JAMA censors circumcision critics:


Circumcision promoters given open slather

An extraordinary feature of the United States today is the widening gulf between popular and professional medical attitudes towards routine circumcision, and the sharp divisions of opinion among medical and health professionals themselves. On one side we can see a flood of attacks on circumcision on blogs, websites, Youtube and in the mass media; more and more young parents deciding not to circumcise their boys; increasing numbers of circumcised men voicing their anger and resentment at having been circumcised, and taking up the onerous task of foreskin restoration; and if that was not a sufficient indication of the way the wind is blowing, it appears that a significant number of Jewish Americans are also abandoning circumcision in favour of peaceful naming ceremonies. Given the swelling flood of critical comment, it looks as though the "tipping point" predicted by Geoffrey Miller is rapidly approaching.

Within professional circles there is obviously no consensus on the issue and probably bitter argument behind closed doors. Both the Centers for Disease Control and the American Academy of Pediatrics have been “working on” new circumcision policy statements for years; every few months they announce that it is just about ready to be released, yet nothing emerges. It would appear either that they cannot find the evidence they need to justify a recommendation of infant circumcision in the United States, or that the members of the various task forces cannot reach agreement on the content or wording of the policy. In the meantime, medical authorities in both Australia and the Netherlands have issued policies that firmly reject routine circumcision, making it far more difficult for those who want to restore the old days. The problem for the CDC is that all the evidence for circumcision having a protective effect against HIV and human papilloma virus comes from experiments on adult men in African countries with extremely high levels of heterosexual HIV infection. These conditions simply do not apply in the USA (or any other developed country); since there are no American studies showing that circumcision has any protective effect against these problems, it becomes very difficult to “recommend” it as a routine health precaution. Quite apart from the bioethical and human rights issues, the so called “medical benefits” are simply not there.

These developments clearly have some sectors of the American medical industry deeply worried, including, the editors of many US medical journals, who seem to think that the African AIDS crisis presents a heaven-sent opportunity to stop the rot. Over the past few years we have seen any number of scaremongering articles, with titles such as “Declining rate of circumcision despite increasing evidence of health benefits”, and numerous opinion pieces by diehard believers in circumcision, who paint lurid scenarios of the public health catastrophe that is sure to unfold if American parents stop circumcising their baby boys. (Indeed, according to one imaginative American senator, the omission could even lead to epidemics of spina bifida and "neurogenic bladder" - whatever that is.)

A recent effusion along these lines was produced by Aaron Tobian and Ronald Gray, both seasoned pro-circumcision warhorses with a long record of such advocacy. [1] Taking time off from their well-funded day job (circumcising ill-informed but trusting Africans), they penned a short opinion piece, published in the Journal of the American Medical Association, in which they asserted that what was good for Swaziland and Zimbabwe was also good for the United States. Now you might well feel that America’s desperate debt situation, unemployment crisis and general social dislocation means that it does have much in common with the less developed parts of darkest Africa, in which case it would perhaps follow that a tribal rite such as circumcision is entirely appropriate. Indeed, by asserting that parental power to circumcise children should not be in any way limited because this would be an affront to religious freedom, Tobian and Gray suggest as much. But their principal argument is to do with that other American dream – health. Because three clinical trials in South Africa, Kenya and Uganda appeared to show that circumcision of sexually active adult men could lower their risk of acquiring HIV in an environment of high heterosexual prevalence, baby boys in America should be circumcised as a precaution.

We have heard this tired old argument so often from circumcision advocates that we must wonder why the editor of JAMA bothered to publish such a poorly-argued rehash of the same old stuff. But not only did he publish it, he also censored or refused to print letters criticizing the obvious flaws in this prescription. To our knowledge, at least 8 letters were submitted to the journal, only 2 of which were published, and one of these was so severely cut that the author complained that he had been censored rather than edited. Not content with suppressing contrary opinion, JAMA also published 2 letters in support of the Tobian and Gray’s position and, on top of that, gave them generous space for a “response” that allowed them to repeat their case all over again. What else could the editor do: if there are no good arguments or relevant evidence for a course of action he wishes to follow, the only thing to do is to keep asserting its necessity in the hope that if it is done often enough, people will come to believe it by sheer dint of repetition.

In an attempt to overcome this blatant censorship, and to restore some semblance of decency and fairness to the medico-scientific debate about circumcision (a debate in which the negative is gagged most of the time), we publish a selection of the letters that JAMA refused to publish. We are not publishing Tobian and Gray’s original article because it was made freely available at the time, and heralded with a media release that was picked up all over the world, thus giving it massive exposure. You can easily get hold of it if you want it through the JAMA website. The letters published here focus on different objections to the circumcision solution, and one theme is indignation and wonderment that one of the world’s leading medical journals should publish such a poorly-argued case, particularly one that ignores the cardinal principle of evidence-based medicine: that treatments should follow directly from the evidence. Tobian and Gray need to go back to school and relearn their geography; contrary to what they seem to think, the United States is not Africa.

We invite readers to compare the Tobian and Gray’s proposals with the arguments of their critics and make their own assessment of the who has the better case.

[1] Tobian AAR, Gray RH. The medical benefits of male circumcision. JAMA 2011; 306: 1479-80.

The letters JAMA refused to publish

Ignores ethical and human rights issues

Tobian and Gray ignore the substantial ethical and human rights implications of male circumcision as an HIV preventive. While they acknowledge that the best interests of the child are a primary consideration, they claim that banning neonatal male circumcision denies religious freedoms to Jewish and Muslim parents, which would be potentially unconstitutional. The opposite is true. Permitting parents to irreversibly mark their religion on the bodies of their children by amputating functional tissue is contrary to the law. After all, upon reaching adulthood, the child might choose to follow a different religion.

In 1891, the United States Supreme Court recognized the right of all citizens to bodily integrity and self-determination. No right is held more sacred or is more carefully guarded by common law than the right of every individual to the possession and control of his own person free from all restraints or interference of others. [1] Joel Feinberg argues for the child’s right to an open future, [2] and the British Medical Association recommends prioritizing options that maximize the patient’s future opportunities and choices. [3]

When children are incapable of consenting, parents possess temporary authority to make health care decisions on their behalf if the procedure is in the child's best interests. Parents do not possess unrestricted authority to make decisions on behalf of their children. Moreover, parents are not permitted to make martyrs of their children. [4] According to the American Academy of Pediatrics, parental permission for medical intervention is authorized only in situations of clear and immediate medical necessity, such as disease, trauma, or deformity. [5] Because parents lack the power to give permission for prophylactic amputation from their children of healthy tissue, and because neonatal circumcision has no universally recognized medical benefit, parental permission for the procedure is not effective.

