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Research Briefs August 2016

Health Care Practitioners and the HPV Vaccine

The human papillomavirus (HPV) vaccine is known to reduce the incidence of infection—but actual vaccination rates continue to fall “well below the national goal of 80%,” according to researchers from the University of Washington, Harvard University, and the University of Minnesota. One of the main barriers, they say, is that many health care practitioners (HCPs) don’t understand or don’t accept the guidelines.

In two surveys, the researchers questioned HCPs in Minnesota and Washington on their views of the timeline (real or imagined) for vaccinating adolescents. In the first, the researchers conducted semistructured, face-to-face interviews with 27 physicians, nurse practitioners, and physician assistants in Minneapolis and St. Paul. The interviews included two questions: “How do you counsel patients and their parents about HPV vaccine?” and “How do you discuss the vaccine with a parent who might be hesitant to get their son or daughter vaccinated against HPV?” In the Washington study, the researchers held telephone interviews with 17 primary care physicians, also asking them: “At what point do you worry that your patients won’t complete the HPV vaccine series?”

In general, the HCPs felt there was an “age gradient,” the researchers found, not only for allowable vaccination but timely vaccination. The Centers for Disease Control and Prevention recommends age 11 or 12 years to begin, but to the respondents, 12 years was not a hard-and-fast rule. In fact, they tended to view increasing age as a “gradually pressing prompt” toward recommending the vaccine. Age 16 was the earliest age at which respondents reported feeling any urgency to initiate or complete the series. Surprisingly, some reported not feeling any urgency until their patients were in their 20s. One HCP said, “You’re supposed to be able to finish it anytime, I think.” Another said, “I delay pretty much everybody. To me, it’s not a problem.”

They mostly guided their decisions about when to broach the topic according to whether they thought their patients would have consistent access to care or whether they were likely to be sexually active. Many reported a relaxed approach for younger patients because they “knew” they’d see them again.

Another reason some HCPs favored a nonurgent attitude was that they wanted to build long-term trust with the parents. So they opted to give less strong recommendations to give parents “time to think about it.”

HCP recommendation of the vaccine is the “strongest, most consistent influence on parents’ decisions” about vaccination, the researchers say. But research suggests that parents prefer clear, unambiguous messages that HPV vaccination is important. ”Softer or deferred” HPV advice, the authors warn, may actually undermine vaccine recommendations.

Source: Preventive Medicine Reports, May 2016

Alcohol and Melanoma

Alcohol is helpful or harmful, depending on what you’re studying. But ethanol and the acetaldehyde associated with alcohol consumption are classified as carcinogens. Moreover, although ethanol’s “carcinogenic ability” is relatively weak, it’s still more harmful than other carcinogens in alcoholic beverages.

The risk depends a lot on how much the drinker drinks. Heavy drinkers have higher risks of cancer compared with nondrinkers and occasional drinkers. In a review of the literature, researchers from Sun Yat-Sen University in Hong Kong found that risks for heavy drinkers were highest for oral and pharyngeal cancer, esophageal squamous cell carcinoma, laryngeal, colorectal, and breast cancer, all of which had a clear dose–response relationship.

The researchers say that, while opinions about the association between total alcohol consumption and risks of skin cancer were controversial, “evidence agreed” on the fact that a higher current intake of certain alcoholic beverages (white wine and spirits) increased the risks of both melanoma and nonmelanoma skin cancer.

Both in vivo and in vitro studies have linked regular and moderate consumption of wine, especially red wine, to lower risk of cancer. Polyphenols, which may have chemoprotective benefits, are higher in red than in white wine. Recent studies, the researchers note, suggest that the efficacy of red wine on carcinogenesis may be due to “synergistic interaction” between bioactive polyphenols.

The deleterious impact of alcohol on skin health may also function through reduced concentration of antioxidants, the researchers say. They point to a recent study that found alcohol consumption significantly reduced the carotenoid concentration in the skin and the minimal erythema dose.

Source: International Journal of Environmental Research and Public Health, May 2016

Legionnaires’ Disease: An Ever-Growing Risk

In 1976, several thousand members of the American Legion were celebrating the Bicentennial in Philadelphia. Many were staying at the Bellevue-Stratford Hotel. Within a week of the convention, more than 182 attendees, mostly men, had been hospitalized with tiredness, chest pains, congestion, and fever, and 29 had died.

