Vax has big impact on chickenpox rates
IN the 15 years since the introduction of varicella vaccine in 1995, rapidly increasing vaccination coverage has been accompanied by a decline in varicella infections in the US, according to research published in Pediatrics. The serial cross-sectional survey was conducted at baseline in 1995 (prevaccine) and in 2000, 2003, 2006 and 2009 among members of the Kaiser Permanente of Northern California. Each survey included a random sample of 8000 children and adolescents aged 5–19 years regardless of vaccination status. The researchers found that over the 15-year survey period the vaccination status of the children increased from 51% to 98.8% in the 5–9 years age group, 11% to 94.7% in 10–14 years, and 3% to 53.6% in the 15–19 years group. They wrote that in the same period and irrespective of vaccination status, varicella incidence decreased by 90%–95% (10–20-fold) in all age categories. No increase in susceptibility rates was observed in any age category compared with the prevaccine era. Varicella hospitalisation rates also dropped, with overall age-adjusted rates per 100 000 person-years down from 2.13 in 1994 to 0.87 in 2000, 0.46 in 2003, 0.52 in 2006, and 0.25 in 2009, corresponding to a 90% reduction in all age categories, “emphasizing the impact of the varicella vaccination program in all age groups, including adolescents and adults”, the researchers wrote. “This study confirms that varicella vaccination has the ability to dramatically decrease varicella burden, both directly and possibly through herd immunity.” A separate study published in CMAJ found less pain but a small increased risk of febrile seizures following vaccination with the combination measles–mumps–rubella–varicella (MMRV) vaccine compared with separate MMR and varicella vaccinations. The researchers wrote that the MMRV decreased pain for children and distress for parents, “thus addressing common barriers to vaccine uptake, and may improve vaccine coverage levels and decrease immunization delivery costs”.

Naevi may be a marker for breast cancer risk
TWO new prospective cohort studies that link cutaneous naevi with breast cancer had “major appeal” from the idea, as yet untested, that naevi may be a useful marker of breast cancer risk, according to an accompanying perspective article published in PLOS Medicine. The studies — one involving more than 74 000 women from the Nurses’ Health Study and the other involving nearly 90 000 French women — found associations between self-reported cutaneous naevi and breast cancer risk. The nurses’ study identified the number of cutaneous naevi as a novel phenotypic marker associated with breast cancer risk. “Given that higher numbers of cutaneous nevi reflect higher levels of plasma free testosterone and free estradiol, the number of cutaneous nevi may be a surrogate for sex hormone exposure”, the researchers wrote. The French study found associations between the number of naevi and the risk of premenopausal breast cancer, history of benign breast disease and a family history of breast cancer. “Because associations were modest and the results for breast cancer were sensitive to adjustment, we mostly consider our findings in terms of enhancement of our knowledge of pathophysiological mechanisms”, they wrote. The authors of the accompanying perspective article wrote that the findings from the studies were broadly consistent, although subgroup findings were different. They said the association between naevi and breast cancer risk was unlikely to be causal but the observed associations “reflect a shared cause or causes”. The studies suggested that “the independent effect of self-reported nevi count on breast cancer risk is weak and therefore the marker may contribute only modestly to predictive models of individual risk”. The authors called for additional studies to investigate melanocytic naevi and other cutaneous features in association with the risks of breast cancer and other oestrogen-related proliferative diseases.

Exercise may improve gut microbiota diversity
A STUDY of 40 elite international rugby players has found exercise may be an important factor in the relationship between gut microbiota, host immunity and host metabolism. The research, published in Gut, also included two groups of healthy male controls (one group with low body mass index (BMI), and the other with high BMI). Compositional analysis of the microbiota was explored by 16S rRNA amplicon sequencing and each participant completed a detailed food frequency questionnaire. The researchers found the athletes’ diversity of gut microbiota was significantly higher than in both control groups and their levels of plasma creatine kinase and creatinine were also significantly elevated, consistent with the high exercise loads. The athletes’ diet was significantly different from that of controls, with increased intake of calories, protein, fat and carbohydrate. Few differences were observed between the two control cohorts. “Of note, the athletes and low BMI group had significantly higher proportions of the genus Akkermansia levels than the high BMI group”, the researchers wrote. “Akkermansia muciniphilla has been identified as a mucin-degrading bacteria that resides in the mucus layer and its abundance has been shown to inversely correlate with obesity and associated metabolic disorders.” They wrote that their results “suggest that the relationship between exercise, diet and the gut microbiota warrants further investigation”. An accompanying commentary said that understanding “the complex relationship among what we choose to eat, activity levels and gut microbiota richness is essential”.

