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Commercial impact of supersaturated calcium phosphate oral rinse (scpor) on the prevention and treatment of oral mucositis

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  • Save Clinical M edicine and Diagnostics 2013, 3(4): 82-87 DOI: 10.5923/j.cmd.20130304.02 A Business Impact Study of the Use of a Supersaturated Calcium Phosphate Oral Rinse (SCPOR) in the Prevention and Treatment of Oral Mucositis D. Wayne Taylor The Cameron Institute and M cM aster University, Hamilton, L7L 5R8, Canada Abstract Oral mucositis (OM) is an inflammat ion of mucous memb ranes in the mouth with symptoms ranging fro m redness to severe ulcerations and pain. It is a condition that affects as many as 45,000 Canadian cancer patients annually, and around 70% of patients undergoing conditioning therapy for bone marrow transplantation (BMT). Almost all patients receiving radiat ion therapy to the head and neck areas develop OM. Basic oral care is often not enough to reduce the duration or severity of OM in cancer patients. The author conducted a business impact study for Canadian hospitals and cancer centres of the use of a prescription, supersaturated, calciu m phosphate, oral rinse (SCPOR) in the prevention and treatment of oral mucositis that occurs due to high-dose chemotherapy in bone marrow t ransplant patients as well as in head and neck cancer patients receiving radiation therapy. Treatment of OM with the SCPOR for BMT patients not only provided positive, clinica l results but net savings of $1,585 for a return on investment of 238.3%. The min imal net savings per head and neck cancer patient, a patient who would also be receiving clinically better care for OM, would be $663 for a return on investment of 49.8% . Keywords Oral Mucositis, Oral Rinse, Calciu m Phosphate, Electro lytes, Business Impact 1. Introduction Oral mucositis (OM ) is an inflammat ion of mucous memb ranes in the mouth with symptoms ranging from redness to sever ulcerations. Extrapolating fro m A merican data, it is a condition that affects as many as 45,000 Canadian cancer patients each year[1], and around 70% of patients undergoing conditioning therapy for bone marrow transplantation (BMT)[2]. Appro ximately 40% of patients receiving chemotherapy develop some form o f OM during the course of their treatment[1]. A lmost all patients receiving radiation therapy to the head and neck areas develop OM[3]. The incidence of severe OM (grades 3/4) often exceeds 50% o f patients receiving radiation to the head and neck, and 60% of BMT patients whose conditioning therapy includes total body irradiation[4]. Severe OM rates as high as 98% have been observed in patients that have received chemotherapy co mb ined with rad iat ion to treat head and neck cancer[5]. OM is one of the major causes of severe pain an d deb ilit at in g t o xicit y as so ciat ed wit h h ig h -d ose chemotherapy and radiation therapy[6]. OM can also lead to dysphagia, infection(s), and depression – all of which are * Corresponding author: (D. Wayne Taylor) Published online at Copyright © 2013 Scientific & Academic Publishing. All Rights Reserved co-mo rbidit ies that can inhibit the progress of cancer treatment. Nurses have identified OM as the most debilitating problem associated with cancer treatment[7]. Since many treat ment regimens include both markedly and mildly mucoto xic agents, predicting the potential for mucositis to develop can be difficu lt[2]. Mucositis is usually an acute event that lasts typically 16 days, in Bone Marrow Transplant (BMT) and solid tu mour patients, after the start of cytotoxic treat ment with healing commencing about day 12[8]. Timing is different for OM resulting fro m rad iation therapy as radiation therapy typically is administered over an extended period of time[3]. No matter the type of tumour or treat ment. OM can have rate-limiting effects on treatment regimens, as discussed below. There is an advanced aqueous electrolyte solution in therapeutic use in the United States and Europe that is clin ically proven[6] to be a significant ad junct in the management of mucositis associated with radiat ion therapy and high-dose chemotherapy. This solution is a prescription, supersaturated, calciu m phosphate, oral rinse (SCPOR) and provides a proven alternative for patients and healthcare professionals who are unsatisfied with current options that focus on good oral hygiene, antibiotics when appropriate, and the management of ora l pa in[9]. The author conducted a business impact study for Canadian hospitals and cancer centres of the use of SCPOR Clinical M edicine and Diagnostics 2013, 3(4): 82-87 83 in the prevention and treatment of oral mucositis that occurs due to high-dose chemotherapy in bone marrow transplant patients as well as oral mucositis in head and neck cancer patients receiving rad iation therapy. 