EXERCISE & WEIGHT LOSS

It’s no secret that our society is the heaviest in the recorded history of mankind.  There have been a number of theories put forth attempting to explain exactly why obesity has become rampant across the globe, and in both wealthy and poor cultures.  Most scientists believe that there are several essential elements underlying our ever-expanding waistlines.  First, like most mammals, humans are genetically primed to preferentially seek high energy foods, namely foods packed with sugar and fat.  For much of human history, these high calorie foods have been difficult to come by for most people, and people have historically subsisted on far less calorie-dense and more nutritious foods.  Now, in our fast food culture, there is easy access to an overabundance of highly processed and inexpensive sugar- and fat-rich foods.  A second element underlying the obesity pandemic is the progressive decline in physical activity levels in our remote control world.

There is a great deal of research that reveals something that most of us already know, and that is the fact that dieting alone rarely leads to meaningful and sustained weight loss.  Other research confirms something that many of us also already know: if you spend most of your day sitting on a chair or laying on a couch, it is darned hard to lose excess weight, even if you are able to overcome that compelling little voice in your head that, primed by those pesky appetite-stimulating genes, keeps pleading for burgers, french fries, and ice cream!

A new study in the Archives of Internal Medicine provides further clinical evidence that it is not only what we eat that drives our bathroom scales to ever higher displays of poundage, but it is also what we do, in terms of physical activity, that determines which hole in our belts we can comfortably use.  This study, from the University of Pittsburgh, assigned 201 overweight and obese women volunteers to 1 of 4 behavioral weight loss intervention groups.  Each group varied from the other based upon assigned physical activity targets (1,000 vs. 2,000 calories per week) and the intensity of the assigned physical activity targets (moderate vs. vigorous activity).  All of the women enrolled in this study were also placed on a diet consisting of 1,200 to 1,500 calories per day.  To improve their chances of success, the researchers also provided the study’s volunteers with standard weight-loss group counseling, and with treadmills as well.  This study was conducted over a period of 24 months.

Six months into the study, there was no significant difference in average weight loss between each of the 4 groups of women, and the average weight loss at this point in the study was 10% of initial body weight.  By 24 months, however, the average amount of lost weight had declined to only 5% of initial body weight. 

The researchers then compared the 25% of women who had successfully maintained a weight loss of at least 10% of their initial body weight, after 24 months, with the women who did not achieve (or did not sustain) at least a 10% weight loss.  After analyzing the average weekly activity levels for all of the women in this study the researchers determined that at least 1,835 calories worth of physical activity per week was necessary to achieve and sustain a 10% weight loss over a period of 2 years (equivalent to about 275 minutes of moderate-to-vigorous activity each week).

What I find to be especially important about this study is that it actually puts some numbers on the table (no pun intended) with respect not only to caloric intake, but caloric expenditure as well.  This study confirms the findings of numerous other studies that have shown that moderate dieting, alone, is not sufficient to lose weight and to keep it off over time.  As with other studies, this study also confirms that you don’t have to sprint 30 miles a week in order to lose weight (and to improve cardiovascular fitness).  Instead, regular and sustained moderate physical activity, such as brisk walking, when combined with a sensible diet, will achieve the same results as were demonstrated in this study.  Indeed, as most of us know, stringent diets and exhausting exercise routines often result in significant weight loss over short periods of time.  However, the vast majority of us are simply not able to sustain lifestyle modifications as severe as this for very long.  Soon enough, most of us return to our sedentary lifestyles and our unhealthy diets, and the weight starts piling back on again.

Watch what you eat, to be sure, but combine a sensible diet with a sensible exercise plan.  If your health permits, takes the stairs instead of the elevator at work.  Park your car at the far end of the parking lot and walk to the store (as a bonus, your car is probably much less likely to get dinged by the car door of an adjacent vehicle!), instead of going to the cafeteria or a nearby fast food joint, pack a healthy lunch and take it to work, and use part of your lunch period to take a brisk stroll.  With these kinds of more moderate lifestyle changes, you are far more likely to keep that excess weight off because you are more likely to be compliant with these less rigorous changes over the long haul.  At the same time, you will be reducing your risk of cardiovascular disease, diabetes, and some forms of cancer.

