Cancer incidence amongst UK firefighters.

Firefighters suffer an increased risk of cancer from exposures to chemicals released from fires. Our earlier research has found that fire toxicants not only remain on firefighters' PPE, but are also tracked back to fire stations. The UK Firefighter Contamination Survey assesses firefighters' risk of developing cancer due to occupational exposure to fire toxins. Over 4% of surveyed firefighters were found to have a cancer diagnosis, with the age-specific cancer rate up to 323% higher (35-39 year olds) than that of the general population. Firefighters who had served ≥ 15 years were 1.7 times more likely to develop cancer than those who had served less time. Firefighters were at least twice as likely to be diagnosed with cancer if they noticed soot in their nose/throat (odds ratio (OR) = 2.0, 1.1-3.5), or remained in their PPE for more than four hours after attending a fire incident (OR = 2.3, 1.1-5.2). Also associated with an increased likelihood of cancer was: eating while wearing PPE (OR = 1.8, 1.2-2.7); failing to store clean/dirty PPE separately (OR = 1.3, 1.0-1.7); working in a station that smells of fire (OR = 1.3, 1.0-1.8) or not having designated (separated) clean and dirty areas (OR = 1.4, 1.1-1.7); using an on-site washing machine to launder fire hoods (OR = 1.3, 1.0-1.7); feeling that cleaning is not taken seriously at work (OR = 1.5, 1.2-2.0).

Returning to Leisure Activity Post-Stroke: Barriers and Facilitators to Engagement.

OBJECTIVES: To identify barriers and facilitators to engagement when returning to, or participating in, leisure activity post-stroke or Transient Ischemic Attack (TIA). DESIGN: Sequential explanatory, mixed methods study. SETTING: 21 hospital sites across England, Wales and Northern Ireland. PARTICIPANTS: Adults with a clinical diagnosis of first/recurrent stroke or TIA. Patients approaching end of life were excluded. Participants were recruited as in-patients or at first clinic appointment and a baseline questionnaire was completed. A 6-month follow-up questionnaire was sent to participants for self-completion. Open-text questions were asked about barriers and facilitators when returning to, or participating in, leisure activity. Responses were thematically analysed and explored by participant characteristics, including type of leisure activity undertaken. Characteristics also included measures of socioeconomic deprivation, mood, fatigue and disability. RESULTS: 2000 participants returned a 6-month follow-up questionnaire (78% stroke, 22% TIA); 1045 participants responded to a question on barriers and 820 on facilitators. Twelve themes were identified and the proportion of responses were reported (%). Barriers: physical difficulties (69%), lower energy levels (17%), loss of independence (11%), psychological difficulties (10%), hidden disabilities (7%), and delay or lack of healthcare provision (3%). Facilitators: family support (35%), healthcare support (27%), well-being and fitness (22%), friendship support (20%), self-management (19%), and returning to normality (9%). 'Physical difficulties' was the most reported barrier across all participant characteristics and activity types. Family support was the most reported facilitator except for those with greater disability, where it was healthcare support and those without fatigue where it was well-being and exercise. CONCLUSIONS: Physical difficulties and lack of energy are problematic for stroke and TIA survivors who want to return to or participate in leisure activity. Healthcare support alone cannot overcome all practical and emotional issues related to leisure activity engagement. Family support and improving well-being are important facilitators and future research should explore these mechanisms further.

Life and Leisure Activities following Stroke or Transient Ischaemic Attack (TIA): An Observational, Multi-Centre, 6-Month Follow-Up Study.

OBJECTIVE: To examine changes in leisure participation following stroke/transient ischaemic attack (TIA) and explore its relationship to modifiable and non-modifiable participant characteristics. DESIGN: An observational study design with self-report questionnaires collected at two time points (baseline and 6-months). SETTING: The study was conducted across 21 hospital sites in England, Wales, and Northern Ireland. PARTICIPANTS: Participants were aged 18+ and had experienced a first or recurrent stroke or TIA and had a post-stroke/TIA modified Rankin score (mRS) of ≤3. PROCEDURE: Research practitioners at each site approached potential participants. Individuals who agreed to participate completed a baseline questionnaire whilst an inpatient or at a first post-stroke/TIA clinic appointment. A follow-up questionnaire was posted to participants with a freepost return envelope. Two questionnaires were developed that collected demographic information, pre-stroke/TIA mRS, social circumstances (e.g., employment situation) and incorporated the shortened Nottingham Leisure Questionnaire (sNLQ). RESULTS: The study recruited eligible participants (N = 3295); 2000 participants returned questionnaires at follow-up. Data showed three participant variables were significant predictors of engagement in leisure activities post-stroke/TIA: age, sex, and deprivation decile. There was an overall decline in the number and variety of leisure activities, with an average loss of 2.2 activities following stroke/TIA. Only one activity, "exercise/fitness" saw an increase in engagement from baseline to follow-up; watching TV remained stable, whilst participation in all other activities reduced between 10% and 40% with an average activity engagement reduction of 22%. CONCLUSIONS: Some groups experienced a greater reduction in activities than others-notably older participants, female participants, and those living in a low socioeconomic area. REGISTRATION: researchregistry4607. STRENGTHS AND LIMITATIONS OF THIS STUDY: 1. This is the largest-ever study to survey life and leisure activity engagement following stroke/TIA. 2. Survey responses were self-reported retrospectively and, therefore, may have been misreported, or misremembered. 3. Despite the large cohort, there were few participants, and so respondents, from ethnic minority groups.

