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Health Information
IfosfamideSkip to the navigation
Drug Information
Common brand names:Ifex
Summary of Interactions with Vitamins, Herbs, & Foods
Replenish Depleted Nutrients
Magnesium and Potassium
The chemotherapy drug cisplatin may cause excessive loss of magnesium and potassium in the urine.1 , 2 Preliminary reports suggest that both potassium and magnesium supplementation may be necessary to increase low potassium levels.3 , 4 Severe magnesium deficiency caused by cisplatin therapy has been reported to result in seizures.5 Severe magnesium deficiency is a potentially dangerous medical condition that should only be treated by a doctor. People receiving cisplatin chemotherapy should ask their prescribing doctor to closely monitor magnesium and potassium status.
The chemotherapy drug cisplatin may cause kidney damage, resulting in depletion of calcium and phosphate.6The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
The chemotherapy drug cisplatin may cause depletion of sodium due to kidney damage which sometimes occurs in people treated with cisplatin.7The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Taurine has been shown to be depleted in people taking chemotherapy.8 It remains unclear how important this effect is or if people taking chemotherapy should take taurine supplements.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Reduce Side Effects
Acetyl-L-carnitine in the amount of 1,000 mg three times per day for eight weeks has been shown to improve nerve damage (neuropathy) caused by the chemotherapy drug cisplatin.9
Fruit-Flavored Drinks
Often, people who undergo chemotherapy develop aversions to certain foods, sometimes making it permanently difficult to eat those foods. Exposing people to what researchers have called a "scapegoat stimulus" just before the administration of chemotherapy can direct the food aversion to the "scapegoat" food instead of more important parts of the diet. In one trial, fruit drinks administered just before chemotherapy were most effective in protecting against aversions to other foods.10
High-dose cisplatin chemotherapy is associated with kidney toxicity and damage, which may be reduced by glutathione administration.11 , 12 , 13 , 14 Nerve damage is another frequent complication of high amounts of cisplatin. Preliminary evidence has shown that glutathione injections may protect nerve tissue during cisplatin therapy without reducing cisplatin's anti-tumor activity.15 , 16 , 17 There is no evidence that glutathione taken by mouth has the same benefits.
Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.18
In a preliminary trial, supplementation with a probiotic (Lactobacillus GG) reduced the frequency of severe diarrhea and the incidence of abdominal discomfort related to the use of 5-FU. The amount of Lactobacillus GG used was 10-20 billion organisms per day during the 24 weeks of chemotherapy.19
In one human study, administration of 4,000 mcg per day of a selenium product, Seleno-Kappacarrageenan, reduced the kidney damage and white blood cell-lowering effects of the chemotherapy drug cisplatin.20 The amount of selenium used in this study is potentially toxic and should only be used under the supervision of a doctor. In another study, patients being treated with cisplatin and cyclophosphamide for ovarian cancer were given a multivitamin preparation, with or without 200 mcg of selenium per day. Compared with the group not receiving selenium, those receiving selenium had a smaller reduction in white blood cell count and fewer chemotherapy side effects such as nausea, hair loss, weakness, and loss of appetite.21
Spleen Peptide Extract
Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga) in a double-blind trial during chemotherapy with cisplatin and 5-FU.22 The spleen preparation had a significant stabilizing effect on certain white blood cells. People taking it also experienced stabilized body weight and a reduction in the fatigue and inertia that usually accompany this combination of chemotherapy agents.
Wheat Grass
In a preliminary trial, taking wheat grass in the amount of 60 ml (about 2 ounces) per day during chemotherapy reduced the incidence of certain chemotherapy-related side effects (including anemia and a decline in white blood cell counts) in women with breast cancer. Taking wheat grass did not appear to interfere with the anticancer effect of the chemotherapy. The chemotherapy used in this study was a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide.23
Chemotherapy frequently causes mouth sores. In one trial, people were given approximately 400,000 IU of beta-carotene per day for three weeks and then 125,000 IU per day for an additional four weeks.24 Those taking beta-carotene still suffered mouth sores, but the mouth sores developed later and tended to be less severe than mouth sores that formed in people receiving the same chemotherapy without beta-carotene.
In a study of chemotherapy-induced mouth sores, six of nine patients who applied vitamin E directly to their mouth sores had complete resolution of the sores compared with one of nine patients who applied placebo.25 Others have confirmed the potential for vitamin E to help people with chemotherapy-induced mouth sores.26 Applying vitamin E only once per day was helpful to only some groups of patients in another trial,27 and not all studies have found vitamin E to be effective.28 Until more is known, if vitamin E is used in an attempt to reduce chemotherapy-induced mouth sores, it should be applied topically twice per day and should probably be in the tocopherol (versus tocopheryl) form.
In a preliminary study, the addition of oral vitamin E (300 IU per day) to cisplatin chemotherapy significantly reduced the incidence of drug-induced damage to the nervous system (neurotoxicity).29 A similar protective effect was seen in another trial in which 600 IU of vitamin E per day was used.30The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
A liquid preparation of German chamomile (Matricaria recutita) has been shown to reduce the incidence of mouth sores in people receiving radiation and systemic chemotherapy treatment in an uncontrolled study. 31The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Ginger (Zingiber officinale) can be helpful in alleviating nausea and vomiting caused by chemotherapy.32 , 33 Ginger, as tablets, capsules, or liquid herbal extracts, can be taken in 500 mg amounts every two or three hours, for a total of 1 gram per day.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Though cancer cells use glutamine as a fuel source, studies in humans have not found that glutamine stimulates growth of cancers in people taking chemotherapy.34 , 35 In fact, animal studies show that glutamine may actually decrease tumor growth while increasing susceptibility of cancer cells to radiation and chemotherapy,36 , 37 though such effects have not yet been studied in humans.
Glutamine has successfully reduced chemotherapy-induced mouth sores. In one trial, people were given 4 grams of glutamine in an oral rinse, which was swished around the mouth and then swallowed twice per day.38 Thirteen of fourteen people in the study had fewer days with mouth sores as a result. These excellent results have been duplicated in some,39 but not all,40 double-blind research. In another study, patients receiving high-dose paclitaxel and melphalan had significantly fewer episodes of oral ulcers and bleeding when they took 6 grams of glutamine four times daily along with the chemotherapy.41
One double-blind trial suggested that 6 grams of glutamine taken three times per day can decrease diarrhea caused by chemotherapy.42 However, other studies using higher amounts or intravenous glutamine have not reported this effect.43 , 44
Intravenous use of glutamine in people undergoing bone marrow transplants, a procedure sometimes used to allow very high amounts of chemotherapy to be used, has led to reduced hospital stays, leading to a savings of over $21,000 for each patient given glutamine.45The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
N-Acetyl Cysteine
NAC, an amino acid-like supplement that possesses antioxidant activity, has been used in four human studies to decrease the kidney and bladder toxicity of the chemotherapy drug ifosfamide.46 , 47 , 48 , 49 These studies used 1-2 grams NAC four times per day. There was no sign that NAC interfered with the efficacy of ifosfamide in any of these studies. Intakes of NAC over 4 grams per day may cause nausea and vomiting.
