Women with epilepsy who want to have children may find it hard to become pregnant — a prospective study from India has found a high rate of infertility among epileptic women.
The study, which followed 375 women with epilepsy for up to 10 years, found that 38.4% failed to conceive, according to Sanjeev Thomas, MD, of the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Trivandrum, India, and colleagues.
Factors associated with a greater likelihood of being infertile included being older than 25, less than 10 years of education, and the use of three or more antiepileptic medications (P<0.05 for all), Thomas and co-authors reported in the Oct. 12 issue of Neurology.

“Based on the findings of this study, women with epilepsy should be counseled about the potential risk of infertility and referred for an infertility evaluation if there is a failure to conceive,” wrote Alison Pack, MD, of Columbia University, in an accompanying editorial.

Thomas and colleagues followed women with epilepsy who enrolled in India’s Kerala Registry of Epilepsy and Pregnancy in the preconception phase (within 15 days of their last menstrual period) from 1998 to 2007. All of the women planned to get pregnant.

Over a follow-up of one to 10 years, among the 375 women included in the analysis, 231 became pregnant and 144 did not. Pregnancy occurred within two years for most of the women who did conceive.

Although the study did not include a control group, the researchers compared the infertility rate with that of a similarly-aged group of married women living in Kerala, finding it to be more than twice as high in the women with epilepsy (38.4% versus 15.13%).

Among the study cohort, only 3.7% were not taking any antiepileptics; most (56.2%) were on monotherapy, 22.9% were taking two drugs, and 15.5% were taking at least three epilepsy medications.

The rate of infertility increased linearly as exposure to antiepileptics increased from none (7.1%) to three or more (60.3%) (P=0.001 for trend).

Polytherapy was associated with a greater likelihood of infertility compared with monotherapy (OR 1.33, 95% CI 1.11 to 1.60).

When looking at specific drugs, the researchers found that only phenobarbital had a definite relationship with the likelihood of infertility — both as monotherapy (OR 1.52, 95% CI 0.94 to 2.46) and as either monotherapy or polytherapy (OR 1.43, 95% CI 1.09 to 1.87).

Other antiepileptics, including valproate, did not appear to be related to infertility.

“The enzyme-inducing antiepileptic drugs like phenobarbital and carbamazepine may influence the concentration of steroid hormones and the sex hormone binding globulin, resulting in decreased bioavailability of estradiol, which in turn may lead to menstrual irregularity,” Thomas and co-authors explained.

Low educational levels and being age 25 or older were both determined to be significant predictors of infertility (P<0.05 for both).

In addition, using at least three antiepileptics was associated with a greater likelihood of infertility, which “may be due to the direct adverse effect of polytherapy or the indirect effect of underlying refractory epilepsy that required polytherapy,” according to the researchers.

The latter explanation was supported by Steven Pacia, MD, director of the Comprehensive Epilepsy Center at Lenox Hill Hospital in New York City.

In a statement, he said that “patients with more severe epilepsy can be expected to have a higher incidence of cognitive problems, mood disorders, and hyposexuality, which may also lead to higher rates of infertility.”

Thomas and colleagues acknowledged that their study was limited by the lack of a control group, and urged that larger studies addressing demographic factors such as age and educational status need to be carried out.

The study was sponsored by the Indian Council of Medical Research.

Thomas reported serving as editor of Annals of Indian Academy of Neurology.

Pack reported serving as a consultant to Pfizer and receiving funding from the NIH.

AUBURN, Ala., Feb. 9 – When parents fight, children lose sleep over it. And when parents fight with hostility or treat each other with indifference, the negative effects on children can be long lasting, reported investigators in two studies.

In separate research published in the January/February issue of Child Development, investigators at Auburn University here and colleagues found that eight- and nine-year old children from high-conflict homes didn’t sleep as long or as soundly as kids from more harmonious homes.

The data suggests that even in families with normal levels of conflict, parental arguments and anger can disrupt children’s sleep, said Mona El-Sheikh, Ph.D. “This is significant because even mild loss of sleep can disrupt attention, alter information processing, weaken motivation, increase irritability and diminish emotion control,” she added.

