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Probiotics for Radiation-Caused Diarrhea
Probiotics may help reduce the severity of one of the most common acute adverse effects of radiation—diarrhea. They just might not show results right away. According to a study by researchers from the Centre Hospitalier Universitaire de Québec in Canada, the effects of probiotics were positive and most effective in the weeks after radiation treatment.
No prophylactic agents are approved for preventing pelvic radiation enteritis, the researchers note, and evidence is weak for nutritional interventions that have been tried. But recently, more research is pointing to a powerful role for probiotics in a variety of gastrointestinal uses.
This study compared the efficacy of the probiotic Bifilact (Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536) with placebo. The main goal was to find whether probiotics would prevent or delay the incidence of moderate-to-severe radiation-induced diarrhea during a radiotherapy treatment. Secondary goals were to assess whether Bifilact reduced or delayed the need of antidiarrheal medication, reduced intestinal pain, reduced the need for hospitalization, minimized interruptions to radiotherapy treatments, and improved patient well-being.
In the study, 229 patients received either placebo or 1 of 2 Bifilact regimens: a standard dose twice a day or a high dose 3 times a day. Patients recorded their digestive symptoms every day and met with a registered dietitian and radiation oncologist every week during treatment.
Although the differences were not statistically significant, probiotics eventually halved the proportion of patients with moderate-to-severe diarrhea. The mean number of bowel movements per 24 hours was 2.3 in the placebo group, 2.3 in the standard-dose, and 2.1 in the high-dose patients (P = .84). During the treatment, those numbers changed to 2.9, 2.7, and 2.8 bowel movements per day (P = .80), respectively. For patients who underwent surgical procedures before radiation, probiotic intake tended to reduce all levels of diarrhea, especially the most severe grade 4 diarrhea. Median abdominal pain was initially 0 for all groups and < 1 during treatment for all groups (P = .23).
To their knowledge, the researchers say, only 6 human clinical studies have been published regarding using probiotics to prevent acute radiation-induced diarrhea, and only 1 for treating diarrhea after radiotherapy. The 6 studies showed positive results on diarrhea toxicity and/or frequency of bowel movement and/or stool consistency. Two of 3 systematic reviews also found a probable beneficial effect on prevention.
Their own study produced some interesting findings, the researchers say. For one, less diarrhea at 60 days meant the benefit began at the end of the treatment or after it. Patients with a standard dose of probiotic experienced less of the moderate-to-severe diarrhea at the end of treatment or during the 2 weeks following treatment. And after 60 days, 35% of patients in the standard-dose group did not have moderate-to-severe diarrhea, compared with 17% in the placebo group (P = .23). The researchers say the probiotic effect may be delayed because of the time required by bacteria to exert their influence on the inflammatory process.
Source
Demers M, Dagnault A, Desjardins J. Clin Nutr. 2014;33(5):761-767.
doi: 10.1016/j.clnu.2013.10.015.
Probiotics may help reduce the severity of one of the most common acute adverse effects of radiation—diarrhea. They just might not show results right away. According to a study by researchers from the Centre Hospitalier Universitaire de Québec in Canada, the effects of probiotics were positive and most effective in the weeks after radiation treatment.
No prophylactic agents are approved for preventing pelvic radiation enteritis, the researchers note, and evidence is weak for nutritional interventions that have been tried. But recently, more research is pointing to a powerful role for probiotics in a variety of gastrointestinal uses.
This study compared the efficacy of the probiotic Bifilact (Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536) with placebo. The main goal was to find whether probiotics would prevent or delay the incidence of moderate-to-severe radiation-induced diarrhea during a radiotherapy treatment. Secondary goals were to assess whether Bifilact reduced or delayed the need of antidiarrheal medication, reduced intestinal pain, reduced the need for hospitalization, minimized interruptions to radiotherapy treatments, and improved patient well-being.
In the study, 229 patients received either placebo or 1 of 2 Bifilact regimens: a standard dose twice a day or a high dose 3 times a day. Patients recorded their digestive symptoms every day and met with a registered dietitian and radiation oncologist every week during treatment.
Although the differences were not statistically significant, probiotics eventually halved the proportion of patients with moderate-to-severe diarrhea. The mean number of bowel movements per 24 hours was 2.3 in the placebo group, 2.3 in the standard-dose, and 2.1 in the high-dose patients (P = .84). During the treatment, those numbers changed to 2.9, 2.7, and 2.8 bowel movements per day (P = .80), respectively. For patients who underwent surgical procedures before radiation, probiotic intake tended to reduce all levels of diarrhea, especially the most severe grade 4 diarrhea. Median abdominal pain was initially 0 for all groups and < 1 during treatment for all groups (P = .23).
To their knowledge, the researchers say, only 6 human clinical studies have been published regarding using probiotics to prevent acute radiation-induced diarrhea, and only 1 for treating diarrhea after radiotherapy. The 6 studies showed positive results on diarrhea toxicity and/or frequency of bowel movement and/or stool consistency. Two of 3 systematic reviews also found a probable beneficial effect on prevention.
Their own study produced some interesting findings, the researchers say. For one, less diarrhea at 60 days meant the benefit began at the end of the treatment or after it. Patients with a standard dose of probiotic experienced less of the moderate-to-severe diarrhea at the end of treatment or during the 2 weeks following treatment. And after 60 days, 35% of patients in the standard-dose group did not have moderate-to-severe diarrhea, compared with 17% in the placebo group (P = .23). The researchers say the probiotic effect may be delayed because of the time required by bacteria to exert their influence on the inflammatory process.
Source
Demers M, Dagnault A, Desjardins J. Clin Nutr. 2014;33(5):761-767.
doi: 10.1016/j.clnu.2013.10.015.
Probiotics may help reduce the severity of one of the most common acute adverse effects of radiation—diarrhea. They just might not show results right away. According to a study by researchers from the Centre Hospitalier Universitaire de Québec in Canada, the effects of probiotics were positive and most effective in the weeks after radiation treatment.
No prophylactic agents are approved for preventing pelvic radiation enteritis, the researchers note, and evidence is weak for nutritional interventions that have been tried. But recently, more research is pointing to a powerful role for probiotics in a variety of gastrointestinal uses.
This study compared the efficacy of the probiotic Bifilact (Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536) with placebo. The main goal was to find whether probiotics would prevent or delay the incidence of moderate-to-severe radiation-induced diarrhea during a radiotherapy treatment. Secondary goals were to assess whether Bifilact reduced or delayed the need of antidiarrheal medication, reduced intestinal pain, reduced the need for hospitalization, minimized interruptions to radiotherapy treatments, and improved patient well-being.
In the study, 229 patients received either placebo or 1 of 2 Bifilact regimens: a standard dose twice a day or a high dose 3 times a day. Patients recorded their digestive symptoms every day and met with a registered dietitian and radiation oncologist every week during treatment.
Although the differences were not statistically significant, probiotics eventually halved the proportion of patients with moderate-to-severe diarrhea. The mean number of bowel movements per 24 hours was 2.3 in the placebo group, 2.3 in the standard-dose, and 2.1 in the high-dose patients (P = .84). During the treatment, those numbers changed to 2.9, 2.7, and 2.8 bowel movements per day (P = .80), respectively. For patients who underwent surgical procedures before radiation, probiotic intake tended to reduce all levels of diarrhea, especially the most severe grade 4 diarrhea. Median abdominal pain was initially 0 for all groups and < 1 during treatment for all groups (P = .23).
To their knowledge, the researchers say, only 6 human clinical studies have been published regarding using probiotics to prevent acute radiation-induced diarrhea, and only 1 for treating diarrhea after radiotherapy. The 6 studies showed positive results on diarrhea toxicity and/or frequency of bowel movement and/or stool consistency. Two of 3 systematic reviews also found a probable beneficial effect on prevention.
Their own study produced some interesting findings, the researchers say. For one, less diarrhea at 60 days meant the benefit began at the end of the treatment or after it. Patients with a standard dose of probiotic experienced less of the moderate-to-severe diarrhea at the end of treatment or during the 2 weeks following treatment. And after 60 days, 35% of patients in the standard-dose group did not have moderate-to-severe diarrhea, compared with 17% in the placebo group (P = .23). The researchers say the probiotic effect may be delayed because of the time required by bacteria to exert their influence on the inflammatory process.
Source
Demers M, Dagnault A, Desjardins J. Clin Nutr. 2014;33(5):761-767.
doi: 10.1016/j.clnu.2013.10.015.
