Risk Of Developing Liver Cancer After HCV Treatment

Sunday, July 31, 2011

Listen- Hepatitis causes over a million deaths a year

WHO: Hepatitis causes over a million deaths a year

A third of the world's population has been infected with a form of hepatitis.
The world health organisation says it's causing more than a million deaths a year.
Sarah White from the British Liver Trust told Radio 5 live's Morning Reports about the risks of contracting the B and C strains of hepatitis

Listen here...........

WHO: Hepatitis toll 'in millions'
Medical experts are calling for global action to tackle the viruses that cause the liver disease hepatitis.

The first worldwide estimates in drug users show 10 million have hepatitis C while 1.3 million have hepatitis B.

Writing in the Lancet, experts say only a fraction of those who could benefit are receiving antiviral drugs.

Only one in five infants around the world are vaccinated against hepatitis B at birth, they say.

The figures, published in the Lancet, show about 67% of injecting drug users in the world have been exposed to hepatitis C, while around 10% have come into contact with hepatitis B.

In the UK, around half of injecting drug users have been infected with the hepatitis C virus, while the rate for exposure to hepatitis B is 9% - the highest in western Europe.

This study provides us with a first step and powerful data to draw attention to the problem of viral hepatitis in people who use drugs”

Dr Joseph Amon
Human Rights Watch
The research was led by Prof Louisa Degenhardt of the Centre for Population Health, Burnet Institute, Melbourne, Australia, and Paul Nelson from the National Drug and Alcohol Research Centre at the University of New South Wales.

They say: "The public-health response to blood-borne virus transmission in injecting drug users has mainly centred on HIV.

"Maintenance and strengthening of the response to HIV in injecting drug users remains crucial, but the significance of viral hepatitis needs to receive greater attention than it does at present."

Commenting on the study in the Lancet, Dr Joseph Amon, of Human Rights Watch, New York City, US, said: "This study provides us with a first step and powerful data to draw attention to the problem of viral hepatitis in people who use drugs.

"The next step is to challenge governments to act, and hold them accountable for implementation of rights-respecting and evidence-based programmes."

Health risks

Hepatitis is caused by five main viruses - A, B and C, and, more rarely D and E.

Hepatitis B is the most common, and can be passed from mother to baby at birth or in early childhood as well as through contaminated injections or injected drug use.

Hepatitis C is also spread through using unsterile needles and less commonly through unsafe sex or sharing razors or toothbrushes.

The E virus, caught from infected water or food, is a common cause of outbreaks of the disease in developing countries, said the World Health Organization.

Many of those carrying hepatitis are not aware they have it and can unknowingly transmit it to others.
http://www.bbc.co.uk/news/health-14314347

Hepatitis News wrap-up for Sunday July 31

Hepatitis: In search of increased protection for a silent infection
By SOLA OGUNDIPE
July 31
FIFTEEN years before the doctor said to him: “Go home and get your affairs in order because there is nothing further we can do for you”, John was already aware that a problem existed.
Blood had started showing up, infrequently and in small amounts in his stools. “I’d kept this information to myself, mainly due to embarrassment and the possibility that it may only be haemorrhoids, something most people would pass off as not worth the hassle, “ he noted.
Time passed quickly. Blotches started appearing on his skin, barely noticeable at first but becoming larger and more numerous and pronounced as time progressed...continue reading..

Side Effects of the Two New Hep C Drugs
Just like any drug, the two newly approved medications for Hepatitis C have side effects.
Both of the new Hepatitis C drugs, Victrelis (boceprevir) and Incivek (telaprevir) are explicitly for use in conjunction with the current combination of pegylated interferon and ribavirin. Thus, any side effects occurring with Victrelis or Incivek are in addition to the side effects seen with the previous standard treatment regimen.
Read more.

Related On This Blog; Hepatitis C Drug Incivek (telaprevir); What are the side effects ?

Doctors to sensitize barbers about Hepatitis C risks
Karachi—

Doctors comprising members of SMC Alumni Association has taken upon themselves to sensitize barbers as well as beauticians, in Karachi, to protect themselves against Hepatitis B and C.

Dr. Natasha Mustafa, Coordinator of the Campaign told APP Friday that beauticians and barbers are also being approached to bring about extremely important changes in handling of their clients.

“This is very important as many a time unassuming people hold chance to contract Hepatitis C and B and even HIV infections during minor cuts experienced during shave or hair cut at a barber’s shop,” she said.

The young doctor also referred to vulnerability of people undergoing pedi-cure or mani-cure due to poor hygienic practices. Re-use of sharp tools, though obsolete, but still used for skin cleaning purposes in many of the beauty parlors, is also a risk that is often ignored, said Dr. Natasha.

“The hair dressers and beauticians are also at risk due to application of contaminated tools, knives and blades,” Dr. Natasha said in reply to a question.The exercise to educate professionals, she said, is part of the ongoing SMC Alumni campaign, focussed on prevention and control of Hepatitis C.

She said more than 500 students of Sindh Medical College had also joined the walk, arranged by SMC Alumni Association, Pakistan chapter, to mark the world hepatitis day.

Dr.Sameer Qureshi, President, SMC Alumni Association (Pakistan) led the walk that started from Emergency Department of the Jinnah Post Graduate Medical Center and ended at its ENT Department.—APP

Transplant

One H1N1 Vaccine Not Enough for Kids With New Livers (CME/CE)
7/30/2011 MedPage Today Gastroenterology (MedPage Today) --
A single dose of the monovalent pandemic 2009 H1N1 influenza vaccine was not enough to protect immunocompromised pediatric liver transplant recipients, a small study suggested.

Pharmaceutical

Merck Hep C Drug Draws More Atttention Than Job Cuts
NEW YORK (TheStreet) --
The 75%/25% market share split in sales between Vertex and Merck had been expected by analysts who cover Vertex, based on third-party drug tracking firm data.
It's obvious that Merck would prefer to be on the 75% market share side of the equation, but no one expected that to be the case, even if Vertex performance was better than existing high expectations....Continue reading...

Off The Cuff

From Reuters Health Information
Medicine Professor Calls Prince Charles, Others "Snake-Oil Salesmen
By Kate Kelland

LONDON (Reuters) Jul 25 - A leading professor of complementary medicine accused Britain's heir-to-the-throne Prince Charles and other backers of alternative therapies on Monday of being "snake-oil salesmen" who promote products with no scientific basis.

Edzard Ernst, who is stepping down from his post as Britain's only professor of complementary medicine at Exeter University, also said a long-running dispute with the Prince about the merits of alternative therapies had cost him his job -- a claim Prince Charles's office denied.

"Almost directly, Prince Charles has managed to interfere in my professional life and almost managed to close my unit," Ernst told reporters at a briefing.

A spokeswoman for Prince Charles told Reuters the royal heir was not involved in the dispute with Ernst and that she would not respond to professor's comments about snake-oil salesmen.

Ernst's complementary medicine research unit at Exeter's Peninsula School of Medicine had been threatened with outright closure, but the university has now offered it a reprieve and says it is seeking a successor to Ernst to lead it.

"It looked as though I had to go, and that was the price for the unit to continue," Ernst said. "I pay the price gladly as it is a small price to pay for the unit to continue."

Ernst said that during his 18 years of researching the efficacy of hundreds of different types of alternative medicine -- from acupuncture, to herbal remedies, to homeopathy and chiropractic therapy -- he has found that "snake-oil salesmen and pseudo-science are ubiquitous and dangerous".

Asked whether he included Prince Charles in that category, he said, "yes".

He said Prince Charles, a long-time advocate of alternative and integrated medicine and sustainable agriculture, was one of the main obstacles to allowing proper scientific analysis of the efficacy of complementary therapies.

Referring to the prince's Duchy Originals food company as "dodgy originals," he said the firm's promotion of a "detox" tincture made from artichoke and dandelion was an example of how the prince peddled scientifically unproven therapies.

In 2009 Ernst accused Prince Charles of "outright quackery" for promoting the detox tincture and other such products "under the banner of holistic and integrative healthcare."

The 62-year-old prince founded Duchy Originals in 1990 to promote organic food and farming, with profits going to charity.

Duchy Originals describes the product as "a food supplement to help eliminate toxins and aid digestion" and a spokeswoman for the firm said it had no comment about Ernst's remarks.