Augmented renal clearance: a retrospective, cohort study of urinary creatinine clearance in critically ill patients in the United Kingdom.

OBJECTIVE: Augmented renal clearance (ARC) is associated with sub-therapeutic antibiotic, anti-epileptic, and anticoagulant serum concentrations leading to adverse patient outcomes. We aimed to describe the prevalence and associated risk factors for ARC development in a large, single-centre cohort in the United Kingdom. METHODS: We conducted a retrospective observational study of critically unwell patients admitted to intensive care between 2014 and 2016. Urinary creatinine clearance was used to determine the ARC prevalence during the first 7 days of admission. Repeated measures logistic regression was used to determine risk factors for ARC development. RESULTS: The ARC prevalence was 47.0% (95% confidence interval [95%CI]: 44.3%-49.7%). Age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and sepsis diagnosis were significantly associated with ARC. ARC was more prevalent in younger vs. older (odds ratio [OR] 0.95 [95%CI: 0.94-0.96]), male vs. female (OR 0.32 [95%CI: 0.26-0.40]) patients with lower vs. higher APACHE II scores (OR 0.94 [95%CI: 0.92-0.96]). CONCLUSIONS: This patient group probably remains unknown to many clinicians because measuring urinary creatinine clearance is not usually indicated in this group. Clinicians should be aware of the ARC risk in this group and consider measurement of urinary creatinine clearance.

Glucocorticoid Therapy in ANCA Vasculitis: Using the Glucocorticoid Toxicity Index as an Outcome Measure.

Background: ANCA-associated vasculitis (AAV) is an autoimmune disease. Induction remission and maintenance treatment typically includes high-dose, tapering glucocorticoids (GC), in addition to other immunosuppressive medication. The use of theGlucocorticoid Toxicity Index (GTI) provides a global, quantifiable assessment tool in which clinicians can assess GC-associated morbidity. Recent trials in AAV have exposed the need for systemic assessment of GC burden. In this small cohort study, we look to address these issues and the justification of newer GC sparing agents, such as C5a inhibitors. Methods: A retrospective cohort study of 43 patients with biopsy AAV was constructed from a single center between 2012-2016, and followed up for 48 months. The GTI table made up of adverse features was used to quantify patients' GC toxicity. Electronic patient records were reviewed and scores calculated according to published methods. GTI scores were compared with cumulative steroid doses at separate intervals and incidences of adverse features in relation to the treatment timeline. Results: The mean age was 65.9 (±11.06) years and treatment regimens consisted of glucocorticoids alongside cyclophosphamide or rituximab. Our results showed statistical significance in the association of cumulative GC doses and GTI scores (P=0.008; 95% CI, 1.31 to 8.05). Adverse features relating to mood disturbance and GC-induced psychosis occurred early, in contrast to adrenal insufficiency, which typically presented later in the follow-up. Infection-related adverse events were consistent throughout. Conclusions: We demonstrated that higher cumulative doses of steroids in AAV lead to worse glucocorticoid-related toxicity. Using the GTI creates the potential to individualize and quantify the adverse effects patients experience as a result of GC treatment and permits more patient-centered management. Although glucocorticoids remain the main adjunctive immunosuppression of AAV treatment, the narrow therapeutic window supports the need for GC-sparing treatments.

Effects of Pulmonary Rehabilitation on Exacerbation Number and Severity in People With COPD: An Historical Cohort Study Using Electronic Health Records.

