Thursday, August 9, 2018
Traditional advice of having a varied diet not so good
When it comes to diet in the Western world of overconsumption where cheap convenience food rules, the age-old adage "everything in moderation" has been put to the test, prompting the American Heart Association (AHA) to issue a science advisory led by researchers at The University of Texas Health Science Center at Houston (UTHealth).
Marcia C. de Oliveira Otto, Ph.D., assistant professor in the Department of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health, explained why variety can also be your waistline's enemy rather than friend in the paper published today in the AHA's scientific journal Circulation.
"The longstanding American public health recommendation to 'eat a variety of foods' was introduced last century in response to widespread nutrient deficiencies, particularly in low-income countries with limited access to nutritious foods," said Otto. "Recent evidence suggests this approach may not help improve people's eating habits, nor prevent obesity in places where processed, unhealthy food options are very common, wide-ranging and relatively inexpensive."
Reviewing findings from numerous studies, the advisory reported that eating a more diverse diet can result in greater consumption of unhealthy foods and may lead to weight gain and obesity.
"For modern adults, eating a wide range of foods has come to mean eating too much of too many unhealthy things far too often," Otto said. "Understanding the influence of diet diversity on eating patterns is increasingly important in middle- and high-income countries where excessive calorie consumption and obesity are common and populations need support in making healthy choices."
The 2015-2020 Dietary Guidelines for Americans, issued by the U.S. Department of Agriculture and U.S. Department of Health and Human Services, defined diet variety as a diverse assortment of food and beverages across recommended food groups. But the new AHA advisory highlights the lack of standardization or consensus about what exactly dietary diversity or variety means and how it is best measured.
The paper also examined the scientific evidence across numerous related areas, including satiation and food consumption. The majority of these studies showed that people ate significantly more when served a wider variety of foods, as opposed to a single item. For instance, one study revealed how adding ketchup or mayonnaise to French fries and cream to brownies for dessert delayed the sense of feeling full and increased consumption by nearly 40 percent.
The advisory recommends establishing standardized, reliable measures to define what diet diversity or diet variety is and how to maximize improved health outcomes. It concludes that the majority of evidence does not support the notion that dietary diversity is an effective way to promote healthy eating habits and a healthy body weight. Instead, the focus should be on emphasizing adequate consumption of fruit and vegetables, protein sources, low-fat dairy products, vegetable oils and nuts, while limiting intake of sweets, beverages with added sugar and red meats.
Women and men experience different benefits from low-calorie diets
A low-calorie diet causes different metabolic effects in women than in men, a new Diabetes, Obesity and Metabolism study suggests.
In the study of more than 2,000 overweight individuals with
pre-diabetes who followed a low-calorie diet for 8 weeks, men lost
significantly more body weight than women, and they had larger
reductions in a metabolic syndrome score, a diabetes indicator, fat
mass, and heart rate. Women had larger reductions in HDL-cholesterol,
hip circumference, lean body mass (or fat free mass), and pulse pressure
than men.
"Despite adjusting for the differences in weight loss, it appears that men benefitted more from the intervention than women. Whether differences between genders persist in the long-term and whether we will need to design different interventions depending on gender will be interesting to follow," said lead author Dr. Pia Christensen, of the University of Copenhagen, in Denmark. "However, the 8-week low-energy diet in individuals with pre-diabetes did result in the initial 10% weight loss needed to achieve major metabolic improvement in the first phase of a diabetes prevention programme."
"Despite adjusting for the differences in weight loss, it appears that men benefitted more from the intervention than women. Whether differences between genders persist in the long-term and whether we will need to design different interventions depending on gender will be interesting to follow," said lead author Dr. Pia Christensen, of the University of Copenhagen, in Denmark. "However, the 8-week low-energy diet in individuals with pre-diabetes did result in the initial 10% weight loss needed to achieve major metabolic improvement in the first phase of a diabetes prevention programme."
Older adults who get physical can lower their heart disease risk
Adults in their early 60s, who spend
less time sitting and more time engaged in light to vigorous physical
activity, benefit with healthier levels of heart and vessel disease
markers, according to new research in Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.
The results from increased physical activity were found to be particularly good among women.
Physical inactivity is a well-known risk factor for cardiovascular disease and premature death from cardiovascular disease. Physical activity's protective effect is likely due in part to its impact on biomarkers in the blood that help predict atherosclerosis risk.
"The 60 to 64 age range represents an important transition between work and retirement, when lifestyle behaviors tend to change," said Ahmed Elhakeem, Ph.D., study author and senior research associate in epidemiology at Bristol Medical School, University of Bristol in the United Kingdom. "It may, therefore, be an opportunity to promote increased physical activity.
"In addition, cardiovascular disease risk is higher in older adults. It's important to understand how activity might influence risk in this age group," Elhakeem said. "We found it's important to replace time spent sedentary with any intensity level of activity."