The newer anti-nausea drugs prescribed for people taking chemotherapy lead to greatly reduced nausea and vomiting for most people. Nonetheless, these drugs often do not totally eliminate all nausea. Natural substances used to reduce nausea should not be used instead of prescription anti-nausea drugs. Rather, under the guidance of a doctor, they should be added to those drugs if needed. At least one trial suggests that NAC at 1,800 mg per day may reduce nausea and vomiting caused by chemotherapy.50The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Vitamin A, Vitamin C, and N-Acetyl Cysteine
Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells.51 However, most scientific research does not support this supposition.
A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research.52 Vitamin C appears to increase the effectiveness of chemotherapy in animals53 and with human breast cancer cells in test tube research.54 In a double-blind study, Japanese researchers found that the combination of vitamin E , vitamin C, and N-acetyl cysteine (NAC) -all antioxidants-protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.55
A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but neither does it show that antioxidants should be avoided for fear that the actions of chemotherapy are interfered with.56 Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Irradiation treatment, especially of head and neck cancers, frequently results in changes to normal taste sensation.57 , 58 Zinc supplementation may be protective against taste alterations caused or exacerbated by irradiation. A double-blind trial found that 45 mg of zinc sulfate three times daily reduced the alteration of taste sensation during radiation treatment and led to significantly greater recovery of taste sensation after treatment was concluded.59The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Support Medicine
Milk Thistle
Milk thistle's (Silybum marianum) major flavonoids, known collectively as silymarin, have shown synergistic actions with the chemotherapy drugs cisplatin and doxorubicin (Adriamycin) in test tubes.60 Silymarin also offsets the kidney toxicity of cisplatin in animals.61 Silymarin has not yet been studied in humans treated with cisplatin. There is some evidence that silymarin may not interfere with some chemotherapy in humans with cancer.62
The mushroom Coriolus versicolor contains an immune-stimulating substance called polysaccharide krestin, or PSK. PSK has been shown in several studies to help cancer patients undergoing chemotherapy. One study involved women with estrogen receptor-negative breast cancer. PSK combined with chemotherapy significantly prolonged survival time compared with chemotherapy alone.63 Another study followed women with breast cancer who were given chemotherapy with or without PSK. The PSK-plus-chemotherapy group had a 25% better chance of survival after ten years compared with those taking chemotherapy without PSK.64 Another study investigated people who had surgically removed colon cancer. They were given chemotherapy with or without PSK. Those given PSK had a longer disease-free period and longer survival time.65 Three grams of PSK were taken orally each day in these studies.
Although PSK is rarely available in the United States, hot-water extract products made from Coriolus versicolor mushrooms are available. These products may have activity related to that of PSK, but their use with chemotherapy has not been studied.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Thymus Extracts
Peptides or short proteins derived from the thymus gland, an important immune organ, have been used in conjunction with chemotherapy drugs for people with cancer. One study using thymosin fraction V in combination with chemotherapy, compared with chemotherapy alone, found significantly longer survival times in the thymosin fraction V group.66 A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone.67 A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone.68 Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Reduces Effectiveness
Potential Negative Interaction
Explanation Required
Vitamin A
A controlled French trial reported that when postmenopausal late-stage breast cancer patients were given very large amounts of vitamin A (350,000-500,000 IU per day) along with chemotherapy, remission rates were significantly better than when the chemotherapy was not accompanied by vitamin A.69 Similar results were not found in premenopausal women. The large amounts of vitamin A used in the study are toxic and require clinical supervision.
Russian research has looked at using eleuthero (Eleutherococcus senticosus) with chemotherapy. One study of patients with melanoma found that chemotherapy was less toxic when eleuthero was given simultaneously. Similarly, women with inoperable breast cancer given eleuthero were reported to tolerate more chemotherapy.70 Eleuthero treatment was also associated with improved immune function in women with breast cancer treated with chemotherapy and radiation.71The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Many chemotherapy drugs can cause diarrhea , lack of appetite, vomiting, and damage to the gastrointestinal tract. Recent anti-nausea prescription medications are often effective. Nonetheless, nutritional deficiencies still occur.72 People undergoing chemotherapy should talk to their doctor about whether supplementing with a multivitamin-mineral will protect them against deficiencies.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
1. Buckley JE, Clark VL, Meyer TJ, Pearlman NW. Hypomagnesemia after cisplatin combination chemotherapy. Arch Intern Med 1984;144:2347.
2. Threlkeld DS, ed. Antineoplastics, alkylating agents, cisplatin (CDDP). In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1999, 652a-2d.
3. Rodriguez M, Solanki DL, Whang R. Refractory potassium repletion due to Cisplatin-induced magnesium depletion. Arch Intern Med 1989;149:2592-4.
4. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern Med 1992;152:40-5.
5. van de Loosdrecht AA, Gietema JA, van der Graaf WT. Seizures in a patient with disseminated testicular cancer due to cisplatin-induced hypomagnesaemia. Acta Oncol 2000;39:239-40.
6. Threlkeld DS, ed. Antineoplastics, alkylating agents, cisplatin (CDDP). In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1999, 652a-2d.
7. Threlkeld DS, ed. Antineoplastics, alkylating agents, cisplatin (CDDP). In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1999, 652a-2d.
8. Desai TK, Maliakkal J, Kinzie JL, et al. Taurine deficiency after intensive chemotherapy and/or radiation. Am J Clin Nutr 1992;55:708-11.
9. Bianchi G, Vitali G, Caraceni A, et al. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Eur J Cancer 2005;41:1746-50.
10. Mattes RD. Prevention of food aversions in cancer patients during treatment. Nutr Cancer 1994;21:13-24.
11. Fontanelli R, Spatti G, Raspagliesi F, et al. A preoperative single course of high-dose cisplatin and bleomycin with glutathione protection in bulky stage IB/II carcinoma of the cervix. Ann Oncol 1992;3:117-21.
12. Plaxe S, Freddo J, Kim S, et al. Phase I trial of cisplatin in combination with glutathione. Gynecol Oncol 1994;55:82-6.
13. Di Re F, Bohm S, Oriana S, et al. Efficacy and safety of high-dose cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced epithelial ovarian cancer. Cancer Chemother Pharmacol 1990;25:355-60.
14. Tedeschi M, De Cesare A, Oriana S, et al. The role of glutathione in combination with cisplatin in the treatment of ovarian cancer. Cancer Treat Rev 1991;18:253-9 [review].
15. Smyth JF, Bowman A, Perren T, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: Results of a double-blind, randomised trial. Ann Oncol 1997;8:569-73.
16. Colombo N, Bini S, Miceli D, et al. Weekly cisplatin ± glutathione in relapsed ovarian carcinoma. Int J Gynecol Cancer 1995;5:81-6.
17. Cascinu S, Cordella L, Del Ferro E, et al. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. J Clin Oncol 1995;13:26-32.
18. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688-92.
19. Osterlund P, Ruotsalainen T, Korpela R, et al. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study. Br J Cancer 2007;97:1028-34.
20. Hu Y-J, Chen Y, Zhang Y-Q, et al. The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace Elem Res 1997;56:331-41.
21. Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol 2004;93:320-7.
22. Borghardt J, Rosien B, Gortelmeyer R, et al. Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients. Arzneimittelforschung 2000;50:178-84.
23. Bar-Sela G, Tsalic M, Fried G, Goldberg H. Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer patients: a pilot study. Nutr Cancer 2007;58:43-8.