Where parents request a procedure that is not medically indicated, courts have required strong evidence that the procedure is in the patient-child's interests and does not entail parents injecting their own preferences into the decision-making process. The benefits of the proposed procedure must clearly outweigh short- and long-term disadvantages, and spiritual considerations may not be incorporated into this analysis. For non-essential treatments—such as neonatal circumcision--that can be deferred without loss of efficacy, the physician and family must wait until the child is old enough to consent. Judging by the low adult circumcision rates, most will hang onto what they have.

References

1. Feigenbaum MS. Minors, medical treatment, and interspousal disagreement: Should Solomon split the child? De Paul L Rev 1992; 41:841-884.

2. Feinberg J. 2007. The Child’s Right to an Open Future. In Curren R, ed. Philosophy of Education: An Anthology. Malden, Massachusetts: Wiley-Blackwell: 112-123.

3. Medical Ethics Committee, British Medical Association. 2006. The Law & Ethics of Male Circumcision. London: British Medical Association.

4. Prince v. Massachusetts, 321 U.S. 158 (1944).

5. American Academy of Pediatrics Committee on Bioethics. Informed consent, parental permission, and assent in pediatric practice. Pediatrics 1995; 95: 314-317.

J. Steven Svoboda, JD Hons (Harvard), MS (Berkeley)
Executive Director, Attorneys for the Rights of the Child

Better methods of HIV control available

Looking past the statistical sleights-of-hand that characterize the African RCTs upon which Gray and Tobian rely so heavily (and forgiving the Tuskegee redux situation which sent HIV infected African men back home untreated), both bioethical and practical issues intrude on their scheme. The fundamental bioethics of surgery generally – and epidemiology in particular – require that the least intrusive methods of disease control be systematically applied before more drastic measures are adopted.

Gray and Tobian fail to mention that ART therapy reduces to near zero the likelihood of sero-conversion between discordant partners. Nor do they mention that barrier methods are themselves much more effective (and affordable) than male circumcision (MC). Neither has been widely available to Africans even while the funding for a massive campaign for MC appears available. Nor do Gray and Tobian discuss the morbidity and mortality (or iatrogenic transmission of HIV itself) such a campaign, whether in Africa or the USA, would entail.

Gray and Tobian concede that the African RCTs may not be directly applicable to the situation in the USA, and admit there is a racial and social-class correlation accounting for the incidence of STIs. But in the USA, at least, this experiment has already been conducted, longitudinally no less, and failed miserably. The United States has the highest rate of HIV among Western countries, and also the highest rate of MC, around 70%. Circumcising American infants in 2011 is not going to shift those numbers significantly, even in the long term. Moreover, Gray and Tobian appear to be recommending a situation in which over-confidence in the prophylactic properties of MC will produce males who “risk compensate” by unprotected sex, thus over-balancing any claimed prophylaxis. We have already seen evidence of this in Sub-Saharan Africa. Mathematical models do not reflect that risk, which should be of great concern to vulnerable female partners, whether in Africa or the US.

American children – circumcised in 2011 as a putative preventative of a disease of which they are not at risk until they become sexually active, and very careless – will have every right to demand in 2031 why less intrusive measures of disease control were not exhausted before they were ensnared in the Gray–Tobian scheme. They might point to Western Europe or New Zealand, where HIV rates are much lower than the USA, and circumcision is rare or non-existent Finally, we have been here before. A similar massive MC campaign, featuring similar tortured reasoning, was proposed to control the American black population in 1914. [1] Mercifully, the proposal failed.

George C. Denniston, MD, MPH,
President
John V. Geisheker, JD, LLM,
Executive Director, Doctors Opposing Circumcision, Seattle

1. Hazen HH. Syphilis in the American Negro. JAMA 1914; 63(6): 463-8.

Violates child’s right to physical integrity and Christian religious teaching

Tobian and Gray suggested that Medicaid should pay for non-therapeutic circumcisions, including religious circumcisions of Jews and Muslims. By law, Medicaid tax dollars are to be used for medically necessary (not religious) services, and not wasted fraudulently on unnecessary surgeries. All fifty states should instead defund all unnecessary circumcisions.

No national medical association in the world recommends routine circumcision, despite the opinions and questionable research of pro-circumcision advocates. Amputating (and selling) healthy body parts from children may be financially profitable for some, but it is unethical and violates Christian teaching. Father Edwin F. Healy, S.J. wrote, “Some physicians, it seems, circumcise all male infants, and their motive appears to be mercenary. Such physicians act in a manner unworthy of their high calling. ” [1] Tobian’s and Gray’s commentary was just the latest high-pressure sales pitch.

Catholics (and other Christians) should not be forced to pay for non-therapeutic circumcisions. Catholic Catechism teaching (# 2297) states, “Except when performed for strictly therapeutic medical reasons, directly intended amputations, mutilations, and sterilizations are against the moral law.” [2] In 1999, the American Academy of Pediatrics described circumcision as “amputation of the foreskin." In 2000, the American Medical Association described elective circumcisions as “non-therapeutic.” [3]

Fr Peter A. Clark, SJ, PhD summarized the problem with circumcision. “God created us in God's image and likeness” (Gen 1:27-28). It follows then that God created males with normal, healthy foreskins for the purpose of protecting the glans, providing natural lubrication to prevent dryness, and contributing significantly to the sexual response of the intact male. To surgically remove the foreskin for hygienic reasons, and/or to obtain other questionable benefits that absorb medical resources costing over $200 million a year is not only ethically unjustifiable but morally irresponsible, especially when such procedures can lead to serious injury and even death. Besides the possible harm the procedure can inflict on a child — which violates the basic tenet of … treating every person with dignity and respect — it also violates Medicaid’s mandate to be responsible stewards of medical resources. When millions of people in the United States and around the world lack basic health care, the provision of a non-therapeutic procedure — especially one that is unnecessary, costly, and in some cases fatal — is irresponsible and a violation of the moral law.” [4]

References

1. Healy EF. Problems connected with surgery. In Medical ethics. Chicago, IL: Loyola University Press; 1956: 129.

2. Catechism of the Catholic Church. Mahwah, New Jersey: Paulist Press; 1994: 553.

3. Fadel P. Respect for bodily integrity: a Catholic perspective on circumcision in Catholic hospitals. Am J Bioethics 2003; 3(2): 1f-3f.

