Clusters of Unvaccinated Children Linked to California Pertussis Outbreaks

Clusters of unvaccinated children may have contributed to a resurgence of pertussis in California, a new study suggests. Image: yangna/iStockphoto.com

Clusters of unvaccinated children may have contributed to a resurgence of pertussis in California, a new study suggests. Image: yangna/iStockphoto.com

Outbreaks of pertussis in California were more likely to occur in areas where many children went unvaccinated, according to results from a study published today in Pediatrics.

A resurgence of pertussis in California and many other parts of the country in recent years is likely the result of many factors. Previous studies have suggested that the protection offered by pertussis vaccines may wane over time, that a newer and safer version of the vaccine may offer less protection than an older version, and that the cyclical nature of the pertussis outbreaks may play a role for some of the uptick in cases.

But many have suspected that vaccine refusal, which has risen in recent years in California, may have also played a role. Most California children are vaccinated (90.7%), but the rate of children who have not been vaccinated before attending kindergarten because they received nonmedical exemptions to the required immunizations has grown from 0.77% in 2000 to 2.33% in 2010, according to the authors. This new study suggests this trend may have contributed to the increase in the state’s pertussis cases.

The researchers identified geographic clusters of children who received nonmedical vaccination exemptions to attend kindergarten and compared them with geographic areas where there was an increase in pertussis cases. The researchers found that areas with many unvaccinated children were 2.5 times more likely to have a cluster of pertussis cases than areas with few unvaccinated children.

The study can’t prove that clusters of unvaccinated children played a role in the pertussis outbreaks. In addition, the researchers did not look at specific vaccination records for the children, so some of the children who received a waiver may have been vaccinated for pertussis but skipped other shots. But the findings are consistent with other studies that have found that clusters of unvaccinated children contribute to outbreaks of pertussis and other illnesses and that children who miss doses of the pertussis vaccine or receive them late may not be fully protected.

Antibiotic Tygacil Gets FDA Boxed Warning About Increased Death Risk

Because of an increased risk of death, tigecycline (Tygacil), an antibacterial drug, should only be used when alternative treatments are not suitable, said the US Food and Drug Administration. (Image: ntmw/iStockphoto.com)

Because of an increased risk of death, tigecycline (Tygacil), an antibacterial drug, should only be used when alternative treatments are not suitable, said the US Food and Drug Administration. (Image: ntmw/iStockphoto.com)

The US Food and Drug Administration (FDA) approved today a new boxed warning, the strongest warning given to a drug, for intravenous tigecycline (Tygacil; Pfizer), a tetracycline-class antibacterial drug. Tigecycline, first approved in 2005, is used for treating complicated skin infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults.

In 2010, the FDA issued a drug safety communication showing, in a meta-analysis of 13 trials, an increased risk of death among patients receiving tigecycline compared with other antibacterial drugs (4.0% vs 3.0% with an adjusted risk difference of 0.6%). The increased risk was greatest in patients with ventilator-associated pneumonia, a use for which the FDA has not approved the drug. Increased risk of death was also seen in patients with complicated skin infections, complicated intra-abdominal infections, and diabetic foot infections—another complication for which the drug has not been approved.

After the 2010 communication, the FDA analyzed data from 10 clinical trials involving tigecycline and only agency-approved uses. Again, analysis showed a higher risk of death among patients receiving tigecycline compared with other antibacterial drugs (2.5% vs 1.8% with an adjusted risk difference of 0.6%). These deaths, in general, resulted from worsening infections, complications of infection, or other underlying medical conditions, but the FDA said the cause of this mortality risk difference has not been established.

The FDA wrote that health care professionals should reserve tigecycline for use in situations when alternative treatments are not suitable. In the prescribing label, the FDA said tigecycline should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Such bacteria include Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Klebsiella pneumoniae, and Legionella pneumophila.

Limited Access to Critical Antibiotic Leaves Patients in Many Parts of the World Vulnerable to Rheumatic Fever

A key antibiotic needed to treat serious group A streptococcus infections is in limited supply in many areas. Image: CDC

A key antibiotic needed to treat serious group A streptococcus infections is in limited supply in many areas. Image: CDC

In many parts of the world, a key antibiotic is out of reach for patients with rheumatic fever or rheumatic heart disease because of supply and quality problems, according to a review published today in Global Heart, a journal of the World Heart Federation.