Ernst's dispute with Prince Charles dates back to 2005, when the professor was asked to look at a report by an economist, Christopher Smallwood, who was investigating whether alternative remedies were cost-effective and should be offered more widely on Britain's taxpayer-funded National Health Service (NHS).

Ernst objected to the report and decided to voice his concerns before it was published. In one section, the report said the NHS could save billions of pounds if some doctors could switch from prescribing conventional medicines to offering alternative therapies. "That was so unspeakable to me that I had to speak out," Ernst said.

Ernst was accused in a letter from an adviser to Prince Charles, Michael Peat, of having breached a confidentiality agreement on the report and an investigation was launched. Ernst was cleared of wrongdoing, but he says he had by that time lost the support of his institution and its commitment to raise more funding for his work.

A spokeswoman for Prince Charles said he "had no knowledge that a letter was being sent to the University of Exeter by Sir Michael Peat about Edzard Ernst's breaching of confidence of the Smallwood report in 2005" and was not involved in the dispute.

Ernst and his team have run many clinical trials and published more than 150 meta-analyses of complementary and alternative medicines.

He says he has identified around 20 such therapies which "demonstrably demonstrate more good than harm" including the herbal remedy St John's Wort for the treatment of mild depression, hypnosis for the relief of labor pain, and hawthorn for the treatment of congestive heart failure.

Healthy You

Low Vitamin D Linked to Chronic Musculoskeletal Pain
By: DIANA MAHONEY, Internal Medicine News Digital Network

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians should consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on the findings of a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, according to Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study, which was conducted during the months of April through September to account for seasonal variation, underwent an initial survey about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya explained. All of the participants underwent a comprehensive clinical examination, during which pain was assessed using the Brief Pain Inventory and Visual Analogue Scale. "Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities," she said. Additionally, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals during follow-up, as was physical performance using activities of daily living, grip strength, six-minute walk distance, and the timed Get up and Go Test of mobility, Dr. Abou-Raya stated. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxy vitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. "The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls," she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency. "We also found that patients with multisite chronic pain had significantly lower levels of vitamin D compared with patients reporting sing-site chronic pain, and patients with more severe pain at baseline had significantly lower vitamin D levels than those with less severe pain."

After multivariate adjustment, "chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance," Dr. Abou-Raya stated. One likely contributing factor is that sun exposure in the chronic pain group was significantly lower than that of the controls, with 40% of the pain patients reporting that they received fewer than 15 minutes of sun exposure weekly compared with 11% of the controls, likely due to limitations on physical activity associated with chronic pain, she said.

The results of this observational study should not be used to infer causation, Dr. Abou-Raya stressed. "They simply demonstrate that patients with chronic musculoskeletal pain have lower levels of vitamin D compared with individuals who are pain free, thus the possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers," she said at the annual European Congress of Rheumatology.

The implication of the findings, she continued, "is that all patients with chronic musculoskeletal pain should receive oral vitamin D supplementation, as optimal vitamin D levels appear to be associated with less pain and better physical performance."

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

For Your Reading Pleasure; Grand Rounds

Grand Rounds is a weekly summary of the best health blog posts on the Internet. Each week a different blogger takes turns hosting Grand Rounds, and summarizing the best submissions for the week.

Hosted By;
Welcome to Better Health’s Grand Rounds Volume 7, Number 44! This is our second time hosting Grand Rounds and we’re excited about sharing the posts we received. The theme of this week’s collection came from a recent Health Affairs blog post by CFAH president, Jessie Gruman, Patient Advocates: Flies In The Ointment Of Evidence-Based Care, which addresses a few of the many challenges of basing health care practices, policies, and decisions on evidence of effectiveness.

A Few Submissions, read all entries here

Val Jones of Better Health tells us Why She’s Afraid For Anyone to Enter the Healthcare System…Ever. Val’s post offers resources for patients, caregivers and health care professionals to ensure they are “on the right diagnostic pathway, getting the most appropriate care that suits their needs and preferences, and protecting them from errors and missteps.”

Rheumatologist Irwin Lim, in One Fracture, Two Fracture, Three Fracture…Enough! writes about the need for targeted interventions for high-risk groups…especially patients with osteoporotic fractures that “are getting a surgical fix or a cast, but not assessed and therefore, not treated for osteoporosis…this causes pain, suffering, disability and loss of independence. It also costs….a lot of…money.”

Amy Berman, of the John A Hartford Foundation HealthAGEnda blog, shares her experience with what she believes was an overly aggressive treatment recommendation in Can Good Care Produce Bad Health?. She says, “It doesn’t matter if care is cutting-edge and technologically advanced; if it doesn’t take the patient’s goals into account, it may not be worth doing.”

Posting a sick kid’s photo on Facebook led to the swift diagnosis of a dangerous, fast-moving illness. David E. Williams, in the Health Business Blog, explores the role of social media and crowd-sourcing in his post, Diagnosing an Illness with Facebook.

Read All Submissions .............

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Saturday, July 30, 2011

Obesity Linked to Risk for Decompensation of Cirrhosis

From Medscape Medical News

Obesity Linked to Risk for Decompensation of Cirrhosis

Laurie Barclay, MD
Authors and Disclosures

July 29, 2011 — Obesity is an independent risk factor for clinical decompensation (CD) in patients with cirrhosis, according to the results of a prospective observational study from the Portal Hypertension Collaborative Group reported online June 26 and to appear in the August print issue of Hepatology.

"Given the prior evidence of the detrimental effects of obesity on chronic liver disease, we hypothesized that increased BMI [body mass index] may increase the risk of transition from compensated to decompensated cirrhosis," said second author Guadalupe Garcia-Tsao, professor of medicine at Yale University School of Medicine in New Haven, Connecticut, in a news release.

Although obesity was previously known to be associated with an aggressive course in patients with chronic viral hepatitis, its effect on patients with established cirrhosis has been undetermined. The investigators therefore assessed the effect of obesity in patients with compensated cirrhosis, in conjunction with that of other known risk factors, on the development of CD.
The study sample consisted of 161 patients with compensated cirrhosis in whom data on BMI were available and who were enrolled in a randomized trial of beta-blockers to prevent varices. At study enrollment, participants underwent laboratory testing and measurement of portal pressure with use of the hepatic venous pressure gradient (HVPG). Follow-up continued until development of CD, defined as ascites, hepatic encephalopathy, or variceal hemorrhage, or until September 2002. Median duration of follow-up was 59 months.

At enrollment, 29% of participants had a normal BMI, 40% were overweight, and 30% were obese. CD occurred in 48 (30%) of 161 patients during follow-up. Rate of CD increased with increasing BMI: 15% in those with a normal BMI, 31% in the overweight group, and 43% in the obese group (P = .011). The groups with an abnormal BMI had a significantly higher actuarial probability of the development of CD (P = .022).

BMI was an independent predictor of CD (hazard ratio, 1.06; 95% confidence interval, 1.01 - 1.12; P = .02), as were HVPG and albumin, in a multivariate model that included factors previously determined to predict CD (HVPG, albumin level, Mayo end-stage liver disease score), cause, and treatment group.

"Patients who are overweight or obese are at greater risk of accelerating the progression of cirrhosis," Dr. Garcia-Tsao said. "Weight reduction may improve patient outcomes in this high-risk population and studies addressing this specific issue are warranted."
Limitations of this study include the fact that the original trial was not performed with the objective of evaluating the impact of obesity on CD.

"[I]ncreased BMI is an independent predictor of clinical decompensation in patients with compensated cirrhosis of various etiologies, suggesting that obesity accelerates the progression of cirrhosis and that its correction could be a valuable nonpharmacological measure to improve prognosis in this patient population," the study authors conclude.

The National Institutes of Health and the Instituto de Salud Carlos III supported this study. The study authors have disclosed no relevant financial relationships.

Hepatology. 2011;54:555-561.

Pre-Operative Risk Factors Predict Post-Operative Respiratory Failure after Liver Transplantation

Pre-Operative Risk Factors Predict Post-Operative Respiratory Failure after Liver Transplantation


Ching-Tzu Huang1,2#, Horng-Chyuan Lin1,3#*, Shi-Chuan Chang2,4, Wei-Chen Lee5*
1 Department of Respiratory Therapy, Chang Gung Memorial Hospital, Taoyuan, Taiwan, 2 Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan, 3 Department of Thoracic Medicine, Chang Gung Memorial Hospital, and Department of Chinese Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan, 4 Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, 5 Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

Abstract

Objective
Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF) after liver transplantation and the impact on short-term survival rates.

