HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

Purpose: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible.

Methods And Materials: HOPON was a randomized, controlled, phase 3 trial.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): a randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible: study protocol for a randomised controlled trial.

Background: Osteoradionecrosis of the mandible is the most common serious complication of radiotherapy for head and neck malignancy. For decades, hyperbaric oxygen has been employed in efforts to prevent those cases of osteoradionecrosis that are precipitated by dental extractions or implant placement. The evidence for using hyperbaric oxygen remains poor and current clinical practice varies greatly.

Refining the definition of mandibular osteoradionecrosis in clinical trials: The cancer research UK HOPON trial (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis).

Introduction: Mandibular osteoradionecrosis (ORN) is a common and serious complication of head and neck radiotherapy for which there is little reliable evidence for prevention or treatment. The diagnosis and classification of ORN have been inconsistently and imprecisely defined, even in clinical trials.

Methods: A systematic review of diagnosis and classifications of ORN with specific focus on clinical trials is presented.

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial.

Background: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer.

Methods: TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals.

Activity of eribulin mesylate in heavily pretreated breast cancer granted access via the Cancer Drugs Fund.

Aim: Eribulin mesylate is a synthetic analog of halichondrin B and is licensed for the treatment of patients with locally advanced or metastatic breast cancer that has progressed following treatment with anthracyclines and taxanes. It was not deemed to be cost effective based on a cost analysis by the National Institute for Health and Care Excellence in England and therefore it is not funded routinely by the National Health Service. The establishment of the Cancer Drugs Fund in England subsequently enabled access.

Validation of the IMPACT outcome prediction score using the Nottingham Head Injury Register dataset.

Background: Comparison of traumatic brain injury (TBI) outcomes is severely limited by the absence of a universally accepted and validated outcome prediction score. The IMPACT group recently reported models predicting mortality and unfavorable outcome after TBI, based on the outcomes of patients with moderate and severe head injury reported in two large clinical trials.

Methods: We have used prospectively collected data from 1,276 adult patients from the Nottingham Head Injury Register admitted to a single UK neurosurgical unit during a 10-year period to validate the IMPACT score models.

P3MC: a double blind parallel group randomised placebo controlled trial of Propranolol and Pizotifen in preventing migraine in children.

Background: A recent Cochrane Review demonstrated the remarkable lack of reliable clinical trials of migraine treatments for children, especially for the two most prescribed preventative treatments in the UK, Propranolol and Pizotifen.Migraine trials in both children and adults have high placebo responder rates, e.g.

Spatial effects should be allowed for in primary care and other community-based cluster RCTS.

Background: Typical advice on the design and analysis of cluster randomized trials (C-RCTs) focuses on allowance for the clustering at the level of the unit of allocation. However often C-RCTs are also organised spatially as may occur in the fields of Public Health and Primary Care where populations may even overlap.

Methods: We allowed for spatial effects on the error variance by a multiple membership model.

Autoimmunity to SOX2, clinical phenotype and survival in patients with small-cell lung cancer.

Objective: Autoantibodies to SOXB1 antigens are commonly found in patients with small-cell lung cancer (SCLC). It has not been established whether the presence of circulating SOX antibodies is associated with a specific paraneoplastic clinical phenotype, or if a tumour immune response to SOX antigens can affect prognosis in patients with SCLC in relation to other established prognostic factors.

Methods: Using recombinant SOX2 in an ELISA, we analysed sera in a prospective study from 212 unselected SCLC patients, which included 35 patients with neurological paraneoplastic disorders, or other well characterised onconeural antibodies.

Effects of dietary intervention and quadriceps strengthening exercises on pain and function in overweight people with knee pain: randomised controlled trial.

Objective: To determine whether dietary intervention or knee strengthening exercise, or both, can reduce knee pain and improve knee function in overweight and obese adults in the community.

Design: Pragmatic factorial randomised controlled trial.

Setting: Five general practices in Nottingham.

Correcting population-based survival for DCOs - why a simple method works and when to avoid it.