Researchers studied more than 1,600 British volunteers, age 60 to 64, who wore heart rate and movement sensors for five days. The sensors revealed not only how much physical activity, in general, they were doing, but also how much light physical activity, such as slow walking, stretching, golfing or gardening, versus moderate-to-vigorous activity, such as brisk walking, bicycling, dancing, tennis, squash, lawn mowing or vacuuming.
Researchers analyzed participants' blood levels for markers of cardiovascular disease, including inflammatory markers C-reactive protein and interleukin 6 (IL-6); endothelial markers, tissue-plasminogen activator (t-PA), the molecule E-Selectin (a cell adhesion molecule that plays an important part in inflammation); and cholesterol markers leptin and adiponectin.
"We focused on these atherosclerosis biomarkers as they are less studied and have been shown to predict risk of cardiovascular events and death," Elhakeem said.
Researchers found:
The study measured activity and biomarkers at the same time and didn't establish whether activity influenced the biomarkers, or the biomarkers influenced activity, Elhakeem said.
To improve overall cardiovascular health, the American Heart Association suggests at least 150 minutes a week of moderate intensity or 75 minutes a week of vigorous-intensity aerobic physical activity (or a combination of the two) and muscle-strengthening exercises two or more days a week.
Physical inactivity is a well-known risk factor for cardiovascular disease and premature death from cardiovascular disease. Physical activity's protective effect is likely due in part to its impact on biomarkers in the blood that help predict atherosclerosis risk.
"The 60 to 64 age range represents an important transition between work and retirement, when lifestyle behaviors tend to change," said Ahmed Elhakeem, Ph.D., study author and senior research associate in epidemiology at Bristol Medical School, University of Bristol in the United Kingdom. "It may, therefore, be an opportunity to promote increased physical activity.
"In addition, cardiovascular disease risk is higher in older adults. It's important to understand how activity might influence risk in this age group," Elhakeem said. "We found it's important to replace time spent sedentary with any intensity level of activity."
Researchers studied more than 1,600 British volunteers, age 60 to 64, who wore heart rate and movement sensors for five days. The sensors revealed not only how much physical activity, in general, they were doing, but also how much light physical activity, such as slow walking, stretching, golfing or gardening, versus moderate-to-vigorous activity, such as brisk walking, bicycling, dancing, tennis, squash, lawn mowing or vacuuming.
Researchers analyzed participants' blood levels for markers of cardiovascular disease, including inflammatory markers C-reactive protein and interleukin 6 (IL-6); endothelial markers, tissue-plasminogen activator (t-PA), the molecule E-Selectin (a cell adhesion molecule that plays an important part in inflammation); and cholesterol markers leptin and adiponectin.
"We focused on these atherosclerosis biomarkers as they are less studied and have been shown to predict risk of cardiovascular events and death," Elhakeem said.
Researchers found:
- Each additional 10-minutes spent in moderate-to-vigorous intensity activity was associated with leptin levels that were 3.7 percent lower in men and 6.6 percent lower in women.
- Each additional 10-minutes spent sedentary was associated with 0.6 percent higher IL-6 levels in men and 1.4 percent higher IL-6 levels in women.
- Each additional 10-minutes spent in light intensity activity was associated with around 0.8% lower t-PA levels in both men and women.
- Less sedentary time and greater time in low-intensity activity were beneficially related to IL-6 and t-PA, regardless of time spent at higher intensity activity.
- Those with better cardiorespiratory fitness (based on an oxygen uptake step test) also had a healthier biomarker profile, though this effect largely disappeared after controlling for related differences in body fat.
- Total activity volume appeared related to these biomarkers independently of underlying cardiorespiratory fitness.
- E-selectin was the only biomarker which showed no notable associations with physical activity and sedentary time (but was related to fitness levels).
The study measured activity and biomarkers at the same time and didn't establish whether activity influenced the biomarkers, or the biomarkers influenced activity, Elhakeem said.
To improve overall cardiovascular health, the American Heart Association suggests at least 150 minutes a week of moderate intensity or 75 minutes a week of vigorous-intensity aerobic physical activity (or a combination of the two) and muscle-strengthening exercises two or more days a week.
Wednesday, August 8, 2018
Soy diets might increase women's bone strength
Osteoporosis, decreased physical
activity and weight gain are serious health concerns for postmenopausal
women. Researchers from the University of Missouri now have discovered
through a new animal study that soy protein found in food might counter
the negative effects of menopause on bone and metabolic health.
Moreover, the researchers believe that soy protein might also have
positive impacts on bone strength for women who have not yet reached
menopause.
"The findings suggest that all women might see improved bone strength
by adding some soy-based whole foods, such as tofu and soy milk, to
their diet," said Pamela Hinton, professor of nutrition and exercise
physiology. "We also believe that soy-based diets can improve metabolic
function for postmenopausal women."
Hinton and Victoria Vieira-Potter, co-author and associate professor of nutrition and exercise physiology, studied the effects of soy versus corn-based diets on rats selectively bred to have low fitness levels. Rats were again divided between those with and without ovaries to mimic effects of menopause. Prior research has found that these rats are good models for menopausal women. They compared the impact of the soy diet on bone strength and metabolic function to rats fed a corn-based, soy-free diet.
