Formal Risk Assessment Research Articles

Establishing robust infection control at a new hospital: the AIIMS Rajkot experience

The establishment of robust infection control practices is crucial in any new healthcare facility to ensure patient safety and prevent healthcare-associated infections (HAIs). All India Institute of Medical Sciences (AIIMS) Rajkot, a newly inaugurated medical institution in Western India, faced the significant challenge of implementing these practices from the ground up, beginning with its Outpatient Department services initiation on 31 December 2021. The AIIMS Rajkot initiated its infection control program by forming a Hospital Infection Control Committee and appointing dedicated Infection Control Officers and Infection Control Nurses. This initiative was supported by comprehensive training programs, the implementation of advanced infection control measures such as bundle care, HAI surveillance, and the development of outbreak investigation teams. Furthermore, the hospital focused on the continuous improvement of these practices through routine audits and the use of a digital Infection Control Risk Assessment form. The institution successfully integrated a structured infection control framework that includes rigorous training sessions, the implementation of a Hospital Infection Control Manual, and the establishment of a robust needle stick injury management team. These measures have led to improved compliance with infection prevention protocols, as evidenced by hand hygiene audits and reduced incidence of HAIs. The journey of establishing infection control practices at AIIMS Rajkot highlights the importance of a structured approach in new healthcare settings. The successful integration of these practices not only enhances patient and staff safety but also sets a standard for future healthcare facilities. The AIIMS Rajkot’s proactive measures and continuous improvement efforts serve as a model for effectively addressing the challenges of infection control in a dynamic healthcare environment.

Pericoronary adipose tissue feature analysis in computed tomography calcium score images in comparison to coronary computed tomography angiography.

We investigated the feasibility and advantages of using non-contrast CT calcium score (CTCS) images to assess pericoronary adipose tissue (PCAT) and its association with major adverse cardiovascular events (MACE). PCAT features from coronary computed tomography angiography (CCTA) have been shown to be associated with cardiovascular risk but are potentially confounded by iodine. If PCAT in CTCS images can be similarly analyzed, it would avoid this issue and enable its inclusion in formal risk assessment from readily available, low-cost CTCS images. To identify coronaries in CTCS images that have subtle visual evidence of vessels, we registered CTCS with paired CCTA images having coronary labels. We developed an "axial-disk" method giving regions for analyzing PCAT features in three main coronary arteries. We analyzed hand-crafted and radiomic features using univariate and multivariate logistic regression prediction of MACE and compared results against those from CCTA. Registration accuracy was sufficient to enable the identification of PCAT regions in CTCS images. Motion or beam hardening artifacts were often prevalent in "high-contrast" CCTA but not CTCS. Mean HU and volume were increased in both CTCS and CCTA for the MACE group. There were significant positive correlations between some CTCS and CCTA features, suggesting that similar characteristics were obtained. Using hand-crafted/radiomics from CTCS and CCTA, AUCs were 0.83/0.79 and 0.83/0.77, respectively, whereas Agatston gave AUC = 0.73. Preliminarily, PCAT features can be assessed from three main coronary arteries in non-contrast CTCS images with performance characteristics that are at the very least comparable to CCTA.

Tree risk and hazard assessment at UMK-Tropical Rainforest Research Centre (UMK-TRaCe), Pulau Banding, Perak, Malaysia

