Can natural language processing be effectively applied for audit data analysis in gynaecological oncology at a UK cancer centre?

BACKGROUND: The British Gynaecological Cancer Society (BGCS) has highlighted the disparity of ovarian cancer outcomes in the UK compared to other European countries. Therefore, cancer quality assurance audits and subspecialty training are important in improving the UK standard of care for these patients. The current workforce crisis afflicting the NHS creates difficulty in dedicating teams of clinicians to these audits. We present a single institution study to evaluate if NLP-generated code can improve the efficiency of ovarian cancer and subspeciality reaccreditations audits. We used the chat bot Google Bard to write Visual Basic Applications algorithms that utilise Excel files from electronic health records. METHODS: Primary ovarian cancer data from 2019 to 2022 was retrospectively collected from the Cambridge University Hospital electronic health records. The surgical subspecialty reaccreditation audit analysed the 2022 surgical database. A modular coding approach with Google Bard was applied to generate audit algorithms. The time to complete these current audits was compared against the 2016 ovarian cancer and 2020 subspeciality reaccreditation audits. RESULTS: The previous ovarian cancer audit conducted in 2016 required 3 clinicians for the 135 cases and data collection required 1800 min. Data analysis was completed in 300 min. The current ovarian cancer audit allocated 2 clinicians to the 600 surgical cases. Data collection was completed in 3120 min, 3360 min for code development and 720 min for testing. The 2020 subspecialty reaccreditation audit was completed in 360 min. The 2022 subspecialty reaccreditation audit was completed in 1680 min, with 960 min for code development, 240 for debugging and 480 min for testing. CONCLUSION: We have demonstrated that NLP-generated code can significantly increase the efficiency of surgical quality assurance audits by eliminating the need for manual data analysis. With the current trajectory of NLP development, increasingly complex algorithms can be developed with minimal programming knowledge.

Neo-adjuvant chemotherapy does not reduce surgical complexity nor the accuracy of intra-operative visual assessment of disease in advanced ovarian cancer.

AIM: Compare the surgical complexity and histological accuracy of visual inspection of disease in patients undergoing primary debulking (PDS) versus delayed debulking surgery (DDS) following neo-adjuvant chemotherapy (NACT) for advanced ovarian cancer (AOC). MATERIALS AND METHODS: All patients undergoing PDS or DDS for stage III / IV AOC at a UK cancer centre between January 2014-October 2021 were included. Retrospective data was collected accessing an electronic gynaecological oncology database, operation and histology records. Comparative frequencies of surgical procedures performed were calculated for primary versus delayed cohorts; and correlation between intra-operative suspicion of disease and specimen histology at PDS and DDS compared. RESULTS: N=232. PDS was performed in 45.3% and DDS in 54.7% of patients; achieving complete cytoreduction in 77.2%. Appendicectomy, pelvic and para-aortic nodal dissection were undertaken significantly more often at primary surgery; whilst right diaphragm stripping, pelvic peritonectomy, splenectomy and cholecystectomy were more likely following NACT. We found no variation in bowel resection rates between cohorts. For the majority of specimens, there was no difference in correlation between intra-operative suspicion of disease and final histopathology - with a significantly lower positive predictive value for visual assessment demonstrated only for liver capsule and pelvic peritoneum at DDS. CONCLUSION: NACT does not appear to reduce the complexity of surgery, including rates of bowel resection; nor accuracy of intra-operative visual assessment of disease. We therefore caution against both deferring to NACT to facilitate less radical delayed debulking; and any presumption that macroscopically abnormal tissue at DDS may represent inert post-NACT 'burn-out', mitigating indication for excision. We instead suggest reservation of the neo-adjuvant pathway for patients with poor PS and radiologically-confirmed surgical stopping points; and advocate equivalent and maximal cytoreductive effort to remove all visibly abnormal tissue in both the upfront and delayed surgical settings.

A cross-sectional follow-up study of physical activity in adults with moderate and severe haemophilia.

