Michigan-CDC study supports value of social restrictions during influenza pandemics

Analysis of 43 US cities during 1918-1919 Spanish flu pandemic uncovers strong link between social restrictions and lower death rates
ANN ARBOR, Mich. — Although physicians have imposed quarantine orders since at least 1374, when the Port of Venice officially isolated foreigners and shippers for 40 days to keep out infectious scourges, there has been no definitive evidence that public health measures like quarantining the sick and isolating people after exposure to ill people would save lives during an influenza pandemic.

Until now.

In a study published in the Aug. 8 Journal of the American Medical Association, a team of University of Michigan medical historians and epidemiologists from the federal Centers for Disease Control and Prevention say that social restrictions allowed 43 U.S. cities to save thousands of lives during the Spanish influenza pandemic of 1918-1919.

Although these urban communities had neither effective vaccines nor antiviral medicines, they were able to organize and execute a suite of classic public health measures – called non-pharmaceutical interventions or NPIs – before the pandemic gained full force.

The new study finds that cities whose NPIs were sustained and layered with multiple tactics had the best outcomes. In addition to quarantine and isolation, the NPIs examined in this study were school closures and cancellation of public gatherings.

“Public health is everyone’s responsibility. In a world faced by the threat of newly emerging and re-emerging infectious diseases, it is critical to determine if costly and potentially socially harsh NPI measures can save lives and reduce the numbers of those infected,” says lead author Howard Markel, M.D., Ph.D., the George E. Wantz Distinguished Professor of the History of Medicine, professor of pediatrics and communicable diseases, and director of the U-M Center for the History of Medicine. “Now we know the answer is ‘yes.’ ”

Markel adds that in today’s world, implementing these measures in a layered, sustained fashion would also provide a cushion of time for the development and distribution of effective vaccines and antivirals, while reducing the crush on essential infrastructure.

“By better understanding what worked in the past, we can better prepare for the future,” says senior author Martin Cetron, M.D., director of the CDC’s Division of Global Migration and Quarantine. “Communities that were most successful during the 1918 pandemic quickly enacted a variety of measures. Those planning for the next pandemic need to carefully consider how to best use these strategies to protect people and decrease the potential impact of the next pandemic in their communities.”

The 43 cities in the study were scattered from coast to coast and represented a combined population of approximately 23 million. In an exhaustive review of 1,144 primary and secondary sources that included U.S. census data, municipal records, newspapers and handbills covering a 24-week period – Sept. 8, 1918 through Feb. 22, 1919 – the researchers identified which NPIs were used in each city and when officials turned them on and off.

Using both actual death rates from pneumonia and influenza, and baseline rates for what would have been normal without a pandemic, the researchers found there were 115,340 excess pneumonia and influenza deaths attributable to the pandemic in these cities during the period studied. In comparing the death rates to when NPIs were turned on and off, they found that NPIs did mitigate the death rate, with a statistically significant association between increased duration of NPIs and reduced mortality.

Further, they discovered that city-to-city variation in mortality was associated with the timing, duration and combination of NPIs. St. Louis, Missouri, for example, closed schools and cancelled public gatherings relatively early in the pandemic and sustained these measures for about 10 weeks. The analysis shows that St. Louis had one of the largest drops in mortality while the NPIs were in force.

As a whole, the study’s findings contrast markedly with the conventional wisdom that the Spanish Flu ravaged the United States and elsewhere, with little that could be done to stop its deadly toll.

Markel predicts that NPI measures will be socially painful in the next pandemic, but that the public’s acceptance of NPIs is essential.

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“We need to have informed concern about what to do in a pandemic – and why,” concludes Markel.

Citation: JAMA, Nonpharmaceutical Interventions Implemented by US Cities During the 1918 -1919 Influenza Pandemic, Aug. 8, 2007, p. 644-654, Vol. 298, No. 6.

