SAO PAULO, Dec. 23 (UPI) — In a Brazilian study, 76 percent of the patients who died of H1N1 had underlying medical conditions such as heart disease or cancer, researchers say.

However, lead author Dr. Thais Mauad of Sao Paulo University in Brazil said there was no clear complicating medical condition in the remaining one-quarter.

Mauad and colleagues examined 21 patients who had died in Sao Paulo with confirmed H1N1 infection in July and August. Most were 30 to 59.

While previous data has shown most patients with a non-fatal infection have fever, cough and achiness, but “most patients with a fatal form of the disease presented with difficulty breathing, fever and achiness being less frequently present.”

All patients died of severe acute lung injury, but there were three distinct patterns of the damage to their lungs, indicating that the infection killed in distinct ways.

“All patients have a picture of acute lung injury,” Mauad says in a statement. “In some patients this is the predominant pattern, in others, acute lung injury is associated with necrotizing bronchiolitis, and in others there is a hemorrhagic pattern.”

Patients with necrotizing bronchiolitis are more likely to have a bacterial co-infection, patients with heart disease and cancer are more likely to have a hemorrhagic condition in their lungs, Mauad says.

This has been a topic of much discussion the last several months.   Here is a medical article that goes into depth regarding the importance of Vitamin D.

From American Journal of Lifestyle Medicine

Vitamin D Supplementation and Cancer Prevention

Thomas L. Lenz, PharmD, MA, PAPHS

Posted: 12/08/2009; Am J Lifestyle Med. 2009;3(5):365-368. © 2009 Sage Publications, Inc.

Abstract and Introduction

Abstract

It is estimated that approximately 1 billion people worldwide have blood concentrations of vitamin D that are considered suboptimal. Much research has been conducted over the past 30 years linking low vitamin D serum concentrations to both skeletal and nonskeletal conditions, including several types of cancers, cardiovascular disease, diabetes, upper respiratory tract infections, all-cause mortality, and many others. Several observational studies and a few prospectively randomized controlled trials have demonstrated that adequate levels of vitamin D can decrease the risk and improve survival rates for several types of cancers including breast, rectum, ovary, prostate, stomach, bladder, esophagus, kidney, lung, pancreas, uterus, non-Hodgkin lymphoma, and multiple myeloma. Individuals with serum vitamin D concentrations less than 20 ng/mL are considered most at risk, whereas those who achieve levels of 32 to 100 ng/mL are considered to have sufficient serum vitamin D concentrations. Vitamin D can be obtained from exposure to the sun, through dietary intake, and via supplementation. Obtaining a total of approximately 4000 IU/d of vitamin D₃ from all sources has been shown to achieve serum concentrations considered to be in the sufficient range. Most individuals will require a dietary supplement of 2000 IU/d of vitamin D₃ to achieve sufficient levels as up to 10 000 IU/d is considered safe. Vitamin D₃ is available as an over-the-counter product at most pharmacies and is relatively inexpensive, especially when compared with the demonstrated benefits.

Introduction

It is well known that a causal link exists between severe vitamin D deficiency and rickets in children and the bone disease osteomalacia in adults. It is also well known that vitamin D insufficiency is associated with osteoporosis, a decrease in muscular strength, and increased fall risk. It is less well known, however, that a low serum concentration of vitamin D is also associated with several other diseases and conditions.

It is estimated that 1 billion people worldwide have vitamin D deficiency or insuffiency.^[1] Patients ranging from children to elderly are affected by vitamin D deficiency. One study showed that 48% of white preadolescent girls had deficient blood levels of vitamin D.^[2] Another study reported that more than half of postmenopausal women taking medication for osteoporosis had suboptimal blood levels of vitamin D.^[3] Several other studies report that from 40% to 100% of community-living elderly men and women in both the United States and Europe have deficient levels of vitamin D.^[1] The estimated cost to our society of vitamin D deficiency is reported to be between $100 and $200 billion per year.^[4]

The recent number of medical publications on the topic of vitamin D is astounding. A PubMed search of the previous 10 years alone using the term “vitamin D” resulted in 17 399 publication displays. The newly appreciated associations between low vitamin D levels and diseases include glucose intolerance, diabetes mellitus, metabolic syndrome, cardiovascular disease, myocardial infarction, hypertension, obesity, heart failure, myopathy, inflammatory bowel disease, multiple sclerosis, psoriasis, tuberculosis, upper respiratory tract infections, polycystic ovarian syndrome, and even all-cause mortality.^[5,6] In addition, a great deal of research has been conducted linking low vitamin D levels with several types of cancers. A follow-up PubMed search of the previous 10 years using the terms “vitamin D AND cancer” resulted in 2870 publication displays, of which two-thirds were published in the past 5 years. The purpose of this article is to briefly review the physiology behind vitamin D, provide an overview of key research linking vitamin D intake with decreased cancer risk, and present the current recommendations for vitamin D intake.