2. Clinical and Economic Implications of OM in the Literature According to 42% of patients on high-dose chemotherapy and 38% of patients treated with head and neck irradiat ion, oral mucositis is the most troubling side effect of their therapy[10]. Severe OM can co mplicate the management of cancer, interrupt cancer treat ments, and compro mise outcomes[5]. OM may lead to missed doses, reduced doses, or treatment failure[2]. OM has also been correlated with: increased risks for life-threatening systemic infections in these immunocomp ro mised patients[11]; a p redisposition of patients to potentially fatal septicemia[3]; the use of opioid analgesics for pain relief along with associated co-mo rbidit ies[3]; and the requirement fo r total parenteral nutrition (TPN)[5], all resulting in increased length of hospital stay (LOS) and associated costs[12]. Healthcare economic studies usually look at three types of costs: direct costs, both medical and non-medical; ind irect costs such as lost wages due to illness; and, intangible costs which may include psychosocial and societal costs. A business impact study, such as this one, is only concerned with direct costs. Evaluations of the economic costs of particular treat ment side-effects, as in the case of OM, are rare; cost-effectiveness studies are virtually non-existent. There have been only a few studies examining the costs of treating oral mucositis in head and neck cancer or bone marrow transplants. Incremental costs due to OM result fro m additional treatment costs that may include mucositis pain relief, IV hydration for mucositis-related dehydration, parenteral nutrition, infection treat ment, increased professional time, longer hospital stay, and so on. In a 1996 U.S. study, the mean incremental cost of OM in head and neck cancer ranged fro m a low of $2,949 to a high $4,037 per treat ment ep isode[13]. Assuming a 5% healthcare inflation mult iplier[14], these costs would be $5,839 and $7,993 respectively in 2010 dollars. The range in mean incremental costs was a result of the two costing methodologies used based largely on, alternatively, U.S. Medicare reimbursement figures and billed charges, representing hospitalization costs – the single largest contributor to incremental costs followed by drug costs, support costs and MD/RN t ime. The d ifference between Medicare reimbu rsement fees and billed charges was significant at the hospital studied given that billed charges in the U.S. generally must also include allowances for bad debt, uncompensated care, and capital costs which Medicare does not reimburse. In both the low and high cost halves of the above study, patients with severe OM had statistically significant higher costs for drugs and support (pain medicat ion, G-tubes, IV hydration, nutritional supplements)[13]. Given that Medicare reimbursements are more in line with Canadian reimbursement figures, rather than billed charges, the lower mean incremental cost should be seen as instructional in studying OM treat ment costs in head and neck cancer in Canada. At the time of writing, the Canadian dollar was just about at par with the U.S, dollar so no exchange rate calculations have been made. Two more studies were conducted a decade later, again looking at the costs of treating OM with head and neck cancer. In both studies over two-thirds of the patients studied had severe, grad 3/4 OM. The 2007 study identified the incremental costs, in 2006 dollars, of treating OM as being $1,700 for grade 1/2 OM and $6,000 for g rade 3/ 4 OM[15]. In 2010 dollars those amounts would be $2,066 and $7,293 respectively. The 2008 study calculated incremental costs, in 2005 dollars, for treating only severe OM for head and neck cancer as $17,244[16]. In 2010 dollars that amount would be $22,008. Severe OM is also associated with significantly worse clin ical and economic outcomes, including mortality, in BMT[12]. Fro m the patient’s viewpoint, OM is often the single most debilitating side-effect of a transplant. A U.S. study concluded that, in BM T patients, OM was statistically correlated with an increase in the: incidence of significant infection; days on TPN; days receiving injectable narcotics; length of stay in hospital; total costs; and, rate of mortality within 100 days of the first day of conditioning[12]. The treatment of OM in hematopoietic stem cell transplantation (HSCT) cost, on average, a total of $42,749 in this 2001 study[12]; in 2010 dollars that would be $66,318. 