Other collaborators on the research were Alexandra Minna Stern, Ph.D., associate director, Center for the History of Medicine; J. Alexander Navarro, Ph.D., senior researcher, Center for the History of Medicine; Joseph R. Michalsen, research associate, Center for the History of Medicine; Alexandra Sloan, research associate, Center for the History of Medicine; and Harvey B. Lipman, Ph.D., (insert title), Centers for Disease Control and Prevention.

This work was funded by the Centers for Disease Control and Prevention and conducted by the University of Michigan Center for the History of Medicine and the CDC Division of Global Migration and Quarantine.

The complete bibliography of the 1,144 primary and secondary sources is available as an online supplement at http://www.cdc.gov/ncidod/dq/index.htm. The supplement provides access to data specific to each of the 43 cities.

The Center for the History of Medicine also has a Web-based source of materials that cover the 1918-919 influenza pandemic, which can be viewed at http://www.med.umich.edu/medschool/chm/influenza/.

More information about community strategies for pandemic influenza is available at http://www.pandemicflu.gov/plan/community/commitigation.html.

The 43 cities examined in this study were:

AL: Birmingham
CA: Los Angeles, Oakland, San Francisco
CO: Denver
CT: New Haven
DC: Washington
IL: Chicago
IN: Indianapolis
KY: Louisville
LA: New Orleans
MA: Boston, Cambridge, Fall River, Lowell, Worcester
MI: Grand Rapids
MD: Baltimore
MN: Minneapolis, St. Paul
MO: Kansas City, St. Louis
NE: Omaha
NJ: Newark
NY: Albany, Buffalo, New York, Rochester, Syracuse
OH: Cincinnati, Cleveland, Columbus, Dayton, Toledo
OR: Portland
PA: Philadelphia, Pittsburgh
RI: Providence
TN: Nashville
VA: Richmond
WA: Seattle, Spokane
WI: Milwaukee

Contact: Mary Beth Reilly
reillymb@umich.edu
734-764-2220
University of Michigan Health System

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Place of death shifting for children with complex chronic conditions

Contact: Rachel Salis-Silverman
267-426-6063
JAMA and Archives Journals

It is becoming more common for children with complex chronic conditions to die in their home than in a hospital, although black and Hispanic children with these conditions are less likely to die in their home, according to a study in the June 27 issue of JAMA, a theme issue on chronic diseases of children.

Chris Feudtner, M.D., Ph.D., M.P.H., of Children’s Hospital of Philadelphia, presented the findings of the study at a JAMA media briefing in New York.

Many pediatric palliative care clinicians suggest that the preferred place of death, by the family, of an infant, child, or adolescent with a medically complex chronic condition is the home. Advances in home-based medical technology and changes in attitudes about pediatric palliative care and hospice services may be making this a more viable option, according to background information in the article.

Dr. Feudtner and colleagues conducted a study to determine if the proportion of complex chronic condition-related deaths occurring at home among children and adolescents increased between 1989 and 2003, and to assess if there were any race and ethnicity disparities in the location of death. The researchers analyzed data from the National Center for Health Statistics’ Multiple Cause of Death Files.

Among the 22.1 percent of deaths (198,160 of 896,509 total deaths) attributed to a complex chronic condition between 1989 and 2003, the percentage of deaths occurring at home increased significantly for all age groups (overall, from 10.1 percent in 1989 to 18.2 percent in 2003), but with larger increases for deaths beyond infancy. The odds of death occurring at home increased by 3.8 percent annually.

The percentage of individuals dying at home increased significantly over time for infants (4.9 percent home deaths in 1989 to 7.3 percent in 2003); 1 to 9-year-olds (17.9 percent to 30.7 percent), and 10 to 19-year-olds (18.4 percent to 32.2 percent). During this same period, there was a significant decline in the percentage of deaths occurring in the hospital for each of these three age categories.

The authors suggest that this gradual change in place of death may be occurring because of advances in medical technology in the home setting and broad shifts in attitudes and decision-making processes regarding palliative and end-of-life care in U.S. culture.