Physiological Facts about Vitamin D

Assessing a patient’s vitamin D level can most accurately be measured with serum 25-hydroxyvitamin D, the primary circulating form of vitamin D.^[1] Serum 25-hydroxyvitamin D is expressed in ng/mL or nmol/L, where 1 ng/mL is equal to 2.5 nmol/L. Currently, there is no consensus among the medical community with regard to the optimal blood level of 25-hydroxyvitamin D. However, most vitamin D researchers generally agree that <20 ng/mL is considered a deficiency, >32 ng/mL is considered sufficient, and vitamin D intoxication is observed at levels of 150 ng/mL or higher.^[1] Table 1 provides a categorical list of serum 25-hydroxyvitamin D levels.

Table 1. Serum 25-Hydroxyvitamin D Concentrations by Category^[1,5,7,8]

Category
25-Hydroxyvitamin D Concentrations, ng/mL (nmol/L)

Deficiency
<20 (<50)

Insufficiency
20-32 (50-80)

Sufficiency
32-100 (80-250)

Excess
>100 (> 250)

Intoxication
>150 (>325)

An individual patient’s 25-hydroxyvitamin D level is determined by many variables, including the amount of solar ultraviolet B (UVB) radiation (determined by the time of day, season, latitude, skin pigmentation, use of sunscreen, and age), dietary habits, obesity, and many others.^[1] UVB radiation penetrates the skin and converts vitamin D precursors to vitamin D₃. Vitamin D obtained from the skin and diet is metabolized to 25-hydroxyvitamin D. This determines a patient’s measured serum level of vitamin D. 25-hydroxyvitamin D is then further metabolized in the kidneys to its active form, 1,25-hydroxyvitamin D. Most tissues and cells in the body possess a vitamin D receptor, and many have the ability to convert 25-hydroxyvitamin D to 1,25-hydroxyvitamin D.^[1] This discovery is thought to be the reason such a broad range of diseases and conditions, including cancer, have benefited from vitamin D supplementation.

Cancer and Vitamin D Research

The emerging evidence showing the relationship between decreased cancer risk and vitamin D intake may be relatively new or even unheard of for many health care professionals. But the first article demonstrating a relationship between solar radiation and cancer mortality in North America was actually published in 1941.^[9] In 1980, the first article was published proposing that vitamin D may be directly related to cancer risk.^[10] Since that time, articles have been published that demonstrate an inverse relationship with solar radiation and cancer mortality for many types of cancers including breast, rectum, ovary, prostate, stomach, bladder, esophagus, kidney, lung, pancreas, uterus, non-Hodgkin lymphoma, and multiple myeloma.^[11] Almost all of the evidence that links vitamin D and cancer has come from observational studies. One study, however, published in 2007 by Lappe et al,^[11] prospectively looked at the effect of vitamin D intake on the incidence of all cancers.

The purpose of the study was to determine if calcium alone or calcium plus vitamin D has an effect on reducing the incidence of all types of cancer.^[11] The study was designed as a 4-year, population-based, double-blind, randomized placebo-controlled trial. The study participants included 1024 community-dwelling women who were randomly selected from a population of healthy postmenopausal women from 9 rural counties in Nebraska. The participants’ mean age was 66.7 years, with a body mass index of 29.0 kg/m² and a baseline serum 25-hydroxyvitamin D level of 71.8 nmol/L. Subjects were randomly assigned to 1 of 3 groups: 1400 to 1500 mg supplemental calcium per day alone, 1400 to 1500 mg supplemental calcium plus 1100 IU vitamin D₃ per day, or placebo.^[11]

The results showed that both the calcium-only and the calcium plus vitamin D groups had lower rates for all cancers compared with the placebo group (P < .03).^[11] The relative risk for the development of cancer at the study’s end was 0.402 for the calcium plus vitamin D group (P = .013) and 0.532 for the calcium-only group (P = .063). The Kaplan-Meier plot of the 3 groups showing survival-free cancer over the course of the study revealed a similar time course up to 1 year, which then began to separate. The 12-month serum 25-hydroxyvitamin D level in the calcium plus vitamin D group increased by 23.9 nmol/L to 96.0 nmol/L compared with statistically unchanged levels in the other 2 groups. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk. This translated to a predicted 35% reduced risk of cancer for every 25-nmol/L (10-ng/mL) increase in serum 25-hydroxyvitamin D. The authors concluded that improving vitamin D nutritional status substantially reduced all-cancer risk in postmenopausal women and that baseline and treatment-induced serum 25-hydroxyvitamin D concentrations were strong predictors of cancer risk.^[11]

Other studies relating cancer to vitamin D have shown that people living at higher latitudes are at increased risk for Hodgkin lymphoma as well as colon, pancreatic, prostate, ovarian, breast, and other cancers. In addition, people living at higher latitudes are more likely to die from these cancers compared with those living at lower latitudes.^[1] Epidemiologic studies, both prospective and retrospective, have shown that individuals who have serum 25-hydroxyvitamin D levels less than 20 ng/mL have an associated 30% to 50% greater risk of colon, prostate, and breast cancer as well as a higher mortality rate from these cancers.^[1] In addition, analysis of the Women’s Health Initiative showed that women who had a serum 25-hydroxyvitamin D level less than 12 ng/mL (30 nmol/L) had a 253% increase in the risk of colorectal cancer over an 8-year follow-up period.^[12]

