i. Two lectures from the Institute for Advanced Studies:
The IAS has recently uploaded a large number of lectures on youtube, and the ones I blog here are a few of those where you can actually tell from the title what the lecture is about; I find it outright weird that these people don’t include the topic covered in the lecture in their lecture titles.
As for the video above, as usual for the IAS videos it’s annoying that you can’t hear the questions asked by the audience, but the sound quality of this video is at least quite a bit better than the sound quality of the video below (which has a couple of really annoying sequences, in particular around the 15-16 minutes mark (it gets better), where the image is also causing problems, and in the last couple of minutes of the Q&A things are also not exactly optimal as the lecturer leaves the area covered by the camera in order to write something on the blackboard – but you don’t know what he’s writing and you can’t see the lecturer, because the camera isn’t following him). I found most of the above lecture easier to follow than I did the lecture posted below, though in either case you’ll probably not understand all of it unless you’re an astrophysicist – you definitely won’t in case of the latter lecture. I found it helpful to look up a few topics along the way, e.g. the wiki articles about the virial theorem (/also dealing with virial mass/radius), active galactic nucleus (this is the ‘AGN’ she refers to repeatedly), and the Tully–Fisher relation.
Given how many questions are asked along the way it’s really annoying that you in most cases can’t hear what people are asking about – this is definitely an area where there’s room for improvement in the context of the IAS videos. The lecture was not easy to follow but I figured along the way that I understood enough of it to make it worth watching the lecture to the end (though I’d say you’ll not miss much if you stop after the lecture – around the 1.05 hours mark – and skip the subsequent Q&A). I’ve relatively recently read about related topics, e.g. pulsar formation and wave- and fluid dynamics, and if I had not I probably would not have watched this lecture to the end.
ii. A vocabulary.com update. I’m slowly working my way up to the ‘Running Dictionary’ rank (I’m only a walking dictionary at this point); here’s some stuff from my progress page:
I recently learned from a note added to a list that I’ve actually learned a very large proportion of all words available on vocabulary.com, which probably also means that I may have been too harsh on the word selection algorithm in past posts here on the blog; if there aren’t (/m)any new words left to learn it should not be surprising that the algorithm presents me with words I’ve already mastered, and it’s not the algorithm’s fault that there aren’t more words available for me to learn (well, it is to the extent that you’re of the opinion that questions should be automatically created by the algorithm as well, but I don’t think we’re quite there yet at this point). The aforementioned note was added in June, and here’s the important part: “there are words on your list that Vocabulary.com can’t teach yet. Vocabulary.com can teach over 12,000 words, but sadly, these aren’t among them”. ‘Over 12.000’ – and I’ve mastered 11.300. When the proportion of mastered words is this high, not only will the default random word algorithm mostly present you with questions related to words you’ve already mastered; but it actually also starts to get hard to find lists with many words you’ve not already mastered – I’ll often load lists with one hundred words and then realize that I’ve mastered every word on the list. This is annoying if you have a desire to continually be presented with both new words as well as old ones. Unless vocabulary.com increases the rate with which they add new words I’ll run out of new words to learn, and if that happens I’m sure it’ll be much more difficult for me to find motivation to use the site.
With all that stuff out of the way, if you’re not a regular user of the site I should note – again – that it’s an excellent resource if you desire to increase your vocabulary. Below is a list of words I’ve encountered on the site in recent weeks(/months?):
Copacetic, frumpy, elision, termagant, harridan, quondam, funambulist, phantasmagoria, eyelet, cachinnate, wilt, quidnunc, flocculent, galoot, frangible, prevaricate, clarion, trivet, noisome, revenant, myrmidon (I have included this word once before in a post of this type, but it is in my opinion a very nice word with which more people should be familiar…), debenture, teeter, tart, satiny, romp, auricular, terpsichorean, poultice, ululation, fusty, tangy, honorarium, eyas, bumptious, muckraker, bayou, hobble, omphaloskepsis, extemporize, virago, rarefaction, flibbertigibbet, finagle, emollient.
iii. I don’t think I’d do things exactly the way she’s suggesting here, but the general idea/approach seems to me appealing enough for it to be worth at least keeping in mind if I ever decide to start dating/looking for a partner.
iv. Some wikipedia links:
Tarrare (featured). A man with odd eating habits and an interesting employment history (“Dr. Courville was keen to continue his investigations into Tarrare’s eating habits and digestive system, and approached General Alexandre de Beauharnais with a suggestion that Tarrare’s unusual abilities and behaviour could be put to military use. A document was placed inside a wooden box which was in turn fed to Tarrare. Two days later, the box was retrieved from his excrement, with the document still in legible condition. Courville proposed to de Beauharnais that Tarrare could thus serve as a military courier, carrying documents securely through enemy territory with no risk of their being found if he were searched.” Yeah…).
1740 Batavia massacre (featured).
v. I am also fun.
“We wrote this book not because we know so much, but because we know we remember so little…the problem is not simply the quantity of information, but the diversity of places from which it is dispensed. Trailing eagerly behind the surgeon, the student is admonished never to forget alcohol withdrawal as a cause of post-operative confusion. The scrap of paper on which this is written spends a month in the pocket before being lost for ever in the laundry. At different times, and in inconvenient places, a number of other causes may be presented to the student. Not only are these causes and aphorisms never brought together, but when, as a surgical house officer, the former student faces a confused patient, none is to hand.”
‘But now you don’t need to look for those scraps of paper anymore because we’ve collected all that information right here, in this book,’ the authors would argue. Or at least some of the important information is included here (despite this being a 900+ page textbook, many books on subtopics covered in the book are much longer than that; for example the Holmes et al. textbook dealing only with sexually transmitted diseases is more than twice as long as this one. Of course a book with that kind of page count will only ever be a ‘handbook’ to someone with acromegaly…).
Anyway, I’m currently reading this book and I figured I should probably talk about a few of the observations made in the book here, to make them easier to remember later on. The book is intended to be used as a reference work for doctors so in a way trying to remember stuff written in it is a strange thing to do – the point of the book is after all that you don’t need to remember all that stuff – but I would prefer to remember some of the things written in this book and this’ll be easier to do if I write about them here on the blog, instead of just ‘keeping them hidden in the book’, so to speak.
