Category: Drugs and Disease

Higher doses independently linked to slower change in emphysema, especially among former smokers

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) might play an important role in the prevention and treatment of emphysema, according to a study published in the May 1 issue of the Annals of the American Thoracic Society.

Megha A. Parikh, from Columbia University in New York City, and colleagues recruited 4,472 patients ages 45 to 84 years from the general population. The authors examined whether ACE inhibitor and ARB dose is associated with progression of percent emphysema by computed tomography (CT).

The researchers found that 12 and 6 percent of participants used an ACE inhibitor and ARB at baseline, respectively. At baseline, the median percent emphysema was 3.0 percent; over a median of 9.3 years the rate of progression was 0.64 percent. There was an independent correlation for higher doses of ACE inhibitor or ARB with slower change in percent emphysema (P = 0.03). Over 10 years the predicted mean increase in emphysema among participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percent, compared with 0.66 percent for those who did not take ARBs or ACE inhibitors (P = 0.01). The greatest magnitude of findings was seen among former smokers (P < 0.001).

“In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers,” the authors write.

Data from trials show weight loss is associated with HbA1c reduction in dose-dependent manner

For overweight and obese adults with type 2 diabetes (T2D), weight loss is associated with a reduction in hemoglobin A1c (HbA1c) in a dose-dependent manner, according to a review published online April 18 in Diabetes, Obesity and Metabolism.

Anders Gummesson, M.D., from Sahlgrenska University Hospital in Gothenburg, Sweden, and colleagues conducted a systematic review of the literature to identify prospective trials of energy-reduced diets, obesity drugs, or bariatric surgery in adult overweight and obese patients with type 2 diabetes. The authors developed a linear model to describe the effect of weight reduction on HbA1c based on data from three to 24 months of follow-up. Data were included for 58 articles with 124 treatment groups and 17,204 adults.

The researchers identified a linear relationship between weight loss and HbA1c reduction; for each 1 kg of reduced body weight there was an estimated mean reduction of 0.1 percent in HbA1c for the overall population. Baseline HbA1c significantly affected the correlation between weight loss and HbA1c: for the same degree of weight loss, high HbA1c at baseline correlated with a greater reduction in HbA1c. There were also weight-loss-dependent reductions in diabetes medication.

“This summary of data from previous trials regarding the effect of weight reduction on HbA1c may be used to support the design and interpretation of future studies that aim to demonstrate the efficacy of weight loss interventions for T2D treatment,” the authors write.

Certain medications seem safer than others, but overall danger is low, researchers say

Use of macrolides, quinolones, tetracyclines, sulfonamides, and metronidazole during pregnancy may increase the risk of miscarriage, according to a study published in the May 1 issue of CMAJ, the journal of the Canadian Medical Association.

Anick Bérard, Ph.D., a professor at the University of Montreal’s Faculty of Pharmacy, and colleagues matched 8,702 cases of spontaneous abortion with 87,020 controls by gestational age and year of pregnancy. The researchers used data from women ages 15 to 45 who were covered by Quebec’s drug insurance plan.

The team found that 16.4 percent of the women who had miscarriages were exposed to antibiotics during early pregnancy, compared to 12.6 percent of the controls. Azithromycin and clarithromycin were linked to a 65 percent and two-fold increased risk of miscarriage, respectively. Norfloxacin was associated with more than a four-fold increased risk.

“After adjustment for potential confounders, use of macrolides (excluding erythromycin), quinolones, tetracyclines, sulfonamides, and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion,” the authors write. “Our findings may be of use to policymakers to update guidelines for the treatment of infections during pregnancy.”

