F.D.A. Requires Cuts to Dosages of Ambien and Other Sleep Drugs

WASHINGTON — For two decades, millions of Americans have taken Ambien to help them sleep at night. But for years, the Food and Drug Administration has gotten complaints that people felt drowsy the morning after taking the medicine or its successors, and sometimes got into car accidents.

On Thursday, after laboratory studies and driving tests confirming the risks of drowsiness, the agency said that women should be taking half as much.

The new recommendation applies to drugs containing the active ingredient zolpidem, by far the most widely used sleep aid. Using lower doses means less of the drug will remain in the blood in the morning hours, and will reduce the risk that people who use it will be impaired while driving.

Sleeping pills have boomed in popularity with the increasingly frantic pace of modern American life. According to IMS, a health care information and technology company, about 60 million prescriptions were dispensed in 2011, up about 20 percent since 2006. About 40 million were for products containing zolpidem.

The agency’s announcement was focused on women because they take longer to metabolize the drug than men. An estimated 10 percent to 15 percent of women will have a level of zolpidem in their blood that could impair driving eight hours after taking the pill, while only about 3 percent of men do, said Dr. Robert Temple, an official in the agency’s Center for Drug Evaluation and Research.

Reports of aftereffects from sleeping pills have circulated for years, and some doctors questioned why the drug agency took so long to act. Mishaps with sleepy driving — and even strange acts of texting, eating or having sex in the night without any memory of it in the morning — have long been familiar to the medical community.

“In this case, the F.D.A. may be behind the 8-ball,” said Daniel Carlat, an associate clinical professor of psychiatry at Tufts University, referring to residual drowsiness. “This has been a known problem. Few doctors will be surprised hearing about this. They’ll say, ‘Oh yeah, we’ve already seen this in our patients.’ ”

He added that Thursday’s announcement “will be good for public health because it will get patients to ask their doctors about the appropriate dosage.”

Agency officials acknowledged that they had received about 700 reports of driving mishaps with people on zolpidem over the years, with a spike in 2007 after a change in labeling caused more people to call in complaints. But they said it was not easy to draw a direct connection between the reports and the drug. Patients often did not remember what time they took the pill. Sometimes they had been drinking.

It was not until the drug agency reviewed driving simulation studies from controlled trials of the drug Intermezzo, which was approved in 2011 for middle-of-the-night waking, that a more complete picture of the risks emerged. The agency linked the driving simulation information with data from manufacturers on the amount of zolpidem in patients’ blood and determined that levels above about 50 nanograms per milliliter increased the risk of crashing while driving, said Dr. Ellis Unger, an official at the agency’s Center for Drug Evaluation and Research.

Dr. Unger said that all makers of new sleeping drugs would now be asked to conduct driving trials; a spokeswoman clarified that it would not be required.

“A lot of people are wondering about the elephant in the room,” Dr. Unger said. “Why did this take so long? This is science, and our thinking evolves over time.”

The drug agency told manufacturers that the recommended dose for women should be lowered to 5 milligrams from 10 for immediate-release products like Ambien, Edluar and Zolpimist. Doses for extended-release products should be lowered to 6.25 milligrams from 12.5, the agency said. Most sleeping drugs containing zolpidem are now generic.

For men, the agency informed manufacturers that labels should recommend that health care providers should “consider” prescribing lower doses.

Patients taking the higher doses should continue them for the time being, officials said, but should consult with their doctors about lowering them. Doctors can still prescribe the higher dose if the lower one does not work. The lower doses are already commercially available, Dr. Unger said, as they are recommended for older patients.

Sanofi, the manufacturer of Ambien and Ambien CR, said in a statement that it agreed that people taking zolpidem “should always talk to their doctor about the most appropriate dose,” and that the label “provides important information” to determine what that is. The company added that it “stands behind the significant clinical data demonstrating the safety and efficacy of Ambien.”

The drug has also been known to cause sleepwalking incidents, and Dr. Unger said there was evidence that the lower dose might ease such events, though it is weaker than the evidence about next-morning-drowsiness. Dr. Carlat said one of his patients discovered that her weight gain while on the drug was from midnight trips to the kitchen she did not even remember taking.

Dr. Daniel Kripke, professor emeritus of psychiatry at the University of California, San Diego, and a leading critic of sleeping pills, welcomed the move but said the agency was still not doing enough to investigate other possible side effects.

“It’s a very small step in the right direction,” he said. He added that sleeping medications like zolpidem might increase total sleep time by 20 minutes a night, but that most studies suggest that the use of sleeping pills impairs a person’s performance the next day.

Critics of the drug agency said the label on Intermezzo, which very clearly denotes the risks for women, indicate that the agency was aware of these problems earlier.