Vitamin D Intake

The current recommended daily allowance of vitamin D in the United States is 200 IU/d for children and adults up to 50 years of age, 400 IU/d for 51 to 70 years, and 600 IU/d for those older than 70 years.^[7] The emerging evidence on the nonskeletal benefits of vitamin D has made these recommendations obsolete. As a general rule of thumb, serum 25-hydroxyvitamin D concentration will increase 1 ng/mL for every 100 IU vitamin D₃.^[1,13] Therefore, if a patient has a baseline concentration of 10 mg/mL, an additional 3000 IU/d would be required to achieve a level of 40 ng/mL and put this patient in the sufficiency category.

Vitamin D can be obtained through exposure to sunlight, food that naturally contains vitamin D, food that is fortified with vitamin D, and prescription and over-the-counter dietary supplementation. Aside from supplementation, the most significant source of vitamin D is through sun exposure. Sensible sun exposure is considered safe and effective for obtaining vitamin D₃. This would entail the exposure of arms and legs for 5 to 30 minutes (depending on season, latitude, and skin pigmentation) between the hours of 10 am and 3 pm 2 times per week. When the body produces excess vitamin D precursors and vitamin D₃, they are destroyed by sunlight; therefore, excessive exposure to sunlight does not cause vitamin D intoxication.^[1] Caution should be used when educating patients regarding sun exposure. Health care professionals should counsel patients on the message that sun exposure ad libitum is not acceptable for the purposes of obtaining adequate serum 25-hydroxyvitamin D concentrations and that a balance between the risk for skin cancer and vitamin D intake should be achieved.

A diet high in oily fish such as salmon, sardines, mackerel, and tuna can supply a range of vitamin D₃ from 250 to 1000 IU per serving. For example, 3.5 oz of fresh, wild salmon can provide 600 to 1000 IU of vitamin D₃, whereas 3.5 oz of fresh, farmed salmon can supply only 100 to 250 IU of vitamin D₃. Likewise, 3.6 oz of canned tuna contains about 230 IU of vitamin D₃. In addition, 8 oz of fortified milk, orange juice, or yogurt contains about 100 IU of vitamin D₃.^[1] Most Americans do not consistently take in enough daily vitamin D through their diet to maintain adequate serum concentrations, and therefore supplementation is most often recommended.

As shown in Table 1, the lower level of serum 25-hydroxyvitamin D considered to be sufficient is 32 ng/mL. To achieve a serum concentration of 32 ng/mL or higher, most individuals will need to obtain about 4000 IU/d or more vitamin D₃ from all sources combined.^[8] Because most individuals do not get enough vitamin D₃ through their diet and/or live under conditions that prohibit adequate sun exposure, most healthy adults will need 2000 IU/d vitamin D₃ supplementation to achieve a serum concentration of 32 ng/mL or greater. Studies have shown that supplementation with vitamin D₃ over a period of about 90 days is needed to reach steady-state concentrations.^[7] Supplementation is available in both vitamin D₂ (ergocalciferol) and vitamin D₃ (cholecalciferol) formulations. Toxicity and overdose have been related to vitamin D₂ intake but not D₃ intake. Doses of vitamin D₂ of more than 50 000 IU/d have been shown to raise serum 25-hydroxyvitamin D concentrations to greater than 150 ng/mL, causing associated hypercalcemia and hyperphosphatemia. Doses of vitamin D₃ of 10 000 IU/d have been shown to be taken without incidence of side effects and is considered to be the safe upper limit of daily intake.^[1] In addition, both vitamin D₂ and D₃ have demonstrated the ability to achieve adequate serum 25-hydroxyvitamin D concentrations; however, vitamin D₃ has been shown to maintain these concentrations for a longer period of time.^[14] As a result, supplementation with vitamin D₃ is generally recommended over vitamin D₂.

Table 1. Serum 25-Hydroxyvitamin D Concentrations by Category^[1,5,7,8]

Category
25-Hydroxyvitamin D Concentrations, ng/mL (nmol/L)

Deficiency
<20 (<50)

Insufficiency
20-32 (50-80)

Sufficiency
32-100 (80-250)

Excess
>100 (> 250)

Intoxication
>150 (>325)

Cost and Availability

Vitamin D₃ can easily be found as an over-the-counter dietary supplement in most pharmacies. As with all supplements, patients should be advised to purchase brands from reputable and well-known companies to ensure quality. Vitamin D₃ is available in a variety of strengths including 400 IU, 1000 IU, 2000 IU, and 10 000 IU. As discussed above, most individuals should take approximately 2000 IU daily, which can be found at most pharmacies, supermarkets, and nutrition stores for less than $10 per bottle of 100 tablets or capsules. This makes vitamin D₃ supplementation relatively inexpensive when compared with the demonstrated benefits.

