Mary Ann Moon

Diets that are low in fat and high in carbohydrates from vegetables, fruits, and whole grains do not cause weight gain in postmenopausal women, reported Barbara V. Howard, Ph.D., and her associates in the Women's Health Initiative Dietary Modification Trial.

These results likely will hold true for younger women and for men of all ages, they said. So proponents of high-protein, high-fat, low-carb diets who blame the obesity epidemic on low-fat diets, are simply wrong, according to the WHI investigators.

“A number of popular diet books have suggested that increasing obesity may be attributed to the diets recommended for chronic disease prevention by various national health organizations,” the investigators wrote. Proponents of low-carb diets claim that the higher proportion of carbohydrates in these recommended diets actually promotes weight gain.

Dr. Howard and her associates found instead that a diet that replaces fat calories with calories from fruits, vegetables, and grains caused a modest weight loss. “Guidelines that restrict fat intake and advocate increases in complex carbohydrates have not been a contributing factor to the weight gain that has been occurring in the United States throughout the past several decades,” they noted (JAMA 2006;295:39–49).

The WHI dietary modification trial is a longitudinal study assessing the long-term effects of diet on breast and colorectal cancers and cardiovascular disease. Dr. Howard, of the MedStar Research Institute, Washington, and her associates used data from the trial to assess whether a low-fat diet caused weight gain.

The study followed 46,808 women of diverse ethnic and socioeconomic backgrounds, aged 50–79 years, for a mean of 7.5 years. Most of the subjects were overweight or obese, and all had a baseline fat intake that comprised at least 32% of their total daily calories.

A total of 27,994 subjects served as controls, adhering to their usual diets. In the intervention group, 18,814 women were encouraged to reduce their fat intake to no more than 20% of daily calories and to consume at least five servings of fruits and vegetables and at least six servings of grains daily.

The dietary intervention did not advocate caloric reduction and did not specifically aim to cause weight loss. Rather, the point was for the subjects to change to a healthier overall dietary pattern, the researchers said.

Nevertheless, mean weight decreased by 2.2 kg in the first year in the intervention group, and the women maintained a modest weight loss for the next several years. In contrast, weight did not change in the control group.

Women with the largest reduction in fat intake showed the greatest weight loss. Similarly, there was a statistical trend for greater weight loss in women who made the largest increases in the number of daily servings of fruits and vegetables, as well as in those who made the largest increases in fiber intake.

Diets that are low in fat and high in carbohydrates from vegetables, fruits, and whole grains do not cause weight gain in postmenopausal women, reported Barbara V. Howard, Ph.D., and her associates in the Women's Health Initiative Dietary Modification Trial.

These results likely will hold true for younger women and for men of all ages, they said. So proponents of high-protein, high-fat, low-carb diets who blame the obesity epidemic on low-fat diets, are simply wrong, according to the WHI investigators.

“A number of popular diet books have suggested that increasing obesity may be attributed to the diets recommended for chronic disease prevention by various national health organizations,” the investigators wrote. Proponents of low-carb diets claim that the higher proportion of carbohydrates in these recommended diets actually promotes weight gain.

Dr. Howard and her associates found instead that a diet that replaces fat calories with calories from fruits, vegetables, and grains caused a modest weight loss. “Guidelines that restrict fat intake and advocate increases in complex carbohydrates have not been a contributing factor to the weight gain that has been occurring in the United States throughout the past several decades,” they noted (JAMA 2006;295:39–49).

The WHI dietary modification trial is a longitudinal study assessing the long-term effects of diet on breast and colorectal cancers and cardiovascular disease. Dr. Howard, of the MedStar Research Institute, Washington, and her associates used data from the trial to assess whether a low-fat diet caused weight gain.

The study followed 46,808 women of diverse ethnic and socioeconomic backgrounds, aged 50–79 years, for a mean of 7.5 years. Most of the subjects were overweight or obese, and all had a baseline fat intake that comprised at least 32% of their total daily calories.

A total of 27,994 subjects served as controls, adhering to their usual diets. In the intervention group, 18,814 women were encouraged to reduce their fat intake to no more than 20% of daily calories and to consume at least five servings of fruits and vegetables and at least six servings of grains daily.

The dietary intervention did not advocate caloric reduction and did not specifically aim to cause weight loss. Rather, the point was for the subjects to change to a healthier overall dietary pattern, the researchers said.

Nevertheless, mean weight decreased by 2.2 kg in the first year in the intervention group, and the women maintained a modest weight loss for the next several years. In contrast, weight did not change in the control group.

Women with the largest reduction in fat intake showed the greatest weight loss. Similarly, there was a statistical trend for greater weight loss in women who made the largest increases in the number of daily servings of fruits and vegetables, as well as in those who made the largest increases in fiber intake.

Diets that are low in fat and high in carbohydrates from vegetables, fruits, and whole grains do not cause weight gain in postmenopausal women, reported Barbara V. Howard, Ph.D., and her associates in the Women's Health Initiative Dietary Modification Trial.

These results likely will hold true for younger women and for men of all ages, they said. So proponents of high-protein, high-fat, low-carb diets who blame the obesity epidemic on low-fat diets, are simply wrong, according to the WHI investigators.

“A number of popular diet books have suggested that increasing obesity may be attributed to the diets recommended for chronic disease prevention by various national health organizations,” the investigators wrote. Proponents of low-carb diets claim that the higher proportion of carbohydrates in these recommended diets actually promotes weight gain.

Dr. Howard and her associates found instead that a diet that replaces fat calories with calories from fruits, vegetables, and grains caused a modest weight loss. “Guidelines that restrict fat intake and advocate increases in complex carbohydrates have not been a contributing factor to the weight gain that has been occurring in the United States throughout the past several decades,” they noted (JAMA 2006;295:39–49).

The WHI dietary modification trial is a longitudinal study assessing the long-term effects of diet on breast and colorectal cancers and cardiovascular disease. Dr. Howard, of the MedStar Research Institute, Washington, and her associates used data from the trial to assess whether a low-fat diet caused weight gain.

The study followed 46,808 women of diverse ethnic and socioeconomic backgrounds, aged 50–79 years, for a mean of 7.5 years. Most of the subjects were overweight or obese, and all had a baseline fat intake that comprised at least 32% of their total daily calories.

A total of 27,994 subjects served as controls, adhering to their usual diets. In the intervention group, 18,814 women were encouraged to reduce their fat intake to no more than 20% of daily calories and to consume at least five servings of fruits and vegetables and at least six servings of grains daily.

The dietary intervention did not advocate caloric reduction and did not specifically aim to cause weight loss. Rather, the point was for the subjects to change to a healthier overall dietary pattern, the researchers said.

Nevertheless, mean weight decreased by 2.2 kg in the first year in the intervention group, and the women maintained a modest weight loss for the next several years. In contrast, weight did not change in the control group.

Women with the largest reduction in fat intake showed the greatest weight loss. Similarly, there was a statistical trend for greater weight loss in women who made the largest increases in the number of daily servings of fruits and vegetables, as well as in those who made the largest increases in fiber intake.

People with clinical depression are at nearly twice the risk for cardiac arrest as those who are not depressed, independently of their other cardiovascular risk factors, said Dr. J.P. Empana of Hôpital Paul Brousse, Villejuif, France, and associates.

There may even be a dose effect in which the risk of cardiac arrest rises as the severity of depression increases, they said.

They assessed the relationship between physician-diagnosed depression and out-of-hospital cardiac arrest using data from a large U.S. HMO. The study compared the prevalence of depression among 2,228 patients aged 40–79 years who had incident cases of cardiac arrest with 4,164 controls.

Unlike previous studies of this issue, this investigation evaluated “a large population with a wide range of demographic and clinical characteristics,” Dr. Empana and associates said (Arch. Intern. Med. 2006;166:195–200).

However, the population studied was not racially diverse; 93% of the subjects were white.

The risk for cardiac arrest was almost twice as high for people with clinical depression than for those without depression, with an odds ratio of 1.88. After the data were adjusted to account for numerous cardiovascular risk factors, the odds ratio remained elevated, at 1.43.

This association between depression and cardiac arrest was seen across all demographic subgroups. Men and women were equally affected, as were elderly people and younger adults. The risk of cardiac arrest increased with increasing severity of depression, so that people who required hospitalization for their depression within the preceding year were at highest risk.

A previous case-control study suggested that the use of tricyclic antidepressants may raise the risk of sudden cardiac death. However, that suggestion seems to be refuted in this study. Excluding the subset of 277 patients who were taking antidepressants, 82% of whom were taking tricyclics, did not alter the results, they said.