But Thomas Roth, director of the sleep center at Henry Ford Hospital in Detroit who has been a consultant to sleeping pill makers, said that the drug agency had always been concerned about the potential risks with driving, “but they care about it more now.” He said he believed the lower dose would still be effective for many patients.

Agency officials say all patients are unique and doses will need to be tailored. They say the drugs should be prescribed at the lowest dose required.

Dr. Daniel J. Buysse, professor of psychiatry at the University of Pittsburgh School of Medicine, said he already prescribed the lower dose when he feels it is necessary, by telling patients to cut a tablet in half along the score.

“This just tells me, maybe be a little bit more cautious,” said Dr. Buysse, who has been a consultant for drug companies including the maker of Ambien. “But I do not think it will have a big effect on what I do.”

Andrew Pollack contributed reporting from San Francisco.

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Electronic Records Systems Have Not Reduced Health Costs, Report Says

The conversion to electronic health records has failed so far to produce the hoped-for savings in health care costs and has had mixed results, at best, in improving efficiency and patient care, according to a new analysis by the influential RAND Corporation.

Jim Wilson/The New York Times

Dr. Alvin Rajkomar tracks patient data on a Samsung Galaxy Note. A new report questions whether electronic records reduce health care costs.

Optimistic predictions by RAND in 2005 helped drive explosive growth in the electronic records industry and encouraged the federal government to give billions of dollars in financial incentives to hospitals and doctors that put the systems in place.

“We’ve not achieved the productivity and quality benefits that are unquestionably there for the taking,” said Dr. Arthur L. Kellermann, one of the authors of a reassessment by RAND that was published in this month’s edition of Health Affairs, an academic journal.

RAND’s 2005 report was paid for by a group of companies, including General Electric and Cerner Corporation, that have profited by developing and selling electronic records systems to hospitals and physician practices. Cerner’s revenue has nearly tripled since the report was released, to a projected $3 billion in 2013, from $1 billion in 2005.

The report predicted that widespread use of electronic records could save the United States health care system at least $81 billion a year, a figure RAND now says was overstated. The study was widely praised within the technology industry and helped persuade Congress and the Obama administration to authorize billions of dollars in federal stimulus money in 2009 to help hospitals and doctors pay for the installation of electronic records systems.

“RAND got a lot of attention and a lot of buzz with the original analysis,” said Dr. Kellermann, who was not involved in the 2005 study. “The industry quickly embraced it.”

But evidence of significant savings is scant, and there is increasing concern that electronic records have actually added to costs by making it easier to bill more for some services.

Health care spending has risen $800 billion since the first report was issued, according to federal figures. The reasons are many, from the aging of the baby boomer population, to the cost of medical advances, to higher usage of medical services over all.

Officials at RAND said their new analysis did not try to put a dollar figure on how much electronic record-keeping had helped or hurt efforts to reduce costs. But the firm’s acknowledgment that its earlier analysis was overly optimistic adds to a chorus of concern about the cost of the new systems and the haste with which they have been adopted.

The recent analysis was sharply critical of the commercial systems now in place, many of which are hard to use and do not allow doctors and patients to share medical information across systems. “We could be getting much more if we could take the time to do a little more planning and to set more standards,” said Marc Probst, chief information officer for Intermountain Healthcare, a large health system in Salt Lake City that developed its own electronic records system and is cited by RAND as an example of how the technology can help improve care and reduce costs.

The RAND researchers pointed to a number of other reasons the expected savings had not materialized. The rate of adoption has been slow, they said, and electronic records do not address the fact that doctors and hospitals reap the benefits of high volumes of care.

Many experts say the available systems seem to be aimed more at increasing billing by providers than at improving care or saving money. Federal regulators are investigating whether electronic records make it easier for hospitals and doctors to bill for services they did not provide and whether Medicare and other federal agencies are adequately monitoring the use of electronic records.

Technology “is only a tool,” said Dr. David Blumenthal, who helped oversee the federal push for the adoption of electronic records under President Obama and is now president of the Commonwealth Fund, a nonprofit health group. “Like any tool, it can be used well or poorly.” While there is strong evidence that electronic records can contribute to better care and more efficiency, Dr. Blumenthal said, the systems in place do not always work in ways that help achieve those benefits.

Federal officials say they are drafting new rules to address many of the concerns about the current systems.

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World Briefing | The Americas: Mexico: Killer Dog Case Widens

A pack of feral dogs may be responsible for the deaths of as many as five people in a Mexico City park, the authorities said Wednesday. Last week, the police said dogs had killed four people, including a woman and a baby boy, whose mutilated bodies were found in the park in December. Now, prosecutors are investigating if the wounds found on a fifth person, a 15-year-old girl who died in December, are consistent with dog bites. The authorities have captured several dogs, spurring an online campaign to save them, but it is not clear if any are the culprits.