4. Clark PA. To circumcise or not to circumcise? A Catholic ethicist argues that the practice is not in the best interest of male infants. Health Prog 2006; 87(5): 30-9.

Petrina Fadel
Director, Catholics Against Circumcision

Ignores African evidence: No consistency in relation between circumcision and HIV status

Tobian and Gray advocate male circumcision (MC) for preventing the transmission of HIV and other sexually transmitted infections (STI’s). Their arguments are serious, but hide counter evidence much displayed in the past 20 years. There is no doubt that male circumcision has an effect on HIV and STI transmission during sexual intercourse. However, this does not guarantee a large population impact, which would be the only rationale for recommending its large scale use. In Africa, groups practicing and not practicing male circumcision have basically the same level of HIV seroprevalence some 25 years after the onset of the epidemic. This has been shown from well conducted large scale Demographic and Health Surveys (DHS), as well as from numerous studies based on selective groups. [1,2] MC has no long term impact because of repeated exposure, and does not confer any “protection” per se. The effect found in clinical trials is similar to that of a low-efficacy vaccine (as cholera vaccine), or that of a low efficacy contraceptive (as rhythm method), none of which being recommended on a large scale because there are much more efficient alternatives. Note that in the Uganda and South-Africa trials, the incidence of HIV in the circumcised groups was about 1% per year, which would lead to massive levels of infection after 30 to 40 years of sexual life.

The argument about potential demographic impact or cost-effectiveness measured by mathematical models seems fallacious. Mathematical models are good as long as they predict the real world. This is the case for highly efficacious vaccines (measles), or highly efficacious contraceptives (pill, IUD), where mathematical models predict accurately the observed population impact. But in the case of MC, where is the mathematical model explaining the situation observed in Lesotho, Malawi or Tanzania, where the HIV seroprevalence is higher in the circumcised groups than in others? Where is the model explaining why the dynamics of the HIV epidemics is the same in circumcised ethnic groups than in others in South Africa?

Likewise, the argument about the long term effect of newborn circumcision does not match what has been found in a long term study in Australia. [3] Condom use and safe behaviour are the only efficacious strategies to protect individuals and to control STI’s at population level. This policy can be implemented on a large scale, as exemplified by the case of Japan.

References

1. Garenne M. Long-term population effect of male circumcision in generalized HIV epidemics in sub-Saharan Africa. African Journal of AIDS Research 2008; 7(1):1-8.

2. Van Howe, RS. Circumcision and HIV infection: review of the literature and meta-analysis. Int J STD&AIDS 1999; 10:8-16.

3. Millett GA, Flores SA, Marks G, Reed JB, Herbst JH. Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis. JAMA 2008; 300(14):1674-84.

Michel Garenne
Institut Pasteur, Epidemiologie des Maladies Emergentes, Paris

Claims not supported by evidence from African circumcision trials

Tobian and Gray [1] recommend that people making decisions about male circumcision in the US consider evidence from three randomized controlled trials (RCTs) in South Africa, Kenya, and Uganda, which reported that circumcision reduced men’s HIV incidence by 51% to 60%. This communication requests additional information from the Ugandan trial, [2] which was funded by the National Institutes for Health (NIH), and from a parallel trial of circumcision to protect men in Uganda, funded by the Bill and Melinda Gates Foundation (BMGF). [3]

Tobian and Gray state “the protective efficacy of circumcision increases with time.” In fact, the evidence shows that the opposite. The NIH-funded Ugandan trial collected data relevant to that statement during follow-up visits after the RCT was stopped in late 2006. [4] To my knowledge, these data have not been reported separately, nor have data from the BMGF-funded trial been reported separately. However, all infections and person-years (PYs) of follow-up in both trials (the NIH trial to December 2006; the NIH trial after December 2006; and the BMGF trial) have been reported in combined form. [4] Subtracting date reported from the NIH trial to December 2006 [2] shows a net of 38 infections in 2,927 PYs during late follow-up in the NIH trial and in the BMGF trial. From these net data, circumcision reduced men’s risk for HIV by 42% – showing that protection waned over time among men in the NIH trial and/or less protection for men in the BMGF trial than in the other three trials.

Other unreported evidence could inform continuing debates about circumcision’s impact on HIV transmission. Data reported from the Ugandan NIH trial to December 2006 suggest that non-sexual transmission was important: 16 of 67 men with incident HIV reported no partners (6 men) or 100% condom use (10 men). [2] Similar data are not available from later follow-up in the NIH trial or from the BMGF trial. The HIV-status of men’s partners is relevant to assess men’s risks. The BMGF protocol reports following more than 3,700 wives, including wives of men in the NIH trial. [3] But neither trial has reported the partner’s HIV-status for any man. Study teams have reported no information about blood exposures. Full report of collected evidence from these studies might improve our understanding of circumcision’s impact on men’s and women’s health, as well as adults’ risks for HIV infection in Africa. [5]

References

1. Tobian AAR, Gray RH. The medical benefits of male circumcision. JAMA 2011; 306: 1479-1480.

2. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomized trial. Lancet 2007; 369: 657-666.

3. ClinicalTrials.gov. Trial of male circumcision: HIV, sexually transmitted disease (STD) and behavioral effects in men, women and the community. ClinicalTrials.gov identifier: NCT00124878, last updated on 9 August 2007. Washington DC: NIH, 2007. Available at: http://clinicaltrials.gov/show/NCT00124878 (accessed 25 June 2011).

4. Gray RH, Serwadda D, Tobian AAR, et al. Effects of genital ulcer disease and herpes simplex virus type 2 on the efficacy of male circumcision for HIV prevention: analyses from the Rakai trials. PLoS Med 2009; e1000187.

