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Research Briefs November 2018

Imiquimod To Enhance Flu Vaccine Effectiveness

Can a cream help a flu vaccine work better? In a phase 1 clinical trial, researchers at Baylor College of Medicine are testing whether imiquimod cream—commonly used to treat genital warts and some skin cancers—can boost the immune response to an H5N1 flu vaccine. Studies have shown imiquimod generates significantly more robust immune responses.

Participants in the Vaccine and Treatment Evaluation Units trial will be given two intradermal doses of an H5N1 vaccine, 21 days apart. In one group, participants will have Aldara (imiquimod cream) applied to their upper arm before each vaccination; in the control group, a placebo cream will be applied.

Participants will return at regular intervals over seven months to have blood drawn; they’ll also keep diaries to record symptoms.

The first participant was vaccinated in June. Early results are expected by the end of the year.

Source: NIH, September 2018

Small Daily Steps Can Keep Heart Attacks at Bay

Despite being largely preventable, heart attacks, strokes, heart failure, and related conditions caused 2.2 million hospitalizations and 415,000 deaths in 2016, according to a Vital Signs report. Many of the events occurred in adults aged 35 to 64—middle-aged adults who would not normally be considered at risk.

But “many opportunities to find and treat risk factors are missed every day,” the CDC says. “Many of these [cardiovascular] events can be prevented through daily actions to help lower risk and better manage medical conditions,” said Dr. Anne Schuchat, Principal Deputy Director of the CDC. For instance, the report reveals that:

  • 9 million American adults are not yet taking aspirin as recommended;
  • 40 million adults with high blood pressure are not yet under safe control;
  • 39 million adults need to better manage their cholesterol;
  • 54 million adults are smokers; and
  • 71 million adults are not physically active.

The CDC recommends that health care professionals help patients by focusing on the ABCS (aspirin, blood pressure, cholesterol, smoking cessation), and using technology, customized processes, and the “skills of everyone in the health care system” to find and fill gaps in care.

Source: CDC, September 2018

Laryngeal Breathing Tubes Improve Survival

Switching breathing tubes may save more lives. A study funded by the National Heart, Lung, and Blood Institute shows that when a laryngeal tube, instead of an endotracheal tube, is used to open and access the airway in someone who has suffered cardiac arrest, the patient is more likely to survive.

The Pragmatic Airway Resuscitation Trial, a multicenter study conducted by the Resuscitation Outcomes Consortium, compared survival rates among 3,000 adults treated for cardiac arrest by paramedic crews from 27 emergency medical services (EMS) agencies. In half of the cases, the EMS team used the newer laryngeal tube, while the other half used traditional endotracheal intubation.

Outcomes were significantly better in the laryngeal group: 18.3% of patients survived three days in the hospital, compared with 15.4% of the endotracheal group. Moreover, 10.8% of the laryngeal group survived until discharge, compared with 8.1% of the other group. The proportion of patients surviving with good brain function was also higher in the laryngeal group.

Source: NIH, August 2018

What Turns Acute Pain Into Chronic Pain?

One major challenge in treating pain is to keep an acute event from becoming chronic. Moreover, “[a] lack of understanding of how acute pain becomes chronic pain has limited our ability to target effective preventive and treatment strategies to patients,” said NIH Director Francis Collins, MD, PhD. So the NIH has launched the Acute to Chronic Pain Signatures (A2CPS) program.

A2CPS researchers hope to identify individual patient features that will provide clinically meaningful, predictive “signatures” of transition or resilience to chronic pain. They will collect data from patients with acute pain associated with surgery or musculoskeletal trauma. Using neuroimaging, high-throughput biomedical measurements, sensory testing, and psychosocial assessments, they’ll form a dataset to help predict which patients will develop chronic pain. Those signatures could be valuable in guiding precision medicine and perhaps reducing reliance on opioids, the NIH says.

A2CPS will have an anticipated $40.4 million four-year budget supplied by the NIH Common Fund.

Source: NIH, August 2018

Which Patients Have the Best Chance With Checkpoint Inhibitors?

Checkpoint inhibitors are so new that not enough patients have received them for clinicians to predict who’ll benefit most. But researchers from the NIH, Harvard University, the University of Pennsylvania, and the University of Maryland may have found a clue: a gene expression predictor.

They began by looking at neuroblastoma cases where the immune system appeared to mount “an unprompted, successful immune response” to cancer, causing spontaneous tumor regression. Researchers were able to define gene expression features that separated regressing from non-regressing disease.