The child’s race, ethnicity, and region of home residence were significantly associated with death occurring at home. The odds of dying at home were reduced by 50 percent among black individuals, and reduced by 48 percent among Hispanic individuals, when compared with whites.

Concerning possible reasons for the observed racial and ethnic differences, “ … differential access to health care services or medical technology, divergent cultural attitudes or approaches to palliative and end-of-life care decision making, or differing levels of financial or other support within the patient’s or family’s social network may make dying at home more or less likely.”

“… as efforts to improve understanding of the sources and remedies of racial and ethnic disparities in pediatric end-of-life care are completed, medical and other concerned professionals need to ensure that all patients have access to necessary care and that all dialogue and interactions regarding decisions about care—whether curative, life-extending, or palliative—are built on mutual understanding, trust, and respect,” the authors conclude.

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(JAMA. 2007;297:2725-2732. Available pre-embargo to the media at http://www.jamamedia.org)

Editor’s Note: The conduct of this study was supported in part by grants from the Agency for Healthcare Research and Quality and the National Institute of Nursing Research of the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

For More Information: Contact the JAMA/Archives Media Relations Department at 312-464-JAMA or email: mediarelations@jama-archives.org.

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Coenzyme Q10 does not improve Parkinson’s disease symptoms

Contact: Alexander Storch
Alexander.Storch@neuro.med.tu-dresden.de
JAMA and Archives Journals

Small doses of the antioxidant coenzyme Q10 appear to increase blood levels of this naturally occurring compound in patients with Parkinson’s disease, but does not improve Parkinson’s disease symptoms, according to an article posted online today that will appear in the July 2007 print issue of Archives of Neurology, one of the JAMA/Archives journals.

Parkinson’s disease is a neurodegenerative disorder characterized by tremors and difficulty with walking or other movements. The biological mechanisms underlying the condition are not fully understood, but researchers suspect a malfunction of the mitochondria, parts of the cells that help convert food to energy, according to background information in the article. Coenzyme (CoQ10), an antioxidant sold as a dietary supplement, is also involved in mitochondrial processes. “Because of these functions, CoQ10 has attracted attention concerning neuroprotective actions in neurodegenerative disorders linked to mitochondrial defects or oxidative [oxygen-related] stress, such as Huntington’s disease and Parkinson’s disease,” the authors write. Previous studies indicate that high doses of CoQ10 (1,200 milligrams) may slow the deterioration associated with Parkinson’s disease.

Alexander Storch, M.D., of the Technical University of Dresden, Germany, and colleagues conducted a randomized clinical trial of a 300-milligram dose of CoQ10 in 131 patients with Parkinson’s disease who did not have changes in motor functions and were on stable treatment for their condition. Those assigned to the treatment group took 100 milligrams of CoQ10 three times daily for three months, followed by a two-month “washout” period. The researchers assessed Parkinson’s disease symptoms before treatment began, each month during treatment and again after the washout period. Blood tests were performed at the beginning of the study, after three months of treatment and after the washout period.

A total of 106 patients completed the full three months of the study—55 in the CoQ10 group and 51 in the placebo group. The compound was well tolerated overall, and the percentage of patients who experienced adverse effects—including viral infection, diarrhea and hearing loss—did not differ between the two groups. Blood levels of CoQ10 increased in the treatment group from an average of 0.99 milligrams per liter to an average of 4.46 milligrams per liter after three months.

“Although we demonstrated a significant increase in plasma levels of CoQ10 toward levels observed with high doses of standard CoQ10 formulations in Parkinson’s disease and other disorders, our study failed to show improvement of Parkinson’s disease symptoms and did not meet its primary or secondary end points,” which were changes on scales that measured Parkinson’s disease symptoms and their effects on physical and mental functioning, the authors write. “Our study further demonstrated that 300 milligrams per day of nanoparticular CoQ10 is safe and well tolerated in patients with Parkinson’s disease already taking various antiparkinsonian medications.”