Conclusion

Reports have shown that a large percentage of our population may have serum vitamin D concentrations that are considered suboptimal. Obtaining adequate amounts of vitamin D is important not only for bone health but also for decreasing the risk for several other diseases and conditions, including cancer. Data support the justification for supplementing vitamin D₃ 2000 IU/d in most adults to decrease the risk for several types of cancers and other conditions. Vitamin D₃ is relatively inexpensive and can be found as an over-the-counter product in most pharmacies.

References

1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281.
2. Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine at risk for vitamin D insufficiency. J Am Diet Assoc. 2005;105:971-974.
3. Holick MF, Siris ES, Binkley N, et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90: 3215-3224.
4. GrassrootsHealth. The vitamin D deficiency epidemic. A call to D*action. http://www.grassrootshealth.org/daction/epidemic.php. Accessed May 8, 2009.
5. GrassrootsHealth. Disease incidence prevention by serum 25(OH)D level. http://www.grassrootshealth.org/_download/disease_incidence_prev_chart_101608.pdf. Accessed May 8, 2009.
6. Autier P, Gandini S. Vitamin D supplementation and total mortality. Arch Intern Med. 2007;167(16):1730-1737.
7. Dall T, Anderson J. Vitamin D: merging research into clinical lipid practice. Lipid Spin. 2008;6(3):4-8.
8. Heaney RP. What is a vitamin D deficiency? http://www.grassrootshealth.net/media/download/heaney_whats_vitamin_d_deficiency120208.pdf. Accessed May 8, 2009.
9. Apperly F. The relation of solar irradiation to cancer mortality in North America. Cancer Res. 1941;1:191-195.
10. Garland C, Garland F. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9: 227-231.
11. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-1591.
12. Holick MF. Calcium plus vitamin D and the risk for colon cancer. N Engl J Med. 2006;354:2287-2288.
13. Cannell J, Hollis B, Zasloff M, Heaney R. Diagnosis and treatment of vitamin D deficiency. Pharmacotherapy. 2008;9(1):1-12.
14. Lee JH, O’Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency: an important, common, and easily treatable cardiovascular risk factor. J Am Coll Cardiol. 2008;52:1949-1956. Downloaded from http://ajl.sagepub.com by Janet Kim on November 18, 2009

Authors and Disclosures

Thomas L. Lenz, PharmD, MA, PAPHS
Department of Pharmacy Practice, Creighton University, Omaha, Nebraska.
Address correspondence to
Thomas L. Lenz, PharmD, MA, PAPHS, Department of Pharmacy Practice, Creighton University, Omaha, NE 68178; e-mail: tlenz@creighton.edu.

Updated Interim Recommendations: Special Considerations for Clinicians Regarding 2009 H1N1 Influenza in Severely Immunosuppressed Patients

December 16, 2009, 11:30 AM ET

Epidemiology

Immunosuppression can result from a variety of clinical conditions, and the severity of immunosuppression may vary with the severity of the condition. Immunosuppression may also result from immunosuppressive treatments, the extent of which may depend on factors such as dosage or synergistic medication combinations. Some common conditions and treatments associated with immunodeficiency are shown in the tables below. These interim recommendations refer to patients who are severely immunosuppressed as a result of receiving treatment for malignancies; or as a result of receiving treatment related to solid organ or hematopoietic stem cell transplants; or as a result of autoimmune conditions and treatment. Such patients may be at high risk of influenza-related complications such as more severe illness and hospitalization. These recommendations may be updated as further information becomes available. In addition to this guidance, there are documents available for caregivers of adult and adolescent HIV-infected patients as well as for patients with rheumatological diseases.

Patients with severe immunosuppression from the following conditions or treatments may be at high risk for influenza-related complications.

Some Conditions and Treatment that Suppress the Immune System*

• Hematopoietic stem cell transplant recipient receiving anti-rejection medication
• Solid organ transplant recipient receiving anti-rejection medication
• Congenital immunodeficiency disorder
• Chemotherapy for cancer
• Autoimmune conditions and treatments
• Chronic corticosteroid use

* HIV and Rheumatologic conditions are included in other guidance

Patients with conditions that confer some degree of immunosuppression, e.g., asplenia, may not necessarily have increased risk for influenza-associated complications, but may be at high risk for secondary invasive infection with encapsulated bacteria (e.g., pneumococcal disease).

Patients who use short courses of treatments that weaken the immune system for mild, common ailments (e.g., corticosteroid use for poison ivy), are likely NOT at increased risk of complications from influenza unless they also have other high-risk conditions for influenza complications such as asthma, chronic obstructive pulmonary disease, diabetes, heart disease, pregnancy, cancer, etc.

Clinical Issues

While some severely immunosuppressed patients may develop typical signs and symptoms of influenza, fever may not always be present¹. Therefore, clinicians should suspect influenza in any severely immunosuppressed patient with acute respiratory symptoms, with or without fever, and initiate empiric antiviral treatment as soon as possible and send respiratory specimens for real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) (see Influenza diagnostic testing and Antiviral treatment sections below). Appropriate infection control including isolation should be implemented for any suspected patient as soon as possible even before testing results are available.

