Remembering the terror of AIDS

In June 1981, the US Centre For Disease Control reported the deaths of five young gay men, from a rare form of pneumonia. Around the same time, Kaposi’s sarcoma, a cancer usually seen only in the very old, started to claim the lives of a disproportionate number of gay people. By 1983, the numbers of deaths had become so large that Horizon, the BBC science programme, broadcast a documentary about them, called “Killer in the Village”. I share that childhood memory only to recall how terrifying those early years of the Aids crisis were, before the aetiology of the disease was known, before the virus was identified, before effective therapies were developed; I suspect those years have cast a shadow over every gay man of my generation, whether they fell ill or not, whether they tested positive or not, whether or not they’ve ever taken the test. Thank God HIV was found responsible for the disease. Better a virus, isolated under a microscope, a tractable drug target, than some form of cosmic retribution: though not everyone would agree with that, of course.

The question in those early years was whether or not the infection would be confined to gay people. What would have happened, had that turned out to be the case? A question, 30 years later, I still prefer not to ponder. By 1987, though, the risk to the general population was clear, and one of the most remarkable campaigns seen in post-war Britain was launched. I suspect you’ll remember the government’s Don’t Die Of Ignorance campaign, the tombstone with “AIDS” chiselled onto it, John Hurt’s terrifying voiceover. A leaflet was delivered to every house in the land, warning people to avoid unprotected sex. 

Edited from an article by Graeme Archer published in The Telegraph on 2 December 2011

The Medical College Admission Test — Toward a New Balance — NEJM

The Medical College Admission Test — Toward a New Balance — NEJM: 'via Blog this'

Making Sense of the New Cervical-Cancer Screening Guidelines

Over the past 60 years, U.S. mortality from cervical cancer has dropped by 70%, thanks to a successful screening program. In 1995, the American College of Obstetricians and Gynecologists (ACOG) recommended screening with the Papanicolaou (Pap) smear and pelvic examination at the initiation of sexual activity or by 18 years of age and annually thereafter. Although not evidence-based, this guideline was easy to remember, timed to coincide with the onset of legal adulthood, and well received by patients and clinicians. Linking the Pap smear to an annual visit, and often to the provision of other health care services such as contraception, breast care, and blood-pressure checks, made the patient likely to comply and the physician likely to remember to offer the test as part of routine care. Furthermore, although the Pap smear's sensitivity is poor — roughly 50 to 60% — the frequency of repetition made it likely that in screened patients, an abnormality missed one year would be found the next. Hence, the system worked.

In 2002 and 2003, the ACOG, the American Cancer Society (ACS), and the U.S. Preventive Services Task Force (USPSTF) all issued guidelines addressing many issues related to screening. In 2006, the American Society for Colposcopy and Cervical Pathology (ASCCP) issued management guidelines. Despite being “evidence-based,” these guidelines were different from one another, complicated, and hard to remember. Furthermore, the combination of a Pap smear with a test for human papillomavirus (HPV cotesting), which was addressed in these guidelines, was just being approved by the Food and Drug Administration (FDA) — on the basis of minimal clinical evidence that it added value. Despite recommendations indicating that Pap–HPV cotesting should be performed no more frequently than every 3 years because of its high added cost and limited additional clinical value, many patients, clinicians, and laboratories began cotesting annually.

Between 2009 and 2011, the same organizations, as well as American Society for Clinical Pathology (ASCP),1-4reconvened expert panels to reevaluate the evidence and issue new guidelines. Again, there are some differences of opinion and interpretation. There are, however, many points of agreement (see table in original article) and much opportunity to use the existing evidence to maintain a high-quality cervical-cancer prevention program that also safely addresses cost concerns.

Cervical cancer is rare before 20 years of age, and the incidence doesn't start to rise significantly until women reach the age of 25 or 30. Most cancers detected in screened women tend to be early-stage, so those found through screening are largely curable. For many women with early-stage disease, less-radical, fertility-sparing procedures can be curative, so even if early-stage cancers are detected, morbidity and mortality may be minimal.

Therefore, in 2009, the ACOG recommended that screening for “average-risk” women begin at the age of 21. Although the expert groups all agree that cervical cancer is rare before that age, they define high-risk younger groups somewhat differently; the ACOG defines average-risk women as immunocompetent women. Eliminating earlier screening averts overdiagnosis in young women based on transient cervical changes that their healthy immune systems would generally clear — and thereby also averts painful, costly, and possibly harmful procedures. Because there are no large prospective cohorts of immunocompromised patients, the USPSTF, which tends to be most rigorous in its evidence review, states that there is insufficient information for it to clearly recommend that screening should start before the age of 21 in immunosuppressed patients, but it offers the option of screening within 3 years after the onset of sexual activity, or by the age of 21.

