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Gallbladder removal tied to increased risk of peptic ulcers

9 Aug 2016

Cholecystectomy potentially increases the risk of subsequent peptic ulcers, according to a population-based study from Taiwan.

Surgical removal of the gallbladder is the gold standard for treating symptomatic gallstones. Despite this, a good number of patients (up to 47 percent) remains dissatisfied after the procedure. The dissatisfaction is frequently attributed to postcholecystectomy syndrome (PCS). Evidence shows that cholecystectomy promotes gastritis, which contributes to PCS.

To investigate the subsequent risk of peptic ulcers after cholecystectomy, the researchers examined the medical records of 5,209 patients who underwent cholecystectomy and received a discharge diagnosis of gallstone in comparison with 15,627 matched controls. Follow-up period was 5 years. Geographic location, hypertension, hyperlipidaemia, diabetes, CHD, obesity, alcohol abuse/alcohol dependence syndrome, and tobacco use disorder were included in the analysis as confounding factors.

Peptic ulcers developed in 9.76 percent of patients overall, with the prevalence being higher in the surgery than the control group (674 [12.94 percent] vs 1,359 [8.7 percent]; p<0.001). The likelihood of subsequent diagnosis of peptic ulcers was 2.34-fold (95 percent CI, 1.98 to 2.77) higher at 1 year, 1.84-fold (1.63 to 2.06) higher at 3 years, and 1.56-fold (1.41 to 1.72) higher at 5 years for patients who underwent cholecystectomy than for patients who did not. [Sci Rep 2016;doi:10.1038/srep30702]

On further analysis, after controlling for confounders and excluding cholecystectomy patients who died during the follow-up, the 5-year risk of developing peptic ulcers was attenuated (hazard ratio [HR], 1.48; 1.34 to 1.64). Patients in the surgery group were 1.70 times (1.44 to 1.99) and 1.71 times (1.36 to 2.15) as likely as controls to develop gastric and duodenal ulcers, respectively. Overall, the risk of peptic ulcers, regardless of the type, was higher in the surgery than in the control group.

“The mechanisms underlying the relationship between a cholecystectomy and peptic ulcers remain unclear. One possible explanation could be that [duodenogastric reflux (DRG)], which damages the gastric mucosa by bile acids and pancreatic phospholipase A2, leads to peptic ulcers. In addition, some animal studies demonstrated that DGR suppresses somatostatin concentrations and increases intragastric gastrin and acid secretion,” researchers explained.

As the previous studies suggested, DGR may play a role in the pathogenesis of gastric and duodenal ulcers, in addition to the altered antroduodenal motility and delayed gastric emptying after a cholecystectomy, researchers said, adding that H. pylori is also considered an important risk factor in peptic ulcers.

The current study is limited by the absence of information on H. pylori in gastric biopsies, as well as relevant records on data for laboratory examination, biochemical examination, or diagnostic imaging. The researchers also mentioned that physicians do not routinely biopsy the gastric mucosa to identify bile reflux gastritis in Taiwan, preventing them from identifying the pathogenesis of cholecystitis.

“Despite the aforementioned limitations, this study demonstrated a relationship between a cholecystectomy and a subsequent diagnosis of peptic ulcers,” they said.

“We suggest that clinicians be alert and suspect peptic ulcers with persistent epigastric pain or dyspepsia in patients with a prior cholecystectomy.”

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Mesoblast cell treatment shows promise for rheumatoid arthritis

11 Aug 2016

Mesoblast Ltd has announced that data from a mid-stage trial for its experimental stem-cell therapy indicated that the therapy significantly alleviated symptoms and disease activity in rheumatoid arthritis (RA) patients who have stopped responding to commercially available biotech drugs. The findings hold numerous implications in the development of new, effective therapeutic approaches to rheumatoid arthritis.

A new method of combating RA

The symptoms and progression of RA are caused by pro-inflammatory white blood cells and activated T cells of the immune system. These trigger multiple pro-inflammatory cytokine pathways; that is, they activate many kinds of small proteins which signal to the cells to become inflamed. In other words, there is more than one way to transmit the message to the cells to get inflamed.

Existing therapies each target one way of transmitting the ‘inflammation message’ by inhibiting one type of protein, but none target more than one at the same time. Mesoblast’s treatment, on the other hand, inhibits multiple types of proteins that cause inflammation. Therefore, the patient experiences significant relief from the symptoms.

Hope for those who stopped responding to conventional drugs

Treatment with the Melbourne-based company involved the intravenous delivery of MPC-300-IV, a tier 1 product candidate consisting of 300 million Mesenchymal Precursor Cells (MPCs). The results of their 48-patient, 12-week Phase 2 trial have deemed the treatment to be well-tolerated with no serious side-effects nor any infusion-related accidents.

ACR is a scale to measure change in symptoms of RA. If patients experience a 20% relief of RA symptoms, the trial is said to have achieved ACR20. In patients who had previously been treated with at least one biologic drug, ACR20 was achieved by 55% of those who had received an infusion of 2 million cells per kilogram of their weight. In patients who had received treatment from at least one biologic drug without the infusion, only 33% achieved ACR20.