24. Mills EE. The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis. Br J Cancer 1988;57:416-7.
25. Wadleigh RG, Redman RS, Graham ML, et al. Vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med 1992;92:481-4.
26. Lopez I, Goudou C, Ribrag V, et al. Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents. Ann Med Intern[Paris] 1994;145:405-8.
27. Lopez I, Goudou C, Ribrag V, et al. Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents. Ann Med Intern[Paris] 1994;145:405-8.
28. Legha SS, Wang YM, Mackay B, et al. Clinical and pharmacologic investigation of the effects of alpha-tocopherol on Adriamycin cardiotoxicity. Ann NY Acad Sci 1982;393:411-8.
29. Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol2003;21:927-31.
30. Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology2005;64:26-31.
31. Carl W, Emrich LS. Management of oral mucositis during local radiation and systemic chemotherapy: A study of 98 patients. J Prosthet Dent 1991;66:361-9.
32. Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger) used to prevent 8-Mop associated nausea. Dermatol Nurs 1995;7:242-4.
33. Pace JC. Oral ingestion of encapsulated ginger and reported self care actions for the relief of chemotherapy-associated nausea and vomiting. Dissertation Abstr Int 1987;8:3297.
34. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: A double-blind randomized study Nutr 1997;13:748-51.
35. van Zaanen HCT, van der Lelie H, Timmer JG, et al. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994;74:2879-84.
36. Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am J Surg 1996;172:418-24.
37. Souba WW. Glutamine and cancer. Ann Surg 1993;218:715-28 [review].
38. Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 1996;127:223-8.
39. Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-9.
40. Okuno SH, Woodhouse CO, Loprinzi CL, et al. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. Am J Clin Oncol 1999;22:258-61.
41. Cockerham MB, Weinberger BB, Lerchie SB. Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 2000;34:300-3.
42. Muscaritoli M, Micozzi A, Conversano L, et al. Oral glutamine in the prevention of chemotherapy-induced gastrointestinal toxicity Eur J Cancer 1997;33:319-20.
43. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: A double-blind randomized study Nutr 1997;13:748-51.
44. van Zaanen HCT, van der Lelie H, Timmer JG, et al. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994;74:2879-84.
45. MacBurney M, Young LS, Ziegler TR, Wilmore DW. A cost-evaluation of Glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994;94:1263-6.
46. Holoya PY, Duelge J, Hansen RM, et al. Prophylaxis of ifosfamide toxicity with oral acetylcysteine. Sem Oncol 1983;10(suppl 1):66-71.
47. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine's preventing ifosfamide-induced hematuria. Sem Oncol 1983;10(suppl 1):62-5.
48. Loehrer PJ, Williams SD, Einhorn LH. N-Acetylcysteine and ifosfamide in the treatment of unresectable pancreatic adenocarcinoma and refractory testicular cancer. Sem Oncol 1983;10(suppl 1):72-5.
49. Morgan LR, Donley PJ, Harrison EF. The control of ifosfamide induced hematuria with N-acetylcysteine. Proc Am Assoc Cancer Res 1981;22:190.
50. De Blasio F, et al. N-acetyl cysteine (NAC) in preventing nausea and vomiting induced by chemotherapy in patients suffering from inoperable non small cell lung cancer (NSCLC). Chest 1996;110(4, Suppl):103S.
51. Witenberg B, Kalir HH, Raviv Z, et al. Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem Pharmacol 1999;57:823-32.
52. Sacks PG, Harris D, Chou T-C. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents. Int J Cancer 1995;61:409-15.
53. Taper HS et al. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575-9.
54. Kurbacher CM, Wagner U, Kolster B, et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Letters 1996:103-19.
55. Wagdi P, Fluri M, Aeschbacher B, et al. Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease. Jpn Heart J 1996;37:353-9.
56. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Rev 1997;23:209-40 [review].
57. Henkin RI. Prevention and treatment of hypogeusia due to head and neck irradiation. JAMA 1972;220:870-1.
58. Mossman KL, Henkin RI. Radiation-induced changes in taste acuity in cancer patients. Int J Radiat Oncol Biol Phys 1978;4:663-70.
59. Ripamonti C, Zecca E, Brunelli C, et al. A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer 1998;82:1938-45.
60. Scambia G, De Vincenzo R, Ranelletti FO, et al. Antiproliferative effect of silybin on gynaecological malignancies: Synergism with cisplatin and doxorubicin. Eur J Cancer 1996;32A:877-82.
61. Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant 1996;11:55-62.
62. Invernizzi R, Bernuzzi S, Ciani D, Ascari E. Silymarine during maintenance therapy of acute promyelocytic leukemia. Haemotologia 1993;78:340-1.
63. Toi M, Hattori T, Akagi M, et al. Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. Cancer 1992;70:2475-83.
64. Iino Y, Yokoe T, Maemura M, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995;15:2907-12.
65. Mitomi T, Tsuchiya S, Iijima N, et al. Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa). Dis Colon Rectum 1992;35:123-30.
66. Cohen MH, Chretien PB, Ihde DC, et al. Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer. JAMA 1979;241:1813-5.
67. Macchiarini P, Danesi R, Del Tacca M, Angeletti CA. Effects of thymostimulin on chemotherapy-induced toxicity and long-term survival in small cell lung cancer patients. Anticancer Res 1989;9:193-6.
68. Shoham J, Theodor E, Brenner HJ, et al. Enhancement of the immune system of chemotherapy-treated cancer patients by simultaneous treatment with thymic extract, TP-1. Cancer Immunol Immunother 1980;9:173-80.
69. Israel L, Hajji O, Grefft-Alami A, et al. Augmentation par la vitamine A des effets de la chimiotherapie dans les cancers du sein metastases apres la menopause. Ann Med Interne 1985;136:551-4.
70. Kupin VJ. Eleutherococcus and Other Biologically Active Modifiers in Oncology. Moscow: Medexport, 1984, 21.
71. Kupin VI, Polevaya YB, Sorokin AM. Eleutherococcus extract treatment for immunostimulation in cancer patients. Vopr Onkol 1986;32:21-6 [in Russian].
72. Dreizen S, McCredie KB, Keating MJ, Andersson BS. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med 1990;87(1):163-70.
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|Topic Review (Newest First)
|I had a dog that wouldn't sit for treat. Not for anything. a tennis ball though? Oh yeah. He didn't want to run after it, he didn't want to chew it. He was wanted to hold it in his mouth for a second. So our training was I would give him the ball, then a series of commands. If he failed the commands i would withdraw the ball hold it for a few minutes and then return it and start over. This is actually punishment training. For him, the most effective training. No beating, no strangling, no screaming. Ball goes away, ball comes back. However I am learning that Jager, my GSD puppy, Is HIGHLY food motivated and have had to cope with that.
Terminology always messes me up but these are a couple of articles that seem relevant to me on the topic.
The Jerry Bradshaw article was published in Police K9 Magazine and is a pdf document:
And Deb Palmon, also a PDF on the USPCA Site:
Totally agree with you, but
If done properly and tactfully, even with skitish super soft dogs, it is possible to use nothing but "compulsion" training and come out on the other side with a very happy peppy sporty looking dog. We are talking no food no toys no play just emotions and compulsion. Escaping pressure is in itself a reward.