Infections with group A streptococcus bacteria in the developed world typically lead to common conditions such as “strep throat” or skin infections that usually can be easily treated with antibiotics. But inadequate treatment can lead to the development of more serious conditions, such as rheumatic fever or rheumatic heart disease, which may be life threatening. According to the authors, there are an estimated 471 000 cases of rheumatic fever and 230 000 deaths globally each year, with cases disproportionately concentrated in countries with high poverty rates or in disadvantaged subpopulations in wealthy countries.

For decades, benzathine penicillin G has been an important antibiotic for treating these more serious complications of group A strep infections. (It was also once a first-line treatment for syphilis, yaws, Lyme disease, and the prophylaxis of pneumonia in patients with sickle cell disease, but there are now more treatment options for these conditions.) As rheumatic fever and rheumatic heart disease have become less prevalent in developed countries, the general demand for benzathine penicillin G has declined as new antibiotics emerged. But this has led to growing concerns about the supply of the drug and its availability to populations in need, according to the review authors.

A survey of physicians treating rheumatic fever and rheumatic heart disease in 24 nations in Africa, Asia, and Central and South America, conducted by the World Heart Federation, found that many report limited access to benzathine penicillin G. Shortages have also been reported in North America. The authors also noted concerns about the quality and safety of the supply.

Resolving these issues will take international collaboration, the authors said. “Making this essential medicine available to vulnerable populations is the most important step in reducing death and disability from [rheumatic heart disease],” they said. “Researchers, industry, governments, and communities need to commit to delivering this low-cost, life-changing intervention.”

The JAMA Forum: California Dreamin’—The Story of Senate (Scope-of-Practice) Bill 491

Eli Adashi, MD, MSIt was all but impossible to miss the bevy of “scope-of-practice” bills that flooded the California legislature as it faced up to its 2013-2014 session. Introduced by the February 22, 2013, deadline, the Senate Bills (SBs) and Assembly Bills (ABs) in question hardly left a stone unturned. Legislative initiatives promoting the practice autonomy of nurse practitioners (SB 491), optometrists (SB 492), and pharmacists (SB 493) led the way.

Also on the docket were legislative efforts to grant nurse practitioners (NPs), physician assistants (PAs), and certified nurse midwives (CNMs) broader supervisory authority over medical assistants (SB 352). Rounding out the list was the proposed authorization of properly trained NPs, CNMs, and PAs as providers for first-trimester pregnancy termination (AB 154).

Tracing the progression of SB 491 illustrates its contentious course, which is highly emblematic of the ongoing national scope-of-practice feuds between physicians and nonphysician providers. Sponsored by California State Senator Edward P. Hernandez, OD, SB 491 set out to authorize NPs as independent autonomous providers if they completed specific supervised clinical training, attained national certification, and maintained liability insurance. In so doing, SB 491 sought to allow NPs to launch their own “stand-alone clinics” and to practice to the full extent of their education, training, and competence in the absence of physician supervision. Given a favorable hearing at both the Senate Committee on Business, Professions, and Economic Development and the Senate Committee on Appropriation, a lightly amended version of SB 491 moved on to the Assembly Committee on Business, Professions, and Consumer Protection.

It was there that the gloves came off. After a bruising first hearing, SB 491 was voted down, but not before being granted reconsideration and the right to live to fight another day. No more than a week later, SB 491, now significantly amended, narrowly survived a second hearing, albeit at a steep price. Stripped of its “independent practice pathway” provision, SB 491 was no longer in a position to champion NP-managed stand-alone clinics other than in the “collaborative” context of “a hospital, a clinic, or some other medical facilities.” Alive—if on life support—and on its way to the Assembly Committee on Appropriation, SB 491 could see nothing but headwinds before it.

And so it came to pass. SB 491 never quite made it out of the Committee on Appropriation and onto the Assembly floor for a vote. It will be at least 1 year if not 2 years before SB 491 is reintroduced.

Viewed from a national perspective, SB 491 is but one of many state bills seeking to expand the scope of practice of nonphysician providers. According to the National Conference of State Legislatures, a total of 1795 such bills were proposed in 54 states, territories, or the District of Columbia in the course of calendar years 2011 and 2012. Of those, 349 were adopted or enacted into law. This year alone, as of April 1, 178 scope-of-practice bills have been introduced in 38 states and the District of Columbia.

The driving forces behind this mass movement are hardly surprising. Faced with a shrinking supply of primary care physicians and a growing demand for such services, state legislatures from California to Massachusetts are merely doing their level best to address the imbalance. Looming large as well is the Affordable Care Act, now set to enlarge the ranks of the commercially insured and to expand Medicaid coverage. Limited resources and the ever-growing costs of health care have also done their part. Viewed in this light, it would appear unlikely that the national drive to modify the patchwork of scope-of-practice state laws will abate any time soon.