No benefits in levodopa-sparing therapy in Parkinson’s
RESEARCHERS have found no short- or long-term mobility benefit from initiating levodopa-sparing therapy rather than levodopa when treating patients with early Parkinson’s disease. In an open-label, randomised trial published in The Lancet, 1620 patients newly diagnosed with Parkinson’s disease were randomly assigned to receive levodopa-sparing therapy — either dopamine agonists or monoamine oxidase type B inhibitors (MAOBI) — or levodopa alone. Mobility scores over a median 3-year follow-up were 1.8 points better in patients randomly assigned to levodopa than those assigned to levodopa-sparing therapy, with no increase or attrition of benefit during 7 years’ observation. Mobility scores were also1.4 points better in patients allocated MAOBI than in those allocated dopamine agonists. The researchers found those allocated MAOBI or dopamine agonists were significantly more likely to discontinue medication than those taking levodopa, mainly attributable to side effects. Participants allocated and still taking MAOBI or dopamine agonists were also significantly more likely than those allocated levodopa to need a drug from another class added to their treatment. The researchers wrote that the overall balance of benefits and risks favoured levodopa over levodopa-sparing therapy with better patient-rated quality of life both in the short and long term. An accompanying commentary said the results of the study “will help to persuade physicians and reassure patients that the fears that have served as the groundwork in establishing levodopa phobia — that often results in patients experiencing unnecessary and easily managed disability and reduction in quality of life in the early years of their disease — are unfounded”.

Milk link to diabetes risk in doubt
IN infants at risk for type 1 diabetes, the use of a hydrolysed formula compared with a conventional formula did not reduce the incidence of diabetes-associated autoantibodies after 7 years of follow-up, according to the results of a randomised controlled trial published in JAMA. The 2159 infants in the study were randomly allocated to receive either a casein hydrolysate or a conventional cows’ milk formula supplemented with 20% of the casein hydrolysate. The researchers found the absolute risk of positivity for two or more islet autoantibodies was 13.4% for those on the casein hydrolysate formula (n = 139) v 11.4% for those on conventional formula (n = 117). “This study showed that in this large international trial in children with an HLA genotype conferring increased risk for type 1 diabetes and an affected first-degree relative, weaning to a highly hydrolyzed formula during infancy was not associated with any reduction in the signs of cumulative β-cell autoimmunity”, the researchers wrote. They said their study outcome was in contrast to data from an earlier pilot study, which reported that weaning to an extensively hydrolysed formula in infancy was associated with an almost 50% reduction in the cumulative incidence of β-cell autoimmunity by the age of 10 years in similar children. “Our experience shows that a large-scale primary preventive dietary intervention aimed at decreasing the risk of type 1 diabetes is feasible”, the trial authors wrote. “In contrast to the pilot study and supportive animal and uncontrolled human studies, weaning to a hydrolyzed formula in early infancy had no effect on the development of β-cell autoimmunity. It is, however, possible that the hydrolyzed formula affects the degree and rate of progression of autoimmunity to clinical diabetes in high-risk children, which will be ascertained in the [pilot study] cohort by the 10-year follow-up”, they wrote.

Pharma marketing impacts on junior doctor prescribing
THE authors of a US study on the impact of pharmaceutical marketing on medical trainees, published in JAMA Internal Medicine, say it provides “another reminder of the negative effects those interactions can have on the quality and cost of patient care”. The researchers conducted a national survey of first- and fourth-year medical students and third-year residents by randomly selecting trainees from medical schools. The 1601 student (49.0% response rate) and 735 resident (42.9% response rate) respondents reported common use of unfiltered sources of drug information such as Google (74.2%–88.9%) and Wikipedia (45.2%–84.5%). They found that 48% to 90% of fourth-year students and residents accurately identified evidence-based prescribing choices. However, a higher industry relations index (measured by assessing each trainee’s level of acceptance of pharmaceutical promotion) was associated with 15% lower odds of selecting an evidence-based prescribing choice. There was also a significant association between the industry relations index and greater odds of choosing to prescribe brand-name drugs. The authors wrote that pharmaceutical marketing was associated with fewer evidence-based prescribing choices and a greater inclination to prescribe brand-name products over less expensive generic options or non-drug treatment plans with equal or greater comparative effectiveness. “Overall, our finding that trainees with fewer connections to industry promotional activities had greater knowledge of evidence-based prescribing provides additional support for policies intended to insulate medical trainees from pharmaceutical marketing”, they wrote. An accompanying editor’s note said it was becoming increasingly clear that restricting pharmaceutical marketing interactions during medical school and postgraduate training “leads to higher-quality, more evidence-based prescribing among physicians, which is good for the profession, for patient care, and for the public’s trust in medicine”.

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