Although the type and severity of immune dysfunction that correlates with increased risk of influenza-associated complications is not well defined, transplant patients with significant lymphodepletion (i.e., lymphopenia due to immunosuppression for recent hematopoietic stem cell transplant) or lymphocyte dysfunction have had serious complications of influenza virus infection, prolonged viral shedding, and have acquired resistance to antiviral medications². Sporadic cases of oseltamivir-resistant 2009 H1N1 influenza virus infection have been reported; some of these cases were in severely immunosuppressed patients in whom resistance emerged during treatment for symptomatic illness and who experienced prolonged viral shedding³. Therefore, some experts have recommended that immunosuppressed patients with 2009 H1N1 influenza virus infection should strictly adhere to recommended personal protective equipment and infection control measures until symptoms have resolved and there are serial respiratory specimens that test negative for 2009 H1N1 viral RNA by rRT-PCR ^{4, 5}.

Influenza vaccination and prevention

Although influenza vaccination is the best way to prevent influenza, influenza vaccination may be poorly immunogenic in severely immunosuppressed patients⁶. Therefore, antiviral chemoprophylaxis of influenza can be considered for severely immunosuppressed patients⁷. Immunosuppressed persons aged 6 months and older are recommended to receive both inactivated seasonal influenza vaccine and inactivated 2009 H1N1 monovalent influenza vaccine. In addition, persons aged 6 months and older who are household contacts of severely immunosuppressed persons are recommended for annual inactivated seasonal influenza vaccination. Further details regarding reasons for vaccinating these groups can be found in the 2009 H1N1 Vaccination Recommendations.

Influenza diagnostic testing

Any severely immunosuppressed patient who is ill with suspected influenza should be started on empiric antiviral treatment as soon as possible without waiting for influenza testing to be conducted or influenza testing results. Confirmatory influenza diagnostic testing for 2009 H1N1 influenza with rRT-PCR should be considered for severely immunosuppressed patients with suspected influenza because results will inform decisions regarding clinical care and infection control. Additional influenza testing of respiratory specimens of severely immunosuppressed patients by rRT-PCR is recommended by some experts for determination of prolonged viral shedding. Guidelines for influenza testing in solid organ or hematopoietic stem cell transplant donors with suspected influenza are available^{8, 9}. Recommendations on the use of influenza diagnostic tests for the 2009-2010 influenza season are available.

Antiviral treatment

Antiviral therapy with a neuraminidase inhibitor (oseltamivir, zanamivir) should be initiated empiricallyas early as possible for severely immunosuppressed patients with suspected influenza. Although efficacy of early antiviral treatment (<48 hours from illness onset) of previously healthy persons with uncomplicated influenza has been demonstrated in randomized clinical trials, observational studies indicate that initiation of oseltamivir treatment after 48 hours of onset in hospitalized patients with seasonal influenza or 2009 H1N1 is associated with survival benefit compared to no treatment^{10, 11, 12, 13}. Although there are no prospective data available for neuraminidase inhibitor treatment of immunosuppressed patients with influenza, initiation of therapy beyond 48 hours after symptom onset should be considered.

Clinicians should be aware that severely immunosuppressed persons with influenza may experience prolonged influenza viral replication; those with significant lymphopenia will typically shed for longer than 5 days even with antiviral treatment². Therefore, some experts have recommended consideration of longer duration of neuraminidase inhibitor treatment (e.g. 10 days versus standard 5 days). Infection control precautions should be maintained for as long as such patients have evidence of prolonged influenza viral shedding as detected by rRT-PCR and/or remain symptomatic – whichever is longer. Sporadic cases of oseltamivir resistant 2009 H1N1 virus have been reported in severely immunosuppressed patients who were treated with oseltamivir. This oseltamivir resistance is associated with an H275Y mutation in viral neuraminidase. Patients with suspected or confirmed oseltamivir-resistant 2009 H1N1 influenza virus who require antiviral treatment should receive zanamivir. If orally inhaled zanamivir is contraindicated or not tolerated, then IV zanamivir is available for compassionate use from its manufacturer via an emergency Investigational New Drug (IND) application to the FDA. Patients with highly suspected or documented oseltamivir resistance should not be treated with peramivir because clinical isolates expressing the oseltamivir resistance-associated substitution H275Y in neuraminidase have demonstrated reduced in-vitro susceptibility to peramivir, although the clinical significance of this is currently unknown. Development of resistance to other antiviral medications during treatment is also possible. Such antiviral resistance would be associated with different mutations and can only be detected by robust screening assays that are not specific for the H275Y mutation. Clinicians managing 2009 H1N1 hospitalized patients who have not improved clinically and who have persistent laboratory-confirmed viral shedding may wish to consult infectious disease specialists, their state health department or CDC for questions about antiviral resistance, additional testing and antiviral treatment.

