Conflict of Interest in Medical Research

In September 2018, Dr. José Balsega, chief medical officer of Memorial Sloan-Kettering Cancer Institute, ignominiously resigned from his position after a scandal engulfed the institution. In a searing article of ProPublica, which conducted the investigative reporting together with the New York Times, he was accused of clandestinely receiving millions from pharmaceutical companies and never reporting it in many scientific articles that he produced as first or secondary author.

Co-authors Charles Ornstein and Katie Thomas said: “ he has held board memberships or advisory roles with Roche and Bristol-Myers Squibb, among other corporations; he had a stake in start-ups testing cancer therapies; and played a key role in the development of breakthrough drugs that have revolutionized treatments for breast cancer…Balsega did not follow financial disclosure rules set by the American Association for Cancer Research when he was president of the group. He also left out payments he received from companies connected to cancer research in his articles published in the group’s journal, Cancer Discovery.” There are no rules for those who make them.

Considering that modern medicine, with its over-reliance in the biological model, has the capacity to sanction or condemn any new drug or treatment based on the opinion and data of the peer-reviewed medical journals, this lack of clarity in the disclosure of financial interests is very serious. For two decades there have been many honest professional efforts to police the rank and file. In April 2009 the Institute of Medicine (IOM) released a report where it recommends to “standardize the content format and procedures for disclosing financial relationships” and at the same time that these policies should be publicly available, preferably in the institution’s official website. In the past ten years, institutions and professionals have been grappling with this still searing issue.

In an article in Neurology Today, Dr. Corey Ford, professor of neurology and dean of research at the New Mexico School of Medicine said that: “a researcher may be required to only enroll patients in a study, but not to analyze the data or have any influence in the output portion.” With these institutional firewalls, the risk of a biased opinion of the whole process is greatly diminished. Another troublesome aspect is the channeling of companies’ payments directly to the researchers’ pockets in the form of the consulting fees, stipends for board memberships, speaking fees, etc. Dr. Kenneth Tyler, from the University of Colorado, said that all the outside activities of physicians must be channeled through the physician practice plan of the institution for a better oversight.

At the University of New Mexico there is a special institutional review board for senior officials above a certain level where all the major donations and gifts of private companies are scrutinized; moreover, all the outside collaborators in any program must fill the disclosure forms as well. The relationship of academia and the industry can be mutually beneficial as the latter can provide skills, technologies, scale and capital for bonafide initiatives that will serve the public at large. But it must be outlined in advance of any implementation in a way that is convenient for public access, rather than the often-cryptic institutional electronic disclosure systems. It must be cloud-based. There is still a long way to go before there is a truly honest, accurate and straightforward exposé of all the significant medical data in our society.

What do you think? Please tell us.

Don’t leave me alone.

Gravitational influence of the Moon

Since Ancient Times, humans have realized that the Moon has a big influence on planet Earth. Modern science showed us that the Moon modifies our planet’s tides, weather and temperatures. Elizabeth Merriam wrote: “since the Moon’s gravitational force depends on distance, at any given time, the portion of the Earth closest to the Moon (i.e. directly underneath it) is most strongly influenced by gravity. This means that when the Moon is over an ocean, the water is pulled toward it, creating what is called the tidal bulge. As the Moon orbits the Earth, the tidal bulge acts like a wave sweeping around the Earth. This effect causes the tides.” The relative distances of the Sun, Earth and Moon can affect the size and the magnitude of our planet’s two daily tidal bulges; the shape of the shoreline, including the presence of bays and estuaries, can increase the size of tides.

In any given 24 hours-period there are two low tides and two high tides, separated by a span of about an hour; during the new moon and full moon, high tides further increase in size and the low tides further decrease in size. The first and last quarter moon moderate the size of high and low tides. The weather is influenced through the presence or absence of water currents that can alter the continental temperatures like the Gulf current and the El Niño phenomenon have steadily done. The gravitational pull of the Moon can affect the land and atmosphere in a much-lower levels. What many ancient cultures have done is to study the possible effect of the Moon on human beings.

Animal physiology is affected by the seasonal, lunar and circadian rhythms in varying ways; even though the seasonal and circadian influences were studied, the lunar one is less well known. The lunar cycle supposedly influences the menstruation, fertility and birth rates; researchers have proposed that the level of melatonin and endogenous steroids might be the hormonal mediators. During full moon days, the birds lose the variations of their melatonin and corticosterone levels. The structure of the pineal glands and the taste sensitivity of laboratory rats are affected by the lunar cycles. The gravitational pull  of the moon may trigger the release of hypothalamic hormones. What seemed to have been a “traditional truth” for old cultures is just being unveiled by science.

