Association Between More Intensive vs Less Intensive Blood #Pressure Lowering and Risk of Mortality in Chronic #Kidney Disease Stages 3 to 5
http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2652833

Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups.

Conclusions and Relevance Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.

Association between active #commuting and incident cardiovascular disease, cancer, and #mortality: prospective cohort study
http://www.bmj.com/content/357/bmj.j1456

Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic

A meta-analysis of #nevus-associated #melanoma: Prevalence and practical implications
http://www.jaad.org/article/S0190-9622(17)32051-0/abstract

The reported prevalence of nevus-associated melanoma varies substantially. We performed a systematic review and meta-analysis to determine the incidence and prevalence of this disease; we also performed subanalyses considering age, tumor thickness, and nevus-type classification. In 38 observational cohort and case–control studies, 29.1% of melanomas likely arose from a preexisting nevus and 70.9% de novo. Any given melanoma was 64% less likely to be nevus-associated than de novo (risk ratio 0.36, 95% confidence interval CI 0.29-0.44; P < .001; I2 = 99%); nevus-associated melanomas had a lower mean Breslow thickness than de novo melanomas (mean difference –0.39 mm; 95% CI –0.60 to –0.18; P = .0003; I2 = 66%). No significant differences were noted regarding the association of nevus-associated melanomas with nondysplastic nevi or dysplastic nevi (risk ratio 0.77, 95% CI 0.49-1.20; P = .24; I2 = 98%)

A Comparison of Alkaline Water and #Mediterranean Diet vs Proton #Pump Inhibition for Treatment of Laryngopharyngeal #Reflux
http://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2652893

Laryngopharyngeal reflux (LPR) is a common disorder with protean manifestations in the head and neck. In this retrospective study, we report the efficacy of a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions compared with that of the traditional treatment approach of proton pump inhibition (PPI) and standard reflux precautions

Conclusions and Relevance Our data suggest that the effect of PPI on the RSI Reflux Symptom Index based on proportion reaching a 6-point reduction in RSI is not significantly better than that of alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions, although the difference in the 2 treatments could be clinically meaningful in favor of the dietary approach. The percent reduction in RSI was significantly greater with the dietary approach. Because the relationship between percent change and response to treatment has not been studied, the clinical significance of this difference requires further study. Nevertheless, this study suggests that a plant-based diet and alkaline water should be considered in the treatment of LPR. This approach may effectively improve symptoms and could avoid the costs and adverse effects of pharmacological intervention as well as afford the additional health benefits associated with a healthy, plant-based diet

The cumulative burden of surviving #childhood #cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE)

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31610-0/fulltext?elsca1=tlpr

Survivors of childhood cancer develop early and severe chronic health conditions (CHCs).

The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9–99·9) for grade 1–5 CHCs and 96·0% (95% CI 95·3–96·8%) for grade 3–5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2–18·1) CHCs of any grade, of which 4·7 (4·6–4·9) were CHCs of grade 3–5. The cumulative burden in matched community controls of grade 1–5 CHCs was 9·2 (95% CI 7·9–10·6; p<0·0001 vs total study population) and of grade 3–5 CHCs was 2·3 (1·9–2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1–5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 95% CI 20·9–27·5) and lowest in survivors of germ cell tumours (14·0 11·5–16·6). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs

Final efficacy, immunogenicity, and safety analyses of a nine-valent human #papillomavirus #vaccine in women aged 16–26 years: a randomised, double-blind trial
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31821-4/abstract

Primary analyses of a study in young women aged 16–26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine.

Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0–99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related.

Interpretation
The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide

Development and risk factors of type 2 #diabetes in a nationwide population of women with #polycystic ovary syndrome

https://academic.oup.com/jcem/article-abstract/doi/10.1210/jc.2017-01354/4096783/Development-and-risk-factors-of-type-2-diabetes-in?redirectedFrom=fulltext

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Prospective population-based data regarding development and possible predictors of type 2 diabetes (T2D) in PCOS are limited The median (quartiles) follow up was 11.1 (6.9 - 16.0) years. The Hazard ratio (95% CI) for development of T2D in PCOS Denmark was 4.0 (3.7; 4.3) (p<0.001) and the total event rate of T2D was 8.0 per 1000 patient years in PCOS Denmark vs. 2.0 per 1000 patient years in controls (p<0.001). The median age at diagnosis of T2D was 31 (26-37) years in PCOS Denmark vs. 35 (27-44) years in controls (p<0.001). In multiple regression analyses, body mass index, HbA1c, fasting blood glucose, 2 hour blood glucose, homeostasis model assessment of insulin resistance, and triglycerides were positively associated with development of T2D, whereas higher number of births was negatively associated with development of T2D.
Conclusion
The event rate of T2D was higher in PCOS compared to controls and T2D was diagnosed at a younger age

#Tezepelumab in Adults with Uncontrolled #Asthma
http://www.nejm.org/doi/full/10.1056/NEJMoa1704064

In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell–derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids

The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the placebo group (148 patients). Thus, exacerbation rates in the respective tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo group (P<0.001 for all comparisons). Similar results were observed in patients regardless of blood eosinophil counts at enrollment. The prebronchodilator forced expiratory volume in 1 second at week 52 was higher in all tezepelumab groups than in the placebo group (difference, 0.12 liters with the low dose P=0.01, 0.11 liters with the medium dose P=0.02, and 0.15 liters with the high dose P=0.002). A total of 2 patients in the medium-dose group, 3 in the high-dose group, and 1 in the placebo group discontinued the trial regimen because of adverse events.