There is a term used to refer to a higher degree of improvement, ACR70, when patients report a 70% relief from RA. This was achieved by 36% after a single infusion of the Mesoblast treatment, compared to the placebo group which obviously showed no improvement. The biotechnology company also claims that the cell therapy improved patients’ physical function and reduced overall disease activity.

According to a statement made by Dr Allan Gibofsky, a rheumatologist at the Hospital for Special Surgery, New York, Mesoblast’s cell infusion therapy has ‘the potential to fill the major unmet medical need’ for patients that gain no benefit from popular biological treatments. The effects of new treatment methods for RA must be twofold – alleviating pain from RA and stopping the disease from getting worse simultaneously.

 

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Guidelines on treatment and prevention of UTIs in children

1 Aug 2016

Urinary tract infections (UTIs) occur in 1 percent of boys and 3 percent of girls, with a 30 to 50 percent chance of recurrence, according to the AAUS Guidelines for UTIs in Children presented at the 14th Urological Association for Asia Congress in Singapore.

In addition, UTI is also associated with significant morbidities, including renal scar, hypertension, and chronic kidney disease, said Shang-Jen Chang from the Department of Urology at Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation in Taiwan.

UTIs in children are classified according to site (cystitis and pyelonephritis), episode (first infection and recurrent infection), severity (simple UTI and severe UTI), symptom (asymptomatic bacteriuria and symptomatic bacteriuria), and complicating factor (uncomplicated UTI and complicated UTI).

UTI diagnosis requires both positive urine culture and urinalysis that suggests infection, said Chang.

In treating UTI, the appropriate antibiotics should be given immediately after urine specimen for culture has been obtained; final antibiotic choice should be adjusted to the narrowest spectrum antibiotic when susceptibility result is available; and the choice of empirical antibiotic agents is guided by the pathogen and the local resistance patterns.

“For children with febrile UTI, the total course of antibiotic therapy should be 7 to 14 days,” said Chang, adding that “[p]rompt treatment of a febrile UTI is important to eradicate the acute infection, to prevent bacteraemia, to improve the clinical condition, and … to reduce the likelihood of renal damage.”

He also noted that antibiotics prophylaxis may be considered to prevent recurrent UTI in infants and children with or without vesicoureteral reflux (VUR) after a first UTI, but that its benefits must be weighed against the risk of antimicrobial resistance with future infections.

For children with febrile UTI, renal and bladder ultrasonography (RBUS) should be regularly conducted as soon as possible, said Chang, before adding that top-down or bottom-up approach is recommended for VUR diagnosis.

To prevent UTI in infants and children, Chang recommends breast feeding, as well as the consumption of probiotics, cranberry and related products.

Circumcision

The risk of febrile UTI in males and breakthrough febrile UTI in males with VUR may be diminished by circumcision, according to the guidelines, but that it should only be performed if the practice is accepted by the general population.

“In countries where childhood circumcision is rarely performed, other measures for febrile UTI/VUR should be the preferred choice,” it said.

 

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Opioid use potentially life-threatening for elderly COPD patients

5 Aug 2016

Initiation of opioid use in elderly patients with chronic obstructive pulmonary disease (COPD) more than doubled the risk of death from respiratory-related complications compared with non-opioid users, according to a retrospective population-based cohort study in Canada.

“The fact that incident opioids are frequently initiated in older adults with COPD makes these results particularly worrisome,” the researchers said. “Our findings suggest that a careful, individualized approach needs to be taken when administering opioids to older adults with COPD, given the potential for adverse respiratory outcomes.”

“These data raise concerns regarding the degree and manner with which opioids are used among vulnerable older adults with COPD,” said study authors Dr. Nicholas Vozoris from the Division of Respirology at the Department of Medicine of St. Michael’s Hospital in Ontario, Canada, and Dr. Denis O’Donnell of the Department of Medicine at Queen’s University in Ontario, Canada.

These findings showed that adverse outcomes could also develop in new lower-dose opioid users (≤30 mg morphine equivalents per day) and not limited to higher-dose opioid users as suggested in previous studies, the authors added.

When comparing the subgroup of patients using opioid-only medication with controls, new opioid users had a higher risk of outpatient exacerbations (p<0.0001).

The subgroup of new opioid-only users were also more likely to visit the emergency department or be hospitalized for COPD or pneumonia, or die from COPD or pneumonia or any other cause compared with controls (all p<0.0001).

Opioid-only agents usually contain more potent opioids like codeine and were indicated at a higher dose than opioid/non-opioid combination therapy, which might explain the difference in exacerbation risk in the subgroup analysis, the authors said.

“I almost never use opioids for my COPD patients. I would think that opioid-containing medication may be used to suppress cough or try to relieve the sensation of dyspnoea in these patients [in the study],” said Dr. Ong Kian Chung, a consultant respiratory specialist from the KC Ong Chest & Medical Clinic at Mount Elizabeth Medical Centre, Singapore, who was unaffiliated with the study.

“I would be cautious if the patients are very frail, elderly, already requiring oxygen supplementation and/or non-invasive ventilatory support,” he said.

For such vulnerable groups of patients, antihistamines, mucolytics or dextromethophan can be used to manage cough, while long-acting bronchodilators such as methylxanthines can be used for chronic dyspnoea, and steroids for COPD exacerbation, suggested Ong.

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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.