In a separate but thematically related study, psychologist Patrick T. Davies, Ph.D., of the University of Rochester (N.Y.) and colleagues found that in households where parents treat one another either with hostility, or with disengagement or indifference, children have significantly heightened distress reactions, even when the parents treat the children warmly.

“Our results highlight the possibility that several different types of conflict between parents may negatively affect the well-being of children over time,” said Dr. Davies. “Conflict between parents may have distinct meanings and implications for the child and family system even after considering the effects of parenting difficulties.”

In the sleep study, Dr. El-Sheikh and colleagues looked at martial conflict as a predictor of the quality and quantity of sleep in 54 healthy eight- to nine- year-olds in the community.

The investigators asked mothers, fathers and children to report separately on marital conflict. They measured the quantity and quality of the child’s sleep on seven consecutive nights using an actigraph, a lightweight device the size of a wristwatch that the child wears during sleep. The actigraph measures sleep onset time, sleep end or morning awakening time, total sleep minutes, sleep duration, and percentage of deep sleep.

The authors found that “increased marital conflict was associated with disruptions in the quantity and quality of children’s sleep as well as subjective sleepiness, even after controlling for child age, ethnic group membership, socio-economic status, sex, and body mass index (p

VIENNA — After the introduction of highly active antiretroviral therapy (HAART) for people living with HIV infection, the number of patients being treated grew five-fold in one Canadian province, but the number of new cases has been cut in half.

Between 1996 and 2009, the number of patients receiving combination HAART therapy increased from 837 individuals to 5,413 (P=0.002), according to Julio Montaner, MD, of the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, writing online in The Lancet.

During the same time period, the number of new HIV diagnoses tumbled from 702 a year to 338 — a 52% decrease (P=0.001).

“The overall correlation between number of individuals on HAART and number of new HIV diagnoses per year was -0.89 (P<0.0001),” Montaner observed in his paper, published in conjunction with the International AIDS Conference here.

The researchers observed three distinct phases of therapy, which correlated with changes in treatment paradigms: Between 1996 and 1999, during the initial rollout of HAART, there was a steep increase in number of individuals on the therapy (258%, P=0.021). During this period, new HIV diagnoses per year decreased sharply (-40%, P=0.003). Between 2000 and 2003, HAART use increased slightly (9%, P<0.0001) because of the balance between treatment interruptions and HAART initiations involving new and returning patients. During this period, new HIV diagnoses per year also remained fairly stable (5%, P=0.954). Between 2004 and 2009, there was a second slow but steady increase in the number of individuals on HAART (51%, P<0.0001), attributable to new IAS-USA guidelines, which recommended against structured treatment interruptions. During this third period, new HIV diagnoses per year decreased substantially (-23%, P<0.0001).

“Our results show a strong and significant association between increased HAART coverage, reduced community viral load, and decreased number of new HIV diagnoses per year,” Montaner wrote.

He noted that residents of British Columbia have centralized and free access to healthcare making the ecological study possible. However, he observed that as an ecological study, “our results cannot be taken as definitive proof of causality.”

Montaner argued, however, that, “taken together, the available evidence strongly suggests that community viral load is a key driving force of new HIV diagnoses and can be successfully modulated through effective expansion of HAART coverage within medical guidelines.

In commenting on the trial, also in The Lancet, Franco Maggiolo, MD, and Sebastiano Leone, MD, of Ospedali Riuniti, in Bergamo, Italy, wrote, “The beneficial effect of HAART in epidemic terms occurs because the widespread use of antiretroviral drugs reduces, at a population level, the average viral load, translating into an average reduction of infectivity and transmission.”

“To obtain these results, two conditions are fundamental: First, the availability of potent effective drugs that could prevent the selection of resistant mutants over time. And second, effective programs to identify HIV-infected individuals who are unaware of their status. The latter group is nowadays the most demanding problem, and today’s data draw attention to this challenge,” they added.

The study was funded by the Ministry of Health Services and Ministry of Healthy Living and Sport, Province of British Columbia; the U.S. National Institute on Drug Abuse; the U.S. National Institutes of Health; and the Canadian Institutes of Health Research.

Montaner disclosed financial relationships with Merck, Gilead, ViiV Healthcare, and Clinical Care Options. Other researchers reported financial relationships with GlaxoSmithKline, Merck, Viiv, Virco, Quest, Abbott and Pfizer.

