Hepatitis C tests continue after NH tech's arrest

Hospitals across the country recommended hepatitis C testing for about 7,900 patients last summer after a traveling medical worker was accused of stealing drugs and infecting patients with tainted syringes in New Hampshire. But five months later, nearly half of those who were possibly exposed to the liver-destroying disease in other states have yet to be tested. Described by prosecutors as a "serial infector," David Kwiatkowski is accused of stealing syringes of the powerful painkiller fentanyl from the cardiac catheterization lab at New Hampshire's Exeter Hospital and replacing them with saline-filled syringes tainted with his own blood. In jail since his arrest in July, he pleaded not guilty to 14 federal drug charges earlier this month and is expected to go to trial next fall. Before April 2001, when he was hired in New Hampshire, Kwiatkowski worked as a traveling cardiac technologist in 18 hospitals in seven states, moving from job to job — despite being fired twice over allegations of drug use and theft. Thirty-two people in New Hampshire have been diagnosed with the same strain of hepatitis C that Kwiatkowski carries, along with six in Kansas, five in Maryland and one in Pennsylvania. At least 3,700 people outside New Hampshire have yet to be tested, hospitals and public health officials told The Associated Press. For example, in Michigan, where Kwiatkowski grew up and started his career, about 2,300 patients at five hospitals were notified that they may have been exposed to hepatitis C by Kwiatkowski. As of early December, only about 500 had gone in for testing, none of whom were diagnosed with a strain linked to the New Hampshire outbreak, according to the Michigan Department of Community Health. In Pennsylvania, 2,280 patients at the University of Pittsburgh Medical Center Presbyterian were notified that they should get tested, but only 840 have, one of whom was diagnosed with a matching strain of hepatitis C. Kwiatkowski was fired a few weeks into his temporary job at UPMC in 2008 after a co-worker accused him of swiping a fentanyl syringe from an operating room and sticking it down his pants. Citing a lack of evidence, hospital authorities didn't call police, and neither the hospital nor the medical staffing agency that placed him in the job informed the national accreditation organization for radiological technicians. Within days, Kwiatkowski was starting a new job at the Baltimore VA Medical Center, where one patient also has since been diagnosed with hepatitis C linked to Kwiatkowski. Though the VA center initially said it had identified 168 patients who may have been exposed, that number was later lowered, and 68 patients ultimately were tested. Two other Maryland hospitals where Kwiatkowski worked also have completed their testing, with no diagnosed cases of hepatitis C matching Kwiatkowski. But at the fourth, The Johns Hopkins Hospital in Baltimore, four patients have been diagnosed with the strain of disease linked to Kwiatkowski. About 500 of the 1,567 patients notified by Johns Hopkins have yet to be tested, according to hospital spokeswoman Kim Hoppe. Kwiatkowski had been referred by a staffing agency that assured Johns Hopkins that it had followed a vigorous vetting process, Hoppe said. He worked there for two 13-week stints, from July 2009 to January 2010. Saint Francis Hospital in Poughkeepsie, N.Y., where Kwiatkowski worked in late 2007 and early 2008, notified and tested 31 patients without finding any linked cases to Kwiatkowski. In Kansas, nearly all of the 416 patients who may have been exposed at Hays Medical Center have been tested and six have been diagnosed with infections linked to the New Hampshire outbreak. There have been no cases linked to Kwiatkowski in Arizona, where about 300 patients from two hospitals have been asked to get tested and about 280 have done so. Kwiatkowski worked at Maryvale Hospital in Phoenix in 2009 and the Arizona Heart Hospital in 2010. He was fired from the latter job after 10 days after a co-worker found him passed out in a bathroom stall with a stolen fentanyl syringe floating in the toilet. That incident was reported to police, Kwiatkowski's staffing agency, a state regulatory board and the national accreditation organization, but the accreditation group dropped its inquiry after learning police hadn't filed charges. Days later, Kwiatkowski landed a new job filling in for striking technicians at Temple University Hospital in Philadelphia. That hospital has recommended testing for 312 patients but won't say how many have followed through or have been diagnosed with hepatitis C. A hospital spokesman referred questions to the city health department, which did not return calls. Testing also is still under way in the last place Kwiatkowski worked before heading to New Hampshire — Houston Medical Center in Warner Robins, Ga. According to the hospital, fewer than 100 people have yet to be tested, and there haven't been any cases yet linked to Kwiatkowski. In New Hampshire, where about 3,300 patients were tested, Kwiatkowski is charged with seven counts of illegally obtaining drugs and seven counts of tampering with a consumer product, though prosecutors have said further charges are possible. Although New Hampshire cannot charge him for possible violations in other states, it can use evidence gathered in those jurisdictions in its trial, U.S. Attorney John Kacavas said. Other states are waiting to see the outcome of New Hampshire's case before deciding whether to file charges, he said. "We continue to reach out to other states affected by this matter," Kacavas said this week. "Other health organizations and departments continue to do their work in their states, but nothing has changed in the sense that our prosecution will go forward. At this point, we are the only prosecution in the country, and we'll see how it rolls out.