GREEN TEA, FOLIC ACID & BREAST CANCER RISK

Regular readers of this column already know that I have a strong interest in cancer and cardiovascular disease prevention, particularly through lifestyle and dietary modifications.  Recently, there has been a great deal of high quality research looking at the effects of green tea and other dietary supplements on human diseases, including cancer.  A great deal of rather simple laboratory research, often using cancer cells growing in a Petri dish or in a mouse, suggests that polyphenols, the biologically active components of green tea, may have some anti-tumor properties.  However, the results of most human epidemiological studies have been less compelling.

A newly published study of green tea, in the journal Carcinogenesis, evaluated the impact of green tea consumption among ethnic Chinese women living in Singapore.  As previous research has suggested that deficiencies of folic acid (Vitamin B9) might be linked to an increased risk of breast cancer (as well as colorectal cancer and cardiovascular disease), this study also evaluated the effects of green tea consumption in Singaporean women with both normal and decreased folic acid intake.  Finally, the effects of green tea on breast cancer risk were also assessed in Singaporean women with genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene that results in increased activity of the enzyme that is responsible for metabolizing folic acid.  This study was conducted by the University of Minnesota, the University of Southern California, and the National University of Singapore.

The results of this study, which included 380 women who developed breast cancer and 662 women who did not, appear to confirm that green tea polyphenols may exert a breast cancer prevention effect through their effects on the folic acid metabolism pathway.  In this study, women with inadequate folic acid intake and frequent green tea consumption appeared to experience a 55% reduction in breast cancer risk when compared to women with inadequate folic acid intake and only occasional green tea intake.  Similarly, women who were found to have a genetic variant of MTHFR that resulted in rapid metabolism of folate were found to have lower risk of breast cancer when they frequently consumed green tea.  Among all women with this genetic variant, frequent green tea consumption reduced the risk of breast cancer by 34%.  Among women with both poor folic acid intake in their diet and the high activity MTHFR enzyme, daily or weekly green tea consumption reduced the apparent risk or breast cancer by 56% (frequent green tea consumption by women with both high folic acid intake and the normal activity MTHFR gene variant only reduced their apparent risk of breast cancer by 8%).

The findings of this suggest (but do not prove) that green tea polyphenols may be able to reduce the risk of breast cancer, but only in women who either have MTHFR variants that increase folic acid metabolism, or (and) in women with inadequate dietary folic acid intake.  A prospective, randomized clinical trial, which would take many years to conduct, would be the best way to confirm the findings of this epidemiological study.  However, the results of this Singaporean study are still intriguing, nonetheless.

FOREIGN LANGUAGE INTERPRETERS & ICU PATIENTS

In our multicultural, multiethnic society, physicians must often rely on interpreters to communicate with patients and families who do not speak English well.  Most of the time, these volunteer or paid interpreters have little if any medical training.  Additionally, foreign-born translators are often, themselves, not fully fluent in English, and they often miss both subtle and complicated nuances that the physician may be trying to communicate to the patient, or to the patient’s family.

A new study in the journal Chest, and conducted at the University of Washington, has rather creatively quantified the extent of clinically important errors made during family conferences requiring a translator for patients in the intensive care unit (ICU).

Ten family conferences, arranged to discuss end-of-life issues and requiring an interpreter, were audiotaped with the families’ permission.  Research interpreters with a clinical background then reviewed these audiotapes and translated the non-English discussion into English.

When the physicians who conducted the family conferences analyzed the transcribed translations, they determined that mistranslations by the interpreter present during the conference had occurred 55% of the time.  Moreover, three-quarters of these mistranslations were deemed to have been clinically significant translations.  Even worse, 93% of these mistranslations were considered to be associated with potentially negative effects on communication between the physicians and the families. 