A high proportion of cancer registrations solely based on a death certificate (DCOs) indicates poor data quality and biases cancer survival estimates. Intensive trace-back of registrations initiated after death (DCIs) can reduce the proportion of DCOs to an acceptable level and also improve data quality in other areas (such as increasing the information on disease extent, morphology and treatment) but is expensive in staff time. Our approach - based on a proportional hazards model for DCOs relative to all other cases - can be used to predict what the likely effect of the trace-back will be on survival and to justify the extra work involved.

Local recruitment experience in a study comparing the effectiveness of a low glycaemic index diet with a low calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with polycystic ovary syndrome (PCOS).

Objective: Feasibility of a clinical-trial comparing a low-glycaemic diet with a low-calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with PCOS.

Design: A pilot Randomised-Controlled-Trial using different recruitment strategies.

Setting: A University Hospital in the United Kingdom.

Simulation modelling to validate the flow method for estimating completeness of case ascertainment by cancer registries.

Background: To validate estimates of completeness of cancer ascertainment obtained by the flow method.

Methods: We generated a computer simulation of patient-level cancer registration processes, based loosely on the age distribution and survival of colorectal carcinoma patients, and utilizing a mixture of 'cured' and 'killed' subjects with an age-dependent fraction of 'cured' cases. The simulated data were then used in an analysis of completeness using the flow method.

Risk of malignancy after gamma knife stereotactic radiosurgery.

Objective: To assess the risk of radiosurgery to cause malignant transformation in benign tumors or to induce new malignancies.

Methods: A retrospective cohort study comparing the Sheffield, England, radiosurgery patient database with national mortality and cancer registries. This data set comprises approximately 5000 patients and 30,000 patient-years of follow-up, with more than 1200 patients having a follow-up period longer than 10 years.

Effect of chemotherapy on skeletal health in male survivors from testicular cancer and lymphoma.

Purpose: There are concerns over the late effects of cancer therapy, including accelerated bone loss leading to increased risk of osteoporosis. Treatment-related bone loss is well recognized in breast and prostate cancer, due to overt hypogonadism, but there has been little evaluation of the skeletal effects of chemotherapy alone in adults. This study assesses the extent of bone loss due to previous chemotherapy in men.

An easy approach to the Robins-Breslow-Greenland variance estimator.

The Mantel-Haenszel estimate for the odds ratio (and its logarithm) in stratified case control studies lacked a generally acceptable variance estimate for many years. The Robins-Breslow-Greenland estimate has met this need, but standard textbooks still do not provide an explanation of how it is derived. This article provides an accessible derivation which demonstrates the link between the Robins-Breslow-Greenland estimate and the familiar Woolf estimate for the variance of the log odds ratio, and which could easily be included in Masters level courses in epidemiology.

The effects of twins, parity and age at first birth on cancer risk in Swedish women.

The effect of reproductive history on the risk of cervical, colorectal and thyroid cancers and melanoma has been explored but the results to date are inconsistent. We aimed to examine in a record-linkage cohort study the risk of developing these cancers, as well as breast, ovarian and endometrial cancers, among mothers who had given birth to twins compared with those who had only singleton pregnancies. Women who delivered a baby in Sweden between 1961 and 1996 and who were 15 years or younger in 1961 were selected from the Swedish civil birth register and linked with the Swedish cancer registry.

Using BNP to develop a risk score for heart failure in primary care.

Aims: Chronic heart failure is a common condition with high mortality. Accurate diagnosis in primary care is difficult. Elevated B-type natriuretic peptide (BNP) is associated with left ventricular systolic dysfunction and increased mortality.

Completeness of ascertainment by cancer registries: putting bounds on the number of missing cases.

Background: When comparing cancer incidence or mortality rates between different regions, it is important to know how complete the registration data are on which these figures are based. A number of ways of estimating completeness have been proposed, but it is often difficult to say how precise these estimates are. We describe a computer program developed to produce measures of precision for estimates of completeness obtained by one such method, the flow method.

Invasion by Neisseria meningitidis varies widely between clones and among nasopharyngeal mucosae derived from adult human hosts.

Colonization of the human nasopharynx is a feature of some species of Neisseria, and is a prerequisite of invasive meningococcal disease. The likelihood of colonization by Neisseria meningitidis varies widely between humans, and very few develop invasive disease. Explants of nasal mucosa derived from adult patients with non-allergic nasal obstruction were infected experimentally with Neisseria spp.