5. Gisselquist D. Randomized controlled trials for HIV/AIDS prevention among men and women in Africa: untraced infections, unasked questions, and unreported data. Social Science Research Network 2011. Available at: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1940999 (accessed 11 October 2011); and at http://dontgetstuck.wordpress.com/downloads/ (accessed 11 October 2011).

David Gisselquist, independent consultant

Claims about Human Papilloma Virus untrue

Why did JAMA publish the recent commentary by Tobian and Gray when there is good reason to ignore their studies? When studying the impact of circumcision on human papillomavirus (HPV) infections, Tobian and Gray found a 35% reduction in the incidence of HPV in those randomized to early circumcision. [1] Unfortunately, the entire treatment effect can be attributed to sampling bias, as the researchers failed to sample the penile shaft where circumcised men are more likely to harbor the virus. [2] Similarly, the reduction in genital herpes infections, when properly adjusted for lead-time bias, is not statistically significant. [2] Their study found no association between circumcision and gonorrhea and a slight, non-significant increased risk of syphilis in those randomized to early circumcision.

Their study on HPV transmission to women, whose husbands had been randomized to early or delayed circumcision, also has methodological flaws. The researchers made no attempt to determine the source of the infections, half of the women were infected at the beginning of the trial, infections were determined using an insensitive method, and 17% were lost to follow-up. Interestingly, condom use was associated with increased HPV incidence. For HPV 16 and 18, which account for 70% of cervical cancers, no difference was found based on the partner’s circumcision status. Consequently, their positive findings apply to viruses responsible for only 30% of cervical cancers.

Studies from the United States have failed to confirm these flawed African studies. A prospective study of 603 female university students found no association between new HPV infections and circumcision status of the partner. [3] Similarly, in 477 male university students, there was no association between the incidence of HPV and circumcision status. [4] A national survey using a complex, stratified, multistage probability sampling design found that circumcision was not associated with herpes simplex virus type 2. [5] Fortunately, some of this discussion is moot, as effective HPV vaccines are currently available. It appears that JAMA is allowing well-financed zealots to promote their own unethical, poorly designed research. In the future commentaries should be also be carefully vetted for factual accuracy.

References

1. Tobian AAR, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med 2009; 360: 1298-309.

2. Storms MR. Male circumcision for the prevention of HSV-2 and HPV infections. N Engl J Med 2009; 361: 307.

3. Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003; 157: 218-26. Erratta 2003; 157: 858.

4. VanBuskirk K, Winer RL, Hughes JP, Feng Q, Arima Y, Lee S-K, et al. Circumcision and the acquisition of human papillomavirus infection in young men. Sex Transm Dis 2011 (December); e-pub ahead of print. See summary on this site.

5. Xu F, Markowitz LE, Sternberg MR, Aral SO. Prevalence of circumcision and herpes simplex type 2 infection in men in the United States: the National Health and Nutrition Examination Survey (NHANES), 1999-2004. Sex Transm Dis 2007; 34: 479-84.

Robert S. Van Howe, MD, MS, FAAP
Clinical Professor, Department of Pediatrics and Human Development
Michigan State College of Human Medicine
Marquette, Michigan

Ignores harm to women

Imagine my surprise to see JAMA allow Tobian and Gray a commentary promoting the benefits of male circumcision while ignoring how their own research showed a 50% increase in HIV transmission to the partners of circumcised males. [1] Why would any ethical physician promote a procedure that will ultimately infect a greater number of females who will then infect their babies? Furthermore, infant circumcision has been shown to negatively impact the primal period by decreasing bonding and breastfeeding, [2] causing increased pain to the newborn because they lack inhibitory pathways, and imprinting violence onto their brains. [3] It is barbaric and unethical to cut off healthy, normal body parts on people without their consent. Parental rights do not trump basic human rights in such situations. Saying that infant circumcision prevents some unforeseen adult disease is like promoting mastectomies for infant females. It is ludicrous. The only thing circumcision prevents is normal sexual function. [4]

What is particularly galling is that their studies are not only flawed with multiple biases, but they would never have been allowed in the U.S. because of the ethical red flags. [5] Tobian and Gray have moved Tuskegee to Africa, and Johns Hopkins continues to make millions off these unethical experiments using American taxpayers’ money. Tobian and Gray’s professional careers depend on promulgating the myth that male circumcision prevents HIV. Yet, they state they have no conflict of interest. Their impassioned pleas can only undermine their credibility, which can only be rescued by making their data public. Any reluctance to do so should be suspect.

Michelle R. Storms, MD
Northern Michigan University

References

1. Wawer MJ, Makumbi K, Kigozi G, Serwadda D, Watya S, Nalugoda F, Buwembo D, Ssempijja V, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Opendi P, Iga B, Ridzon R, Laeyendecker O, Gray RH. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 2009; 374: 229-37.

2. Howard CR, Howard FM, Weitzman ML. Acetaminophen analgesia in neonatal circumcision: the effect on pain. Pediatrics 1994; 93: 641-6.

3. Fitzgerald M. The birth of pain. MRC News 1998; (Summer): 20-3.

4. Frisch M, Lindholm M, Grønbæk. Male circumcision and sexual function in men and women: a survey-based, cross-sectional study in Denmark. Int J Epidemiol  40.5 (October 2011): 1367-1381. See news item at Science Nordic.

5. Van Howe RS, Storms MR. How the circumcision solution will increase HIV infections. J Publ Health Afr 2011; 2(e4):11-5.

Ignores flaws and limitations of African studies

The commentary by Tobian and Gray placed too much importance on the results of their own and other randomized clinical trials (RCTs), which have serious problems with both internal and external validity. Internal validity problems include selection bias (only men willing to be circumcised were recruited), expectation bias, lead-time bias, duration bias (one of the studies found the protective effect began to disappear at 18 months and valid long-term follow-up was not possible), and attrition bias (205 men became infected, yet 703 were lost to follow-up). The studies were halted early, which, in studies with a small percentage having the outcome of interest, can result in marked overestimates of treatment effect and exaggeration of lead-time bias. There were also unexplained anomalies. Men who reported no unprotected sex accounted for 23 of 69 infections in the South African study and 16 of 67 infections in the Ugandan study. In the Ugandan study, men who consistently used condoms had a higher frequency of HIV infection than men who never used condoms (1.03 versus 0.91 per 100 person-years). The researchers made no attempt to determine the source of new HIV infections, so the number of sexually transmitted infections is unclear.