Banning Smoking in Tribal Casinos
In American Indian (AI) communities that have casinos, health is improving, thanks to more employment and less poverty. But it is not all good news because casino workers (of whom 1 in 4 is an AI) and patrons are still exposed to secondhand smoke in many casinos, say researchers from the Great Lakes Inter-Tribal Council (GLITC) in Lac du Flambeau (LDF), Wisconsin; Northwest Portland Area Indian Health Board, in Oregon; and the University of Oklahoma in Tulsa. Tribal casinos are exempt from statewide bans on smoking because of tribal sovereignty. However, though smoking has declined in other segments of the population, it has not among AIs, where the incidence is 40%—more than twice that of the general U.S. population. Moreover, the tobacco industry has increasingly targeted tribal casinos, the researchers add.
Only 6 of 237 tribes operating casinos have voluntarily implemented casino-wide smoking bans. The tribal community is aiming to do something about that, though. The GLITC, a consortium of 12 member tribes in Wisconsin and Upper Michigan, and the LDF tribal nation, a member of GLITC, collaborated with the Lake of the Torches Resort Casino in northern Wisconsin to survey casino patrons to find out whether a smoking ban could get passed.
The project team’s analysis was based on survey responses from 957 casino patrons who were questioned about their opinions on smoking, secondhand smoke, and smoking bans. Most respondents were white and nonsmokers. A majority (69%) were bothered to some extent by smoke in the casino, and 81% believed secondhand smoke is harmful. Those who preferred a smoke-free casino were older, white, and gambled less. Over half (54%) said they were likely to visit more often, 28% said they were indifferent to a smoke-free casino, and 18% said they would visit less if the casino were smoke free.
The researchers cite other studies that have found that only 20% of casino patrons smoke. They also say smoking bans are not cited as reasons people visit casinos less, and smoking bans do not result in revenue loss for casinos.
This is the first study to employ a community-based and tribally led approach. The access would not have been possible without the “significant trust” between GLITC and the LDF tribal nation, the researchers say. The casino, owned and operated by the tribal nation whose members indirectly benefit from casino revenue, was responsive to community concerns about secondhand smoke, they add. This suggests that tribal communities may be “uniquely suited…to play a leadership role in a smoke-free casino movement.”
Source
Brokenleg IS, Barber TK, Bennett NL, Peart Boyce S, Blue Bird Jernigan V. Am J Prev Med. 2014;47(3):290-299.
doi: 10.1016/j.amepre.2014.04.006.
In American Indian (AI) communities that have casinos, health is improving, thanks to more employment and less poverty. But it is not all good news because casino workers (of whom 1 in 4 is an AI) and patrons are still exposed to secondhand smoke in many casinos, say researchers from the Great Lakes Inter-Tribal Council (GLITC) in Lac du Flambeau (LDF), Wisconsin; Northwest Portland Area Indian Health Board, in Oregon; and the University of Oklahoma in Tulsa. Tribal casinos are exempt from statewide bans on smoking because of tribal sovereignty. However, though smoking has declined in other segments of the population, it has not among AIs, where the incidence is 40%—more than twice that of the general U.S. population. Moreover, the tobacco industry has increasingly targeted tribal casinos, the researchers add.
Only 6 of 237 tribes operating casinos have voluntarily implemented casino-wide smoking bans. The tribal community is aiming to do something about that, though. The GLITC, a consortium of 12 member tribes in Wisconsin and Upper Michigan, and the LDF tribal nation, a member of GLITC, collaborated with the Lake of the Torches Resort Casino in northern Wisconsin to survey casino patrons to find out whether a smoking ban could get passed.
The project team’s analysis was based on survey responses from 957 casino patrons who were questioned about their opinions on smoking, secondhand smoke, and smoking bans. Most respondents were white and nonsmokers. A majority (69%) were bothered to some extent by smoke in the casino, and 81% believed secondhand smoke is harmful. Those who preferred a smoke-free casino were older, white, and gambled less. Over half (54%) said they were likely to visit more often, 28% said they were indifferent to a smoke-free casino, and 18% said they would visit less if the casino were smoke free.
The researchers cite other studies that have found that only 20% of casino patrons smoke. They also say smoking bans are not cited as reasons people visit casinos less, and smoking bans do not result in revenue loss for casinos.
This is the first study to employ a community-based and tribally led approach. The access would not have been possible without the “significant trust” between GLITC and the LDF tribal nation, the researchers say. The casino, owned and operated by the tribal nation whose members indirectly benefit from casino revenue, was responsive to community concerns about secondhand smoke, they add. This suggests that tribal communities may be “uniquely suited…to play a leadership role in a smoke-free casino movement.”
Source
Brokenleg IS, Barber TK, Bennett NL, Peart Boyce S, Blue Bird Jernigan V. Am J Prev Med. 2014;47(3):290-299.
doi: 10.1016/j.amepre.2014.04.006.
In American Indian (AI) communities that have casinos, health is improving, thanks to more employment and less poverty. But it is not all good news because casino workers (of whom 1 in 4 is an AI) and patrons are still exposed to secondhand smoke in many casinos, say researchers from the Great Lakes Inter-Tribal Council (GLITC) in Lac du Flambeau (LDF), Wisconsin; Northwest Portland Area Indian Health Board, in Oregon; and the University of Oklahoma in Tulsa. Tribal casinos are exempt from statewide bans on smoking because of tribal sovereignty. However, though smoking has declined in other segments of the population, it has not among AIs, where the incidence is 40%—more than twice that of the general U.S. population. Moreover, the tobacco industry has increasingly targeted tribal casinos, the researchers add.
Only 6 of 237 tribes operating casinos have voluntarily implemented casino-wide smoking bans. The tribal community is aiming to do something about that, though. The GLITC, a consortium of 12 member tribes in Wisconsin and Upper Michigan, and the LDF tribal nation, a member of GLITC, collaborated with the Lake of the Torches Resort Casino in northern Wisconsin to survey casino patrons to find out whether a smoking ban could get passed.
The project team’s analysis was based on survey responses from 957 casino patrons who were questioned about their opinions on smoking, secondhand smoke, and smoking bans. Most respondents were white and nonsmokers. A majority (69%) were bothered to some extent by smoke in the casino, and 81% believed secondhand smoke is harmful. Those who preferred a smoke-free casino were older, white, and gambled less. Over half (54%) said they were likely to visit more often, 28% said they were indifferent to a smoke-free casino, and 18% said they would visit less if the casino were smoke free.
The researchers cite other studies that have found that only 20% of casino patrons smoke. They also say smoking bans are not cited as reasons people visit casinos less, and smoking bans do not result in revenue loss for casinos.
This is the first study to employ a community-based and tribally led approach. The access would not have been possible without the “significant trust” between GLITC and the LDF tribal nation, the researchers say. The casino, owned and operated by the tribal nation whose members indirectly benefit from casino revenue, was responsive to community concerns about secondhand smoke, they add. This suggests that tribal communities may be “uniquely suited…to play a leadership role in a smoke-free casino movement.”
Source
Brokenleg IS, Barber TK, Bennett NL, Peart Boyce S, Blue Bird Jernigan V. Am J Prev Med. 2014;47(3):290-299.
doi: 10.1016/j.amepre.2014.04.006.
Methotrexate: Finding the Right Starting Dose
Decades of experience have narrowed the most effective dose of methotrexate (MTX) for rheumatoid arthritis to somewhere between 15 mg and 25 mg per week. However, experience has also suggested that early and rapid control of the disease activity minimizes damage. The result has been a quicker escalation of MTX dosing, with a starting dose of 10 mg to 15 mg per week and escalating by 5 mg every month, rather than the more traditional 5 mg every 3 months.
But researchers from Post Graduate Institute of Medical Education and Research in Chandigarh, India, point out that the recommendation to start with the higher dose of 15 mg is based on “weak evidence.” What’s more, they say, only a limited number of studies had compared fixed MTX doses head-to-head, and of those studies, many are 20 to 30 years old. No study had compared starting doses of 7.5 mg and 15 mg MTX, the researchers say.
Starting higher may have some benefits of efficacy, but that higher dose can also lead to adverse effects (AEs), intolerance, and withdrawal from therapy, say the researchers. They decided to find a balance between efficacy, speed, and tolerability by comparing 2 dosage regimens of oral MTX, starting at either 7.5 mgor 15 mg per week and escalating 2.5 mg every 2 weeks over 12 weeks, to a possible maximum of 25 mg per week. In group one, 47 patients were started on the lower dose, reaching a mean dose at 12 weeks of 17.3 mg per week. In group two, 53 patients were started on the higher dose and reached a mean dose of 23.6 mg per week. In patients who completed the study, the mean doses were 19.2 mg per week and 24.5 mg per week, respectively (P < .001).
Nine patients withdrew from group 1, and 7 patients withdrew from group 2. The numbers withdrawing from each group due to AEs were not statistically significant (P = .9). However, group 2 had a higher incidence of nausea and vomiting (42%, vs 19% in group 1), although the severity and duration of nausea were similar in both groups. There were no significant differences in frequency of cytopenia (P = .09) or transaminitis (P = .08). There was no difference in disease activity at weeks 4, 8, or 12.
