From International Journal of Clinical Practice
M. Affronti; P. Mansueto; M. Soresi; A. M. Abbene; A. Affronti; M. Valenti; L. Giannitrapani; G. Montalto
Posted: 02/18/2010; Int J Clin Pract. 2010;64(3):316-321. © 2010
Abstract
Background and aim: Low-grade fever (LGF) is defined as a body temperature between 37.5 and 38.3 °C, which is below the classical value reported for fever of unknown origin (FUO). We attempted to characterise its epidemiology, aetiology and clinical aspects to improve the methodological approach to diagnosis.
Design and Methods: We reviewed and evaluated a survey of patients with LGF, followed as outpatients of our Department, a tertiary referral centre from 1997 to 2008. The same classifications were applied for classical FUO, and in the patients diagnosed with LGF, we also investigated for habitual hyperthermia (HH).
Results: Seventy-three patients were selected and divided into two groups: group A included 32 patients classified with organic fever and group B included 41 patients with HH. Aetiology of organic LGF was: infectious disease 59%; neoplasm 3.1%; inflammatory non-infectious disease 6.2%; miscellaneous 18.7%; undiagnosed 12.5%. Mean age was significantly higher in the organic fever than in the HH group (p < 0.02). Splenomegaly and loss of weight were significantly associated with organic fever (p < 0.05), while dizziness and general malaise were associated with HH. Lack of any pathological signs at physical examination was significantly more frequent in HH (p < 0.0001). Among the biochemical tests, white blood cells and C-reactive protein were more frequently above normal limits in group A than in group B (p < 0.05).
Conclusions: In our experience, LGF requires the same methodological diagnostic approach as FUO, because there is no relationship between body temperature values and the severity of the underlying diseases, and the aetiological spectrum is also the same.
Introduction
Fever is one of the most common clinical manifestations referred by patients to their physicians.[1] The challenge is to distinguish between fevers caused by the more or less serious pathologies, requiring a specific therapy, and those caused by the vast majority of other ailments, which instead often present a self-limited pathology.
Fever is defined as an increase in body temperature mediated by a functional alteration of the regulatory centre of the hypothalamus, causing a rise in temperature towards the upper values of the set-point, the activation of the peripheral mechanisms of thermogenesis and the inhibition of those of thermodispersion.[2,3]
Hyperthermia, on the contrary, is an increase in body temperature independent of the physiological homeostatic control mechanisms, which do not, however, raise the hypothalamus set-point. In other words, it arises from a 'peripheral' alteration of the mechanisms of thermoproduction and thermodispersion.
Another important condition is the fever of unknown origin (FUO), which poses considerable problems for physicians, because although most diseases underlying FUO are treatable, they can be difficult to diagnose in a particular patient and for reasons which are not always clear.[4–11]
Low-grade fever (LGF) commonly refers to a condition with a body temperature continually or intermittently between 37.5 and 38.3 °C. As in the case of fever, it is absolutely a symptom accompanying very many infectious, and autoimmune and neoplastic diseases. Sometimes, however, there is no particular organic pathology, as in the case of habitual hyperthermia (HH), which, rather than a disease, should be considered a paraphysiological variant of normal body temperature.[6]
Habitual hyperthermia is a clinical condition characterised by a body temperature never higher than 38.3 °C, with an erratic circadian rhythm. It may persist for years and for rather complex reasons, and the normal body temperature of an otherwise perfectly healthy subject remains elevated. It is typical of young asthenic women prone to headaches and with vasomotor liability. Its diagnosis today is still possible, but only after an adequately prolonged period of observation and measurement of body temperature.[6] Although FUO is widely recognised and is frequently reported, in our opinion, LGF has not received adequate attention in the literature. This work, therefore, reviews our clinical experience of patients with LGF, with the aim of shedding further light on its frequency, causes, management, work-up, prognosis and possible links with the much better-known forms of FUO.
Sunday, February 28, 2010
Tuesday, February 23, 2010
Walking Plus Glucosamine May Improve Symptoms of Osteoarthritis
From Medscape Medical News
Fran Lowry
February 22, 2010 — A 30-minute walk taken at least 3 days a week combined with glucosamine sulfate supplements may reduce symptoms of mild to moderate hip or knee osteoarthritis (OA), researchers report in a new study published online February 12 in Arthritis Research & Therapy.
"Management of [OA] includes the use of non-pharmacologic and pharmacologic therapies," write Norman T. M. Ng, MD, from the University of Queensland, Brisbane, Australia, and colleagues. "Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA."
The main goal of this feasibility study was to evaluate the combined effects of a progressive walking program and glucosamine sulfate intake on OA symptoms and physical activity participation in people with mild to moderate OA.
In addition, the investigators compared the effectiveness of 2 frequencies of walking (3 vs 5 days per week) and 3 step levels (1500, 3000, and 6000 steps per day), combined with glucosamine sulfate supplements, and also examined compliance with supplement intake and the walking program.
The study included 28 patients aged 42 to 73 years. All patients were given 1500 mg of glucosamine sulfate per day for 6 weeks and then began a 12-week progressive walking program while continuing to take glucosamine.
Fifteen patients were randomly assigned to walk 5 days per week, and the remaining 13 were randomly assigned to walk 3 days per week. The participants received a pedometer to monitor their step counts. Step level of walking was gradually increased to 3000 steps per day during the first 6 weeks of walking and to 6000 steps per day for the next 6 weeks in both groups.
Patients were assessed at baseline and at 6-, 12-, 18-, and 24-week follow-ups.
Glucosamine Alone Was Helpful
The researchers found that during the first 6 weeks of the study, when patients were taking glucosamine supplements only, physical activity levels, physical function, and total Western Ontario and McMaster Universities scores improved (P < .05).
These outcomes continued to improve through to the final follow-up, although most improvements were seen between weeks 6 and 12, the authors report.
In addition, significant improvements were seen in patients' self-efficacy in managing arthritis pain and "other symptoms," in physical activity self-regulation, and in the number of perceived barriers to physical activity.
Compliance with the walking program was the same for both groups.
Walking 5 days per week was not more effective than walking 3 days per week in reducing pain and stiffness, increasing physical function, or improving most other measures used in the study, the authors report.
Participants in the 3-day walking group walked 3 days per week, but participants in the 5-day walking group walked slightly less than 4 days per week, which suggests that it may be difficult to get people with hip or knee OA to walk more than 3 to 4 days a week, the authors write.
Increased Activity Further Improved Results
Increasing the number of steps from 1500 to 3000 steps per day, combined with glucosamine intake, resulted in a 125% increase in minutes of physical activity, a 17% reduction in pain scores, and improvements in physical function. Increasing the steps to 6000 steps per day resulted in a further 57% increase in physical activity participation and further improvements in physical function.
The limitations of the study include the small sample size, the use of self-report data, the fact that joint space narrowing was not measured to assess the effectiveness of glucosamine supplementation, lack of a placebo control group, and lack of radiographic evidence to confirm the diagnosis and severity of OA.
"Although the study included a small sample, the findings provide preliminary evidence that OA sufferers can obtain health-related benefits from the combination of glucosamine supplements and walking," the authors conclude. "If the benefits of this program are confirmed, it could be promoted to increase physical activity among people with hip or knee OA."
Chris Morris, MD, a practicing rheumatologist at Arthritis Associates in Kingsport, Tennessee, commented on this study for Medscape Rheumatology, saying that it supports what many rheumatologists believe — that low- to no-impact exercise can make a difference in OA of the knee.
Glucosamine a Red Herring?
He questioned why glucosamine was added to the walking program, however. "I am perplexed as to why they included the glucosamine in the study. I think it is a bit of a red herring and is a flaw of the study, simply because they had no control group to see if exercise without glucosamine did as well. It is possible that they purposely did this to avoid questions related to glucosamine, using the use of the supplement as a way to standardize the patients," he said.
Dr. Morris added that many patients have unrealistic expectations about the beneficial effects of exercise.
"They expect immediacy in terms of results — they expect to be able to do everything they did 20 years (and often 50 pounds) earlier, and when their knees hurt, they just give up. Patients need to understand that they have to start out light and gradually work their way up — that any program takes time, and that they must commit to the activity long-term."
The study by the Australian researchers "provides yet another study to help support the viewpoint that exercise can help arthritic symptoms and the patient's well-being," Dr. Morris said. "I encourage my patients to exercise and have recommended walking to those who do not have the resources or access to health clubs, wellness centers, water exercise programs. Most people live reasonably near an enclosed shopping mall, many of which are carpeted, and most of which open their doors early for walkers."
Sanofi-aventis Consumer Health Care supplied the glucosamine supplements used in this study. Dr. Ng and Dr. Morris have disclosed no relevant financial interests.
Arthritis Res Therapy. Published online February 12, 2010.
Fran Lowry
February 22, 2010 — A 30-minute walk taken at least 3 days a week combined with glucosamine sulfate supplements may reduce symptoms of mild to moderate hip or knee osteoarthritis (OA), researchers report in a new study published online February 12 in Arthritis Research & Therapy.
"Management of [OA] includes the use of non-pharmacologic and pharmacologic therapies," write Norman T. M. Ng, MD, from the University of Queensland, Brisbane, Australia, and colleagues. "Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA."
The main goal of this feasibility study was to evaluate the combined effects of a progressive walking program and glucosamine sulfate intake on OA symptoms and physical activity participation in people with mild to moderate OA.
In addition, the investigators compared the effectiveness of 2 frequencies of walking (3 vs 5 days per week) and 3 step levels (1500, 3000, and 6000 steps per day), combined with glucosamine sulfate supplements, and also examined compliance with supplement intake and the walking program.
The study included 28 patients aged 42 to 73 years. All patients were given 1500 mg of glucosamine sulfate per day for 6 weeks and then began a 12-week progressive walking program while continuing to take glucosamine.
Fifteen patients were randomly assigned to walk 5 days per week, and the remaining 13 were randomly assigned to walk 3 days per week. The participants received a pedometer to monitor their step counts. Step level of walking was gradually increased to 3000 steps per day during the first 6 weeks of walking and to 6000 steps per day for the next 6 weeks in both groups.
Patients were assessed at baseline and at 6-, 12-, 18-, and 24-week follow-ups.
Glucosamine Alone Was Helpful
The researchers found that during the first 6 weeks of the study, when patients were taking glucosamine supplements only, physical activity levels, physical function, and total Western Ontario and McMaster Universities scores improved (P < .05).
These outcomes continued to improve through to the final follow-up, although most improvements were seen between weeks 6 and 12, the authors report.
In addition, significant improvements were seen in patients' self-efficacy in managing arthritis pain and "other symptoms," in physical activity self-regulation, and in the number of perceived barriers to physical activity.
Compliance with the walking program was the same for both groups.
Walking 5 days per week was not more effective than walking 3 days per week in reducing pain and stiffness, increasing physical function, or improving most other measures used in the study, the authors report.
Participants in the 3-day walking group walked 3 days per week, but participants in the 5-day walking group walked slightly less than 4 days per week, which suggests that it may be difficult to get people with hip or knee OA to walk more than 3 to 4 days a week, the authors write.
Increased Activity Further Improved Results
Increasing the number of steps from 1500 to 3000 steps per day, combined with glucosamine intake, resulted in a 125% increase in minutes of physical activity, a 17% reduction in pain scores, and improvements in physical function. Increasing the steps to 6000 steps per day resulted in a further 57% increase in physical activity participation and further improvements in physical function.
The limitations of the study include the small sample size, the use of self-report data, the fact that joint space narrowing was not measured to assess the effectiveness of glucosamine supplementation, lack of a placebo control group, and lack of radiographic evidence to confirm the diagnosis and severity of OA.
"Although the study included a small sample, the findings provide preliminary evidence that OA sufferers can obtain health-related benefits from the combination of glucosamine supplements and walking," the authors conclude. "If the benefits of this program are confirmed, it could be promoted to increase physical activity among people with hip or knee OA."
Chris Morris, MD, a practicing rheumatologist at Arthritis Associates in Kingsport, Tennessee, commented on this study for Medscape Rheumatology, saying that it supports what many rheumatologists believe — that low- to no-impact exercise can make a difference in OA of the knee.
Glucosamine a Red Herring?
He questioned why glucosamine was added to the walking program, however. "I am perplexed as to why they included the glucosamine in the study. I think it is a bit of a red herring and is a flaw of the study, simply because they had no control group to see if exercise without glucosamine did as well. It is possible that they purposely did this to avoid questions related to glucosamine, using the use of the supplement as a way to standardize the patients," he said.
Dr. Morris added that many patients have unrealistic expectations about the beneficial effects of exercise.
"They expect immediacy in terms of results — they expect to be able to do everything they did 20 years (and often 50 pounds) earlier, and when their knees hurt, they just give up. Patients need to understand that they have to start out light and gradually work their way up — that any program takes time, and that they must commit to the activity long-term."
The study by the Australian researchers "provides yet another study to help support the viewpoint that exercise can help arthritic symptoms and the patient's well-being," Dr. Morris said. "I encourage my patients to exercise and have recommended walking to those who do not have the resources or access to health clubs, wellness centers, water exercise programs. Most people live reasonably near an enclosed shopping mall, many of which are carpeted, and most of which open their doors early for walkers."
Sanofi-aventis Consumer Health Care supplied the glucosamine supplements used in this study. Dr. Ng and Dr. Morris have disclosed no relevant financial interests.
Arthritis Res Therapy. Published online February 12, 2010.
Probiotic Formula Prevents Diarrhea
From Reuters Health Information
NEW YORK (Reuters Health) Feb 19 - A commercially available formula of Lactobacillus acidophilus and L. casei prevents Clostridium difficile infection and diarrhea during antibiotic treatment, according to a single-center study from China.
Although meta-analyses indicate that probiotics decrease antibiotic-associated diarrhea, most trials are flawed, senior author Dr. Larry E. Miller and colleagues state. They say that their randomized, double-blind trial is the largest to address these issues and the first to examine dose effects.
The trial included 255 hospital patients, ages 50 to 70, receiving penicillin, cephalosporin or clindamycin. Within 36 hours of starting antibiotic therapy, patients began to take (each day, 2 hours after breakfast) either 2 probiotic capsules (n = 86), 1 probiotic capsule and 1 placebo capsule (n = 85), or 2 placebo capsules (n = 84). All patients were hospitalized for at least 5 days and received antibiotics for at least 3 days (but not more than 14 days). They continued with their assigned treatment for 5 days after finishing the course of antibiotics.
Each probiotic capsule contained 50 billion colony-forming units of L acidophilus CL1285 and L. casei.
As reported online February 9 in the American Journal of Gastroenterology, at 21 days after the end of their assigned treatments, the incidence of antibiotic-associated diarrhea was 44.1% in the placebo group, 28.2% in the 1-capsule group and 15.5% in the 2-capsule group.
Rates of diarrhea due to C. difficile were 23.8%, 9.4%, and 1.2% with placebo, 1 capsule, and 2 capsules, respectively.
The authors estimate that treating five patients at the higher probiotic dose would prevent one case of C. difficile-associated diarrhea.
Overall, the 2-capsule group had the lowest rate of gastrointestinal symptoms, followed by the 1-capsule group. The investigators observed a similar pattern for symptom duration.
They attribute their high response rates to the high probiotic dosage: "The probiotic load of this quantity likely overwhelms the intestinal tract and repopulates the gut with nonpathogenic flora, as well as enhances immune response to inhibit or destroy pathogenic bacteria."
The researchers note that their findings cannot be generalized to other probiotic products or to younger patients or those of non-Asian descent, and that the effects of probiotic therapy with prolonged antibiotic treatment are unknown.
On the other hand, "this trial used very stringent data collection and data analysis methods...and an intent-to-treat analysis."
The probiotic capsules used in this study are manufactured by Bio-K+ International (Laval, Quebec, Canada) and marketed as Bio-K+ CL1285. Bio-K+ provided financial support for the trial.
Am J Gastroenterol 2010.
NEW YORK (Reuters Health) Feb 19 - A commercially available formula of Lactobacillus acidophilus and L. casei prevents Clostridium difficile infection and diarrhea during antibiotic treatment, according to a single-center study from China.
Although meta-analyses indicate that probiotics decrease antibiotic-associated diarrhea, most trials are flawed, senior author Dr. Larry E. Miller and colleagues state. They say that their randomized, double-blind trial is the largest to address these issues and the first to examine dose effects.
The trial included 255 hospital patients, ages 50 to 70, receiving penicillin, cephalosporin or clindamycin. Within 36 hours of starting antibiotic therapy, patients began to take (each day, 2 hours after breakfast) either 2 probiotic capsules (n = 86), 1 probiotic capsule and 1 placebo capsule (n = 85), or 2 placebo capsules (n = 84). All patients were hospitalized for at least 5 days and received antibiotics for at least 3 days (but not more than 14 days). They continued with their assigned treatment for 5 days after finishing the course of antibiotics.
Each probiotic capsule contained 50 billion colony-forming units of L acidophilus CL1285 and L. casei.
As reported online February 9 in the American Journal of Gastroenterology, at 21 days after the end of their assigned treatments, the incidence of antibiotic-associated diarrhea was 44.1% in the placebo group, 28.2% in the 1-capsule group and 15.5% in the 2-capsule group.
Rates of diarrhea due to C. difficile were 23.8%, 9.4%, and 1.2% with placebo, 1 capsule, and 2 capsules, respectively.
The authors estimate that treating five patients at the higher probiotic dose would prevent one case of C. difficile-associated diarrhea.
Overall, the 2-capsule group had the lowest rate of gastrointestinal symptoms, followed by the 1-capsule group. The investigators observed a similar pattern for symptom duration.
They attribute their high response rates to the high probiotic dosage: "The probiotic load of this quantity likely overwhelms the intestinal tract and repopulates the gut with nonpathogenic flora, as well as enhances immune response to inhibit or destroy pathogenic bacteria."
The researchers note that their findings cannot be generalized to other probiotic products or to younger patients or those of non-Asian descent, and that the effects of probiotic therapy with prolonged antibiotic treatment are unknown.
On the other hand, "this trial used very stringent data collection and data analysis methods...and an intent-to-treat analysis."
The probiotic capsules used in this study are manufactured by Bio-K+ International (Laval, Quebec, Canada) and marketed as Bio-K+ CL1285. Bio-K+ provided financial support for the trial.
Am J Gastroenterol 2010.
High Vitamin D Levels Linked to Reduced Risk for Colon Cancer
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
CME Released: 02/09/2010;
February 9, 2010 — High vitamin D levels are linked to lower risk for colon cancer, according to the results of a nested case-control study reported Online First in the January 22 issue of the BMJ.
"An effect of vitamin D on cancer may be important in the colorectum because both normal and neoplastic colon cells can produce the active hormone from the main circulating form 25-hydroxy-vitamin D(25-(OH) D), suggesting that it may play a direct role in controlling the growth of normal and neoplastic colonic cells," write Mazda Jenab, from the International Agency for Research on Cancer (IARC-WHO), in Lyon, France, and colleagues. "However, the epidemiological evidence is not conclusive and almost no pre-diagnostic data are available from European populations."