But it is as much of an art form as the extremely good force free trainers. You don't just jump into it willy nilly after reading something on the internet.
Have I done it? Yes. Do I typically do it? No. I prefer to sweeten the deal with food or play.
Sticking my hand in too many training discussions lately, so here goes another one.
If you're used to training GSDs and mainly WL GSD or anything with some sort of resilience and hardness, it's interesting when you start working other breeds. It's almost scary. A "correction" that I think is light for my GSD, can shut down some other dog/breed like you've never seen. That's what most people don't like to see.
So…if you start with compulsion, it will work, but it can have the ability to work by shutting the dog completely down, making it "obedient" but turning off everything about it that makes it a dog. The dog ends up not wanting to make any kind of decision due to fear of a correction. But…if you start a dog on PO, you tend to get a happier dog, and then if you realize you need a correction, you have a way of testing it or hopefully by that point you understand the dog more and know if the dog can handle that or not.
I see way too many people starting off with crank and yank because its worked for decades…and they've seen results but their results aren't impressive.
Sorry…I'm coming from the AKC world and entering the IPO world so the type of obedience I see is different. And on top of that, when I compare what I see many people consider "obedient pets" it's very disheartening sometimes.
Yeah, I think the word 'punish' brings a lot of negative associations with it for a lot of people. They assume it means hitting or roughly handling the animal, which is of course, not true for the most part.
Like I said, it's all semantics really.
I also wonder if positive only training would possibly create some stress for the dog. I think sometimes telling them 'no, that's not right' makes things more black and white for them, rather than leave them searching for the right answer.
Right. When I use the term punishment isn't the typical loaded use of the word in the sense of something necessarily super harsh. It's in the scientific use of the word punishment which is by definition any stimulus which when applied following an action decreases the probability of future appearance of that action.
That might be a brow furrow it might be a ah ah it might be a nope or it could be a time out or maybe something considerably stronger than that. If it's doing the job of weakening a behavior it is punishment.
When you train there should be a goal in sight that you're working towards, so every action counts. Good things get immediate rewards and bad things get immediate corrections (mine mostly is a simple calm verbal "ah!" to let them know to stop and try again).
It's a lot easier on both trainer and dog if you have a marker. Think about it this way, we're limited in communication so here's a basic rule - do this and you get a positive and do that and you get a negative. Just like the game 'hot and cold' and the more clues (markers) you give to show the right way the easier and faster the reward comes! The jackpot (correct behaviour) at the end is the reward for both parties
When people use the term punishment I think most jump immediately to physical corrections and pain. Thoughts of a screaming human beating the crap out of the dog because it disobeyed the sit command, for 95% of trainers that assumption is completely false
Foster dogs and rescues are usually screened. The dogs that needed it were already given the needle or are labelled unadoptable and slated for it.
Body blocks raised voices and all that jazz are positive punishment enough for a lot of dogs. Then there are the dogs out there that don't give a crap. When all the force free stuff doesn't work they start wondering if the dog needs to be heavily medicated. Then you hear oh the dog isn't wired right put it down.
Done right positive punishment doesn't need to be applied that often. I don't punish my dog all day. It happens very rarely which is a wonder considering what gets asked of him.
I think positive reinforcement is great for teaching a new command, shaping behaviours, for puppies etc but it has to be balanced. At some point, when the dog knows better and chooses to ignore you, you need to correct it (I don't like using the word punish, training shouldn't be about punishing, but it's all semantics, I suppose).
Leerburg | The Problem with All-Positive Dog Training
Originally Posted by JeanKBBMMMAAN View Post
Here's a neat article:
How Technology from 30 Years Ago is Helping Military Dogs Perform Better Now | Animal Behavior and Medicine Blog | Dr. Sophia Yin, DVM, MS
They do use aversives - but less than 1/1000th of a time.
Strangely (never thought it was strange until I read how many dogs my kind of methods have killed apparently) I have/had dogs who would be dead and have not used positive punishment with them in terms of any aversives stronger than a verbal, or as in the article above if they put themselves or someone else at risk (rare and usually just dog to dog posturing that needs to be body bumped - something that happens when you live with more than 2 dogs integrated as a pack). So it can be done, easily and naturally. I come from a background of working with people/kids, so using strong aversives is not an option, and it is second nature for me to pick behavioral interventions that are clear and that work. I know it works, I have a pack of dogs and former foster dogs that show it.
If people want to train dogs their way, that's their business, just getting tired of reading all over the place on this board that the way that many of the rest of train, is wrong, dangerous, and doesn't work.
Exactly! No one here trains dogs exactly like someone else. I just don't get why people are so brazen about voicing their unsolicited and unwanted opinions on other people's training?
Just like I personally would not want to send my dog off to a trainer to come back trained. But that is how one of my neighbors makes his living. I like his style of training. it works great. But i don't want to send my dog to him, however, the people that do are doing so because it lines up with their value map to have a professional train their dog so they don't accidentally train them incorrectly.
Some people just can't let others be different.
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subset: commoncrawl


text:
Hey, gang.
Well, the girlfriend wants to start her own little bounty hunting, and she loves the Boushh costume.
I'm wondering if anyone knows anyone who makes helmet/ armor/ costume, etc.
Please don't tell me to join that club that they have. Nobody EVER gets back to me on that. It's been a good 5 weeks, and nothing.
I've searched the web, and NOTHING.
Any direct help would be most appreciated.
Thanks my friends.


text:
Hello all!
I'm new here. I'm taking ceramics at the university to help with my sculpting and building. I saw Danger Russ's iron man helmet and it gave me inspiration to make one as well. I wanted to know if is it possible to make the mold out of white clay or terra cotta? I notice that many people use epoxy sculpt but I've never sculpted with that. I'm assuming that there is no difference because its a sculpt and a negative will be made of it with silicone.
Also a quick question on slush casting, smooth cast roto when poured into the mother mold and swished around, is my product is a smooth hollow cast of my negative (I'm sorry I am not using these terms correctly)? Is the strength of smooth cast roto the same as resin? Why do people use smooth cast roto instead of resin?
Thanks for your time to read questions of a newb!


text:
Smith & Wesson model 180 D
Do you have anti-gun Democratic friends who do not seem as 'joyous' as
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Maybe they're worried about their 'security' at home with the increasing
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realize now that the police can't be everywhere to protect them within
Well here's 'good news' for them. Smith & Wesson has just announced a
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The "SW18044L" ('L' signifies 'liberal').. You will note that this
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bears the Democratic "Donkey", & a large capital "D"!
Tell those 'friends' to be sure to get their orders in early, because they
will be in high demand!


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Most Awesome Way To Make Windows Unbootable
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Yesterday I wrote about the new Poor Law Records added to the Ancestry London Collection, I promised that I would report back having taken the time to look into them further. So here I am…..
The announcement by Ancestry said that the records now spanned more than 500 years and were everything from Workhouse Admissions to Registers of Servants. I did question why the poor law records would include a register of servants and I still do, but perhaps as I work through these records over the next few days I will find out. if so I'll let you know!
The first thing to note is that this collection is NOT indexed, you have to browse through them page by page as we used to in the "old days". We are all so used to having indexes that it comes as a surprise when confronted with a non-indexed set of records. However there are advantages to browsing because you get a feel for the records and how they were kept and there is always the chance that you might pick up something that the indexers didn't.