In the eyes of many, SB 491 stands firmly on the side of the angels. Leading this camp is the Institute of Medicine (IOM), the supportive stance of which is articulated in its 2011 report The Future of Nursing: Focus on Scope of Practice. It was the position of the IOM that “now is the time to eliminate the outdated regulations… that limit the ability of nurses to practice to the full extent of their education, training, and competence.” The report further notes that “no studies suggest that advanced practice registered nurses are less able than physicians to deliver care that is safe, effective, and efficient or that care is better in states with more restrictive scope-of-practice regulations.”

A similar position was taken by the National Governors Association (NGA) in its 2012 report The Role of Nurse Practitioners in Meeting Increasing Demand for Primary Care. The NGA is on record stating that “states might consider changing scope-of-practice restrictions and assuring adequate reimbursement for their services as a way of encouraging and incentivizing greater NP involvement in the provision of primary health care.” Additional support was offered by the AARP (formerly the American Association of Retired Persons), which, in its Policy Book, called on states to “amend current scope-of-practice laws and regulations to allow nurses… to perform duties for which they have been educated and certified.” All told, these recommendations reaffirm present-day reality, wherein NPs enjoy practice autonomy in 17 states and the District of Columbia.

The above notwithstanding, the forces opposing the relaxation of extant scope-of-practice state statutes remain formidable. In the case of SB 491, the leading state-based opponent proved to be the California Medical Association, which took the position that “allowing nurse practitioners to practice without… physician supervision reduces patient safety and quality of care.” Similar concerns were raised by the California Academy of Family Physicians and the California Society of Anesthesiologists.

At the national level, SB 491 was opposed by the American Academy of Family Physicians, whose 2012 report Primary Care for the 21st Century argued that “substituting NPs for doctors cannot be the answer.… We must not compromise quality for any American and we don’t have to.” Comparable outlooks were enunciated by the American Medical Association, the American Academy of Pediatrics, and the American Osteopathic Association.

Nurse practitioners are thoroughly trained professionals who have earned a master’s level or doctoral degree and who have been certified by the Board of Registered Nursing. Currently about 180 000 strong and growing, NPs constitute a leading element of the national primary care fabric. By many accounts, the national drive to grant greater independence to NPs is here to stay. Continued opposition by “organized medicine” is equally likely. As for SB 491, it will have to wait until “California dreamin’ is becoming a reality.”

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About the author: Eli Y. Adashi, MD, MS (Eli_Adashi@brown.edu) is Professor of Medical Science at the Warren Alpert Medical School of Brown University in Providence, RI. A member of the Institute of Medicine, the Council on Foreign Relations, the Association of American Physicians, and the American Association for the Advancement of Science, Dr Adashi has focused his writing on domestic and global health policy at the nexus of medicine, law, and ethics. A former Franklin fellow, Dr Adashi served as a senior advisor on Global Women’s Health to the Secretary of State office of Global Women’s Issues during the Obama Administration.

About The JAMA Forum: JAMA has assembled a team of leading scholars, including health economists, health policy experts, and legal scholars, to provide expert commentary and insight into news that involves the intersection of health policy and politics, economics, and the law. Each JAMA Forum entry expresses the opinions of the author but does not necessarily reflect the views or opinions of JAMA, the editorial staff, or the American Medical Association. More information is available here and here.

Author Insights: Although Modest Exercise and Weight Loss Reduce Pain and Disability From Knee Osteoarthritis, More Intense Efforts Appear Even Better

New research finds a more aggressive approach to weight loss and intensive exercise appears more effective in reducing pain and improving quality of life for older adults with knee osteoarthritis than less intensive efforts. Image: JAMA, ©AMA

New research finds a more aggressive approach to weight loss and intensive exercise appears more effective in reducing pain and improving quality of life for older adults with knee osteoarthritis than less intensive efforts. Image: JAMA, ©AMA

Clinicians have long known that modest weight loss and exercise benefit patients with knee osteoarthritis by decreasing the load pressure on the joint, resulting in reduced pain and increased mobility. Now, new research findings appearing today in JAMA suggest that a more aggressive approach to such lifestyle changes can produce even better outcomes.

