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Foot wrap safer alternative to pharmaceuticals for treating RLS

3 Aug 2016

Use of a foot wrap to apply pressure on the abductor hallucis and flexor hallucis brevis muscles may be used as a potential therapeutic in the management of restless leg syndrome (RLS), improving the symptoms of moderate to severe primary RLS sans the negative effects associated with standard treatment agents, a study suggests.

“RLS or Willis-Ekbom disease, is a neurologic disorder causing unpleasant sensations and an urge to move the legs when at rest. Potent medications, such as opioids, central nervous system depressants, anticonvulsants, and dopamine agonists have been used to ease symptoms, each with adverse effects,” the investigators said.

Foot wrap, on the other hand, functions by applying targeted pressure on the muscles in the medial and plantar regions of the foot. It consists of a pressure pad that is held in place by an outer cloth, secured by hook and loop straps, which also serve as adjustable straps to regulate the amount of pressure. In 2013, the US Food and Drug Administration cleared the device as safe for RLS.

In the current study, the investigators evaluated the efficacy and safety of foot wrap in 30 patients (mean age 51.5 years; 73 percent female) with moderate to severe RLS symptoms. The wraps were worn on each foot for set periods intermittently over 8 weeks, as follows: baseline period without the wraps (days 1 to 7), initial treatment with the wraps (days 8 to 28), treatment interruption (days 29 to 35), and treatment resumption (days 36 to 56). Mean follow-up was 15.6 months. [J Am Osteopath Assoc 2016;116:440-450]

Primary outcome measure was mean change in the International Restless Legs Syndrome Study Group (IRLSSG) rating scale, from baseline to day 56. Secondary outcome measure was the Clinical Global Improvement Scale (CGIS) scores. Researchers performed a meta-analysis to compare the foot wrap findings with that of 3 previous studies reporting the effects of ropinirole vs placebo for primary RLS.

The foot wrap treatment arm showed a greater change in mean IRLSSG score compared with the ropinirole and placebo arms (17.22; p<0.001 vs 12 and 8.9, respectively; p<0.05). In the foot wrap arm, sleep disturbance severity decreased from moderate to mild (2.7 to 0.6), and sleep loss significantly diminished from 119.5 minutes to 22.1 minutes per night (p<0.001).

Similarly, CGIS scores improved significantly with the foot wrap versus ropinirole and placebo (90 percent [27/30] vs 63 percent [293/464] and 47 percent [218/467]; p<0.05).

There were reports of mild adverse effects in the foot wrap arm, such as pain and paraesthesia, which were attenuated by loosening the straps. Dopamine agonist treatment-related adverse effects, including augmentation, tolerance, rebound, somnolence, and nausea, did not occur with foot wraps.

The findings suggest that foot wrap “was almost twice as effective as historic placebo medication and 1.4 times as effective as ropinirole in lowering IRLSSG scores,” the investigators said.

They explained: “We believe that continued pressure on the abductor hallucis and flexor hallucis brevis muscles throughout the evening signals the brain to relax rather than contract the muscles, acting as a counter-stimulant. This theory represents a new and unique mechanism of action to suppress the symptoms of RLS. Pressure produced by the device on the muscles may also stimulate a dopamine release, similar to massage therapy or acupressure.”

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Overweight/Obesity Up Incidence of Hand, Hip, Knee Osteoarthritis

Aug. 3, 2016

Being overweight or obese increases incidence of OA, especially in the knee.

The incidence of hand, hip, and knee osteoarthritis (OA) increases with overweight and obesity, particularly in the knee, according to a study published in the August issue of Arthritis & Rheumatology.

Carlen Reyes, M.D., Ph.D., from Universitat Autònoma de Barcelona in Spain, and colleagues conducted a population-based cohort study using primary care records for subjects aged ≥40 years who were without a diagnosis of OA on Jan. 1, 2006, and had body mass index (BMI) data available. A total of 1,764,061 subjects were observed for a median follow-up of 4.45 years.

The researchers found that the incidence rates of knee, hip, and hand OA were 3.7, 1.7, and 2.6 per 1,000 person-years, respectively, for subjects in the normal-weight category, and 19.5, 3.8, and 4.0, respectively, for those with grade II obesity. Being overweight or obese versus normal weight increased the risk of OA at all three joint sites, especially at the knee. The risk of knee OA increased two-, 3.1-, and 4.7-fold with a status of overweight, grade I obesity, and grade II obesity, respectively.

“Being overweight or obese increases the risk of hand, hip, and knee OA, with the greatest risk in the knee, and this occurs on a dose-response gradient of increasing BMI,” the authors write.

