PSA screening: A public health disaster?!

1. A friend of mine had an elevated PSA (Prostate Specific Antigen) level some years ago. He was naturally worried. He had some prostatic symptoms, so he underwent a transurethral resection of prostate which was found to be negative for cancer. Another friend also had an elevated PSA. After few years of worry and repeated tests he had a needle biopsy of the prostate which was negative. He decided not to do the test again. A third friend, a pathologist, also had an elevated PSA and decided to ignore it. He said too many prostates had been removed unnecessarily because of the test, sometimes with tragic consequences like incontinence and impotence.
2. Dr. Richard Ablin, who discovered the prostate specific antigen in 1970, recently published a book about it titled "The great prostate hoax"⁽¹⁾. In the book and prior to that in an article in the New York Times⁽²⁾ he described screening for prostate cancer using PSA as a "public health disaster"!
3. In a thought provoking interview with Dr. Ablin on Medscape on  August 8, 2014⁽³⁾ he told the story of the test, a story that makes one scratch his head:
1. In 1970 he, an immunologist, was working with two urologists studying freezing prostates (cryosurgery) as a treatment of prostate cancer. They noticed that cryosurgery in animals induced an immune response which increased when freezing was repeated. They also noticed that in some patients with metastasizing prostate cancer who underwent cryosurgery of prostate, metastasis were reduced in size which may have been, they thought, due to antibodies induced by the surgery. Dr. Albin could then isolate the antigen responsible for the immune response. He thought first it was a cancer specific antigen but later realized it was a tissue specific antigen (i.e. prostate specific) and not cancer specific because it was also present in normal prostate tissue and in benign prostatic hypertrophy. He also noticed that in cancer patients its concentration decreased with treatment and increased again with recurrence which makes it suitable for following patients and detecting recurrence. In 1986 the test was approved by the FDA (Food and Drug Administration) as a harbinger of recurrence.
2. In 1989, Schering-Plough Company paid $1.2 million to a marketing firm to promote PSA screening in asymptomatic men to detect prostate cancer. Primary care physicians were brainwashed that they needed to order PSA tests for patients. Many doctors started to use the test, off label, for detecting prostate cancer!
3. In 1994 it was approved by the FDA as a test to detect cancer in spite of the fact that it was pointed out to the group discussing its approval that the test has a false positive rate of 78% i.e. it is wrong in nearly 80% of the time!!
4. The latest statistics show that the annual budget for the National Cancer Institute (of the USA) is about $5.1 billion; of that, approximately $300 million goes for urologic research. Compared to this, every year $3 billion are spent, in the United States on PSA screening in asymptomatic men!⁽³⁾

                                                                                                                                

1. Ablin RJ, Piana R. The Great Prostate Hoax: How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster. New York: Macmillan Publishers; 2014.
2. http://www.nytimes.com/2010/03/10/opinion/10Ablin.html
3. http://www.medscape.com/viewarticle/828854?src=

The side room laboratory

 When I was a final year medical student, many years ago, we used to have a side room laboratory in every medical ward. It was the job of the final year student to do the simple laboratory tests needed by the patients like urinalysis, stool exam, blood counts etc. We used to spend a considerable time in that laboratory which also served as our meeting place to discuss medical issues and also chat about various subjects. When I became a resident doctor I also used to spend a significant time during afternoons and nights in the side room laboratory doing simple tests that were needed by newly admitted patients. That was part of the job of the resident doctor. Even in my membership examination in London, when I was given my long case I was shown the side room laboratory and asked to do, if I want to, whatever test I thought useful in reaching a diagnosis. When I was training in kidney disease, they used to say: a good nephrologist is one who looks at the urine himself.

Things gradually changed. By the time I was on the teaching staff, medical students were relieved from this duty although some hospitals retained a simple side room laboratory used by the occasional keen student or resident. These also gradually disappeared. All tests came to be sent to the general laboratory of the hospital.

Was that a change for the better?