AIM: To conduct a cross-sectional follow-up assessment of physical activity (PA) in people with moderate and severe haemophilia (PwMSH) from the Irish Personalised Approach to the Treatment of Haemophilia (iPATH) study. METHODS: Between June-December 2021, participants' PA was measured over one week using accelerometery, and was compared with their previously measured data from the original iPATH assessment. Self-awareness of PA and the impact of the Covid-19 pandemic on PA, pain, mobility and function were retrospectively examined using a survey. RESULTS: Of 30 participants who returned surveys [n = 19, severe (FVIII, <.01 IU/mL); n = 4, moderate (FVIII, .01-.05 IU/mL); n = 7, severe (FIX, <.01 IU/mL); age: 47 (36, 55) years], 28 completed accelerometery (follow-up time: 3 years). There were no significant differences in accelerometer PA (all p > .05), but achievement of World Health Organisation guidelines increased (67.9%-75.0%; p = .646). Increased self-awareness of PA was reported by 76.7%, and 66.7% reported desires to become more physically active. Compared to normal, most reported either no differences or lower levels of PA during lockdown restrictions. Self-reported PA increased for most when restrictions eased from April 2021 onwards. Beyond the pandemic, concerns included pain and access to exercise resources. CONCLUSION: Self-reported PA throughout the pandemic was variable, whilst there were no significant differences in objectively measured PA between assessment periods, despite reports of increased self-awareness and desires to be physically active at follow-up. Further qualitative research is needed to design personalised PA and health interventions, capturing perspectives of patients, their families, and multi-disciplinary haemophilia healthcare providers.

Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor.

BACKGROUND: Previous studies have reported marked interindividual variation in factor VIII (FVIII) clearance in patients with hemophilia (PWH) and proposed a number of factors that influence this heterogeneity. OBJECTIVES: To investigate the importance of the clearance rates of endogenous von Willebrand factor (VWF) compared with those of other FVIII half-life modifiers in adult PWH. METHODS: The half-life of recombinant FVIII was determined in a cohort of 61 adult PWH. A range of reported modifiers of FVIII clearance was assessed (including plasma VWF:antigen and VWF propeptide levels; VWF-FVIII binding capacity; ABO blood group; and nonneutralizing anti-FVIII antibodies). The FVIII-binding region of the VWF gene was sequenced. Finally, the effects of variation in FVIII half-life on clinical phenotype were investigated. RESULTS: We demonstrated that heterogeneity in the clearance of endogenous plasma VWF is a key determinant of variable FVIII half-life in PWH. Both ABO blood group and age significantly impact FVIII clearance. The effect of ABO blood group on FVIII half-life in PWH is modulated entirely through its effect on the clearance rates of endogenous VWF. In contrast, the age-related effect on FVIII clearance is, at least in part, VWF independent. In contrast to previous studies, no major effects of variation in VWF-FVIII binding affinity on FVIII clearance were observed. Although high-titer immunoglobulin G antibodies (≥1:80) were observed in 26% of PWH, these did not impact FVIII half-life. Importantly, the annual FVIII usage (IU/kg/y) was significantly (p = .0035) increased in patients with an FVIII half-life of <12 hours. CONCLUSION: Our data demonstrate that heterogeneity in the half-life of FVIII concentrates in patients with hemophilia A is primarily attributable to variability in the clearance of endogenous VWF.

Physical activity, physical fitness and cardiometabolic risk amongst adults with moderate and severe haemophilia.

AIM: This study aimed to examine physical activity (PA), physical fitness and cardiometabolic risk amongst people with moderate and severe haemophilia (PwMSH). METHODS: The following domains were examined: PA (accelerometry); functional aerobic capacity (6-Minute Walk Test); grip strength (dynamometry); balance (One Leg Stand Test); body composition (anthropometry and bioimpedance analysis); blood pressure; arterial stiffness; and cardiometabolic disorders. RESULTS: A total of 53 PwMSH (44 years) and 33 controls (43 years; p = .679) were recruited. Compared to controls, PwMSH were significantly less active in moderate and vigorous PA parameters (all p < .05), and less physically fit indicated by 6-Minute Walk distance (p < .0005), grip strength (p = .040) and balance (p < .0005). PwMSH had higher rates of abdominal adiposity compared to controls measured by waist circumference indices (all p < .05). Resting blood pressure and arterial stiffness were not significantly different (p = .797 and .818, respectively). With respect to overall PA, World Health Organisation recommended targets for adults were achieved by the majority of both groups (haemophilia: 72.9% vs. controls: 90.0%; p = .069). Importantly, the number of PwMSH who achieved guideline recommended PA via longer, sustained bouts of moderate-vigorous PA was significantly lower compared to controls (18.8% vs. 56.7%; p = .001). Lastly, clinically diagnosed hypertension, insulin resistance and hyperlipidaemia were more prevalent amongst PwMSH compared to controls. CONCLUSION: Low levels of PA and physical fitness, and significant rates of abdominal adiposity and hypertension may collectively influence the risk and severity of various cardiometabolic and/or musculoskeletal health issues amongst ageing PwMSH. Personalised multi-disciplinary health interventions involving PA, dietary and health psychology input for PwMSH warrant future investigation.