Abstract The UMK-Tropical Rainforest Research Centre (UMK-TRaCe) in Pulau Banding, Perak, Malaysia, is an environmentally sensitive research facility that aims to integrate technology with nature. However, certain tree components have resulted in harm to the buildings and infrastructure within the center. This study presents a comprehensive tree risk assessment conducted at UMK-TRaCe using the standardized ISA Basic Tree Risk and Hazard Assessment Form. The assessment evaluated all 37 individual trees surrounding the facilities area comprising 19 species from 15 families, analyzing various parameters such as site factors, tree health, species proKile, load factors, tree defects, and conditions affecting the likelihood of failure and risk categorization using a standardized survey form of the International Society of Arboriculture (ISA). The results show that 24.3% of the trees (9 trees) fall under the category of potential tree risk hazard, while 43.2% (16 trees) are considered low risk. Notably, 21.6% (8 trees) are classiKied as high-risk, with Alstonia scholaris identiKied as the most hazardous and high-risk tree. These Kindings hold signiKicant importance for the management of UMK-TRaCe, as they provide valuable insights for planning and maintaining the health of trees, as well as ensuring the safety of the surrounding environment. The study recommends the implementation of a comprehensive tree risk management plan, including regular monitoring, targeted maintenance, and, if necessary, the removal or replacement of high-risk trees. By addressing tree risks, UMK-TRaCe can continue to serve as a guardian of the forest while ensuring the safety and well-being of its visitors and infrastructure.

Patient Positional Uncertainty and Margin Reduction in Lung Stereotactic Ablative Radiation Therapy Using Pneumatic Abdominal Compression.

Motion management presents a significant challenge in thoracic stereotactic ablative radiation therapy (SABR). Currently, a 5.0-mm standard planning target volume (PTV) margin is widely used to ensure adequate dose to the tumor. Considering recent advancements in tumor localization and motion management, there is merit to reassessing the necessary PTV margins for modern techniques. This work presents a large-scale analysis of intrafraction repositioning for lung SABR under forced shallow breathing to determine the margin requirements for modern delivery techniques. Treatment data for 124 lung SABR patients treated in 607 fractions on a linear accelerator were retrospectively collected for analysis. All patients were treated using pneumatic abdominal compression and intrafraction 4-dimensional (4D) cone beam computed tomography (4D CBCT)-guided repositioning halfway through treatment. Executed repositioning shifts were collected and used to calculate margin requirements using the 2-SD method and an analytical model which accounts for systematic and random errors in treatment. A total of 85.7% of treated fractions had 3-dimensional repositioning shifts under 5.0 mm. Fifty-three fractions (8.7%) had shifts ≥ 5.0 mm in at least 1 direction. Margins in the right-left, inferior-superior, and posterior-anterior directions were 3.62 mm, 4.34 mm, and 3.50 mm, respectively, calculated using the 2-SD method. The analytical approach estimated that 4.01 mm, 4.37 mm, and 3.95 mm margins were appropriate for our workflow. Executing intrafraction repositioning reduced margin requirements by 0.73 ± 0.07 mm. Clinical data suggest that the uniform 5.0-mm margin is conservative for our workflow. Using modern techniques such as 4D CT, 4D CBCT, and effective motion management can significantly reduce required margins, and therefore necessary healthy tissue dose. However, the limitations of margin calculation models must be considered, and margin reduction must be approached with caution. Users should conduct a formal risk assessment prior to adopting new standard PTV margins.

Kaiser model-based hazard vulnerability analysis in event risk assessment and emergency management of operating room in a hospital in China.

This study aimed to identify the high-risk events in the operating room so as to provide a decision-making basis for emergency management. The Kaiser model-based Hazard vulnerability analysis (HVA) was used to determine the risk matrix. The Delphi method was used to create the risk assessment form. The potential risk events were quantitatively evaluated. The relative risk percentages of the risk events were calculated to identify the top high-risk events. A risk matrix containing 4 components (natural disasters; technological hazards; human hazards; and hazardous materials) was determined, and a risk assessment form was created using the Delphi method. The top three high-risk events are as follows: internal radiation exposure (41%), infectious disease outbreaks (38%), and internal fires (33%). The emergency management measures for high-risk events were developed. The Kaiser model-based HVA in event risk assessment of operating room can effectively identify potential high-risk events, determine emergency priorities, and optimize resource allocation, thereby ensuring the quality and safety of surgical treatment.

Knowledge, Attitudes, and Practice of Master Nursing Specialist Students Toward Catheter-Related Thrombosis: A Cross-Sectional Study.