People with clinical depression are at nearly twice the risk for cardiac arrest as those who are not depressed, independently of their other cardiovascular risk factors, said Dr. J.P. Empana of Hôpital Paul Brousse, Villejuif, France, and associates.

There may even be a dose effect in which the risk of cardiac arrest rises as the severity of depression increases, they said.

They assessed the relationship between physician-diagnosed depression and out-of-hospital cardiac arrest using data from a large U.S. HMO. The study compared the prevalence of depression among 2,228 patients aged 40–79 years who had incident cases of cardiac arrest with 4,164 controls.

Unlike previous studies of this issue, this investigation evaluated “a large population with a wide range of demographic and clinical characteristics,” Dr. Empana and associates said (Arch. Intern. Med. 2006;166:195–200).

However, the population studied was not racially diverse; 93% of the subjects were white.

The risk for cardiac arrest was almost twice as high for people with clinical depression than for those without depression, with an odds ratio of 1.88. After the data were adjusted to account for numerous cardiovascular risk factors, the odds ratio remained elevated, at 1.43.

This association between depression and cardiac arrest was seen across all demographic subgroups. Men and women were equally affected, as were elderly people and younger adults. The risk of cardiac arrest increased with increasing severity of depression, so that people who required hospitalization for their depression within the preceding year were at highest risk.

A previous case-control study suggested that the use of tricyclic antidepressants may raise the risk of sudden cardiac death. However, that suggestion seems to be refuted in this study. Excluding the subset of 277 patients who were taking antidepressants, 82% of whom were taking tricyclics, did not alter the results, they said.

People with clinical depression are at nearly twice the risk for cardiac arrest as those who are not depressed, independently of their other cardiovascular risk factors, said Dr. J.P. Empana of Hôpital Paul Brousse, Villejuif, France, and associates.

There may even be a dose effect in which the risk of cardiac arrest rises as the severity of depression increases, they said.

They assessed the relationship between physician-diagnosed depression and out-of-hospital cardiac arrest using data from a large U.S. HMO. The study compared the prevalence of depression among 2,228 patients aged 40–79 years who had incident cases of cardiac arrest with 4,164 controls.

Unlike previous studies of this issue, this investigation evaluated “a large population with a wide range of demographic and clinical characteristics,” Dr. Empana and associates said (Arch. Intern. Med. 2006;166:195–200).

However, the population studied was not racially diverse; 93% of the subjects were white.

The risk for cardiac arrest was almost twice as high for people with clinical depression than for those without depression, with an odds ratio of 1.88. After the data were adjusted to account for numerous cardiovascular risk factors, the odds ratio remained elevated, at 1.43.

This association between depression and cardiac arrest was seen across all demographic subgroups. Men and women were equally affected, as were elderly people and younger adults. The risk of cardiac arrest increased with increasing severity of depression, so that people who required hospitalization for their depression within the preceding year were at highest risk.

A previous case-control study suggested that the use of tricyclic antidepressants may raise the risk of sudden cardiac death. However, that suggestion seems to be refuted in this study. Excluding the subset of 277 patients who were taking antidepressants, 82% of whom were taking tricyclics, did not alter the results, they said.

The duration of anesthesia does not correlate with morbidity or mortality in facial plastic surgery performed in an office-based facility, reported Dr. Neil A. Gordon of Yale University, New Haven, and Dr. Marc E. Koch of the State University of New York at Stony Brook.

The investigators conducted what they described as the first study to quantify morbidity and mortality in in-office procedures lasting longer than 4 hours, because no study to date has presented specific outcomes data on such surgery. Despite this lack of data, "state medical boards and government agencies have rushed to regulate office-based surgery" in response to reports of six patient deaths in Florida, they said (Arch. Facial Plast. Surg. 2006;8:47–53).

Their study included a retrospective analysis of 492 cases of facial plastic surgery performed at a single private-practice surgical facility from July 1995 through March 2000 and a prospective analysis of 708 cases performed from April 2000 through February 2005. The cases were divided into those lasting less than 4 hours (168 cases) and those lasting longer (1,032 cases).

Most of the latter group underwent combined procedures for facial rejuvenation, such as rhytidectomies, blepharoplasties, brow lifts, and laser surgery to resurface the skin. The procedures required an average of 306 minutes. Combined procedures that take a relatively long time often are necessary "to appropriately treat the aging face as a unit, thereby preventing the disharmonious appearance produced when portions of the aging face are treated and portions are left untreated," the investigators said.

The shorter procedures were mostly isolated rhinoplasties. The average patient age was 55.7 years. Just over half the patients were older than 51 years, and almost 12% were older than 65.

There were no deaths, no myocardial infarctions, no cardiac arrhythmias, and no pulmonary embolisms.

Three cases of major morbidity occurred (a 0.25% rate), none of which were directly related to procedure duration. A 59-year-old man developed aspiration pneumonia secondary to an obstruction event on extubation, a 53-year-old woman had a cerebral hemorrhage for unknown reasons, and a 52-year-old woman had an anaphylactic reaction to cephalosporin.

"We had no cases … in which inpatient care would have prevented these major morbidity events from occurring or being treated optimally," the researchers said. In fact, it can be argued that receiving intubation for general anesthesia rather than local anesthesia in the office setting actually helped the latter two patients. Because they had secure airways at the time of the events, the surgical team was able to immediately and continuously oxygenate these patients while resuscitating and treating them. "This directly maximized their outcomes and prevented further morbidity, if not mortality," Dr. Gordon and Dr. Koch noted.

"Contrary to reports that longer procedure duration causes a higher incidence of intractable postoperative nausea, vomiting, and pain, thus necessitating higher precautionary hospitalization rates if performed in the office-based environment, we had no cases with any of these complications," they said.

According to the researchers, guidelines including "arbitrary" 4-hour cutoffs for in-office surgery duration—which have been adopted in Pennsylvania and Tennessee—are imposing "inappropriate, non-data-driven regulation" on office-based plastic surgeons.

The duration of anesthesia does not correlate with morbidity or mortality in facial plastic surgery performed in an office-based facility, reported Dr. Neil A. Gordon of Yale University, New Haven, and Dr. Marc E. Koch of the State University of New York at Stony Brook.

The investigators conducted what they described as the first study to quantify morbidity and mortality in in-office procedures lasting longer than 4 hours, because no study to date has presented specific outcomes data on such surgery. Despite this lack of data, "state medical boards and government agencies have rushed to regulate office-based surgery" in response to reports of six patient deaths in Florida, they said (Arch. Facial Plast. Surg. 2006;8:47–53).

Their study included a retrospective analysis of 492 cases of facial plastic surgery performed at a single private-practice surgical facility from July 1995 through March 2000 and a prospective analysis of 708 cases performed from April 2000 through February 2005. The cases were divided into those lasting less than 4 hours (168 cases) and those lasting longer (1,032 cases).

Most of the latter group underwent combined procedures for facial rejuvenation, such as rhytidectomies, blepharoplasties, brow lifts, and laser surgery to resurface the skin. The procedures required an average of 306 minutes. Combined procedures that take a relatively long time often are necessary "to appropriately treat the aging face as a unit, thereby preventing the disharmonious appearance produced when portions of the aging face are treated and portions are left untreated," the investigators said.

The shorter procedures were mostly isolated rhinoplasties. The average patient age was 55.7 years. Just over half the patients were older than 51 years, and almost 12% were older than 65.

There were no deaths, no myocardial infarctions, no cardiac arrhythmias, and no pulmonary embolisms.

Three cases of major morbidity occurred (a 0.25% rate), none of which were directly related to procedure duration. A 59-year-old man developed aspiration pneumonia secondary to an obstruction event on extubation, a 53-year-old woman had a cerebral hemorrhage for unknown reasons, and a 52-year-old woman had an anaphylactic reaction to cephalosporin.

"We had no cases … in which inpatient care would have prevented these major morbidity events from occurring or being treated optimally," the researchers said. In fact, it can be argued that receiving intubation for general anesthesia rather than local anesthesia in the office setting actually helped the latter two patients. Because they had secure airways at the time of the events, the surgical team was able to immediately and continuously oxygenate these patients while resuscitating and treating them. "This directly maximized their outcomes and prevented further morbidity, if not mortality," Dr. Gordon and Dr. Koch noted.

"Contrary to reports that longer procedure duration causes a higher incidence of intractable postoperative nausea, vomiting, and pain, thus necessitating higher precautionary hospitalization rates if performed in the office-based environment, we had no cases with any of these complications," they said.

According to the researchers, guidelines including "arbitrary" 4-hour cutoffs for in-office surgery duration—which have been adopted in Pennsylvania and Tennessee—are imposing "inappropriate, non-data-driven regulation" on office-based plastic surgeons.

