Real-world evaluation of an acceptance and commitment therapy-based group programme for breast cancer survivors with fear of cancer recurrence.

PURPOSE: To evaluate the effectiveness and acceptability of a 6-week acceptance and commitment therapy (ACT)-based group programme on participants' fear of cancer recurrence (FCR), quality of life (QoL), psychological distress and psychological flexibility at the end of the programme and 12-week follow-up. METHODS: A one-group, post-test service evaluation of a real-world psychological programme was carried out to evaluate collected outcome measures and attendance for a total of 21 groups facilitated between 2017 and 2019. Participants were breast cancer survivors who attended a 6-week group programme led by NHS clinicians. Descriptive statistics and repeated measures ANOVA analyses were carried out for each outcome measure. Attendance levels were examined to assess acceptability. RESULTS: A total of 97 group participants who had completed curative treatment for breast cancer took part. Of whom, 89% completed at least 4 of the 6 weekly group sessions and 76% attended the 12-week follow-up session. Eighty-four (87%) participants returned outcome measures at all three time points relative to group participation (T1 = pre, T2 = post T3 = 12-week follow-up). Group participants were female, mean age 51.9 years. FCR was highest at T1 (mean 25.2, SD 4.7), reduced T2 (mean 21.2, SD 5.4) and further lowered T3 (mean 19.5, SD 6.2). This difference was statistically significant (p < 0.001). QoL was lowest at T1 (mean 62.4, SD 15.7), increased T2 (mean 71.7, SD 18.1) and further increased at T3 (mean 75.9, SD 17.5). This difference was statistically significant (p < 0.001). Psychological distress measures were shown to reduce, and psychological flexibility increased. CONCLUSIONS: This real-world evaluation of an ACT-based group programme led to improvements in FCR, QoL, psychological distress and psychological flexibility in this population. This evaluation provides basis for further investigation to determine if these results can be replicated by controlled research design across diverse populations.

Hospitalisation events in people with chronic kidney disease as a component of multimorbidity: parallel cohort studies in research and routine care settings.

BACKGROUND: Chronic kidney disease (CKD) typically co-exists with multimorbidity (presence of 2 or more long-term conditions: LTCs). The associations between CKD, multimorbidity and hospitalisation rates are not known. The aim of this study was to examine hospitalisation rates in people with multimorbidity with and without CKD. Amongst people with CKD, the aim was to identify risk factors for hospitalisation. METHODS: Two cohorts were studied in parallel: UK Biobank (a prospective research study: 2006-2020) and Secure Anonymised Information Linkage Databank (SAIL: a routine care database, Wales, UK: 2011-2018). Adults were included if their kidney function was measured at baseline. Nine categories of participants were used: zero LTCs; one, two, three and four or more LTCs excluding CKD; and one, two, three and four or more LTCs including CKD. Emergency hospitalisation events were obtained from linked hospital records. RESULTS: Amongst 469,339 UK Biobank participants, those without CKD had a median of 1 LTC and those with CKD had a median of 3 LTCs. Amongst 1,620,490 SAIL participants, those without CKD had a median of 1 LTC and those with CKD had a median of 5 LTCs. Compared to those with zero LTCs, participants with four or more LTCs (excluding CKD) had high event rates (rate ratios UK Biobank 4.95 (95% confidence interval 4.82-5.08)/SAIL 3.77 (3.71-3.82)) with higher rates if CKD was one of the LTCs (rate ratios UK Biobank 7.83 (7.42-8.25)/SAIL 9.92 (9.75-10.09)). Amongst people with CKD, risk factors for hospitalisation were advanced CKD, age over 60, multiple cardiometabolic LTCs, combined physical and mental LTCs and complex patterns of multimorbidity (LTCs in three or more body systems). CONCLUSIONS: People with multimorbidity have high rates of hospitalisation. Importantly, the rates are two to three times higher when CKD is one of the multimorbid conditions. Further research is needed into the mechanism underpinning this to inform strategies to prevent hospitalisation in this very high-risk group.