The researchers say one limitation of their study is the short duration. They chose 12 weeks, because guidelines had suggested 3 months as a decision point, when other drugs could be added if the patient did not respond to MTX. However, they note that the European League Against Rheumatism 2013 update now specifies that the 3-month period relates “solely to assessing improvements” and says it takes 6 months to see maximal efficacy. The researchers, agreeing with this, say they found “a relatively poor response” by week 12. Indeed, they say, in view of the relatively slow decline in disease activity, future studies might benefit from extending the follow-up period to 24 weeks.
Source
Dhir V, Singla M, Gupta N, et al. Clin Ther. 2014;36(7):1005-1015.
doi: 10.1016/j.clinthera.2014.05.063.
Decades of experience have narrowed the most effective dose of methotrexate (MTX) for rheumatoid arthritis to somewhere between 15 mg and 25 mg per week. However, experience has also suggested that early and rapid control of the disease activity minimizes damage. The result has been a quicker escalation of MTX dosing, with a starting dose of 10 mg to 15 mg per week and escalating by 5 mg every month, rather than the more traditional 5 mg every 3 months.
But researchers from Post Graduate Institute of Medical Education and Research in Chandigarh, India, point out that the recommendation to start with the higher dose of 15 mg is based on “weak evidence.” What’s more, they say, only a limited number of studies had compared fixed MTX doses head-to-head, and of those studies, many are 20 to 30 years old. No study had compared starting doses of 7.5 mg and 15 mg MTX, the researchers say.
Starting higher may have some benefits of efficacy, but that higher dose can also lead to adverse effects (AEs), intolerance, and withdrawal from therapy, say the researchers. They decided to find a balance between efficacy, speed, and tolerability by comparing 2 dosage regimens of oral MTX, starting at either 7.5 mgor 15 mg per week and escalating 2.5 mg every 2 weeks over 12 weeks, to a possible maximum of 25 mg per week. In group one, 47 patients were started on the lower dose, reaching a mean dose at 12 weeks of 17.3 mg per week. In group two, 53 patients were started on the higher dose and reached a mean dose of 23.6 mg per week. In patients who completed the study, the mean doses were 19.2 mg per week and 24.5 mg per week, respectively (P < .001).
Nine patients withdrew from group 1, and 7 patients withdrew from group 2. The numbers withdrawing from each group due to AEs were not statistically significant (P = .9). However, group 2 had a higher incidence of nausea and vomiting (42%, vs 19% in group 1), although the severity and duration of nausea were similar in both groups. There were no significant differences in frequency of cytopenia (P = .09) or transaminitis (P = .08). There was no difference in disease activity at weeks 4, 8, or 12.
The researchers say one limitation of their study is the short duration. They chose 12 weeks, because guidelines had suggested 3 months as a decision point, when other drugs could be added if the patient did not respond to MTX. However, they note that the European League Against Rheumatism 2013 update now specifies that the 3-month period relates “solely to assessing improvements” and says it takes 6 months to see maximal efficacy. The researchers, agreeing with this, say they found “a relatively poor response” by week 12. Indeed, they say, in view of the relatively slow decline in disease activity, future studies might benefit from extending the follow-up period to 24 weeks.
Source
Dhir V, Singla M, Gupta N, et al. Clin Ther. 2014;36(7):1005-1015.
doi: 10.1016/j.clinthera.2014.05.063.
Decades of experience have narrowed the most effective dose of methotrexate (MTX) for rheumatoid arthritis to somewhere between 15 mg and 25 mg per week. However, experience has also suggested that early and rapid control of the disease activity minimizes damage. The result has been a quicker escalation of MTX dosing, with a starting dose of 10 mg to 15 mg per week and escalating by 5 mg every month, rather than the more traditional 5 mg every 3 months.
But researchers from Post Graduate Institute of Medical Education and Research in Chandigarh, India, point out that the recommendation to start with the higher dose of 15 mg is based on “weak evidence.” What’s more, they say, only a limited number of studies had compared fixed MTX doses head-to-head, and of those studies, many are 20 to 30 years old. No study had compared starting doses of 7.5 mg and 15 mg MTX, the researchers say.
Starting higher may have some benefits of efficacy, but that higher dose can also lead to adverse effects (AEs), intolerance, and withdrawal from therapy, say the researchers. They decided to find a balance between efficacy, speed, and tolerability by comparing 2 dosage regimens of oral MTX, starting at either 7.5 mgor 15 mg per week and escalating 2.5 mg every 2 weeks over 12 weeks, to a possible maximum of 25 mg per week. In group one, 47 patients were started on the lower dose, reaching a mean dose at 12 weeks of 17.3 mg per week. In group two, 53 patients were started on the higher dose and reached a mean dose of 23.6 mg per week. In patients who completed the study, the mean doses were 19.2 mg per week and 24.5 mg per week, respectively (P < .001).
Nine patients withdrew from group 1, and 7 patients withdrew from group 2. The numbers withdrawing from each group due to AEs were not statistically significant (P = .9). However, group 2 had a higher incidence of nausea and vomiting (42%, vs 19% in group 1), although the severity and duration of nausea were similar in both groups. There were no significant differences in frequency of cytopenia (P = .09) or transaminitis (P = .08). There was no difference in disease activity at weeks 4, 8, or 12.
The researchers say one limitation of their study is the short duration. They chose 12 weeks, because guidelines had suggested 3 months as a decision point, when other drugs could be added if the patient did not respond to MTX. However, they note that the European League Against Rheumatism 2013 update now specifies that the 3-month period relates “solely to assessing improvements” and says it takes 6 months to see maximal efficacy. The researchers, agreeing with this, say they found “a relatively poor response” by week 12. Indeed, they say, in view of the relatively slow decline in disease activity, future studies might benefit from extending the follow-up period to 24 weeks.
Source
Dhir V, Singla M, Gupta N, et al. Clin Ther. 2014;36(7):1005-1015.
doi: 10.1016/j.clinthera.2014.05.063.
Hypercalcemia From Diuretics and Vitamin D
African Americans have higher rates of high blood pressure and lower levels of 25-hydroxyvitamin D, compared with those of whites, and may be prescribed both thiazide diuretics and vitamin D supplements concurrently. But with thiazide diuretics, the kidneys excrete less calcium, and with vitamin D, the intestines absorb more calcium. Is there a risk of hypercalcemia for these patients?
To find out, researchers from Brigham and Women’s Hospital, Harvard Medical School and School of Public Health, Massachusetts General Hospital, and Dana-Farber Cancer Institute, all in Boston, Massachusetts; Michigan State University in East Lansing; Washington University School of Medicine in St. Louis, Missouri; Duke University in Durham, North Carolina; and Medical University of South Carolina in Charleston assigned 328 healthy African American volunteers to receive 1,000 IU, 2,000 IU, or 4,000 IU of vitamin D or placebo once a day for 3 months during the winters from 2007 to 2010. Of the participants, 84 were taking hydrochlorothiazide (HCTZ) and had serum calcium levels assessed. A comparison group of 44 participants who were not taking HCTZ had serum calcium measurements at 3 months but not at baseline. Participants were assessed for adverse events in person at the beginning of each month and by telephone during the second week of each month.
Five of the participants taking HCTZ had a serum calcium level above the upper limit of normal. The 4 participants who had hypercalcemia during month 1 were asked to stop taking the study medication and were withdrawn from the study.
Only 5.9% of the participants taking concurrent HCTZ and vitamin D developed hypercalcemia. At 1 month, 3 of the HCTZ participants in the 1,000 IU group and 1 in the 2,000 IU group had hypercalcemia. After 1 month of the vitamin D supplementation, 4 participants taking HCTZ had modestly elevated serum calcium levels, ranging from 10.7 mg/dL to 11.0 mg/dL. At 3 months, only 1 HCTZ participant had elevated calcium. The late appearance of 1 case of hypercalcemia may mean hypercalcemia can occur later in therapy, or it may have been a random event, the researchers say.
This is the first analysis to directly assess the effect of concurrent use of vitamin D and HCTZ in otherwise healthy adults with hypertension. Although the optimal plasma levels of vitamin D have yet to be established, their study is critical, the researchers say, because lower doses of vitamin D may not be enough to correct the vitamin D deficiency common in African Americans.
Source
Chandler PD, Scott JB, Drake BF, et al. Am J Med. 2014;127(8):772-778.
doi: 10.1016/j.amjmed.2014.02.044.
African Americans have higher rates of high blood pressure and lower levels of 25-hydroxyvitamin D, compared with those of whites, and may be prescribed both thiazide diuretics and vitamin D supplements concurrently. But with thiazide diuretics, the kidneys excrete less calcium, and with vitamin D, the intestines absorb more calcium. Is there a risk of hypercalcemia for these patients?