Organ-sparing central pelvic compartment resection for the treatment of vulvo-vaginal melanomas.

Vulvo-vaginal melanomas are one of the rarest gynecological oncology diseases with a poor survival compared with other malignancies. The 5-year survival varies from 13% to 32.3%. Vulvo-vaginal melanomas involving the upper 2/3rds of the vagina are usually treated with total pelvic exenteration (TPE). TPE surgery carries a 50% risk of major complications and also morbidity associated with double stomas. Central pelvic compartment resection is a novel organ-sparing surgical approach entailing radical total laparoscopic hysterectomy, bilateral salpingo-oophrectomy, laparoscopic vaginectomy and vulvectomy to reduce morbidity compared with TPE. Permanent suprapubic catheters are used if there is urethral involvement but require quality of life studies to assess their long-term outcomes.

Does the presence of single compared to multiple endometrial polyps alter the risk of cancer in post-menopausal women?

OBJECTIVE: To evaluate the relative rates of malignancy in women with single and multiple polyps presenting to a UK Cancer Centre with postmenopausal bleeding (PMB). STUDY DESIGN: A retrospective review of patients treated at Royal Derby Hospital (RDH) for PMB who underwent outpatient hysteroscopy based on ultrasonographic suspicion of endometrial polyps between May 2014 to December 2019. The main outcome measure was the rates of precancerous and malignant histology for single or multiple polyps. The secondary outcomes assessed the influence of risk factors on the rates of malignancy within the single and multiple polyps groups. RESULTS: The study population was 851 women of which 533 were in the single polyp group and 318 in the multiple polyps group. The multiple polyps group (mean age 65.2 years) was older compared to the single polyp group (mean age 62.1 years), P = 0.0001. Elevated rates of cancer was driven most significantly by endometrioid cancer in the multiple polyps compared to single polyp group, with rates of 50/314 (16 %) and 28/512 (5.5 %) respectively, P=< 0.00001. For rarer histologies there was no significant difference between the proportion of serous, carcinosarcomas and clear cell cancers between those with single compared to multiple polyps (P > 0.05). Significantly more endometrial hyperplasia with atypia (AEH) was found in the multiple polyps compared to single polyp group, with rates of 18/314 (5.7 %) and 15/512 (2.9 %) respectively, P = 0.046. CONCLUSION: Our study found increased rates of endometrioid cancer and its precursor, AEH within the multiple polyps compared to the single polyps groups. Future risk predicting algorithms should consider incorporating single and multiple polyps as part of their risk model.

Does the character of the hospital of primary management influence outcomes in patients treated for presumed early stage endometrial cancer and atypical endometrial hyperplasia: a comparison of outcomes from a cancer unit and cancer centre.

A retrospective study from 2015 to 2020 comparing overall survival (OS) outcomes of a cancer unit and centre for presumed early stage endometrial cancers is presented. Cancer centres manage these presumed early endometrial cancer (EC) in situations of complex co-morbidities, surgical challenges as well as their own local unit patients. Our analysis compares 138 patients at KMH (unit) and 282 patients at RDH (centre) on OS, patient demographics, grading histology and final histology. Patients with presumed early stage EC can be reassured regarding no difference in OS between the cancer unit and centre management (p = .05). However, rates of minimal access surgery were higher at the cancer centre compared to the unit (93.2% versus 68.1%). The rates of upstaged disease were 4% and 8.8% at the cancer unit and centre respectively (p = .096). Sentinel node biopsy and genomic assessment may change future thresholds for centre-level management due to rates of upstaged disease.Impact StatementWhat is already known on this subject? Presumed lower risk endometrial cancers (endometrioid grades 1 and 2) have a rate of occult nodal involvement of only 1.4%. The BGCS does not recommend lymphadenectomy for low-risk endometrial cancers. These low-risk endometrial cancers should be managed with a hysterectomy and bilateral salpingo-ophrectomy via minimal access surgery. In view of the low rates of occult nodal involvement in low-risk endometrial cancer, surgery can be offered at a cancer unit.What do the results of this study add? Our study demonstrates there is no disadvantage in overall survival in the surgical management of presumed low-risk endometrial cancers at cancer units and centres. However, cancer centres have higher rates of minimal access to surgery despite managing a more elderly population. Our rates of upstaged disease of 4% and 8.8% at the cancer unit and centre indicate a potential benefit of pelvic lymph node assessment.What are the implications of these findings for clinical practice and/or further research? Sentinel lymph node biopsy does not have the surgical morbidity associated with systematic lymph node dissection. Therefore, when applied to presumed early stage endometrial cancer, there are potential changes in the threshold for centre-level management to improve overall survival.