Studies consistently show that for previously well-screened healthy women 30 years of age or older, the interval between Pap screenings can be lengthened to 3 years without significantly increasing their risk of cancer. It's also known that when screening takes place only every 5 years, or when women with abnormal Pap tests are not correctly triaged and treated to prevent cervical dysplasia from progressing to cancer, cancer rates increase. For women between 20 and 30 years of age, the optimal frequency is less well studied, but given the poor sensitivity of any single Pap test, the goal is to obtain at least two consecutive normal Pap results during this period to ensure that there are no missed opportunities for detecting and treating a precancerous lesion before lengthening the interval.

All the evidence and guidelines agree that HPV testing has no role in adolescents and should be performed in women 21 to 30 years of age only if a Pap test reveals atypical squamous cells of undetermined significance, an approach referred to as reflex testing. They also agree on reflex HPV testing for women 30 years of age or older under the same conditions. It is recommended that laboratories and clinicians not perform HPV screening in adolescents and that they use it only as a reflex test in women in their 20s.

The USPSTF, ACOG, and ASCCP–ACS–ASCP vary dramatically on whether evidence supports HPV cotesting for women 30 years of age or older. The USPSTF argues that Pap testing every 3 years for women over 30 is both safe and more cost-effective than cotesting and that no data support cotesting at the current screening intervals. It seems reasonable to use Pap testing alone every 3 years in this age group, unless the clinician seeks reassurance about lengthening the interval for a particular woman — for instance, if she has an uncertain Pap history or impaired immune status or may have difficulty complying with returning in 3 years. In such cases, HPV testing could be added or the Pap-testing interval shortened.

There is general agreement that in well-screened, low-risk women with no history of cancer or high-grade precancerous lesions, there comes a point when additional screening confers little added benefit. The USPSTF, ASCCP, and ACS agree on 65 as the age to stop screening such women. If the clinician cannot document a history of three normal Pap tests within the previous 10 years, then a Pap test should be obtained. If a patient has vaginal bleeding, vulvar discomfort, or other gynecologic or urologic symptoms, a complete pelvic examination and appropriate diagnostic testing should be performed. Furthermore, vaginal cancer is rare among women who have undergone hysterectomy, and all the guidelines agree that if such women are otherwise healthy and have no history of cancer or dysplasia, vaginal Pap testing may be discontinued.

In patients who have been treated for high-grade dysplasia, the risk of cervical cancer is increased by a factor of two to three for at least 20 years, but the risk of dying from cervical cancer is low, since most cancers are diagnosed at an early stage. Because it has long been the standard of care to screen these patients annually, we don't have good prospective data on whether this more frequent testing has contributed to early cancer diagnoses. Given that mortality rates have remained low with current practices, however, all groups recommend screening this population for at least 20 years after treatment.

Increasing screening in previously unscreened populations will further reduce the incidence of cervical cancer and related mortality. Reaching out to patients who face cultural, language, or educational barriers to care is important. Creating systems to remind clinicians that patients who come for episodic care must have appropriate cancer-screening tests is essential. Finally, making the guidelines for managing abnormalities easier for patients and clinicians to follow is important for both optimizing outcomes and containing costs for unnecessary referrals and treatment.

Health care is a limited resource, and providing the best care at the best price will become increasingly important. We need to use and understand actual data about risk and the long-term effects and costs of various strategies. Experts are often in the best position to review the data and make recommendations, but different expert panels may interpret data differently and emphasize different results in making their decisions. And even with the best consensus guidelines, some clinical judgment and personalized attention to each patient remains necessary.

1. ACOG practice bulletin no109: cervical cytology screening. Obstet Gynecol 2009;114:1409-1420

2. Preventive Services Task Force. Opportunities for public comment (http://www.uspreventiveservicestaskforce.org/tfcomment.htm).

3. American Society for Colposcopy and Cervical Pathology. Cervical cancer screening and prevention: the role of molecular testing (http://www.asccp.org/practice-management/molecular-screening-symposium).

4. Vesco KK, Whitlock EP, Eder M, Burda BU, Senger CA, Lutz K. Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force. Ann Intern Med 2011 October 17 (Epub ahead of print).

From an article by Sarah Feldman Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston).published on November 23, 2011, at NEJM.org

Polycystic Ovary Syndrome Boosts Risk for Poor Pregnancy Outcomes

Polycystic Ovary Syndrome Boosts Risk for Poor Pregnancy Outcomes: 'via Blog this'

You Have to Gamble On Your Health

You Have to Gamble On Your Health

EARLY October brought two developments in the world of cancer screening: the beginning of Breast Cancer Awareness Month, with its calls for regular mammograms for women, and a new recommendation from the United States Preventive Services Task Force that healthy men not undergo screening for prostate cancer.

