Evolution of surgical approach to rectal cancer resection: A multinational registry assessment.

PURPOSE: Surgical approach to rectal cancer has evolved in recent decades, with introduction of minimally invasive surgery (MIS) techniques and local excision. Since implementation might differ internationally, this study is aimed at evaluating trends in surgical approach to rectal cancer across different countries over the last 10 years and to gain insight into patient, tumour and treatment characteristics. METHODS: Pseudo-anonymised data of patients undergoing resection for rectal cancer between 2010 and 2019 were extracted from clinical audits in the Netherlands (NL), Sweden (SE), England-Wales (EW) and Australia-New Zealand (AZ). RESULTS: Ninety-nine thousand five hundred ninety-seven patients were included (38,413 open, 55,155 MIS and 5416 local excision). An overall increase in MIS was observed from 29.9% in 2010 to 72.1% in 2019, with decreasing conversion rates (17.5-9.0%). The MIS proportion was highly variable between countries in the period 2010-2014 (54.4% NL, 45.3% EW, 39.8% AZ, 14.1% SE, P < 0.001), but variation reduced over time (2015-2019 78.8% NL, 66.3% EW, 64.3% AZ, 53.2% SE, P < 0.001). The proportion of local excision for the two periods was highly variable between countries: 4.7% and 11.8% in NL, 3.9% and 7.4% in EW, 4.7% and 4.6% in AZ, 6.0% and 2.9% in SE. CONCLUSIONS: Application and speed of implementation of MIS were highly variable between countries, but each registry demonstrated a significant increase over time. Local excision revealed inconsistent trends over time.

Hemodiafiltration for children with stage 5 chronic kidney disease: technical aspects and outcomes.

Despite significant medical and technical improvements in the field of dialysis, the morbidity and mortality among patients with chronic kidney disease (CKD) stage 5 on dialysis remains extremely high. Hemodiafiltration (HDF), a dialysis method that combines the two main principles of hemodialysis (HD) and hemofiltration-diffusion and convection-has had a positive impact on survival when delivered with a high convective dose. Improved outcomes with HDF have been attributed to the following factors: HDF removes middle molecular weight uremic toxins including inflammatory cytokines, increases hemodynamic stability, and reduces inflammation and oxidative stress compared to conventional HD. Two randomized trials in adults have shown improved survival with HDF compared to high-flux HD. A large prospective cohort study in children has shown that HDF attenuated the progression of cardiovascular disease, improved bone turnover and growth, reduced inflammation, and improved blood pressure control compared to conventional HD. Importantly, children on HDF reported fewer headaches, dizziness, and cramps; had increased physical activity; and improved school attendance compared to those on HD. In this educational review, we discuss the technical aspects of HDF and results from pediatric studies, comparing outcomes on HDF vs. conventional HD. Convective volume, the cornerstone of treatment with HDF and a key determinant of outcomes in adult randomized trials, is discussed in detail, including the practical aspects of achieving an optimal convective volume.

Inequalities in the recovery of colorectal cancer services during the COVID-19 pandemic: a national population-based study.

AIM: Evidence is lacking on whether there were inequalities in the recovery of colorectal cancer (CRC) services within the English National Health Service (NHS) following the COVID-19 pandemic. The aim of this study was to evaluate recovery according to patient age and socioeconomic status. METHOD: Using routinely collected data, CRC patients diagnosed and treated in the English NHS were identified for two timeframes: the 'initial pandemic period' (April-June 2020) and the 'pandemic period' (April 2020-March 2022). Poisson models evaluated changes in numbers of diagnoses, major resections, adjuvant chemotherapy and neoadjuvant radiotherapy use for each timeframe, relative to the equivalent pre-pandemic timeframe (April-June 2019 and April 2018-March 2020, respectively), stratified by age and socioeconomic status. Tumour stage at presentation was evaluated over time. RESULTS: Substantial deficits in diagnoses, major resections and adjuvant chemotherapy were identified in the initial pandemic period, whilst the use of neoadjuvant radiotherapy increased. Overall, these deficits recovered. Patients outside screening age, and in the most deprived group, had greater deficits in diagnoses and major resections. There was no evidence of stage migration by June 2021. CONCLUSIONS: CRC services showed recovery to baseline during the pandemic. However, evident inequalities must be addressed in ongoing recovery efforts. Long-term outcomes will fully establish the impact of the pandemic on CRC patients.