They then computed Immuno-PREdictive Scores (IMPRES) for each patient sample. The higher the score, the greater the likelihood of spontaneous regression. Analyzing 297 samples from several studies, they found the predictor identified nearly all patients who responded to the inhibitors and more than half of those who did not. Importantly, the researchers said, their predictor was accurate across many different melanoma patient datasets.

Source: NIH, August 2018

Obesity Rates Are Up From 2016

In 2017, seven states reported an adult obesity prevalence at or above 35%, an increase of two states since 2016. In 2012, obesity prevalence was lower than 35% in all states.

The highest levels were in Alabama, Arkansas, Iowa, Louisiana, Mississippi, Oklahoma, and West Virginia. The lowest prevalence was 22.6% in Colorado.

Adults aged 45 to 54 years were twice as likely as young adults to report obesity (36% vs. 17%). Non-Hispanic blacks had the highest prevalence (39%), followed by Hispanics (32.4%), and non-Hispanic whites (29.3%). When education was factored in, adults without a high school degree had the highest prevalence (35.6%), followed by high school graduates (32.9%), adults with some college (31.9%), and college graduates (22.7%).

The new data, from the Behavioral Risk Factor Surveillance System, are detailed in the CDC’s 2017 Adult Obesity Prevalence Maps, available at Maps showing obesity levels overall, as well as by race and ethnicity, are also available for 2011 through 2016.

Source: CDC, September 2018

Anti-Inflammatory Drug Could Help Prevent Brain Tissue Loss in MS

Findings from a recent study of ibudilast, an anti-inflammatory drug, “provide a glimmer of hope” for people with progressive multiple sclerosis, according to National Institute of Neurological Disorders and Stroke researchers.

Ibudilast is a phosphodiesterase inhibitor with bronchodilator, vasodilator, and neuroprotective effects, mainly used in the treatment of asthma and stroke.

In the placebo-controlled study, 255 participants were assigned to take up to 10 capsules of ibudilast or placebo per day for 96 weeks. Every six months, they had magnetic resonance imaging (MRI) brain scans. Researchers observed a difference in brain shrinkage of about 2.5 mL of brain tissue per year between the two groups. (The human brain has a volume of about 1,350 mL.) It is unknown whether the difference had an effect on symptoms or loss of function.

Reported adverse events were similar in both groups, the most common with ibudilast being gastrointestinal, headaches, and depression.

Source: NIH, August 2018

“Don’t You Smell That?”

“Phantom odor”—an unexplained and nonexistent smell, such as burning hair—is a fact of life for one in 15 American adults over 40 years old, according to a study at the National Institute on Deafness and Other Communication Disorders. And it can complicate daily life: The sense of smell has an impact on appetite, food preferences, and the ability to detect dangerous smells, such as gas leaks and spoiled food. People with the disorder may even have trouble maintaining a healthy weight.

Researchers analyzed data from 7,417 participants in the 2011--2014 National Health and Nutrition Examination Survey. The survey included the question “Do you sometimes smell an unpleasant, bad, or burning odor when nothing is there?”

Adults aged between 40 and 60 years had the highest prevalence of phantom odor perception. Women were twice as likely as men to report the odors; female predominance was “particularly striking” for those under age 60, said researchers. Interestingly, phantom odor perception is not related to the individual’s ability to correctly identify odors.

What causes the problem is poorly understood. It might be related to overactive odor-sensing cells in the nasal cavity or perhaps a malfunction in the part of the brain that understands odor signals, said Kathleen Bainbridge, PhD, study leader.

Risk factors for smelling phantom odors include head injury, dry mouth, and poor health. Low socioeconomic status is also a factor: Poor people may be exposed to more environmental pollutants and toxins. Other possibilities include the effects of medicines.

To find out the cause—and ultimately develop treatments— a “good first step,” says Bainbridge, “is a clear description of the phenomenon.”

Source: NIH, August 2018

Diabetes Programs Fail to Reach Their Targets

The CDC’s lifestyle change program (LCP), part of the National Diabetes Prevention Program, teaches people with prediabetes practical, real-life changes. Those changes can be enough to reduce the risk of type 2 diabetes by as much as 58%––or even 71% for people over 60. But are enough people getting the opportunity to participate?

CDC researchers assessed the availability of in-person LCP classes by diabetes incidence and socioeconomic status at the county level. They mapped 1,558 LCP class locations and found classes in 711 (23%) U.S. counties as of March 2017. (There may be more now, the researchers say.)

