Showing posts with label Health. Show all posts
Showing posts with label Health. Show all posts

Sunday 24 December 2023

Eat Carrots and Prevent Cancer: Unveiling the Superfood's Hidden Powers

https://drive.google.com/uc?export=view&id=1BLcCLldQJer0cfPQjlx0QWTnMWVf9CUL
Harnessing the Power of Carrots: A Bite into Cancer Prevention
In a world constantly seeking natural ways to combat illness, a recent meta-analysis led by Kirsten Brandt of Newcastle University, published by Critical Reviews in Food Science and Nutrition, brings to light the cancer-fighting properties of a familiar vegetable: the humble carrot.

Carrots: More Than Just a Crunchy Snack
The study's in-depth analysis of 50 prospective cohort studies, involving 52,000 cancer cases, reveals a striking correlation between carrot consumption and reduced cancer risk. Spanning various cancer types and geographical regions, the findings suggest that carrots cut cancer risk by 10%-20%.

The Science Behind the Orange Crunch
Carrots are known for their high beta-carotene content. However, this study focused on another compound, alpha-carotene, due to limited cancer reduction benefits seen in previous studies on beta-carotene. Remarkably, alpha-carotene levels, as measured in plasma in 30 prospective cohorts with 9,331 cancer cases, showed a relative risk reduction of 20% in cancer.

A Serving a Week Keeps the Doctor Away
The study highlights a significant linear dose-response relationship. Consuming just one serving of carrots per week can reduce cancer risk by 4±2%, while five servings can slash the risk by 20±10%. This finding underlines the practicality and accessibility of carrots as a dietary choice for cancer prevention.

A Robust Inverse Association
The authors describe the inverse relationship between carrot intake and cancer risk as “robust,” advocating for the encouragement of carrot consumption. They also call for further research into the causal mechanisms through randomised clinical trials, which could offer deeper insights into how carrots combat cancer.

Methodology and Limitations
The meta-analysis compiled data from a wide array of studies, considering different cancer types, geographic regions, and exposure types. However, it's crucial to note that all included studies were observational, not randomised clinical trials. This factor presents a limitation in definitively establishing causality between carrot intake and reduced cancer risk.

In Practice: Integrating Carrots into Daily Diets
This study's findings present a compelling case for integrating carrots into our daily diets. As a versatile and widely available vegetable, carrots can easily be incorporated into meals, offering both flavor and health benefits.

A Step Forward in Cancer Prevention
The study, funded by the Agricultural and Horticultural Board, UK, among others, stands as a testament to the potential of natural food sources in disease prevention. It paves the way for future research and reinforces the importance of a balanced, vegetable-rich diet in maintaining health and preventing illness.

Conclusion: Embracing Carrots for Health
As we navigate an era where lifestyle diseases are prevalent, simple, evidence-based dietary changes like increasing carrot intake can have profound health impacts. The study not only highlights the cancer-fighting potential of carrots but also serves as a reminder of the power of natural foods in preserving our health. So, the next time you're at the grocery store, remember to stock up on carrots - your body might just thank you for it.
Reference: 

Wednesday 15 November 2023

The Link Between Sleep and Dementia Risk: A Wake-Up Call

https://drive.google.com/uc?export=view&id=1eoahDo6jW4HHss-aRH-WDqHS6jrgT4iw
In our fast-paced lives, sleep often falls down our list of priorities, but recent research from Monash University, Clayton, Victoria, Australia, is a stark reminder of its critical importance, especially deep sleep. A retrospective cohort study, published in JAMA Neurology, reveals a compelling link between the loss of deep sleep and an increased risk of dementia, particularly Alzheimer's Disease (AD).

The Study: A Deep Dive into Sleep and Dementia
The study hinged on participants from the renowned Framingham Heart Study, focusing on a subset aged 60 or over. These individuals underwent two polysomnographic sleep studies between 1995-1998 and 2001-2003. They were then monitored until 2018 for signs of dementia.