To find out, researchers from Brigham and Women’s Hospital, Harvard Medical School and School of Public Health, Massachusetts General Hospital, and Dana-Farber Cancer Institute, all in Boston, Massachusetts; Michigan State University in East Lansing; Washington University School of Medicine in St. Louis, Missouri; Duke University in Durham, North Carolina; and Medical University of South Carolina in Charleston assigned 328 healthy African American volunteers to receive 1,000 IU, 2,000 IU, or 4,000 IU of vitamin D or placebo once a day for 3 months during the winters from 2007 to 2010. Of the participants, 84 were taking hydrochlorothiazide (HCTZ) and had serum calcium levels assessed. A comparison group of 44 participants who were not taking HCTZ had serum calcium measurements at 3 months but not at baseline. Participants were assessed for adverse events in person at the beginning of each month and by telephone during the second week of each month.
Five of the participants taking HCTZ had a serum calcium level above the upper limit of normal. The 4 participants who had hypercalcemia during month 1 were asked to stop taking the study medication and were withdrawn from the study.
Only 5.9% of the participants taking concurrent HCTZ and vitamin D developed hypercalcemia. At 1 month, 3 of the HCTZ participants in the 1,000 IU group and 1 in the 2,000 IU group had hypercalcemia. After 1 month of the vitamin D supplementation, 4 participants taking HCTZ had modestly elevated serum calcium levels, ranging from 10.7 mg/dL to 11.0 mg/dL. At 3 months, only 1 HCTZ participant had elevated calcium. The late appearance of 1 case of hypercalcemia may mean hypercalcemia can occur later in therapy, or it may have been a random event, the researchers say.
This is the first analysis to directly assess the effect of concurrent use of vitamin D and HCTZ in otherwise healthy adults with hypertension. Although the optimal plasma levels of vitamin D have yet to be established, their study is critical, the researchers say, because lower doses of vitamin D may not be enough to correct the vitamin D deficiency common in African Americans.
Source
Chandler PD, Scott JB, Drake BF, et al. Am J Med. 2014;127(8):772-778.
doi: 10.1016/j.amjmed.2014.02.044.
African Americans have higher rates of high blood pressure and lower levels of 25-hydroxyvitamin D, compared with those of whites, and may be prescribed both thiazide diuretics and vitamin D supplements concurrently. But with thiazide diuretics, the kidneys excrete less calcium, and with vitamin D, the intestines absorb more calcium. Is there a risk of hypercalcemia for these patients?
To find out, researchers from Brigham and Women’s Hospital, Harvard Medical School and School of Public Health, Massachusetts General Hospital, and Dana-Farber Cancer Institute, all in Boston, Massachusetts; Michigan State University in East Lansing; Washington University School of Medicine in St. Louis, Missouri; Duke University in Durham, North Carolina; and Medical University of South Carolina in Charleston assigned 328 healthy African American volunteers to receive 1,000 IU, 2,000 IU, or 4,000 IU of vitamin D or placebo once a day for 3 months during the winters from 2007 to 2010. Of the participants, 84 were taking hydrochlorothiazide (HCTZ) and had serum calcium levels assessed. A comparison group of 44 participants who were not taking HCTZ had serum calcium measurements at 3 months but not at baseline. Participants were assessed for adverse events in person at the beginning of each month and by telephone during the second week of each month.
Five of the participants taking HCTZ had a serum calcium level above the upper limit of normal. The 4 participants who had hypercalcemia during month 1 were asked to stop taking the study medication and were withdrawn from the study.
Only 5.9% of the participants taking concurrent HCTZ and vitamin D developed hypercalcemia. At 1 month, 3 of the HCTZ participants in the 1,000 IU group and 1 in the 2,000 IU group had hypercalcemia. After 1 month of the vitamin D supplementation, 4 participants taking HCTZ had modestly elevated serum calcium levels, ranging from 10.7 mg/dL to 11.0 mg/dL. At 3 months, only 1 HCTZ participant had elevated calcium. The late appearance of 1 case of hypercalcemia may mean hypercalcemia can occur later in therapy, or it may have been a random event, the researchers say.
This is the first analysis to directly assess the effect of concurrent use of vitamin D and HCTZ in otherwise healthy adults with hypertension. Although the optimal plasma levels of vitamin D have yet to be established, their study is critical, the researchers say, because lower doses of vitamin D may not be enough to correct the vitamin D deficiency common in African Americans.
Source
Chandler PD, Scott JB, Drake BF, et al. Am J Med. 2014;127(8):772-778.
doi: 10.1016/j.amjmed.2014.02.044.
Gemcitabine: Best Alone or in Combination?
Gemcitabine (GEM) is the standard treatment for patients with locally advanced/metastatic pancreatic cancer (LA/MPC). Many studies have focused on finding combinations that might extend the efficacy of GEM. However, most studies have not found an improvement in overall survival (OS) for patients using GEM combination therapy, say researchers from Beijing Friendship Hospital in China. That is until recently, when researchers found that compared with GEM monotherapy, nanoparticle albumin-bound paclitaxel plus GEM significantly improved OS (8.5 months vs 6.7 months; P < .001) and progression-free survival (5.5 months vs 3.7 months; P < .001).
Other research has found that combining GEM with platinum, fluoropyrimidine, irinotecan, biotherapy, and others, for example, marginally but significantly affects OS, again compared with GEM monotherapy (P = .001). The combinations were associated with increased toxicity.
According to the researchers, the use of targeted therapies in cancer treatment is a “significant focus” of cancer research and has brought great clinical benefits in treating a variety of solid tumors. Studies that combined drugs to target epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic tumors and associated with poor prognosis, had mixed results for patients with LA/MPC. This prompted researchers in this study to conduct a systematic survey of 10 randomized controlled trials: 3 phase 2 trials and 7 phase 3 trials. Of 3,899 patients, 1,989 received GEM + targeted agents and 1,910 received GEM as monotherapy or combined with placebo (PLC). In a subgroup of GEM + antiangiogenic agents, 733 patients received GEM + axitinib or bevacizumab and cilengitide, and 693 received GEM ± PLC.
No significant difference was seen in the OS rate between the GEM + targeted agents and GEM ± PLC groups (P = .85), and only a marginal difference was found in the 1-year survival rate (P = .05). In the subgroup analysis, the researchers found a significant increase in objective response rate with GEM + antiangiogenic agents vs GEM ± PLC (95% CI, 0.42-0.98; P = .04). However, they found no significant difference in OS, 1-year survival, or progression-free survival between those 2 groups.
The researchers advise further research concentrated on clarifying the “concrete targets” involved in the occurrence and progression of pancreatic cancer. They add that personalized therapy based on a patient’s stratification, tumor stage, and genetic background should also be considered.
Source
Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Clin Ther. 2014;36(7):1054-1063.
doi: 10.1016/j.clinthera.2014.05.066.
Gemcitabine (GEM) is the standard treatment for patients with locally advanced/metastatic pancreatic cancer (LA/MPC). Many studies have focused on finding combinations that might extend the efficacy of GEM. However, most studies have not found an improvement in overall survival (OS) for patients using GEM combination therapy, say researchers from Beijing Friendship Hospital in China. That is until recently, when researchers found that compared with GEM monotherapy, nanoparticle albumin-bound paclitaxel plus GEM significantly improved OS (8.5 months vs 6.7 months; P < .001) and progression-free survival (5.5 months vs 3.7 months; P < .001).
Other research has found that combining GEM with platinum, fluoropyrimidine, irinotecan, biotherapy, and others, for example, marginally but significantly affects OS, again compared with GEM monotherapy (P = .001). The combinations were associated with increased toxicity.
According to the researchers, the use of targeted therapies in cancer treatment is a “significant focus” of cancer research and has brought great clinical benefits in treating a variety of solid tumors. Studies that combined drugs to target epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic tumors and associated with poor prognosis, had mixed results for patients with LA/MPC. This prompted researchers in this study to conduct a systematic survey of 10 randomized controlled trials: 3 phase 2 trials and 7 phase 3 trials. Of 3,899 patients, 1,989 received GEM + targeted agents and 1,910 received GEM as monotherapy or combined with placebo (PLC). In a subgroup of GEM + antiangiogenic agents, 733 patients received GEM + axitinib or bevacizumab and cilengitide, and 693 received GEM ± PLC.
No significant difference was seen in the OS rate between the GEM + targeted agents and GEM ± PLC groups (P = .85), and only a marginal difference was found in the 1-year survival rate (P = .05). In the subgroup analysis, the researchers found a significant increase in objective response rate with GEM + antiangiogenic agents vs GEM ± PLC (95% CI, 0.42-0.98; P = .04). However, they found no significant difference in OS, 1-year survival, or progression-free survival between those 2 groups.