3. Treatment of Oral Mucositis–Clinical and Economic Outcomes Oral Mucositis is an underestimated and under-treated condition that severely affects quality-of-life and success of cancer treatment. Basic ora l care may not be enough to treat OM in cancer patients[17]. The development of effective treatments to prevent and/or reduce the severity of OM has been slow. At present there is considerable variation amongst OM treatment guidelines. Few interventions have proven effective in reducing the duration or severity of OM. SCPOR is one agent that has been proven to reduce the frequency and severity of OM[6]. A unit dose product, SCPOR is not for systemic use but should be initiated at the onset of cancer treatment. In a prospective, randomized, double-blind, placebo-cont rolled trial of treating OM in hematopoietic stem cell transplantation (HSCT) patients, the SCPOR-treated patients, in conjunction with standard oral care, had significantly reduced incidence, intensity and duration of OM over those patients who had received a fluoride rinse and standard oral care[6]. A mongst the SCPOR-treated patients, 40% d id not 84 D. Wayne Taylor: A Business Impact Study of the Use of a Supersaturated Calcium Phosphate Oral Rinse (SCPOR) in the Prevention and Treatment of Oral M ucositis develop OM whereas only 19% of the control group avoided OM. This study also demonstrated that the treatment of OM by SCPOR statistically significantly reduced the: number of days of mucositis (3.72 days versus 7.20 days); duration of pain (2.86 days versus 7.67 days); nu mber of days of morph ine (1.26 days versus 4.02); and dose of morphine (34.54 mg versus 122.78)[6]. SCPOR proved to be superior to placebo in reducing the frequency, intensity, and duration of OM in patients undergoing HSCT. SCPOR is an oral rinse not intended to be ingested. The Federal Drug Administration (FDA) approved SCPOR as a device indicated as an adjunct to standard oral care in treating the mucositis that may be caused by radiation or high-dose chemotherapy. This indication received premarket ing clearance in 2003. There are no known contraindications. No adverse effects have been reported following the use of SCPOR. If accidentally swallowed, no adverse effects are anticipated. There are no known interactions with medicinal or other products[18]. A retrospective study, covering a two-year time period, of two groups of non-Hodgkin’s ly mphoma patients who had received autologous peripheral blood stem cell transplantations revealed that the group that received standard care and SCPOR for the treat ment of their OM fared better than those who only received standard care[19]. The mean nu mber of days on patient-controlled analgesia (PCA) was 3.8 for SCPOR patients and 5.5 for those receiving only standard care. The mean daily dose of PCA hydro morphone was 9.5 mg for SCPOR patients versus 12.5 for standard care patients. Average length of hospital stay was reduced 1.5 days (~10%) for SCPOR-treated BMT patients fro m 16.2 days to 14.6 days for a cost savings of $6,141 in 2010 dollars. The study concluded that SCPOR had a positive effect on both clinical and economic outcomes of OM for BMT p atien ts . Fro m February 2007 to May 2008, a retrospective, match controlled study of SCPOR versus supportive care for OM in head and neck cancer patients was conducted to determine the effectiveness of SCPOR for reducing the inc idence and severity of OM – which it d id[14] (see Figure 1). On ly 38% of patients treated with SCPOR developed severe OM whereas 71% of the control patients developed severe OM. Conversely, 62% of SCPOR-treated patients contracted low grade OM versus only 29% of the control patients. In addition, no adverse effects associated with the use of SCPOR were observed. The study also concluded that the use of SCPOR reduced the costs associated with treating OM through reduced hospitalization stay and reduced associated supportive care costs such as fewer PEG tube p lacements. Using the two different cost models and the associated cost data fro m the two articles cited above[15],[16] the study by Miyamoto[14] calculated the cost savings fro m treat ing OM with SCPOR