Impact of patient choice and hospital competition on patient outcomes after rectal cancer surgery: A national population-based study.

BACKGROUND: The objective of the current national cohort study was to analyze the correlation between choice and competition on outcomes after cancer surgery in rectal cancer. METHODS: The analysis included all men who underwent rectal cancer surgery in the English National Health Service between March 2015 and April 2019 (n = 13,996). Multilevel logistic regression was used to assess the effect of a rectal cancer surgery center being located in a competitive environment (based on the number of centers within a threshold distance) and being a successful competitor (based on the ability to attract patients from other hospitals) on eight patient-level outcomes: 30- and 90-day emergency readmissions, 30-day re-operation rates, 90-day postoperative mortality, length of stay >14 days, circumferential resection margin status, rates of primary procedure with a permanent stoma, and rates of persistent stoma 18 months after anterior resection. RESULTS: With adjustment for patient characteristics, patients who underwent surgery in centers located in a stronger competitive environment were less likely to have an abdominoperineal excision or a Hartman's procedure (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.55-0.97, p = .04). Additionally, individuals who received treatment at hospitals that were successful competitors had a lower risk of a 90-day readmission following rectal cancer surgery (OR, 0.86; 95% CI, 0.76-0.97, p = .03) and were less likely to have a persistent stoma at 18 months after anterior resection (OR, 0.75; 95% CI, 0.61-0.93, p = .02). CONCLUSIONS: Hospitals located in areas of high competition are associated with better patient outcomes and improved processes of care for rectal cancer surgery.

Machine learning-based mortality prediction models using national liver transplantation registries are feasible but have limited utility across countries.

Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We used data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90-day post-LT mortality within and across countries. Predictive performance and external validity of each model were assessed. Prospectively collected data of adult patients (aged ≥18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Health Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United States) were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined (variables in common between the registries [harmonized]). The model performance was evaluated using area under the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, n = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, 0.71; range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance across countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making in future LTs.

Outcomes after liver transplantation using deceased after circulatory death donors: A comparison of outcomes in the UK and the US.

BACKGROUND AND AIMS: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight. METHODS: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes. RESULTS: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001). CONCLUSIONS: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries.

Iatrogenic and spontaneous preterm birth in England: A population-based cohort study.

OBJECTIVE: To describe the rates of and risk factors associated with iatrogenic and spontaneous preterm birth and the variation in rates between hospitals. DESIGN: Cohort study using electronic health records. SETTING: English National Health Service. POPULATION: Singleton births between 1 April 2015 and 31 March 2017. METHODS: Multivariable Poisson regression models were used to estimate adjusted risk ratios (adjRR) to measure association with maternal demographic and clinical risk factors. MAIN OUTCOME MEASURES: Preterm births (<37 weeks of gestation) were defined as iatrogenic or spontaneous according to mode of onset of labour. RESULTS: Of the births, 6.1% were preterm and of these, 52.8% were iatrogenic. The proportion of preterm births that were iatrogenic increased after 32 weeks. Both sub-groups were associated with previous preterm birth, extremes of maternal age, socio-economic deprivation and smoking. Iatrogenic preterm birth was associated with higher body mass index (BMI) (BMI >40 kg/m2 adjRR 1.59, 95% CI 1.50-1.69) and previous caesarean (adjRR 1.88, 95% CI 1.83-1.95). Spontaneous preterm birth was less common in women with a higher BMI (BMI >40 kg/m2 adjRR 0.77, 95% CI 0.70-0.84) and in women with a previous caesarean (adjRR 0.87, 95% CI 0.83-0.90). More variation between NHS hospital trusts was observed in rates of iatrogenic, compared with spontaneous, preterm births. CONCLUSIONS: Just over half of all preterm births resulted from iatrogenic intervention. Iatrogenic births have overlapping but different patterns of maternal demographic and clinical risk factors to spontaneous preterm births. Iatrogenic and spontaneous sub-groups should therefore be measured and monitored separately, as well as in aggregate, to facilitate different prevention strategies. This is feasible using routinely acquired hospital data.