The duration of anesthesia does not correlate with morbidity or mortality in facial plastic surgery performed in an office-based facility, reported Dr. Neil A. Gordon of Yale University, New Haven, and Dr. Marc E. Koch of the State University of New York at Stony Brook.

The investigators conducted what they described as the first study to quantify morbidity and mortality in in-office procedures lasting longer than 4 hours, because no study to date has presented specific outcomes data on such surgery. Despite this lack of data, "state medical boards and government agencies have rushed to regulate office-based surgery" in response to reports of six patient deaths in Florida, they said (Arch. Facial Plast. Surg. 2006;8:47–53).

Their study included a retrospective analysis of 492 cases of facial plastic surgery performed at a single private-practice surgical facility from July 1995 through March 2000 and a prospective analysis of 708 cases performed from April 2000 through February 2005. The cases were divided into those lasting less than 4 hours (168 cases) and those lasting longer (1,032 cases).

Most of the latter group underwent combined procedures for facial rejuvenation, such as rhytidectomies, blepharoplasties, brow lifts, and laser surgery to resurface the skin. The procedures required an average of 306 minutes. Combined procedures that take a relatively long time often are necessary "to appropriately treat the aging face as a unit, thereby preventing the disharmonious appearance produced when portions of the aging face are treated and portions are left untreated," the investigators said.

The shorter procedures were mostly isolated rhinoplasties. The average patient age was 55.7 years. Just over half the patients were older than 51 years, and almost 12% were older than 65.

There were no deaths, no myocardial infarctions, no cardiac arrhythmias, and no pulmonary embolisms.

Three cases of major morbidity occurred (a 0.25% rate), none of which were directly related to procedure duration. A 59-year-old man developed aspiration pneumonia secondary to an obstruction event on extubation, a 53-year-old woman had a cerebral hemorrhage for unknown reasons, and a 52-year-old woman had an anaphylactic reaction to cephalosporin.

"We had no cases … in which inpatient care would have prevented these major morbidity events from occurring or being treated optimally," the researchers said. In fact, it can be argued that receiving intubation for general anesthesia rather than local anesthesia in the office setting actually helped the latter two patients. Because they had secure airways at the time of the events, the surgical team was able to immediately and continuously oxygenate these patients while resuscitating and treating them. "This directly maximized their outcomes and prevented further morbidity, if not mortality," Dr. Gordon and Dr. Koch noted.

"Contrary to reports that longer procedure duration causes a higher incidence of intractable postoperative nausea, vomiting, and pain, thus necessitating higher precautionary hospitalization rates if performed in the office-based environment, we had no cases with any of these complications," they said.

According to the researchers, guidelines including "arbitrary" 4-hour cutoffs for in-office surgery duration—which have been adopted in Pennsylvania and Tennessee—are imposing "inappropriate, non-data-driven regulation" on office-based plastic surgeons.

Women who discontinue antidepressant medication when they become pregnant have nearly a 70% rate of depression relapse during the course of the pregnancy, reported Dr. Lee S. Cohen of Massachusetts General Hospital, Boston, and his associates.

“Pregnancy has historically been described as a time of emotional well-being, providing general 'protection' against psychiatric disorder.

“However, systematic data to support this impression are sparse,” the researchers noted.

They undertook what they described as the first study to examine the risk of depression relapse during pregnancy in women with recurrent depression, noting that there is an almost uniform belief that antidepressants should be discontinued during pregnancy to avert prenatal exposure to the drugs.

The 4-year prospective study involved 201 pregnant women with diverse socioeconomic backgrounds who had histories of recurrent depression and were being treated at one of three medical centers “with specific expertise in the treatment of psychiatric illness during pregnancy,” they wrote (JAMA 2006;295:499–507).

The mean age at onset of depression was 18 years, and the mean duration of depression was 15 years. A total of 44% of the women reported five or more prior recurrences. All had been taking antidepressants for at least 3 months before enrolling in the study, and almost all (92%) were taking SSRIs or dual-action antidepressants either alone or in combination with other agents.

Of the 65 women who discontinued their medication, 44 (68%) relapsed during pregnancy. About half of them relapsed during the first trimester and another 40% during the second trimester. This compares with a 26% relapse rate among women who maintained their medication throughout pregnancy.

After the data were adjusted to account for several variables such as type of medication used and number of prior episodes of depression, “women who discontinued their medication had a fivefold increased risk of relapse over the course of their pregnancy, compared with women who maintained their medication,” the researchers wrote.

Of the patients who discontinued (65 women) or decreased (34 women) their antidepressant medications, 61% resumed taking the drugs during pregnancy because of resurgence of depressive symptoms.

These findings have significant implications, “given the prevalence of depression in reproductive-age women, the prevalence of antidepressant use in this population, and the frequency of unplanned pregnancy,” according to the investigators.

Women should be made aware of the risk of depressive relapse following discontinuation of antidepressants. More of those who have recurrent depressive illness may well choose to maintain antidepressant therapy during attempts to conceive and during pregnancy, Dr. Cohen and his associates noted.

“These women must weigh concerns about prenatal exposure to these medications … [but] should also consider the risks of depressive relapse during pregnancy and the effects of untreated depression on fetal and maternal well-being,” they added.

Women who discontinue antidepressant medication when they become pregnant have nearly a 70% rate of depression relapse during the course of the pregnancy, reported Dr. Lee S. Cohen of Massachusetts General Hospital, Boston, and his associates.

“Pregnancy has historically been described as a time of emotional well-being, providing general 'protection' against psychiatric disorder.

“However, systematic data to support this impression are sparse,” the researchers noted.

They undertook what they described as the first study to examine the risk of depression relapse during pregnancy in women with recurrent depression, noting that there is an almost uniform belief that antidepressants should be discontinued during pregnancy to avert prenatal exposure to the drugs.

The 4-year prospective study involved 201 pregnant women with diverse socioeconomic backgrounds who had histories of recurrent depression and were being treated at one of three medical centers “with specific expertise in the treatment of psychiatric illness during pregnancy,” they wrote (JAMA 2006;295:499–507).

The mean age at onset of depression was 18 years, and the mean duration of depression was 15 years. A total of 44% of the women reported five or more prior recurrences. All had been taking antidepressants for at least 3 months before enrolling in the study, and almost all (92%) were taking SSRIs or dual-action antidepressants either alone or in combination with other agents.

Of the 65 women who discontinued their medication, 44 (68%) relapsed during pregnancy. About half of them relapsed during the first trimester and another 40% during the second trimester. This compares with a 26% relapse rate among women who maintained their medication throughout pregnancy.

After the data were adjusted to account for several variables such as type of medication used and number of prior episodes of depression, “women who discontinued their medication had a fivefold increased risk of relapse over the course of their pregnancy, compared with women who maintained their medication,” the researchers wrote.

Of the patients who discontinued (65 women) or decreased (34 women) their antidepressant medications, 61% resumed taking the drugs during pregnancy because of resurgence of depressive symptoms.

These findings have significant implications, “given the prevalence of depression in reproductive-age women, the prevalence of antidepressant use in this population, and the frequency of unplanned pregnancy,” according to the investigators.

Women should be made aware of the risk of depressive relapse following discontinuation of antidepressants. More of those who have recurrent depressive illness may well choose to maintain antidepressant therapy during attempts to conceive and during pregnancy, Dr. Cohen and his associates noted.

“These women must weigh concerns about prenatal exposure to these medications … [but] should also consider the risks of depressive relapse during pregnancy and the effects of untreated depression on fetal and maternal well-being,” they added.

Women who discontinue antidepressant medication when they become pregnant have nearly a 70% rate of depression relapse during the course of the pregnancy, reported Dr. Lee S. Cohen of Massachusetts General Hospital, Boston, and his associates.

“Pregnancy has historically been described as a time of emotional well-being, providing general 'protection' against psychiatric disorder.

“However, systematic data to support this impression are sparse,” the researchers noted.

They undertook what they described as the first study to examine the risk of depression relapse during pregnancy in women with recurrent depression, noting that there is an almost uniform belief that antidepressants should be discontinued during pregnancy to avert prenatal exposure to the drugs.

The 4-year prospective study involved 201 pregnant women with diverse socioeconomic backgrounds who had histories of recurrent depression and were being treated at one of three medical centers “with specific expertise in the treatment of psychiatric illness during pregnancy,” they wrote (JAMA 2006;295:499–507).