Evaluating Master of Nursing Specialist (MNS) students' knowledge, attitudes, and practice regarding catheter-related thrombosis (CRT) prevention and treatment is beneficial in developing effective CRT training for them. This study thus aimed to explore their knowledge, attitudes, and practice toward CRT. This was a cross-sectional study that included 1046 MNS students in China. The results revealed that the median scores for the participants' knowledge, attitudes, and practice were 12 (interquartile range: 9-14), 55 (interquartile range: 50-65), and 62 (interquartile range: 51-71), respectively. There was a positive correlation between knowledge and attitudes, as well as attitudes and practice. Age, school level, proactively learning CRT knowledge, gender, enrolment method, participation in clinical practice time, and attendance at CRT training were related to knowledge (p < 0.05). Attendance at CRT training and experience using thrombosis risk assessment forms were related to attitude and practice (p < 0.05). Gender and experience caring for CRT patients were associated with practice (p < 0.05). MNS students have insufficient knowledge of CRT prevention and treatment, and the practice needs to be improved. However, their attitudes are positive.

Risk Assessment of Diabetes Using Diabetes Mellitus Risk Assessment form among Population of Kothanavadi Village Chamarajanagra District

Risk Assessment of Diabetes Using Diabetes Mellitus Risk Assessment form among Population of Kothanavadi Village Chamarajanagra District

An Approach to a Priori Assessment of Fuzzy Classification Models in Monitoring Tasks

The article addresses the problems of using automation tools to perform monitoring and management tasks applicable to assessing the quality of fuzzy classification models, where the classification procedure is implemented on the basis of knowledge (rules) in the absence of the training set. An approach is proposed to obtain a priori assessments of the classification quality based on the study of the used model sensitivity to changes in the values of internal parameters during the corresponding modeling. The interpretation of the modeling results in the form of risk assessment caused by the self-imperfection of the classification models is obtained. The article provides an example of a fuzzy classification model based on a comparison of the current state of a monitoring object described using fuzzy features with a set of predefined typical states, which form corresponding fuzzy equal (close) states (monitoring situations). The comparison is carried out using the fuzzy implication operation provided that the required reliability is met. The example of this model demonstrates how the type of implication operation, as well as the internal features of the model, affect the results of classification, and appropriate indicators are proposed, which are both an interpretation of generally accepted indicators for assessing the classification quality, and unique, inherent in the considered model. Computational experiments were carried out, which made it possible to obtain graphs of changes in classification quality assessment indicators for the considered model and its modification and visualize the influence of internal parameters of the model on the results of its application. A number of indicators are proposed that allow for an a priori assessment of the risks arising from the application of the model before its actual application.

Cross-contamination Risk Assessment using FMEA tool

In pharmaceutical manufacturing facilities, products with different therapeutic properties and potencies are manufactured in shared spaces, which poses a potential risk for cross-contamination. During the manufacturing process, cross-contamination may occur due to the uncontrolled release of dust, gases/vapors, mix-ups with other materials, residues on equipment, and contamination from operator’s clothing. By implementing adequate facility design and manufacturing operations aligned with Quality Risk Management principles, the risk of cross-contamination can be controlled. If a shared facility is used for manufacturing pharmaceutical products, strategic controls for identifying and managing the risks of cross-contamination should be in place. This article provides a structured and systematic framework for the risk-based identification of the worst-case product and manufacturing process among the products manufactured in the solid oral facility, addressing the high risk of cross-contamination. Keywords: Cross-contamination, Contamination, Risk Assessment, Formal risk assessment, Quality Risk Management (QRM), Failure Mode Effect Analysis (FMEA), Oral Solid Dosage (OSD), Worst case, Contamination Control Strategies (CCS)

EP349 - Use of Pre-operative Risk and Frailty Assessment in patients undergoing Emergency Laparotomy