"Prior research has shown that these rats are good models, as average American women are relatively inactive both before, and especially after, menopause," Vieira-Potter said. "As such, understanding how dietary protein sources, such as soy, can impact metabolism and bone health in these rats can help us better understand how such diets might impact women's health across the lifespan."
The researchers found that the tibia bones of the rats that were fed soy were stronger compared to the rats who were fed the corn-based diet, regardless of ovarian hormone status. Moreover, they found that the soy-based diet also improved metabolic function of the rats both with and without ovaries.
"Bottom line, this study showed that women might improve bone strength by adding some soy-based whole foods to their diet," Hinton said. "Our findings suggest that women don't even need to eat as much soy as is found in typical Asian diets, but adding some tofu or other soy, for example foods found in vegetarian diets, could help strengthen bones."
Hinton and Victoria Vieira-Potter, co-author and associate professor of nutrition and exercise physiology, studied the effects of soy versus corn-based diets on rats selectively bred to have low fitness levels. Rats were again divided between those with and without ovaries to mimic effects of menopause. Prior research has found that these rats are good models for menopausal women. They compared the impact of the soy diet on bone strength and metabolic function to rats fed a corn-based, soy-free diet.
"Prior research has shown that these rats are good models, as average American women are relatively inactive both before, and especially after, menopause," Vieira-Potter said. "As such, understanding how dietary protein sources, such as soy, can impact metabolism and bone health in these rats can help us better understand how such diets might impact women's health across the lifespan."
The researchers found that the tibia bones of the rats that were fed soy were stronger compared to the rats who were fed the corn-based diet, regardless of ovarian hormone status. Moreover, they found that the soy-based diet also improved metabolic function of the rats both with and without ovaries.
"Bottom line, this study showed that women might improve bone strength by adding some soy-based whole foods to their diet," Hinton said. "Our findings suggest that women don't even need to eat as much soy as is found in typical Asian diets, but adding some tofu or other soy, for example foods found in vegetarian diets, could help strengthen bones."
ADHD medications: Methylphenidate should be first option for short-term treatment in children
Of the drugs available for
attention-deficit hyperactivity disorder (ADHD), the most effective and
safe for short-term treatment is methylphenidate for children, and
amphetamines for adults, according to the most comprehensive evidence
yet from a network meta-analysis and systematic review comparing the
effectiveness and safety of seven ADHD drugs against placebo, published
in The Lancet Psychiatry journal.
The study compared the effectiveness and side effects of amphetamines
(including lisdexamfetamine), atomoxetine, bupropion, clonidine,
guanfacine, methylphenidate, and modafinil with each other or with
placebo over 12 weeks of treatment. However, more research to confirm
longer term effects of ADHD medications is urgently needed.
Although they are commonly prescribed for people with ADHD, the study did not include antipsychotic drugs or antidepressants as they do not treat ADHD core symptoms. The study also does not include psychological therapies used for ADHD, but the authors say that these should be regularly discussed with people with ADHD and their family members or carers, and possibly offered before ADHD medications, if appropriate, especially for children and adolescents.
"Medication can be an important tool for people with ADHD, and our study illustrates that in the short term, these can be effective and safe treatment options for children, adolescents and adults," says Dr Andrea Cipriani, University of Oxford, UK. "It's important to note that the data available only allow us to compare the effectiveness at 12 weeks, when we know that both children and adults can be on these medications for longer. More research is needed into the long-term effects of medication. Environmental modifications -- such as changes made to minimise the impact of ADHD in day-to-day living -- and non-pharmacological therapies should be considered first in ADHD treatment, but for people who require drug treatments, our study finds that methylphenidate should be the first drug offered for children and adolescents, and amphetamines should be the first drug offered for adults."
ADHD is estimated to affect 5% of school-age children and 2.5% of adults worldwide. The disorder is characterised by age-inappropriate levels of inattention, hyperactivity or impulsivity, or all of these. The annual costs associated with ADHD are substantial in many countries, including US$143-266 billion in the USA.
ADHD medications are not a permanent cure for ADHD but may help patients concentrate better, be less impulsive, feel calmer, and learn and practice new skills. Treatment breaks are occasionally recommended to assess whether the medication is still needed, but the treatment for ADHD can be taken for periods longer than 12 weeks.
Over the past few decades, prescriptions for drugs for ADHD have increased in the USA and other countries, but treatment guidelines are inconsistent as there are a few head-to-head comparisons of ADHD drugs available.
Currently, the UK National Institute for Health and Care Excellence (NICE) recommends methylphenidate as first-line drug treatment in children and adolescents (with lisdexamfetamine as the second option, and atomoxetine or guanfacine recommended as third-line drugs), and recommend methylphenidate and lisdexamfetamine as first choices in adults. Other guidelines in Europe recommend psychostimulants as first-line treatment without any distinction between methylphenidate and amphetamines being made.
This study compared the available drugs based on how effectively they reduce ADHD symptoms and improve general functioning over 12 weeks of treatment. It also studied the drugs' side effects (including blood pressure and weight loss), and acceptability was assessed according to how many people dropped out of trials for any reason.