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Delegation to North Korea Urges More Access to Internet and Cellphones

PYONGYANG, North Korea (AP) — A private delegation to North Korea that includes Google’s executive chairman, Eric E. Schmidt, is urging North Korea to allow more open Internet access and cellphones, although it is unclear how that message is being heard by a leadership that has long depended on a near-total ban on outside information to maintain its totalitarian rule.

Bill Richardson, the former New Mexico governor leading the delegation, said Wednesday in an interview in Pyongyang, the North’s capital, that his nine-member group had also called on North Korea to put a moratorium on missile launchings and nuclear tests that have prompted United Nations sanctions.

He said the group had also asked for “fair and humane treatment” for Kenneth Bae, a naturalized American citizen born in South Korea who was detained by the North in November and charged with unspecified “hostile acts.”

The delegation’s visit has been criticized as appearing to hijack United States diplomacy and bolster North Korea’s profile after its latest, widely condemned rocket launching less than a month ago.

The State Department characterized the trip as unhelpful at a time when the United States is rallying support for sanctions by the United Nations Security Council as a response to the launching.

North Korea has shown no inclination to back off its nuclear program or to stop the launchings that it depicts as needed to send satellites into orbit, but that Western countries believe are tests for technology to create missiles that could eventually be used to deliver nuclear weapons.

Mr. Schmidt is the highest-profile American business executive to visit North Korea since Kim Jong-un took power a year ago. A vocal proponent of Internet freedom and openness, Mr. Schmidt has not said publicly what he hopes to get out of the visit. On Wednesday, he toured the frigid brick building in central Pyongyang that was presented as the heart of North Korea’s computer industry, at one point briefly donning a pair of 3-D goggles.

Mr. Kim has emphasized the importance of computerizing factories, many of which have fallen into disrepair in the years since the collapse of the former Soviet Union deprived the country of its main provider of technology. But he also has vowed in recent weeks to crack down on the “enemy’s ideological and cultural infiltration,” apparently a reference to the growing flow of information over the border with China.

That flow has been driven in part by North Koreans who sneak into China to bring much-needed food and goods back home, but who also bring back news of the outside world and sometimes DVDs and thumb drives containing banned South Korean dramas.

Mr. Richardson, who has described the delegation as a private humanitarian mission, said the members were bringing a message that more openness would benefit North Korea. Almost no one in the impoverished country owns computers, and even many of the computers that are allowed are not hooked up to the Internet, according to analysts who study the North. They say that even the small number of North Koreans allowed onto the Web — a group said to include party loyalists and computer science students — are severely restricted in what they can access.

On Tuesday, Mr. Schmidt, Mr. Richardson and other delegation members chatted with students who have permission to access the Internet for research at the elite Kim Il-sung University in Pyongyang.

On Wednesday, the group toured the main library in Pyongyang, the Grand People’s Study House, where people were crowded into drafty, unheated halls at computers with intranet access to the library’s archive of books, documents and newspapers.

Later, the delegation visited the Korea Computer Center, the hub of North Korea’s efforts to develop software, where a quote from the current leader’s father and predecessor as leader, Kim Jong-il, reads: “Now is the era for science and technology. It is the era of computers.”

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Pap Test May Prove Useful at Detecting More Types of Cancer, Study Suggests

The Pap test, which has prevented countless deaths from cervical cancer, may eventually help to detect cancers of the uterus and ovaries as well, a new study suggests.

For the first time, researchers have found genetic material from uterine or ovarian cancers in Pap smears, meaning that it may become possible to detect three diseases with just one routine test.

But the research is early, years away from being used in medical practice, and there are caveats. The women studied were already known to have cancer, and while the Pap test found 100 percent of the uterine cancers, it detected only 41 percent of the ovarian cancers. And the approach has not yet been tried in women who appear healthy, to determine whether it can find early signs of uterine or ovarian cancer.

On the other hand, even a 41 percent detection rate would be better than the status quo in ovarian cancer, particularly if the detection extends to early stages. The disease is usually advanced by the time it is found, and survival rates are poor. About 22,280 new cases were expected in the United States in 2012, and 15,500 deaths. Improved tests are urgently needed.

Uterine cancer has a better prognosis, but still kills around 8,000 women a year in the United States.

These innovative applications of the Pap test are part of a new era in which advances in genetics are being applied to the detection of a wide variety of cancers or precancerous conditions. Scientists are learning to find minute bits of mutant DNA in tissue samples or bodily fluids that may signal the presence of hidden or incipient cancers.

Ideally, the new techniques would find the abnormalities early enough to cure the disease or even prevent it entirely. But it is too soon to tell.

“Is this the harbinger of things to come? I would answer yes,” said Dr. Bert Vogelstein, director of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, and a senior author of a report on the Pap test study published on Wednesday in the journal Science Translational Medicine. He said the genomes of more than 50 types of tumors had been sequenced, and researchers were trying to take advantage of the information.