Abstract Aims Formal preoperative assessment of risk of complications and death in all patients undergoing Emergency Laparotomy is recommended by NELA (National Emergency Laparotomy Audit) in the UK. In addition, frailty assessment in patients who are 65years or older and frail undergoing Emergency Laparotomy is also recommended. In a previous 2018 audit, we had recorded Preoperative Mortality Risk in 77% patients undergoing Emergency Laparotomy and Frailty was not part of our assessment in these patients. In this audit our aim was to evaluate documentation of preoperative frailty and risk assessment in patients undergoing Emergency Laparotomy from 2019 to 2023. Methods Details of all patients who underwent Emergency Laparotomy at a University Hospital under care of one surgical team between January 2019 and December 2023 were obtained from theatre logbooks. Patient notes were retrospectively reviewed to see if frailty assessment and preoperative risk assessment scores were recorded. This data was collected and analyzed using Microsoft Excel. Results During this period, sixty-seven patients were identified. The median age was sixty-seven with an age range from four to ninety-one. Of these 38 (57%) were females. A preoperative p-possum score was documented in 59 (88.1%), 39 (58.2%) patients were 65 years or older of these 26 (66.7%) had frailty assessment carried out. Conclusions Our data suggests that we have over time made progress in the use of Perioperative Risk assessment scores and incorporated frailty assessment in our perioperative practice in patient’s undergoing Emergency Laparotomy. However there remains room for improvement.

EP465 - Transfusion Associated Circulatory Overload (TACO) Audit - A prospective analysis of adherence to standards ensuring safe transfusions

Abstract Aims TACO is defined as acute or worsening respiratory compromise during or up to 12 hours of transfusion, with additional features including cardiovascular system changes not explained by the patient’s underlying medical condition. In the UK, TACO remains a major cause of Morbidity in surgical post operative patients. The aim of this audit was to assess whether the current trust transfusion practices are synchronous with the NICE guidelines and SHOT recommendations. Methods We reviewed 27 incidences of transfusion during the whole month in acute general surgical ward. Patient’s notes, trust intranet and EPMA were used for data collection. The adherence to Ng24 as well as latest SHOT recommendations was checked. Following standards were taken into account: A formal pre-transfusion risk assessment for transfusion-associated circulatory overload (TACO) should be undertaken for all patients receiving blood transfusion and mitigating actions taken. (Serious hazards of transfusion SHOT recommendation) Patients who develop respiratory distress during or up to 24 hours following transfusion where transfusion is suspected to be the cause must be reported to SHOT. A structured incident review should be undertaken for every case of TACO. Weight-adjusted red cell dosing should be used. (NICE Guidelines Ng24) Result TACO assessment checklist was only completed for 15% of transfusions (compared to 35% nationally) while mitigation actions were only considered for 4% of patients. There appeared discordance among junior doctors regarding TACO Management. Conclusions Interventions like teaching sessions, information leaflets and posters, presentation for induction pack and liaison with Transfusion practitioner team to modify transfusion pathway significantly reduced inconsistencies regarding safe transfusions and immensely improved patient management.

Understanding Musculoskeletal Risks in Retail Workers: An Ergonomic Assessment of Store 24H

Musculoskeletal disorders (MSDs) are prevalent in retail environments, often resulting from repetitive tasks, awkward postures, and prolonged standing. This study examined musculoskeletal discomfort and ergonomic risk factors within the retail environment of convenience stores, focusing on the prevalence of MSDs among employees of Store 24H, Dungun, Terengganu, Malaysia. The assessment began with a job task description, followed by workplace observation and worker input. Utilising a systematic approach, the research integrated two standardized assessment tools; the Cornell Musculoskeletal Questionnaire (CMQ) and the Initial Ergonomic Risk Assessment (ERA) Form Checklist, to identify the discomfort area and ergonomic risk factors associated with job tasks. Three job tasks were identified in the Store 24H environment; operating cash registers, customer service and restocking. The findings indicate a notable prevalence of MSDs associated with the identified high-risk tasks. Repetitive motions, awkward postures, prolonged standing, and forceful exertion were observed as primary ergonomic risk factors for these tasks which contribute to musculoskeletal discomfort in the neck, shoulder, back, hip, and knee. Additionally, forceful exertion and vibration exhibit high risks towards restocking tasks, resulting in restocking as the top contributor towards the MSDs. Hence, the findings highlight the need for advanced ERA and mitigation strategies, including workstation redesign, task rotation, ergonomic training and accessories, to promote employee well-being and reduce the incidence of MSDs among employees of Store 24H. Implementing these measures is essential for promoting the health and well-being of employees, decreasing the occurrence of musculoskeletal disorders, and improving overall safety and productivity in the workplace.

