News in brief

Warning on paracetamol toxicity
RESEARCHERS have called on doctors to be aware of their patients’ individual responses to paracetamol after finding evidence that it is more toxic than generally believed, especially at the upper end of standard analgesic doses. The systematic review of observational studies, published in the Annals of Rheumatic Diseases, was based on eight cohort studies, which showed a consistent dose–response relationship between paracetamol at standard analgesic doses and adverse events (AEs) which were often observed with non-steroidal anti-inflammatory drugs. “This includes a dose–response relationship between paracetamol and increasing incidence of mortality, cardiovascular, [gastrointestinal] and renal AEs in the general adult population”, the authors wrote. They described the main limitations of the review as the low number of studies and quality of available evidence. “While these limitations are important to consider, the striking trend of dose–response is consistent across multiple outcomes and studies”, they wrote. The authors said that doctors and patients might be willing to accept the level of risk demonstrated in the review to provide adequate analgesia or antipyresis. “ However, when analgesic benefit is uncertain, as has been recently suggested for paracetamol in the treatment of [osteoarthritis], joint pain and low back pain, more careful consideration of its usage is required”, they wrote.

Minority of asymptomatic thyroid nodules increase in size
THE “vast majority” of asymptomatic thyroid nodules exhibit no significant size change or they actually decreased in size over a 5-year follow-up period, according to research published in JAMA. The prospective, multicentre, observational study included 992 consecutive patients who had one to four asymptomatic, sonographically or cytologically benign thyroid nodules Overall, 174 (11.1%) of the 1567 original nodules increased in size, with a mean 5-year largest diameter increase of 4.9 mm (from 13.2 mm to 18.1 mm), mainly restricted to the main nodule in patients with multinodular disease. Nodule growth was associated with multiple nodules, with an odds ratio of 2.2 for two nodules; 3.2 for three nodules; and 8.9 for four nodules. The researchers wrote that growth considered significant by American Thyroid Association standards was observed in only 15% of the patients Nodule size changes occurred early, starting from the 1-year follow-up visit. The most relevant baseline characteristics associated with nodule growth were multinodular disease, nodule diameters of 7.5 mm or more, and age at diagnosis of 43 years or less. Growth of solitary nodules was less likely, and also inversely associated with age. The researchers wrote that only seven patients (0.7% of the study population) were diagnosed with thyroid cancer during the 5-year follow-up period, and in two of these cases, the malignancy was in a nodule not present at baseline. “These findings justify reconsideration of the current guideline recommendations for follow-up of asymptomatic thyroid nodules”, they wrote. An accompanying editorial said the study findings represented “an important step in improving the efficiency and mitigating the expense of follow-up for the vast majority of thyroid nodules that are either cytologically or sonographically benign”.

Positive health effects as air quality improves
LONG-term improvements in air quality are associated with significant positive effects on childhood lung function, according to a US study published in the New England Journal of Medicine. The researchers examined the relationship between declining pollution levels in southern California and the respiratory health of 2120 children drawn from three cohorts from separate time periods: 1994‒1998, 1997‒2001 and 2007‒2011.The mean ages of children within each cohort were 11 years at the beginning of the period, and 15 years at the end. The authors measured lung-function development as the increase in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) during a 4-year period. Over the 13 years spanned by the three cohorts, improvements in 4-year growth of both FEV1and FVC were associated with declining levels of nitrogen dioxide and particulate matter diameter. The authors wrote that significant improvements in lung-function development were observed in both boys and girls, and in children with and without asthma. As the air quality improved, the proportions of children with clinically low FEV1 at 15 years of age declined significantly, from 7.9% to 6.3% to 3.6% across the three periods. They said their analysis showed how even modest improvements in air quality could lead to improved health outcomes. However, they said only five communities were included in this study and more data were required to make “definitive conclusions about the exposure–response relationship”. An accompanying editorial said the study highlighted that “further improvement in air quality may have beneficial public health effects”.

Lifelong effects of late preterm birth
NEUROCOGNITIVE impairment in late adulthood may be one of the lifelong consequences of late preterm birth, according to research published in Pediatrics. The research included 919 Finnish men and women in a birth cohort group born between 1934 and 1944. Participants underwent the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) at a mean age of 68.1 years. After adjusting for major confounders the researchers found those born late preterm scored lower on word list recognition (mean difference: – 0.33 SD; P = 0.03) than those born at term. Among those who had attained a basic or upper secondary education, late preterm birth was associated with lower scores for episodic memory, executive functioning and visual reproduction, and they had a 2.70 times higher risk of mild cognitive impairment than those born at term. The associations were not found for those with tertiary levels of education. The researchers described the study as the longest follow-up investigation of neurocognitive performance of individuals born late preterm and the first to show that late preterm birth was associated with poorer episodic memory performance in late adulthood. The researchers acknowledged that there had been considerable improvements in prenatal and neonatal care and increased affluence in the past few decades, saying the present findings might not be generalisable to cohorts born more recently in high-resource settings, but would still be relevant in low-resource areas. They wrote that the findings also suggested that maximum attained lifetime education could mitigate ageing-related neurocognitive impairment, especially among those born late preterm.

