Ann Robinson’s research reviews—19 February 2019

Ann Robinson reviews the latest research from the top medical journals

Hepatitis C: antivirals work, especially for the most sick

How successful are direct acting antiviral treatments in people with chronic hepatitis C virus? This prospective study compared outcomes in patients treated with direct acting antivirals with patients who didn’t receive treatment. The treated group showed a drop in all cause mortality and liver cancer, especially in patients who had developed cirrhosis. The authors say that these results support offering treatment to people with the most advanced liver disease because they are the most likely to benefit. However, we still don’t know enough about the long term effects of direct acting antivirals that are given to people with less severe disease who are now expected to live a normal lifespan; further follow-up studies would be useful. Hepatitis C virus was identified in 1989 and within 25 years it has become effectively curable. It’s one of the triumphs of modern medicine.

Annals of Internal Medicine
Overweight and unfit army conscripts: how do they shape up?
Are obese and unfit adolescents more likely to be chronically disabled as adults? It may seem like a no brainer, but evidence is sparse. A Swedish population based study makes use of the fact that Sweden has a captive adolescent population because of mandatory military conscription. More than a million 16-19 year old young men who were conscripted between 1972 and 1994 had their cardiorespiratory fitness and body mass index (BMI) measured at conscription. The researchers determined whether these measures correlated with later receipt of a disability pension. Around 5% got a disability pension; the men who had been fittest as adolescents were over three times less likely to be on the disability pension at any point in time than the least fit men. Severe obesity in adolescence predicted an increase in disability pension, but being fit was protective whatever the BMI. The study had limitations: it included no women, information on smoking and alcohol was partial, and there were no repeated measurements of other variables. But it supports the idea that if you’re obese and unfit in adolescence, you’re at increased risk of chronic disability in later life—with all the personal and societal cost that implies. I’d be interested to know; does mandatory conscription improve fitness levels and lower the rate of obesity and disability in later life?

Ibuprofen to drive down morphine use
How can we reduce the use and misuse of opioid drugs? This clinical trial examines whether a combination of paracetamol 1000 mg and ibuprofen 400 mg or either drug given alone reduces the need for postoperative morphine after total hip arthroplasty? Morphine usage in the first 24 hours was lowest in patients given combined treatment, although the difference in usage between the combination group and the ibuprofen alone group was only 6 mg—lower than the study’s predefined minimal clinically relevant difference of 10 mg. Ibuprofen was also shown to be relatively safe; the proportion of patients with serious adverse events was the same (15%) for the ibuprofen plus paracetamol group and ibuprofen alone group compared with 11% for paracetamol alone, which was not statistically significant. On the basis of this study, giving ibuprofen postoperatively seems to be a safe and effective way to reduce the amount of morphine needed after a hip replacement.

JAMA Internal Medicine
Even the French eat junk food . . . what hope for the rest of us?
Ultra processed food is bad, but does it kill you? In this cohort study of 44 551 French adults 45 years or older, a 10% increase in the proportion of ultra processed food people consumed (crisps, chicken nuggets, pizza etc) was associated with a statistically significant increase in death rate14% rise on the 1.4% overall death rate over the seven year study period. Unsurprisingly, the consumption of ultra processed food was higher among people who were younger (45-64 years), had a lower income and educational level, lived alone, and had a higher body mass index and lower physical activity level. This apparent association between ultra processed food and increased mortality warrants further prospective study to flush out the variables, test the findings, and tease out possible mechanisms of action. It’s hardly surprising that people who eat a lot of junk food are (a bit) more likely to die in a given period of time. I’m not sure what this study adds to the sum of human knowledge.

Pushing up disease free survival in breast cancer
Women with residual invasive breast cancer after treatment with neoadjuvant chemotherapy and human epidermal growth factor receptor 2–targeted therapy for positive early breast cancer may welcome the results of this pharma funded trial. The researchers found that invasive disease or death occurred in 12.2% of women given trastuzumab emtansine, which is a combination of an antibody and cytotoxic drug, compared with 22.2% who were given trastuzumab alone. At three years, an estimated 88.3% of the combination group were free of invasive disease compared with 77% in the trastuzumab group. More adverse events occurred in the combination group but there seems to be a net benefit to the combination drug, compared with the antibody alone. The high rates of disease free survival at three years will be reassuring to women who have to face the news that they have residual disease despite initial treatment.

E-cigarettes or nicotine replacement for smoking cessation
Are electronic cigarettes better than nicotine replacement therapy if you’re trying to stop smoking? Eight hundred and eighty six people attending an NHS smoking cessation service were randomly assigned to nicotine replacement of their choice or an e-cigarette starter pack. Both groups received weekly behavioural support for a month. One year later, 18% remained non-smokers in the e-cigarette group, compared with about 10% in the nicotine replacement group. But abstainers who used e-cigarettes remained reliant on their product; 80% were still vaping daily after a year compared with only 9% of abstainers who used nicotine replacement. The vapers reported more oral irritation, less nausea, less cough and phlegm, and the same levels of wheeze and breathlessness as the nicotine replacement group, but the differences were small and self-reported. It would be helpful to know whether vaping without behavioural support is as effective and how long the effect persists?

Heart failure—some progress, more to be done
Heart failure is common, growing (as we live longer), costly, and treatable. But to manage and plan for this condition, we need accurate data on diagnosis, survival, and demographics. Step forward this useful retrospective population based cohort study that uses data drawn from the electronic patient records of more than 700 UK general practices over an 18 year period, and links them with inpatient and mortality data. Some of the findings seem prosaic; people who didn’t require hospital admission around the time of diagnosis lived longer, which, as the authors point out, could just reflect detection at an earlier stage of the disease. But other findings are important, if depressing; socioeconomic differences in diagnosis and survival persist (a median survival gap of 2.4 years). And although survival rates have improved by around 7% at one, five, and 10 years, the prognosis remains poor in the long term (26% 10 year survival rate). One positive finding is that since 2007 the gap in 10 year survival rates between the least and most deprived improved. The authors suggest that the Quality and Outcomes Framework (QOF), which incentivises GPs to diagnose and treat heart failure in line with best practice, may be partially responsible.

Coeliac disease: what are the triggers?
Who develops coeliac disease and why? There’s clearly a genetic tendency (HLA genotype DR4-DQ8/DR3-DQ2) and a great deal of interest in potential triggers. A Norwegian case-control study examined monthly stool samples from babies aged 3-36 months to detect exposure to two common gastrointestinal viruses (enterovirus and adenovirus) and took regular blood samples for coeliac disease antibodies up to the age of 10. Of the genetically susceptible children, 11% developed evidence of coeliac disease and they were more likely to have had enterovirus species Enterovirus A or B in their stool than the children who didn’t get coeliac disease. There was no association between adenovirus and coeliac disease. The authors’ theory is that the enterovirus infection may disrupt gut mucosa, increase translocation of gluten peptides, and trigger coeliac disease. Or it could be the other way round: a gut that is genetically predisposed to malabsorption and inflammation may be more vulnerable, or mount a stronger immune response, to enterovirus. There’s obviously more to it than genetics alone; 30-40% of northern Europeans have HLA DQ2 or DQ8 variants but only 3% of them will develop clinical coeliac disease. The search for infective and other triggers goes on.

Ann Robinson is an NHS GP and health writer/broadcaster. She works within her local community and is a trustee of the Anthony Nolan charity.

Competing interests: None declared.