So what is in this collection
Admission and discharge books of workhouses
Registers of individuals in the infirmary
Creed registers
School registers
Registers of children boarded out or sent to various other institutions
Registers of apprentices
Registers of lunatics
Registers of servants
Registers of children
Registers of relief to wives and children
Registers of inmates
Registers of indoor poor
Registers of deserted children
Births & Deaths
Apprenticeship Papers
There are also quite a few groups of documents titled Miscellaneous, I would recommend that you always take a good look at these for the parish or poor law union where your ancestors lived. It's a bit like a raffle, but you never know what you might find. I think that most genealogists are optimists always hoping that some document or paper still exists that will solve all our family history riddles!!
If you are new to these sorts of records I suggest you visit Peter Higginbotham's website http://www.workhouses.org.uk/ which gives excellent background information on the poor law system and also has pages regarding individual workhouses.
The London Metropolitan Archives who hold the originals of the documents in this collection has a good guide to the collection which can be downloaded as a PDF file. http://www.cityoflondon.gov.uk/things-to-do/visiting-the-city/archives-and-city-history/london-metropolitan-archives/Documents/visitor-information/04-poor-law-records-in-london-and-elsewhere.pdf
Almost everyone is going to have an ancestor who has lived in London at some stage in their lives, this collection is a must if you think those individuals may have fallen on hard times whilst there. Take you time, locate which borough or poor law union area your family lived in and then browse and see what you can find.


text:
just in case we have a batman collector here, do not buy from this auction:
Batman TDK UD Suit Costume Cowl Dark Knight Rises Full Costume Suit Boots | eBay
this guys sold me a hells kitchen suit over the rpf.com forums
after sending payment via paypal he sent me a letter envelope. I refuse package and got my money back. his name is Jesse.. a "female" and uses 2 addresses from CA and NY email email@example.com, support@unchartedthreads and firstname.lastname@example.com among others.
if this is not the place to do this sorry please move or delete.
this is the same person on other forums using the same cute batman pics of her smoking that she posted over the rpf.com:
is the same picture she placed on this forums on her sales thread..batman cowl
and smoking, same address
this is a scam report on those forums:
and paypal limited members:


text:
The genetic system does not consist of DNA alone. Enzymes must read the DNA code; mRNA will be produced from that reading. The mRNA will take that code to ribosomes and bond to them for production. Carrier RNA will transport the amino acids to be used in production to the ribosome. And countless other highly complex enzymes that will permit intermediate processes to be carried out must all be present.
In addition, such an environment can only be one like the cell, in which all the raw materials and energy sources are present, and which is completely isolated and controlled. (See DNA, Ribosomes;RNA World Thesis, the.)2009-08-15 13:20:32


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text:
Ed FitzGerald pushes voting rights legislation
(Cleveland) - Cuyahoga County Executive Ed FitzGerald formally submitted voting rights legislation to the County Council during this afternoon's meeting.
FitzGerald tells Newsradio WTAM 1100, "The right to vote is a cornerstone of our democratic system of government, and it is critical that we ensure all Cuyahoga County citizens have an equal opportunity to exercise this right on Election Day."
FitzGerald is very disappointed with a bill signed by Governor John Kasich which he contends will make it more difficult to vote, and will create long lines at Cuyahoga County polling places.
He says the legislation he submitted to the County Council will ensure that Cuyahoga County will have proper ballot access, by allowing the Board of Elections to send out its own unsolicited absentee ballots, through the home rule process.
FitzGerald's proposal follows a series of recent actions at the state level to curtail early, absentee, and provisional voting - efforts that may disproportionately affect working families.
The Cuyahoga County Voting Rights Law is co-sponsored by Councilwoman Sunny Simon.
(Photo by Ken Robinson/WTAM)
Get breaking news sent to your mobile phone. Text "news" to 21095.
(Copyright © 2014 by Clear Channel, all rights reserved.)


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Results 1 to 2 of 2
Threaded View
OBYs thugs go after Gallup on polls they don't like
Like the poll where Gallup had Romney up by 5 points.
So there's supposed to be an alleged whistleblower somewhere alleging
that Gallup over-charged the gov't on polling work so Alexrod, OBYs campaign manager got the Justice Dept to join the alleged whistleblower in a law suit vs Gallup.
This is a scene right out of the Communist Manefesto to be sure as
employees at the venerable Gallup polling firm suggested they felt threatened by Obama campaign adviser David Axelrod when he questioned the methodology of a mid-April poll showing Mitt Romney leading the president – according to internal emails published Thursday."
Guess there won't be any more negative polls on OBY from Gallup. OBYs stealing this election like Kennedy stole the 1960 election from Nixon with
all those dead people voting in Chicago. It's always something new with
the DEMs. One thing for sure, they sure are desperate.
Our country is being stolen from under our noses.
Last edited by AirFlacco; 09-10-2012 at 05:33 PM.


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text:
Moderator: Skyblaster7
tenfingergrip wrote:Here's an idea if you want to try it. It's something I made several years ago to be able to use my floaters for field decoys. It's simple and it works. I simply bent a heavy steel wire ( about 9 gauge, the wire that is used to hold political signs) into a stand that the keel of the floater would slide into. The double bend at the top (I used a vise with a bolt tightened in it to bend the wire around) gave a support for the decoy to rest on and the bend held the keel tight. (You can squeeze the bends tighter with your hand to adjust the tightness) I even went to the extreme and slid a couple of pieces of orange pneumatic hose, that I drilled a hole thru, up and over the wire and up to the support platform to resemble mallard legs. (The legs of the stand are vertical and the double bends are horizontal to the ground)
There are several postings on floater to field mallards on the forum, just seach for them.
Here's a couple of pics and the rest of the pictures are on photobucket:
Don't you want motion on your decoys instead of them just standing there?
Indaswamp wrote:jaysweet3 wrote:Looks a little small.
Dat's what She said....
Underradar wrote:We, the unsigned members of the HH, are not allowed to address such questions. But thank you for asking.
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Wayne Law Alumna Deborah LaBelle Reflects on 13-year Lawsuit, $100 Million Settlement
DETROIT (Aug. 18, 2009) – Thirteen years is a long time to devote to a lawsuit. Just ask Wayne State University Law School alumna Deborah LaBelle.
LaBelle, a long-time human rights attorney based out of Ann Arbor, Mich., filed Nunn v. Michigan Department of Corrections (MDOC) and Neal v. MDOC in 1996 after working on a class action lawsuit addressing the lack of comparable rehabilitative training and educational opportunities for women as opposed to male prisoners in Michigan's prison system. Both lawsuits related to wrongful treatment of women prisoners in Michigan.
"As I was working on the training and education class action, I noticed more women started to report abuse," said LaBelle. "They were very concerned that it was getting worse and younger girls were being targeted – girls as young as 14 are placed in the general women's prisons. We had started to get apprenticeships and educational classes in the prisons; however, the sexual abuse was interfering with the women's abilities to take part in these opportunities."
It was time to rally and take action. Something that, according to LaBelle, took time and a great deal of courage on behalf of those filing.