If you are working in a place where a reliable laboratory is available and easy to reach all the time, then clinicians probably do not need to involve themselves in doing laboratory tests. That will save them more time to spend with their patients. Laboratory people are also more skilled and experienced in laboratory work and their results should be more reliable.

But, do all clinicians work in such convenient circumstances?

Many do not, especially in less developed countries. For these, some simple laboratory tests done on the patient's bedside or in a small side room laboratory can be immensely useful. Examining the urine can be done in minutes in the presence of dipsticks that test for various chemicals like protein, sugar, ketones, hemoglobin, bilirubin, urinobilingen etc. Vital information about the state of the urinary system and the whole body can then be obtained. Looking at a urine drop under the microscope searching for various cells gives important information about the urinary system. Seeing bacteria swimming in that drop may be more reliable in diagnosing urinary infection  than a urine culture done by a laboratory of a questionable quality. It also gives a rough idea about the number of bacteria (knowing that one bacterium in a high power field corresponds roughly to 30,000 bacteria in a milliliter of the urine sample). Looking at a drop of cerebrospinal fluid under the microscope in the middle of the night when the hospital laboratory is not open yet, can be sufficient to start treatment of meningitis and probably save life. Many more examples can be cited.

Clinicians' performance of simple laboratory tests still has a place in medical practice and medical education especially in less developed countries.

نقاش بلا صراع

ما الهدف من الدخول في نقاش؟

الهدف الامثل هو تبادل الرأي للوصول الى الحقيقة او الى افضل الطرق لحل مشكلة او خلاف. في احيان اخرى يكون الهدف هو الترويج لراي واثبات انه الراي الصحيح وان الراي الاخر خطأ وهو ما نراه في المناقشات التي تجرى في وسائل الاعلام في السياسة على وجه الخصوص ولا يكون الامر تبادلا للرأي وانما صراع يسعى كل طرف ان يكون الفائز فيه. ما يعنيني هنا هو النوع الاول الذي يبدؤه المتناقشون بقصد تبادل الراي والوصول الى الحقيقة ولكنه قد يتحول الى صراع يطلب فيه كل طرف الفوز على الطرف الثاني.  كل طرف له رأي مسبق يصبح هدفه الدفاع عنه وليس الوصول الى الحقيقة. سلاحه في ذلك الكلام ولذا يحاول ان يتكلم اكثر الوقت وكثيرا ما نرى المتناقشين كلهم يتكلمون ولا احد يستمع واذا اضطر الى الاستماع فانما يستمع ليرد وليس ليفهم  (على حد قول الكاتب الامريكي ستيفن كوفي) وكثيرا ما تدخل العاطفة والحماس وتطغى على الفكر والتدبر. تختلف قوة عنصر الصراع باختلاف مستوى المتناقشين وتقل كلما زادت ثقافتهم وتحضرهم ونضجهم الفكري.

ان نجاح النقاش يعتمد الى حد كبير على نزع عنصر الصراع منه. وذلك باحترام راي الطرف المقابل وتجنب وصمه بالخطأ وابداء الراي بهدوء وتواضع وعدم الالحاح في الجدل منتظرا ان يرفع الطرف الاخر الراية البيضاء ويسلم بانك على حق فانك حتى لو كنت فعلا على حق فان تغيير الراي كثيرا ما يحتاج الى وقت فاترك المقابل ليتمعن مع نفسه في ما قلت له. واذا لم تتوصلوا الى اتفاق ثم حدث ما يدلل على انك كنت على حق فلا تظهر بمظهر المنتصر المنتشي بانتصاره وتذكره بما قلت له فان مثل هذا قد يدفعه على الاصرار على رأيه حتى مع اقتناعه بخطئه حفاظا على كرامته.

