"As Nurses it is our
responsibility to meet the
shortage head on, take
charge of our future and
to see that their future
is better than our past"
Nursing, a profession that recalls the name of Florence Nightingale is indeed one of the noblest professions in the world. It is the art of caring for sick people with the science of health care. It is a vital component of any form of medical care.
responsibility to meet the
shortage head on, take
charge of our future and
to see that their future
is better than our past"
|
|
Nursing duties are manifold and cover a wide range of functions and responsibilities, that depends with the level of qualification and the working environment. At the initial level, nurses are required for the bedside care of patients, while at senior level they are required to manage special group of people like psychiatric, pediatric, intensive care patients etc which require specialised skills.
They are also involved in dispensing medication, keeping records of the patients progress, setting up and operating medical equipment, administration and several other routine chores.
This field is both mentally and physically demanding and nurses are often exposed to health risks from infectious diseases. As such this profession demands long hours of work and duties which incorporate both skill and understanding of patients needs. Those who come forward to take up this as a career has to be patient, courageous, have a service mentality and at the same time be ready to work for extra hours even night shifts.
Job Prospects and career options : They can find employment in Hospitals, Nursing homes, Clinics and Heath Departments, Orphanages and old age homes, Military etc. Click here for more information
Remuneration : Remuneration of nurses depends on the level of seniority reached.Nurses employed by government hospitals receive a monthly salary of Rs 6,500. Click here for more information
Institutes : A large number of institutes in India offer diploma, graduate and postgraduate courses in nursing as well as midwifery courses.Click here for a comprehensive list of Institutions in India
Nursing, a world of opportunity
Working in the medical field today has great rewards. Right now male nurses make up just six percent of the workforce in the United States, meaning the opportunities for men in this field are endless.
Hosted by Chris Cashman, an Emmy Award-winning personality in the Seattle-Tacoma television market, the video examines the growth within the healthcare industry and delves into the day-to-day responsibilities of a nurse.
Packed with interviews from more than 15 men in the nursing field, this DVD will open your eyes to the world of nursing in today's workplace and explain how nursing is more than a job.
Scope in nursing career in India and abroad
With increasing health consciousness in India, the quality of health services has improved. Skilled and specialized nurses are in high demand by the health organizations. The nurses can get excellent employment opportunities in government or private hospitals, clinics, nursing homes, orphanages, old age homes, military services, industries and schools.
Majority of the nurses in India go abroad. Most of the nurses working throughout the world are from the Indian state of Kerala. The skilled nurses can get the employment in specialized fields like Surgical, Medical, ICUPacked with interviews from more than 15 men in the nursing field, this DVD will open your eyes to the world of nursing in today's workplace and explain how nursing is more than a job. Click here for a comprehensive list of Institutions in India
Nursing, Why I Love My Work As A Male Nurse
In this video I describe why IPacked with interviews from more than 15 men in the nursing field, this DVD will open your eyes to the world of nursing in today's workplace and explain how nursing is more than a job. Click here for a comprehensive list of Institutions in India
This speech was given for Moorestown Area Toastmasters, http://www.matoast.org
I have belonged to this club since 2004 and joined Toastmasters to improve my public speaking skills, get over my nervousness in front of groups of people while speaking.
More like this: http://www.4nursing.com/p2p/
Thanks, Andrew Lopez, RN
l
Cesarean Delivery May Increase Risk of Developing Asthma
Infants delivered by cesarean delivery had a moderately higher risk for the development of asthma vs those not delivered by cesarean delivery, according to the results of a population-based cohort study reported in the July issue of the Journal of Pediatrics.
"Whether CS [cesarean section] is associated with asthma has been widely debated in recent years, and the issue remains far from resolved," write Mette C. Tollånes, MD, from the University of Bergen in Bergen, Norway, and colleagues. "Several studies have reported a moderately increased risk of asthma in children delivered by CS, whereas others have found no such association. "With few exceptions, these studies were characterized by rather small study populations and short follow-up periods."
The goal of this study was to evaluate the relationship between cesarean delivery and later development of asthma with use of a population-based cohort of 1,756,700 singletons reported to the Medical Birth Registry of Norway between 1967 and 1998. The primary outcome was asthma registered in the National Insurance Scheme, which provides cash benefits to families of children with severe chronic illnesses, during follow-up to age 18 years or the year 2002. Multivariate Cox proportional hazard models were used to determine associations between exposure (spontaneous vaginal delivery, instrumental vaginal delivery, or cesarean delivery, with planned and emergency cesarean delivery analyzed separately from 1988 onward) and outcome.
During follow-up, the cumulative incidence of asthma was 4.0 per 1000. Compared with children delivered by spontaneous vaginal delivery, those delivered by cesarean delivery had a 52% increased risk for asthma (adjusted hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.42 - 1.62). Between 1988 and 1998, planned cesarean delivery was associated with a 42% increased risk for asthma (HR, 1.42; 95% CI, 1.25 - 1.61), and emergency cesarean delivery was associated with a 59% increased risk for asthma (HR, 1.59; 95% CI, 1.44 - 1.75).
Limitations of this study include lack of data on other possible risk factors for asthma, inability to rule out underreporting of maternal asthma, and possible confounding factors."We found a moderately increased risk of asthma in the children delivered by CS," the study authors write. "The possibly stronger association with emergency CS compared with planned CS could be worth pursuing to investigate possible causal mechanisms."
The Research Council of Norway funded this study. The study authors have disclosed no relevant financial relationships.
Estrogen Hampers Lp(a) Use for Risk Prediction
The utility of lipoprotein(a) [Lp(a)] in predicting future risk of heart disease is markedly attenuated among women taking hormone therapy, a new study suggests [1].
The study, published online July 1, 2008 in the Journal of the American College of Cardiology, was conducted by a team led by Dr Jacqueline Suk Danik (Brigham and Women's Hospital, Boston, MA). They note that Lp(a) is a lipoprotein different from low-density lipoprotein (LDL) cholesterol because it contains an apo(a) component, and it has been shown to be associated with an increased incidence of cardiovascular disease (CVD). To explore whether this relationship is modified in women who use hormone therapy, they analyzed data from the Women's Health Study, which followed 27,736 apparently healthy women, aged 45 years or older, for up to 13 years. They assessed the effect of low-dose aspirin and vitamin E in the primary prevention of heart disease and cancer in this cohort. Of these women, 12,075 indicated the active use of hormone therapy at study initiation.
For the purpose of the current study, the researchers assessed the risk of a first major cardiovascular event (myocardial infarction [MI], cerebrovascular event, coronary revascularization, or cardiovascular death) over a 10-year period, on the basis of Lp(a) levels and hormone use. Results showed that Lp(a) values were lower among women taking hormones than among women not taking hormones.
Lp(a) values according to hormone use
|
| Hormone use | No hormone use | p |
| Lp(a) level | 9.4 mg/dL | 11.6 mg/dL | <> |
Hazard ratio for future heart disease risk, according to Lp(a) quintile
| Status | Quintile 1 (0.10 - 3.00 mg/dL) | Quintile 2 (3.10 - 6.80 mg/dL) | Quintile 3 (6.90 - 13.60 mg/dL) | Quintile 4 (13.70 - 41.90 mg/dL) | Quintile 5 (42.00 - 221.90 mg/dL) | p for trend |
| Not taking hormones
(n = 15,661) | 1.00 | 0.97 (0.72 - 1.31) | 0.92 (0.68 - 1.26) | 0.97 (0.72 - 1.30) | 1.77 (1.36 - 2.30) | <> |
| Taking hormones
(n = 12,075) | 1.00 | 1.04 (0.76 - 1.42) | 0.74 (0.52 - 1.04) | 0.79 (0.56 - 1.11) | 1.13 (0.84 -1.53) | 0.18 |
Adjusted for Framingham covariates of age, blood pressure categories, current smoking status, total cholesterol, high-density lipoprotein (HDL) cholesterol values, as well as body mass index, diabetes, C-reactive protein, and treatment arms.
Danik et al said they believe there are at least two explanations for the effect modification seen: it could be attributable to the biologic interaction between plasma Lp(a) levels and concurrent hormone use; or it could be that hormone use is a surrogate variable for a healthy lifestyle, which is not fully captured by the covariates adjusted for, that ameliorates the deleterious relationships between lipid biomarkers and heart disease.