Protective link particularly significant for hormone receptor-positive/HER2-negative cancer

Regularly taking low-dose aspirin appears to protect women from hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, according to a study published online May 1 in Breast Cancer Research. Christina Clarke, Ph.D., M.P.H., of the Cancer Prevention Institute of California in Fremont, and colleagues looked at the medication use of women enrolled in the ongoing California Teachers Study. That trial, begun in 1995, recruited 133,479 active and retired women teachers, administrators, and other public school professionals. In 2005, 57,164 participants answered questions about their use of aspirin and other medications, family history of cancer, use of hormone therapy, alcohol use, exercise, height, and weight. By 2013, 1,457 had developed invasive breast cancer. Overall, the researchers found that use of low-dose aspirin at least three times a week was associated with a 16 percent reduced risk of breast cancer. But the more significant finding was the risk reduction for developing hormone receptor-positive/HER2-negative cancer. The researchers found a protective link with use of low-dose aspirin, but not with regular-dose aspirin or other nonsteroidal anti-inflammatory drugs such as ibuprofen or acetaminophen. “Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at aspirin without differentiation by dose. This is the first report to suggest that the reduction in risk occurs for low-dose aspirin and not for regular-dose aspirin and only among women with the hormone receptor-positive/HER2-negative subtype,” the authors write. “This preliminary study builds on previous knowledge and further supports the need for formal cancer chemoprevention studies of low-dose aspirin.”

The millions of Americans prescribed short-term oral corticosteroids are taking a dose of risk along with their medication, according to a cohort study of more than 1.5 million adults.

Within 30 days of initiating these drugs, even at relatively low doses, users had a nearly twofold increased risk for fracture, a threefold increased risk for venous thromboembolism, and a fivefold increased risk for sepsis.

“Greater attention to initiating prescriptions of these drugs and monitoring for adverse events may potentially improve patient safety,” write Akbar K. Waljee, MD, an assistant professor of gastroenterology at the University of Michigan in Ann Arbor, and colleagues. They present their findings in an article published April 12 in the BMJ.

They found that more than one in five adults included in the Clinformatics DataMart, a large national database of commercial insurance claims, received prescriptions for short-term oral corticosteroids during the 3-year study, which ran from January 1, 2012, to December 31, 2014.

Although corticosteroids are among the most common cause for hospitalization for drug-related adverse events, and various specialties have long focused on optimizing their long-term use, the short-term risks associated with the drugs have been less carefully studied.

“Although physicians focus on the long-term consequences of steroids, they don’t tend to think about potential risks from short-term use,” said Dr Waljee in a university news release. “We see a clear signal of higher rates of these three serious events within 30 days of filling a prescription. We need to understand that steroids do have a real risk and that we may use them more than we really need to. This is so important because of how often these drugs are used.”

Of 1,548,945 adults aged 18 to 64 years included in the database, 327,452 (21.1%) received at least one outpatient prescription for short-term oral corticosteroids (30 or fewer days). The mean age of users was 45.5 years (standard deviation [SD], 11.6 years) compared with 44.1 years (SD, 12.2 years) for nonusers (P < .001). The median duration of use was 6 days (interquartile range, 6 – 12 days).

The six most common indications for the drugs were upper respiratory tract infections, spinal conditions, intervertebral disc disorders, allergies, bronchitis, and nonbronchitic lower respiratory tract disorders. Together, those indications accounted for about half of all prescriptions. The two most common physician specialties prescribing short-term oral corticosteroids were family medicine and general internal medicine.

Nearly half (46.9%) of recipients were prescribed a 6-day prepackaged methylprednisolone “dosepak,” which tapers the dose from highest to lowest. Dr Waljee noted in the news release that although individual oral steroid pills can cost less than a dollar each for a 7-day course, the prepackaged version may cost several times that and often initiates therapy with a higher high dose than may be necessary.

Use was more frequent among older patients, women, and white adults, with significant regional variation (all P < .001).

Within 30 days of drug initiation, there was an increase in incidence rate of the following: sepsis, with a rate ratio of 5.30 (95% CI, 3.80 – 7.41); venous thromboembolism, with a rate ratio of 3.33 (95% CI, 2.78 – 3.99); and fracture, with a rate ratio of 1.87 (95% CI, 1.69 – 2.07).

The increased risk persisted at prednisone equivalent doses of less than 20 mg/day, with an incidence rate ratio of 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture (all P < .001).

Rate ratios decreased during the following subsequent 31 to 90 days, however.

Although rare, hospitalizations were also more frequent in users than nonusers, with 0.05% of users admitted for sepsis compared with 0.02% of nonusers. For blood clots, the admission rate was 0.14% versus 0.09%, and for fractures, it was 0.51% vs 0.39%.