I’m assuming nobody reading along here are planning on reading this book so I wasn’t sure how much sense it would make to add impressions about the way it’s written etc. here, but I decided to note down a few things on these topics anyway. I have noted along the way that the authors sometimes include comments about a condition which they only cover later in the same chapter, and this has bothered me a few times; on the other hand I’m well aware that when you’re trying to write a book where it’s supposed to be easy to look things up quickly you need to make some key decisions here and there which will be likely to impact the reading experience of people who read the book from cover to cover the way I am negatively. Most chapters are structured a bit the same way the ‘[Topic X] At a glance…’ textbooks I’ve read in the past were (Medical Statistics at a Glance, Nutrition at a Glance, The Endocrine System at a Glance); the chapters vary in length (for example there are roughly 70 pages about cardiovascular medicine, 40 pages about endocrinology, 50 pages about gastroenterology, and 30 pages about renal medicine) but they generally seem to be structured in much the same way; the chapters are segmented – many chapter segments are two-page segments, which were also predominant in the At a glance texts – and each segment deals with a specific topic in some detail, with details about many aspects of the disease/condition in question, such as information about e.g. incidence/prevalence, risk factors, some notes on pathophysiology, presentation/symptoms/signs, diagnostics (tests to perform, key symptoms to keep in mind, etc.), treatment options (drugs/surgery/etc.?, dosage, indications/contraindications, side effects, drug interactions, etc.), potential complications, and prognostic information. Not all chapters are structured in the ‘two-page-segments’ way even though this seems to be the baseline structure in many contexts; it’s clear that they’ve given some thought as to how best to present the information included in the coverage. I recall from the At a glance texts that I occasionally thought that the structure felt unnatural, and that they seemed to have committed to a suboptimal coverage format in the specific context – I have not thought along such lines while reading this book, which to me is a sign that they’ve handled these things well. Deviation from the default format occurs e.g. in the chapter on cardiovascular medicine, which has quite a few successive pages on which various types of ECG abnormalities are illustrated (I looked at that stuff and I like to think that I understand this stuff better than I used to now, but I must admit that this was one of the sections of this book into which I did not put a lot of effort, as it in some sense felt like ‘irrelevant knowledge’ – so don’t expect me to be able to tell a right bundle branch block from an acute anterior myocardial infarction on an EEG without having access to this book…). It’s perhaps important to point out that despite the condensed structure of the book the coverage is reasonably detailed; this is not a book with two pages about ‘heart disease’, it’s a book with two pages about rheumatic fever, two pages about right heart valve disease, two pages about infective endocarditis, two pages about broad complex tachycardia, etc. And many of the pages include a lot of information. I have read textbooks dealing with many of the topics they cover and this is also not my first general ‘clinical medicine’ text (that was McPhee et al.), but I’m learning new stuff from the book even about topics with which I’m familiar, which is really nice. It’s a pretty good book so far, even if it’s not perfect; I’m probably at a four star rating at the moment.
In the parts to follow I’ll talk about some of the observations included in the book which I figured might be worth repeating here.
The first observation: They note in the book that 80% of people above the age of 85 years (in Britain) live at home and that 70% of those people can manage stairs; they argue in the same context that any deterioration in an elderly patient should be considered to be from treatable disease until proven otherwise (i.e., the default should not be to say that ‘that’s probably just ageing’).
“Unintentional weight loss should always ring alarm bells”.
A diabetic is probably well-advised to be aware of some of the signs of peripheral arterial disease. These include loss of hair, pallor, shiny skin, cyanosis (bluish discoloration of the skin), dry skin, scaling, deformed toenails, and lowered skin temperature.
“Normally 400-1300mL of gas is expelled PR in 8-20 discrete (or indiscrete) episodes per day. […] most patients with ‘flatulence’ have no GI disease. Air swallowing (aerophagy) is the main cause of flatus; here N2 is the chief gas. If flatus is mostly methane, N2 and CO2, then fermentation by bowel bacteria is the cause, and reducing carbohydrate intake (eg less lactose and wheat) may help.”
If there are red blood cells in the urine, this is due to cancer or glomerulonephritis (let’s not go into details here – we’ll just call this one ‘kidney disease’ for now) until proven otherwise. Painless visual haematuria (blood in the urine) usually equals bladder cancer – it’s definitely a symptom one should have a talk with a doctor about. The book does not mention this, but it’s important to keep in mind however that red/brownish urine is not always due to blood in the urine; it can also be caused by drugs and vegetable dyes (link). I was very surprised about this one in the context of ways to prevent UTIs: “There is no evidence that post-coital voiding, or pre-voiding, or advice on wiping patterns in females is of benefit.” Drinking more water and drinking cranberry or lingo berry juice daily works/lowers risk.
Kidney function is often impaired in people who are hospitalized, with acute kidney injury (-AKI) occurring in up to 18% of hospital patients. It’s an important risk factor for mortality. Mortality can be very high in people with AKI, for example people admitted with burns who develop AKI have an 80% mortality rate, and with trauma/surgery it’s 60%. Up to 30 % of cases are preventable, and preventable causes include medications (continuing medications as usual e.g. after surgery can be catastrophic, and some of the drugs that can cause kidney problems are drugs people take regularly for chronic conditions such as high blood pressure or diabetes (metformin in particular)) and contrast material used in CT scans and procedures. Kidney function is incidentally often also (chronically) impaired in old people, most of which have no symptoms; “many elderly people fall into CKD [chronic kidney disease] stage 3 but have little or no progression over many years.” Symptoms of chronic kidney disease will usually not present until stage four is reached, but if onset of kidney failure is slow even people in the later stages may remain asymptomatic. The authors question whether it makes sense to label the old people in stage 3 with an illness; I’m not sure I completely agree (lowered kidney function increases cardiovascular risk, and some of those people may want to address this, if possible), but I’d certainly agree with the position that there’s a risk of overdiagnosis here.
A few more observations about kidneys. The chief cause of death from renal failure is cardiovascular disease, and in the first two stages of chronic kidney disease, the risk of dying from cardiovascular disease is higher than the risk of ever reaching stage 5, end-stage-renal-failure. Blood pressure control is very important in kidney disease as the authors argue that even a small drop in blood pressure may save significant kidney function. The causal link between BP and kidney disease goes both ways: “Hypertension often causes renal problems […] and most renal diseases can cause hypertension”. Once people require renal replacement therapy (RRT) such as haemodialysis mortality is high: Annual mortality is ~20%, mainly due to cardiovascular disease. The authors talk a little bit about diabetes and kidney disease in the book and among other things include the following observations:
“Diabetes is best viewed as a vascular disease with the kidney as one of its chief targets for end-organ damage. The single most important intervention in the long-term care of DM is the control of BP, to protect the heart, the brain, and the kidney. Renal damage may be preventable with good BP and glycaemic control.