The mean age at onset of depression was 18 years, and the mean duration of depression was 15 years. A total of 44% of the women reported five or more prior recurrences. All had been taking antidepressants for at least 3 months before enrolling in the study, and almost all (92%) were taking SSRIs or dual-action antidepressants either alone or in combination with other agents.

Of the 65 women who discontinued their medication, 44 (68%) relapsed during pregnancy. About half of them relapsed during the first trimester and another 40% during the second trimester. This compares with a 26% relapse rate among women who maintained their medication throughout pregnancy.

After the data were adjusted to account for several variables such as type of medication used and number of prior episodes of depression, “women who discontinued their medication had a fivefold increased risk of relapse over the course of their pregnancy, compared with women who maintained their medication,” the researchers wrote.

Of the patients who discontinued (65 women) or decreased (34 women) their antidepressant medications, 61% resumed taking the drugs during pregnancy because of resurgence of depressive symptoms.

These findings have significant implications, “given the prevalence of depression in reproductive-age women, the prevalence of antidepressant use in this population, and the frequency of unplanned pregnancy,” according to the investigators.

Women should be made aware of the risk of depressive relapse following discontinuation of antidepressants. More of those who have recurrent depressive illness may well choose to maintain antidepressant therapy during attempts to conceive and during pregnancy, Dr. Cohen and his associates noted.

“These women must weigh concerns about prenatal exposure to these medications … [but] should also consider the risks of depressive relapse during pregnancy and the effects of untreated depression on fetal and maternal well-being,” they added.

Local complications are common after postmastectomy reconstructive breast implantation, with an adverse event rate of 31% in one large prospective study, reported Dr. Trine F. Henriksen of the Danish Registry for Plastic Surgery of the Breast, Copenhagen, and associates.

In what they described as “the first prospective epidemiological study to provide quantitative data on short-term local complications among women receiving implants for breast reconstruction,” the investigators found that unplanned surgical or medical intervention is often required during the course of reconstruction. Some 20% of women needed surgical procedures to treat complications within the first 2 years of mastectomy, a rate that is nearly four times higher than that with cosmetic implantation.

“When evaluating benefits and risks associated with breast reconstruction, the surgeon and patient should consider that the reconstructive process often requires additional surgical intervention to treat local complications or to achieve the desired cosmetic result. Detailed information on the likelihood of local complications … should be an essential part of adequate informed consent” for mastectomy patients seeking breast implantation, Dr. Henriksen and associates said (Arch. Surg. 2005;140:1152–9).

They studied the issue using data from the Danish Registry for Plastic Surgery of the Breast, which provided the world's “first systematic collection of preoperative, perioperative, and postoperative data in relation to mammoplasty procedures.”

The study included all 574 women who underwent 901 postmastectomy breast implantations in Denmark between June 1999 and July 2003.

There were 484 initial implant procedures and 417 reimplant procedures—implant exchanges or implant reinsertion after a prior removal. Just over half (51%) of these secondary procedures were unplanned; the remaining 49% were planned second-stage operations after tissue expansion. The mean patient age at initial implantation was 50 years, and the subjects were followed for a mean of 23 months after initial implantation and 24 months after subsequent implantation.

Unplanned repeat procedures were performed for a range of reasons, and patients often had more than one indication. Capsular contraction was the most common cause for repeat procedures (23%), followed by unacceptable asymmetry (20%), displacement of the implant (16%), and suspicion of implant rupture (5%).

After initial implantation, 31% of women experienced at least one adverse event, ranging from delayed wound healing to severe capsular contraction. Sixteen percent developed two adverse events, and 8% developed at least three. Wound infection was the most common immediate adverse event, affecting 7% of women. Skin perforation, seroma, periprosthetic infection, and hematoma each affected 3% of the women.

After a repeat implantation procedure, 36% of the women developed one adverse event, 19% developed two, and 8% developed three or more adverse events. Asymmetry and displacement of the implant were the most frequently reported problems, affecting 19% of women. Hematoma, capsular contraction, prolonged pain, wrinkles, and scar indentation each affected 3% of the women.

A total of 21% of the women required surgical intervention after initial implantation and another 3% required other treatments.

Approximately half of the complications occurred within the first 3 months after implantation, 67% within the first 6 months, and 91% within the first year.

Local complications are common after postmastectomy reconstructive breast implantation, with an adverse event rate of 31% in one large prospective study, reported Dr. Trine F. Henriksen of the Danish Registry for Plastic Surgery of the Breast, Copenhagen, and associates.

In what they described as “the first prospective epidemiological study to provide quantitative data on short-term local complications among women receiving implants for breast reconstruction,” the investigators found that unplanned surgical or medical intervention is often required during the course of reconstruction. Some 20% of women needed surgical procedures to treat complications within the first 2 years of mastectomy, a rate that is nearly four times higher than that with cosmetic implantation.

“When evaluating benefits and risks associated with breast reconstruction, the surgeon and patient should consider that the reconstructive process often requires additional surgical intervention to treat local complications or to achieve the desired cosmetic result. Detailed information on the likelihood of local complications … should be an essential part of adequate informed consent” for mastectomy patients seeking breast implantation, Dr. Henriksen and associates said (Arch. Surg. 2005;140:1152–9).

They studied the issue using data from the Danish Registry for Plastic Surgery of the Breast, which provided the world's “first systematic collection of preoperative, perioperative, and postoperative data in relation to mammoplasty procedures.”

The study included all 574 women who underwent 901 postmastectomy breast implantations in Denmark between June 1999 and July 2003.

There were 484 initial implant procedures and 417 reimplant procedures—implant exchanges or implant reinsertion after a prior removal. Just over half (51%) of these secondary procedures were unplanned; the remaining 49% were planned second-stage operations after tissue expansion. The mean patient age at initial implantation was 50 years, and the subjects were followed for a mean of 23 months after initial implantation and 24 months after subsequent implantation.

Unplanned repeat procedures were performed for a range of reasons, and patients often had more than one indication. Capsular contraction was the most common cause for repeat procedures (23%), followed by unacceptable asymmetry (20%), displacement of the implant (16%), and suspicion of implant rupture (5%).

After initial implantation, 31% of women experienced at least one adverse event, ranging from delayed wound healing to severe capsular contraction. Sixteen percent developed two adverse events, and 8% developed at least three. Wound infection was the most common immediate adverse event, affecting 7% of women. Skin perforation, seroma, periprosthetic infection, and hematoma each affected 3% of the women.

After a repeat implantation procedure, 36% of the women developed one adverse event, 19% developed two, and 8% developed three or more adverse events. Asymmetry and displacement of the implant were the most frequently reported problems, affecting 19% of women. Hematoma, capsular contraction, prolonged pain, wrinkles, and scar indentation each affected 3% of the women.

A total of 21% of the women required surgical intervention after initial implantation and another 3% required other treatments.

Approximately half of the complications occurred within the first 3 months after implantation, 67% within the first 6 months, and 91% within the first year.

Local complications are common after postmastectomy reconstructive breast implantation, with an adverse event rate of 31% in one large prospective study, reported Dr. Trine F. Henriksen of the Danish Registry for Plastic Surgery of the Breast, Copenhagen, and associates.

In what they described as “the first prospective epidemiological study to provide quantitative data on short-term local complications among women receiving implants for breast reconstruction,” the investigators found that unplanned surgical or medical intervention is often required during the course of reconstruction. Some 20% of women needed surgical procedures to treat complications within the first 2 years of mastectomy, a rate that is nearly four times higher than that with cosmetic implantation.

“When evaluating benefits and risks associated with breast reconstruction, the surgeon and patient should consider that the reconstructive process often requires additional surgical intervention to treat local complications or to achieve the desired cosmetic result. Detailed information on the likelihood of local complications … should be an essential part of adequate informed consent” for mastectomy patients seeking breast implantation, Dr. Henriksen and associates said (Arch. Surg. 2005;140:1152–9).

They studied the issue using data from the Danish Registry for Plastic Surgery of the Breast, which provided the world's “first systematic collection of preoperative, perioperative, and postoperative data in relation to mammoplasty procedures.”

The study included all 574 women who underwent 901 postmastectomy breast implantations in Denmark between June 1999 and July 2003.

There were 484 initial implant procedures and 417 reimplant procedures—implant exchanges or implant reinsertion after a prior removal. Just over half (51%) of these secondary procedures were unplanned; the remaining 49% were planned second-stage operations after tissue expansion. The mean patient age at initial implantation was 50 years, and the subjects were followed for a mean of 23 months after initial implantation and 24 months after subsequent implantation.

Unplanned repeat procedures were performed for a range of reasons, and patients often had more than one indication. Capsular contraction was the most common cause for repeat procedures (23%), followed by unacceptable asymmetry (20%), displacement of the implant (16%), and suspicion of implant rupture (5%).