Concerning a possible direct biologic effect, they note that recent data show that estrogen might induce increased uptake of Lp(a) by the LDL receptor; that estrogen might cause a reduction of Lp(a) production by the liver, where Lp(a) production is likely modulated; and that certain cholesterol metabolites might interact directly with hormones in the vasculature.
Challenges in using Lp(a) as a risk marker
In an accompanying editorial [2], Drs Lars Berglund and Erdembileg Anuurad (University of California, Davis) explain that Lp(a) has many features in common with LDL but, unlike LDL, its distribution is very skewed, with plasma levels ranging from <> 300 mg/dL; a minority of people have levels > 30 mg/dL, which are commonly associated with cardiovascular risk. These factors, along with the difficulty standardizing its measurement, represent challenges in firmly associating Lp(a) with disease, they say.The editorialists note that Danik et al's results show a nonlinear association between Lp(a) and cardiovascular risk. The fact that increased risk is only evident at the highest Lp(a) quintile suggests that there is a threshold effect in the role of Lp(a) as a risk factor. Further, the interaction observed between Lp(a) and LDL levels indicates that Lp(a) might have more pronounced risk-factor properties in a high-risk environment, they add.
They point out that currently there are no guidelines recommending intervention based on high Lp(a) levels. Although findings from the current study and other studies suggest that Lp(a)-lowering therapy might be beneficial, at least in some subgroups of patients with high Lp(a) levels, details are lacking about how to define such subgroups according to Lp(a) levels, apo(a) size, and the presence of other risk factors.
They say the current findings "are encouraging because they provide evidence that high Lp(a) levels in a high-risk setting might be appropriate to consider an intensified intervention. However, further studies are needed to firmly assess any possible therapeutic benefits of a reduction of Lp(a) levels."Dr. Danik has received support from the National Heart, Lung, and Blood Institute and the Michael Lerner Foundation. Another study author has received grant support from Merck Research Laboratories and has served as a consultant to Sanofi-Aventis. A complete list of disclosures is available in the original article.Dr. Berglund has received consulting fees from Merck, Novartis, and Merck/Schering-Plough; has received lecture fees from Merck, AstraZeneca, and Merck/Schering-Plough; and has equity interest in Pfizer. This work was supported in part by the University of California, Davis Clinical and Translational Science Center. Dr. Anuurad is a recipient of an American Heart Association Postdoctoral Fellowship.
Coffee Drinking May Protect Against Risk for Liver Cancer
Higher coffee consumption was associated with lower liver cancer risk but higher levels of gamma-glutamyltransferase (GGT) may increase risk for this disease, according to the results of a study reported in the July issue of Hepatology.
"Only three Japanese prospective studies have suggested an inverse association between coffee drinking and liver cancer risk," write Gang Hu, from the Department of Public Health, University of Helsinki in Finland, and colleagues. "No prospective studies on the association between ... GGT and liver cancer risk have been reported. We aimed to determine the single and joint associations of coffee consumption and serum GGT with the risk of primary liver cancer."
The study cohort consisted of 60,323 Finns who were 25 to 74 years of age and free of any cancer at enrollment. Median follow-up was 19.3 years (interquartile range, 9.3 - 29.2 years). Incident liver cancer was diagnosed in 128 participants during follow-up. Hazard ratios for liver cancer risk as a function of coffee consumption were multivariable-adjusted for age, sex, alcohol consumption, education, smoking, diabetes and chronic liver disease at baseline and during follow-up, body mass index was assessed.Adjusted hazard ratios of liver cancer in participants who drank 0 to 1, 2 to 3, 4 to 5, 6 to 7, and more than 8 cups of coffee daily were 1.00, 0.66, 0.44, 0.38, and 0.32, respectively (P for trend = .003), and further adjustment for serum GGT in subgroup analysis affected the results only slightly. For the highest vs the lowest quartile of serum GGT, the multivariable-adjusted and coffee-adjusted hazard ratio of liver cancer was 3.13 (95% confidence interval, 1.22 - 8.07).
Stratification by baseline factors did not abolish the multivariable-adjusted inverse association between coffee consumption and liver cancer risk; these factors included age younger than 50 years and 50 years and older, current smoker/never smoked/ever smoked, alcohol drinker/never drinker, obese/nonobese, and the highest/lowest 3 quartiles of serum GGT. Risk was increased nearly 9-fold for the combination of very low coffee consumption and high level of serum GGT.
"Coffee drinking has an inverse and graded association with the risk of liver cancer," the study authors write. "High serum GGT is associated with an increased risk of liver cancer."Limitations of this study include use of self-reported data on coffee intake only at baseline; lack of data about other main sources of caffeine; no data on history of either hepatitis B virus or hepatitis C virus infections at baseline; use of only a dichotomized measure of alcohol consumption in the whole sample; and inability to completely exclude the effects of residual confounding due to measurement error."The biological mechanisms behind the association of coffee consumption with the risk of liver cancer are not understood at present," the study authors conclude. "It would be interesting to find out whether the modification of coffee drinking would modify the risk of liver cancer in people positive for either HBV [hepatitis B virus] or HCV [hepatitis C virus] infection."
In an accompanying editorial, Carlo La Vecchia, from Universitá degli Studi di Milano in Milan, Italy, notes the difficulties in translating the inverse relation between coffee drinking and liver cancer risk into potential implications for preventing liver cancer by increasing coffee consumption.
"Together with avoidance of lung cancer through tobacco control, primary liver cancer is the other common neoplasm which is most largely avoidable, through HBV vaccination, control of HCV transmission, and reduction of alcohol drinking," Dr. La Vecchia writes. "These three measures can, in principle, avoid more than 90% of primary liver cancers worldwide. Whether coffee drinking has an additional role in liver cancer prevention remains open to discussion, but in any case any such role would be limited — if not negligible — as compared to that achievable through control of HBV, HCV, and alcohol consumption, which are the major recognized risk factors for liver cancer."
The Finnish Academy and Special Research Funds of the Social Welfare and Health Board, City of Oulu, supported this study. The authors have disclosed no relevant financial relationships.The Italian Association for Cancer Research and the Italian League Against Cancer supported this work.
Clinical Context
According to the current authors, liver cancer is the third most common cause of death from cancer worldwide.
The incidence rate is high in western and central Africa and southeastern and eastern Asia and low in most developed countries except Japan, and hepatitis B and C virus infections have been identified as causative factors in more than 75% of cases. However, according to the current authors, coffee consumption has been found to be inversely related to risk for primary liver cancer, whereas GGT levels has been linked to increased risk.
Finns drink coffee daily and have a higher per capita consumption of coffee (11.4 kg/year) than others such as the Japanese (3.2 kg/year) and Americans (4.1 kg/year). The prevalence of primary liver cancer and of hepatitis B and C virus infection is low in the Finnish population, making it a good setting to test the hypothesis that coffee consumption protects against primary liver cancer.
This is a population-based prospective cohort study to examine the association between coffee consumption and GGT level and risk for primary liver cancer during 19 years of follow-up in the Finn population.
Smoke-Free Policies Bring Health Benefits
The International Agency for Research on Cancer (IARC) has announced that the implementation of smoke-free policies in many Western countries has reduced the prevalence of smoking and had subsequent health benefits [1]. Furthermore, such smoking bans have not had adverse financial effects on the bar and restaurant industry, it says.
Dr John Pierce (University of California, San Diego) and Dr Maria Leon (IARC, Lyon, France) have prepared a special report on the subject, published in the July 2008 issue of Lancet Oncology. Leon told heartwire that the latest handbook from IARC is currently being prepared and is the first one to focus on assessing the effects of smoke-free policies; previous handbooks have concentrated on tobacco control. "We show that comprehensive smoke-free laws significantly reduce exposure to secondhand smoke, which has been associated with undesirable health outcomes," she said. Studies of the effects of smoke-free policies consistently show that passive smoking is reduced by 80% to 90% in high-exposure settings. In turn, this has had health benefits in terms of a reduction in heart-disease morbidity, a reduction in respiratory symptoms, and an expected decline in lung cancer, she noted.