The goal of this study was to evaluate the association between prediagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk for colorectal cancer in European populations, using the European Prospective Investigation into Cancer and Nutrition (EPIC) study cohort of more than 520,000 participants from 10 western European countries. After enrollment into the EPIC cohort, incident colorectal cancer developed in 1248 patients, and these case patients were matched to 1248 control subjects.
Primary study endpoints were circulating vitamin D concentration (25-[OH]D) measured by enzyme immunoassay, and dietary and lifestyle data collected with questionnaires.
Although higher dietary intake of calcium was associated with a lower risk for colorectal cancer, dietary vitamin D intake was not associated with disease risk. Sex, season, and month of blood donation did not affect the findings
BMJ. Published online January 22, 2010. Abstract
Clinical Context
Although epidemiologic research has suggested an inverse relationship between calcium and vitamin D and the risk for colorectal cancer, an analysis of the Women's Health Initiative cohort by Wactawski-Wende and colleagues suggested that oral supplementation of calcium and vitamin D might not ameliorate the risk for colorectal cancer among women.
Specifically, the results of the study, which were published in the February 16, 2006, issue of the New England Journal of Medicine, found that daily calcium supplements at a dose of 1000 mg with vitamin D3 400 IU were not superior to placebo in reducing the risk for colorectal cancer. This result was unchanged on subgroup analysis.
In addition to being consumed through the diet, vitamin D is synthesized through sun exposure. The current study focuses the association between circulating levels of vitamin D, in the form of 25-(OH)D, diet, and the risk for colorectal cancer in a large cohort of European adults.
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD
CME Released: 02/09/2010;
February 9, 2010 — High vitamin D levels are linked to lower risk for colon cancer, according to the results of a nested case-control study reported Online First in the January 22 issue of the BMJ.
"An effect of vitamin D on cancer may be important in the colorectum because both normal and neoplastic colon cells can produce the active hormone from the main circulating form 25-hydroxy-vitamin D(25-(OH) D), suggesting that it may play a direct role in controlling the growth of normal and neoplastic colonic cells," write Mazda Jenab, from the International Agency for Research on Cancer (IARC-WHO), in Lyon, France, and colleagues. "However, the epidemiological evidence is not conclusive and almost no pre-diagnostic data are available from European populations."
The goal of this study was to evaluate the association between prediagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk for colorectal cancer in European populations, using the European Prospective Investigation into Cancer and Nutrition (EPIC) study cohort of more than 520,000 participants from 10 western European countries. After enrollment into the EPIC cohort, incident colorectal cancer developed in 1248 patients, and these case patients were matched to 1248 control subjects.
Primary study endpoints were circulating vitamin D concentration (25-[OH]D) measured by enzyme immunoassay, and dietary and lifestyle data collected with questionnaires.
Although higher dietary intake of calcium was associated with a lower risk for colorectal cancer, dietary vitamin D intake was not associated with disease risk. Sex, season, and month of blood donation did not affect the findings
BMJ. Published online January 22, 2010. Abstract
Clinical Context
Although epidemiologic research has suggested an inverse relationship between calcium and vitamin D and the risk for colorectal cancer, an analysis of the Women's Health Initiative cohort by Wactawski-Wende and colleagues suggested that oral supplementation of calcium and vitamin D might not ameliorate the risk for colorectal cancer among women.
Specifically, the results of the study, which were published in the February 16, 2006, issue of the New England Journal of Medicine, found that daily calcium supplements at a dose of 1000 mg with vitamin D3 400 IU were not superior to placebo in reducing the risk for colorectal cancer. This result was unchanged on subgroup analysis.
In addition to being consumed through the diet, vitamin D is synthesized through sun exposure. The current study focuses the association between circulating levels of vitamin D, in the form of 25-(OH)D, diet, and the risk for colorectal cancer in a large cohort of European adults.
Monday, February 22, 2010
Red Flags May Help Identify Serious Infection in Children
From MedscapeCME Clinical Briefs
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
February 11, 2010 — Rapid breathing, parental concern, and the clinician's instinct are among the red flags warning of serious infection in children in developed countries, according to the results of a systematic review reported online in the February 3 issue of The Lancet.
Clinical Context
The World Health Organization has defined some criteria as red flags for serious infection in children in developing countries. These include reduced consciousness, convulsions, cyanosis, rapid breathing, and low capillary refill. However, in the United Kingdom, serious infection accounts for 20% of deaths in children, but in a primary care setting, only 1% of children assessed will have a serious illness.
This is a systematic review of studies to examine the clinical features most useful for ruling in and ruling out serious infection in children in developed countries.
Clinical Implications
Parental concern and clinician instinct followed by cyanosis, rapid breathing, poor peripheral circulation, and petechial rash are predictive of serious infection in children.
Absence of parental or clinician concern and absence of breathlessness are helpful for ruling out pneumonia in children.
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
February 11, 2010 — Rapid breathing, parental concern, and the clinician's instinct are among the red flags warning of serious infection in children in developed countries, according to the results of a systematic review reported online in the February 3 issue of The Lancet.
Clinical Context
The World Health Organization has defined some criteria as red flags for serious infection in children in developing countries. These include reduced consciousness, convulsions, cyanosis, rapid breathing, and low capillary refill. However, in the United Kingdom, serious infection accounts for 20% of deaths in children, but in a primary care setting, only 1% of children assessed will have a serious illness.
This is a systematic review of studies to examine the clinical features most useful for ruling in and ruling out serious infection in children in developed countries.
Clinical Implications
Parental concern and clinician instinct followed by cyanosis, rapid breathing, poor peripheral circulation, and petechial rash are predictive of serious infection in children.
Absence of parental or clinician concern and absence of breathlessness are helpful for ruling out pneumonia in children.
Sunday, February 21, 2010
Gout Treatment & Prevention
Gout Treatments and drugs By Mayo Clinic
Treatment for gout usually involves medications. What medications you and your doctor choose will be based on your current health and your own preferences.
Different medications are prescribed to:
Treat acute gout attacks and prevent future attacks
Reduce the risk of gout complications, such as the deposits of urate crystals that cause nodules to form under the skin (tophi)
Drugs used to treat acute attacks and prevent future attacks include:
Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs may control inflammation and pain in people with gout. Your doctor may prescribe a higher dose to stop an acute attack, followed by a lower daily dose to prevent future attacks.
NSAIDs include over-the-counter options such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve, others), as well as more powerful prescription NSAIDs such as indomethacin (Indocin). NSAIDs carry risks of stomach pain, bleeding and ulcers.
Colchicine. If you're unable to take NSAIDs, your doctor may recommend colchicine, a type of pain reliever that effectively reduces gout pain — especially when started soon after symptoms appear. The drug's effectiveness is offset in most cases, however, by intolerable side effects, such as nausea, vomiting and diarrhea.
After an acute gout attack resolves, your doctor may prescribe a low daily dose of colchicine to prevent future attacks.
Corticosteroids. Corticosteroid medications, such as the drug prednisone, may control gout inflammation and pain. Corticosteroids may be administered in pill form, or they can be injected into your joint. Corticosteroids are generally reserved for people who can't take either NSAIDs or colchicine.
Side effects of corticosteroids may include thinning bones, poor wound healing and a decreased ability to fight infection. To reduce the risk of these serious side effects, your doctor will try to find the lowest dose that controls your symptoms and prescribe steroids for the shortest possible time.
Drugs used to prevent the complications associated with frequent gout attacks include:
Medication that blocks uric acid production. Drugs called xanthine oxidase inhibitors, including allopurinol (Zyloprim, Aloprim) and febuxostat (Uloric), limit the amount of uric acid your body makes. This may lower your blood's uric acid level and reduce your risk of gout. Side effects of allopurinol include a rash and low blood counts. Febuxostat side effects include rash, nausea and reduced liver function.
Xanthine oxidase inhibitors may trigger a new, acute attack if taken before a recent attack has totally resolved. Taking a short course of low-dose colchicine before starting a xanthine oxidase inhibitor has been found to significantly reduce this risk.
Medication that improves uric acid removal. Probenecid (Probalan) improves your kidneys' ability to remove uric acid from your body. This may lower your uric acid levels and reduce your risk of gout, but the level of uric acid in your urine is increased. Side effects include a rash, stomach pain and kidney stones.
Lifestyle and home remedies
Medications are the most proven, effective way to treat gout symptoms. However, making certain changes to your diet also may help.
The American Dietetic Association recommends following these guidelines during a gout attack:
Drink 8 to 16 cups (about 2 to 4 liters) of fluid each day, including at least half water.
Avoid alcohol.
Eat a moderate amount of protein, preferably from healthy sources, such as low-fat or fat-free dairy, tofu, eggs, and nut butters.
Limit your daily intake of meat, fish and poultry to 4 to 6 ounces (114 to 170 grams).
Alternative medicine
If gout treatments aren't working as well as you'd hoped, you may be interested in trying complementary and alternative treatments for your gout. Discuss these treatments with your doctor first. Your doctor can help you weigh the benefits and risks and tell you if the treatments will interfere with your gout medications.
Though you may be reluctant to discuss complementary and alternative medicine with your doctor, many mainstream doctors are becoming more open to discussing these options. But, since few of these treatments have been extensively studied in clinical trials, it's difficult to assess whether these treatments are helpful for gout pain. In some cases, the risks of these treatments aren't known.
Some complementary and alternative treatments that have been studied include:
Coffee. Studies have found an association between coffee drinking — both regular and decaffeinated coffee — and lower uric acid levels, though no study has demonstrated how or why coffee may have an influence on uric acid in your body. The available evidence isn't enough to encourage noncoffee drinkers to start, but it may give researchers clues to new ways of treating gout in the future.
Vitamin C. Supplements containing vitamin C may reduce the levels of uric acid in your blood. However, vitamin C hasn't been studied as a treatment for gout. Don't assume that if a little vitamin C is good for you, then lots is better. Megadoses of vitamin C may increase your body's uric acid levels. Talk to your doctor about what a reasonable dose of vitamin C may be. And don't forget that you can increase your vitamin C intake by eating more fruits and vegetables, especially oranges.
Cherries. Cherries have been associated with lower levels of uric acid in studies, but it isn't clear if they have any effect on gout signs and symptoms. Adding cherries and other dark-colored fruits, such as blackberries, blueberries, purple grapes and raspberries, to your diet may be a safe way to supplement your gout treatment, but discuss it with your doctor first.
Other complementary and alternative medicine treatments may help you cope until your gout pain subsides or your medications take effect. For instance, relaxation techniques, such as deep-breathing exercises and meditation, may help take your mind off your pain.
Prevention
Medications
If you experience several gout attacks each year or if your gout attacks are less frequent but particularly painful, your doctor may recommend medication to reduce your risk of future gout attacks and of gout-related complications.
You usually begin taking preventive medications once your acute gout attack has subsided. Options include:
Low-dose NSAIDs
Low-dose colchicine
Allopurinol or febuxostat
Probenecid
Dietary changes
During symptom-free periods, these dietary guidelines may help protect against future gout attacks:
Keep your fluid intake high. Aim for 8 to 16 cups (about 2 to 4 liters) of fluid each day, including at least half water.
Limit or avoid alcohol. Talk with your doctor about whether any amount or type of alcohol is safe for you. Recent evidence suggests that beer may be particularly likely to increase the risk of gout symptoms, especially in men.
Eat a balanced diet following the Dietary Guidelines for Americans. Your daily diet should emphasize fruits, vegetables, whole grains, and fat-free or low-fat milk products.
Get your protein from low-fat dairy products. Low-fat dairy products may actually have a protective effect against gout, so these are your best-bet protein sources.
Limit your intake of meat, fish and poultry. A small amount may be tolerable, but pay close attention to what types — and how much — seem to cause problems for you.
Maintain a desirable body weight. Choose portions that allow you to maintain a healthy weight. Losing weight may decrease uric acid levels in your body. But avoid fasting or rapid weight loss, since doing so may temporarily raise uric acid levels
Treatment for gout usually involves medications. What medications you and your doctor choose will be based on your current health and your own preferences.
Different medications are prescribed to:
Treat acute gout attacks and prevent future attacks
Reduce the risk of gout complications, such as the deposits of urate crystals that cause nodules to form under the skin (tophi)
Drugs used to treat acute attacks and prevent future attacks include:
Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs may control inflammation and pain in people with gout. Your doctor may prescribe a higher dose to stop an acute attack, followed by a lower daily dose to prevent future attacks.
NSAIDs include over-the-counter options such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve, others), as well as more powerful prescription NSAIDs such as indomethacin (Indocin). NSAIDs carry risks of stomach pain, bleeding and ulcers.
Colchicine. If you're unable to take NSAIDs, your doctor may recommend colchicine, a type of pain reliever that effectively reduces gout pain — especially when started soon after symptoms appear. The drug's effectiveness is offset in most cases, however, by intolerable side effects, such as nausea, vomiting and diarrhea.
After an acute gout attack resolves, your doctor may prescribe a low daily dose of colchicine to prevent future attacks.
Corticosteroids. Corticosteroid medications, such as the drug prednisone, may control gout inflammation and pain. Corticosteroids may be administered in pill form, or they can be injected into your joint. Corticosteroids are generally reserved for people who can't take either NSAIDs or colchicine.
Side effects of corticosteroids may include thinning bones, poor wound healing and a decreased ability to fight infection. To reduce the risk of these serious side effects, your doctor will try to find the lowest dose that controls your symptoms and prescribe steroids for the shortest possible time.
Drugs used to prevent the complications associated with frequent gout attacks include:
Medication that blocks uric acid production. Drugs called xanthine oxidase inhibitors, including allopurinol (Zyloprim, Aloprim) and febuxostat (Uloric), limit the amount of uric acid your body makes. This may lower your blood's uric acid level and reduce your risk of gout. Side effects of allopurinol include a rash and low blood counts. Febuxostat side effects include rash, nausea and reduced liver function.
Xanthine oxidase inhibitors may trigger a new, acute attack if taken before a recent attack has totally resolved. Taking a short course of low-dose colchicine before starting a xanthine oxidase inhibitor has been found to significantly reduce this risk.
Medication that improves uric acid removal. Probenecid (Probalan) improves your kidneys' ability to remove uric acid from your body. This may lower your uric acid levels and reduce your risk of gout, but the level of uric acid in your urine is increased. Side effects include a rash, stomach pain and kidney stones.
Lifestyle and home remedies
Medications are the most proven, effective way to treat gout symptoms. However, making certain changes to your diet also may help.
The American Dietetic Association recommends following these guidelines during a gout attack:
Drink 8 to 16 cups (about 2 to 4 liters) of fluid each day, including at least half water.
Avoid alcohol.
Eat a moderate amount of protein, preferably from healthy sources, such as low-fat or fat-free dairy, tofu, eggs, and nut butters.
Limit your daily intake of meat, fish and poultry to 4 to 6 ounces (114 to 170 grams).
Alternative medicine
If gout treatments aren't working as well as you'd hoped, you may be interested in trying complementary and alternative treatments for your gout. Discuss these treatments with your doctor first. Your doctor can help you weigh the benefits and risks and tell you if the treatments will interfere with your gout medications.
Though you may be reluctant to discuss complementary and alternative medicine with your doctor, many mainstream doctors are becoming more open to discussing these options. But, since few of these treatments have been extensively studied in clinical trials, it's difficult to assess whether these treatments are helpful for gout pain. In some cases, the risks of these treatments aren't known.
Some complementary and alternative treatments that have been studied include:
Coffee. Studies have found an association between coffee drinking — both regular and decaffeinated coffee — and lower uric acid levels, though no study has demonstrated how or why coffee may have an influence on uric acid in your body. The available evidence isn't enough to encourage noncoffee drinkers to start, but it may give researchers clues to new ways of treating gout in the future.
Vitamin C. Supplements containing vitamin C may reduce the levels of uric acid in your blood. However, vitamin C hasn't been studied as a treatment for gout. Don't assume that if a little vitamin C is good for you, then lots is better. Megadoses of vitamin C may increase your body's uric acid levels. Talk to your doctor about what a reasonable dose of vitamin C may be. And don't forget that you can increase your vitamin C intake by eating more fruits and vegetables, especially oranges.
Cherries. Cherries have been associated with lower levels of uric acid in studies, but it isn't clear if they have any effect on gout signs and symptoms. Adding cherries and other dark-colored fruits, such as blackberries, blueberries, purple grapes and raspberries, to your diet may be a safe way to supplement your gout treatment, but discuss it with your doctor first.
Other complementary and alternative medicine treatments may help you cope until your gout pain subsides or your medications take effect. For instance, relaxation techniques, such as deep-breathing exercises and meditation, may help take your mind off your pain.
Prevention
Medications
If you experience several gout attacks each year or if your gout attacks are less frequent but particularly painful, your doctor may recommend medication to reduce your risk of future gout attacks and of gout-related complications.
You usually begin taking preventive medications once your acute gout attack has subsided. Options include:
Low-dose NSAIDs
Low-dose colchicine
Allopurinol or febuxostat
Probenecid
Dietary changes
During symptom-free periods, these dietary guidelines may help protect against future gout attacks:
Keep your fluid intake high. Aim for 8 to 16 cups (about 2 to 4 liters) of fluid each day, including at least half water.
Limit or avoid alcohol. Talk with your doctor about whether any amount or type of alcohol is safe for you. Recent evidence suggests that beer may be particularly likely to increase the risk of gout symptoms, especially in men.
Eat a balanced diet following the Dietary Guidelines for Americans. Your daily diet should emphasize fruits, vegetables, whole grains, and fat-free or low-fat milk products.
Get your protein from low-fat dairy products. Low-fat dairy products may actually have a protective effect against gout, so these are your best-bet protein sources.
Limit your intake of meat, fish and poultry. A small amount may be tolerable, but pay close attention to what types — and how much — seem to cause problems for you.
Maintain a desirable body weight. Choose portions that allow you to maintain a healthy weight. Losing weight may decrease uric acid levels in your body. But avoid fasting or rapid weight loss, since doing so may temporarily raise uric acid levels
Saturday, February 20, 2010
North American Menopause Society Issues Guidelines on Hormone Therapy
From Medscape Medical News
Laurie Barclay, MD
February 18, 2010 — The benefit-risk ratio for menopausal hormone therapy (HT) is favorable for women beginning HT close to menopause but decreases in older women and with time since menopause in previously untreated women, according to the latest evidence-based position statement of the North American Menopause Society (NAMS), posted online February 16 and will be published in the March/April issue of Menopause.
"From a clinical perspective, the latest NAMS position statement on HT considers the current best practice of medicine," NAMS Executive Director Margery L. S. Gass, MD, NCMP, said in a news release. "The Panel of world famous authorities clarified a broad spectrum of topics related to HT benefits and risks for postmenopausal women."
Development of the Guidelines
The goal of the latest guidelines was to update clinicians as well as the lay public regarding NAMS' recommendations for menopausal HT for postmenopausal women, considering the therapeutic benefit-risk ratio at various times through and beyond menopause.
