Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England.

BACKGROUND: The National Health Service Bowel Cancer Screening Programme (BCSP) in England uses a guaiac-based faecal occult blood test (gFOBt). A quantitative faecal immunochemical test (FIT) for haemoglobin (Hb) has many advantages, including being specific for human blood, detecting Hb at a much lower concentration with a single faecal sample and improved uptake. METHODS: In 2014, a large comparative pilot study was performed within BCSP to establish the acceptability and diagnostic performance of FIT. Over a 6-month period, 40 930 (1 in 28) subjects were sent a FIT (OC-SENSOR) instead of a gFOBt. A bespoke FIT package was used to mail FIT sampling devices to and from FIT subjects. All participants positive with either gFOBt or FIT (cut-off 20 µg Hb/g faeces) were referred for follow-up. Subgroup analysis included cut-off concentrations, age, sex, screening history and deprivation quintile. RESULTS: While overall uptake increased by over 7 percentage points with FIT (66.4% vs 59.3%, OR 1.35, 95% CI 1.33 to 1.38), uptake by previous non-responders almost doubled (FIT 23.9% vs gFOBt 12.5%, OR 2.20, 95% CI 2.10 to 2.29). The increase in overall uptake was significantly higher in men than women and was observed across all deprivation quintiles. With the conventional 20 µg/g cut-off, FIT positivity was 7.8% and ranged from 5.7% in 59-64-year-old women to 11.1% in 70-75-year-old men. Cancer detection increased twofold and that for advanced adenomas nearly fivefold. Detection rates remained higher with FIT for advanced adenomas, even at 180 µg Hb/g. CONCLUSIONS: Markedly improved participation rates were achieved in a mature gFOBt-based national screening programme and disparities between men and women were reduced. High positivity rates, particularly in men and previous non-respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource.

Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms.

A polyT repeat in an intronic polymorphism (rs10524523) in the TOMM40 gene, which encodes an outer mitochondrial membrane translocase involved in the transport of amyloid-ß and other proteins into mitochondria, has been implicated in Alzheimer's disease and APOE-TOMM40 genotypes have been shown to modify disease risk and age at onset of symptoms. Because of the similarities between Alzheimer's disease and sporadic inclusion body myositis (s-IBM), and the importance of amyloid-ß and mitochondrial changes in s-IBM, we investigated whether variation in poly-T repeat lengths in rs10524523 also influence susceptibility and age at onset in a cohort of 90 Caucasian s-IBM patients (55 males; age 69.1 ± 9.6). In carriers of APOE ε3/ε3 or ε3/ε4, genotypes with a very long (VL) poly-T repeat were under-represented in s-IBM compared to controls and were associated with a later age at symptom onset, suggesting that these genotypes may be protective. Our study is the first to suggest that polymorphisms in genes controlling mitochondrial function can influence susceptibility to s-IBM and have disease modifying effects. However, further studies in other s-IBM populations are needed to confirm these findings, as well as expression studies of different TOMM40 alleles in muscle tissue.

The impact of Jade Goody's diagnosis and death on the NHS Cervical Screening Programme.

OBJECTIVES: In August 2008 the British reality TV star Jade Goody made public her diagnosis of cervical cancer. In February 2009 it was announced that she was terminally ill and she died a few weeks later. A surge in cervical screening attendances associated with these events was widely reported. This paper aims to quantify the size of that effect across England, its duration, and whether it affected some groups of women more than others. SETTING: The Cervical Screening Programme in England. METHODS: Routinely collected statistics for the months around Jade Goody's diagnosis and death were compared with those for other periods. RESULTS: About half a million extra cervical screening attendances occurred in England between mid-2008 and mid-2009, the period during which Jade Goody was diagnosed and died; among these were 370 attendances where the test result was suspected neoplasia. At its peak in March 2009, attendance was 70% higher than expected. Increases were seen in both initial and follow-up screening attendances and in colposcopy attendances, and at all ages, though the magnitude was greater for women aged under 50. A substantially greater proportion of the extra attendances of women aged 25-49 on routine recall occurred in women whose attendance was overdue (28% occurred at 60 months or more) and relatively little represented over-screening (8% had been screened within the last 30 months). CONCLUSIONS: The pattern of increased attendance mirrored the pattern of media coverage of Jade Goody's diagnosis and death. It is likely that the increased screening resulted in a number of lives saved.

Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation.

A two generation family of Greek origin with mild myotonia, predominantly proximal muscle weakness, and cataracts compatible with the syndrome of proximal myotonic myopathy, is reported. In addition, brain MRI showed a diffuse leukoencephalopathy in the propositus. Molecular genetic studies showed the R894X mutation in exon 23 of the muscle chloride channel gene in the propositus but in only one of her two clinically affected offspring, indicating that it is not the mutation causing disease in this family.

