Merkel cell tumour rates highest in Queensland
AUSTRALIAN researchers have found the incidence rate of Merkel cell carcinoma (MCC) in Queensland is at least double that of anywhere else in the world. The retrospective population-based cohort study of Queensland data from 1993 to 2010, published in JAMA Dermatology, included 879 eligible cases of MCC, an uncommon but highly invasive form of skin cancer. The researchers found 340 of these cases were diagnosed between 2006 and 2010, corresponding to an incidence rate of 1.6 per 100 000 population, with men (2.5 per 100 000) having a higher incidence than women (0.9 per 100 000). Rates peaked at 20.7 per 100 000 in those aged 80 years or older. The researchers wrote that the overall incidence of MCC increased by an average of 2.6% per year from 1993 onwards. “Relative survival [calculated by dividing the observed survival probability for the study group by the expected survival within the Queensland population] was 41% after 5 years, with significantly better survival found for those younger than 70 years at diagnosis (56%-60%), those with tumors on the face or ears (51%), and those with stage I lesions (49%)”, they wrote. A high level of exposure to ultraviolet (UV) radiation in a mainly fair-skinned population was considered the main reason for the high rates of MCC. “While the greater attention placed on melanoma may be warranted given its higher incidence, people diagnosed as having MCC have greatly reduced survival expectations”, the researchers wrote. “In light of these findings, it is imperative that clinical practice guidelines for the diagnosis and management of MCC be developed and implemented within Australia as soon as possible, similar to those that already exist for other countries. Public awareness campaigns are also required to alert people that melanoma is not the only lethal form of skin cancer.”
Benefit doubts in routine hepatocellular carcinoma screening
A SYSTEMATIC review of 22 studies on routine screening for hepatocellular carcinoma (HCC) in patients with chronic liver disease has found “very-low-strength evidence” about the effects of HCC screening on mortality in high-risk patients. The review, published in Annals of Internal Medicine, found that screening could identify more patients with earlier-stage disease who were candidates for potentially curative treatments, “but there is limited evidence from which to draw firm conclusions about the balance of health outcome benefits and harms of using routine screening to identify HCC”. The researchers wrote that periodic ultrasonography and α-fetoprotein testing were the most commonly evaluated screening methods, and patients with viral hepatitis have been the most frequently studied population. “The body of evidence on which current recommendations for screening are based has substantial shortcomings”, they wrote. “If screening is pursued, it will be important to implement programs in ways that minimize potential harms, especially given the limited empirical evidence of benefit. For example, targeting screening to higher-risk individuals with less severe underlying liver disease and developing a better understanding of how to target invasive treatment to those with more aggressive screen-detected tumors might help to increase the detectable benefits of screening while limiting the population exposed to potential harms.” The authors of an accompanying editorial agreed that current screening should not be expanded and new screening programs should not be initiated but said “the range of uncertainty includes a clinically important benefit of screening”. The authors wrote that screening had much greater potential to produce benefits exceeding harms in the highest-risk patients, such as those with hepatitis C and cirrhosis, than in the general population. “It is appropriate to allow clinicians caring for these patients to continue to offer screening, but offers should be targeted to those who are good candidates for treatment and should include a shared decision-making approach …”, they wrote.
Questions over target systolic BP in hypertension
PATIENTS with hypertension with a systolic blood pressure (SBP) reading lower than 120 mmHg do not have reduced longitudinal risk of incident cardiovascular (CV) events compared with patients with an SBP of 120–139 mmHg, according to research published in JAMA Internal Medicine. The study included a total of 4480 men and women with hypertension but without prevalent CV disease at baseline (1987–1989), with SBP measurements taken at baseline and at three triennial visits. The researchers used SBP as a time-dependent variable, with measurements categorised as elevated (≥ 140 mmHg), standard (120–139 mmHg), and low (< 120 mmHg). After a median follow-up of 21.8 years, there were 1622 incident CV events. Participants with elevated SBP developed incident CV events at a significantly higher rate than those in the low BP group but there was no difference in incident CV event-free survival among those in the standard versus low SBP group. Further adjustment for BP medication use or diastolic BP did not significantly affect the results. “Although our results reinforce that control of elevated BP is beneficial to prevent incident cardiovascular events, our results suggest that once SBP is controlled below 140 mmHg, an SBP below 120 mmHg does not appear to provide additional benefit in terms of preventing incident cardiovascular events”, the researchers wrote. They said a treatment goal of 120–139 mmHg might be acceptable in most patients with hypertension, but said further studies were needed to support this conclusion. The author of an accompanying commentary urged doctors to prioritise the right care for the right patients with hypertension. “By aggressively treating individuals who may have marginal benefit, we remain distracted from the hard work of achieving goal BPs for all patients with [hypertension] — the right patients, the right medicines, every time.”
New evidence on autism traits in families
A LARGE intergenerational case–control study has demonstrated the strong familiality of measures of social responsiveness in autism spectrum disorder (ASD) as well as subclinical ASD traits in families unaffected and affected by autism. The research, published in JAMA Psychiatry, included 1649 women from the Nurses’ Health Study II, with case participants being children with reported ASD and controls matched by year of birth among those not reporting ASD. The research included 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Participants were assigned a Social Responsiveness Score (SRS) using a validated questionnaire that assessed social impairment, with established thresholds for ASD. The researchers found the risk of ASD was increased by 85% among children whose parents had concordantly elevated SRS scores and by 52% when the score of either parent was elevated. Elevated scores of the father significantly increased the ASD risk in the child, but no association was seen with elevated scores of the mother. “Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 [SRS] points”, the authors wrote, saying that this demonstrated that “parental [quantitative autistic traits] elevations predict risk of ASD among offspring”. “We found evidence that parents of children with ASD had greater social impairment than control parents as measured by the SRS and that concordantly elevated SRS scores in parents significantly increased the risk of ASD in the child.” The authors found the risk of ASD in children increased significantly when parental SRS scores were in the top 20% of the distribution, which supported “the vast literature” suggesting strong heritability of ASD. “Our findings suggest that typical variation in parental social functioning and autistic traits is correlated in spousal pairs, predicts differences among offspring for these same traits, and at higher levels elevates risk of clinical autistic syndromes in children.”
Not all trauma patients benefit from transfusion
RED blood cell (RBC) transfusion is associated with an increased risk of death in trauma patients whose baseline predicted risk of death is low, according to a secondary analysis published in PLOS Medicine. The analysis, based on the “CRASH-2” trial, which was designed to evaluate the effect of tranexamic acid on mortality in trauma patients, examined the association of RBC transfusion with mortality in 10 227 patients who had received at least one transfusion. “We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death”, the researchers wrote. Transfusion was associated with an increase in all-cause mortality in patients with a 6% and 6%–20% predicted risk of death (odds ratio [OR], 5.40 and 2.31, respectively), but with a decrease in all-cause mortality in patients with > 50% predicted risk of death (OR, 0.59). It was also associated with an increase in fatal and non-fatal vascular events (OR, 2.58). The researchers warned that the study was observational and that “important biases cannot be ruled out, and we cannot claim a causal link”. They wrote that their hypothesis should be prospectively evaluated in a randomised controlled trial. An accompanying editorial said that while RBC transfusions could save lives, they “can cost lives too, and it is possible, and perhaps likely, that they do so at some of the haemoglobin and clinical thresholds currently used”. It said the value of the current research was that it told us “that current clinical practice is dangerously uninformed”, saying the evidence base for transfusions in trauma was poor.