The researchers advise further research concentrated on clarifying the “concrete targets” involved in the occurrence and progression of pancreatic cancer. They add that personalized therapy based on a patient’s stratification, tumor stage, and genetic background should also be considered.
Source
Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Clin Ther. 2014;36(7):1054-1063.
doi: 10.1016/j.clinthera.2014.05.066.
Gemcitabine (GEM) is the standard treatment for patients with locally advanced/metastatic pancreatic cancer (LA/MPC). Many studies have focused on finding combinations that might extend the efficacy of GEM. However, most studies have not found an improvement in overall survival (OS) for patients using GEM combination therapy, say researchers from Beijing Friendship Hospital in China. That is until recently, when researchers found that compared with GEM monotherapy, nanoparticle albumin-bound paclitaxel plus GEM significantly improved OS (8.5 months vs 6.7 months; P < .001) and progression-free survival (5.5 months vs 3.7 months; P < .001).
Other research has found that combining GEM with platinum, fluoropyrimidine, irinotecan, biotherapy, and others, for example, marginally but significantly affects OS, again compared with GEM monotherapy (P = .001). The combinations were associated with increased toxicity.
According to the researchers, the use of targeted therapies in cancer treatment is a “significant focus” of cancer research and has brought great clinical benefits in treating a variety of solid tumors. Studies that combined drugs to target epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic tumors and associated with poor prognosis, had mixed results for patients with LA/MPC. This prompted researchers in this study to conduct a systematic survey of 10 randomized controlled trials: 3 phase 2 trials and 7 phase 3 trials. Of 3,899 patients, 1,989 received GEM + targeted agents and 1,910 received GEM as monotherapy or combined with placebo (PLC). In a subgroup of GEM + antiangiogenic agents, 733 patients received GEM + axitinib or bevacizumab and cilengitide, and 693 received GEM ± PLC.
No significant difference was seen in the OS rate between the GEM + targeted agents and GEM ± PLC groups (P = .85), and only a marginal difference was found in the 1-year survival rate (P = .05). In the subgroup analysis, the researchers found a significant increase in objective response rate with GEM + antiangiogenic agents vs GEM ± PLC (95% CI, 0.42-0.98; P = .04). However, they found no significant difference in OS, 1-year survival, or progression-free survival between those 2 groups.
The researchers advise further research concentrated on clarifying the “concrete targets” involved in the occurrence and progression of pancreatic cancer. They add that personalized therapy based on a patient’s stratification, tumor stage, and genetic background should also be considered.
Source
Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Clin Ther. 2014;36(7):1054-1063.
doi: 10.1016/j.clinthera.2014.05.066.
Linezolid Contributes to “Clinical Success” in MRSA Pneumonia
Veterans with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia who were treated with linezolid were 53% more likely to be discharged as “clinical successes,” according to researchers from Providence VAMC and Brown University, both in Providence; and University of Rhode Island in Kingston, all in Rhode Island; and Pfizer Inc. in Collegeville, Pennsylvania.
The researchers conducted a nested case-control study among 3,732 VA patients with MRSA pneumonia who received linezolid or vancomycin between January 2002 and September 2010. They compared a number of factors that might contribute to clinical success, which was defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation. The 1,290 control patients represented nonsuccess, defined as therapy change, intubation, admission to ICU, readmission, or death between treatment initiation and day 14. The researchers chose 14 days to replicate the average end-of-treatment time frame in existing clinical trials of linezolid and vancomycin. The potential predictors included treatment, patient demographic and admission characteristics, previous health care and medication, comorbidities, and medical history. The clinical-success patients were more likely to be older (aged 69.5 years vs 68.5 years in the nonsuccess group), have a current diagnosis of respiratory disease, and to have had a diagnosis of pneumonia in the year before the MRSA pneumonia admission.
Only 2 predictors of clinical success were significant: Treatment with linezolid (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.12-2.10) and previous complication of an implant or graft, including mechanical complications and infections, in the year before admission for MRSA pneumonia (adjusted OR, 1.55; 95% CI, 1.17-2.06). Clinical success also was more likely when the length of therapy was shorter. The researchers were not sure why having an implant or graft complication was associated with clinical success, but they theorize that those instances might have prompted more aggressive treatment.
Predictors with adjusted ORs of < 1 were associated with nonsuccess. These included diagnosis of concomitant urinary tract infection, IV line, previous coagulopathy, previous amputation procedure, current coagulopathy diagnosis, dialysis, multiple inpatient procedures, inpatient surgery, and previous endocarditis.
Of all the variables, the researchers say, only the linezolid treatment was modifiable. However, they note that the few trials that support their findings have been criticized for methodological and statistical flaws. Their study adds to the developing literature, they say, by assessing a large national cohort of patients with MRSA pneumonia and by using objective clinical outcomes. They add that MRSA pneumonia tends to affect patients with complex care, and their findings may help clinicians identify patients who may benefit from alterations in treatment or require additional attention.
Source
Caffrey AR, Morrill HJ, Puzniak LA, LaPlante KL. Clin Ther. 2014;36(4):552-559.
doi: 10.1016.j.clinthera.2014.02.013.
Veterans with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia who were treated with linezolid were 53% more likely to be discharged as “clinical successes,” according to researchers from Providence VAMC and Brown University, both in Providence; and University of Rhode Island in Kingston, all in Rhode Island; and Pfizer Inc. in Collegeville, Pennsylvania.
The researchers conducted a nested case-control study among 3,732 VA patients with MRSA pneumonia who received linezolid or vancomycin between January 2002 and September 2010. They compared a number of factors that might contribute to clinical success, which was defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation. The 1,290 control patients represented nonsuccess, defined as therapy change, intubation, admission to ICU, readmission, or death between treatment initiation and day 14. The researchers chose 14 days to replicate the average end-of-treatment time frame in existing clinical trials of linezolid and vancomycin. The potential predictors included treatment, patient demographic and admission characteristics, previous health care and medication, comorbidities, and medical history. The clinical-success patients were more likely to be older (aged 69.5 years vs 68.5 years in the nonsuccess group), have a current diagnosis of respiratory disease, and to have had a diagnosis of pneumonia in the year before the MRSA pneumonia admission.
Only 2 predictors of clinical success were significant: Treatment with linezolid (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.12-2.10) and previous complication of an implant or graft, including mechanical complications and infections, in the year before admission for MRSA pneumonia (adjusted OR, 1.55; 95% CI, 1.17-2.06). Clinical success also was more likely when the length of therapy was shorter. The researchers were not sure why having an implant or graft complication was associated with clinical success, but they theorize that those instances might have prompted more aggressive treatment.
Predictors with adjusted ORs of < 1 were associated with nonsuccess. These included diagnosis of concomitant urinary tract infection, IV line, previous coagulopathy, previous amputation procedure, current coagulopathy diagnosis, dialysis, multiple inpatient procedures, inpatient surgery, and previous endocarditis.
Of all the variables, the researchers say, only the linezolid treatment was modifiable. However, they note that the few trials that support their findings have been criticized for methodological and statistical flaws. Their study adds to the developing literature, they say, by assessing a large national cohort of patients with MRSA pneumonia and by using objective clinical outcomes. They add that MRSA pneumonia tends to affect patients with complex care, and their findings may help clinicians identify patients who may benefit from alterations in treatment or require additional attention.
Source
Caffrey AR, Morrill HJ, Puzniak LA, LaPlante KL. Clin Ther. 2014;36(4):552-559.
doi: 10.1016.j.clinthera.2014.02.013.
Veterans with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia who were treated with linezolid were 53% more likely to be discharged as “clinical successes,” according to researchers from Providence VAMC and Brown University, both in Providence; and University of Rhode Island in Kingston, all in Rhode Island; and Pfizer Inc. in Collegeville, Pennsylvania.
The researchers conducted a nested case-control study among 3,732 VA patients with MRSA pneumonia who received linezolid or vancomycin between January 2002 and September 2010. They compared a number of factors that might contribute to clinical success, which was defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation. The 1,290 control patients represented nonsuccess, defined as therapy change, intubation, admission to ICU, readmission, or death between treatment initiation and day 14. The researchers chose 14 days to replicate the average end-of-treatment time frame in existing clinical trials of linezolid and vancomycin. The potential predictors included treatment, patient demographic and admission characteristics, previous health care and medication, comorbidities, and medical history. The clinical-success patients were more likely to be older (aged 69.5 years vs 68.5 years in the nonsuccess group), have a current diagnosis of respiratory disease, and to have had a diagnosis of pneumonia in the year before the MRSA pneumonia admission.