But the classes were not necessarily located where they could do the most good, researchers found. Only 17% of the counties with the highest diabetes incidence and 10% of counties with the greatest socioeconomic disadvantage had a publicly available class location. By contrast, 26.8% of counties in the lowest tertile of incidence had class locations.

The researchers say policy-makers, program planners, and others engaged in expanding the availability of the classes can use the information to prioritize locations, especially for underrepresented populations.

Source: Preventing Chronic Disease: Public Health Research, Practice, and Policy, September 2018

“Unique” Challenges for Screening Native American Women

American Indian/Alaska Native (AI/AN) women face the same barriers all low-income minority women face in accessing preventive care, but according to researchers from Rutgers University and the University of Arizona, they also face “unique challenges and circumstances.” The researchers reviewed 18 studies to find out more about facilitators of, and barriers to, breast cancer screening.

Low-income women are more likely to be diagnosed at a later stage and to die from breast cancer, one study found. The factors are well known: cost, lack of a usual source of care, lack of insurance, distance from a facility, and lack of transportation.

“Compounding these barriers,” the researchers of the meta-analysis said, AI/AN women expressed the belief that preventive care is not a priority, especially when it is their own preventive care. Moreover, some barriers that might be unique to AI/AN women included concern about “manifest destiny”: the assumption that thinking or talking about breast cancer can cause it, for instance. One study examined “traditionality” and found that women who could be seen as more traditional, defining themselves as living an “Indian way of life,” were less likely to be current with screening. Other women expressed mistrust in the screening technology, or spoke about perceived discrimination in the health care system.

Although this population has access to screening through Indian Health Service (IHS) facilities, women who also have insurance (typically Medicaid) are more likely to get screened. Women in rural areas who lived near an IHS facility were more likely than urban women to get mammograms. The researchers suggested this could be because rural women are more likely to be isolated from other mammogram facilities. Also, as IHS is “chronically underfunded,” they noted, it could be a cause of the health disparities and limited scope of services.

Their review made clear that efforts to intervene with AI/AN women to increase breast cancer screening have been limited. The intervention studies they reviewed “were not successful in improving screening rates or adherence.” The qualitative studies, on the other hand, suggest that women may be more responsive to locally supportive, targeted, and culturally appropriate interventions that respect traditionality yet encourage trust in the medical system.

Source: Journal of Transcultural Nursing, August 2018

Does Residential Mobility Affect Childhood Leukemia?

Studies that look at the relationship between environment and chidhood leukemia usually consider exposure at only a single residential address, such as the child’s home at birth or at time of diagnosis, say researchers from the University of California and the University of Southern California. But residential mobility, they contend, can have an impact on a number of relevant factors.

For instance, mobility can affect selection through the availability of data; cases are usually required to reside and be diagnosed in the same geographic area. It can affect exposure to electromagnetic fields and overhead power lines. Mobility can also function as a marker for other risk factors for childhood leukemia, such as maternal place of birth and younger maternal age at birth, as well as increased exposure to viruses or other infections potentially linked to higher leukemia risk. Finally, the type of dwelling can affect not only exposure but exposure assessment. Mobile homes and apartments, for instance, are more likely to lead to poor geographic information system (GIS)-matching of the residential address.

The researchers hoped that their study would “disentangle the effect of mobility.” Using the California Power Lines Study, they analyzed data from 4,879 childhood leukemia patients born in California and diagnosed between 1988 and 2008.

Many childhood leukemia cases were mobile, the researchers found: 2,982 (61%) children changed residence between birth and diagnosis. Of those who moved, 618 stayed within 2 km of their birth home; 1,992 moved outside of their birth neighborhood. Children who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status.

However, the effects of distance to power lines and magnetic field exposure on childhood leukemia were similar for a subset of residentially stable cases, and overall results were unchanged when the researchers controlled for proxies of mobility (except for dwelling). They found an odds ratio (OR) for childhood leukemia of 1.44 for those whose birth residence was within 50 m of a 200+ kV line, and an OR of 1.50 for the highest exposure of calculated fields, compared with an OR of 1.62 and 1.71, respectively, among children who stayed in place.

While they believe their findings on mobility are relevant to other environmental exposures and other childhood outcome studies, the researchers concluded that confounding by mobility is an unlikely explanation for the associations observed between power lines exposure and childhood leukemia.

