At the next consultation, Dr. Ramon explained the format of the trial to us and introduced Inma, a nurse who had been appointed to take care of my wife throughout the trial

At one point during our discussion the secretary to Dr. Ramon expressed concern at the fact we didn't speak Spanish (it is safe to say we speak enough Spanish to survive). He then explained to us that there might be a problem if the auditor wanted to question us (although I do not know who the auditor is or what they audit).

Dr. Ramon said that we would be reimbursed for any expenses during the trial and I asked if that included the cost of medication as well. He said it did not and also that my wife would need to take CellCept, which is made by the trial sponsor, Roche, instead of Myfortic, which is made by another company. When I asked why she would have to take 3g of the Roche drug, CellCept, when she had been taking only 2g of Myfortic, Dr. Ramon said it was to do with the way the different drugs were assimilated in the body. When we asked why Roche could not also supply its own tablets, Dr. Ramon said that existing prescription medicines that were not part of the clinical trial would not be paid for by the sponsor. However, we had already purchased several hundred generic Myfortic tablets from India. Dr. Ramon was aware that my wife was taking these (he had calculated that it was actually cheaper than if we had been receiving Social Security) so when I complained at the prospect of having to buy more of the new drug he asked how many we had and said we could change to Cellcept once she had used all the Myfortic.

My wife was also to be screened for the trial, which involved extraction of blood and urine for testing. Over one year later we received a bill from the hospital for my wife's treatment during the period of the trial, which included these tests. One of the tests was called an Anti-Nuclear Antibody (ANA) and cost a whopping $1200. Three of these were conducted over the period of the trial even though my wife had already been diagnosed as having Lupus Nephritis Type 4 through a kidney biopsy. The same test in India costs $6. That's right, six dollars, not six hundred or sixty dollars.

The senior consultant during my wife’s second period of hospitalization was Dr. Ramon and it is he whom we returned to see for the next appointment

I do not know why there was a change in the primary consultant but his treatment of Sherna’s condition was very different to that of Dr. Angel with more prescription drugs and three times the dosage of Myfortic. He also said that Sherna was going be his patient for the foreseeable future whereas Dr. Angel had implied that she would only need to consult with him if the leucocytes dropped below a certain level.

He prescribed amongst other medicines 3 x 1g Myfortic twice daily and another tablet called Bonviva once per month. The cost of the Myfortic was around $4 per pill ($25 daily) and the Bonviva a staggering $45 per pill. However, my wife's mother was able to buy a generic Myfortic in India for one-third of the price and a generic Bonviva for less than $5!

It was during this consultation that Dr. Ramon asked my wife to participate in the trial of a new drug, Ocrelizumab. Later that day I discussed it with my wife and her parents (who had arrived in Spain from India after she had been hospitalized for a second time) and we decided it was better for her to return with them to India to be treated, at least until her condition had stabilized. My wife was not entitled to Social Security in Spain and the hospitals and medication in India are much cheaper. We were also concerned that she would require dialysis or a kidney transplant, so at the next meeting with Dr. Ramon we explained the situation and our decision. Dr. Ramon told us that my wife’s kidney problem would not require either dialysis or a transplant. He then explained the importance of clinical trials in treating disease and the cultural obstacle in convincing conservative Spanish patients to participate. He said that because my wife came from a liberal Anglo-Saxon background, she should not be as influenced by the wishes of her family (actually she is Indian, has never lived in the UK, and her parents were not happy at her joining the trial of a new drug). He said that the trial was paid for by the sponsor, Roche, but in Spain it was illegal to pay people to participate in a clinical trial. We said we were not interested in being paid, only that we were not willing to pay for the treatment in Spain. On this basis we agreed in principal that my wife would participate but needed to talk to her parents before confirming our decision.

The best way to describe my wife's behaviour would be the way demonic possession is portrayed in a horror movie.

I have never seen anyone in this state and it was incredibly disturbing for our four children to witness. On the morning of February 6^th, 2009, I had to call friends to assist me in taking her to the hospital. They too were shocked at her mental state. She was admitted to the emergency ward of Carlos Haya hospital. In her psychotic state she was reliving the births of our five children over and over again and later said that she thought days were passing in minutes. For me it brought back terrible memories of our first child's death in the emergency ward of a hospital. Eventually she was sedated. When I visited her later she refused to open her eyes to avoid the pain of giving birth. She was attended by various young doctors who assessed her mental state by asking what day it was, if she knew where she was and what was wrong with her, and her relationship to me and my eldest daughter. After two days she was moved into a ward and underwent a number of diagnostic tests including a lumbar puncture and MRI scan. After the fourth or fifth day a doctor told me that they had decided her condition was a reaction to the steroid and administered an antidote. She recovered in a matter of hours and was discharged on the sixth day.