The researchers randomized 454 overweight and obese adults (average body mass index about 33.5) aged 55 years or older to 3 groups: exercise (1 hour of aerobic walking, strength training, and a cool-down period, 3 days a week), diet only (with a weight loss goal of 10% to 15%), or both. At 18 months, 399 participants completed the study. Those in the group that focused on both diet and exercise and those in the diet-only group lost more weight and experienced greater reductions in inflammation compared with those in the exercise-only group. Furthermore, those in the diet and exercise group reported decreases in pain and improved function compared with the exercise-only group.

Lead author Stephen P. Messier, PhD, a professor and director of the J. B. Snow Biomechanics Laboratory at Wake Forest University in Winston-Salem, North Carolina, discusses his team’s findings.

news@JAMA: Why did you do the study?

Dr Messier: We knew from a previous study that modest walking exercise and strength training decreased the progression of disability, so we know exercise should be part of the standard of care. Another study looked at diet with a goal of 5% weight loss and found that when combined with exercise it decreased pain. So we thought if 5% weight loss works, then maybe 10% or 15% would work better.

news@JAMA: And it did work better.

Dr Messier: We were very pleased. Clearly, losing 10% of body weight resulted in less pain, better function, and less inflammation. We also found a dose response with weight loss.

news@JAMA: So should this more aggressive approach be adopted by treating physicians?

Dr Messier: We think it should be part of the standard of care. The big question is, “Can you put this into a community?” We showed it works in a controlled environment; now we want to do a pragmatic trial in the community. When I talk to rheumatologists, they say, “We’d love to do this, but we don’t have the infrastructure. When a patient comes in, we say they need to exercise and lose weight, but we lose them in follow-up.”

news@JAMA: If a 10% loss of weight produced better results than a 5% weight loss, why not suggest 20% or 30% weight reduction?

Dr Messier: What we were trying to do is keep it practical. We found 10% weight loss is obtainable, and we felt it would not be so much that it discouraged people from even trying. We did have people who lost up to 30% of their body weight and we could look at their outcome in secondary analysis, but we haven’t gotten there yet.

news@JAMA: So is weight loss the key to reducing pain and disability from knee osteoarthritis?

Dr Messier: Within the body weight people lost, most of it was fat mass. But there was also loss of muscle mass, and with older adults you don’t want to lose muscle weight. So one of the things we’re thinking of recommending is to combine the intensive diet with even more intensive exercising so muscle mass can be maintained.

Chronic Low-Level Arsenic Exposure Linked to Heart Risk

 Low to moderate arsenic exposure through drinking water or certain foods may increase the risk of developing heart-related health problems, according to a new study. Image to come: Elenathewise/iStockphoto.com


Low to moderate arsenic exposure through drinking water or certain foods may increase the risk of developing heart-related health problems, according to a new study. Image: Elenathewise/iStockphoto.com

Individuals who are exposed to low to moderate levels of arsenic over many years may have a greater risk of developing cardiovascular disease and dying of cardiovascular problems than individuals with less exposure, according to a study published today in the Annals of Internal Medicine. The findings are likely to stoke concerns about long-term arsenic exposure in the United States through drinking water, as well as rice and other dietary staples containing the substance.

It is well established that high levels of arsenic exposure can cause illness. Studies conducted have suggested that individuals exposed to high levels of arsenic in drinking water (more than 100 μg/L) are at greater risk of peripheral artery disease, coronary heart disease, stroke, and atherosclerosis, according to the study’s authors. But less is known about the health effects of chronic low- or mid-level exposure.

To examine the relationship between lower levels of arsenic exposure and health, the researchers examined cardiovascular health and arsenic levels in urine samples from 3575 American Indian men and women participating in the Strong Heart Study. These participants were between the ages of 45 and 74 years and lived in Arizona, Oklahoma, North Dakota, or South Dakota. They were first examined in 1989-1991 and were followed up through 2008. The researchers found that those with the highest levels of arsenic in their urine were more likely to develop cardiovascular disease and more likely to die as a result of cardiovascular disease than participants with lower levels of arsenic in their urine.

The health effects of exposure to low to moderate levels of arsenic is a particular concern in many small rural US communities, where well water arsenic levels may exceed the Environmental Protection Agency standard of 10 μg/L or less. At the time the study was conducted, the authors said, arsenic levels in public drinking water ranged from less than 10 to 61 μg/L in Arizona, less than 10 μg/L in Oklahoma, and from less than 1 to 21 μg/L in the Dakotas. The authors concluded that drinking water was a likely source of arsenic exposure in Arizona and the Dakotas, while arsenic in grains and other foods were likely the primary source of exposure in the other communities examined.

