which could significantly reduce the risks of developing complications, such as phlebitis, infiltration/extravasation and dislodgement, as well as bloodstream infections [25, 26]. Besides an increased safety profile for patients, the use of Nexiva would simultaneously offer protection to healthcare professionals, reducing the risk of exposure associated with needlestick injury [27]. Furthermore, the use of Posiflush as a medical device for washing-up activities would reduce catheter-related bloodstream infections, thus improving the standards of practice for catheter maintenance and management [28]. Posiflush is a specific pre-filled syringe containing 0.9% sodium chloride, whose main aim is to eliminate any blood reflux and maintain the patency of the cannula, while also reducing the risk of contamination. In order to guarantee the implementation of the clinical procedure as requested by the most diffuse Italian and European Guidelines [10–12, 15], the use of all three of the above-mentioned disposable medical devices (ChloraPrep, Nexiva and Posiflush) should be integrated with the following targets activities: i) number of insertion attempts lower than four; ii) PVC replacement in 96 hours; and iii) number of washes higher or equal to the number of PVC insertion. Based on the above, the use of all three disposable medical devices and the conduction of all three target activities would represent the standardized optimal procedure for PVC management.

Based on these considerations, the present study aims at analyzing the management of the PVC process in clinical practice in term of the outcomes measures achieved (from the hospital perspective) in the implementation of a standardized optimal procedure for PVC implant and management (composed of skin antisepsis, insertion and washing up activities). In addition, both the organizational and economic incremental benefits were defined to understand the potential optimization area for the hospitals taking in charge patients requiring a PVC but not having yet implemented a procedure optimizing skin antisepsis, insertion, and washing-up activities.

Methods

For the achievement of the above objective, a Health Technology Assessment analysis was conducted by means of the Danish Mini-HTA hospital-based model [29], which is useful to explore the clinical, economic, and organizational implications related to the standardized optimal procedure for PVC management, in comparison with the current situation, where this procedure is not utilized for all patients.

Real-word data were collected during a prospective observational study. It should be noted here that the present study does not have an interventional nature: even though the standardized optimal procedure was well-known in the hospitals involved, thus being integrated in the standard clinical practice, nurses would voluntarily choose the medical devices to be used in the skin antisepsis, insertion and washing-up phases of the PVC management process. As a result, they often only partially followed the entire process or diverged completely from the standardized optimal procedure (the use of the three above-cited disposable medical devices—ChloraPrep, Nexiva and Posiflush—in the three-step phase: i) number of insertion attempts lower than four; ii) PVC replacement in 96 hours; and iii) number of washes higher or equal to the number of PVC insertion-).

This study was approved by the Ethical Committee of the hospitals involved (ASL 2 Azienda Sociosanitaria Ligure 2, Savona, Italy). The informed consent form was collected, and patients who did not sign the form were excluded from the study.

Consecutive cases of patients were enrolled within 5 Operative Units of Medical or Surgical Departments, involving two Hospitals in the Liguria Region (Italy), from September 2018 to January 2019. This occurred after approval of the Ethics Committee (ASL 2 Azienda Sociosanitaria Ligure 2, Savona, Italy) and according to the following inclusion criteria: i) age older than 18 years; ii) length of hospitalization ranging from 4 to 15 days; and iii) use of PVC.

Adult patients’ consecutive cases were enrolled and placed into either a “being in a standardized optimal procedure” (Scenario 1) or a “not being in a standardized optimal procedure” group (Scenario 2), for whom demographic (age, gender) clinical (body max index-BMI, presence of comorbidities, vein status) and economic data were gathered. It should be noted here that Scenario 1 (i.e., being in a standardized optimal procedure) refers to the simultaneous use of the three disposable medical devices (ChloraPrep, Nexiva and Posiflush), integrated with the proper conduction of the previous targets’ activities described and required by guidelines: (i) number of insertion attempts lower than four; ii) PVC replacement in 96 hours; and iii) number of washes higher or equal to the number of PVC insertion), for the proper conduction of skin antisepsis, insertion and washing-up phases. On the contrary, Scenario 2 (i.e., not being in a standardized optimal procedure) refers to the use of only one or two out of the three disposable medical devices (thus using different devices for antisepsis, insertion and washing-up phases), with target activities missing.

From an economic perspective, the evaluation of PVC management costs was accordingly developed by means of an Activity-Based Costing (ABC) analysis [30]. In particular, the following drivers of hospital management costs were valorized, considering the entire PVC management process and prospectively collected for each patient enrolled in the study:

i) Involvement of human resources, in terms of time for executing the PCV-related activities, valorized in accordance with the Italian National Labour Contracts per professional class; ii) number and typology of medical devices used, considering both the medical devices composing the standardized optimal procedure and other comparable medical devices; iii) consumables; iv) general and fixed costs, considering not only cleaning services and meals, but also energy, maintenance services or third party and service contracts. All the above items of healthcare expenditure were derived from accounting flows by cost center provided by the management control of the hospitals involved and were evaluated considering the purchasing costs plus related VAT.

The economic analysis assumed the hospital’s perspective and estimated the hospital costs sustained up to 12 months, considering all the PVC implants performed on an annual basis.

The economic evaluation of the process was integrated with a budget impact analysis to define the economic sustainability of the overall adoption of the standardized optimal procedure [31]. To design the budget impact analysis, a baseline scenario (or base-case scenario) consisting of the real-life implementation of the PVC procedure was compared to different innovative scenarios, diverging from a different use of implementation of standardized optimal PVC procedure. Specifically, the baseline scenario considered the adoption of the standardized optimal PVC procedure for only 18% of the PVC implants, as observed considering real-world evidence from the hospitals involved in the study, evaluating an overall number of 156,624 PVC devices implanted on an annual basis. The base-case scenario was compared with three innovative scenarios where the standardized optimal PVC procedure would be implemented to an incremental portion of patients (35%, 50% and 100%).

Once having collected the above information, data were first analyzed considering descriptive statistics, frequencies, and distributions to give a comprehensive picture of the sample of reference.

After having verified the normal distribution of all the variables under assessment, independent sample T-tests were used to describe the existence of statistically significant differences between “being in a standardized optimal procedure” and “not being in a standardized optimal procedure” groups, from a demographic, clinical and economic point of view.

Finally, a hierarchical sequential linear regression model (with enter methodology), was implemented to define patterns and determinants of effectiveness and costs, using the Adjusted R2 to check the explanatory power of each model [32]. According to the above, effectiveness and costs acted as dependent variables of the model, which could be influenced by the following independent variables: i) the implementation or not of the standardized optimal PVC procedure; ii) typology of medical devices used for skin preparation, implant and washing-up activities, considering not only medical devices composing the standardized optimal procedure, but also other comparable medical devices; iii) patient’s BMI; iv) vein characteristics, assessed by means of the A-DIVA Scale [33]; v) number of PVCs days in situ; vi) PCV-related activities execution time.

