Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment (SCOT) Trial Findings in colorectal cancer at a National Level.

AIMS: The Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland. MATERIALS AND METHODS: A retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility. RESULTS: In total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14-24) prior to June 2017 to 12 weeks (interquartile range 12-21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends. DISCUSSION: A significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.

The association between diabetes medication and weight change in a non-surgical weight management intervention: an intervention cohort study.

AIM: To compare weight change in a lifestyle-based weight management programme between participants taking weight-gaining, weight-neutral/loss and mixed diabetes medications. METHODS: Electronic health records for individuals (≥ 18 years) with Type 2 diabetes who had been referred to a non-surgical weight management programme between February 2008 and May 2014 were studied. Diabetes medications were classified into three categories based on their effect on body weight. In this intervention cohort study, weight change was calculated for participants attending two or more sessions. RESULTS: All 998 individuals who took oral diabetes medications and attended two or more sessions of weight management were included. Some 59.5% of participants were women, and participants had a mean BMI of 41.1 kg/m2 (women) and 40.2 kg/m2 (men). Of the diabetes medication combinations prescribed, 46.0% were weight-neutral/loss, 41.3% mixed and 12.7% weight-gaining. The mean weight change for participants on weight-gaining and weight-neutral/loss diabetes medications respectively was -2.5 kg [95% confidence interval (CI) -3.2 to -1.8) and -3.3 kg (95% CI -3.8 to -2.9) (P = 0.05) for those attending two or more sessions (n = 998). Compared with those prescribed weight-neutral medications, participants prescribed weight-gaining medication lost 0.86 kg less (95% CI 0.02 to 1.7; P = 0.045) in a model adjusted for age, sex, BMI and socio-economic status. CONCLUSIONS: Participants on weight-neutral/loss diabetes medications had a greater absolute weight loss within a weight management intervention compared with those on weight-gaining medications. Diabetes medications should be reviewed ahead of planned weight-loss interventions to help ensure maximal effectiveness of the intervention.

Toxicity and Efficacy of Stereotactic Ablative Body Radiotherapy for Moderately Central Non-small Cell Lung Cancers Using 50 Gy in Five Fractions.

AIMS: Stereotactic ablative body radiotherapy doses for peripheral lung lesions caused high toxicity when used for central non-small cell lung cancer (NSCLC). To determine a safe stereotactic ablative body radiotherapy dose for central tumours, the phase I/II Radiation Therapy Oncology Group RTOG 0813 trial used 50 Gy/five fractions as a baseline. From 2013, 50 Gy/five fractions was adopted at the Beatson West of Scotland Cancer Centre for inoperable early stage central NSCLC. We report our prospectively collected toxicity and efficacy data. MATERIALS AND METHODS: Patient and treatment characteristics were obtained from electronic medical records. Tumours were classed as moderately central or ultra-central tumours using published definitions. Toxicity was assessed in a centralised follow-up clinic at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years after treatment. RESULTS: Fifty patients (31 women, 19 men, median age 75.1 years) were identified with T1-2N0M0 moderately central NSCLC; one patient had both an ultra-central and a moderately central tumour. Eighty-four per cent were medically unfit for surgery. Forty per cent had biopsy-proven NSCLC and 60% were diagnosed radiologically using 18-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Fifty-six per cent of patients were Eastern Cooperative Oncology Group (ECOG) performance status 2 or worse. All patients received 50 Gy/five fractions on alternate days on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. There was one episode of early grade 3 oesophagitis and one grade 3 late dyspnoea. There was no grade 4 toxicity. Over a median follow-up of 25.2 months (range 1-70 months), there were 34 deaths: 18 unrelated to cancer and 16 due to cancer recurrence. The median overall survival was 27.0 months (95% confidence interval 20.6-35.9) and cancer-specific survival was 39.8 months (95% confidence interval 28.6, not reached). CONCLUSION: This study has shown that 50 Gy/five fractions is a safe dose and fractionation for early stage inoperable moderately central NSCLC, with outcomes comparable with other series, even with patients with a poor performance status.

Socio-economic inequalities in the incidence of four common cancers: a population-based registry study.