The studies also lack external validity. [1] In African national surveys, HIV rates are higher in circumcised males for 10 of the 18 countries. [2] Subsequent African studies have failed to find an association between circumcision status and HIV. [3] There is a major problem when extrapolating the RCT results, conducted under highly sterile conditions with research-supported and supervised personnel, to the scale-up for African health care at large, in which shortages of personnel, sterile conditions, and equipment, would likely produce more infections. The men in the trials received continuous counselling, extensive education, free condoms, free health care, and high levels of compensation not available to other Africans.

Extrapolating these results to infants in the United States is an even further unjustified leap. There are no studies of infant circumcision or of heterosexual males in the United States that support circumcision as a preventative for reducing HIV infection. With nearly 50 million Americans lacking health insurance, and poor children going without many basic services, it is ethically and morally inappropriate that Medicaid fund an unproven procedure. The focus should be on interventions that work. Abstinence, limiting the number of sexual partners, condom use, and testing for and treating HIV, are much better options to be pursued. [4]

References

1. Green LW, Travis JW, McAllister RG, Peterson KW, Vardanyan AN, Craig A. Male circumcision and HIV prevention: Insufficient evidence and neglected external validity. Am J Prev Med. 2010; 39: 479-82.

2. Vinod M, Medley A, Hong R, Gu Y, Robey R. Levels and spread of HIV seroprevalence and associated factors: evidence from national household surveys. DHS Comparative Reports No. 2. 2009:209.

3. Heffron R, Chao A, Mwinga A, et al. High prevalent and incident HIV-1 and herpes simplex virus 2 infection among male migrant and non-migrant sugar farm workers in Zambia. Sex Transm Infect 2011; 87: 283-8.

4. Lima V, Anema A, Wood R, et al. The combined impact of male circumcision, condom use and HAART coverage on the HIV-1 epidemic in South Africa: a mathematical model. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WECA105, 2009.

John W. Travis, MD, MPH
RMIT University, Melbourne, Australia

Ignores principles of evidence-based medicine

Tobian and Gray have cherry picked the medical evidence in favour of neonatal circumcision and ignored both arguments and evidence to the contrary. A similar exercise was performed in Australia last year by Cooper et al, [1] which received an immediate rebuttal in the circumcision policy statement released by the Royal Australasian College of Physicians, and so much additional criticism that the journal published eight letters in reply. [2] After an exhaustive review of the evidence the RACP found that “in low prevalence populations … circumcision does not provide significant protection against STIs and HIV,” and concluded that there was no medical case for neonatal circumcision. [3] A longer critique argued that the proposal was flawed because it ignored doubts about the African clinical trials and the interpretation of the WHO recommendations arising from them; was irrelevant to the specifics of Australia’s HIV problem; departed from the principles of evidence-based medicine; underplayed the harm and risks of circumcision; ignored basic principles of medical ethics and human rights; and was marred by unscientific thinking in describing circumcision as a “surgical vaccine.” [4]

Tobian and Gray’s appeal suffers from the same flaws, the most serious of which is its violation of the principles of evidence-based medicine. Evidence of circumcision as an acceptable tactic from underdeveloped countries with high sero-prevalence and predominantly female to male transmission cannot be transposed to developed countries with low sero-prevalence and transmission predominantly in MSM or injecting drug users. Where is the United States evidence that uncircumcised men are at greater risk of HIV, and that circumcision without consent is an effective and ethically acceptable response? Evidence that circumcision of adult men has a protective effect against HIV cannot be extrapolated to children [5], and the same is true of the claim that the Africans experienced no loss of sexual sensation; circumcision in infancy may well have a different impact from circumcision after sexual maturity.

Tobian and Gray assert that surrogate consent from parents overcomes the ethical and human rights problem because they can consent to vaccination. This hackneyed analogy fails because children are vaccinated against diseases that affect them as children and, unlike circumcision, it does not entail the amputation of a functional body part that the individual may appreciate. Children are not at risk of HIV or any other STIs: since there is no urgency to intervene we can safely wait until they are old enough to provide their own informed consent.

References

1. Cooper DA, Wodak AD, Morris BJ. The case for boosting infant male circumcision in the face of rising heterosexual transmission of HIV [editorial]. Med J Aust 2010;193:318-319.

2. “The case for boosting infant male circumcision in the face of rising heterosexual transmission of HIV” ... and now the case against. Med J Aust 2011;194(1)97-101.

3. Royal Australasian College of Physicians. Circumcision – RACP Position Statement. Sydney (AUST): RACP; 2010 September.

4. Darby R, Van Howe R. Not a surgical vaccine: There is no case for boosting infant male circumcision to combat heterosexual transmission of HIV in Australia. Aust N Z J Public Health 2011;35(5):459-465.

5. Perera CL, Bridgewater FHG, Thavaneswaran P, Maddern GJ. Safety and efficacy of nontherapeutic male circumcision: A systematic review. Ann Fam Med 2010; 8 (1): 64-72. See summary on this site.

Robert Darby
Canberra, Australia

NOTE: JAMA did publish an “edited” (i.e. censored) version of this letter; we publish the original, full version here.

Circumcision commentary ignores risks

In making their case for more explicit promotion of neonatal circumcision in the United States, Tobian and Gray cursorily dismiss or simply ignore the arguments against it, including such fundamentally crucial factors as the true range and incidence of risks. The claimed 0.2% to 0.6% neonatal complication rate is a falsely minimized representation of potential harm, already suspect due to the retrospective, short-term design of the source studies. Data exists to show, for example, at least a 1% risk of circumcised boys needing some kind of repeat surgery,(1) and up to a 20% incidence of meatal stenosis (found virtually only in circumcised males, and often requiring painful surgical correction).(2) Other real concerns left unacknowledged include the risk of circumcision-related MRSA infection,(3) and underreporting of rarer but catastrophic complications.(4)

The United States does not, in fact, have in place any comprehensive system of prospective surveillance for adverse events following circumcision. The truth is that no one actually knows how many circumcised boys need to be rehospitalized, how many require specialist follow-up, IV antibiotics, or blood transfusions, how many lose part or all of their glans or penile shaft, or die due to circumcision complications, nor is there precise prospective data on the incidence of a host of other documented problems. But our lack of understanding of the scope of circumcision’s risks is not limited only to those problems directly associated with surgical outcomes. There is, in addition, little scientific knowledge of or attention paid to the possible harmful effects of genital cutting of children on later sexual functionality or emotional health.(5)

Without such information, flatly, no valid risk-benefit comparison, cost-benefit analysis, or policy pronouncements can be made. Nor indeed, when deprived of such risk information, can any parent be said to be giving valid informed consent. Promoting circumcision for its potential benefits, yet with such a limited and inadequate analysis of it potential risks and harms – let alone its ethical problems – is scientifically unsupportable and ethically improper.

