Striking differences in the risk factors for developing heart failure (HF) and patient prognosis exist between men and women. Men and women may also respond differently to treatment, raising concerns about whether current practices provide the best care and reinforcing the urgency for sex-specific clinical trials for HF, according to a review article published in the August 4, 2009, issue of the Journal of the American College of Cardiology.

“Current practice is to treat heart failure similarly in men and women,” said Eileen Hsich, M.D., director of the Women’s Heart Failure Clinic at the Cleveland Clinic in Ohio. “Yet, our review of published reports suggests compelling sex differences, not only in terms of how and when heart failure develops, but also possible responses to treatments and how the disease impacts quality of life.”

The data show that HF - a life-threatening condition in which the heart cannot pump enough blood throughout the body - affects women at an older age and often with a stronger heart compared to men. Hypertension and valvular disease are more likely the culprits for HF in women, whereas men are more likely to have coronary artery disease (CAD) as the underlying cause. And while women live longer with the disease, they also tend to have lower quality of life than men due to greater physical limitations with exercise, more HF-related hospital stays and depression.

“The reasons why survival is better for women remain unclear, but it may be due to differences in the underlying disease,” said Dr. Hsich. “Our findings also raise questions as to whether certain diagnostic tests or criteria need to be changed to better reflect how HF presents in female versus male patients.”

For example, “normal” values for brain natriuretic peptide - a biomarker that is being used more frequently to identify patients with symptoms of HF and stratify patients by risk - are higher for women versus men and abnormal values with a BNP > 500 pg/ml may be a stronger predictor of death in women with HF than in men. There is also evidence that sex-specific differences may result when performing a cardiopulmonary stress test, which is often used to evaluate patients for heart transplantation. Women with HF tend to have a better prognosis for any given peak oxygen consumption value when compared to men, yet the cut-off values to determine need for heart transplantation are the same for both sexes. The potential benefits of certain HF therapies both in terms of reducing morbidity and mortality appear to be different among women.

“We found that some of the available medications may not be as effective in women, while other therapies, for example, beta blockers, aldosterone antagonists and pacemakers, may be very beneficial,” said Dr. Hsich, although she cautions that these finding should in no way prompt women to deviate from what their doctor recommends.

“We need to remember that the therapy women are receiving must be working because they are living longer,” she added. “Still, we need to gain a better understanding of HF in women so that we know whether we are providing the best possible care.”

A critical challenge remains enrolling women in clinical trials and inspiring researchers to conduct sex-specific studies.

“This is a disease that affects women just as much as men, yet it remains poorly understood and women are still underrepresented in studies,” said Dr. Hsich, adding that major multicenter HF trials in the last decade on average only included 28 percent women. “It is really important for women to speak up and not wait for their doctor to approach them about participating in a clinical trial. In doing so, we can help ensure that future advances in HF treatments are applicable to women and supported by sound research.”

Notes:
Approximately 2.7 million women have HF, which accounts for 35 percent of the total female cardiovascular mortality.


Dr. Hsich and co-author, Ileana Pina, M.D., Case Western Reserve University, performed a systematic review of the literature and also contacted the lead investigators of the major CV trials to request sex-specific data if it was not provided in their original publication.


Dr. Hsich reports no conflicts of interest.

Source:
Amanda Jekowsky

American College of Cardiology

A comprehensive analysis of nearly 1,600 tumor samples has found that CT-X genes are expressed in nearly half the breast cancers that lack the estrogen receptor (ER). CT-X gene products are the targets of therapeutic cancer vaccines already in phase III clinical trials for lung cancer and melanoma. The study - to be published in the Early Edition of the Proceedings of the National Academy of Sciences this week - was led by the international Ludwig Institute for Cancer Research (LICR).

ER negative breast cancers, which account for a third of all breast cancer cases, are a group of tumors that has a generally poor prognosis and few therapy options. A subgroup of the ER negative group is triple-negative breast cancer (TNBC), which lacks the estrogen, progesterone and HER2 receptors. TNBC is responsible for most of the breast cancers that strike down African American and young women.

In the current study, gene and protein expression studies showed that nearly half of primary ER negative and triple-negative breast cancers express members of either or both the MAGEA and NY-ESO-1/CTAG1B families of CT-X genes. Approximately half of the primary tumor samples from patients with the basal-like form of breast cancer, which is usually ER negative, also expressed either or both of these gene families, and nearly two-thirds of metastases from basal-like tumors also expressed these genes.