Sedative pre-med offers no benefits
A RANDOMISED controlled trial has found a lack of benefit from sedative premedication for patients having surgery under general anaesthesia. The trial, published in JAMA, included 1062 patients younger than 70 years who were scheduled to undergo various elective surgeries under general anaesthesia, with 24% of patients displaying “very high levels of perioperative anxiety”. The patients were equally randomised to three groups to receive 2.5 mg of lorazepam, no premedication or placebo. The researchers found patients taking lorazepam did not report an improved experience the day after surgery compared with the patients on placebo or no premedication. However, they did find those taking lorazepam had a modestly prolonged time to extubation and a lower rate of early cognitive recovery. The anaesthetists, surgeons and nurses involved in the surgeries were blinded to all three groups. The authors wrote that the approach taken to randomisation and blinding had revealed “some interesting nocebo effects”. They said an important part of surgical outcomes was the patient’s perception of the result of the intervention and overall experience in the perioperative setting. “To improve a patient’s overall perioperative experience, anesthesiologists frequently administer preoperative anxiolytic medications to calm patients before they enter the operating room”, they wrote, saying this was despite not knowing how well these medications treated anxiety and how they influenced the overall perioperative experience.
    
Cohort study shows magnitude of diabetes risk with statins
A LARGE follow-up cohort study has found statin treatment was associated with a 46% increase in the risk of type 2 diabetes, which the researchers have attributed to decreases in both insulin sensitivity and insulin secretion. The study, published in Diabetologia, included 8749 non-diabetic men in Finland aged 45-73 years, who were followed up for 5.9 years. A total of 2142 men were taking statins at baseline. New diabetes was diagnosed in 625 men by means of an oral glucose tolerance test, HbA1c of 6.5% or more, or glucose-lowering medication started during the follow-up period. The researchers found that at entry the men who developed diabetes were older, more obese, less physically active, had lower levels of high-density lipoprotein cholesterol and higher levels of total triacylglycerols and HbA1c. They were also more insulin resistant and had lower insulin secretion than those who did not develop diabetes, independently of statin treatment. The men treated with statins were more likely to develop diabetes than those not using statins (11.2% vs 5.8%), with a twofold increased risk of type 2 diabetes during the follow-up period (hazard ratio [HR] 2.01). After adjusting for age, body mass index, waist circumference, physical activity, smoking, alcohol intake, family history of diabetes, and beta-blocker and diuretic treatment, the HR was 1.46. The risk was dose dependent for simvastatin and atorvastatin. The authors of the study reported other novel findings including that statin therapy was associated with a worsening of hyperglycaemia, especially 2-hour glucose, and with a 24% reduction in insulin sensitivity and 12% reduction in insulin secretion compared with men not receiving statin therapy. However, they wrote that although the cohort was large, “the power of our study to demonstrate significant associations of less frequently used statins with the risk of type 2 diabetes and underlying mechanisms was limited”.

Children easily buy e-cigarettes online
CHILDREN can easily purchase e-cigarettes online because internet vendors fail to apply age-verification measures, a US study published in JAMA Pediatrics has found. The researchers assessed the state of North Carolina’s 2013 e-cigarette age-verification law by asking 11 non-smoking minors (aged 14-17 years) to make supervised e-cigarette purchases from 98 internet e-cigarette vendors. The children successfully received deliveries of e-cigarettes from 76.5% of the purchase attempts. There were no attempts by the delivery companies to verify their ages, and 95% of delivered orders were simply left at the door. The authors found that all delivered packages came from shipping companies that, according to company policy or US federal regulation, did not ship cigarettes to consumers. Of the total orders, 18 failed for reasons unrelated to age verification. The authors said only five of the remaining 80 purchase attempts were rejected due to age verification, which resulted in an e-cigarette purchase rate for the children of 93.7%. “Even in the face of state laws like North Carolina’s requiring age verification, most vendors continue to fail to even attempt to verify age in accordance with the law, underscoring the need for careful enforcement”, the authors wrote. They said US federal law should require rigorous age verification for all e-cigarette sales similar to the current federal policy, which bans internet cigarette sales to minors. “Future studies should assess the success, extent, and enforcement of these regulations”, they concluded.