After initial implantation, 31% of women experienced at least one adverse event, ranging from delayed wound healing to severe capsular contraction. Sixteen percent developed two adverse events, and 8% developed at least three. Wound infection was the most common immediate adverse event, affecting 7% of women. Skin perforation, seroma, periprosthetic infection, and hematoma each affected 3% of the women.

After a repeat implantation procedure, 36% of the women developed one adverse event, 19% developed two, and 8% developed three or more adverse events. Asymmetry and displacement of the implant were the most frequently reported problems, affecting 19% of women. Hematoma, capsular contraction, prolonged pain, wrinkles, and scar indentation each affected 3% of the women.

A total of 21% of the women required surgical intervention after initial implantation and another 3% required other treatments.

Approximately half of the complications occurred within the first 3 months after implantation, 67% within the first 6 months, and 91% within the first year.

Cyclo-oxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England).

They also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said (BMJ 2005;331:1310–6).

The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but data on their long-term safety are lacking. The University of Nottingham researchers calculated the comparative risks of GI events in patients who took these prescription pain relievers between 2000 and 2004.

After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events. Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (OR 1.89) than were control subjects.

Celecoxib was the only agent out of 27 pain relievers used by the study subjects to show no link with adverse GI events. However, the number of celecoxib users was small, so this finding remains “difficult to interpret,” they noted.

Use of ulcer-healing drugs such as proton pump inhibitors cut the risk for GI events in users of both COX-2 inhibitors and NSAIDs, again suggesting that the GI risks of the two types of pain relievers are similar, the authors wrote.

Cyclo-oxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England).

They also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said (BMJ 2005;331:1310–6).

The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but data on their long-term safety are lacking. The University of Nottingham researchers calculated the comparative risks of GI events in patients who took these prescription pain relievers between 2000 and 2004.

After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events. Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (OR 1.89) than were control subjects.

Celecoxib was the only agent out of 27 pain relievers used by the study subjects to show no link with adverse GI events. However, the number of celecoxib users was small, so this finding remains “difficult to interpret,” they noted.

Use of ulcer-healing drugs such as proton pump inhibitors cut the risk for GI events in users of both COX-2 inhibitors and NSAIDs, again suggesting that the GI risks of the two types of pain relievers are similar, the authors wrote.

Cyclo-oxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England).

They also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said (BMJ 2005;331:1310–6).

The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but data on their long-term safety are lacking. The University of Nottingham researchers calculated the comparative risks of GI events in patients who took these prescription pain relievers between 2000 and 2004.

After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events. Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (OR 1.89) than were control subjects.

Celecoxib was the only agent out of 27 pain relievers used by the study subjects to show no link with adverse GI events. However, the number of celecoxib users was small, so this finding remains “difficult to interpret,” they noted.

Use of ulcer-healing drugs such as proton pump inhibitors cut the risk for GI events in users of both COX-2 inhibitors and NSAIDs, again suggesting that the GI risks of the two types of pain relievers are similar, the authors wrote.

Dietary fiber intake showed no effect on the risk of colorectal cancer in an analysis that pooled data from 13 prospective cohort studies, reported Dr. Yikyung Park of Harvard School of Public Health, Boston, and associates.

Pooling the results of studies netted 8,081 cases of colorectal cancer, giving the analysis a level of statistical power such that “a substantial effect of fiber is unlikely to have been missed,” the researchers said (JAMA 2005:294:2849–57).

The pooled analysis was undertaken because the results of many epidemiologic studies and randomized clinical trials have been conflicting, and there is still much debate over whether dietary fiber decreases colorectal cancer risk.

Each of the 13 prospective cohort studies Dr. Park and associates identified for their analysis included at least 50 cases of colorectal cancer and adequately assessed dietary fiber intake. The data yielded over 7,300,000 person-years of follow-up (6–20 years of follow-up across the studies), and included incident colorectal cancer cases in 2,776 men and 5,305 women.

The initial age-adjusted analysis showed a significant link between fiber intake and colorectal cancer, with the highest levels of intake associated with a 16% lower risk than the lowest levels. However, after the data were adjusted for potentially confounding risk factors including nondietary factors, milk and red meat intake, and alcohol consumption, “only a nonsignificant weak inverse association was found,” they said.

The findings were similar after the studies were combined and analyzed as a single data set. Likewise, dietary fiber showed no effect on cancer risk when the data were analyzed by subjects' body mass index and by sources of fiber.

Although the findings indicate that dietary fiber “may not have a major effect on the risk of colorectal cancer,” a diet rich in whole plant foods can still be advocated because it may reduce risks of other disorders. “A true association between dietary fiber intake and risk of colorectal cancer may be underestimated in our study” because the analysis was limited by possible errors in measuring fiber intake, they noted.

Dietary fiber intake showed no effect on the risk of colorectal cancer in an analysis that pooled data from 13 prospective cohort studies, reported Dr. Yikyung Park of Harvard School of Public Health, Boston, and associates.

Pooling the results of studies netted 8,081 cases of colorectal cancer, giving the analysis a level of statistical power such that “a substantial effect of fiber is unlikely to have been missed,” the researchers said (JAMA 2005:294:2849–57).

The pooled analysis was undertaken because the results of many epidemiologic studies and randomized clinical trials have been conflicting, and there is still much debate over whether dietary fiber decreases colorectal cancer risk.

Each of the 13 prospective cohort studies Dr. Park and associates identified for their analysis included at least 50 cases of colorectal cancer and adequately assessed dietary fiber intake. The data yielded over 7,300,000 person-years of follow-up (6–20 years of follow-up across the studies), and included incident colorectal cancer cases in 2,776 men and 5,305 women.

The initial age-adjusted analysis showed a significant link between fiber intake and colorectal cancer, with the highest levels of intake associated with a 16% lower risk than the lowest levels. However, after the data were adjusted for potentially confounding risk factors including nondietary factors, milk and red meat intake, and alcohol consumption, “only a nonsignificant weak inverse association was found,” they said.

The findings were similar after the studies were combined and analyzed as a single data set. Likewise, dietary fiber showed no effect on cancer risk when the data were analyzed by subjects' body mass index and by sources of fiber.

Although the findings indicate that dietary fiber “may not have a major effect on the risk of colorectal cancer,” a diet rich in whole plant foods can still be advocated because it may reduce risks of other disorders. “A true association between dietary fiber intake and risk of colorectal cancer may be underestimated in our study” because the analysis was limited by possible errors in measuring fiber intake, they noted.

Dietary fiber intake showed no effect on the risk of colorectal cancer in an analysis that pooled data from 13 prospective cohort studies, reported Dr. Yikyung Park of Harvard School of Public Health, Boston, and associates.

Pooling the results of studies netted 8,081 cases of colorectal cancer, giving the analysis a level of statistical power such that “a substantial effect of fiber is unlikely to have been missed,” the researchers said (JAMA 2005:294:2849–57).

The pooled analysis was undertaken because the results of many epidemiologic studies and randomized clinical trials have been conflicting, and there is still much debate over whether dietary fiber decreases colorectal cancer risk.

Each of the 13 prospective cohort studies Dr. Park and associates identified for their analysis included at least 50 cases of colorectal cancer and adequately assessed dietary fiber intake. The data yielded over 7,300,000 person-years of follow-up (6–20 years of follow-up across the studies), and included incident colorectal cancer cases in 2,776 men and 5,305 women.

The initial age-adjusted analysis showed a significant link between fiber intake and colorectal cancer, with the highest levels of intake associated with a 16% lower risk than the lowest levels. However, after the data were adjusted for potentially confounding risk factors including nondietary factors, milk and red meat intake, and alcohol consumption, “only a nonsignificant weak inverse association was found,” they said.

The findings were similar after the studies were combined and analyzed as a single data set. Likewise, dietary fiber showed no effect on cancer risk when the data were analyzed by subjects' body mass index and by sources of fiber.

Although the findings indicate that dietary fiber “may not have a major effect on the risk of colorectal cancer,” a diet rich in whole plant foods can still be advocated because it may reduce risks of other disorders. “A true association between dietary fiber intake and risk of colorectal cancer may be underestimated in our study” because the analysis was limited by possible errors in measuring fiber intake, they noted.

Hypertonic saline inhalation using a nebulizer reduced pulmonary exacerbations in patients with cystic fibrosis and decreased their absenteeism from school, work, and their usual activities, researchers found in two separate randomized clinical trials.