Read More..

Analysis: Stop-gap fix most likely outcome of "fiscal cliff" talks

The "fiscal cliff" deadline is days away and the U.S. Congress and President Barack Obama have left town for Christmas. But even if they were still here, it wouldn't have mattered, according to Steny Hoyer, the second-ranking Democrat in the House of Representatives. He says they were going nowhere to resolving the disagreement over how to fix the nation's fiscal problems. Last month's dreams of a "grand bargain" of tax hikes and spending cuts seem long gone. They had been reduced to more modest bargains in mid-December, and as 2013 approaches, are on the verge of relegation to a "stop-gap measure," at best the sort of temporary fix that Congress undertook in 2011. A stop-gap that puts everything off for a while but resolves nothing is now the most promising alternative, if there is to be one, to the across-the-board tax hikes and spending cuts described as a "fiscal cliff" because they threaten to send the U.S. economy plunging into another recession. It is also the way fiscal showdowns have ended in Washington in recent years. Such a fix, at best, would delay the spending cuts and tax hikes further into 2013 as well as work to address in a long-term way a government budget that has generated deficits exceeding $1 trillion in each of the last four years. Even worse, it would set up a huge fight in January and February over raising the U.S. debt ceiling, which controls the amount of money the federal government can borrow. Dysfunction in Washington was specifically cited as one of the reasons rating agency Standard & Poor's cut the U.S. debt rating to AA-plus after a battle over the debt ceiling in 2011. That alone - not to mention going over the cliff - could lead to another rating cut. At worst, the new year could start with a full-fledged jump off the 'cliff,' with an understanding, communicated to financial markets, that Congress and the White House would come back and try again for a solution. Given the apparent deadlock, some congressional aides this week said that Washington needed to begin telegraphing to Wall Street that markets should not panic if a "fiscal cliff" deal is not struck in December. The goal, one aide said on condition of anonymity, is to avoid starting 2013 with a steep stock market drop like the one the U.S. suffered in 2008, when the country's financial industry was falling apart and Congress was divided over what to do. On Friday, Obama acknowledged that only small steps might be possible with so little time remaining. Those, the Democratic president said, would consist of extending benefits for the long-term unemployed and keeping income tax rates low for 98 percent of Americans - meaning raising taxes on households with net incomes above $250,000 a year but not for those earning less. He held out the possibility of something "comprehensive," as he put it, but it had a hollow ring at the close of a work week that saw House Speaker John Boehner step back from negotiations and pursue a partisan plan that even some of his fellow Republicans could not stomach. MARKET PRESSURE The steps that Obama outlined were immediately rejected by Republicans, who have given ground on their previous steadfast opposition to any tax hikes but are still demanding that the White House agree to more substantial spending cuts. "The president has failed to offer any solution that passes the test of balance," declared Boehner spokesman Brendan Buck, minutes after the end of Obama's statement on Friday. On Saturday, a spokesman for Senate Republican leader Mitch McConnell was similarly dismissive, noting Obama's call had neither bipartisan support nor spending cuts to ride along with tax increases. McConnell, on Friday, suggested bringing up a House-passed bill that extends current tax rates for all Americans, including the top earners, and then pushes for comprehensive tax reform next year that theoretically could raise new revenues to help cut deficits. But Obama has promised repeatedly to veto any extension of the expiring Bush-era tax cuts that fail to hike rates for the wealthy. And Democrats, who control the Senate, have dismissed the McConnell idea, arguing that Obama ran his successful 2012 re-election campaign on a promise of forcing the wealthy to bear more of the burden of deficit reduction. Democratic aides in Congress think their own bill implementing Obama's $250,000 income threshold, which passed the 100-member Senate in July with 51 votes, could breeze through this month, or next year after the "fiscal cliff" is breached. The prospect of a breach is being discussed far more seriously now, and not just as a bluff or to set up the other side for blame. "I think we're going to go over the cliff," said Republican Representative Patrick Tiberi of Ohio. "I don't see something getting done." In an MSNBC interview Friday, Hoyer, a 31-year veteran of Congress from Maryland, said it wouldn't matter if everyone was in Washington instead of on holiday. "Frankly, we've been in town for four weeks and members haven`t been doing much," he said, calling it "one of the least productive times that I've been in Congress." Even Obama speaks of "a mismatch" between how people are thinking about the looming tax hikes and spending cuts "outside of this town and how folks are operating here. And we've just got to get that aligned," he said in his statement. ITG Investment Research Chief Economist Steve Blitz on Saturday said sliding the "fiscal cliff" negotiations into the new year was not a huge deal. "I think markets will pressure for a deal in January," he said. The "pressure" could be in the form of a significant stock market drop, which would hit workers' retirement plans, threaten to deter consumer and business spending, and possibly rattle other countries' economies at a time when the global economy is far from robust.