All statistical analyses were performed using the statistical software SPSS 22.0.

Results

Description of the sample

The sample under assessment was composed of 380 patients, referring to five Operating Units of two Italian Hospitals.

Out of them, only 68 patients (18%) were treated according to the above-mentioned PVC standardized optimal procedure. In the comparison among groups (being in a standardized optimal procedure–Scenario 1—vs not being in a standardized optimal procedure–Scenario 2), the populations under assessment are well-matched and superimposable concerning demographic and clinical indicators, since no statistically significant differences emerged (p-value > 0.05), demonstrating the possibility to compare groups both for effectiveness and cost results (Table 1).

Table 1

Description of the sample under assessment.

	Entire Sample N = 380	Being in a standardized optimal procedure N = 68	Not being in a standardized optimal procedure N = 312	p-value
Age [Average Value ± standard error]	71.18 ± 0.78	72.48±2.03	70.87±0.95	0.476
Gender—Female [%]	55%	52.9%	55.4%	0.403
Body Max Index—BMI [Average Value Standard Error]	24.99±0.19	24.66±0.39	25.06±0.22	0.422
Presence of Comorbidities [%]	72.90%	72.1%	73.1%	0.486
Vein Characteristics—visible and palpable [%]	43.94%	45.6%	43.6%	0.061
Length of Hospitalization [Average Value ± standard error]	11.69±0.37	11.93±1	11.51±0.40	0.674
Number of attempts at PVC cannulation [Average Value ± standard error]	2.21±0.23	1.92±0.11	2.22±0.31	0.314
Days PVC stay in situ [Average Value ± standard error]	7.02±0.45	7.91±0.61	6.85±0.31	0.098

Results from effectiveness and safety indicators

The effectiveness measure was related to the percentage of patients for whom PVC removal was due to the end of therapy. Real-life data revealed that for patients being in a standardized optimal procedure 86.8% of the PVC removal was due to the end of the therapy and not associated to adverse events, as in Scenario 2 (39.4%, p-value = 0.000)–Table 2.

Table 2

Effectiveness indicators.

	PVC removal due to the end of therapy [%]	PVC removal due to the adverse events [%]
Being in a standardized optimal procedure–Scenario 1	86.8%	13.2%
Not being in a standardized optimal procedure–Scenario 2	39.40%	60.60%
p-value	0.000

Focusing on the patients for whom the PVC removal was due to the development of adverse events (Table 3), it emerged that the implementation of the standardized optimal procedure guaranteed the lower level of occurrence for complications, considering, in particular, conditions of occlusion and phlebitis (p-value = 0.000).

Table 3

A focus on the development of adverse events.

	PVC extravasation	Accidental Displacement	PVC removal by patient	Occlusion	Phlebitis
Being in a standardized optimal procedure–Scenario 1	0.00%	0.00%	8.82%	2.94%	1.47%
Not being in a standardized optimal procedure–Scenario 2	2.95%	10.86%	8.33%	12.48%	14.43%
p-value	0.000	0.000	0.314	0.000	0.000

While accidental displacement is an adverse event related to the implant procedure (with an incidence rate increase in case of no standardized optimal procedure implementation, p-value = 0.000), PVC removal by the patient only depends on the specific patient’s clinical conditions, such as potential neurological or movement disorders. The use of the procedure would allow for a significant improvement, especially regarding a reduced occurrence of complications and adverse events, greater stability of venous access, better prevention of the risk of displacement and reduction in the number of needlestick injuries.

The above-mentioned considerations were confirmed by the multivariate analysis. The regression model for effectiveness (Table 4) revealed that the different use of technologies (specifically the use of certain types of PVCs, as well as the Posiflush), and a standard value of BMI, could predict a variability of the effectiveness of the therapy (Adj R2 = 0.340), determining the achievement of a greater clinical outcome.

Table 4

Regression models for effectiveness.

	Model 1	Model 2	Model 3	Model 4	Model 5
Being in a standardized optimal procedure	0.361*	0.052	-0.140	-0.226*	-0.211*
Medical devices used for skin antisepsis		-0.402*	-0.500*	-0.549*	-0.539*
PVC Typology			0.327*	0.320*	0.312*
Medical devices used for washing-up activities				0.233*	0.231*
BMI					-0.110*
R 2	0.130	0.197	0.286	0.336	0.348
Adj R 2	0.128	0.193	0.280	0.329	0.340
F Value	56.541*	46.238*	50.156*	47.526*	39.984*
AR 2	0.130	0.067	0.089	0.051	0.012
F (AR)	56.541*	31.389*	46.767*	28.592*	6.853*

Results from the economic and the organizational assessments

The economic evaluation (Table 5) shows the feasibility of the implementation of the standardized optimal PVC procedure: despite higher costs in the technology used, “being in a standardized optimal procedure” group was related to a lower overall process cost (p-value = 0.019), given the occurrence of fewer adverse events requiring both a repositioning of the PVC and the clinical management of the patient for their resolution (p-value = 0.000).

Table 5

Economic evaluation of the process.

	Human Resources [€]a	Cost of Accessories [€]	Cost of technology at first positioning [€] b	Cost of technology after first positioning [€] b	Sub-total Procedure [€]	Repositioning for adverse events [€] c	Assessment of adverse events [€] d	Sub-total adverse events [€]	Total Cost [€]
Being in a standardized optimal procedure–Scenario 1	€ 4.60	€ 0	€ 5.04	€ 8.24	€ 17.88	€ 1.39	€ 1.05	€ 2.44	€ 19.60
Not being in a standardized optimal procedure–Scenario 2	€ 5.28	€ 0.79	€ 5.04	€ 7.73	€ 18.82	€ 3.46	€ 1.48	€ 4.93	€ 21.71
P-value	0.004	0.000	0.412		0.021	0.000	0.000	0.000	0.019

a Economic evaluation of the time spent by healthcare professional along the entire PVC process, from skin antisepsis to washing up

b Economic evaluation of the devices used for the entire PVC process, considering all the attempts conducted for PVC insertion

c Economic evaluation of the devices used if an adverse event had occurred

d Economic evaluation of the management of adverse events, in terms of time spent by healthcare professionals as well as potential exams or procedure conducted for the hospital resolution of the complications occurred, according to the incidence rates presented in Table 3

A longer duration of PVC stay in situ, a higher execution time, as well as the removal of the PVC before the end of therapy due to the occurrence of an adverse event and/or a complication, significantly determined a higher peripheral venous access process cost (Adj R2 = 0.630), as detailed in Table 6.

Table 6

Regression model for costs.