Of the 133 randomised clinical trials included, 81 were in children and adolescents, 51 were in adults and one trial was in both. Of these, 89 randomised controlled trials included unpublished data or were completely unpublished. Drug effectiveness was reviewed in 10068 children and adolescents and in 8131 adults, while side effects were evaluated in 11018 children and adolescents and 5362 adults.
Symptom rating came from teachers and clinicians for children, and for adults these were given by clinicians.
Based on clinician ratings in children and adolescents, all drugs were more effective than placebo in controlling ADHD symptoms. But teachers only rated methylphenidate and modafinil as more effective than placebo (there was no data for teacher ratings of amphetamines and clonidine).
In adults, there was no data for guanfacine and clonidine. Clinicians rated all other drugs, except modafinil, as more effective than placebo in controlling ADHD symptoms.
Comparing all seven drugs, amphetamines were more effective than modafinil, atomoxetine and methylphenidate in children, adolescents, and adults.
Generally, ADHD drugs were less effective and less tolerable for adults than children and adolescents, and the cause of this is unknown.
Amphetamines, methylphenidate, atomoxetine, and modafinil caused weight loss in children, adolescents and adults. Amphetamines and atomoxetine increased blood pressure in children and adolescents blood, and methylphenidate did so in adults.
In children and adolescents, methylphenidate was the only drug with better acceptability than placebo, and in adults, only amphetamines had better acceptability than placebo.
Taking all of the outcomes into account, the authors conclude that methylphenidate should be the first option drug for children and adolescents with ADHD. In adults, they conclude that amphetamines should be the first drug to be offered.
However, there was not enough evidence available to confirm whether lisdexamfetamine -- which is currently recommended by NICE for adults with ADHD -- was more effective and tolerable for adults with ADHD than other amphetamines available. In addition, although NICE recommends atomoxetine and guanfacine as third-line drugs in children, the study found these to be as tolerable or less tolerable than placebo.
"Our findings will hopefully help people with ADHD in the USA find the best treatment for them by clarifying which drugs should be first, second and third line treatments. With an increasing number of people being diagnosed with ADHD and given a drug prescription in the USA, our study provides a starting point for medication, and hopefully helps patients more quickly find a drug that works for them." says Dr Cipriani.
The authors note some limitations, including that, despite efforts to include all available trials and unpublished data, they cannot rule out missing studies. They had also planned to study the drugs over the long-term (26 and 52 weeks), but were unable to do so as there was little data available.
Dr Cipriani continues: "The lack of randomised controlled trials with outcomes beyond 12 weeks highlights the need for research funding to assess the long-term effects of these drugs. However, the evidence we have about methylphenidate and amphetamines from our study is robust, and should help inform clinical decisions."
Writing in a linked Comment, Mark Stein, Seattle Children's Hospital, USA, says: "As diagnostic rates of attention-deficit hyperactivity disorder (ADHD) increase worldwide, the most common questions asked by patients are whether to start a medication, which one, and for how long... By including studies published up to April, 2017, and previously unpublished information, Cortese and colleagues' results clarify inconsistencies in earlier reviews and meta-analyses, some of which have generated much controversy... Regarding the three common questions patients ask, the extant literature meant that the network meta-analysis could derive only part answers, including general support for short-term medication use, basic guidelines about first-line medications based on age, and little to no data for duration of treatment. These results -- and particularly limitations of the data obtained -- call for future research that translates directly to clinical practice."
Although they are commonly prescribed for people with ADHD, the study did not include antipsychotic drugs or antidepressants as they do not treat ADHD core symptoms. The study also does not include psychological therapies used for ADHD, but the authors say that these should be regularly discussed with people with ADHD and their family members or carers, and possibly offered before ADHD medications, if appropriate, especially for children and adolescents.
"Medication can be an important tool for people with ADHD, and our study illustrates that in the short term, these can be effective and safe treatment options for children, adolescents and adults," says Dr Andrea Cipriani, University of Oxford, UK. "It's important to note that the data available only allow us to compare the effectiveness at 12 weeks, when we know that both children and adults can be on these medications for longer. More research is needed into the long-term effects of medication. Environmental modifications -- such as changes made to minimise the impact of ADHD in day-to-day living -- and non-pharmacological therapies should be considered first in ADHD treatment, but for people who require drug treatments, our study finds that methylphenidate should be the first drug offered for children and adolescents, and amphetamines should be the first drug offered for adults."
ADHD is estimated to affect 5% of school-age children and 2.5% of adults worldwide. The disorder is characterised by age-inappropriate levels of inattention, hyperactivity or impulsivity, or all of these. The annual costs associated with ADHD are substantial in many countries, including US$143-266 billion in the USA.
ADHD medications are not a permanent cure for ADHD but may help patients concentrate better, be less impulsive, feel calmer, and learn and practice new skills. Treatment breaks are occasionally recommended to assess whether the medication is still needed, but the treatment for ADHD can be taken for periods longer than 12 weeks.