References

1. Van Howe RS. A cost-utility analysis of neonatal circumcision. Med Decis Making 2004;24:584-601.

2.  Joudi M, Fathi M, Hiradfar M. Incidence of asymptomatic meatal stenosis in children following neonatal circumcision. J Ped Urol 2011;7(5):526-8. Epub 2010 Sep 18.

3.  Nguyen DM, Bancroft E, Mascola L et al. Risk factors for neonatal methicillin-resistant staphylococcus aureus infection in a well-infant nursery. Infect Control Hosp Epidemiol 2007;28(4):406-11.

4.  Pediatric Death Review Committee: Office of the Chief Coroner of Ontario. Circumcision: A minor procedure? Paediatr Child Health. 2007;12(4);311-312.

5.  Bollinger D, Van Howe RS. Alexithymia and circumcision trauma: A preliminary investigation. Int J Mens Health 2011;10(2):184-195.

Gillian Longley RN,

Colorado, USA

Further objections to the circumcision solution

Full of factual errors

The new editor of JAMA needs to find a competent fact checker to assure that the commentaries published by the journal are factually accurate. A case in point is the recent commentary on the need for more infant circumcision by Tobian and Gray. Contrary to their article:

1. The California ballot initiative did not propose a “ban” on circumcision.

2. There are no observational studies in the United States (let alone a large number) which found that male circumcision reduces the risk of HIV infection in men. On the contrary, American studies show either that circumcision makes no difference, or that circumcised men (especially if Black) are at greater risk of HIV.  A study by Sansom et al, actually cited by Tobian and Gray as though it supported their case, actually showed the lifetime risk of HIV among Black men to be 6.23% with 73% circumcised, yet a lifetime risk to Hispanics of only 2.88% and a circumcision rate of 42%. [1] This would suggest either that there is no connection between circumcision and reduced susceptibility to HIV; that circumcision increases the risk of HIV; or that being Black in the USA is a far greater risk factor for HIV than “lack of circumcision”.

3. Very few of the observational studies document the age at which the participants were circumcised.

4. Blacks in the United States do not have “the lowest rates of male circumcision” but have circumcision rates which are similar to or greater than the circumcision rates in whites.

5. Circumcision has not been shown to reduce the risk of cervical cancer. Even if it did, that is not a valid reason to circumcise infant boys.

6. The American Academy of Pediatrics recommends that decisions be delayed until the child is competent enough to provide fully informed consent. The age of this depends on the child, but is usually around 14 years of age.

7. Meatitis has repeatedly been shown to be more common in circumcised males. Two studies have shown that balanitis is more common in circumcised boys, especially in the first three years of life. There have been three studies that compared the rates of phimosis based on circumcision status: none of which found a significant difference.

8. The complication rate of 0.2% given by the commentators is from a typographical error in the abstract of a study that found a 2% risk of complications. [2] The 0.6% figure is from a letter to the editor [3] . Based on actual studies, the rate of immediate complications is 2% to 10%. The rate of meatal stenosis, which is a delayed complication, is between 5% and 20%. [4]

9. There is no evidence that complication rate of neonatal male circumcision is substantially lower than the complication rates of adult male circumcision. Two studies have directly compared neonatal circumcision to later circumcision. One found no difference in complications, one found a higher rate of complications for the neonate.

10. Sexual dysfunction has been documented in a national survey in Denmark and multiple other studies. These are not anecdotal reports.

11. Vaccines with only 30% to 60% effectiveness are rarely if ever promoted or used, especially when other less expensive, more effective, less invasive options are available.

References

1. Sansom SL, Prabhu VS, Hutchinson AB, An Q, Hall HI, et al. Cost-effectiveness of newborn circumcision in reducing lifetime hiv risk among U.S. males. PLoS ONE 2010:5(1): e8723. doi:10.1371/journal.pone.0008723. Informative comment by Hanabi at http://www.plosone.org/article/comments/info%3Adoi/10.1371/journal.pone.0008723.  See also comment on this site.

2.  Gee WF, Ansell JS. Neonatal circumcision: a ten-year overview: with comparison of the Gomco clamp and the Plastibell device. Pediatrics 1976; 58: 824-7.

3.  Harkavy KL. The circumcision debate. Pediatrics 1987; 79: 649-50.

4.  Joudi M, Fathi M, Hiradfar M. Incidence of asymptomatic meatal stenosis in children following neonatal circumcision. J Pediatr Urol 2011; 7: 526-8.

Ignores functions of the foreskin

Before recommending unlimited government funding of infant male circumcision, Tobian and Gray should at least make a good will effort to acknowledge the impact of amputating the prepuce. The prepuce is a specialized, pentalaminar, junctional tissue, similar to lips and eyelids, that has skin on the outer surface and a mucosal membrane on the inner surface. Near the transition of the inner and outer surface is a pleated region with an extremely high concentration of fine-touch neuroreceptors. This region, which contains nearly all of the penis’s fine-touch neuroreceptors, is removed in virtually all circumcisions. [1] By contrast, the glans is a neurologically dumb organ and contains primarily free nerve endings that transmit only deep pressure and pain. [2] When tested for fine-touch thresholds, the foreskin was found to be the most sensitive portion of the penis, which was more sensitive that the most sensitive portion of the circumcised penis, which was the circumcision scar. The glans in circumcised adult men was significantly less sensitive than the glans in men not circumcised. [3] Similarly, the vibrotactile thresholds of the glans increase significantly following circumcision. [4]

Circumcision also severs the frenular artery and interrupts the blood supply to the ventral aspect of the urinary meatus. This results in scarring and narrowing meatus. Consequently, between 5% and 10% of males circumcised as infants will require a meatotomy to correct their acquired meatal stenosis. [5, 6] In absolute contrast to what is stated by Tobian and Gray, meatitis has been documented almost exclusively in circumcised males.