Design
The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not.

Measurements and Main Results
Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS) use, source of organ transplantation, model for end-stage liver disease score (MELD) and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05). Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001).

Conclusions
The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation.


Citation: Huang C-T, Lin H-C, Chang S-C, Lee W-C (2011) Pre-Operative Risk Factors Predict Post-Operative Respiratory Failure after Liver Transplantation. PLoS ONE 6(8): e22689. doi:10.1371/journal.pone.0022689
Editor: Holger K. Eltzschig, University of Colorado Denver, United States of America
Received: March 10, 2011; Accepted: June 28, 2011; Published: August 1, 2011
Copyright: © 2011 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: weichen@cgmh.org.tw (WCL); lin53424@ms13.hinet.net (HCL)
# These authors contributed equally to this work.

Introduction
Liver transplantation (LT) is currently the only definite treatment for acute liver failure and chronic end-stage liver diseases. Because of a shortage of liver donations, patients may have to wait for a long time for a liver transplantation. When liver transplantations are performed, the patients are already very sick. These patients may also have a high incidence of common respiratory disorders including atelectasis, pleural effusion and poor compliance of the respiratory system due to edema of the chest wall or high intra-abdominal pressure. All of these respiratory disorders can affect the function of alveolar gas exchange. Some patients may even need intubation and ventilation.


Liver transplantation is an upper abdominal surgery which involves an extensive operation field and a long operation time. The surgical wound transects the abdominal oblique muscles and rectus muscles which are usually associated with respiratory movements [1]. Patients undergoing upper abdominal surgery are prone to diaphragmatic dysfunction which results in a 50–60% reduction in vital capacity and 30% reduction in functional residual capacity [2], [3]. In addition, the usage of anesthetics and the inhibitory effect of wound pain on coughing and mucous removal usually contribute to the development of post-operative pulmonary complications. In the literature, 5–10% of patients with general surgery develop post-operative pulmonary complications, especially in the patients with abdominal surgery [4]. Glanemann et al. [1], [5] observed that 11% of liver transplantation patients required ventilator assistance after transplantation and 36.1% required re-intubation. Among the patients who developed pulmonary complications and needed re-intubation, 44.6% of the patients were intubated within 24 hours after liver transplantation. All of these pulmonary complications contribute to a significant reduction in short-term survival.


Post-operative respiratory failure (PRF) [6], [7] is one of the most common post-operative pulmonary complications and may result in mortality. Pre-transplant risk factors that affect mortality and morbidity after liver transplantation have been investigated. However, the impact of PRF on LT patients' prognosis is still unclear.
The objective of this study was to identify which pre-transplant risk factors are likely to cause PRF.

Results

Patients
A total of 147 liver transplant patients, 113 males and 34 females, were included in this study. The average age of these patients was 50.2±8.7 years. The most common indication for liver transplantation was liver cirrhosis (76.2%), followed by fulminate hepatic failure (14.3%) and hepatocellular carcinoma (8.8%). There was no significant difference regarding total ischemic time (41.6±11.4 minutes vs. 39.0±10.4 minutes, p = 0.40, including cold and warm ischemic time) and duration of surgery (12.9±2.1 hours vs. 14.2±2.1 hours, p = 0.97). The demographic characteristics of the patients are shown in Table 1. Pre-operative co-morbidities included diabetes mellitus in 15% of patients, impaired renal function in 17.7%, and ventilator usage in 10.2%. Pre-operative pulmonary function tests showed restrictive defects in 17.7% of the patients. According to the Taiwan Organ Registry and Sharing Center, the model for end-stage liver disease (MELD) score is divided into three categories, 10–18, 19–24, and ≥ 25, which accounted for 35.4%, 28.6%, and 36.1% of the patients, respectively.

Table 1. Demographic data of the study subjects.doi:10.1371/journal.pone.0022689.t001

Univariate analysis
Among the 147 patients, 62 (42.2%) patients developed PRF and 85 (57.8%) did not (Table 2). Among the 62 patients with PRF, 14 (22.6%) required ventilation to support gas exchange pre-operatively, and 32 (51.6%) required re-intubation after operation. Among the 85 patients without PRF, only 1 (1.2%) required pre-operative ventilation to support gas exchange (p<0.001). There was no difference in age or sex between the two groups. The etiology of liver disease in both groups was different (p = 0.020). The PRF group had more patients with fulminant liver failure than the non-PRF group. There was a significant difference in MELD categories between these two groups (p = 0.004). Thirty (48.4%) PRF group patients had a MELD score ≥ 25 while only 23 (27.1%) of the non-PRF group patients had a MELD score ≥ 25. The severity of diseases was higher in the PRF group than in the non-PRF group.

Table 2. Pre-operative clinical parameters of the patients who underwent liver transplantation (n = 147), by univariate analysis.doi:10.1371/journal.pone.0022689.t002
Pre-operative pulmonary function tests showed 27.4% restrictive defects in the PRF group, which was higher than in the non-PRF group (p = 0.008). Pre-operative co-morbidities including diabetes mellitus and renal function insufficiency were also higher in the PRF group than in the non-PRF group. Moreover, more patients in the PRF group than in the non-PRF group required MARS while waiting for liver transplantation (p = 0.009). For operation type, patients in the PRF group had a higher rate of deceased donor liver transplantation than patients in the non-PRF group (p = 0.004). All of the deceased donors were brain-dead donors.

Multivariate analysis
To determine the independent factors between these two groups, all significant factors in univariate analysis were further analyzed by logistic regression. The results showed that the risk factors for PRF were diabetes mellitus, impaired renal function, pre-operative ventilator support, usage of MARS, and deceased donor liver transplantation (Table 3).

Table 3. Pre-operative predictors of post-operative respiratory failure by multivariate analysis.doi:10.1371/journal.pone.0022689.t003


Once PRF developed, significant differences in post-operative prognosis were observed in both groups (Table 4). The length of ICU stay and duration of hospitalization were both longer in the PRF group than in the non-PRF group. Thirty-day, three-month, and one-year mortality rates were higher in the PRF group than in the non-PRF group. Kaplan-Meier survival curves showed that the survival rate at one year was 43.5% for the patients with PRF and 90.6% for the patients without PRF (p<0.001) (Fig. 1). A total of 43 patients died during the one-year study period (Table 4). The causes of death of 35 PRF patients included sepsis with multiorgan failure (29 patients), rejection (2), gastrointestinal hemorrhage (2), cardiac dysfunction (arrhythmia, 1), and pulmonary embolism (1). All the deaths in non-PRF group were due to sepsis with multiorgan failure (8 patients).

Figure 1. The survival rate for patients with or without PRF by Kaplan Meier analysis.doi:10.1371/journal.pone.0022689.g001

Table 4. Pre-operative predictors of short-term morbidity and mortality rate.doi:10.1371/journal.pone.0022689.t004


There were 15 (10.2%) patients who required ventilator support before transplantation. According to the medical records, there were no preoperative ventilator associated pneumonias in our patient population.

Discussion
This retrospective study showed that pre-operative ventilator support, diabetes mellitus, impaired renal function, and deceased transplant recipients were all pre-operative risk factors for PRF. Once PRF developed, the length of stay at the intensive care unit and total duration of hospitalization both increased and caused a significant impact on short-term mortality after liver transplantation. Liver transplantation, compared with heart and kidney transplantations, are particularly prone to PRF and acute pulmonary damage. Previous study [9] had mentioned about “the risk of respiratory failure and acute lung injury is considerably lower after heart and kidney transplantation than liver transplantation”. Only 4.4% heart transplantation patients require tracheostomy for the development of prolong respiratory failure. Similarly, perioperative respiratory failure was documented in 4% recipients of kidney transplantation. Once PRF develops, both patient prognosis and survival rate are affected [9]. Glanemann et al. [5] reported that of 546 liver transplantation patients, 11% needed ventilator support for more than 24 hours, and 14.8% underwent extubation within 24 hours but required re-intubation later on. The patients in need of re-intubation have significantly reduced survival rates [1]. Arozullah et al. [7] adopted a prospective cohort model to predict the multi-factorial risk index for PRF after major noncardiac surgery. They discovered that 37% of liver transplant patients developed PRF and were unable to undergo extubation, while 29% of the patients who developed PRF required re-intubation. For those patients who were unable to undergo extubation, the mortality rate increased to 23% within 30 days. For those patients who were re-intubated, the mortality rate increased to as high as 31% within 30 days. Golfieri et al. [10] also described that 4–16% of patients who developed pulmonary complications after liver transplantation deteriorated into acute respiratory distress syndrome with a mortality rate as high as 80–100%. Clearly therefore, patients suffering from PRF after transplantation have a higher incidence of short-term mortality.