The trials provided the first evidence of the long-term efficacy of this safe and relatively inexpensive treatment. The therapy appears to work by restoring the volume of liquid on the airway surfaces, which is depleted because of excessive absorption of salt from the airway lumen. This rehydration seems to produce a sustained acceleration of mucus clearance, both groups of investigators theorized.

In the first study, 164 adults and children with stable cystic fibrosis (CF) were randomly assigned to inhale 4 mL of either hypertonic (7%) saline plus a taste-masking agent or a control solution (isotonic saline) plus a taste-masking agent via nebulizer twice a day for 48 weeks. A bronchodilator was administered before each treatment to prevent or minimize narrowing of CF patients' hyperresponsive airways during nebulizer therapy, reported Dr. Mark R. Elkins, of Royal Prince Alfred Hospital, Sydney, Australia, and the University of Sydney, and his associates.

The treatment had only a moderate effect on lung function as measured by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁), and no apparent effect on the typical decline in lung function over the course of the year-long study. However, it had “dramatic” effects on several clinical factors, they noted (N. Engl. J. Med. 2006;354:229–40).

The mean number of symptom exacerbations was 1.32 per person in the treatment group, compared with 2.74 per control subject. The mean duration of exacerbations was 22 days in the treatment group, compared with 69 days in the control group. And the length of time spent free of exacerbations, expressed as “48-week exacerbation-free survival rate,” was 41% in the treatment group, compared with 16% in the controls. All of these differences were highly statistically significant. Similarly, antibiotic use during exacerbations was much lower for the active treatment group.

Patients in the active treatment group reported a mean of 7 days (range, 0–21) when they could not participate in school, work, or usual activities, compared with a mean of 24 days (range, 12–48) for the controls. The treatment group also scored significantly higher on quality of life measures.

The treatment did not alter the levels of Pseudomonas aeruginosa or Staphylococcus aureus in the sputum, nor did it affect the rate of acquisition of these organisms, Burkholderia cepacia, Stenotrophomonas maltophilia, Candida albicans, aspergillus species, or Hemophilus influenzae.

In the other clinical trial, investigators reasoned that slowing the absorption of nebulized hypertonic saline by premedicating CF patients with amiloride, a sodium channel blocker, would enhance patient response by extending the duration of airway rehydration. Twenty-four CF patients aged 14 years and older were randomized to pretreatment with either amiloride or a taste-masked placebo, followed by hypertonic saline via nebulizer four times daily for 14 days. All the subjects received a bronchodilator via inhaler 30–60 minutes before the nebulizer treatment.

The study confirmed that hypertonic saline improved CF symptoms, lung function, and quality of life, reported Dr. Scott H. Donaldson and Dr. William D. Bennett of the University of North Carolina at Chapel Hill Cystic Fibrosis Research and Treatment Center and their associates. Perhaps as important, the treatment hastened the rate of mucus clearance from the lungs and “produced a larger and more sustained increase in the volume of airway surface liquid” in CF patients than in healthy controls (N. Engl. J. Med. 2006;354:241–50).

The findings suggest inhaled hypertonic saline may be an option for CF patients, Dr. Felix Ratjen of the University of Toronto said in an editorial comment accompanying the publication of both reports.

It was previously shown that hypertonic saline inhalation increased mucociliary transport in CF patients—but the effect was presumed to be short-lived because sodium deposited on epithelial surfaces would be taken up rapidly. The new research shows that the treatment “not only had a prolonged effect on the amount of airway surface liquid in epithelial cells … but also resulted in a sustained improvement of mucociliary transport,” Dr. Ratjen said (N. Engl. J. Med. 2006;354:291–3).

Dr. Ratjen noted that the treatment has an unpleasant taste, induces coughing, and would add at least 30 minutes to patients' daily treatment schedules.

Hypertonic saline inhalation using a nebulizer reduced pulmonary exacerbations in patients with cystic fibrosis and decreased their absenteeism from school, work, and their usual activities, researchers found in two separate randomized clinical trials.

The trials provided the first evidence of the long-term efficacy of this safe and relatively inexpensive treatment. The therapy appears to work by restoring the volume of liquid on the airway surfaces, which is depleted because of excessive absorption of salt from the airway lumen. This rehydration seems to produce a sustained acceleration of mucus clearance, both groups of investigators theorized.

In the first study, 164 adults and children with stable cystic fibrosis (CF) were randomly assigned to inhale 4 mL of either hypertonic (7%) saline plus a taste-masking agent or a control solution (isotonic saline) plus a taste-masking agent via nebulizer twice a day for 48 weeks. A bronchodilator was administered before each treatment to prevent or minimize narrowing of CF patients' hyperresponsive airways during nebulizer therapy, reported Dr. Mark R. Elkins, of Royal Prince Alfred Hospital, Sydney, Australia, and the University of Sydney, and his associates.

The treatment had only a moderate effect on lung function as measured by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁), and no apparent effect on the typical decline in lung function over the course of the year-long study. However, it had “dramatic” effects on several clinical factors, they noted (N. Engl. J. Med. 2006;354:229–40).

The mean number of symptom exacerbations was 1.32 per person in the treatment group, compared with 2.74 per control subject. The mean duration of exacerbations was 22 days in the treatment group, compared with 69 days in the control group. And the length of time spent free of exacerbations, expressed as “48-week exacerbation-free survival rate,” was 41% in the treatment group, compared with 16% in the controls. All of these differences were highly statistically significant. Similarly, antibiotic use during exacerbations was much lower for the active treatment group.

Patients in the active treatment group reported a mean of 7 days (range, 0–21) when they could not participate in school, work, or usual activities, compared with a mean of 24 days (range, 12–48) for the controls. The treatment group also scored significantly higher on quality of life measures.

The treatment did not alter the levels of Pseudomonas aeruginosa or Staphylococcus aureus in the sputum, nor did it affect the rate of acquisition of these organisms, Burkholderia cepacia, Stenotrophomonas maltophilia, Candida albicans, aspergillus species, or Hemophilus influenzae.

In the other clinical trial, investigators reasoned that slowing the absorption of nebulized hypertonic saline by premedicating CF patients with amiloride, a sodium channel blocker, would enhance patient response by extending the duration of airway rehydration. Twenty-four CF patients aged 14 years and older were randomized to pretreatment with either amiloride or a taste-masked placebo, followed by hypertonic saline via nebulizer four times daily for 14 days. All the subjects received a bronchodilator via inhaler 30–60 minutes before the nebulizer treatment.

The study confirmed that hypertonic saline improved CF symptoms, lung function, and quality of life, reported Dr. Scott H. Donaldson and Dr. William D. Bennett of the University of North Carolina at Chapel Hill Cystic Fibrosis Research and Treatment Center and their associates. Perhaps as important, the treatment hastened the rate of mucus clearance from the lungs and “produced a larger and more sustained increase in the volume of airway surface liquid” in CF patients than in healthy controls (N. Engl. J. Med. 2006;354:241–50).

The findings suggest inhaled hypertonic saline may be an option for CF patients, Dr. Felix Ratjen of the University of Toronto said in an editorial comment accompanying the publication of both reports.

It was previously shown that hypertonic saline inhalation increased mucociliary transport in CF patients—but the effect was presumed to be short-lived because sodium deposited on epithelial surfaces would be taken up rapidly. The new research shows that the treatment “not only had a prolonged effect on the amount of airway surface liquid in epithelial cells … but also resulted in a sustained improvement of mucociliary transport,” Dr. Ratjen said (N. Engl. J. Med. 2006;354:291–3).

Dr. Ratjen noted that the treatment has an unpleasant taste, induces coughing, and would add at least 30 minutes to patients' daily treatment schedules.

Hypertonic saline inhalation using a nebulizer reduced pulmonary exacerbations in patients with cystic fibrosis and decreased their absenteeism from school, work, and their usual activities, researchers found in two separate randomized clinical trials.

The trials provided the first evidence of the long-term efficacy of this safe and relatively inexpensive treatment. The therapy appears to work by restoring the volume of liquid on the airway surfaces, which is depleted because of excessive absorption of salt from the airway lumen. This rehydration seems to produce a sustained acceleration of mucus clearance, both groups of investigators theorized.

In the first study, 164 adults and children with stable cystic fibrosis (CF) were randomly assigned to inhale 4 mL of either hypertonic (7%) saline plus a taste-masking agent or a control solution (isotonic saline) plus a taste-masking agent via nebulizer twice a day for 48 weeks. A bronchodilator was administered before each treatment to prevent or minimize narrowing of CF patients' hyperresponsive airways during nebulizer therapy, reported Dr. Mark R. Elkins, of Royal Prince Alfred Hospital, Sydney, Australia, and the University of Sydney, and his associates.