Over the past few decades, prescriptions for drugs for ADHD have increased in the USA and other countries, but treatment guidelines are inconsistent as there are a few head-to-head comparisons of ADHD drugs available.
Currently, the UK National Institute for Health and Care Excellence (NICE) recommends methylphenidate as first-line drug treatment in children and adolescents (with lisdexamfetamine as the second option, and atomoxetine or guanfacine recommended as third-line drugs), and recommend methylphenidate and lisdexamfetamine as first choices in adults. Other guidelines in Europe recommend psychostimulants as first-line treatment without any distinction between methylphenidate and amphetamines being made.
This study compared the available drugs based on how effectively they reduce ADHD symptoms and improve general functioning over 12 weeks of treatment. It also studied the drugs' side effects (including blood pressure and weight loss), and acceptability was assessed according to how many people dropped out of trials for any reason.
Of the 133 randomised clinical trials included, 81 were in children and adolescents, 51 were in adults and one trial was in both. Of these, 89 randomised controlled trials included unpublished data or were completely unpublished. Drug effectiveness was reviewed in 10068 children and adolescents and in 8131 adults, while side effects were evaluated in 11018 children and adolescents and 5362 adults.
Symptom rating came from teachers and clinicians for children, and for adults these were given by clinicians.
Based on clinician ratings in children and adolescents, all drugs were more effective than placebo in controlling ADHD symptoms. But teachers only rated methylphenidate and modafinil as more effective than placebo (there was no data for teacher ratings of amphetamines and clonidine).
In adults, there was no data for guanfacine and clonidine. Clinicians rated all other drugs, except modafinil, as more effective than placebo in controlling ADHD symptoms.
Comparing all seven drugs, amphetamines were more effective than modafinil, atomoxetine and methylphenidate in children, adolescents, and adults.
Generally, ADHD drugs were less effective and less tolerable for adults than children and adolescents, and the cause of this is unknown.
Amphetamines, methylphenidate, atomoxetine, and modafinil caused weight loss in children, adolescents and adults. Amphetamines and atomoxetine increased blood pressure in children and adolescents blood, and methylphenidate did so in adults.
In children and adolescents, methylphenidate was the only drug with better acceptability than placebo, and in adults, only amphetamines had better acceptability than placebo.
Taking all of the outcomes into account, the authors conclude that methylphenidate should be the first option drug for children and adolescents with ADHD. In adults, they conclude that amphetamines should be the first drug to be offered.
However, there was not enough evidence available to confirm whether lisdexamfetamine -- which is currently recommended by NICE for adults with ADHD -- was more effective and tolerable for adults with ADHD than other amphetamines available. In addition, although NICE recommends atomoxetine and guanfacine as third-line drugs in children, the study found these to be as tolerable or less tolerable than placebo.
"Our findings will hopefully help people with ADHD in the USA find the best treatment for them by clarifying which drugs should be first, second and third line treatments. With an increasing number of people being diagnosed with ADHD and given a drug prescription in the USA, our study provides a starting point for medication, and hopefully helps patients more quickly find a drug that works for them." says Dr Cipriani.
The authors note some limitations, including that, despite efforts to include all available trials and unpublished data, they cannot rule out missing studies. They had also planned to study the drugs over the long-term (26 and 52 weeks), but were unable to do so as there was little data available.
Dr Cipriani continues: "The lack of randomised controlled trials with outcomes beyond 12 weeks highlights the need for research funding to assess the long-term effects of these drugs. However, the evidence we have about methylphenidate and amphetamines from our study is robust, and should help inform clinical decisions."
Writing in a linked Comment, Mark Stein, Seattle Children's Hospital, USA, says: "As diagnostic rates of attention-deficit hyperactivity disorder (ADHD) increase worldwide, the most common questions asked by patients are whether to start a medication, which one, and for how long... By including studies published up to April, 2017, and previously unpublished information, Cortese and colleagues' results clarify inconsistencies in earlier reviews and meta-analyses, some of which have generated much controversy... Regarding the three common questions patients ask, the extant literature meant that the network meta-analysis could derive only part answers, including general support for short-term medication use, basic guidelines about first-line medications based on age, and little to no data for duration of treatment. These results -- and particularly limitations of the data obtained -- call for future research that translates directly to clinical practice."
Journal Reference:
- Samuele Cortese, Nicoletta Adamo, Cinzia Del Giovane, Christina Mohr-Jensen, Adrian J Hayes, Sara Carucci, Lauren Z Atkinson, Luca Tessari, Tobias Banaschewski, David Coghill, Chris Hollis, Emily Simonoff, Alessandro Zuddas, Corrado Barbui, Marianna Purgato, Hans-Christoph Steinhausen, Farhad Shokraneh, Jun Xia, Andrea Cipriani. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry, 2018; DOI: 10.1016/S2215-0366(18)30269-4
Cite This Page:
The
Lancet. "ADHD medications: Of all available drugs, methylphenidate
should be first option for short-term treatment in children."
ScienceDaily. ScienceDaily, 7 August 2018.