Lactate Is a Reliable Predictor of ICU Length of Stay Following Ultra-radical Ovarian Cancer Surgery.

BACKGROUND/AIM: With a greater proportion of women with advanced ovarian cancer (AOC) successfully undergoing radical cytoreductive surgery, the demand on peri-operative resources - including intensive care (ICU) beds - is also on the rise. Extended post-operative ICU length of stay (LOS) confers increased patient morbidity and mortality. Several variables associated with prolonged ICU LOS following AOC surgery have been identified. We aimed to evaluate the predictive value of serum lactate levels. PATIENTS AND METHODS: All patients undergoing ultra-radical surgery for AOC in a large cancer centre over a 34-month period between 2018-2021 were identified via the institution tumour registry. Data were collected retrospectively via electronic care and operating records; biochemistry, radiology, and histopathology databases. RESULTS: In total, 63 patients were identified. Elevated intra-operative serum lactate levels were associated with significantly longer length of ICU post-operative stay. Longer time for hyperlactaemia to normalise following surgery also conferred significantly longer ICU, high dependency and total hospital LOS. Greater blood loss, higher surgical complexity and peritoneal carcinomatosis score, and longer operating time were associated with higher - and persistently elevated - peri-operative lactate levels. CONCLUSION: Serum lactate in the context of ultra-radical surgery for AOC represents an accessible and inexpensive marker with potential to not only reliably predict LOS, but also to serve as a dynamic prompt for early targeted intervention. Early recognition and correction of hyperlactaemia following AOC may reduce ICU LOS limiting both the resource pressure and patient morbidity/mortality sequelae.

Pain and functional disability amongst adults with moderate and severe haemophilia from the Irish personalised approach to the treatment of haemophilia (iPATH) study.

OBJECTIVES: To establish the prevalence of pain and functional disability in Irish adults with moderate and severe haemophilia, and to examine demographic and lifestyle influences. METHODS: Males ≥18 years with moderate or severe haemophilia participated. Pain and function were examined using the PROBE questionnaire. RESULTS: Of 49 participants [median age 44 (IQR 32, 52) years], most had severe haemophilia (Factor VIII = 30; Factor IX = 13) and were on regular prophylaxis (88%). Those with moderate haemophilia (Factor VIII = 5; Factor IX = 1) treated on demand (12%). Acute (72%) and chronic pain (71%), functional difficulties (58%), and analgesic requirements (92%) were prevalent. Age was significantly associated with more advanced haemophilic arthropathy (p = .002), chronic pain (p = .029) and functional difficulties (p = .036). Adults who reported chronic pain commenced prophylaxis significantly later in life [32 (20, 51) vs. 8 (1, 23) years; p = .004]. Physical activity was significantly lower in those with functional difficulties (p < .05). A disparity between self-perceived 'target joints' and clinically defined target joints was also identified (76% vs. 23%). CONCLUSION: Haemophilic arthropathy, pain and functional disability were prevalent amongst Irish adults with moderate and severe haemophilia. Age-dependent lifestyle, analgesic and treatment influences on pain and function warrant further investigation.

Single centre, real-world experience of perioperative rFIXFc use in adult patients with haemophilia B undergoing major and minor surgery.