Only 2 predictors of clinical success were significant: Treatment with linezolid (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 1.12-2.10) and previous complication of an implant or graft, including mechanical complications and infections, in the year before admission for MRSA pneumonia (adjusted OR, 1.55; 95% CI, 1.17-2.06). Clinical success also was more likely when the length of therapy was shorter. The researchers were not sure why having an implant or graft complication was associated with clinical success, but they theorize that those instances might have prompted more aggressive treatment.
Predictors with adjusted ORs of < 1 were associated with nonsuccess. These included diagnosis of concomitant urinary tract infection, IV line, previous coagulopathy, previous amputation procedure, current coagulopathy diagnosis, dialysis, multiple inpatient procedures, inpatient surgery, and previous endocarditis.
Of all the variables, the researchers say, only the linezolid treatment was modifiable. However, they note that the few trials that support their findings have been criticized for methodological and statistical flaws. Their study adds to the developing literature, they say, by assessing a large national cohort of patients with MRSA pneumonia and by using objective clinical outcomes. They add that MRSA pneumonia tends to affect patients with complex care, and their findings may help clinicians identify patients who may benefit from alterations in treatment or require additional attention.
Source
Caffrey AR, Morrill HJ, Puzniak LA, LaPlante KL. Clin Ther. 2014;36(4):552-559.
doi: 10.1016.j.clinthera.2014.02.013.
More Reasons Not to Binge Drink
Even a single alcohol binge can rapidly raise levels of endotoxin and bacterial DNA, say researchers from University of Massachusetts Medical School in Worcester. Even modest increases have “substantial biological effects,” the researchers report.
In the study, 11 men and 14 women aged between 21 and 56 years with no history of alcohol use disorder were given about 2 mL vodka 40% v/v ethanol per kg body weight in 300 mL orange/strawberry juice. Blood was drawn at baseline, every 30 minutes for 4 hours, and 24 hours after alcohol consumption.
The acute alcohol binge produced maximum blood alcohol level (BAL) 60 minutes after consumption; levels declined gradually thereafter. Women showed a slower decline in BAL; even 24 hours later, their levels were higher than those of the men. Serum endotoxin levels rapidly increased 30 minutes after consumption, remained high for 3 hours, and returned to lower than baseline levels by 24 hours after alcohol intake. Here, too, women’s levels were higher than those of the men’s, and a significant difference in endotoxin levels was seen at 4 hours between men and women (P < .05).
Circulating endotoxin led to elevations in acute phase proteins, including “rapid and prolonged” increases in serum lipoprotein binding protein and soluble CD14 (a gene that encodes immune system protein). By contrast, the volunteers who drank no alcohol showed no changes.
Serum levels of endotoxin, also known as lipopolysaccharide (LPS), a component of Gram-negative bacteria, rose. The noteworthy aspect, according to the researchers, is that the increase in circulating bacterial components not only included Gram-negative bacteria, but other enteric bacterial elements as well, such as 16S rDNA, a marker of bacterial translocation from the gut. They found a significant increase in serum 16S bacterial rDNA levels at 1, 4, and even 24 hours after binge drinking.
When the researchers evaluated the effect of the biologically comparable concentrations of LPS in whole blood of normal volunteers, they found that the concentrations of endotoxin observed in the serum after acute binge drinking had “significant biological activity,” with a significant induction of inflammatory cytokines tumor necrosis factora and IL-6, and the chemokine MCP1 (monocyte chemoattractant protein-1) (P < .05). LPS, the researchers note, is a “potent trigger” of the inflammatory cascade. In animal studies, LPS administration has contributed to alcohol dependence and promoted increased alcohol intake.
This is the first study to show that acute alcohol binge drinking translocates 16S rDNA into the systemic circulation in otherwise healthy adults, the researchers say. They theorize that the persistent increase in bacterial components after repeated binge drinking could result in immune activation and inflammation and initiation of alcoholic liver disease. In chronic alcohol use, they point out, activation of the inflammatory cascade is a major component of organ damage in the brain and liver.
Source
Bala S, Marcos M, Gattu A, Catalano D, Szabo G. PLoS ONE. 2014;9(5):e96864.
doi: 10.1371/journal.pone.0096864.
Even a single alcohol binge can rapidly raise levels of endotoxin and bacterial DNA, say researchers from University of Massachusetts Medical School in Worcester. Even modest increases have “substantial biological effects,” the researchers report.
In the study, 11 men and 14 women aged between 21 and 56 years with no history of alcohol use disorder were given about 2 mL vodka 40% v/v ethanol per kg body weight in 300 mL orange/strawberry juice. Blood was drawn at baseline, every 30 minutes for 4 hours, and 24 hours after alcohol consumption.
The acute alcohol binge produced maximum blood alcohol level (BAL) 60 minutes after consumption; levels declined gradually thereafter. Women showed a slower decline in BAL; even 24 hours later, their levels were higher than those of the men. Serum endotoxin levels rapidly increased 30 minutes after consumption, remained high for 3 hours, and returned to lower than baseline levels by 24 hours after alcohol intake. Here, too, women’s levels were higher than those of the men’s, and a significant difference in endotoxin levels was seen at 4 hours between men and women (P < .05).
Circulating endotoxin led to elevations in acute phase proteins, including “rapid and prolonged” increases in serum lipoprotein binding protein and soluble CD14 (a gene that encodes immune system protein). By contrast, the volunteers who drank no alcohol showed no changes.
Serum levels of endotoxin, also known as lipopolysaccharide (LPS), a component of Gram-negative bacteria, rose. The noteworthy aspect, according to the researchers, is that the increase in circulating bacterial components not only included Gram-negative bacteria, but other enteric bacterial elements as well, such as 16S rDNA, a marker of bacterial translocation from the gut. They found a significant increase in serum 16S bacterial rDNA levels at 1, 4, and even 24 hours after binge drinking.
When the researchers evaluated the effect of the biologically comparable concentrations of LPS in whole blood of normal volunteers, they found that the concentrations of endotoxin observed in the serum after acute binge drinking had “significant biological activity,” with a significant induction of inflammatory cytokines tumor necrosis factora and IL-6, and the chemokine MCP1 (monocyte chemoattractant protein-1) (P < .05). LPS, the researchers note, is a “potent trigger” of the inflammatory cascade. In animal studies, LPS administration has contributed to alcohol dependence and promoted increased alcohol intake.
This is the first study to show that acute alcohol binge drinking translocates 16S rDNA into the systemic circulation in otherwise healthy adults, the researchers say. They theorize that the persistent increase in bacterial components after repeated binge drinking could result in immune activation and inflammation and initiation of alcoholic liver disease. In chronic alcohol use, they point out, activation of the inflammatory cascade is a major component of organ damage in the brain and liver.
Source
Bala S, Marcos M, Gattu A, Catalano D, Szabo G. PLoS ONE. 2014;9(5):e96864.
doi: 10.1371/journal.pone.0096864.
Even a single alcohol binge can rapidly raise levels of endotoxin and bacterial DNA, say researchers from University of Massachusetts Medical School in Worcester. Even modest increases have “substantial biological effects,” the researchers report.
In the study, 11 men and 14 women aged between 21 and 56 years with no history of alcohol use disorder were given about 2 mL vodka 40% v/v ethanol per kg body weight in 300 mL orange/strawberry juice. Blood was drawn at baseline, every 30 minutes for 4 hours, and 24 hours after alcohol consumption.
The acute alcohol binge produced maximum blood alcohol level (BAL) 60 minutes after consumption; levels declined gradually thereafter. Women showed a slower decline in BAL; even 24 hours later, their levels were higher than those of the men. Serum endotoxin levels rapidly increased 30 minutes after consumption, remained high for 3 hours, and returned to lower than baseline levels by 24 hours after alcohol intake. Here, too, women’s levels were higher than those of the men’s, and a significant difference in endotoxin levels was seen at 4 hours between men and women (P < .05).
Circulating endotoxin led to elevations in acute phase proteins, including “rapid and prolonged” increases in serum lipoprotein binding protein and soluble CD14 (a gene that encodes immune system protein). By contrast, the volunteers who drank no alcohol showed no changes.
Serum levels of endotoxin, also known as lipopolysaccharide (LPS), a component of Gram-negative bacteria, rose. The noteworthy aspect, according to the researchers, is that the increase in circulating bacterial components not only included Gram-negative bacteria, but other enteric bacterial elements as well, such as 16S rDNA, a marker of bacterial translocation from the gut. They found a significant increase in serum 16S bacterial rDNA levels at 1, 4, and even 24 hours after binge drinking.