What sets this study apart is its meticulous methodology. Participants were assessed not just for sleep patterns but also for genetic predispositions to Alzheimer's. This comprehensive approach sheds light on the intricate interplay between our genetics, our sleep, and our brain health.

The Findings: A Startling Association
The results are alarming yet informative. Over an average of 12 years after the second sleep study, 52 of the 346 participants developed dementia, with 44 of these cases being Alzheimer's. The startling revelation was that each percentage decrease in Slow-Wave Sleep (SWS), or deep sleep, per year corresponded to a 27% increase in all-cause dementia risk and a 32% increase in the risk for Alzheimer's.

These findings point towards the critical role of SWS in brain health. As lead investigator Dr. Matthew Pase notes, "Slow-wave sleep, or deep sleep, supports the ageing brain in many ways, including the clearance of metabolic waste." This is particularly significant in the context of Alzheimer's, where the failure to clear certain proteins is a hallmark of the disease.

 The Implications: A Modifiable Risk Factor
This research is a wake-up call, highlighting SWS loss as a potentially modifiable dementia risk factor. It suggests that by prioritizing deep sleep in our later years, we could significantly lower our risk of dementia. 

 In Practice: What Can We Do?
While there are limitations to the study, such as the absence of gold-standard AD biomarkers and its observational nature, the implications are too significant to ignore. Enhancing the quality of our sleep, particularly deep sleep, could be a key strategy in mitigating dementia risk.

 Final Thoughts
In an age where sleep is often sacrificed at the altar of productivity, this study is a crucial reminder of its importance. It's not just about the quantity of sleep but the quality, particularly the deep, restorative stages that could hold the key to our cognitive well-being in our later years. As we understand more about the links between sleep and dementia, perhaps it's time to re-evaluate our sleep habits and give our brains the rest they deserve.

Monday 31 July 2023

Snoring Could Be Harming Your Brain

Snoring and Your Brain: What the Nightly Rumble May Mean for Your Brain Health

https://drive.google.com/uc?export=view&id=1z1TKxNyOzBEqWVnAGYEKuIuM-eWe8AfT

Do you snore, or know someone who does? While it may be a source of light-hearted teasing or frustration within a family, the implications of snoring could be far more serious than we think. Recent research from the Faculty of Medicine at the University of Paris-Cité suggests that habitual snorers might be fast-forwarding the aging process of their brains and inadvertently compromising their brain health.

The underlying factor in the harm caused by snoring is the deprivation of deep sleep, the phase of sleep crucial for physical and mental restoration. The study finds that the regular, loud snorers with obstructed breathing, often the tell-tale signs of sleep apnea, stand at higher risk of developing symptoms of grave conditions like stroke, Alzheimer's disease, or general cognitive decline. 

The evidence for this alarming theory lies in the presence of tiny lesions on the brain, known as white matter hyperintensities. These biomarkers give an indication of the brain's health status and are more prevalent with age or uncontrolled high blood pressure. However, these lesions appeared more abundantly in participants with severe sleep apnea compared to those with mild or moderate conditions. This suggests a correlation between the severity of sleep-disordered breathing and the state of the brain's health.

Astonishingly, the study found that for every 10% decrease in deep sleep, there was an increase in these white matter hyperintensities, equivalent to the brain aging 2.3 years. This process signifies a decrease in the integrity of the axons, the elongated part of a nerve cell that allows communication between cells. Alarmingly, the same 10% reduction of deep sleep was also associated with reducing the integrity of these axons, leading to an effect similar to the brain appearing 3 years older.

This groundbreaking research emphasises the importance of quality sleep and paints a grim picture of the potential implications of untreated snoring. However, as the understanding of the relationship between snoring, deep sleep, and brain health continues to evolve, individuals have the opportunity to take control of their sleep health.

So, if you or a loved one is a chronic snorer, consider seeking professional medical advice. Simple lifestyle changes, or in more severe cases, medical interventions, could not only lead to quieter nights but also contribute significantly to preserving your cognitive health. In essence, protecting your sleep could mean protecting your brain, and that's something worth losing a little sleep over.

