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On The Pulse - April 2017

On The Pulse

Tertius Lydgate

Friday, 28 April 2017

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Levothyroxine’s benefits in doubt
Patients in later life can commonly be seen to have a borderline under-active thyroid gland showing mild elevations of TSH level. While treatment with levothyroxine is common, it is also controversial, and a study published in The New England Journal of Medicine suggests that older people with subclinical hypothyroidism do not actually benefit from it. 737 participants (mean age 74.4 years, 53.7% women) with persisting subclinical hypothyroidism were randomly assigned to receive either levothyroxine with dose adjustment (n=368), or placebo (n=369). The mean (±SD) thyrotropin level was 6.40±2.01 mIU per litre at baseline. At 1 year, this level had decreased to 5.48 mIU per litre in the placebo group, and 3.63 mIU per litre in the levothyroxine group, at a median dose of 50 μg. There were no differences in the mean change at 1 year in the hypothyroid symptoms score (between-group difference, 0.0; 95% CI, −2.0 to 2.1) or the tiredness score (0.4; 95% CI, −2.1 to 2.9). In light of the results, the authors concluded that current guidelines should be updated.

Undiagnosed chest pain
Chest pain in primary care is a common diagnostic challenge with potentially serious consequences if cardiovascular disease is missed. Researchers, writing in The BMJ, looked at the long-term cardiovascular outcomes of undiagnosed chest pains six months after first presentation. Out of the 172,180 adults presenting with a first episode of recorded chest pain, 72.4% did not have a cause attributed to it; and 95.2% of these did not receive any type of cardiovascular diagnosis over the next six months. The long-term incidence of cardiovascular events was higher in those whose chest pain remained unattributed after six months (4.7%) compared with patients with an initial diagnosis of non-coronary pain (3.0%), for 3-5.5 years. The authors say improved chest pain assessments are needed to reduce these patients’ cardiovascular risk.

Rapidly ruling out acute myocardial infarction
It is well known that patients need to wait for a second troponin level when presenting with chest pain to hospital to check for any rise. A single cardiac troponin T (hs-cTnT) concentration below the limit of detection (<0.005 µg/L) in combination with a non-ischaemic electrocardiogram (ECG) may successfully rule out acute myocardial infarction (AMI) in patients presenting to emergency departments with possible emergency acute coronary syndrome. This is the conclusion of a meta-analysis published in the Annals of Internal Medicine. Of 9,241 patients in 11 cohort studies, 30.6% were classified as low risk and 0.5% low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; and pooled sensitivity was 98.0% (CI, 94.7% to 99.3%).

Vitamin D and CVD prevention
An increased incidence of cardiovascular disease (CVD) has been reported among individuals with low vitamin D status. A study published in JAMA Cardiology found, however, that CVD is not prevented by monthly high-dose vitamin D supplementation. Researchers randomly assigned adults to receive oral vitamin D3 (n= 2,558; an initial dose of 200,000 IU, followed a month later by monthly doses of 100,000 IU) or placebo (n= 2,552), for a median of 3.3 years. Of the 5,108 participants included in the primary analysis, 25% were vitamin D deficient. Cardiovascular disease occurred in 11.8% and 11.5% of the participants in the vitamin D and placebo group respectively. Similar results were seen for participants with vitamin D deficiency at study entry and for other outcomes such as heart attack, angina, heart failure, hypertension, and stroke. Yet, the authors point out that the effects of daily or weekly dosing on CVD risk require further study.

Vitamin D and cancer outcome
Vitamin D has been linked with improved cancer outcome. A systematic review and meta-analysis in the British Journal of Cancer looked at the relationship between cancer outcomes and both vitamin D-related genetic variation and circulating 25-hydroxyvitamin D (25OHD) concentration. A total of 44,165 cases from 64 studies were included. Higher 25OHD was associated with better overall survival (hazard ratio HR=0.74, 95% CI: 0.66–0.82) and progression-free survival (HR=0.84, 95% CI: 0.77–0.91), and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link. The authors conclude that the analysis provides powerful background rationale to instigate clinical trials to investigate the potential beneficial effect of vitamin D in the context of stratification by genotype.

Antibiotics and colorectal cancer
It is known that antibiotics alter the gut microbiome and new evidence suggests that long-term antibiotic use in early-to-middle adulthood is associated with an increased risk of colorectal adenoma, a precursor for the majority of colorectal cancers. The research, published in Gut, included 16,642 women aged ≥60 from the Nurses’ Health Study. 1,195 cases of adenoma were documented. Increasing duration of antibiotic use (≥2 months) at age 20–39 and 40–59 was significantly associated with an increased risk of colorectal adenoma (36% and 69% respectively) compared with non-users. However, the association did not appear with recent antibiotic use within the past four years. The authors concluded that, should the findings be confirmed by other studies, there could be a need to limit the use of antibiotics and sources of inflammation that may drive tumour formation.

Inhaled steroids and pneumonia risk
While previous research established that the use of inhaled corticosteroids (ICS) is linked to excess pneumonia risk in COPD patients, a new study, published the British Journal of Clinical Pharmacology, found that the risk is also increased in asthma. The cohort included 152,412 asthma patients, of whom 1,928 had a pneumonia event during follow-up. Current use of ICS was associated with an 83% increased risk of being hospitalised for pneumonia. This risk was greatest with higher doses, and dispensing of 500 µg or more of fluticasone-equivalent per day was associated with a 96% increase. Increased risks were seen with both budesonide and fluticasone (167% and 93% increase in risk respectively). When accounting for potential protopathic bias, exposure to ICS was still found to be associated with a 48% increase risk of pneumonia.

The dangers of marathons
With the increased popularity of long-distance running, the effects of marathons on the body are attracting more scrutiny. A small observational study, published in the American Journal of Kidney Disease, has highlighted the potential risk of acute kidney injuries in marathon runners. Findings showed that 82% of the 22 runners included in the study (mean age 44 years, 41% men) developed an increase in creatinine level equivalent to AKIN-defined AKI stages 1 and 2. 73% had microscopy diagnoses of tubular injury. Serum creatinine, urine albumin, and injury and repair biomarker levels peaked on day 1 and were significantly elevated compared to day 0 and day 2. Serum creatine kinase levels continued to significantly increase from day 0 to day 2. The authors now call for larger cohorts with longer follow-up of kidney function to validate the results.

Author's Image

Tertius Lydgate

Originally from Northumberland, Tertius Lydgate studied medicine in Edinburgh, London and Paris. There he developed a special interest in communicable diseases and hoped to make great advances in treating and preventing them. But, after a promising start in a provincial centre of excellence in middle England, he was forced by circumstances (please, don't inquire) to abandon his high ideals. He now scrapes a living by pouring cold water on the over-enthusiastic at his private cryohydrotherapy clinic. Dreaming of the contributions he once hoped to make himself, he finds consolation in the latest medical journals and is happy to share his discoveries with his readers. He thinks that his creator, George Eliot, would have approved.
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