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On The Pulse - January 2017

On The Pulse

Tertius Lydgate

Friday, 27 January 2017

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MRI scan in suspected prostate cancer
Current biopsy test for prostate cancer can be inaccurate and cannot reliably distinguish between aggressive and harmless forms of cancers. A multicentre, paired-cohort, confirmatory study, published in The Lancet, looked at 576 men with suspected prostate cancer who were given a multi-parametric magnetic resonance imaging (MP-MRI) scan followed by two types of biopsy in 11 NHS hospitals. On template prostate mapping (TPM) biopsy, 71% of men had cancer with 40% of patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88–96%) than transrectal ultrasound-guided (TRUS) biopsy (48%, 42–55%; p<0·0001) and less specific (41%, 36–46% for MP-MRI vs 96%, 94–98% for TRUS biopsy; p<0·0001). The researchers suggested that MP-MRI could be used before TRUS biopsy as the findings showed that using the two tests could reduce over-diagnosis of harmless cancers by 5%, prevent one in four men having an unnecessary biopsy, and improve the detection of aggressive cancers from 48% to 93%.

Flexible sigmoidoscopy screening
Flexible sigmoidoscopy screening has been shown to reduce both incidence and mortality from colorectal cancer, but its effect by patient sex and age was unknown. Researchers, writing in The BMJ, have therefore conducted a pooled analysis of randomised trials (n= 287,928) comparing screening to usual care. Screening reduced the incidence of colorectal cancer in men (relative risk 0.76; 95% CI 0.70 to 0.83) and women (0.83; 0.75 to 0.92). No difference in the effect of screening was seen between men younger than 60 and those older than 60. Screening reduced the incidence of colorectal cancer in women younger than 60 (relative risk 0.71; 95% CI 0.59 to 0.84), but not significantly in those aged 60 or older (0.90; 0.80 to 1.02). Colorectal cancer mortality was significantly reduced in both younger and older men, and in women younger than 60. The findings suggest the effectiveness of flexible sigmoidoscopy screening in older women may be small or negligible, which would warrant screening recommendations for colorectal cancer to be reconsidered.

In November, Dr Lydgate pointed out research highlighting the varying cut-off points used to diagnose pre-diabetes. A new study in The BMJ has evaluated the diagnostic accuracy of screening tests for pre-diabetes and the efficacy of interventions in preventing onset of type 2 diabetes in people with pre-diabetes. The analysis of 49 studies of screening tests and 50 intervention trials revealed that HbA1c had a mean sensitivity of 0.49 (95% CI 0.40 to 0.58) and specificity of 0.79 (0.73 to 0.84), for identification of pre-diabetes, although different studies used different cut-off values. Fasting plasma glucose had a mean sensitivity of 0.25 (0.19 to 0.32) and specificity of 0.94 (0.92 to 0.96). Different measures of glycaemic abnormality identified different subpopulations. Lifestyle interventions were associated with a 36% (28% to 43%) reduction in relative risk of type 2 diabetes over six months to six years, attenuating to 20% (8% to 31%) at follow-up in the period after the trials. The authors conclude that HbA1c is therefore of limited value as it is neither sensitive nor specific for detecting pre-diabetes, while fasting glucose is specific but not sensitive. Interventions in people with pre-diabetes show to have some efficacy in preventing or delaying onset of type 2 diabetes in trial populations.

Asthma not found in previously diagnosed patients
A prospective, multicentre cohort study in JAMA has shown that among adults with physician-diagnosed asthma, a current diagnosis of asthma could not be established in 33.1% who were not using daily asthma medications or had medications weaned. All the eligible participants who agreed to enter the study (n=701) were assessed with home peak flow and symptom monitoring, spirometry, and serial bronchial challenge tests, and those participants using daily asthma medications had their medications gradually tapered off over four study visits. Current asthma was ruled out in 203 of the 613 study participants who completed the study. Findings suggest that for 11.8% of participants, spontaneous remission of their asthma was possible. However, 2% were found to have serious cardiorespiratory conditions that had been previously misdiagnosed as asthma in the community, prompting authors to call for the use of objective tests, such as prebronchodilator and postbronchodilator spirometry, serial peak flow measurements, or bronchial challenge tests, to confirm asthma at the time of initial diagnosis.