OBJECTIVES: To investigate the relationship between socio-economic circumstances and cancer incidence in Scotland in recent years. STUDY DESIGN: Population-based study using cancer registry data. METHODS: Data on incident cases of colorectal, lung, female breast, and prostate cancer diagnosed between 2001 and 2012 were obtained from a population-based cancer registry covering a population of approximately 2.5 million people in the West of Scotland. Socio-economic circumstances were assessed based on postcode of residence at diagnosis, using the Scottish Index of Multiple Deprivation (SIMD). For each cancer, crude and age-standardised incidence rates were calculated by quintile of SIMD score, and the number of excess cases associated with socio-economic deprivation was estimated. RESULTS: 93,866 cases met inclusion criteria, comprising 21,114 colorectal, 31,761 lung, 23,757 female breast, and 15,314 prostate cancers. Between 2001 and 2006, there was no consistent association between socio-economic circumstances and colorectal cancer incidence, but 2006-2012 saw an emerging deprivation gradient in both sexes. The incidence rate ratio (IRR) for colorectal cancer between most deprived and least deprived increased from 1.03 (95% confidence interval [CI] 0.91-1.16) to 1.24 (95% CI 1.11-1.39) during the study period. The incidence of lung cancer showed the strongest relationship with socio-economic circumstances, with inequalities widening across the study period among women from IRR 2.66 (95% CI 2.33-3.05) to 2.91 (95% CI 2.54-3.33) in 2001-03 and 2010-12, respectively. Breast and prostate cancer showed an inverse relationship with socio-economic circumstances, with lower incidence among people living in more deprived areas. CONCLUSION: Significant socio-economic inequalities remain in cancer incidence in the West of Scotland, and in some cases are increasing. In particular, this study has identified an emerging, previously unreported, socio-economic gradient in colorectal cancer incidence among women as well as men. Actions to prevent, mitigate, and undo health inequalities should be a public health priority.

Study of diffusion weighted MRI as a predictive biomarker of response during radiotherapy for high and intermediate risk squamous cell cancer of the oropharynx: The MeRInO study.

INTRODUCTION AND BACKGROUND: A significant proportion of patients with intermediate and high risk squamous cell cancer of the oropharynx (OPSCC) continue to relapse locally despite radical chemoradiotherapy (CRT). The toxicity of the current combination of intensified dose per fraction radiotherapy and platinum based chemotherapy limits further uniform intensification. If a predictive biomarker for outcomes from CRT can be identified during treatment then individualised and adaptive treatment strategies may be employed. METHODS/DESIGN: The MeRInO study is a prospective observational imaging study of patients with intermediate and high risk, locally advanced OPSCC receiving radical RT or concurrent CRT Patients undergo diffusion weighted MRI prior to treatment (MRI_1) and during the third week of RT (MRI_2). Apparent diffusion coefficient (ADC) measurements will be made on each scan for previously specified target lesions (primary and lymph nodes) and change in ADC calculated. Patients will be followed up and disease status for each target lesion noted. The primary aim of the MeRInO study is to determine the threshold change in ADC from baseline to week 3 of RT that may identify the sub-group of non-responders during treatment. DISCUSSION: The use of DW-MRI as a predictive biomarker during RT for SCC H&N is in its infancy but studies to date have found that response to treatment may indeed be predicted by comparison of DW-MRI carried out before and during treatment. However, previous studies have included all sub-sites and biological sub-types. Establishing ADC thresholds that predict for local failure is an essential step towards using DW-MRI to improve the therapeutic ratio in treating SCC H&N. This would be done most robustly in a specific H&N sub-site and in sub-types with similar biological behaviour. The MeRInO study will help establish these thresholds in OPSCC.

Critical care provision after colorectal cancer surgery.

BACKGROUND: Colorectal cancer (CRC) is the 2nd largest cause of cancer related mortality in the UK with 40 000 new patients being diagnosed each year. Complications of CRC surgery can occur in the perioperative period that leads to the requirement of organ support. The aim of this study was to identify pre-operative risk factors that increased the likelihood of this occurring. METHODS: This is a retrospective observational study of all 6441 patients who underwent colorectal cancer surgery within the West of Scotland Region between 2005 and 2011. Logistic regression was employed to determine factors associated with receiving postoperative organ support. RESULTS: A total of 610 (9 %) patients received organ support. Multivariate analysis identified age ≥65, male gender, emergency surgery, social deprivation, heart failure and type II diabetes as being independently associated with organ support postoperatively. After adjusting for demographic and clinical factors, patients with metastatic disease appeared less likely to receive organ support (p = 0.012). CONCLUSIONS: Nearly one in ten patients undergoing CRC surgery receive organ support in the post operative period. We identified several risk factors which increase the likelihood of receiving organ support post operatively. This is relevant when consenting patients about the risks of CRC surgery.

Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Orlistat is an effective adjunctive treatment to lifestyle modifications in the treatment of obesity. While the majority of current evidence is on the effect of orlistat in obese patients without diabetes, some studies suggest that patients who are obese and have diabetes mellitus lose more weight and have greater improvements in diabetic outcomes when treated with orlistat plus a lifestyle intervention than when treated by lifestyle interventions alone. The aim of this study was to review the evidence of the effects of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes. A systematic review of randomized controlled trials of orlistat in people with type 2 diabetes reporting diabetes outcomes in studies published between January 1990 and September 2013 was conducted. We searched for articles published in English in MEDLINE and EMBASE. Inclusion criteria included all randomized controlled trials of orlistat carried out on adult participants with a body mass index of 25 kg m(-2) or over diagnosed with type 2 diabetes, which reported weight change and at least one diabetic outcome. A total of 765 articles were identified out of which 12 fulfilled the inclusion criteria. The overall mean weight reduction (3, 6 and 12 months) in the orlistat group was -4.25 kg (95% CI: -4.5 to -3.9 kg). The mean weight difference between treatment and control groups was -2.10 kg (95% CI: -2.3 to -1.8 kg, P < 0.001), the mean HbA1c difference was -6.12 mmol mol(-1) (95% CI: -10.3 to -1.9 mmol mol(-1) , P < 0.004) and the mean fasting blood glucose difference was -1.16 mmol L(-1) (95% CI: -1.4 to -0.8 mmol L(-1) , P < 0.001). Treatment with orlistat plus lifestyle intervention resulted in significantly greater weight loss and improved glycaemic control in overweight and obese patients with type 2 diabetes compared with lifestyle intervention alone.

Diet, exercise, obesity, smoking and alcohol consumption in cancer survivors and the general population: a comparative study of 16 282 individuals.

BACKGROUND: Cancer survivors may be particularly motivated to improve their health behaviours. METHODS: We compared health behaviours and obesity in cancer survivors with the general population, using household survey and cancer registry data. RESULTS: Cancer survivors were more likely than those with no history of cancer to eat fruit and vegetables (ORadj 1.41, 95% CI 1.19-1.66), less likely to engage in physical activity (ORadj 0.79, 95% CI 0.67-0.93) and more likely to have stopped smoking (ORadj 1.25, 95% CI 1.09-1.44). CONCLUSIONS: Most health-related behaviours were better in cancer survivors than the general population, but low physical activity levels may be amenable to health promotion interventions.

Changes in BMI and waist circumference in Scottish adults: use of repeated cross-sectional surveys to explore multiple age groups and birth-cohorts.

OBJECTIVE: To document changes in body mass index (BMI) and waist circumference (WC) over a 10-year period 1998-2008, in representative surveys of adults. SUBJECTS: Adults aged 18-72 in the Scottish Health Surveys conducted in 1998, 2003 and 2008 were divided, separately for men and women, into eleven 5-year age bands. 'Synthetic birth-cohorts' were created by dividing participants into thirteen 5-years-of-birth bands (n=20 423). Weight, height and WC were objectively measured by trained observers. RESULTS: SUBJECTS with data available on BMI/WC were 7743/6894 in 1998, 5838/4437 in 2003 and 4688/925 in 2008 with approximately equal gender distributions. Mean BMI and waist were both greater in successive surveys in both men and women. At most specific ages, people were consistently heavier in 2008 than in 1998 by about 1-1.5 BMI units, and WCs were greater by about 2-6 cm in men and 5-7 cm in women. Greater increases were seen at younger ages between 1998 and 2003 than between 2003 and 2008, however increases continued at older ages, particularly in waist. All birth-cohorts observed over the 10 years 1998-2008 showed increases in both BMI and waist, most marked in the younger groups. The 10-year increases in waist within birth-cohorts (mean 7.4 cm (8.1%) in men and 8.6 cm (10.9%) in women) were more striking than in BMI (mean 1.8 kg m(-2) (6.6%) in men and 1.5 kg m(-2) (6.4%) in women) were particularly steep in older women. CONCLUSION: People were heavier and fatter in 2003 than those of the same age in 1998, with less marked increases in WC between 2003 and 2008 than between 1998 and 2003. There were proportionally greater increases in WC than in BMI, especially in older women. This suggests a disproportionate increase in body fat, compared with muscle, particularly among older women.