Handbook to be Published in February 2009 Leon said the handbook being prepared will be published in February 2009 and will consist of nine chapters dedicated to specific subjects, seven of which will present results from scientific studies "and, based on that evidence, certain conclusions have been made."
The chapters will focus on: the effects of smoking bans on smoking behavior; exposure to secondhand smoke; effects of smoking bans on business; effects of voluntary implementation of smoke-free homes; and the health outcomes of these changes, among other things.
"Studies suggest that smoke-free workplace policies are followed by a 10% to 20% decrease in hospital admissions for acute coronary events in the first year after implementation [of a smoking ban]," say Pierce and Leon. "There is strong evidence suggesting that the introduction of a smoke-free legislation decreases heart-disease morbidity," they add.
Smoking bans also benefit employees in the hospitality industry, with "sufficient evidence that the introduction of smoke-free policies decreases respiratory symptoms in workers,' they note. And although cancer cases are expected to drop also, it will take some time for this to register, say the scientists.
"In view of the long lag time between secondhand smoke exposure and the development of lung cancer, data are not yet available regarding the expected decline in lung cancer after implementation of smoke-free policies," they note.
Tobacco Industry Tries to Impede Smoke-Free Policies There is a momentum, and countries want to emulate the good that is happening in our places. Leon told heartwire that one chapter in the book is also dedicated to the role of the tobacco industry in trying to impede the introduction of smoke-free policies. "They have done this by, for example, casting doubts on the adverse health effects associated with exposure to secondhand smoke," she explained. Also, cigarette firms will often try to promote alternatives to total smoking bans, she notes, suggesting environments that allow both smoking and smoke-free areas or encouraging other solutions to smoking, such as ventilation, rather than outright bans.
The researchers conclude that most of the research to date has been done in high-resource countries, but the challenge now is to expand smoke-free policies to low-resource and medium-resource nations. Leon believes the tide is starting to turn: "Around 150 countries worldwide have signed the WHO's Framework on Tobacco, which makes reference to smoke-free legislation. Now there is a momentum, and countries want to emulate the good that is happening in our places," she concludes.
Substance Abuse Treatment May Effectively Integrate With Prenatal Care
Substance abuse treatment integrated with prenatal visits as part of Early Start was associated with a positive effect on maternal and newborn health, according to the results of a study reported in the June 26 Online First issue of the Journal of Perinatology.
"Initial research on Early Start demonstrated that pregnant women who were screened positive, assessed and treated for substance abuse problems by Early Start had neonatal outcome rates for assisted ventilation, preterm delivery and low birth weight similar to control women, and significantly lower than substance abusers who were screened positive only or screened positive and assessed but not treated," write Nancy C. Goler, MD, from the Permanente Medical Group, Department of Obstetrics and Gynecology, Northern California Region, Oakland, California, and colleagues
. "The purpose of this study which looked over a longer time period and at maternal outcomes not included in the original study was to provide a more comprehensive evaluation of Early Start on maternal and neonatal outcomes to support this becoming the standard of care for all prenatal clinics and establish the program as a gold standard for replication."
The study cohort consisted of 49,985 women who completed prenatal substance abuse screening questionnaires at obstetric clinics from January 1, 1999, through June 30, 2003, had urine toxicology screening tests, and either live births or intrauterine fetal demises. The investigators compared 10 neonatal and maternal outcomes in 4 groups: women screened or assessed positive and treated by Early Start ("SAT" [n = 2073]), women screened or assessed positive without treatment ("SA" [n = 1203]), women screened positive only ("S" [n = 156]), and control subjects who screened negative (n = 46,553).For most outcomes, women in the SAT group had either similar or slightly higher rates of negative outcomes vs the women in the control group, but they had significantly lower rates vs the women in the S group. Compared with the SAT and S groups, the SA group generally had intermediate rates. Outcomes were significantly worse in the S vs the SAT group on the basis of multivariable analysis. For preterm delivery, odds ratio [OR] was 2.1 (95% confidence interval [CI], 1.3 - 3.2); for placental abruption, OR was 6.8 (95% CI, 3.0 - 15.5); and for intrauterine fetal demises, OR was 16.2 (95% CI, 6.0 - 43.8). "Substance abuse treatment integrated with prenatal visits was associated with a positive effect on maternal and newborn health," the study authors write.
Limitations of this study include retrospective evaluation of a current treatment program in a health maintenance organization setting, which was not designed as a research study; lack of randomization; and failure to exclude medical comorbidities such as diabetes, hypertension, psychiatric illness, or uterine anomalies.
"Early Start's replicable model of integrating substance abuse treatment with prenatal care is cost-effective and significantly decreases negative birth outcomes as well as maternal morbidity," the study authors conclude. "The women and babies served by Early Start are healthier; therefore the impact of the program reaches beyond them to also positively influence the health and well-being of the community at large, and consequently must also be considered from a public health perspective. The results of this study reflect the importance of widespread implementation of this model of care as a national standard."
Clinical Context
Substance abuse during pregnancy is associated with multiple negative pregnancy outcomes, yet this condition can be difficult to diagnose and treat.
The Early Start program was developed to improve the identification and recovery from substance abuse by providing universal screening questions and urine toxicology testing, brief intervention, and referral to treatment within the department of obstetrics and gynecology.
The Early Start specialist is a licensed clinical social worker or marriage and family therapist who uses motivational therapy, cognitive/behavioral therapy, and psychodynamic therapy to treat women who are either practicing substance abuse or are at high risk for substance abuse. Appointments for substance abuse counseling are made to coincide with routine prenatal visits.
Previous research suggested that women with a history of substance abuse who were treated in the Early Start program had similar neonatal outcomes vs women with a negative result on screening examination for substance abuse. The current study examines a larger cohort of women participating in the Early Start program.
Oral Capecitabine Can Replace IV 5-FU in Gastrointestinal Cancers
Oral capecitabine (Xeloda, Roche) is at least as effective as intravenous 5-fluorouracil (5-FU) and can replace it in the treatment of gastrointestinal (GI) cancers.
This is the conclusion from a meta-analysis of 6 large manufacturer-sponsored phase3 trials comprising a total of 6171 patients with colorectal, colon, and stomach cancer. It was presented by Jim Cassidy, MD, from the Beatson Oncology Center and University of Glasgow, in the United Kingdom, at the 10th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
"Time after time, oral capecitabine has proven to be effective at keeping patients with colorectal, colon, and stomach cancers alive," Dr. Cassidy commented. He was involved in 2 of the clinical trials examined in the meta-analysis, and has long been an enthusiastic proponent of the oral drug, because it "allows patients to get on with their lives by reducing the time they spend in the hospital for infusional therapy." "We should now accept that oral capecitabine is as effective as infusional 5-FU and that it can be prescribed in any line and in any combination for the treatment of various GI cancers," Dr. Cassidy said in a statement.
There is increasing agreement about this view among the medical community, said Eric van Cutsem, MD, PhD, from University Hospital Gasthuisberg, in Leuven, Belgium, who was not involved in any of the trials. There are some experts who disagree with this view, but "I don't know any other area of medicine where there is 100% agreement," he pointed out.
Robert Mayer, MD, from the Dana-Farber Cancer Institute, in Boston, Massachusetts, agrees that oral capecitabine is equivalent in efficacy to infusional 5-FU, but said that there are other factors that need to be taken into consideration, such as adverse effects, cost, and convenience. In an interview he pointed out that capecitabine is more expensive than 5-FU, and some evidence from the United States suggests that it is not as well tolerated. Dr. Mayer was not involved in any of the trials, and he discussed many of these issues in an editorial published in September 2007 (J Clin Oncol. 2007;25:4165-4167), as reported at the time by Medscape Oncology.
There is also a regulatory issue. Capecitabine is approved for use as monotherapy for the first-line treatment of metastatic colorectal cancer in both Europe and the United States. However, in Europe it is also licensed for use in combination with any chemotherapy in any line of treatment with or without bevacizumab (Avastin, Roche); this additional indication is still pending in the United States.