Source: Environmental Research, July 2018

“Flexible” Intervention Helps Patients Overcome Barriers to HIV/Drug Treatment

People living with HIV who inject drugs often encounter multiple obstacles, both personal and system-related, to beginning and adhering to treatment. But NIH researchers found that an “integrated and flexible intervention” not only helped patients overcome those barriers, but cut deaths by 50%.

The study, HPTN 074, took place in Indonesia, Ukraine, and Vietnam—three countries with HIV epidemics driven by injection drug use. Researchers enrolled 502 adults with HIV who inject drugs, and 806 adults without HIV who inject drugs with them (their injection partners). At least one injection partner of every person in the study enrolled. The HIV participants were assigned either the national standard of care for HIV infection and drug use, or the standard of care plus the intervention designed to facilitate treatment. Participants were followed for one to two years.

Intervention group participants were referred to local healthcare providers for anti-HIV therapy. They were also each assigned a systems navigator, who helped the patient identify and overcome structural barriers to starting and staying in care, such as unfamiliarity with how to enroll in medical care or difficulty with keeping appointments. Psychosocial counselors helped participants overcome their unique psychological obstacles, such as lack of interest in therapy or fear of stigma.

At the end of the study, 15% of the participants with HIV who received standard care had died, compared with 7% of the intervention patients. About 26% of deaths among HIV participants were “clearly” HIV-related; 3% were due to drug overdose. Among the 42% of patients who died of unknown cause, 24% had weak immune systems.

The intervention had a “remarkably positive impact” on the participants, said Protocol Chair William Miller, MD, PhD. After one year, 41% of the intervention group had undetectable levels of HIV, compared with 24% of the standard-care group. Moreover, 72% of the intervention group were still in treatment, compared with 43% of the standard-care group. Similarly, 41% of intervention patients were in treatment for substance use, compared with 25% of standard-care patients.

The study is designed to be scalable to other settings. Investigators have offered the intervention to all the study participants living with HIV. They will be followed for a second year to find out whether the positive impact is sustained.

Source: NIH, August 2018

What is the Impact of Osteoporosis in Multiple Myeloma?

Osteoporosis is common among patients with multiple myeloma (MM), partly because both conditions largely affect older adults. And more than half of MM patients will have MM skeletal-related events, which are painful and can lead to complications (such as spinal cord compression) and death.

But how does pre-existing bone disease contribute to clinical outcomes in MM? Osteoporosis is a “silent condition” and very little is known about its role in MM, say researchers from The Ohio State University and the University of Massachusetts. The standard diagnostic evaluation for MM doesn’t include dual-energy x-ray absorptiometry, therefore assessments of underlying osteoporosis are not routine. Furthermore, it’s a challenge to distinguish osteoporotic fragility fractures from pathologic MM-induced fractures. Skeletal surveys underestimate bone involvement by about 40%, the researchers note, and are even less specific for distinguishing myeloma-related secondary osteoporosis from primary osteoporosis.

The researchers examined the relationship between the Fracture Risk Assessment Tool (FRAX) and the risk of death in women who developed MM. They analyzed data from 161,808 women in the Women’s Health Initiative (WHI). Of those, 409 developed MM; 362 had no history of cancer.

At baseline, 98 (27%) women had high FRAX scores and 264 (73%) had low scores. The median follow-up period was 10.5 years from enrollment and 7.2 years from the time of MM diagnosis. Of the patients with MM, 226 died during the follow-up period, including 71 with high FRAX scores and 155 with low scores. MM mortality was higher among those with high FRAX scores (72%) than those with low scores (59%). Poor bone health was associated with greater MM mortality but was not related to delay in time to diagnosis.

During the evaluation, 57 fractures were reported, 65% of them before MM diagnosis. Fewer than half of the women had a first fracture after diagnosis. The probability of fracture was similar among the women, regardless of FRAX score. Not surprisingly, older women with a lower BMI were most at risk.

As WHI does not include information on staging, chemotherapy, or use of bisphosphonates, the impact of bisphosphonates could not be determined in this study. Also, researchers did not know how many patients might have had pre-existing monoclonal gammopathy of undetermined significance, a disorder in about 3% of the aging population that progresses to MM in 1% of those individuals per year.