In type 1 DM nephropathy is rare in the first 5yrs, after 10yrs annual incidence rises to a peak at 15yrs, then falls again. Those who have not developed nephropathy at 35yrs are unlikely to do so. In type 2 DM around 10% have nephropathy at diagnosis and up to half will go on to develop it over the next 20yrs. 20% of people with type 2 DM will develop ESRF.”
I was surprised by the observation above that “Those who have not developed nephropathy at 35yrs are unlikely to do so”, and I’m not sure I’d agree with the authors about that. The incidence of diabetes-related nephropathy peaks after a diabetes duration of 10-20 years and declines thereafter, but it doesn’t go to zero: “The risk for the development of diabetic nephropathy is low in a normoalbuminuric patient with diabetes’ duration of greater than 30 years. Patients who have no proteinuria after 20-25 years have a risk of developing overt renal disease of only approximately 1% per year.” (link). I’d note that a risk of 1% per year translates to a roughly 25% risk of developing overt renal disease over a 30 year time-frame, and that diabetics with the disease might not agree that a risk of that magnitude means that they are ‘unlikely’ to develop nephropathy, even if the annual risk is not high. Even if the annual risk were only half of that, 0,5%, the cumulative risk over a 30 year period would still be 14%, or roughly one in seven – are people with risks of that magnitude really ‘unlikely’ to develop nephropathy? This is certainly arguable. Many type 1 diabetics are diagnosed in childhood (peak incidence is in the early teenage years) and they can expect to live significantly longer than 20-25 years with the disease – if you disregard the ‘tail risk’ here, you seem in my opinion to be likely to neglect a substantial proportion of the total risk. This is incidentally not the only part of the book where I take issue with their coverage of topics related to diabetes, elsewhere in the book they note that:
“People who improve and maintain their fitness live longer […] Avoiding obesity helps too, but weight loss per se is only useful in reducing cardiovascular risk and the risk of developing diabetes when combined with regular exercise.”
Whereas in the case of nephropathy you can sort of argue about the language being imprecise and/or words meaning different things to different people, here things are a bit more clear because this is just plain WRONG. See e.g. Rana et al. (“Obesity and physical inactivity independently contribute to the development of type 2 diabetes; however, the magnitude of risk contributed by obesity is much greater than that imparted by lack of physical activity”). This is in my opinion the sort of error you should not find in a medical textbook.
Moving on to other parts of the coverage, let’s talk about angina. There are two types of angina – stable and unstable angina. Stable angina is induced by effort and relieved by rest. Unstable angina is angina of increasing severity or frequency, and it occurs at rest or minimal exertion. Unstable angina requires hospital admission and urgent treatment as it dramatically increases the risk of myocardial infarction. Some more stuff on related topics from the book:
“ACS [acute coronary syndrome] includes unstable angina and evolving MI [myocardial infarction], which share a common underlying pathology—plaque rupture, thrombosis, and inflammation”. Symptoms are: “Acute central chest pain, lasting >20min, often associated with nausea, sweatiness, dyspnoea [shortness of breath], palpitations [awareness of your heart beat]. May present without chest pain (‘silent’ infarct), eg in the elderly or diabetics. In such patients, presentations may include: syncope [fainting], pulmonary oedema, epigastric pain and vomiting, […] acute confusional state, stroke, and diabetic hyperglycaemic states.”
The two key questions to ask in the context of ACS are whether troponin (a cardiac enzyme) levels are elevated and whether there is ST-segment elevation. If there’s no ST-segment elevation and symptoms settle without a rise in troponin levels -> no myocardial damage (that’s the best case scenario – the alternatives are not as great..). In ACS, many deaths occur very soon after symptoms present; 50 % of deaths occur within two hours of symptom onset. “Up to 7% die before discharge.” Some MI complications have very high associated mortalities, for example a ventricular septal defect following an MI implies a 50% mortality rate during the first week alone.
Heart failure is a state in which the cardiac output is inadequate for the requirements of the body. It’s actually not that uncommon; the prevalence is 1-3% of the general population, increasing to roughly 10% “among elderly patients”. 25-50% die within 5 years of diagnosis, and if admission is needed the five year mortality rises to 75%.
Hypertension is a major risk factor for stroke and MI and according to the authors causes ~50% of all vascular deaths. Aside from malignant hypertension, which is relatively rare, hypertension is usually asymptomatic; the authors note specifically that “Headache is no more common than in the general population.” Isolated systolic hypertension, the most common form of hypertension, affects more than half of all people above the age of 60. “It is not benign: doubles risk of MI, triples risk of CVA [cerebrovascular accident, i.e. stroke].” The authors argue that: “Almost any adult over 50 would benefit from [antihypertensives], whatever their starting BP.” I think that’s downplaying the potential side effects of treatment, but it’s obvious that many people might benefit from treatment. Steps you can take to lower your BP without using medications according to the authors include: Reducing alcohol and salt intake, increasing exercise, reducing weight if obese, stop smoking, low-fat diet. They talk quite a bit about the different medications used to treat hypertension – I won’t cover that stuff in much detail, but I thought it was worth including the observation that ACE-inhibitors may be the 1st choice option in diabetics (especially if there’s renal involvement). On a related note, beta-blockers and thiazides may both increase the risk of new-onset diabetes.
Here’s my first post about the book. As I mentioned in that post, I figured I should limit detailed coverage to the parts of the book dealing with stuff related to diabetic/metabolic neuropathies. There’s a chapter specifically about ‘diabetic and uraemic neuropathies’ in the book and most of the coverage below relates to content covered in that chapter, but I have also included some related observations from other parts of the book as they seemed relevant.