In the nineteenth century the medical community adopted circumcision as a cure for masturbation. Physicians at the time recognized that if the most sensitive portion of the penis were removed, this might help decrease the temptation to masturbate. Circumcision has been failing to deliver the promises of its promoters ever since.

References

1. Cold CJ, Taylor J. The prepuce. BJU Int 1999; 83 (suppl 1): 34-44.

2. Halata Z. Munger BL. The neuroanatomical basis for the protopathic sensibility of the human glans penis. Brain Res 1986; 371: 205-30.

3. Sorrells ML, Snyder JL, Reiss MD, Eden C, Milos MF, Wilcox N, Van Howe RS. Fine-touch pressure thresholds in the adult penis. BJU Int 2007; 99: 864-9.

4. Yang DM, Lin H, Zhang B, Guo W. [Circumcision affects glans penis vibration perception threshold]. Zhonghua Nan Ke Xue 2008; 14: 328-30.

5. Van Howe RS. Incidence of meatal stenosis following neonatal circumcision in a primary care setting. Clin Pediatr (Phila) 2006; 45; 49-54.

6. Joudi M, Fathi M, Hiradfar M. Incidence of asymptomatic meatal stenosis in children following neonatal circumcision. J Pediatr Urol 2011; 7: 526-8.

Smacks of racism and sexism

The commentary by Tobian and Gray suggests an underlying racism and sexism. Studies of circumcision were performed in Africa because they were not ethically permissible in the United States. HIV investigators in Africa have uniformly accepted the theory that the African epidemic is fuelled by frequent sexual contacts with multiple partners because it fits an unsubstantiated racial stereotype rather than the facts. This theory requires African men to have sexual contact with each of their partners on a daily basis to generate the current infection rates. [1] African men and women have been used as guinea pigs to fortify the American cultural practice of circumcision. In the most egregious of these studies, HIV infected men were randomized to circumcision or not. The HIV status of the participants was not disclosed to the participants or their female sexual partners. The female sexual partners were followed to determine how long it took for them to become HIV infected. Eighteen per cent of the women with circumcised partners became HIV infected and 12% of women with uncircumcised partners became HIV infected before the study was terminated. Amazingly, the researchers concluded that it was more important to circumcise HIV infected men so they could avoid stigmatization than to protect their female partners from the 50% increase in HIV infection risk. [2] In other words, they believe African women are dispensable. At least in Tuskegee, the men were no longer contagious.

In 2009 Gray and colleagues suggested promoting circumcision primarily to blacks and Hispanics. [3] While HIV infections are concentrated in the economically deprived, Hispanics have a much lower prevalence of HIV and a much lower circumcision rate than blacks. This would suggest that circumcision in the economically deprived may increase HIV infection rates. Blacks actually have the highest circumcision rates in the U.S. and yet also have the highest HIV rates.

Blacks have circumcision rates between 81% and 91%, depending on the decade of birth, which are similar or higher than the rates seen in whites. [4,5] Rather than admit circumcision has failed to protect black males from heterosexually transmitted HIV infection and focusing on more effective means of preventing HIV infection (such as condoms and anti-retroviral therapy), the commentators appear to think that some benefit may come from increasing an already high circumcision rate. This defies logic and suggests that there is a lingering fear of black sexuality.

References

1. Sawers L, Stillwaggon E. Concurrent sexual partnerships do not explain the HIV epidemics in Africa: a systematic review of the evidence. J Int AIDS Soc 2010; 13: 34.

2. Wawer MJ, Makumbi K, Kigozi G, Serwadda D, Watya S, Nalugoda F, Buwembo D, Ssempijja V, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Opendi P, Iga B, Ridzon R, Laeyendecker O, Gray RH. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 2009; 374: 229-37.

3. Gray RH, Wawer MJ, Serwadda D, Kigozi G. The role of male circumcision in the prevention of human papillomavirus and HIV infection. J Infect Dis 2009; 199: 1-3.

4. Xu F, Markowitz LE, Sternberg MR, Aral SO. Prevalence of circumcision and herpes simplex type 2 infection in men in the United States: the National Health and Nutrition Examination Survey (NHANES), 1999-2004. Sex Transm Dis 2007; 34: 479-84.

5. Mor Z, Kent CK, Kohn RP, Klausner JD. Declining rates in male circumcision amidst increasing evidence of its public health benefit. PLoS ONE 2007; 2(9): e861.

Discriminates in favour of minority religions

Tobian and Gray have suggested that Medicaid pay for the religious circumcisions of Jewish and Muslim boys. This clearly violates the separation between church and state as set up in the First Amendment of the Constitution. While the commentators use a selective bibliography to espouse their beliefs about the medical benefits of circumcision, parents do not circumcise their sons for some imaginary medical benefits, they circumcise them for cultural, cosmetic, and religious reasons.

One could more easily argue that marriage is associated with improved health, including lower rates of STIs, and lower rates of HIV infections. If Medicaid is asked to pay for circumcisions for religious reasons, Medicaid should also be expected to pay for religious weddings. Why should Jews and Muslims get a benefit from the state that is not available to people of other religions? The commentators obviously did not think this through. It is not the role of the state to favor those with one set of religious beliefs over another.

This is also a slap in the face of those from cultural or religious backgrounds who believe that they are required to have the genitals of their daughters cut. Over the past five years there has been increasing evidence in medical literature that cutting of female genitals may have medical benefits and minimal risks. [1-4] So, why focus only on boys, when girls could benefit as well?

References

1. Stallings RY, Karugendo E. Female circumcision and HIV infection in Tanzania: for better or for worse?[abstract] Third International AIDS Society Conference on HIV Pathogenesis and Treatment. Rio de Janeiro, July 25-27, 2005.

2. Essén B, Sjöberg N-O, Gudmundsson S, Östergren P-O, Lindqvist PG. No association between female circumcision and prolonged labour: a case control study of immigrant women giving birth in Sweden. Eur J Obstet Gynecol Reprod Biol 2005; 121: 182-5.

