April 1, 2018. In Metformin and Prostate Cancer we added: Since then a 2016 paper found, in a cross sectional study of 326 cancer-free diabetic men, that metformin lowered PSA; however, in contrast other blood glucose lowering medications (sulfonylureas, thazodlidinediones) they looked at did not lower it. This suggests that other mechanisms than blood glucose lowering are responsible. These might be androgen receptor (AR) down-regulation, other non-AR mechanisms or reduction of inflammation or reduction of lipid levels. This study also found a dose-response effect between metformin and PSA -- those who used more than 2000 mg/day of metformin had 37% lower PSA than those who used less than 1000 mg/day. See [PMID: 27403913] [Full Free Text].

A second study, this one reporting in 2017, of 1363 diabetic cancer-free men also found that metformin users had lower PSA than non-users. [PMID: 29390570] [Full Free Text].

# The Palpable Prostate

Prostate cancer topics, links and more. Now at 200+ posts!

**News:**Health Day, Medical News Today, ScienceDaily, Urol Times, Urotoday, Zero Cancer

**Papers:**Pubmed (all), Pubmed (Free only), Amedeo

Journals: Eur Urol, J Urol, JCO, The Prostate Others Pubmed Central Journals (Free): Adv Urol, BMC Urol, J Endourol, Kor J Urol, Rev Urol, Ther Adv Urol, Urol Ann

Reviews: Cochrane Summaries, PC Infolink Newsletters: PCRI, US Too General Medical Reviews: f1000, Health News Review

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## Sunday, April 1, 2018

## Monday, August 7, 2017

### Blog Updates for July 2017

July 14, 2017. The 2017 Miror Mirror report providing international comparisons of health care systems is out and freely available [here]. The Benchmarking line under Links in the right panel of this blog has a link to it as well as links to some of their past reports.

## Friday, July 14, 2017

### Blog Updates for June 2017

June 6, 2017. In Metformin and Prostate Cancer we added: A June 2017 review paper by Whitburn et al on metformin and prostate cancer is available here: [PMID: 28444639] [Full Free Text]

## Sunday, June 4, 2017

### Eat your carrots

A December 2014 Chinese meta-analysis of prior studies on carrot consumption and prostate cancer reported that while there were some inconsistent results it nevertheless found an inverse relationship, i.e. eating more carrots cut the risk of getting prostate cancer. Importantly, it found a dose-response relationship -- for every 10 grams of carrots per day consumed there was a 5 percentage point reduction in relative risk. If this holds for sufficiently large increments of consumption and if the association is causal then given that a small/medium/large carrot weights 50/61/73 grams (see [hannaone]) one could reduce one's risk by 25%/30%/36% by consuming a small/medium/large carrot per day. The abstract of the study can be found here: [Pubmed: 24519559]

The existence of a dose-response relationship is one of the Bradford Hill criteria of causation. See: Bradford Hill Criteria of Causation on this blog.

The existence of a dose-response relationship is one of the Bradford Hill criteria of causation. See: Bradford Hill Criteria of Causation on this blog.

## Saturday, April 8, 2017

### Finding freely available research articles

A new Firefox and Chrome browser extension creates a small button on the right
side of the screen whenever you visit a journal article's web page. If it is
green then it found the article freely and legally available on a pre-print server
or the article was not pay-walled in the first place.

To install the extension simply go the unpaywall.org site using Firefox or Chrome and click on the large button.

Once it is installed any time you visit an article it will place the aforementioned button on the right side of the screen. If green click the button to get to an open access version of the article. If the button is grey then it was unable to find a free legal source. The unpaywall.org FAQ also refers to Gold and Blue buttons but none of the sites I visited had those.

This article discusses unpaywall.org as well as some other similar sites for uncovering open access material: chronicle.com.

To install the extension simply go the unpaywall.org site using Firefox or Chrome and click on the large button.

Once it is installed any time you visit an article it will place the aforementioned button on the right side of the screen. If green click the button to get to an open access version of the article. If the button is grey then it was unable to find a free legal source. The unpaywall.org FAQ also refers to Gold and Blue buttons but none of the sites I visited had those.

This article discusses unpaywall.org as well as some other similar sites for uncovering open access material: chronicle.com.

## Tuesday, January 3, 2017

### Female physicians, saunas

*Female vs. Male Physicians*In a recent study that Harvard researchers published in JAMA, it was found that patients over 65 years old had lower death rates and lower hospital re-admission rates if they were treated by a female physician rather than a male doctor. The difference was small (11.07% vs 11.49% in adjusted 30-day mortality and 15.02% vs 15.57% in adjusted re-admissions) but if applied to the entire US population would represent a potential 32,000 fewer deaths. The study was done over the period January 1, 2011, to December 31, 2014 using a 20% random sample of all Medicare patients in this category. This represents over 1.5 million hospitalizations. Their results are consistent with a previous study [PMID: 8769910] that found that female doctors were more likely to provide preventative tests and counseling. See this [NPR article]. [PMID: 27992617] [Full Text].