"It took a number of years for the women to come together and agree to support each other," LaBelle said. "They had to be willing to face the inevitable retaliation that would result in filing the litigation as they would still be imprisoned with the men charged with sexually assaulting them and under the authority of the administration that was charged with deliberate indifference to their safety."
Nunn v. MDOC was heard in Washtenaw County Circuit Court in 1997 and led to a signed settlement in 2000 by MDOC that stopped cross gender pat downs and removed male staff members from direct supervision of incarcerated women prisoners. Neal v. MDOC proved to be a much longer battle.
The class action lawsuit brought by 500 women prisoners who were sexually assaulted and/or raped by Michigan prison guards lasted until 2009. Though faced with a number of obstacles throughout the duration of the lawsuit, LaBelle and her team – Shannon Dunn, '98, Cary McGehee, Michael Pitt, '74, Peggy Goldberg Pitt, Molly Reno, '78, Ronald Reosti, Ralph Sirlin, Richard Soble and Patricia Streeter, '73 (WSU undergraduate degree) – maintained their focus and commitment to the case.
"Our challenges had to be kept in perspective in light of the ongoing abuse and retaliation that our clients were faced with on a daily basis," LaBelle said. "The hardest times were the stays that were granted by the appellate courts resulting in our inability to take any action to stop the ongoing abuse."
A $100 million settlement was reached with the state July 15, 2009, ending the 13-year-long legal battle. The Honorable Timothy P. Connors, '80, presided over the case.
A Detroit Free Press article that ran at that time quoted LaBelle as saying "This is a good deal for the state. The damage had gone on so long and the harm had occurred was so deep. If we tried all of these, the cost to the state would have been a billion dollars."
Today, she remains pleased that her team was able to make some significant positive changes in the culture of the women's prisons – not only in Michigan but nationally.
"Advocates in other states relied upon the rulings in this state to file litigation, change the staffing in other state prisons and to enact preventative protocols to address custodial sexual abuse," she said. "I am happy with the recognition of the depth of the violation of the basic human dignity of our clients and the fact that the juries understood that what was at stake. I am also happy that the state recognized the harm that was caused and that our clients will have the opportunity to obtain treatment to begin the healing process."
Thirteen years on a case can certainly impact one's career and life. Through this lawsuit, LaBelle has begun working with international human rights organizations and expanding the framework for challenging the violations of her clients' rights through the lens of domestic human rights violations.
"My clients and the opportunity to work with them and an amazing group of lawyers changed me as an attorney in such a broad and deep manner that I really can't detail it and probably haven't yet absorbed it," she said. "I would do it all again but am grateful I don't have to."
LaBelle maintains a private practice and currently serves as the director of the Juvenile Life Without Parole Initiative with the Michigan American Civil Liberties Union. She has authored a vast number of publications and spoken on a variety of issues related to gender and civil rights. Select honors include the Wade McCree Justice Award (2009), the National Lawyers Guild Lawyer for the People Award (2009) and the Public Interest Foundation Trial Lawyer of the Year Award (2008).
About Wayne Law
Wayne State University Law School has educated and served the Detroit metropolitan area since its inception as Detroit City Law School in 1927. Located at 471 West Palmer Street in Detroit's re-energized historic cultural center, the Law School remains committed to student success and features modern lecture and court facilities, multi-media and distance learning classrooms, a 250-seat auditorium, and the Arthur Neef Law Library, which houses one of the nation's 40 largest legal collections. Taught by an internationally recognized and expert faculty, Wayne Law students experience a high-quality legal education via a growing array of hands-on curricular offerings, client clinics, and access to well over 100 internships with local and non-profit entities each year. Its 11,000 living alumni, who work in every state of the nation and more than a dozen foreign countries, are experts in their disciplines and include leading members of the local, national and international legal communities. For more information, visit www.law.wayne.edu.


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Rounding out the FY 2014 Annual Data Collection training series offered by ESS Data Management, we are pleased to present webinars geared towards the Final Submission Process. Please see the dates and times offered below; registration is required. To register, click on the date you wish to attend.
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First time shooting in six months. Met a coworker at the Marksman in Puyallup. Last time was with another coworker at Bullseye in Tacoma. Awesome shop with knowledgeable and courteous staff. Being my first time there as a shooter, I had to take their orientation class. $10 one-time fee for it and it took about 10 minutes. Read and sign a form with the rules and legalities then sit in a classroom where the rules and consequences were explained. The staff demonstrated points with dummy weapons to provide a visual of the behavior and/or consequences resulting. A demonstration of the target mechanism was done and the class concluded with a question period. The rules are basic and clear as they should be.
Indoor facility with lines on the wall downrange at distances of 15, 25 and 35 feet. Run the target all the way back and itll be set at 50 feet. Lighting on the range is adequate at the benchmark distances. Better than at Bullseye in that it is consistent all the way down each lane but far from stellar. There is a platform at each position for your gun, mags, ammo and such. Each lane position is separated by plastic dividers rear of the line and a steel armor plate in front of the line. Still the occasional brass would find its way from one position to another, but no big deal. Ventilation was decent but far from great. Of course I am somewhat spoiled as I left this facility in Colorado Springs: https://www.whistlingpinesgunclub.com/index.asp
I started my warm up with my P220. It was smooth as ever and my shots grouped mostly within 6 inches at 25 feet with a few fliers. Next up my P226 and the experience was much like the P220. Groups were smaller (about 4 inches) as I am more comfortable with 9mm than .45.
Next up I (finally) deflowered my SP2022. Not a huge fan of the standard sights, but thatll get rectified with TFOs one day (hopefully soon). Trigger was smooth. Ive been practicing drills and dry firing with it since I got it in May. I like it, a lot. If there was a way to get one into my P228, my favorite would be as perfect as possible in this imperfect world. That said, it was VERY smooth even in DA. A near flawless performance for its first time out. The only problem encountered was minor, IMO. Loading 10 rounds into each mag, there were 2 instances where it only partially closed when returning it into battery. It closed about half way but a slight tap on the rear of the slide with the heel of my non grip hand and all was ready for action. Having read about that particular thing on the SiGForum, I wasnt and am not concerned. That is one part of the break in process I couldnt simulate at home with snap caps.
The next part of my session was spent on my P228. Being my primary carry (the SP will join the rotation for day use only until the TFOs get installed) and so not getting out to shoot as much as I would like, I spent the most time with it. Groups were good, IMO, for not having shot in six months. For my qualification target I went with 40 shots center mass and 10 head shots. We are our own worst critics, but Im still confident in my ability to place my shots.
While at the range, I shot my friends XD9SC. It was a bit small for my hands but shot well. I wouldnt buy one but cant say anything against it if it fits your hands. Also tried a rental P229SAS in .40 as well as a P250. Still not impressed by .40 as a caliber though the P229 has been the most comfortable thing Ive shot in this caliber. The P250 was okay. I wasnt thrilled with the trigger and action, but I was comparing it to my SP (as far as polymer frames go). Overall it was not a terrible experience, but I will not be adding it to my personal inventory.
I HAVE to find somewhere closer to shoot than the 50 minute drive to Puyallup. Sure it was more enjoyable shooting with a friend compared to punching holes alone. Still there has to something closer and if there isnt, there should be.


