Alex Nowbar’s weekly research review—17 January 2020

Alex Nowbar reviews the latest research from the top medical journals.

Annals of Internal Medicine

Oh-so-sensitive troponin testing

In the empire of stable angina, all roads no longer lead to revascularisation. But the pursuit of inducible ischaemia marches on. Walter et al assessed whether high sensitivity troponin measurement could exclude inducible ischaemia in 1896 patients with symptomatic coronary artery disease. As a diagnostic test in this context, troponin was insufficiently accurate. The “gold standard” for inducible ischaemia used in this study was an adjudicated assessment of the myocardial perfusion imaging with single photon emission computed tomography. Where available, angiography and fractional flow reserve could also be used in the assessment. This may sound reasonable, but why test one surrogate against another surrogate? Perhaps we should be assessing whether troponin measurement helps diagnose symptoms, but there is no gold standard for this because we cannot definitively confirm if a coronary obstruction is the cause of a patient’s symptoms.


Zinc and folate supplementation for male infertility

There may be a role for zinc in male fertility, but the theory that zinc supplementation increases the chance of a man’s partner getting pregnant needed to be verified. Schisterman et al randomised 2370 couples seeking infertility treatment at four US centres to use of zinc and folate supplementation versus placebo in a double-blind fashion. After six months of treatment, there was no difference in live birth rates or semen quality. I commend the authors for conducting this well designed fertility trial. It is disappointing that zinc and folate were ineffective, but not altogether surprising because the underlying causes of infertility in these couples could easily have been factors not remediable with zinc and folate. This trial is a stark reminder that the heterogeneity of infertility makes it challenging to research. Interventions that target one element in the plethora of fertility elements may only be shown to be effective if tested in the “right” couples but there is limited ability to identify such couples. 

Pleurodesis techniques for malignant pleural effusion

Bhatnagar et al compared two methods of talc pleurodesis at 17 hospitals in the UK—talc slurry via chest drain or talc poudrage (powder) via thoracoscopy in an open-label randomised trial. They assessed which had lower pleurodesis failure rates with failure defined as the need for a further intervention on the same side. The need for further intervention was determined by imaging which followed any patient who presented with worsening breathlessness. This primary outcome seems fitting because it reflects the way in which these patients might be followed up in real-world practice. Pleurodesis failure rates and quality of life scores were similar in both groups and there was no difference in mortality. What then should dictate the method offered to a patient? Clinician and patient preferences? Perhaps. Even if they are based on no more than convenience.


Mental health in Hong Kong

Ni et al performed a prospective cohort study tracking rates of depression and post-traumatic stress disorder from 2009 to 2019 in Hong Kong. The period from 2009 to 2014 was considered baseline, as the Occupy Central or Umbrella Movement protests took place in 2014. Prevalence of depression and post-traumatic stress disorder rose considerably with the social unrest. This has been observed previously in cases of social unrest in other regions. The magnificence of this study lies in the robust identification of factors associated with these mental health outcomes. Heavy use of social media, defined as two or more hours a day, was associated with depression and post-traumatic stress disorder. The directionality of this relationship with social media use is unclear. Family support mitigated against probable depression. Age, sex, educational attainment, and household income were not linked to the mental health outcomes. The main implication of the dramatic increase in prevalence of these outcomes will be the demand for professional care.

JAMA Internal Medicine

Unnecessary bimanual examinations and cervical smear tests

Researchers in the US surveyed women aged 15 to 20 to determine the number of unnecessary bimanual examinations and cervical smear tests each had had in the previous 12 months. A fifth had had a bimanual examination with over half being potentially unnecessary, for example done in non-pregnant asymptomatic women. For the cervical smear test, a fifth of the women had undergone this with over 70% of these being potentially unnecessary. These are outrageously high rates of procedures in young people that are not only unnecessary, but come with significant consequences including anxiety, over diagnosis, and costs. The figures cover the time period from 2011 to 2017 so I can only hope these practices are fading out. Screening for sexually transmitted infections doesn’t require bimanual examination. It is abhorent that clinicians perform these unnecessary procedures on young women. Even if the nature of this survey to be based on participant recall limits the accuracy of the findings, the proportions having unnecessary procedures is so high that it is difficult to doubt the veracity.

Ozone exposure in heavy smokers

Heavy smokers are already at risk of respiratory morbidity but does long-term ozone exposure increase this risk? Paulin et al studied smokers with and without COPD at a number of US locations. They found that long-term ozone exposure was associated with worse respiratory outcomes in this population. In particular ozone exposure was associated with more severe breathlessness, exacerbations and greater emphysema and air trapping on CT scan. The effects were greater in people who spend more time outdoors. These data confirm the significance of ozone exposure for people with or at risk of respiratory disease. A key feature of this study was the thorough way in which ozone exposure levels were determined—“two-week mean outdoor concentrations of ozone outside each participant’s home were predicted using spatiotemporal modeling methods”. Using ozone concentrations over the past 10 years for each participant’s address, makes these findings particularly robust.

Surgery for asymptomatic aortic stenosis

In a multicentre Korean trial, 145 patients with very severe aortic stenosis were randomised to early surgery or conversative care. Of the 73 patients in the early surgery group, only five died during follow-up. In the conservative care group, 15 of 72 patients died during follow-up. These are quite convincing data that point toward the benefit of early aortic valve replacement surgery in asymptomatic, very severe aortic stenosis. The choice of primary endpoint was a little odd and perhaps is misleading because it wasn’t cardiovascular death or all-cause death. It was a composite of death within 30 days and cardiovascular death throughout the follow-up period. This seems to me an extremely selective endpoint tailored to favour surgery. Nevertheless, I don’t doubt the conclusion.

New drug in myelodysplasia

Luspatercept was tested in a pharma-sponsored double-blind randomised controlled trial at 65 sites in 11 countries. The aim was to see if it resulted in higher rates of transfusion independence for 8 weeks or longer over a 24 week follow-up period in patients with low-risk myelodysplastic syndrome with ring sideroblasts. Patients had to have been receiving regular red-cell transfusions and been refractory to erythropoiesis-stimulating agents to qualify for the study (or were unlikely to respond or had stopped such agents due to an adverse event). In the luspatercept group, 38% of patients achieved transfusion independence but only 13% in the placebo group did. This is a highly significant finding both statistically and clinically. There was no obvious adverse signal in the safety profile. But, I would caution that these are relatively short term results and recombinant fusion protein, luspatercept, is merely a holding post, not a prognostic treatment.

Healthcare hotspotting for super utilisers

When I first started medicine I was struck by repeat attenders for medical or social reasons or both. Addressing this could help with spiraling healthcare costs. This US trial randomised 800 hospitalised patients with medically and socially complex conditions (but excluded people who were uninsured, had cognitive impairment, or were receiving cancer care or mental health care) who had been hospitalised at least once in the previous six months to a “hotspotting” programme or to usual care to see if hotspotting reduced readmission rates. The hotspotting programme was a care-transition programme with intensive clinical and social components including home visits with social workers and community nurses. Sadly, there was no difference in between the two groups in readmission rates over the following 180 days. The authors bemoan regression to the mean to explain the null result, but I wonder if the exclusion criteria might have ruled out some of the heavy healthcare users whom the hotspotting programme might have been most likely to affect.

Alex Nowbar is a clinical research fellow at Imperial College London

Competing interests: None declared