3. Catania L, Abdulcadir O, Puppo V, Verde JB, Abdulcadir J, Abdulcadir D. Pleasure and orgasm in women with Female Genital Mutilation/Cutting (FGM/C). J Sex Med 2007; 4: 1666-78.

4. Applebaum J, Cohen H, Matar M, Rabia JA, Kaplan Z. Symptoms of posttraumatic stress disorder after ritual female genital surgery among Bedouin in Israel: myth or reality? Prim Care Companion J Clin Psychiatry 2008; 10: 453-6.

Cavalier and selective attitude to the medical literature

Tobian and Gray’s commentary on infant male circumcision refers to “anecdotal reports that male circumcision can cause sexual dysfunction.” This statement indicates that the commentators are either unfamiliar with or are purposely mischaracterizing the medical literature. Several small studies that documented a lack or improvement or decline in sexual function following circumcision in adult males circumcised for medical indications. [1] There are several studies, with the exception of two performed in Turkey, that have shown a higher rate of premature ejaculation in adult male who are circumcised compared to the non-circumcised. In one study of 207 men, premature ejaculation was nearly five times greater in circumcised adults (adjusted OR 4.88, 95%CI=2.35-10.15).[2] These are not anecdotal reports.

In a study of 139 women who had sexual experience with both circumcised and non-circumcised men these women reported that sex with a non-circumcised partner had significantly less vaginal discomfort, a higher likelihood of vaginal and multiple orgasms, longer duration of coitus, and more positive post-coital feeling. On a rating scale between –10 and +10 these women rated coitus with circumcised men at an average of 1.81 and with non-circumcised men at an average of 8.03.[3] This study may have been influenced by a selection bias; however, a national health survey of 5552 adults in Denmark confirmed these findings. In this survey circumcised men reported a greater number of sexual partners and a greater rate of reporting frequent difficulties with orgasm (adjusted OR=3.26, 95%CI=1.42-7.47). Women with a circumcised male sexual partner reported greater rates of incomplete sexual fulfillment (AdOR=2.09, 95%CI=1.05-4.16), difficulties with orgasm (AdOR=2.66,95%CI=1.07-6.66), and dyspareunia (AdOR=8.45, 3.01-23.74).[4] A national survey is not an anecdotal report.

The studies from Africa mentioned by the commentators need to be taken with a grain of salt. The participants in these trials were extremely well compensated by African standards, so both the Hawthorne effect and willingness to please the participant’s benefactors may have been in play. These studies focused on changes in overall sexual satisfaction, leaving readers uninformed about the actual levels of sexual satisfaction reported. The men in the study also reported implausibly high levels of sexual satisfaction. This suggests that the measure of sexual satisfaction used may not have been able to measure a difference if it existed. In the future it would be better if JAMA published commentaries written by individuals who are familiar with the medical literature and unwilling to mischaracterize it.

References

1. Coursey JW, Morey AF, McAninch JW, Summerton DJ, Secrest C, White P, Miller K, Pieczonka C, Hochberg D, Armenakas N. Erectile function after anterior urethroplasty. J Urol 2001; 166: 2273-6.

2. Tang WS, Khoo EM. Prevalence and correlates of premature ejaculation in a primary care setting: a preliminary cross-sectional study. J Sex Med 2011; epub ahead of print.

3. O’Hara K, O’Hara J. The effect of male circumcision on the sexual enjoyment of the female partner. BJU Int 1999; 83 (suppl 1): 79-84.

4. Frisch M, Lindholm M, Grønbæk. Male circumcision and sexual function in men and women: a survey-based, cross-sectional study in Denmark. Int J Epidemiol  40.5 (October 2011): 1367-1381. See news item at Science Nordic.

Violates research and publications ethics

One of the first ethical questions a new editor of a medical journal faces is, how does a journal deal with well-financed zealots who want to promote their own unethical, poorly designed research? It appears that for the new editor of JAMA that the answer is to give them open slather and silence any critical voices.

In the last year Tobian and Gray have authored numerous opinion pieces to promote male infant circumcision in the United States. [1] Hot on the heels of their multi-million dollar NIH- and Gates Foundation-funded studies in adults, these researchers, turned lobbyists, are telling us that infants in the USA are really adults in Africa and need to be circumcised. Unfortunately, their enthusiasm is hollow and desperate, and their studies were unethical. Before their studies began, it was known that more effective, less expensive, less invasive methods for preventing HIV infection were available. To include humans in an experiment knowing that the intervention is inferior and more invasive than currently available options was clearly unethical. To follow HIV-infected men, without informing them or their partners of their infection status, to see how long it took before their female sexual partners became infected may be the most unethical study in several generations. It remains unclear how these clearly unethical studies were approved by the Investigational Review Board of Johns Hopkins or published by a well-respected journal such as The Lancet.
The methodological shortcomings of the studies out of Johns Hopkins have been discussed in detail elsewhere and may explain why these studies lack external validity. [2,3]

Finally, from reading Tobian and Gray, you would never know that there is a study on circumcision that does not list one of them among the authors. Such academic narcissism should not be encouraged, although it provides insight to the commentators’ motives. In 2005 certain sceptics suggested that circumcision advocates were studying circumcision and HIV in Africa as method of shoring up waning support for infant male circumcision in the USA [4] It looks like this prediction has come true. Readers of JAMA do not want to read unsubstantiated propaganda. Fresh on the job, and the new editor has already earned a failing grade.

References

1. Tobian AAR, Gray RH, Quinn TC. Male circumcision for the prevention of acquisition and transmission of sexually transmitted infections: the case for neonatal circumcision. Arch Pediatr Adolesc Med 2010; 164: 78-84.

2. Garenne M. Long-term population effect of male circumcision in generalised HIV epidemics in sub-Saharan Africa. Afr J AIDS Res 2008; 7: 1-8.

3. Green LW, Travis JW, McAllister RG, Peterson KW, Vardanyan AN, Craig A. Male circumcision and HIV prevention insufficient evidence and neglected external validity. Am J Prev Health 2010; 39: 479-82.

4. Van Howe RS, Svoboda JS, Hodges FM. HIV infection and circumcision: cutting through the hyperbole. J R Soc Health 2005; 125: 259-65.


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