Optimal therapy for severely immunosuppressed patients with oseltamivir-resistant 2009 H1N1 influenza virus has not been defined. Some severely immunosuppressed patients with 2009 H1N1 have been treated with a combination of IV zanamivir and aerosolized ribavirin^{3, 14} therapy, or IV zanamivir monotherapy¹⁵. Clinicians should note that orally inhaled zanamivir may not be tolerated by critically ill patients with lower respiratory tract disease. Clinicians should be aware that intravenous antiviral medications are available, IV peramivir¹⁶ through an Emergency Use Authorization; and IV zanamivir¹⁵ through an Emergency Investigational New Drug Application) for treatment of critically ill 2009 H1N1 patients or for hospitalized patients who cannot tolerate orally inhaled zanamivir or oral oseltamivir when treatment is indicated. Critically ill immunosuppressed patients are particularly susceptible to secondary bacterial and fungal infections that can cause pneumonia and disseminated infection, including sepsis, and should be empirically treated with antibiotics based on clinical judgment.

¹ Peck AJ, Englund JA, Kuypers J et al. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection. Blood. 2007 Sep 1;110(5):1681-8.
² Khanna N, Steffen I, Studt JD et al. Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2009 Apr;11(2):100-5.
³ CDC. Oseltamivir-Resistant Novel Influenza A (H1N1) Virus Infection in Two Immunosuppressed Patients — Seattle, Washington, 2009. MMWR, 2009. 58(32);893-896.
⁴ Gooskens J et al. Prolonged Influenza Virus Infection during Lymphocytopenia and Frequent Detection of Drug-Resistant Viruses. The Journal of Infectious Diseases 2009; 199:1435– 41
⁵ Lee N, Chan PK, et al. Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza. J Infect Dis. 2009; 200:492-500.
⁶ Hodges GR, Davis JW, Lewis HD, et al. Response to influenza A vaccine among high-risk patients. South Med J 1979;72:29-32.
⁷ ASBMT Guidelines
⁸ Danziger-Isakov LA, Husain S, Mooney ML, Hannan MM; for the ISHLT Infectious Diseases Council. The Novel 2009 H1N1 Influenza Virus Pandemic: Unique Considerations for Programs in Cardiothoracic Transplantation.
J Heart Lung Transplant. 2009 Oct 21. [Epub ahead of print]
⁹ Kumar D, Morris MI, Kotton CN et al. Guidance on Novel Influenza A/H1N1 in Solid Organ Transplant Recipients. American Journal of Transplantation 2009; 9: 1–8.
¹⁰ Lee N, Cockram CS, Chan PK, Hui DS, Choi KW, Sung JJ. Antiviral treatment for patients hospitalized with severe influenza infection may affect clinical outcomes. Clin Infect Dis 2008;46:1323-1324.
¹¹ Hanshaoworakul W, Simmerman JM, Narueponjirakul U, et al. Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome. PLoS One 2009;4(6):e6051.
¹² Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009;361:1935-1944.
¹³ Domínguez-Cherit G, Lapinsky SE, Macias AE, et al. Critically ill patients with 2009 influenza A(H1N1) in Mexico. JAMA 2009;302:1880-1887.
¹⁴ Chan-Tack KM, Murray JS, Birnkrant DB. Use of ribavirin to treat influenza. N Engl J Med. 2009 Oct 2;361(17):1713-4.
¹⁵ Kidd IM, Down J, Nastouli E, Shulman R, Grant PR, Howell DC, Singer M. H1N1 pneumonitis treated with intravenous zanamivir. Lancet. 2009 Sep 19;374(9694):1036.
¹⁶Birnkrant D, Cox E. The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza. N Engl J Med. 2009 Nov 3. [Epub ahead of print]

Contact Your Senators!

Urgent! Ask Your Senators to Support Kerry/Wyden et. al IVIG Amendment!

Take Action!

Your help is needed! This could be our last chance this year!

With Majority Leader Harry Reid’s introduction of the Senate’s merged health care reform bill, the Senate debate on health care reform has begun.

Senators Kerry (D-MA), Wyden (D-OR) and others have filed an IVIG access amendment to the bill. The amendment is based on S. 701, the Medicare Patient IVIG Access Act, but scaled back. It establishes a three year demonstration project that would authorize payment for the items and services necessary to infuse IVIG in the home setting.

IDF supports this amendment as the only viable means to strengthen the Medicare Part B home infusion benefit for the next few years. Current law does not allow coverage of nursing services in the home and therefore Medicare patients with primary immunodeficiency diseases (PIDD) do not have access to IVIG home infusion. Currently, Medicare will pay for the plasma product, but not pay for the items and services for a home infusion, making the benefit ineffective. Passage of this amendment can make the difference between Medicare patients with PIDD receiving their treatment or going without.

Also, the Kerry/Wyden et al. IVIG Amendment requires additional studies on IVIG access and reimbursement, including an update of the February 2007 government report entitled “Analysis of Supply, Distribution, Demand and Access Issues Associated with Immune Globulin Intravenous (IGIV).”