Late radiation associated neurological injury.

Late radiation-associated neurological injury is a recognised and often fatal complication of therapeutic ionising radiation. This retrospective study outlines its highly variable presentation, radiological findings and prognosis over a 6 year period in a major teaching hospital.

Migraine and other vascular headaches. An overview of diagnosis and management.

The author reviews the diagnosis of various vascular headaches, with an emphasis on migraine, and explains their pharmacological and non pharmacological treatments. In addition, difficult areas such as 'status migranosus', complicated migraine and migraine in pregnancy are discussed. Finally, some unusual headache variants are presented.

Spatial dispersion of magnetic stimulation in peripheral nerves.

To assess the longitudinal dispersion of the stimulus induced by the magnetic coil, collision experiments were performed in seven normal ulnar nerves. A supramaximal electrical stimulus S1 was delivered at the wrist, and followed by a supramaximal stimulus S2 in the upper arm, which was either electrical (electrical collision studies), or magnetic (magnetic collision studies). The interstimulus interval was varied by 0.2 msec increments from the time of complete cancellation of the S2 evoked motor response onwards, to include the entire span of recovery of that compound motor action potential. Collision curves were obtained for both magnetic and electrical stimuli by plotting the amplitude of the motor response elicited by S2 as a function of the interstimulus interval. In all seven normal ulnar nerves, comparison of the collision curves showed that the S2 evoked motor response is restored significantly more slowly when magnetic stimulation is used. This finding is best explained by longitudinal dispersion of the stimulus induced by the magnetic coil relative to conventional electrical stimulation, the large fibers being stimulated further away from the coil than the small ones. This interpretation is confirmed by the findings obtained with the same method in two cases of ulnar neuropathy, and by comparison of different intensities of magnetic stimulation.

RR interval variation and the sympathetic skin response in the assessment of autonomic function in peripheral neuropathy.

The diagnostic value of two simple tests of autonomic function, the RR interval variation and the sympathetic skin response, was evaluated relative to symptoms of dysautonomia in 53 patients with peripheral neuropathy. Of 22 patients with peripheral neuropathy and clinical dysautonomia, 15 showed abnormal results on both tests, and 7 had abnormal results on one test only. In none of the patients with dysautonomia were both tests' results normal. Conversely, all 15 patients with abnormal results of both sympathetic skin response and RR interval variation had symptoms of dysautonomia, while 7 of 15 patients with abnormalities limited to one test had such symptoms. No patient with normal results on both tests had clinical dysautonomia. These data indicate that RR interval variation and sympathetic skin response, both of which can easily be performed in the electromyography laboratory, are helpful in combination in the assessment of autonomic function in peripheral neuropathies.

Analysis of H2 clearance curves used to measure blood flow in rat sciatic nerve.

1. By use of the H2 clearance technique, blood flow was measured in the sciatic nerve of healthy, anaesthetized Sprague-Dawley rats at rest, during inferior vena cava occlusion and during 5-hydroxytryptamine infusion. The purpose was to clarify the mechanisms underlying the biexponential curves which are commonly obtained using this technique. 2. An analysis of the frequency distribution of rate constants of 270 nerve and thirty-three arterial samples indicated that H2 clearance rates cluster below 20 ml min-1 100 g-1 and between 70 and 100 ml min-1 100 g-1. This suggests that at least two compartments are present. 3. The contribution of diffusion was studied by recording H2 clearance immediately following circulatory arrest. Slow clearance rates (median = 2.4 ml min-1 100 g-1) were observed, indicating that diffusion is not likely to contribute significantly to nutritive flow under most situations. 4. The contribution of arteriovenous shunts to H2 clearance was assessed by determining H2 clearance during inferior vena cava occlusion and the infusion of 5-hydroxytryptamine. Both manoeuvres caused abolition of, or a significant reduction in the weight of, the fast component which indicates that this compartment is closely related to arteriovenous shunts in nerve. 5. By use of a multi-compartmental model, it was shown that H2 clearance should follow a multi-exponential course, where the weights of the components reflect the relative volumes of each compartment and the exponents represent the relative flow (i.e. flow per unit volume) in each compartment. 6. By use of other mathematical models, estimates were made for the clearance rates attributable to polarographic oxidation of H2 at the tip of the microelectrode (0.2 ml min-1 100 g-1) and to diffusion to air (2 ml min-1 100 g-1). The latter estimate is very close to the measured value of 2.4 ml min-1 100 g-1. 7. These findings indicate that it is possible to separately assess nutritive and non-nutritive flow by application of biexponential analysis to H2 clearance curves. The data suggest that the fast component of a H2 clearance curve is closely associated with arteriovenous shunts, while the slower component is likely to represent capillary flow. Processes such as diffusion to air or oxidation of H2 by the electrode are very slow and therefore are unlikely to distort the assessment of blood flow by using this technique.