BACKGROUND: In previous systematic reviews (predominantly of randomized controlled trials), pulmonary rehabilitation (PR) has been shown to reduce hospital admissions for acute exacerbations of COPD (AECOPD). However, findings have been less consistent for cohort studies. The goal of this study was to compare rates of hospitalized and general practice (GP)-treated AECOPD prior to and following PR. METHODS: Using anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics, hospital admissions and GP visits for AECOPD were compared 1 year prior to and 1 year following PR in patients referred for PR. Exacerbation rates were also compared between individuals eligible and referred for PR vs those eligible and not referred. RESULTS: A total of 69,089 (64%) of the patients with COPD in the cohort were eligible for PR. Of these, only 6,436 (9.3%) were recorded as having been referred for rehabilitation. A total of 62,019 (89.8%) were not referred, and 634 (0.98%) declined referral. When combining GP and hospital exacerbations, patients who were eligible and referred for PR had a slightly higher but not statistically significant exacerbation rate (2.83 exacerbations/patient-year; 95% CI, 2.66-3.00) than those who were eligible but not referred (2.17 exacerbations/patient-year; 95% CI, 2.11-2.24). CONCLUSIONS: This study found that < 10% of patients who were eligible for PR were actually referred. Patients who were eligible and referred for (but not necessarily completed) PR did not have fewer GP visits and hospitalizations for AECOPD in the year following PR compared with those not referred or compared with the year prior to PR.

Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms.

BACKGROUND: The CRASH-2 trial showed that tranexamic acid (TXA) administration reduces mortality in bleeding trauma patients. However, the effect appeared to depend on how soon after injury TXA treatment was started. Treatment within 3 h reduced bleeding deaths whereas treatment after 3 h increased the risk. We examine how patient characteristics vary by time to treatment and explore whether any such variations explain the time-dependent treatment effect. METHODS: Exploratory analysis were carried out, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo-controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examine how patient characteristics (age, type of injury, presence or absence of head injury, Glasgow coma scale (GCS), systolic blood pressure and capillary refill time) vary with time to treatment and use univariable (restriction) and multivariable methods to examine whether any such variations explain the time-dependent effect of TXA. If not explained by differences in patient characteristics, we planned to conduct separate prespecified subgroup analyses for the early benefit and late harm. RESULTS: There was no substantial variation in age or capillary refill by time to treatment. However, the proportion of patients with blunt trauma, the proportion with head injury and mean systolic blood pressure increased as time to treatment increased. Mean GCS decreased as time to treatment increased. Analyses restricted to patients with blunt trauma, those without head injury and those with a systolic blood pressure <100 mmHg showed that these characteristics did not explain the time-dependent treatment effect. In a multivariable analysis the interaction with time to treatment remained highly significant (p < 0.0001). Separate subgroup analyses that examine how the benefits of early TXA treatment and the harms of late TXA treatment vary by systolic blood pressure (≤75, 76-89, >89 mmHg); GCS (severe 3-8, moderate 9-12, mild 13-15); and type of injury (penetrating versus blunt) showed no significant heterogeneity. CONCLUSIONS: The time-dependent effect of TXA in bleeding trauma patients is not explained by the type of injury, the presence or absence of head injury or systolic blood pressure. When given within 3 h of injury, TXA reduces death due to bleeding regardless of type of injury, GCS or blood pressure. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00375258 . Registered on 11 September 2006.

Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.

There is a paucity of data on incidence, prevalence and mortality associated with non-cystic fibrosis bronchiectasis.Using the Clinical Practice Research Datalink for participants registered between January 1, 2004 and December 31, 2013, we determined incidence, prevalence and mortality associated with bronchiectasis in the UK and investigated changes over time.The incidence and point prevalence of bronchiectasis increased yearly during the study period. Across all age groups, the incidence in women increased from 21.2 per 100 000 person-years in 2004 to 35.2 per 100 000 person-years in 2013 and in men from 18.2 per 100 000 person-years in 2004 to 26.9 per 100 000 person-years in 2013. The point prevalence in women increased from 350.5 per 100 000 in 2004 to 566.1 per 100 000 in 2013 and in men from 301.2 per 100 000 in 2004 to 485.5 per 100 000 in 2013. Comparing morality rates in women and men with bronchiectasis in England and Wales (n=11 862) with mortality rates in the general population from Office of National Statistics data showed that in women the age-adjusted mortality rate for the bronchiectasis population was 1437.7 per 100 000 and for the general population 635.9 per 100 000 (comparative mortality figure of 2.26). In men, the age-adjusted mortality rate for the bronchiectasis population was 1914.6 per 100 000 and for the general population 895.2 per 100 000 (comparative mortality figure of 2.14).Bronchiectasis is surprisingly common and is increasing in incidence and prevalence in the UK, particularly in older age groups. Bronchiectasis is associated with a markedly increased mortality.

