Randomised feasibility study to compare the use of Therabite® with wooden spatulas to relieve and prevent trismus in patients with cancer of the head and neck.

Our aim was to compare the efficacy of the Therabite® jaw motion rehabilitation system (Atos Medical) with that of wooden spatulas to relieve and prevent trismus in patients who have had radiotherapy for stage three and four oral and oropharyngeal cancer. Secondary aims were to assess the feasibility and the impact of exercise on health-related quality of life (QoL), and the use of health services after treatment. We designed a randomised, open-label, controlled, three-centre feasibility study to compare the effectiveness and cost of the Therabite® and wooden spatulas. We studied compliance with exercises and health-related QoL, assessed cost using three health economics measures, and conducted semistructured interviews with patients. Patients were randomised into two groups: the Therabite® group (n=37) and the wooden spatula group (n=34). All patients had some sense of jaw tightening before the study started. Mean mouth opening after six months increased in both groups, but the difference between the groups was not significant (p=0.39). Completion rates for the three economic measures were good. There was no significant difference between the two groups in frequency of contact with care services or in QoL. Exercises during and after radiotherapy can ameliorate trismus in patients with stage three and four oral and oropharygeal cancers, but differences between groups in efficacy, compliance, QoL, or use of hospital or community health services, were not significant.

Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention.

INTRODUCTION: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. METHODS AND ANALYSIS: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. ETHICS AND DISSEMINATION: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. TRIAL REGISTRATION NUMBER: ISRCTN04240319; NCT01604005; Pre-results.

Age, co-morbidity and poor mobility: no evidence of predicting in-patient death and acute hospital length of stay in the oldest old.

BACKGROUND: The oldest old (aged over 90 years) are the fastest growing section of the UK population. Limited data exist regarding the effect of age, location, co-morbidity and physical performance status on outcome of acute illness in this age group. METHODS: We performed a prospective study in people aged ≥ 90 years using hospital audit data in three hospitals in England and Scotland. We examined the characteristics of those admitted over three consecutive calendar months and calculated risk ratios of death and prolonged length of acute hospital stay (>7 days). RESULTS: A total of 419 patients were included in this study (68% female, median age 93 years). There were similarities in presentation and diagnoses, but patients in Scotland (n = 164) were more likely to be admitted from sheltered housing or nursing homes than those in England (n = 255). Patients in England were significantly less likely to be able to mobilize < 10 m (41 vs. 34%, P < 0.001) but had lower prevalence of hypertension (40 vs. 55%, P = 0.02), ischaemic heart disease (30% vs. 45%, P = 0.02) and fewer prescribed medications (median 2 vs. 3, P < 0.001). Mortality was similar for the England and Scotland centres (P = 0.98). Previously recognized risk factors for death following hospital admission and length of stay e.g. older age, higher number of co-morbidities and poor mobility were not predictive in this study. CONCLUSION: The 'oldest old' should not be considered as a homogenous group and findings from single-centre studies involving this age group may not be generalizable. We found no conclusive evidence that patient-related factors predict outcome in this age group in acute medical admission settings.

Influence of aldosterone vs. endothelin receptor antagonism on renovascular function in liquorice-induced hypertension.

BACKGROUND: The enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) provides mineralocorticoid receptor specificity for aldosterone by metabolizing glucocorticoids to their receptor inactive 11-dehydro derivatives. Inhibition of 11beta-HSD2 by liquorice-derived glycyrrhizic acid (GA) therefore results in sodium retention and hypertension. The present study investigated the effect of the aldosterone receptor antagonist spironolactone in comparison with the endothelin ET(A) receptor antagonist darusentan on renovascular endothelial function in liquorice-induced hypertension. METHODS: GA, a recognized inhibitor of 11beta-HSD2 was supplemented to the drinking water (3 g/l) of Wistar Kyoto rats over a period of 21 days. From day 8 to 21, spironolactone (5.8+/-0.6 mg/kg/day), darusentan (45.2+/-6.5 mg/kg/day), or placebo was added to chow (n=7 per group). After the animals were killed, vascular function of isolated renal artery segments was assessed by isometric tension recording. RESULTS: Relaxation of pre-constricted renal artery segments in response to acetylcholine (10(-10) to 10(-5) mol/l) was impaired by GA as compared with controls (12+/-4% vs 98+/-5% of norepinephrine 3x10(-7) mol/l), whereas endothelium independent relaxations were unaffected. Endothelin receptor antagonism improved renovascular endothelium-dependent relaxation (32+/-4%, P<0.05 vs placebo) whereas endothelium-dependent relaxation was completely normalized by aldosterone receptor antagonism (85+/-4%, P<0.01 vs placebo). CONCLUSIONS: In GA-induced hypertension, both aldosterone receptor antagonism and endothelin receptor antagonism normalize blood pressure and improve renovascular function and, thus, may represent a new therapeutic approach in cardiovascular disease associated with impaired 11beta-HSD2 activity.