It is noted in the book’s coverage that diabetes is the commonest cause of neuropathy in industrialized countries. There are many ways in which diabetes can affect the nervous system, and not all diabetes-related neuropathies affect peripheral nerves. Apart from distal symmetric polyneuropathy, which can probably in this context be thought of as ‘classic diabetic neuropathy’, focal or multifocal involvement of the peripheral nervous system is also common, and so is autonomic neuropathy. Diabetics are also at increased risk of inflammatory neuropathies such as CIDP – chronic inflammatory demyelinating polyneuropathy (about which the book also has a chapter). Late stage complications of diabetes usually relate to some extent to vessel wall abnormalities and their effects, and the blood vessels supplying the peripheral nerves can be affected just like all other blood vessels; in that context it is of interest to note that the author mentions elsewhere in the book that “tissue ischaemia is more likely to be symptomatic in nerves than in most other organs”. According to the author there isn’t really a great way to classify all the various manifestations of diabetic neuropathy, but most of them fall into one of three groups – distal symmetrical sensorimotor (length-dependent) polyneuropathy (DSSP); autonomic neuropathy; and focal- and multifocal neuropathy. The first one of these is by far the most common, and it is predominantly a sensory neuropathy (‘can you feel this?’ ‘does this hurt?’ ‘Is this water hot or cold?’ – as opposed to motor neuropathy: ‘can you move your arm?’) with no motor deficit.
Neuropathies in diabetics are common – how common? The author notes that the prevalence in several population-based surveys has been found to be around 30% “in studies using restrictive definitions”. The author does not mention this, but given that diabetic neuropathy usually has an insidious onset and given that diabetes-related sensory neuropathy “can be totally asymptomatic”, survey-based measures are if anything likely to underestimate prevalence. Risk increases with age and duration of diabetes; the prevalence of diabetic peripheral neuropathy is more than 50% in type 1 diabetics above the age of 60.
DSSP may lead to numbness, burning feet, a pins and needles sensation and piercing/stabbing pain in affected limbs. The ‘symmetric’ part of the abbreviation means that it usually affects both sides of the body, instead of e.g. just one foot or hand. The length-dependence mentioned in the parenthesis earlier relates in a way to the pathophysiological process. The axons of the peripheral nervous system lack ribosomes, and this means that essential proteins and enzymes needed in distal regions of the nervous system need to be transported great distances through the axons – which again means that neurons with long axons are particularly vulnerable to toxic or metabolic disturbances (introducing a length-dependence aspect in terms of which nerves are affected) which may lead to so-called dying-back axonal degeneration. The sensory loss can be restricted to the toes, extend over the feet, or it can migrate even further up the limbs – when sensory loss extends above the knee, signs and symptoms of nerve damage will usually also be observed in the fingers/hands/forearms. In generalized neuropathies a distinction can be made in terms of which type of nerve fibres are predominantly involved. When small fibres are most affected, sensory effects relating to pain- and temperature perception predominate, whereas light touch, position and vibratory senses are relatively preserved; on the other hand abnormalities of proprioception and sensitivity to light touch, often accompanied by motor deficits, will predominate if larger myelinated fibres are involved. DSSP is a small fibre neuropathy.
One of the ‘problems’ in diabetic neuropathy is actually that whereas sensation is affected, motor function often is not. This might be considered much better than the alternative, but unimpaired motor function actually relates closely to how damage often occurs. Wounds/ulcers developing on the soles of the feet (plantar ulcers) are very common in conditions in which there is sensation loss but no motor involvement/loss of strength; people with absent pain sensation will not know when their feet get hurt, e.g. because of a stone in the shoe or other forms of micro-trauma, but they’re still able to walk around relatively unimpaired and the absence of protective sensation in the limbs can thus lead to overuse of joints and accidental self-injury. A substantial proportion of diabetics with peripheral neuropathy also have lower limb ischaemia from peripheral artery disease, which further increases risk, but even in the absence of ischaemia things can go very wrong (for more details, see Edmonds, Foster, and Sanders – I should perhaps warn that the picture in that link is not a great appetite-stimulant). Of course one related problem here is that you can’t just stop moving around in order to avoid these problems once you’re aware that you have peripheral sensory neuropathy; inactivity will lead to muscle atrophy and ischaemia, and that’s not good for your feet either. The neuropathy may not ‘just’ lead to ulcers, but may also lead to the foot becoming deformed – the incidence of neuroarthropathy is approximately 2%/year in diabetics with peripheral neuropathy. Foot deformity is sometimes of acute onset and may be completely painless, despite leading to (painless) fractures and disorganization of joints. In the context of ulcers it is important that foot ulcers often take a *very* long time to heal, and so they provide excellent entry points for bacteria which among other things can cause chronic osteomyelitis (infection and inflammation of the bone and bone marrow). Pronounced motor involvement is as mentioned often absent in DSSP, but it does sometimes occur, usually at a late stage.
The author notes repeatedly in the text that peripheral neuropathy is sometimes the presenting symptom in type 2 diabetes, and I thought I should include that observation here as well. The high blood glucose may not be what leads the patient to see a doctor – sometimes the fact that he can no longer feel his toes is. At that point the nerve damage which has already occurred will of course usually be irreversible.
When the autonomic nervous system is affected (this is called Diabetic Autonomic Neuropathy, -DAN), this can lead to a variety of different symptoms. Effects of orthostatic hypotension (-OH) are frequent complaints; blackouts, faintness and dizziness or visual obscuration on standing are not always due to side effects of blood pressure medications. The author notes that OH can be aggravated by tricyclic antidepressants which are often used for treating chronic neuropathic pain (diabetics with autonomous nervous system disorder will often have, sometimes painful, peripheral neuropathy as well). Neurogenic male impotence seems to be “extremely common”; this leads to the absence of an erection at any time under any circumstances. The bladder may also be involved, which can lead to increased intervals between voiding and residual urine in the bladder after voiding, which can lead to UTIs. It is noted that retrograde ejaculation is frequent in people with bladder atony. The gastrointestinal system can be affected; this is often asymptomatic, but may lead to diarrhea and constipation causing weight loss and malnutrition. Associated diarrhea may be accompanied by fecal incontinence. DAN can lead to hypoglycemia unawareness, making glycemic control more difficult to accomplish. Sweating disorders are common in the feet. When a limb is affected by neuropathy the limb may lose its ability to sweat, and this may lead to other parts of the body (e.g. the head or upper trunk) engaging in ‘compensatory sweating’ to maintain temperature control. Abnormal pupil responses, e.g. in the form of reduced light reflexes and constricted pupils (miosis), are common in diabetics.