The treatment had only a moderate effect on lung function as measured by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁), and no apparent effect on the typical decline in lung function over the course of the year-long study. However, it had “dramatic” effects on several clinical factors, they noted (N. Engl. J. Med. 2006;354:229–40).

The mean number of symptom exacerbations was 1.32 per person in the treatment group, compared with 2.74 per control subject. The mean duration of exacerbations was 22 days in the treatment group, compared with 69 days in the control group. And the length of time spent free of exacerbations, expressed as “48-week exacerbation-free survival rate,” was 41% in the treatment group, compared with 16% in the controls. All of these differences were highly statistically significant. Similarly, antibiotic use during exacerbations was much lower for the active treatment group.

Patients in the active treatment group reported a mean of 7 days (range, 0–21) when they could not participate in school, work, or usual activities, compared with a mean of 24 days (range, 12–48) for the controls. The treatment group also scored significantly higher on quality of life measures.

The treatment did not alter the levels of Pseudomonas aeruginosa or Staphylococcus aureus in the sputum, nor did it affect the rate of acquisition of these organisms, Burkholderia cepacia, Stenotrophomonas maltophilia, Candida albicans, aspergillus species, or Hemophilus influenzae.

In the other clinical trial, investigators reasoned that slowing the absorption of nebulized hypertonic saline by premedicating CF patients with amiloride, a sodium channel blocker, would enhance patient response by extending the duration of airway rehydration. Twenty-four CF patients aged 14 years and older were randomized to pretreatment with either amiloride or a taste-masked placebo, followed by hypertonic saline via nebulizer four times daily for 14 days. All the subjects received a bronchodilator via inhaler 30–60 minutes before the nebulizer treatment.

The study confirmed that hypertonic saline improved CF symptoms, lung function, and quality of life, reported Dr. Scott H. Donaldson and Dr. William D. Bennett of the University of North Carolina at Chapel Hill Cystic Fibrosis Research and Treatment Center and their associates. Perhaps as important, the treatment hastened the rate of mucus clearance from the lungs and “produced a larger and more sustained increase in the volume of airway surface liquid” in CF patients than in healthy controls (N. Engl. J. Med. 2006;354:241–50).

The findings suggest inhaled hypertonic saline may be an option for CF patients, Dr. Felix Ratjen of the University of Toronto said in an editorial comment accompanying the publication of both reports.

It was previously shown that hypertonic saline inhalation increased mucociliary transport in CF patients—but the effect was presumed to be short-lived because sodium deposited on epithelial surfaces would be taken up rapidly. The new research shows that the treatment “not only had a prolonged effect on the amount of airway surface liquid in epithelial cells … but also resulted in a sustained improvement of mucociliary transport,” Dr. Ratjen said (N. Engl. J. Med. 2006;354:291–3).

Dr. Ratjen noted that the treatment has an unpleasant taste, induces coughing, and would add at least 30 minutes to patients' daily treatment schedules.

Statins neither raise nor lower the risk of cancer or cancer mortality, according to a metaanalysis of 26 randomized clinical trials.

Several retrospective studies have suggested that statins reduce the risk of developing cancer by as much as 50%. However, three metaanalyses have failed to confirm that statins exert a protective effect against cancer.

To shed light on the issue, Krista M. Dale, Pharm.D., of the University of Connecticut School of Pharmacy, Hartford, and her associates conducted a much larger metaanalysis of 26 randomized clinical trials involving 86,936 subjects. The participants were followed up for 2–10 years for the development of cancer.

The trials included only placebo-controlled or standard treatment-controlled studies enrolling a minimum of 100 subjects each. Most of these trials assessed the ability of statins to prevent coronary artery disease, but all examined cancer diagnosis or cancer death as a primary or secondary end point.

Statins did not reduce the risk of cancer or of cancer death, Dr. Dale and her associates said (JAMA 2006;295:74–80).

When six major subtypes of cancer—breast, colon, gastrointestinal, prostate, respiratory tract, and skin cancers—were considered individually, statins did not reduce the risk of any of these types.

Similarly, when pravastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, and lovastatin were considered individually, none of the agents reduced the risk of cancer or cancer death.

And when the metaanalysis was narrowed to assess natural versus synthetic statins and low-lipophilic versus high-lipophilic statins, the results did not change.

“We thought hydrophilic statins, with their impaired ability to penetrate biological membranes, might provide different effects than lipophilic statins, which readily enter cells, but this was not evident in our study. Similarly, naturally derived statins have a markedly different structure than synthetic statins, but neither type affected the results,” the investigators noted.

Statins neither raise nor lower the risk of cancer or cancer mortality, according to a metaanalysis of 26 randomized clinical trials.

Several retrospective studies have suggested that statins reduce the risk of developing cancer by as much as 50%. However, three metaanalyses have failed to confirm that statins exert a protective effect against cancer.

To shed light on the issue, Krista M. Dale, Pharm.D., of the University of Connecticut School of Pharmacy, Hartford, and her associates conducted a much larger metaanalysis of 26 randomized clinical trials involving 86,936 subjects. The participants were followed up for 2–10 years for the development of cancer.

The trials included only placebo-controlled or standard treatment-controlled studies enrolling a minimum of 100 subjects each. Most of these trials assessed the ability of statins to prevent coronary artery disease, but all examined cancer diagnosis or cancer death as a primary or secondary end point.

Statins did not reduce the risk of cancer or of cancer death, Dr. Dale and her associates said (JAMA 2006;295:74–80).

When six major subtypes of cancer—breast, colon, gastrointestinal, prostate, respiratory tract, and skin cancers—were considered individually, statins did not reduce the risk of any of these types.

Similarly, when pravastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, and lovastatin were considered individually, none of the agents reduced the risk of cancer or cancer death.

And when the metaanalysis was narrowed to assess natural versus synthetic statins and low-lipophilic versus high-lipophilic statins, the results did not change.

“We thought hydrophilic statins, with their impaired ability to penetrate biological membranes, might provide different effects than lipophilic statins, which readily enter cells, but this was not evident in our study. Similarly, naturally derived statins have a markedly different structure than synthetic statins, but neither type affected the results,” the investigators noted.

Statins neither raise nor lower the risk of cancer or cancer mortality, according to a metaanalysis of 26 randomized clinical trials.

Several retrospective studies have suggested that statins reduce the risk of developing cancer by as much as 50%. However, three metaanalyses have failed to confirm that statins exert a protective effect against cancer.

To shed light on the issue, Krista M. Dale, Pharm.D., of the University of Connecticut School of Pharmacy, Hartford, and her associates conducted a much larger metaanalysis of 26 randomized clinical trials involving 86,936 subjects. The participants were followed up for 2–10 years for the development of cancer.

The trials included only placebo-controlled or standard treatment-controlled studies enrolling a minimum of 100 subjects each. Most of these trials assessed the ability of statins to prevent coronary artery disease, but all examined cancer diagnosis or cancer death as a primary or secondary end point.

Statins did not reduce the risk of cancer or of cancer death, Dr. Dale and her associates said (JAMA 2006;295:74–80).

When six major subtypes of cancer—breast, colon, gastrointestinal, prostate, respiratory tract, and skin cancers—were considered individually, statins did not reduce the risk of any of these types.

Similarly, when pravastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, and lovastatin were considered individually, none of the agents reduced the risk of cancer or cancer death.

And when the metaanalysis was narrowed to assess natural versus synthetic statins and low-lipophilic versus high-lipophilic statins, the results did not change.

“We thought hydrophilic statins, with their impaired ability to penetrate biological membranes, might provide different effects than lipophilic statins, which readily enter cells, but this was not evident in our study. Similarly, naturally derived statins have a markedly different structure than synthetic statins, but neither type affected the results,” the investigators noted.

Aspirin therapy for the primary prevention of cardiovascular disease may reduce the risk of ischemic stroke in women and the risk of myocardial infarction in men, according to a metaanalysis specifically designed to tease out gender-based differences in response to aspirin therapy.

But the results should be interpreted with caution because aspirin dose, duration of treatment, and length of follow-up were not uniform among the six trials in the metaanalysis. Moreover, the populations studied were healthy and at low risk for cardiovascular events, and the number of events was low.

Few data are available on aspirin for primary cardiovascular disease prevention in women, and the one large, randomized trial to examine the issue showed different effects in women than those found in studies that enrolled men predominantly or exclusively, said Dr. Jeffrey S. Berger of Duke University, Durham, N.C., and his associates.

To clarify any possible differences in the benefits for men and women, the investigators performed a metaanalysis of six prospective, randomized, controlled trials that included data on cardiovascular death, MI, and stroke. Three trials included only men, one included only women, and two involved both sexes.