An advisory panel of 17 clinicians and researchers with special expertise in HT reviewed each section of the previous position statement, published by NAMS in July 2008, in light of new studies and findings, and reached consensus on recommendations. The NAMS board of trustees then approved the updated official position statement, which highlights recent evidence regarding risks for breast cancer, cognitive dysfunction and decline, dementia, coronary heart disease (CHD), and stroke, as well as new recommendations regarding discontinuing HT.
The updated guidelines also include new sections on HT and ovarian and lung cancer, a listing of areas that vary from the 2008 position statement, and a suggested bibliography of key references published since the last statement.
The American Medical Women's Association, the Asociación Mexicana para el Estudio del Climaterio, the Endocrine Society, Healthy Women (formerly the National Women's Health Resource Center), the National Association of Nurse Practitioners in Women's Health, and the Society of Obstetricians and Gynaecologists of Canada all had representatives participating fully in the editorial process and have endorsed the newest NAMS position statement.
"Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered," the statement authors write.
"Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both.
The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women."
The Women's Health Initiative (WHI) trial of estrogen therapy (ET) offered evidence of considerable safety for 0.625 mg/day of oral conjugated estrogen, supporting the position that at least for this form of HT, the potential absolute risks are low.
In the WHI trial of combined estrogen-progestogen therapy (EPT), most risks were determined to be rare, using the criteria of the Council for International Organizations of Medical Sciences, except for stroke, which was above the rare category.
"For women younger than age 50 or those at low risk of CHD, stroke, osteoporosis, breast cancer, or colon cancer, the absolute risk or benefit from ET or EPT is likely to be even smaller than that demonstrated in the WHI, although the relative risk at different ages may be similar," the statement authors write. "There is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects. Further research remains essential."
Cancer and HT
Evidence to date is conflicting regarding the role of HT and risk for ovarian cancer, with no association or a modest increase in most epidemiologic studies, but with an association between HT use and increased ovarian cancer risk based on a relatively large volume of observational trial data. The statement suggests that the association between ovarian cancer and HT beyond 5 years, if any, should be considered as rare or very rare, but that women with a positive family history or other increased risk for ovarian cancer should be counseled about this rare association.
Overall data, including those from WHI analysis, suggest that starting EPT in older women with a positive smoking history may promote the growth of existing lung cancers. In contrast, evidence from the WHI and some case-control and cohort studies suggests that use of HT in women younger than 60 years offers some protection against lung cancer.
Although safety of EPT in survivors of breast cancer is controversial, with observational studies suggesting that it is safe and possibly even protective against recurrence, a randomized controlled trial showed a statistically significant 2.4-fold increase in new breast cancer events. ET use in breast cancer survivors has not been proven to be safe and may be associated with an increased risk for recurrence.
Cognitive Impairment, CHD, and HT
For the sole or main indication of preventing cognitive aging or dementia, the statement does not recommend HT at any age, and HT is actually linked to increased incidence of dementia when started in women age 65 years and older.
Available data do not adequately address whether HT started soon after menopause increases or decreases later dementia risk, and limited evidence does not support the use of HT as a treatment of Alzheimer's disease.
In terms of cardiovascular effects, the statement authors note that HT is currently not recommended as a sole or main indication for coronary protection in women of any age.
Starting HT by age 50 to 59 years or within 10 years of menopause to treat typical menopausal symptoms does not seem to increase the risk for CHD events, and there is some recent evidence that starting ET in early postmenopause may lower CHD risk.
Findings of observational studies have been inconsistent regarding stroke risk with HT. The Nurses Health Study and WHI showed an increased risk for ischemic stroke, but other studies showed no effect on stroke risk.
Current data suggest that when HT is either tapered or abruptly discontinued, rates of vasomotor symptom recurrence are similar. The statement therefore makes no recommendation concerning how to discontinue therapy.
"When HT is desired by patients, individualization of therapy is key to providing health benefits with minimal risks, thereby enhancing [quality of life]," the statement authors conclude. "Women should be informed of known risks, but it cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy.
A woman's willingness to accept risks of HT will vary depending on her individual situation, particularly whether HT is being considered to treat existing symptoms or to lower risk for osteoporotic fractures that may or may not occur."
Financial disclosures of the statement authors are available online at the end of the position statement.
Menopause. 2010;17:242-255.
Laurie Barclay, MD
February 18, 2010 — The benefit-risk ratio for menopausal hormone therapy (HT) is favorable for women beginning HT close to menopause but decreases in older women and with time since menopause in previously untreated women, according to the latest evidence-based position statement of the North American Menopause Society (NAMS), posted online February 16 and will be published in the March/April issue of Menopause.
"From a clinical perspective, the latest NAMS position statement on HT considers the current best practice of medicine," NAMS Executive Director Margery L. S. Gass, MD, NCMP, said in a news release. "The Panel of world famous authorities clarified a broad spectrum of topics related to HT benefits and risks for postmenopausal women."
Development of the Guidelines
The goal of the latest guidelines was to update clinicians as well as the lay public regarding NAMS' recommendations for menopausal HT for postmenopausal women, considering the therapeutic benefit-risk ratio at various times through and beyond menopause.
An advisory panel of 17 clinicians and researchers with special expertise in HT reviewed each section of the previous position statement, published by NAMS in July 2008, in light of new studies and findings, and reached consensus on recommendations. The NAMS board of trustees then approved the updated official position statement, which highlights recent evidence regarding risks for breast cancer, cognitive dysfunction and decline, dementia, coronary heart disease (CHD), and stroke, as well as new recommendations regarding discontinuing HT.
The updated guidelines also include new sections on HT and ovarian and lung cancer, a listing of areas that vary from the 2008 position statement, and a suggested bibliography of key references published since the last statement.
The American Medical Women's Association, the Asociación Mexicana para el Estudio del Climaterio, the Endocrine Society, Healthy Women (formerly the National Women's Health Resource Center), the National Association of Nurse Practitioners in Women's Health, and the Society of Obstetricians and Gynaecologists of Canada all had representatives participating fully in the editorial process and have endorsed the newest NAMS position statement.
"Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered," the statement authors write.
"Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both.
The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women."
The Women's Health Initiative (WHI) trial of estrogen therapy (ET) offered evidence of considerable safety for 0.625 mg/day of oral conjugated estrogen, supporting the position that at least for this form of HT, the potential absolute risks are low.
In the WHI trial of combined estrogen-progestogen therapy (EPT), most risks were determined to be rare, using the criteria of the Council for International Organizations of Medical Sciences, except for stroke, which was above the rare category.
"For women younger than age 50 or those at low risk of CHD, stroke, osteoporosis, breast cancer, or colon cancer, the absolute risk or benefit from ET or EPT is likely to be even smaller than that demonstrated in the WHI, although the relative risk at different ages may be similar," the statement authors write. "There is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects. Further research remains essential."
Cancer and HT
Evidence to date is conflicting regarding the role of HT and risk for ovarian cancer, with no association or a modest increase in most epidemiologic studies, but with an association between HT use and increased ovarian cancer risk based on a relatively large volume of observational trial data. The statement suggests that the association between ovarian cancer and HT beyond 5 years, if any, should be considered as rare or very rare, but that women with a positive family history or other increased risk for ovarian cancer should be counseled about this rare association.
Overall data, including those from WHI analysis, suggest that starting EPT in older women with a positive smoking history may promote the growth of existing lung cancers. In contrast, evidence from the WHI and some case-control and cohort studies suggests that use of HT in women younger than 60 years offers some protection against lung cancer.
Although safety of EPT in survivors of breast cancer is controversial, with observational studies suggesting that it is safe and possibly even protective against recurrence, a randomized controlled trial showed a statistically significant 2.4-fold increase in new breast cancer events. ET use in breast cancer survivors has not been proven to be safe and may be associated with an increased risk for recurrence.
Cognitive Impairment, CHD, and HT
For the sole or main indication of preventing cognitive aging or dementia, the statement does not recommend HT at any age, and HT is actually linked to increased incidence of dementia when started in women age 65 years and older.
Available data do not adequately address whether HT started soon after menopause increases or decreases later dementia risk, and limited evidence does not support the use of HT as a treatment of Alzheimer's disease.
In terms of cardiovascular effects, the statement authors note that HT is currently not recommended as a sole or main indication for coronary protection in women of any age.
Starting HT by age 50 to 59 years or within 10 years of menopause to treat typical menopausal symptoms does not seem to increase the risk for CHD events, and there is some recent evidence that starting ET in early postmenopause may lower CHD risk.
Findings of observational studies have been inconsistent regarding stroke risk with HT. The Nurses Health Study and WHI showed an increased risk for ischemic stroke, but other studies showed no effect on stroke risk.
Current data suggest that when HT is either tapered or abruptly discontinued, rates of vasomotor symptom recurrence are similar. The statement therefore makes no recommendation concerning how to discontinue therapy.
"When HT is desired by patients, individualization of therapy is key to providing health benefits with minimal risks, thereby enhancing [quality of life]," the statement authors conclude. "Women should be informed of known risks, but it cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy.
A woman's willingness to accept risks of HT will vary depending on her individual situation, particularly whether HT is being considered to treat existing symptoms or to lower risk for osteoporotic fractures that may or may not occur."
Financial disclosures of the statement authors are available online at the end of the position statement.
Menopause. 2010;17:242-255.
Friday, February 19, 2010
Gastric Bypass Patients at Risk of Kidney Stones
From Reuters Health Information
NEW YORK (Reuters Health) Feb 16 - Roux-en-Y gastric bypass surgery might increase patients' risk for kidney stones, researchers report in the March Journal of Urology.
As lead author Dr. Naim M. Maalouf told Reuters Health by email, "We found that the amount of oxalate -- a material found in kidney stones -- in urine was elevated in about half of the patients after Roux-en-Y gastric bypass surgery, even in those without kidney stones."
"The amount of citrate -- a compound that inhibits or slows down stone formation -- in the urine was low in two-thirds of the bypass patients," he added.
Dr. Maalouf and colleagues at the University of Texas Southwestern Medical Center, Dallas, compared 19 bariatric surgery patients with matched obese controls. Neither the patients (at an average of 3.5 years after surgery) nor the controls had any history of nephrolithiasis.
Compared to controls, the patients had significantly higher urinary oxalate than controls (45 versus 30 mg/day) and significantly lower urinary citrate (358 versus 767 mg/day). Patients' urinary calcium was also significantly lower (115 versus 123 mg/day).
Overall 47% of patients and 10.5% of controls had hyperoxaluria (urinary oxalate >45 mg/day), and 63% and 5%, respectively, had hypocitraturia (urinary citrate < 320 mg/day).
The relative hypocalciuria in the studied patients, the researchers point out, "offsets these lithogenic risk factors. The true incidence of nephrolithiasis and optimal treatment for lithogenic risk factors in this population remain to be established."
Dr. Maalouf points out, however: "The majority of patients are at risk for kidney stone formation after Roux-en-Y gastric bypass surgery. This complication is not well recognized because it tends to occur months to years after the bypass surgery."
J Urol 2010;183:1026-1030.
NEW YORK (Reuters Health) Feb 16 - Roux-en-Y gastric bypass surgery might increase patients' risk for kidney stones, researchers report in the March Journal of Urology.
As lead author Dr. Naim M. Maalouf told Reuters Health by email, "We found that the amount of oxalate -- a material found in kidney stones -- in urine was elevated in about half of the patients after Roux-en-Y gastric bypass surgery, even in those without kidney stones."
"The amount of citrate -- a compound that inhibits or slows down stone formation -- in the urine was low in two-thirds of the bypass patients," he added.
Dr. Maalouf and colleagues at the University of Texas Southwestern Medical Center, Dallas, compared 19 bariatric surgery patients with matched obese controls. Neither the patients (at an average of 3.5 years after surgery) nor the controls had any history of nephrolithiasis.
Compared to controls, the patients had significantly higher urinary oxalate than controls (45 versus 30 mg/day) and significantly lower urinary citrate (358 versus 767 mg/day). Patients' urinary calcium was also significantly lower (115 versus 123 mg/day).
Overall 47% of patients and 10.5% of controls had hyperoxaluria (urinary oxalate >45 mg/day), and 63% and 5%, respectively, had hypocitraturia (urinary citrate < 320 mg/day).
The relative hypocalciuria in the studied patients, the researchers point out, "offsets these lithogenic risk factors. The true incidence of nephrolithiasis and optimal treatment for lithogenic risk factors in this population remain to be established."
Dr. Maalouf points out, however: "The majority of patients are at risk for kidney stone formation after Roux-en-Y gastric bypass surgery. This complication is not well recognized because it tends to occur months to years after the bypass surgery."
J Urol 2010;183:1026-1030.
Increased Risk of Diabetes Observed Among Statin-Treated Patients
From Heartwire
Michael O’Riordan
February 17, 2010 (Glasgow, Scotland) — New data from a large meta-analysis of major statin trials suggests the LDL-cholesterol–lowering drugs slightly increase the risk of developing diabetes mellitus [1].
Investigators stress, however, that clinical practice should remain unchanged in patients with moderate or high cardiovascular risk, given the low absolute risk of developing diabetes, particularly when when compared with the benefit of statins.
"We found that there was indeed a risk of diabetes, about 9%, but it isn't a worrying increase as had been suggested by other studies," said co–lead investigator Dr David Preiss (University of Glasgow, Scotland). "Then again, it wasn't a completely flat result. We did see something. Our message would be that people on statins should be those we think are at moderate to high cardiovascular risk in the future. If you look at that group of patients, then what we really want to see come out of the study is a reassuring message, because there is little question that the protective effects in reducing heart attacks, strokes, and so on heavily outweigh this risk of developing diabetes."
Dr Steven Nissen (Cleveland Clinic, OH), who was not involved in the meta-analysis, praised the researchers, calling their interpretation of the data "responsible." Most important, he agreed with their conclusions, stating that the benefits of statins exceed the risk of diabetes and that physicians should not alter clinical practice based on these findings.
"In all of these trials, the population with diabetes or the population with new-onset diabetes had the same benefit in terms of reduction in morbidity and mortality as did people who received statins who were not insulin resistant or who had prediabetes," Nissen told heartwire . "Whatever this effect is, it doesn't lessen the favorable effect of statins on clinical outcomes. I don't think people should hesitate to give prediabetic patients statins because they might develop diabetes a few weeks or a few months later and deny them all the other benefits of these drugs."
The results of the study, which was also led by Dr Naveed Sattar (University of Glasgow), are published online February 17, 2010 in the Lancet.
Diabetes Concern Raised in JUPITER
Speaking with heartwire , Preiss explained that previous statin trials have reported conflicting results with regard to the risk of developing diabetes in patients taking the lipid-lowering medication.
In the West of Scotland Coronary Prevention Study (WOSCOPS), for example, there was a reduction in diabetes in patients treated with pravastatin, whereas in the large, highly publicized Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, previously reported by heartwire , researchers showed that significantly more patients in the rosuvastatin (Crestor, AstraZeneca) arm developed new diabetes after a median treatment of 1.9 years. It was this finding that raised some red flags, he noted.
To address the possibility of an increased risk of diabetes with statin therapy, Preiss and colleagues performed a meta-analysis of 13 statin studies. The group included statin studies with more than 1000 patients, those that had identical follow-up in both treatment arms, and those with more than one-year duration in follow-up.
In total, 91 140 participants were included in the meta-analysis. During a mean follow-up of four years, 4278 individuals developed diabetes mellitus, including 2226 patients treated with statins and 2052 assigned to a control therapy.
Treatment with statins was associated with a statistically significant 9% increase in the risk of incident diabetes, with little heterogeneity between trials. As with the overall results, the increased risk was maintained when the analysis was restricted to placebo-controlled trials only and when JUPITER and the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study, a Japanese patient population, were each excluded from the analysis.
Association Between Statins and Development of Diabetes Statin Odds ratio (95% CI)
Overall (n=91 140) 1.09 (1.02–1.17)
Atorvastatin only (n=7773) 1.14 (0.89–1.46)
Simvastatin only (n=18 815) 1.11 (0.97–1.26)
Rosuvastatin only (n=24 714) 1.18 (1.04–1.33)
Pravastatin (n=33 627) 1.03 (0.90–1.19)
Lovastatin (n=6211) 0.98 (0.70–1.38)
Overall, the 174 more cases of diabetes among patients treated with statins translates into one additional case of diabetes per 255 patients taking statins for four years, report the researchers.
Using the data from the Cholesterol Trialists' Collaboration, Preiss said this compares favorably with the 5.4 deaths or MIs that are avoided over four years for every patient treated with statins.
This benefit is even larger when the reduction in revascularizations and strokes are accounted for with statin therapy.
Investigators report that there was no clear difference between hydrophilic statins (pravastatin and rosuvastatin) and lipophilic statins (atorvastatin, simvastatin, and lovastatin), although there was a statistically significant increased risk among individuals treated with rosuvastatin.
To heartwire , Preiss said the risk appears to be a class effect and that no one statin should be singled out. The 18% increased risk of diabetes in rosuvastatin-treated patients included two heart-failure trials, he noted, a patient population already at an increased risk of diabetes. Similarly, Nissen noted that the PROSPER trial first raised the diabetes issue when investigators observed a statistically significant 32% increased risk of diabetes among pravastatin-treated patients.
Continue to Treat With Statins, Urge Clinicians
Also commenting on the results for heartwire , Dr Richard Karas (Tufts Medical Center, Boston, MA), who was not part of the study, said the concern about diabetes is an important question that needs to be addressed given the widespread use of the drugs worldwide.
This is another opportunity for the media to really scare the pants off people, and I think their findings are very carefully worded--there is a statistically significant but slight increase in the risk of diabetes.”
"The possibility of small risks, when multiplied by the number of people who take statins, is an extremely important issue," said Karas. "I think the paper is well done and careful in its interpretation. This is another opportunity for the media to really scare the pants off people, and I think their findings are very carefully worded--there is a statistically significant but slight increase in the risk of diabetes. It's a provocative finding, but it's also of modest strength because it's information culled from studies not designed to answer this question."
Karas pointed out that a similar issue exists with niacin, in that there are concerns about its use among patients at risk for diabetes. Despite the drugs' adverse metabolic effect in patients at risk for diabetes, clinicians are still very aggressive in using statins and niacin because these are patients who are at an increased risk of cardiovascular events. "It's very important that clinicians don't get the message to shy away from treating patients most in need of lipid-altering therapies," Karas told heartwire .
Preiss reiterated those concerns, saying that the benefits of statin therapy are outweighed by the reduction of cardiovascular events, although the risk/benefit trade-off applies only to patients studied in these 13 trials, those with moderate to high risk of cardiovascular disease, and that the risk/benefit ratio is less clear in low-risk patients treated with statins.
