The Problem With Probiotics


There are potential harms as well as benefits, and a lot of wishful thinking and imprecision in the marketing of products containing them.

A lot of trust has been put into the idea that gut bacteria can be a key to good health.

 

Even before the microbiome craze — the hope that the bacteria in your gut holds the key to good health — people were ingesting cultures of living micro-organisms to treat a host of conditions. These probiotics have become so popular that they’re being marketed in foods, capsules and even beauty products.

Probiotics have the potential to improve health, including by displacing potentially harmful bugs. The trouble is that the proven benefits involve a very small number of conditions, and probiotics are regulated less tightly than drugs. They don’t need to be proved effective to be marketed, and the quality control can be lax.

In a recent article in JAMA Internal Medicine, Pieter Cohen, an associate professor of medicine at Harvard Medical School, urges us to consider the harms as well as the benefits. Among immune-compromised individuals, for instance, probiotics can lead to infections.

Consumers can’t always count on what they’re getting. From 2016 to 2017, the Food and Drug Administration inspected more than 650 facilities that produce dietary supplements, and determined that more than 50 percent of them had violations. These included issues with the purity, strength and even the identity of the promised product.

Probiotic supplements have also been found to be contaminated with organisms that are not supposed to be there. In 2014, such a supplement’s contamination arguably caused the death of an infant.

Given all of this, what are the benefits? The most obvious use of probiotics would be in the treatment of gastrointestinal disorders, given that they are focused on gut health. There have been many studies in this domain, so many that early this year the journal Nutrition published a systematic review of systematic reviews on the subject.

The takeaway: Certain strains were found useful in preventing diarrhea among children being prescribed antibiotics. A 2013 review showed that after antibiotic use, probiotics help prevent Clostridium difficile-associated diarrhea. A review focused on acute infectious diarrhea found a benefit, again for certain strains of bacteria at controlled doses. There’s also evidence that they may help prevent necrotizing enterocolitis (a serious gastrointestinal condition) and death in preterm infants.

Those somewhat promising results — for very specific uses of very specific strains of bacteria in very specific instances — are just about all the “positive” results you can find.

Many wondered whether probiotics could be therapeutic in other gastrointestinal disorders. Unfortunately, that doesn’t appear to be the case. Probiotics didn’t show a significant benefit for chronic diarrhea. Three reviews looked at how probiotics might improve Crohn’s disease, and none could find sufficient evidence to recommend their use. Four more reviews looked at ulcerative colitis, and similarly declared that we don’t have the data to show that they work. The same was true for the treatment of liver disease.

Undaunted, researchers looked into whether probiotics might be beneficial in a host of disorders, even when the connection to gut health and the microbiome was tenuous. Reviews show that there is insufficient evidence to recommend their use to treat or prevent eczema, preterm labor, gestational diabetes, bacterial vaginosis, allergic diseases or urinary tract infections.

Reviews looking at the treatment or prevention of vulvovaginal candidiasis in women, pneumonia in patients hooked up to respirators, and colds in otherwise healthy people show some positive results. But the authors note that the studies are almost all of low quality, small in size, and often funded by companies with significant conflicts of interest.

Individual studies are similarly disappointing for probiotics. One examining obesity found limited effects. Another showed they don’t prevent cavities in teeth. They don’t help prevent infant colic, either.

None of this has prevented probiotics from becoming more popular. In 2012, almost four million Americans used them. In 2014, the global market for probiotics was more than $32 billion.

It’s not clear why. Even in specific diarrhea-focused areas, the case for them isn’t as strong as many think. As with nutrition research, much of this has to do with study design and how proof of efficacy doesn’t translate into real-world applications.

“Sometimes small studies suggest strains work, but when a larger more well-done study is performed, they no longer seem to,” Dr. Cohen said.

When research is done on probiotics, it usually involves a specific organism, defined by genus, species and even strain. When used in studies, they are pure and carefully dosed. But when we buy probiotics off the shelf, especially when they are in food products, we often have no idea what we’re getting.

Yet that’s how probiotics are often offered. They can be distributed in the United States as food, supplements or drugs. The regulations for each are very different. Most people looking for probiotics don’t see the distinctions. Ideally, the ways in which we use and consume probiotics would conform to the data and evidence that back them up. That rarely happens.

Further, there’s still a lot we don’t know. A recent study published in Cell compared how the microbiome of the gut reconstituted itself after antibiotic treatment with and without probiotic administration. The researchers found that probiotics (which might have improved diarrhea symptoms) led to a significant delay in microbiome reconstitution, if it occurred at all. And — again — this study was with purified strains of bacteria, which is not what you’re getting in probiotic-containing food.