Glanemann et al. [11] special attention should be focused on liver transplant recipients in poor clinical condition at the time of orthotopic liver transplantation, undergoing complicated surgery, or receiving liver grafts with severe preservation injury. Our work provides a worthwhile scientific study on the field of risk factors for post-operative respiratory failure after liver transplantation and the impact on short-term survival rates. Postoperative respiratory failure is one of the most common post-operative pulmonary complications and may result in mortality [12]. González et al. [12] suggested that the development of acute respiratory failure after liver transplantation is affected by the following factors: female sex, Child-Pugh class, pulmonary edema, postoperative acute renal failure, cerebral dysfunction, and respiratory infection. However, only few studies have addressed the impact of pre-transplantation risk factors on the post-operative respiratory failure after liver transplantation. Besides, pre-transplantation risk factors that affect mortality and morbidity after liver transplantation have been investigated. For example, Preeti JR et al. [13] reported that preexisting diabetes is associated with a significant post-orthotopic liver transplantation morbidity and mortality. However, the impact of post-operative respiratory failure on liver transplantation patients' prognosis is still unclear. Therefore, our paper will provide comprehensive and potential information for clinical physician to improve the critical care for these patients.


Multisystem organ failure (MSOF) is important for liver transplantation patients. In our study, liver transplantation patients were tightly monitored once they are on the waiting list. Multisystem organ failure occurred before surgery is not suitable for liver transplantation. Actually, in our previous study [14] entitled “Scoring Short-Term Mortality After Liver Transplantation”, we used Sequential Organ Failure Assessment (SOFA) score for measuring multiple organ failure for patients and found that SOFA scores calculated before liver transplantation were statistically significant predictors of 3-month and 1-year posttransplant mortality. However, only SOFA on post–liver transplant day 7 had the best discriminative power for predicting 3-month and 1-year mortality after liver transplantation. Interestingly, in our study, we found that the PRF on post-liver transplant day 2 was associated with a higher SOFA score on post-liver transplant day 7, compared with those in patients without PRF (8.1±3.4 vs. 4.9±1.8, p<0.001). It suggested that PRF on post–liver transplant day 2 is an earlier predictor for the outcome than the SOFA score as described in the previous study.
There was a higher rate of post-operative respiratory failure in our population. It might be a matter of local differences in anesthetic and ICU management, or differences in patient or donor graft characteristics compared to other reports. We had reviewed the previous studies on early extubation in liver transplant recipients and found that there are some discrepancies in the patient's enrollment. The exclusion criteria in the literature on early extubation in transplant recipients included acute hepatic failure, ventilator required pretransplantion [15] and living donors [16]. However, in our study, we did not exclude the patients mentioned above. In addition, given the limited source of organ donors, the waiting time for prospective liver transplantation is long, making it difficult to control the disease severity. Concerning the donor group in our data, there is 36.7% patients received deceased donors. Obviously, deceased donors group had higher MELD score (25.6±8.4) compared with living donors and deceased donor liver transplantation belongs to the urgent surgery. While comparing the severity of liver disease before surgery, patients with Child's class C occupied 79.6%, which was higher than that in previous study [17], [18]. Those are the reasons why there is a higher prevalence of respiratory failure in our population. The outcomes differ among institutions and dependent upon experience, resources and the patient population. While the description of respiratory failure in their patient population is of some interest, most readers will reject the data if it is not similar to their own experience. It is very apparent that there are a number of peer reviewed publications with different outcomes. However, the one thing that is applicable to all centers is the systematic study of risk factors for each institution.


Impairment of renal function is an independent risk factor for the development of post-operative pulmonary complications. In this study, pre-operative impairment of renal function between the PRF and non-PRF patients was significantly different. Multivariate analysis also showed that impaired renal function was an independent factor with an adjusted odds ratio of 5.93 (95% CI, 1.82–19.35; p = 0.003). All the patients in our study with preoperative renal insufficiency did not require preoperative dialysis, as well as intraoperative dialysis or ultrafiltration. Impaired renal function with an imbalanced pH value increases the work of breathing and reduces pulmonary compliance. Once respiratory failure occurs and mechanical ventilation is adopted, the high intra-thoracic pressure will affect the systemic and renal hemodynamics leading to a drop in cardiac output that will in turn affect renal blood flow [19]. Nair et al. [8] showed that pre-operative serum level of creatinine (>1.5 mg/dl) was an important indicator for assessing post-operative ICU stay as well as short-term survival rate [20], [21], [22]. These results imply that it is better to perform liver transplantation before renal function becomes impaired. In our study, we did not perform combined liver kidney transplantation in our renal failure patients.


Diabetes mellitus patients are prone to have delayed wound healing after major surgery and an increased risk of infection and morbidity. The results in this study showed that patients suffering from diabetes mellitus prior to surgery had a higher chance of developing PRF after surgery. The hazard ratio for diabetes mellitus was 7.55 (95% CI, 2.28–25.02; p = 0.001). Immunosuppressive agents such as tacrolimus and steroids may influence the metabolism of glucose. Impaired renal function and gastric emptying may both interfere with blood levels of immunosuppressants and ultimately lead to poor blood glucose control and infections. Preeti et al. [13] discovered that compared to non-diabetic patients, diabetic patients had a significantly higher serum creatinine level prior to liver transplantation and a higher incidence of pulmonary complications after transplantation (p = 0.001).


The usage of MARS was a risk factor to develop post-operative PRF. Eleven patients in the current study received MARS combined with dialysis treatment. Of these 11 patients, 9 (81.8%) developed PRF, which was significantly higher than in the patients who did not receive MARS (p = 0.009). Using an artificial liver/biological artificial liver as a support system to extend the waiting time increases the opportunity of liver transplantation for acute liver failure patients. Most toxins produced by liver failure bind to albumin, and traditional hemodialysis cannot effectively remove the toxicity for acute liver failure patients. Non-biologic artificial liver support therapies, MARS, combine a molecular adsorbent re-circulating system and a dialysis system to remove water-soluble and protein-bound toxins. The mortality rate within one week has been shown to be 100% and 63% for the control group and the MARS-treatment group, respectively [23]. Although MARS treatment extends the waiting time for liver transplantation and possibly improves the survival rate for the patients with hepato-renal syndrome, the usage of MARS is still a risk factor to develop PRF.


According to previous report, the criteria of MARS including acute decompensation on chronic liver disease, acute liver failure, primary graft dysfunction, liver failure post-liver surgery and intractable pruritus in chronic cholestatic syndromes [24]. The waiting time for prospective liver transplantation is long, making it difficult to control the disease severity. In aid of extending the waiting time, 11 patients (7%) in our study received MARS to increase the opportunities of liver transplantation for acute decompensation on chronic liver disease and acute liver failure patients requiring intubation.


The patients were divided into three groups according to a MELD score of 10–18, 19–24, and ≥ 25 in this study. Thirty among 62 patients (48.4%) with PRF had a MELD score ≥ 25, compared to 23/85 (27.1%) patients in the non-PRF group. Among all 53 patients with a MELD score ≥ 25, the incidence of PRF was 56.6% (30/53), compared to 45.2% (19/42) for the patients with a MELD score between 19 to 24 and 25% (13/52) for the patients with a MELD score between 10 to 18. These results implied that the patients with a high MELD score had a higher incidence of PRF. Saab et al. [25] reported that the one-year survival rate was significantly different when the patients were divided into MELD scores < 24 and > 24. Previous studies have noted that MELD score could more accurately predict ventilator usage for gas exchange support in liver pre-transplantation than the CTP score, however, it could not be used to predict short-term survival rate [26], [27], [28], [29]. In this study, MELD score was not an independent factor to predict PRF, however, the patients with high MELD scores may have had a higher rate of comorbidities.