Rosuvastatin Approved Last Week
Last week, the Food and Drug Administration agreed to broader labeling for rosuvastatin based on the results of the JUPITER study. Asked about the decision in light of the newly identified diabetes risks, particularly since more patients will now be eligible for statins, Nissen told heartwire that the patients captured by the new label are at moderate to high risk given their age, elevated C-reactive protein (CRP) levels, and one additional risk factor. As such, the degree that they stand to benefit from statins is greater than the risk they face for developing diabetes, he said
In an editorial accompanying the published study [2], Dr Christopher Cannon (Brigham and Women's Hospital, Boston, MA) calls the increased diabetes risk "almost paradoxical" given statins' benefit of reducing cardiovascular events in patients with known diabetes. He points out, though, that other cardiovascular drugs, including thiazide diuretics, beta blockers, and niacin have similar associations. He writes that this newly identified risk warrants monitoring and that "it seems reasonable to add glucose to the list of tests to monitor in older patients who are on statins."
Asked about mechanisms, no one who spoke with heartwire was sure why there is an increased risk of type 2 diabetes. It is possible, noted Preiss, that the risk is the result of an off-target effect of treatment, or even an indirect result, where those experiencing muscle pain or weakness caused by statins are less likely to exercise, resulting in more diabetes. However, he emphasized more study is needed. Next up, he said, is an investigation of the effects of high-dose vs low-dose statins on the risk of diabetes.
Michael O’Riordan
February 17, 2010 (Glasgow, Scotland) — New data from a large meta-analysis of major statin trials suggests the LDL-cholesterol–lowering drugs slightly increase the risk of developing diabetes mellitus [1].
Investigators stress, however, that clinical practice should remain unchanged in patients with moderate or high cardiovascular risk, given the low absolute risk of developing diabetes, particularly when when compared with the benefit of statins.
"We found that there was indeed a risk of diabetes, about 9%, but it isn't a worrying increase as had been suggested by other studies," said co–lead investigator Dr David Preiss (University of Glasgow, Scotland). "Then again, it wasn't a completely flat result. We did see something. Our message would be that people on statins should be those we think are at moderate to high cardiovascular risk in the future. If you look at that group of patients, then what we really want to see come out of the study is a reassuring message, because there is little question that the protective effects in reducing heart attacks, strokes, and so on heavily outweigh this risk of developing diabetes."
Dr Steven Nissen (Cleveland Clinic, OH), who was not involved in the meta-analysis, praised the researchers, calling their interpretation of the data "responsible." Most important, he agreed with their conclusions, stating that the benefits of statins exceed the risk of diabetes and that physicians should not alter clinical practice based on these findings.
"In all of these trials, the population with diabetes or the population with new-onset diabetes had the same benefit in terms of reduction in morbidity and mortality as did people who received statins who were not insulin resistant or who had prediabetes," Nissen told heartwire . "Whatever this effect is, it doesn't lessen the favorable effect of statins on clinical outcomes. I don't think people should hesitate to give prediabetic patients statins because they might develop diabetes a few weeks or a few months later and deny them all the other benefits of these drugs."
The results of the study, which was also led by Dr Naveed Sattar (University of Glasgow), are published online February 17, 2010 in the Lancet.
Diabetes Concern Raised in JUPITER
Speaking with heartwire , Preiss explained that previous statin trials have reported conflicting results with regard to the risk of developing diabetes in patients taking the lipid-lowering medication.
In the West of Scotland Coronary Prevention Study (WOSCOPS), for example, there was a reduction in diabetes in patients treated with pravastatin, whereas in the large, highly publicized Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, previously reported by heartwire , researchers showed that significantly more patients in the rosuvastatin (Crestor, AstraZeneca) arm developed new diabetes after a median treatment of 1.9 years. It was this finding that raised some red flags, he noted.
To address the possibility of an increased risk of diabetes with statin therapy, Preiss and colleagues performed a meta-analysis of 13 statin studies. The group included statin studies with more than 1000 patients, those that had identical follow-up in both treatment arms, and those with more than one-year duration in follow-up.
In total, 91 140 participants were included in the meta-analysis. During a mean follow-up of four years, 4278 individuals developed diabetes mellitus, including 2226 patients treated with statins and 2052 assigned to a control therapy.
Treatment with statins was associated with a statistically significant 9% increase in the risk of incident diabetes, with little heterogeneity between trials. As with the overall results, the increased risk was maintained when the analysis was restricted to placebo-controlled trials only and when JUPITER and the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study, a Japanese patient population, were each excluded from the analysis.
Association Between Statins and Development of Diabetes Statin Odds ratio (95% CI)
Overall (n=91 140) 1.09 (1.02–1.17)
Atorvastatin only (n=7773) 1.14 (0.89–1.46)
Simvastatin only (n=18 815) 1.11 (0.97–1.26)
Rosuvastatin only (n=24 714) 1.18 (1.04–1.33)
Pravastatin (n=33 627) 1.03 (0.90–1.19)
Lovastatin (n=6211) 0.98 (0.70–1.38)
Overall, the 174 more cases of diabetes among patients treated with statins translates into one additional case of diabetes per 255 patients taking statins for four years, report the researchers.
Using the data from the Cholesterol Trialists' Collaboration, Preiss said this compares favorably with the 5.4 deaths or MIs that are avoided over four years for every patient treated with statins.
This benefit is even larger when the reduction in revascularizations and strokes are accounted for with statin therapy.
Investigators report that there was no clear difference between hydrophilic statins (pravastatin and rosuvastatin) and lipophilic statins (atorvastatin, simvastatin, and lovastatin), although there was a statistically significant increased risk among individuals treated with rosuvastatin.
To heartwire , Preiss said the risk appears to be a class effect and that no one statin should be singled out. The 18% increased risk of diabetes in rosuvastatin-treated patients included two heart-failure trials, he noted, a patient population already at an increased risk of diabetes. Similarly, Nissen noted that the PROSPER trial first raised the diabetes issue when investigators observed a statistically significant 32% increased risk of diabetes among pravastatin-treated patients.
Continue to Treat With Statins, Urge Clinicians
Also commenting on the results for heartwire , Dr Richard Karas (Tufts Medical Center, Boston, MA), who was not part of the study, said the concern about diabetes is an important question that needs to be addressed given the widespread use of the drugs worldwide.
This is another opportunity for the media to really scare the pants off people, and I think their findings are very carefully worded--there is a statistically significant but slight increase in the risk of diabetes.”
"The possibility of small risks, when multiplied by the number of people who take statins, is an extremely important issue," said Karas. "I think the paper is well done and careful in its interpretation. This is another opportunity for the media to really scare the pants off people, and I think their findings are very carefully worded--there is a statistically significant but slight increase in the risk of diabetes. It's a provocative finding, but it's also of modest strength because it's information culled from studies not designed to answer this question."
Karas pointed out that a similar issue exists with niacin, in that there are concerns about its use among patients at risk for diabetes. Despite the drugs' adverse metabolic effect in patients at risk for diabetes, clinicians are still very aggressive in using statins and niacin because these are patients who are at an increased risk of cardiovascular events. "It's very important that clinicians don't get the message to shy away from treating patients most in need of lipid-altering therapies," Karas told heartwire .
Preiss reiterated those concerns, saying that the benefits of statin therapy are outweighed by the reduction of cardiovascular events, although the risk/benefit trade-off applies only to patients studied in these 13 trials, those with moderate to high risk of cardiovascular disease, and that the risk/benefit ratio is less clear in low-risk patients treated with statins.
Rosuvastatin Approved Last Week
Last week, the Food and Drug Administration agreed to broader labeling for rosuvastatin based on the results of the JUPITER study. Asked about the decision in light of the newly identified diabetes risks, particularly since more patients will now be eligible for statins, Nissen told heartwire that the patients captured by the new label are at moderate to high risk given their age, elevated C-reactive protein (CRP) levels, and one additional risk factor. As such, the degree that they stand to benefit from statins is greater than the risk they face for developing diabetes, he said
In an editorial accompanying the published study [2], Dr Christopher Cannon (Brigham and Women's Hospital, Boston, MA) calls the increased diabetes risk "almost paradoxical" given statins' benefit of reducing cardiovascular events in patients with known diabetes. He points out, though, that other cardiovascular drugs, including thiazide diuretics, beta blockers, and niacin have similar associations. He writes that this newly identified risk warrants monitoring and that "it seems reasonable to add glucose to the list of tests to monitor in older patients who are on statins."
Asked about mechanisms, no one who spoke with heartwire was sure why there is an increased risk of type 2 diabetes. It is possible, noted Preiss, that the risk is the result of an off-target effect of treatment, or even an indirect result, where those experiencing muscle pain or weakness caused by statins are less likely to exercise, resulting in more diabetes. However, he emphasized more study is needed. Next up, he said, is an investigation of the effects of high-dose vs low-dose statins on the risk of diabetes.
Pipe and Cigar Smoking Linked to Decreased Lung Function and COPD
From Medscape Medical News
Fran Lowry
February 17, 2010 — Pipe and cigar smoking has been found to increase urine cotinine levels and is associated with decreased lung functio and increased odds of airflow obstruction, even in individuals who had never smoked cigarettes, according to the results of a large cohort study published February 16 in the Annals of Internal Medicine.
"Cigarette smoking is the main cause of chronic obstructive pulmonary disease [COPD]," write Josanna Rodriguez, MD, from Columbia University Medical Center, New York, NY, and colleagues, "but studies on the contribution of other smoking techniques are sparse."
The aim of this study was to determine whether pipe and cigar smoking resulted in absorption of tobacco smoke, as assessed by urine cotinine levels, as well as decrements in lung function and increased odds of airflow obstruction.
The investigators collected information on 3528 subjects aged 48 to 90 years, with no clinical evidence of cardiovascular disease, who were participants in the Multi-Ethnic Study of Atherosclerosis (MESA) trial.
They used self-administered items from the American Thoracic Society questionnaire to elicit participants' smoking histories for pipes, cigars, and cigarettes and measured cotinine levels from urine that was collected on the same day the questionnaire was administered.
Lung function was measured on spirometry according to American Thoracic Society and European Respiratory Society guidelines, and information on the following confounders was obtained: age; sex; race or ethnicity; educational level; medical history; occupational exposure to dust, fumes, or smoke; depth of inhalation of cigarettes; environmental tobacco smoke exposure; and family history of emphysema.
The study found that 9% of the participants reported pipe smoking (median, 15 pipe-years; interquartile range [IQR], 4 - 46 pipe-years), 11% reported cigar smoking (median, 6 cigar-years; IQR, 0 - 26 cigar-years), and 52% reported cigarette smoking (median, 18 pack-years).
Median cotinine levels were less than 10 ng/mL in never-smokers, 43 ng/mL in current cigar smokers, 1324 ng/mL in current pipe smokers, and 4304 ng/mL in current cigarette smokers (all P < .001 vs never-smokers). Median cotinine levels were also elevated in current cigar and current pipe smokers who reported never smoking cigarettes, the study authors report.
They also found that pipe-years were associated with decrements in forced expiratory volume in 1 second (FEV1), and cigar-years were associated with decrements in the FEV1-forced vital capacity (FVC) ratio. Furthermore, participants who smoked pipes or cigars had increased odds of airflow obstruction, whether they had also smoked cigarettes (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.75 - 6.71; P < .001) or not (OR, 2.31; CI, 1.04 - 5.11; P = .039) vs participants with no smoking history.
"These results, together with the extensive literature on the effects of tobacco smoke on the development of COPD and the increase in cotinine levels among current pipe and cigar smokers in this cohort, suggest that pipe and cigar smoking produce a measurable increase in the risk for COPD," the study authors write.
Limitations of this study are the cross-sectional design, the retrospective ascertainment of cumulative pipe and cigar smoking, and the relatively small proportion of participants who smoked pipes or cigars but not cigarettes.
The study authors conclude that their findings suggest that long-term pipe and cigar smoking may damage the lungs and contribute to the development of COPD. "Physicians should consider pipe and cigar smoking a risk factor for COPD and counsel cessation of pipe and cigar smoking regardless of cigarette smoking history."
In an accompanying editorial, Michael B. Steinberg, MD, MPH, from Robert Wood Johnson Medical School, New Brunswick, New Jersey, and coauthor Christine D. Delnevo, PhD, MPH, from the University of Medicine and Dentistry of New Jersey, School of Public Health, New Brunswick, New Jersey, write that as long as the marketing of cigars and pipes remains under the radar of public health advocates and legislative bodies, their use will continue to increase.
"Rodriguez and colleagues have shown that smoke, whether from cigarette, pipe, or cigar, will result in absorption of one of the most addictive chemicals known, nicotine, and will produce measurable lung damage," they conclude. "Tobacco users and health care providers alike need to fully understand the true harms caused by all tobacco products and the role that these products play in a larger public health battle."
The National Heart, Lung, and Blood Institute, National Institutes of Health, supported this study. Disclosure information for the study authors and the editorialists can be obtained in the original article, available on the Annals Web site .
Ann Intern Med. 2010;152:201-210, 259-260. Abstract
Fran Lowry
February 17, 2010 — Pipe and cigar smoking has been found to increase urine cotinine levels and is associated with decreased lung functio and increased odds of airflow obstruction, even in individuals who had never smoked cigarettes, according to the results of a large cohort study published February 16 in the Annals of Internal Medicine.
"Cigarette smoking is the main cause of chronic obstructive pulmonary disease [COPD]," write Josanna Rodriguez, MD, from Columbia University Medical Center, New York, NY, and colleagues, "but studies on the contribution of other smoking techniques are sparse."
The aim of this study was to determine whether pipe and cigar smoking resulted in absorption of tobacco smoke, as assessed by urine cotinine levels, as well as decrements in lung function and increased odds of airflow obstruction.
The investigators collected information on 3528 subjects aged 48 to 90 years, with no clinical evidence of cardiovascular disease, who were participants in the Multi-Ethnic Study of Atherosclerosis (MESA) trial.
They used self-administered items from the American Thoracic Society questionnaire to elicit participants' smoking histories for pipes, cigars, and cigarettes and measured cotinine levels from urine that was collected on the same day the questionnaire was administered.
Lung function was measured on spirometry according to American Thoracic Society and European Respiratory Society guidelines, and information on the following confounders was obtained: age; sex; race or ethnicity; educational level; medical history; occupational exposure to dust, fumes, or smoke; depth of inhalation of cigarettes; environmental tobacco smoke exposure; and family history of emphysema.
The study found that 9% of the participants reported pipe smoking (median, 15 pipe-years; interquartile range [IQR], 4 - 46 pipe-years), 11% reported cigar smoking (median, 6 cigar-years; IQR, 0 - 26 cigar-years), and 52% reported cigarette smoking (median, 18 pack-years).
Median cotinine levels were less than 10 ng/mL in never-smokers, 43 ng/mL in current cigar smokers, 1324 ng/mL in current pipe smokers, and 4304 ng/mL in current cigarette smokers (all P < .001 vs never-smokers). Median cotinine levels were also elevated in current cigar and current pipe smokers who reported never smoking cigarettes, the study authors report.
They also found that pipe-years were associated with decrements in forced expiratory volume in 1 second (FEV1), and cigar-years were associated with decrements in the FEV1-forced vital capacity (FVC) ratio. Furthermore, participants who smoked pipes or cigars had increased odds of airflow obstruction, whether they had also smoked cigarettes (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.75 - 6.71; P < .001) or not (OR, 2.31; CI, 1.04 - 5.11; P = .039) vs participants with no smoking history.
"These results, together with the extensive literature on the effects of tobacco smoke on the development of COPD and the increase in cotinine levels among current pipe and cigar smokers in this cohort, suggest that pipe and cigar smoking produce a measurable increase in the risk for COPD," the study authors write.
Limitations of this study are the cross-sectional design, the retrospective ascertainment of cumulative pipe and cigar smoking, and the relatively small proportion of participants who smoked pipes or cigars but not cigarettes.
The study authors conclude that their findings suggest that long-term pipe and cigar smoking may damage the lungs and contribute to the development of COPD. "Physicians should consider pipe and cigar smoking a risk factor for COPD and counsel cessation of pipe and cigar smoking regardless of cigarette smoking history."
In an accompanying editorial, Michael B. Steinberg, MD, MPH, from Robert Wood Johnson Medical School, New Brunswick, New Jersey, and coauthor Christine D. Delnevo, PhD, MPH, from the University of Medicine and Dentistry of New Jersey, School of Public Health, New Brunswick, New Jersey, write that as long as the marketing of cigars and pipes remains under the radar of public health advocates and legislative bodies, their use will continue to increase.
"Rodriguez and colleagues have shown that smoke, whether from cigarette, pipe, or cigar, will result in absorption of one of the most addictive chemicals known, nicotine, and will produce measurable lung damage," they conclude. "Tobacco users and health care providers alike need to fully understand the true harms caused by all tobacco products and the role that these products play in a larger public health battle."
The National Heart, Lung, and Blood Institute, National Institutes of Health, supported this study. Disclosure information for the study authors and the editorialists can be obtained in the original article, available on the Annals Web site .
Ann Intern Med. 2010;152:201-210, 259-260. Abstract
Maternal Physical Characteristics, Lifestyle Habits Predict Early Fetal Growth
From Medscape Medical News
Laurie Barclay, MD
February 18, 2010 — Maternal physical characteristics and lifestyle habits are independently associated with early fetal growth, according to the results of a study reported in the February 10 issue of the Journal of the American Medical Association.
"Adverse environmental exposures lead to developmental adaptations in fetal life," write Dennis O. Mook-Kanamori, MD, MSc, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues. "The influences of maternal physical characteristics and lifestyle habits on first trimester fetal adaptations and the postnatal consequences are not known."
The goal of this study was to determine the risk factors and outcomes associated with first-trimester growth restriction. In Rotterdam, the Netherlands, between 2001 and 2005, a total of 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle were enrolled. The investigators evaluated associations of maternal physical characteristics and lifestyle habits with first-trimester fetal growth, and then subsequently looked at the associations of first-trimester fetal growth restriction with the risks for adverse birth outcomes and postnatal growth acceleration until age 2 years.
Between gestational ages of 10 weeks 0 days and 13 weeks 6 days, an ultrasound study was performed to measure first-trimester fetal growth based on crown-to-rump length. Primary study endpoints included preterm birth, defined as gestational age of less than 37 weeks; low birth weight (< 2500 g); and small size for gestational age (lowest fifth birth centile); as well as postnatal growth measured until age 2 years.
Maternal age was positively associated with first-trimester fetal crown-to-rump length, based on multivariate analysis (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 -1.18 per SD score increase). Factors associated with a shorter crown-to-rump length were higher diastolic blood pressure and higher hematocrit level (differences, −0.40 mm; 95% CI, −0.74 to −0.06 and −0.52 mm; 95% CI, −0.90 to −0.14 per SD increase, respectively).
Shorter fetal crown-to-rump lengths were reported for mothers who both smoked and did not use folic acid supplements vs mothers who were nonsmokers and optimal users of folic acid supplements (difference, −3.84 mm; 95% CI, −5.71 to −1.98).
