Test Soil and Material Affinity for Reusable Device Cleaning Validations.

While selecting the test variables for a cleaning validation for reusable medical devices, the manufacturer must provide a simulative and clinically representative challenge for the device. An appropriate challenge must be identified with care so as not to overchallenge the cleaning process by selecting the worst case for every variable, thus leading to an impossible validation or unrealistic processing requirements. To appropriately select the testing variables, an understanding of the challenge to the cleaning process is important. The relationship among device material, test soil, and application method was investigated by testing 140 variable combinations, including seven materials (stainless steel, polyoxymethylene, polyether ether ketone, nitinol, aluminum, titanium, and silicone), four test soils (defibrinated blood soil, coagulated blood, modified coagulated blood, and Miles soil), and five soil application methods (pipetting neat, pipetting spreader, painting, handling with soiled gloves, and immersion). Stainless steel was the only material that showed consistent soil application in a thickness (at ~6 µL/cm2) that fully covered the test surface without some element of pooling, cracking, flaking, or soil migration with all test soils and application methods. The data collected using solubility testing indicated that a complex relationship for material adherence may exist between device materials and test soil. Stainless steel was the most challenging material tested.

Effects of Time, Temperature, and Humidity on Soil Drying on Medical Devices.

In the healthcare environment, delays can occur that prevent reusable devices from being processed within the specified time outlined in manufacturers' instructions for use. It has been suggested in the literature and industry standards that residual soil components, such as proteins, may undergo a chemical change when they are exposed to heat or experience prolonged drying times under ambient conditions. However, little experimental data are available in the literature to document this change or how is may be addressed for cleaning efficacy. This study presents the effects of time and environmental conditions on contaminated instrumentation from the point of use until the cleaning process begins. It demonstrates that soil drying after a period of eight hours changes the solubility of the soil complex, with a significant change occurring after 72 hours. Temperature also contributes to chemical changes in protein. Although no significant difference occurred between 4°C and 22°C, temperatures greater than 22°C demonstrated a decrease in soil solubility in water. An increase in humidity prevented the soil from completely drying and prevented the chemical changes affecting solubility from occurring.

Chemical Changes Over Time Associated with Protein Drying.

Upon drying, physical changes of the characteristics of proteins are observed by coagulation, but the nature and chronology of these changes have not been well studied. Coagulation changes the structure of protein from liquid to a solid or a thicker liquid by heat, mechanical action, or acids. Changes may have implications regarding the cleanability of reusable medical devices; therefore, an understanding of the chemical phenomena associated with drying of proteins is essential to ensuring adequate cleaning and mitigation of retained surgical soils. Using a high-performance gel permeation chromatography analysis with right-angle light-scattering detector at 90°, it was demonstrated that as soils dry, the molecular weight distribution changes. From the experimental evidence, the molecular weight distribution trends over time with drying to higher values. This is interpreted as a combination of oligomerization, degradation, and entanglement. As water is removed through evaporation, the distance between proteins decreases and their interactions increase. Albumin will polymerize into higher-molecular-weight oligomers, decreasing its solubility. Mucin, commonly found in the gastrointestinal tract to prevent infection, will degrade in the presence of enzymes releasing low-molecular-weight polysaccharides and leaving behind a peptide chain. The research described in this article investigated this chemical change.

Improving Protein Assay Methods to More Accurately Assess Medical Device Cleanliness.

Protein assays commonly used to evaluate reusable device cleanliness do not always accurately measure the low concentrations of protein that are expected on reusable medical devices after processing. Methods often are adapted to provide an estimation of protein concentration; however, sensitivity issues in the portion of standard curves at the acceptance criteria of 6.4 µg/cm2 protein have been reported. Using analytical validation criteria, method improvements for the micro-bicinchoninic acid assay for protein residuals are demonstrated by incorporating a standard addition method, increasing the well volume, and changing the working reagent ratio. These improvements increased method sensitivity and accuracy in the reliable detection of protein levels for device cleaning validations.

Cleaning Challenges: Can Extended Soil Dry Times Be Reversed?