Management of Impacted Fetal Head at Caesarean Birth: Scientific Impact Paper No. 73.

Over one-quarter of women in the UK have a caesarean birth (CB). More than one in 20 of these births occurs near the end of labour, when the cervix is fully dilated (second stage). In these circumstances, and when labour has been prolonged, the baby's head can become lodged deep in the maternal pelvis making it challenging to deliver the baby. During the caesarean birth, difficulty in delivery of the baby's head may result - this emergency is known as impacted fetal head (IFH). These are technically challenging births that pose significant risks to both the woman and baby. Complications for the woman include tears in the womb, serious bleeding and longer hospital stay. Babies are at increased risk of injury including damage to the head and face, lack of oxygen to the brain, nerve damage, and in rare cases, the baby may die from these complications. Maternity staff are increasingly encountering IFH at CB, and reports of associated injuries have risen dramatically in recent years. The latest UK studies suggest that IFH may complicate as many as one in 10 unplanned CBs (1.5% of all births) and that two in 100 babies affected by IFH die or are seriously injured. Moreover, there has been a sharp increase in reports of babies having brain injuries when their birth was complicated by IFH. When an IFH occurs, the maternity team can use different approaches to help deliver the baby's head at CB. These include: an assistant (another obstetrician or midwife) pushing the head up from the vagina; delivering the baby feet first; using a specially designed inflatable balloon device to elevate the baby's head and/or giving the mother a medicine to relax the womb. However, there is currently no consensus for how best to manage these births. This has resulted in a lack of confidence among maternity staff, variable practice and potentially avoidable harm in some circumstances. This paper reviews the current evidence regarding the prediction, prevention and management of IFH at CB, integrating findings from a systematic review commissioned from the National Guideline Alliance.

What is the impact of hospital and surgeon volumes on outcomes in rectal cancer surgery?

AIM: Evidence for a positive volume-outcome relationship for rectal cancer surgery is unclear. This study aims to evaluate the volume-outcome relationship for rectal cancer surgery at hospital and surgeon level in the English National Health Service (NHS). METHOD: All patients undergoing a rectal cancer resection in the English NHS between 2015 and 2019 were included. Multilevel multivariable logistic regression was used to model relationships between outcomes and mean annual hospital and surgeon volumes (using a linear plus a quadratic term for volume) with adjustment for patient characteristics. RESULTS: A total of 13 858 patients treated in 166 hospitals were included. Six hospitals (3.6%) performed fewer than 10 rectal cancer resections per year, and 381 surgeons (45.0%) performed fewer than five such resections per year. Patients treated by high-volume surgeons had a reduced length of stay (p = 0.016). No statistically significant volume-outcome relationships were demonstrated for 90-day mortality, 30-day unplanned readmission, unplanned return to theatre, stoma at 18 months following anterior resection, positive circumferential resection margin and 2-year all-cause mortality at either hospital or surgeon level (p values > 0.05). CONCLUSION: Almost half of colorectal surgeons in England do not meet national guidelines for rectal cancer surgeons to perform a minimum of five major resections annually. However, our results suggest that centralizing rectal cancer surgery with the main focus of increasing operative volume may have limited impact on NHS surgical outcomes. Therefore, quality improvement initiatives should address a wider range of evidence-based process measures, across the multidisciplinary care pathway, to enhance outcomes for patients with rectal cancer.

The acceptability and feasibility of a randomised trial exploring approaches to managing impacted fetal head during emergency caesarean section: a qualitative study.