Together the studies yielded data on 51,342 women and 44,144 men followed for a mean of 6.4 years after they began aspirin therapy or a placebo/control treatment.

Major cardiovascular events occurred in 1,285 women and 2,047 men. Pooled results showed a statistically significant 12% decrease in the risk of cardiovascular events in women taking aspirin and a significant 14% reduction in men taking aspirin, the investigators said (JAMA 2006;295:306–13).

The absolute risk reduction for cardiovascular events was 0.30% for women and 0.37% for men, and the number needed to treat to prevent one cardiovascular event over the mean follow-up of 6.4 years was 333 for women and 270 for men.

However, aspirin's effects differed between the sexes when specific cardiovascular events were examined.

A total of 469 women developed MI (0.9%), and the rate was similar between those taking aspirin and those taking a placebo/control treatment. In contrast, 1,023 men developed MI (2.3%), and the rate was 32% lower in those taking aspirin.

Strokes occurred in 625 women (1.2%), and the rate was 17% lower in those taking aspirin—a significant difference. For women, aspirin cut ischemic stroke by 24% but did not appear to affect hemorrhagic stroke. In contrast, strokes occurred in 597 men (1.3%), and the rate was nonsignificantly increased in those taking aspirin. For men, aspirin had no effect on ischemic stroke but raised the risk for hemorrhagic stroke by a significant 69%.

Aspirin therapy did not affect the death rate from cardiovascular causes or all-cause mortality in either men or women. It raised the risk of major bleeding events, usually GI bleeding, for both sexes.

The reason for these apparent gender-related differences in response to aspirin therapy remains unclear. It may be related to the fact that overall risk for MI is lower in women than in men, while overall risk for stroke is higher in women than in men. There also may be differences between men and women in aspirin metabolism and aspirin resistance, the investigators said.

The findings should be interpreted cautiously because the six trials were not consistent in terms of aspirin dose, duration of treatment, and length of follow-up; in addition, the number of events was low.

In particular, the relatively small number of MIs among women and of ischemic strokes among men “suggest that further studies are needed before we can [definitively] conclude that men and women differ in their cardiovascular response to aspirin,” Dr. Berger and his associates said.

The results should be interpreted with caution because the six trials included in the metaanalysis were not consistent. DR. BERGER

Aspirin therapy for the primary prevention of cardiovascular disease may reduce the risk of ischemic stroke in women and the risk of myocardial infarction in men, according to a metaanalysis specifically designed to tease out gender-based differences in response to aspirin therapy.

But the results should be interpreted with caution because aspirin dose, duration of treatment, and length of follow-up were not uniform among the six trials in the metaanalysis. Moreover, the populations studied were healthy and at low risk for cardiovascular events, and the number of events was low.

Few data are available on aspirin for primary cardiovascular disease prevention in women, and the one large, randomized trial to examine the issue showed different effects in women than those found in studies that enrolled men predominantly or exclusively, said Dr. Jeffrey S. Berger of Duke University, Durham, N.C., and his associates.

To clarify any possible differences in the benefits for men and women, the investigators performed a metaanalysis of six prospective, randomized, controlled trials that included data on cardiovascular death, MI, and stroke. Three trials included only men, one included only women, and two involved both sexes.

Together the studies yielded data on 51,342 women and 44,144 men followed for a mean of 6.4 years after they began aspirin therapy or a placebo/control treatment.

Major cardiovascular events occurred in 1,285 women and 2,047 men. Pooled results showed a statistically significant 12% decrease in the risk of cardiovascular events in women taking aspirin and a significant 14% reduction in men taking aspirin, the investigators said (JAMA 2006;295:306–13).

The absolute risk reduction for cardiovascular events was 0.30% for women and 0.37% for men, and the number needed to treat to prevent one cardiovascular event over the mean follow-up of 6.4 years was 333 for women and 270 for men.

However, aspirin's effects differed between the sexes when specific cardiovascular events were examined.

A total of 469 women developed MI (0.9%), and the rate was similar between those taking aspirin and those taking a placebo/control treatment. In contrast, 1,023 men developed MI (2.3%), and the rate was 32% lower in those taking aspirin.

Strokes occurred in 625 women (1.2%), and the rate was 17% lower in those taking aspirin—a significant difference. For women, aspirin cut ischemic stroke by 24% but did not appear to affect hemorrhagic stroke. In contrast, strokes occurred in 597 men (1.3%), and the rate was nonsignificantly increased in those taking aspirin. For men, aspirin had no effect on ischemic stroke but raised the risk for hemorrhagic stroke by a significant 69%.

Aspirin therapy did not affect the death rate from cardiovascular causes or all-cause mortality in either men or women. It raised the risk of major bleeding events, usually GI bleeding, for both sexes.

The reason for these apparent gender-related differences in response to aspirin therapy remains unclear. It may be related to the fact that overall risk for MI is lower in women than in men, while overall risk for stroke is higher in women than in men. There also may be differences between men and women in aspirin metabolism and aspirin resistance, the investigators said.

The findings should be interpreted cautiously because the six trials were not consistent in terms of aspirin dose, duration of treatment, and length of follow-up; in addition, the number of events was low.

In particular, the relatively small number of MIs among women and of ischemic strokes among men “suggest that further studies are needed before we can [definitively] conclude that men and women differ in their cardiovascular response to aspirin,” Dr. Berger and his associates said.

The results should be interpreted with caution because the six trials included in the metaanalysis were not consistent. DR. BERGER

Aspirin therapy for the primary prevention of cardiovascular disease may reduce the risk of ischemic stroke in women and the risk of myocardial infarction in men, according to a metaanalysis specifically designed to tease out gender-based differences in response to aspirin therapy.

But the results should be interpreted with caution because aspirin dose, duration of treatment, and length of follow-up were not uniform among the six trials in the metaanalysis. Moreover, the populations studied were healthy and at low risk for cardiovascular events, and the number of events was low.

Few data are available on aspirin for primary cardiovascular disease prevention in women, and the one large, randomized trial to examine the issue showed different effects in women than those found in studies that enrolled men predominantly or exclusively, said Dr. Jeffrey S. Berger of Duke University, Durham, N.C., and his associates.

To clarify any possible differences in the benefits for men and women, the investigators performed a metaanalysis of six prospective, randomized, controlled trials that included data on cardiovascular death, MI, and stroke. Three trials included only men, one included only women, and two involved both sexes.

Together the studies yielded data on 51,342 women and 44,144 men followed for a mean of 6.4 years after they began aspirin therapy or a placebo/control treatment.

Major cardiovascular events occurred in 1,285 women and 2,047 men. Pooled results showed a statistically significant 12% decrease in the risk of cardiovascular events in women taking aspirin and a significant 14% reduction in men taking aspirin, the investigators said (JAMA 2006;295:306–13).

The absolute risk reduction for cardiovascular events was 0.30% for women and 0.37% for men, and the number needed to treat to prevent one cardiovascular event over the mean follow-up of 6.4 years was 333 for women and 270 for men.

However, aspirin's effects differed between the sexes when specific cardiovascular events were examined.

A total of 469 women developed MI (0.9%), and the rate was similar between those taking aspirin and those taking a placebo/control treatment. In contrast, 1,023 men developed MI (2.3%), and the rate was 32% lower in those taking aspirin.

Strokes occurred in 625 women (1.2%), and the rate was 17% lower in those taking aspirin—a significant difference. For women, aspirin cut ischemic stroke by 24% but did not appear to affect hemorrhagic stroke. In contrast, strokes occurred in 597 men (1.3%), and the rate was nonsignificantly increased in those taking aspirin. For men, aspirin had no effect on ischemic stroke but raised the risk for hemorrhagic stroke by a significant 69%.

Aspirin therapy did not affect the death rate from cardiovascular causes or all-cause mortality in either men or women. It raised the risk of major bleeding events, usually GI bleeding, for both sexes.

The reason for these apparent gender-related differences in response to aspirin therapy remains unclear. It may be related to the fact that overall risk for MI is lower in women than in men, while overall risk for stroke is higher in women than in men. There also may be differences between men and women in aspirin metabolism and aspirin resistance, the investigators said.

The findings should be interpreted cautiously because the six trials were not consistent in terms of aspirin dose, duration of treatment, and length of follow-up; in addition, the number of events was low.

In particular, the relatively small number of MIs among women and of ischemic strokes among men “suggest that further studies are needed before we can [definitively] conclude that men and women differ in their cardiovascular response to aspirin,” Dr. Berger and his associates said.

The results should be interpreted with caution because the six trials included in the metaanalysis were not consistent. DR. BERGER