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Case Study: Child's Lobectomy Reveals Brain's Ability to Reorganize Its Visual SystemCatch-up HPV vaccine effective for women aged up to 20 years
US study confirms effectiveness of
quadrivalent human papillomavirus (HPV) vaccine in women aged up to 20
years who receive all three doses, but more research is needed in women
aged 21-26 years.
For women aged 14-20 years, catch-up HPV vaccination -- offered if
American women miss the recommended vaccination series at 11-12 years --
is effective against the risk of important cervical precancers if women
receive all three doses, according to a population case-control study
of over 25000 people published in The Lancet Child & Adolescent Health journal.
The study analysed cases of CIN2+ or CIN3+ (cervical intraepithelial neoplasia -- abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer) in a population of women and girls in California (USA).
In the USA, HPV vaccination is recommended for girls aged 11-12. For those who did not receive the vaccine at this age, catch-up vaccination is recommended for girls and women aged 13-26 years. The vaccine is approved as a three-dose series, and the US Centers for Disease Control and Prevention also allows for a two-dose series for girls aged 9-14.
However, rates of adolescent HPV vaccination are relatively low in the USA, with less than half of girls aged 13-17 years up to date with the HPV vaccine series.
The findings of the new study suggest catch-up with the full three-dose series for girls and women who receive the first dose at age 14-20 years will offer significant protection. However, they find that more research is needed to confirm the effectiveness of catch-up vaccination in older women aged 21-26 years.
Importantly, the study looked at the effectiveness of the quadrivalent HPV vaccine, and not of the more recently introduced nonavalent HPV vaccine, which is anticipated to prevent more CIN2+ cases than the quadrivalent HPV vaccine. Therefore, further research, including in women aged over 21 years, will be important as new vaccines become more widely used.
The study included 4357 women with CIN2+ or CIN3+ who were aged 26 or younger when the quadrivalent HPV vaccine was introduced in 2006. For each case, five age-matched controls without CIN2+ or CIN3+ were randomly selected (21773). All women were enrolled at Kaiser Permanente North California. A total of 2837 women enrolled in the study had received at least one dose of the vaccine between 2006 and 2014.
The strongest protection against CIN2+ and CIN3+ was identified for women who had received at least three vaccine doses and had received their first dose aged 14-17 years, or aged 18-20 years. No significant protection was found in women who received their first dose aged 21 years or older, or who received fewer than the full three dose in the series.
"In comparison to other countries, HPV vaccine uptake in the US has been relatively low. Our findings show that girls and women who did not receive the full vaccine series at age 11-12 can still benefit from significant protection if they receive the full three doses of vaccine by the age of 20. The evidence suggests that protection is strongest the earlier the vaccine is initiated, and after the age of 21, the evidence of effectiveness is unclear. Further research in other settings, and using the recently introduced nonavalent vaccine, will now be needed to assess the effectiveness of vaccinating women aged 21-26 years," says lead author Michael J. Silverberg, a research scientist with Kaiser Permanente Northern California's Division of Research, Oakland (USA).
The authors note that only 23 women were diagnosed with cervical cancer in the study, of which only 3 had had prior HPV vaccination. All three women had received at least three doses, and all were 21 or older at the age of the first dose. However, the small numbers limit the researchers' ability to quantify the effect of the HPV vaccine on cervical cancer incidence, rather than the composite outcomes of CIN2+ and CIN3+, which includes both cancer and precancerous lesions.
Additionally, the authors note that the study was conducted in a single health-care setting, meaning that it may only be generalizable to other integrated health care settings and insured women in the area, which may not represent the most at-risk populations. The study did not look at the effect of the HPV vaccine on other clinically important outcomes such as low-grade dysplasia (i.e., CIN1), persistent HPV infection, or genital warts.
Writing in a linked Comment, Sarah Dilley and Warner Huh, Division of Gynecologic Oncology, University of Alabama, Birmingham (USA) advise caution before abandoning the practice of catch-up vaccination in women aged over 21 years: "The results of this study confirm existing research which showed that the HPV vaccine is most effective when given at younger ages, but no benefit was found in patients older than 21 years. Efforts towards increasing HPV vaccine uptake should be focused on younger adolescents -- with a priority on vaccinating children aged 11-12 years -- and providing catch-up dosing for older adolescents. However, in the setting of low rates of HPV vaccination in the USA, the importance of catch-up dosing in young women should not be ignored. Given that prospective efficacy studies have shown benefits for catch-up vaccination up to at least age 26 years, more data is needed before abandoning this practice."
The study analysed cases of CIN2+ or CIN3+ (cervical intraepithelial neoplasia -- abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer) in a population of women and girls in California (USA).
In the USA, HPV vaccination is recommended for girls aged 11-12. For those who did not receive the vaccine at this age, catch-up vaccination is recommended for girls and women aged 13-26 years. The vaccine is approved as a three-dose series, and the US Centers for Disease Control and Prevention also allows for a two-dose series for girls aged 9-14.
However, rates of adolescent HPV vaccination are relatively low in the USA, with less than half of girls aged 13-17 years up to date with the HPV vaccine series.