Lifestyle changes for improving disease-specific quality of life in sedentary men on long-term androgen-deprivation therapy for advanced prostate cancer: a randomised controlled trial.

BACKGROUND: Prostate cancer is a key driver of cancer-related global disability-adjusted life-years. Androgen-deprivation therapy (ADT) for advanced disease is linked to fatigue, reduced physical function, and quality of life (QoL). OBJECTIVE: To evaluate the effect of a lifestyle intervention on disease-specific QoL, diastolic blood pressure, and cancer-related fatigue in sedentary men receiving long-term ADT for advanced prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 100 hundred sedentary men with locally advanced or metastatic prostate cancer on long-term ADT were randomised to an intervention or usual care group. INTERVENTION: A 12-wk lifestyle intervention consisting of aerobic and resistance exercise with parallel dietary advice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Disease-specific QoL was measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaires at 12 wk postintervention and at 6 mo following withdrawal of support. Analysis of covariance and mixed regression were conducted. RESULTS AND LIMITATIONS: Clinically relevant improvements in FACT-P were seen at 12 wk in the intervention group compared with controls (mean difference: 8.9 points; 95% confidence interval [CI], 3.7-14.2; adjusted p=0.001). No difference was apparent at 6 mo (mean difference: 3.3 points; 95% CI, -2.6 to 9.3; adjusted p=0.27). No difference in diastolic blood pressure was seen at either follow-up (all p > 0.05). Clinically relevant improvements in FACT-F were seen at 12 wk (mean difference: 5.3 points; 95% CI, 2.7-7.9; adjusted p<0.001) and maintained following withdrawal of supervision (mean difference: 3.9 points; 95% CI, 1.1-6.8; adjusted p=0.007). Improvements in exercise tolerance and behaviour were maintained at 6 mo (adjusted p<0.001 and 0.038). CONCLUSIONS: A lifestyle intervention resulted in a clinically meaningful improvement in disease-specific QoL that was not maintained postintervention. No effect on blood pressure occurred. Durability of response was seen in fatigue and exercise behaviour. Further evaluation of support structures is essential. TRIAL REGISTRATION: ISRCTN88605738.

Manipulation or intra-articular steroids in the management of adhesive capsulitis of the shoulder? A prospective randomized trial.

BACKGROUND: The management of adhesive capsulitis (frozen shoulder) is controversial. The authors present a prospective randomized study comparing the outcome, at a two-year follow-up period, of two groups of patients treated either by manipulation of the shoulder under anaesthetic or by intra-articular shoulder injections using steroid with distension. METHODS: Fifty-three patients suffering from Idiopathic "Primary" Frozen Shoulder were prospectively randomized into two treatment groups and followed up for two years from the start of treatment. Patients were assessed using the Constant score, a Visual Analogue Score, and the SF36 questionnaire. RESULTS: No statistical differences were found between the two groups of patients with regards to the outcome measures. CONCLUSION: Treatment using steroid injections with distension as an out-patient is therefore recommended for the treatment of Idiopathic "Primary" Frozen Shoulder. This has the same clinical outcome as a manipulation under anaesthetic with less attendant risks.

Urinary diaries: a comparison of data collected for three days versus seven days.

OBJECTIVE: To compare the quality of data recorded in urinary diaries completed for 3 days compared with those completed for 7 days. METHODS: Men and women enrolled in a randomized study of a nurse-led intervention for urinary incontinence were eligible for the study. Participants completed either a 7-day diary or a 3-day diary at baseline and after 8 weeks of the trial intervention. Data quality was assessed by categorizing each day as complete or incomplete. Incomplete days were those with fewer than four entries and those with obvious discrepancies from the rest of the diary days. Data were compared by percentage differences with 95% confidence intervals (95% CI). RESULTS: Two hundred forty-eight patients completed the 3-day diary, and 40 patients competed the 7-day diary. The majority of the respondents were women. There were more completed 3-day diaries (90.7%) compared with 7-day diaries (50%) (difference 40.7%, 95% CI 28.8-52.6%). When compared with the first 3 days of the 7-day diary, the 3-day diary contained more complete data (90.7% versus 65%; difference 25.7%, 95% CI 14.6-36.9%). These differences were seen in all data types except nocturnal incontinence. There was no evidence of association between diary completion and demographic characteristics. CONCLUSION: Our data demonstrated that the 7-day diary included less complete data than the 3-day diary, even in the first 3 days of the longer diary. This finding suggests elements of both diary "fatigue" and also diary "despair" may be acting. We would suggest that a 3-day diary is superior in terms of data quality. LEVEL OF EVIDENCE: III.