The correlation of the lunar cycles and fertility/births has been contested by meta-analysis of data. The records of 11,961 live births and 8,142 natural births (not induced by drugs or C-sections)  during 1974-1978 In the University of California at Los Angeles Medical Center did not show any significant relationship with the lunar cycles. The study of 564.039 births in North Carolina from 1997 to 2001 did not show a significant correlation either. A 2001 review of 70,000,000,000 birth records from the National Center for Health Statistics also failed to find a meaningful correlation.

Two studies have found evidence that a full moon can exacerbate the aggressiveness of patients with Mental Disorders, especially Schizophrenia; a methodical analysis of data confirmed it. People with Epilepsy have less seizures when the moon is less illuminated and there is a clear sky. The Sussex Police in the UK claimed that there was a rise in violent crime in their streets during the full moon period, which has been reiterated by their peers in Ohio, Kentucky and New Zealand. A statistically dubious study found an increase of fatalities in Dade County during the full moon.

What do you think? Please tell us.

Don’t leave me alone.

Love and Libido after a Total Mastectomy

Women have a strong sense of self and body that helps them visualize themselves at all times. A small physical defect will hardly ever pass unnoticed and unacknowledged by the dear women. In a mirror image, they will perceive “what the other sees” in her, especially the other women. Then it should come as no surprise that the utterly traumatic surgical event of a Total Mastectomy for Breast Cancer often has a devastating physical and psychological tally on their minds and moods.  In order to experience libido or “the desire for sexual company”, women have to feel at ease from the physical and emotional standpoints, which is hardly the case in post-surgical patients. This is one of the least discussed issues in our medical practices, compounded by the fact that it is almost never addressed in medical schools’ curriculums, even in the supposedly “enlightened” countries. Physicians and other health care personnel are left with the extremely bad option of learning sur-le-champ, often quasi-alone.

After forty years of medical practice, we have collected a few nuggets of wisdom for these patients, even though we never practiced Gynecology and we have always avoided doing any Gyn exams ever since we were in medical school. However, talking to patients and friends after undergoing that procedure, we found these challenging issues:

  1. Toxicity of associated medication.
  2. The unwise hurry to have a Prosthesis.
  3. The lack of an honest discussion between partners
  4. The absence of a proper bereavement process

A – Toxicity of associated medication

In 1998 the Food and Drug Administration (FDA) approved the use of Tamoxifen for the use in both men and women that were diagnosed with hormone-receptor-positive early-stage Breast Cancer to avoid the recurrence of the disease after surgery; similarly it is being used for patients with advanced-stage of the disease and had metastases of a hormone-receptor-positive neoplasia. The pharmacological activity is dependent on its conversion to its active metabolite, endoxifen, by the enzyme CYP2D6, which acts as an estrogen modulator to competitively inhibit the binding of endogenous estrogens. It is available in a pill form (Nolvadex) or  a liquid from, easier to swallow (Soltamox) Almost ten percent of Breast Cancer patients have a slow-functioning CYP2D6, which can hamper the effectiveness of the drug and several medications, most notably the selective serotonin re-uptake inhibitors (SSRIs) like the anti-depressants, can block its activity. This drug has serious side effects like blood clots, Stroke and Endometrial Cancer but also less prominent ones like vaginal bleeding, dryness of vagina and loss of libido that affect the quality of life.

B – The unwise hurry to have a Prosthesis

Many surgeons precipitously offer the possibility of having a prosthesis installed right after the resection, in a kind of “two-for-one” deal to supposedly expedite the healing process of women. Unfortunately, most women would surely miss “the part that was taken away” and consider that prosthesis as an alien object that does not have the necessary seal of approval by her hormonal and psychological self. If there was an honest discussion with her family and sexual partner about the traumatic aftermath of the procedure, why rush through the protocols and insert the prosthesis?

C – The lack of an honest discussion between partners

There is not a hint of sexual enticement or libidinal drive in a woman that feels nausea and pain after the surgical act, compounded by the psychological stigma of “being uglier’ than before. Patients have to take charge of the physical and emotional distress to slowly research and find the pharmacological, hormonal, psychological and sociological interventions to ease her burden. One of the most damaging approaches consist of “sticking the head in the ground’ like an ostrich to avoid facing the dark undertones of this radical procedure. Nothing will be the same after it. Patients, partners and family members must honestly deal with the reality and find ways to heal. Women should make clear to their partners that they cannot recover the same kind of sex life. There will be times of physical discomfort, depressive states, untoward side effects and frustration. The patient, partner and family should carefully consult the caring professionals to find the proper pharmacological solutions and psychological help to overcome the trauma post-mastectomy.

D – The absence of a proper bereavement process

When we lose a loved one, we must sadly go through one the worst human processes: bereavement. After the initial shock and denial stages, we progressively start accepting that most tragic fact. Only after we methodically go through each and every stage, will we be able to overcome grief. Similarly, a woman, that was aesthetically and psychologically attached to her own body before,  must go through the same stages until she can find a way (or ways) to cope with the stark reality. In those circumstances, the sustained support of her partner and family play a pivotal role.