Conclusions
Among patients treated with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids, those who received tezepelumab had lower rates of clinically significant asthma exacerbations than those who received placebo, independent of baseline blood eosinophil counts

Clinical Practice #Guideline: Evaluation of the #Neck Mass in Adults
http://journals.sagepub.com/doi/full/10.1177/0194599817722550

Neck masses are common in adults, butoften the underlying etiology is not easily identifiable. While infections cause most of the neck masses in children, most persistent neck masses in adults are neoplasms. Malignant neoplasms far exceed any other etiology of adult neck mass. Importantly, an asymptomatic neck mass may be the initial or only clinically apparent manifestation of head and neck cancer, such as squamous cell carcinoma (HNSCC), lymphoma, thyroid, or salivary gland cancer. Evidence suggests that a neck mass in the adult patient should be considered malignant until proven otherwise. Timely diagnosis of a neck mass due to metastatic HNSCC is paramount because delayed diagnosis directly affects tumor stage and worsens prognosis

This guideline strives to bring a coherent, evidence-based, multidisciplinary perspective to the evaluation of the neck mass with the intention to facilitate prompt diagnosis and enhance patient outcomes

#Palmitoylation-dependent activation of MC1R prevents #melanomagenesis
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23887.html

The melanocortin-1 receptor (MC1R), a G-protein-coupled receptor, has a crucial role in human and mouse pigmentation Activation of MC1R in melanocytes by α-melanocyte-stimulating hormone (α-MSH)9 stimulates cAMP signalling and melanin production and enhances DNA repair after ultraviolet irradiation Individuals carrying MC1R variants, especially those associated with #red hair colour, fair skin and poor tanning ability (denoted as RHC variants), are associated with higher risk of melanoma

However, how MC1R activity is modulated by ultraviolet irradiation, why individuals with red hair are more prone to developing melanoma, and whether the activity of RHC variants might be restored for therapeutic benefit are unknown. Here we demonstrate a potential MC1R-targeted intervention strategy in mice to rescue loss-of-function MC1R in MC1R RHC variants for therapeutic benefit by activating MC1R protein palmitoylation. MC1R palmitoylation, primarily mediated by the protein-acyl transferase ZDHHC13, is essential for activating MC1R signalling, which triggers increased pigmentation, ultraviolet-B-induced G1-like cell cycle arrest and control of senescence and melanomagenesis in vitro and in vivo. Using C57BL/6J-Mc1re/eJ mice, in which endogenous MC1R is prematurely terminated, expressing Mc1r RHC variants, we show that pharmacological activation of palmitoylation rescues the defects of Mc1r RHC variants and prevents melanomagenesis.

The results highlight a central role for MC1R palmitoylation in pigmentation and protection against melanoma

#Romosozumab or Alendronate for Fracture Prevention in Women with #Osteoporosis
http://www.nejm.org/doi/full/10.1056/NEJMoa1708322

Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption

Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% 127 of 2046 patients) than in the alendronate-to-alendronate group (11.9% 243 of 2047 patients) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients 8.7% vs. 217 of 2047 patients 10.6%; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients 2.0% vs. 66 of 2047 patients 3.2%; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients 2.5% vs. 38 of 2014 patients 1.9%). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed

CONCLUSIONS
In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone

Patterns of #Sedentary Behavior and #Mortality in U.S. Middle-Aged and Older Adults: A National Cohort Study
http://annals.org/aim/article/2653704/patterns-sedentary-behavior-mortality-u-s-middle-aged-older-adults

Excessive sedentary time is ubiquitous in Western societies. Previous studies have relied on self-reporting to evaluate the total volume of sedentary time as a prognostic risk factor for mortality..

Sedentary time was measured using a hip-mounted accelerometer. Prolonged, uninterrupted sedentariness was expressed as mean sedentary bout length. Hazard ratios (HRs) were calculated comparing quartiles 2 through 4 to quartile 1 for each exposure (quartile cut points: 689.7, 746.5, and 799.4 min/d for total sedentary time; 7.7, 9.6, and 12.4 min/bout for sedentary bout duration) in models that included moderate to vigorous physical activity

Evaluation of their joint association showed that participants classified as high for both sedentary characteristics (high sedentary time ≥12.5 h/d and high bout duration ≥10 min/bout) had the greatest risk for death

Both the total volume of sedentary time and its accrual in prolonged, uninterrupted bouts are associated with all-cause mortality, suggestive that physical activity guidelines should target reducing and interrupting sedentary time to reduce risk for death