When the researchers evaluated the effect of the biologically comparable concentrations of LPS in whole blood of normal volunteers, they found that the concentrations of endotoxin observed in the serum after acute binge drinking had “significant biological activity,” with a significant induction of inflammatory cytokines tumor necrosis factora and IL-6, and the chemokine MCP1 (monocyte chemoattractant protein-1) (P < .05). LPS, the researchers note, is a “potent trigger” of the inflammatory cascade. In animal studies, LPS administration has contributed to alcohol dependence and promoted increased alcohol intake.
This is the first study to show that acute alcohol binge drinking translocates 16S rDNA into the systemic circulation in otherwise healthy adults, the researchers say. They theorize that the persistent increase in bacterial components after repeated binge drinking could result in immune activation and inflammation and initiation of alcoholic liver disease. In chronic alcohol use, they point out, activation of the inflammatory cascade is a major component of organ damage in the brain and liver.
Source
Bala S, Marcos M, Gattu A, Catalano D, Szabo G. PLoS ONE. 2014;9(5):e96864.
doi: 10.1371/journal.pone.0096864.
Vitamin D Deficiency and Orthostatic Hypotension
Here is another reason to keep watch on older patients’ vitamin D levels: Too-low levels may contribute to orthostatic hypotension (OH), say researchers from Dokuz Eylül University in Izmir and Bezmialem Vakif University in Istanbul, both in Turkey. Their study of 546 patients found that about 32% of patients with vitamin D deficiency (levels < 20 ng/mL) had OH, compared with about 24% of those whose vitamin D levels were ≥ 20 ng/mL. This study is the largest to date examining vitamin D levels in patients with OH.
The patients were evaluated retrospectively. Data on blood pressure (BP), polypharmacy, cognitive and nutritional status, activities of daily living (ADL), and other patient information were obtained from hospital files. The researchers also had access to laboratory test results, including complete blood count; kidney and liver functions; cholesterol levels; thyroid-stimulating hormone (TSH); A1c; and vitamins B12, D, and folic acid levels.
The first BP measurement was taken after the patient rested for 10 minutes while lying down. Afterwards the patient was raised upright and the measurement was repeated on the same arm after 1 and 3 minutes. A diagnosis of OH was defined as a drop of ≥ 20 mm Hg in systolic BP and/or 10 mm Hg in diastolic BP after changing position.
The analysis revealed that 150 participants had OH (35% of men and 65% of women). Of those with OH, 17% had a drop in systolic BP, almost 20% had a drop in diastolic BP, and about 9% had a drop in both.
Albumin, hemoglobin, calcium, triglyceride, low-density and high-density lipoprotein cholesterol, TSH, A1c, folic acid, and vitamin B12 levels were not significantly different between the groups (P > .05). Only serum levels of vitamin D were found to be lower in patients with OH, compared with those without OH (P = .005). The researchers found a significant relation between serum 25-hydroxy vitamin D levels and both reduced systolic BP (P = .003) and diastolic BP (P = .032).
The researchers point to other studies that have shown vitamin D can affect BP through various mechanisms and that vitamin D deficiency causes endothelial and vascular smooth muscle dysfunction, increasing the risk of cardiovascular events. Studies have also associated vitamin D deficiency with autonomic dysfunction, one of the most important causes of OH.
Orthostatic hypotension is closely linked to mortality and morbidity. In this study, patients with OH had lower scores on ADL indexes. OH can also lead to falls, impaired sleep, depression, and stroke. One study, the researchers say, found that 80,000 hospitalizations each year in the U.S. are due to OH-related falls, syncope, and consequent injuries. They also note that asymptomatic OH is more common in elderly patients than might be suspected: About one-third of patients have OH, although they describe no complaints.
Thus, the researchers conclude, recording changes in postural BP should be part of the routine examination in older patients. And since vitamin D deficiency is both avoidable and correctable, keeping an eye on vitamin D levels is a good idea.
Source
Soysal P, Yay A, Isik AT. Arch Gertontol Geriatr. 2014;59(1):74-77.
doi: 10.1016/j.archger.2014.03.008.
Here is another reason to keep watch on older patients’ vitamin D levels: Too-low levels may contribute to orthostatic hypotension (OH), say researchers from Dokuz Eylül University in Izmir and Bezmialem Vakif University in Istanbul, both in Turkey. Their study of 546 patients found that about 32% of patients with vitamin D deficiency (levels < 20 ng/mL) had OH, compared with about 24% of those whose vitamin D levels were ≥ 20 ng/mL. This study is the largest to date examining vitamin D levels in patients with OH.
The patients were evaluated retrospectively. Data on blood pressure (BP), polypharmacy, cognitive and nutritional status, activities of daily living (ADL), and other patient information were obtained from hospital files. The researchers also had access to laboratory test results, including complete blood count; kidney and liver functions; cholesterol levels; thyroid-stimulating hormone (TSH); A1c; and vitamins B12, D, and folic acid levels.
The first BP measurement was taken after the patient rested for 10 minutes while lying down. Afterwards the patient was raised upright and the measurement was repeated on the same arm after 1 and 3 minutes. A diagnosis of OH was defined as a drop of ≥ 20 mm Hg in systolic BP and/or 10 mm Hg in diastolic BP after changing position.
The analysis revealed that 150 participants had OH (35% of men and 65% of women). Of those with OH, 17% had a drop in systolic BP, almost 20% had a drop in diastolic BP, and about 9% had a drop in both.
Albumin, hemoglobin, calcium, triglyceride, low-density and high-density lipoprotein cholesterol, TSH, A1c, folic acid, and vitamin B12 levels were not significantly different between the groups (P > .05). Only serum levels of vitamin D were found to be lower in patients with OH, compared with those without OH (P = .005). The researchers found a significant relation between serum 25-hydroxy vitamin D levels and both reduced systolic BP (P = .003) and diastolic BP (P = .032).
The researchers point to other studies that have shown vitamin D can affect BP through various mechanisms and that vitamin D deficiency causes endothelial and vascular smooth muscle dysfunction, increasing the risk of cardiovascular events. Studies have also associated vitamin D deficiency with autonomic dysfunction, one of the most important causes of OH.
Orthostatic hypotension is closely linked to mortality and morbidity. In this study, patients with OH had lower scores on ADL indexes. OH can also lead to falls, impaired sleep, depression, and stroke. One study, the researchers say, found that 80,000 hospitalizations each year in the U.S. are due to OH-related falls, syncope, and consequent injuries. They also note that asymptomatic OH is more common in elderly patients than might be suspected: About one-third of patients have OH, although they describe no complaints.
Thus, the researchers conclude, recording changes in postural BP should be part of the routine examination in older patients. And since vitamin D deficiency is both avoidable and correctable, keeping an eye on vitamin D levels is a good idea.
Source
Soysal P, Yay A, Isik AT. Arch Gertontol Geriatr. 2014;59(1):74-77.
doi: 10.1016/j.archger.2014.03.008.
Here is another reason to keep watch on older patients’ vitamin D levels: Too-low levels may contribute to orthostatic hypotension (OH), say researchers from Dokuz Eylül University in Izmir and Bezmialem Vakif University in Istanbul, both in Turkey. Their study of 546 patients found that about 32% of patients with vitamin D deficiency (levels < 20 ng/mL) had OH, compared with about 24% of those whose vitamin D levels were ≥ 20 ng/mL. This study is the largest to date examining vitamin D levels in patients with OH.
The patients were evaluated retrospectively. Data on blood pressure (BP), polypharmacy, cognitive and nutritional status, activities of daily living (ADL), and other patient information were obtained from hospital files. The researchers also had access to laboratory test results, including complete blood count; kidney and liver functions; cholesterol levels; thyroid-stimulating hormone (TSH); A1c; and vitamins B12, D, and folic acid levels.
The first BP measurement was taken after the patient rested for 10 minutes while lying down. Afterwards the patient was raised upright and the measurement was repeated on the same arm after 1 and 3 minutes. A diagnosis of OH was defined as a drop of ≥ 20 mm Hg in systolic BP and/or 10 mm Hg in diastolic BP after changing position.
The analysis revealed that 150 participants had OH (35% of men and 65% of women). Of those with OH, 17% had a drop in systolic BP, almost 20% had a drop in diastolic BP, and about 9% had a drop in both.
Albumin, hemoglobin, calcium, triglyceride, low-density and high-density lipoprotein cholesterol, TSH, A1c, folic acid, and vitamin B12 levels were not significantly different between the groups (P > .05). Only serum levels of vitamin D were found to be lower in patients with OH, compared with those without OH (P = .005). The researchers found a significant relation between serum 25-hydroxy vitamin D levels and both reduced systolic BP (P = .003) and diastolic BP (P = .032).
The researchers point to other studies that have shown vitamin D can affect BP through various mechanisms and that vitamin D deficiency causes endothelial and vascular smooth muscle dysfunction, increasing the risk of cardiovascular events. Studies have also associated vitamin D deficiency with autonomic dysfunction, one of the most important causes of OH.