Similar studies are under way or are being considered to look for mutant DNA in blood, stool, urine and sputum, both to detect cancer and also to monitor the response to treatment in people known to have the disease.

But researchers warn that such tests, used for screening, can be a double-edged sword if they give false positive results that send patients down a rabbit hole of invasive tests and needless treatments. Even a test that finds only real cancers may be unable to tell aggressive, dangerous ones apart from indolent ones that might never do any harm, leaving patients to decide whether to watch and wait or to go through surgery, chemotherapy and radiation with all the associated risks and side effects.

“Will they start recovering mutations that are not cancer-related?” asked Dr. Christopher P. Crum, a professor at Harvard Medical School who was not involved in the research.

But he also called the study a “great proof of principle,” and said, “Any whisper of hope to women who suffer from endometrial or ovarian cancer would be most welcome.”

DNA testing is already performed on samples from Pap tests, to look for the human papillomavirus, or HPV, which causes cervical cancer. Dr. Vogelstein and his team decided to try DNA testing for cancer. They theorized that cells or DNA shed from cancers of the ovaries and the uterine lining, or endometrium, might reach the cervix and turn up in Pap smears.

The team picked common mutations found in these cancers, and looked for them in tumor samples from 24 women with endometrial cancer and 22 with ovarian cancer. All the cancers had one or more of the common mutations.

Then, the researchers performed Pap tests on the same women, and looked for the same DNA mutations in the Pap specimens. They found the mutations in 100 percent of the women with endometrial cancer, but in only 9 of the 22 with ovarian cancer. The test identified two of the four ovarian cancers that had been diagnosed at an early stage.

Finally, the team developed a test that would look simultaneously for cancer-associated mutations in 12 different genes in Pap samples. Used in a control sample of 14 healthy women, the test found no mutations — meaning no false-positive results.

Dr. Luis A. Diaz, the other senior author of the report and an associate professor of oncology at Johns Hopkins, called the research a step toward a screening test that at first blush appears very effective at detecting endometrial cancer, though obviously less so at finding ovarian cancer.

“Probably one of the most exciting features of this approach,” Dr. Diaz said, “is that we wanted a test that would seamlessly integrate with routine medical practice that could be utilized with the same test that women get every day all over the world, the Pap smear.”

But, he added: “We can’t say it’s ready for prime time. Like all good science, it needs to be validated.”

He and other members of the team said it might be possible to improve the detection rate for ovarian cancer by looking for more mutations and by changing the technique of performing Pap tests to increase the likelihood of capturing cells from the ovary. The change might involve timing the test to a certain point in a woman’s monthly cycle, using a longer brush to collect cells from deeper within the cervix or prescribing a drug that would raise the odds of cells being shed from the ovary.

The technique also needs to be tested in much larger groups of women, including healthy ones, to find out whether it works, particularly at finding cancers early enough to improve survival. And studies must also find out whether it generates false positive results, or identifies cancers that might not actually need to be treated.

Michael H. Melner, a program director in molecular genetics and biochemistry for the American Cancer Society, called the research “very promising,” in part because it is based on finding mutations.

“It tells you not just that cancer is there, but which mutation is there,” Dr. Melner said. “As we learn more and more about which mutations are associated with more or less severe forms of cancer, it’s more information, and possibly more diagnostic.”

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Pap Test May Prove Useful at Detecting More Types of Cancer, Study Suggests

The Pap test, which has prevented countless deaths from cervical cancer, may eventually help to detect cancers of the uterus and ovaries as well, a new study suggests.

For the first time, researchers have found genetic material from uterine or ovarian cancers in Pap smears, meaning that it may become possible to detect three diseases with just one routine test.

But the research is early, years away from being used in medical practice, and there are caveats. The women studied were already known to have cancer, and while the Pap test found 100 percent of the uterine cancers, it detected only 41 percent of the ovarian cancers. And the approach has not yet been tried in women who appear healthy, to determine whether it can find early signs of uterine or ovarian cancer.

On the other hand, even a 41 percent detection rate would be better than the status quo in ovarian cancer, particularly if the detection extends to early stages. The disease is usually advanced by the time it is found, and survival rates are poor. About 22,280 new cases were expected in the United States in 2012, and 15,500 deaths. Improved tests are urgently needed.

Uterine cancer has a better prognosis, but still kills around 8,000 women a year in the United States.

These innovative applications of the Pap test are part of a new era in which advances in genetics are being applied to the detection of a wide variety of cancers or precancerous conditions. Scientists are learning to find minute bits of mutant DNA in tissue samples or bodily fluids that may signal the presence of hidden or incipient cancers.

Ideally, the new techniques would find the abnormalities early enough to cure the disease or even prevent it entirely. But it is too soon to tell.