“These findings support the importance of low to moderate arsenic exposure as a cardiovascular risk factor with no apparent threshold,” the authors said.

The findings may have some wider implications as well, as the US Food and Drug Administration (FDA) and other scientists are currently weighing the long-term risks of low-level exposure to arsenic from rice. A recent FDA analysis of more than 1300 rice and rice product samples found that average arsenic levels ranged from 0.1 to 7.2 μg  per serving, levels the agency said are too low to cause immediate or short-term health concerns. But the agency continues to assess the long-term health effects of these levels of exposure.

Study Confirms Shorter Course of Radiation for Breast Cancer Is Safe and Effective After 10 Years

A shorter course of radiation for breast cancer may work  as well as a longer course after 10 years of follow-up. Photo: Varian.com

A shorter course of radiation for breast cancer may work as well as a longer course after 10 years of follow-up. Photo: Varian.com

Longer may not be better when it comes to radiation treatment for breast cancer.

For women who underwent radiation treatment after surgery and chemotherapy for breast cancer, a radiation regimen consisting of 15 treatment sessions over 3 weeks appeared to be as effective as an alternate regimen of 25 sessions over 5 weeks after a 10-year follow-up period, according to findings from a large trial released yesterday in The Lancet Oncology. This conclusion was based on the 10-year follow-up results of the UK Standardisation of Breast Radiotherapy (START) trials, 2 randomized controlled trials investigating the optimal regimen of adjuvant radiation therapy for breast cancer.

In the United Kingdom as well as in Canada, the 3-week regimen has been the standard practice in breast cancer treatment for decades. In the United States, however, the long-time standard practice has been the longer 5-week regimen, and until recently no official guidelines on the shorter regimen existed.

The 2 trials (START-A and START-B) began in the United Kingdom in 1998 and randomized more than 4000 women to receive various radiation therapy regimens. START-B looked at longer versus shorter durations of treatment. It compared a radiation regimen of 50 Gy (gray, a standardized measurement of radiation dose) divided into 25 treatment sessions or “fractions” (2 Gy per fraction) over 5 weeks with an alternate regimen of 40 Gy divided into 15 fractions (2.67 Gy per fraction) over 3 weeks. The primary end points of the START trials were local-regional relapse, defined as cancer recurrence in the breast, chest wall, or lymph nodes on the same side of the body, and local radiation-induced toxicity or “tissue effects,” as assessed by clinician examination and photographs.

In 2008, 5-year results of the START trials were published and showed that the 2 regimens were equally effective and that the 3-week regimen had fewer adverse tissue effects. Another randomized (although smaller) Canadian trial published similar results in 2010. These results solidified practice guidelines in the United Kingdom and Canada.

In the United States, the American Society of Radiation Oncology (ASTRO) released new practice guidelines in 2011 to state that the 3-week regimen may be appropriate for a specific subset of patients with early breast cancer. However, this recommendation was not strong and thus has been loosely adopted into clinical practice. The guidelines put greater emphasis on the conventional 5-week regimen, which remains widely used in practice. According to the guidelines, a major rationale for continuing to recommend the 5-week regimen was concern that the higher per-fraction radiation dose in the 3-week regimen (2.67 vs 2 Gy per fraction) may have potential “late” radiation toxicity effects that appear only after 10 or more years, such as late tissue effects, cardiovascular events, and pulmonary toxicity.

The just-released 10-year START trial results may help address these concerns. The new data essentially confirm the 5-year results: the 3-week 40-Gy regimen was just as effective as the 5-week 50-Gy regimen with respect to local-regional relapse, and it also had fewer adverse effects, although the studies focused on local tissue effects and not cardiovascular or pulmonary effects. Nonetheless, these results suggest that the 3-week 40-Gy regimen was less harmful to normal tissue and not less effective in treating cancerous tissue.

There also was an unexpected survival benefit in the group that underwent the 3-week regimen. In other words, it’s possible that the 3-week regimen may be not only equivalent to, but actually somewhat better than, the 5-week regimen. However, because survival was a secondary (and not primary) outcome in these studies, this result needs to be investigated further.

Given the immense cost and convenience benefits of a shorter radiation therapy course in breast cancer, this large follow-up study may have the potential to influence future US clinical practice patterns. On the other hand, it may not be enough to spur immediate change: a US phase 3 clinical trial investigating the same issue is currently recruiting patients, with an estimated completion date of 2020 for final data on primary outcome measures.