Ann Robinson’s research reviews—5 December 2019

Ann Robinson reviews the latest research from the top medical journals


Diagnosis of pulmonary embolism with D-dimer testing

Patients with pulmonary embolism with a substantial risk of recurrence or progression need anticoagulation. CT scanning is currently the investigation of choice, but it isn’t ideal because it’s expensive, time consuming, involves radiation exposure, can yield false positives and negatives, and often identifies other chance findings. This prospective study found that a combination of clinical assessment using clinical pre-test probability (C-PTP) and D-dimer testing successfully identified patients at low risk of pulmonary embolism during a follow-up period of three months. Pulmonary embolism can effectively be ruled out with a low C-PTP and D-dimer level of <1000 ng/mL or moderate C-PTP and D-dimer <500 ng/mL.

MRI screening for women with dense breast tissue

Women with extremely dense breast tissue have an increased risk of breast cancer, but mammography is less reliable than in women with normal density breasts. This Dutch study found that supplemental magnetic resonance imaging (MRI) improved early detection and reduced interval breast cancers over a two year period (2.5/1000 screenings in those invited for MRI group v 5/1000 in mammography-only group). Of the 300 women who had a breast biopsy after MRI, 79 were found to have cancer (specificity of 92%). The impact of having a false positive result (79.8 per 1000 screenings) isn’t known, but otherwise MRI is safe with an adverse event rate of only 0.1%. Simulation studies and larger, longer trials are needed to tease out whether adding MRI reduces mortality rates. And minimising false positive rates and reducing the cost of MRI would help to justify its routine inclusion in screening.

Treating refractory status epilepticus

How do you treat status epilepticus that doesn’t respond to benzodiazepines? Surprisingly perhaps, the answer is unknown. This randomised, blinded adaptive trial of 384 children and adults compared the safety and efficacy of intravenous levetiracetam, fosphenytoin, and valproate. Interestingly, 10% of enrolled patients were deemed to have had psychogenic non-epileptic seizures. Cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in just under half in all three groups. One problem is that cessation of seizures was judged on clinical grounds and not EEG, so that those who stopped having seizures but whose conscious level didn’t improve within an hour could have been suffering from postictal or benzodiazepine-induced drowsiness or could have had continuing non-convulsive status epilepticus. Further studies to clarify this would be helpful, as would be testing of different doses of these three drugs and of others needed for the 50% who didn’t respond.


Hands up for hope

The optimistically named HOPE study found that a daily dose of 10 mg of oral prednisolone for six weeks was effective and safe in treating patients with painful hands caused by a flare-up of osteoarthritis. Pain, function, and imaging markers improved substantially, which is helpful for clinicians because we don’t have much else to offer. The problem is that, after treatment, symptoms revert to the baseline, and this study couldn’t determine whether treating acute flare-ups alters the course of this painful condition. The six week course may be safe, but repeated or long term use of corticosteroids clearly confer risk. And I can foresee that it will be hard to persuade elderly patients with painful hands to come off the steroids, given that they clearly work.

Treatment of non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) causes a range of chronic liver diseases and increases the risk of cirrhosis. It’s the progressive form of non-alcoholic fatty liver disease (NAFLD) both of which have increased as rates of obesity have increased. No drug treatments exist. This phase 2 study found that resmetirom, a liver-directed thyroid hormone analogue, reduced hepatic fat and markers of inflammation and fibrosis after 12 weeks and 36 weeks of treatment in patients with NASH. Adverse events were mild or moderate, although resmetirom caused more cases of transient mild diarrhoea and nausea. The study suggested that imaging and serial biomarkers can be used to assess liver damage without recourse to invasive liver biopsies. A larger phase 3 study is now underway.

JAMA Internal Medicine

Does continuity of care improve outcomes?

Here’s a good question. If the doctor caring for you while you are in hospital works for several days in a row as opposed to intermittent shifts, does it affect your outcome? A three year cohort study used Medicare data of over 100 000 patients admitted to hospital for 3-6 days. It found that patients with doctors who had schedules that allowed for continuity of care did better. They had a lower 30 day mortality after discharge, lower readmissions, and higher rates of discharge. Continuity of care brings obvious advantages such as increased trust and communication. The authors also note that discontinuity can mean a fresh pair of eyes and improved diagnosis. Limitations of this observational study include selection bias and methodological difficulty in identifying hospital schedules. It’s possible that the sickest and most complex patients see multiple doctors, and that this explains their poorer outcomes rather than the lack of continuity of care.

Ann Robinson is an NHS GP and health writer and broadcaster