Whole-body UVB (TL-01) or UVA-1 irradiation does not alter the levels of immunomodulatory cytokines in the serum of human volunteers.

BACKGROUND/PURPOSE: Ultraviolet (UV) exposure of mammalian skin induces local and systemic immunosuppression. In mice it has been proposed that systemic immunosuppression is mediated by an UV-induced cytokine cascade involving systemic interleukin (IL)-4 and IL-10 and a reduction in IL-12 activity. To investigate whether there was a parallel mechanism in humans we examined the effect of whole-body narrowband ultraviolet B (UVB) (311-313 nm; TL-01) and ultraviolet A (UVA)-1 (340-400 nm) on serum cytokine levels. METHODS/RESULTS: In a first study, five male psoriatic subjects were whole-body irradiated with three sessions of a standard UVB (TL-01) phototherapy regimen previously shown to cause downregulation of natural killer cell activity and T helper 1 (Th1) and Th2 cytokine production by peripheral blood mononuclear cells. Enzyme-linked immunoabsorbent assay (ELISA) of sera taken before and after the third session showed no effect of phototherapy on IL-10 and tumour necrosis factor-alpha (TNF-alpha). In a second study, five healthy subjects received three whole-body exposures of UVB (TL-01) and five other healthy subjects received three exposures of UVA-1 on alternate days (total 22 J/cm(2)). Blood samples were taken before the first irradiation and at 0, 4, 8, 12, 14, 24 and 48 h after the third irradiation. The sera were subsequently analysed for IL-10, IL-12, IL-8, IL-1beta and TNF-alpha, by ELISA. The levels of IL-1beta and TNF-alpha were below detection limits (<5 pg/ml), while no significant change in the levels of IL-10, IL-12 or IL-8 was detected as a result of either TL-01 or UVA-1. CONCLUSIONS: It seems unlikely that a modulation in these circulating cytokines assessed in this study accounts for systemic UV-induced immunosuppression in human subjects.

Changing patterns of hospital admission for asthma, 1981-97.

BACKGROUND: Hospital admission rates for asthma have stopped rising in several countries. The aim of this study was to use linked hospital admission data to explore recent trends in asthma admissions in Scotland. METHODS: Linked Scottish Morbidity Records (SMR1) for asthma (ICD-9 493 and ICD-10 J45-6) from 1981 to 1997 were used to describe rates of first admissions and readmissions by age and sex. As a measure of resource use, annual trends in bed days used were also explored by age and sex. RESULTS: There were 160 039 hospital admissions for asthma by 82 421 individuals in Scotland during the study period. The overall hospital admission rate increased by 122% (from 106.7 to 236.7 per 100 000 population) but this varied by sex, age, and admission type. First admissions rose by 70% from 73.2 per 100 000 in 1986 to 124.8 per 100 000 in 1997 while readmissions fell. Children (<15 years) experienced a decline in overall admissions after 1992 due to falls in both new admissions and readmissions. By 1997 the ratio of female to male admissions was 0.57 in children, but 1.50 above 14 years of age. Mean lengths of stay fell from 10.7 days to 3.7 days between 1981 and 1997 and bed days used showed little change except for a decline after 1992 in children. CONCLUSIONS: After a period of increasing hospitalisation for asthma in Scotland, rates of admission among children have begun to fall but among adults admissions continue to rise.

Seasonal variation in mortality in Scotland.

BACKGROUND: Seasonal patterns in mortality have been recognized for many years. This study assesses seasonal variation in mortality in Scotland between 1981 and 1993 and considers its association with socioeconomic status and outdoor temperature. METHODS: Lagged Poisson regression analysis of numbers of deaths and average weekly temperature with adjustment for serial autocorrelation and influenza epidemics. RESULTS: There was significant seasonal variation in weekly death rates with a difference of about 30% between a summer trough and a winter peak. This variation was principally attributable to respiratory disease, cerebrovascular disease and coronary artery disease. Seasonal variation in mortality fell from around 38% in 1981-1983 to around 26% in 1991-1993. There was no clear evidence of a relationship between socioeconomic status and seasonal mortality, however the extent of the fall in seasonal variation was greater in deprived areas than in affluent areas. Overall, a 1 degree C decrease in mean temperature was associated with a 1% increase in deaths one week later. The lag in this relationship varied by cause of death and underlying temperature. CONCLUSIONS: Seasonal variations in mortality and the relationship between temperature and mortality are a significant public health problem in Scotland. It is likely that the strength of this relationship is a result of the population being unable to protect themselves adequately from the effects of temperature rather than the effects of temperature itself.