Factors associated with intensive care admission in patients with lung cancer: a population-based observational study of 26, 731 patients.

BACKGROUND: Lung cancer is the most common cause of cancer related death worldwide and survival is poor. Patients with lung cancer may develop a critical illness, but it is unclear what features are associated with an Intensive Care Unit (ICU) admission. METHODS: This retrospective, observational, population-based study of linked cancer registration, ICU, hospital discharge and mortality data described the factors associated with ICU admission in patients with lung cancer. The cohort comprised all incident cases of adult lung cancer diagnosed between 1st January 2000 and 31st December 2009 in the West of Scotland, UK, who were subsequently admitted to an ICU within 2 years of cancer diagnosis. Multiple logistic regression was used to determine factors associated with admission. RESULTS: 26,731 incident cases of lung cancer were diagnosed with 398 (1.5%) patients admitted to an ICU. Patients were most commonly admitted with respiratory conditions and there was a high rate of invasive mechanical ventilation. ICU, in-hospital and six-month survival were 58.5, 42.0 and 31.2%, respectively. Surgical treatment of lung cancer increased the odds of ICU admission (OR 7.23 (5.14-10.2)). Odds of admission to ICU were reduced with older age (75-80 years OR 0.69 (0.49-0.94), > 80 years OR 0.21 (0.12-0.37)), female gender (OR 0.73 (0.59-0.90)) and radiotherapy (OR 0.54 (0.39-0.73)) or chemotherapy treatment (OR 0.52 (0.38-0.70)). CONCLUSION: 1.5% of patients diagnosed with lung cancer are admitted to an ICU but both short term and long term survival was poor. Factors associated with ICU admission included age < 75 years, male gender and surgical treatment of cancer.

Comparative cohort study of volumetric modulated arc therapy for squamous cell cancer of unknown primary in the head and neck-Involved neck only versus mucosal irradiation.

OBJECTIVES: Target volumes for irradiation remain ill-defined for squamous cell cancer of unknown primary in the head and neck (SCCUP). The aim of this study was to compare involved neck only (INO) radiotherapy (RT) with irradiating involved neck plus potential mucosal primary sites and contralateral neck (MUC) in patients diagnosed and treated with modern diagnostics and techniques. DESIGN: This is a retrospective cohort study. Patients with a diagnosis of SCCUP with unilateral neck disease were included. RESULTS: Thirty patients were identified. All underwent FDG PET-CT. 47% of patients had HPV-positive SCC. 20 patients received RT to INO, 10 patients to MUC, all with volumetric modulated arc therapy (VMAT). A significantly lower dose for each organ at risk was delivered in INO-treated patients, with mean dose to contralateral parotid gland 57% less. The proportion of patients with late grade 2 or worse xerostomia was higher in MUC patients. The incidence of grade 2-3 mucositis (89% vs 45%) and grade 3 or worse dysphagia (50% vs 10%) was higher in MUC patients. Median follow-up was 31 months. No mucosal primaries emerged. Progression-free survival at 2 years was 74.7% for INO patients, 70% in the MUC group. Overall survival at 2 years was 79.7% in the INO group and 70% in the MUC patients. CONCLUSION: INO radiotherapy for patients with SCCUP of the head and neck is a safe treatment strategy resulting in clinically significant lower RT doses to OARS. Acute and late toxicities are reduced without detriment to patient survival.

Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study.

BACKGROUND: There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks. METHODS: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI). RESULTS: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged <50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to 2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head & neck (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head & neck cancer patients had increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head & neck tumours (SIR = 6.10, 95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to 3.30) cancer. CONCLUSIONS: Relative risks of second primary cancers may be smaller than previously reported. Premenopausal women with breast cancer and patients with malignant melanomas, bladder and head & neck cancers may benefit from increased surveillance and advice to avoid known risk factors.

Risk of child obesity from parental obesity: analysis of repeat national cross-sectional surveys.