Compared with normal first-trimester fetal growth, adverse outcomes associated with first-trimester growth restriction included preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 - 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 - 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 - 4.25).
For each SD decrease in first-trimester fetal crown-to-rump length, there was a postnatal growth acceleration until age 2 years (SD score increase, 0.139 per 2 years; 95% CI, 0.097 - 0.181).
"Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth," the study authors write. "First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood....Further studies are needed to assess the associations of first-trimester growth variation on the risks of disease in later childhood and adulthood."
Limitations of this study include possible misclassification of gestational age because of inability to measure the timing of ovulation and implantation, and possible recall bias confounding dating of the last menstrual period.
In an accompanying editorial, Gordon C.S. Smith, MD, PhD, from the University of Cambridge in Cambridge, United Kingdom, notes that this study adds to the body of evidence suggesting that growth and placental function in the first trimester of pregnancy significantly affect fetal and infant growth.
"Hence, complications of late pregnancy may, at least for some women, already be determined in the first 3 months postconception, even before a woman has sought prenatal care," Dr. Smith writes. "The multiple associations described suggest that combined ultrasonic and biochemical screening in early pregnancy may be able to identify women at high risk of complications in late pregnancy. The challenges for future research are to produce robust screening tests with acceptable levels of detection and prediction, and to identify interventions that are effective in improving outcome when a pregnancy has been identified as high risk."
JAMA. 2010;303:527-534, 561-562. Abstract
Laurie Barclay, MD
February 18, 2010 — Maternal physical characteristics and lifestyle habits are independently associated with early fetal growth, according to the results of a study reported in the February 10 issue of the Journal of the American Medical Association.
"Adverse environmental exposures lead to developmental adaptations in fetal life," write Dennis O. Mook-Kanamori, MD, MSc, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues. "The influences of maternal physical characteristics and lifestyle habits on first trimester fetal adaptations and the postnatal consequences are not known."
The goal of this study was to determine the risk factors and outcomes associated with first-trimester growth restriction. In Rotterdam, the Netherlands, between 2001 and 2005, a total of 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle were enrolled. The investigators evaluated associations of maternal physical characteristics and lifestyle habits with first-trimester fetal growth, and then subsequently looked at the associations of first-trimester fetal growth restriction with the risks for adverse birth outcomes and postnatal growth acceleration until age 2 years.
Between gestational ages of 10 weeks 0 days and 13 weeks 6 days, an ultrasound study was performed to measure first-trimester fetal growth based on crown-to-rump length. Primary study endpoints included preterm birth, defined as gestational age of less than 37 weeks; low birth weight (< 2500 g); and small size for gestational age (lowest fifth birth centile); as well as postnatal growth measured until age 2 years.
Maternal age was positively associated with first-trimester fetal crown-to-rump length, based on multivariate analysis (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 -1.18 per SD score increase). Factors associated with a shorter crown-to-rump length were higher diastolic blood pressure and higher hematocrit level (differences, −0.40 mm; 95% CI, −0.74 to −0.06 and −0.52 mm; 95% CI, −0.90 to −0.14 per SD increase, respectively).
Shorter fetal crown-to-rump lengths were reported for mothers who both smoked and did not use folic acid supplements vs mothers who were nonsmokers and optimal users of folic acid supplements (difference, −3.84 mm; 95% CI, −5.71 to −1.98).
Compared with normal first-trimester fetal growth, adverse outcomes associated with first-trimester growth restriction included preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 - 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 - 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 - 4.25).
For each SD decrease in first-trimester fetal crown-to-rump length, there was a postnatal growth acceleration until age 2 years (SD score increase, 0.139 per 2 years; 95% CI, 0.097 - 0.181).
"Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth," the study authors write. "First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood....Further studies are needed to assess the associations of first-trimester growth variation on the risks of disease in later childhood and adulthood."
Limitations of this study include possible misclassification of gestational age because of inability to measure the timing of ovulation and implantation, and possible recall bias confounding dating of the last menstrual period.
In an accompanying editorial, Gordon C.S. Smith, MD, PhD, from the University of Cambridge in Cambridge, United Kingdom, notes that this study adds to the body of evidence suggesting that growth and placental function in the first trimester of pregnancy significantly affect fetal and infant growth.
"Hence, complications of late pregnancy may, at least for some women, already be determined in the first 3 months postconception, even before a woman has sought prenatal care," Dr. Smith writes. "The multiple associations described suggest that combined ultrasonic and biochemical screening in early pregnancy may be able to identify women at high risk of complications in late pregnancy. The challenges for future research are to produce robust screening tests with acceptable levels of detection and prediction, and to identify interventions that are effective in improving outcome when a pregnancy has been identified as high risk."
JAMA. 2010;303:527-534, 561-562. Abstract
Monday, February 15, 2010
Management of Acute Poisoning From Medication Ingestion Reviewed
From Medscape Medical News
Laurie Barclay, MD
February 8, 2010 — Family physicians should be familiar with treatment of accidental and intentional medication ingestions, according to a review of the management of acute poisoning caused by medication ingestion published in the February 1 issue of American Family Physician.
"Poisoning from medications can happen for a variety of reasons, including intentional overdose, inadvertently taking an extra dose, dispensing or measuring errors, and exposure through breast milk," write Ivar L. Frithsen, MD, and William M. Simpson, Jr, MD, from Medical University of South Carolina in Charleston.
"The most common medication poisonings in adults (in order of prevalence) include analgesics; sedatives, hypnotics, and antipsychotics; antidepressants; cardiovascular drugs; anticonvulsants; antihistamines; hormones and hormone antagonists; antimicrobials; stimulants and illicit drugs; cough and cold preparations; muscle relaxants; topical preparations; gastrointestinal preparations; and miscellaneous drugs," Drs. Frithsen and Simpson write. "The most common medication poisonings in children (in order of prevalence) include analgesics; topical preparations; cough and cold preparations; vitamins; antihistamines; gastrointestinal preparations; antimicrobials; hormones and hormone antagonists; electrolytes and minerals; cardiovascular drugs; dietary supplements, herbal medications, and homeopathic medications; asthma therapies; antidepressants; and sedatives, hypnotics, and antipsychotics."
In the United States, several million episodes of poisoning are reported each year, causing significant morbidity and mortality rates. Nearly one half of all poisonings reported in the United States are attributed to acute medication poisonings, which should be considered in patients with an acute change in mental status.
Steps in Treatment of Poisoning
The first steps in treatment of a patient who has been poisoned are to evaluate the airway, breathing, and circulation, and to perform a complete history. Poisoning with drugs from certain classes, notably anticholinergics, cholinergics, opioids, and sympathomimetics, are associated with constellations of symptoms known as toxidromes. For example, anticholinergic poisoning is associated with delirium; hyperthermia; ileus; mydriasis; tachycardia; urinary retention; and warm and dry skin.
For identification of electrolyte imbalances and/or impairment of liver and renal function, basic laboratory studies, such as a complete metabolic profile, are an important part of the workup for possible medication poisonings. Clinical presentation and history should help determine what other laboratory studies are indicated.
Unless a specific antidote is available, management is supportive in most cases, because less than 1% of poisonings are fatal. Although single-dose activated charcoal is the preferred modality of gastrointestinal tract decontamination, it should not be used in all patients. The review includes specific therapies for acute medication poisoning based on the type of drug ingested.
For unstable patients who have ingested toxic medications, ongoing treatment should aim to correct hypoxia and acidosis and to maintain adequate circulation. Even when these patients appear to be compensating, their mental or hemodynamic status may deteriorate rapidly. Children are particularly susceptible to profound effects from even small amounts of medication.
Multiple factors, including pharmacokinetics of the ingested substance and the ability to be monitored in the home environment, must be considered in the disposition of a person who has been poisoned. Longer monitoring is required for patients with signs or symptoms of toxicity. For patients who have attempted suicide, psychiatric evaluation and often psychiatric hospitalization are indicated. Counseling referral is recommended for patients with evidence of substance abuse.
Key Recommendations
Specific key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:
For most medication ingestions, single-dose activated charcoal is the modality of choice for gastrointestinal decontamination. This treatment can generally be used up to 1 hour after ingestion of a potentially toxic amount of medication (level of evidence, C).
There is no indication for using ipecac syrup in a healthcare setting (level of evidence, C).
"For unstable patients, admission to an intensive care unit is appropriate, and transfer to a tertiary care facility should be considered, especially with children," the review authors conclude. "For stable patients, the amount of observation time is based on the half-life of a medication, the amount ingested, and the formulation. Any patient who develops signs or symptoms of toxicity that do not reverse during the observation period should be admitted for further observation."
The review authors have disclosed no relevant financial relationships.
Am Fam Physician. 2010;81:316-323. Abstract
Laurie Barclay, MD
February 8, 2010 — Family physicians should be familiar with treatment of accidental and intentional medication ingestions, according to a review of the management of acute poisoning caused by medication ingestion published in the February 1 issue of American Family Physician.
"Poisoning from medications can happen for a variety of reasons, including intentional overdose, inadvertently taking an extra dose, dispensing or measuring errors, and exposure through breast milk," write Ivar L. Frithsen, MD, and William M. Simpson, Jr, MD, from Medical University of South Carolina in Charleston.
"The most common medication poisonings in adults (in order of prevalence) include analgesics; sedatives, hypnotics, and antipsychotics; antidepressants; cardiovascular drugs; anticonvulsants; antihistamines; hormones and hormone antagonists; antimicrobials; stimulants and illicit drugs; cough and cold preparations; muscle relaxants; topical preparations; gastrointestinal preparations; and miscellaneous drugs," Drs. Frithsen and Simpson write. "The most common medication poisonings in children (in order of prevalence) include analgesics; topical preparations; cough and cold preparations; vitamins; antihistamines; gastrointestinal preparations; antimicrobials; hormones and hormone antagonists; electrolytes and minerals; cardiovascular drugs; dietary supplements, herbal medications, and homeopathic medications; asthma therapies; antidepressants; and sedatives, hypnotics, and antipsychotics."
In the United States, several million episodes of poisoning are reported each year, causing significant morbidity and mortality rates. Nearly one half of all poisonings reported in the United States are attributed to acute medication poisonings, which should be considered in patients with an acute change in mental status.
Steps in Treatment of Poisoning
The first steps in treatment of a patient who has been poisoned are to evaluate the airway, breathing, and circulation, and to perform a complete history. Poisoning with drugs from certain classes, notably anticholinergics, cholinergics, opioids, and sympathomimetics, are associated with constellations of symptoms known as toxidromes. For example, anticholinergic poisoning is associated with delirium; hyperthermia; ileus; mydriasis; tachycardia; urinary retention; and warm and dry skin.
For identification of electrolyte imbalances and/or impairment of liver and renal function, basic laboratory studies, such as a complete metabolic profile, are an important part of the workup for possible medication poisonings. Clinical presentation and history should help determine what other laboratory studies are indicated.
Unless a specific antidote is available, management is supportive in most cases, because less than 1% of poisonings are fatal. Although single-dose activated charcoal is the preferred modality of gastrointestinal tract decontamination, it should not be used in all patients. The review includes specific therapies for acute medication poisoning based on the type of drug ingested.
For unstable patients who have ingested toxic medications, ongoing treatment should aim to correct hypoxia and acidosis and to maintain adequate circulation. Even when these patients appear to be compensating, their mental or hemodynamic status may deteriorate rapidly. Children are particularly susceptible to profound effects from even small amounts of medication.
Multiple factors, including pharmacokinetics of the ingested substance and the ability to be monitored in the home environment, must be considered in the disposition of a person who has been poisoned. Longer monitoring is required for patients with signs or symptoms of toxicity. For patients who have attempted suicide, psychiatric evaluation and often psychiatric hospitalization are indicated. Counseling referral is recommended for patients with evidence of substance abuse.
Key Recommendations
Specific key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:
For most medication ingestions, single-dose activated charcoal is the modality of choice for gastrointestinal decontamination. This treatment can generally be used up to 1 hour after ingestion of a potentially toxic amount of medication (level of evidence, C).
There is no indication for using ipecac syrup in a healthcare setting (level of evidence, C).
"For unstable patients, admission to an intensive care unit is appropriate, and transfer to a tertiary care facility should be considered, especially with children," the review authors conclude. "For stable patients, the amount of observation time is based on the half-life of a medication, the amount ingested, and the formulation. Any patient who develops signs or symptoms of toxicity that do not reverse during the observation period should be admitted for further observation."
The review authors have disclosed no relevant financial relationships.
Am Fam Physician. 2010;81:316-323. Abstract
Sunday, February 14, 2010
Radiation Therapy for Rectal Cancer: Current Status and Future Directions
From Cancer Control: Journal of the Moffitt Cancer Center
Sarah E. Hoffe, MD; Ravi Shridhar, MD, PhD; Matthew C. Biagioli, MD
Abstract
Background: Treatment for rectal cancer has evolved over the past 70 years from surgery alone to the selective use of trimodality therapy for high-risk patients. Radiotherapy (RT) has improved the potential for tumor downstaging, thus enhancing sphincter preservation and local control.
Methods: This article reviews the evolution of strategies that incorporate pelvic RT, intraoperative RT, and high-dose-rate endorectal brachytherapy (HDRBT). By tracing the arc of the pendulum that has swung from postoperative RT to preoperative RT, we address the current standard of care and explore the potential of novel radiation techniques and radiosensitizing agents to improve outcomes.
Results: With randomized trial data confirming that preoperative RT in addition to chemotherapy improves local control and decreases acute and late morbidity, neoadjuvant programs have now demonstrated the prognostic significance of downstaging as well. Patients with tumors that have a good response to preoperative treatment have superior survival.
Conclusions: Future studies will determine the optimal regimen to enhance the pathologic complete or near complete response rates for locally advanced disease. Advances in radiation technology are being investigated to determine whether efficacy can be increased and toxicity decreased so that more aggressive chemotherapeutic agents can be combined. With the growing improvements in combined modality therapy, a future of better rectal cancer outcomes looms brighter than ever before.
Introduction
Colorectal cancer is the third most common malignancy in the United States.[1]
Each year, over 40,000 patients are diagnosed with rectal cancer, a malignancy defined by the National Cancer Institute panel of experts as occurring in the distal large bowel 12 cm or less from the anal verge by rigid proctoscopy.[2]
This consensus definition has been adopted based on the fact that it is measurable and reproducible. However, considerable differences in terminology exist, with some authors reporting that the most useful landmark to discriminate sigmoid colon from rectum is the loss of taenia coli, the appendices epiploicae, and the surgical mesocolon at approximately the level of the third sacral vertebra.[3]
By 1940, pathologic analysis of rectal cancer resection specimens had identified penetration of the primary tumor through the bowel wall and involved lymph nodes as factors associated with worse outcomes.[4,5] In 1954, Astler and Coller[6] confirmed the prognostic significance of direct cancer extension outside the bowel wall. In the 1970s, areas of failure found at reoperation following an initially curative resection for rectal adenocarcinoma were investigated, with results showing that survival and disease relapse rates are indeed related to the degree of bowel wall penetration and the extent of nodal disease.[7] This early work paved the way for the identification of those patients with high-risk disease, described in the modern TNM staging system as T3/T4 and/or node-positive. This review traces the evolution of pelvic radiation therapy (RT) and brachytherapy into the treatment arsenal for these patients, with emphasis on our current and future practice.
In the era before the adoption of total mesorectal excision (TME), surgery alone for transmural or node-positive rectal adenocarcinoma was associated with local failure rates of up to 50%.[8–10] This setting provided the foundation for exploration of strategies to improve outcomes following resection. The first trial was conducted by the Gastrointestinal Tumor Study Group (GITSG 7175), which randomized patients to surgery alone vs semustine and 5-fluorouracil (5-FU) vs pelvic RT alone vs chemoradiation.[11]
The arm that combined chemo therapy and RT showed a significant improvement in local control and survival.[12] Following this trial, investigators at the Mayo Clinic/North Central Cancer Treatment Group (Mayo/NCCTG) explored the question of postoperative RT alone vs postoperative chemoradiation with semustine and 5-FU on protocol NCCTG 794751.[13] With over 7 years of median follow-up, there was a 34% reduction in tumor recurrence (P = .002) and a 36% reduction in cancer-related death (P = .007) in favor of the chemoradiation arm. These two positive trials set a new standard for the postoperative management of highrisk rectal cancer. In 1990, the NCI issued a consensus conference statement declaring that combined-modality therapy is the new standard of care in this setting.
http://www.medscape.com/viewarticle/715159?src=mp&spon=17&uac=71630FV
Sarah E. Hoffe, MD; Ravi Shridhar, MD, PhD; Matthew C. Biagioli, MD
Abstract
Background: Treatment for rectal cancer has evolved over the past 70 years from surgery alone to the selective use of trimodality therapy for high-risk patients. Radiotherapy (RT) has improved the potential for tumor downstaging, thus enhancing sphincter preservation and local control.
Methods: This article reviews the evolution of strategies that incorporate pelvic RT, intraoperative RT, and high-dose-rate endorectal brachytherapy (HDRBT). By tracing the arc of the pendulum that has swung from postoperative RT to preoperative RT, we address the current standard of care and explore the potential of novel radiation techniques and radiosensitizing agents to improve outcomes.
Results: With randomized trial data confirming that preoperative RT in addition to chemotherapy improves local control and decreases acute and late morbidity, neoadjuvant programs have now demonstrated the prognostic significance of downstaging as well. Patients with tumors that have a good response to preoperative treatment have superior survival.
Conclusions: Future studies will determine the optimal regimen to enhance the pathologic complete or near complete response rates for locally advanced disease. Advances in radiation technology are being investigated to determine whether efficacy can be increased and toxicity decreased so that more aggressive chemotherapeutic agents can be combined. With the growing improvements in combined modality therapy, a future of better rectal cancer outcomes looms brighter than ever before.
Introduction
Colorectal cancer is the third most common malignancy in the United States.[1]
Each year, over 40,000 patients are diagnosed with rectal cancer, a malignancy defined by the National Cancer Institute panel of experts as occurring in the distal large bowel 12 cm or less from the anal verge by rigid proctoscopy.[2]
This consensus definition has been adopted based on the fact that it is measurable and reproducible. However, considerable differences in terminology exist, with some authors reporting that the most useful landmark to discriminate sigmoid colon from rectum is the loss of taenia coli, the appendices epiploicae, and the surgical mesocolon at approximately the level of the third sacral vertebra.[3]
By 1940, pathologic analysis of rectal cancer resection specimens had identified penetration of the primary tumor through the bowel wall and involved lymph nodes as factors associated with worse outcomes.[4,5] In 1954, Astler and Coller[6] confirmed the prognostic significance of direct cancer extension outside the bowel wall. In the 1970s, areas of failure found at reoperation following an initially curative resection for rectal adenocarcinoma were investigated, with results showing that survival and disease relapse rates are indeed related to the degree of bowel wall penetration and the extent of nodal disease.[7] This early work paved the way for the identification of those patients with high-risk disease, described in the modern TNM staging system as T3/T4 and/or node-positive. This review traces the evolution of pelvic radiation therapy (RT) and brachytherapy into the treatment arsenal for these patients, with emphasis on our current and future practice.