Saturday 22 April 2023

The New Obesity Breakthrough Drugs

https://drive.google.com/uc?export=view&id=1QY44lhbkX9y0uoTlNntfeOg_9aFSTw6B

There are many holy grails in medicine, with failure after failure, like finding a way to prevent Alzheimer's disease or a non-invasive means for accurately measuring ambulatory blood pressure. But one of the biggest and most daunting has been finding drugs that can tackle obesity — achieving a substantial amount of weight loss without serious side effects. Many attempts to get there now fill a graveyard of failed drugs, such as fen-phen in the 1990s when a single small study of this drug combination in 121 people unleashed millions of prescriptions, some leading to serious heart valve lesions that resulted in withdrawal of the drug in 1995. The drug rimonabant, an endocannabinoid receptor blocker (think of blocking the munchies after marijuana) looked encouraging in randomized trials. However, subsequently, in a trial that I led of nearly 19,000 participants in 42 countries around the world, there was a significant excess of depression, neuropsychiatric side-effects and suicidal ideation which spelled the end of that drug's life.

 

In the United States, where there had not been an anti-obesity drug approved by the FDA since 2014, Wegovy (semaglutide), a once-weekly injection was approved in June 2021. The same drug, at a lower dose, is known as Ozempic (as in O-O-O, Ozempic, the ubiquitous commercial that you undoubtedly hear and see on TV) and had already been approved in January 2020 for improving glucose regulation in diabetes. The next drug on fast track at FDA to be imminently approved is tirzepatide (Mounjaro) following its approval for diabetes in May 2022. It is noteworthy that the discovery of these drugs for weight loss was serendipitous: they were being developed for improving glucose regulation and unexpectedly were found to achieve significant weight reduction.

Both semaglutide and tirzepatide underwent randomized, placebo-controlled trials for obesity, with marked reduction of weight as shown below. Tirzepatide at dose of 10 to 15 mg per week achieved >20% body weight reduction. Semaglutide at a dose of 2.4 mg achieved ~17% reduction. These per cent changes in body weight are 7-9 fold more than seen with placebo (2-3% reduction). Note: these levels of per cent body weight reduction resemble what is typically achieved with the different types of bariatric surgery, such as gastric bypass.

 https://drive.google.com/uc?export=view&id=1ZlJgSm2f8c4TGFTztQueJ4m9mgh-JvC7


Another way to present the data for the 2 trials is shown here, with an edge for tirzepatide at high (10-15 mg) doses, extending to >25% body weight reduction.

 

 https://drive.google.com/uc?export=view&id=1_UND3vq9gu4HXTLzsgDgAmjbBQ8DTF9U

The results with semaglutide were extended to teens in a randomized trial (as shown below), and a similar trial with tirzepatide is in progress.

 https://drive.google.com/uc?export=view&id=1uyIrQH6LS3AgZ6e5H8CtxzVyXYLLwjm-


How Do These Drugs Work?

 

These are peptides in the class of incretins, mimicking gut hormones that are secreted after food intake which stimulate insulin secretion.

 https://drive.google.com/uc?export=view&id=1umrt_61ViSDZGGSHYDQX0XdZNdaJtC0S


These 2 drugs have in common long half-lives (~ 5 days), which affords once-weekly dosing, but have different mechanisms of action. Semaglutide activates (an agonist) the GLP-1 receptor, while tirzepatide is in a new class of dual agonists: it activates (mimics) both the GLP-1 receptor and GIP receptors (Gastric inhibit polypeptide is also known as glucose-dependent insulinotropic polypeptide.) The potency of activation for tirzepatide is 5-fold more for GIPR than GLP1. As seen below, there are body wide effects that include the brain, liver, pancreas, stomach, intestine, skeletal muscle and fat tissue. While their mode of action is somewhat different, their clinical effects are overlapping, which include enhancing satiety, delaying gastric emptying, increasing insulin and its sensitivity, decreasing glucagon, and, of course, reducing high glucose levels. The overlap extends to side effects of nausea, vomiting, abdominal pain, constipation and diarrhea. Yet only 4 to 6% of participants discontinued the drug in these trials, mostly owing to these GI side effects (and 1-2% in the placebo group discontinued the study drug for the same reasons).