Source: Clinical Lymphoma, Myeloma & Leukemia, September 2018

T. Marneffei Infection: Risk Extends to Non-HIV Patients

HIV/AIDS patients are vulnerable to Talaromyces marneffei infection (T. marneffei, formerly penicilliosis), but in recent years, more cases have been seen in non–HIV-infected patients too. Most cases originate in Southeast Asia: 10% of AIDS patients in Hong Kong and 30% of patients in North Thailand, for instance, have T. marneffei infections. But patients with AIDS and T. marneffei travel, as do other immunocompromised patients. Thus, the first-reported case of a patient with longstanding pulmonary sarcoidosis who developed T. marneffei infection may have significance for clinicians caring for people with, or without, HIV.

Most patients with T. marneffei infection have fever, weight loss, and malaise. Subcutaneous abscesses and papule-like ulcers are common (sometimes the lesions are very small). Anemia, hepatosplenomegaly, lymphadenopathy, and diarrhea are also relatively common. However, while coughing is a notable symptom, pneumonia is rare, even though the organism is inhaled.

The patient in this report, a native of Cangnan County (an endemic fungal area) in southeast China, was admitted to the hospital with a three-week history of daily hyperpyrexia and coughing sputum. When antibiotics didn’t help, a fungal culture revealed why: he had T. marneffei infection. The clinicians say the pre-existing pulmonary sarcoidosis covered up the clinical features of T. marneffei, and initially misled them.

After three months of antifungal treatment, the patient’s physical condition improved. In fact, the lung lesions were “markedly absorbed” after that time. The respiratory signs and skin lesions disappeared gradually after eight days of treatment.

T. marneffei infection is fatal if untreated. Early diagnosis and treatment with antifungals can be life-saving.

Source: BMC Infectious Diseases, August 2018

Cancer Survivors’ Risk of Mood Disorders

Cancer survivors have a higher risk of depression within two years after diagnosis, according to a meta-analysis. But is that true of survivors of all cancer types? In fact, risk is multifactorial because patients, cancers, comorbidities, and impact of treatments are all different, say researchers who conducted a study comparing the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. Median follow-up times were 8.13 and 8.49 years, respectively. The three most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, two and five years later, the risk was similar between the two groups. After five years, the risk was even lower in the survivor group than in the control group.

The researchers found that patients fell into three main categories: persistently increasing risk, higher risk in the first few years and after five years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck, nasopharyngeal, and esophageal cancers were in the first group, with distinct longitudinal patterns. Their risk at five years was greater than that of the general population.

Independent risk factors for mood disorders included: being female, aged 40--59 years, and having more than two primary cancers, two or more treatment modalities, Charlson comorbidity index scores higher than 3, a higher urbanization level, and a lower income level. The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early post-diagnosis years, but in late follow-up for patients with a “persistent” risk.

Source: Journal of Affective Disorders, August 2018

What’s the Impact of Occult HBV in Chronic HCV? Findings are Still “Inconclusive”

The reported prevalence of occult hepatitis B virus (HBV) infection (OBI) varies widely: from less than 1% to as high as 89.5% in HIV patients, for instance. Among patients with chronic hepatitis, the prevalence again ranges widely, from 0% to 52%, but is highest in patients with chronic hepatitis C (CHC).

The clinical impact of OBI on patients with CHC has been extensively investigated, say researchers from the Institute of Liver and Biliary Sciences in New Delhi, India, but the available data are conflicting. And, when they conducted their own study to assess the prevalence of OBI and evaluate its impact on clinical outcomes and response to antiviral therapy in CHC, their findings were “largely inconclusive.”

The study included 80 patients, 32 of whom (40%) had seropositive OBI. Hepatitis C virus (HCV) genotype information was available for 59 patients, with genotype 3 being most common.

However, analysis of clinical, biochemical, histopathological, and treatment response, based on seropositivity and a semiquantitative estimate of antibody to hepatitis B core antigen (anti-HBc), didn’t yield statistically significant results.14 patients’ plasma samples were reactive for anti-HBc, 12 for anti-HBs, and 6 for both antibodies. HBV DNA (34 IU/mL) was detected in the plasma sample of only one patient by quantitative polymerase chain reaction.

Therefore, said researchers, the prevalence of OBI was 1.25%. HBc total antibody levels did not influence clinical outcomes and response to directly acting antiviral therapy. Nor did genotype make a significant difference: 90.7% of genotype 3 patients and 92.8% of genotype 1 patients attained sustained virological response.

The researchers urged that more studies should be conducted, to further explore “this seemingly enigmatic issue.”

Source: Journal of Laboratory Physicians, July–Sept. 2018