Read More..

Violence, fear & suspicion imperil Pakistan's war on polio

Pakistani health worker Bushra Bibi spent eight years trekking to remote villages, carefully dripping polio vaccine into toddlers' pursed mouths to protect them from the crippling disease. Now the 35-year-old mother is too scared to go to work after masked men on motorbikes gunned down nine of her fellow health workers in a string of attacks this week. "I have seen so much pain in the eyes of mothers whose children have been infected. So I have never seen this as just a job. It is my passion," she said. "But I also have a family to look after ... Things have never been this bad." After the deaths, the United Nations put its workers on lockdown. Immunizations by the Pakistani government continued in parts of the country. But the violence raised fresh questions over stability in the South Asian nation. Pakistan's Taliban insurgency, convinced that the anti-polio drive is just another Western plot against Muslims, has long threatened action against anyone taking part in it. The militant group's hostility deepened after it emerged that the CIA - with the help of a Pakistani doctor - had used a vaccination campaign to spy on Osama bin Laden's compound before he was killed by U.S. special forces in a Pakistan town last year. Critics say the attacks on the health workers are a prime example of the government's failure to formulate a decisive policy on tackling militancy, despite pressure from key ally the United States, the source of billions of dollars in aid. For years, authorities were aware that Taliban commanders had broadcast claims that the vaccination drive was actually a plot to sterilize Muslims. That may seem absurd to the West, but in Pakistan such assertions are plausible to some. Years of secrecy during military dictatorships, frequent political upheaval during civilian rule and a poor public education system mean conspiracy theories run wild. "Ever since they began to give these polio drops, children are reaching maturity a lot earlier, especially girls. Now 12 to 13-year-old girls are becoming women. This causes indecency in society," said 45-year-old Mir Alam Khan, a carpet seller in the northern town of Dera Ismail Khan. The father of four didn't allow any of his children to receive vaccinations. "Why doesn't the United States give free cures for other illnesses? Why only polio? There has to be an agenda," he said. While health workers risk attacks by militants, growing suspicions from ordinary Pakistanis are lowering their morale. Fatima, a health worker in the northwestern city of Peshawar, said that reaction to news of the CIA polio campaign was so severe that many of her colleagues quit. "People's attitudes have changed. You will not believe how even the most educated and well-to-do people will turn us away, calling us U.S. spies and un-Islamic," said the 25-year-old who did not give her last name for fear of reprisals. "Boys call us names, they say we are 'indecent women'." Pakistan's government has tried to shatter the myths that can undermine even the best-intentioned health projects by turning to moderate clerics and urging them to issue religious rulings supporting the anti-polio efforts. Tahir Ashrafi, head of the All Pakistan Ulema Council, said the alliance of clerics had done its part, and it was up to the government to come to the rescue of aid workers. "Clerics can only give fatwas and will continue to come together and condemn such acts," he said. "What good are fatwas if the government doesn't provide security?" RISK OF POLIO RETURNING That may be a tall order in Pakistan, where critics allege government officials are too busy lining their pockets or locked in power struggles to protect its citizens, even children vulnerable to diseases that can cripple or disfigure them. Pakistani leaders deny such accusations. Politicians also have a questionable track record when it comes to dealing with all the other troubles afflicting nuclear-armed Pakistan. The villages where health workers once spent time tending to children often lack basic services, clinics, clean water and jobs. Industries that could strengthen the fragile economy