My favourite of all time is James Lind's 1747 trial of treatments for
scurvy. Non-randomised, non-blinded - yet it is adequate evidence n
itself for using citrus fruits to treat scurvy. What is interesting here
is of course the size of the treatment effect. I would suggest that the
greater the size of the treatment effect (here 100% compared with 0%)
the less important is randomisation or blinding. If you calculate p it
turns out to be zero.
Toby
Of the Prevention of the Scurvy
I shall conclude the precepts relating to the preservation of seamen
with showing the best means of obviating many inconveniences which
attend long voyages and of removing the several causes productive of
this mischief.
The following are the experiments.
On the 20th May, 1747, I took twelve patients in the scurvy on board the
Salisbury at sea. Their cases were as similar as I could have them. They
all in general had putrid gums, the spots and lassitude, with weakness
of their knees. They lay together in one place, being a proper apartment
for the sick in the fore-hold; and had one diet in common to all, viz.,
water gruel sweetened with sugar in the morning; fresh mutton broth
often times for dinner; at other times puddings, boiled biscuit with
sugar etc.; and for supper barley, raisins, rice and currants, sago and
wine, or the like. Two of these were ordered each a quart of cyder a
day. Two others took twenty five gutts of elixir vitriol three times a
day upon an empty stomach, using a gargle strongly acidulated with it
for their mouths. Two others took two spoonfuls of vinegar three times a
day upon an empty stomach, having their gruels and their other food well
acidulated with it, as also the gargle for the mouth. Two of the worst
patients, with the tendons in the ham rigid (a symptom none the rest
had) were put under a course of sea water. Of this they drank half a
pint every day and sometimes more or less as it operated by way of
gentle physic. Two others had each two oranges and one lemon given them
every day. These they eat with greediness at different times upon an
empty stomach. They continued but six days under this course, having
consumed the quantity that could be spared. The two remaining patients
took the bigness of a nutmeg three times a day of an electuary
recommended by an hospital surgeon made of garlic, mustard seed, rad.
raphan., balsam of Peru and gum myrrh, using for common drink barley
water well acidulated with tamarinds, by a decoction of which, with the
addition of cremor tartar, they were gently purged three or four times
during the course.
The consequence was that the most sudden and visible good effects were
perceived from the use of the oranges and lemons; one of those who had
taken them being at the end of six days fit four duty. The spots were
not indeed at that time quite off his body, nor his gums sound; but
without any other medicine than a gargarism or elixir of vitriol he
became quite healthy before we came into Plymouth, which was on the 16th
June. The other was the best recovered of any in his condition, and
being now deemed pretty well was appointed nurse to the rest of the sick
…
As I shall have occasion elsewhere to take notice of the effects of
other medicines in this disease, I shall here only observe that the
result of all my experiments was that oranges and lemons were the most
effectual remedies for this distemper at sea. I am apt to think oranges
preferable to lemons, though it was principally oranges which so
speedily and surprisingly recovered Lord Anson's people at the Island of
Tinian, of which that noble, brave and experienced commander was so
sensible that before he left the island one man was ordered on shore
from each mess to lay in a stock of them for their future security. …
Perhaps one history more may suffice to put this out of doubt.
--
Toby Lipman
General practitioner, Newcastle upon Tyne
Chair, Northern Faculty Board, Royal College of General Practitioners
R&D lead, Newcastle upon Tyne Primary Care Trust
Tel 0191-2811060 (home), 0191-2437000 (surgery)
Northern and Yorkshire Evidence-Based Practice Workshops
http://www.eb-practice.fsnet.co.uk/
|