Meta-Analysis Confirms Therapeutic Equivalence
The meta-analysis presented at the meeting examined 6 studies, all sponsored by Roche:
- 2 studies of capecitabine as a single agent in the first-line treatment of metastatic colorectal cancer;
- 2 studies of capecitabine in combination with oxaliplatin chemotherapy in the first- and second-line treatment of colorectal cancer;
- 1 study of capecitabine as a single agent in the treatment of colon cancer after surgery (the X-ACT study);
- 1 study of capecitabine in combination with cisplatin in the first-line treatment of stomach cancer (the REAL study).
-
These data "are the icing on the cake," Dr. Cassidy commented in an interview with Medscape Oncology. Each of the trials individually showed equivalent therapeutic efficacy with the oral and infusional drug; the meta-analysis confirms this conclusion.
Oral Capecitabine Can Replace IV 5-FU
Oral capecitabine can replace intravenous 5-FU and can be considered an option, Dr. van Cutsem commented in an interview with Medscape Oncology. The data are strong, he said: "They were strong for the individual trials and they are now strong for the meta-analysis. They have shown that the oral drug is at least as good as the infusion."
Dr. Mayer agreed that capecitabine can replace intravenous 5-FU. "There is nothing wrong with the word can, that it can replace," he said in an interview. "But to say that it should replace, it must replace, has been shown to replace...that's marketing, and that's a little bit too much."
Dr. Mayer pointed out that the meta-analysis shows equality, but the press release issued by Roche about this meta-analysis talked about superiority, with the headline: "Confirmed: Oral Xeloda should consistently replace IV 5-FU in treatment of all GI cancers." This is an overstatement, Dr. Mayer commented. Dr. Cassidy agreed that this was "overgilding," and Dr. van Cutsem also said that it went too far.
Other Factors That Need to be Considered
The studies in the meta-analysis "have shown that there is no statistical difference in the outcome, and that I agree with completely," Dr. Mayer commented. "But when there is no difference, one has to ask what other parameters are important, and whether one approach is better than, equal to, or inferior to the other, and that includes tolerance, side effects, convenience, and cost."
In terms of adverse effects, most of the studies with capecitabine have been conducted in Europe. When the drug was studied in the United States, it was found to be less tolerable than in Europe, Dr. Mayer said. One American study (known as TREE-2) had to reduce the dose; another American study (known as BIC-C) showed that capecitabine was more toxic than and not as effective as 5-FU with irinotecan. Why there should be such a difference between the results from Europe and those from the United States is not clear, Dr. Mayer commented. One theory suggests that it might be the higher levels of folic acid in the American diet.
"There is fairly consistent reporting that European patients tolerate full-dose capecitabine, and that there is no difference in the quality of side effects between the infusional 5-FU regimens and capecitabine," he said. "But this has not been the general American experience, and I can't explain why."
"I don't know many American investigators who have used capecitabine who haven't come back and said, 'how did they get away with those doses in Europe, because my patients are complaining of vomiting and diarrhea and swelling of the hands (hand and foot syndrome),' " he commented. As a result, many American doctors have been reducing the dose of the drug so that it becomes tolerable. And then you have the question of whether it is still therapeutically equivalent, he said.
As for cost, Dr. Mayer emphasized that 5-FU is very inexpensive and that capecitabine is clearly more expensive. In the United States, there is also the issue of copayment for an oral medicine, where the patient is asked to personally pay a component of the price of the drug.
When it comes to convenience, Dr. Mayer argues that many of the original projections for capecitabine were based on its use as monotherapy; in practice, the oral drug is used alongside intravenous oxaliplatin or irinotecan, so patients are going to the infusion clinic anyway. "The original model of a patient receiving just oral therapy is not really valid," he added.
"If a drug is equally effective but perhaps a bit more toxic and a bit more expensive, I'm not sure that it has been proven to be a standard or a better option," Dr. Mayer said. "It is an option, but I'm not sure that it is a better option."
"The option of oral capecitabine is probably not as well embraced in the United States as it is in Europe, and much of this has reflected the enthusiasm of the manufacturer and the enthusiasm of several prominent investigators who have run with the drug." Dr. Mayer said.
There is no universal acceptance of capecitabine in place of 5-FU, Mace Rothenberg, MD, from the Vanderbilt-Ingram Cancer Center, in Nashville, Tennessee, told Medscape Oncology. "We have recognized and published on regional differences in tolerability for capecitabine alone and in combination with oxaliplatin, with Americans experiencing more toxicities than others. Until we learn more, 5-FU will continue to have a place in the treatment of colorectal cancer, especially in the United States."
Differences in Tolerability are "Actually Quite Small"
Dr. Cassidy acknowledges that there is a difference in tolerance between American and non-American patients. "That's absolutely true," he said, but the difference "is actually quite small," and is not a reason for American patients not to receive this drug. "The advantages of oral treatment hugely outweigh, in my mind, any minor differences there may be in the side effects," he said Dr. Cassidy also asserted that American physicians have a bias toward infusional drugs because there is a financial incentive for administering intravenous therapies. There is a direct reimbursement for intravenous therapy that is paid either to the physicians or to their institutions, and "they will not come clean on this particular aspect," he said in an interview.
Capecitabine is clearly a much more expensive drug than 5-FU, Dr. Cassidy noted, "but the studies we have carried out and published show that the whole package of care comes out to a fairly close call between the 2 different treatment approaches." Administration of 5-FU involves a central line, an infusion pump, and multiple visits to the physician; all of these things add to the cost of the drug, he explained. As for convenience, even when capecitabine is used along with other intravenous therapies, these regimens are still easier to administer, Dr. Cassidy explained. For example, intravenous oxaliplatin is administered through a peripheral line in a 2-hour infusion, whereas 5-FU is given through a central line in a 48-hour infusion, so "you are not comparing oranges with oranges here," he commented.
HIV-Related Mortality Near Normal in First 5 Years on HAART
NEW YORK (Reuters Health) Jul 01 - In countries with good patient access to highly active antiretroviral therapy (HAART), persons infected with HIV currently experience mortality rates similar to that of the general population in the first 5 years after seroconversion, members of the CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe) collaboration report.
According to their report in the July 2 issue of the Journal of the American Medical Association, an excess mortality persists in persons who seroconverted following injection drug use and among those infected for more than 5 years.
In contrast to CASCADE findings, previous investigations into the effect of HAART on mortality lacked information about the duration of HIV infection, project leader Dr. Kholoud Porter, at the UK Medical Research Council Clinical Trials Unit in London, and colleagues note.
CASCADE is a collaboration of 23 cohorts in Europe, Australia, and Canada, with well-estimated data on HIV seroconversion. The current analysis involves individuals 15 years of age or older at seroconversion who contracted HIV through sexual exposure or injection drug use. Included are 16,534 individuals followed for a median of 6.3 years (range 1 day to 23.8 years).
"We found that the gap in mortality rates between HIV-infected individuals in our study and the general population narrowed in every calendar period from 1996 onward," the authors report. For the period 2004-2006, excess mortality was 94% lower than pre-1996 levels.
Exposure to HIV through injection drug use was associated with a 4-fold higher mortality risk compared with rates among men who have sex with men. Apart from risks directly associated with substance abuse, the investigators attribute the greater mortality in these patients to co-infections, comorbid mental illness, and differences in access and adherence to HAART.
The excess mortality observed with longer duration of infection is based on data that include individuals infected prior to the HAART era, Dr. Porter's team explains.
"Nevertheless," they add, "it is likely that even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time receiving HAART."
The CASCADE collaborators conclude: "Ongoing monitoring of excess mortality will be important as new treatment advances are implemented in an attempt to further reduce mortality rates among HIV-infected individuals."
Dark Chocolate Reduces Blood Pressure for Short Term
When it comes to dark chocolate and blood-pressure reduction, it would seem that a little goes a long way. A new randomized controlled study has shown that just one square of dark chocolate a day reduces blood pressure by a few mm Hg in healthy people with above-optimum blood pressure.
Dr Dirk Taubert (University Hospital of Cologne, Germany) and colleagues report their findings in the July 4, 2007 issue of the Journal of the American Medical Association. Taubert told heartwire that this is the first research to show the benefits of cocoa in dark chocolate long-term — the study lasted 18 weeks. They were also able to demonstrate a feasible mechanism for the BP-lowering effects of dark chocolate, he noted.