The mistranslations were further analyzed and classified.  Following this analysis, the mistranslations were attributed to additions, omissions or substitutions of information other than what was intended by the physicians, and editorializations, on the part of the translators.

I can certainly attest to similar anecdotal experiences myself in dealing with non-English speaking patients, families and interpreters.  In such cases, particularly when I haven’t worked with an individual translator before, I usually ask the translator to have the patient or family members repeat what I have just told them, using the same translator.  If there appears to be any significant deviation from what I have said, then I work with the translator to convey the same information in a slightly different way.  As this study reveals, conducting important conferences with the non-English speaking families of gravely ill patients can be potentially hazardous for all concerned.

 

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

 

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VIAGRA & SEXUAL FUNCTION IN WOMEN

In previous columns, I have reviewed research studies of female sexual function and dysfunction (please see my Archives).  This is a very complex area of research, given the large number of both biological and behavioral factors at work in human sexuality.  Further complicating matters is the enormous difference in sexual behavior and physiology between men and women.  Male sexual dysfunction, which most commonly results from an inability to obtain a satisfactory erection (erectile dysfunction), is often treatable with Viagra and similar drugs.  These medications function by dilating the arteries that supplies the erectile tissues in the penis, thus improving blood flow to these tissues.  In the absence of sexual arousal, however, these medications do not have any significant effect on erectile function.  Because the majority of cases of sexual dysfunction in women are related to a decreased level of sexual desire, or libido, previous research trials of Viagra, and similar drugs, in women have been disappointing, as these medications do not directly affect the sexual arousal pathways in the brain.

However, a new prospective, double-blinded clinical research trial in the Journal of the American Medical Association suggests that women who are experiencing decreased libido associated with antidepressant medications may, in fact, benefit from Viagra.  This study was performed by researchers at the University of New Mexico, and an important disclaimer has been made by both the study’s authors and the Pfizer Corporation, which manufactures Viagra.  Not only was this research conducted with the financial support of Pfizer, but several of the study’s authors (including the primary author) have a history of receiving funding grants from Pfizer. 

Financial links between clinical researchers and for-profit pharmaceutical and medical device companies are coming under increasing scrutiny by medical ethicists due to the obvious potential for conflicts of interest (I often receive offers to speak on behalf of such companies, or to participate in research projects with their funding, and I have always politely declined such offers from for-profit companies).  Unfortunately, due to the very modest pool of research funding available from governmental and non-profit sources, research scientists increasingly find themselves between the proverbial “rock and a hard place” when it comes to obtaining sufficient funds to conduct their research.  In the case of this particular research trial, all authors disclosed their fiduciary relationships with Pfizer, and Pfizer published a disclaimer indicating that the company had no role in the design or conduct of this study, or in the writing of the manuscript that resulted from this research.  While these disclaimers do not completely exclude the possibility of bias in favor of Viagra by the Pfizer-sponsored researchers, these public disclaimers, as well as the randomized double-blinded design of this prospective clinical trial, represent the most open and honest way of performing clinical research with a commercial sponsor which is also the manufacturer of the drug being studied.  Nonetheless, all research studies that are conducted with financial support from commercial entities that have a vested interest in the outcomes of such studies should be viewed with a very critical eye.

This multi-institutional research trial enrolled 98 women with a diagnosis of major depression.  All of these women gave a history of normal sexual desire and function prior to beginning treatment with antidepressant medications known as “SRIs,” or serotonin reuptake inhibitors.  (These medications are known to cause decreased libido in both men and women as a side effect.)  A crucial difference in this particular study, when compared to previous research looking at the treatment of sexual dysfunction in women with Viagra, is that the women in this study reported previously normal sexual function prior to starting treatment with SRI antidepressant medications.  In previous Viagra studies, women volunteers reported decreased baseline sexual desire, and without any apparent medical or pharmaceutical causes.