as being between $1,722 (32.5% of the costs of the control patients) and $6,917 (46.5%). In 2010 dollars those savings would be $1,993 - $8,007. The weighted average savings per SCPOR-treated patient was 37.1% of the control patient cost, or $3,958 in 2010 dollars. The cost of treat ment with SCPOR is not prohibitive. In 2008 the cost of SCPOR was US$154.00/30 doses or US$559.36/ 120 doses. According to another 2007/2008 study, head and neck cancer patients treated for OM with SCPOR were ad ministered, on average, 4.56 rinses per day and the average course of treatment was for 8 weeks[20]. Both the incidence and severity of OM was significantly less with the use of SCPOR. High levels of co mp liance were observed due to the ease of administration, as well as high levels of both patient and physician satisfaction. In this study, the average cost of treating OM with SCPOR in head and neck cancer patients was $1,190 - $1,311 depending upon the dose size purchased. In 2010 dollars those costs would be $1,378 - $1,518 (see Table 1). 60 52 50 40 38 33 30 20 14 10 10 19 14 0 0 0 1 2 3 SCPOR Control 19 Percentage of patients 0 4 Grade of oral mucositis Figure 1. Results of SCPOR vs. control (supportive care) Simp le arith metic calculations showed that the difference, in a worst case scenario, between the highest cost of SCPOR and the lowest clin ical savings fro m the use of SCPOR yielded a net savings of $475 per patient or a return on the investment in SCPOR of 31%. On the other hand, in a best case scenario assuming the lowest cost for SCPOR and maximu m clinical savings, a net savings of $6,695 is realized per patient for an ROI of 441%. On average, net savings of $2,543 per head and neck cancer patient could be realized y ield ing an ROI o f 180% Table 1. Net Savings and ROI from the Use of SCPOR in Treating OM for Head & Neck Cancer 2010 $ Low High Average Savings from SCPOR $1,993 $8,007 $3,958 Cost of SCPOR $1,312 $1,518 $1,415 Net Savings $475 $6,695 $2,543 Return on Investment (ROI) 31.3% 510.3% 179.7% Clinical M edicine and Diagnostics 2013, 3(4): 82-87 85 The average course of treat ment of OM with SCPOR in BMT patients was 4 weeks. Using the same calculat ions as above, this time for BMT patients, net savings from using SCPOR would be $5,582 for an ROI of almost 10-fo ld or 1,000%. The most recent prospective, randomized, control study was conducted in 2009 wherein 40 allogeneic HSCT patients were rando mized and stratified (by the type of conditioning regime, type of transplant and age) into two equal groups. One group received SCPOR four times daily fro m the first day of conditioning; the control group received standard topical mouth care[21]. Th is study had very similar results to the previous studies. The severity of OM was reduced 50%; the duration of OM was reduced from 7.1 days to 3.2 days; the average subjective peak pain in the mouth was rated as 0.85 for SCPOR versus 1.75 for the control group on a 10-point scale. Analgesics were required by 45% o f the control group whereas only 15% of the SCPOR patients required analgesics; duration of usage was 3.4 days for the control group and 1.1 days for the SCPOR group. No SCPOR patients required TPN co mpared to 30% in the control group who required it, on average, for 1.9 days. 4. Business Impact of SCPOR for Canadians In 2005 there were 3,756 reported cases of head and neck cancer in Canada[22]. By 2010 it had been estimated that figure would grow to 4,550 cases[23], exh ibit ing an annual growth rate of 4% versus a population growth rate of 1.5% per annum[24]. Between 2004 and 2008 bone marrow transplants numbered as many as 1,600 in one year[25] . 4.1. Treatment of OM with SCPOR in B one Marrow Trans plant Patients Assuming there are 1,600 BMT patients per year in Canada, and that the most significant pro xy for better clinical and economic outcomes fro m treating OM in these patients with SCPOR is the 10% (1.5 days) reduction in length of hospital stay (LOS), then the direct cost saving would total 2,400 patient bed-days. The “fully loaded” average cost of a BMT bed-day ranges fro m $2,500 to $4,500[26]. Again, assuming a 10% reduction in LOS, treating OM with SCPOR for bone marrow transplants would save a hospital $3,750 - $6,750 per patient, depending upon their cost structure, and provide better clinica l outcomes. Given the distribution in Tab le 2 o f BMT procedures across the country, a weighted national average, fully loaded cost of a BMT bed-day would be approximately $3,677. At