These findings suggest that a therapeutic vaccine combining members of the two CT-X families could be a new therapy approach to filling a critical unmet need.

Dr. Andrew Simpson, LICR scientific director and an author of the study, said that clinical trials based on the findings of the PNAS study could theoretically be initiated in the near future. “Vaccines targeting MAGEA3 are already in phase III trials, and the Cancer Vaccine Collaborative, a partnership between the Ludwig Institute and the Cancer Research Institute, has demonstrated the safety of different forms of the NY-ESO-1 antigen in phase I and II trials in a variety of tumor types.”

According to LICR’s Dr. A. Munro Neville, the senior author of the study, obtaining clinic-grade material for more members of the CT-X families and funding for a clinical trial will be the next steps in determining if therapeutic cancer vaccines can meet a critical need in breast cancer therapy.

CT genes - the X denotes chromosome localization - encode CT antigens, proteins that are recognized by the immune system. Spontaneous immune responses against CT antigens are thought to be a natural form of cancer control and might be the mechanism behind spontaneous remission.

Therapeutic cancer vaccines are being developed to induce, strengthen and/or sustain immune responses against cancer. GlaxoSmithKline (GSK), which licensed MAGEA3 and NY-ESO-1 from LICR, is currently conducting phase III clinical trials of a MAGEA3-based cancer vaccine, or “antigen-specific cancer immunotherapy” (ASCI) in non-small cell lung cancer and melanoma.

Source:
Sarah L. White, Ph.D.

Ludwig Institute for Cancer Research

The Royal Pharmaceutical Society of Great Britain has published its fourth Pharmacy
Workforce Census, reflecting the working patterns of pharmacists registered in August 2008.
The reports findings reveal changes in workforce patterns since the last census in 2005,
together with new and emerging trends in the workforce.
Census forms were sent out to all pharmacists with a registered address in Great Britain.

The
survey achieved a high response rate of 69.6%. Key findings included:

- The Register increased by 1.7% overall between August 2007 and August 2008. The
Register has grown by about 2% annually since 1991; therefore the increase is in keeping
with the previous upward trend.

- Pharmacists reported working the same mean number of hours as the 2005 census (35
hours), although men worked longer hours than women. The proportion of pharmacists
working 49 hours or more per week has risen by 1% since the last census.

- There has been a slight increase in the numbers of actively employed pharmacists working
part-time, with these pharmacists representing a significant proportion (32.3%) of the
working population. Part-time working (defined as working 32 hours or less) was most
prevalent in the primary care sector (39.5%).

- More than a third of pharmacists (41.9%) reported that they usually worked long hours and
this figure rose to 52.2% for male pharmacists.

- Almost a third of pharmacists (30.3%) felt that they didn’t have enough time to socialize
with their family and friends and a similar proportion (30.7%) wanted to reduce their
working hours, but felt they had no control.

- Male pharmacists consistently recorded higher scores for the work-life balance measures
than females, indicating that men may perceive they experience more problems with worklife
balance than females. The only exception to this was in the case of pharmacists
working part-time: male part-timers recorded lower work-life balance scores than females
working part-time.

- More than one in ten pharmacists (13.0%) are considering leaving the sector in which they
currently work within the next two years. A similar proportion (10.9%) are considering
quitting the profession altogether.

The findings provide full and fundamental data for the General Pharmaceutical Council (GPhC)
when it is established in 2010, and will be used to help inform workforce planning and policy
development across the profession. Findings relating specifically to work/life balance will also
inform initiatives such as the Society’s ongoing workplace pressures campaign.
Sue Ambler, Head of Research and Development at the Society said: “Thank you to all those
pharmacists that took the time to complete and return the census questionnaire. The data will
be utilised to help identify how both the GPhC and the new professional leadership body can
further and strengthen support for pharmacists in their advancing and evolving roles.”
A copy of the report is available on the Society’s website:
http://www.rpsgb.org.uk/pdfs/census08.pdf

Notes

The research on which the Census report is based was commissioned by the Research
Division at the Society.
The research was undertaken by a team at the School of Pharmacy, University of Manchester
and funded by the Department of Health.
The 2008 Census report is the Society’s fourth. The first census was conducted in 2002, the
second in 2003 and the third in 2005.

Source
Royal Pharmaceutical Society of Great Britain