Of course, people with no immune deficiencies should feel free to eat yogurt and sauerkraut, which can absolutely be part of a healthy diet. Eat them because they’re delicious, and most likely better for you than many other foods, not because of any health claims.

“It’s important that consumers understand that all those nicely labeled containers on store shelves are not vetted by the F.D.A.,” Dr. Cohen said. “They’re not carefully watching over the probiotic space, leaving consumers to be the guinea pigs for these science experiments.”

For too long we’ve assumed that probiotics are doing some good and little harm. That might be true for some, but it’s not assured in the current environment.

Factors Predicting Long-term Benzodiazepine Use Identified


Poor-quality sleep, prescribing in an extended manner, and white race are key factors that predict conversion to long-term benzodiazepine use in the elderly, a practice that is strongly tied to poor outcomes, including death.

Dr Lauren Gerlach

 

The results highlight the need to “start with the end in mind” when prescribing a benzodiazepine, author Lauren B. Gerlach, DO, a geriatric psychiatrist and assistant professor in the Department of Psychiatry and the Program for Positive Aging, University of Michigan, Ann Arbor, told Medscape Medical News.

This means “beginning with a short-duration prescription and engaging patients in discussions of when to reevaluate their symptoms and begin tapering the patient off,” she said.

Gerlach said more work is needed to improve access to effective nonpharmacologic treatments, such as cognitive-behavioral therapy, as well as to provide access to education regarding such treatments.

The study was published online September 10 in JAMA Internal Medicine.

A Common Practice

Treatment guidelines recommend that if benzodiazepines are to be used at all, they should be used on a short-term basis. However, research suggests that up to one third of use is long term and that use is most common among older adults.

The investigators point out that the factors that predict extended benzodiazepine use are poorly understood.

To identify these risk factors, the researchers used data from the Supporting Seniors Receiving Treatment and Intervention (SUSTAIN) program, which provides a supplement to a Pennsylvania medication coverage program for low-income older adults.

Program services included detailed interviews to screen for mental health problems, such as anxiety, depression, and sleep problems, as well as pain, and analysis of prescription records and other clinical data.

The investigators examined how many older adults who received a new benzodiazepine prescription from a nonpsychiatric provider went on to long-term use of the medication. They also evaluated patient and clinical characteristics that predicted long-term use.

Long-term use was defined as a medication possession ratio (MPR) greater than 30% in the year following the initial prescription. Gerlach explained that the MPR was calculated by dividing the number of days of medication supplied by 365 days.

The study included 576 older adults (mean age, 78.4 years).

The analysis showed that 1 year after the index prescription, 26.4% of patients met the criteria for long-term use. They were prescribed benzodiazepines for a mean of 232.7 days.

Although treatment guidelines recommend only short-term prescribing, “these long-term patients were prescribed nearly 8 months’ worth of medication after their initial prescription,” said Gerlach.

In adjusted analyses, white race (odds ratio [OR], 4.19; 95% confidence interval [CI] 1.51 – 11.59; P = .006), days supplied in the index prescription (OR, 1.94; 95% CI, 1.52 – 2.47; P < .001), and poor sleep quality (OR for very, very bad vs very good, 4.05; 95% CI, 1.44 – 11.43; P = .008) were factors associated with increased long-term benzodiazepine use.

“Cause for Concern”

It’s a “cause for concern” that nonclinical factors are associated with benzodiazepine prescribing, said Gerlach.

“The decision to prescribe and then continue a benzodiazepine — or any other medical treatment — should be driven by a clinical need,” she said.

Gerlach said it was “particularly striking” that for every 10 additional days of medication prescribed, “a patient’s risk of long-term use nearly doubled over the next year.”

This finding “suggests that providers should pause and think more cautiously when providing a new prescription for benzodiazepines, such as considering a 14-day supply rather than a 30-day supply of medication,” said Gerlach.

Also concerning was the average age of the study participants when they first received a benzodiazepine prescription (78 years), because national guidelines say these drugs “should rarely be given to adults over age 65,” she said.

Of the clinical measures the researchers evaluated, which included depression, anxiety, sleep, and pain, only poor sleep was associated with the likelihood of continued benzodiazepine use.

“This is despite the fact that benzodiazepines are not recommended for long-term use as sleep aids, and may even worsen sleep outcomes the longer they’re used,” said Gerlach.

Because nonpsychiatric clinicians increasingly prescribe psychotropic drugs to older adults, the authors write that it is “critical” to improve access to and education about nonpharmacologic treatments.

