Commuters may play a key role in spreading the flu virus across the United States, according to a study published online in 

    The authors analyzed data on the spread of flu viruses between 1972 and 2002 in the lower 48 states and the District of Columbia. They then correlated this with information on human travel, including commuting and long-distance trips.

    The results indicated that people traveling to and from work are largely responsible for spreading the flu from city to city and state to state. The speed at which the virus spreads depends in large part on where it originated, explained co-author Mark Miller, the associate director of research at the National Institutes of Health’s Fogarty International Center.

    Connectivity, not size or population, is the most important factor in predicting how long it will take a flu virus to reach neighboring cities or states, Miller said. For example, the paper explains, an outbreak in relatively isolated Wyoming would take longer to spread to other states than an outbreak in California, which is well connected to other states and nations.

    The paper notes that the spread of a virus that begins the flu season often takes place in California. Miller added that an outbreak of avian flu in humans would likely begin in California as well, because of the state’s large population. Some people speculate that high rate of travel between California and Asia makes the Golden State particularly susceptible, because many strains of influenza originate in Asia.

    But Miller noted that there is no sure way to predict where such an outbreak would take place.

    An avian flu epidemic is difficult to predict, Miller said, because it could enter the United States having already mutated to be transmissible between humans. On the other hand, this mutation could occur in the United States, after the virus spread to birds in the country.

    The study found that in a normal flu season, a virus takes five to seven weeks to cross the country, Miller said. In years when a more virulent strain causes a pandemic, the virus spreads more quickly. If the virus is a strain -- such as avian flu -- that the general population has never encountered before, it could spread across the nation in two to four weeks, he added.

    These results indicate that encouraging people to work from home could significantly slow down a potentially pandemic virus’ spread, Miller said.

    He thinks policy makers should study possible methods for controlling a pandemic, such as identifying populations that should be vaccinated to slow the spread of an outbreak.

    Miller and his colleagues plan to expand their research to include data about children, who are thought to be responsible for spreading flu viruses through local communities. They also plan to look at the spread of flu viruses in other countries, he said.

Articles

New research shows that travel to and from work is important in spreading influenza from city to city and state to state.

Commuting Plays a Major Role in the Spread of Influenza

Novartis AG increased its bid to acquire 56 percent of shares in Chiron Corp. to $48 per share, April 3. 

    The Swiss company, which already owns the other 44 percent of Chiron shares, had previously offered $45 per share, which was accepted by the non-Novartis members of the Chiron board. But the deal met with resistance from ValueAct Capital and CAM North America, funds which held large blocks of shares, as well as from one of the two proxy advisors evaluating the company, Institutional Shareholder Services. 

    After a weekend of negotiations, Novartis agreed to amend its offer. Chiron’s shareholders, including those from Novartis, are scheduled to decide on the bid April 19. 

    Chiron’s board rejected a $40-per-share bit from Novartis last fall. 

    Russell Gilbertson, analyst for Caris and Company, predicted in an April 4 report that the offer will be accepted, because ValueAct Capital and CAM North America are both on board with the deal.

    “Everyone seems to agree that $48 makes sense,” said Peter Young, president of specialized investment banking firm Young and Partners.

    Young added that Chiron was uniquely difficult to value because of the complexity of players involved.

    The two proxy advisors were split on the previous $45 per share offer, leaving Chiron in a difficult position, Young explained. In addition, ValueAct Capital had disagreements with Chiron’s management about their portrayal of the company leading up to the deal. 

    “It’s not that common for a big fund to have a position that could make or break a deal,” Young said.

    Lastly, Chiron had to please the plaintiffs in several shareholder lawsuits prompted by the board’s acceptance of the $45 offer, Young explained.

    Roger Aguinaldo, chief executive officer and publisher of M&A Advisor, speculated that the two companies had trouble negotiating a price because Novartis believed that its 44 percent stake in the company contributed to Chiron’s value. 

    “The value Novartis gave is reflected in the increased value of the rest of the stock,” Aguinaldo said.

    One way for other companies to avoid a similar predicament would be to agree on a formula to calculate the value of remaining shares when they purchase a stake in a company, Aguinaldo said.

    Young pointed to another reason for questions about Chiron’s value. Novartis is particularly interested in Chiron’s vaccine arm, and the vaccine market is facing a period of increased competition, according to Young. 