The end of the health care reform process is near. Please contact your Senators to urge them to help address IVIG access in health reform. Use IDF’s Action Alert to ask your Senators to support the Kerry/Wyden et al. IVIG Access Floor Amendment.

BioRx Offers Berinert ® to Patients with Hereditary Angioedema
Cincinnati, Ohio (December 7, 2009)

BioRx, a specialty pharmacy company, has been named one of a small number of approved providers of Berinert®. Berinert® is a plasma?derived concentrate of C1 esterase
inhibitor (human) indicated for the treatment of acute abdominal or facial attacks of hereditary
angioedema (HAE) in adult and adolescent patients. CSL Behring, the manufacturer of Berinert® selected
BioRx as part of their distribution network to launch this exciting new product in the United States.
BioRx will be launching a dedicated website, www.haefreedom.com, to provide information about HAE,
treatment options, and related BioRx services.
HAE is a very rare, potentially life threatening genetic condition that causes episodes of swelling (edema)
and fluid retention in various body parts, including the hands, feet, face, and airway. Patients who have
abdominal attacks can experience episodes of severe pain, diarrhea, nausea, and vomiting caused by
swelling of the intestinal wall. Attacks that involve the face and larynx can result in airway closure,
asphyxiation, and, if untreated, death.
Diagnosis of HAE requires a blood test to confirm low or abnormal levels of C1?INH. An estimated 6,000 to
10,000 people in the United Sates have HAE.
BioRx is one of a limited number of specialty pharmacies selected by CSL Behring to dispense Berinert ®,
which was just recently approved by the US Food and Drug Administration (FDA) for the treatment of adult
and adolescent patients with acute abdominal or facial attacks of HAE. CSL Behring manufactures and sells
C1?INH concentrate in Germany, Austria, Switzerland, and several other countries under the trade name
Berinert P®.
Mark Kestler, General Manager of BioRx, says “Recognition by CSL Behring as an approved Berinert®
provider validates BioRx as a leading quality provider of specialized pharmaceutical services. We are excited
to be able to offer this valuable treatment option to HAE patients.”
Berinert® is appropriate for those who want the freedom and convenience of safe home administration of
C1?INH therapy, with approval from their physician. BioRx will provide specialized training and in? home
nursing, as well as the drug and any other supplies needed for treatment. “This new therapy for HAE
patients is consistent with similar drugs that our nurses handle every day. Highly individualized care plans
will result in our nurses either administering the drugs, or concurrently working with the families over an
extended period of time to ensure that they are comfortable and competent to manage the treatment
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More information about Berinert® at BioRx is available by calling 866?442?4679, or via email at
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About BioRx
Based in Cincinnati Ohio, BioRx is a national specialty pharmacy dedicated to providing highly customized care for
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H1N1 virus attacks deep into the lungs

By Stephanie Smith, CNN Medical Producer

December 8, 2009 4:18 p.m. EST

Damaged lung tissue is seen as light gray and healthy lung tissue is seen as dark gray in this cross-sectional CT scan of a deceased patient with pulmonary bacterial infection caused by the H1N1 virus. The other organs are white.

STORY HIGHLIGHTS

• Doctors examined records, autopsy reports, and slides of 34 people who died due to H1N1
• Inflammation and damage in the lungs extended all the way to the farthest end of airways
• More than half of the deaths were caused by bacterial pneumonia.
• 91 percent had underlying health condition; obesity was a factor in 72 percent of deaths

New York (CNN) — In the rare cases when the H1N1 virus kills, scientists have found, it penetrates deep into the lungs, creating widespread damage — a pattern similar to what killed millions during previous flu pandemics in 1918 and 1957.

The New York Office of Chief Medical Examiner examined medical records, autopsy reports and microscopic slides of 34 people with H1N1 who died between May 15 and July 9, 2009, during the early days of the pandemic.

The report found that among those deaths, inflammation and damage in the lungs extended all the way to the alveoli, tiny sacs at the farthest end of the lungs’ airways.

“Generally, flu stays in the upper airways,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “What this shows is clearly this virus has capability of infecting and causing inflammation and destruction of cells from the trachea, all the way down into smaller cells of the lungs.

“The cells of the lung get directly attacked by the virus,” said Fauci.

CDC : Fewer states are reporting widespread flu activity

RELATED TOPICS

• Swine Flu
• National Institute of Allergy and Infectious Diseases
• Obesity

The damage appears in computerized scans as opaque patches that normally would not appear in the lungs, and which obstruct lung function.

Get complete coverage of H1N1 — Fighting the flu

Echoing previous reports, the study, published online in the Archives of Pathology and Laboratory Medicine, also revealed that 91 percent of those who died were people with underlying health problems, and most occurred in people between 25 and 49 years old.

More than half of the deaths were caused by bacterial pneumonia.