The authors note that the study did not account for as-needed medication use, which may have had an effect on the calculation of long-term use. As well, the analysis was limited to low-income older adults from Pennsylvania, which may limit generalizability.

The authors also point out that definitions of long-term benzodiazepine use vary and that it is possible that a different definition of long-term use might have yielded different results. However, the investigators used three alternative definitions, with no significant variation in the findings.

Important Message

Commenting on the article for Medscape Medical News, Peter Yellowlees, MD, professor of psychiatry and vice chair for faculty development, Department of Psychiatry, University of California, Davis, said he was somewhat surprised that not more patients converted to long-term benzodiazepine prescriptions and that whites and not minority groups were more likely to be prescribed these drugs long term.

He said the “single most important message” from the study is that patients should know from the beginning that their benzodiazepine prescription will be short term.

In his own practice, Yellowlees said he “very seldom” prescribes benzodiazepines and “is much more likely” to taper patients off these drugs.

He aims to have patients to take these addictive medicines only three or four times a week — not every day — to avoid “getting hooked on them” and to taper patients off the drugs “extremely slowly” — over 3 to 6 months.

“Most people try to taper patients off in a matter of maybe 2 or 3 weeks; they will go, say, from 10 mg one week, to 5 mg the next, to whatever the next, and honestly, that’s just too hard for many patients,” he said.

The problem is that such a slow tapering approach can be time consuming, and primary care practitioners may have only a 15-minute consult per patient.

Benzodiazepines have been linked to falls and cognitive impairment, said Yellowlees.

“The effects can mimic early dementia. People get confused, and that leads to falling down and not being able to manage at home, with patients then having to go into a nursing home,” he said.

There are also risks of taking these drugs and then driving, said Yellowlees.

In lieu of benzodiazepines, he often uses cognitive-behavioral therapy for patients who have problems sleeping or who have anxiety.

Pulmonary Embolism Causes <1% of Syncope, Study Confirms


Rarity of lung clots contradicts PESIT data

Researchers confirmed in a retrospective study that pulmonary embolism is unlikely to cause syncope that results in a trip to the emergency room.

Fewer than 1% of nearly 1.7 million patients treated at emergency departments for syncope had pulmonary embolism, according to databases from Canada, Denmark, Italy, and the U.S., reported Giorgio Constantino, MD, of Italy’s Ospedale Maggiore Policlinico in Milan, and colleagues.

Pulmonary embolism was responsible for syncope in just 0.06% to 0.55% of those cases, they wrote in JAMA Internal Medicine; among those admitted, PE was the cause in 0.15% to 2.10%.

“Pulmonary embolism was rarely identified in patients with syncope. Although pulmonary embolism should be considered in every patient, not all patients should undergo evaluation for pulmonary embolism,” the authors concluded. “The unnecessary exposure to radiation and the risk of contrast allergy is significant. Furthermore, the false-positive rate of tests, such as the D-dimer assay and computed tomographic pulmonary angiograms, is high, leading to more tests and overdiagnosis and including risks of unnecessary anticoagulation.”

“Pulmonary embolism has always been considered an uncommon cause of syncope,” according to Constantino’s group. The new data confirm this belief and fly in the face of the PESIT study, which estimated the prevalence of pulmonary embolism to be as high as 3.7% in patients going to the emergency department with syncope.

Still, no studies so far have been perfect.

“Because PESIT used a structured algorithm to assess for the presence of pulmonary embolism, one could hypothesize that previous studies, as well as clinical practice, might have underestimated pulmonary embolism prevalence. Even in the present study, some pulmonary embolism diagnoses could have been missed because they were not suspected, and therefore no information relevant to pulmonary embolism was reported in the administrative data,” the investigators acknowledged.

To identify as many cases of pulmonary embolism as possible, they determined the prevalence of lung clots at 90-day follow-up (assuming they were also there at emergency department arrival) and determined it lay in the 0.14%-0.83% range of all those who fainted and went to the emergency room (or 0.35%-2.63% of the hospitalized subset).

“Even in this case, pulmonary embolism was identified in less than 1% of patients, suggesting that, even if some pulmonary embolism had been missed at first evaluation, most were not clinically relevant,” Constantino and colleagues emphasized.

The findings make it hard to justify initiating standard diagnostic algorithms for pulmonary embolism in every syncope patient, they concluded.

Just How Often Do Patients Turn Post-Surgical Opioids Into a Habit?