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Clinician Summary – Aug. 30, 2012
Venous Thromboembolism Prophylaxis in Orthopedic Surgery
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Table of Contents
- Research Focus for Clinicians
- Background
- Conclusions
- Clinical Bottom Line
- Summary of RECORD Trials Outcomes
- Gaps in Knowledge
- What To Discuss With Your Patients
- Resource for Patients
- Source
Research Focus for Clinicians
A systematic review of 179 articles published between January 1980 and May 2011 sought to determine the comparative effectiveness, benefits, and adverse effects of venous thromboembolism (VTE) prophylaxis for patients undergoing orthopedic surgery. The review did not cover the effectiveness of the oral direct factor Xa inhibitor, rivaroxaban. However, after the report was prepared, rivaroxaban was approved by the U.S. Food and Drug Administration (FDA). The comparative effectiveness of rivaroxaban versus enoxaparin from four large phase III trials are briefly reviewed in a separate section of this summary. This summary is provided to inform discussions of options with patients and to assist in decisionmaking that considers a patient's values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines. The full report is available at www.effectivehealthcare.ahrq.gov/thrombo.cfm.
Major orthopedic surgical procedures—total hip replacement (THR), total knee replacement (TKR), and hip fracture surgery—carry a high risk of VTE.
Strategies to prevent VTE include pharmacological and mechanical modalities, used alone or in combination. Pharmacological prophylaxis carries risks and limitations including bleeding.
The magnitude of benefit and adverse effects in contemporary practice in the United States among the orthopedic population are not well known. This summary highlights findings from the review including baseline risk for VTE with major orthopedic surgery, the comparative effectiveness of different pharmacological or mechanical modalities, how duration of prophylaxis affects outcomes, and evidence regarding combination pharmacological and mechanical prophylaxis.
The estimated native (i.e., without pharmacological prophylaxis) incidence of deep vein thrombosis (DVT) after THR and TKR was 39 percent and 46 percent, respectively. Pharmacological prophylaxis decreases the risk of DVT with some increased risk of minor bleeding when compared with no pharmacological prophylaxis. There is some evidence that low-molecular-weight heparin (LMWH) decreases risk for DVT when compared with warfarin at the expense of increases in major and minor bleeding. LMWH provides greater protection against DVT and pulmonary embolism (PE) when compared with unfractionated heparin (UFH) while reducing the risk of bleeding and heparin-induced thrombocytopenia.
In contrast, LMWH was not as effective in protecting against the risk of DVT when compared with an injectable factor Xa inhibitor, although the odds of bleeding were reduced. Prolonged prophylaxis decreased the risk of thromboembolism at the risk of increased minor bleeding when compared with standard-duration prophylaxis. No differences in mortality outcomes were observed for any of the interventions compared; however, this may be related to the infrequency of this outcome and length of followup.
After the review was completed, rivaroxaban, an oral factor Xa inhibitor, was approved by the FDA for this population of patients primarily based on the four Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) trials. Rivaroxaban decreased the risk of the composite primary outcome of DVT, nonfatal PE, or all-cause mortality in patients undergoing major orthopedic surgery. RECORD 1 and 2 showed superiority of prolonged prophylaxis with rivaroxaban versus enoxaparin (prolonged or standard-duration prophylaxis) with a decreased risk of the primary outcome in patients undergoing THR. RECORD 3 and 4 suggested that rivaroxaban decreases the risk of the primary outcome versus enoxaparin when used for prophylaxis for patients undergoing TKR. There were no significant differences in mortality or the risk for bleeding outcomes in all four trials.
Clinical Bottom Line
Baseline Incidence of VTE
Most of the literature evaluated THR and TKR surgery with very little evaluation of hip fracture surgery. The baseline risk of VTE and bleeding outcomes in the absence of pharmacological prophylaxis are as follows (THR percentage, TKR percentage):
- Pulmonary embolism (6%, 1%)
- Major bleeding (1% , 3% )
- Minor bleeding (5% , 5% )
Pharmacological Versus No Pharmacological Prophylaxis
Pharmacological prophylaxis:
- Decreased risk of proximal DVT or distal DVT ; DVT ; VTE ; and asymptomatic DVT .
- Increased risk for minor bleeding.
Comparative Effectiveness of Pharmacological Prophylaxis
LMWH, when compared with warfarin:
- Decreased risk of DVT and distal DVT .
- Increased risk for minor bleeding and increased the odds of surgical site bleeding and major bleeding .
LMWH, when compared with UFH:
- Decreased risk of proximal DVT and DVT , and decreased the odds of PE .
- Decreased the odds of major bleeding and heparin-induced thrombocytopenia .
UFH versus the direct thrombin inhibitor desirudin increased the risks for DVT and proximal DVT by 2-fold and more than 5-fold, respectively.
The LMWH enoxaparin, when compared with the factor Xa inhibitor fondaparinux, demonstrated:
- Increased risk of DVT and distal DVT , and increased odds of proximal DVT .
- Decreased odds of major and minor bleeding.
Standard Versus Prolonged Prophylaxis
- Decreased odds of PE , symptomatic DVT , and nonfatal PE , as well as decreased risk of asymptomatic DVT , proximal DVT , symptomatic, objectively confirmed VTE , and DVT .
- No increased odds of major bleeding , although the odds of minor bleeding did increase .
Pharmacological and Mechanical ProphylaxisWarfarin, when compared with mechanical prophylaxis, decreased the risk of proximal DVT by 66 percent.
Aspirin, when compared with mechanical prophylaxis, had a higher rate of DVT.
Pharmacological plus mechanical prophylaxis reduced the risk of DVT when compared with pharmacological prophylaxis alone.
Characteristics That May Affect Risk of VTEPatients who receive general anesthesia may have a higher risk of DVT than those who receive regional anesthesia.
No difference in risk of DVT or proximal DVT was found among patients receiving cemented versus noncemented arthroplasty.
Observational data suggest that patients with congestive heart failure were at an increased risk for symptomatic, objectively confirmed VTE when compared with those without it.
Strength of Evidence Scale
There is high confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect.
Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of effect and may change the estimate.
Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of effect and is likely to change the estimate.
Evidence either is unavailable or does not permit estimation of an effect.
