Ann Robinson’s research reviews—15 October 2018

Ann Robinson reviews the latest research from the top medical journals


A surfeit of Caesareans

Caesarean section was originally performed to deliver a baby when the mother had died in childbirth. I was taught that the name comes from Julius Caesar, but his mum, Aurelia, apparently survived his birth, so perhaps this isn’t the case. The word may come from the Latin “caesus” meaning “cutting.” The procedure was certainly known about in Ancient Rome and has been around ever since. Shakespeare’s audiences were familiar enough with caesarean section that they appreciated the plot twist when Macbeth is killed by “none of woman born,” which doesn’t seem possible until Macduff is revealed as having been “from his mother’s womb, untimely ripped,” or born by caesarean section. But caesarean section rates have gone from being rare emergencies to commonplace. Many experts think current rates are too high.

A new Lancet Series on optimising use of caesarean section says that global rates nearly doubled from 2000 to 2015 from an estimated 12% to 21% of all births. This major rise, that is continuing at a rate of 4% a year, is “unprecedented” and “unjustified.” The main driver is that many more women now give birth in health facilities and that the facilities are doing more caesarean sections. There is huge variation between regions (44.3% of births in Latin America to 4.1% in West Africa) and between countries (0.6% in South Sudan to a whopping 58.1% in the Dominican Republic.) And, within middle and low income countries, caesarean section use reflects income (the richest women were up to five times more likely to have a caesarean section than the poor, even if they are low risk.) For comparison, rates in England are currently 29%. Caesarean section is obviously medically necessary in cases of fetal distress, placenta praevia, and abnormal positioning. In some under-resourced areas, women who need a caesarean section can’t get one. But overuse of caesarean section is now a growing concern—population rates over 10-15% are considered excessive and unnecessary caesarean sections can cause harm. “Women who do not need a caesarean section and their infants can be harmed or die from the procedure, especially when done in the absence of adequate facilities, skills, and comprehensive healthcare,” warns the report.

Elevated lipoprotein A and heart disease

Lp (a) is a lipoprotein subclass that is similar to LDL, but has an extra protein molecule—apoprotein (a). Genetic and epidemiological studies have suggested that it may be an independent risk factor for atherosclerotic lesions and cardiovascular disease (CVD). The level of Lp (a) in an individual seems to be genetic and lifestyle changes don’t necessarily have a strong impact. This study was funded by Novartis who are investing heavily in treatments designed to reduce CVD risk in people with raised Lp (a). The question was: once you have established CVD or are already taking a statin, to what extent does an elevated Lp (a) matter? Seven randomised, placebo-controlled, statin outcomes trials were analysed for fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures for different levels of Lp (a). Having a high Lp (a) level before starting statins and while on them, showed an independent approximately linear relation with CVD risk. Expect new drug treatments targeting Lp(a) soon.


Vaginal births—push early or wait?

Everyone wants the same outcome from childbirth—a healthy baby and mother with minimum harm to either and, as a bonus, rational use of resources. But it’s not clear what the optimal approach to the management of labour is. There’s consensus that a prolonged second stage of labour (from complete cervical dilation until delivery of the fetus) isn’t good for mother or baby. But should women be encouraged to push immediately or try to hang on for an hour or more until the urge to push is irresistible or the presenting part is already at the perineum? A Cochrane review asked this question last year and said there didn’t seem to be a difference, but further higher quality evidence was needed. And here it is. 2414 nulliparous women who had epidural analgesia were randomised to immediate versus delayed pushing. There was no significant difference in rates of spontaneous vaginal delivery (a very respectable rate of around 85% in both groups), neonatal morbidity, or perineal tears. Second stage was much shorter for women who could push immediately (102 vs 134 minutes) and, even with an epidural, that’s got to be a plus. So Cochrane’s conclusion is confirmed, and maybe women can get to choose whether they push sooner or later.

Gout hurts—don’t hold back the allopurinol

Are we unduly worried about the effect of allopurinol on renal function? And does that mean that people with gout are under treated and suffer more than they have to? Only one third of eligible patients are on urate lowering treatment such as allopurinol. A population-based UK cohort study has found that the use of allopurinol in patients with gout didn’t increase the risk of kidney function decline, and was associated with a 13% lower risk at doses of 300 mg or more per day. If kidney function does decline in people with gout, clinicians are advised to look for alternative causes rather than assuming that the allopurinol is responsible. Allopurinol is, according to this study, unlikely to make CKD worse and may even protect kidney function by reducing high urate levels that cause nephropathy.