	Model 1	Model 2	Model 3	Model 4	Model 5
Vein status	0.158*	0.137*	0.066	0.059	0.046
PVC Stay in situ		0.683*	0.669*	0.676*	0.659*
Average execution time			0.326*	0.318*	0.311*
Being in a standardized optimal procedure				0.062*	0.013*
PVC effectiveness					0.212*
R 2	0.025	0.491	0.592	0.596	0.634
Adj R 2	0.023	0.489	0.589	0.592	0.630
F Value	9.737*	182.001*	182.030*	138.250*	129.791*
AR 2	0.025	0.466	0.101	0.004	0.038
F (AR)	9.737*	345.393*	93.132*	3.410*	39.371*

According to a 12-month time horizon and assuming the hospital perspective (Table 7), in the comparison between Scenario A and Scenario D (moving from 18% of the standard procedure use, to 35%), hospitals could benefit from economic savings equal to 3.51% for the implantation of 156,624 PVCs on an annual basis. The more the standardized optimal procedure based on disposable devices implant is implemented, the more the economic savings become higher, ranging from 5.09% (in case of 50% of market share for innovative implant procedure–comparison between Scenario A and Scenario C) to 9.71% (in case of 100% of market share for innovative implant procedure–comparison between Scenario A and Scenario B).

Table 7

Budget impact analysis.

Scenarios under assessment	Total healthcare costs related to the implantation of 156,624 PVCs on annual basis
Baseline Scenario A–% of hospital standardized optimal procedure penetration equal to 18%—real life Scenario	€ 1,770,719
Innovative Scenario B—% of hospital standardized optimal procedure penetration equal to 100%—best case Scenario	€ 1,598,871
Innovative Scenario C—% of hospital standardized optimal procedure penetration equal to 50%	€ 1,684,933
Innovative Scenario D—% of hospital standardized optimal procedure penetration equal to 35%	€ 1,710,751
Δ € B-A	- € 171,848
Δ % B-A	- 9.71%
Δ € C-A	- € 85,786
Δ % C-A	- 5.09%
Δ € D-A	- € 59,968
Δ % D-A	- 3.51%

The above advantage would not be relegated only to the economic sphere. The implementation of the standardized optimal procedure, given a lower execution time along the entire PVC management process (4.39 minutes versus 5.72 minutes, p-value = 0,001), would also generate significant organizational advantages, from a hospital capacity perspective.

In this regard, considering the 156,624 PVC devices implanted on an annual basis and assuming the same scenarios of the BIA (Table 8), the organizational benefits would range from a minimum of 5.53% of time savings (in case of 35% of standardized optimal procedure introduction), to a maximum of 20.78% (in case of 100% of standardized optimal procedure implementation), in terms of overall minutes spent for all the PVC-related activities.

Table 8

Organizational benefits.

Scenarios under assessment	Total organizational advantages related to the implantation of 156,624 PVCs on annual basis
Baseline Scenario A–% of hospital standardized optimal procedure penetration equal to 18%—real life Scenario	452,046.09 minutes
Innovative Scenario B—% of hospital standardized optimal procedure penetration equal to 100%—best case Scenario	358,114.54 minutes
Innovative Scenario C—% of hospital standardized optimal procedure penetration equal to 50%	412,158.02 minutes
Innovative Scenario D—% of hospital standardized optimal procedure penetration equal to 35%	428,371.07 minutes
Δ € B-A	-93,931.54 minutes
Δ % B-A	-20.78%
Δ € C-A	-39,888.06 minutes
Δ % C-A	-9.68%
Δ € D-A	-23,675.02 minutes
Δ % D-A	-5.53%

Discussion

PVCs are now an essential part of medical care, and their management has an important effect on the incidence of catheter associated infections. Thus, any strategies that are able to prevent the occurrence of PVC-related infection and maximize the clinical outcomes for patients need to be deeply considered, as most complications associated with the use of PVCs are preventable [34].

Some of the traditional preventive measures are represented by training and education of healthcare professionals and patients, performance feedback, specialized intravenous treatment teams, documentation with peripheral cannula care plans, hand hygiene, skin preparation, use of sterile semipermeable dressings, selection of catheter insertion site and catheter replacement strategies [5, 35, 36].

The present analysis could be considered the first Italian attempt to investigate the impact of a specific standardized optimal procedure for the management of PVCs, designed according to the most recent guidelines on the topic [10–12, 15], not only from an effectiveness perspective, but also considering the potential economic and organizational impacts for the hospitals taking in charge patients requiring a PVC. The clinical course of each patient who received a PVC for any reason in two Italian hospitals were closely followed by trained nurses until removal of the catheter.

The implementation of the standardized optimal procedure reported the preferable solution of a lower incidence of adverse events and a reduced number of attempts at PVC cannulation, with a consequent minimization of costs.

From an organizational point of view, a higher PVC stay in situ, and a lower execution time for the PVC procedure meant an increase in operational efficiency related to the procedure and a decrease in the nursing activities devoted to the weaker patients. From an economic perspective, the BIA reported marginal investments related to the acquisition of new technologies, strictly dependent on the baseline scenario of the hospital choosing to implement new technologies.

The above considerations are strengthened by inferential analysis conducted for the definition of the predictors of costs optimization and effectiveness maximization. On the one hand, the use of certain types of PVCs, as well as the Posiflush, and a standard value of BMI, could determine the achievement of a greater clinical outcome. On the other hand, a longer duration of PVC stay in situ, a higher execution time, as well as the removal of the PVC before the end of therapy due to the occurrence of an adverse event and/or a complication, significantly determined a higher economic resource absorption devoted to patients requiring a PVC.

Even though the main strength of the study was that it relied on real-life data, it has some limitations. The study was implemented in two hospitals and was supported by nursing leadership. In this view, a further validation in other hospitals may be needed to support the generalizability of the results, in particular concerning the different base-case use of the standardized optimal procedure, as well as the definition of the different devices used along the entire PVC management process.

In conclusion, the results of the study suggested the strategic relevance of the standardized optimal procedure for the management of PVC implementation in the improvement of the clinical pathway for patients, with important economic and organizational savings for hospitals.

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31 May 2021

PONE-D-21-00993

PERIPHERAL VENOUS ACCESS PROCESS and BEYOND: RESULTS FROM THE FIELD

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Reviewer #1: No

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: Although the article treats a relevant topic, I think it needs additional work and a careful revision to be considered for publication. Many aspects are not clear and should be improved.

- Throughout the article you mention PVCs standard procedure. Honestly, it’s not so clear what you mean by standard. Who defined this standard? Are there any clinical guidelines or hospital guidelines? Or is it just a hypothesis you want to test? In case it’s a gold standard (the word standard implicitly refers to a gold standard) you should add a reference. If it is a standard, why is it applied only to 18% of patients? Who decides whether the standard has to be applied or not?