In previous study [30], patients were initially stratified into 7 groups based on the MELD score of <10, 11–15, 16–20, 21–25, 26–30, 31–35, and >36. Graft and patient survival were compared among the groups. Groups with similar results were merged to develop 3 larger categories as defined by pretransplantation MELD of <15 (low risk), 16–25 (medium risk), and >25 (high risk). It is consistent with our stratification for the pretransplant MELD scores. Based on this MELD scoring system, patients are equally distributed in the three categories and are suitable for analysis. In our study, it did show that a MELD score of 25–40 is significantly associated with a higher rate of PRF, compared with those in other groups.


Feng et al. [31] suggested that the donor risk index (DRI), calculated by eight-parameter formula, was an important predictor of graft failure. In another cohort study, Maluf et al. [32] found that a DRI of more than or equal to 1.7 is a cutoff value in defining an extended criteria for donor graft. In our study, the DRI between non-PRF and PRF patients was not significantly different (1.423±0.210 and 1.499±0.342; p = 0. 578), both were less than 1.7, suggesting that DRI may not a predictor of post-operative respiratory failure in our patient population.
Intraoperative care is also an important issue. Actually, we found that there was significant difference in the perioperative blood loss between non-PRF and PRF patients (3954±3921 ml and 6657±6566 ml; p = 0.013). More patients in non-PRF group completed the surgical procedure without the need for blood transfusion compared with the PRF group. We believe that perioperative care of transplant recipients should be an important predictor of outcome. However, our present study highlights the role of pre-operative risk factors. It needs further study to investigate the perioperative risk factors associated with PRF.


Previous papers have found encephalopathy, massive transfusion requirements, primary graft failure, cardiac failure, multiorgan transplant, and retransplantation were all contraindications to early (<24 h) extubation after liver transplantation. However, in our study population, there were no patients who were primary graft failure, cardiac failure, multiorgan transplant, and retransplantation. Similarly, no patients had required massive transfusion before transplantation. In our study, encephalopathy was a fluctuated factor that is difficult to evaluate from the medical record. It needs further study to investigate the indicator.


In our study, 93 (63.3%) patients received living donor liver transplantation (Table 1). Previous studies [16] have suggested living donation is a contraindication to early extubation. However, in our data, we found that living donor liver transplantation had a lower rate (31/93, 33.3%) of PRF, in contrast with deceased donor liver transplantation (31/54, 57.4%)(Table 2). Our finding is interesting and provides a potential therapeutic direction for clinical practice.


There were significant differences in ICU stay after surgery, hospital stay, 30-day mortality, three-month mortality, and one-year mortality between patients with or without PRF. Kaplan-Meier survival analysis showed that the prognosis for the patients with or without PRF was also significantly different.


Although transplantation is effective, the possibility of transplantation depends on the availability of a liver donor. Therefore, predictors of mortality risk and models for the short term prognosis of end-stage liver disease are needed to help clinicians and policymakers predict the outcomes of liver transplantation. In our previous study [14], we found that among 4 evaluated scoring systems: (1) The Sequential Organ Failure Assessment (SOFA) score, (2) Child-Pugh points, (3) Model for End-Stage Liver Disease score, and RIFLE (risk of renal dysfunction, injury to the kidney, failure of the kidney, loss of kidney function, and end-stage kidney disease) criteria, only the SOFA scores calculated before liver transplantation were statistically significant predictors of 3-month and 1-year posttransplant mortality. SOFA on post–liver transplant day 7 had the best discriminative power for predicting 3-month and 1-year mortality after liver transplantation. Moreover, Preoperative hyponatremia was also a significant risk for postoperative complications and short-term graft loss [33]. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in deceased donor liver transplantation. Older patient and donor age [34], male sex of recipient, retransplantation, and high pre-transplant MELD score are associated with poor post-transplant outcome [30]. Our study provided a new concept that post-operative respiratory failure is a key factor in liver transplant that carries prognostic impact in the recipients.


After liver transplantation, patients need to receive regular immunosuppressive treatment, compared with other surgical patients. It is supposed that patients would have a high infection opportunity. However, only few studies have addressed the impact of infection on the short-term mortality after liver transplantation. Better predictive models are needed to assess the infection associated short-term mortality.


Conclusion
In conclusion, this study identified several pre-operative risk factors for PRF, which lead to a prolonged ICU and hospital stay and admission duration and affected morbidities and mortality. We recommend that ventilated patients should be weaned, and impaired renal function and coagulation function be well controlled prior to liver transplantation in order to reduce PRF and thereby improve outcomes.

Materials and Methods Patients
The study design was a retrospective review of patient records with approval of Institutional Review Board (IRB), Chang Gung Medical Foundation (IRB no.: 97-0567B). Methodology and patient confidentiality were approved by our IRB. The IRB confirmed that this study constituted an audit, which did not require patient consents to this retrospective study. From September 2002 to July 2007, the medical records of 153 patients who had liver transplantations in Chang-Gung Memorial Hospital were reviewed. Six patients were excluded due to incomplete data collection. Therefore, 147 patients were included in this study.


Definition of post-operative respiratory failure
In our ICU, a weaning protocol was followed to wean the ventilator after transplantation surgery. Briefly, weaning was started after reversal of neuromuscular function, under adequate of cardiovascular, respiratory and metabolic function, and the weaning criteria were fulfilled: rapid shallow breathing index or respiratory rate/tidal volume ratio ≤105 breaths/min/L (tidal volume>5 ml/Kg, frequency less than 30 breaths/min; maximum inspiratory pressure or negative inspiratory force less than - 30 cmH2O). The arterial blood gas analysis was within normal limit under FiO2≤0.4 and PaO2/FiO2 ratio>350. When the patient was stable and could maintain spontaneous breathing for 30–60 minutes, the surgeon and respiratory therapist determined whether an extubation should be performed in accordance with the above weaning criteria.


Post-operative respiratory failure (PRF) [6], [7] was defined as patients requiring ventilator support for more than 48 hours or patients having re-intubation. All 147 patients were divided into two groups: PRF patients, who developed post-operative respiratory failure, and non-PRF patients, who did not develop post-operative respiratory failure.


Anesthetic regimen and early enteral feeding protocol
Short-acting anesthetic drugs were used as anesthetic regimen for our patients, including midazolam, fentanyl, and rocuronium that were administered on a dose per weight basis at induction. Anesthesia was maintained with an oxygen-air-isoflurane mixture and intermittent doses of cis-atracurium were given for continuing muscle relaxation. A standardized surgical technique performed by the same surgical team was used for all patients. The specific time for inferior vena cava clamping, portal venous reperfusion, and hepatic artery reperfusion was protocol-controlled to within 10 to 15 minutes. All patients were transferred to the ICU for post-transplantation care, including early enteral feeding protocol. Once patients exhausted, enteral feeding was started.


Data collection
The data collected included patient profiles, etiology of diseases, history of systemic diseases (diabetes mellitus, hypertension, heart disease, or rental insufficiency), the definition of renal insufficiency as serum creatinine more than 1.5 mg/dL, or creatinine clearance (CCr) less than 70 mL/min following a previous report [8], pre-operative ventilator usage, model for end-stage liver disease score (MELD), Child-Turcotte-Push (CTP) Classification, pre-operative usage of molecular adsorbent re-circulating system (MARS), pre-operative pulmonary function tests (most recent pulmonary function (≤3 months) on file as relevant reference for liver transplantation), pre-operative laboratory data, length of intensive care unit (ICU) stay, and duration of hospitalization. The post-operative mortality within 30 days, three months, and one year were also collected.


Statistical analysis
Data were analyzed using the statistical software package SPSS (Version 15 SPSS, Chicago, IL). Data were shown as mean ± SD, median with range, or percentages. The univariate relationship between each variable and PRF was tested using Pearson's chi-square or Fisher's exact tests. All significant variables in univariate analysis were analyzed by multiple regression logistic models. Overall patient survival was estimated using the Kaplan-Meier survival analysis. A p value < 0.05 was considered statistically significant.


Big Pharma Wants to 'Friend' You

Direct-to-Consumer Advertising:

Big Pharma Wants to 'Friend' You

Drug makers are using social media to market products in ways that the brand affiliation is not always obvious

Adriana Barton
(The Globe and Mail, Toronto, July 25, 2011)

"According to a formal complaint submitted in November to the U.S. Federal Trade Commission [FTC]…by four separate watchdog groups…pharmaceutical marketing on the Web…'threatens consumer privacy and engages in unfair and deceptive practices'...the British Medical Journal cited the report in an article that suggests Big Pharma’s online marketing activities pose a threat to public health.