OBJECTIVE: To estimate the potential to reduce childhood obesity through targeted interventions of overweight households. DESIGN: Cross-sectional nationally representative samples of the Scottish population. SETTING: Households in Scotland during 2008 and 2009. PARTICIPANTS: A total of 1651 households with parents and children aged 2-15 years. MAIN OUTCOME MEASURES: The WHO cut-off points for adult body mass index (BMI): overweight (25 to <30 kg/m2) and obese (≥30 kg/m2). Overweight and obesity in childhood respectively defined as a BMI 85th to <95th percentile and ≥95th percentile based on 1990 reference centiles. RESULTS: Thirty-two percent (600/1849) of children and 75% (966/1290) of adults were overweight or obese. Seventy-five percent (1606/2128) of all children lived with a parent who was overweight or obese. Among obese children, 58% (185/318) lived with an obese parent. The population attributable risk percentage of child obesity associated with parental obesity was 32.5%. Targeting obese households would require substantial falls in adult weight and need to reach 38% of all children; it might achieve a reduction in the prevalence of childhood obesity of 14% in these households (from 26% to 12%). Targeting parents with BMI ≥ 40 might reduce the overall prevalence of child obesity by 9%. Such an intervention would require large weight loss, consistent with approaches used for morbidly obese adults; it would involve 4% of all children and lead to a reduction in the prevalence of obesity in these households from 57% to 16%. CONCLUSIONS: Family-based interventions for obesity would be most efficiently targeted at obese children whose parents are morbidly obese.

The incidence of cancer following hospitalisation for a burn injury in Scotland 2009-2019: A retrospective cohort study.

BACKGROUND: Studies suggest increased occurrence of cancer in persons who have experienced a burn injury with hospital admission. OBJECTIVE: To determine the incidence of cancer among those hospitalised for burn injuries in Scotland compared with a similar group without a history of burn injury hospitalisation. METHOD: A retrospective cohort design was used to compare cancer (ICD10 C00-97, excluding C44) incidence in two groups: 6805 burn injury patients discharged from Scottish hospitals between 2009 and 2019, and 25,946 subjects from the general population who were matched to burn patients by sex, year of birth, and degree of social deprivation. Cancer incidence was identified from the Scottish cancer registry. Cox proportional hazard regression was used to model time to cancer incidence adjusting for age, sex, degree of deprivation and presence of a comorbidity. Cancer risk was presented as standardised incidence ratios (SIRs) and hazard ratios (HR). RESULTS: We found a higher prevalence of pre-existing conditions, particularly alcohol abuse among patients with burns. Pre-existing cancers were more common in the burn cohort (3.5%) than the comparison group (1.7%) and were excluded from further analysis. Over a median follow-up of 4-5 years, a total of 236 (3.5%) burn patients and 969 (3.7%) persons in the comparison group were diagnosed with cancer. At 0-6 months the cancer SIR for burn patients was 1.88 95% CI (1.40-2.52). After excluding the first six months of follow-up, the overall incidence of cancer was marginally elevated in burn patients (SIR 1.04, 95% CI 0.90-1.19, p = 0.62) and not statistically different from the incidence in comparison subjects (adjusted HR 1.03, 95% CI 0.88-1.21, p = 0.71). CONCLUSIONS: Patients that suffer burn injury have a higher incidence of cancer than the general population and a group matched by age, sex and degree of deprivation. A higher incidence of adverse health-related behaviours such as smoking, alcohol use and pre-existing health conditions among many patients that suffer a burn most likely explain this observed increase. Any persisting inflammatory or immune dysfunction following burn injury is unlikely to account for the increase in cancers in this study.

How did the COVID-19 pandemic change patient experience during radiation therapy for head and neck cancer: A single centre survey.