Focal (one nerve) and occasionally also multi-focal (more than one nerve) neuropathic syndromes also occur in the diabetic setting. The book spends quite a bit of time talking about what different nerves do and what happens when they stop working, so it’s hard to paint a broad picture of how these types of problems may present – it all depends on which nerve(s) is (are) affected. Usually in the setting of these disorders the long-term prognosis is good, or at least better than in the setting of DSSP; nerve damage is often not permanent. It seems that in terms of cranial nerve involvement, oculomotor nerve palsies are the most common, but still quite rare, affecting 1-2% of diabetics. Symptoms are rapid onset pain followed by double vision, and “spontaneous and complete recovery invariably occurs within 2-3 months” – I would like to note that as far as diabetes complications go, this is probably about as good as it gets… In so-called proximal diabetic neuropathy (-PDN), another type of mononeuropathy/focal neuropathy, the thighs are involved, with numbness or pain, often of a burning character which is worse at night, as well as muscle wasting. That syndrome progresses over weeks or months, after which the condition usually stabilizes and the pain improves, though residual muscle weakness seems to be common. Unlike in the case of DSSP, deficits in PDN are usually asymmetric, and both motor involvement and gradual recovery is common – it’s important to note in this context that DSSP virtually never improves spontaneously and often has a progressive course. Multi-focal neuropathies affect only a small proportion of diabetics, and in terms of outcome patterns they might be said to lie somewhere in between mononeuropathies and DSSP; outcomes are better than in the case of DSSP, but long-term sequelae are common.
Diabetics are at increased risk of developing pressure palsies in general. According to the author carpal tunnel syndrome occurs in 12% of diabetic patients, and “the incidence of ulnar neuropathy due to microlesions at the elbow level is high”.
In diabetics with renal failure caused by diabetic nephropathy (or presumably for that matter renal failure caused by other things as well, but most diabetics with kidney failure will have diabetic nephropathy) neuropathy is common and often severe. Renal failure impairs nerve function and is responsible for sometimes severe motor deficits in these patients. “Recovery from motor deficits is usually good after kidney transplant”. Carpal tunnel syndrome is very common in patients on long-term dialysis; 20 to 50 % of patients dialysed for 10 years or more are reported to have carpal tunnel syndrome. The presence of neuropathy in renal patients is closely related to renal function; the lower renal function, the more likely neurological symptoms become.
As you’ll learn from this book, a lot of things can cause peripheral neuropathies – and so the author notes that “In focal neuropathy occurring in diabetic patients, a neuropathy of another origin must always be excluded.” It’s not always diabetes, and sometimes missing the true cause can be a really bad thing; for example cancer-associated paraneoplastic syndromes are often associated with neuropathy (“paraneoplastic syndromes affect the PNS [Peripheral Nervous System] in up to one third of patients with solid tumors”), and so missing ‘the true cause’ in the case of a focal neuropathy may mean missing a growing tumour.
In terms of treatment options, “There is no specific treatment for distal symmetric polyneuropathy.” Complications can be treated/ideally prevented, but we have no drugs the primary effects of which are to specifically stop the nerves from dying. Treatment of autonomic neuropathy mostly relates to treating symptoms, in particular symptomatic OH. Treatment of proximal diabetic neuropathy, which is often very painful, relates only to pain management. Multifocal diabetic neuropathy can be treated with corticosteroids, minimizing inflammation.
Due to how common diabetic neuropathy is, most controlled studies on treatment options for neuropathic pain have involved patients with distal diabetic polyneuropathy. Various treatment options exist in the context of peripheral neuropathies, including antidepressants, antiepileptic drugs and opioids, as well as topical patches. In general pharmacological treatments will not cause anywhere near complete pain relief: “For patients receiving pharmacological treatment, the average pain reduction is about 20-30%, and only 20-35% of patients will achieve at least a 50% pain reduction with available drugs. […] often only partial pain relief from neuropathic pain can be expected, and […] sensory deficits are unlikely to respond to treatment.” Treatment of neuropathic pain is often a trial-and-error process.
i. “A topologist is someone who can’t tell the difference between his ass and a hole in the ground, but who can tell the difference between his ass and two holes in the ground.” (Source unknown, quote from the book Mathematically Speaking)
ii. “If you’re trying to choose between two theories and one gives you an excuse for being lazy, the other one is probably right.” (Paul Graham)
iii. “Research is the process of going up alleys to see if they are blind.” (Marston Bates)
iv. “Common sense is not really so common.” (Antoine Arnauld)
v. “Discovery consists of seeing what everybody has seen and thinking what nobody has thought.” (Albert von Szent-Györgyi)
vi. “All screening programmes do harm; some do good as well, and, of these, some do more good than harm at reasonable cost” (Sir Muir Gray, as quoted in the book Simply Rational: Decisionmaking in the Real World, by Gerd Gigerenzer).
vii. “according to rationality norms requiring only internal coherence, one can be perfectly consistent, and yet wrong about everything” (Gerd Gigerenzer, ibid.)
viii. “The rightness of a thing isn’t determined by the amount of courage it takes.” (Mary Renault)
ix. “Boredom on social occasions is an inescapable hazard for the over-educated”. (Susan Howatch)
x. “Life deserves laughter, hence people laugh at it.” (Henryk Sienkiewicz)
xi. “A man is the sum of his misfortunes. One day you’d think misfortune would get tired, but then time is your misfortune.” (William Faulkner)
xii. “Man knows so little about his fellows. In his eyes all men or women act upon what he believes would motivate him if he were mad enough to do what the other man or woman is doing.” (-ll-)
xiii. “True opinions can prevail only if the facts to which they refer are known; if they are not known, false ideas are just as effective as true ones, if not a little more effective.” (Walter Lippmann)
xiv. “Anyone can be heroic from time to time, but a gentleman is something which you have to be all the time. Which isn’t easy.” (Luigi Pirandello)
xv. “Our lies reveal as much about us as our truths.” (J. M. Coetzee)
xvi. “An honorable man will not be bullied by a hypothesis.” (Bergen Evans)
xvii. “Error is a hardy plant; it flourisheth in every soil”. (Martin Tupper)
xviii. “Well-timed silence hath more eloquence than speech.” (-ll-)
xix. “If a mistake is not a stepping stone, it is a mistake.” (Eli Siegel)
xx. “Mathematicians are a kind of Frenchman. They translate into their own language whatever is said to them and forthwith the thing is utterly changed.” (Goethe)
“This monograph introduces, defines, exemplifies, and characterizes hope that is directed toward others rather than toward the self. […] Because vicarious hope remains a relatively neglected topic within hope theory and research, the current work aims to provide, for the first time, a robust conceptualization of other-oriented hope, and to review and critically examine existing literature on other-oriented hope.”