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Third Dose of MMR Vaccine Can Help Control Mumps Outbreaks

Aug. 3, 2016

CDC advised third dose in recent outbreak with transmission despite high two-dose coverage.

A third dose of measles-mumps-rubella (MMR) vaccine is recommended in cases of mumps outbreak in which transmission is sustained despite high two-dose MMR coverage, according to research published in the July 29 issue of the U.S. Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

Justin P. Albertson, from the University of Illinois at Urbana-Champaign, and colleagues conducted an investigation into a confirmed mumps outbreak in 2015. They identified 317 cases of mumps during April 2015 to May 2016.

The researchers recommended a third MMR vaccine because of sustained transmission in a population with high two-dose coverage with MMR. The Advisory Committee on Immunization Practices did not formally recommend for or against use of a third dose. However, the CDC provided guidelines for use of a third dose as a control measure during outbreaks in a setting in which transmission is sustained despite high two-dose MMR coverage. The final case in this outbreak occurred in May 2016.

“Although evidence of its effectiveness is needed, a third dose of MMR vaccine may be considered as a control measure during mumps outbreaks occurring in settings in which persons are in close contact with one another, when transmission is sustained despite high two-dose MMR coverage, and when traditional control measures fail to slow transmission,” the authors write.

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Adlyxin (lixisenatide) for Treatment of Adults With Type 2 Diabetes

July 27, 2016

Sanofi announced today that the U.S. Food and Drug Administration (FDA) approved Adlyxin (lixisenatide), a once-daily mealtime GLP-1 receptor agonist injection indicated as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes.

The approval of Adlyxin was based on FDA review of results from the GetGoal clinical program and findings from the ELIXA trial, which successfully addressed the FDA’s request to demonstrate CV safety. The GetGoal clinical program, which included 13 clinical trials involving more than 5,000 adults with type 2 diabetes worldwide, evaluated the safety and efficacy of lixisenatide in adults with type 2 diabetes. All studies of the GetGoal program successfully met the primary efficacy endpoint of HbA1c reduction. The most common adverse events reported for Adlyxin included nausea, hypoglycemia and vomiting.

Adlyxin will be available in a disposable pre-filled pen in a single dose of 20 micrograms. Patients will also receive a disposable pre-filled pen in a single dose of 10 micrograms that they should initiate once daily for 14 days. On Day 15, patients will increase dosage to 20 micrograms once daily.

Adlyxin is approved under the proprietary name, Lyxumia® in more than 60 countries and marketed in over 40. Commercial launches include most EU countries, Japan, Brazil, Mexico and India. Adlyxin was in-licensed from Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL), www.zealandpharma.com.

About Adlyxin

Adlyxin is a once-daily glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise. GLP-1 is a peptide hormone that is released within minutes after eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate glucose-dependent insulin secretion by pancreatic beta cells. Adlyxin increases glucose-dependent insulin release, decreased glucagon secretion, and slows gastric emptying.

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First absorbable stent for coronary artery disease

July 5, 2016

The U.S. Food and Drug Administration today approved the first fully absorbable stent to treat coronary artery disease. The Absorb GT1 Bioresorbable Vascular Scaffold System (BVS), which releases the drug everolimus to limit the growth of scar tissue, is gradually absorbed by the body in approximately three years.

“The FDA’s approval of the Absorb GT1 BVS offers a new treatment option for individuals who are candidates for angioplasty, but would prefer an absorbable device rather than a permanent metallic coronary stent,” said Bram Zuckerman, M.D., director of the division of cardiovascular devices at the FDA’s Center for Devices and Radiological Health.

Coronary heart disease is responsible for about 370,000 deaths each year in the U.S., according to the National Heart, Lung, and Blood Institute. The condition develops when cholesterol-containing deposits build up and narrow the coronary arteries, decreasing blood flow to the heart. This can cause chest pain (angina), shortness of breath, fatigue or other heart disease symptoms. Doctors often treat coronary artery disease with a procedure called angioplasty to widen the artery using a metal stent. Scar tissue can form within the stent causing the artery to narrow again (restenosis). Drug-eluting stents temporarily release a drug, typically for a few months after stent placement, to combat the formation of scar tissue.

The Absorb GT1 BVS is manufactured from a biodegradable polymer called poly(L-lactide), which is similar to materials used in other types of absorbable medical devices, such as sutures. The device’s absorption by the body gradually eliminates the presence of foreign material in the artery once the stent is no longer needed. After absorption, there are only four very small platinum markers embedded in the walls of the artery, which help cardiologists identify where the Absorb GT1 BVS was originally placed.

