Picking an aggressive melanoma
AN Australian study has found that patients with higher mitotic rate melanomas are more likely to be older and male with a history of significant solar field damage, who present with a rapidly growing primary melanoma most likely on the head and neck. The research, published in JAMA Dermatology, found that melanomas with high mitotic activity (≥ 10 mitoses/mm2) were predominantly thick and ulcerated nodular tumour subtypes. The cross-sectional study of patients of a public hospital melanoma clinic included 2397 cases reviewed over 5 years by the Victorian Melanoma Service. It included 1441 patients with 1500 primary invasive melanomas. The mitotic rate of tumours was measured as number of mitoses per mm2 and analysed according to patient demographics, phenotypic markers, historical data, tumour presentation and histopathologic features. The researchers found a mitotic rate of less than 1/mm2 in 41.7% of melanomas, between 1 and 2 mitoses/mm2 in 28.8%, and a mitotic rate of 3 or more in the remaining 29.5%. There were strong associations between older age (70 years and older) and being male with increasing mitotic rate, with a ratio of 2.2 men to one women in the highest mitotic rate group (≥ 10/mm2). The authors wrote that these tumours could present with nodular structure and amelanosis. “Such atypical clinical features may pose a challenge to timely detection; thus a high index of suspicion is warranted when the patient reports a history of morphologic change and rapid growth”, they wrote. The authors of an accompanying editorial wrote that the most important finding of the study was that a history of blistering sunburns, family history of melanoma and the presence of pre-existing naevi within the melanoma were all associated with lower mitotic activities, suggesting either that tumours arising from pre-existing naevi were less aggressive than those arising de novo, or that melanomas in patients with these risk factors were detected earlier, before they had an opportunity to rapidly divide. The study provided clinicians with “more data and ultimately another tool to factor into their clinical decision-making process”, the editorial authors wrote.

Fenofibrate benefits for women with diabetes
RESEARCH led by Australian experts has found that both men and women with diabetes taking fenofibrate therapy had significantly improved lipoproteins, with changes being greater in women than in men. The double-blind, placebo-controlled trial, supported by a grant from Laboratories Fournier and the NHMRC, was published in Diabetologia. It included 3657 women and 6138 men with type 2 diabetes not using statins who were assigned to receive fenofibrate (200 mg/day) or placebo for 5 years, with the effects on lipoproteins and total cardiovascular events evaluated by sex. The researchers, from Australia, New Zealand and Finland, found that fenofibrate reduced total cardiovascular outcomes (cardiovascular death [CVD], fatal and non-fatal stroke, and carotid and coronary revascularisation) by 30% in women and 13% in men. Fenofibrate reduced total, low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) cholesterol and apolipoprotein B more in women, independent of menopausal status and statin uptake. In patients with high triacylglycerol levels and low HDL cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% in women and 24% in men. The researchers wrote that although the primary end point of non-fatal myocardial infarction plus coronary death was not significantly reduced among those taking fenofibrate, the secondary end point of total CVD events was reduced. “Women allocated fenofibrate, including those with dyslipidaemia at baseline, had risk reductions in CVD events that did not differ statistically significantly from those in men, and for some event types tended to have greater benefit”, they wrote. The “significant differences” between men and women in the effects of fenofibrate on lipids and apolipoprotein were described as “unexpected”.

Nursing key in weekend stroke admissions
A LARGE prospective, “real world” multicentre sample of English stroke units (SUs), published in PLOS Medicine, has found an overall weak association between weekend patient admission and mortality. However, the study, which included 103 SUs and data on 56 666 patients with stroke, did show big variations between SUs in their organisation of weekend care and mortality outcomes. After adjusting for confounders, the researchers found no significant difference in mortality risk for patients who were admitted to SUs where stroke specialist physician rounds were conducted on fewer than 7 days a week compared to those where rounds were conducted every day. However, they did find a dose–response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in SUs with the lowest nurse/bed ratios. In a multivariable analysis, patients admitted on a weekend to an SU with 1.5 nurses for every 10 beds had an estimated adjusted 30-day mortality risk of 15.2% compared to 11.2% for patients admitted to a unit with three nurses per 10 beds — equivalent to one excess death per 25 admissions. “There was wide variation in the intensity of clinical staffing on weekends, and evidence that a significant proportion of SUs were already providing weekend staffing levels similar to those during the week”, the researchers wrote. “These observational data support the hypothesis that nursing levels are an important mediator of excess mortality for patients admitted with stroke on a weekend.” In an accompanying perspective article, the authors wrote that the study “is a call to research, a call to face the challenge to scientifically understand organizational factors that can inform policies such as the seven-day services model”.

Big jump in parent-reported disability in children
RESEARCH published in Pediatrics has found that parent-reported neurodevelopmental or mental health disability in childhood has increased by more than 20% in the US in the 10 years to 2011. The researchers used secondary data analysis of US National Health Interview Survey datasets between 2001 and 2011 to calculate the prevalence, rate of change, severity, and sociodemographic disparities of parent-reported childhood disability. They found that childhood disability had continued to increase, growing by 15.6% in the study period from about 4.9 million to 5.9 million US children in 2010–2011. The percentage of disability related to any physical health condition declined by 11.8% during the decade, whereas neurodevelopmental or mental health cases increased by 20.9%.  Children living in poverty experienced the highest rates of disability — 102.6 cases per 1000 population — but “unexpectedly” the researchers found children living in households with incomes that were more than 400% above the federal poverty level experienced the largest increase (28.4%) over the 10-year period. The researchers speculated that expanded use of diagnostic and treatment services by advantaged families might explain why more children were identified with disabilities. “The consequences of these trends are profound and certainly affect how pediatricians and mental health professionals practice and prepare to address the needs of their patients”, the researchers wrote. They also called for “greater clarity on the concept of disability” for future research.

Kidney dangers in atypical antipsychotic scripts
A POPULATION-based cohort study has found that new use of an atypical antipsychotic drug is common in routine care of older adults and associated with an increased 90-day risk for hospitalisation with acute kidney injury (AKI). The research, published in Annals of Internal Medicine, included 97 777 adults aged 65 years or older who had received a new outpatient prescription for an oral atypical antipsychotic drug matched with those who did not receive a prescription.  Antipsychotic recipients were older than the non-recipients, more likely to be residents of a long-term care facility and more likely to be diagnosed with dementia, psychiatric diseases, Parkinson disease and cardiovascular diseases. The most frequently prescribed atypical antipsychotic drug was risperidone (45.7%), followed by quetiapine (35.3%) and olanzapine (19.0%). The risk for hospitalisation with AKI, assessed using a hospital diagnosis code, was 1.02% of recipients (1002) v 0.62% of non-recipients (602). As well as AKI, drug use was associated with an increased risk for other adverse outcomes, including hypotension, acute urinary retention, pneumonia and acute cardiac events, which are also known potential causes of AKI. The association between antipsychotic use and AKI was more pronounced in community dwellers than those in long-term facilities, which the researchers speculated was because older adults living in the community might have less follow-up surveillance than those living in a care facility. “We also observed a higher 90-day risk for all-cause mortality after new use of an atypical antipsychotic drug (6.8% in recipients vs. 3.1% in nonrecipients)”, the researchers wrote, saying this was similar to the results from randomised trials. “The current available evidence calls for a careful reevaluation of prescribing atypical antipsychotic drugs in older adults, especially for the unapproved indication of managing behavioral symptoms of dementia”, the researchers wrote, saying the drugs should be used only after other approaches have been exhausted and that when prescribed, “patients must be warned about potential adverse effects”.

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