“Is this the harbinger of things to come? I would answer yes,” said Dr. Bert Vogelstein, director of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, and a senior author of a report on the Pap test study published on Wednesday in the journal Science Translational Medicine. He said the genomes of more than 50 types of tumors had been sequenced, and researchers were trying to take advantage of the information.

Similar studies are under way or are being considered to look for mutant DNA in blood, stool, urine and sputum, both to detect cancer and also to monitor the response to treatment in people known to have the disease.

But researchers warn that such tests, used for screening, can be a double-edged sword if they give false positive results that send patients down a rabbit hole of invasive tests and needless treatments. Even a test that finds only real cancers may be unable to tell aggressive, dangerous ones apart from indolent ones that might never do any harm, leaving patients to decide whether to watch and wait or to go through surgery, chemotherapy and radiation with all the associated risks and side effects.

“Will they start recovering mutations that are not cancer-related?” asked Dr. Christopher P. Crum, a professor at Harvard Medical School who was not involved in the research.

But he also called the study a “great proof of principle,” and said, “Any whisper of hope to women who suffer from endometrial or ovarian cancer would be most welcome.”

DNA testing is already performed on samples from Pap tests, to look for the human papillomavirus, or HPV, which causes cervical cancer. Dr. Vogelstein and his team decided to try DNA testing for cancer. They theorized that cells or DNA shed from cancers of the ovaries and the uterine lining, or endometrium, might reach the cervix and turn up in Pap smears.

The team picked common mutations found in these cancers, and looked for them in tumor samples from 24 women with endometrial cancer and 22 with ovarian cancer. All the cancers had one or more of the common mutations.

Then, the researchers performed Pap tests on the same women, and looked for the same DNA mutations in the Pap specimens. They found the mutations in 100 percent of the women with endometrial cancer, but in only 9 of the 22 with ovarian cancer. The test identified two of the four ovarian cancers that had been diagnosed at an early stage.

Finally, the team developed a test that would look simultaneously for cancer-associated mutations in 12 different genes in Pap samples. Used in a control sample of 14 healthy women, the test found no mutations — meaning no false-positive results.

Dr. Luis A. Diaz, the other senior author of the report and an associate professor of oncology at Johns Hopkins, called the research a step toward a screening test that at first blush appears very effective at detecting endometrial cancer, though obviously less so at finding ovarian cancer.

“Probably one of the most exciting features of this approach,” Dr. Diaz said, “is that we wanted a test that would seamlessly integrate with routine medical practice that could be utilized with the same test that women get every day all over the world, the Pap smear.”

But, he added: “We can’t say it’s ready for prime time. Like all good science, it needs to be validated.”

He and other members of the team said it might be possible to improve the detection rate for ovarian cancer by looking for more mutations and by changing the technique of performing Pap tests to increase the likelihood of capturing cells from the ovary. The change might involve timing the test to a certain point in a woman’s monthly cycle, using a longer brush to collect cells from deeper within the cervix or prescribing a drug that would raise the odds of cells being shed from the ovary.

The technique also needs to be tested in much larger groups of women, including healthy ones, to find out whether it works, particularly at finding cancers early enough to improve survival. And studies must also find out whether it generates false positive results, or identifies cancers that might not actually need to be treated.

Michael H. Melner, a program director in molecular genetics and biochemistry for the American Cancer Society, called the research “very promising,” in part because it is based on finding mutations.

“It tells you not just that cancer is there, but which mutation is there,” Dr. Melner said. “As we learn more and more about which mutations are associated with more or less severe forms of cancer, it’s more information, and possibly more diagnostic.”

Read More..

Shares Rise as Companies Report Earnings

Stocks rose on Wall Street on Wednesday after corporate earnings reports got off to a good start.

The Dow Jones industrial average climbed 61.66 points to 13,390.51. The Standard & Poor’s 500-stock index gained 3.87 points to 1,461.02, and the Nasdaq composite rose 14 to 3,105.81.

Stocks are facing their first big challenge of the year as companies start to report earnings for the fourth quarter of 2012. Throughout last year, analysts cut their outlook for earnings growth in the period and now expect them to rise by 3.21 percent, according to data from S&P Capital IQ.

“Maybe earnings expectations were a little too low,” Ryan Detrick, a strategist at Schaeffer’s Investment Research, said. “You don’t need to have great earnings, you just need to beat those expectations” for stocks to rally, he said.

Early indications were decent. The aluminum maker Alcoa reported late Tuesday that it swung to a profit for the fourth quarter, with earnings that met Wall Street’s expectations. The company brought in more revenue than analysts had expected, and the company predicted rising demand for aluminum this year as the aerospace industry gains strength. Alcoa is usually the first Dow component to report earnings every quarter.