BACKGROUND: Caesarean sections (CS) account for 26% of all births in the UK, of which at least 5% are done at full dilatation, in the second stage of labour. Second stage CS may be complicated by the fetal head being deeply impacted in the maternal pelvis, requiring specialist skills to achieve a safe birth. Numerous techniques are used to manage impacted fetal head, however, there are no national clinical guidelines in the UK. AIM: To explore health professionals' and women's views on the acceptability and feasibility of a randomised controlled trial (RCT) designed to explore approaches to managing an impacted fetal head during emergency CS. METHODS: Semi-structured interviews with 10 obstetricians and 16 women (6 pregnant and 10 who experienced an emergency second stage CS). Interviews were transcribed and analysed using systematic thematic analysis. RESULTS: The findings considered the time at which you obtain consent, how and when information about the RCT is presented, and barriers and facilitators to recruiting health professionals and women into the RCT. Obstetricians emphasised the importance of training in the techniques, as well as the potential conflict between the RCT protocol and current site or individual practices. Women said they would trust health professionals' to use the most appropriate technique and abandon the RCT protocol if necessary. Similarly, obstetricians raised the tension between the RCT protocol versus safety in reverting to what they knew under emergency situations. Both groups reflected on how this might affect the authenticity of the results. A range of important maternal, infant and clinical outcomes were raised by women and obstetricians. However, there were varying views on which of the two RCT designs presented to participants would be preferred. Most participants thought the RCT would be feasible and acceptable. CONCLUSIONS: This study suggests an RCT designed to evaluate different techniques for managing an impacted fetal head would be feasible and acceptable. However, it also identified a number of challenges that need to be considered when designing such an RCT. Results can be used to inform the design of RCTs in this area.

Women's knowledge of and attitudes towards group B streptococcus (GBS) testing in pregnancy: a qualitative study.

BACKGROUND: 20-25% pregnant women in the UK carry group B streptococcus (GBS) which, if left undetected, is transmitted from pregnant mothers to their babies during birth in 36% of cases. This transmission leads to early onset GBS infection (EOGBS) in 1% of babies which is a significant cause of mortality and morbidity in newborns. The literature available suggests women's knowledge of GBS is low, with many women unaware of the GBS bacterium. In addition, attitudes towards GBS testing have not been widely examined, with research mostly focusing on attitudes towards potential GBS vaccination. AIM: To examine women's knowledge of GBS in pregnancy and their attitudes towards GBS testing. METHODS: Semi-structured interviews with 19 women (5 pregnant and 14 postpartum). Interviews were transcribed and analysed using systematic thematic analysis. RESULTS: Four main theme categories were identified. Participants had varying levels of awareness of GBS, with the information provided by health professionals not being clearly explained or the importance of GBS being downplayed. Participants wanted more information and to feel informed. Overall, the majority had positive attitudes towards being offered and taking up GBS testing, and this study identified some of the key factors influencing their decision. These included: seeing GBS testing as just another routine procedure during pregnancy; that it would lower the risk of their baby becoming unwell; provide reassurance; and allow them to prepare; and provide informed choices. Participants also expressed a few common concerns about GBS testing: questioning the invasiveness of the procedure; risks to themselves and the baby; and the risk of receiving antibiotics. CONCLUSIONS: Women need clear, detailed information about GBS and GBS testing, and women's concerns are important to address if routine GBS testing is implemented. The efficacy of implementing routine universal testing in the UK is currently being investigated in a large multi-centre clinical trial; the GBS3trial, further qualitative research is needed to look at the acceptability of different methods of GBS testing, as well as the acceptability of GBS testing to women in specific groups, such as those planning a home birth or those from different ethnic backgrounds.

Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: A national population-based study.

The impact of cycle completion rates of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer in real-world practice is unknown. We assessed its impact, and that of treatment modification, on 3-year cancer-specific mortality. Four thousand one hundred and forty-seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3-year cancer-specific mortality was performed according to completion of <6, 6-11, or 12 5-fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4-7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. Thirty-two per cent of patients had at least one comorbidity. Forty-two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6 cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56-3.03] or 6-11 cycles (sHR 1.40; 95% CI 1.09-1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53-2.67) or 4-7 cycles (sHR 1.63; 95% CI 1.27-2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer-specific survival in real-world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.

Adverse pregnancy outcomes attributable to socioeconomic and ethnic inequalities in England: a national cohort study.