Failing kidneys in sepsis—act early or wait?

Septic shock has a high mortality rate and is often complicated by acute kidney injury (AKI), which increases the risk of dying even more. Severe AKI at failure stage means the kidneys are no longer working adequately and renal replacement therapy or RRT (dialysis, haemofiltration, or transplantation) needs to be considered. The failure stage is characterised by a threefold increase in serum creatinine above baseline, no urine at all for 12 hours, or extremely low urine output. The question is, once failure stage AKI that is severe but not yet life threatening is diagnosed, should RRT start immediately (within 12 hours) or can doctors hold off for 48 hours in the hope that the kidneys will recover on their own? This French multicenter, randomized, controlled trial set out to answer the questions by assigning 488 patients with early stage septic shock and failure stage AKI to immediate (within 12 hours) or delayed (after 48 hours if there was no spontaneous recovery or need for emergency intervention) RRT. Rather starkly, the primary outcome was “death at 90 days.” The trial was stopped early for futility i.e. interim results suggest it is unlikely to achieve statistical significance. 58% of the 477 patients followed up in the early-strategy group had died within the 90 days and 54% in the delayed-strategy group. Over a third of those in the delayed strategy group never needed RRT, although 17% needed it as an emergency measure. RRT carries its own risks so a strategy of judicious delay may be warranted.

Annals of internal medicine

Statins—making sense of the headlines

It’s hard to know what to make of statins. There are strident and conflicting headlines saying that they “raise the risk of diabetes by nearly a third” while others talk of “slashing breast cancer death rates”? What advice can we give to patients who are scared to take statins despite being at high risk of cardiovascular disease (CVD)? Or, less commonly, individuals at low risk of CVD who ask for statins for its perceived non CVD benefits? Researchers have crunched a lot of numbers (an umbrella review of 112 meta-analyses of observational studies and 144 meta-analyses of RCTs) to tease out whether 278 unique non-CVD outcomes are related to statin use. Basically the answer is “no” and the authors recommend that current guidelines remain unchanged. Statins do decrease all-cause mortality in patients with chronic kidney disease. They may decrease cancer mortality in patients with cancer and decrease exacerbation in patients with chronic obstructive pulmonary disease. And while observational studies suggest that statins increase the risk of diabetes and myopathy, RCTs don’t show statistically significant effects on myopathy, myalgia, or rhabdomyolysis.

JAMA Internal Medicine

Tai Chi to prevent falls

There’s no pill that can stop older people falling, but we badly need interventions that can help reduce falls. Falls are largely preventable, and exercise is a safe and effective way of lowering the risk. But it’s hard to know what sort of exercise to advise as evidence is limited. Is walking enough? Pilates? Yoga? Stretching? This randomized clinical trial of 670 adults aged 70 and over, with a history of falls or impaired mobility, found that a 24 week therapeutic tai ji quan (Tai Chi) balance training programme, effectively reduced falls by 58% compared with the stretching exercise (control intervention) and by 31% compared with a multimodal exercise intervention. This is just the kind of social prescribing that is gaining popularity among commissioners and patients alike; other benefits of a programme like this would be that it does no harm and can bring people together in a community setting. One criticism of social prescribing is that it lacks a solid evidence base, but this study is a step in the right direction.


Gallstone attack in seriously unwell people-drain or operate?

If you were in seriously unwell in ITU and had an attack of acute cholecystitis because of gallstones, would you prefer laparoscopic cholecystectomy or percutaneous catheter drainage? This five year multicentre Dutch study (winningly known as CHOCOLATE trial) compared the two approaches in 142 high risk patients (APACHE 11 score of 7 or more) with acute cholecystitis due to stones. There was no difference in mortality within a year (3-9%), but the drainage group fared worse in terms of major complications (infections and cardiopulmonary) in the first month and the need for further intervention or recurrent biliary disease in the following year. Cholecystectomy was also 30% cheaper in terms of use of healthcare resources and cost. The whole grim scenario makes me think that I’d opt to have my gallbladder out at the first hint of acute cholecystitis, while I’m still reasonably fit and well.

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.