Maggiolo disclosed financial relationships with Abbott, Basyer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp and Dohme, Roche, and Tibotec. Leone disclosed financial relationships with from Pfizer and Wyeth Lederle.

AARHUS, Denmark, Feb. 4 — The first-trimester death of a mother’s close relative may be associated with the child’s eventual development of schizophrenia, according to a national registry.

The adjusted relative risk that a child would develop schizophrenia after age 10 was 1.67 (95% CI 1.02 to 2.73) when the mother’s husband, parent, or other close relative of the mother died during the first trimester, found Preben Bo Mortensen, M.D., of the University of Aarhus, and colleagues.

But family members’ deaths at other times did not increase the relative risk; nor did illness in the family at any point in pregnancy, the investigators reported in the February issue of the Archives of General Psychiatry.

They calculated that about 0.3% of all schizophrenia cases could be attributed to deaths of mothers’ family members in early pregnancy. The researchers said theirs is the largest such study ever done with data on clearly defined and specifically timed severe maternal stress events.

Dr. Mortensen and colleagues examined records associated with 1.38 million Danish births from 1973 to 1995.

The country’s national health registry allowed the researchers to check maternal records against those of close relatives, as well as tracking later diagnoses of schizophrenia among the offspring.

A total of 7,331 cases of schizophrenia developed in this population.

The researchers identified 21,987 mothers who lost a husband, parent, sibling, or another child from six months before conception through pregnancy. Another 14,206 mothers had close relatives diagnosed with cancer, heart attack, or stroke during this period.

Relative risks were calculated with the rate of schizophrenia in people whose mothers did not experience a family death or illness during the study period serving as the baseline. They were adjusted for calendar year, age, gender, place of birth, and maternal age.

Serious illness in the family did not significantly increase the risk that the unborn child would later develop schizophrenia.

Nor did a relative’s death increase the risk when it occurred up to six months before conception or in the second or third trimester.

Family history of mental illness did not put offspring at greater risk of schizophrenia associated with severe maternal stress.

In fact, the risk of schizophrenia in offspring was higher when a mother suffering a close relative’s death during the first trimester had no family history of mental illness (RR 2.64, 95% CI 1.31 to 5.29).

There was no significant increase in risk when women with a family history of mental illness had a close relative die during the first trimester (RR 1.87, 95% CI 0.70 to 4.99). But the researchers noted that only four cases fell into this category.

In sum, the researchers said, the effect of severe first-trimester maternal stress on schizophrenia in offspring “is independent of a range of factors known to influence risk of schizophrenia, such as offspring sex, age, family history of mental illness, place of birth, and maternal age.”

They noted that their data on maternal family members were incomplete for mothers who left their parents’ homes before 1968, about 49% of their sample. These women were different in some demographic respects from the other mothers in the study. But Dr. Mortensen and colleagues said sensitivity analyses indicated that the potential confounding effects were small or negligible.

Their study did not examine potential mechanisms directly. Dr. Mortensen and colleagues said that stress-induced increases in maternal corticotrophin-releasing hormone may affect neuronal development early in fetal gestation. They cited earlier research suggesting that a feto-placental barrier protects the fetus’s developing brain from maternal stresses, but it is not fully functional until later in pregnancy.

The researchers pointed out that other maternal stressors might also have an impact on schizophrenia.

“Less catastrophic, more common events may also increase the risk of schizophrenia in offspring and that maternal stress in a broader sense may have a greater population impact,” they wrote.

The study was funded by Tommy’s the Baby Charity and the Stanley Medical Research Institute.

No potential conflicts of interest were reported.

Primary source: Archives of General Psychiatry

Source reference:

Khashan A, et al “Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events” Arch Gen Psychiatry 2008; 146-52.

CHICAGO — Patients with rheumatoid arthritis (RA) who respond well initially to methotrexate monotherapy may be able to maintain a good outcome on that drug alone, with no radiographic progression, a researcher said here.

Among patients who stayed on methotrexate monotherapy, mean progression in radiographic Sharp scores was only 0.15 after two years, according to James R. O’Dell, MD, of the University of Nebraska Medical Center in Omaha, and colleagues.