Despite the better revenue number, Alcoa’s stock performance Wednesday was lackluster. It traded higher for part of the day, then ended down 2 cents at $9.08 a share.

Other companies fared better after reporting earnings. Helen of Troy, which sells personal care products under brands like Dr. Scholl’s and Vidal Sassoon, rose 2.7 percent, up 90 cents to $34.43 after reporting a 15 percent increase in quarterly net income.

Boeing was the biggest gainer of the 30 stocks in the Dow. It jumped 3.5 percent, up $2.63 to $76.76, after two days of sharp declines set off by new problems for its 787 Dreamliner. Boeing said it had “extreme confidence” in the plane even as federal investigators tried to determine the cause of a fire on Monday aboard an empty Japan Airlines plane in Boston and a fuel leak in another Japan Airlines 787 on Tuesday.

The wireless network operator Clearwire rose 7.2 percent, or 21 cents, to $3.13, after Dish network made an unsolicited offer to buy the company, which has already agreed to sell itself to Sprint. Dish rose 88 cents to $36.85, and Sprint fell 9 cents to $5.88.

The online education company Apollo Group fell 7.8 percent after reporting a sharp decline in fall term student sign-ups at the University of Phoenix, which it operates. The stock fell $1.62, to $19.32 a share.

Interest rates were steady. The Treasury’s benchmark 10-year note rose 1/32, to 97 29/32, and the yield was unchanged at 1.86 percent.

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Communists and Liberals Face Off in China Censorship

GUANGZHOU, China — Protests over censorship at one of China’s most liberal newspapers descended into ideological confrontation in this southeastern provincial capital on Tuesday, pitting advocates of free speech against supporters of Communist Party control, who wielded red flags and portraits of Mao Zedong.

The face-off between liberals and leftists outside the headquarters of the company that publishes the weekly newspaper, Southern Weekend, came after disgruntled editors and reporters at the paper last week deplored what they said was crude meddling by the top propaganda official in Guangdong Province, which has long had a reputation as a bastion of a relatively free press.

With a number of celebrities and business leaders rallying online to the liberal cause, senior propaganda officials in Beijing began this week to roll out a national strategy of demonizing the rebel journalists and their supporters. The Central Propaganda Department issued a directive to news organizations saying that the defiant outburst at Southern Weekend, also known as Southern Weekly, had involved “hostile foreign forces.”

The order, translated by China Digital Times, a research group at the University of California, Berkeley, that studies Chinese news media, said that Chinese journalists must drop their support for Southern Weekend and insisted that “party control of the media is an unwavering basic principle.”

An editor at a party news organization said the term “hostile forces” had been used in an internal discussion with a senior editor about the Southern Weekend conflict. Several Chinese journalists outside Guangdong said Tuesday that a positive outcome for the frustrated Southern Weekend reporters and editors appeared uncertain, and that their call for the dismissal of Tuo Zhen, the top provincial propaganda official, who took up his post in May, was probably too radical for higher authorities to accept.

The protesting journalists at Southern Weekend blame Mr. Tuo, a former journalist himself, for ordering a drastic change in a New Year’s editorial that had originally called for greater respect for constitutional rights. The revised editorial instead praised party policies. Mr. Tuo has not commented.

A former editor at the Nanfang Media Group, which includes Southern Weekend, said negotiations continued on Tuesday between provincial propaganda officials and representatives of the disgruntled journalists and editors.

The former editor, who asked that his name not be used for fear it could jeopardize his current job, said the talks focused on the protesting journalists’ demands for an inquiry into the New Year’s episode and for the newspaper’s managers to rescind a statement that absolved Mr. Tuo of responsibility for the editorial.

“They want that statement to be removed, and they also want assurances about relaxing controls on journalists — not removing party oversight, but making it more reasonable, allowing reporters to challenge officials,” he said. “The other main demand is for an impartial explanation of what happened, an accounting so it won’t happen again.”

The former editor said a continued standoff into Wednesday could jeopardize the newspaper’s usual publication on Thursday. “In effect, it’s a strike,” he said. “It looks unclear whether it can come out on Thursday.”

So far, senior Chinese officials have not commented publicly on the censorship dispute at the paper, which could test how far the recently appointed Communist Party leader, Xi Jinping, will go in support of more open economic and political policies. “I don’t believe that Xi is totally hypocritical when he talks about reform,” said Chen Min, a prominent former opinion writer for Southern Weekend who was forced out of the newspaper in 2011 during a party-led crackdown on potential dissent.

Defenders of Communist orthodoxy turned up at the newspaper headquarters on Tuesday to make the case for firm party control of the media.

“We support the Communist Party, shut down the traitor newspaper,” said a cardboard sign held up by one of 10 or so conservative demonstrators.

“Southern Weekend has an American dream,” another sign said. “We don’t want the American dream, we want the Chinese dream.”