In randomized trials among people with Type 2 diabetes, the drugs achieved HbA1c reduction of at least an absolute 2 percentage points which led to their FDA approvals (For semaglutide in January 2020, and for tirzepatide in May 2022). The edge that tirzepatide has exhibited for weight loss reduction may be related to its dual agonist role, but the enhancement via GIP receptor activation is not fully resolved (as seen below with GIP? designation). The Amgen drug in development (AMG-133) has a marked weight loss effect but inhibits GIP rather than mimics it, clouding our precise understanding of the mechanism.

 https://drive.google.com/uc?export=view&id=1P0vEd8zA8KgSSYsrGYUb4U0IXKql0MDL

The gut-brain regulation of food intake with the many gut hormones (including leptin, gherlin, PYY, amylin) and targets in the body and brain regions. From Muller et al, Nature Reviews Drug Discovery March 2022. 


Nevertheless, when the two drugs were directly compared in a randomized trial for improving glucose regulation, tirzepatide was superior to semaglutide, as shown below. Of note, both drugs achieved very favorable effects on lipids, reducing triglycerides, LDL and raising HDL cholesterol, along with reduction of blood pressure, an outgrowth of the indirect effect of weight reduction and direct metabolic effects of the drugs.

 https://drive.google.com/uc?export=view&id=10axmmVFiL90sf5DWTzZXEWsGN7RUYbBu

While there has been a concern about other side effects besides the GI ones noted above, review of all the trials to date in these classes of medication do not reinforce a risk of acute pancreatitis. Other rare side effects that have been noted with these drugs include allergic reactions, gallstones (which can occur with a large amount of weight loss), and potential of medullary thyroid cancer (so far only documented in rats, not people), which is why they are contraindicated in people with Type 2 multiple endocrine neoplasia syndrome.


How They Are Given and Practical Considerations

 

For semaglutide, which has FDA approval, the indication is a BMI of 30 kg/m2 or greater than 27 kg/m2 and a weight related medical condition (such as hypertension. hypercholesterolemia or diabetes). To reduce the GI side effects, which mainly occur in the early dose escalation period, semaglutide is given in increasing doses by a prefilled pen by self-injection under the skin (abdomen, thigh or arm) starting at 0.25 mg for a month and gradual increases each month reaching the maximum dose of 2.4 mg at month 5. The FDA label for dosing of tirzepatide has not been provided yet but in the weight loss trial there was a similar dose escalation from 2.5 mg up to 15 mg by month 5. The escalation is essential to reduce the frequent GI side effects, such as seen below in the tirzepatide trial.

 https://drive.google.com/uc?export=view&id=1Ez9Rl6xpRWT9t6juU5w1x-DI4UkK1mal

Semaglutide is very expensive, ~$1500 per month, and not covered by Medicare. There are manufacturer starter coupons from Novo Nordisk, but that is just for the first month. These drugs have to be taken for a year to 18 months to have their full effect and without changes in lifestyle that are durable, it is likely that weight will be regained after stopping them.


What Does This Mean?

 

More than 650 million adults are obese and 13% of the 8 billion world's population (including over 340 million ages 5-18) is obese — that sums us to over 1 billion people. The global obesity epidemic has been relentless, worsening each year, and a driver of "diabesity," the combined dual epidemic. We now have a breakthrough class of drugs that can achieve profound weight loss equivalent to bariatric surgery, along with the side benefits of reducing cardiovascular risk factors (hypertension and hyperlipidemia), improving glucose regulation, reversing fatty liver, and the many detrimental long-term effects of obesity such as osteoarthritis and various cancers. That, in itself, is remarkable. Revolutionary.

 

But the downsides are also obvious. Self-injections, even though they are once a week, are not palatable for many. We have seen far more of these injectables in recent years such as the PCSK-9 inhibitors for hypercholesterolemia or the TNF blockers for autoimmune conditions. That still will not make them a popular item for such an enormous population of potential users.