are hobbled by chronic power cuts. Deepening frustrations with those issues often encourage Pakistanis to give up on the state and join the Taliban. So far it's unclear who is behind the shootings. The main Taliban spokesman said they were opposed to the vaccination scheme but the group distanced itself from the attacks. But another Taliban spokesman in South Waziristan said their fighters were behind an attack on a polio team in the northwestern town of Lakki Marwat on Monday. "The vaccinations were part of "a secret Jewish-American agenda to poison Pakistanis", he said. What is clear is the stakes are high. Any gaps in the program endanger hard-won gains against a disease that can cause death or paralysis within hours. A global effort costing billions of dollars eradicated polio from every country except Nigeria, Afghanistan and Pakistan. Vaccinations cut Pakistan's polio cases from 20,000 in 1994 to 56 in 2012 and the disease seemed isolated in a pocket in the north. But polio is spread person-to-person, so any outbreak risks re-infecting communities cleared of the disease. Last year, a strain from Pakistan spread northeast and caused the first outbreak in neighboring China since 1999. Oliver Rosenbauer, a spokesman for the World Health Organization, said the group had been coming closer to eradicating the disease. "For the first time, the virus had been geographically cornered," he said. "We don't want to lose the gains that had been made ... Any suspension of activities gives the virus a new foothold and the potential to come roaring back and paralyze more children." MOURNING FAMILIES Condemnation of the killings has been nearly universal. Clerics called for demonstrations to support health workers, the government has promised compensation for the deaths and police have vowed to provide more protection. For women like Fehmida Shah, it's already too late. The 44-year-old health worker lived with her family in a two-room house before gunmen shot her on Tuesday. Her husband, Syed Riaz Shah, said she spent her tiny salary - the equivalent of just $2 a day - on presents for their four daughters. Even though the family was struggling, she always found some spare money for any neighbor in need. "She was very kind and big hearted. All the women in our lane knew her," he said. "The entire neighborhood is in shock. Pray for my daughters. I will get through this. But I don't know how they will.

Read More..

Meanwhile, Deep Inside Your Belly Button …

Researchers have found that more than 2,000 different species of bacteria live in our umbilicus – the medical word for belly button. That means you have more kinds of bacteria in your belly button than there are different kinds of ants or birds in North America, according to the study. The majority of these bacteria were rare and occurred in just one individual. No single type was common to all 60 belly buttons sampled. “I don’t find it alarming,” said Dr. William Schaffner, an expert in infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn. “We knew belly buttons weren’t sterile.” However, Schaffner believes that this does not minimize the study’s findings. “This is in the context of a much larger study, which is trying to … get greater insight into the source of pathogens and how the [bacteria on our body] changes with antimicrobial therapy and age.” Perhaps, he said, we can “use this to develop new antimicrobials.” The benefits may extend beyond antibiotics. “Understanding the biodiversity of our bodies and how it differs among people may play an important role in understanding why some … people are susceptible to the same pathogen or respond to the same drug or diet,” said Dr. Rob Knight, associate professor of molecular biophysics at the University of Colorado – Boulder. Although the findings of the study do not have any immediate implications, this is good timing for a public service announcement from Dr. Gregory Poland, infectious disease expert at the Mayo Clinic in Rochester, Minn. “The current fad of women piercing their umbilicus has led to many case reports of infections,” Poland said. “And with today’s multiple drug-resistant bacteria, it can lead to disasters.