a reduced LOS of 1.5 days that would provide an overall savings of $8,824,800 - with improved clinica l outcomes. The Canadian pricing of SCPOR was $665 per month of therapy. Treat ment of OM with SCPOR in the case of BMT patients normally lasts 4 weeks; therefore it is safe to say that the cost of treatment per patient would be $665. Table 2. Numbers of Pat ient Cases Reported by Province BC AB SK MB ON QC NB NS PE NL Canada Head & Neck 582 371 90 145 1310 850 85 120 10 55 4550 Bone Marrow Transplant 218 287 47 70 526 332 0 96 0 28 1604 Source: Canadian Cancer Statistics 2010; BC Cancer Registry Statistics 2007; Alberta Cancer Registry 2006; Canadian Bone Marrow Transplant Statistics 2004-2008; head and neck national total of 4,550 includes larynx cancer (1,150) which is not included by province except British Columbia and Alberta Given that SCPOR is a patient-admin istered oral rinse that takes 2 minutes for ad ministration, addit ional treat ment costs are insignificant. Treat ment of OM with SCPOR for BMT patients will not only provide positive clinica l results but net savings (savings fro m reduced LOS net the cost of SCPOR) $3,085 - $6,085 per patient for a return on investment (ROI) on SCPOR of 464.9% - 915.0%. On a national basis, using the weighted national average cost of a bed-day, net savings would total $7,784,800. The overall national average cost of a hospital bed/day was approximately $1,100 in 2008 recognizing, of course, that there is great variability across provinces, within provinces, and most certainly amongst different types of and levels of care with hospitals[27]. Based upon information provided by a major cancer centre in the Province of Saskatchewan it has been estimated that the marginal cost of a bone marrow transplant bed-day in that province was approximately $1,500. Supportive care net cost-savings of the nature being analyzed in this study will be accrued at the margin. Since this marginal cost is only slightly more than the national average for all bed/days this provides for a conservative analysis of the cost-savings of treating OM in BMT patients. Using the same methodology, as above, in the case of Saskatchewan a reduced length of stay of 1.5 days would yield a savings of $2,250. Subtracting the cost of the SCPOR produced a net savings of $1,585 for a return on the investment in using SCPOR of 238.3%. If 30% of BMT patients required 2 days of TPN because of the severity of their OM[21] and TPN costs $360 per day[28] then an addit ional $720 would be saved per BMT patient who otherwise would have received TPN. Although net savings would only be $55 yielding an incremental increase of ROI of 8% the clinical benefits remain s ig n ifican t. 86 D. Wayne Taylor: A Business Impact Study of the Use of a Supersaturated Calcium Phosphate Oral Rinse (SCPOR) in the Prevention and Treatment of Oral M ucositis 4.2. Treatment of OM with SCPOR in Head and Neck Cancer Patients Given the variability in the A merican cost savings data in using SCPOR for head and neck cancer this portion of the study assumed the most conservative savings of $1,993. In the case of head and neck cancer patients, a two month course of treatment is usually indicated so the cost of the SCPOR per patient would be $1,330. The min imal net savings per head and neck cancer patient (savings minus cost of SCPOR), a patient who would also be receiving clin ically better care for OM, would be $663 for an ROI on SCPOR of 49.8% . Given 4,550 cases of head and neck cancer, national net savings would amount to a min imu m of $3,016,650. 5. Conclusions [5] Redding SW. Cancer therapy-related oral mucositis. J Dent Educ. 2005; 69(8):919-929. [6] Papas AS, Clark RE, M artuscelli G, O’Loughlin KT, Johansen E, M iller KB. A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplantation. 2003; 31:705-712. [7] Bruce SD, Quinn A. The Pain of Oral M ucositis. US Oncological Disease. 