- You define as intervention the “implementation of an innovative PVCs standard procedure” and as comparator the “standard procedure is not utilized for all the patients”. What do you mean by innovative: using the innovative BD Nexive PVC or using the so-called standard procedure (i.e. the three BD devices) for all patients? Also, in line 123 what do you mean by innovative scenario? It seems to me you are simply simulating different penetration rate of PVC.

- It’s not very clear what you mean by “being in procedure” and “not being in procedure” groups. Please explain more clearly. Also explain how the patients are assigned to the two groups: randomly? based on clinical considerations?

- When you explain the goal of the study in the introduction, you say “based on these considerations”, that seems to be linked to the choice of the appropriate medical device and presenting appropriate knowledge and skills (previous sentence). None of these elements is mentioned in the article. But then, in the regression analysis you mention PVC typology, so one can argue that nurses have to possibility to choose the type of device and the three BD devices are not used for all the patients. Please explain.

- In the abstract you mention ABC was performed, but this is not mentioned in the body of the article. The method used to collect the data in table 5 should be explained. You should also explain the meaning of each variable in table 5.

- In table 1 you mention Vein Characteristics - visible and palpable: how is this variable measured? Is there an objective measure or it relies on the nurse perception? Does the operator experience influence the evaluation of this aspect?

- Please clarify which patients’ comorbidities are considered in the analysis.

- Five wards were belonging to two different hospitals participated in the study. Did you find any differences (e.g. % of in procedure patients) among hospitals and medical vs surgical wards?

- In table 4 please make clear the dependent variable. Moreover, in the text you should explain more clearly the meaning of the coefficients: for instance, how to interpret the meaning of the coefficient of disinfection?

- What do you mean by “simulated the healthcare expenditure sustained up to 12 months?” It seems to me you mean costs born by the hospitals instead of healthcare expenditure. Purchasing cost?

- The costs that have been considered in the economic analysis are not clear. Where can I find the cost of the devices (three in the treatment group, 1 or 2 in the control)? Any costs for the management of adverse events?

- Budget impact analysis: it’s not clear to me how the numbers in table 7 were computed.

- In the economic?

- Last, I can guess that the BD products mentioned in the paper are purchased through regional tenders. In case another economic operator will award next tender, will the results be valid anyhow? On other words, are the results product-specific o procedure-specific?

Minor aspects:

- Lines 74-79: the paragraph is too long and as a result not clear.

- Not very clear what BD Chloraprep and Posiflush are.

- What do you mean by “BD Nexiva innovative PVC”? The presence of a stabilization platform? What is this?

- What do you mean by “reducing the risk of exposure associated with needlestick injury”?

- Line 102 perspective: do you mean prospective?

- Line 106: sign instead of signed (same in the abstract)

- Line 120-121 What do you mean by “assuming 156,624 PVCs”? what type of assumption is this? Is it the volume of PVCs in the 5 analyzed departments?

- You say “Real-life data revealed that, for patients being in procedure, 86.8% of the PVC removal was due to the end of the therapy, and not associated to adverse events, as in the other scenario (13.2%, p-value=0.000)” It’s not clear to me what you mean by “as in the other scenario”: 13from the table it seems that 13.2% relates to the same scenario, to removal due to adverse events.

- It’s not clear who is the sponsor of the study.

Reviewer #2: The authors used a single group of continuous measurement and observation to compare the correlation between the applied of ultrasonographic and PIVC failure or survival. This is an interesting topic, however, there are still great doubts about the rigor of the research design which influencing the internal and external validity of the study:

1.There is no control group and sample size are too small without any theoretical sample size estimation. This may also be the reason why most of the statistical results are not significantly different.

2.How consistent is the assessment of EMR and ultrasound operation between different researchers? Performing a test of internal and external consistency of the researcher could be considered.

3.Author should consider and analysis that the working years and professional abilities of ER nurses may also be the key factors that affect the placement of PIVC and the judgment of PIVC failure or survival.

4.The definition of subcutaneous edema in the image needs more precisely descript rather just presents the photo.

Some parts in the article are not clearly described:

1.There are inconsistent descriptions of PIVC failures in the text, such as line 164 and line 221, which may cause confusion for readers.

2.The primary outcome is not clear enough in line 219. What is the definition of “increased risk of PIVC failure” and how to measure it?

3.“Day idle”, a significant variable between groups in the outcome measurement, but there is no any discussion about that.

4.If the ultrasonographic shows subcutaneous edema, but the clinical standard assessment process by ER nurse is not abnormal, is it necessary to remove the PIVC preventively? Are there any other suggestions for the above condition? I don’t see any discussion for that.

In the end, I agree with the reviewer#5 point out the problem of result application. I think the suggestion is also not specific for clinical practice in ER.

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Reviewer #1: No

Reviewer #2: No

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18 Sep 2021

Replies to the Editor

Dear Editor,

Thank you very much for your comments.

We confirm that in the amended manuscript, you could find the Ethics statements, with regard to the name of the ethics committee/institutional review board(s) that approved your specific study. In particular, the study, whose results are here presented, was approved by the Regional Ethical Committee of the hospitals involved (ASL 2 Azienda Sociosanitaria Ligure 2, Savona, Italy), according to the Liguria Region protocol number 231/2018 dated 18/10/2018. The informed consent form was collected, and patients who did not signed the form were excluded from the study.

Furthermore, we have made the following changes as requested.

- Modification of the title, in “Organizational, efficiency and effectiveness impacts of a standardized optimal procedure, for the PVCs management”.

- Inclusion of all the tables as part of the main manuscript, with the consequent removal of the individual files.

- Upload of the minimal data set used for data analysis, as a Supporting Information file.

- Integration in the cover letter of specific statement, with regard to the previous divulgation of the results presented in this manuscript.

With regard to other submissions related to the present manuscript, we confirm that it has been presented only in Italian and English informative conferences, without the requirement to publish any abstracts or full text. In particular, the audience of the above conferences were nurses and clinicians currently using the medical devices investigated, thus taking in charge patients needing a peripheral venous access. According to the above, we confirm that no conference proceedings emerged, and no documents related to the present topic was reviewed and formally published.

Besides the above conferences, we have presented an abstract related to the results of the present research activity to ISPOR Conference in 2020, with an abstract and a consequent poster presentation. The abstract was then published in the Special Issue of Value in Health (DOI:https://doi.org/10.1016/j.jval.2020.08.1064). This is the rational because you have found an overlapping between the present paper and the abstract previously published. According to your kind request, we have carefully revised the text and rephrased the duplicated sentences, both in the abstract section and in the methods section of the manuscript. In this view, we confirm the originality of the present paper, since in the previous publication results have been presented partially, without any explanation of the results achieved. As mentioned above, only one single abstract have been published.

