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Nathan Goodyear

Cardiovascular disease in Europe: epidemiological update 2016 | European Heart Journal ... - 0 views

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    Cancer will soon overtake cardiovascular disease as the #1 cause of mortality in the US and worldwide as happened in 12 European countries. The current dogma for cancer treatment is not working; the goal must be prevention. The 12 countries include: Spain, France, Belgium, Denmark, Italy, Israel, Luxembourg, The Netherlands, Norway, Portugal, Slovenia, and UK.
Nathan Goodyear

Availability of evidence of benefits on overall survival and quality of life of cancer ... - 0 views

  • Although the goal of cancer treatment is to improve the quantity and quality of life,123 clinical trials designed to gain regulatory approval for new drugs often evaluate indirect or “surrogate” measures of drug efficacy. These endpoints show that an agent has biological activity, but they are not reliable surrogates for improved survival4567891011 or quality of life46111213
  • two recent systematic reviews suggest that the strength of association between surrogates in cancer clinical trials and life extension is generally low
  • Available data from the US show that only a small proportion of cancer treatments approved by the US Food and Drug Administration (FDA) unequivocally show benefits on survival or quality of life.30
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  • We sought to systematically evaluate the evidence base for all new drugs and new indications for the treatment of solid tumours and haematological malignancies approved by the EMA in the five year period 2009-13
  • Three investigators (AP, EP, and EG) independently extracted data on and descriptively analysed the following trial features: characteristics of the participant population, study design (randomisation, crossover from experimental to control group, and blinding of investigators and participants), experimental and control groups, enrolment, primary and secondary endpoints, magnitude of benefit on survival and quality of life, and narrative interpretation of the findings
  • Only 18 of the 68 (26%) were supported by a pivotal study powered to evaluate overall survival as the primary outcome
  • From 2009 to 2013, the EMA approved use of 48 oncology drugs
  • Seventeen drugs were approved for treatment of haematological malignancies and 51 for treatment of solid tumours
  • Overall, 72 clinical trials supported the approval of 68 novel drug uses
  • Our scoring was limited to drugs for solid tumours
  • Among 68 cancer drug indications approved by the EMA in the period 2009-13, and with a median of 5.4 years’ follow-up, only 35 (51%) were associated with a significant improvement in survival (26/35) or quality of life (9/35) over existing treatment options, placebo, or as add on treatment
  • Only two of the 26 drugs shown to extend life also showed benefits on quality of life
  • 33 (49%) had not shown any improvement on survival or quality of life
  • This systematic evaluation of oncology drug approvals by the EMA in 2009-13 shows that most of the drugs (39/68, 57%) entered the market without evidence of improved survival or quality of life
  • At a minimum 3.3 years after market entry, there was still no conclusive evidence that 33 of these 39 cancer drugs either extended or improved life
  • What are potential reasons for the paucity of drug approvals with demonstrable survival advantages over existing treatments?
  • Firstly, only 18 (26%) indications for use in our cohort were supported by trials in which extension of life was the primary outcome
  • None of the pivotal studies supporting oncology drug approvals from 2009 to 2013 included quality of life as a primary outcome measure
  • Most new oncology drugs authorised by the EMA in 2009-13 came onto the market without clear evidence that they improved the quality or quantity of patients’ lives
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    New study from European Medicines Agency questions alot of the new cancer drugs brought to the market 2009-2013.  57% of the new drugs (39/68) were brought to the market without evidence of improved survival or quality of life.
arunaraayala

Indian doctors flown in to meet UK staff shortages - Locality News - 0 views

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    Britain's exit from the European Union is likely to impact NHS workforce, leading to the UK governme...
Nathan Goodyear

Weight changes after adjuvant treatment in Korean women with early breast cancer - Spri... - 0 views

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    study of adjuvant chemotherapy in Asian women found no weight gain post treatment; this is in contrast to American and European women in other studies.
Nathan Goodyear

Vitamin D may help lower blood pressure - UPI.com - 0 views

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    European study showed that vitamin D replacement in those with low vitamin D levels, had benefits of lowered blood pressure.
Nathan Goodyear

Salivary cortisol as a diagnostic tool for ... [Eur J Endocrinol. 2012] - PubMed - NCBI - 0 views

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    European Journal of Endocrinology finds that salivary cortisol can be used as a diagnostic tool for Cushing's syndrome and adrenal insufficiency.  Thus both hypercortisol and hypocortisol states can be followed using saliva.  This statement was using immunoassay.  Mass spectroscopy provides even better results
Nathan Goodyear

Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary di... - 0 views

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    European journal of endocrinology article compared serum to salivary cortisol and found them to be equal, but due to ease of collection, salivary cortisol to be preferable.  This article was using cortisol to assess HPA axis dysfunction.
Nathan Goodyear

Relationship Between Benign Prostatic Hyperplasia/... [J Sex Med. 2014] - PubMed - NCBI - 0 views

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    European study finds no correlation with Total Testosterone levels and lower urinary tract symptoms and benign prostatic hypertrophy.
Nathan Goodyear

The question of declining sperm density revisited: an analysis of 101 studies published... - 0 views

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    Re-analysis of Carlsen's work on sperm count finds consistent decline in sperm count.  Swan and authors found a 1.5% decline in US men from 1934-1996 and 3% annual decline in European/Australian men over same time frame.  This was a meta-analysis of 101 studies from 1934-1996.  Yes, there is geographical variation, but the overall trend is one of decline.
Nathan Goodyear

Late-Onset Hypogonadism and Mortality in Aging Men: The Journal of Clinical Endocrinolo... - 0 views