Aortic occlusion and reperfusion and conduction, blood flow, and the blood-nerve barrier of rat sciatic nerve.

We studied the effect of ischemia and reperfusion on blood flow, electrophysiology, and the blood-nerve barrier of the sciatic nerve of the rat. Ischemia for 10 to 60 min, with up to 3 h of reperfusion, was produced by closure and then release of a noose around the abdominal aorta. Nerve blood flow and function were measured serially using microelectrode-hydrogen polarography and electrophysiologic recordings, respectively. The integrity of the blood-nerve barrier was assessed using the permeability surface area product to [14C]sucrose. Ischemia of up to 30 min did not impair reperfusion. One hour of ischemia resulted in reperfusion abnormalities that affected about half of the nerves. The ischemic and reperfusion stresses did not disrupt the blood-nerve barrier to [14C]sucrose nor produce conduction block. Possible mechanisms for this resistance to ischemic and reperfusion injury are discussed.

Peripheral sympathetic conduction velocity calculated from surface potentials.

A simple, non-invasive and well tolerated technique is described for measuring autonomic nerve conduction velocity (ANCV) using proximal and distal peripheral autonomic surface potential (PASP) recordings. ANCV were obtained in 90% of subjects, and are comparable to values measured by intraneural recording. This technique may have applications in the assessment of autonomic neuropathies and can be readily performed in a standard EMG laboratory.

Depot-glucagon in the treatment of McArdle's disease.

Glucagon has been reported to improve exercise tolerance in some patients with myophosphorylase deficiency (McArdle's disease) but a placebo effect was not excluded in previous trials. A single-blind controlled trial of glucagon in a patient with myophosphorylase deficiency is described. Although an improved exercise endurance of the forearm muscles was demonstrated with both short-acting and depot-glucagon, this was not statistically significant when compared with placebo or no treatment.

Familial motor neurone disease associated with non-specific organic dementia. A clinico-pathological study of a family.

Two sisters developed motor neurone disease (MND), which was associated with progressive intellectual impairment in one; they survived for 18 and 24 months, respectively. At necropsy, the features of MND were confirmed, and the demented patient had severe non-specific cerebral atrophy. No evidence of Alzheimer's disease was found. Organic dementia of non-specific type can be associated with up to 15% of the familial cases of MND and with about 2% of the sporadic cases of MND in the Western world.

Cerebrospinal-fluid abnormalities associated with migraine.

Cerebrospinal-fluid (CSF) abnormalities have been reported infrequently in patients with migraine. Four cases of CSF pleocytosis and raised pressure found in young women during the course of an attack of protracted prodromal migraine, which was followed by complete recovery, are reported. In the absence of any other detectable cause, the CSF changes were attributed to the effects of the migrainous process on meningeal vascular permeability.

Campylobacter fetus subspecies jejuni isolated from Syrian hamsters with proliferative ileitis.

Two groups of Syrian hamsters received 3 weeks apart from a commercial supplier became ill and were found to have proliferative ileitis (transmissible ileal hyperplasia). Seventy-five of 200 hamsters from one group and 60 of 200 from another group were evaluated by bacteriological and histopathological techniques. Campylobacter fetus subspecies jejuni was isolated from all hamsters showing clinical signs of proliferative ileitis. The organism was recovered from fecal swabs and the ileum. Many asymptomatic animals had microscopic lesions characteristic of proliferative ileitis, and all except one were culture positive for C fetus subspecies jejuni. A group of 48 hamsters from another commercial source and free of the disease were culture negative for C fetus subspecies jejuni. These animals were inoculated by gavage with one of the following: extract of affected ileum (eight hamsters), 1 X 10(8) viable C fetus subspecies jejuni organisms (28 hamsters), or sterile saline (12 hamsters). Ileal-extract inoculated hamsters were culture positive and five of eight developed clinical signs of ileal hyperplasia. Pure-culture-inoculated hamsters had colonization of the ileum by C fetus subspecies jejuni but did not develop hyperplasia of the ileum. With this data and the tendency of C fetus subspecies jejuni to be associated with clinical enteric disease in a variety of animals and man, we suggest that C fetus subspecies jejuni may have an etiologic role in proliferative ileitis of hamsters. Other synergisms or predisposing factors also may be involved.