2007; 1:86-90. [8] Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004; 4:277-284. [9] The brand name of the SCPOR is Caphosol®. [10] Stokman M A, Spijkervet FKL, Boezen HM , Schouten JP, Roodenburg JLN, de Vries EGE. Preventive intervention possibilities in radiotherapy- and chemotherapy-induced oral mucositis: results of meta-analyses. J Dent Res. 2006; 85(8):690-700. Using SCPOR to treat OM would yield co mbined national savings for both BMT and head and neck cancer of $10,801,450, while providing better clinical care fo r cancer patients suffering fro m OM. Unfortunately, adequate data was not available for head and neck cancer for a case examp le to be constructed. There was plenty of data available for the top four cancers (breast, colorectal, lung and prostate) but very little for the others – either known or being collected. Likewise the costs of treating cancers other than the top four were not known at the time of this study. Future research in this area is required for a better understanding of the costs and benefits from innovative treatment options. ACKNOWLEDGEMENTS The Industrial Research Assistance Programme of the National Research Council of Canada is acknowledged for its financia l support of this study. REFERENCES [1] M eraw SJ, Reeve CM . Dental considerations and treatment of the oncology patient receiving radiation therapy. J Am Dent Assoc. 1998:129:201-205. [2] Köstler WJ, Hejna M , Wenzel C, Zielinski C. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin. 2001; 51(5): 290-315. [3] Sonis ST. Oral mucositis in cancer therapy. J Support Oncol. 2004; 2 (suppl 3):3-8. [4] Sonis St, Elting LS, Keefe D, for the M ucositis Study Section of the M ultinational Association of Supportive Care in Cancer and the International Society for Oral Oncology. Perspective on cancer therapy-induced mucosal injury. Cancer. 2004; 100 (suppl 9):1995-2025. [11] Brennen M T, von Bültzingslöwen I, Schubert MM , Keefe D. Alimentary mucositis: putting the guidelines into practice. Support Care Cancer. 2006; 14:573-579; and, Sonis ST. Oral mucositis in cancer therapy. [12] Sonis ST, Oster G, Fuchs H, Oral mucositis and the clinical and economic outcomes of hematopoietic stem cell transplantation. J Clin Oncol. 2001; 19:2201-2205. [13] Peterman A, Celia D, Giandon G, Dobrez D, Yount S. M ucositis in head and neck cancer: economic and quality-of-life outcomes. J Natl Cancer Inst Monogr. 2001; 29:45-51. [14] M iyamoto C, Wobb J, M icaily B, Li S, Achary M . A Retrospective M atch Controlled Study of Supersaturated Calcium Phosphate Oral Rinse (SCPOR) vs. Supportive Care for Radiation-Induced Oral M ucositis. Support Care Cancer. 2009; 27:911. [15] Elting LS, Cooksley CD, Chambers M S, Garden AS. Risk, Outcomes and Costs of Radiation-Induced Oral M ucositis among Patients with Head-and-Neck M alignancies. Int J Radiat Oncol Biol Phys. 2007; 68(4):1110-1120. [16] Nonzee NJ, Dand ade NA, M arkossian T, Agulnik M , Evaluating the Supportive Care Costs of Severe Radiochemotherapy-Induced M ucositis and Pharyngitis. Cancer. 2008; 113(6):1446-1452. [17] Trotti A, Garden A, Warde P, A multinational, randomized phase III trial of Iseganan HCI oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for heck-and-neck malignancy. Int J Radiat Oncol Bio Phys. 2004; 58:674-681. [18] Caphosol Prescribing Information. Princeton NJ: Cytogen Corporation; August 2007. [19] Bechtel T, Devine S. Use of a Calcium/Phosphate Oral Rinse (Caphosol) to Lessen the M ucositis Following An Autologous Peripheral Blood Stem Cell Transplantation. 2009 BM T Tandem meetings; Tampa FL (February 2009). Poster. [20] Haas M L, M ercedes T, M anyak M J. Reduction of Painful Oral M ucositis by Supersaturated Calcium Phosphate Oral Rinse in Head and Neck Cancer Patients Receiving Clinical M edicine and Diagnostics 2013, 3(4): 82-87 87 Chemotherapy and Radiation. American Society for [25] Canadian Bone M arrow Transplant Group, Canadian Bone Therapeutic Radiology and Oncology Annual Meeting 2008. Marrow Transplant Statistics 2004-2008, as provided to the Poster. author by Superna Life Sciences, Inc. [21] M arkiewicz M , M ietla M D, Zielinska P, Krizel T, et. al. Caphosol M outh Rinse Diminishes Oral M ucositis IN Allo-HSCT Recipients. American Society of Haematology Conference, 2010. Poster. [22] Public Health Agency of Canada, Cancer Surveillance On-Line, accessed 11/8/2010. [23] Canadian Cancer Society, 2010 Canadian Cancer Statistics, accessed 11/18/10. [24] As calculated from Statistics Canada population data 2005-2010(e). [26] Costs provided to the author by Superna Life Sciences, Inc. [27] This figure was calculated by the author based upon published CIHI data for teaching and research purposes at M cM aster University in September, 2010. [28] In the absence of available Canadian data, again it is assumed that M edicare costs in the U.S. are reflective of costs in Canada. M edicare’s reimbursement for TPN in 1998 was $1,400 per week; assuming 5% inf lation for healthcare costs, in 2010 dollars that would be $360 per day.

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