In the era before the adoption of total mesorectal excision (TME), surgery alone for transmural or node-positive rectal adenocarcinoma was associated with local failure rates of up to 50%.[8–10] This setting provided the foundation for exploration of strategies to improve outcomes following resection. The first trial was conducted by the Gastrointestinal Tumor Study Group (GITSG 7175), which randomized patients to surgery alone vs semustine and 5-fluorouracil (5-FU) vs pelvic RT alone vs chemoradiation.[11]
The arm that combined chemo therapy and RT showed a significant improvement in local control and survival.[12] Following this trial, investigators at the Mayo Clinic/North Central Cancer Treatment Group (Mayo/NCCTG) explored the question of postoperative RT alone vs postoperative chemoradiation with semustine and 5-FU on protocol NCCTG 794751.[13] With over 7 years of median follow-up, there was a 34% reduction in tumor recurrence (P = .002) and a 36% reduction in cancer-related death (P = .007) in favor of the chemoradiation arm. These two positive trials set a new standard for the postoperative management of highrisk rectal cancer. In 1990, the NCI issued a consensus conference statement declaring that combined-modality therapy is the new standard of care in this setting.
http://www.medscape.com/viewarticle/715159?src=mp&spon=17&uac=71630FV
The Effects of Obesity and Obesity-related Conditions on Colorectal Cancer Prognosis
From Cancer Control: Journal of the Moffitt Cancer Center
Erin M. Siegel, PhD, MPH; Cornelia M. Ulrich, PhD; Elizabeth M. Poole, PhD; Rebecca S. Holmes, MD, MPH; Paul B. Jacobsen, PhD; David Shibata, MD
Abstract
Background: Colorectal cancer is the second-leading cause of cancer death in the United States among men and women combined.
Refinements in screening, staging, and treatment strategies have improved survival from this disease, with over 65% of patients diagnosed with colorectal cancer surviving over 5 years after diagnosis.
In the prognosis of colorectal cancer, clinicopathological factors are important. However, modifiable prognostic factors are emerging as significant contributors to cancer outcomes, including obesity and obesity-related inflammation and metabolic conditions.
Methods: This report reviews the literature on obesity and obesity-related inflammation and metabolic disturbances and colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality).
A PubMed search was conducted of all English-language papers published between August 2003 and 2009 and cited in MEDLINE.
Results: Primary research papers were reviewed for colorectal cancer outcomes related to obesity, inflammation, or metabolic conditions. An association between body size and colorectal cancer recurrence and possibly survival was found; however, reports have been inconsistent. These inconsistent findings may be due to the complex interaction between adiposity, physical inactivity, and dietary intake. Circulating prognostic markers such as C-reactive protein, insulin-like growth factor, and insulin, alone or in combination, have been associated with prognosis in observational studies and should be evaluated in randomized trials and considered for incorporation into surveillance.
Conclusions: The literature suggests that obesity and obesity-related inflammation and metabolic conditions contribute to the prognosis of colorectal cancer; however, comprehensive large scale trials are needed. Interventions to reduce weight and control inflammation and metabolic conditions, such as diabetes, need to be evaluated and rapidly translated to behavior guidelines for patients.
Introduction
In 2009, approximately 146,000 individuals were diagnosed with colorectal cancer in the United States, and more than 49,000 individuals died of this disease.[1]
This makes colorectal cancer the second leading cause of cancer death in the United States among men and women combined.[1] Despite refinements in screening, staging, and treatment strategies, over 35% of patients diagnosed with colorectal cancer die within 5 years of diagnosis. Only 40% of patients with colorectal cancer are diagnosed at a localized stage, for which 5-year survival rates are greater than 90%. The majority of patients are diagnosed with either regional or distant spread, and the 5-year survival rates at these stages are approximately 68% and 11%, respectively.[2]
At the same time, the number of colorectal cancer survivors in the population continues to increase. This trend is accelerated by the increasing compliance to screening and the availability of more effective colorectal cancer treatment regimens. In 2002, the National Cancer Institute and the Centers for Disease Control and Prevention estimated that there were 10.1 million survivors of all cancers in the United States, a number that has tripled since 1971.[3] Among these are more than 1 million colorectal cancer survivors. Unfortunately, most survivors remain at risk for colorectal cancer recurrence (about 30% for all stages) and continue to endure posttreatment effects during survivorship.
At the time of cancer diagnosis and during surveillance, prognostic factors are utilized by clinicians to predict the probable course of disease in each patient and the likely outcome of the disease. The current gold standard for cancer prognosis is clinicopathological staging. However, outcome is independently influenced by other factors: histological characteristics of the tumor, patient age, presentation of disease, and performance status. Recently, molecular testing for mutations has proven effective in predicting tumor response to chemo therapy.[4] However, while clinicopathological factors are important, modifiable factors are emerging as key predictors of patient prognosis.
One such factor is obesity, which is modifiable. Cancer patients are increasingly interested in what lifestyle-related measures can be taken to optimize their recovery, to prevent recurrent or secondary tumors, and to assist in their return to an active, healthy life.[5] Therefore, a review of modifiable prognostic factors for co lo rectal cancer is needed.
Obesity and obesity-related inflammation and metabolic conditions have been proposed as modifiable prognostic factors in colorectal cancer. This report reviews the evidence regarding the effects of obesity and the resulting chronic inflammation and metabolic disturbances on colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality).
Erin M. Siegel, PhD, MPH; Cornelia M. Ulrich, PhD; Elizabeth M. Poole, PhD; Rebecca S. Holmes, MD, MPH; Paul B. Jacobsen, PhD; David Shibata, MD
Abstract
Background: Colorectal cancer is the second-leading cause of cancer death in the United States among men and women combined.
Refinements in screening, staging, and treatment strategies have improved survival from this disease, with over 65% of patients diagnosed with colorectal cancer surviving over 5 years after diagnosis.
In the prognosis of colorectal cancer, clinicopathological factors are important. However, modifiable prognostic factors are emerging as significant contributors to cancer outcomes, including obesity and obesity-related inflammation and metabolic conditions.
Methods: This report reviews the literature on obesity and obesity-related inflammation and metabolic disturbances and colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality).
A PubMed search was conducted of all English-language papers published between August 2003 and 2009 and cited in MEDLINE.
Results: Primary research papers were reviewed for colorectal cancer outcomes related to obesity, inflammation, or metabolic conditions. An association between body size and colorectal cancer recurrence and possibly survival was found; however, reports have been inconsistent. These inconsistent findings may be due to the complex interaction between adiposity, physical inactivity, and dietary intake. Circulating prognostic markers such as C-reactive protein, insulin-like growth factor, and insulin, alone or in combination, have been associated with prognosis in observational studies and should be evaluated in randomized trials and considered for incorporation into surveillance.
Conclusions: The literature suggests that obesity and obesity-related inflammation and metabolic conditions contribute to the prognosis of colorectal cancer; however, comprehensive large scale trials are needed. Interventions to reduce weight and control inflammation and metabolic conditions, such as diabetes, need to be evaluated and rapidly translated to behavior guidelines for patients.
Introduction
In 2009, approximately 146,000 individuals were diagnosed with colorectal cancer in the United States, and more than 49,000 individuals died of this disease.[1]
This makes colorectal cancer the second leading cause of cancer death in the United States among men and women combined.[1] Despite refinements in screening, staging, and treatment strategies, over 35% of patients diagnosed with colorectal cancer die within 5 years of diagnosis. Only 40% of patients with colorectal cancer are diagnosed at a localized stage, for which 5-year survival rates are greater than 90%. The majority of patients are diagnosed with either regional or distant spread, and the 5-year survival rates at these stages are approximately 68% and 11%, respectively.[2]
At the same time, the number of colorectal cancer survivors in the population continues to increase. This trend is accelerated by the increasing compliance to screening and the availability of more effective colorectal cancer treatment regimens. In 2002, the National Cancer Institute and the Centers for Disease Control and Prevention estimated that there were 10.1 million survivors of all cancers in the United States, a number that has tripled since 1971.[3] Among these are more than 1 million colorectal cancer survivors. Unfortunately, most survivors remain at risk for colorectal cancer recurrence (about 30% for all stages) and continue to endure posttreatment effects during survivorship.
At the time of cancer diagnosis and during surveillance, prognostic factors are utilized by clinicians to predict the probable course of disease in each patient and the likely outcome of the disease. The current gold standard for cancer prognosis is clinicopathological staging. However, outcome is independently influenced by other factors: histological characteristics of the tumor, patient age, presentation of disease, and performance status. Recently, molecular testing for mutations has proven effective in predicting tumor response to chemo therapy.[4] However, while clinicopathological factors are important, modifiable factors are emerging as key predictors of patient prognosis.
One such factor is obesity, which is modifiable. Cancer patients are increasingly interested in what lifestyle-related measures can be taken to optimize their recovery, to prevent recurrent or secondary tumors, and to assist in their return to an active, healthy life.[5] Therefore, a review of modifiable prognostic factors for co lo rectal cancer is needed.
Obesity and obesity-related inflammation and metabolic conditions have been proposed as modifiable prognostic factors in colorectal cancer. This report reviews the evidence regarding the effects of obesity and the resulting chronic inflammation and metabolic disturbances on colorectal cancer outcomes (recurrence, disease-free survival, and/or mortality).
New FDA Initiative to Reduce Unnecessary Radiation Exposure From Medical Imaging
From Medscape Medical News
Robert Lowes
February 10, 2010 — In a move that promises more regulation for imaging device manufacturers and imaging facilities, the US Food and Drug Administration (FDA) yesterday announced it was launching a campaign to reduce unnecessary radiation exposure from 3 types of procedures — computed tomography (CT), nuclear medicine studies, and fluoroscopy.
The FDA said it would work to promote the safe use of these 3 modalities, help physicians make more informed decisions about ordering tests, and increase patient awareness of their individual radiation exposure.
CT, nuclear medicine studies, and fluoroscopy subject patients to ionizing radiation that can increase their lifetime cancer risk, according to the FDA. In addition, accidental exposure to very high amounts of radiation can cause skin burns, hair loss, and cataracts.
"The amount of radiation Americans are exposed to from medical imaging has dramatically increased over the past 20 years," Jeffrey Shuren, MD, JD, director of the FDA's Center for Devices and Radiological Health, said in a news release. "The goal of FDA's initiative is to support the benefits associated with medical imaging while minimizing the risks."
The agency cites a March 2009 report from the National Council on Radiation Protection and Measurements showing that nationwide exposure to ionizing radiation has nearly doubled during the past 2 decades, with the increase largely attributable to CT, nuclear medicine studies, and fluoroscopy. According to the FDA, the 3 modalities account for 26% of imaging procedures involving radiation but contribute 89% of the annual exposure that patients have from medical imaging.
The new FDA campaign follows on the heels of an investigation last year into roughly 250 patients at Cedars-Sinai Medical Center in Los Angeles, California, who were exposed to excessive levels of radiation during CT perfusion scans of their brains.
Building Smarter Imaging Devices
The FDA plans to attack the problem of excessive radiation exposure with a 3-pronged approach. The first prong involves the safe use of imaging devices. The agency said Tuesday that it would issue requirements for makers of CT and fluoroscopic equipment to provide safety training for clinicians as well as include safeguards in the design of the devices. Such safeguards might be the ability to display, record, and report equipment settings and radiation doses; alert users when a dose exceeds a diagnostic reference level; and transmit dose data to a patient's electronic health record or dose registry. The FDA plans to hold a public meeting on March 30 and March 31 to solicit ideas about what these requirements should be.
The FDA also plans to work with the Centers for Medicare and Medicaid Services to incorporate quality-assurance practices for medical imaging in the Centers for Medicare and Medicaid Services accreditation of stand-alone imaging facilities, as well as its conditions of participation for hospitals in the Medicare program.
Another component of safer medical imaging is nationally recognized diagnostic radiation reference levels for imaging procedures so that clinicians can assess whether a radiation dose is reasonable. The FDA said it would help promote the development of local and national radiation dose registries to achieve this end.
Helping Physicians and Patients Make Wiser Choices
Because physicians are responsible for ordering diagnostic imaging procedures, the FDA said it wants to support informed clinical decision-making as part of its initiative. Proposed "smart" features such as alerts built into imaging devices are part of that thrust. At the same time, the FDA is recommending that physicians develop and adopt "appropriate use criteria" for ordering CT, fluoroscopy, and nuclear medicine studies. Physicians may order these procedures without sufficient justification — and expose patients unnecessarily to radiation — because they are unaware of recommended clinical criteria to guide their decisions, according to an FDA white paper.
The third prong of the FDA initiative is increasing individual patients' awareness of their exposure to radiation from medical imaging. The FDA said it would collaborate with other organizations, such as the American College of Radiology and the Radiological Society of North America, to develop and distribute a patient "medical imaging card" to help individuals track their procedures and share that information with clinicians.
Robert Lowes
February 10, 2010 — In a move that promises more regulation for imaging device manufacturers and imaging facilities, the US Food and Drug Administration (FDA) yesterday announced it was launching a campaign to reduce unnecessary radiation exposure from 3 types of procedures — computed tomography (CT), nuclear medicine studies, and fluoroscopy.
The FDA said it would work to promote the safe use of these 3 modalities, help physicians make more informed decisions about ordering tests, and increase patient awareness of their individual radiation exposure.
CT, nuclear medicine studies, and fluoroscopy subject patients to ionizing radiation that can increase their lifetime cancer risk, according to the FDA. In addition, accidental exposure to very high amounts of radiation can cause skin burns, hair loss, and cataracts.
"The amount of radiation Americans are exposed to from medical imaging has dramatically increased over the past 20 years," Jeffrey Shuren, MD, JD, director of the FDA's Center for Devices and Radiological Health, said in a news release. "The goal of FDA's initiative is to support the benefits associated with medical imaging while minimizing the risks."
The agency cites a March 2009 report from the National Council on Radiation Protection and Measurements showing that nationwide exposure to ionizing radiation has nearly doubled during the past 2 decades, with the increase largely attributable to CT, nuclear medicine studies, and fluoroscopy. According to the FDA, the 3 modalities account for 26% of imaging procedures involving radiation but contribute 89% of the annual exposure that patients have from medical imaging.
The new FDA campaign follows on the heels of an investigation last year into roughly 250 patients at Cedars-Sinai Medical Center in Los Angeles, California, who were exposed to excessive levels of radiation during CT perfusion scans of their brains.
Building Smarter Imaging Devices
The FDA plans to attack the problem of excessive radiation exposure with a 3-pronged approach. The first prong involves the safe use of imaging devices. The agency said Tuesday that it would issue requirements for makers of CT and fluoroscopic equipment to provide safety training for clinicians as well as include safeguards in the design of the devices. Such safeguards might be the ability to display, record, and report equipment settings and radiation doses; alert users when a dose exceeds a diagnostic reference level; and transmit dose data to a patient's electronic health record or dose registry. The FDA plans to hold a public meeting on March 30 and March 31 to solicit ideas about what these requirements should be.
The FDA also plans to work with the Centers for Medicare and Medicaid Services to incorporate quality-assurance practices for medical imaging in the Centers for Medicare and Medicaid Services accreditation of stand-alone imaging facilities, as well as its conditions of participation for hospitals in the Medicare program.
Another component of safer medical imaging is nationally recognized diagnostic radiation reference levels for imaging procedures so that clinicians can assess whether a radiation dose is reasonable. The FDA said it would help promote the development of local and national radiation dose registries to achieve this end.
Helping Physicians and Patients Make Wiser Choices
Because physicians are responsible for ordering diagnostic imaging procedures, the FDA said it wants to support informed clinical decision-making as part of its initiative. Proposed "smart" features such as alerts built into imaging devices are part of that thrust. At the same time, the FDA is recommending that physicians develop and adopt "appropriate use criteria" for ordering CT, fluoroscopy, and nuclear medicine studies. Physicians may order these procedures without sufficient justification — and expose patients unnecessarily to radiation — because they are unaware of recommended clinical criteria to guide their decisions, according to an FDA white paper.
The third prong of the FDA initiative is increasing individual patients' awareness of their exposure to radiation from medical imaging. The FDA said it would collaborate with other organizations, such as the American College of Radiology and the Radiological Society of North America, to develop and distribute a patient "medical imaging card" to help individuals track their procedures and share that information with clinicians.
Management of Erectile Dysfunction Reviewed
From Medscape Medical News
Laurie Barclay, MD
February 9, 2010 — The best practices to manage erectile dysfunction (ED) in the family practice setting are reviewed in an article published in the February 1 issue of American Family Physician.
"...ED is defined by the National Institutes of Health as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance," writes Joel J. Heidelbaugh, MD, from the University of Michigan in Ann Arbor.
"ED is the most common sexual problem in men; it often causes serious distress, prompting men to seek medical attention they may not otherwise seek. It often has a profound effect on intimate relationships, quality of life, and overall self-esteem [and] may also be the presenting symptom or harbinger of undetected cardiovascular disease."
ED may result from organic causes related to vascular, neurogenic, hormonal, anatomic, or drug-induced conditions; psychological causes; or a combination of both.
ED will affect up to one third of men during their lifetime, and it increases in incidence with age. Predictive factors associated with a greatly increased risk for ED are obesity, sedentary lifestyle, and smoking.
In most cases, history and physical examination are sufficient to diagnose ED. Medical history should determine the presence of diabetes or other comorbid conditions that can increase the risk for ED, medication history may reveal use of medications with sexual adverse effects, and sexual history should assess libido and ability to reach orgasm and to ejaculate. Physical examination should include cardiovascular and neurologic assessment, genital inspection, and digital rectal examination.
Although there is no preferred first-line diagnostic test, initial diagnostic evaluation should usually consist only of a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level. Optional laboratory tests may include complete blood count; free testosterone, luteinizing hormone, and prolactin levels; sex hormone–binding globulin test; and/or urinalysis.
Evaluations that may be considered in selected patients with ED include psychological or psychiatric consultation, in-depth psychosexual and relationship evaluation, neurophysiologic penile and sphincter testing, nocturnal penile tumescence and rigidity assessment, specialized endocrinologic testing, and/or vascular diagnostics.
First-line treatment of ED consists of lifestyle interventions (weight loss, increased exercise, and smoking cessation), discontinuation or changing of medications that may cause ED, and pharmacotherapy with phosphodiesterase type 5 (PDE5) inhibitors.
The most effective orally administered drugs for treatment of ED are the PDE5 inhibitors, which have been shown to be effective for ED associated with diabetes mellitus, spinal cord injury, and antidepressant use.
"The three PDE5 inhibitors are considered to be relatively similar in effectiveness, but there are differences in dosing, onset of action, and duration of therapeutic effect," Dr. Heidelbaugh writes. "An open-label trial found that patients preferred tadalafil and vardenafil over sildenafil, yet most evidence supports equal effectiveness between sildenafil and vardenafil. PDE5 inhibitors are generally well tolerated, with mild transient adverse effects of headache, flushing, dyspepsia, rhinitis, and abnormal vision."