It’s a stark juxtaposition: screening is good for women and bad for men. But just how different are these two cancer screening tests?

The answer is: not very. Neither is like the decision of whether or not to be treated for really high blood pressure. That’s an easy one — do it. Instead, both breast and prostate cancer screening are really difficult calls, and the statistical differences between them are only of degrees. Reasonable individuals, in the same situation, could make different decisions based on their valuation of the benefits and harms of screening.

Personally, as a 56-year-old man, I choose not to be screened for prostate cancer (and, were I female, I believe I would choose not to be screened for breast cancer). Some of my patients have made the same choice, while others choose to be screened. That’s O.K., because there is no single right answer.

Screening is like gambling: there are winners and there are losers. And while the few winners win big, there are a lot more losers. It’s easy to understand why. When doctors screen for early cancer, all the incentives — cultural, financial, professional and legal — line up in one direction: Don’t miss it. As a result, doctors overreact to even the tiniest abnormalities, which leads to the two basic harms of screening: false-positive tests and overdiagnoses.

False positives are really common in both breast and prostate cancer screening. (When it comes to screening, all numbers should be viewed as estimates because the data vary for different populations and practice settings, but numbers do help give a sense of the order of magnitude.) Approximately 15 to 20 percent of women and men who are screened annually over a 10-year period will have to undergo at least one biopsy because of a false-positive mammogram or P.S.A. — prostate-specific antigen — test.

It’s a matter of opinion to what extent patients with false-positive tests are losers — the physical complications of biopsies are generally short-lived. But they certainly don’t benefit from the procedures. And in the interim, they’re made to worry that they have cancer.

Overdiagnosis is less common, but much more consequential because it leads to unnecessary treatment. Screening finds abnormalities that meet the pathological definition of cancer, yet will never go on to grow or cause any symptoms, let alone death. Sometimes patients choose to wait and see if the cancer grows, but most opt to treat it; once you’re told you have cancer, it’s difficult to wait and see what happens next.

Patients who are overdiagnosed are the big losers here. They undergo surgery, radiation and chemotherapy unnecessarily. And then there are the associated complications: chemotherapy can cause nausea and radiation can burn normal tissue; breast surgery can be disfiguring, and prostate surgery can lead to bladder and sexual dysfunction.

Doctors don’t know which patients they are treating unnecessarily, but they know how the unnecessarily treated patients got there in the first place — because they were screened for cancer.

Now let’s consider the winners — those who have avoided dying from breast or prostate cancer by getting screened. While there is some debate about whether they really exist, my reading of the data is that they do, but they are few and far between — on the order of less than 1 breast or prostate cancer death averted per 1,000 people screened over 10 years. That’s less than 0.1 percent.

Overall, in breast cancer screening, for every big winner whose life is saved, there are about 5 to 15 losers who are overdiagnosed. In prostate cancer screening, for every big winner there are about 30 to 100 losers.

You may look at these numbers and decide that both tests are good gambles — or that both are bad gambles.

Or you might try to distinguish between the two. Overdiagnosis is more common following prostate cancer screening and is arguably more consequential, as there is a higher risk of long-term complications from prostate cancer treatment. So maybe mammography is the better gamble.

Or you might make a different calculation and consider what happens without screening. For breast cancer the first sign is typically a breast lump, which in most cases can now be treated very successfully. (The real success in the war against breast cancer has been improved treatment, not screening.) But the first sign of prostate cancer typically occurs too late for the disease to be treated successfully. So maybe P.S.A. testing is the gamble to take.

The truth is that neither test works that well. Even with screening, most people destined to develop deadly, untreatable cancers will still do so.

When it comes to breast and prostate cancer screening, there are no right answers, just trade-offs.

From an article by H Gilbert Wrench in The New York Times 10 October 2011. H. Gilbert Welch, a professor of medicine at the Dartmouth Institute for Health Policy and Clinical Practice, is a co-author of “Overdiagnosed: Making People Sick in the Pursuit of Health.”

The Phantom Menace of Sleep Deprived Doctors - NYTimes.com

The Phantom Menace of Sleep Deprived Doctors - NYTimes.com

Drospirenone Associated With Increased Risk for VTE

Drospirenone Associated With Increased Risk for VTE

April 26, 2011 Women without risk factors for venous thromboembolism (VTE) who are taking the third-generation oral contraceptive drospirenone have an increased risk for nonfatal VTE compared with women taking the second-generation contraceptive levonorgestrel, according to the findings of 2 new case-control studies. Susan S. Jick, Dsc, from the Boston Collaborative Drug Surveillance Program at the Boston School of Medicine, in Massachusetts, and colleagues reported their findings in 2 separate articles published online April 21 in the BMJ.