Genetic Counselors' attitudes & perceptions regarding suicide risk assessment and identification in practice.

While the heritability of suicidal tendencies is debated, receipt of various genetic diagnoses has shown an increased risk of suicidal ideation and behavior while simultaneously conferring risk to mental health concerns that may further increase this risk. However, the role of genetic counselors (GCs) in assessing and addressing suicide risk remains underutilized. A 15-item recruitment survey was distributed via the National Society of Genetic Counselors Student Research Survey Listserv, and interested individuals could opt to be contacted for an interview after completion. The data analysis included 107 survey responses and 15 semi-structured interviews, which were conducted to explore whether GCs feel that formal suicide risk assessment (SRA) falls within their scope of practice and the frequency with which it is employed during counseling sessions. Additionally, the study examined GCs' experiences, comfort levels, and training in assessing for suicide risk. All interviews were transcribed verbatim and independently coded by two researchers. The coding scheme was systematically constructed, integrating both deductive and inductive coding methods to inform the authors' interpretive description of SRA in the clinic, with four major themes identified by content analysis. Most respondents reported that they had worried about a patient harming themselves or having suicidal thoughts. Most respondents agreed or strongly agreed that SRA is within a GC's scope of practice. Lack of training emerged as the primary barrier to assessing suicide risk and conducting risk assessments. Other barriers included low self-efficacy, societal stigma, and personal discomfort, while access to social workers, natural inclination, and standardized screening tools served as facilitators. Despite encountering patients at risk of self-harm and suicide, most GCs do not utilize SRA tools. Furthermore, GCs expressed a strong desire for additional training to enhance their skills in identifying and managing at-risk patients. A multifocal approach to suicide risk reduction and education is required.

Application of Analytical Quality by Design to the development and validation of reduced and non-reduced capillary electrophoresis analytical procedures for mAb purity determination

Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) is a common analytical procedure used to quantitate critical quality attributes relating to the purity and glycosylation of monoclonal antibodies (mAbs). In this study, the application of an Analytical Quality by Design framework incorporating Design of Experiments was used to develop and validate both non-reduced (CE-NR) and reduced (CE-R) versions of this analytical procedure. Formal risk assessments were used to identify critical method attributes for optimization based on their potential impacts to performance criteria outlined in an analytical target profile. The resulting response surfaces connecting these critical factors to method performance were then utilized to generate a harmonized procedure to reduce execution risk across CE-R and CE-NR applications. Validation of these procedures according to regulatory guidelines support that they meet their required performance criteria, and a multivariate assessment of procedure robustness indicates that method parameters are in a sufficient state of control to ensure appropriate quantitation of mAb quality. Overall, this study demonstrates the utility of adopting an Analytical Quality by Design framework to leverage multidimensional knowledge from multiple critical method parameters to ensure an analytical procedure is fit-for-purpose.

524 Outcomes From Preoperative Risk Scoring for Emergency Laparotomy

Abstract Aim Risk scoring systems can be used to predict outcome, facilitate perioperative decision making and guide management in emergency laparotomy (EL). This study aims to evaluate the differences in outcome between EL patients who were prospectively risk assessed and those who were not. Method A retrospective study was conducted on all 782 patients aged over 18 years who underwent EL at four Australian hospitals between 1 January 2018 and 31 December 2019. Data recorded included demographics, preoperative risk assessment, case urgency, involvement of anaesthetic and intensive care consultants, critical care bed requirement, mortality, and discharge destination. NELA scores were retrospectively calculated for all patients. Results 209 patients had been preoperatively risk assessed, with a mean NELA score of 16.45%, compared to 8.72% for those who were not preoperatively risk assessed. They tended towards a higher ASA score, were booked as a higher urgency operation, and were more likely to receive consultant led care by anaesthetics and intensivists. Postoperatively these patients had increased critical care bed utilisation, 30-day mortality was 14.4% compared to 5.8%, and by 365 days mortality rose to 24.9% compared to 13.8%. Conclusions Use of preoperative risk prediction scores does not in itself reduce risk of mortality. In a health system that does not mandate formal preoperative risk assessment, it appears that clinicians use preoperative risk assessment tools when they perceive risk to be higher, rather than as a routine part of emergency laparotomy care.