Direct-to-consumer advertising that includes the name of a prescription drug, health claim and contraindications is prohibited in Canada and highly regulated in the United States. But transparency has become murky on the Internet, says Jeff Chester, co-author of the complaint to the FTC and executive director of the Washington, D.C.-based Center for Digital Democracy…

The pharmaceutical industry’s growing presence online coincides with a pivotal shift in health care…As many as 80 per cent of Internet users go online to find health information, according to a 2011 report published by the non-profit Pew Research Center in Washington, D.C. And almost 20 per cent go online to find others with similar health problems. Big Pharma is gearing up to 'friend' and 'tweet' them…

According to a 2010 report in Pharma Marketing News, there may be hundreds of patients in social networks earning thousands of dollars from drug companies to provide 'real patient stories' as part of online branded drug or disease-awareness campaigns.

The article describes these 'online opinion leaders' as [the social media marketing]…'secret sauce' [for Big Pharma]…And unless drug companies comply with FTC regulations, consumers have no way of knowing which online 'friends' are on the payroll…Pharmaceutical companies…argue that social media provides an important channel…[With regard to one drug company’s social media forays]

The U.S. Federal Drug Administration [FDA] ruled the Facebook widget provided 'misleading' shared content because it failed to disclose serious risks associated with the drug…[overall] brand recognition plays a major role in doctors’ offices, points out Barbara Mintzes, a specialist in direct-to-consumer advertising at the University of British Columbia’s Centre for Health Services and Policy Research.

Her research and a 2005 study by Richard Kravitz at the University of California suggest that when patients ask for a medication by name, they have a 50- to 75-per-cent chance of walking out of the doctor’s office with a prescription for that drug -- often despite physicians’ ambivalence about the treatment choice."

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Cannabis use linked to earlier psychosis onset

Cannabis use linked to earlier psychosis onset

By Springer
July 26, 2011
MedWire News: Cannabis use is associated with an earlier onset of psychosis, conclude US and Australian scientists in findings that support the notion that cannabis has a causal association with the development of psychosis in some patients.

While it is clear that there is a link between substance use, particularly cannabis, and psychotic illness, some researchers have argued that the link could be explained by confounding variables such as demographic factors.

To investigate further, Matthew Large, from Prince of Wales Hospital in Randwick, New South Wales, Australia, and colleagues searched multiple literature databases for peer-reviewed publications reporting age at onset of psychosis in substance-using and nonsubstance-using groups.

Substances included cannabis, alcohol, and other psychoactive drugs/chemicals; tobacco was not included. In all, 443 articles were identified, of which 83, comprising a total of 8167 substance-using patients and 14,352 nonsubstance-using patients, met the inclusion criteria.
A meta-analysis of the studies revealed that the age at onset of psychosis was 2.7 years lower among cannabis users, and 2.0 years lower among nonspecified substance users, than in nonsubstance-using controls.

The mean age of the substance-using patients across all samples was 1.73 years younger than in controls. The pooled effect size of substance use on psychosis onset was greater in heavy or continuous users than in those who were lighter users or had stopped use, at -2.72 years versus -2.07 years, respectively, compared with controls. However, this difference was not statistically significant.

On both meta-regression and multiple meta-regression, a higher proportion of cannabis users in substance-using groups was associated with a greater negative effect size, suggesting an earlier mean age at onset of psychosis.

There was no association between psychosis age at onset and alcohol use.
The team writes in the Archives of General Psychiatry: "The results of this study provide strong evidence that reducing cannabis use could delay or even prevent some cases of psychosis.
"Reducing the use of cannabis could be one of the few ways of altering the outcome of the illness because earlier onset of schizophrenia is associated with a worse prognosis and because other factors associated with age at onset, such as family history and sex, cannot be changed."

MedWire (www.medwire-news.md ) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Liam Davenport

High fish intake reduces diabetes risk in men

July 28, 2011

High fish intake reduces diabetes risk in men

By Springer
MedWire News: Results from a Japanese study suggest that eating fish can help men reduce their risk for Type 2 diabetes.

However, the investigators found no significant association between fish consumption and diabetes risk in women.

Some studies suggest that consumption of fish and omega-3 fatty acids can help prevent Type 2 diabetes, but other results have suggested that fish consumption might increase diabetes risk.
To investigate further, Akiko Nanri (National Center for Global Health and Medicine, Tokyo) and colleagues analyzed data from 22,921 men and 29,759 women who took part in the second survey of the Japan Public Health Center-based Prospective Study. The participants were aged between 45 and 75 years and had no previous history of diabetes.

Dietary information was obtained using a 147-item food frequency questionnaire at baseline and the participants were divided into quartiles for fish consumption, ranging from a median of 36.6 to 171.7 g/day for men and 35.3 to 163.1 g/day for women.

During 5 years of follow-up, 971 cases of Type 2 diabetes were reported (572 men, 399 women).
The team found that when compared with men in the lowest quartile for overall fish consumption, those in the highest quartile for consumption had a significant 27% reduced risk for developing Type 2 diabetes.

When only small and medium sized fish (mackerel, sardine, saury, and eel) were considered, the reduction in risk for diabetes in the top versus the bottom quartile of consumption was even greater, at 32%.

Men in the middle two quartiles also had a reduced risk for diabetes compared with men in the lowest quartile for total fish, and small and medium fish intake, but these reductions were not statistically significant.

Of note, fish consumption appeared to have no effect on risk for Type 2 diabetes in women.
Nanri and colleagues speculate that "the null finding in women in the current study may have been due to their relatively high proportion of body fat mass, which may have been responsible for higher levels of accumulation of fat-soluble chemicals, which negated the benefit of fish intake on glucose metabolism."

They also suggest: "The high consumption of nonfried fish in the Japanese might partly account for the inverse association between fish intake and Type 2 diabetes in the current study."
Preserving techniques such as salting and drying could also modify the association between fish intake and Type 2 diabetes risk, explain the authors. Excess salt intake can deteriorate insulin metabolism and drying may cause oxidation of polyunsaturated fatty acids in the fish, which can induce inflammation - a known risk factor for Type 2 diabetes.
Writing in the American Journal of Clinical Nutrition, Nanri et al conclude: "Biological mechanisms underlying the inverse association between fish intake and Type 2 diabetes need to be clarified."

MedWire (www.medwire-news.md ) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Helen Albert

Friday, July 29, 2011

Get Tested; Free Hepatitis C Test







World Hepatitis Day -- Get Screened
From: AmerGastroAssn Jul 28, 2011 33 views

AGA member Vinod Rustgi spreads the word about hepatitis screening in a new public service announcement.


GET TESTED
Click here to order a FREE Home Access Hepatitis C Test Kit


How Soon Should I Get Tested After Exposure ?


After the exposure (especially if the blood exposure involved another person known to have the hepatitis C virus), it is recommended that testing for the hepatitis C antibody be performed at 4 to 6 months after the exposure OR that testing for the hepatitis C virus itself (a test often called an HCV PCR or hepatitis C viral load test) be performed 4 to 6 weeks after the potential exposure. These tests are done to determine whether or not hepatitis C infection has occurred as a result of the exposure.


Hepatitis C Testing Facilities by State
The HCCAP HCV Testing Sites map lists only facilities offering free or low cost hepatitis C screening services for those with limited resources due to lack of health insurance, lack of coverage for such testing, and/or limited financial resources.
People with health insurance coverage who want to be screened for hepatitis C are advised to see their doctor to request a hepatitis C screening test.
Availability of hepatitis C testing at a given site is subject to change. HCCAP recommends calling a facility to verify the current availability of hepatitis C testing and the process involved before scheduling or visiting that facility. Be aware that many facilities have limited hours or require appointments.


Click Here To view facilities offering free or low cost hepatitis C screening services


Friday News Digest;Hepatitis a risk to everyone

Hepatitis a risk to everyone
By Joseph MortonWORLD-HERALD BUREAU

WASHINGTON — Nebraskan Evelyn McKnight offered a sobering point Thursday at a White House event on hepatitis.
Much of the afternoon's conversation dealt with "at-risk populations," such as IV drug users and people who had received blood transfusions many years ago.

"I brought forward that we talked a lot about at-risk population, but everybody in the room, everybody in the country, who accesses health care is an at-risk population," McKnight said. "That's how I contracted hepatitis C, was just accessing regular health care."
McKnight was one of 99 people infected with hepatitis C while receiving treatment at the Fremont Cancer Center.
State health officials linked the infections to reused syringes and other poor infection control practices at the clinic. The 2002 outbreak was the largest in U.S. history at the time.
Continue reading......