According to the researchers, a series of case reports beginning in 2002 first raised concerns about an increased risk for VTE in users of oral contraceptives containing drospirenone. This risk has since been assessed in several studies that included women with risk factors for VTE. However, the risk attributable to oral contraceptives in the absence of other causes was unknown. In the current studies, one conducted in the United Kingdom and the other in the United States, the study populations, both consisting of women aged 15 to 44 years, was restricted to patients with idiopathic VTE, each matched with up to 4 control case patients by age and calendar time of drug exposure.

Data for the UK cohort came from the UK General Practice Research Database, which contains data from more than 3 million people. Data for the US cohort were acquired from the PharMetrics database, which contains prescription data on 55 million people reaching back to 1995. The UK study included 61 cases of idiopathic VTE among current users of drospirenone and levonorgestrel; these patients were matched with 215 control patients. All patients were receiving oral contraceptives containing 30 μg of estrogen in combination with either drospirenone or levonorgestrel. The US study included 186 cases of idiopathic VTE; these patients were matched with 681 control patients, with contraceptives including either drospirenone or levonorgestrel.

Although the absolute risk was low, both studies showed a 2- to 3-fold increased risk for nonfatal VTE with drospirenone compared with levonorgestrel. The UK study showed an odds ratio (OR) of 3.3 (95% confidence interval [CI], 1.4 - 7.6), and the US study showed an OR of 2.4 (95% CI, 1.7 - 3.4). In the UK study, the incidence rates for idiopathic VTE were 23 (95% CI, 13.4 - 36.9) per 100,000 woman/years with drospirenone and 9.1 (95% CI, 6.6 - 12.2) per 100,000 woman/years with levonorgestrel. The corresponding incidence rates in the US study were 30.8 (95% CI, 25.6 - 36.8) per 100,000 woman/years with drospirenone and 12.5 (95% CI, 9.61 - 15.9) per 100,000 woman/years with levonorgestrel.

These results would add to emerging data that suggest the use of the oral contraceptive containing drospirenone is associated with a higher risk of [VTE] than are preparations containing levonorgestrel. Since no clear evidence exists to show that the use of the drospirenone pill confers benefits above those of other oral contraceptives in preventing pregnancy, treating acne, alleviating premenstrual syndrome, or avoiding weight gain, prescribing lower risk levonorgestrel preparations as the first line choice in women wishing to take an oral contraceptive would seem prudent.

Medscape Medical News

Letter from CAP

Concern over HPV vaccines

(Fri, 24 Dec 2010) 

THE Consumers Association of Penang is aghast that the relevant authorities, particularly the Health Ministry, have kept silent over the raging controversies on the rush to get young girls vaccinated against cervical cancer. There are many areas of concern over the human papillomavirus (HPV) vaccine which is said to prevent infection against certain species of human papillomavirus associated with cervical cancer, genital warts and some less common cancers.

Many countries are going slow on this vaccine because of many doubts raised. However, Malaysia is rushing into it. HPV vaccines, given in a series of three shots, are to make the body’s immune system produce antibodies against HPV types 16 and 18, which cause seven out of 10 cases of cervical cancer. The antibodies supposedly protect one from getting infected with HPV.

And yet the authorities are not giving the people any details. Even the type of vaccine used seems to be top secret. Two HPV vaccines are in the market: Gardasil and Cervarix. Which one is Malaysia using? And experts tell us that the regular Pap smear screening must be continued to be done even after vaccination because the vaccine only covers some high-risk types of HPV.

The World Health Organisation warned late last year that those vaccinated and do not continue with screening, such as Pap smear because they wrongly believe they are protected against cervical cancer, can raise the death figures, especially with the vaccine protection waning over time.

Some concerns have been raised by the US Centers for Disease Control and Prevention:

As of Sept 1, 2009, there were 15,037 Vaccine Adverse Event Reporting System (VAERS) cases of adverse events following Gardasil vaccination in the US. Of these reports, 93% were reports of events considered to be non-serious, and 7% were reports of events considered to be serious.

Reports on non-serious adverse events after Gardasil vaccination have included fainting, pain and swelling at the injection site (the arm), headache, nausea and fever.

VAERS defines serious adverse events as those that involve hospitalisation, permanent disability, life-threatening illnesses and death.

As of Sept 1, 2009, there have been 44 reports of death among females in the US who have received the vaccine.

CAP calls on the authorities to stop the vaccine programme until the people are clear about it. In September 2009, when the government announced its intention to vaccinate some 300,000 13-year-old-schoolgirls, we voiced our objections. We reiterate that inoculating schoolgirls with the vaccine is a symptomatic and simplistic solution to the problem of cervical cancer in children who may contract cervical cancer due to early sexual activity when instead, the root cause for contracting HPV - sexual relations with multiple partners; should be countered by education.

S.M. Mohamed Idris
President
Consumers Association of Penang