In the followings you could also find detailed reply to your questions, related to the financial disclosures.

1. Please state whether any of the research costs or authors' salaries were funded, in whole or in part, by a tobacco company (our policy on tobacco funding is at http://journals.plos.org/plosone/s/disclosure-of-funding-sources)

We confirm that the research cost or authors’ salaries are not funded by a tobacco company.

2. Please state whether the donor has any competing interests in relation to this work (see http://journals.plos.org/plosone/s/competing-interests).

The funder of the present research activity had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This was a decision totally dependent from the authors.

3. Please state whether the identity of the donor might be considered relevant to editors or reviewers’ assessment of the validity of the work.

The authors are not aware of any competing interests.

Replies to Reviewer #1

We would thank the Reviewer # 1 for the comments.

1. Throughout the article you mention PVCs standard procedure. Honestly, it’s not so clear what you mean by standard. Who defined this standard? Are there any clinical guidelines or hospital guidelines? Or is it just a hypothesis you want to test? In case it’s a gold standard (the word standard implicitly refers to a gold standard) you should add a reference. If it is a standard, why is it applied only to 18% of patients? Who decides whether the standard has to be applied or not?

Thank you very much for your comment. We realized that we did not explain well the rationale behind our evaluation, as well as the word “standard” is not the correct adjective to use in this case.

The rationale behind our evaluation was a sort of a performance monitoring activities, with regard to the real-life implementation of a specific hospital PVCs management procedure, developed and proposed by the Risk Management and Quality Office of the hospitals involved with the collaboration of Nurses and Healthcare Professionals Directorate. After the approval to implement the hospital PVCs management procedure from the Healthcare Directorate, and the related practical introduction, it was necessary to verify and evaluate the effective adoption of this procedure in terms of effectiveness, safety and efficiency profiles.

Moving on from this premise, we have accordingly modified the introduction section, to better explain the innovative PVC management process, that we have now defined as “PVCs standardized optimal procedure”. In this view, and according to literature evidence available on the topic, the simultaneous and standardized use of three specific medical devices could be able to optimize the entire management process of patients requiring a PVC. Based on the above the PVCs standardized optimal procedure consisted in the use of three different disposable medical devices, such as ChloraPrep (disposable device used for skin antisepsis), Nexiva (innovative PVC, to be inserted), and Posiflush (disposable device to be used for staying “in situ” and for washing up the patients after the catheter removal) use. On one hand, the use of ChloraPrep, implemented for skin preparation, would rapidly kill micro-organism, thus also maintaining the antimicrobial activity for at least 48 hours (Florman et al., 2007; Crosby et al., 2001), and leading to a decrease in PCV associated infections’ occurrence rate (Manoury et al., 2008; McCann et al., 2016). On the other hand, the PVC Nexiva, in the comparison with traditional cannula, incorporates a stabilization platform, which could significantly reduce the risks of developing complications, such as phlebitis, infiltration/extravasation and dislodgement (Bausone-Gazda et al., 2010; Van Zundert, 2005). Beside an increased safety profile for patients, the use of the PVC Nexiva would simultaneously offer protection to the healthcare professionals, in terms of reducing the risk of exposure associated with needlestick injury (Lee et al., 2005). Furthermore, using Posiflush at the same time, would reduce catheter-related bloodstream infections, thus improving standards of practice for catheter maintenance and management (Can & Yan, 2012).

The use of all the above mentioned three devices, should also be integrated with the following targets activities, in order to guarantee the implementation of the clinical procedure, as requested by the most diffuse Italian and European Guidelines (O’Grady et al., 2011; RCN, 2010; INS, 2016; Scales, 2008): i) number of insertion attempts lower than four; ii) PVC replacement in 96 hours; and iii) number of washes higher or equal to the number of PVC insertion.

The integration of the above targets’ activities with the use of all the three disposable medical devices represents the so-called “PVCs standardized optimal procedure”.

In the present research activity, we would like to define the incremental advantages in the clinical practice related to the implementation of the so-called PVCs standardized optimal procedure, based on the real-life practice of two hospitals (in Liguria Region) involved in the analysis. In this view, according to the study design and the inclusion/exclusion criteria for patients being enrolled in the observational prospective study, in 2019 only 18% of patients were treated coherently with the PVCs standardized optimal procedure.

It should be noted here that the results presented in the paper show a real-life picture concerning the clinical practice of the two hospitals involved, where despite the standardized optimal procedure is known and it represents an internal hospital protocol, its use is not yet standardized. According to the above, we would like to highlight the fact that our study does not present an interventional nature. We just observed the current clinical practice with the comparison of the two different scenarios (implementation of the PVC standardized optimal procedure versus not implementation of the PVC standardized optimal procedure), in the same organizational context.

2. You define as intervention the “implementation of an innovative PVCs standard procedure” and as comparator the “standard procedure is not utilized for all the patients”. What do you mean by innovative: using the innovative BD Nexive PVC or using the so-called standard procedure (i.e. the three BD devices) for all patients? Also, in line 123 what do you mean by innovative scenario? It seems to me you are simply simulating different penetration rate of PVC.

Thank you for remarking this point. We would like to confirm that the innovative procedure is represented by the so-called “PVC standardized optimal procedure”, consisting of the use of all the three disposable medical devices and the implementation of targets’ activities, along the three phases of the process: skin antisepsis, insertion and washing up.

In line 123 you could find the terms “innovative scenario”, because we simulated the hospital costs related to a different use of the so-called “PVC standardized optimal procedure”. According to the budget impact analysis methodology, a baseline scenario (the current standard of care, that in this case consists of the use of PCV standardized optimal procedure only for 18% of patients, representing the percentage of penetration in the real life setting) was compared to three different innovative scenarios (differing from the baseline because of a higher use of the PVC standardized optimal procedure, so diverging from the percentage of penetration in real life).

We have amended the revised version so that it could be clearer and easier to understand. We hope to have revised the Methods section properly.

3. It’s not very clear what you mean by “being in procedure” and “not being in procedure” groups. Please explain more clearly. Also explain how the patients are assigned to the two groups: randomly? based on clinical considerations?

Thank you for the comment. As previously mentioned in the reply at your first comment, our study does not present an interventional nature. Since it was designed as an observational study, it only observed what happened in the hospitals involved regarding the use of specific medical devices as well as to conduct specific targets’ activities.

According to the above and to the detailed explanation of the PVC standardized optimal procedure, the term “being in procedure” means that all the three disposable medical devices are correctly implemented and integrated with the targets activities recommended by guidelines available on the topic, for the three phases of the PVC management process: skin antisepsis, insertion and washing-up. On the contrary, the term “not being in procedure” refers to the use of only one or two disposable medical devices. In this case other medical devices are utilized, and not all the recommended targets’ activities are performed.