Over the 8-week course of this study, half of the women volunteers received Viagra and the other half received a sugar pill (placebo) that was identical in appearance to Viagra.  The women were instructed to take their assigned pills just prior to engaging in sexual activity.  None of the women volunteers, or the research personnel conducting the study, were aware of which pills were Viagra and which were placebo pills in this double-blinded study.  Throughout the study, previously validated female sexual dysfunction surveys were administered to all of the study volunteers, and all of the women maintained a personal diary of their sexual activity.  Additionally, blood levels of female sex hormones were measured in all of the volunteers.

During the course of this study, 22 women (22% of the women who entered the study) dropped out of the study for various reasons.  However, the researchers also, appropriately, included these 22 women in their final analysis.  When the data was analyzed, the researchers noted a 60% improvement in sexual function among the women who had received Viagra pills (when compared to the patients who had received the placebo pills).  In all patients, sex hormone levels in the blood were within the normal range, and did not significantly differ between the women taking Viagra versus those taking the placebo pill.

Although this study is the first ever to find a favorable effect on female sexual function with Viagra, it is important to understand that the results of this study are probably not applicable to the general population.  Viagra, and related drugs, have no effect on the areas of the brain that control baseline sexual desire.  These drugs work, very specifically, on the genitals (and not on the brain).  Therefore, it is not at all surprising that these drugs have been shown, by multiple studies, to have no effect on women who are experiencing decreased libido that is not due to the side effects of other medications.  In this study, however, women who reported previously normal levels of sexual desire and function, and who secondarily developed sexual dysfunction as a side effect of SRI antidepressants, appeared to benefit from Viagra.  Because the mechanisms of sexual dysfunction are different when comparing primary sexual dysfunction versus that caused by SRI medications, Viagra may offer the latter group of women an effective therapy by improving genital function. 

The most important clinical consideration arising from this study is that both men and women with major depression frequently stop taking their antidepressant medications because of the sexual dysfunction that can be induced by these drugs.  If, indeed, depressed women can benefit from Viagra, as men have, then they are more likely to continue taking their antidepressant medications.  Nothing in this study contradicts previous studies that have shown no benefit from Viagra in women with primary sexual dysfunction.  However, for women taking SRIs for major depression, Viagra, and similar drugs, may help to reverse SRI-associated sexual dysfunction, and may therefore improve compliance with antidepressant therapy.  This would, clearly, represent a “win-win” situation for such patients.

 

PATIENT-REPORTED ADVERSE HOSPITAL EVENTS

In 1999, the prestigious Institute of Medicine (IOM) estimated that nearly 100,000 Americans die every year due to medical errors (the vast majority of which involve errors in dispensing medications).  Although this report subsequently set off a firestorm of debate regarding the accuracy of the IOM’s data and conclusions, there is no doubt but that numerous injuries and deaths result, every year, from negligence and errors in medical and surgical care.  Today, primarily as a result of the IOM’s landmark report on medical errors, there is an enormous emphasis on improving the quality of care in the United States, using multiple approaches to drive down the incidence of preventable medical and surgical errors.  Currently, the careful review of patient medical records is one of the most important methods in use to detect evidence of medical errors and patient complications.

A new research study, just published in the Annals of Internal Medicine, offers a sobering assessment of how well our current approaches to medical error discovery are functioning, as well as suggesting how we might further improve medical error detection.  This study was performed by researchers at Harvard University and Brown University.

In this study, the medical records of patients who were recently discharged from the hospital were randomly selected and reviewed for evidence of medical errors.  Additionally, these patients were contacted and interviewed, and additional evidence of potential medical errors was collected directly from these patients.  The researchers then compared the medical records of these patients with the results of patient interviews in an effort to assess how well the medical records documented apparent medical errors.