I really should be blogging more interesting books here instead, such as e.g. Gigerenzer’s book, but this one is easy to blog.
I’ll make this post short, but I do want to make sure no-one misses this crucial point, which is the most important observation in the context of this book: The book is a terrible book. Given that I’ve already shared (some of) my negative views about the book on goodreads I won’t go into all the many reasons why you probably shouldn’t read it here as well; instead I’ll share below a few observations from the book which might be of interest to some of the people reading along.
“Whereas other-interest encapsulates a broad and generalized orientation toward valuing, recognizing, facilitating, promoting, and celebrating positive outcomes for others that have occurred in the past or present, or that may occur in the future, other-oriented hope cleaves that portion of other-interest specific to the harbouring of future-oriented hope for others and (where possible) attendant strivings toward meeting those ends. […] Other-oriented hope is viewed as a specific form of other-interest, one in which we reveal our interest in the welfare of others by apportioning some of our future-oriented mental imaginings to others’ welfare in addition to our own, more self-focused, hope. […] we define other-oriented hope as future-oriented belief, desire, and mental imagining surrounding a valued outcome of another person that is uncertain but possible. […] The dimensions emphasized by Novotny (1989) within an illness context are that hope: is future-oriented; involves active engagement; is an inner resource; reflects possibility; is relational; and concerns issues of importance.”
“Schrank et al. (2010) factor analyzed 60-items taken from three existing hope scales. Four dimensions of hope arose, labelled trust and confidence (e.g., goal striving, positive past experience), positive future orientation (e.g., looking forward, making plans), social relations and personal value (e.g., feeling loved and needed), and lack of perspective (e.g., feeling trapped, becoming uninvolved). […] In the most influential psychological perspective on hope, […] Snyder and colleagues posit that hope is “a positive motivational state that is based on an interactively derived sense of successful (a) agency (goal-directed energy), and (b) pathways (planning to meet goals)” […]. According to this view, hope-agency beliefs provide motivation to pursue valued goals, and hope-pathways beliefs provide plausible routes to meet those goals. […] hope is most often construed as an emotion or as an emotion-based coping process.”
“Lapierre et al. (1993) report that wishes for others is a more frequent category among relatively younger elderly participants and among non-impaired relative to impaired participants. The authors suggest that less healthy individuals (i.e., relatively older and impaired) are more self-focused in their aspirations, emphasizing such fundamental goals as preserving their health. […] Herth identified changes [in hope patterns] as a function of age and impairment level of respondents, with those older than 80 and experiencing mild to moderate impairment being more likely to harbour hope focused on others compared to those who were higher functioning. Moreover, those living in long-term care facilities with moderate to severe impairment directed their hope almost entirely toward others. […] [research] strongly points to the element of vulnerability in another person as a situational influence on other-oriented hope. Learning about others’ vulnerability likely triggers compassion or empathy which, in turn, elicits other-oriented hope. […] In addition to other-oriented hope occurring in response to another’s vulnerability, vicarious hope appears also to be triggered by one’s own vulnerability. […] In related work, Hollis et al. (2007) discuss borrowed hope; for those with no hope, others who have hope for them can be impactful, because hope can be viewed as ‘contagious’.”
“Similar to recognized drawbacks or risks of self-oriented hope, other-oriented hope may be associated with a failure to accept things the way they are, frustration upon hope being dashed, risk taking, or the failure to limit losses […] There is also an opportunity-cost to other-oriented hope: Time spent hoping for another is time not spent generating, contemplating, or acting toward either one’s own hope or to yet other people’s hope. […] There may be costs to the recipient of other-oriented hope in the form of feeling coerced or controlled by others whose vicarious hope is not shared by the recipient. Therefore, some forms of other-oriented hope may reveal only the desired outcomes of the hoping agent as opposed to the person to whom the hope applies. In the classic example, a parent’s hope for a child may not be hope that is held by the child him- or herself, and therefore may be experienced as a significant source of undue pressure and stress by the child. Such coercive hope is, in turn, likely to be harmful to the relationship between the person harbouring the other-oriented hope and the target of that hope. […] In an extreme form, other-oriented hope bears resemblance to other-oriented perfectionism. Hewitt and Flett (2004) argue that perfectionism can be directed toward the self or others. In the former case, perfectionism involves expectations placed upon oneself for unreasonably high performance, whereas in the latter case, perfectionism involves expecting others to uphold an unreasonably high standard and expressing criticism when others fail to meet this expectation. It is possible that other-oriented hope occasionally takes the form of other-oriented expectations for perfection. For example, a parent may hope that a child performs well in school, but this could take the form of an overly demanding standard of achievement that is difficult or impossible for the child to attain, creating distress in the child’s life and conflict within the parent-child relationship.”
“McGeer (2004) argues for responsive hope being an optimal point between wishful hope, on the one hand (i.e., desire but too little agency, as in wishful thinking) and willful hope, on the other hand (desire but too much agency, as in an incautious or unrealistic pursuit of one’s dreams). To expand on McGeer’s views, responsive other-oriented hope would fall between wishful other-oriented hope, on the one hand (i.e., desires aimed at others but divorced from an action-orientation toward the fulfillment of such desires), and willful other-oriented hope, on the other hand (i.e., desire for, and overzealous facilitation of, others’ future outcomes, ignoring whether such actions are in the other’s best interest or are endorsed by the other). […] Like self-oriented hope, other-oriented hope can be contested and, in extreme instances, such hope may impede coping, such as by encouraging ongoing denial among family members of the objective circumstances faced by their loved one. Hoping against hope for others may, at times, be more costly than beneficial.”
“Acceptance toward others may be exhibited through not judging others, being tolerant of others who are perceived as different than oneself, being willing to engage with others, and not avoiding others who might be predicted to displease us or upset us. It would appear, therefore, that acceptance, like hope, can be directed toward the self or toward others. Interestingly, acceptance of the self and acceptance of others are included, respectively, in measures of psychological well-being and social well-being (Keyes 2005), suggesting that both self-acceptance and other-acceptance are considered key aspects of psychological health.”