When PDE5 inhibitors are ineffective, alternative therapeutic options may include intraurethral and intracavernosal injections of alprostadil, vacuum pump devices, and surgically implanted penile prostheses.
For men with hypogonadism, testosterone supplementation generally improves ED and libido but is associated with a higher risk for prostate adenocarcinoma. Interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels is therefore required.
Cognitive behavioral therapy and therapy aiming to improve the quality of relationships may be helpful for couples affected by ED.
Risk for coronary, cerebrovascular, and peripheral vascular diseases is increased in men with ED. Because symptoms of ED may occur 3 years earlier, on average, than symptoms of coronary artery disease, screening for cardiovascular risk factors should be considered in men with ED.
Key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:
Diagnostic workup for ED should usually be limited to a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and a morning total testosterone level (level of evidence, C).
Oral PDE5 inhibitors should be first-line treatment of ED (level of evidence, A).
PDE5 inhibitors are most effective in treating ED associated with diabetes mellitus and spinal cord injury, and sexual dysfunction associated with antidepressants (level of evidence, A).
Psychosocial therapy may be a useful adjunctive treatment of ED, as well as testosterone supplementation in men with hypogonadism (level of evidence, B).
Testosterone supplementation improves ED and libido in men with hypogonadism (level of evidence, B).
Screening for cardiovascular risk factors should be considered in men with ED (level of evidence, C).
"The economic impact of ED is multifactorial, with direct costs that include physician evaluation, pharmacotherapy, and diagnostic testing, and indirect costs that include lost time at work, lost productivity, and effects on the man's partner, family, and co-workers," Dr. Heidelbaugh concludes. "The Prostate Cancer Prevention Trial determined that men with ED have a significantly greater likelihood of having angina, myocardial infarction, stroke, transient ischemic attack, congestive heart failure, or cardiac arrhythmia compared with men without ED. Because most men are asymptomatic before an acute coronary syndrome, ED may serve as a sentinel marker for prompting discussions centered on promotion of cardiovascular risk stratification and modification."
Dr. Heidelbaugh has disclosed no relevant financial relationships.
Am Fam Physician. 2010;81:305-312. Abstract
Laurie Barclay, MD
February 9, 2010 — The best practices to manage erectile dysfunction (ED) in the family practice setting are reviewed in an article published in the February 1 issue of American Family Physician.
"...ED is defined by the National Institutes of Health as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance," writes Joel J. Heidelbaugh, MD, from the University of Michigan in Ann Arbor.
"ED is the most common sexual problem in men; it often causes serious distress, prompting men to seek medical attention they may not otherwise seek. It often has a profound effect on intimate relationships, quality of life, and overall self-esteem [and] may also be the presenting symptom or harbinger of undetected cardiovascular disease."
ED may result from organic causes related to vascular, neurogenic, hormonal, anatomic, or drug-induced conditions; psychological causes; or a combination of both.
ED will affect up to one third of men during their lifetime, and it increases in incidence with age. Predictive factors associated with a greatly increased risk for ED are obesity, sedentary lifestyle, and smoking.
In most cases, history and physical examination are sufficient to diagnose ED. Medical history should determine the presence of diabetes or other comorbid conditions that can increase the risk for ED, medication history may reveal use of medications with sexual adverse effects, and sexual history should assess libido and ability to reach orgasm and to ejaculate. Physical examination should include cardiovascular and neurologic assessment, genital inspection, and digital rectal examination.
Although there is no preferred first-line diagnostic test, initial diagnostic evaluation should usually consist only of a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level. Optional laboratory tests may include complete blood count; free testosterone, luteinizing hormone, and prolactin levels; sex hormone–binding globulin test; and/or urinalysis.
Evaluations that may be considered in selected patients with ED include psychological or psychiatric consultation, in-depth psychosexual and relationship evaluation, neurophysiologic penile and sphincter testing, nocturnal penile tumescence and rigidity assessment, specialized endocrinologic testing, and/or vascular diagnostics.
First-line treatment of ED consists of lifestyle interventions (weight loss, increased exercise, and smoking cessation), discontinuation or changing of medications that may cause ED, and pharmacotherapy with phosphodiesterase type 5 (PDE5) inhibitors.
The most effective orally administered drugs for treatment of ED are the PDE5 inhibitors, which have been shown to be effective for ED associated with diabetes mellitus, spinal cord injury, and antidepressant use.
"The three PDE5 inhibitors are considered to be relatively similar in effectiveness, but there are differences in dosing, onset of action, and duration of therapeutic effect," Dr. Heidelbaugh writes. "An open-label trial found that patients preferred tadalafil and vardenafil over sildenafil, yet most evidence supports equal effectiveness between sildenafil and vardenafil. PDE5 inhibitors are generally well tolerated, with mild transient adverse effects of headache, flushing, dyspepsia, rhinitis, and abnormal vision."
When PDE5 inhibitors are ineffective, alternative therapeutic options may include intraurethral and intracavernosal injections of alprostadil, vacuum pump devices, and surgically implanted penile prostheses.
For men with hypogonadism, testosterone supplementation generally improves ED and libido but is associated with a higher risk for prostate adenocarcinoma. Interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels is therefore required.
Cognitive behavioral therapy and therapy aiming to improve the quality of relationships may be helpful for couples affected by ED.
Risk for coronary, cerebrovascular, and peripheral vascular diseases is increased in men with ED. Because symptoms of ED may occur 3 years earlier, on average, than symptoms of coronary artery disease, screening for cardiovascular risk factors should be considered in men with ED.
Key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:
Diagnostic workup for ED should usually be limited to a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and a morning total testosterone level (level of evidence, C).
Oral PDE5 inhibitors should be first-line treatment of ED (level of evidence, A).
PDE5 inhibitors are most effective in treating ED associated with diabetes mellitus and spinal cord injury, and sexual dysfunction associated with antidepressants (level of evidence, A).
Psychosocial therapy may be a useful adjunctive treatment of ED, as well as testosterone supplementation in men with hypogonadism (level of evidence, B).
Testosterone supplementation improves ED and libido in men with hypogonadism (level of evidence, B).
Screening for cardiovascular risk factors should be considered in men with ED (level of evidence, C).
"The economic impact of ED is multifactorial, with direct costs that include physician evaluation, pharmacotherapy, and diagnostic testing, and indirect costs that include lost time at work, lost productivity, and effects on the man's partner, family, and co-workers," Dr. Heidelbaugh concludes. "The Prostate Cancer Prevention Trial determined that men with ED have a significantly greater likelihood of having angina, myocardial infarction, stroke, transient ischemic attack, congestive heart failure, or cardiac arrhythmia compared with men without ED. Because most men are asymptomatic before an acute coronary syndrome, ED may serve as a sentinel marker for prompting discussions centered on promotion of cardiovascular risk stratification and modification."
Dr. Heidelbaugh has disclosed no relevant financial relationships.
Am Fam Physician. 2010;81:305-312. Abstract
Death of Rep. John Murtha Highlights Limitations of Laparoscopic Cholecystectomy
From Medscape Medical News
Robert Lowes
February 9, 2010 — Laparoscopic cholecystectomy (LC) is one of the most common surgeries in the nation, but yesterday's death of Rep. John Murtha (D-PA) points out the rare, but unique, risks of this high-tech procedure, which include lack of depth perception and limitations in inspecting for operative damage.
Murtha died of major complications from LC at Virginia Hospital Center in Arlington. He had undergone an LC at the National Naval Medical Center in Bethesda, Maryland, on January 28, and was admitted to Virginia Hospital Center 3 days later. Several news organizations have independently reported that Rep. Murtha suffered an infection after his intestine was inadvertently cut during the cholecystectomy. Neither hospital, when contacted by Medscape Medical News, would confirm the nature of the complication.
Medical authorities typically put the complication rate for LC at roughly 2%. A study published in the April 1995 issue of the Annals of Surgery, for example, reported a morbidity rate of 1.9% for LC compared with 7.7% for open-field cholecystectomy.
Among LC complications, a nicked intestine is one of the least common, according to a study by Thomas McLean, MD, JD, published in July 2006 in the Archives of Surgery. Dr. McLean, a staff thoracic surgeon at the Dwight D. Eisenhower Veterans Affairs Medical Center in Leavenworth, Kansas, found that bowel injuries accounted for 2% of adverse events in LCs that triggered a malpractice suit. The leading cause of litigation — 78% — was injury to the bile duct. Such bile duct injuries are more common in LC than open-field cholecystectomy, Dr. McLean told Medscape Medical News.
Intestinal injuries, he said, are usually caused by trocar insertion. "There may be as many as 5 [trocars] inserted. This tends to be feel-only."
The intestine also can be injured when a surgeon is trying to separate it from an inflamed gallbladder that has adhered to it, said Nathaniel Soper, MD, chairman of the Department of Surgery at Northwestern University Feinberg School of Medicine, Chicago, Illinois. The pressure of the carbon dioxide gas used to inflate the abdomen during LC can seal up intestinal punctures that leak only after the gas is gone, Dr. Soper told Medscape Medical News. He noted that either the small or large intestine can be accidentally cut during LC, although the duodenum of the small intestine is the more likely candidate because of its proximity to the gallbladder. It is not clear from published accounts which intestine of Murtha's was accidentally cut.
Limitations of Laparoscopic Vision
Dr. Soper said the risk for accidental cuts increases with the distorted, depthless vision of the laparoscope.
"You're dependent on a 2-dimensional image," said Dr. Soper. "Because the image is very magnified, you're looking only at a very small part of the (surgical) field, and you don't have a normal sense of feel using 2-foot long instruments."
In contrast, surgeons performing an open-field cholecystectomy enjoy a direct, 3-dimensional, panoramic view, added Dr. McLean. That improved view helps them not only avoid a scalpel accident but also spot any accidents that occur during surgery. In addition, if surgeons are worried about inadvertently cutting an intestine, they can pick it up and gently squeeze it to check for a leak.
Another risk factor for accidental intestinal cuts is obesity. In noting that the intestines can be injured during LC, the American College of Surgeons states on its Web site that "patients who are obese...make it more difficult to move and manipulate instruments." However, an open-field cholecystectomy for a morbidly obese person carries its own special risk — an incision that can be double the normal length, noted Dr. Soper.
Rep. Murtha, who was 77 years old, had represented the 12th Congressional District in southwestern Pennsylvania since 1974. An ex-Marine and Vietnam War combat veteran, he was chairman of the House Appropriations Subcommittee on Defense.
Robert Lowes
February 9, 2010 — Laparoscopic cholecystectomy (LC) is one of the most common surgeries in the nation, but yesterday's death of Rep. John Murtha (D-PA) points out the rare, but unique, risks of this high-tech procedure, which include lack of depth perception and limitations in inspecting for operative damage.
Murtha died of major complications from LC at Virginia Hospital Center in Arlington. He had undergone an LC at the National Naval Medical Center in Bethesda, Maryland, on January 28, and was admitted to Virginia Hospital Center 3 days later. Several news organizations have independently reported that Rep. Murtha suffered an infection after his intestine was inadvertently cut during the cholecystectomy. Neither hospital, when contacted by Medscape Medical News, would confirm the nature of the complication.
Medical authorities typically put the complication rate for LC at roughly 2%. A study published in the April 1995 issue of the Annals of Surgery, for example, reported a morbidity rate of 1.9% for LC compared with 7.7% for open-field cholecystectomy.
Among LC complications, a nicked intestine is one of the least common, according to a study by Thomas McLean, MD, JD, published in July 2006 in the Archives of Surgery. Dr. McLean, a staff thoracic surgeon at the Dwight D. Eisenhower Veterans Affairs Medical Center in Leavenworth, Kansas, found that bowel injuries accounted for 2% of adverse events in LCs that triggered a malpractice suit. The leading cause of litigation — 78% — was injury to the bile duct. Such bile duct injuries are more common in LC than open-field cholecystectomy, Dr. McLean told Medscape Medical News.
Intestinal injuries, he said, are usually caused by trocar insertion. "There may be as many as 5 [trocars] inserted. This tends to be feel-only."
The intestine also can be injured when a surgeon is trying to separate it from an inflamed gallbladder that has adhered to it, said Nathaniel Soper, MD, chairman of the Department of Surgery at Northwestern University Feinberg School of Medicine, Chicago, Illinois. The pressure of the carbon dioxide gas used to inflate the abdomen during LC can seal up intestinal punctures that leak only after the gas is gone, Dr. Soper told Medscape Medical News. He noted that either the small or large intestine can be accidentally cut during LC, although the duodenum of the small intestine is the more likely candidate because of its proximity to the gallbladder. It is not clear from published accounts which intestine of Murtha's was accidentally cut.
Limitations of Laparoscopic Vision
Dr. Soper said the risk for accidental cuts increases with the distorted, depthless vision of the laparoscope.
"You're dependent on a 2-dimensional image," said Dr. Soper. "Because the image is very magnified, you're looking only at a very small part of the (surgical) field, and you don't have a normal sense of feel using 2-foot long instruments."
In contrast, surgeons performing an open-field cholecystectomy enjoy a direct, 3-dimensional, panoramic view, added Dr. McLean. That improved view helps them not only avoid a scalpel accident but also spot any accidents that occur during surgery. In addition, if surgeons are worried about inadvertently cutting an intestine, they can pick it up and gently squeeze it to check for a leak.
Another risk factor for accidental intestinal cuts is obesity. In noting that the intestines can be injured during LC, the American College of Surgeons states on its Web site that "patients who are obese...make it more difficult to move and manipulate instruments." However, an open-field cholecystectomy for a morbidly obese person carries its own special risk — an incision that can be double the normal length, noted Dr. Soper.
Rep. Murtha, who was 77 years old, had represented the 12th Congressional District in southwestern Pennsylvania since 1974. An ex-Marine and Vietnam War combat veteran, he was chairman of the House Appropriations Subcommittee on Defense.
Blood Test May Predict Rheumatoid Arthritis
From WebMD Health News
Jennifer Warner
January 29, 2010 - Elevated levels of inflammatory proteins called cytokines and related factors in the blood may be an early warning sign of impending rheumatoid arthritis (RA), according to a new study.
Researchers have found that levels of certain cytokines and related factors in the blood increase significantly prior to the development of rheumatoid arthritis, long before symptoms emerge. They say the finding paves the way for developing a blood test for early diagnosis of the mysterious disease.
"Our findings present an opportunity for better predicting the risk of developing RA and possibly preventing disease progression," says researcher Solbritt Rantapää-Dahlqvist, MD, of University Hospital in Umea, Sweden, in a news release.
Rheumatoid arthritis is a painful, progressive condition that can be difficult to diagnose in the early stages because it often begins with only subtle symptoms, such as achy joints or early morning stiffness. Other conditions, such as lupus, osteoarthritis, and fibromyalgia may also mimic the early symptoms of rheumatoid arthritis, which makes a definitive diagnosis difficult.
But studies have shown that early diagnosis and treatment of rheumatoid arthritis can help sufferers live a more active life and potentially avoid the type of joint damage that leads to disability.
Early Signs of RA
The cause of rheumatoid arthritis is not understood, but various components of the immune system and synovial tissue, which lubricates the joints, are thought to be involved.
Cytokines are pro-inflammatory proteins that are often found in the synovial tissue after rheumatoid arthritis has developed.
In the study, published in Arthritis & Rheumatism, researchers examined whether particular cytokines and related factors are elevated prior to the emergence of rheumatoid arthritis symptoms.
They analyzed blood samples from 86 people in Sweden without symptoms of rheumatoid arthritis at the time of donation who later developed RA and compared them with samples from 256 healthy individuals.
The results showed levels of several cytokines and related factors were elevated up to years before diagnosis with rheumatoid arthritis.
Researchers say the findings support the idea that the immune system was already stimulated and rheumatoid arthritis was developing. If further studies confirm these results, a blood test to screen for these elevated cytokines may help diagnose RA before symptoms emerge.
SOURCES:
Kokkonen, H. Arthritis & Rheumatism, Feb. 2, 2010; vol 62: pp 383-391.
Jennifer Warner
January 29, 2010 - Elevated levels of inflammatory proteins called cytokines and related factors in the blood may be an early warning sign of impending rheumatoid arthritis (RA), according to a new study.
Researchers have found that levels of certain cytokines and related factors in the blood increase significantly prior to the development of rheumatoid arthritis, long before symptoms emerge. They say the finding paves the way for developing a blood test for early diagnosis of the mysterious disease.
"Our findings present an opportunity for better predicting the risk of developing RA and possibly preventing disease progression," says researcher Solbritt Rantapää-Dahlqvist, MD, of University Hospital in Umea, Sweden, in a news release.
Rheumatoid arthritis is a painful, progressive condition that can be difficult to diagnose in the early stages because it often begins with only subtle symptoms, such as achy joints or early morning stiffness. Other conditions, such as lupus, osteoarthritis, and fibromyalgia may also mimic the early symptoms of rheumatoid arthritis, which makes a definitive diagnosis difficult.
But studies have shown that early diagnosis and treatment of rheumatoid arthritis can help sufferers live a more active life and potentially avoid the type of joint damage that leads to disability.
Early Signs of RA
The cause of rheumatoid arthritis is not understood, but various components of the immune system and synovial tissue, which lubricates the joints, are thought to be involved.
Cytokines are pro-inflammatory proteins that are often found in the synovial tissue after rheumatoid arthritis has developed.
In the study, published in Arthritis & Rheumatism, researchers examined whether particular cytokines and related factors are elevated prior to the emergence of rheumatoid arthritis symptoms.
They analyzed blood samples from 86 people in Sweden without symptoms of rheumatoid arthritis at the time of donation who later developed RA and compared them with samples from 256 healthy individuals.
The results showed levels of several cytokines and related factors were elevated up to years before diagnosis with rheumatoid arthritis.
Researchers say the findings support the idea that the immune system was already stimulated and rheumatoid arthritis was developing. If further studies confirm these results, a blood test to screen for these elevated cytokines may help diagnose RA before symptoms emerge.
SOURCES:
Kokkonen, H. Arthritis & Rheumatism, Feb. 2, 2010; vol 62: pp 383-391.
Gout. Imaging of Gout: Findings and Utility
From Arthritis Research & Therapy
Fernando Perez-Ruiz; Nicola Dalbeth; Aranzazu Urresola; Eugenio de Miguel; Naomi Schlesinger
Abstract
Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation.
Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques.
Plain radiographs show typical changes only in advanced chronic gout.
Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes.
Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation.
Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy.
Introduction
Gout is a disease caused by deposition of monosodium urate (MSU) monohydrate crystals that induce not only acute episodes of inflammation, but also, in the long-term history of the disease, chronic inflammation that is associated with changes in articular and periarticular structures.