Background: Cleaning is essential to ensuring the safe processing of reusable medical devices, and most manufacturers' instructions for use (IFUs) specify that clinical soil should not be allowed to dry on devices. If soil is allowed to dry, the cleaning challenge could be increased due to change in soil solubility. As a result, an additional step could be needed to reverse the chemical changes and return a device to a state where cleaning instructions are appropriate. Methods: Using a solubility test method and surrogate medical devices, the experiment described in this article challenged eight remediation conditions to which a reusable medical device might be exposed if soil is dried on a device. These conditions included soaking with water or neutral pH, enzymatic, or alkaline detergent cleaning agents, as well as conditioning with an enzymatic humectant foam spray. Results: The results demonstrated that only the alkaline cleaning agent was able to solubilize the extensively dried soil as effectively as the control, with a 15-minute soak being as effective as a 60-minute soak. Discussion: Although opinions vary, the overall data demonstrating the risk and chemical changes that occur when soil dries on medical devices are limited. Further, in cases in which soil is allowed to dry on devices for an extended time outside of the guidance from leading practices and manufacturers' IFUs, what additional steps or processes may be necessary to ensure that cleaning can be effective? Conclusion: This experiment demonstrated the effectiveness of a soaking step with an alkaline cleaning agent as an additional step if soil is dried on reusable medical devices, thus reversing the effect of an extended soil dry time.

Validation of the Device Feature Approach for Reusable Medical Device Cleaning Evaluations.

The identification of worst-case device (or device set) features has been a well-established validation approach in many areas (e.g., terminal sterilization) for determining process effectiveness and requirements, including for reusable medical devices. A device feature approach for cleaning validations has many advantages, representing a more conservative approach compared with the alternative compendial method of testing the entirety of the device. By focusing on the device feature(s), the most challenging validation variables can be isolated to and studied at the most difficult-to-clean feature(s). The device feature approach can be used to develop a design feature database that can be used to design and validate device cleanliness. It can also be used to commensurately develop a quantitative cleaning classification system that will augment and innovate the effectiveness of the Spaulding classification for microbial risk reduction. The current study investigated this validation approach to verify the efficacy of device cleaning procedures and mitigate patient risk. This feature categorization approach will help to close the existing patient safety gap at the important interface between device manufacturers and healthcare facilities for the effective and reliable processing of reusable medical devices. A total of 56,000 flushes of the device features were conducted, highlighting the rigor associated with the validation. Generating information from design features as a critical control point for cleaning and microbiological quality will inform future digital transformation of the medical device industry and healthcare delivery, including automation.

Nucleus accumbens fast-spiking interneurons in motivational and addictive behaviors.

The development of drug addiction is associated with functional adaptations within the reward circuitry, within which the nucleus accumbens (NAc) is anatomically positioned as an interface between motivational salience and behavioral output. The functional output of NAc is profoundly altered after exposure to drugs of abuse, and some of the functional changes continue to evolve during drug abstinence, contributing to numerous emotional and motivational alterations related drug taking, seeking, and relapse. As in most brain regions, the functional output of NAc is critically dependent on the dynamic interaction between excitation and inhibition. One of the most prominent sources of inhibition within the NAc arises from fast-spiking interneurons (FSIs). Each NAc FSI innervates hundreds of principal neurons, and orchestrates population activity through its powerful and sustained feedforward inhibition. While the role of NAc FSIs in the context of drug addiction remains poorly understood, emerging evidence suggests that FSIs and FSI-mediated local circuits are key targets for drugs of abuse to tilt the functional output of NAc toward a motivational state favoring drug seeking and relapse. In this review, we discuss recent findings and our conceptualization about NAc FSI-mediated regulation of motivated and cocaine-induced behaviors. We hope that the conceptual framework proposed in this review may provide a useful guidance for ongoing and future studies to determine how FSIs influence the function of NAc and related reward circuits, ultimately leading to addictive behaviors.

Connecting Across Competencies: Leveraging Best Practices for Processing.

The AAMI working group ST/WG 93 is finalizing a standard (AAMI ST98) for the cleaning validation of reusable medical devices based on guidance from the technical information report AAMI TIR30:2011/(R)2016. A number of analytical best practices are being considered for this new standard. Test method suitability for processing cleaning validations historically has been established using one positive control and performing an extraction efficiency. The new cleaning validation standard is proposed to require a change from only one replicate test sample to three when performing method suitability. This change will affect manufacturers; therefore, the value of and consideration for performing these additional replicates requires explanation. This article discusses how variation of validation parameters can affect the accuracy and precision during method suitability testing. Multiple replicates are needed to understand the variability of method extraction and impact on cleaning validations of reusable medical devices.

Assessing Detergent Residuals for Reusable Device Cleaning Validations.