World Hepatitis Day
Sudbury - Around the globe, an estimated one in 12 people live with chronic hepatitis B or C.





Safe injection sites needed Canada-wide to fight hep B, C
By: The Canadian Press
Date: Thursday Jul. 28, 2011 8:04 AM PT
Canada needs safe-injection sites in every region to curb the spread of hepatitis B and C, says a health-care coalition that is calling for a more aggressive approach to combat the diseases.
The Canadian Coalition of Organizations Responding to Hepatitis B and C has issued a report card on Canada's performance and found that resources are inconsistent across the country.
Co-ordination appears particularly poor in Prince Edward Island, Nunavut and the Northwest Territories and prison inmates across the country are especially vulnerable, the group says in its report.

"Governments are essentially failing in terms of the prison population," the report says.
"There is no consistency from one institution to the next. Harm-reduction measures, resources and equipment must be available and accessible in all provincial and federal institutions."
The report notes that besides safe-injection sites, all regions also need methadone clinics and needle exchanges.

"All governments need to adopt a broader perspective on the determinants of health if they are to be able to address the harms associated with drug use and drug use policy," the report says.
It also suggested some prison policies actually hinder harm reduction.
Vancouver hosts North America's only safe-injection site, known as Insite, and the facility has been the subject of lengthy court wrangling after the Conservative government indicated its intention to have the facility closed. The case is currently before the Supreme Court of Canada.
Hepatitis B and C are infectious diseases of the liver. They can lead to serious liver damage, prompting the need for transplants, and can cause liver cancer.

While needle sharing has long been fingered as a vehicle for spreading hepatitis, as well as HIV, a study earlier this month from the University of Victoria concluded hepatitis may also be spread through shared crack pipes.

The report gave governments a grade of C- for ensuring every infant born in Canada is given a free vaccination against the diseases and the same grade was given to efforts to identify and offer vaccinations to those who didn't get it as an infant.

"It remains clear that too many people remain undiagnosed and untreated for (hepatitis C). Screening based on age, as well as risk, needs to be enforced," the report says.
Ultimately, the treatment for someone who has suffered the full effects of the diseases is a liver transplant, but the report says the numbers of transplants are too low.
The group recommends the federal government take a more active role in prompting organ donation.

The group also recommends the government add hepatitis B to the list of reportable diseases. Hepatitis C is currently on the list.

WHO renews push to cut hepatitis in babies in Asia
HONG KONG (Reuters) - Nine Asia Pacific countries will not meet a 2012 target to reduce hepatitis B infections among children, according to the World Health Organization which plans to intensify its fight against the disease.
Nine out of 10 remain chronically infected for the rest of their lives because their immune systems are undeveloped, which can lead to cirrhosis and then liver cancer later on.
But a WHO expert said the goal of reducing infection rates among children to below 2 percent by 2012 will not be met in Cambodia, Kiribati, Laos, Papua New Guinea, the Philippines, Samoa, Solomon Islands, Vanuatu and Vietnam.
"These nine countries don't look like they are going to make the 2 percent goal," said Karen Hennessey, technical officer for WHO's expanded program on hepatitis B immunization.
Hennessey, who spoke by telephone from Manila, said infection rates among children in these countries were around 8 percent before vaccination programs were introduced at different times starting from the 1980s.
While infection rates have fallen to about 3 to 4 percent, these programs have stalled because of the lack of technical expertise and training, or money, she said.
China is one of the exceptions with infection rates among its children down dramatically in the last five years to below 2 percent due to a successful vaccination program, Hennessey said. However, it still has a huge 10 percent pool of infected adults.
Hepatitis B, which is 50 to 100 times more infectious than HIV, is mostly passed from mother to child when the mother's infected blood comes into contact with open wounds on her newborn during delivery. But a vaccine given within the first 24 hours of birth can prevent infection.
To renew efforts to fight the virus, WHO wants to push a three-pronged approach, which includes getting more pregnant women to deliver in healthcare facilities so that their babies can be immunized soon after delivery.
"If it's very difficult to get women into hospitals, either because (their homes are) remote or very poor, the other possibility is to make sure there is a skilled attendant at every birth ... who are trained to give vaccine within 24 hours," Hennessy said.
The WHO will also help with providing training, she said.
"It is important to get that first dose within 24 hours. But it's not clear. Is it the first hour, first three hours? Who is responsible? Who writes it down? That is enough for people to not want to do it. There has to be training," she said.
About 2 billion people worldwide have been infected by this virus and 350 million of them live with chronic infection. About 600,000 people die each year from the virus, which is also passed through sexual contact and unclean needles. Apart from hepatitis B, other common forms of hepatitis are A, C and E.

Source: DGNews
Study: Viral Hepatitis Rates Forecast a Liver Health Crisis

NEW YORK -- July 27, 2011 -- To coincide with World Hepatitis Day, The Lancet has published an article online detailing the first global estimates of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection prevalence in injecting drug users (IDUs). Around 10 million IDUs are thought to have been exposed to HCV (range 6 to 15 million), or approximately 67% of the global IDU population, while 1.3 million have HBV infection (range 0.3 to 2.7 million), conclude the authors.

“The public-health response to blood-borne virus transmission in IDUs has mainly centred on HIV,” write the authors, who include Prof. Louisa Degenhardt, Centre For Population Health, Burnet Institute, Melbourne, Australia, and Paul Nelson, National Drug and Alcohol Research Centre, University of New South Wales (UNSW), Sydney, Australia. “Maintenance and strengthening of the response to HIV in IDUs remains crucial, but the significance of viral hepatitis needs to receive greater attention than it does at present.”

The costs of HIV drugs once made their use in resource-poor countries unlikely; but global efforts have ensured that access to these drugs has substantially improved for people living with HIV in developing countries. The authors say: “There are growing efforts to bring viral hepatitis treatments into the same (lower cost) access framework as HIV antiretrovirals.” These efforts are reflected in the Viral Hepatitis resolution passed by the 63rd World Health Assembly in 2010, which requested the WHO Director General “to collaborate with other organizations in the United Nations system, partners, international organizations and other relevant stakeholders in enhancing access to affordable treatments in developing countries.”
Access to treatments for viral hepatitis must also be enhanced in high-income countries, with recent estimates suggesting that only a fraction of those who could benefit are currently receiving antiviral therapy.

About 80% of individuals exposed to HCV develop chronic infection, and 3% to 11% of people with chronic HCV infection will develop liver cirrhosis within 20 years, with associated risks of liver failure and liver cancer.

HBV is transmitted through parenteral, sexual, and mother-to-child routes.
About 5% of adults exposed to HBV develop chronic HBV infection, compared with 90% of infants; this is why most of the 350 million chronically infected people worldwide were infected in childhood. It is also why universal infant vaccination against hepatitis B is so crucial to long-term control of this virus, which is the second most important known human carcinogen, after tobacco. Cirrhosis and death from liver cancer are important consequences of HBV infection, occurring in approximately one-quarter of those chronically infected.

In this study, infection was determined via presence of hepatitis C antibody (anti-HCV) and hepatitis B core antibody (anti-HBC) or surface antigen (HBsAg).

For hepatitis C infection, the authors located eligible reports with data for prevalence of anti-HCV in IDUs for 77 countries. Prevalence estimates suggested that 60% to 80% of IDUs had anti-HCV in 25 countries, including Spain (80%), Norway (76%), Germany (75%), France (74%), USA (73%), China (67%), Canada (64%); and more than 80% of IDUs did so in a further 12 countries, including Italy (81%), Portugal (83%), Pakistan (84%), Netherlands (86%), Thailand (90%), and Mexico (97%). The United Kingdom (50%), New Zealand (52%), and Australia (55%) all had lower prevalence. China (1.6 million), USA (1.5 million), and Russia (1.3 million) are thought to contain the largest IDU populations infected with HCV.