“Davis and Asliturk (2011) review research showing that a realistic orientation toward future outcomes, in which one considers both positive and negative possibilities, is associated with coping more effectively with adversity.”
“Weis and Speridakos (2011) conducted a meta-analysis on 27 studies that employed strategies to enhance hope among both mental health clients and community members. They reported modest effects of such psychotherapy on measures of hope and life satisfaction, but not on measures of psychological distress. The authors caution that effects were relatively small in comparison to other psychoeducational or psychotherapeutic interventions.”
As I’ve observed many times before, a wordpress blog like mine is not a particularly nice place to cover mathematical topics involving equations and lots of Greek letters, so the coverage below will be more or less purely conceptual; don’t take this to mean that the book doesn’t contain formulas. Some parts of the book look like this:
That of course makes the book hard to blog, also for other reasons than just the fact that it’s typographically hard to deal with the equations. In general it’s hard to talk about the content of a book like this one without going into a lot of details outlining how you get from A to B to C – usually you’re only really interested in C, but you need A and B to make sense of C. At this point I’ve sort of concluded that when covering books like this one I’ll only cover some of the main themes which are easy to discuss in a blog post, and I’ve concluded that I should skip coverage of (potentially important) points which might also be of interest if they’re difficult to discuss in a small amount of space, which is unfortunately often the case. I should perhaps observe that although I noted in my goodreads review that in a way there was a bit too much philosophy and a bit too little statistics in the coverage for my taste, you should definitely not take that objection to mean that this book is full of fluff; a lot of that philosophical stuff is ‘formal logic’ type stuff and related comments, and the book in general is quite dense. As I also noted in the goodreads review I didn’t read this book as carefully as I might have done – for example I skipped a couple of the technical proofs because they didn’t seem to be worth the effort – and I’d probably need to read it again to fully understand some of the minor points made throughout the more technical parts of the coverage; so that’s of course a related reason why I don’t cover the book in a great amount of detail here – it’s hard work just to read the damn thing, to talk about the technical stuff in detail here as well would definitely be overkill even if it would surely make me understand the material better.
I have added some observations from the coverage below. I’ve tried to clarify beforehand which question/topic the quote in question deals with, to ease reading/understanding of the topics covered.
On how statistical methods are related to experimental science:
“statistical methods have aims similar to the process of experimental science. But statistics is not itself an experimental science, it consists of models of how to do experimental science. Statistical theory is a logical — mostly mathematical — discipline; its findings are not subject to experimental test. […] The primary sense in which statistical theory is a science is that it guides and explains statistical methods. A sharpened statement of the purpose of this book is to provide explanations of the senses in which some statistical methods provide scientific evidence.”
On mathematics and axiomatic systems (the book goes into much more detail than this):
“It is not sufficiently appreciated that a link is needed between mathematics and methods. Mathematics is not about the world until it is interpreted and then it is only about models of the world […]. No contradiction is introduced by either interpreting the same theory in different ways or by modeling the same concept by different theories. […] In general, a primitive undefined term is said to be interpreted when a meaning is assigned to it and when all such terms are interpreted we have an interpretation of the axiomatic system. It makes no sense to ask which is the correct interpretation of an axiom system. This is a primary strength of the axiomatic method; we can use it to organize and structure our thoughts and knowledge by simultaneously and economically treating all interpretations of an axiom system. It is also a weakness in that failure to define or interpret terms leads to much confusion about the implications of theory for application.”
It’s all about models:
“The scientific method of theory checking is to compare predictions deduced from a theoretical model with observations on nature. Thus science must predict what happens in nature but it need not explain why. […] whether experiment is consistent with theory is relative to accuracy and purpose. All theories are simplifications of reality and hence no theory will be expected to be a perfect predictor. Theories of statistical inference become relevant to scientific process at precisely this point. […] Scientific method is a practice developed to deal with experiments on nature. Probability theory is a deductive study of the properties of models of such experiments. All of the theorems of probability are results about models of experiments.”
But given a frequentist interpretation you can test your statistical theories with the real world, right? Right? Well…
“How might we check the long run stability of relative frequency? If we are to compare mathematical theory with experiment then only finite sequences can be observed. But for the Bernoulli case, the event that frequency approaches probability is stochastically independent of any sequence of finite length. […] Long-run stability of relative frequency cannot be checked experimentally. There are neither theoretical nor empirical guarantees that, a priori, one can recognize experiments performed under uniform conditions and that under these circumstances one will obtain stable frequencies.” [related link]
What should we expect to get out of mathematical and statistical theories of inference?
“What can we expect of a theory of statistical inference? We can expect an internally consistent explanation of why certain conclusions follow from certain data. The theory will not be about inductive rationality but about a model of inductive rationality. Statisticians are used to thinking that they apply their logic to models of the physical world; less common is the realization that their logic itself is only a model. Explanation will be in terms of introduced concepts which do not exist in nature. Properties of the concepts will be derived from assumptions which merely seem reasonable. This is the only sense in which the axioms of any mathematical theory are true […] We can expect these concepts, assumptions, and properties to be intuitive but, unlike natural science, they cannot be checked by experiment. Different people have different ideas about what “seems reasonable,” so we can expect different explanations and different properties. We should not be surprised if the theorems of two different theories of statistical evidence differ. If two models had no different properties then they would be different versions of the same model […] We should not expect to achieve, by mathematics alone, a single coherent theory of inference, for mathematical truth is conditional and the assumptions are not “self-evident.” Faith in a set of assumptions would be needed to achieve a single coherent theory.”
On disagreements about the nature of statistical evidence:
“The context of this section is that there is disagreement among experts about the nature of statistical evidence and consequently much use of one formulation to criticize another. Neyman (1950) maintains that, from his behavioral hypothesis testing point of view, Fisherian significance tests do not express evidence. Royall (1997) employs the “law” of likelihood to criticize hypothesis as well as significance testing. Pratt (1965), Berger and Selke (1987), Berger and Berry (1988), and Casella and Berger (1987) employ Bayesian theory to criticize sampling theory. […] Critics assume that their findings are about evidence, but they are at most about models of evidence. Many theoretical statistical criticisms, when stated in terms of evidence, have the following outline: According to model A, evidence satisfies proposition P. But according to model B, which is correct since it is derived from “self-evident truths,” P is not true. Now evidence can’t be two different ways so, since B is right, A must be wrong. Note that the argument is symmetric: since A appears “self-evident” (to adherents of A) B must be wrong. But both conclusions are invalid since evidence can be modeled in different ways, perhaps useful in different contexts and for different purposes. From the observation that P is a theorem of A but not of B, all we can properly conclude is that A and B are different models of evidence. […] The common practice of using one theory of inference to critique another is a misleading activity.”