Cleaning chemistries are detergent-based formulations that are used during the processing of reusable medical devices. Manufacturers are responsible for demonstrating the safety of cleaning formulations when they are used during a device processing cycle, including the risk of device-associated cytotoxicity over the concentration ranges for recommended use and rinsing during cleaning. However, no regulation currently exists requiring manufacturers to demonstrate such safety. Although manufacturers' safety data sheets (SDSs) provide information on the safe use of chemicals for users, this information may not provide sufficient detail to determine the risks of residual chemicals on device surfaces. SDSs are not required to contain a comprehensive list of chemicals used, only those of risk to the user. They should be supplemented with information on the correct concentrations that should be used for cleaning, as well as instructions on the rinsing required to reduce the levels of chemicals to safe (nontoxic) levels prior to further processing. Supporting data, such as toxicity profiles or cytotoxicity data that support the instructions for use, would provide medical device manufacturers and healthcare personnel with the necessary information to make informed decisions about selection and correct use of detergents. In the current work, cytotoxicity profiles for eight commonly used cleaning formulations available internationally were studied. Although all of these products are indicated for use in the cleaning of reusable medical devices, results vary across the serial dilution curves and are not consistent among detergent types. The information presented here can be leveraged by both medical device manufacturers and processing department personnel to properly assess residual detergent risks during processing. This work also serves as a call to cleaning formulation manufacturers to provide this information for all chemistries.

Thermal Disinfection Validation: The Relationship Between A0 and Microbial Reduction.

Validating a thermal disinfection process for the processing of medical devices using moist heat via direct temperature monitoring is a conservative approach and has been established as the A0 method. Traditional use of disinfection challenge microorganisms and testing techniques, although widely used and applicable for chemical disinfection studies, do not provide as robust a challenge for testing the efficacy of a thermal disinfection process. Considerable research has been established in the literature to demonstrate the relationship between the thermal resistance of microorganisms to inactivation and the A0 method formula. The A0 method, therefore, should be used as the preferred method for validating a thermal disinfection process using moist heat.

Research: Dry Heat Processing of Single-Use Respirators and Surgical Masks.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has challenged healthcare providers in maintaining the supply of critical personal protective equipment, including single-use respirators and surgical masks. Single-use respirators and surgical masks can reduce risks from the inhalation of airborne particles and microbial contamination. The recent high-volume demand for single-use respirators and surgical masks has resulted in many healthcare facilities considering processing to address critical shortages. The dry heat process of 80°C (176°F) for two hours (120 min) has been confirmed to be an appropriate method for single-use respirator and surgical mask processing.

Mitochondrial genome analysis in penile carcinoma.

Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.

Breast cancer and sentinel lymph node micrometastases: indications for lymphadenectomy and literature review.

An increasingly early diagnosis for discovering breast cancer, an improvement of surgical procedures with refining techniques for research and study of sentinel node, currently allow a more conservative surgical approach. Association with suitable chemo-radiotherapy allows a good control of breast disease. Our study, although modest, was carried out on 63 patients suffering from breast cancer, who underwent surgical treatment with assessment of sentinel lymph node. Aim of study was to establish the most correct strategy in the presence of isolated tumor cells (ITC) and/or micro-metastases of sentinel lymph node. Many studies have been carried out to find which was the most appropriate treatment, nevertheless, in the absence of univocal guidelines, we prefer to proceed to axillary dissection, though the topic is very debated and controversial. Following this strategy we obtained quite satisfactory results.

Rapid Root Cause Analysis: Improving OBGYN Resident Exposure to Quality Improvement and Patient Safety Curricula.

Introduction Each year, millions of patients in the United States experience harm as a result of the healthcare they receive. One mechanism used by health systems to learn how and why errors occur is root cause analysis (RCA). RCA teams develop action plans to create and implement systemic changes in healthcare delivery in order to prevent future harm. The American Council on Graduate Medical Education (ACGME) recognizes the importance of analyzing adverse events, and it requires that all residents participate in real or simulated patient safety activities, such as RCAs. Often, institutional RCAs necessitate the assimilation of participants on short notice and demand considerable time investment, limiting the feasible participation of graduate medical education (GME) trainees. This presents a gap between ACGME expectations and the reality of resident involvement in patient safety activities. We present the first iteration of a quality improvement project encompassing a three-hour resident physician training course with simulated RCA-experiential learning. The purpose of this project was to produce a condensed, educational RCA experience that adequately trains all GME learners to serve as informed healthcare safety advocates while also satisfying ACGME requirements. Methods The course ("rapid RCA") was conducted during protected weekly academic training. All residents of the San Antonio Uniformed Services Health Education Consortium (SAUSHEC) Obstetrics and Gynecology (OBGYN) residency program who had not previously participated in a real or simulated RCA were required to take the "rapid RCA." Pre- and post-course surveys were completed anonymously to assess baseline knowledge, new knowledge gained from the course, and attitudes toward the course and its importance to resident training. Results Fourteen OBGYN residents attended the "rapid RCA," indicating that 64% (14 out of 22) of the program had no previous experience or opportunity to participate in a real or simulated RCA. Participation in the course demonstrated a significant gain of new knowledge with an increase from 0/14 to 10/14 (71%) residents correctly answering all pre- and post-course questions, respectively (p < 0.001). Additionally, on a Likert scale from 1 to 5, with 5 indicating "expert level," residents indicated they felt more comfortable on patient safety topics after taking the course (mean pre-course score 1.85 to post-course score 3.64, p < 0.001). All participants indicated they would prefer to take the "rapid RCA" as opposed to the only available local alternative option for a simulated RCA, currently offered as a full-day intensive course. Conclusion A meaningful increase in patient safety knowledge and attitudes toward topics covered in an RCA was demonstrated through the implementation of a "rapid RCA" in OBGYN residents. We plan to incorporate this into our annual curriculum to satisfy ACMGE requirements. This format could be adapted for other specialties as applicable.