After a Total Mastectomy, a savvy woman will learn the new parameters of her new physical and psychological coordinates and, eventually, she will recover her lost desire for sex and company. She will need the continued assistance, tolerance and patience of all those who love her dearly. Piercing through her dense fog of dire despair, we should be a beacon of hope and encouragement so she can resume her life journey in earnest.

What do you think? Please tell us.

Don’t leave me alone.


New therapies for Multiple Sclerosis

Last Saturday we attended the MS Forum VI in the Mandarin Oriental of Brickell Key, Florida, where we discussed with prestigious academicians and colleagues the latest developments in the treatment of myriad clinical presentation of Multiple Sclerosis. Amongst the topics that were exposed about, we selected to discuss three with you:

  1. Anti-CD20 Monoclonal antibodies
  2. Oral therapies for relapsing MS
  3. Autologous Mesenchymal Stem Cells.

A – Anti-CD20 Monoclonal antibodies

These antibodies have been used to deplete the B cells proliferative disorders like leukemia and Hodgkin’s Disease for a few years already. CD-20 is a transmembrane calcium channel implicated in the B cell activation and differentiation; anti-CD20 target the B cells in an intermediate stage of their evolution, safeguarding the needed long-term immunological memory and the production of cells after depletion. The drug Rituximab was the first one approved for auto-immune disorders but it soon generated side effects due to the patients’ formation of anti-chimeric antibodies. At present there are many humanized versions of it that are being tested in clinical trials. In 2004 the Food and Drug Administration (FDA) approved the use of Natalizumab for the treatment of Multiple Sclerosis, heralding the era of MABs for its treatment. Alemtuzumab and ocrelizumab followed in the pipeline and were approved; at present ublituximab and ofatumumab are in the Phase III of their clinical trials. When we discussed a young patient with new onset of MS, most of us opted for Natalizumab as the drug of choice because it shows greater efficacy to thwart the symptoms early on with the caveat that it also elicits a quick rebound phenomenon.

B – Oral therapies for relapsing MS

Even though Interferon B or Copaxone are often the first drugs of choice, many patients prefer the oral therapies like Fingolimod, Teriflunomide and Dimethyl Fumarate. In 2010 Fingolimod became the first FDA-approve oral therapy. In the Confine and Define clinical trials, Dimethyl Fumarate has been shown to reduce the relapse rates, the number of lesions in the MRI scans and the physical disabilities; its efficacy might be due to its anti-inflammatory properties to decrease oxidation; it modulates the sphingosine-1-receptor and decreased the lymphocyte migration to the CNS. Compared to Interferon beta-1a has been shown to reduce 52% the yearly relapses in one study; after one year, 13% of patients did not have any relapses. In the Temso trial, Terifluamide reduced the yearly rates of relapses, the MRI lesions and the physical disability limitations; the drug blocks the pyrimidine synthesis, which decreases the inflammatory process, including the production of white cells in the CNS and the protection of the myelin sheaths of the nerves.

C – Autologous Mesenchymal Stem Cells

Stem Cell transplant is an emerging, promising new therapy for MS, which has been discussed in the professional and public forums for the past few years. Patient that come to the office invariably ask us: “what do you think about Stem Cells, doctor?’ However there has been a dearth of reliable clinical trials with proper peer supervision until the early results of a Swedish study where presented in the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) that was held in Stockholm last September. The researchers discussed the positive data from the Nordic study of the Autologous Hematopoietic Stem Cell Transplant (AHSCT) that implies the harvesting of bone marrow from the patient and the use of chemotherapy to wipe out the rest. The patient’s own stem cells are then re-introduced in another surgical procedure. The results of a phase III randomized  clinical trial showed that the NEDA (no evidence of disease) in the cohort treated with the AHSCT was 78.% compared to only 2.97% of patients treated with the conventional methods; the risks are the expected ones for the surgical interventions.

What do you think? Please tell us.

Don’t leave me alone.




Superstitious artists – Frida Kahlo

When she had a miscarriage in 1931, Frida Kahlo asked her physician to see the dead fetus; he adamantly refused but he gave her a medical textbook where she could learn about fetal growth. She had three traumatic miscarriages during her lifetime, and she carried an emotional burden. She wrote in her dairy that: “ I am not sick, I am broken. But I am happy to be alive as long as I can paint.” Her profound angst and suffering were positively sublimated in her artistic creation.