    Chiron’s vaccine business lost revenue to manufacturing problems during the last two flu seasons. But Morningstar analyst Jill Kiersky predicted in an April 4 report that the vaccine arm will bounce back.

    “[T]he vaccine should be a major contributor to the company’s bottom line in the future, given the strong demand for flu vaccines and limited suppliers,” she wrote.

    Kiersky noted that if the Novartis acquisition goes through as predicted, no flu vaccine manufacturers will be based in the United States.

Industry experts weigh in on what could be the resolution of a long saga.

Novartis Ups Bid for Chiron

A large, government-funded clinical trial comparing schizophrenia drugs highlights differences between these medications. But experts say that rather than pointing to a clear winner, the trial demonstrates the importance of choice in tailoring a treatment regimen for schizophrenic patients.

    Two articles published in the April issue of the 

contain the second phase of results from the National Institute of Mental Health’s (NIMH) Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. The two trials examined the efficacy and tolerability of second-generation antipsychotic drugs among patients who had discontinued therapy in the first phase of the study. The results of the first phase were published in September 2005. 

    The most groundbreaking results came from the arm of the trial that included Clozaril (clozapine), which was not part of the first phase. Patients on clozapine must be monitored closely by their doctors, because the drug is associated with some serious side effects including heart muscle inflammation and drastic drops in white blood cell counts, according to the NIMH.

    Doctors are often wary of using clozapine because of these side effects, said CATIE co-investigator J. Steven Lamberti of the University of Rochester Medical Center.

    But forty-four percent of the patients assigned to clozapine stayed on the drug through the end of the 18-month study. Only 18 percent of the patients re-assigned to the trial’s three other drugs – Seroquel (quetiapine), Risperdal (risperidone), and Zyprexa (olanzapine) – stayed on those drugs for the rest of the study.

    These results indicated that no patient should be considered a “poor responder,” someone who does not show significant improvements from medication, until he or she has tried clozapine, explained Stephen Marder, professor of psychology at the Semel Institute of the University of California Los Angeles. In contrast, people who respond very well to medication should try a different antipsychotic, with fewer side effects, before clozapine, he added.

    The second arm of the trials compared quetiapine, risperidone, and olanzapine with a newer drug, Geodon (ziprasidone). Unlike the other antipsychotics used in the CATIE trial, ziprasidone is not associated with weight gain and metabolic problems. All four of these drugs were included in the first phase of CATIE.

    Investigators thought that patients on ziprasidone would use that drug for the longest periods before changing therapies, Lamberti said.But patients stayed on risperidone and olanzapine for the longest periods. Olanzapine was also considered the most effective of the four at improving symptoms, even though it is associated with metabolic side effects.

    These results show that efficacy is more important than a patient’s ability to tolerate side effects, according to Lamberti.

    “No matter what, if a drug does not improve symptoms, then it is useless,” said Leslie Citrome, a professor of psychiatry at New York University’s medical school. “The balance between efficacy and tolerability is what individualized treatment is all about.”

    Taken together, the two paper’s outcomes demonstrate the importance of tailoring treatment to each patient’s individual needs, Lamberti explained.

    “There’s no clear better drug for everybody,” Marder said, adding that doctors and patients need access to “a broad range of choices.”

    But Citrome is concerned about the results that point to clozapine as the most effective choice for patients who already failed on another drug. Patients in this arm of the CATIE trial knew if they were assigned to clozapine, he explained, because the potential side effects require extra patient monitoring. What’s more, he explained, patients were only enrolled in this arm of the study if they expressed interest in taking clozapine. 

    As a result, Citrome is worried that some patients who agreed to participate in the clozapine arm, but were assigned to one of the other three drugs in the trial, discontinued because they knew they were not receiving clozapine.

    “If they were dissatisfied with the therapeutic response with the drug from phase I, and were not randomized to clozapine, both the clinician and patient may have been inclined to discontinue earlier, as the expectation may have been ‘more of the same’ as in phase I,” he said.

    But Citrome added that the results are consistent with other literature about clozapine.

Psychiatrists offer insight on the second phase of results from a National Institutes of Health study comparing different anti-psychotic drugs.

Pharmaceutical Executive-04-12-2006

Commuting Plays a Major Role in the Spread of Influenza

Novartis Ups Bid for Chiron

Study Compares Schizophrenia Treatments