Clinical predictors in the evaluation of a pelvic mass.

OBJECTIVE: To determine the frequency by age of ovarian malignancies in women with a pelvic mass and to assess preoperative indicators for ovarian cancer. METHODS: Inpatient charts from June 1, 1990, to August 30, 1992, were reviewed with preoperative diagnoses of a pelvic mass. Preoperative evaluation, surgical procedure, and pathologic diagnoses were recorded. Comparisons were made using the Fisher exact test. RESULTS: In patients with ovarian disease, benign masses were found more commonly than malignancies (72 versus 13%, respectively). Ovarian malignancies were more common in patients over age 50 than in patients younger than 50 (25.6 versus 5.1%; p < 0.001). Preoperative platelet count, CA 125, and ultrasound findings did not identify patients with ovarian malignancy. CONCLUSIONS: Ovarian malignancies are uncommon in young women, but the risk of malignancy increases with age. Elevated CA 125 levels may prove to be helpful in evaluating pelvic masses in postmenopausal women.

The effect of indomethacin tocolysis on maternal coagulation status.

OBJECTIVE: To investigate the effect of indomethacin tocolysis on maternal coagulation. METHODS: Twenty gravidas at 24-32 weeks' gestation were treated for preterm labor with 50 mg indomethacin orally, followed by 25 mg every 6 hours for 3 days. Bleeding time, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were measured before and 48 hours after initiation of therapy. Statistical analysis was performed by paired t test and Fisher exact test. RESULTS: The typical participant was 22 years old, nulliparous, and 26.2 weeks' gestational age at enrollment. The mean bleeding time was 4.5 minutes before therapy and 8.8 minutes after therapy (P < .0001, mean difference 4.3 minutes, 95% confidence interval 2.9-5.8). Nineteen of the 20 subjects experienced an increase in bleeding time and 13 had abnormal bleeding times. No clinically significant changes in PT or aPTT were noted. The mean period from treatment to delivery was 60.2 days. No cases of neonatal intraventricular hemorrhage or maternal postpartum hemorrhage were noted. CONCLUSION: Oral indomethacin treatment for tocolysis has no impact on PT and aPTT; however, profound acute changes in maternal bleeding time occur.

Familial hypercholesterolaemia: pilot study to identify children at risk.

AIMS: To evaluate a more effective method of identifying children with familial hypercholesterolaemia by screening a population at high risk. METHODS: Domiciliary measurement of random cholesterol concentration was made in 200 children who were first or second degree relatives of subjects with premature onset coronary artery disease. Measurements were taken by a health visitor using a portable analyser. RESULTS: Twelve new cases of familial hypercholesterolaemia were identified during the first nine months of the study. Random cholesterol concentrations were within the normal range (< 5.2 mmol/l) in 70.5% of samples tested. Forty two (21%) of patients tested had a borderline cholesterol (5.2-5.9 mmol/l) but 50% of these fell within the normal range when fasting capillary samples were analysed. Children with significant hypercholesterolaemia on random testing (concentrations of > 5.9 mmol/l) (8.5%) also had fasting venous blood assayed for high density lipoprotein (HDL) cholesterol and tri-glyceride in the laboratory. Results indicated that 6.5% of patients screened were at high risk of cardiovascular disease (ratio of total: HDL cholesterol of > 4.5), and 1% had a moderately increased risk (ratio 3.5-4.5). CONCLUSIONS: Children with familial hypercholesterolaemia can be identified from a selected "high risk" population by measuring random capillary cholesterol concentration.