BP therapy continues to reduce death in diabetes
AN Australian-based follow-up trial of older patients with type 2 diabetes assigned to a combination blood pressure (BP)-lowering therapy or intensive blood glucose control has observed an attenuated, but still significant, reduction in mortality only in those on the BP-lowering therapy. The research, published in the NEJM, invited surviving participants of the Action in Diabetes and Vascular Disease: Peterax and Diamicron Modified Release Controlled Evaluatiobrn (ADVANCE) to participate in a post-trial follow-up evaluation. The original randomised control trial of 11 140 people with type 2 diabetes had shown the combination of perindopril and indapamide reduced mortality, but intensive glucose control, treating glycated haemoglobin of less than 6.5%, did not. The new study included 8494 patients who were followed for a median of 5.9 years (BP-lowering comparison) or 5.4 years (glucose control comparison). “After following the current cohort for a total of 10 years, including the in-trial period and the post-trial follow-up, we observed attenuated but still significant reductions in the rates of death from any cause and from cardiovascular causes resulting from the 4.5-year period of blood-pressure–lowering treatment with perindopril–indapamide (average difference in blood pressure of 5.6/2.2 mm Hg between the perindopril–indapamide group and the placebo group during the original trial)”, the researchers wrote. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group. However, they did observe a persistent benefit in end-stage renal disease but no new benefit in serious eye complications from intensive glucose control. The researchers did note “divergent outcomes” between their study and other studies of glucose control in patients with diabetes, saying this might be explained, in part, by differences in the response to the lowering of glucose across the trial populations.

PET scan best follicular lymphoma predictor
RESEARCHERS have found that positron emission tomography–computed tomography (PET-CT) is more accurate than conventional CT scanning in measuring response to treatment and predicting survival in patients with follicular lymphoma. The study, published in The Lancet Haematology and led by an Australian researcher, pooled analysis data from three multicentre prospective studies of first-line rituximab chemotherapy for patients with high-tumour-burden follicular lymphoma who had received at least six cycles of rituximab and chemotherapy before response assessment with conventional contrast-enhanced CT and PET low-dose CT. The two largest studies reported that patients with a positive PET-CT scan after first-line rituximab chemotherapy for follicular lymphoma had worse progression-free and overall survival than those who had a negative post-induction PET-CT scan. The researchers wrote that identifying an inferior overall survival in patients who had a positive post-induction PET-CT scan after only a median 4.6 years of follow-up showed the “highly predictive power of PET in this otherwise indolent lymphoma”, although they said there were few events reported in the time period. The researchers wrote that this confirmed that it was “appropriate that PET-CT is the new internationally recommended imaging modality for response assessment in follicular lymphoma”. However, although the results were reassuring for patients who had a negative PET-CT scan, those with a positive scan after first-line therapy could not be regarded as having an indolent disease and should be closely monitored. “We expect post-induction PET-CT assessment will be a platform for studies of response-adapted therapy aimed to improve the poor prognosis of patients with a positive post-induction PET scan.” The researchers recommended that PET scan should be used routinely in clinical practice. An accompanying commentary said that the study results “provide valuable support that PET-CT provides a readily available surrogate endpoint with which to more rapidly develop better therapies for a population of patients with a predictably poor outcome”.

No long-term benefits from preterm magnesium
AUSTRALIAN researchers have found that magnesium sulfate given to pregnant women at imminent risk of preterm birth was not associated with long-term benefits for their children. The randomised clinical trial (RCT), published in JAMA, evaluated neurological, cognitive, behavioural, growth and functional outcomes at early school age of surviving children, finding there was a non-significant reduction in mortality in the magnesium sulfate group. The trial was conducted in 16 centres in Australia and New Zealand, comparing magnesium sulfate with placebo given to pregnant women (magnesium, n = 535; placebo, n = 527) who planned or expected imminent birth before 30 weeks’ gestation. Children who survived and participated in the school-age follow-up (magnesium, n = 443; placebo, n = 424) were invited for an assessment at 6–11 years of age between 2005 and 2011. The researchers wrote that magnesium sulfate given to mothers just before preterm birth as neuroprotection for the fetus was one of the few therapies to offer any promise of improving neurological outcome for preterm survivors. “Given that this treatment is being introduced into clinical practice, it is important to know if there are any adverse long-term effects”, they wrote.  However, they said the absence of benefit associated with antenatal magnesium sulfate into school age from the current trial “does not negate the proven value of magnesium sulfate in reducing cerebral palsy, based on the collective evidence from all of the RCTs”.