In approving the Absorb GT1 BVS, the FDA evaluated data from a randomized trial of 2,008 patients, which compared the rate of major adverse cardiac events between the Absorb GT1 BVS and a drug-eluting metallic stent. After one year, the Absorb GT1 BVS group showed a major cardiac adverse event rate of 7.8 percent, which was clinically comparable to the rate of 6.1 percent observed in the control group. In addition, after one year, the rate of blood clots forming within the devices was 1.54 percent for the Absorb GT1 BVS and 0.74 percent rate for the control.

Possible adverse events that may be associated with the procedure to insert the Absorb GT1 BVS or with the Absorb GT1 BVS itself include allergic reactions to materials in the device or medications used during the procedure, allergic reaction to the drug everolimus, infection or irritation at the catheter insertion site, internal bleeding, the development of abnormal connections between arteries and veins, embolism, or other coronary artery complications that may require medical intervention and that could lead to death.

The Absorb GT1 BVS is contraindicated for patients who have a known hypersensitivity or allergy to everolimus or the materials used in the device, such as poly(L-lactide), poly(D,L-lactide), or platinum. It is also contraindicated for those who are not candidates for angioplasty, have sensitivity to contrast, or who cannot take long-term aspirin therapy along with other blood-thinning medications (antiplatelet agents).

The Absorb GT1 BVS is manufactured by Abbott Vascular in Santa Clara, California.

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FDA updates warnings for fluoroquinolone antibiotics

July 26, 2016

Limits use for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections.

The U.S. Food and Drug Administration today approved safety labeling changes for a class of antibiotics, called fluoroquinolones, to enhance warnings about their association with disabling and potentially permanent side effects and to limit their use in patients with less serious bacterial infections.

“Fluoroquinolones have risks and benefits that should be considered very carefully,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “It’s important that both health care providers and patients are aware of both the risks and benefits of fluoroquinolones and make an informed decision about their use.”

Fluoroquinolones are antibiotics that kill or stop the growth of bacteria. While these drugs are effective in treating serious bacterial infections, an FDA safety review found that both oral and injectable fluroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system. These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent.

Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated urinary tract infections, the FDA has determined that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options. For some serious bacterial infections, including anthrax, plague and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option.

FDA-approved fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin and gemifloxacin (Factive). The labeling changes include an updated Boxed Warning and revisions to the Warnings and Precautions section of the label about the risk of disabling and potentially irreversible adverse reactions that can occur together. The label also contains new limitation-of-use statements to reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections. The patient Medication Guide that is required to be given to the patient with each fluoroquinolone prescription describes the safety issues associated with these medicines.

In November 2015, an FDA Advisory Committee discussed the risks and benefits of fluoroquinolones for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections based on new safety information. The new information focused on two or more side effects occurring at the same time and causing the potential for irreversible impairment. The advisory committee concluded that the serious risks associated with the use of fluoroquinolones for these types of uncomplicated infections generally outweighed the benefits for patients with other treatment options.

Today’s action also follows a May 12, 2016, drug safety communication advising that fluoroquinolones should be reserved for these conditions only when there are no other options available due to potentially permanent, disabling side effects occurring together. The drug safety communication also announced the required labeling updates to reflect this new safety information.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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New medication for dry eye disease

July 12, 2016

The U.S. Food and Drug Administration approved Xiidra (lifitegrast ophthalmic solution) for the treatment of signs and symptoms of dry eye disease, on Monday, July 11, 2016. Xiidra is the first medication in a new class of drugs, called lymphocyte function-associated antigen 1 (LFA-1) antagonist, approved by the FDA for dry eye disease.

“Normal tear production is needed for clear vision and eye health,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a new treatment option for patients with dry eye disease.”

Dry eye disease includes a group of conditions in which the eye does not produce an adequate volume of tears or when the tears are not of the correct consistency. The chance of experiencing dry eye increases with age, affecting approximately five percent of the adult population age 30-40 and 10 to 15 percent of adults over age 65, and is more common among women. When severe and left untreated, this condition can lead to pain, ulcers or scars on the part of the eye called the cornea. Dry eye can make it more difficult to perform some activities, such as using a computer or reading for an extended period of time, and it can decrease tolerance for dry environments, such as the air inside an airplane.

The safety and efficacy of Xiidra was assessed in over a thousand patients, in four separate, randomized, controlled studies. These studies included patients 19–97 years of age, of which the majority were female (76 percent). Patients were randomized equally to receive either Xiidra eyedrops or placebo eyedrops, which were used twice a day for twelve weeks. The studies found that groups treated with Xiidra demonstrated more improvement in both the signs and the symptoms of eye dryness than the groups treated with placebo.