That brings me to Rybelsus, the oral form of semaglutide, which is approved for glucose regulation improvement but not obesity. It effects for weight loss have been modest compared to Wegovy (5 to 8 pounds for the 7 and 14 mg dose, respectively). But the potential for the very high efficacy of an injectable to be achievable via a pill represents an important path going forward—it could help markedly reduce the cost and uptake.


The problem of discontinuation of the drugs is big, since there are limited data and the likelihood is that the weight will be regained unless there are substantial changes in lifestyle. We know how hard it is to durably achieve such changes, along with the undesirability (and uncertainty with respect to unknown side-effects) of having to take injectable drugs for many years, no less the cost of doing that.


The cost of these drugs will clearly and profoundly exacerbate inequities, since they are eminently affordable by the rich, but the need is extreme among the indigent. We've already seen celebrities take Wegovy for weight loss who are not obese, a window into how these drugs can and will be used without supportive data. As one physician recently observed, "Other than Viagra and Botox, I've seen no other medication so quickly become part of modern culture's social vernacular." Already there are concerns that such use is preventing access to the drugs for those who qualify and need them.

 

There are multiple agents in the class under development which should help increase competition and reduce cost, but they will remain expensive. There is private insurance reimbursement, often with a significant copay, for people who tightly fit the inclusion criteria. Eventual coverage by Medicare will markedly expand their use, and we can expect cost-effectiveness studies to be published showing how much saving there is for the drugs compared with bariatric surgery or not achieving the weight loss. But that doesn't change the cost at the societal level. Even as we've seen with generics, which will ultimately be available, the alleviation of the cost problem isn't what we'd hoped.

 

This is not unlike the recent triumphs of gene therapy, as in $3.5 million for a cure of hemophilia that just got FDA approval, but instead of a rare disease we are talking about the most common medical condition in the world. We finally get across the long sought after (what many would qualify as miraculous) goal line, but the economics collide with the uptake and real benefit.

 

These concerns can't be put aside in the health inequity-laden world we live in, that will unquestionably be exacerbated. However, we cannot miss that this represents one of the most important, biggest medical breakthroughs in history. This may signify the end or marked reduction in the need for bariatric surgery. These drugs will likely become some of the most prescribed of all medications in the upcoming years. While there are many drawbacks, we shouldn't miss such an extraordinary advance in medicine—the first real, potent and safe treatment of obesity.

Thursday 20 April 2023

Intermittent Fasting Plus Early Eating May Prevent Type 2 Diabetes

https://drive.google.com/uc?export=view&id=16AGzdRq_5KkSpt793GXJYVKziR5bKfWJ

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 AM to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

"Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes," said senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, in a press release.

This is "the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal," with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

"The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice," Teong added.

Adherence Difficult to IF Plus Early Time-Restricted Eating

Asked to comment, Krista Varady, PhD, said that the study design "would have been stronger if the time-restricted eating and IF interventions were separated" and compared.

"Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day," she told Medscape Medical News, "so I'm not sure why the investigators chose to combine [it] with IF. It...defeats the point of time-restricted eating."

Varady, who recently coauthored a review of the clinical application of intermittent fasting for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. "In all honesty, I don't think anyone would follow this diet for very long," she said.

She added that the feasibility of this particular approach is "very questionable. In general, people don't like diets that require them to skip dinner with family/friends on multiple days of the week," explained Varady, professor of nutrition at the University of Illinois, Chicago.  "These regimens make social eating very difficult, which results in high attrition."

"Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening," she noted.

Varady therefore suggested that future trials should test "more feasible time-restricted eating approaches," such as those with later eating windows and without "vigilant calorie monitoring."

"These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes," she observed.

A Novel Way to Cut Calories? 

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF — defined as fasting interspersed with days of ad libitum eating — gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the direct trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 AM and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

Two hundred and nine individuals were enrolled between September 26, 2018 and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index (BMI) was 34.8 kg/m2.