Most of the party supporters refused to give their names. One who did, Yang Xingfa, 50, from Hunan Province, said: “Southern Weekend belongs to the people. However, the paper always ignores the achievements of the Chinese Communist Party and asks why China isn’t more like the United States. Outrageous!”

Some of the participants held portraits of Mao; others waved the red flags of China and of the Communist Party. They said they had come on their own initiative and not at the behest of officials.

The dueling protests outside the newspaper headquarters reflected the political passions and tensions raised by the quarrel over censorship. Internet chatter about the conflict has become widespread, and finding a resolution to the standoff poses a challenge both to the central authorities and to Hu Chunhua, the new party chief of Guangdong and a potential candidate to succeed Mr. Xi in a decade.

Hundreds of bystanders watched and took photos on cellphones as the leftists shouted at the 20 or more protesters who had gathered to denounce censorship, and shoving matches broke out between the demonstrators. The 70 or so police officers and security guards mostly watched, stepping in on occasion to separate the two sides.

At one point, leftists were showered with 50-cent renminbi currency notes, which are worth about 8 United States cents. The Fifty-Cent Party has become a popular term used to disparage pro-party leftists, who are accused by critics of taking 50 cents as payment for each pro-party message they post on the Internet.

One defender of the Southern Weekend journalists was Liang Taiping, 28, a poet who wore a mask popularized by the Hollywood movie and British comic book “V for Vendetta.” Mr. Liang said he had bought the mask after watching the movie recently on state-run China Central Television, which had surprised many Chinese with its willingness to show the film uncut, since the film advocates the overthrow of a one-party dictatorship.

“It’s the only newspaper in China that’s willing to tell the truth,” said Mr. Liang, who added that he had traveled by train about 350 miles from the southern city of Changsha to show his support. “What’s the point of living if you can’t even speak freely?”

Edward Wong reported from Guangzhou, and Chris Buckley from Hong Kong. Jonah M. Kessel contributed reporting from Guangzhou, and Jonathan Ansfield from Beijing. Mia Li contributed research from Guangzhou.

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Baseball Dumping Dugout-to-Bullpen Landlines

The reserve clause is dead. And so are wool uniforms. There are no longer eight teams in each league. And the Houston Astros have departed the National League.

 Major League Baseball is now about to disconnect the landlines that link dugouts to bullpens. Long after the rest of society embraced cellphones, managers and coaches will soon be able to discuss pitching changes on Samsung Galaxy S III phones.

The 21st century 4G dugout-to-bullpen connection that is being created by T-Mobile USA as part of its wireless sponsorship with Major League Baseball was announced Tuesday at the International Consumer Electronics Show in Las Vegas.

 “This is baseball’s continued push into the digital age,” said Tim Brosnan, Major League Baseball’s executive vice president for business. “It’s also about a very aggressive wireless provider that sought us out to create this unique communications platform.”

Baseball had not thought of a dugout-to-bullpen phone system in its talks with various wireless providers about a national sponsorship over the past decade, Brosnan said.

The wireless system will be tested at the World Baseball Classic in Arizona in March; after assessing how it worked, and fixing any problems, it will be rolled out in the major leagues. Whether each stadium will have it in 2013 has not been determined.

T-Mobile’s sponsorship plans also include enhancing network connectivity for fans at all ballparks and helping MLB Advanced Media create content for smartphones and tablets.

To create the dugout-to-bullpen communications system, each ballpark will get the equivalent of a small cellular system with a miniature cell tower.

But while wireless companies like T-Mobile are continuously trying to broaden their national coverage territory, the dugout-to-bullpen system will have limits enforced by a technology called geo-fencing. So, managers and pitching coaches will not be able to chat with the bullpen coach from the pitcher’s mound. And bullpen coaches cannot ask, “Can you hear me now?” once they leave the bullpen’s environs.

“The guidance we’ve been given is that we shouldn’t fundamentally change what makes baseball baseball,” said Mark McDiarmid, T-Mobile’s vice president for engineering. “There is reason to be cautious about how far the coach could move away from the dugout before the umpires might think it’s inappropriate.”

Baseball is not shifting to cellphones because of an incident during the eighth inning of Game 5 of the 2011 World Series when the noise at Rangers Ballpark in Arlington caused Derek Lilliquist, the Cardinals’ bullpen coach, to misunderstand Manager Tony La Russa’s instructions about which relievers should start warming up.

Twice, La Russa asked that Jason Motte get up. Lilliquist apparently did not hear the first request. When La Russa called again to get Motte ready, Lilliquist thought he was asking for Lance Lynn. The miscommunication led to La Russa’s surprise when he summoned a right-hander and Lynn arrived at the mound, not Motte. Lynn stayed in long enough to issue an intentional walk; Motte quickly got ready and replaced him.