Dr Waljee and associates found it significant that the most frequent corticosteroid prescribers were not rheumatologists or other subspecialists experienced in treating inflammatory conditions long-term. “A substantial challenge to improving use of oral corticosteroids will be the diverse set of conditions and types of providers who administer these drugs in brief courses,” they write. “This raises the need for early general medical education of clinicians about the potential risks of oral corticosteroids and the evidence basis for their use, given that use may not be specific to a particular disease or specialty.”

On the basis of these findings, Dr Waljee recommended prescribing the smallest possible amount of corticosteroids for treating the condition in question. “If there are alternatives to steroids, we should be use those when possible,” he said in the release. “Steroids may work faster, but they aren’t as risk-free as you might think.”

BMJ. 2017;357:j1415

Infection Transmission in Dental Healthcare

Reports of transmission of infectious agents between patients and dental healthcare personnel (DHCP) in dental settings are rare. However, a recent Centers for Disease Control and Prevention (CDC) article in the Journal of the American Dental Association^[1] identified three published reports describing the transmission of hepatitis B virus and hepatitis C virus in dental settings since 2003. In addition, the Morbidity and Mortality Weekly Report^[2]—published April 8, 2016—described a 2015 outbreak of Mycobacterium abscessus infection at a pediatric dentistry practice.

In most cases, investigators have failed to link a specific lapse of infection prevention and control practice with a particular transmission. However, reported breakdowns in basic infection prevention practices included unsafe injection practices, failure to heat-sterilize dental handpieces between patients, failure to monitor (eg, conduct spore testing of) autoclaves, and failure to maintain dental unit waterlines. These reports highlight the need to improve understanding of and compliance with current infection prevention recommendations.

Key information and recommendations relevant to the above identified breaches include:

• When administering local anesthesia, use needles and anesthetic cartridges for one patient only and clean and heat-sterilize the dental cartridge syringe between patients.
• If multidose vials are used (such as for conscious sedation), dedicate multidose vials to a single patient whenever possible.
• If multidose vials must be used for more than one patient, restrict them to a centralized medication area and do not allow them to enter the treatment area.
• If a multidose vial enters the immediate patient treatment area, it should be dedicated for single-patient use and discarded immediately after use.
• Date multidose vials when first opened and discard within 28 days, unless the manufacturer specifies a shorter or longer date for discarding that opened vial.
• Clean and heat-sterilize all handpieces (high-speed and low-speed) and attachments that attach to air and waterlines (including motors) between patients unless they are single-use, disposable items. For handpieces that do not connect to air and waterlines, use US Food and Drug Administration–cleared devices and follow the validated manufacturer’s instructions for reprocessing.
• Monitor sterilizers at least weekly by using a biological indicator with a matching control (ie, biological indicator and control from same lot number). Results of biological monitoring should be recorded and sterilization monitoring records (mechanical, chemical, and biological) retained long enough to comply with state and local regulations.
• Ensure that all dental units use systems that treat water to meet drinking water standards (ie, ≤ 500 colony forming units/mL of heterotrophic water bacteria). Consult with the dental unit manufacturer for appropriate water maintenance methods and recommendations for monitoring dental water quality.

CDC Division of Oral Health

Chikungunya (pronunciation: \chik-en-gun-ye) virus is transmitted to people by mosquitoes. During the first week of infection, chikungunya virus can be found in the blood and passed from an infected person to a mosquito through mosquito bites. An infected mosquito can then spread the virus to other people. Outbreaks have occurred in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans.
In late 2013, chikungunya virus was found for the first time in the Americas on islands in the Caribbean. There is a risk that the virus will be imported to new areas by infected travelers. There is no vaccine to prevent or medicine to treat chikungunya virus infection. Travelers can protect themselves by preventing mosquito bites. When traveling to countries with chikungunya virus, use insect repellent, wear long sleeves and pants, and stay in places with air conditioning or that use window and door screens.