Speech and language therapy caseloads in seven districts in the UK.

This paper provides managers and clinicians with an analysis of routine data collected by seven speech and language therapy services in the UK. Managers in seven districts in the UK of varying size and location were asked to provide information on referrals, waiting times and attendances during the six month period, and to give a breakdown of the types of intervention offered and type of clients seen. These data were aggregated and comparisons were made with existing data on speech and language therapy services. The results revealed considerable variations in prevalence, staffing ratios and client management practices. The implications for service planning are discussed.

The value of in-patient dermatology: a survey of in-patients in Scotland and Northern England.

Dermatology in-patient units are frequently threatened with reduction or closure, yet there are few objective data regarding the nature and use of in-patient management with which to assess their value. We have surveyed 300 patients admitted during March 1997 to dermatology units throughout Scotland and Northern England, to establish their clinical and social profile, and the outcome of admission. All departments provided phototherapy and out-patient treatment services, and 84% of those admitted lived within an hour's travel of one of these. Three diagnostic groups (psoriasis, eczema and leg ulcers) accounted for 83% of in-patient days. Patients were admitted principally because of disease severity but many, including half of those with psoriasis, had concurrent medical problems such as alcohol abuse, psychiatric disorder or arthropathy. Many patients with psoriasis and leg ulcers were from socially deprived areas, as defined by low Carstairs index scores, and a similar proportion received income support. Eighteen per cent of patients, mainly those with acute disorders, would have needed admission irrespective of dermatology bed availability. Out-patient management was considered the next best alternative for only 28% of patients, and many patients would have been expected to treat themselves. By contrast, 84% of patients admitted were cleared or substantially improved, or had procedures completed as planned, and another 12% were partially improved. Outcomes were particularly good in psoriasis, eczema and infection groups. We have demonstrated that in-patient management is highly effective in providing remission in chronic skin disease, and our survey also suggests that concomitant disability or social factors mean that for many such patients ambulatory care cannot replace this service.

Does the availability of prescribed drugs affect rates of self poisoning?

The trends in self-poisoning rates and in rates of prescribing of the major drug groups were compared. Over the period 1981-91, barbiturate prescribing and self poisoning both fell by 80%; for antidepressants, prescribing increased by over 40% and self poisoning by 30%; for antipsychotics, both rose by 30%; for benzodiazepines, poisoning fell by 30% and prescribing by 20%. Even for analgesic drugs, which are also available over the counter, there was a correspondence between changes in self poisoning and prescribing. The availability of prescribed drugs is directly related to their use for self poisoning. Restricting the availability of these drugs is a possible preventative strategy, although further research on this is needed.

Hospitalisation for deliberate self-poisoning in Scotland from 1981 to 1993: trends in rates and types of drugs used.

BACKGROUND: Rates of self-poisoning fell during the 1980s, although recent reports suggest this trend may have reversed. METHODS: Data on all hospital discharges with a diagnosis of deliberate self-poisoning were obtained from the Information and Statistics Division of the NHS in Scotland. Rates of self-poisoning were investigated by overall trend, and for trends by age and by type of drug. RESULTS: Deliberate self-poisoning rates for men and women began increasing in the late 1980s, and did so steadily during the early 1990s. Because the rates are increasing faster in men, the traditional excess of self-poisoning among women is being eroded. For men rates increased in all age groups up to the age of 60, but the greatest rise occurred between ages 15-29. For women the increase was largely restricted to 15-24-year-olds, and rates fell among women over the age of 50. Self-poisoning with paracetamol increased most rapidly; in contrast to aspirin which showed little change. Opiate analgesics, antirheumatics, antidepressants and antipsychotics have also shown some increase in their use in both genders. There has been a substantial fall in the use of benzodiazepines in women, but little change among men. CONCLUSION: Rapid increases in self-poisoning particularly among young adults present a serious public health problem. Controlling this epidemic is made difficult because the principal drug involved, paracetamol, is readily available.