HBV infection among IDUs was estimated from eligible reports of HBsAg for 59 countries, with prevalence estimates of 5% to 10% in 21 countries and more than 10% in ten countries, including the USA at 12%. The United Kingdom had the highest rate in Western Europe at 9%. Worldwide, the highest rates were seen in Vietnam (20%), Estonia (19%), Saudi Arabia (18%), and Taiwan (17%). The authors estimate that globally 6.4 million IDUs have ever been infected with HBV (anti-HBC positive), with 1.2 million having active HBV infection (HBsAg positive).
The authors say: “Efforts to prevent, treat, and reduce harms related to liver disease in IDUs are essential -- especially in situations in which HIV has successfully been prevented or managed -- because the large numbers of IDUs infected with HCV and significant morbidity resulting from this infection mean that the health and economic costs of HCV transmitted by injected drug use might be as high as (or higher than) those of HIV. Nonetheless, HCV treatment is underused. … Part of the reason for this neglect is the high cost, which will remain a substantial barrier to increasing of treatment coverage in low-resource settings until costs are reduced.”

The authors stress that not only have prevention, treatment, and care been neglected in this field, but also, attention to high quality surveillance of viral hepatitis. They conclude: “We made the best efforts to identify the most representative studies of IDUs across countries, but there was considerable variation in the quality and recentness of the studies that these estimates are based upon. This reflects a similar lack of emphasis upon surveillance of viral hepatitis among people who inject drugs, as there has been upon prevention and treatment of these viruses. Until there are a more coordinated and sustained efforts to understand and respond to hepatitis, considerable uncertainty will remain in our estimates of the scale of the problem, and the best way to respond.”

The study was funded by the US National Institutes of Health, the World Health Organization’s HIV Department, and the National Drug and Alcohol Research Centre, UNSW.
SOURCE: The Lancet

Source: Int J Cancer
Liver cancer and non-hodgkin lymphoma in hepatitis C virus-infected patients: results from the danvir cohort study
Omland LH, Jepsen P, Krarup H, Christensen PB, Weis N, Nielsen L, Obel N, Sørensen HT, Stuver SO, on behalf of the DANVIR cohort study; International Journal of Cancer (Jul 2011)
Get Full Text

Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection.

Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from an age- and gender-matched general population cohort. Within DANVIR, 4,158 patients with chronic HCV-infection and 2,427 patients with cleared HCV-infection were studied.
The 10-year risks of HCC and NHL in HCV-infected patients were 1.0% (95% confidence interval (CI): 0.8 - 1.3%) and 0.1% (95% CI: 0.1 - 0.2%), respectively. Compared to the general population, HCV-infected patients had a 62.91 -fold increased risk of HCC (95% CI: 28.99 - 136.52), a 29.97 -fold increased risk of NHL during the first year of follow-up (95% CI: 6.08 - 147.84), and a 1.26-fold increased risk of NHL after the first year (95% CI: 0.36 - 4.41).

Chronic HCV-infection was associated with a 4.71-fold increased risk of HCC (95% CI: 1.67 - 13.32) compared to cleared HCV-infection; 5 and 0 events of NHL occurred in patients with chronic and cleared HCV-infection, respectively. HCC-risk is increased substantially in HCV-infected patients compared to the general population. Chronic as opposed to cleared HCV-infection increases the risk of HCC and perhaps NHL.

Source: J Hepatol
Comparison of 9 blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study
Zarski JP, Sturm N, Guechot J, Paris A, Zafrani ES, Asselah T, Boisson RC, Bosson JL, Guyader D, Renversez JC, Bronowicki JP, Gelineau MC, Tran A, Trocme C, de Ledinghen V, Lasnier E, Poujol-Robert A, Ziegler F, Bourliere M, Voitot H, Larrey D, Rosenthal-Allieri MA, Hubert IF, Bailly F, Vaubourdolle M; Journal of Hepatology (Jul 2011)

BACKGROUND&AIMS:
Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of 9 blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, versus liver biopsy, in untreated patients with chronic hepatitis C (CHC).
METHODS:
This was a multicenter prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length = 25±8.4mm).
Performance was assessed using ROC curves corrected by Obuchowski's method.
RESULTS:
Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer(®) (0.86), Fibrotest(®) (0.84), Hepascore(®) (0.84) and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest(®), Fibrometer(®), or Hepascore(®) with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer(®)) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer(®)) and Hepascore(®) to 0.83 (FIB-4) for cirrhosis.
CONCLUSION:
Contrarily to blood tests, performance of Fibroscan™ was reduced due uninterpretable results. Fibrotest(®), interpretable Fibroscan™, Fibrometer(®), and Hepascore(®) perform best and similarly for diagnosis of significant fibrosis and cirrhosis.

Healthy You

Blueberries, A Cup A Day May Keep Cancer Away
Blueberries are among the nutrient-rich foods being studied by UAB Comprehensive Cancer Center investigators exploring the link between disease and nutrition.
Dieticians there say as little as a cup a day can help prevent cell damage linked to cancer.

Why are blueberries considered healthful?
They're full of antioxidants, flavonoids and other vitamins that help prevent cell damage. "Antioxidants protect cells by stabilizing free radicals and can prevent some of the damage they cause," says Laura Newton M.A.Ed., R.D., an associate professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham.Free radicals, atoms that contain an odd number of electrons and are highly reactive, can cause cellular damage, one of the factors in the development of cancer; many believe a diet filled with fruits and vegetables may help reduce the risk. "Studies suggest that antioxidants may help prevent the free-radical damage associated with cancer," says Newton, a licensed dietician who often works with cancer patients.

Blueberries also are rich in vitamin C, which helps the immune system and can help the body to absorb iron. "Vitamin C also helps to keep blood vessels firm, offering protection from bruising," Newton says.Blueberry juice and other products may be nutritious but often contain less fiber than the whole fruit, and added sugar or corn syrup may decrease their nutritional value. Consuming fresh, raw blueberries provides the most benefits; the average serving size of raw blueberries is one cup, which contains about 80 calories.

Blueberry season is in full swing, and now is the perfect time to stock up on this delicious, nutritious fruit from farms located here in Alabama. "They can be frozen, so store some in the freezer to enjoy year round," says Newton. "To freeze blueberries, put them in a single layer on a cookie sheet. Freeze them and then transfer to an airtight bag or container and store. Rinse them with water prior to using."
Source: University of Alabama at Birmingham

Dr. Ashton answers viewer health questions
CBS News medical correspondent Dr. Jennifer Ashton answers viewer health questions on issues like high blood pressure, hydrating in the heat, lyme disease and food allergies.
Read more: http://www.cbsnews.com/video/watch/?id=7374935n#ixzz1TVdthLjb



Diet Detective: Fiber One 90 Calorie Chocolate Peanut Butter Bar Deconstructed
By Charles Stuart Platkin
Published: Jul 27, 2011 at 10:10 AM PDT
This is the first in an ongoing series of columns that will be looking at the various products we consume on a regular basis and dissecting the ingredients. We'll start with Fiber One bars, which, I must say, are very tasty, but not exactly comparable to eating an apple.

Pharmaceutical

Incivek storms hep C market with $75M
July 29, 2011 — 10:52am ET By

There's no doubt that the hepatitis C market was waiting for Incivek. In its first five weeks on the market, the Vertex Pharmaceuticals drug reaped nearly $75 million in sales. That's more than twice the $31 million analysts had been expecting. The question now is whether that pace can be sustained.

Incivek is one of two new game-changing drugs to hit the hepatitis C market. Both the Vertex drug and Merck's Victrelis are designed to be added to standard hepatitis C therapy, and they've proven to increase the cure rate and shorten the duration of the sometimes-painful treatment. But Incivek had been widely predicted to garner a bigger share of the market, thanks to data showing a 79% cure rate and to the possibility of even shorter treatment. Plus, Incivek is considered easier to use.

As Reuters notes, more than 3,000 patients had started on Incivek by mid-July, with a mix of people who had failed on older drugs and those who were new to hep C therapy. There's no way to tell how many of those scrips went to patients who had delayed treatment in anticipation of the new drug, but market-watchers had speculated that thousands were waiting on the sidelines for Incivek to make its debut.

"This is a really, really impressive revenue ramp," Sanford Bernstein analyst Geoffrey Porges told Reuters. "You run this trend forward and you get to $200 million in revenue in the third quarter." The strong sales helped offset the high cost of Incivek's launch, plus higher R&D expenses at the company, giving it a smaller-than-expected loss.
So far, Incivek scripts are outpacing Victrelis three to one. Merck didn't break out the drug's sales in its Q2 earnings announcement, so we have no way to compare dollar figures, at least not yet; executives will probably discuss it during today's conference call.
- read the Reuters news- get more from the Boston Globe