Study shows PSA screening cuts prostate cancer deaths
A LARGE European randomised study, published in The Lancet, which included more than 162 000 men from eight countries who were followed for up to 13 years, has found that prostate-specific antigen (PSA) screening could reduce deaths from the disease by about a fifth. However, the researchers wrote that despite the new evidence, doubts remained about whether the benefits of screening outweighed the harms, and they recommended routine PSA screening should not be introduced at this time. The trial included eligible men aged 55–69 years, identified from population registries and randomly assigned to PSA screening every 4 years or no intervention (control). Men were referred for biopsy if their PSA concentration was higher than 3.0 ng/mL. Results showed that screening appeared to reduce prostate cancer deaths by 15% at 9 years, and this improved to 22% at 11 years. Over the 13 years of follow-up, there was no further improvement in the relative reduction in prostate cancer deaths, which decreased by 21% in the screening group compared with the control group, although men who were actually screened had a 27% lower chance of dying of prostate cancer. The researchers did find that the absolute benefit of screening steadily increased with longer follow-up. The number of men screened to prevent one death from prostate cancer dropped dramatically from 1410 after 9 years of follow-up to 781 at 13 years. The number needed to be diagnosed and treated to prevent one prostate cancer death also fell from 48 to 27, with the risk of advanced prostate cancer also smaller in the screening group. An accompanying commentary said the new findings “are crucially important”. The authors wrote that in future publications based on the research, the distribution of prostate cancer deaths by Gleason score and PSA at diagnosis “will be important to understand how to tailor screening and treatment”.

Gene mutation increases breast cancer risk
WOMEN with mutations in the PALB2 gene (partner and localiser of BRCA2) have on average a one in three chance of developing breast cancer by the age of 70 years, according to research published in the New England Journal of Medicine. The research analysed data from 154 families, which included 311 women with PALB2 mutations (229 with breast cancer), and 51 men with PALB2 mutations (seven with breast cancer). The researchers found that by 70 years of age, breast cancer risk ranged from 33% for a female carrier with no affected relatives to 58% for a female carrier with two first-degree relatives who had breast cancer diagnosed by 50 years of age. “Such differences in risk are consistent with previous observations, and it is possible that family history and PALB2 genotype should be considered together in determining the risk level and appropriate management”, the researchers wrote. “On the basis of our estimates of risk, women with loss-of-function mutations in PALB2 should be studied to determine whether enhanced surveillance for breast cancer, in line with that offered to women with mutations in BRCA2, can influence outcomes. Risk-reducing surgical options could also be tested.” The researchers also found “a nonsignificant increase” in the risk of ovarian cancer for PALB2 carriers. Although only a very small proportion of women worldwide carry the mutations, the researchers wrote that with the widespread availability of multigene panels and whole-exome sequencing, screening for inherited loss-of-function mutations in PALB2 had begun to enter clinical practice. “As families with PALB2 mutations are identified, it will be valuable to collect family history and other data for future analysis, in order to refine estimates of the cancer risks for PALB2 mutation carriers”, they wrote. An accompanying editorial said the research findings highlighted “emerging opportunities to treat breast cancer by pursuing the synthetic lethality of cancer therapy”.

Cognitive training improves schizophrenia symptoms
METACOGNITIVE training (MCT) — a low-threshold and low-intensity group training program that targets cognitive biases involved in the formation and maintenance of psychotic symptoms — has led to substantial symptom improvements in patients diagnosed with schizophrenia spectrum disorders, according to research published in JAMA Psychiatry. The researchers found the improvements were sustained 3 years after training and were also accompanied by a delayed improvement in quality of life and self-esteem. The randomised, controlled, assessor-blind, parallel group trial was conducted at two centres and included 150 in- and outpatients with schizophrenia spectrum disorders who had been prescribed antipsychotic medication. A second follow-up assessment took place 3 years later after the training program ended. Intention-to-treat analyses showed patients in the MCT group had significantly greater reductions in delusion scores after 3 years compared with the control group, which involved a neuropsychological training program aimed at improving neuropsychological functions such as memory. Among secondary outcomes, intention-to-treat analyses also demonstrated that patients in the MCT group had significantly greater reductions in positive syndrome scores and delusional scores. “The destigmatizing/normalizing approach of the program, which highlights similarities to normal behavior while not downplaying psychotic symptoms, may have contributed to the improvement by reducing feelings of stress, guilt, and stigmatization”, the authors wrote. They reported significant group differences at the 3-year follow-up on measures of self-esteem and quality of life, which had not distinguished the groups in earlier assessments. The completion rate of MCT was 61.3% after 3 years.