Read More..

Cancer Immunotherapy Where Are We Going?

The compelling concept of utilizing the patient's own immune system for a stronger and more effective way to attack cancer cells is not a new one. William Coley observed in 1891 that infections produced in patients with inoperable cancer following an injection of streptococcal organisms (Gram-positive bacteria) led to tumor shrinkage especially when the patients developed fever and other signs of a full-blown infection.1 Since then, research has embraced approaches to "train" the patient's own immune system to recognize certain biomarkers or proteins that are mainly found on cancer cells and to destroy the cells. After several setbacks the first cellular immunotherapy, Dendreon's Sipuleucel-T (Provenge(R)), was approved for the treatment of prostate cancer in 2010. Today, new promising cancer immunotherapy approaches are in clinical trials. Most recently, researchers at the 54th American Society of Hematology (ASH) meeting reported early success with a developmental-stage cell-based cancer vaccine for the treatment of leukemia and have shown remission in several patients 2,3, including a 7-year old girl who relapsed twice after chemotherapy. Cancer immunotherapy can be thought of as either active or passive immunotherapy. The most prominent passive immunotherapies, which have revolutionized cancer therapy, are monoclonal antibodies that either target tumor-specific antigens and receptors or block important pathways central to tumor growth and survival. Therapeutic monoclonal antibodies are the market leader in the targeted cancer therapy space and include blockbusters such as trastuzumab (Herceptin(R)) or rituximab (Rituxan(R)). In general, antibodies are significant elements of the body's adaptive immune system. They play a dominant role in the recognition of foreign antigens and the stimulation of the immune response. Therapeutic antibodies target and bind to antigens, usually proteins that are mainly expressed on diseased cells such as cancer cells. After binding, cancer cells can be destroyed by different mechanisms such as antibody-dependent cellular cytotoxicity, the activation of the complement system -- an important part of the immune system -- and triggering cell death. Although very successful, especially in oncology, therapeutic antibodies have a significant limitation: they don't generate a memory response by the immune system, and thus, repeated antibody infusions are required. Further, monoclonal antibodies are only able to recognize specific proteins present of the cell surface. Monoclonal antibodies are mostly produced in cell culture systems which are often costly. Humanization of murine monoclonal antibodies by replacing of certain parts of the antibody with human sequences has improved the tolerability of antibodies and made them less immunogenic, but even fully human sequence-derived antibodies can carry some immunological risk. Novel approaches in the passive immunization strategy include antibody drug conjugates, a combination of targeting antibody with a very potent drug such as the recently approved brentuximab vedotin (ADCETRIS(TM)) for Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). ADCETRIS comprises an anti-CD30 monoclonal antibodyanti-CD30 monoclonal antibody and a cytotoxic (cell-killing) agent that is released upon internalization into CD30-expressing tumor cells. Currently, the development of next generations of ADCs is underway. Alternatively, specific and durable cancer immunotherapies designed to actively "train" or stimulate the patient's intrinsic immune response have been more problematic; however, recent success stories, such as the cell-based immunotherapy Provenge, have revitalized this field. Dendreon's approach modifies the patients' own dendritic cells to present a protein specific to prostate cancer cells. Dendritic cells are the most potent, "professional" antigen-presenting cells. They process the antigen material and present it on their surface to other cells of the immune system. Once activated, the dendritic cells migrate to the lymphoid tissues where they interact with T-cells and B-cells -- white blood cells and important components of the immune system -- to initiate and shape the adaptive immune response. To develop Provenge, each patient's own dendritic cells are harvested and then loaded ex vivo with the tumor-associated antigen. Now "presenting" the antigen, the dendritic cells are administered back into the patient to induce a potent, cell-mediated anticancer immune response resulting in tumor shrinkage and clinical benefit. In another experimental approach for the treatment of leukemia, patients' own modified T-cells were infused back into the patients. Prior to this, the