The findings of the new study suggest catch-up with the full three-dose series for girls and women who receive the first dose at age 14-20 years will offer significant protection. However, they find that more research is needed to confirm the effectiveness of catch-up vaccination in older women aged 21-26 years.
Importantly, the study looked at the effectiveness of the quadrivalent HPV vaccine, and not of the more recently introduced nonavalent HPV vaccine, which is anticipated to prevent more CIN2+ cases than the quadrivalent HPV vaccine. Therefore, further research, including in women aged over 21 years, will be important as new vaccines become more widely used.
The study included 4357 women with CIN2+ or CIN3+ who were aged 26 or younger when the quadrivalent HPV vaccine was introduced in 2006. For each case, five age-matched controls without CIN2+ or CIN3+ were randomly selected (21773). All women were enrolled at Kaiser Permanente North California. A total of 2837 women enrolled in the study had received at least one dose of the vaccine between 2006 and 2014.
The strongest protection against CIN2+ and CIN3+ was identified for women who had received at least three vaccine doses and had received their first dose aged 14-17 years, or aged 18-20 years. No significant protection was found in women who received their first dose aged 21 years or older, or who received fewer than the full three dose in the series.
"In comparison to other countries, HPV vaccine uptake in the US has been relatively low. Our findings show that girls and women who did not receive the full vaccine series at age 11-12 can still benefit from significant protection if they receive the full three doses of vaccine by the age of 20. The evidence suggests that protection is strongest the earlier the vaccine is initiated, and after the age of 21, the evidence of effectiveness is unclear. Further research in other settings, and using the recently introduced nonavalent vaccine, will now be needed to assess the effectiveness of vaccinating women aged 21-26 years," says lead author Michael J. Silverberg, a research scientist with Kaiser Permanente Northern California's Division of Research, Oakland (USA).
The authors note that only 23 women were diagnosed with cervical cancer in the study, of which only 3 had had prior HPV vaccination. All three women had received at least three doses, and all were 21 or older at the age of the first dose. However, the small numbers limit the researchers' ability to quantify the effect of the HPV vaccine on cervical cancer incidence, rather than the composite outcomes of CIN2+ and CIN3+, which includes both cancer and precancerous lesions.
Additionally, the authors note that the study was conducted in a single health-care setting, meaning that it may only be generalizable to other integrated health care settings and insured women in the area, which may not represent the most at-risk populations. The study did not look at the effect of the HPV vaccine on other clinically important outcomes such as low-grade dysplasia (i.e., CIN1), persistent HPV infection, or genital warts.
Writing in a linked Comment, Sarah Dilley and Warner Huh, Division of Gynecologic Oncology, University of Alabama, Birmingham (USA) advise caution before abandoning the practice of catch-up vaccination in women aged over 21 years: "The results of this study confirm existing research which showed that the HPV vaccine is most effective when given at younger ages, but no benefit was found in patients older than 21 years. Efforts towards increasing HPV vaccine uptake should be focused on younger adolescents -- with a priority on vaccinating children aged 11-12 years -- and providing catch-up dosing for older adolescents. However, in the setting of low rates of HPV vaccination in the USA, the importance of catch-up dosing in young women should not be ignored. Given that prospective efficacy studies have shown benefits for catch-up vaccination up to at least age 26 years, more data is needed before abandoning this practice."
Tuesday, August 7, 2018
Probiotic use is a link between brain fogginess, severe bloating
Probiotic use can result in a significant accumulation of bacteria in the small intestine that can result in disorienting brain fogginess as well as rapid, significant belly bloating, investigators report.
In a published study of 30 patients, the 22 who reported problems like confusion and difficulty concentrating, in addition to their gas and bloating, were all taking probiotics, some several varieties.
When investigators looked further, they found large colonies of bacteria breeding in the patients' small intestines, and high levels of D-lactic acid being produced by the bacteria lactobacillus' fermentation of sugars in their food, says Dr. Satish S.C. Rao, director of neurogastroenterology/motility and the Digestive Health Clinical Research Center at the Medical College of Georgia at Augusta University.
D-lactic acid is known to be temporarily toxic to brain cells, interfering with cognition, thinking and sense of time. They found some patients had two to three times the normal amount of D-lactic acid in their blood. Some said their brain fogginess - which lasted from a half hour to many hours after eating - was so severe that they had to quit their jobs.
The report in the journal Clinical and Translational Gastroenterology appears to be the first time the connection has been made between brain fogginess, bacterial overgrowth in the small intestine, high levels of D-lactic acid in the gut and probiotic use, Rao says.
"What we now know is that probiotic bacteria have the unique capacity to break down sugar and produce D-lactic acid. So if you inadvertently colonize your small bowel with probiotic bacteria, then you have set the stage for potentially developing lactic acidosis and brain fogginess," Rao says.
While probiotics can be beneficial in some scenarios, like helping a patient restore his gut bacteria after taking antibiotics, the investigators advised caution against its excessive and indiscriminate use.