The most common side effects of Xiidra include eye irritation, discomfort or blurred vision and an unusual taste sensation (dysgeusia).

Dry eye disease does not routinely occur in children. Safety and efficacy in pediatric patients below the age of 17 years has not been studied.

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Empagliflozin offers clear CV benefits in patients with T2DM

16 Jul 2016

Empagliflozin has high SGLT2 selectivity

“SGLT2 inhibitors such as empagliflozin offer a novel, insulin-independent approach for achieving glycaemic control,” said Lee.

He noted that glycosuria is absent under normal physiological circumstances because glucose from the glomerular filtrate is reabsorbed by the kidneys. SGLT2 is a transporter that facilitates this process, and it is associated with approximately 90 percent of glucose reabsorption in the kidneys. Thus, glycaemic control can be achieved by halting renal glucose reabsorption through SGLT2 inhibition.

“Of the SGLT2 inhibitors currently available for T2DM treatment, empagliflozin has a higher SGLT2 selectivity than dapagliflozin and canagliflozin,” said Lee. (Table) [Jardiance Product Information; Forxiga Product Information;  Invokana Product Information; Diabetes Obes Metab 2015;17:188-197]

 

Empagliflozin has been shown to produce clinically meaningful HbA1c reduction in patients on different background therapies for glycaemic control, including those with suboptimal response to metformin, metformin plus sulphonylurea, basal insulin, and multiple insulin injections. [Diabetes Care2013;36:3396-3404; Diabetes Care 2014;37:1650-1659; Diabetes Obes Metab 2015;17:936-948;Diabetes Care 2014;37:1815-1823]

“Despite the availability of a variety of effective glucose-lowering agents for T2DM patients, many patients have other comorbidities and cardiovascular [CV] risk factors that cannot be adequately addressed with glucose control alone. We therefore need to look for agents that may also address some of these CV risk factors,” suggested Lee.

Optimal management of dysglycaemia

“Optimal management of patients with dysglycaemia requires more than lifestyle modification and glycaemic control,” said Rydén. “Their blood pressure and lipid levels also need to be adequately controlled and platelets stabilized. Ideally, any glucose-lowering agent for these patients should affect as many of these mechanisms as possible.”

“It is well known that elevation in blood glucose levels causes vascular damages. Therefore, normalization of blood glucose levels should theoretically be CV protective,” he noted. “However, trials of most existing therapies have generally been disappointing in this respect.

“There has been plenty of controversy over whether glucose-lowering therapies have adverse or beneficial effects on CV outcomes among patients with T2DM, but much seems to depend on the class of agent used. Recently, the SGLT2 inhibitor empagliflozin has been shown to have beneficial CV effects when administered as an add-on therapy to standard care,” remarked Rydén.

Empagliflozin reduces adverse CV outcomes

Empagliflozin has been proven to reduce the risk of adverse CV outcomes. In the ground-breaking EMPA-REG OUTCOME (Empagliflozin-Renal Excretion of Glucose Outcome) study, 7,020 adult patients with T2DM and established CVD were randomized to receive placebo (n=2,333), empagliflozin 10 mg/day (n=2,345) or empagliflozin 25 mg/day (n=2,342) in addition to standard care. [N Engl J Med2015;373:2117-2128; Eur Heart J 2016;37:1526-1534]

“As expected, the researchers observed a relatively modest decrease in HbA1c levels, small reductions in systolic blood pressure and weight, and slightly elevated LDL-cholesterol levels. However, the most surprising and impressive finding was the 14 percent reduction in the composite primary endpoint of CV death, non-fatal MI or stroke,” said Rydén.

The study also showed that empagliflozin significantly reduced the risk of hospitalization for heart failure, CV mortality and all-cause mortality even among high-risk patients with heart failure at baseline. (Figure 2) [Eur Heart J 2016;37:1526-1534]

 

Conclusion

“The 34 percent reduction in first hospitalization for heart failure or CV death and the 39 percent reduction in all-cause mortality with empagliflozin are striking, particularly since the benefits were clearly observed in patients with and without heart failure at baseline,” said Rydén.

“A hypothetical mechanism to explain these findings is the reduction in myocardial preload and afterload due to volume and sodium depletion by empagliflozin. What is interesting is that we are now talking about a glucose-lowering drug that has completely different capacities. The drug is available in the market for treating patients of the kind investigated in the EMPA-REG OUTCOME trial. Moreover, the results open a new field of research, which may offer further hope for patients with T2DM,” concluded Rydén.