This was not significantly different than radiographic outcomes for patients who began treatment with combination therapy, whose mean Sharp score was 1.01 at two years or for patients who started on methotrexate alone but stepped up to a combination regimen after an inadequate response.

Those step-up patients had a mean Sharp score of 1.22 at 24 months, O’Dell said in an oral presentation at the annual meeting of the American College of Rheumatology (ACR).

Current guidelines from both the ACR and the European League Against Rheumatism recommend methotrexate as the first disease-modifying drug for patients with RA.

“However, there have been no data from randomized trials comparing methotrexate alone, with step-up only after a lack of initial response, or as part of an early combination regimen,” said O’Dell, who is the incoming president of ACR.

To explore this issue, his group analyzed data from the large, randomized, investigator-initiated trial known as TEAR (Treatment of Early Aggressive Rheumatoid Arthritis), which included 755 patients with early RA.

All patients had early but poor-prognosis disease, meaning they were positive for either rheumatoid factor or antibodies to anti-cyclic citrullinated protein, or who already had two joint erosions visible radiographically.

The regimens compared in TEAR were: Methotrexate alone, beginning in doses of 10 mg and gradually increased to 20 mg if any swollen or tender joints remained at six and 12 weeks Methotrexate plus the tumor necrosis factor inhibitor etanercept (Enbrel) Methotrexate plus sulfasalazine and hydroxychloroquine

In the original trial, by 24 weeks, patients in the combination arms showed clinically better responses on the Disease Activity Score in 28 joints (DAS28). But by 36 weeks, after nonresponders had stepped up to combination therapy, the difference was lost.

With regard to radiographic erosions, from weeks 48 through 102, there were no differences between the groups in Sharp scores, “suggesting that there was no radiographic penalty for waiting to make a clinical decision to step up,” O’Dell said.

In the original trial, 28% of patients on methotrexate monotherapy achieved a DAS28 of 3.2 or less, indicating low disease activity and therefore remained on methotrexate alone for the remainder of the trial.

At baseline, patients who had a “durable excellent response” to methotrexate were more often men, had slightly shorter disease duration, and somewhat lower body mass index, though these differences were not statistically significant.

They also had lower mean DAS28 scores, at 5 compared with 5.9, but this difference was not large enough to select patients at baseline who might ultimately have the best response, O’Dell said.

Among patients on methotrexate alone, a 20% reduction in signs and symptoms of disease (ACR20) was seen in 84% of those who did not step up to combination therapy compared with 34% of those who did step up because, by definition, they had an inadequate response.

A decrease of 1.2 points on the DAS28 is considered clinically significant, which was seen in 57% of the methotrexate monotherapy patients at 24 weeks, he noted.

At that time point, the same percentage of patients also had reached the DAS28 target of 3.2.

In conclusion, almost one-third of patients given methotrexate alone had an “excellent” response that persisted out to two years with no evidence of radiographic progression, he said.

“These findings are reassuring because we are often told that even patients who are doing very well on conventional therapy can have substantial radiographic progression. That clearly was not seen in this very large randomized study,” O’Dell said.

The study was funded by the National Institutes of Health, the Veterans Administration, and by a grant from Amgen.

O’Dell had no disclosures, while co-investigators reported receiving grant support from various companies including Pfizer, Abbott, Roche, Genentech, Centocor, and Amgen.

Adults who had had herpes zoster were 31% more likely to suffer a stroke within a year than were people who had not had shingles, Taiwanese researchers reported online in Stroke.

“We confirmed that in the general population, the risk for stroke increased after a zoster attack and additionally found that strokes after such attacks were more frequent than expected,” Jiunn-Horng Kang, MD MSc, of Taipei Medical University Hospital, and colleagues wrote.

Since the 1970s, vasculopathy and stroke have been reported following cases of shingles, yet little hard data is available regarding the exact frequency and risk of stroke occurring after herpes zoster attacks, the researchers said.

So, they used the Taiwan National Health Research Institute database to estimate the incidence of stroke among 7,760 adult patients treated for herpes zoster between 1997 and 2001. These patients were compared with 23,280 who had not been diagnosed with shingles.