Nearly 1,000 patients participated in this study, and 11% were found to have experienced at least 1 adverse event during their hospitalization, based upon a review of their medical records.  Based upon direct patient interviews, however, the researchers determined that at least 23% of the patients had experienced some sort of adverse event (or events) during their hospital stay.  Moreover, many of these adverse events were not only serious but preventable as well.

Although the authors of this study pointed out that patients may not be able to clearly recall every in-hospital adverse event when being interviewed months after discharge, the findings of this study still raise the very worrisome possibility that our current mechanisms of medical error discovery are missing many serious and potentially preventable errors.  The results of this study strongly suggest that hospitals should implement routine post-discharge interviews of patients as part of the important process of identifying medical errors.  This patient-centered approach may represent a very important new tool in our efforts to reduce medical and surgical errors to the lowest achievable level.

  

CURCUMIN & PANCREATIC CANCER

Regular readers of this column already know that cancer of the pancreas is a particularly nasty type of cancer.  More than 90% of patients diagnosed with this disease will eventually succumb to it.  (Dr. Randy Pausch, the Carnegie Mellon Computer Sciences professor who touched the world with his poignant book, The Last Lecture, died yesterday of pancreatic cancer, at the age of 47.)

Currently, surgery is the mainstay of pancreatic cancer treatment, but the overwhelming majority of patients with pancreatic cancer are not candidates for surgery by the time their disease has been discovered and diagnosed.  Even among the minority of patients with pancreatic cancer who are candidates for the radical surgery used to treat this dismal disease, the long term survival rates are very poor.  Although chemotherapy and radiation therapy are often used, particularly in advanced cases of pancreatic cancer, their impact on this disease has not been highly effective.  Therefore, a tremendous amount of research is underway to try and find more effective treatments for one of the most formidable causes of cancer-related death in the world.

Curcumin is well known to connoisseurs of Indian food, as it is a principle component of tumeric, which is used to make curry.  Numerous laboratory studies have demonstrated that curcumin has both anti-cancer and anti-inflammatory activities, and so there is a great deal of interest in testing curcumin in humans as an anti-cancer medication.  A new study, just published in the journal Clinical Cancer Research, examines the clinical effects of curcumin supplements in patients with advanced pancreatic cancer.  This study was performed by researchers from the University of Texas M.D. Anderson Cancer Center. 

In this study, 21 patients with advanced pancreatic cancer received oral curcumin supplements, and were reassessed for response every 2 months during the course of this study.  In addition to radiographic imaging studies of their tumors, blood levels of proteins associated with both pancreatic cancer tumor activity and response to cancer treatment were measured every 2 months.

In one patient who received curcumin, no tumor growth or spread was noted for more than 18 months, which is remarkable for advanced pancreatic cancer.  In a second patient, curcumin supplementation was associated with a 73% reduction in tumor size, which is also a remarkable response for pancreatic cancer, although this dramatic response was only temporary in this patient.  Although the tumors of the remaining patients did not appear to respond as dramatically as was observed in these two patients, the blood levels of proteins associated with cancer treatment response revealed a significant biochemical response to curcumin supplements in the remaining patients as well.

Why two patients’ tumors clinically responded, however transiently, so well to curcumin and the others did not is unclear at this time.  However, all patients who received curcumin showed biochemical evidence of anti-cancer activity in their blood.  Although the overall clinical effects of curcumin in this early-phase clinical research study were not very dramatic in absolute terms, the fact that any of the patients with advanced pancreatic cancer in this study experienced any clinical benefit from this non-toxic dietary supplement is actually quite remarkable.  In highly lethal cancers, like pancreatic cancer, which are refractory to most of our treatments, even incremental clinical signs of progress, such as were demonstrated in this study, are cause for celebration.  As this was only a small early-phase clinical study, additional and larger prospective, randomized, double-blinded clinical research trials with curcumin are warranted, based upon the results of this small study.

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net

http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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