"Probiotics should be treated as a drug, not as a food supplement," Rao says, noting that many individuals self-prescribe the live bacteria, which are considered good for digestion and overall health.
Others have implicated probiotics in the production of D-lactic acid - and brain fogginess - in patients with a short bowel so their small intestine does not function properly, and in newborns fed formula containing the popular product. Short bowel syndrome results in a lot of undigested carbohydrates that are known to cause small intestinal bacterial overgrowth, or SIBO, and the high levels of D-lactic acid. Severe liver and kidney problems can produce similar problems.
Whether there was also a connection when the gut is intact was an unknown. "This is the first inroad," says Rao.
All patients experiencing brain fogginess took probiotics and SIBO was more common in the brain fogginess group as well, 68 percent compared to 28 percent, respectively. Patients with brain fogginess also had a higher prevalence of D-lactic acidosis, 77 versus 25 percent, respectively.
When brain-foggy patients stopped taking probiotics and took a course of antibiotics, their brain fogginess resolved.
Movement of food through the gastrointestinal tract was slow in one third of the brain foggy patients and one fourth of the other group. Slower passage, as well as things like obesity surgery, can increase the chance of bacterial buildup, or SIBO.
"Now that we can identify the problem, we can treat it," Rao says. Diagnosis includes breath, urine and blood tests to detect lactic acid, and an endoscopy that enables examination of fluid from the small intestines so the specific bacteria can be determined and the best antibiotics selected for treatment.
Normally there is not much D-lactic acid made in the small intestines, but probiotic use appears to change that. SIBO, which was present in most with brain fogginess, can cause bacteria to go into a feeding frenzy that ferments sugars resulting in production of uncomfortable things like hydrogen gas and methane that explain the bloating.
Probiotics added to that feeding frenzy the bacterium lactobacillus, which produces D-lactic acid as it breaks down sugars, The acid get absorbed in the blood and can reach the brain.
All those with brain fogginess, SIBO and/or D-lactic acidosis, were given antibiotics that targeted their bacterial population and asked to discontinue probiotics. Those without SIBO were asked to halt probiotics and stop eating yogurt, which is considered one of the best sources of probiotics. Those with SIBO and D-lactic acidosis but no brain fogginess also took antibiotics.
Following treatment, 70 percent of patients reported significant improvement in their symptoms and 85 percent said their brain fogginess was gone. Those without brain fogginess but with SIBO and high levels of D-lactic acid reported significant improvement in symptoms like bloating and cramping within three months.
Abdominal pain was the most common symptom in both groups and before treatment, six of those with brain fogginess reported a tremendous increase in their abdominal size within just a few minutes of eating.
All patients received extensive examination of their gastrointestinal tract, including a motility test, to rule out other potential causes of their symptoms. They filled out questionnaires about symptoms like abdominal pain, belching and gas and answered questions about related issues like antibiotic and probiotic use as well as food fads and yogurt consumption.
They were given carbohydrates followed by extensive metabolic testing looking at the impact on things like blood glucose and insulin levels. Levels of D-lactic acid and L-lactate acid, which results from our muscles' use of glucose as energy and can cause muscle cramps, also were measured.
Probiotic use may be particularly problematic for patients who have known problems with motility, as well as those taking opioids and proton pump inhibitors, which reduce stomach acid secretion and so the natural destruction of excessive bacteria.
Probiotics are supposed to work in the colon and not the small intestines or stomach, Rao says, so motility issues can result in problems with probiotic bacteria reaching the proper place. A wide variety of problems, from conditions like diabetes to drugs like antidepressants and minerals like iron, can slow movement and increase the possibility that probiotics will remain too long in the upper gut where they can cause harm, he says.
Probiotics definitely can help, for example, people who have gastroenteritis, or stomach flu, or are left with diarrhea and other problems after antibiotics wipe out their natural gut bacteria, Rao says.
"In those situations, we want to build up their bacterial flora so probiotics are ideal," he says.
Rao's pursuit of a possible connection between probiotics, brain fogginess and bloating started with a memorable patient who developed significant amounts of both problems within a minute of eating.
"It happened right in front of our eyes," Rao says of the dramatic abdominal distention. They knew the woman had diabetes, which can slow motility. When they looked in the blood and urine at a variety of metabolic compounds, they found the high levels of D-lactic acid and soon learned the patient used probiotics and regularly ate yogurt.
Next steps include additional studies in which the investigators better quantify and characterize the brain fogginess reported by patients and following patients for longer periods to ensure their problems remain resolved. Some patients in the current study required a couple of rounds of antibiotics, Rao notes.
Good food sources of probiotics include yogurt, sauerkraut, kimchi, kefir and dark chocolate, which are generally safe because of the small amounts of bacteria present, Rao says.
The 19-foot long small intestine has been a bit of an understudied organ, likely in part because it's hard to visualize via the mouth or anus, Rao says. "I think the small bowel can be a source of huge mystery," Rao says.
Your helpful gut bacteria, or microbiome, which are essential to things like a well-functioning immune system and general health, are largely in the large intestine and colon.
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