Using guidelines? Think carefully

1. Guidelines are meant to help the doctor deal with an individual patient but they are based on information obtained from groups of patients. Description of groups has to rely on statistics using averages to describe various characteristics and results.
2. When you apply the results of various medical interventions obtained in a group (frequently in the thousands) to your individual patient, you are presuming that your patient is similar to the patients in the group so that you expect him to respond to the treatment in a similar way to that of the group. But the response of different patients in the group is not the same. You do not know the characteristics of various individuals in the group and how each one responded. What you may know is the averages of their characteristics and the averages of their responses. Those who wrote the guidelines for you based their guidelines on these.
3. The critical question then is whether your patient is sufficiently similar to the average of the group (or the groups) studied so that you can reasonably apply the guidelines to him.
4. This can best be explained by an example. Guidelines on the treatment of non valvular atrial fibrillation using CHAD or CHADS2 score lump together patients with permanent atrial fibrillation and patients with paroxysmal atrial fibrillation. Treating the two types similarly is based on studies that showed similar prognosis regarding their liability to develop strokes. The cause of this is not clear but it may be related to the fact that the patient with paroxysmal fibrillation is more prone to develop a stroke  when fibrillation reverts to sinus rhythm and this may offset his decreased risk when he is in sinus rhythm. The vital question is this: are we justified to treat a patient who has two or three attacks a year each lasting several minutes in the same way as a patient who has daily (or every few days) attacks each lasting many hours because both patients carry the same label of paroxysmal fibrillation?!
5. Applying guidelines to your patient without considering his individual characteristics and circumstances is like a tailor who, when asked to make a suit for an Iraqi man, does not take his measures; instead he makes the suit relying on statistical figures describing the physical characteristics of Iraqi men. If the man happened to be much taller (or shorter) than the average Iraqi, it is just bad luck!
6. This does not mean that we should not use guidelines but that we should take into consideration the individual characteristics and circumstances of the patient we are treating. You should ask yourself whether your patient is sufficiently similar to the average patient with that condition to justify applying the guidelines in his case. If not, you should modify your application of the guidelines according to your judgment of the magnitude of the difference.

No News is Good News

"No news is good news" is not always right.

If you were among the relatives of the passengers of the Malaysian Airlines flight 370 waiting for the daily news conference to update them about the search and rescue operation of the plane that went missing last March and you say "no news is good news" you would likely have been kicked and beaten by the angry crowd.

If you look for a situation in which the proverb is right, you do not need to think long or go far. For years we have been used to the daily news of killing and destruction in our country. When I listen to news bulletins or ask family members or relatives about the news of Iraq and the answer is no news, I breathe a sigh of relief and say "no news isgood news."

Should we combine ACE inhibitors and Angiotensin Receptor Blockers?

1. Theory: The Renin Angiotensin System plays a pivotal role in sodium metabolism and blood pressure regulation. It also affects the function of the endothelium, induces inflammatory changes, growth and fibrosis in various target organs like the heart and the kidney. Its hyperactivity is responsible for many of the deleterious changes in these organs that occur in hypertensive and diabetic patients. Blocking the system should therefore reduce blood pressure and delay the progress of cardiac and renal disease. Blocking can be done at different sites. Direct Renin Inhibitors (DRI) block the action of renin. Angiotensin Converting Enzyme Inhibitors (ACEI) block the transformation of angiotensin I to angiotensin II in the lungs. Angiotensin Receptor Blockers (ARBs) block Angiotensin II (type 1) receptors. Aldosterone antagonists block the action of Aldosterone on target tissues.
   Practice: ACEI, ARBs and Antialdosterone drugs are established hypotensive drugs and have been in use for a long time. ACEI and ARBs have been shown in various studies to delay or prevent the progress of hypertensive and atherosclerotic cardiovascular disease decreasing the incidence of myocardial infarction and heart failure. They have also been shown to delay the progress of chronic kidney disease in diabetic and non diabetic subjects leading to a less rapid rise of serum creatinine and delaying or preventing the onset of dialysis or death from renal failure. These beneficial effects are independent of the effects of these drugs on blood pressure.