Nurses choose the devices for the PVCs management process, and not always act by selecting the three devices indicated in the standardized optimal procedure, despite the patients’ characteristics being superimposable, as demonstrated in the results section, analyzing the sample, for which there are no statistically significant differences in the two populations.

4. When you explain the goal of the study in the introduction, you say “based on these considerations”, that seems to be linked to the choice of the appropriate medical device and presenting appropriate knowledge and skills (previous sentence). None of these elements is mentioned in the article. But then, in the regression analysis you mention PVC typology, so one can argue that nurses have to possibility to choose the type of device and the three BD devices are not used for all the patients. Please explain.

Thank you for your consideration. We have coherently revised the Introduction and the Methods sections following your consideration.

The present study does not have an interventional nature: despite the standardized optimal procedure was well-known in the hospitals involved, thus being integrated in the standard clinical practice, and presented as a hospital procedure, nurses would voluntarily choose the medical devices to be used in the skin antisepsis, insertion and washing up phases of the PVCs management process, having different type of devices available for these activities, thus following only partially, or completely diverging from the standardized implant procedure (requiring the use of the three cited devices, in the three process phases).

For instance, the Beta coefficient related to the variable “disinfection” refers to the different typology of medical devices used for skin antisepsis or skin preparation activity, that were numerically coded (in the amended table, we have modified the variable in “medical devices used for skin antisepsis”. According to the above, a lower number refers to the use of ChloraPrep, as disposable device for skin antisepsis activities. In this case, the use of ChloraPrep is significantly related to the achievement of a higher outcome for the patients.

5. In the abstract you mention ABC was performed, but this is not mentioned in the body of the article. The method used to collect the data in table 5 should be explained. You should also explain the meaning of each variable in table 5.

Thank you for remarking this point. We have accordingly revised the Methods section, with regard not only the implementation of the ABC methodology, but also with regard the methods used for data collection.

6. In table 1 you mention Vein Characteristics - visible and palpable: how is this variable measured? Is there an objective measure or it relies on the nurse perception? Does the operator experience influence the evaluation of this aspect?

Thank you for this comment. The vein characteristics and the classification of the veins was made according to the A-DIVA (Adult Difficult Intravenous Access) Scale (Van Loon et al., 2016), a specific tool validated in literature evidence, whose utilization is not influenced by the healthcare professionals experience. This scale was developed with the main aim to prospectively identify patients with a high probability of a difficult intravenous access based on easily available clinical data, which may improve clinical practice and patient’s comfort.

The A-DIVA scale can be applied across clinical settings and patient cohorts basing its assessment on five items: (i) palpability of the target vein; (ii) the patient’s history of difficult intravenous access; (iii) visibility of the target vein; (iv) patients’ access in a department emergency area, in terms of unplanned indication for surgery; (v) the diameter of the target vein is less than 2 millimeters. Each confirmed item adds one point to the scale’s score (ranging from 0 to 5), where a higher score indicates a higher risk of difficult intravenous access and risk of failed PVC insertion. According to this score, patients could be classified in three different groups: 1) patients considered at low risk to experience a failed PVC insertion (score range: 0-1); 2) patients considered at medium risk to experience a failed PVC insertion (score range: 2-3); 3) patients considered at high risk to experience a failed PVC insertion (score range: 4-5).

7. Please clarify which patients’ comorbidities are considered in the analysis.

Thank you for this consideration. Since the present research activity was designed as a prospective observational study, all the potential comorbidities developed by the patients enrolled, were included. In fact, the typology of comorbidities was not considered neither as an inclusion or an exclusion criterion.

According to the above, the distribution of patients concerning the typology of comorbidities is reported in the following table, considering only the 72.90% of the overall sample presenting a concomitant disease.

Typology of comorbidities %

Cardiovascular disease 31.70%

Pulmonary disease 21.20%

Neurological disease 11.40%

Oncological disease 9.10%

Infectious disease 6.30%

Psychiatric disease 6.30%

Renal disease 5.80%

Rheumatological disease 3.00%

Integumentary System disease 2.10%

Diabetes 1.90%

Musculoskeletal disorders 1.20%

8. Five wards were belonging to two different hospitals participated in the study. Did you find any differences (e.g. % of in procedure patients) among hospitals and medical vs surgical wards?

Thank you for the comment. We involved two hospitals referring to the same organizational structure. Before implementing our analyses to achieve the primary study’ objective, a preliminary assessment was performed to understand potential “ex-ante” differences among groups. We confirm that no differences emerged, so that both hospitals and wards were comparable. The habit of the nurses in the two hospitals of using the standardized optimal procedure, did not change significantly, as well as in the different medical and surgical departments.

9. In table 4 please make clear the dependent variable. Moreover, in the text you should explain more clearly the meaning of the coefficients: for instance, how to interpret the meaning of the coefficient of disinfection?

Thank you for your consideration. We have amended the Results section, referred to Table 4. In particular, the dependent variable was the effectiveness of the PVC standardized optimal procedure, in terms of PVCs removal reasons.

In general terms, the two regression analyses performed and reported in Table 4 and in Table 6, considered effectiveness and costs acting as dependent variables of the model. These variables could be influenced by the following independent variables: i) the implementation or not of the PVC standardized optimal procedure; ii) typology of medical devices used for skin antisepsis, implant and washing-up activities, considering not only the disposable medical devices composing the standardized optimal procedure, but also other comparable medical devices; iii) patient’s BMI; iv) vein characteristics; v) number of PVCs days in situ; vi) PCV-related activities execution time.

10. What do you mean by “simulated the healthcare expenditure sustained up to 12 months?” It seems to me you mean costs borne by the hospitals instead of healthcare expenditure. Purchasing cost?

Thank you for the comment. We have accordingly revised the sentence, since we have currently assumed the hospital point of view and we have defined all the costs directly sustained by hospitals in performing such procedure. Besides the purchasing costs of the medical devices investigated, we economically evaluated all the hospital clinical pathway costs of a patients requiring PVC management.

11. The costs that have been considered in the economic analysis are not clear. Where can I find the cost of the devices (three in the treatment group, 1 or 2 in the control)? Any costs for the management of adverse events?

Thank you for the comment. According to your kind request, we have modified the Methods section, to better define the economic analysis conducted. In addition, we confirm that we have included in the analysis also the cost for the management of adverse events. In Table 5 you could find both costs related to need of PVC repositioning due to the development of any adverse events, as well as economic evaluation to manage the adverse events occurred.

12. Budget impact analysis: it’s not clear to me how the numbers in table 7 were computed. In the economic?

Thank you for remarking this point. We have tried to better explain the rationale behind the budget impact analysis development, in the Method section.

