Ann Robinson’s research reviews—7 January 2019

Ann Robinson reviews the latest research from the top medical journals


Ibrutinib for untreated chronic lymphocytic leukaemia

Ibrutinib, a B cell receptor inhibitor, has been approved for the treatment of untreated chronic lymphocytic leukaemia since 2016.  But it hasn’t been compared with other chemoimmunotherapy options until this phase 3 trial of patients aged 65 years or older with untreated chronic lymphocytic leukaemia. The conclusion is that ibrutinib gives longer progression-free survival (87% at 2 years) than bendamustine plus rituximab (74%), and that ibrutinib on its own is as good as ibrutinib plus rituximab.

Fixing secondary mitral regurgitation

Mitral regurgitation is often secondary to a diseased left ventricle rather than a primary problem with the mitral valve itself. Early surgery for severe primary mitral regurgitation is accepted practice, but it’s unclear what to do in secondary mitral regurgitation. Two new studies come to different conclusions. One found that percutaneous mitral valve repair with medical therapy was no better than medical therapy alone in preventing death or hospital admission with heart failure at 1 year. A second study found the opposite. Transcatheter mitral valve repair resulted in a lower rate of hospitalisation for heart failure and lower all cause mortality within 24 months of follow-up than medical therapy alone.


Drink-driving—no easy solutions

Fatal road traffic incidents in the UK have fallen substantially (72% reduction from 1979-2017), but alcohol remains a major risk factor for deaths related to driving. Scotland lowered the legal blood alcohol concentration limit for drivers from 0.08 g/dL to 0·05 g/dL in 2014. This study looked at data on road traffic incidents and alcohol consumption in Scotland and in England and Wales—where the limit has not been lowered. It didn’t find any reduction in road traffic incidents, but there was a small fall in alcohol sales. Just lowering the legal blood alcohol concentration limit may not be enough to prevent deaths. Other public health measures, such as better legal enforcement and social attitudinal shifts, may help.

JAMA Intern Med

Encouraging exercise for older people

Exhorting older people to exercise has become standard advice for a wide range of conditions, but do we have evidence to support this? This meta-analysis of 40 long term randomised clinical trials including 21,868 participants found that long term exercise (a year or more), particularly moderate intensity multicomponent training with balance exercises, performed 2 to 3 times per week, appears to be safe and effective and reduces the risk of falling in older people. The effect is modest; to prevent one older person from falling or being injured in a fall, 20 and 27 individuals, respectively, would need to participate in a long term exercise intervention and 100 would need to take part to prevent a fracture. There was no overall reduction in mortality and exercise did not reduce the risk of multiple falls and hospitalisation.

Targeted electronic health record alerts

Cardiac monitoring, or telemetry, can provide early detection of sudden cardiac death, arrhythmias, and ECG changes, but can be used unnecessarily or for too long. “Alarm fatigue”desensitization to alarms when they are frequently false or irrelevantcan set in so that potentially important signals are ignored. In this cluster-randomized clinical trial of 1066 hospitalisations, teams on a general medicine service received an electronic health record (EHR) alert when a patient’s telemetry had run its pre-set duration. “In response to the alert, physicians chose to discontinue monitoring 62% of the time, resulting in a reduction of monitoring duration per hospitalisation with no increase in potential adverse events’” say the authors. A targeted EHR alert appears to safely reduce unnecessary cardiac monitoring without the need for human beings to check on the devices. No mention is made of the potential benefit of checking on the patient.


Pain caused by knee osteoarthritis: what helps?

Older people come into GP surgeries with pain caused by knee osteoarthritis and GPs have so little to offer. So, I welcome this systematic review and meta-analysis of 33 pharmacological interventions which included 22037 patients with knee osteoarthritis in 47 randomised clinical trials lasting at least 12 months. Unfortunately, the conclusion is that nothing works convincingly. The authors say: “there was uncertainty around the estimates of effect size for change in pain for all comparisons with placebo, including the two medications that were associated with improved pain (celecoxib and glucosamine sulfate).”

Bring me sunshine; but vitamin D is no panacea

Vitamin D is not the panacea it was heralded to be despite its important roles in calcium metabolism and the immune system. This study asked whether treatment with active vitamin D reduces cardiovascular risk in patients undergoing haemodialysis; the rationale being that patients with renal failure have an increased susceptibility to heart disease. An open-label randomized clinical trial of 976 patients on maintenance dialysis without secondary hyperparathyroidism, found that adding oral alfacalcidol (the active component of vitamin D) over a median of 4 years did not reduce cardiovascular events, which occurred in 21.1% of  patients.

Annals of Internal Medicine

Childbirth increases the risk of breast cancer

I was taught that women who had never been pregnant were at increased risk of breast cancerthe implication was that the more menstrual cycles you have, the greater your exposure to oestrogen, and the higher the risk. But although pregnancy, with its break from periods, may be protective, there appears to be an increase in diagnosis of breast cancer shortly after giving birth. Pooled data from 15 prospective cohort studies of women under 55 found just over 18,000 diagnoses of breast cancer in 9.6 million person-years of follow-up. Compared with nulliparous women, parous women had an increased risk of estrogen receptor positive breast cancer which peaked around five years after birth; the risk was greater in women with a family history of breast cancer, those who were older at first birth or who went on to give birth again. Breastfeeding made no difference. As time went on (24 years after childbirth), the risk of breast cancer in nulliparous women overtook the risk in parous women. The authors say “compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Healthcare providers should consider recent childbirth a risk factor for breast cancer in young women.”

Diabetes drug canagliflozin doesn’t increase fractures

Canagliflozin is used in the treatment of diabetes. It has been approved by the National Institute for Health and Care Excellence as monotherapy if metformin is inappropriate, or as an add on to insulin or other diabetes drugs. But canagliflozin can affect calcium, phosphate, and vitamin D homeostasis and is associated with decreased bone mineral density. The question is whether taking the drug increases the risk of fractures?  This cohort study of nearly 80,000 people has reassuring news. In middle aged patients with type 2 diabetes and relatively low risk of fracture (just over 2/1000 person years), canagliflozin was not associated with an increased risk of fractures compared with GLP-1 agonists.


Artificial sweeteners and health

This systematic review of 56 studies of adults and children found that use of non-sugar sweeteners (NSS) made little or no difference to a wide range of health outcomes. “No evidence was seen for health benefits from NSSs and potential harms could not be excluded,” say the authors. The main outcomes were body weight or body mass index, glycaemic control, cardiovascular and kidney disease, cancer, oral health, preference for a sweet taste, eating behaviour, mood, behaviour, neurocognition and adverse effects. Most people use NSSs to cut down calories and exposure to sugar which could lead to obesity and diabetes. But there’s an argument that NSSs encourage a “sweet tooth” and do nothing to encourage healthy eating, which offsets the benefits. In the 17 randomised controlled trials studied, adults given NSSs didn’t lose significantly more weight than those given different sugars or placebo. The authors admit that  “the certainty of the included evidence ranged from very low to moderate, and our confidence in the reported effect estimates is accordingly limited.”

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.