BACKGROUND: Socioeconomic deprivation and minority ethnic background are risk factors for adverse pregnancy outcomes. We aimed to quantify the magnitude of these socioeconomic and ethnic inequalities at the population level in England. METHODS: In this cohort study, we used data compiled by the National Maternity and Perinatal Audit, based on birth records from maternity information systems used by 132 National Health Service hospitals in England, linked to administrative hospital data. We included women who gave birth to a singleton baby with a recorded gestation between 24 and 42 completed weeks. Terminations of pregnancy were excluded. We analysed data on stillbirth, preterm birth (<37 weeks of gestation), and fetal growth restriction (FGR; liveborn with birthweight <3rd centile by the UK definition) in England, and compared these outcomes by socioeconomic deprivation quintile and ethnic group. We calculated attributable fractions for the entire population and specific groups compared with least deprived groups or White women, both unadjusted and with adjustment for smoking, body-mass index (BMI), and other maternal risk factors. FINDINGS: We identified 1 233 184 women with a singleton birth between April 1, 2015, and March 31, 2017, of whom 1 155 981 women were eligible and included in the analysis. 4505 (0·4%) of 1 155 981 births were stillbirths. Of 1 151 476 livebirths, 69 175 (6·0%) were preterm births and 22 679 (2·0%) were births with FGR. Risk of stillbirth was 0·3% in the least socioeconomically deprived group and 0·5% in the most deprived group (p<0·0001), risk of a preterm birth was 4·9% in the least deprived group and 7·2% in the most deprived group (p<0·0001), and risk of FGR was 1·2% in the least deprived group and 2·2% in the most deprived group (p<0·0001). Population attributable fractions indicated that 23·6% (95% CI 16·7-29·8) of stillbirths, 18·5% (16·9-20·2) of preterm births, and 31·1% (28·3-33·8) of births with FGR could be attributed to socioeconomic inequality, and these fractions were substantially reduced when adjusted for ethnic group, smoking, and BMI (11·6% for stillbirths, 11·9% for preterm births, and 16·4% for births with FGR). Risk of stillbirth ranged from 0·3% in White women to 0·7% in Black women (p<0·0001); risk of preterm birth was 6·0% in White women, 6·5% in South Asian women, and 6·6% in Black women (p<0·0001); and risk of FGR ranged from 1·4% in White women to 3·5% in South Asian women (p<0·0001). 11·7% of stillbirths (95% CI 9·8-13·5), 1·2% of preterm births (0·8-1·6), and 16·9% of FGR (16·1-17·8) could be attributed to ethnic inequality. Adjustment for socioeconomic deprivation, smoking, and BMI only had a small effect on these ethnic group attributable fractions (13·0% for stillbirths, 2·6% for preterm births, and 19·2% for births with FGR). Group-specific attributable fractions were especially high in the most socioeconomically deprived South Asian women and Black women for stillbirth (53·5% in South Asian women and 63·7% in Black women) and FGR (71·7% in South Asian women and 55·0% in Black women). INTERPRETATION: Our results indicate that socioeconomic and ethnic inequalities were responsible for a substantial proportion of stillbirths, preterm births, and births with FGR in England. The largest inequalities were seen in Black and South Asian women in the most socioeconomically deprived quintile. Prevention should target the entire population as well as specific minority ethnic groups at high risk of adverse pregnancy outcomes, to address risk factors and wider determinants of health. FUNDING: Healthcare Quality Improvement Partnership.

Risk of postpartum haemorrhage is associated with ethnicity: A cohort study of 981 801 births in England.

OBJECTIVE: To determine the association between ethnic group and risk of postpartum haemorrhage in women giving birth. DESIGN: Cohort study. SETTING: Maternity units in England. SAMPLE: A total of 981 801 records of births between 1 April 2015 and 31 March 2017 in a national clinical database. METHODS: Multivariable logistic regression analyses with multiple imputation to account for missing data and robust standard errors to account for clustering within hospitals. MAIN OUTCOME MEASURE: Postpartum haemorrhage of ≥1500 ml (PPH). RESULTS: A total of 28 268 (2.9%) births were complicated by PPH. Risks were higher in women from black (3.9%) and other (3.5%) ethnic backgrounds. Following adjustment for maternal and fetal characteristics, and care at birth, there was evidence of an increased risk of PPH in women from all ethnic minority groups, with the largest increase seen in black women (adjusted OR 1.54, 95% CI 1.45-1.63). The increase in risk was robust to sensitivity analyses, which included changing the outcome to PPH of ≥3000 ml. CONCLUSIONS: In England, women from ethnic minority backgrounds have an increased risk of PPH, when maternal, fetal and birth characteristics are taken into account. Factors contributing to this increased risk need further investigation. Perinatal care for women from ethnic minority backgrounds should focus on preventative measures to optimise maternal outcomes. TWEETABLE ABSTRACT: Women with an ethnic minority background giving birth in England have an increased risk of postpartum haemorrhage, even when characteristics of the mother, the baby and the care received are taken into account.