Magdalena Carmen Frida Kahlo y Calderón was born on July 6, 1907 in Coyoacán, a small city in the outskirts of Mexico City, to Guillermo Kahlo, a German-born photographer, and Matilde Calderón y Gonzales, a homemaker of mestizo (mixed-race)origins. Her childhood was particularly sad as her parents did not love each other and the Mexican revolution bankrupted the father’s photography business; at age 6 she contracted polio, which made her right leg shorter and thinner than the left one. She became a recluse at her home where she was mentored by her loving father in art, literature and photography. She started school later than her sisters and did not follow them to a convent school ( her mother was a religious fanatic) and went to a German school. After being expelled from it, she went to a vocational school where she was sexually abused by a female teacher. She was accepted in the National Preparatory School that fostered the indigenismo—the assertion of the cultural values of native people to counteract the European colonizing influences of the elite classes. When she was about to enter medical school, a traffic accident disabled her.

After a slow recovery, she began to socialize in an artistic circle with overtly leftist leanings; she joined the Communist Party and in 1928 she married Diego Rivera, a famous painter who was twenty years her senior and had two common-law wives. In 1929, Kahlo and Rivera moved to Cuernavaca, which had been the theater of some of the worst fighting in the Civil War; there Frida’s sense of Mexican identity surfaced as she  dressed with the traditional colorful dresses of the Mexican peasantry, especially from the matriarchal society of the Isthmus of Tehuantepec. In 1930 the couple moved to San Francisco, California, where Diego Rivera was commissioned with several high-profile murals and they were entertained by the polite society of the time. Extremely annoyed by her husband’s frequent infidelities, Frida started her agitated life as a lover of many men and women, a fact she never cared to conceal to anyone, including Diego himself.  In 1931 the couple returned to Mexico but soon left for New York City for the opening of Diego Rivera’s retrospective in the Museum of Modern Art (MOMA) Being very fluent in English and a good communicator, Frida interacted naturally with the American press, unabashedly claiming that she was in fact the best painter of the two. Brave girl.

In her self-portraits, Frida used many images and symbols of Pre-Columbian people like the Aztecs and the heavily Christian-influenced colonial culture; her work is embedded with Superstition. In order to search for her true identity and gender, she used different costumes and masks with a troubling surrealist perspective, mixing life and death in her work. Her painting evoked the strong yet protective matriarchal figures of tehuanas, mythical goddesses of Ancient Times in Mexico. In her well-illustrated  book, Suzanne Barbezat said: “as a teen and young adult, Frida experimented with different styles of dresses. She was clearly aware of the power of clothing in crafting her identity and enjoyed making a statement and even shocking people with her different looks.” The symbology of roots is present everywhere as both a testimony to her heritage and her feelings of entrapment. She considered that trees were the natural agents that linked us humans through the different generations and that they were a symbol of hope.

Frida bared her soul and body in her paintings in order to “exorcise” the profound angst that she felt all her life due to her many physical disabilities and her three failed attempts at motherhood. Her canvas is brutally splattered with human tissue and drips warm blood, one drop at a time. She was branded as the feminine voice of Surrealism. When she arrived in a traumatized Paris in January 1939, due to the looming signs of war, she had difficulty to retrieve her tableaus from the Customs Agency and the gallery’s owners that agreed to show her work vetoed all of them except two for the exhibition because they considered her work “too shocking for the Parisian public.” In spite of the limited exhibition, she was admired and the Musée du Louvre bought The Frame, the first time that the haughty European institution acquired a painting from a Mexican artist.

As a physician that delivered several babies with the aid of midwifes and nurses during many stints as an Emergency Ward attending, we can attest to the bloody brutishness of the birthing process. It is a terribly stressful experience for all of those present, foremost for the mother, but yet fabulously exhilarating. Our first delivery occurred  in a Saturday night shift in the city hospital of San Miguel del Monte in the Provincia de Buenos Aires of Argentina. Fast asleep in the on-call room, we were suddenly awakened by the on-duty nurse: “Doctor, a pregnant woman just came in…It’s happening.” Half-awake, we jumped into our shoes from the bunk and we followed her, shaking, to the Obstetrics ward.

There we found two scrubbed-up nurses , at the ready, staring at us, waiting for our instructions. It must have been one of the scariest moments of our life. By far. Gently, the nurses lead us through the tried-out routine from the clinical protocols that we have learned in Medical School, which allowed us to put our knowledge into action . Suddenly our mind’s dense fog cleared out and we found our purpose as a physician. After a few minutes of gentle coaching to the mother and a timely episiotomy to open up the canal  (the midwife slammed the knife on our hand and showed us where and how to cut), so the baby could have more space to pass, she was able to push the baby in our hands. In that instant we knew that there was a much higher entity that had enabled that miracle. Bedazzled by the first cry of the newborn, we showed him to the sweaty, happy mother.

–“What is his name?” we asked her.

-“Federico,” she whispered.

That same night we prepared a long letter to our dear grandmother Yolanda who always reminded us of the feat. It was, and still is, one of the proudest moments of our whole medical career.

What do you think? Please tell us.

Don’t leave me alone.