2.Theory: Blocking the system in one point results in a feed back response leading to an increase in the production of renin by the kidney and the production of other angiotensin converting enzymes in tissues other than the lung. These changes can result in a significant reduction in the effects of the blocking agents over time. It sounds logical to block the system at more than one point to get a more pronounced inhibition of the system and stop or reduce the rebound increase in angiotensin II with time (angiotensin escape).
Practice: Combining the two drugs has not so far been shown to produce the expected results.

1. In hypertension the combination did not produce a better control of blood pressure than either of the two alone and led to more side effects. The recent American and European hypertension guidelines advised against it.
2. The effect on cardiac disease progress was similar in patients receiving ACEI, ARBs and in patients receiving both. Some studies showed some additional benefit in patients with advanced heart failure receiving the combination.
3. In diabetic and non diabetic patients with chronic kidney disease some studies have shown mild beneficial effects of the combination over the use of monotherapy on the progress of proteinuria but these effects were not translated into beneficial effects on clinical outcomes (rate of rise of serum creatinine, onset of dialysis or death).

In all of these studies side effects (hyperkalemia, decreased GFR) were more in patients receiving the combination.

The issue of combining ACEI and ARBs is still unresolved and awaiting further studies.

Guidelines, calculators and clinical judgement

http://www.iasj.net/iasj?func=fulltext&aId=83477

Hypertension guidelines

In 2003 the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure published its seventh guideline on hypertension (JNC7). The committee had published guidelines on hypertension every four or five years since the seventies. The eighth guideline (JNC8), however, was long delayed.

In June 2013 the ESH/ESC (European Society of Hypertension/European Society of Cardiology) published its guideline on hypertension. In Dec 2013 ASH/ISH (American Society of Hypertension/International Society of Hypertension) published a guideline on hypertension. One day after, members of the Joint National Committee published their long delayed JNC8.

Now we also learn that ASH/AHA/ACC (American society of hypertension/American Heart Association/American College of Cardiology) intend to publish a guideline on hypertension during 2014.

This plethora of guidelines appearing within a short period of time may produce some confusion for the practicing doctor as the various documents agree on points and differ on others.

Agreements and differences:

Some of the main points of agreement and difference are:

1. JNC7 classified blood pressure into: prehypertension, stage 1 and stage 2 hypertension. The new ESH/ECC guideline was more elaborate and classified blood pressure into optimal, normal, grade 1, grade 2 and grade 3 hypertension. JNC8 and the ASH/ISH guidelines did not address the issue.
2. JNC8 guideline increased the treatment threshold (level at which to treat) and treatment target (level you aim at) of blood pressure in adults over 60y of age to 150/90. The other guidelines kept it at 140/90.
3. JNC7 advised a threshold and target of 130/80 for people with diabetes and people with CKD (Chronic Kidney Disease). All new guidelines advised the same figure of 140/90 for these patients as it is for other patients (except in certain specified situations).
4. JNC7 ­­­advised initiation of treatment with a thiazide like diuretic except when there is a compelling reason to choose a drug from one of the other three groups of drugs, namely: ACEI (Angiotensin Converting Enzyme Inhibitors) or ARB (Angiotensin Receptor Blockers), CCB (Calcium Channel Blockers) and Beta Blockers. The new ESH/ESC accepted any of the four groups to start treatment with. JNC8 dropped Beta Blockers from the list and advised to choose any drug from the other three groups. The ASH/ISH advised to start with ACEI or ARB.
5. All new guidelines advised ACEI or ARB in patients with diabetes or CKD.
6. All new guidelines advised against combining ACEI and ARB (because of increased possibility of side effects of these drugs).

So, what will a practicing physician treating a specific patient do in the face of different advices?

He has to remember that guidelines are based on studies done on large number of patients with various characteristics in different countries. They depend on averages of these various characteristics and averages of results. They are not talking specifically about your patient and they cannot include in their calculations all his variables. They are a great help in throwing light on the general picture but do not make decisions for the doctor. What you exactly do with each patient in his specific circumstances will ultimately depend on your clinical judgement assisted by these guidelines.