Outcomes of colorectal cancer resection in patients with inflammatory bowel disease: a national population-based analysis in England and Wales.

AIM: The aim was to compare early postoperative outcomes and 2-year cancer-specific mortality following colorectal cancer (CRC) resection in patients with and without inflammatory bowel disease (IBD) in England and Wales. METHOD: Records for patients in the National Bowel Cancer Audit who had major CRC resection between April 2014 and December 2017 were linked to routinely collected hospital level administrative datasets and chemotherapy and radiotherapy datasets. Multivariable regression models were used to compare outcomes with adjustment for patient and tumour characteristics. RESULTS: In all, 63 365 patients were included. 1285 (2.0%) had an IBD diagnosis: 839 (65.3%) ulcerative colitis, 435 (33.9%) Crohn's disease and 11 (0.9%) were indeterminate. IBD patients were younger, had more advanced cancer staging and a higher proportion of right-sided tumours. They also had a higher proportion of emergency resection, total/subtotal colectomy, open surgery and stoma formation at resection, with longer hospital admissions and higher rates of unplanned readmission and reoperation. Fewer rectal cancer patients with IBD received neoadjuvant radiotherapy (24.8% vs. 36.0%, P = 0.005) whilst similar proportions of Stage III colon cancer patients received adjuvant chemotherapy. Ninety-day postoperative mortality was similar, but unadjusted 2-year cancer-specific mortality was significantly higher in patients with IBD (subdistribution hazard ratio 1.35, 95% CI 1.18-1.55). Risk adjustment for patient and tumour factors reduced this association (adjusted subdistribution hazard ratio 1.22, 95% CI 1.05-1.43). CONCLUSION: Patients with IBD and CRC are a distinct patient group who develop CRC at a younger age and undergo more radical surgery. They have worse cancer survival, with the difference in prognosis appearing after the early postoperative period.

Older Individuals Convicted of Sexual Offenses: A Literature Review.

The population of older individuals convicted of sexual offenses (OSOs) is rapidly increasing. However, we have little understanding of their characteristics (e.g., demographic, psychological, individual, offense, and risk) and needs. To identify any similarities or differences that are unique to older individuals convicted of sexual offending, it is important to compare such characteristics across the adult lifespan. Therefore, the aim of this systematic review was to specify and synthesize the current knowledge of characteristics across the adult lifespan of the population of individuals convicted of sexual offenses. Five databases were searched and 10,680 results were screened, resulting in 100 studies included in the final review. The findings were grouped into four emergent themes: age of onset and prevalence; offender and offense characteristics; age and the risk of reoffending; and treatment. Implications of the findings from this review are discussed in relation to future research and clinical practice.

Assessing the Time-Dependent Impact of Performance Status on Outcomes After Liver Transplantation.

BACKGROUND AND AIMS: Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period ("epoch") after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non-HCC recipients. APPROACH AND RESULTS: We assessed pre-LT PS using the 5-point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow-up (0-90 days and 90 days to 1 year) and in different eras of transplantation (1995-2005 and 2006-2016). 2107 HCC and 10,693 non-HCC patients were included. One-year survival decreased with worsening PS in non-HCC recipients where 1-year survival was 91.9% (95% confidence interval [CI], 88.3-94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7-80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4-93.2) and 83.1% (95% CI, 61.0-93.3), respectively. Reduction in survival in non-HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post-LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40-0.74) and non-HCC recipients (0.48; 95% CI, 0.42-0.55), but this did not differ according to PS score (P = 0.39 and 0.61, respectively). CONCLUSIONS: Impact on mortality of the recipient's pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non-HCC recipients and across the full range of PS.