INTRODUCTION/BACKGROUND: Patients receiving treatment for head and neck cancer (HNC) with curative intent, will potentially undergo primary or adjuvant radiation therapy (RT). These patients require supportive management from an extended multi-disciplinary team, to manage the severe toxicities and distress that a course of treatment can bring. A survey was designed to determine if there were changes in the experience of HNC patients attending for radical RT, from the beginning to the end of their treatment course. During the conduct of the survey the COVID-19 pandemic began. As a result cancer services were adapted to keep patients receiving treatment protected from the virus, while continuing to treat their malignant disease. This enabled a comparison of HNC patient experiences pre-pandemic (PP) and during the pandemic (DP). The study aimed to assess the impact of changes in treatment logistics, implemented as a result of the COVID-19 pandemic, on the patient experience, analysing and comparing how well patients understood the information provided to them, their level of distress and anxiety during treatment, and their overall satisfaction with the experience. METHODS: Eligible patients were receiving radical RT for HNC of any sub-site or histological type. Identical, anonymous surveys were distributed to patients at week 1 and the final week of RT. The initial PP questionnaire (distributed December 2019 to 11th March 2020) contained 22 questions with space for free text. The questionnaire was amended DP to include 6 additional COVID-19 related questions (distributed June to November 2020). RESULTS: One hundred and eighty two surveys were returned; 95 (52%) PP and 87 (48%) DP. Patients were moderately distressed from wearing the immobilisation mask towards the end of treatment DP with a statistically significant difference in the final week, median (IQR) values of 1 (0-4) PP and 2 (1-6) DP, p=0.024. Patients reported increased distress by attending daily for treatment by the final week of RT DP, with a PP and DP median of 1 (0-3) and 2 (1-4) respectively, p=0.039. Patients reporting increased levels of distress about attending for RT also reported high levels of anxiety about COVID-19 (r=0.40, p=0.005). COVID-19 anxiety score displayed a weak inverse association with overall treatment satisfaction score (r=-0.28, p=0.008). CONCLUSION: Despite the adapted COVID-19 working practices implemented and the challenges a course of head and neck RT entails, patients reported a positive experience attending for treatment, both PP and DP.

A community pharmacy weight management programme: an evaluation of effectiveness.

BACKGROUND: Community pharmacies may offer an accessible way of delivering weight-management programmes but there have been few trials that use clinically significant weight loss outcomes, objective measures of weight and follow-up to 12 months. We aimed to evaluate weight change among patients who used the Counterweight weight management programme delivered by community pharmacies. METHODS: The Counterweight Programme was introduced into community pharmacies in Fife, Scotland in 2009 for patients with a BMI ≥ 30 kg/m(2) or a BMI ≥ 2830 kg/m(2) with a co-morbidity in localities in which Counterweight was not available at GP practices. The aim was to achieve an energy deficit of 500-600 kcal per day. Counterweight specialist dietitians delivered training, support and patient information materials to community pharmacies. Patient weight was measured by pharmacy staff at each weight management session. Weight data recorded at each weight management session were used to estimate weight change and attendance at 3, 6 and 12 months. RESULTS: Between March 2009 and July 2012, 458 patients were enrolled by the community pharmacies. Three-quarters of patients were women, mean age was 54 (SD 7.4) years and mean BMI 36.1 (SD 5.9) kg/m(2). Of 314 patients enrolled for at least 12 months, 32 (10.2% on an intention to treat basis) had achieved the target weight loss of ≥5%; this was 41.6% of those who attended at 12 months representing a mean weight loss of 4.1 kg. Using Last Observation Carried Forward, 15.9% achieved the target weight loss within 12 months of enrolling. There was no significant effect of sex, baseline BMI or age on weight loss. CONCLUSIONS: The Counterweight pharmacy programme has a similar effectiveness to other primary care based weight management programmes and should be considered as part of a range of services available to a community to manage overweight and obesity.

Risk of stroke-specific mortality after radiotherapy in patients with primary brain tumours.

