Ann Robinson’s research reviews—9 April 2019

Ann Robinson reviews the latest research from the top medical journals


Amyloid PET scans change management in dementia

Does amyloid positron emission tomography (PET) neuroimaging change the subsequent management (at 90 days) of patients with mild cognitive impairment (MCI) or dementia of uncertain cause? In this longitudinal study of 11 409 participants with MCI or dementia of uncertain cause who had a pre-PET management plan, the PET findings led to a change of plan (starting, stopping, or modifying drug or behavioural treatments) in just under two thirds of cases and a change of diagnosis (from Alzheimer’s disease to non-Alzheimer’s disease and vice versa) in just under a third. A change of management is the outcome measure because there’s still no disease modifying treatment that works for MCI and dementia. Finessing the diagnosis and fine tuning management is a step in the right direction, but until there’s evidence that this results in better clinical outcomes, it’s of limited value.


Fruit, grains, and low salt diet important for good health

What is a suboptimal diet, and does it matter? This major and important study has examined the consumption of major foods and nutrients across 195 countries and tried to quantify the impact of suboptimal intake on non-communicable disease mortality and morbidity using a comparative risk assessment approach that estimates the proportion of disease-specific burden attributable to each dietary risk factor in adults aged over 25. In 2017, 11 million deaths and 255 million disability-adjusted life-years (DALYs) were attributable to dietary risk factors such as high intake of sodium and low intake of whole grains and fruit, which is consistent with previous findings. Detailed conclusions should be taken with a pinch of salt, as nutritional data are notoriously unreliable and causality hard to prove. But population-level intervention to improve diet is emerging as the most important factor in improving global health.


Off with the cuffs

Critically ill patients are at high risk of deep vein thrombosis (DVT) and are given heparin prophylactically. Despite that, 5-20% of critically ill patients still develop a DVT. Does adding intermittent pneumatic compression (cuffs around the legs that fill with air and increase venous blood flow) for at least 18 hours a day, in addition to the heparin, lower the incidence of DVTs? This study found that around 4% of 2003 patients admitted to intensive care units (ICUs) developed a new DVT regardless of whether they received heparin alone or heparin and compression. Around 10% developed a pulmonary embolus or any lower limb DVT, and just over a quarter had died after 90 days. The compression device made no significant difference to any of the outcomes. I wonder whether ICU decision makers will be persuaded to abandon the cuffs?

Organ donation from donors with hepatitis C

In 2018, less than a third of the 113,000 US adults on a waiting list for organ donation, received one. Nearly a tenth of those on the waiting list were removed because they had become too sick or had already died. A bigger pool of donors is urgently needed and recent successful kidney and liver transplantation between HIV positive donor and recipient has been hopeful. But the pool of donors would be substantially widened if people with hepatitis C virus (HCV)—2.4 million people in the US—could be donors for recipients who don’t have HCV infection (HCV mismatched transplantation). In the past, mismatched transplantation has led to chronic HCV in over 80% of recipients and poorer long term results.

In this study, 36 HCV negative adults had a lung transplant and eight had a heart transplant from HCV positive donors; all recipients were given four weeks of anti-HCV treatment (Sofosbuvir-velpatasvir) starting within hours of transplantation. 95% of the recipients showed detectable HCV load in their bloodstream immediately after transplantation, but it became undetectable within two weeks with no serious adverse effects attributable to the antiviral drugs. The transient presence of HCV doesn’t seem to have significantly  affected outcome; after 6 months, a remarkable 100% of the first 35 patients to enrol in the study, had survived the transplant. I found myself wondering what became of the other nine? Two factors may account for the high success rate; both donors and recipients—especially the former—were younger than usual and the wider availability of donor organs meant than recipients may have been less ill. The 36 who had lung transplants from HCV infected donors were more likely to suffer acute cellular rejection requiring treatment, than recipients of 77 non HCV infected donors, but the differences were not significant after adjusting for confounders. This is a small trial that needs to be interpreted cautiously, but potentially offers good news for people on the waiting list. Hopefully though, prompt and effective care of people living with HCV will mean that this pool of donors will soon shrink.

Annals of Internal Medicine

No magic bullet for ME

Myalgic encephalopathy (ME) or chronic fatigue syndrome (CFS) may be an autoimmune condition. There have been reports of improvement in symptoms when individuals with ME/CFS received chemotherapy for lymphoma or cancer, and an increased risk of B cell lymphoma in elderly patients with ME/CFS. So does B lymphocyte depletion with rituximab (a monoclonal antibody to CD20), which is used in conditions such as rheumatoid arthritis, relieve fatigue and improve physical activity in people with ME/CFS? This trial of 151 patients was well designed (which is particularly important in a condition such as this without specific biomarkers) but relied on self referral and self reported symptoms over two years, with possible recall bias. Results demonstrated the role of placebo (response rate 35.1%, adverse effects 18.9%) but were disappointing for rituximab (response rate 26%, adverse effects 26%). Few patients in either group showed a major or sustained improvement, and 10% got worse. The quest for an effective way of helping people with ME/CFS goes on.

Treatments for urinary incontinence in women

Urinary incontinence—and the fear of leaking or smelling of urine—is a huge, oft ignored and poorly managed problem for women. What can we offer that works? This systematic review of 84 trials examined non-pharmacological approaches (pelvic floor exercises or behavioural change) and pharmacological treatments (drugs that affect bladder and urethral sphincter function). Most interventions were better than none, except for hormones and periurethral bulking agents (such as collagen injections). Behavioural therapy generally trumps drugs in stress and urge urinary incontinence. Neuromodulation, behavioral therapy, and α-agonists were more effective than hormones or no treatment for women with stress urinary incontinence. For urgency urinary incontinence, behavioral therapy was more effective than anticholinergics; neuromodulation and botox (onabotulinum toxin A) were better than nothing, and botox may have been better than neuromodulation. The quality of evidence is mixed, and potential for harm differs, so women should be informed and make their own choice, say the authors. This is the case in all health matters; how strange that it still needs to be said.


Insulin for kids with type 1 diabetes: pump or multiple daily injections?

Young people with Type 1 diabetes (T1D) need good glycaemic control to ensure that their adult lives are not blighted, and shortened, by vascular complications. Giving insulin by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) are the best two options available, but which is better?  I know that if I had a child with T1D, I’d push for a pump; intuitively it seems easier for child and caregivers to manage. But the evidence base to support the growing popularity of CSII over MDI is limited and flawed (short observation periods, use of older insulins and inherent risk of bias.) This study aimed to address these shortcomings and answer the questions; which method results in better glycaemic control (measured by hba1c result at 12 months and percentage within target range), fewer adverse effects (severe hypoglycaemia or diabetic ketoacidosis), and is most cost effective? Two things surprised me about the study participants; less than half of the 689 patients invited to participate agreed to do so and over 66% of those who declined to take part, expressed a strong preference for MDI, with only 10% saying they’d opt for CSII. But the choice was offered soon after diagnosis and it may be that CSII becomes a more attractive option once families have had a chance to adjust to the distressing diagnosis and its treatment. In this study, there was no significant difference in glycaemic control (which was suboptimal in both groups) or cost effectiveness between CSII and MDI in the first year of diagnosis. There was an increased number of admissions with ketoacidosis with CSII but no difference in admissions with hypoglycaemia. Advances in technology should make CSII cheaper, safer, and more effective in future, but for now, it seems that there’s not enough robust evidence to support a pump over multiple injections in the first year of diagnosis of T1D in under 18’s.

Ann Robinson is an NHS GP and health writer and broadcaster