Ann Robinson’s research reviews—26 November 2018

Ann Robinson reviews the latest research from the top medical journals


Life in the old drug yet

Cisplatin has been around for 50 years. It kills cells by damaging nuclear DNA and is used to treat a wide range of cancers. But it’s far from perfect. Resistance and reduced uptake by cancer cells and side effects such as nausea, are good reasons to seek an alternative.

The current gold standard treatment for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (around 70% of total) is radiotherapy plus cisplatin. This study looked at whether replacement of cisplatin with cetuximab—an antibody against the epidermal growth factor receptor—can preserve high survival and reduce treatment toxicity. The cisplatin group fared better. The estimated 5-year overall survival was 77·9% in the cetuximab group versus 84·6% in the cisplatin group, with similar levels of toxicity. So there’s life in the old drug yet, and the search for something better goes on.

Aspirin and fish oils to prevent colon cancer

The management of colorectal cancer has improved, but it remains the second most common cause of cancer deaths in the UK. This randomised study asked whether the omega-3 fatty acid, eicosapentaenoic acid (EPA) and/or aspirin were better than placebo in preventing sporadic colorectal cancer in a high risk population. Unfortunately, EPA and aspirin didn’t reduce the proportion of individuals who had one or more colorectal adenomas, but they both decreased the recurrence of some subtypes of adenoma. The authors say, “the larger effect size of aspirin adds to the weight of evidence for its use in combination with endoscopic screening and surveillance, which provides suboptimal protection against right-sided colorectal cancer.” Not all adenomas are equal and, as we move to a precision medicine approach, it’s likely that molecular stratification of individual subtypes will replace the more crude counting of total adenomas.


New hope for peanut allergy

Peanut allergy is becoming more prevalent and is the cause of more allergy-related deaths than any other food. A lifetime of vigilance and avoidance are the only solutions at present. Enter AR101a new peanut-derived, oral biologic drug that delivers a specified amount of peanut protein. The name evokes Orwell’s sinister Room 101 where prisoners are exposed to their own worst nightmare. I’m not sure whether this is intentional or unfortunate. This well-conducted trial found that highly allergic children who were given AR101 could eat higher doses of peanut protein and had a milder allergic reaction during a subsequent challenge, than those who hadn’t received AR101. There were no deaths or life-threatening adverse events. Study limitations included a narrow demographic (predominantly white males), short follow up period (the exit challenge was 6 months after the intervention, so we don’t know how long desensitisation lasts), and exclusion of those with severe asthma (who may be most likely to benefit from desensitisation) for safety reasons.

Probiotics for children’s tummy bugs

The season of colds and tummy bugs is upon us and GPs, paediatricians, and A&E doctors are seeing lots of children with gastroenteritis. Parents and caregivers get a lot of random advicefeed them/starve them, stop the milk/don’t stop it, give them probiotics, and so on. A prospective, double-blind trial enrolled nearly a thousand children aged 3 months to 4 years of age with acute gastroenteritis who presented to one of 10 US paediatric emergency departments and randomised them to a 5-day course of the probiotic Lactobacillus rhamnosus GG, or to placebo. Just over 10% got worse rather than better over a two week period, but in most, the diarrhoea lasted around two days. Other household members were infected in 10-14% of cases. There was no significant difference between the two groups for any of the measured outcomes. One piece of advice that I will be confident about giving the parents of children with gastroenteritis isdon’t bother with probiotics.

Lung cancer: some positive results for brigatinib, but is it cost effective?

The five year survival rate for lung cancer remains shockingly low in the UK, at 9.5% overall. About 85% are non-small-cell lung cancers (NSCLC) and a small proportion (3-5%) of these are associated with a mutation of anaplastic lymphoma kinase (ALK) gene. The question asked in this pharma-funded study, is whether brigatinib, which inhibits ALK, is more effective in advanced ALK-positive cases of NSCLC than the drug crizotinib. Progression-free survival over 12 months was higher with brigatinib than with crizotinib (67% vs 43%) with no new safety concerns. NICE preliminary guidance in September said it couldn’t recommend brigatinib to treat ALK-positive advanced NSCLC on cost-effectiveness grounds, but final guidance is awaited.


Intensive care for ICU staff

Medicine and nursing are stressful professions, and nowhere more so than in intensive care units (ICUs). The question is whether a 5-day, multimodal programme, including education, role-play, and debriefing could reduce job related stress among ICU nurses? A French study found that it worked well. Job strain (as measured by questionnaires) was only reported by 13% of the intervention group compared to 67% in the control group. Absenteeism over the 6 month period went down from 8% in the control group, to 1%which seems remarkably low. The training course consisted of a recap of nursing theory, simulation scenarios based on best practice that focused on patients with deteriorating conditions, and debriefing sessions that discussed soft skills and practices. I wonder whether it was having five days away from the daily stress of ICU to reflect and talk to colleagues, as much as the actual content of the course, that made a difference to these nurses.

JAMA Internal Medicine

Pause for thought

The authors of this US study ask two questions: “How common are intimate partner violence (IPV), sexual assault, and posttraumatic stress (PTSD) among midlife and older women?” and “Are these exposures associated with women’s experience of menopause?”

In a cohort of 2016 women aged 40-80, around 1 in 5 reported IPV and/or sexual assault, and almost 1 in 4 had clinically significant symptoms of PTSD. After adjusting for obvious confounders, such as age, race/ethnicity, educational level, body mass index, menopause status, hormone therapy, and parity, they found that emotional IPV and/or current symptoms of PTSD was associated with difficulty sleeping, vasomotor symptoms, and vaginal symptoms. Women with a history of physical IPV were more likely to report night sweats, and sexual assault was (unsurprisingly) associated with vaginal symptoms.

The authors admit to the problems of studies like this; “symptoms including difficulty sleeping and night sweats are common with both PTSD and menopause, making these associations difficult to interpret.” But there are two important messages for me: abuse is a common experience for many women, which leaves an indelible mark on their lives. And consultations about the menopause can be an opportunity to explore the life behind the symptoms.


Night shifts and takeaways

The combination of night shifts and an unhealthy lifestyle increases the risk of developing diabetes. Data from a large cohort in the US, the Canadian Nurses’ Health Study, and Nurses’ Health Study II, was mined to follow 143 410 healthy women with no diagnosis of type 2 diabetes, cardiovascular disease, or cancer at baseline, to see whether they developed diabetes over the subsequent 22-24 years. Working at least three night shifts per month (in addition to day and evening shifts) was an independent risk factor for developing diabetes. Unsurprisingly, leading an unhealthy lifestyle (smoking, physical activity levels below 30 minutes per day, poor diet assessed, and body mass index of 25 or above) was also a significant risk factor for diabetes. The proportions of the joint association were “17% for duration of rotating night shift work alone, 71% for unhealthy lifestyle alone, and 11% for an additive interaction between rotating night shift work duration and unhealthy lifestyle.” The authors say “most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.” Hospital administrators take note; night staff shouldn’t have to rely on takeaways to sustain them.

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.