Audit of outcomes in motor neuron disease (MND) patients treated with riluzole.

A review of riluzole in MND by NICE concluded that riluzole was modestly effective. NICE however suggested that further studies were needed to gain further insights into its clinical effectiveness. As these studies have not been carried out we audited outcomes in our use of riluzole. Median survival of 148 MND patients receiving riluzole was 3.07 years (2.25 years for 327 patients not given riluzole), hazard ratio 1.66, 95% confidence interval (CI) 1.32-2.12; 3.61 years in 103 limb onset patients given riluzole (2.62 years for 124 limb onset patients not given riluzole), hazard ratio 1.50, 95% CI 1.09-2.05; 2.19 years in 43 bulbar onset patients receiving riluzole (1.84 years for 103 bulbar onset patients not given riluzole), hazard ratio 1.34, 95% CI 0.89-2.07 and 3.80 years in 87 patients with a PEG given riluzole (2.21 years for 261 patients with a PEG not given riluzole), hazard ratio 1.86, 95% CI 1.44-2.39. These findings are comparable with the results of similar analyses from other groups. The uncertainties they raise emphasize the importance of adequate randomized studies being completed prior to licensing of new drugs. They further illustrate the desirability of controlled introduction of new drugs into clinical practice when RCTs have only suggested a modest level of efficacy.

Proportional growth of craniofacial regions.

OBJECTIVE: The ratio of the cranium to the face has been traditionally reported in textbooks without any firm evidence base. The present study was undertaken to measure the increase in size with age of the cranium, face, upper and lower face components. METHOD: Bolton standard mean outlines for ages 1 to 18 years were analysed by the Autoceph computer program. We measured the area of each craniofacial component outline. RESULTS: The ratio of the size of the cranium to the face was less than previously reported at birth, 2 years, and 5 years of age, but more nearly correct in the adult. Growth of the cranium largely ceased by 9-years indicating precocious growth of the brain in relation to the face. The size of the face increased relative to the cranium by 69%. The lower face increased relative to the upper face by 22%. The average percentage increase in area was 78% lower face, 68.9% total face, 58.8% upper face, 26% cranium. The absolute growth rate of the face was greater than that of the cranium, and that of the lower face was greater than that of the upper face. The 95% confidence intervals for the growth rates did not overlap, indicating a statistically significant difference. The relative growth rate (cm2/cm2/yr) was 0.0444 lower face, 0.0391 total face, 0.0328 upper face, 0.0084 cranium. CONCLUSIONS: There was a differential gradient of change increasing from the cranium to the upper face to the lower face. This gradient was most clearly expressed by the relative growth rates and average percentage increases in area.

Prediction of cardiac risk prior to elective abdominal aortic surgery: role of multiple gated acquisition scan.

Debate continues regarding the value of cardiac testing before major vascular surgery. Studies looking at whether a low radioisotope left ventricular ejection fraction (LVEF) could reliably predict postoperative cardiac events have produced conflicting results. Technetium-99m multiple gated acquisition (MUGA) scanning was employed in 122 patients undergoing elective abdominal aortic aneurysm surgery to estimate the resting LVEF and to detect regional or global myocardial wall motion abnormalities (WMAs). Adverse cardiac outcomes were predicted using logistic regression analysis. Among this group of patients, 20 did not proceed to surgery for a variety of reasons, and 102 underwent surgical repair. More than half of the patients (55%) had a history of cardiac disease. The mean +/- SD LVEF was 55.5% +/- 11.1%. Altogether, 31 patients had WMAs, and 21 had both WMAs and an abnormal LVEF (< or = 50%). Altogether, 20 cardiac complications were encountered in 17 patients (17%). Logistic regression analysis identified four significant predictors of cardiac complications: history of cardiac disease [odds ratio (OR) 10.43; 95% confidence interval (CI) 1.3 and 80.5], the presence of WMAs (OR 10.1, CI 1.4 and 74.6), additional procedures (OR 12.1, CI 1.4 and 103.0), and reoperation during the postoperative period (OR 6.4, CI 1.4 and 30.4). This is the largest reported British series of cardiac testing using MUGA scans prior to abdominal aortic reconstruction. Only the presence of WMAs (not the resting LVEF) was useful for predicting postoperative cardiac events. A history of cardiac disease, additional procedures, and reoperation during the postoperative period also place a patient at high risk for cardiac complications. A normal LVEF is by no means reassuring that a patient is at low risk of suffering an adverse cardiac outcome.