Ann Robinson’s research reviews—13 March 2020

Ann Robinson reviews the latest research from the top medical journals

Annals of Internal Medicine

Flu jabs for over 65s don’t reduce hospital admissions or mortality

The race to find a vaccine for covid-19 is on. Presumably, older and frailer people would be vaccinated first. But this recent well designed (albeit observational) study of the flu vaccine provides food for thought. The vast data set from 2000 to 2014, included 170 million episodes of care and 7.6 million deaths among 55-75 year olds in England and Wales. Over 65s were more likely to get a flu jab, but there was no evidence that it reduced hospitalisations or mortality in this older age group. Additional strategies may be needed to reduce the risk of flu, say the authors.


Proportion of cancer deaths rise as CVD rates fall worldwide

This huge prospective cohort study (PURE) of variations in common diseases, hospital admissions, and deaths in middle aged (35-70 year old) adults in 21 high, middle, and low income countries (HIC, MIC and LIC) across 5 continents, makes fascinating reading. Cardiovascular disease (CVD) causes the most deaths globally, but cancer is now the main cause of death in HICs (twice that of CVD) and some upper MIC’s as rates of CVD have fallen. Relatively high CVD death rates in LIC’s (three times that of cancer) are not due to known risk factors but may reflect lack of access to healthcare. The trend seems to be for CVD rates to fall and the proportion of cancer deaths to rise, as countries become richer, independent of changes in demographics (age, sex, urban drift), behaviours (alcohol, tobacco use, exercise) and risk factors (diabetes, hypertension, and obesity). The participating countries weren’t chosen at random so caution is needed in extrapolating results to all countries. But it seems likely that as we are increasingly effective in preventing and treating infectious diseases and CVD, cancer will become the main challenge worldwide.


Long acting injectables for adults with HIV-1 infection

In our species’ eternal fight against pathogenic viruses, the treatment of HIV infection with combination antiretroviral agents is a triumph. Long acting injectables offer a chance to simplify therapy for adults with HIV-1 infection. This phase III, randomised, open label trial gave 20 weeks of standard daily oral induction therapy with three drugs (doltegravir-abacavir-lamivudine) to HIV-1 infected individuals who had never previously had antiretrovirals. The authors then assigned responders to continue oral therapy or to switch to monthly injections of two long acting drugs (cabotegravir and rilpivirine) after one month on an oral dose. After 48 weeks, the long acting therapy was non-inferior to daily oral therapy (2.1% v 2.5% had evidence of persistent, significant viral load). Despite injection site reactions being common, 91% of patients preferred the long acting therapy. If ongoing trials (ATLAS, FLAIR, and LATITUDE) demonstrate that the long acting drugs are safe, effective, and adhered to over a longer period, they’re likely to be a popular option, especially if someone can work out how to reduce pain at the injection site.


Pharma profits: ensuring value for money

Large pharmaceutical companies were more profitable than similar sized non-pharmaceutical companies during 2000-18 (median net income as a fraction of revenue of 13.8% v 7.7%) according to this fascinating cross-sectional study. The difference was admittedly smaller once differences in company size, research and development expense, and time trends were taken into account. A viable pharma industry is widely thought to be important to innovate and produce drugs, but profits and costs clearly need to be contained to ensure that the public gets value for money. One might argue that studies such as this one have no place in an academic medical journal, but I think evidence based debate about the role of the state in the pharmaceutical industry is both valid and vital.

JAMA Internal medicine

Buying influence

What does Pharma spend its vast profits on? One answer comes from this observational study that found that the pharmaceutical and health product industry spent $4.7 billion between 1999 and 2018, an average of $233 million per year, on lobbying the US federal government, $414 million on contributions to presidential and congressional electoral candidates, national party committees, and outside spending groups; and $877 million on contributions to state candidates and committees. Senior legislators in Congress involved in drafting health care laws and state committees involved in drug pricing and regulation were particularly targeted. The authors say that understanding these enormous sums can “inform discussions about how to temper the influence of industry on US health policy” but they don’t spell out how. In the UK, there may be less scope for direct aggressive lobbying but no room for complacency.

Non-obstructive chronic bronchitis—it’s not COPD</u<

This prospective cohort study of 22,325 US adults found that non-obstructive chronic bronchitis (chronic bronchitis without airflow obstruction or clinical asthma) is associated with adverse respiratory health outcomes, particularly among those who have ever smoked. The adverse outcomes included worse lung function tests, more hospital admissions, and greater mortality rates from both respiratory and other causes. People with non-obstructive chronic bronchitis who had never smoked fared better; they had more hospital admissions and mortality due to respiratory causes, but no significant difference in the rate of lung function decline or all cause mortality compared with non-smokers without chronic bronchitis. I was surprised that this form of chronic bronchitis that causes chronic cough and sputum seems to be clinically distinct from spirometry-defined COPD. Smoking cessation is essential in both clinical scenarios.

QT-prolonging drugs increase sudden cardiac deaths—but why?

QT-prolonging medications (QTPMs), such as some antipsychotics and antibiotics, are a reported risk factor for sudden cardiac death as a result of sudden arrhythmic death. But previous studies may have overestimated the risk of sudden arrhythmic death, says this case-control autopsy study of 525 presumed sudden cardiac deaths defined by standard consensus criteria and 104 matched control deaths due to trauma. QT-prolonging medications were associated with increased odds of presumed sudden cardiac death, but not because of arrhythmias or QT prolongation. The results do not exclude an increased risk of sudden arrhythmic death with QTPMs, so caution should continue in prescribing them, but “it remains unclear whether routine screening and QT interval-guided tailoring of therapy is beneficial or sufficient to alter the risk of sudden death.”

Ann Robinson is an NHS GP and health writer and broadcaster