Introduction: Stroke is an established complication in cancer patients, amongst whom brain tumour patients have the highest risk of fatal stroke. Radiotherapy is an important treatment for brain tumours and is associated with increased risk of cerebrovascular disease. However, the impact of brain irradiation on stroke-related deaths in brain tumour patients is unknown, and the timing of any effect uncertain. This study investigates the relationship between radiotherapy and stroke-specific mortality (SSM) in patients with primary brain tumours. Methods: Patients of any age diagnosed with histologically confirmed primary brain tumours between 1992 and 2015 were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database. Primary outcome was impact of radiotherapy on 5-year SSM. Cumulative SSM rates under competing risk assumptions were estimated and stratified by intervention type. Time-dependent hazard ratios were estimated to identify when the radiotherapy impact was greatest. Results: 85,284 patients with primary brain tumour diagnoses were analysed. Overall, the 5-year cumulative SSM rate was low (0.6%) with the highest rate (0.76%) in patients receiving no treatment, in whom it mainly occurred < 1 month after diagnosis. SSM rates were lower in patients treated with radiotherapy alone (0.27%) or radiotherapy plus surgery (0.24%); stroke-related deaths also occurred later in these groups. While these patterns were observed in both glioblastoma and non-glioblastoma patients, stroke deaths tended to occur later in non-glioblastoma patients receiving radiotherapy. Relative to the 'no treatment' group, the highest risk of stroke mortality in radiotherapy treated patients occurred 3.5-4 years after diagnosis. Conclusion: The risk of SSM is low in patients with primary brain tumours and is not increased by radiotherapy. Two different patterns were observed: acute stroke mortality in patients receiving no treatment, and delayed stroke mortality in patients receiving radiotherapy (+/- surgery) with the latter peaking 3.5-4 years after diagnosis.

Association between risk, duration and cause of hospitalisations in people with rheumatoid arthritis and multimorbidity in the UK Biobank and Scottish Early Rheumatoid Arthritis (SERA) cohorts: Longitudinal observational study.

OBJECTIVES: To investigate association between presence of multimorbidity in people with established and early rheumatoid arthritis (RA) and risk, duration and cause of hospitalisations. DESIGN: Longitudinal observational study. SETTING: UK Biobank, population-based cohort recruited between 2006 and 2010, and the Scottish Early Rheumatoid Arthritis (SERA), inception cohort recruited between 2011 and 2015. Both linked to mortality and hospitalisation data. PARTICIPANTS: 4757 UK Biobank participants self-reporting established RA; 825 SERA participants with early RA meeting the 2010 ACR/EULAR classification criteria. Participants stratified by number of long-term conditions (LTCs) in addition to RA (RA only, RA + 1 LTC and RA + ≥ 2 LTCs) and matched to five non-RA controls. MAIN OUTCOME MEASURES: Number and duration of hospitalisations and their causes. Incidence rate ratios (IRR) and 95% confidence intervals (CI) calculated using negative binomial regression models. RESULTS: Participants with RA + ≥ 2 LTCs experienced higher hospitalisation rates compared to those with RA alone (UK Biobank: IRR 2.10, 95% CI 1.91 to 2.30; SERA: IRR 1.74, 95% CI 1.23 to 2.48). Total duration of hospitalisation in RA + ≥ 2 LTCs was also higher (UK Biobank: IRR 2.48, 95% CI 2.17 to 2.84; SERA: IRR 1.90, 95% CI 1.07 to 3.38) than with RA alone. Rate and total duration of hospitalisations was higher in UK Biobank RA participants than non-RA controls with equivalent number of LTCs. Hospitalisations for respiratory infection were higher in early RA than established RA and were the commonest cause of hospital admission in early RA. CONCLUSIONS: Participants with established or early RA with multimorbidity experienced a higher rate and duration of hospitalisations than those with RA alone and with non-RA matched controls.

Classification of long-term condition patterns in rheumatoid arthritis and associations with adverse health events: a UK Biobank cohort study.