Is mathematics a science?
“Is mathematics a science? It is certainly systematized knowledge much concerned with structure, but then so is history. Does it employ the scientific method? Well, partly; hypothesis and deduction are the essence of mathematics and the search for counter examples is a mathematical counterpart of experimentation; but the question is not put to nature. Is mathematics about nature? In part. The hypotheses of most mathematics are suggested by some natural primitive concept, for it is difficult to think of interesting hypotheses concerning nonsense syllables and to check their consistency. However, it often happens that as a mathematical subject matures it tends to evolve away from the original concept which motivated it. Mathematics in its purest form is probably not natural science since it lacks the experimental aspect. Art is sometimes defined to be creative work displaying form, beauty and unusual perception. By this definition pure mathematics is clearly an art. On the other hand, applied mathematics, taking its hypotheses from real world concepts, is an attempt to describe nature. Applied mathematics, without regard to experimental verification, is in fact largely the “conditional truth” portion of science. If a body of applied mathematics has survived experimental test to become trustworthy belief then it is the essence of natural science.”
Then what about statistics – is statistics a science?
“Statisticians can and do make contributions to subject matter fields such as physics, and demography but statistical theory and methods proper, distinguished from their findings, are not like physics in that they are not about nature. […] Applied statistics is natural science but the findings are about the subject matter field not statistical theory or method. […] Statistical theory helps with how to do natural science but it is not itself a natural science.”
I should note that I am, and have for a long time been, in broad agreement with the author’s remarks on the nature of science and mathematics above. Popper, among many others, discussed this topic a long time ago e.g. in The Logic of Scientific Discovery and I’ve basically been of the opinion that (‘pure’) mathematics is not science (‘but rather ‘something else’ … and that doesn’t mean it’s not useful’) for probably a decade. I’ve had a harder time coming to terms with how precisely to deal with statistics in terms of these things, and in that context the book has been conceptually helpful.
Below I’ve added a few links to other stuff also covered in the book:
Radon-Nikodyn theorem. (not covered in the book, but the necessity of using ‘a Radon-Nikodyn derivative’ to obtain an answer to a question being asked was remarked upon at one point, and I had no clue what he was talking about – it seems that the stuff in the link was what he was talking about).
A very specific and relevant link: Berger and Wolpert (1984). The stuff about Birnbaum’s argument covered from p.24 (p.40) and forward is covered in some detail in the book. The author is critical of the model and explains in the book in some detail why that is. See also: On the foundations of statistical inference (Birnbaum, 1962).
This one was mostly review for me, but there was also some new stuff and it was a ‘sort of okay’ lecture even if I was highly skeptical about a few points covered. I was debating whether to even post the lecture on account of those points of contention, but I figured that by adding a few remarks below I could justify doing it. So below a few skeptical comments relating to content covered in the lecture:
a) 28-29 minutes in he mentions that the cutoff for hypertension in diabetics is a systolic pressure above 130. Here opinions definitely differ, and opinions about treatment cutoffs differ; in the annual report from the Danish Diabetes Database they follow up on whether hospitals and other medical decision-making units are following guidelines (I’ve talked about the data on the blog, e.g. here), and the BP goal of involved decision-making units evaluated is currently whether diabetics with systolic BP above 140 receive antihypertensive treatment. This recent Cochrane review concluded that: “At the present time, evidence from randomized trials does not support blood pressure targets lower than the standard targets in people with elevated blood pressure and diabetes” and noted that: “The effect of SBP targets on mortality was compatible with both a reduction and increase in risk […] Trying to achieve the ‘lower’ SBP target was associated with a significant increase in the number of other serious adverse events”.
b) Whether retinopathy screenings should be conducted yearly or biennially is also contested, and opinions differ – this is not mentioned in the lecture, but I sort of figure maybe it should have been. There’s some evidence that annual screening is better (see e.g. this recent review), but the evidence base is not great and clinical outcomes do not seem to differ much in general; as noted in the review, “Observational and economic modelling studies in low-risk patients show little difference in clinical outcomes between screening intervals of 1 year or 2 years”. To stratify based on risk seems desirable from a cost-effectiveness standpoint, but how to stratify optimally seems to not be completely clear at the present point in time.
c) The Somogyi phenomenon is highly contested, and I was very surprised about his coverage of this topic – ‘he’s a doctor lecturing on this topic, he should know better’. As the wiki notes: “Although this theory is well known among clinicians and individuals with diabetes, there is little scientific evidence to support it.” I’m highly skeptical, and I seriously question the advice of lowering insulin in the context of morning hyperglycemia. As observed in Cryer’s text: “there is now considerable evidence against the Somogyi hypothesis (Guillod et al. 2007); morning hyperglycemia is the result of insulin lack, not post-hypoglycemic insulin resistance (Havlin and Cryer 1987; Tordjman et al. 1987; Hirsch et al. 1990). There is a dawn phenomenon—a growth hormone–mediated increase in the nighttime to morning plasma glucose concentration (Campbell et al. 1985)—but its magnitude is small (Periello et al. 1991).”
I decided not to embed this lecture in the post mainly because the resolution is unsatisfactorily low so that a substantial proportion of the visual content is frankly unintelligible; I figured this would bother others more than it did me and that a semi-satisfactory compromise solution in terms of coverage would be to link to the lecture, but not embed it here. You can hear what the lecturer is saying, which was enough for me, but you can’t make out stuff like effect differences, p-values, or many of the details in the graphic illustrations included. Despite the title of the lecture on youtube, the lecture actually mainly consists of a brief overview of pharmacological treatment options for diabetes.
If you want to skip the introduction, the first talk/lecture starts around 5 minutes and 30 seconds into the video. Note that despite the long running time of this video the lectures themselves only take about 50 minutes in total; the rest of it is post-lecture Q&A and discussion.