Warning on extending breast screening age
EXTENDING the upper age limit to 75 years for mass breast cancer screening in the Netherlands since 1998 has not resulted in a big decrease in the incidence of advanced breast cancer, but there has been a large jump in the incidence of early stage breast cancer in older patients, according to research published in the BMJ. The prospective, nationwide, population-based study included 25 414 patients aged 70–75 years with a diagnosis of invasive or ductal carcinoma in situ breast cancer between 1995 and 2011. The researchers found that after the age extension for screening was introduced, the incidence of early stage tumours in these women significantly increased, from 248.7 cases per 100 000 women to 362.9 cases. At the same time the incidence of advanced stage breast cancers decreased to a far lesser extent — from 58.6 cases per 100 000 women to 51.8 cases. The researchers wrote that Cancer Research UK was currently undertaking a large randomised controlled trial within the UK breast cancer screening program in women aged 71–73 years in which an age extension from 70 to 73 years was being randomly phased in, allowing the investigators to evaluate the effects of screening on breast cancer incidence and mortality. “Until the results of this trial become available, we propose that routine breast cancer screening in women aged more than 70 years should not be performed on a large scale”, they wrote. “Instead, the harm and benefits of screening should be weighed on a personalised basis, taking remaining life expectancy, breast cancer risk, functional status, and patients’ preferences into account.” While saying there were limitations in their study, including the length of the follow-up period, the researchers wrote that their results implied that the effect of the screening program in older women “is limited and may lead to overdiagnosis”.

PTSD linked to food addiction
THE number of lifetime post-traumatic stress disorder (PTSD) symptoms in women has been linked to the prevalence of food addiction in middle adulthood in a study published in JAMA Psychiatry. The cross-sectional analysis found the food addiction prevalence appeared to be further elevated when PTSD symptoms occurred earlier in life. The analysis included 49 408 participants of the Nurses’ Health Study II, a cohort of women nurses aged 25–42 years at the 1989 recruitment, which ascertained lifetime trauma exposure and PTSD symptoms in 2008 and current food addiction in 2009. The researchers found about 80% of the study sample reported some type of trauma exposure, with 66% of trauma-exposed participants reporting at least one lifetime PTSD symptom. They wrote that 8% of the cohort met the criteria for food addiction, defined as three or more clinically significant symptoms. “The prevalence of food addiction increased with the number of lifetime PTSD symptoms, and women with the greatest number of PTSD symptoms (6-7 symptoms) had more than twice the prevalence of food addiction as women with neither PTSD symptoms nor trauma histories”, the researchers wrote, saying the PTSD–food addiction association did not differ substantially by trauma type. “Our findings are relevant to ongoing questions regarding the mechanisms behind observed associations between PTSD and obesity, and they provide support for hypotheses suggesting that associations between PTSD and obesity might partly originate in maladaptive coping and use of food to blunt trauma-associated distress.” The researchers wrote that if the results were replicated longitudinally, their findings suggested that “interrupting the pathway from PTSD to obesity may require psychological and behavioral interventions that address dependence on eating to cope with distress”.

Ultrasound suitable for initial kidney stones test
PATIENTS with suspected kidney stones who undergo initial ultrasonography have lower cumulative radiation exposure than patients who have initial computed tomography (CT), without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department (ED) visits or hospitalisations. In a multicentre, pragmatic, comparative effectiveness trial, published in the NEJM, patients aged 18–76 years who presented to the ED with suspected nephrolithiasis were randomly assigned to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Of the 2759 patients in the trial, 908 were assigned to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The overall incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. However, the mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group. The researchers wrote that the use of CT in the US for the diagnosis of suspected renal stones had increased by a factor of 10 in the past 15 years, probably because of its greater sensitivity and because it could be performed “at will” in most EDs. They said that although ultrasonography was less sensitive than CT for the diagnosis of nephrolithiasis, “using ultrasonography as the initial test in patients with suspected nephrolithiasis (and using other imaging as needed) resulted in no need for CT in most patients, lower cumulative radiation exposure, and no significant differences in the risk of subsequent serious adverse events”. An accompanying editorial, said that based on the study findings, “it is reasonable for a physician to use ultrasonography as the initial imaging method for a patient presenting to the emergency department with suspected nephrolithiasis, remembering that additional imaging studies should be used when clinically indicated”.

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