Hypertension expert Dr Franz H Messerli (Columbia University, New York), who was not involved in this research, told heartwire: "This is now study 6 showing the same phenomenon. It is an exceedingly well-done, very thorough study, which I think is nothing short of revolutionary."
Dark Chocolate Increases Production of Nitric Oxide
Taubert et al say that short-term studies have previously shown that high doses of cocoa for two weeks can improve endothelial function and reduce blood pressure, due to the action of cocoa polyphenols. "But the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear."
They conducted a randomized, controlled, investigator-blinded, parallel-group trial with 44 adults, aged 56 to 73, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The participants were randomly assigned to receive either one square (6.3 g) of a commercial brand of dark chocolate per day, constituting just 30 kcal, or matching polyphenol-free white chocolate for 18 weeks.
The primary outcome measure was change in BP after 18 weeks. Secondary outcomes included changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane) and bioavailability of cocoa polyphenols.
From baseline to 18 weeks, dark-chocolate intake reduced mean systolic BP by 2.9 mm Hg (p<0.001)>Clinical Context
Cocoa is rich in polyphenols, specifically flavanols, which can induce expression of nitric oxide and stimulate improved endothelial function. Therefore, it is logical to expect that dark chocolate rich in flavanols might have a beneficial effect on blood pressure (BP), whereas white chocolate, which does not contain high levels of polyphenols, may not have an effect on BP. In a study of 15 healthy subjects assessed after consuming white or dark chocolate for 7 days, Grassi and colleagues demonstrated a reduction in insulin resistance and as well as a reduction in systolic BP among subjects receiving dark chocolate. However, the study, which was published in the March 2005 issue of The American Journal of Clinical Nutrition, failed to demonstrate a benefit of dark chocolate in terms of diastolic BP. This failure may have resulted from underpowering in this small study.
The current study examines whether consumption of dark chocolate can continue to have a salutary effect on BP during a longer treatment period, when its healthy effects might be negated by its high calorie content.
Vitamin-D Deficiency Now Associated With Increased Mortality
Another study suggesting a link between low levels of vitamin D and cardiac risk has been published, this time showing that vitamin-D deficiency is associated with both cardiovascular mortality and all-cause mortality [1].
The study, published in the June 23, 2008 issue of the Archives of Internal Medicine, was conducted by a group led by Dr Harald Dobnig (Medical University of Graz, Austria).They note that it has been estimated that 50% to 60% of people do not have satisfactory vitamin-D status, and this is probably related to factors such as urbanization, demographic shifts, decreased outdoor activity, air pollution and global dimming, and decreases in the cutaneous production of vitamin D with age.
The minimum desirable serum level of 25-hydroxyvitamin D has been suggested to be 20 to 30 ng/mL, and levels lower than this are clearly related to compromised bone-mineral density, falls, and fractures and more recently have also been linked to cancer and immune dysfunction, as well as cardiovascular disease, hypertension, and metabolic syndrome, the authors report.
They point out that recent studies have shown an association of low 25-hydroxyvitamin-D levels with important cardiovascular risk factors, supporting previous findings that demonstrated positive effects of vitamin D and its analogs on fibrinolysis, blood lipids, thrombogenicity, endothelial regeneration, and smooth-muscle-cell growth. "Together, these findings strongly suggest that 25-hydroxyvitamin D has beneficial effects, some involving the cardiovascular system, that are independent of calcium metabolism," they comment.
Noting that there are few large studies addressing associations of endogenous serum vitamin-D levels with overall and cardiovascular mortality, they set to look at this issue in a large cohort of patients referred for coronary angiography in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. All patients underwent detailed baseline examinations, which allowed adjustment for possible confounders.
The 3258 patients included were followed for a median of 7.7 years, during which time 737 patients (22.6%) died, including 463 from cardiovascular causes. Results showed patients in the lower two 25-hydroxyvitamin-D quartiles at baseline (median, 7.6 and 13.3 ng/mL) and those in the lowest 1,25-dihydroxyvitamin-D quartile had a significantly higher risk of all-cause mortality during follow-up.
Hazard ratios (95% CI) for all-cause mortality according to 25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D quartiles Variable Quartile 1 Quartile 2 Quartile 3 Quartile 4
| 25-hydroxyvitamin D | 2.08 (1.60 - 2.70) | 1.53 (1.17 - 2.01) | 1.24 (0.94 - 1.65) | 1 (reference) |
| 1,25-dihydroxyvitamin D | 1.61 (1.25 - 2.07) | 1.26 (0.97 - 1.64) | 1.16 (0.89 - 1.51) | 1 (reference) |
Similar results were seen for cardiovascular mortality, which was approximately doubled in patients in the lowest quartiles compared with those in the highest quartiles. Low 25-hydroxyvitamin-D levels were also significantly correlated with markers of inflammation (C-reactive protein [CRP] and interleukin 6 [IL-6]), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 levels).
Dobnig et al say that these results show that a low 25-hydroxyvitamin-D level can be considered a strong risk indicator for all-cause mortality in women and in men.
They note that while the percentage of patients with low 25-hydroxyvitamin-D values in this study may seem unexpectedly high, with roughly two-thirds of those included having levels below 20 ng/mL, they point out that the mean value of 17.3 ng/mL compares well with values reported from other large trials performed in middle European countries such as France, Italy, and Germany.The authors also report that the increase in risk of all-cause mortality with lower levels of vitamin D was seen regardless of the degree of coronary artery disease seen on angiography, and they comment: "Low 25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D levels seem to be important mediators of mortality even when there is little or no indication of overt vascular disease."
They say they are unable to tell, based on these results, whether the association between low 25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D levels and mortality is causal or not. But they believe there are a few indications pointing to a possible link. These include the association with elevated inflammatory markers, which suggests these compounds may have anti-inflammatory properties, and the effects related to oxidative stress and increased cell adhesion suggest that low levels of vitamin D may detrimentally affect vascular biologic function in multiple ways. They add that other mechanisms whereby low vitamin-D levels may be associated with mortality include effects on matrix metalloproteinases, which have been shown to affect plaque production and stability, increased susceptibility to arterial calcification, or an increase in renin messenger-RNA expression.
They conclude: "This prospective cohort study demonstrates for the first time, to our knowledge, that low 25-hydroxyvitamin-D and 1,25-dihydroxyvitamin-D levels are associated with increased risk in all-cause and cardiovascular mortality compared with patients with higher serum vitamin-D levels. Both vitamins seem to have synergistic biologic action that is largely independent of each other.… Based on the findings of this study, a serum 25-hydroxyvitamin-D level of 20 ng/mL or higher may be advised for maintaining general health."
Clinical Context
According to the 13th Workshop Consensus for Vitamin D Nutritional Guidelines reported by Norman and colleagues in the March 2007 issue of the Journal of Steroid Biochemistry and Molecular Biology, the minimum recommended serum level of 25-hydroxyvitamin D is 20 to 30 ng/mL. However, up to 60% of older populations have inadequate vitamin D status. Possible reasons include shifts in demographics, less outdoor activity, air pollution, and decrease in vitamin D production in the skin with age.In the June 11, 2007, issue of the Archives of Internal Medicine, Martins and colleagues noted that low 25-hydroxyvitamin D levels were associated with cardiovascular risk factors.
Winkelmann and colleagues described the LURIC Study in the February 2001 issue of Pharmacogenomics that investigated the effect of genetic polymorphisms and plasma biomarkers on cardiovascular health status. This prospective cohort study uses the LURIC study population to evaluate the association of endogenous serum vitamin D levels with cardiovascular and all-cause mortality.
Estrogen-Only Hormone Replacement Therapy May Lower Coronary Artery Disease
A new analysis of the Women's Health Initiative (WHI) trial has found that younger postmenopausal women treated with estrogen-only hormone replacement therapy (HRT) had significantly less coronary artery calcification than their counterparts taking placebo. Dr JoAnn E Manson (Harvard Medical School, Boston, MA) and colleagues report the findings of the WHI-Coronary Artery Calcium Study (WHI-CACS) in the June 21, 2007, issue of the New England Journal of Medicine.