Development of a Preoperative Screening Tool to Reduce Morbidity and Mortality of COVID-19-positive Hepatobiliary Patients

PurposeThis study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality. DesignBased on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients. MethodsA preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery. FindingsThe experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators. ConclusionsThe preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

The role of intuition in social work practice: differing understandings and attitudes

ABSTRACT There has been a long debate about the use of intuition in helping professions, including social work. Often viewed negatively in professional contexts, intuition is nonetheless used as a form of risk assessment. The current research examined methods of identifying child sexual abuse. A mixed methods approach was taken, with 98 participants completing an online questionnaire and 24 taking part in in-depth interviews. The participants demonstrated varied perceptions of intuition and its usefulness. Although some participants were strongly critical of its use, for others, intuition or ‘gut feelings’ were preferred to formal assessment tools. However, what was discussed as intuition, rather than a form of ‘sixth sense’, was often based on tacit knowledge; for example, abused young people’s observable behaviours combined with known risk factors such as certain family characteristics. Therefore, concerns about the use of intuition may be based on incorrect assumptions.

Communicating cardiovascular health information and improving coordination with primary care: A Childhood Cancer Survivor Study randomized trial.

10011 Background: Childhood cancer survivors are at risk of early cardiovascular disease (CVD). We conducted a survivorship care plan (SCP)-based counseling intervention to improve CVD risk factor control in adult-aged survivors. Methods: Randomized (1:1) trial of survivors at high CVD risk based on history of anthracycline or chest radiotherapy exposures with undertreated hypertension (≥130/80 mmHg), dyslipidemia (LDL ≥160 mg/dL or triglyceride ≥200 mg/dL), and/or glucose intolerance (threshold varied if history of pre-diabetes or diabetes) based on in-home testing. Approximating a survivorship clinic visit, the intervention consisted of a remotely delivered session with an advanced practice provider to review results, a SCP with personalized CVD risk information, and an action plan to help manage CVD risk factors. A remote booster session was provided 4 months later with the action plan updated. Control participants only received a copy of their in-home results with abnormalities noted and written encouragement to follow-up with their primary care provider (PCP). Blood pressure, lipid profile, and glucose tolerance were retested after 1y. For both groups, all participant materials were sent to PCPs throughout the study, and PCP medical records were abstracted at study completion. Logistic regression assessed the odds ratio (OR) for undertreatment at 1y associated with the intervention, adjusting for pre-specified variables (sex, current age, time since cancer, insurance status, recent history of survivorship clinic visit, and undertreated CVD risk factor). Results: Among 644 survivors who completed in-home testing, 347 met inclusion criteria and were randomized (175 intervention; overall 52% male, mean age 40y, 31y since cancer diagnosis); 264 with 1y follow-up (126 intervention). At baseline, rates of hypertension, dyslipidemia, and glucose intolerance were 53%, 52%, and 49%, respectively; 43% had &gt; 1 undertreated condition. Although the intervention achieved &gt; 95% satisfaction, it was not associated with reduced undertreatment vs control (OR 0.9, 95% CI 0.7-1.3). Notably, 48% of intervention and 44% of control participants had less undertreatment after 1y. In secondary analysis, greater internal locus of control was associated with less undertreatment at 1y (OR 0.7, 95% CI 0.6-0.9). The intervention group was more likely than controls to have CVD risk (+10 vs -1%), SCP (+17 vs -2%), and some late effects surveillance plan (+8 vs +2%) documented within PCP records at 1y vs baseline (p &lt; 0.05 for all). Conclusions: While a remotely delivered counseling intervention did not reduce CVD risk factor undertreatment compared with provision of test results alone, both study arms had &gt; 40% reduction in undertreatment. These results suggest that simply providing a formal CVD risk assessment to high-risk cancer survivors and their PCPs may be effective. Clinical trial information: NCT03104543 .