Long-term aspirin use cuts cancer
THE effects of aspirin on cancer are not apparent until at least 3 years after starting use, and some benefits are sustained for several years after cessation in long-term users, according to the authors of research published in the Annals of Oncology. The research, which reviewed the literature on aspirin use and colorectal, oesophageal, stomach, pancreatic, lung, prostate and breast cancers, as well as myocardial infarction (MI), stroke, major extracranial and gastrointestinal bleeds, and peptic ulcer, found prophylactic aspirin use for a minimum of 5 years at doses of 75−325 mg/day appeared to have a favourable benefit–harm profile. The researchers wrote that higher doses of aspirin did not appear to confer additional benefit but did increase toxicities. “Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age”, they wrote. The researchers called for further research to determine the optimum dose and duration of use, identify individuals at increased risk of bleeding, and test the effectiveness of Helicobacter pylori screening and eradication before starting aspirin prophylaxis. The research showed that for average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, MI or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. The researchers wrote that “absolute” reductions were age and sex dependent. They wrote that “analysis of benefits and harms in the general population in the developed world suggests a net benefit for a minimum 5 years of aspirin prophylaxis starting between ages 50 and 65, for both men and women, with larger benefits for 10 years of use. Continuing aspirin use for a longer duration also appears to be beneficial; however, there is uncertainty about the age at which it should be stopped”.

TB vax also protects against infection
A NEW meta-analysis published in the BMJ has shown that Bacille Calmette-Guérin (BCG) vaccination protects children against Mycobacterium tuberculosis infection as well as protecting against progression to tuberculosis disease. The systematic review authors said their results “support a paradigm shift in the understanding of how antimycobacterial vaccines (new and old) can work”. The primary analysis included 14 studies and 3855 vaccinated and unvaccinated children aged under 16 years with known recent exposure to patients with pulmonary tuberculosis. The children were screened for infection with M. tuberculosis with two interferon-γ release assays. The estimated overall risk ratio was 0.81, indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the assays. When the analysis was restricted to six studies (n = 1745) with information on progression to active tuberculosis at the time of screening, it showed protection against infection of 27% compared with 71% against active tuberculosis. Among those infected, protection against progression to disease was 58%. “Our results provide evidence that BCG protects against tuberculosis infection from multiple epidemiologically different settings and independent of the type of interferon γ release assay used to detect infection”, the researchers wrote. “Our results also suggest that models of BCG impact should be revised to include an effect against infection and consequently latent M tuberculosis infection and reactivation as without this the effect of BCG would be underestimated.”

Crowdsourcing benefits for dieters
RESEARCHERS have found that a large group of untrained peers can provide feedback to assist in dietary monitoring that is comparable to trained raters familiar with the US Dietary Guidelines. The research, published in the Journal of the American Medical Informatics Association, assessed how closely crowdsourced ratings of 450 pictures of foods and beverages from a mobile app using a simple “healthiness” scale were related to the ratings of the same pictures by trained observers. The 1-year observational study used data collected from 5006 users of the app, designed to allow users to take pictures of the foods they eat and post them for users to view. Users rate the healthiness of the foods pictured and the crowdsourced ratings are provided back to the original user who receives feedback on their diet, which they can use to modify their diet. The researchers found that the average of the scores from three trained raters was highly correlated with the peer healthiness score for all photos. “Self-monitoring energy intake is one of the key components of behavioral weight loss programs”, the researchers wrote, saying diet tracking mobile apps hold promise as a way to increase the frequency of diet self-monitoring. “Crowdsourcing has potential as a way to improve adherence to dietary self-monitoring over a longer period of time. This study represents the first step in assessing the utility and accuracy of using crowdsourcing to provide very general diet feedback.”

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