It wasn’t until a year later that the deadly bacterium infecting them all was identified. Named Legionella pneumophila (although it was also responsible for earlier outbreaks), it had been breeding in the hotel’s cooling towers. An important clue, overlooked early on, was that even people simply walking by the hotel got sick.

Although that outbreak led to changes in how water management and climate control systems are monitored, the bacterium still takes about 5,000 lives a year. According to the Centers for Disease Control and Prevention (CDC), between 2000 and 2014, reported cases of legionellosis, which comprises both Legionnaires’ disease and a milder form, Pontiac fever, jumped 286%.

The data come from 27 field investigations of outbreaks, involving 415 cases. Of those, health care-associated outbreaks accounted for 57%. Although 44% of the cases were travel related, the health care-related outbreaks resulted in more deaths.

The CDC-investigated outbreak sources all had at least one deficiency, and half had deficiencies in more than two categories. Most cases were linked to process failures, such as contaminated potable water, and human error.

The infection is fatal for about one in 10 people. Those at highest risk are people more than 50 years old, smokers, and those with chronic lung disease, weakened immune systems, or other underlying medical conditions.

Widespread use of effective water management programs, the CDC advises, in addition to early diagnosis, might reduce the number and size of Legionnaires’ disease outbreaks.

Sources: CDC, June 2016; and Legionella: Molecular Microbiology, 2008

The Head and Heart Connection

Migraine has been linked consistently to the risk of stroke but not as clearly to other cardiovascular diseases. One reason is that migraine tends to peak in midlife, whereas cardio vascular events increase “exponentially” with age, say researchers from Brigham and Women’s Hospital and Chan School of Public Health in Boston and Washington University in St. Louis. It takes a long—really long—follow-up to observe any associations. Luckily, the Nurses’ Health Study II, one of the longest-running studies around, is more than 20 years old, giving the researchers needed scope. What they found was that migraine boosted the risk of cardiovascular events by 50%.

Of the 115,541 women in the study, 17,531 reported a physician’s diagnosis of migraine at baseline in 1989. Another 6,389 women reported a diagnosis of migraine on subsequent questionnaires. Women with migraine were more likely to have cardiovascular risk factors, such as hypertension, high cholesterol, a family history of myocardial infarction (MI), and a body mass index of 30 or above. They were also more likely to smoke and use aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs.

During follow-up, there were 1,329 major cardiovascular disease events, including MIs, strokes, and angina/coronary revascularization procedures; 223 women died. Those with migraine had a hazard ratio of 1.50 for developing major cardiovascular disease. The highest estimates were for stroke and angina/coronary revascularization. The associations between migraine and cardiovascular disease outcomes were not modified by age, postmenopausal hormone use, current contraceptive use, current smoking, or hypertension.

In the Women’s Health Study, migraine was associated with an increased risk of major cardiovascular disease events, but only for migraine with aura. Information on aura wasn’t available from the Nurses’ Health Study.

The researchers suggest evaluating women with migraine for their cardiovascular risk.

Source: BMJ, May 2016

Comparing Pneumococcal Vaccines

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for immunocompromised adults at risk for invasive pneumococcal diseases. But the booster doses reportedly can cause “hyporesponsiveness,” making it less suitable for some human immunodeficiency virus (HIV)-infected patients, say researchers at Catholic University of the Sacred Heart, University of Siena, University Division of Infectious Diseases, and University of Milano-Bicocca in Italy. They cite studies that have found humoral response to PPSV23 is weaker in HIV-infected adults and that patients with acquired immune deficiency syndrome are not protected.

Protein-conjugated pneumococcal vaccines (PCVs), both seven-valent and 13-valent, may prime the immune system for better, faster responses to booster doses, the researchers say, and could be an optimal primary prophylaxis strategy for HIV-infected patients. But to the best of their knowledge, data regarding the effectiveness of PCV13 in HIV-positive adults are still “scanty,” and no studies have directly compared the immunogenicity of PCV13 with PPSV23 in those patients.

The researchers conducted two parallel studies of 100 HIV-infected adult outpatients who had never been vaccinated with any pneumococcal vaccine. In the first, 50 patients were given two doses of PCV13 eight weeks apart; in the second, patients were given their first routine vaccination with PPSV23. A third group of 100 HIV-negative adults who received no vaccination was used for comparison.