In particular, we have compared the current standard of care in the hospitals involved with different innovative scenarios, presenting a different use of the standardized optimal procedure. The base-case scenario, that in Table 7 is labelled as Scenario A, consisting of the use of the PVC standardized optimal procedure only for 18% of patients, resulting from the analysis of the real life. The residual 82% presented an overall economic absorption as for “not being in a standardized optimal procedure), that is equal to € 21.71 (versus € 19.60 for those being in a standardized optimal procedure). The above base-case scenario (Scenario A) was compared to Scenario B, C and D, presenting a higher implementation rate of the PVC standardized optimal procedure.

- Innovative Scenario B refers to the implementation of the PVC standardized optimal procedure for 100% of patients requiring a PVC, with a cost per patient equal to € 19.60. Scenario B represents a sort of “best-case scenario”, in which the standardized optimal procedure has a total percentage of penetration in the clinical practice.

- Innovative Scenario C refers to the implementation of the PVC standardized optimal procedure for 50% of patients requiring a PVC (with a cost per patient equal to € 19.60). For the other 50%, the standardized optimal procedure is not implemented, thus presenting a cost per patient equal to € 21.71.

- Innovative Scenario D refers to the implementation of the PVC standardized optimal procedure for 35% of patients requiring a PVC (with a cost per patient equal to € 19.60). For the other 65%, the standardized optimal procedure is not implemented, thus presenting a cost per patient equal to € 21.71.

All the above innovative Scenarios were thus compared to Scenario A, considering the overall PVC implants performed on an annual basis by the hospitals involved, thus being equal to 156,624.

The same above Scenarios were considered with reference to the analysis of the organizational impact. In this regard, despite conducting the analysis with euros spent for patients, we conducted the analysis, in terms of system capacity, considering the time spent (in minutes) for performing all the PVC-related activities.

13. Last, I can guess that the BD products mentioned in the paper are purchased through regional tenders. In case another economic operator will award next tender, will the results be valid anyhow? On other words, are the results product-specific o procedure-specific?

Thank you for your comment. We confirm that the different medical devices comprising the standardized optimal procedure for PVC management are purchased through regional tenders. All the results could be replicable also for other economic operators, in terms of other medical devices Companies, but only if the technical characteristics of the disposable medical devices are superimposable.

14. Lines 74-79: the paragraph is too long and as a result not clear

Thank you for remarking this point. We have accordingly revised the paragraph.

15. Not very clear what BD Chloraprep and Posiflush are.

Chloraprep is a specific disposable medical device used for skin preparation and antisepsis, presenting the main aim to ensure an optimal skin disinfection and maintenance of sterility during the procedure. Chloraprep is composed of 2% chlorhexidine gluconate and 70% isopropyl alcohol in single-dose applicator and sterile solution.

On the other hand, Posiflush is a specific pre-filled syringe, containing 0.9% sodium chloride, presenting the main aim to eliminate any blood reflux and maintain the patency of the cannula, also reducing the risk of contamination. This specific medical device is used for washing-up the patients, after the PVC removal.

We have added detailed information with regard to both disposable medical devices (Chloraprep and Posiflush) in the amended manuscript, to better explain the devices characteristics.

16. What do you mean by “BD Nexiva innovative PVC”? The presence of a stabilization platform? What is this?

Thank you for your comment. We realized to have used the term “innovative” in an unproper manner. We have revised the manuscript accordingly.

In particular, the specific feature of the PVC NEXIVA is the presence of a stabilization platform or feature, an extension set and a needle-less access site. According to the above, because PVC insertion is not considered a sterile procedure, the pre-assembly of these components greatly reduces the risk of accidental contamination of the device during the process, which could lead to bloodstream infections.

17. What do you mean by “reducing the risk of exposure associated with needlestick injury”?

Since the PVC NEXIVA represents a closed intravenous (IV) catheter system, its main features exposed above, besides preventing patients from complications or bloodstream infections, would limit healthcare professionals’ exposure blood, limiting the risk of needlestick injuries. In fact, this safety-engineered system, is also designed to reduce needlestick injury by using passive needle-shielding technology that does not compromise the insertion techniques.

18. Line 102 perspective: do you mean prospective?

Thank you for the comment. We are so sorry for the typo. We have amended the revised manuscript with term “prospective” instead of “perspective”.

19. Line 106: sign instead of signed (same in the abstract).

Thank you for the comment. We are so sorry for the typo. We have amended the revised manuscript with term “sign” instead of “signed”.

20. Line 120-121 What do you mean by “assuming 156,624 PVCs”? what type of assumption is this? Is it the volume of PVCs in the 5 analyzed departments?

Thank you for remarking this point. We have revised the sentence, to make it clearer. Actually, we refer to 156,624 PVC inserted on an annual basis, as the volume of PVC in the hospitals involved in the analysis.

21. You say “Real-life data revealed that, for patients being in procedure, 86.8% of the PVC removal was due to the end of the therapy, and not associated to adverse events, as in the other scenario (13.2%, p-value=0.000)” It’s not clear to me what you mean by “as in the other scenario”: 13from the table it seems that 13.2% relates to the same scenario, to removal due to adverse events.

Thank you for the comment, and we are so sorry for this typo. We have revised the entire sentence, because the other scenario refers to the absence of implementation of the investigated standardized optimal procedure for PVC management. We also have corrected the proper percentage rate, now equal to 39.4%.

22. It’s not clear who is the sponsor of the study.

The Principal Investigator of the study was one of the authors, Roberta Rapetti, who also proposed the implementation of the hospital standardized optimal procedure inside the hospital and who wanted, few years away from the standardized optimal procedure implementation, to validate the efficiency and effectiveness of the procedure proposed, asking for the support of LIUC for the methodological part related to the Danish Mini HTA implementation.

Replies to Reviewer #2

We would thank the Reviewer # 2 for the comments.

1. There is no control group and sample size are too small without any theoretical sample size estimation. This may also be the reason why most of the statistical results are not significantly different.

Thank you very much for your comment. Despite the small sample size, in our opinion results could be replicable and successful, thus demonstrating the feasibility of the adoption of a standardized optimal procedure for PVC management, both from an economic and an effectiveness point of view.

With regard to the sample size, we have deeply analyzed the sample of patients to enroll in the present study. In particular, based on a research conducted in 2017 by the hospital involved, considering a confidence interval of 99% and a power of the sample equal to 90%, our expectation was to enroll 380 patients within the present observational study. In particular, the following inclusion criteria were considered: i) age older than 18 years; ii) length of hospitalization ranging from 4 to 15 days; and iii) use of PVCs.

The informed consent form was collected, and patients who did not sign the form were excluded from the study.