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    severe hypogonadism was associated with a 5 fold increase risk of cardiovascular mortality and all cause mortality in men ages 40-79 in European study.
Nathan Goodyear

Physical activity and all-cause mortality across levels of overall and abdominal adipos... - 0 views

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    Mortality increased by sedentary lifestyle.  The risk is on par with that of BMI and waist circumference.
Nathan Goodyear

PosterSessionOnline - 0 views

  • Poster number: 552 No. visits: 16 Title: ALCAT test results in the treatment of gastrointestinal symptoms Authors : Mara De Amici , Centre: Foundation IRCCS Hospital San Matteo
  • Poster number: 553 No. visits: 12 Title: Evaluation of ALCAT test results in the non IgE-mediated pathology of the skin Authors : Mara De Amici , Centre: Foundation IRCCS Hospital San Matteo
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    Recent Poster presentation at European Academy of Allergy and Clinical Immunology reveals 66 % improvement in skin conditions with ALCAT diet.  Read poster #552
Nathan Goodyear

Physical activity and all-cause mortality across levels of overall and abdominal adipos... - 0 views

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    New study finds that inactive lifestyle leads to more early deaths than obesity.  Of course, the 2 are interrelated.  The study found a 16-30% reduction in early death due to 20 minutes of walking daily.  This came from analysis of the EPIC study
Nathan Goodyear

Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views

  • defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
  • the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
  • most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
    • Nathan Goodyear
       
      this equals 251 to 366 in serum Total Testosterone
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  • Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
  • −0.124 nmol/L/year in serum total testosterone
    • Nathan Goodyear
       
      this equates to a 4 ng/dl decline annually in total Testosterone.
  • In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
  • In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
  • testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
  • by promoting lipolysis and myogenesis, testosterone might lead to improved insulin resistance
  • testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
  • In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
  • independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
  • In short, androgen improves insulin resistance by changing body composition and reducing body fat.
  • Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
  • In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
  • leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
  • Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
    • Nathan Goodyear
       
      So what is "unequivocal"?
  • Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
  • 30–44% sex hormone binding globulin (SHBG)-bound testosterone and 54–68% albumin-bound testosterone
  • As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
  • Serum total testosterone is composed of 0.5–3.0% of free testosterone unbound to plasma proteins
  • alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
  • listed in Table​T
  • A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
  • Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
  • subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
  • In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
  • Asians, higher values, ranging from 18.1 to 19.1 nmol/L, were seen in Korea and Japan
  • Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
  • The reduction of total testosterone was 0.4% per year in both groups
  • HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
  • pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
  • In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
  • Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
  • Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
  • The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
  • In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
  • a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
  • In India, men with CAG ≤19 had increased risk of prostate cancer
  • the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
  • assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
  • In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
  • a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
  • A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
  • Low testosterone is commonly associated with a high prevalence of MES
  • most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
  • MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
  • Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
  • In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
  • weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
  • To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
  • In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
  • low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
  • Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
  • low serum total testosterone predicted increased risk of cardiovascular mortality with a HR of 1.38
  • low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
  • European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
  • Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
  • serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
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    Nice review of Testosterone levels and some of the evidence linking Diabetes with low T.  However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling.  The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
Nathan Goodyear

The rs5934505 single nucleotide polymorphism (SNP) is associated with low testosterone ... - 0 views

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    Four SNPs, rs12150660, rs727428, rs5934505, and rs10822184 associated with late-onset hypogonadism (low T) and obesity in men of European descent.  In Chinese populations, rs5934505 was associated with increased risk of low Total Testosterone and calculated free Testosterone.  OR was 2.01 for low TT and 2.14 for low calculated free Testosterone.
Nathan Goodyear

European Journal of Clinical Nutrition - C-reactive protein concentration and concentra... - 0 views

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    This study shows that inflammation, CRP in this study, was inversely associated with low antioxidants ie. vitamin C.  This makes since as ROS are known to stimulate inflammation.  Vitamin C should be considered as a therapeutic option in those with inflammation.
Nathan Goodyear

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and... - 0 views

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    weight gain and obesity are associated with a dysfunctional HPA axis and low testosterone in men.  Reduction in weight will restore HPA axis function.
Nathan Goodyear

A Preliminary Study of Daily Interpersonal Stress and C-Reactive Protein Levels Among A... - 0 views

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    stress increases inflammation
Nathan Goodyear

Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 par... - 0 views

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    IV vitamin C is the only delivery method shown to increase serum vitamin C levels.  Additionally, the stroke incidence is this study was found to be lowered by 42% with the elevation of serum vitamin C levels, which  can only be done by IV.
Nathan Goodyear

Vitamin D is associated with testosterone and hypogonadism in Chinese men: Results from... - 0 views

  • lower 25(OH)D level was significantly associated with lower total T, E2, SHBG, LH and FSH levels after adjusting for age, residence area, economic status and current smoker
  • association between 25(OH)D status and hypogonadism in Chinese men and confirms that this relationship is present in a large population
  • VDR knockout mutant mice showed gonadal insufficiencies
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  • High LH and FSH levels in the male mice indicated hypergonadotropic hypogonadism
  • Another mouse study reported a tendency towards low testosterone/LH ratio and Leydig cell hyperplasia in VDR null mice
  • The serum testosterone levels could increase to normal values in vitamin D-deficient rats replete with vitamin D
  • VDR knockout mice had decreased sperm count, reduced sperm motility, and histological abnormality of the testis
  • vitamin D supplementation increases testosterone levels in non-diabetic subjects
  • The data from the European Male Ageing Study [9] indicated that 25(OH)D is positively associated with total T
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    Study of 713 Chinese men finds a correlation between low vitamin D and low total Testosterone.
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