They found that 439 patients (1.41%) suffered strokes during a one-year follow-up period. Of those, 133 strokes were among patients with herpes zoster (1.71% of that group) and 306 occurred among those in the comparison group (1.31%). The difference was significant at P<0.05.

A log rank test indicated that patients who had been treated for shingles had significantly lower one-year stroke-free survival rates than the control subjects (P<0.001).

The group with herpes zoster differed from controls in incidence of hypertension, diabetes, coronary heart disease, renal disease, heart failure, and carotid/peripheral vascular disease. The differences between cohorts were statistically significant for all of these conditions.

The researchers also found that patients with herpes zoster infections that included eye complications (herpes zoster ophthalmicus) were more than 300% more likely to suffer stroke within a year (95% CI 2.01 to 9.03; P<0.001).

Patients 45 or older were at the greatest risk for stroke after treatment for shingles and the researchers theorized that the frequency and severity of vasculopathy may increase in elderly individuals with atherosclerosis and weakened immune systems.

However, they noted, vasculopathy directly related to varicella zoster virus did not explain the unexpectedly high risk of stroke in these patients.

They suggested that the infection could initiate a secondary atherosclerosis that progresses over time to cause a delayed stroke or that chronic pain resulting from shingles could distress patients enough to put them at risk of stroke.

Another possibility, the researchers said, was that in some cases an underlying medical condition or stressful conditions could put patients at risk for both shingles and stroke, and that the two conditions are not causally related.

Finally, the researchers also found a higher frequency of several cardiovascular risk factors among the patients with herpes zoster, suggesting that the presence of the herpes virus could accelerate atherosclerosis development.

“In addition, the patient who has cardiovascular factors might also have poorer health, putting them at risk of herpes zoster,” the authors wrote. “We postulate that this cause-and-effect relationship between shingles and cardiovascular risk factors is bidirectional. Nevertheless, stroke development risk remained higher in patients with herpes zoster after adjusting for these cardiovascular risk factors.”

The authors cautioned that shingles patients who did not develop skin lesions could have gone undiagnosed and that herpes zoster vasculopathy can manifest in various ways, such as encephalitis, which the study did not include.

Also, they said, the database used for the study did not included information on potentially confounding factors such as obesity, smoking, and family history.

The authors reported no outside sources of funding or financial conflicts of interest.

Cachexia, a syndrome marked by anorexia, significant weight loss, and muscle wasting, occurs in approximately 50% of oncology patients, with even higher rates in patients with gastrointestinal tumors. In pancreatic cancer, for example, approximately 80% of patients become severely malnourished.

The cancer cachexia syndrome is not only distressing for patients and their families, it is also associated with a much worse clinical outcome. Malnourished patients undergoing surgery for cancer have morbidity and mortality rates three or four times greater than their better-nourished counterparts, and weakened, wasted patients also tolerate chemoradiation poorly.

Evidence exists that cytokines play a role in the pathogenesis of the anorexia commonly associated with cachexia. It has been suggested, for instance, that by mimicking the hypothalamic effects of excessive negative feedback signaling from leptin by persistent stimulation of anorexigenic peptides, such as corticotrophin releasing factor, or by inhibition of the neuropeptide Y pathway, cytokines could induce anorexia. Thus, modulating cytokine expression in cancer patients may also affect cancer-associated anorexia.

Accordingly, a team of British researchers embarked on a study based on the hypothesis that thalidomide would be effective in attenuating or reversing the weight loss seen in patients with cancer cachexia.

In a report published in the latest issue of the gastroenterology journal Gut, the researchers noted that thalidomide has complex immunomodulatory and anti-inflammatory properties. It has been shown, for example, to downregulate the production of TNF-a and other proinflammatory cytokines and to inhibit angiogenesis and previous studies suggested that it may have beneficial effects in patients with cachexia. As an example, in several small clinical trials thalidomide has been effective in ameliorating HIV associated wasting and the weight loss seen in subjects with active pulmonary tuberculosis. Further, an open label pilot study of thalidomide in the treatment of cachexia in 11 patients with inoperable oesophageal cancer reported that thalidomide reversed weight loss over the two weeks of the trial and this was associated with an increase in lean body mass.