“The secondary bacterial infection evokes inflammation,” said Dr. William Schaffner, professor in the Division of Infectious Diseases at Vanderbilt University School of Medicine. “It socks it in the lung and all of a sudden the lung as an organ can’t do its principal job.”

Obesity was a factor in 72 percent of H1N1 deaths, a finding that has caused concern among infectious disease experts.

“That was a striking finding,” said Schaffner. “It contributes in a very material way to what we know about risks for a severe outcome with H1N1 infection. We are keeping an eye on obesity as a risk factor for H1N1 death.”

Track the H1N1 virus in your state

The study gives interesting insight into the mechanism behind H1N1 deaths, but will not change the current response to the virus, said Fauci.

Key Flu Indicators

Each week CDC analyzes information about influenza disease activity in the United States and publishes findings of key flu indicators in a report called FluView. During the week of November 15-21, 2009, influenza activity decreased in some key indicators and increased in others. Overall influenza activity remains high for this time of year. Below is a summary of the most recent key indicators:

• Visits to doctors for influenza-like illness (ILI) nationally decreased sharply this week over last week with all regions showing declines in ILI. This is the fourth consecutive week of national decreases in ILI after four consecutive weeks of sharp increases While ILI has declined, visits to doctors for influenza-like illness remain high.
• Influenza hospitalization rates remain higher than expected for this time of year. Hospitalization rates continue to be highest in younger populations with the highest hospitalization rate reported in children 0-4 years old.
• The proportion of deaths attributed to pneumonia and influenza (P&I) based on the 122 Cities Report continues to be higher than expected for this time of year. This proportion has remained elevated for eight weeks now. In addition, 35 flu-related pediatric deaths were reported this week: 27 of these deaths were associated with laboratory confirmed 2009 H1N1; 7 were influenza A viruses, but were not subtyped and one death was associated with a seasonal influenza A (H1) virus. The one death associated with seasonal influenza A (H1) virus infection reported this week actually occurred in March, during the 2008-09 season. Since April 2009, CDC has received reports of 234 laboratory-confirmed pediatric deaths:  198 due to 2009 H1N1, 35 pediatric deaths that were laboratory confirmed as influenza, but the flu virus subtype was not determined, and one pediatric death associated with a seasonal influenza virus. (Laboratory-confirmed deaths are thought to represent an undercount of the actual number. CDC has provided estimates about the number of 2009 H1N1 cases and related hospitalizations and deaths.)
• Thirty-two states are reporting widespread influenza activity at this time; a decline of 11 states from last week. They are: Alabama, Alaska, Arizona, California, Connecticut, Delaware, Florida, Idaho, Illinois, Indiana, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, Tennessee, Utah, Vermont, Virginia, and West Virginia).
• Almost all of the influenza viruses identified so far continue to be 2009 H1N1 influenza A viruses. These viruses remain similar to the virus chosen for the 2009 H1N1 vaccine, and remain susceptible to the antiviral drugs oseltamivir and zanamivir with rare exception.

*All data are preliminary and may change as more reports are received.

Learn more >>

U.S. Situation Update

Weekly Flu Activity Estimates

U.S. Patient Visits Reported for Influenza-like Illness (ILI)

U.S. Influenza-like Illness (ILI) Reported by Regions

U.S. Laboratory Confirmed Influenza-Associated Hospitalizations
and Deaths from August 30 to November 21, 2009
Posted November 30, 2009, 11:00 AM ET
Data reported to CDC by November 24, 2009, 12:00 AM ET

Cases Defined by

Hospitalizations

Deaths

Influenza Laboratory-Tests**
29,348
1,224

*Reports can be based on syndromic, admission or discharge data, or a combination of data elements that could include laboratory-confirmed and influenza-like illness hospitalizations.

*Laboratory confirmation includes any positive influenza test (rapid influenza tests, RT-PCR, DFA, IFA, or culture), whether or not typing was done.

The table shows aggregate reports of all laboratory confirmed influenza hospitalizations and deaths (including 2009 H1N1 and seasonal flu) since August 30, 2009 received by CDC from U.S. states and territories**. This table will be updated weekly each Friday at 11 a.m. For the 2009-2010 influenza season, states are reporting based on new case definitions for hospitalizations and deaths effective August 30, 2009.

CDC will continue to use its traditional surveillance systems to track the progress of the 2009-2010 influenza season. For more information about influenza surveillance, including reporting of influenza-associated hospitalizations and deaths, see Questions and Answers: Monitoring Influenza Activity, Including 2009 H1N1.

The number of 2009 H1N1 hospitalizations and deaths reported to CDC from April - August 2009 is available on the Past Situation Updates page.

For state level information, refer to state health departments.

International Human Cases of 2009 H1N1 Flu Infection
See: World Health Organization.

**States report weekly to CDC either 1) laboratory-confirmed influenza hospitalizations and deaths or 2) pneumonia and influenza syndrome-based cases of hospitalization and death resulting from all types or subtypes of influenza. Although only the laboratory confirmed cases are included in this report, CDC continues to analyze data both from laboratory confirmed and syndromic hospitalizations and deaths.