T-cells were transduced with a lentivirus to express the CD19-specific chimeric antigen receptor. CD19 is an antigen which is found on B-cell neoplasms, cancerous B-cells, and the lentivirus was the vehicle to transfer the genetic material for CD19 into the cells. A case report published in the New England Journal of Medicine stated that a patient with chronic lymphocytic leukemia (CLL) was in ongoing remission 10 months after treatment.3 These promising results have spurred continued research for new and safe ways to achieve effective tumor vaccination, and drug developers have explored many cancer immunotherapy strategies. To generate an effective antitumor immunity, therapeutic intervention should drive several functions; specifically, it should promote the antigen presentation functions of dendritic cells, promote the production of protective T-cell responses, stimulate B-cells and overcome immunosuppression characteristics that are common to tumor cells.4 Cell-based therapeutic vaccines are most frequently produced outside the patient's body and involve isolation of the specific cells, such as dendritic cells, and the introduction of preselected antigens, often with the use of specific vehicle, into the cells. The antigens can be encoded in viral vectors (frequently DNA) or administered as peptides or proteins in a suitable adjuvant and carrier through a long and cumbersome process. During my doctoral thesis, I conducted immunization experiments using RNA as a negative control, assuming that the RNA would be degraded during the experiment thus making it impossible to use as a vaccine. The physiological role of messenger (m) RNA is to transfer genetic information from the nucleus to the cytoplasm where this information is translated into the corresponding protein. mRNA is known to be very unstable and has a relatively short half-life. But astonishingly, we were able to measure a solid T-cell immune response. We repeated the experiment and confirmed that the RNA we had produced had the potential to be used as a vaccine. Importantly, we didn't need to isolate the patients' cells: mRNA-based vaccines can be injected directly into the skin (intradermal). The mRNA-based vaccines are then taken up by antigen-presenting cells, such as dendritic cells, and are then able to induce an immune response. Importantly, mRNA-vaccines can also be synthesized quickly for any antigen sequence identified.5 The first mRNA-based vaccines (RNActive(R)) are now in the clinic for the treatment of prostate cancer and lung cancer and have demonstrated that they do what they are supposed to do - induce a balanced humoral, as well as T cell-mediated, immune response that is entirely HLA independent. The HLA (human leukocyte antigen) system is used to differentiate the body's own cells (self) and non-self cells. Additionally, RNA-vaccines do not need a vehicle such as a virus for delivery to the cells, nor do they contain virus-derived elements that are often found in DNA-vaccines. These attributes make RNActive a very safe therapeutic. The risk of integration of the RNA into the host-genome is minimized (RNA would have been transcribed first to DNA, and then it has to be transported to the nucleus), as is the residual risk of DNA-based vaccines for inactivating or activating genes or affecting cellular regulatory elements, which can induce oncogenesis. Thus, the favorable safety profile of mRNA-based therapies broadens their potential use not only for the treatment of diseases but for use as prophylactic vaccinations. A recent proof-of-concept study using mRNA-based vaccines (RNActive) in animal models for influenza was published in Nature Biotechnology.6 Therapeutic cancer immunotherapies and vaccines have come a long way, and novel, promising approaches give hope for safe and effective treatment options. This may one day lead to the treatment of all cancers as chronic diseases. Literature 1Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P, Ferrone S: Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012 2June CH, Blazar BR: T-Cell Infusions: A New Tool for Transfusion Medicine That Has Come of Age. Presentation at 54th ASH Annual Meeting 2013 3Porter DL, Levine BL, Kalos M, Bagg A, and June CH: Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia. N Engl J Med 2011 4Mellman I, Coukos G, Dranoff G: Cancer immunotherapy comes of age. Nature. 2011 Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, Schlake T, Thess A, Kallen KJ, 5Hoerr I, Obst R, Rammensee HG, Jung G: In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol. 2000 6Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, Schlake T, Thess A, Kallen KJ, Stitz L, Kramps T: Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol. 2012

Read More..