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Metformin risks in non-diabetes
RESEARCHERS have called for further large trials to provide evidence of outcomes before metformin is recommended for cardiovascular benefit in patients without diabetes. A single-centre, double-blind, placebo-controlled trial in Glasgow, UK, published in The Lancet, found metformin had no effect on carotid intima-media thickness (cIMT) and little or no effect on several surrogate markers of cardiovascular disease in patients with high cardiovascular risk but without diabetes who were taking statins and who had a large waist circumference. The 173 participants, with an average age of 63 years, were randomly assigned to receive metformin (850 mg twice daily) or matching placebo. At baseline, mean cIMT was 0.717 mm (SD, 0.129) and mean carotid plaque score was 2.43 (SD, 1.55). The researchers found that after 18 months, cIMT progression and change of carotid plaque score did not differ significantly between the groups. However, they found patients taking metformin did have a significant reduction in weight, and improvements in other risk factors for type 2 diabetes including lower HbA1c, insulin resistance, and tissue plasminogen activator compared with those taking placebo. Their findings follow previous trials showing metformin reduced the risk of myocardial infarction in patients with diabetes.
Reflux surgery in infants questioned
ANTIREFLUX procedures (ARPs) are among the most common procedures performed by paediatric general surgeons in the US despite most gastro-oesophageal reflux disease (GORD) in infants and children resolving spontaneously, according to research published in JAMA Surgery. A retrospective cohort study examined inpatient data for more than 140 000 children with a primary diagnosis of GORD treated at 41 US children’s hospitals. The researchers found that 8.2% of children underwent ARPs during the study period, with more than half of these patients aged 6 months or younger. “Although most patients in the ARP group had preoperative upper gastrointestinal tract fluoroscopy (65.0%), these patients did not undergo a uniform workup”, the researchers wrote. “Antireflux procedures are most commonly performed in children during a period of life when regurgitation is normal and physiologic and objective measures of [GORD] are difficult to interpret.” The researchers called for greater efforts to develop and disseminate best practice standards for the diagnosis and treatment of children, especially infants, with possible GORD. “We must clarify the indications for ARP and clarify its use to treat [GORD] vs its use as an adjunct to a durable long-term feeding plan.”
Trials must balance safety and efficacy
A STUDY that was stopped early because of safety concerns for patients taking a combination therapy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) to treat diabetic nephropathy has highlighted the need for better designed trials, according to an editorial published in the New England Journal of Medicine. The multicentre, double-blind, randomised controlled trial, also published in the NEJM, involving 1448 veterans and aimed to test the efficacy of combining of losartan (an ARB) with lisinopril (an ACE inhibitor) compared with standard treatment of losartan alone to slow the progression of proteinuric diabetic kidney disease. The researchers wrote that the dual therapy was associated with increased adverse events, particularly acute kidney injury and hyperkalaemia, with the risk of kidney injury evident from treatment initiation through 42 months of follow-up. The accompanying editorial noted that this was the third trial to show that dual therapy does not decrease cardiovascular and renal morbidity and carries increased risks. “We need to find ways to design trials that ultimately provide a better balance between efficacy and safety”, the editorial said.
Home diagnosis of pharyngitis
US researchers have developed a patient-driven approach to group A streptococcal (GAS) pharyngitis based on patient history and recent GAS pharyngitis disease patterns in the local area, without the need for physical examination, that they say could save hundreds of thousands of doctor visits and antibiotic scripts. The authors, in research published in Annals of Internal Medicine, said the patient-driven home-score approach to pharyngitis diagnosis “could save hundreds of thousands of visits annually by identifying patients at home who are unlikely to require testing or treatment”. The research involved 71 776 patients aged 15 years or older with pharyngitis who visited a chain of retail health clinics over 2 years. The authors created the home score using information from patient-reported clinical variables plus the incidence of local disease and compared it with traditional scores that require clinician-elicited signs. They included 48 089 patients in a derivation set, of whom 11 614 (24%) tested positive for GAS pharyngitis. In the validation set of 23 687 patients, 5728 (24%) tested positive. In both groups, patients who tested positive for GAS pharyngitis were more likely to present with tonsillar exudates, swollen anterior cervical lymph nodes, absence of cough, and fever in the previous 24 hours. “Even without information from physical examination findings, the home score approaches the accuracies and overall performances of the existing validated scores”, they wrote. “Clinicians could use the home score to interact with patients online or over the telephone.” However, two editorials published in the same issue questioned the practicalities of the home-score system.
Be wary of testosterone
THE use of testosterone therapy in older men with low testosterone levels (less than 300 ng/dL) and significant medical comorbidities who undergo coronary angiography is associated with increased risk of mortality, myocardial infarction (MI), or ischaemic stroke, according to research published in JAMA. The researchers said their findings were not modified by the presence of coronary artery disease (CAD). The retrospective national cohort study of 8079 men in the US Veterans Affairs system included 1223 patients who started testosterone therapy a median of 531 days following coronary angiography. Of the 1710 outcome events recorded during the study period, 748 men died, 443 had MIs and 519 had strokes. In the no-testosterone group of 7486 patients, 681 died, 420 had MIs and 486 had strokes. Among patients receiving testosterone therapy, 67 died, 23 had MIs and 33 had strokes. The absolute rate of events was 19.9% in the no-testosterone group versus 25.7% in the testosterone group, with an absolute risk difference of 5.8% 3 years after their coronary angiography. The researchers called for future studies “to properly characterize the potential risks of testosterone therapy in men with comorbidities”. An accompanying editorial said that with the high volume of prescriptions and aggressive marketing of testosterone, “prescribers and patients should be wary”. “There is mounting evidence of a signal of cardiovascular risk, to which [the current study] contributes. This signal warrants both cautious testosterone prescribing and additional investigation”, the author said.
Endometriosis linked to pesticides
EXPOSURE to organochlorine pesticides (OCPs) has been linked to endometriosis in research published in Environmental Health Perspectives. The population-based case–control study, from the Women’s Risk of Endometriosis (WREN) study, included women aged 18–49 years enrolled in a large state health care system in the US. OCP concentrations were measured in sera from 248 patients with surgically confirmed endometriosis first diagnosed between 1996 and 2001, and 538 population-based controls. The researchers said the data suggested an increased risk of endometriosis in relation to serum concentrations of β-hexachlorocyclohexane (HCH). They said β-HCH was a component of technical-grade HCH, used as an agricultural insecticide in the US until the mid 1970s. The extensive past use of environmentally persistent OCPs in the US, or present use in other countries, “may impact the health of the current generation of reproductive-age women with regard to a hormonally-mediated disease”, the researchers wrote.