Purpose: We aimed to classify individuals with RA and ≥2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes. Methods: We used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with ≥2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC. Persons with RA without LTCs were the reference group. Analyses were adjusted for demographic characteristics, smoking, BMI, alcohol consumption and physical activity. Results: A total of 2,566 (46%) participants reported ≥2 LTCs in addition to RA. This involved 1,138 distinct LTC combinations of which 86% were reported by ≤2 individuals. LCA identified 5 morbidity-classes. The distinctive condition in the class with the highest mortality was cancer (class 5; HR 2.66 95%CI (1.91-3.70)). The highest MACE (HR 2.95 95%CI (2.11-4.14)) and emergency hospitalisations (rate ratio 3.01 (2.56-3.54)) were observed in class 3 which comprised asthma, COPD & CHD. There was an increase in mortality, MACE and emergency hospital admissions within each class as the number of LTCs increased. Conclusions: The risk of adverse health outcomes in RA varied with different patterns of multimorbidity. The pattern of multimorbidity should be considered in risk assessment and formulating management plans in patients with RA.

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up.

BACKGROUND: High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis. METHODS: We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay. RESULTS: 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score≥8) prostate cancer incidence (n = 119). The association was greatest among men in the 2nd highest quintile for cholesterol, 6.1 to < 6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of < 5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status. CONCLUSIONS: Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer.

Tea consumption and the risk of overall and grade specific prostate cancer: a large prospective cohort study of Scottish men.

Tea may be a potentially modifiable and highly prevalent risk factor for the most common cancer in men, prostate cancer. However, associations between black tea consumption and prostate cancer in epidemiological studies have been inconsistent, limited to a small number of studies with small numbers of cases and short follow-up periods and without grade-specific information. We conducted a prospective cohort study of 6,016 men who were enrolled in the Collaborative Cohort Study between 1970 and 1973 and followed up to December 31, 2007. We used Cox proportional hazards models to investigate the association between tea consumption and overall as well as grade-specific risk of prostate cancer incidence. Three hundred and eighteen men developed prostate cancer in up to 37 years of follow-up. We found a positive association between consumption of tea and overall risk of prostate cancer incidence (P = 0.02). The association was greatest among men who drank ≥ 7 cups of tea per day (HR: 1.50, 95% CI: 1.06 to 2.12), compared with the baseline of 0-3 cups/day. However, we did not find any significant association between tea intake and low- (Gleason <7) or high-grade (Gleason 8-10) prostate cancer incidence. Men with higher intake of tea are at greater risk of developing prostate cancer, but there is no association with more aggressive disease. Further research is needed to determine the underlying biological mechanisms for the association.

Coffee consumption and prostate cancer risk: further evidence for inverse relationship.

BACKGROUND: Higher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk. METHODS: We conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence. RESULTS: Higher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption. CONCLUSION: Coffee consumption reduces the risk of aggressive PC but not the overall risk.

The in-silico feasibility of dose escalated, hypofractionated radiotherapy for rectal cancer.

Background and purpose: Short course radiotherapy (SCRT) has a low biological prescription dose. Rectal cancer has a dose response relationship and moderate α/ß ratio (∼5). We hypothesise hypofractionated dose escalation has radiobiological advantages. We assessed in-silico dose escalation to the primary tumour using a simultaneous integrated boost (SIB) technique. Materials and methods: Patients who had received 25 Gy/5# were enrolled. GTV was macroscopic tumour including lumen. CTVA was GTV + 10 mm. CTVB included elective nodes. PTV_Low was created from CTVF (CTVA + CTVB) + 7 mm. PTV_High (SIB) was GTV + 5 mm margin. OAR were as per RTOG guidelines. Each patient had 4 plans created at increasing dose levels (27.5 Gy, 30 Gy, 32.5 Gy and 35 Gy) to PTV_High. PTV_Low was 25 Gy/5#.5 test plans were created for each patient in Eclipse™ v15.5 and consisted of 2 VMAT full arcs (6 MV), Varian Truebeam (2.7). Planning objectives were set in the Photon optimiser (PO) and recalculated using Acuros v15.5. A priori feasibility was defined as 90% of plans achieving the planning objectives at 32.5 Gy dose level (EqD2 53.4 Gy). Results: 20 SCRT patients median age 70, F (n = 5), M (n = 15). Rectum level; low (n = 12), mid (n = 3) and upper (n = 5). 100 plans were analysed. Mean volume of PTV_High was 130 cm3 (SD 81.5) and PTV_Low 769.6 cm3 (SD 241.1). 100% plans complied with mandatory planning dose metrics for each structure at the 25 Gy/5# plan and each dose level. Conclusion: Hypofractionated dose escalation to the primary tumour up to 35 Gy/5# is technically feasible in rectal cancer radiotherapy.