Last May, researchers at Johns Hopkins University presented results of an internal study showing that most orthopedic surgery patients didn’t take all the opioid pills they were given at discharge, nor were many told what to do with unused pills.  In this follow-up, we look at additional research on this topic appearing since then.

As 2017 rolled on, more research as well as anecdotal contributions suggested that opioid prescribing after surgery is a reason the nation appears to be awash in the drugs, and their abuse.

The Hopkins group, led by Mark Bicket, MD, followed up on the May presentation with a meta-analysis published in August that pulled together results from six studies by other groups. It confirmed the group’s experience in their own center: from 42% to 71% of pills dispensed at discharge were never used.

In November, Kaiser Health News reporter Michelle Andrews shared her own experience, in which her surgeon prescribed 90 oxycodone/acetaminophen (Percocet) tablets after what she termed a minor laparoscopic knee surgery. When she asked her surgeon why so many, he said it was the default in his hospital’s ordering system for knee procedures. “If you had real surgery, like a knee replacement, you wouldn’t think [90] was so many,” she quoted him as saying.

Andrews didn’t say what she had done with her unused pills, but Bicket’s group said safe disposal is uncommon. People who do want to get rid of them usually throw them in the trash or flush them down the toilet, but it’s just as common, if not more so, to hoard them for some future pain episode. Or give them to friends and relatives who complain of pain.

Still another study, published in December in JAMA Surgery by a group in Boston, found a high rate of “potential overprescription:” patients discharged with opioid prescriptions even though they hadn’t received any opioids during their last 24 hours as inpatients. More than 40% of patients who were opioid-free at discharge in the study still went home with prescriptions.

A key question is whether, and how often, patients turn their post-surgical opioid prescription into a long-term habit. A study appearing in JAMA Surgery on June 21 gave an unwelcome answer: yes, they do, at a rate of about one in 16.

 The study examined claims data involving some 36,000 surgical patients. The likelihood of persistent use beyond the first 90 days was not affected by whether the surgery was deemed major or minor. Instead, risk factors included comorbid substance use (including alcohol, tobacco, and other drugs), mood disorders, and pre-surgical pain diagnoses.

“This suggests [persistent opioid] use is not due to surgical pain but addressable patient-level predictors,” wrote the authors, led by Chad Brummett, MD, of the University of Michigan in Ann Arbor.

Earlier studies had reached similar conclusions. In 2016, a paper in JAMA Internal Medicine, also drawing on claims data, found that previously opioid-naive surgical patients were at increased risk of long-term opioid use (defined as more than a 120-day supply or 1o consecutive prescriptions), compared with nonsurgical patients without previous history of opioid prescriptions.

And in 2013, researchers presenting at the North American Spine Society reported that about one-third of patients undergoing back surgery were still taking opioids a year later. About half of those on opioids prior to surgery were still using them, as were 18% of those without a prior opioid history.

One obvious approach to minimizing risk that post-surgical opioid prescriptions will lead to addiction is to use non-opioid painkillers instead. NSAIDs sometimes have been proposed but are largely viewed as inadequate for this purpose.

 Another suggestion has been gabapentin, and it was the subject of a clinical trial reported just 2 weeks ago. It enrolled patients undergoing a variety of orthopedic surgeries (open and laparoscopic) and mastectomy and randomized them to receive gabapentin or placebo, both pre- and post-operatively, in addition to post-op opioids. Those assigned to gabapentin stopped opioid use after a mean of 25 days versus 32 days for the placebo group.

The authors said gabapentin had “a modest effect on promoting opioid cessation after surgery.” (Unclear, though, was whether patients were still sent home with 90 Percocets.)

Another view of the relationship between in-hospital opioids and subsequent long-term use came from Suneel Kamath, MD, a hematology/oncology fellow in Chicago’s Northwestern Memorial Hospital. In a poignant personal recollection written for MedPage Today, he suggested that simply wanting to be liked may influence hospital physicians to prescribe opioids for patients who ask.

“To some extent, human nature drives physicians to prescribe more opioids to make patients happy,” Kamath wrote.

He noted as well that refusing a patient’s request often leads to a discussion, and sometimes a time-consuming and uncomfortable one. “I have to believe that at some point in residency, I gave a patient opioids to avoid the emotional toll of the conflict and to move on more quickly to my other patients. I suspect I am not alone.”

Porridge could be key to a long and healthy life, says Harvard University.