Between 1999 and 2003, the researchers undertook a prospective, randomized, double-blind, placebo-controlled study on 50 patients with cachexia due to inoperable pancreatic cancer. At baseline, the patients underwent a detailed physical examination that included measurement of height, weight, upper arm circumference, and triceps skinfold thickness.

The patients, all of whom had already lost 10% of their normal body weight, were then randomized to receive either 200 mg daily of thalidomide or placebo for 24 weeks. The primary outcome of the study was change in the patients’ weight and nutritional status.

Due to the withdrawal of 17 patients, mainly due to death or disease progression, only 33 of the subjects (17 thalidomide and 13 placebo) were available for assessment at four weeks and 20 (12 thalidomide and eight placebo) were available at eight weeks. These assessments yielded the following results:

At four weeks, patients who received thalidomide had gained, on average, 0.37 kg in weight and 1.0 cm in arm muscle mass compared with a loss of 2.21 kg in weight and 4.46 cm in arm muscle mass in the placebo group.

At eight weeks, patients in the thalidomide group had lost 0.06 kg in weight and 0.5 cm in arm muscle mass compared to a loss of 3.62 kg in weight and 8.4 cm in arm muscle mass in the placebo group.

Improvement in physical functioning correlated positively with weight gain.

Based on their findings, the researchers concluded that thalidomide is safe and effective in attenuating severe weight loss in patients with advanced pancreatic cancer, and that this is associated with a reduction in loss of lean body mass.

They noted that this conclusion is clinically important, since it has previously been shown that patients with unresectable pancreatic cancer show inexorable weight loss, with death occurring when patients have lost approximately 30% or their premorbid weight.

It remains to be seen, the researchers pointed out, whether the results of their study can be generalized to all cancers and whether attenuation of weight loss leads to prolonged survival.

In the future, they said, a combination of thalidomide with nutritional supplements and pharmacologic agents may ultimately lead to a better clinical outcome.

Primary source: Gut

Source reference:
Gordon J, et al. Thalidomide in the Treatment of Cancer Cachexia: A Randomised Placebo Controlled Trial. Gut. 2005;54:540-545

Additional source: Gut

Source reference:
Thalidomide and cancer cachexia: Old Problem, New Hope. Gut. 2005;54:447-448

Both smoking and exposure to secondhand smoke appear to increase the risk for breast cancer among postmenopausal women, new research shows.

Although earlier studies had found little or no connection between breast cancer and smoking, as more women smokers reach menopause the connection may be surfacing for the first time, experts noted.

“The findings are important because smoking was not previously thought to increase the risk of breast cancer, but this study adds to the increasing evidence that it does,” said lead researcher Dr. Karen Margolis, a senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

However, Susan Gapstur, vice president of epidemiology for the American Cancer Society, said earlier research had shown some connection between smoking and breast cancer.

“When you put together the body of work in the last few years, it calls for more studies,” she said. “This study has answered that call.”

“This certainly adds to the evidence that long-term smoking increases the risk for breast cancer,” Gapstur said. “On the on the flip side, it appears that 20 years after stopping the risk goes down to that of an average individual. I think that’s good news.”

Many risk factors for breast cancer cannot be changed, such as age, genetics and family history of the disease, Margolis noted.

“Now smoking can be added to the list of things that can lower breast cancer risk that already include having children, breast-feeding, keeping alcohol consumption low, avoiding weight gain, being physically active and avoiding hormone therapy with estrogen plus progestin,” she said.

The report is published in the March 1 online edition of the BMJ.

For the study, Margolis’s group collected data on 79,990 women aged 50 to 79 who took part in the Women’s Health Initiative study. Over 10 years of follow-up, 3,250 women developed breast cancer.

As part of the study, the women were asked if they smoked, had stopped smoking or had never smoked. The women were also asked about their exposure to secondhand smoke at home and at work.

The researchers found that women who smoked had a 16 percent increased risk of developing breast cancer. Among women who quit, the increased risk was 9 percent, they added.

The greatest risk was for women who had smoked for 50 years or longer, compared with women who never smoked, Margolis’s team found. The risk was also high for women who started smoking when they were teenagers. Even after quitting, the risk continued for up to 20 years, the researchers noted.