Comorbidity and survival after admission to the intensive care unit: A population-based study of 41,230 patients.

PURPOSE: To describe the relationship between comorbidities and survival following admission to the intensive care unit. METHODS: Retrospective observational study using several linked routinely collected databases from 16 general intensive care units between 2002 and 2011. Comorbidities identified from hospitalisation in the five years prior to intensive care unit admission. Odds ratios for survival in intensive care unit, hospital and at 30 days, 180 days and 12 months after intensive care unit admission derived from multiple logistic regression models. RESULTS: There were 41,230 admissions to intensive care units between 2002 and 2011. Forty-one percent had at least one comorbidity - 24% had one, 17% had more than one. Patients with comorbidities were significantly older, had higher Acute Physiology and Chronic Health Evaluation II scores and were more likely to have received elective rather than emergency surgery compared with those without comorbidities. After excluding elective hospitalisations, intensive care unit and hospital mortality for the cohort were 24% and 29%, respectively. Asthma (odds ratio 0.79, 95% confidence interval 0.63-0.99) and solid tumours (odds ratio 0.74, 0.67-0.83) were associated with lower odds of intensive care unit mortality than no comorbidity. Intensive care unit mortality was raised for liver disease (odds ratio 2.98, 2.43-3.65), cirrhosis (odds ratio 2.61, 1.9-3.61), haematological malignancy (odds ratio 2.29, 1.85-2.83), chronic ischaemic heart disease (odds ratio 1.53, 1.19-1.98), heart failure (odds ratio 1.79, 1.35-2.39) and rheumatological disease (odds ratio 1.53, 1.18-1.98). CONCLUSIONS: Comorbidities affect two-fifths of intensive care unit admission and have highly variable effects on subsequent outcomes. Information on the differential effects of comorbidities will be helpful in making better decisions about intensive care unit support and understanding outcomes beyond surviving intensive care unit.

Feasibility of DW-MRI analysis of salivary glands during head and neck radiotherapy.

INTRODUCTION: With no effective treatment for xerostomia, there remains an unmet need to reduce radiation induced toxicity. Measuring physiological changes during RT in salivary glands using DW-MRI may predict which patients are most at risk of severe toxicity. This study evaluated the feasibility of measuring apparent diffusion coefficient (ADC) in the major salivary glands and describes the observed changes in volume and ADC during RT. METHODS: Scans were acquired at baseline (MR_base) and after 10 fractions (MR_rpt). Sequences included T1 post contrast fat saturated (T1PCFS) and DW-MRI (5b values, 0-1000 s/mm2). Ipsilateral and contralateral parotid (iPG/cPG), submandibular (iSMG/cSMG) and sublingual glands (iSLG/cSLG) were delineated on T1PCFS, modified on b0 and copied to the ADC map. RESULTS: 31 patients with intermediate/high risk squamous cell carcinoma (SCC) of the oropharynx were evaluated. On 124 scans, SMG and SLG delineations were successful on all; parotids were fully contoured in 90.7%. Baseline mean ADC were significantly different between each gland type (p < 0.0001). IPG and cPG volume decreased during treatment by 6.7% and 11.2%. ISMG, cSMG, iSLG and cSLG volume increased by 6.9, 0.9, 60.8 and 60.3% respectively. All structures showed an increase in mean_ADC values. For each gland the increase in ADC was statistically significant p < 0.0001. A smaller mean percentage increase in ADC was observed in the group experiencing a higher grade (2 or > ) of toxicity. CONCLUSION: It is feasible to measure volume and ADC of the salivary glands prior to and during RT for HNC. Early data suggests a lower rise in ADC during treatment is associated with more severe late xerostomia.