Ocrelizumab in multiple sclerosis
The NEJM has published the finding of two phase III trials for ocrelizumab in multiple sclerosis. In the first trial, researchers randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a pre-specified number of confirmed disability progression events had occurred. Ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (HR, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, the total volume of brain lesions on T2-weighted magnetic resonance imaging decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo. In the second study, researchers randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. Results showed that ocrelizumab was associated with lower rates of disease activity and progression than interferon beta-1a.

The Boss of My Sleep
BMJ Case Reports describes the positive outcome from a novel sleep management method in a toddler displaying fear and trauma. The three-year-old boy had been living with his foster mother and non-biological foster sister since he was 20 months of age, and had been twice withdrawn from his birth mother by the relevant state authority for child protection due to neglect and abuse. He had never been able to sleep alone since living with his foster mother. The strategy in the Boss of My Sleep book was an immediate success. The method, a non-cry, online sleep intervention, based on psychological behaviour change theory and positive reinforcement rather than ignoring or punishment, aims to allow toddlers to be confident enough to sleep alone. Improvements in this case were sustained after six months, which suggests that this type of intervention shows promise, particularly for parents who do not want to use cry-intensive methods.

Attentional effect of tinnitus
Individuals with tinnitus have poorer working memory, slower processing speeds and reaction times and deficiencies in selective attention. A study, published in JAMA Otolaryngology-Head & Neck Surgery, evaluated the effect of a cognitive training: ‘Brain Fitness Programme-Tinnitus’ (BFP-T), which contains 11 interactive training exercises, such as simple acoustic stimuli, continuous speech, and visual stimuli. Forty adults with bothersome tinnitus for more than six months and 20 age-matched healthy controls were randomly assigned to a BFP-T (one hour per day online training, five days per week for eight weeks) or non-BFP-T control group. The BFP-T group showed improvements in domains of tinnitus perception, attention, memory, and concentration, as well as neuroimaging changes in brain systems responsible for attention and cognitive control. While no changes in behavioural measures were observed between the two study groups, the authors conclude that cognitive training programmes might have a role in the future treatment of patients with tinnitus.

Reducing salt intake
Excessive salt intake is known to be linked to cardiovascular burdens in most countries. Researchers attempted to evaluate the cost effectiveness of a government policy combining targeted industry agreements and public education to reduce sodium intake in 183 countries worldwide. The study, published in The BMJ, looked a range of scenarios, including 10%, 30%, 0.5 g/day, and 1.5 g/day sodium reductions achieved over 10 years. Worldwide, a 10% reduction in sodium consumption over 10 years within each country was projected to avert approximately 5.8 million DALYs/year related to cardiovascular diseases, at a population weighted mean cost of I$1.13 per capita over the 10-year intervention. The research’s findings suggest that a government “soft regulation” strategy would be highly cost effective worldwide, even without accounting for potential healthcare savings.

Author's Image

Tertius Lydgate

Originally from Northumberland, Tertius Lydgate studied medicine in Edinburgh, London and Paris. There he developed a special interest in communicable diseases and hoped to make great advances in treating and preventing them. But, after a promising start in a provincial centre of excellence in middle England, he was forced by circumstances (please, don't inquire) to abandon his high ideals. He now scrapes a living by pouring cold water on the over-enthusiastic at his private cryohydrotherapy clinic. Dreaming of the contributions he once hoped to make himself, he finds consolation in the latest medical journals and is happy to share his discoveries with his readers. He thinks that his creator, George Eliot, would have approved.
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