“We also observed some evidence that extensive exposure to passive smoking may raise the risk of breast cancer,” Margolis said.

Nonsmokers exposed to secondhand smoke for more than 10 years as children, more than 20 years as adults at home and more than 10 years at work had a 32 percent increased risk of developing breast cancer, the researchers found.

However, the link between breast cancer and secondhand smoke was seen in those exposed to the greatest amount of passive smoking and “therefore more research is needed to confirm these findings,” the researchers noted.

Dr. Paolo Boffetta, deputy director of the Tisch Cancer Institute and Institute for Transitional Epidemiology at Mount Sinai School of Medicine in New York City and co-author of an accompanying journal editorial, said that “tobacco smoking, particularly when started early in life, may increase the risk of breast cancer.”

“This evidence is becoming stronger and stronger,” he said. “In previous studies, the evidence was not so strong. It is only now that women who started smoking in large numbers are getting to the age where the risk of breast cancer is getting high.”

Right now, the association between smoking and breast cancer is still not a sure thing, Boffetta said, “but, it is getting more likely.”

More information

For more information on breast cancer, visit the American Cancer Society.

VANCOUVER, British Columbia, Feb. 16 — It can take more than a decade, but multiple sclerosis patients in a state of “permanent arrest” can find their relatively benign disease progressing.

Among patients who 10 years after a MS diagnosis still had only mild symptoms or no disability, nearly half had significant disease progression after another 10 years, reported Ana-Luiza Sayao, M.D., of the University of British Columbia here, and colleagues.

Approximately 21% became severely disabled and mobility restricted, requiring the use of a cane, and 23% went on to develop secondary progressive MS two decades after symptom onset, the investigators reported in the Feb. 13 issue of Neurology.

“We hoped to identify risk factors that make people more likely to progress in the disease after 10 years of a benign course, but we did not find that gender, the symptoms when the disease began, or age when the disease began were associated with either disease progression or remaining benign,” said Virginia Devonshire, M.D., a co-author. “More research needs to be done to identify criteria to determine which people will remain with mild disability over the long term.”

As other investigators have shown, the Expanded Disability Status Scale (EDDS) score at 10 years was the only predictor of benign disease at 20 years, yet even this marker was inadequate for describing the disease in the cohort, the authors said.

But as researchers from the Netherlands reported in a separate study in a different journal, MRI scans showing brain changes at the time of diagnosis appear to hold clues to disease progression.

“In patients with recently diagnosed multiple sclerosis, the extent of accumulated brain tissue loss and overall lesion load partly explain the subsequent rate of cerebral atrophy,” wrote Bas Jasperse, M.D., and colleagues from VU University Medical Center in Amsterdam, in the February issue of Archives of Neurology.

In the Canadian study, Dr. Sayao and colleagues in Vancouver evaluated disease status after 20 years in a cohort of patients with benign MS, defined as an EDSS score of three or less 10 years after disease onset. Of 200 patients who met the criteria at 10 years, 20-year follow-up was available for 169.

“Patients for whom we were unable to obtain 20-year follow-up were analyzed through ‘best-case’ and ‘worst-case’ scenarios, with best case assuming the same EDSS score at 20 years as at 10 years, and worst case being death due to MS (EDSS score = 10),” the investigators wrote.

The primary study outcome was clinical progression in the cohort, determined by the EDSS score at 20 years, with comparisons between patients who still had benign disease and those whose disease had progressed.

The authors also conducted a regression analysis controlling for age at onset, sex, onset symptoms (optic neuritis, sensory, motor, and cerebellar/ataxia/brainstem), and EDSS score at 10 years.

They found that of the 169 patients for whom 20-years EDSS scores were available, 52.1% (88 patients) continued to have a benign course, but 21.3% (36 patients) had progressed to require the use of a cane (EDSS score > 6), and of the 196 who originally had a relapsing-remitting disease course, 23% (45 patients) had conversion to secondary progressive MS.

In the logistic regression analysis, they determined that the only variable associated with disease progression at 20 years was the EDSS score at 10 years (P 3) at 20 years.

“At 10 years from onset, neither an Expanded Disability Status Scale score