Lilliquist might well have heard La Russa’s instructions if they had used the cellphone system, with multiple microphones, noise mitigation and the ability to raise audio levels.

 Given T-Mobile’s investment over the next three years, it is not surprising that each dugout’s branded cellphone docking station — about the size of a personal computer tower — will be about as visible to TV cameras as the Gatorade vessel is.

But, Brosnan said, baseball has not ordained the obvious commercial tie-in: that each call to the bullpen on Fox, ESPN and TBS’s national telecasts be sponsored by T-Mobile.

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Gaps Seen in Therapy for Suicidal Teenagers

Most adolescents who plan or attempt suicide have already received at least some mental health treatment, raising questions about the effectiveness of current approaches to helping troubled youths, according to the largest in-depth analysis to date of suicidal behaviors in American teenagers.

The study, in the journal JAMA Psychiatry, found that 55 percent of suicidal teenagers had received some therapy before they thought about suicide, planned it or tried to kill themselves, contradicting the widely held belief that suicide is due in part to a lack of access to treatment.

The findings, based on interviews with a nationwide sample of more than 6,000 teenagers and at least one parent of each, linked suicidal behavior to complex combinations of mood disorders like depression and behavior problems like attention-deficit and eating disorders, as well as alcohol and drug abuse.

The study found that about one in eight teenagers had persistent suicidal thoughts at some point, and that about a third of those who had suicidal thoughts had made an attempt, usually within a year of having the idea.

Previous studies have had similar findings, based on smaller, regional samples. But the new study is the first to suggest, in a large nationwide sample, that access to treatment does not make a big difference.

The study suggests that effective treatment for severely suicidal teenagers must address not just mood disorders, but also behavior problems that can lead to impulsive acts, experts said. According to the Centers for Disease Control and Prevention, 1,386 people between the ages of 13 and 18 committed suicide in 2010, the latest year for which numbers are available.

“I think one of the take-aways here is that treatment for depression may be necessary but not sufficient to prevent kids from attempting suicide,” said Dr. David Brent, a professor of psychiatry at the University of Pittsburgh, who was not involved in the study. “We simply do not have empirically validated treatments for recurrent suicidal behavior.”

The report said nothing about whether the therapies given were state of the art or carefully done, said Matt Nock, a professor of psychology at Harvard and the lead author, and it is possible that some of the treatments prevented suicide attempts. “But it’s telling us we’ve got a long way to go to do this right,” Dr. Nock said. His co-authors included Ronald C. Kessler of Harvard and researchers from Boston University and Children’s Hospital Boston.

Margaret McConnell, a consultant in Alexandria, Va., said her daughter Alice, who killed herself in 2006 at the age of 17, was getting treatment at the time. “I think there might have been some carelessness in the way the treatment was done,” Ms. McConnell said, “and I was trusting a 17-year-old to manage her own medication. We found out after we lost her that she wasn’t taking it regularly.”

In the study, researchers surveyed 6,483 adolescents from the ages of 13 to 18 and found that 9 percent of male teenagers and 15 percent of female teenagers experienced some stretch of having persistent suicidal thoughts. Among girls, 5 percent made suicide plans and 6 percent made at least one attempt (some were unplanned).

Among boys, 3 percent made plans and 2 percent carried out attempts, which tended to be more lethal than girls’ attempts.

(Suicidal thinking or behavior was virtually unheard-of before age 10.)

Over all, about one-third of teenagers with persistent suicidal thoughts went on to make an attempt to take their own lives.

Almost all of the suicidal adolescents in the study qualified for some psychiatric diagnosis, whether depression, phobias or generalized anxiety disorder. Those with an added behavior problem — attention-deficit disorder, substance abuse, explosive anger — were more likely to act on thoughts of self-harm, the study found.

Doctors have tested a range of therapies to prevent or reduce recurrent suicidal behaviors, with mixed success. Medications can ease depression, but in some cases they can increase suicidal thinking. Talk therapy can contain some behavior problems, but not all.

One approach, called dialectical behavior therapy, has proved effective in reducing hospitalizations and suicide attempts in, among others, people with borderline personality disorder, who are highly prone to self-harm.

But suicidal teenagers who have a mixture of mood and behavior issues are difficult to reach. In one 2011 study, researchers at George Mason University reduced suicide attempts, hospitalizations, drinking and drug use among suicidal adolescent substance abusers. The study found that a combination of intensive treatments — talk therapy for mood problems, family-based therapy for behavior issues and patient-led reduction in drug use — was more effective than regular therapies.

“But that’s just one study, and it’s small,” said Dr. Brent of the University of Pittsburgh. “We can treat components of the overall problem, but that’s about all.”

Ms. McConnell said that her daughter’s depression had seemed mild and that there was no warning that she would take her life. “I think therapy does help a lot of people, if it’s handled right,” she said.

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