While the results provide further reassurance to younger women that estrogen is unlikely to have an adverse effect on their risk of coronary events, "there is also a suggestion from the data that estrogen may slow the early stages of atherosclerosis," Manson told heartwire. These possible protective effects have been leaped on by at least one body as a vindication of HRT, with the International Menopause Society (IMS) issuing a press release calling the results of WHI-CACS "encouraging," adding that "women can be reassured that estrogen therapy is cardioprotective until at least 65."
But others caution against such extrapolation. Chief of the National Heart, Lung, and Blood Institute WHI branch and second author on the new study, Dr Jacques E Roussouw, told heartwire: "There are two issues that need to be addressed. One is the use of short-term use of HRT around the time of menopause, and I think we can conservatively state that there is no increased risk from this, and there may even be a trend toward benefit in terms of heart disease.""The second issue is the long-term use of HRT for the prevention of chronic disease. We cannot assume that any possible short-term, cardiovascular benefit from hormone therapy to postmenopausal women in their 50s would extend into older ages if they were to continue using hormones. We already know that starting hormone therapy in older women increases their risk of heart disease. And long-term hormone therapy has other risks, such as strokes and venous thromboembolism, and, with the use of combination therapy, breast cancer."
Unfortunately, there will never be an answer as to whether long-term use of HRT is cardioprotective or not, he says, explaining that any trial examining this would likely be unethical and certainly unfeasible. "We no longer believe that estrogen is the elixir of life," he noted, pointing out that there are many other options for the prevention of chronic disease. He is therefore critical of the stance taken by the IMS: "They are quite explicit, stating that there is no reason to be against long-term use of HRT. I totally disagree."
"Clear and Striking" Cardioprotective Effect of Estrogen in Young Women Requires Confirmation
In this latest ancillary study, coronary artery calcium was measured by cardiac computed tomography (CT) scans in 1064 women aged 50 to 59 years from 28 of the original 40 WHI centers across the US, who were randomly assigned to estrogen or placebo at the start of the WHI estrogen-alone trial.
The CT scans were completed an average of 1.3 years after the study was halted prematurely in 2004. No CT scans were performed at baseline.
The findings reveal that those women receiving estrogen (for an average of 7.4 years) were 42% less likely to have severe coronary artery calcium (a score of > 300) than women receiving placebo. And among those who were particularly compliant, women receiving estrogen had a 61% lower risk of severe coronary calcium.
Odds Ratios for Various Categories of Elevation in the CAC Score*CAC scoreConjugated equine estrogensPlaceboOdds ratio (multivariate)Multivariate p
| Intention-to-treat analysis† | n = 537 | N = 527 |
|
|
| <> | 348 | 302 | 1.00 |
|
| 10 - 100 | 100 | 106 | 0.82 |
|
| > 100 - 300 | 48 | 61 | 0.72 |
|
| > 300 | 41 | 58 | 0.58 | 0.03 |
| Analyses restricted to those with 80% or greater adherence to study medication‡ | n = 387 | n = 352 |
|
|
| <> | 262 | 191 | 1.00 |
|
| 10 - 100 | 71 | 78 | 0.67 |
|
| > 100 - 300 | 29 | 45 | 0.43 |
|
| > 300 | 25 | 38 | 0.39 | 0.004 |
*Higher calcium scores indicate greater calcification. All odds ratios were calculated for the estrogen group as compared with the placebo group. Multivariate odds ratios for a calcium score of ≥ 10 (as compared with a score of <>
†In the intention-to-treat group, data in multivariate analyses were from the 858 women with full covariate data
‡Data in multivariate analyses were from the 601 women with full covariate data
"These findings suggest that estrogen leads to less calcified plaque in the coronary arteries, and this is a marker for the extent of atherosclerosis and a predictor of future risk," Manson told heartwire.
The results thus provide support for the hypothesis that estrogen therapy may have cardioprotective effects in younger women, the researchers say, although they emphasize that this requires confirmation in future studies.
For example, there is no way to know whether the reduced plaque levels seen in WHI-CACS will continue to be a reliable indicator of the progression of coronary artery disease in these women as they age.
And "it is also possible that estrogen could reduce the CAC scores but still increase the risk of clinical CHD events, owing to adverse effects on thrombosis and plaque rupture, which are more likely in older women with advanced stages of atherosclerosis. Such a duality of effects would not necessarily apply to younger women with lower burdens of atherosclerosis," they state.In an accompanying editorial, Drs Michael E Mendelsohn and Richard H Karas (Tufts University School of Medicine, Boston, MA) say the results of WHI-CACS "are clear and striking ... [and are] supportive of estrogen's having a cardioprotective effect in younger menopausal women."
"However, it remains important to continue to emphasize that HRT should not be considered as a strategy to prevent cardiovascular disease in women," the editorialists state. "There are proven therapies for cardiovascular disease that remain underused in women."
WHI-CACS Results Do Not Necessarily Support the Timing Hypothesis
The new data add to results reported from WHI in April showing that coronary heart disease risk associated with combined as well as estrogen-only HRT was not significantly increased in women taking it within 10 years of menopause. "I think there is mounting evidence that a woman's age and time since the menopause influence her health outcomes on estrogen, particularly her risk of heart disease," Manson commented to heartwire.
Manson believes that younger women appear to get coronary benefit from estrogen because their endothelia are still healthy, elastic, and able to dilate. "The endothelium needs to be responsive to estrogen and estrogen-receptor function needs to be normal. Once it's already a hardened pipe, you're not going to get the same benefits, and you are more likely to get the risks," she noted.This explanation is the basis for the so-called "timing hypothesis" for HRT, which states that any benefits of HRT in preventing atherosclerosis occur only when the therapy is started during a "window of opportunity" before advanced atherosclerosis develops.
In their editorial, Mendelsohn and Karas say WHI-CACS and the other recent WHI studies support the "timing hypothesis," which "provides a scientific framework within which to understand much of the clinical data from the past two decades, including data from observational studies of HRT, the original HRT reports and now, WHI-CACS."
But not all of the WHI-CACS investigators are comfortable with this concept. Senior author of WHI-CACS Dr Marcia Stefanick (Stanford University, Palo Alto, CA) told heartwire: "I don't think we have evidence that there is a critical time window in which estrogen must be initiated to get benefit, after which there is an adverse response. I agree that older women are worse off if they initiate estrogen than young women are, but I don't think we have evidence that young women are better off by initiating estrogen than by not initiating it, as far as actual heart disease is concerned — rather, we have bits and pieces that relate to risk factors which may or may not provide useful information about long-term risk."
"It might sound like a nuance, but I think it's important not to resurrect the idea that estrogen is cardioprotective for younger women, as we do not have data to support that — certainly not from the data being presented in NEJM this week — though it does provide some reassurance that estrogen is not harmful for younger women, who are the group that may benefit from estrogen's effects on menopausal symptoms," she continues.
In addition, Stefanick says the WHI-CACS results, "do not address the timing hypotheses because we only studied women aged 50 to 59 and we have only one (cross-sectional) time point, so there are no longitudinal data — I don't think the whole author group believes in the concept; however, this is different from agreeing that the data may support the hypothesis — they clearly do not provide evidence against it — but a very different kind of study would be needed to test the hypothesis.
A New Safety Margin of 65?
Despite all of these caveats, the IMS has issued an incredibly upbeat press release: "This study reaffirms what was actually known for many years ... estrogen has a wide range of well-documented beneficial metabolic and vascular effects: it reduces the pace of accumulation of atherosclerosis, and decreases the risk of coronary events, provided the treatment is started early in the menopause."
And because the CT scans in WHI-CACS were performed at a mean age of 64.8 years, the results suggest a "new safety margin" for age and duration of estrogen therapy, it states. "Women can be reassured that estrogen therapy is cardioprotective until at least 65."IMS does point out, however, that: "since most, if not all, women do not start HRT at an old age, safety concerns on its possible adverse cardiac effects are actually invalid for the vast majority of users."
Roussouw says he has no problem with the use of HRT for moderate to severe menopausal symptoms, at the lowest effective dose for the shortest duration, but the menopause societies, "speak out of both sides of their mouths."