Clinical Signs & Symptoms
The majority of people infected with chikungunya virus become symptomatic. The incubation period is typically 3–7 days (range, 1–12 days). The disease is most often characterized by acute onset of fever (typically >39°C [102°F]) and polyarthralgia. Joint symptoms are usually bilateral and symmetric, and can be severe and debilitating. Other symptoms may include headache, myalgia, arthritis, conjunctivitis, nausea/vomiting, or maculopapular rash. Clinical laboratory findings can include lymphopenia, thrombocytopenia, elevated creatinine, and elevated hepatic transaminases.

Acute symptoms typically resolve within 7–10 days. Rare complications include uveitis, retinitis, myocarditis, hepatitis, nephritis, bullous skin lesions, hemorrhage, meningoencephalitis, myelitis, Guillain-Barré syndrome, and cranial nerve palsies. Persons at risk for severe disease include neonates exposed intrapartum, older adults (e.g., > 65 years), and persons with underlying medical conditions (e.g., hypertension, diabetes, or cardiovascular disease). Some patients might have relapse of rheumatologic symptoms (e.g., polyarthralgia, polyarthritis, tenosynovitis) in the months following acute illness. Studies report variable proportions of patients with persistent joint pains for months to years. Mortality is rare and occurs mostly in older adults.

Symptoms
Most people infected with chikungunya virus will develop some symptoms.
Symptoms usually begin 3–7 days after being bitten by an infected mosquito.
The most common symptoms are fever and joint pain.
Other symptoms may include headache, muscle pain, joint swelling, or rash.
Chikungunya disease does not often result in death, but the symptoms can be severe and disabling.
Most patients feel better within a week. In some people, the joint pain may persist for months.
People at risk for more severe disease include newborns infected around the time of birth, older adults (≥65 years), and people with medical conditions such as high blood pressure, diabetes, or heart disease.
Once a person has been infected, he or she is likely to be protected from future infections.

Diagnosis
Laboratory diagnosis is generally accomplished by testing serum or plasma to detect virus, viral nucleic acid, or virus-specific immunoglobulin (Ig) M and neutralizing antibodies. Viral culture may detect virus in the first 3 days of illness; however, chikungunya virus should be handled under biosafety level (BSL) 3 conditions. During the first 8 days of illness, chikungunya viral RNA can often be identified in serum. Chikungunya virus antibodies normally develop toward the end of the first week of illness. Therefore, to definitively rule out the diagnosis, convalescent-phase samples should be obtained from patients whose acute-phase samples test negative.

Treatment
There is no vaccine to prevent or medicine to treat chikungunya virus.

Treat the symptoms:
Get plenty of rest.
Drink fluids to prevent dehydration.
Paracetamol to reduce fever and pain.
Do not use aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS until dengue can be ruled out to reduce the risk of bleeding).

Prevention
No vaccine exists to prevent chikungunya virus infection or disease.
Prevent chikungunya virus infection by avoiding mosquito bites.
The mosquitoes that spread the chikungunya virus bite mostly during the daytime.
Protect from Mosquito Bites
Use air conditioning or window/door screens to keep mosquitoes outside. Use mosquito bed net.
Help reduce the number of mosquitoes outside home or hotel room by emptying standing water from containers such as flowerpots or buckets.
When weather permits, wear long-sleeved shirts and long pants.
Use insect repellents

The World Health Organization (WHO) endorsed the world’s first-ever vaccine Dengvaxia for dengue fever. Known as Dengvaxia, the vaccine is the product of two decades of research by French-based Sanofi Pasteur.

To date the vaccine has been approved in Mexico, Philippines, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand and Singapore.

The vaccine is given in three injections spaced out over one year. It is designed for those over the age of nine who have been previously exposed to the virus and is best suited for people living in endemic areas, as opposed to short-term travellers, according to Dr. Alain Bouckanooge, associate vice president of clinical research and development at Sanofi’s division in Thailand.

Studies have shown that overall, the vaccine is effective at reducing dengue by 60 per cent, and reducing severe dengue by 84 per cent.

Against the Den-1 and Den-2 strains – which account for three-quarters of the dengue cases in Singapore – the vaccine’s efficacy is 50 per cent and 40 per cent respectively, compared with 75 and 77 per cent for the other two strains.