Eating porridge, brown rice or corn each day could protect the heart against disease, Harvard University has found

Porridge could be key to a long and healthy life, says Harvard University

Youngsters who eat oats regularly are 50 per cent less likely to be overweight, one study of 10,000 children found

A small bowl of porridge each day could be the key to a long and healthy life, after a major study by Harvard University found that whole grains reduce the risk of dying from heart disease.

Although whole grains are widely believed to be beneficial for health it is the first research to look at whether they have a long-term impact on lifespan.

Researchers followed more than 100,000 people for more than 14 years monitoring their diets and health outcomes.

Everyone involved in the study was healthy in 1984 when they enrolled, but when they were followed up in 2010 more than 26,000 had died.

However those who ate the most whole grains, such as porridge, brown rice, corn and quinoa seemed protected from many illnesses and particularly heart disease.Oats are already the breakfast of choice for many athletes and also for dieters, who find the high fibre levels give them energy for longer.

But scientists found that for each ounce (28g) of whole grains eaten a day – the equivalent of a small bowl of porridge – the risk of all death was reduced by five per cent and heart deaths by 9 per cent.

“These findings further support current dietary guidelines that recommend increasing whole-grain consumption,” said lead author Dr Hongyu Wu of Harvard School of Public Health.

“They also provide promising evidence that suggests a diet enriched with whole grains may confer benefits towards extended life expectancy.”

The findings remained even when allowing for different ages, smoking, body mass index and physical activity.

Whole grains, where the bran and germ remain, contain 25 per cent more protein than refined grains, such as those that make white flour, pasta and white rice.

Previous studies have shown that whole grains can boost bone mineral density, lower blood pressure, promote healthy gut bacteria and reduce the risk of diabetes. One particular fibre found only in oats – called beta-glucan – has been found to lower cholesterol which can help to protect against heart disease. A bioactive compound called avenanthramide is also thought to stop fat forming in the arteries, preventing heart attacks and strokes.

Whole grains are also widely recommended in many dietary guidelines because they contain high levels of nutrients like zinc, copper, manganese, iron and thiamine. They are also believed to boost levels of antioxidants which combat free-radicals.

The new research suggests that if more people switched to whole grains, thousands of lives could be saved each year. Coronary heart disease is Britain’s biggest killer, responsible for around 73,000 deaths in the UK each year. Around 2.3 million people are living with the condition and one in six men and one in 10 women will die from the disease.

Health experts said the study proved that whole grains were beneficial to health

Victoria Taylor, Senior Dietician at the British Heart Foundation, said: “This is an interesting study and reinforces existing dietary recommendations to eat more foods high in fibre.

“People with a higher intake of whole grains also tended to have a healthier overall lifestyle and diet so it might not be the whole grains alone that are having the benefit in relation to cardiovascular disease.

“But at this time of year when we are all making resolutions to eat better, switching to whole-grain versions of bread, breakfast cereals, pasta and rice is a simple change to make.”

Source:  JAMA: Internal Medicine.

Hormone Therapy in Younger Postmenopausal Women Does Not Impair Cognitive Function.


Hormone therapy with estrogen-based regimens does not affect long-term cognitive function when prescribed to younger postmenopausal women, according to an analysis from the Women’s Health Initiative, published inJAMA Internal Medicine.

Researchers studied some 1300 women who, between ages 50 and 55, were randomized to estrogen-based hormone therapy or placebo. Treatment lasted roughly 7 years, and cognitive tests were performed about 7 years after treatment ended. Overall, cognitive scores did not differ significantly between active treatment and placebo, a finding that held true for estrogen combined with medroxyprogesterone acetate and for estrogen alone.

The authors conclude: “Our findings provide reassurance that [estrogen]-based therapies when administered to women earlier in the postmenopausal period do not seem to convey long-term adverse consequences for cognitive function.”

Source: JAMA

 

About a Quarter of Screening Colonoscopies in U.S. Elderly Seem Inappropriate.


Roughly 25% of screening colonoscopies done among the elderly may be inappropriate, according to a JAMA Internal Medicine study of Medicare data.

Researchers examined claims data on some 75,000 Texas Medicare recipients aged 70 or older who underwent complete colonoscopy in a 1-year period starting in 2008. Procedures that were repeated early without a clear indication, or those that were done contrary to published guidelines with regard to age, were considered possibly inappropriate. In addition, a 5% national Medicare sample was also examined.

Overall, 23.4% of the cohort were found to have undergone a potentially inappropriate procedure. There was marked variation geographically both within Texas and the U.S., as well as among colonoscopists, some of whom had rates of potentially inappropriate colonoscopies above 45% (they tended to be surgeons and graduates of U.S. medical schools).

Source: JAMA