Orthostatic hypotension is closely linked to mortality and morbidity. In this study, patients with OH had lower scores on ADL indexes. OH can also lead to falls, impaired sleep, depression, and stroke. One study, the researchers say, found that 80,000 hospitalizations each year in the U.S. are due to OH-related falls, syncope, and consequent injuries. They also note that asymptomatic OH is more common in elderly patients than might be suspected: About one-third of patients have OH, although they describe no complaints.
Thus, the researchers conclude, recording changes in postural BP should be part of the routine examination in older patients. And since vitamin D deficiency is both avoidable and correctable, keeping an eye on vitamin D levels is a good idea.
Source
Soysal P, Yay A, Isik AT. Arch Gertontol Geriatr. 2014;59(1):74-77.
doi: 10.1016/j.archger.2014.03.008.
Pre-PCI Statins: Useful or Not?
Current American College of Cardiology/American Heart Association guidelines recommend routine use of statins prior to percutaneous coronary interventions (PCIs). But is that recommendation followed? And does it improve patient outcomes?
Researchers for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium in Ann Arbor, Mt. Clemens, Kalamazoo, and Farmington Hills, all in Michigan; and Miami, Florida, evaluated the incidence and in-hospital outcomes associated with statin pretreatment among 80,493 patients. Their key finding, they say, was that many patients—26,547 (33%)—did not receive guideline-recommended statins before PCI, even if they were hemodynamically stable and had no documented contraindication. The researchers found the relatively high incidence of nonuse even more surprising, given that all the hospitals included in the study participated in an active multicenter quality improvement collaborative.
However, that nonuse did not appear to make much of a difference. Patients who did not receive statins had a similar rate of in-hospital mortality (43% in nonusers of statin vs 42% in statin users) and periprocedural myocardial infarction (MI) (2.34% in nonusers of statin vs 2.10% in statin users). Most notably, there was no reduction in postprocedural MI, a finding that some smaller studies suggested was related to statins’ effects.
Similarly, the researchers found no statin-related difference in the rate of coronary artery bypass grafting, cerebrovascular accident, or contrast-induced nephropathy. Finally, they found no statistically significant benefit from statins on mortality after a 36-month follow-up.
The researchers conclude that more studies need to be completed to support the role for statin administration prior to PCI as currently recommended in the guidelines.
Source
Kenaan M, Seth M, Aronow HD, et al. Am Heart J. 2014;168(1):110-116.e3.
doi: 10.1016/j.ahj.2014.03.016.
Current American College of Cardiology/American Heart Association guidelines recommend routine use of statins prior to percutaneous coronary interventions (PCIs). But is that recommendation followed? And does it improve patient outcomes?
Researchers for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium in Ann Arbor, Mt. Clemens, Kalamazoo, and Farmington Hills, all in Michigan; and Miami, Florida, evaluated the incidence and in-hospital outcomes associated with statin pretreatment among 80,493 patients. Their key finding, they say, was that many patients—26,547 (33%)—did not receive guideline-recommended statins before PCI, even if they were hemodynamically stable and had no documented contraindication. The researchers found the relatively high incidence of nonuse even more surprising, given that all the hospitals included in the study participated in an active multicenter quality improvement collaborative.
However, that nonuse did not appear to make much of a difference. Patients who did not receive statins had a similar rate of in-hospital mortality (43% in nonusers of statin vs 42% in statin users) and periprocedural myocardial infarction (MI) (2.34% in nonusers of statin vs 2.10% in statin users). Most notably, there was no reduction in postprocedural MI, a finding that some smaller studies suggested was related to statins’ effects.
Similarly, the researchers found no statin-related difference in the rate of coronary artery bypass grafting, cerebrovascular accident, or contrast-induced nephropathy. Finally, they found no statistically significant benefit from statins on mortality after a 36-month follow-up.
The researchers conclude that more studies need to be completed to support the role for statin administration prior to PCI as currently recommended in the guidelines.
Source
Kenaan M, Seth M, Aronow HD, et al. Am Heart J. 2014;168(1):110-116.e3.
doi: 10.1016/j.ahj.2014.03.016.
Current American College of Cardiology/American Heart Association guidelines recommend routine use of statins prior to percutaneous coronary interventions (PCIs). But is that recommendation followed? And does it improve patient outcomes?
Researchers for the Blue Cross Blue Shield of Michigan Cardiovascular Consortium in Ann Arbor, Mt. Clemens, Kalamazoo, and Farmington Hills, all in Michigan; and Miami, Florida, evaluated the incidence and in-hospital outcomes associated with statin pretreatment among 80,493 patients. Their key finding, they say, was that many patients—26,547 (33%)—did not receive guideline-recommended statins before PCI, even if they were hemodynamically stable and had no documented contraindication. The researchers found the relatively high incidence of nonuse even more surprising, given that all the hospitals included in the study participated in an active multicenter quality improvement collaborative.
However, that nonuse did not appear to make much of a difference. Patients who did not receive statins had a similar rate of in-hospital mortality (43% in nonusers of statin vs 42% in statin users) and periprocedural myocardial infarction (MI) (2.34% in nonusers of statin vs 2.10% in statin users). Most notably, there was no reduction in postprocedural MI, a finding that some smaller studies suggested was related to statins’ effects.
Similarly, the researchers found no statin-related difference in the rate of coronary artery bypass grafting, cerebrovascular accident, or contrast-induced nephropathy. Finally, they found no statistically significant benefit from statins on mortality after a 36-month follow-up.
The researchers conclude that more studies need to be completed to support the role for statin administration prior to PCI as currently recommended in the guidelines.
Source
Kenaan M, Seth M, Aronow HD, et al. Am Heart J. 2014;168(1):110-116.e3.
doi: 10.1016/j.ahj.2014.03.016.
Fixed-Dose Combination for Heart Failure
Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.
Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.
The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.
The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.
At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).
However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.
Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.
The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.
However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.
Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.
Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.
Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.
The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.
The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.
At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).
However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.
Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.
The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.
However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.
Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.
Both patients and doctors were hopeful that a fixed-dose combination of cardiovascular drugs would be the answer to improving risk factors for patients at a high risk of cardiovascular disease. Unfortunately, although patients were extremely adherent, their symptoms did not improve in a statistically significant way, say researchers from the University of Auckland in New Zealand.
Whereas the results were not what researchers had hoped, physicians found satisfactory or very satisfactory results on several measures: starting treatment, blood pressure (BP) control, cholesterol control, tolerability, and prescribing. Furthermore, patients found the regimen “very easy” to use—even 12 months later.
The study, IMPACT (Improving Adherence using Combination Therapy), involved 513 adults with a history of cardiovascular disease or a high risk of cardiovascular disease. Of the enrollees, 497 (97%) completed a 12-month follow-up.
The participants were randomly assigned to continue usual care or to a fixed-dose treatment with aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg, with either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Their general practitioners could choose the combination, change combinations, or discontinue treatment at any stage during the trial. There were no limitations on the use of any concomitant (including cardiovascular) drugs.
At 12 months, 81% of fixed-dose patients were adherent to all 4 recommended drugs, compared with the 46% of usual-care patients. For each drug individually, the fixed-dose patients also showed greater adherence, although adherence was generally high in both groups. Improved adherence with the fixed-dose combination remained significant to the end of the trial (P < .001).
However, the study found no statistically significant improvement in control of risk factors between the 2 groups. The difference was only –2.2 mm Hg in systolic BP; –1.2 mm Hg in diastolic BP; and –0.05 mmol/L in low-density lipoprotein cholesterol. Despite some concern among the general practitioners that the fixed-dose combination treatment might impede their ability to individualize treatment, the study showed that this did not, in fact, lead to worsened risk factor control, even compared with a relatively high standard of usual care.
Of the fixed-dose group, 94 discontinued, usually because of an adverse effect. The researchers cite other factors that might have contributed to discontinuations: a lack of variety in the components and dosages of fixed-dose combination treatment, such as a version with an angiotensin-receptor blocker for patients who developed cough, and unfamiliarity with the treatment and the trial itself of doctors who were not part of the trial, such as those who treated participants during outpatient visits.
The main drawback seemed to be that the patients were already very well treated, with “little room for improvement,” the researchers say. At baseline, 82% were taking an antiplatelet, a statin, and at least 1 BP-lowering agent, compared with 59% nationally. Thus, the researchers found limited scope for truly testing the effects of the fixed-dose combination treatment among patients who most need strategies to improve adherence—those taking few or no preventive drugs.
However, as a treatment regimen, the fixed-dose combination was a success: Ninety percent of the general practitioners said they would start other heart failure patients on the treatment if it were available.
Source
Selak V, Elley CR, Bullen C, et al. BMJ. 2014;348:g3318.
doi: 10.1136/bmj.g3318.