I do not know why it took them so long to decide the psychosis was steroid-induced or why Dr. Angel didn’t show more concern at the time for that matter. The clinical classification of psychological response to steroids is as follows:
 

1        Mild euphoria, lessened fatigue, improved sensation, increased sense of intellectual capacity.

2        Heightened euphoria. Patients are effusive, expansive, volatile, hypomanic, exhibit flight of ideas, impaired judgment, refractory insomnia.

3        Difference responses to reflecting the ego characteristics of the patient, such as anxiety, phobia, rumination, obsessional preoccupation, hypomania, or depression.

4        Grossly psychotic reaction with hallucinations, delusions, extreme variations in mood.

(Data from Rome H, Braceland F. The psychological response to ACTH, cortisone, hydrocortisone, and related steroid substances. American Journal of Psychiatry. 1952;108(9):641-651)

From what I had observed Sherna was between grade 3 and 4 when we visited Dr. Angel. She had only been taking prednisone for a few days so there would have been no danger in stopping it immediately and evaluating her for possible steroid side effects.

On the day of the appointment with Dr. Angel she was reluctant to have her blood taken because she thought I wanted her dead.

The doctor confirmed the diagnosis and the nature of the illness, which although serious was treatable using the same autoimmune suppressants administered to patients following organ transplants. But we had to sign a disclaimer because the drugs weren't as yet recognised by the medical board in Spain for the treatment of Lupus. And they turned out to be bloody expensive at $10 a pill!

During the appointment I expressed grave concern at my wife's mental state, which was obvious from her demeanour in front of the consultant, sitting with her head bowed and shaking her head rather than answer his questions. He decided to take her blood pressure, which I seem to remember was incredibly high, so much so that he gave her a tablet to take there and then as well as adding a drug to control blood pressure (Parapres 16) to the prescribed treatment.

So we were sent on our way with the prospect of regular visits to the clinic to monitor her blood and, in particular, the level of leucocytes (whit blood cells) that would be affected by the immunosuppressants.

However, over the next two days my wife became manic.

Looking much better for her stay and with her appetite back to normal my wife was released from the hospital.

That's the good news. The bad news is that she is suffering from Lupus Nephritis Type 4, an autoimmune condition in which the body's defences attack the kidneys. She's put on 55mg of steroids daily and a visit to the day hospital is scheduled for a week later.

Over the next few days her mental health deteriorated. It started with her either not remembering what she had said or repeating herself. She was finding it difficult to sleep and soon lost track of time, getting out of bed in the middle of the night to undertake household chores. At one point she was convinced there were people in the house and asked why I had invited them, although there was no one of course. On another occasion she imagined a jigsaw puzzle was the picture of me with our first daughter who had died in 1998. She believed our two younger children belonged to her sister. Much of how she felt at the time became apparent only after her recovery but at the time she thought she was going to die.

Having lost around 15kg in weight and barely able to walk my wife was finally admitted to the Nephrology department of Carlos Haya Hospital in Malaga, Spain.

I say "finally" because we had been here one week before on the recommendation of the local hospital in Velez-Malaga. At that time they had suspected her of being anaemic but were concerned that it was something worse. The Nephrology staff had dismissed it as anaemia without any further tests and told me to give my wife an injection of Aranesp and a daily iron supplement. Following the treatment my wife developed a rash that covered one half of her body and after one week her physical condition had deteriorated to the point where she could barely walk, so I had taken her to the local clinic where a doctor referred her immediately to the emergency ward at the Velez-Malaga hospital. We waited until 2:30 the following morning for a consultation after which, once again, my wife was referred for admission to the Nephrology unit of Carlos Haya hospital in Malaga. When we explained what had happened during our visit to the hospital the previous week the doctors decided it was better to keep my wife at the emergency ward until it was convenient for her to be taken to Carlos Haya for admission. They succeeded where we had failed and we awaited the results of blood tests and, ultimately, a kidney biopsy.