He is most critical of the IMS, pointing out that the British and North American menopause societies encourage prescribing on an individual basis, and only for a maximum of 10 years. Nevertheless, he feels that 5 years would be a better option, and points out that most women discontinue HRT after a year or two anyway.
But in terms of the prevention of chronic disease, he believes doctors should steer clear of HRT. "Hormones are so unusual, they have so many adverse effects and don't have a good profile. Cardiologists have many options for the prevention of heart disease, and they have never been that comfortable with HRT anyway," he says.
And even the Osteoporosis Foundation in the US no longer recommends HRT as first-line use for the prevention of osteoporosis in those at risk, he notes.[IMS did not respond to heartwire's request for an interview.]New Engl J Med. 2007;356:2591-2602, 2639-2641.
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Clinical Context
According to the current authors, in the WHI, among women aged 50 to 59 years who had undergone a hysterectomy and received estrogen-only hormone replacement therapy, there was a reduced rate of coronary revascularization, with a hazard ratio (HR) of 0.55.
This finding was consistent with earlier observational findings that younger women who initiated estrogen replacement had a lower rate of coronary artery events.
According to the authors, calcified atheroma detected by CT scan of the heart reflect the chronic inflammatory process associated with atherosclerosis and may be used as a measure of cardiovascular risk factor.
This is a cross-sectional study of postmenopausal women aged 50 to 59 who had undergone hysterectomy and had been randomized to the estrogen and placebo group of the WHI. The study examines coronary artery calcium plaque burden as determined by noninvasive CT heart scan after completion of the WHI trial.
Can You Identify these Common Gynecological Problems?
Introduction
Whether you're actively studying for the United States Medical Licensing Examination (USMLE) or just trying to keep up with all the information being thrown your way during medical school, these quizzes will help you sharpen your skills. Read the question thoroughly, choose the best answer, then click to the next page to see if you are right.We'll provide a new practice quiz each week, so check back regularly!
Question 1
A 50-year-old woman complains of leakage of urine. After genuine stress urinary incontinence, which of the following is the most common cause of urinary leakage?
- Detrusor dyssynergia
- Unstable bladder
- Unstable urethra
- Urethral diverticulum
- Overflow incontinence
Breast Cancer Within 2 Years of Childbirth Linked to Poor PrognosisWomen who have breast cancer within 2 years of their last pregnancy, or 2 to 4 years after delivery, are more likely to have a poor prognosis, according to the results of a study reported in the May issue of Obstetrics & Gynecology.
"Recent research suggests that childbirth occurring shortly before a breast cancer diagnosis appears to have a growth-enhancing effect on malignant or premalignant cells, resulting in more advanced disease at diagnosis and less chance of survival," write Linda Dodds, PhD, from Dalhousie University in Halifax, Nova Scotia, Canada, and colleagues. "The availability of a provincewide perinatal database and a provincial cancer registry enabled us to evaluate the effect of the time interval between delivery and diagnosis on the extent of disease at diagnosis and survival after breast cancer diagnosis."
Women who delivered an infant in Nova Scotia, Canada, between 1980 and 2001 were identified from a provincial perinatal database. Linkage to the Nova Scotia Cancer Registry allowed ascertainment of primary breast cancer diagnoses among women younger than 50 years. Relative risks and Cox proportional hazards ratios were used to determine the relationship of time from childbirth and other pregnancy factors to diagnosis of breast cancer, extent of disease at diagnosis, and survival after diagnosis.
Of 123,323 women who gave birth during the study period, 716 were diagnosed with invasive breast cancer. Compared with women diagnosed with breast cancer more than 5 years after their last delivery, women diagnosed with breast cancer less than 5 years after their last delivery were more likely to be diagnosed with later-stage disease and had poorer survival, even after adjustment for stage of disease (<>Clinical Context
Previous research has suggested that breast cancer diagnosed within 2 years after childbirth is associated with multiple negative prognostic factors vs breast cancer diagnosed at least 5 years after childbirth.
In a study by Daling and colleagues of 1174 women with invasive ductal breast cancer, which was published in the March 2002 issue of Cancer Epidemiology, Biomarkers, and Progression, women with breast cancer diagnosed within 2 years after childbirth were more likely to have tumors that were progesterone receptor negative, p53 positive, and have a high histologic grade and mitotic count. Also the mortality rate among women with breast cancer within 2 years of childbirth was double that of women whose last delivery occurred at least 5 years ago.
The current study uses a large women's health database to determine the effect of different pregnancy and maternal factors on the prognosis of breast cancer.
Smokers Might Benefit From Earlier Colon Cancer Screening
An examination of 3540 patients has found that current smokers were diagnosed with colon cancer approximately 7 years earlier than people who had never smoked. The study is also among the first to link exposure to second-hand smoke, especially early in life, with a younger age for the onset of colon cancer.
The article was published in the February 9 Online First issue of the Journal of Cancer Research and Clinical Oncology.
"The message for physicians and patients is clear: When making decisions about colon cancer screening, you should take into account smoking history as well as family history of disease and age," said lead author Luke J. Peppone, PhD, research assistant professor of radiation oncology at the James P. Wilmot Cancer Center at the University of Rochester, in Rochester, New York.
Dr. Peppone's group examined data from patients diagnosed with colorectal cancer between 1957 and 1997 at Roswell Park Cancer Institute (RPCI) in Buffalo, New York. (Dr. Peppone joined the University of Rochester in 2007, coming from RPCI. His coauthors are from RPCI.)
During the 40-year period, smoking habits changed with a decrease in the percentage of current or active smokers and an increase in the percentage of former smokers. Still, the age at diagnosis of colon cancer was 6.8 years younger among current smokers and 4.3 years younger among former smokers who quit less than 5 years earlier, the results showed. People who quit more than 5 years earlier had no significant increased risk.
However, people who reported starting smoking in their early teens (before age 17 years) or who smoked heavily (≥ 1 pack a day) were the most likely to be diagnosed with cancer at a much younger age than their never-smoking counterparts. Past exposure to second-hand smoke was an additional significant risk factor. In fact, when active and passive smoking were combined into 1 subgroup, the age at diagnosis was nearly 10 years earlier, Dr. Peppone said.
Although smoking is a well-known risk factor for many cancers, only recent studies have suggested that cigarettes might cause colon cancer.
The biologic reasons for the association between cigarette smoke and the risk for colon cancer are unclear. However, researchers believe that cigarette smoke reduces the body's resistance to malignant neoplasms, just as smoking can depress immune function in general, impairing the body's ability to fight off infections and viruses. After smoke is swallowed, carcinogens from smoke reach the bowel through direct circulation or through the intestines.
Colorectal cancer is the third most commonly diagnosed cancer among men and women. Genetics account for approximately 10% of new cases, the study said, whereas more than 75% of cases arise from sporadic mutations and environmental and lifestyle factors, such as smoking, poor diet, alcohol use, lack of exercise, and obesity.
Clinical Context
Colorectal cancer is the third most commonly diagnosed cancer in the United States, and family history is a significant risk factor for this cancer.
However, 75% of cases of colorectal cancer are estimated to arise from modifiable risk factors and sporadic mutations. Modifiable risk factors for colorectal cancer include a diet high in red meat or low in vegetables, a high body mass index, and a low rate of physical activity. However, the use of nonsteroidal anti-inflammatory drugs may reduce the risk for colorectal cancer.
Smoking has also been associated with an increased risk for colorectal cancer, but few studies have examined how smoking affects the timing of diagnosis of colorectal cancer. The current study addresses this issue.
Long-Term Use of Ibuprofen Lowers Alzheimer's Disease Risk
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, lowers the risk for Alzheimer's disease.
A new study by investigators at Boston University School of Medicine found that individuals who specifically used ibuprofen for more than 5 years had a 40% reduced risk for Alzheimer's disease. In addition, there appeared to be a dose-response effect so that the longer ibuprofen was used, the greater the risk reduction.
Individuals who used other types of NSAIDs for more than 5 years were 25% less likely to have the disease vs nonusers.
Although other NSAIDs such as indomethacin were associated with lower risk, agents such as celecoxib did not appear to have an effect on the risk for dementia. "These results suggest that the effect may be due to specific NSAIDs rather than all NSAIDs as a class," study author Steven Vlad, MD, said in a statement from the American Academy of Neurology.