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

"To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment," the authors underline.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.

Calorie Restriction Easier to Stick to, Less Likely to Cause Fatigue 

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2 to 3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.

Nat Med. Published online April 6, 2023. Full text

Thursday 6 April 2023

Some Diets Better Than Others for Heart Protection


https://drive.google.com/uc?export=view&id=1h5sdv4O7TMIC_zbEL7Wt7a2H33w_uSh0

A new analysis of randomized trials suggests that the Mediterranean diet and low-fat diets probably reduce the risk of death and nonfatal myocardial infarction (MI) in adults at increased risk for cardiovascular disease (CVD), while the Mediterranean diet also likely reduces the risk of stroke.

Five other popular diets appeared to have little or no benefit with regard to these outcomes.

"These findings with data presentations are extremely important for patients who are skeptical about the desirability of diet change," write the authors, led by Giorgio Karam, with University of Manitoba, Winnipeg, Canada.

The results were published online March 29 in The BMJ.

Dietary guidelines recommend various diets along with physical activity or other cointerventions for adults at increased CVD risk, but they are often based on low-certainty evidence from nonrandomized studies and on surrogate outcomes.

Several meta-analyses of randomized controlled trials with mortality and major CV outcomes have reported benefits of some dietary programs, but those studies did not use network meta-analysis to give absolute estimates and certainty of estimates for adults at intermediate and high risk, the authors note.

For this study, Karam and colleagues conducted a comprehensive systematic review and network meta-analysis in which they compared the effects of seven popular structured diets on mortality and CVD events for adults with CVD or CVD risk factors.

The seven diet plans were the Mediterranean, low fat, very low fat, modified fat, combined low fat and low sodium, Ornish, and Pritikin diets. Data for the analysis came from 40 randomized controlled trials that involved 35,548 participants who were followed for an average of 3 years.

There was evidence of "moderate" certainty that the Mediterranean diet was superior to minimal intervention for all-cause mortality (odds ratio [OR], 0.72), CV mortality (OR, 0.55), stroke (OR, 0.65), and nonfatal MI (OR, 0.48).

On an absolute basis (per 1000 over 5 years), the Mediterranean diet let to 17 fewer deaths from any cause, 13 fewer CV deaths, seven fewer strokes, and 17 fewer nonfatal MIs.

There was evidence of moderate certainty that a low-fat diet was superior to minimal intervention for prevention of all-cause mortality (OR, 0.84; nine fewer deaths per 1000) and nonfatal MI (OR, 0.77; seven fewer deaths per 1000). The low-fat diet had little to no benefit with regard to stroke reduction.

The Mediterranean diet was not "convincingly" superior to a low-fat diet for mortality or nonfatal MI, the authors note.

The absolute effects for the Mediterranean and low-fat diets were more pronounced in adults at high CVD risk. With the Mediterranean diet, there were 36 fewer all-cause deaths and 39 fewer CV deaths per 1000 over 5 years.

The five other dietary programs generally had "little or no benefit" compared with minimal intervention. The evidence was of low to moderate certainty.

The studies did not provide enough data to gauge the impact of the diets on angina, heart failure, peripheral vascular events, and atrial fibrillation.

The researchers say that strengths of their analysis include a comprehensive review and thorough literature search and a rigorous assessment of study bias. In addition, the researchers adhered to recognized GRADE methods for assessing the certainty of estimates.

Limitations of their work include not being able to measure adherence to dietary programs and the possibility that some of the benefits may have been due to other factors, such as drug treatment and support for quitting smoking.

The study had no specific funding. The authors have disclosed no relevant financial relationships. 

BMJ. Published online March 29, 2023. Full text


Wednesday 22 March 2023

Parkinson Disease

Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites.