After immunization, immunoglobulin G (IgG) titers significantly increased in both study groups at each time point compared with baseline, although response to serotype 3 was blunted in the first group. Antibody titers for each antigen did not differ between the groups at week 48. Seroprotection and seroconversion to all serotypes were comparable.

Over time, the researchers observed a “marked decrease” in IgG levels with both vaccines.

Both vaccines were safe and well tolerated; no relevant adverse reactions were seen in either group. No HIV-infected patients developed Streptococcus pneumoniae infection during the follow-up.

Source: PLOS One, June 2016

Follow-Up Findings From ACCORD

Intensive control of blood sugar levels can cut the risk of diabetic retinopathy in half, according to a follow-up study to the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Eye Study.

The finding, from the ACCORD Follow-on Eye Study (ACCORDION), “sends a powerful message to people with type-2 diabetes who worry about losing vision,” said Emily Chew, MD, Deputy Director of the National Eye Institute Division of Epidemiology and Clinical Applications and lead author of the study report.

ACCORDION is an assessment of diabetic retinopathy progression in 1,310 people who participated in ACCORD. That study tested three treatment strategies to reduce the risk of cardiovascular disease in people with long-standing type-2 diabetes: maintaining near-normal blood sugar levels (intensive control), improving blood lipid levels, and lowering blood pressure.

ACCORD, however, was discontinued at 3.5 years due to an increase in death among participants in the intensive glycemic control group. (The increased mortality, which was due to a range of causes, was seen in both the intensive and standard groups.) From the data they had, the researchers found tight control reduced glycemia to an average of 6.4% HbA1C, compared with 7.7% among those in the standard control group. It did not cut the risk of cardiovascular disease, but it had cut retinopathy progression by about one-third when the study abruptly ended.

The follow-up study reassessed diabetic retinopathy four years after the intensive control portion of ACCORD had ended, eight years after enrollment. Average HbA1C was nearly the same. Diabetic retinopathy, however, had advanced in only 5.8% of participants in the intensive group, compared with 12.7% of the standard treatment group.

The continuing beneficial effects—an approximately 50% reduction in risk of further retinopathy progression—are attributed to “metabolic memory,” a phenomenon also known as the “legacy effect.” Similar effects have been seen in two other large, long studies: the 10-year Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Project.

Sources: National Institutes of Health, June 13, 2016; and Medscape, August 20, 2010

Standard Versus Intensive Emergency Stroke Treatment

Standard and intensive blood pressure treatments are equally effective in emergency treatment of acute intracerebral hemorrhage, according to a study funded by the National Institute of Neurological Disorders and Stroke. That is, reducing systolic blood pressure rapidly to 140–179 mm Hg worked as well as reducing it to 110–139 mm Hg.

“For decades, doctors wondered whether intensive blood pressure management was more effective than standard treatment for controlling intracerebral hemorrhage,” says principal investigator Adnan Qureshi, MD, Professor of Neurology, Neurosurgery, and Radiology at the University of Minnesota’s Zeenat Qureshi Stroke Research Center. “Our results may help patients and their doctors make better treatment decisions.”

In the 110-site international study, 1,000 patients were treated within 4.5 hours of a stroke. Half were assigned to intensive treatment and half to standard treatment. Brain scans taken 24 hours after treatment showed no difference in the rates of hemorrhage growth between the two groups. In fact, the study was stopped after enrolling 1,000 patients rather than 1,280 because the researchers found no differences.

Moreover, after 90 days, the rate of death or severe disability was about 38% in both groups—a number much lower than the expected 60%. Patients in the intensive treatment group had a slightly higher rate of serious adverse events in the 90 days post-stroke, but also at lower levels than expected. The researchers say that may be because more than half of the enrolled patients had had mild strokes and had a better chance of good results.

The findings suggest that intensive reduction in the systolic blood pressure level does not provide “an incremental clinical benefit,” the researchers say. Dr. Qureshi adds, “Rapidly lowering blood pressure to normal levels may further damage the brain. The levels we used are tolerable for emergencies. Normal levels can be safely obtained gradually.”

Sources: National Institutes of Health, June 8, 2016; and New England Journal of Medicine, June 2016