*Saunas*A recent 20 year follow up study out of Finland found that men taking a sauna 4-7 times a week were 66% less likely to be diagnosed with dementia than those taking a sauna once a week. Not only was the effect very large but a dose response relationship was found increasing the likelihood that the effect is meaningful. (This is one of the Bradford Hill criteria for assessing studies). This follows a long list of other [claimed benefits] from saunas. See [Science Bulletin] [Abstract]

## Friday, November 25, 2016

### The Rule of 72 and PSA Doubling Time

A common approximation used in finance is that an investment which grows at x% per year will double in roughly 72/x years. It is known as the rule of 72. What is of interest here is that it not only applies to finance but also PSA doubling time.

First consider the case of an investment. Suppose an investment grows at 12% per year. Then according to the aforementioned rule it will double in about

This is close to the exact value (rounded to one decimal place) of
This can be double checked by entering that formula into the Google search bar.

(Here log2(x) represents the logarithm to the base 2 of x. In the case that x is a power of 2 the value of log2(x) is the number of 2's to multiply together to get the argument. For example, log2(8) = 3 because multiplying three twos gives 8, i.e. 2 * 2 * 2 = 8. If x is not a power of 2 then it will be between the log2 values of the nearby powers of 2. For example, log2(5)=2.321928 is between log2(4) = 2 and log2(8) = 3.)

We can use this rule to approximate PSA doubling time (PSADT). Suppose the PSA is 0.100 at the beginning of the year and 0.112 at the end of the year. Thus, it is increasing at .112 / .100 - 1 = .12 = 12% per year. Using the rule of 72 this implies that the PSA will double in

which, as before, is close to the exact value of

Although we used years above we can use any time period. For example, suppose the PSA were growing at 2% per quarter. Then it will double in

This is close to the exact number of

There are some significant caveats.

1. The use of PSADT assumes constant exponential growth of the cancer cells. That is, the percentage increase from period to period does not systematically change. Such constant exponential growth would be the case if a plot of log2(PSA) vs. time were roughly linear. If the entire plot were not roughly linear but sections of the plot were then each such section may have a different PSADT value. For example, before and after a treatment intervention one might see different PSADT values.

2. The discussion above uses the Rule of 72 to approximate doubling time using only two PSA values but that is normally regarded as insufficient. Typically PSADT should be calculated based on at least 3 PSA values to help eliminate the natural variation in PSA values. Thus the above is only a first approximation before performing a more reliable calculation.

There is a more comprehensive discussion of PSADT calculations in this series of 4 blog posts:

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-1.html

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-2.html

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-3-diy.html

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-4-online.html

Also, Wikipedia discusses the accuracy of the Rule of 72 on this page: [Wikipedia Rule of 72]

First consider the case of an investment. Suppose an investment grows at 12% per year. Then according to the aforementioned rule it will double in about

```
72/12 = 6 years (rule of 72 approximation)
```

```
1/log2(1+12/100) = 1/log2(1.12) = 6.1 years (exact)
```

(Here log2(x) represents the logarithm to the base 2 of x. In the case that x is a power of 2 the value of log2(x) is the number of 2's to multiply together to get the argument. For example, log2(8) = 3 because multiplying three twos gives 8, i.e. 2 * 2 * 2 = 8. If x is not a power of 2 then it will be between the log2 values of the nearby powers of 2. For example, log2(5)=2.321928 is between log2(4) = 2 and log2(8) = 3.)

We can use this rule to approximate PSA doubling time (PSADT). Suppose the PSA is 0.100 at the beginning of the year and 0.112 at the end of the year. Thus, it is increasing at .112 / .100 - 1 = .12 = 12% per year. Using the rule of 72 this implies that the PSA will double in

```
PSADT = 72/12 = 6 years (rule of 72 approximation)
```

```
PSADT = 1/log2(1+12/100) = 1/log2(1.12) = 6.1 years (exact)
```

```
PSADT = 72/2 = 36 quarters = 9 years (rule of 72)
```

```
PSADT = 1/log2(1+2/100) = 1/log2(1.02) = 35 quarters = 8.75 years (exact)
```

1. The use of PSADT assumes constant exponential growth of the cancer cells. That is, the percentage increase from period to period does not systematically change. Such constant exponential growth would be the case if a plot of log2(PSA) vs. time were roughly linear. If the entire plot were not roughly linear but sections of the plot were then each such section may have a different PSADT value. For example, before and after a treatment intervention one might see different PSADT values.

2. The discussion above uses the Rule of 72 to approximate doubling time using only two PSA values but that is normally regarded as insufficient. Typically PSADT should be calculated based on at least 3 PSA values to help eliminate the natural variation in PSA values. Thus the above is only a first approximation before performing a more reliable calculation.

There is a more comprehensive discussion of PSADT calculations in this series of 4 blog posts:

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-1.html

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-2.html

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-3-diy.html

http://palpable-prostate.blogspot.ca/2007/03/psa-doubling-time-psadt-part-4-online.html

Also, Wikipedia discusses the accuracy of the Rule of 72 on this page: [Wikipedia Rule of 72]

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