Nomuraea rileyi as biological control agents of Rhipicephalus microplus tick.

Nomuraea rileyi, a fungus pathogenic to insects, has been widely used for biological control of agricultural pests in Brazil. This study investigates the effects of N. rileyi, isolates Nr 138, Nr 151, and Nr 177, to eggs, larvae, and engorged females of Rhipicephalus microplus tick. Specimens were immersed in 1 ml of conidial suspension for 3 min, whereas the control group was immersed in 0.01% Tween 80 water solution. The isolate Nr 138 controlled 67.37% of ticks when the highest conidial concentration was used, 10(8) conidia ml(-1). The isolate Nr 177 significantly reduced the percentage of hatch of larvae from eggs treated with 10(8) conidia ml(-1). Conversely, the isolate Nr 151 was not virulent to eggs, larvae, or adults. Variability in virulence was observed among the N. rileyi isolates investigated in the current study-Nr 138 was more virulent to engorged females, while Nr 177 was more virulent to unfed larvae. Although N. rileyi proved to be virulent to several stages of R. microplus, the results obtained in this study indicate that N. rileyi does not appear to be a remarkable biological control agent for R. microplus.

Vaccine regulation should require and enforce the inclusion of pregnant and breastfeeding women in prelicensure clinical trials.

Exclusion of pregnant and breastfeeding women from the pivotal randomized controlled trials for COVID-19 vaccines that led to emergency regulatory approval created gaps in data needed for vaccine policy, healthcare provider recommendations, and women's decisions about vaccination. We argue that such knowledge gaps increase potential for vaccine hesitancy and misinformation relating to the health of women and infants, and that these gaps in evidence are avoidable. Over several decades, ethical and scientific guidance, scholarship, and advocacy in favor of pregnant and breastfeeding women's participation in clinical development of vaccines has accumulated. Guidance on how to include pregnant and breastfeeding women in vaccine trials ethically and safely predates the COVID-19 pandemic but has yet to be routinely incorporated in vaccine development. We highlight the important role regulatory authorities could play in requiring that pregnant and breastfeeding women be eligible as volunteer participants in prelicensure vaccine trials for products that are expected to be used in this population. Inclusion of pregnant and breastfeeding populations in clinical trials leading to market approval or emergency use authorization should be undertaken early or concurrently at the time of trials in the general population.

Healthcare providers' interpretations of product labelling information developed through a consensus stakeholder approach.

BACKGROUND: The World Health Organization recommends immunization with inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. Yet, product labelling information for IIV and Tdap sends a different message. In a previous study, we developed evidence-based statements about vaccination in pregnancy that could be included in product information. This study compares healthcare providers' perceptions of the revised statements to those currently used in vaccine product labelling information. METHODS: A 30-item online survey with qualitative and quantitative components was distributed to Canadian maternal healthcare providers via professional organizations and public health. Participants read excerpts from revised and existing IIV and Tdap product labelling information and answered questions about how they perceived the safety and effectiveness of the vaccines, whether they would recommend each vaccine during pregnancy, and which statements they preferred. RESULTS: From June to August 2018, 449 healthcare providers completed the survey, including physicians (45%), nurses (24%), midwives (27%) and others (5%). Most participants perceived the vaccines to be safe and effective based on the revised statements. Over twice as many participants said they would recommend the IIV and Tdap vaccines in pregnancy based on the revised rather than the existing statements (64% versus 21% for IIV and 63% versus 27% for Tdap). Most participants selected that the revised statements better explained the risks and benefits of vaccination in pregnancy (65% versus 21% for IIV; 51% versus 27% for Tdap). Qualitative comments highlighted the strengths of the revised statements and areas for improvement. CONCLUSIONS: The majority of participants demonstrated preferences for the revised IIV and Tdap product label statements over the existing statements. Comments suggested the revised statements include improvements to the evidence-base and readability. Involving stakeholders improved the development of product labelling information, but further improvement is needed to support the evidence-based use of vaccines in pregnancy.