Imaging may be useful to evaluate the severity of disease (measurement of structural joint changes), the extent of MSU deposition (location and magnitude of urate deposition), and the presence of chronic inflammation.[1]
In addition, as an outcome measure, imaging may allow estimation of the change of these variables during urate-lowering therapy; that is, as MSU crystals dissolute due to the long-term effect of subsaturating serum urate levels achieved during urate-lowering therapy.[2] If so, imaging would also provide a useful tool to monitor the response to urate-lowering therapy.
http://www.medscape.com/viewarticle/715155?src=mp&spon=27&uac=71630FV
Fernando Perez-Ruiz; Nicola Dalbeth; Aranzazu Urresola; Eugenio de Miguel; Naomi Schlesinger
Abstract
Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation.
Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques.
Plain radiographs show typical changes only in advanced chronic gout.
Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes.
Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation.
Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy.
Introduction
Gout is a disease caused by deposition of monosodium urate (MSU) monohydrate crystals that induce not only acute episodes of inflammation, but also, in the long-term history of the disease, chronic inflammation that is associated with changes in articular and periarticular structures.
Imaging may be useful to evaluate the severity of disease (measurement of structural joint changes), the extent of MSU deposition (location and magnitude of urate deposition), and the presence of chronic inflammation.[1]
In addition, as an outcome measure, imaging may allow estimation of the change of these variables during urate-lowering therapy; that is, as MSU crystals dissolute due to the long-term effect of subsaturating serum urate levels achieved during urate-lowering therapy.[2] If so, imaging would also provide a useful tool to monitor the response to urate-lowering therapy.
http://www.medscape.com/viewarticle/715155?src=mp&spon=27&uac=71630FV
Friday, February 12, 2010
Polycarbonate Bottle Use and Urinary Bisphenol A Concentrations
From Environmental Health Perspectives
Jenny L. Carwile; Henry T. Luu; Laura S. Bassett; Daniel A. Driscoll; Caterina Yuan; Jennifer Y. Chang; Xiaoyun Ye; Antonia M. Calafat; Karin B. Michels
Abstract
Background: Bisphenol A (BPA) is a high-production-volume chemical commonly used in the manufacture of polycarbonate plastic. Low-level concentrations of BPA in animals and possibly in humans may cause endocrine disruption. Whether ingestion of food or beverages from polycarbonate containers increases BPA concentrations in humans has not been studied.
Objectives: We examined the association between use of polycarbonate beverage containers and urinary BPA concentrations in humans.
Methods: We conducted a nonrandomized intervention of 77 Harvard College students to compare urinary BPA concentrations collected after a washout phase of 1 week to those taken after an intervention week during which most cold beverages were consumed from polycarbonate drinking bottles. Pairedt-tests were used to assess the difference in urinary BPA concentrations before and after polycarbonate bottle use.
Results: The geometric mean urinary BPA concentration at the end of the washout phase was 1.2 μg/g creatinine, increasing to 2.0 μg/g creatinine after 1 week of polycarbonate bottle use. Urinary BPA concentrations increased by 69% after use of polycarbonate bottles (p < 0.0001). The association was stronger among participants who reported ≥ 90% compliance (77% increase; p < 0.0001) than among those reporting < 90% compliance (55% increase; p = 0.03), but this difference was not statistically significant (p = 0.54).
Conclusions: One week of polycarbonate bottle use increased urinary BPA concentrations by two-thirds. Regular consumption of cold beverages from polycarbonate bottles is associated with a substantial increase in urinary BPA concentrations irrespective of exposure to BPA from other sources.
Introduction
The endocrine-disrupting chemical bisphenol A (BPA) has recently garnered heightened attention because of widespread human exposure and disruption of normal reproductive development in laboratory animals [Center for the Evaluation of Risks to Human Reproduction (CERHR) 2008; Chapin et al. 2008; Goodman et al. 2006; European Union 2003; vom Saal and Hughes 2005]. BPA is thought to disrupt normal cell function by acting as an estrogen agonist (Wozniak et al. 2005) as well as an androgen antagonist (Lee et al. 2003). In animal studies, prenatal and neonatal exposure to BPA has been linked to early onset of sexual maturation (Howdeshell et al. 1999), altered development and tissue organization of the mammary gland (Markey et al. 2001), induction of preneoplastic mammary gland (Durando et al. 2007) and reproductive tract lesions (Newbold et al. 2007), increased prostate size (Timms et al. 2005), and decreased sperm production (vom Saal et al. 1998) in offspring. Most recently, exposure to BPA has also been associated with chronic disease in humans, including cardiovascular disease, diabetes, and serum markers of liver disease (Lang et al. 2008).
Orally administered BPA is rapidly metabolized by glucuronidation during first-pass metabolism, with a biological half-life of approximately 6 hr and nearly complete elimination within 24 hr (Volkel et al. 2002). However, because of continuous and widespread exposure, > 92% of the 2,517 participants ≥ 6 years of age in the U.S. 2003–2004 National Health and Nutrition Examination Survey (NHANES) had detectable concentrations of BPA in their urine (Calafat et al. 2008). The geometric mean (GM) urinary BPA concentration in that study was 2.6 μg/L (2.6 μg/g creatinine), and the 95th percentile was 15.9 μg/L (11.2 μg/g creatinine).
An important source of human exposure is thought to be the ingestion of food and drink that has been in contact with epoxy resins or polycarbonate plastics (Kang et al. 2006). Polycarbonate is a durable, lightweight, and heat-resistant plastic, making it popular for use in plastic food and beverage containers. Indeed, nearly three-fourths of the 1.9 billion pounds of BPA used in the United States in 2003 was used for the manufacture of polycarbonate resin (CERHR 2008). Other common uses of BPA include the manufacture of epoxy resins used as composites and sealants in dentistry and in the lacquer lining of aluminum food and beverage cans (CERHR 2008; European Union 2003).
Laboratory studies have demonstrated that biologically active BPA is released from polycarbonate bottles after simulated normal use (Brede et al. 2003; Le et al. 2008). High temperatures as well as acidic and alkali solutions cause polymer degradation via hydrolysis, resulting in increased BPA migration. After incubation for 8, 72, and 240 hr in food-simulating solvents (10% ethanol at 70°C and corn oil at 100°C), mean BPA migration increased with incubation time (Onn Wong et al. 2005). After a sequence of washing and rinsing, Le et al. (2008) found that new polycarbonate bottles leached 1.0 ± 0.3 μg/mL BPA (mean ± SD) into the bottle content after incubation at room temperature for 7 days. Although exposure to boiling water increased the rate of BPA migration up to 55-fold, used bottles did not leach significantly more BPA than new ones. However, other studies have found that higher concentrations of BPA leach from used polycarbonate plastic than from new. BPA has been observed to leach from polycarbonate animal cages after 1 week of incubation at room temperature, with higher levels of migration from used versus new cages (Howdeshell et al. 2003). Similarly, after incubation in 100°C water for 1 hr, the amount of BPA leached from baby bottles subjected to simulated use (including dishwashing, boiling, and brushing into the bottle) exceeded the amount that leached from new baby bottles (Brede et al. 2003).
Recently, some polycarbonate bottle manufacturers voluntarily eliminated BPA from their products (Nalgene Outdoor 2008), and several retailers withdrew polycarbonate bottles from their stores altogether (Mui 2008). Canada has imposed a ban on the use of BPA in polycarbonate baby bottles in order to reduce exposure of infants to BPA (Health Canada 2008), and similar legislation is being considered by several U.S. states (Austen 2008). However, such actions have been largely preemptive, as no epidemiologic study has evaluated the physiologic consequences of polycarbonate bottle use. Therefore, we studied the impact of cold beverage consumption from polycarbonate bottles on measurable urinary BPA concentrations among a Harvard College population. We also measured exposure to the phenols triclosan (TCS), methyl paraben (MePB), propyl paraben (PrPB), and benzophenone-3 (BP-3), which occurs mainly through the use of personal care products. Therefore, because exposure of these chemicals is considered unrelated to polycarbonate bottle use, we assessed their association with polycarbonate bottle use as a negative control
Furthermore, we assessed the impact of polycarbonate bottle use in a normal use setting. The present study could be considered a conservative estimate of true use, as students did not have access to dishwashers and were instructed to use their containers for cold beverages only, whereas the storage of hot liquids is common, especially in outdoor recreation settings. Because heating is thought to increase the amount of BPA leached from the polycarbonate (Le et al. 2008), we would anticipate higher urinary BPA concentrations after ingestion of hot beverages stored in the same bottles.
http://www.medscape.com/viewarticle/710617?src=mp&spon=9&uac=71630FV
Jenny L. Carwile; Henry T. Luu; Laura S. Bassett; Daniel A. Driscoll; Caterina Yuan; Jennifer Y. Chang; Xiaoyun Ye; Antonia M. Calafat; Karin B. Michels
Abstract
Background: Bisphenol A (BPA) is a high-production-volume chemical commonly used in the manufacture of polycarbonate plastic. Low-level concentrations of BPA in animals and possibly in humans may cause endocrine disruption. Whether ingestion of food or beverages from polycarbonate containers increases BPA concentrations in humans has not been studied.
Objectives: We examined the association between use of polycarbonate beverage containers and urinary BPA concentrations in humans.
Methods: We conducted a nonrandomized intervention of 77 Harvard College students to compare urinary BPA concentrations collected after a washout phase of 1 week to those taken after an intervention week during which most cold beverages were consumed from polycarbonate drinking bottles. Pairedt-tests were used to assess the difference in urinary BPA concentrations before and after polycarbonate bottle use.
Results: The geometric mean urinary BPA concentration at the end of the washout phase was 1.2 μg/g creatinine, increasing to 2.0 μg/g creatinine after 1 week of polycarbonate bottle use. Urinary BPA concentrations increased by 69% after use of polycarbonate bottles (p < 0.0001). The association was stronger among participants who reported ≥ 90% compliance (77% increase; p < 0.0001) than among those reporting < 90% compliance (55% increase; p = 0.03), but this difference was not statistically significant (p = 0.54).
Conclusions: One week of polycarbonate bottle use increased urinary BPA concentrations by two-thirds. Regular consumption of cold beverages from polycarbonate bottles is associated with a substantial increase in urinary BPA concentrations irrespective of exposure to BPA from other sources.
Introduction
The endocrine-disrupting chemical bisphenol A (BPA) has recently garnered heightened attention because of widespread human exposure and disruption of normal reproductive development in laboratory animals [Center for the Evaluation of Risks to Human Reproduction (CERHR) 2008; Chapin et al. 2008; Goodman et al. 2006; European Union 2003; vom Saal and Hughes 2005]. BPA is thought to disrupt normal cell function by acting as an estrogen agonist (Wozniak et al. 2005) as well as an androgen antagonist (Lee et al. 2003). In animal studies, prenatal and neonatal exposure to BPA has been linked to early onset of sexual maturation (Howdeshell et al. 1999), altered development and tissue organization of the mammary gland (Markey et al. 2001), induction of preneoplastic mammary gland (Durando et al. 2007) and reproductive tract lesions (Newbold et al. 2007), increased prostate size (Timms et al. 2005), and decreased sperm production (vom Saal et al. 1998) in offspring. Most recently, exposure to BPA has also been associated with chronic disease in humans, including cardiovascular disease, diabetes, and serum markers of liver disease (Lang et al. 2008).
Orally administered BPA is rapidly metabolized by glucuronidation during first-pass metabolism, with a biological half-life of approximately 6 hr and nearly complete elimination within 24 hr (Volkel et al. 2002). However, because of continuous and widespread exposure, > 92% of the 2,517 participants ≥ 6 years of age in the U.S. 2003–2004 National Health and Nutrition Examination Survey (NHANES) had detectable concentrations of BPA in their urine (Calafat et al. 2008). The geometric mean (GM) urinary BPA concentration in that study was 2.6 μg/L (2.6 μg/g creatinine), and the 95th percentile was 15.9 μg/L (11.2 μg/g creatinine).
An important source of human exposure is thought to be the ingestion of food and drink that has been in contact with epoxy resins or polycarbonate plastics (Kang et al. 2006). Polycarbonate is a durable, lightweight, and heat-resistant plastic, making it popular for use in plastic food and beverage containers. Indeed, nearly three-fourths of the 1.9 billion pounds of BPA used in the United States in 2003 was used for the manufacture of polycarbonate resin (CERHR 2008). Other common uses of BPA include the manufacture of epoxy resins used as composites and sealants in dentistry and in the lacquer lining of aluminum food and beverage cans (CERHR 2008; European Union 2003).
Laboratory studies have demonstrated that biologically active BPA is released from polycarbonate bottles after simulated normal use (Brede et al. 2003; Le et al. 2008). High temperatures as well as acidic and alkali solutions cause polymer degradation via hydrolysis, resulting in increased BPA migration. After incubation for 8, 72, and 240 hr in food-simulating solvents (10% ethanol at 70°C and corn oil at 100°C), mean BPA migration increased with incubation time (Onn Wong et al. 2005). After a sequence of washing and rinsing, Le et al. (2008) found that new polycarbonate bottles leached 1.0 ± 0.3 μg/mL BPA (mean ± SD) into the bottle content after incubation at room temperature for 7 days. Although exposure to boiling water increased the rate of BPA migration up to 55-fold, used bottles did not leach significantly more BPA than new ones. However, other studies have found that higher concentrations of BPA leach from used polycarbonate plastic than from new. BPA has been observed to leach from polycarbonate animal cages after 1 week of incubation at room temperature, with higher levels of migration from used versus new cages (Howdeshell et al. 2003). Similarly, after incubation in 100°C water for 1 hr, the amount of BPA leached from baby bottles subjected to simulated use (including dishwashing, boiling, and brushing into the bottle) exceeded the amount that leached from new baby bottles (Brede et al. 2003).
Recently, some polycarbonate bottle manufacturers voluntarily eliminated BPA from their products (Nalgene Outdoor 2008), and several retailers withdrew polycarbonate bottles from their stores altogether (Mui 2008). Canada has imposed a ban on the use of BPA in polycarbonate baby bottles in order to reduce exposure of infants to BPA (Health Canada 2008), and similar legislation is being considered by several U.S. states (Austen 2008). However, such actions have been largely preemptive, as no epidemiologic study has evaluated the physiologic consequences of polycarbonate bottle use. Therefore, we studied the impact of cold beverage consumption from polycarbonate bottles on measurable urinary BPA concentrations among a Harvard College population. We also measured exposure to the phenols triclosan (TCS), methyl paraben (MePB), propyl paraben (PrPB), and benzophenone-3 (BP-3), which occurs mainly through the use of personal care products. Therefore, because exposure of these chemicals is considered unrelated to polycarbonate bottle use, we assessed their association with polycarbonate bottle use as a negative control
Furthermore, we assessed the impact of polycarbonate bottle use in a normal use setting. The present study could be considered a conservative estimate of true use, as students did not have access to dishwashers and were instructed to use their containers for cold beverages only, whereas the storage of hot liquids is common, especially in outdoor recreation settings. Because heating is thought to increase the amount of BPA leached from the polycarbonate (Le et al. 2008), we would anticipate higher urinary BPA concentrations after ingestion of hot beverages stored in the same bottles.
http://www.medscape.com/viewarticle/710617?src=mp&spon=9&uac=71630FV
diseases of nails - slideshow
http://www.medscape.com/features/slideshow/nail-diseases?src=mp&spon=17&uac=71630FV
Saturday, February 6, 2010
Missing Genes Linked to Extreme Obesity
From WebMD Health News
Jennifer Warner
February 4, 2010 — Missing genes may be behind at least some cases of morbid or extreme obesity, according to a new study.
Researchers found that a small but significant portion of morbidly obese people are missing a section of their DNA that may contribute to their obesity.
The results suggest around seven in every 1,000 morbidly obese people are missing this section of their DNA, which contains about 30 genes. This genetic variation was not found in any people of normal weight.
"Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic," says researcher Philippe Froguel, of the School of Public Health at Imperial College London, in a news release.
Overall, researchers say about one in 20 cases of morbidly obese people is caused by genetics, including previously identified genetic mutations and these missing genes. But many more genetic mutations linked to obesity are yet to be found.
The researchers hope that identifying genetic variations that cause people to be morbidly obese will lead to the development of genetic tests that can help determine the best treatment.
"If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight loss surgery, to improve their long-term health," says Froguel.
In the study, published in Nature, researchers first identified the missing genes in teenagers and adults who had learning difficulties or delayed development.
The results showed 31 people had nearly identical deletions in one copy of their DNA. All of the adults with this genetic variation had a BMI of over 30, which means they were obese.
People inherit two copies of their DNA, one copy from their mother and one from their father. Sometimes one copy of one or more genes is missing and can affect a person’s development, as shown by this study.
In the second part of the study, researchers examined the genomes or genetic maps of 16,053 European people who were either obese or normal weight. They found 19 more people with the same set of missing genes. All of these individuals were morbidly obese.
The study showed people with the genetic deletion tended to be normal-weight toddlers who became overweight during childhood and morbidly obese as adults.
Researchers did not find the genetic deletion in any normal-weight people. Although they do not know the function of the missing genes, previous studies suggest some of them may be involved with delayed development, autism, and schizophrenia.
SOURCES:
Walters, R. Nature, Feb. 3, 2010, online advance edition.
News release, Imperial College London.
Jennifer Warner
February 4, 2010 — Missing genes may be behind at least some cases of morbid or extreme obesity, according to a new study.
Researchers found that a small but significant portion of morbidly obese people are missing a section of their DNA that may contribute to their obesity.
The results suggest around seven in every 1,000 morbidly obese people are missing this section of their DNA, which contains about 30 genes. This genetic variation was not found in any people of normal weight.
"Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic," says researcher Philippe Froguel, of the School of Public Health at Imperial College London, in a news release.
Overall, researchers say about one in 20 cases of morbidly obese people is caused by genetics, including previously identified genetic mutations and these missing genes. But many more genetic mutations linked to obesity are yet to be found.
The researchers hope that identifying genetic variations that cause people to be morbidly obese will lead to the development of genetic tests that can help determine the best treatment.
"If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight loss surgery, to improve their long-term health," says Froguel.
In the study, published in Nature, researchers first identified the missing genes in teenagers and adults who had learning difficulties or delayed development.
The results showed 31 people had nearly identical deletions in one copy of their DNA. All of the adults with this genetic variation had a BMI of over 30, which means they were obese.
People inherit two copies of their DNA, one copy from their mother and one from their father. Sometimes one copy of one or more genes is missing and can affect a person’s development, as shown by this study.
In the second part of the study, researchers examined the genomes or genetic maps of 16,053 European people who were either obese or normal weight. They found 19 more people with the same set of missing genes. All of these individuals were morbidly obese.
The study showed people with the genetic deletion tended to be normal-weight toddlers who became overweight during childhood and morbidly obese as adults.
Researchers did not find the genetic deletion in any normal-weight people. Although they do not know the function of the missing genes, previous studies suggest some of them may be involved with delayed development, autism, and schizophrenia.
SOURCES:
Walters, R. Nature, Feb. 3, 2010, online advance edition.
News release, Imperial College London.
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