INTRODUCTION: Recombinant factor IX fusion protein concentrate (rFIXFc) is increasingly used for prophylaxis in people with haemophilia B (PWHB), but experience in the perioperative setting is limited. AIMS: To evaluate real-world perioperative factor usage, bleeding and complications in PWHB (≥18 years) who received rFIXFc for surgical haemostasis and to describe the treatment regimens used. METHODS: Single centre, retrospective review of all PWHB who underwent a major or minor surgical procedure between June 2017 and July 2020 and received rFIXFc perioperatively for maintenance of surgical haemostasis. RESULTS: A total of 56 PWHB (45 male and 11 female), including people with mild (n = 32), moderate (n = 4) and severe (n = 20) haemophilia B, underwent 11 major and 131 minor procedures with rFIXFc for surgical haemostasis. Haemostasis was rated as excellent (9/11) or good (2/11) in all major procedures. Median total rFIXFc consumption for orthopaedic surgeries was 972 IU/kg (range 812-1031 IU/kg) and for other major (non-orthopaedic) surgeries was 323 IU/kg (range 167-760 IU/kg). The median number of perioperative rFIXFc infusions was 19 (range 17-26) for orthopaedic surgery and 7 (range 5-17) for other major surgeries. The number of infusions in the postoperative period was determined by procedure and patient factors. Complications included bowel ileus and wound infection. Most minor procedures were managed with single infusion of rFIXFc, with no bleeding complications in 95% of minor procedures. There were no thromboembolic events or inhibitor formation. CONCLUSION: This unique data provides real-world evidence that rFIXFc is safe and effective in achieving haemostasis in PWHB undergoing surgery.

A Newton-like iterative method implemented in the DelPhi for solving the nonlinear Poisson-Boltzmann equation.

DelPhi is a popular scientific program which numerically solves the Poisson-Boltzmann equation (PBE) for electrostatic potentials and energies of biomolecules immersed in water via finite difference method. It is well known for its accuracy, reliability, flexibility, and efficiency. In this work, a new edition of DelPhi that uses a novel Newton-like method to solve the nonlinear PBE, in addition to the already implemented Successive Over Relaxation (SOR) algorithm, is introduced. Our tests on various examples have shown that this new method is superior to the SOR method in terms of stability when solving the nonlinear PBE, being able to converge even for problems involving very strong nonlinearity.

Telehealth for delivery of haemophilia comprehensive care during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic caused an unprecedented impact to haemophilia healthcare delivery. In particular, rapid implementation of telehealth solutions was required to ensure continued access to comprehensive care. AIMS: To explore patient and healthcare provider (HCP) experience of telehealth in a European Haemophilia Comprehensive Care Centre. METHOD: A systematic evaluation was performed to survey patient and HCP experience and compare clinical activity levels with telehealth to in-person attendances. RESULTS: Public health measures implemented in March 2020 to reduce COVID-19 spread resulted in a 63% decrease in medical/nursing clinic consultation activity compared to the same period in 2019. Implementation of digital care pathways resulted in marked increase in activity (52% greater than 2019). Importantly, enhanced patient engagement was noted, with a 60% reduction in non-attendance rates. Survey of patients who had participated in medical/nursing teleconsultations demonstrated that teleconsultations improved access (79%), reduced inconvenience (82%), was easy to use (94%) and facilitated good communication with the HCP (97%). A survey exploring the telemedicine experience of HCPs, illustrated that HCPs were satisfied with teleconsultation and the majority (79%) would like to continue to offer teleconsultation as part of routine patient care. In addition to medical/nursing reviews, continued access to physiotherapy with virtual exercise classes for people with haemophilia and teleconsultation for acute dental issues was equally successful. CONCLUSION: During an unprecedented public health emergency, telehealth has enabled continued access to specialized haemophilia comprehensive care. Our novel findings show that this alternative is acceptable to both patients and HCPs and offers future novel opportunities.

The predictive validity of the Structured Assessment of Violence Risk in Youth in secondary educational settings.

Current developments in violence risk assessment warrant consideration for use within educational settings. Using a structured professional judgment (SPJ) model, the present study investigated the predictive validity of the Structured Assessment of Violence in Youth (SAVRY) within educational settings. The predictive accuracy of the SAVRY scales was assessed using a retrospective file review to gather data on 87 adolescents ranging in age from 12 to 18 years. Receiver-operating characteristic analyses were used to gauge the predictive accuracy. With an area under the curve of .72 (p = .001), the accuracy of the SAVRY total score in correctly identifying violent youth exceeds the accuracy of identifications based on chance predictions in this sample. Logistic regression analyses assessed the relative contribution of the SAVRY subscales, whereas the omnibus equation using all subscale scores correctly classified 82% of those adolescents who were nonviolent and 45% of those adolescents who were violent. These results build on previous research and provide support for the use of the SAVRY in educational settings for identification as well as directing intervention efforts. Practical implications and areas for future research are also discussed.