2. How consistent is the assessment of EMR and ultrasound operation between different researchers? Performing a test of internal and external consistency of the researcher could be considered.

Thank you for the comment. In our research setting, EMR was not considered for the evaluation of the patients and of the standardized optimal procedure.

3. Author should consider and analysis that the working years and professional abilities of ER nurses may also be the key factors that affect the placement of PIVC and the judgment of PIVC failure or survival.

Thank you for your kind suggestion. It could be surely a topic of further research to consider the healthcare professionals seniority and the professional abilities, to be included in the regression models both for costs and for effectiveness.

4. The definition of subcutaneous edema in the image needs more precisely descript rather just presents the photo. Some parts in the article are not clearly described.

Thank you for your comment. We did not present photos, because we did not consider the subcutaneous edema in the insertion of the PVC or in the PVC removal.

5. There are inconsistent descriptions of PIVC failures in the text, such as line 164 and line 221, which may cause confusion for readers.

Thank you for your comment. We have accordingly modified the introduction and methods section, in order to better define the advantages related to PVC NEXIVA, as a closed IV catheter system capable to reduce the risk of accidental contamination of the device during the process, which could lead to bloodstream infections.

6. The primary outcome is not clear enough in line 219. What is the definition of “increased risk of PIVC failure” and how to measure it?

Thank you for your comment. We have revised the amended manuscript, detailing the primary objective of the analysis. In particular, the present study aims at analyzing the process of management of PVCs in the clinical practice, considering the hospital point of view, in relation with outcome measures achieved, in the standardized implementation of an optimal procedure for PVCs implant. In addition, both the organizational and economic incremental benefits were defined, to understand optimization area for the hospitals taking in charge patients requiring a PVC.

7. “Day idle”, a significant variable between groups in the outcome measurement, but there is no any discussion about that.

Thank you for your kind suggestion. It could be surely a topic of further research to consider also the “day-idle” variable to be included in the regression models both for costs and for effectiveness.

8. If the ultrasonographic shows subcutaneous edema, but the clinical standard assessment process by ER nurse is not abnormal, is it necessary to remove the PIVC preventively? Are there any other suggestions for the above condition? I don’t see any discussion for that.

Thank you for your comment. The assessment process by the ER nurse is not applicable in the present investigated setting, because the insertion of the PVC and the management process start in the medical or surgical departments and not in the ER.

Submitted filename: 2021-09-15 Response letter to Reviewers v.4.docx

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5 Oct 2021

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Additional Editor Comments (if provided):

What is "PVC"? Don't use acronyms or abbreviation upfront at the Title! Readers have no idea of your Title!

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Reviewers' comments:

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11 Oct 2021

Dear Editor,

Thank you for your kind comment and suggestion with regard to the modification of the title of our manuscript. According to your kind request, we have revised the title from “Organizational, efficiency and effectiveness impacts of a standardized optimal procedure, for the PVCs management” to “The implementation of a standardized optimal procedure for peripheral venous catheters’ management: results from a multi-dimensional assessment”.

Submitted filename: 2021-10-11 Response letter.docx

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24 Nov 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

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Kind regards,

Robert Jeenchen Chen, MD, MPH

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PLOS ONE

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Reviewer #3: (No Response)

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Partly

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Reviewer #3: Yes

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Reviewer #3: Yes

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Reviewer #3: No

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Reviewer #3: The introduction, methods, results and discussion sections need to be reviewed and properly written in good English. The method section do not clearly explain the scenario 2.

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Reviewer #3: Yes: Henry Egi Aloh

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16 Dec 2021

Dear Dr. Henry Egi Aloh,

We thank you for the revisions made to our manuscript.

According to your kind suggestions, we confirm we have revised the entire manuscript to make it presented in an intelligible fashion and written in standard English.

In addition, we have clarified and better explained the investigated technological scenarios, with specific detailed for Scenario 1 and Scenario 2.

Scenario 1 refers to the adoption of a “PVCs standardized optimal procedure”, that is the one suggested and implemented in the hospitals referring to Liguria Region (Italy) where the analysis was conducted. Scenario 1 refers to the simultaneous use of three specific medical devices suggested by the main guidelines available on the topic (O’Grady et al., 2011; RCN, 2010; INS, 2016; Scales, 2008): ChloraPrep (disposable device used for skin antisepsis), Nexiva (innovative PVC, to be inserted), and Posiflush (disposable device to be used for staying “in situ” and for washing up the patients after the catheter removal). The use of ChloraPrep, implemented for skin preparation, would rapidly kill micro-organism, thus also maintaining the antimicrobial activity for at least 48 hours (Florman et al., 2007; Crosby et al., 2001), and leading to a decrease in PCV associated infections’ occurrence rate (Manoury et al., 2008; McCann et al., 2016). The PVC Nexiva, in the comparison with traditional cannula, incorporates a stabilization platform, which could significantly reduce the risks of developing complications, such as phlebitis, infiltration/extravasation and dislodgement (Bausone-Gazda et al., 2010; Van Zundert, 2005). Beside an increased safety profile for patients, the use of the PVC Nexiva would simultaneously offer protection to the healthcare professionals, in terms of reducing the risk of exposure associated with needlestick injury (Lee et al., 2005). Using Posiflush at the same time, would reduce catheter-related bloodstream infections, thus improving standards of practice for catheter maintenance and management (Can & Yan, 2012).

The use of all the above mentioned three devices, should also be integrated with the following targets activities, to guarantee the implementation of the clinical procedure, as requested by the most diffuse Italian and European Guidelines (O’Grady et al., 2011; RCN, 2010; INS, 2016; Scales, 2008): i) number of insertion attempts lower than four; ii) PVC replacement in 96 hours; and iii) number of washes higher or equal to the number of PVC insertion.

On the contrary, Scenario 2 (i.e., not being in a standardized optimal procedure) refers to the use of only one or two out of the three disposable medical devices (thus using different devices for antisepsis, insertion, and washing-up phases), with target activities missing.

For being clearer and more comprehensive, we have produced a table of synthesis of the two scenarios investigated that you could find in the response letter.

With best regards,

The Authors

Submitted filename: Response to Reviewer.docx

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18 Jan 2022

The implementation of a standardized optimal procedure for peripheral venous catheters’ management: results from a multi-dimensional assessment

PONE-D-21-00993R3

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Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: (No Response)

Reviewer #5: The implementation of a standardized optimal procedure for peripheral venous

catheters’ management: results from a multi-dimensional assessment

Manuscript Number: PONE-D-21-00993R3

The author has made substantial modification in this manuscript.

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Reviewer #4: No

Reviewer #5: No

20 Jan 2022

PONE-D-21-00993R3

The implementation of a standardized optimal procedure for peripheral venous catheters’ management: results from a multi-dimensional assessment

Dear Dr. Ferrario:

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