National time trends in mortality and graft survival following liver transplantation from circulatory death or brainstem death donors.

BACKGROUND: Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods. METHODS: Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008-2011 and 2012-2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure. RESULTS: A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipients (P for interaction = 0.001). No time period-specific improvements in 3-year graft failure were observed for DCD (adjusted HR 0.80, 95% c.i. 0.61 to 1.05; P = 0.116) or DBD recipients (adjusted HR 0.95, 95% c.i. 0.79 to 1.14; P = 0.607). A slight increase in retransplantation rates occurred between time period 1 and 2 in those who received a DCD liver (from 7.3 to 11.8 per cent; P = 0.042), but there was no change in those receiving a DBD liver (from 4.9 to 4.5 per cent; P = 0.365). In time period 2, no difference in mortality rates between those receiving a DCD liver and those receiving a DBD liver was observed (adjusted HR 0.78, 95% c.i. 0.56 to 1.09; P = 0.142). CONCLUSION: Mortality rates more than halved in recipients of a DCD liver over a decade and eventually compared similarly to mortality rates in recipients of a DBD liver. Regions with high waiting list mortality may mitigate this by use of DCD livers.

Suboptimal mid-luteal progesterone concentrations are associated with aberrant endometrial gene expression, potentially resulting in implantation failure.

RESEARCH QUESTION: What is the difference in endometrial transcriptomics between women with normal and with low mid-luteal progesterone during the implantation window? DESIGN: An endometrial biopsy and serum progesterone concentration were taken from participants during the mid-luteal phase (LH+7 to LH+9). A total of 12 participants were recruited and categorized into two groups based on their progesterone concentrations: normal progesterone (>15 ng/ml, n = 6) and low progesterone (<15 ng/ml, n = 6). Global endometrial gene expression between the two groups was compared by microarray techniques. Principal component analysis was used to display the gene's expression pattern. Pathway and gene ontology enrichment analysis were performed to determine the biological mechanism of progesterone on the endometrium. RESULTS: Several key genes related to endometrial receptivity were found to be regulated by progesterone. With regard to gene ontology and pathway analysis, progesterone was shown to be mainly involved in structure morphogenesis predominantly during a process of decidualization, extracellular matrix-receptor interaction and cell adhesion. Distinct differences were observed in the transcriptomic profiles between the two groups, indicating potential impairment of endometrial receptivity in women with suboptimal progesterone concentrations. There was a relatively similar pattern of gene expression between endometrial samples with progesterone concentrations approximately 10 ng/ml and >15 ng/ml. Thus, a progesterone concentration of between 10 and 15 ng/ml appears to be sufficient to induce endometrial receptivity. CONCLUSIONS: Abnormally low progesterone below the threshold of 10-15 ng/ml during the implantation window results in aberrant endometrial gene expression that may affect implantation potential.

Inferior outcomes in young adults undergoing liver transplantation - a UK and Ireland cohort study.

Graft loss incidence is reported to be inversely related to recipient age. We used a national cohort of liver transplant (LT) recipients from the United Kingdom and Ireland to compare the age-dependent risk of graft failure in different post-transplantation time-periods ('epochs'). A cohort of first-time LT recipients (1995-2016) were identified (11 006). Cox regression was used to estimate hazard ratios (HR) comparing graft loss between age-groups (18-29, 30-39, 40-49, 50-59 and 60-76 years) and graft loss in different post-transplant epochs: 0-90 days, 90 days-2 years and 2-10 years. The risk of graft failure was highest in those transplanted between age 18 and 29 (adjusted HR 1.25, 95% CI: 1.00-1.57, P = 0.04) and in those aged 30-39 (adjusted HR 1.31, 95% CI: 1.11-1.55, P = 0.02). Graft failure in those under the age of 40 was similar in the first 90 days but worse 2-10 years' post-LT (18-29 years HR 1.36, 95% CI: 0.96-1.93, P < 0.001). Graft failure because of chronic rejection (CR) was more common in recipients aged 18-29 (P < 0.001). Adults transplanted between age 18 and 39 are at risk of late graft loss. CR is a concern for young adults (18-29 years). Our data highlights the need for specialist young adult services within adult healthcare.