"Some of these medications taken long-term decrease the risk of Alzheimer's disease, but it's very dependent on the exact drugs used. It doesn't appear that all NSAIDs decrease the risk at the same rate. One reason ibuprofen may have come out so far ahead is that it is by far the most commonly used," he added.
The study is published in the May 6 issue of Neurology.
Suppressors More Likely to Have a Protective Effect?
The aim of the study was to examine the effects of long-term use of specific NSAIDs on the risk for incident Alzheimer's disease. The investigators also looked at whether NSAIDs that suppress levels of amyloid beta-1-42 (Aβ 1-42), a major component of senile plaques in Alzheimer's disease amyloid, would be more likely to have a protective effect against the disease.
Study subjects included US veterans 50 years and older who received medical care and prescriptions through the US National Veterans Affairs Health Care system.
Researchers identified 49,349 subjects in whom incident Alzheimer's disease developed from 1998 to 2005 and compared their use of NSAIDs with that of 196,850 matched control subjects from the same population.
Exposure to NSAIDs was categorized into 7 periods of duration of use: no use, up to 1 year, more than 1 year but up to 2 years, more than 2 years but up to 3 years, more than 3 years but up to 4 years, more than 4 years but up to 5 years, and more than 5 years.
The investigators then tested the link between the development of the disease and the use of any NSAID, any NSAID excluding nonacetylated salicylates, each NSAID class, each individual NSAID, and Aβ 1-42–suppressing NSAIDs (which in this study included ibuprofen, indomethacin, sulindac, and diclofenac).
Among the study subjects, 42.2% of case patients and 40.2% of control subjects received at least 1 prescription for a NSAID during the study period. Arylpropionic acids, which include the agents ibuprofen and naproxen, were the most frequently prescribed class.
No Clinical Implications
Approximately 15% of case patients and control subjects used NSAIDs for longer than 1 year, with almost half of these using either ibuprofen or naproxen. A total of 400 case patients and 1952 control subjects used NSAIDs for longer than 5 years.
Compared with individuals who did not use NSAIDs, the adjusted odds of Alzheimer's disease decreased from 0.98 for those with 1 year of use or less to 0.76 in those with more than 5 years of use. Among ibuprofen users, it decreased from 1.03 to 0.56.
The researchers found no protective effect for cyclooxygenase-2 inhibitors or nonacetylated NSAIDs.
Unfortunately, say the researchers, because of the small numbers of patients taking other Aβ 1-42–suppressing NSAIDs such as sulindac and flurbiprofen, it was not possible to determine whether they had a similar protective effect as ibuprofen.
For the same reason, the study also could not confirm that other non–Aβ 1-42 suppressors had no effect.
Because this research is observational, no clinical recommendations can be extrapolated from these results. However, the researchers note, the study has implications for future trials of NSAIDs in Alzheimer's disease, particularly with ibuprofen.
Clinical Context
NSAIDs might postpone the onset of Alzheimer's disease, as reported by de Craen and colleagues in the January 2005 issue of the American Journal of Epidemiology. However, results from the Alzheimer's Disease Anti-Inflammatory Prevention Trial, published in the May 22, 2007, issue of Neurology, showed that naproxen or celecoxib did not decrease the risk for Alzheimer's disease after 3 years of follow-up.
Different NSAIDs might differ in their effect on Alzheimer's disease. For example, Morihara and colleagues noted in the June 2005 issue of Neuropsychopharmacology that the NSAID ibuprofen reduces serum levels of Aβ 1-42, which is present in senile plaques in Alzheimer's disease amyloid.
Guidelines Issued for Screening Men for Osteoporosis
The American College of Physicians (ACP) has issued new clinical practice guidelines for screening men for osteoporosis, which are published in the May 6 issue of the Annals of Internal Medicine, along with a systematic review of the evidence. The new guidelines recommend that clinicians assess risk factors for osteoporosis in older men and that clinicians obtain a dual-energy x-ray absorptiometry (DXA) scan for men at increased risk for osteoporosis who are candidates for drug therapy.
"Older men, especially those over the age of 65, need to be assessed regularly for risk factors for osteoporosis," lead author Amir Qaseem, MD, PhD, MHA, a senior medical associate in ACP's Clinical Programs and Quality of Care Department, says in a news release. "Osteoporosis is not just a women's disease."
Osteoporosis, which is characterized by low bone mass and structural deterioration of bone tissue, results in bone fragility and increased risk for hip, spine, and wrist fractures. The prevalence of osteoporosis is currently estimated to be 7% in white men, 5% in African American men, and 3% in Hispanic American men.
Supporting Dr. Qaseem's statement that osteoporosis is not just a women's health issue are rising rates of osteoporosis among men, which are projected to increase by nearly 50% during the next 15 years, with rates of hip fracture expected to double by 2040.
The National Osteoporosis Foundation has recommended that men 70 years of age and older undergo bone mineral density (BMD) testing. Also, BMD testing is recommended in postmenopausal women and men aged 50 to 70 years when the patient's risk factor profile indicates potential problems. And, in those who have had a fracture, BMD testing is recommended to assess the severity of the fracture.
The evidence to date shows that osteoporotic fractures are associated with significant morbidity and mortality in men, resulting in substantial disease burden, death, and healthcare costs. For men, the 1-year mortality rate after hip fracture is twice that in women.
The guidelines are based on a systematic review of evidence from previously published studies, authored by Hau Liu, MD, MBA, MPH, and colleagues. The reviewers searched MEDLINE from 1990 to July 2007 for articles that evaluated risk factors for osteoporotic fracture in men or that evaluated a non-DXA screening test against a gold standard of DXA. They also searched references of previous reviews and solicited articles from experts.
Two reviewers independently abstracted data from each article, assessed performance characteristics of the screening tests, and evaluated the quality of 167 studies included in the meta-analysis.
Based on this meta-analysis, risk factors for low BMD–related fracture in men and women were age (> 70 years), body mass index (BMI) less than 20 to 25 kg/m2, weight loss of more than 10%, physical inactivity or sedentary lifestyle, previous osteoporotic fractures not resulting from significant trauma, prolonged or ongoing use of certain drugs (eg, prednisone or other corticosteroids), and low-calcium diet.
In men, androgen deprivation therapy and spinal cord injury were also associated with the risk for osteoporosis.
The reviewers also looked at 102 additional studies evaluating 15 other potential risk factors, but data in men were too limited to allow firm conclusions.
Based on 20 articles reporting on diagnostic studies and use of a T-score threshold of –1.0, calcaneal ultrasonography had a sensitivity of 75% and a specificity of 66% for osteoporosis diagnosed with DXA as the gold standard. Sensitivity for osteoporosis detected with DXA was 81%, and specificity was 66% for the Osteoporosis Self-Assessment Screening Tool, with use of a risk score threshold of –1.
The reviewers concluded that non-DXA tests were either insufficiently sensitive or were lacking sufficient data to draw firm conclusions regarding their value for screening.Limitations of this review were paucity of data on radiography, bone geometry variables, and other screening tests.
Based on this review, the ACP issued the following recommendations:
- Clinicians should periodically evaluate older men for risk factors for osteoporosis, using an individualized assessment (grade: strong recommendation; moderate quality evidence).
- For men who are at increased risk for osteoporosis and who are candidates for drug therapy, a DXA scan should be performed (grade: strong recommendation; moderate quality evidence).
- The ACP also recommends additional research to evaluate osteoporosis screening tests in men.
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Clinical Context
During the next 15 years, rates of osteoporosis among men are projected to increase by nearly 50%, and by 2040, rates of hip fracture in men are expected to double. Previous studies have shown that osteoporotic fractures are linked to significant morbidity and mortality in men, with 1-year mortality rate after hip fracture twice that of women.
Previous guidelines and systematic reviews have addressed management of osteoporosis in women, but the US Preventive Services Task Force has not issued guidelines for screening for osteoporosis in men. The only existing recommendation before the ACP issued the present guidelines regarding osteoporosis screening in men was issued by the National Osteoporosis Foundation. That group has recommended that men 70 years of age and older undergo BMD testing.
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