Ann Robinson’s weekly research reviews—2 April 2019

Ann Robinson reviews the latest research from the top medical journals

Annals of Internal Medicine

How harmful is cannabis?

Is it more dangerous to smoke or eat cannabis? This report from an emergency department in Colorado notes an increase in cannabis-related visits after liberalisation of cannabis laws in 2014. This, presumably, could be a true rise or just that patients feel safer to disclose their habit. The study showed that 10.7% of the 10 000 cannabis-related emergency department attendances were related to edible cannabis, despite making up only 0.3% of total cannabis sales throughout the state. Edible cannabis was associated with slower onset and longer lasting symptoms than inhaled cannabis, including acute psychiatric events (acute anxiety or psychosis) and cardiovascular symptoms. Inhaled cannabis was more likely to cause hyperemesis syndrome, which was the main reason for admission. “These findings should be considered carefully in states considering legalization of recreational cannabis,” say the authors.


The risks of caesarean section in low and middle income countries

Access to timely, preferably planned, caesarean section when indicated is essential for safe childbirth. But having a caesarean section in a low or middle income country (LMIC), especially in sub-Saharan Africa, carries its own risks. Both maternal and perinatal deaths after caesarean section are disproportionately high in LMICs, where many are performed as emergencies. Most maternal deaths are due to postpartum haemorrhage, and 99% of the 300 000 maternal deaths that occur worldwide each year are in an LMIC. This extensive study shows that countries with low rates of caesarean section have high maternal death rates. In the UK, there are eight maternal deaths per 100 000 caesarean sections. In the sub-Saharan region, one in 10 babies born by caesarean section is stillborn. Better management of labour, surgical training, resource allocation, management of postpartum haemorrhage, and neonatal resuscitation could improve the outcome for mother and baby alike.


Extreme prematurity: heartening news from Sweden

Should life sustaining treatment be given to extremely premature babies? Difficult decisions about whether, when, and how to treat babies born in a “periviable” period need data about interventions and survival. This high quality study from Sweden reports that extremely premature babies (22-26 weeks’ gestational age) who were born between 2004 and 2007 had a 70% chance of still being alive at one year. Ten years later, the chance of survival had increased to 77%. The proportion of all births that occur between 22 and 26 weeks has remained constant at 3.4/1000 births. Over two thirds (68%)  of the babies born in 2004-7 had major neonatal morbidity compared with 62% of those born between 2014 and 2016. The stillbirth rate fell from 30% (2004-7) to 23% (2014-16). Sweden has a small population (10 million) with among the lowest overall perinatal mortality rates in the world; whether these findings translate to other countries is unknown. It is also not clear what Sweden is doing that may account for the impressive outcomes: universal, uniform, high quality prenatal care or specific interventions such as administration of antenatal corticosteroids from 22 weeks’ gestation are both possibilities.

Mending broken hearts

Patients with severe heart failure, including those waiting for a heart transplant, may be offered a left ventricular assist device (LVAD) implant which acts as an artificial pump. The question of whether stem cells can improve outcomes and allow the LVAD to be removed was tested in this randomised controlled trial of 159 patients. Unfortunately, injection of mesenchymal precursor cells (MPCs) into the myocardium of patients with LVADs didn’t improve the proportion of patients that could be successfully weaned off their device over a six month period. This might be because the treatment doesn’t work or because of factors such as route of administration and timing. Younger patients who are more likely to have non ischaemic, potentially reversible heart failure may be more responsive to MPCs, but this study wasn’t powered to explore that possibility.

New England Journal of Medicine

The quest to cure drug-resistant TB

Multidrug-resistant tuberculosis is a global problem, with 500 000 new cases worldwide each year. Fewer than a quarter of these patients start treatment, and just over half of those who are treated achieve a successful result (culture-negative at 132 weeks). This non-inferiority study from Bangladesh, of people with rifampicin-resistant TB that is sensitive to fluoroquinolones and aminoglycosides, suggests that a shorter treatment period (9-11 months) may be as effective as the longer period (20 months) recommended by the WHO. Surprisingly, the safety profiles of longer and shorter drug regimens are similar, but, if these results are confirmed, the offer of the shorter treatment is likely to push up the numbers treated. This study is useful, and WHO guidelines have been amended to reflect the possibility of using shorter regimens. The holy grail is to find a short, simple treatment regimen for multidrug-resistant TB that is as safe and effective as treatments for non-drug-resistant strains.

Extending life in metastatic breast cancer

Metastatic breast cancer is currently considered to be incurable, with a median survival of under four years. Postmenopausal women with hormone receptor-positive metastatic breast cancer may be offered a third generation aromatase inhibitor such as anastrozole. Does the addition of a selective oestrogen receptor downregulator (fulvestrant) improve overall and progression-free survival? In this study, 71% of the combination treatment group died (median survival 49.8 months) compared with 76% in the anastrozole-only group (median survival 42 months) over a seven year period. The safety profiles were similar. A subgroup who had not previously been treated with adjuvant hormone therapy such as tamoxifen seemed to respond particularly well to the combination treatment, although numbers were small.


Brain stimulation for major depression

Do non-surgical brain stimulation techniques for depression work? I confess to scepticism about their effectiveness and anxiety about safety. This network meta-analysis of over 6750 adults with major and bipolar depression examined 113 randomised controlled trials of electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation (TBS), magnetic seizure therapy and transcranial direct current stimulation (tDCS). The quality of the evidence was limited and the risk of bias high, but the available evidence suggests that non-surgical brain stimulation techniques may provide useful add on or alternative treatments for adults with major depression. In particular, various forms of rTMS (bilateral, low frequency right, high frequency left) should be prioritised over novel protocols with a more limited evidence base, say the authors.

Globally, we’re (mostly) living longer and better

Across the globe, people lived nearly five and a half years longer in full health in 2013 than in 1990. This is mainly because of improvements in communicable, maternal, neonatal, and nutritional diseases and, to a lesser extent, the better management of non-communicable diseases and injuries. Health adjusted life expectancy (HALE) is the number of years of good health that an individual can expect to live at a given age and under current conditions. It’s a useful measure of trends in population health and health inequalities. This study used data from the Global Burden of Disease Study (GBD) 2013 to quantify and compare the contribution of 306 diseases and injuries to the changes in health adjusted life expectancy at birth (HALE0) in 187 countries, between 1990 and 2013. Overall, HALE0 increased by just over 5 years over the time period and health inequality between countries narrowed. But in 11 countries (6%), population health declined; HIV/AIDS caused the biggest fall in HALE0 (-0.28 years), mostly in sub-Saharan Africa, followed by diabetes (-0.12 years) which affected a wide range of countries. Heart disease, strokes and hypertension negatively affected HALE0 in many low and middle income regions. Diabetes, primary headache with medication overuse, and depressive disorders were the most important negative factors and mainly affected HALE0 changes through disability.

Ann Robinson is an NHS GP and health writer and broadcaster