“Since we did not find symptomatic effects of CoQ10 in Parkinson’s disease, our study does not support the hypothesis that restoring the impaired energy metabolism of the diseased dopaminergic neurons leads to symptomatic benefits in Parkinson’s disease,” the authors conclude. “Future studies will need to explore the protective effects of CoQ10 at the highest effective dose (equivalent to about 2,400 milligrams per day of a standard formulation) over a long treatment period and in a large cohort of patients both sufficient to clearly define the protective potential of this compound in Parkinson’s disease.”

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(Arch Neurol. 2007;64:(doi:10.1001/archneur.64.7.nct60005). Available pre-embargo to the media at http://www.jamamedia.org.)

Editor’s Note: This study was supported by a grant from the Deutsche Parkinson-Vereinigung eV (German Parkinson Association), Neuss, Germany, and MSE Pharmazeutika GmbH, Bad Homburg, Germany. The co-enzyme Q10 and matching placebo were formulated and packaged without charge by MSE Pharmazeutika. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Testosterone may help men with multiple sclerosis

Contact: Mark Wheeler
310-794-2265
JAMA and Archives Journals

A small pilot study suggests that testosterone treatment is safe, well tolerated and may reduce symptoms, slow brain degeneration and increase muscle mass in men with relapsing-remitting multiple sclerosis, the most common form of the disease, according to a report in the May issue of Archives of Neurology, one of the JAMA/Archives journals.

Multiple sclerosis is a progressive disease involving the immune and central nervous systems. MS and many other autoimmune diseases (in which the body attacks its own systems or tissues) are less common in men than in women, according to background information in the article. This is especially true during reproductive years. Sex hormones, including testosterone and estrogen, may be responsible for the difference. Testosterone has been shown to protect against an MS–like condition and other autoimmune diseases in animals.

Nancy L. Sicotte, M.D., of the David Geffen School of Medicine at UCLA, Los Angeles, and colleagues conducted a study of testosterone treatment in 10 men with relapsing-remitting MS, characterized by periods of neurologic symptoms (such as numbness or difficulty walking) followed by periods of remission. The men, who had an average age of 46, were enrolled in the study and then entered a six-month pre-treatment phase, during which symptoms were monitored but no therapies were administered. Then, each man applied 10 grams of a gel containing 100 milligrams of testosterone to his upper arms once daily for 12 months.

“One year of treatment with testosterone gel was associated with improvement in cognitive performance and a slowing of brain atrophy [deterioration],” the authors write. During the first nine months of the study—the period of time before the men began taking testosterone, plus the first three months of treatment, before it had time to take effect—brain volume decreased an average of -0.81 percent per year. In the second nine months, this decline slowed by 67 percent to an annual rate of -0.25 percent. “Because the protective effect of testosterone treatment on brain atrophy was observed in the absence of an appreciable anti-inflammatory effect, this protection may not be limited to MS, but may be applicable to those with non-inflammatory neurodegenerative diseases,” including amyotrophic lateral sclerosis or Lou Gehrig’s disease, the authors write.

In addition, lean body mass (muscle mass) increased an average of 1.7 kilograms (about 3.74 pounds) during the treatment phase. Participants did not report any adverse effects, there were no abnormalities in blood tests taken during the trial and the men’s prostate examination results remained stable.

“Overall, in this first trial of testosterone treatment in men with relapsing-remitting MS, the treatment was shown to be safe and well tolerated,” the authors conclude. “In addition, exploratory findings reported herein suggest a possible neuroprotective effect of testosterone treatment in men, which warrants further investigation.”

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(Arch Neurol. 2007;64:683-688. Available pre-embargo to the media at http://www.jamamedia.org.)

Editor’s Note: This study was supported by grants from the National Multiple Sclerosis Society, the General Clinical Research Centers at Harbor-UCLA Medical Center, the Sherak Family Foundation and the Skirball Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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