 

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Empagliflozin delays kidney disease and dialysis in diabetes outcome trial

20 Jun 2016

Empagliflozin significantly delays the progression of kidney disease and reduces renal events in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular (CV) risk, new data from the EMPA-REG OUTCOME (Empagliflozin-Renal Excretion of Glucose Outcome) trial have shown.

A 39 percent reduction in risk of incident or worsening nephropathy was demonstrated with empagliflozin vs placebo (p<0.001) in a trial population with one-third of patients having prevalent kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2 and/or macroalbuminuria) at baseline. [N Engl J Med 2016; doi: 10.1056/NEJMoa1515920]

“Both the 10 mg and 25 mg doses of empagliflozin demonstrated the same effect on nephropathy,” reported lead author Professor Christoph Wanner of the Wurzburg University Clinic, Wurzburg, Germany, at the American Diabetes Association’s 76th Scientific Sessions in New Orleans, LA, US. “The effect was consistent in different subgroups of patients.”

While empagliflozin’s effect on nephropathy was driven by a 38 percent risk reduction in new-onset macroalbuminuria (p<0.0001), the results also showed a 55 percent reduced risk of initiation of dialysis (p=0.049) and a 44 percent reduced risk of doubling of serum creatinine (p=0.0009) with empagliflozin vs placebo.

“When the ‘hard’ renal outcomes of doubling of serum creatinine, initiation of dialysis and death due to renal disease were analyzed together, a 46 percent risk reduction was seen with empagliflozin vs placebo [p<0.001], with the curves beginning to diverge at 1.5 years,” said Wanner.

The researchers also analyzed renal outcomes in patients with prevalent kidney disease at baseline. In these patients, empagliflozin reduced the risk of incident or worsening nephropathy by 42 percent (p<0.001).

“eGFR remained stable in the empagliflozin arms throughout the study, but a natural progression was seen in the placebo arm,” said Wanner.

“The adjusted mean difference in eGFR change from baseline with empagliflozin vs placebo was 4.7 mL/min/1.73m2 when patients were followed up at a median of 34 days after their last on-treatment eGFR measurement,” he continued. “As nephrologists, we all know what 4.7 mL/min/1.73m2 means in pushing dialysis further down the road.”

“The safety and tolerability of empagliflozin in patients with chronic kidney disease at baseline were similar to that in the overall trial population,” added Wanner. “Acute renal failure and acute kidney injury occurred at lower rates in the empagliflozin vs placebo arm.”

The EMPA-REG OUTCOME trial was conducted in 7,020 T2DM patients with established CV disease. Patients were randomized to receive empagliflozin 10 mg or 25 mg daily or placebo, and assessed for the primary outcome of major adverse CV events (CV mortality, nonfatal MI, nonfatal stroke). Assessment of renal outcomes was a pre-specified objective, with incident or worsening nephropathy defined as progression to macroalbuminuria, doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73m2, initiation of dialysis, or death due to renal disease.

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Poor hydration linked to higher BMI, obesity

20 Jul 2016

Lack of hydration is associated with a higher obesity risk, according to a recent US study.

Individuals with inadequate hydration were more likely to be obese (odds ratio [OR], 1.59, 95 percent confidence interval [CI], 1.35-1.88; p<0.001) than those who with adequate hydration. Inadequate hydration was also linked to higher body mass index (BMI; 1.32 kg/m2 higher than adequately hydrated individuals, 95 percent CI, 0.85-1.79; p<0.001). [Ann Fam Med 2016;14:320-324]

“[Findings of this study] highlight a novel relationship between hydration and BMI that may have important clinical implications,” said the authors. “[The relationship between hydration, BMI and obesity] suggests that water, an essential nutrient, may deserve greater focus in weight management research and clinical strategies,” they said.

Using data from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2012, researchers from the University of Michigan, Ann Arbor, Michigan, US recruited 9,528 adults (aged 18-64 years) to identify a link between inadequate hydration and BMI or obesity. Urine osmolality was utilized as a marker of hydration; almost 33 percent of the participants did not have adequate hydration (urine osmolality ≥800 mOsm/kg).

According to the authors, adequate hydration is not included in many treatment guidelines for weight management. “Obese individuals have higher water needs than nonobese individuals,” they said, suggesting that clinicians who may not be aware of the difference in water requirements between individuals with higher and lower BMIs may not be advising their obese patients accurately.

The authors cautioned that due to the cross-sectional nature of the study, causality and directionality could not be established, and that one-time measurement of urine osmolality may not necessarily indicate the participants’ usual hydration levels.