Insulin Resistance in Systemic Lupus Erythematosus

The objective: to analyze the frequency of insulin resistance (IR) in patients with systemic lupus erythematosus (SLE), study of traditional and rheumatic disease-related risk factors for the development of IR, assessment of the possibility of using of Finnish Type 2 Diabetes Risk Assessment Form (FINDRISC) to detect IR. Materials and methods. 58 patients with SLE (53 women and 5 men) without diabetes mellitus (DM) and hyperglycemia were included in the one-time study. The patients have received the inpatient treatment at the regional medical and diagnostic center of the communal enterprise “Poltava Regional Clinical Hospital named after M. V. Sklifosofsky PRC” in 2020-2023. The average age of patients was 38 [28; 43] years, the average duration of the disease is 4.0 [0.6; 6.0] years. 49 (85%) patients received glucocorticoids (GC), 20 (34%) – hydroxychloroquine, 26 (45%) – immunosuppressants, 2 (3%) persons received biological drugs. In all patients fasting glucose and insulin levels were determined, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. The value of the HOMA-IR index ≥2.77 corresponded to the presence of IR. Traditional risk factors for type 2 DM and the risk of its development in the next 10 years in patients with SLE were assessed using the FINDRISC questionnaire. Results. IR was determined in 14 (24%) of 58 patients with SLE. The average value of the HOMA-IR index was 1.8 [1.3; 2,6]. The data of patients with and without IR were similar in terms of sex, age, duration and activity of SLE, therapy performed at the time of examination, frequency of traditional risk factors for type 2 DM. Body mass index (BMI), waist circumference (WC), and insulin concentration were higher in patients with IR. The HOMA-IR index was correlated with BMI (r=0.7; p&lt;0.001), WC (r=0.6; p&lt;0.001), risk categories for the development of type 2 diabetes according to FINDRISС (r=0.4; p=0.04), the SLEDAI-2K index (r=–0.3; p&lt;0.02), the serum concentration of C3 complement (r=0.4; p=0.035) and the duration of GC therapy (r=0.4; p=0.02). Conclusions. IR was diagnosed in 24% of patients with SLE without a history of DM and with a normal fasting venous blood glucose level. The HOMA-IR index increased as SLE activity decreased and the duration of GC treatment increased. However, the development of IR was statistically significantly associated only with an increase in BMI and WC. The use of the FINDRISC questionnaire, which allows to assess the risk of developing type 2 DM in the general population, did not help to detect IR in patients with SLE.

Analytical Quality by Design as applied to the development of a SEC-HPLC platform procedure for the determination of monoclonal antibody purity without mobile phase additives

This work presents the application of AQbD principles to the development of a size exclusion chromatography (SEC) HPLC procedure for the determination of monoclonal antibody (mAb) product purity using state-of-the-art column technology available via the Waters™ XBridge Premier Protein SEC column. Analytical Quality by Design (AQbD) emphasizes a systematic, risk-based lifecycle approach to analytical procedure development based on sound statistical methodologies. It has recently become increasingly recommended by regulatory agencies as a response to the need for greater efficiency, improved reliability, and increased robustness among modern analytical procedures in the pharmaceutical industry. Use of an Analytical Target Profile (ATP) and formal risk assessments informed the application of Design of Experiments (DoE) to optimize this analytical procedure, as well as assess its robustness and ruggedness. Importantly, our ruggedness results demonstrated the transferability of this procedure between two laboratories within the Catalent Biologics Global Network. Application of this analytical procedure as a platform approach for evaluating mAb purity is expected to support expedited, first-in-human timelines of mAb molecules by enabling great quantitative performance with simple mobile phase buffer compositions. Taken together, this case study demonstrates the utility of adopting AQbD principles in analytical procedure development.