Signs and symptoms
https://drive.google.com/uc?export=view&id=1kEMxO4RssoNR94qTF5velJErtk-kw_S5



Initial clinical symptoms of Parkinson disease include the following:

  • Tremor
  • Subtle decrease in dexterity
  • Decreased arm swing on the first-involved side
  • Soft voice
  • Decreased facial expression
  • Sleep disturbances
  • Rapid eye movement (REM) behavior disorder (RBD; a loss of normal atonia during REM sleep)
  • Decreased sense of smell
  • Symptoms of autonomic dysfunction (eg, constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
  • A general feeling of weakness, malaise, or lassitude
  • Depression or anhedonia
  • Slowness in thinkin

Onset of motor signs include the following:

  • Typically asymmetric
  • The most common initial finding is a resting tremor in an upper extremity
  • Over time, patients experience progressive bradykinesia, rigidity, and gait difficulty
  • Axial posture becomes progressively flexed and strides become shorter
  • Postural instability (balance impairment) is a late phenomenon

Nonmotor symptoms

Nonmotor symptoms are common in early Parkinson disease. Recognition of the combination of nonmotor and motor symptoms can promote early diagnosis and thus early intervention, which often results in a better quality of life.

Diagnosis

Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.

Clinical diagnosis requires the presence of 2 of 3 cardinal signs:

  • Resting tremor
  • Rigidity
  • Bradykinesia

Management

The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects.

Symptomatic drug therapy

  • Usually provides good control of motor signs of Parkinson disease for 4-6 years
  • Levodopa/carbidopa: The gold standard of symptomatic treatment
  • Monoamine oxidase (MAO)–B inhibitors: Can be considered for initial treatment of early disease
  • Other dopamine agonists (eg, ropinirole, pramipexole): Monotherapy in early disease and adjunctive therapy in moderate to advanced disease
  • Anticholinergic agents (eg, trihexyphenidyl, benztropine): Second-line drugs for tremor only

Treatment for nonmotor symptoms

  • Sildenafil citrate (Viagra): For erectile dysfunction
  • Polyethylene glycol: For constipation
  • Modafinil: For excessive daytime somnolence
  • Methylphenidate: For fatigue (potential for abuse and addiction)

Deep brain stimulation

  • Surgical procedure of choice for Parkinson disease
  • Does not involve destruction of brain tissue
  • Reversible
  • Can be adjusted as the disease progresses or adverse events occur
  • Bilateral procedures can be performed without a significant increase in adverse events

Prognosis

Before the introduction of levodopa, Parkinson disease caused severe disability or death in 25% of patients within 5 years of onset, 65% within 10 years, and 89% within 15 years. The mortality rate from Parkinson disease was 3 times that of the general population matched for age, sex, and racial origin. With the introduction of levodopa, the mortality rate dropped approximately 50%, and longevity was extended by many years. This is thought to be due to the symptomatic effects of levodopa, as no clear evidence suggests that levodopa stems the progressive nature of the disease.

The American Academy of Neurology notes that the following clinical features may help predict the rate of progression of Parkinson disease :
Older age at onset and initial rigidity/hypokinesia can be used to predict (1) a more rapid rate of motor progression in those with newly diagnosed Parkinson disease and (2) earlier development of cognitive decline and dementia; however, initially presenting with tremor may predict a more benign disease course and longer therapeutic benefit from levodopa
A faster rate of motor progression may also be predicted if the patient is male, has associated comorbidities, and has postural instability/gait difficulty (PIGD)
Older age at onset, dementia, and decreased responsiveness to dopaminergic therapy may predict earlier nursing home placement and decreased survival
Patient Education

Patients with Parkinson disease should be encouraged to participate in decision making regarding their condition. In addition, individuals and their caregivers should be provided with information that is appropriate for their disease state and expected or ongoing challenges. Psychosocial support and concerns should be addressed and/or referred to a social worker or psychologist as needed.

Prevention of falls should be discussed. The UK National Institute for Health and Clinical Excellence has several guidance documents including those for patients and caregivers.

Other issues that commonly need to be addressed at appropriate times in the disease course include cognitive decline, personality changes, depression, dysphagia, sleepiness and fatigue, and impulse control disorders. Additional information is also often needed for financial planning, insurance issues, disability application, and placement (assisted living facility, nursing home).