|Magnitude of Effect; Risk/Odds (95% CI), NNT/NNH, SOE
|Proximal DVT
|Symptomatic VTE
|Major Bleeding
|Minor Bleeding
|95% CI = 95-percent confidence interval; DVT = deep vein thrombosis; LMWH = low-molecular-weight heparin; major bleeding (e.g., bleeding leading to greater transfusion requirements and/or reoperation); minor bleeding (e.g., surgical site bleeding, bleeding leading to infection, or bleeding leading to transfusion but not reoperation); NNH = number needed to harm (the calculated range); NNT = number needed to treat (the calculated range); NR = not reported or insufficient evidence to permit conclusions; OR = odds ratio; PE = pulmonary embolism; SOE = strength of evidence rating; THR = total hip replacement surgery; TKR = total knee replacement surgery; UFH = unfractionated heparin; VTE = venous thromboembolism
|Pharmacological prophylaxis vs. no prophylaxis
|Decreased risk by 44%; RR 0.56 (0.47 to 0.68), NNT 3 to 33
|Decreased risk by 47%; RR 0.53 (0.39 to 0.74), NNT 4 to 213
|No difference; OR 0.38 (0.13 to 1.07)
|No difference; RR 0.74 (0.36 to 1.51)
|Relative risk is higher for prophylaxis by 67%; RR 1.67 (1.18 to 2.38), NNH 30 to 75
|LMWH vs. UFH
|Decreased risk by 20%; RR 0.80 (0.65 to 0.99), NNT 12 to 100
|Decreased risk by 40%; RR 0.60 (0.38 to 0.93), NNT 14 to 50
|Decreased odds by 52%; OR 0.48 (0.24 to 0.95), NNT 8
|Decreased odds by 35%; OR 0.57 (0.37 to 0.88), NNT 41
|No difference; RR 0.90 (0.63 to 1.28)
|Enoxaparin vs. fondaparinux
|Relative risk is higher for enoxaparin by 99%; RR 1.99 (1.57 to 2.51), NNH 13 to 26
|Odds are higher for enoxaparin by 219%; OR 2.19 (1.52 to 3.16), NNH 44 to 122
|No difference; OR 0.70 (0.48 to 1.02)
|No difference; OR 3.34 (0.58 to 19.32)
(SOE not rated)
|Decreased odds by 35%; OR 0.65 (0.48 to 0.89), NNT 74 to 145
|Decreased odds by 43%; OR 0.57 (0.35 to 0.94), NNT 31 to 60
|LMWH vs. warfarin
|Decreased risk by 34%; RR 0.66 (0.55 to 0.79), NNT 6 to 13
|No difference; RR 0.63 (0.39 to 1.00)
|No difference; OR 1.00 (0.69 to 1.46)
|No difference; OR 1.11 (0.57 to 2.19)
|Odds are higher for LMWH by 92%; OR 1.92 (1.27 to 2.91), NNH 57 to 220
|Relative risk is higher for LMWH by 23%; RR 1.23 (1.06 to 1.43), NNH 18 to 218
|UFH vs. desirudin
|Relative risk is higher for UFH by 231%; RR 2.31 (1.34 to 4.00), NNH 5 to 11
|Odds are higher for UFH by 477%; OR 4.74 (2.99 to 7.49), NNH 11
|No difference; OR 3.23 (0.56 to 18.98)
|Prolonged vs. standard-duration prophylaxis
|Decreased risk by 63%; RR 0.37 (0.21 to 0.64), NNT 5 to 32
|Decreased risk by 71%; RR 0.29 (0.16 to 0.52), NNT 9 to 71
|Decreased risk by 62%; RR 0.38 (0.19 to 0.77), NNT 8 to 54
|Decreased odds by 87%; OR 0.13 (0.04 to 0.47), NNT 24 to 232
|No difference; OR 2.18 (0.73 to 6.51)
|Odds are higher for prolonged prophylaxis by 244%; OR 2.44 (1.41 to 4.20), NNH 11 to 118
|Pharmacological + mechanical vs. pharmacological only
|Decreased risk by 52%; RR 0.48 (0.32 to 0.72), NNT 3 to 67
|No difference; RR 0.33 (0.09 to 1.22)
|No difference; OR 1.03 (0.14 to 7.34)
Summary of RECORD Trials Outcomes
- After the comparative effectiveness review was prepared, an oral direct factor Xa inhibitor, rivaroxaban, was approved by the FDA for preventing DVT, which may be associated with PE, in patients undergoing knee- or hip-replacement surgery. This decision was based, in part, on the findings of four phase III trials known as the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) trials. The RECORD program investigated various regimens of rivaroxaban for preventing VTE after THR (RECORD 1 and 2) or TKR (RECORD 3 and 4) when compared with enoxaparin.
- The RECORD 1 and 2 trials demonstrated a consistent reduction in the risk of the composite primary outcome of DVT, nonfatal PE, or all-cause mortality with prolonged rivaroxaban (started 6–8 hours postoperatively, for 35 ± 4 days) when compared with enoxaparin given as either prolonged (started the evening before surgery, for 36 ± 4 days) or standard-duration (started the evening before surgery, for 13 ± 2 days) prophylaxis.
- The RECORD 3 and 4 trials suggested that rivaroxaban decreased the risk of the composite primary outcome of DVT, nonfatal PE, or all-cause mortality when compared with enoxaparin in patients who had TKR.
- In all four trials, there were no significant differences in the risk for the primary safety outcome of major bleeding as well as minor bleeding or mortality.
Gaps in Knowledge
- Inadequate data did not permit conclusions about the comparative benefits and adverse effects associated with VTE prophylaxis in non–joint-replacement surgery.
- More information is needed on the following aspects of VTE prophylaxis in the setting of major orthopedic surgery:
- Clinically important outcomes including symptomatic VTE, post-thrombotic syndrome, clinically relevant bleeding, prosthetic infection, reoperation, and mortality and whether intermediate outcomes predict health outcomes
- Surgical, postsurgical, or patient factors that predict outcomes
- The optimal followup period needed to determine longer term outcomes
- Optimal duration of thromboprophylaxis
- The role of combined pharmacological and mechanical prophylaxis
What To Discuss With Your Patients
- General background information on the risk of thromboembolic disease
- That thromboembolic disease is a major risk after joint-replacement surgery and why some form of prophylactic treatment is indicated
- Options for prophylaxis
- Bleeding as the major risk of pharmacological prophylaxis
Resource for Patients
Preventing Blood Clots After Hip or Knee Replacement Surgery or Surgery for a Broken Hip, A Review of the Research for Adults is a free companion to this clinician research summary. It can help patients talk with their health care professionals about the many options for treatment. It provides information about:
- Pharmacological options for preventing VTE
- Nonpharmacological options for preventing VTE
- Current evidence of the effectiveness and harms associated with VTE-prevention methods
- Questions for patients to ask their doctor
The information in this summary is based on Venous Thromboembolism Prophylaxis in Orthopedic Surgery, Comparative Effectiveness Review No. 49, prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center under Contract No. 290-2007-10067-I for the Agency for Healthcare Research and Quality, March 2012. Available at www.effectivehealthcare.ahrq.gov/thrombo.cfm.
This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX. It was written by Kim Farina, Ph.D., Andrea Humphries, Ph.D., Thomas Workman, Ph.D., Melvyn Harrington, Jr, M.D., and Michael Fordis, M.D


text:
Circa 1900
A large and muscular Louis XVI style carved wood chandelier in its original gilded finish.
Current height: 238 cm
Minimum height: 142 cm
Overall: 123 cm diameter
Height to loop: 128 cm
CE wiring available, contact sales for a quote.
CE Lamping: 6 SES/E14 sockets, maximum 60 watts per socket.
1 fixture total available. 1 on hold.
On display at our 28th Street showroom.


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|Topic Review (Newest First)
You can buy rolls of 3" wide stick-it sandpaper in grits from 50-400 that will fit your 24" sanding block. Just tear off the amount you need and stick it to the block. Carborundum gets my vote for quality and price, 3M, Mirka, and Norton are also options.
If your epoxied parts set over the summer just sand it some and apply a fresh coat when you start on the project again.
Thanks Barry,
I do understand your technique. Just recently I read a post or two where someone had sprayed their car with epoxy and the car sat a long while before they got back to it. Person had wondered if they could just scuff and shoot their primer/filler and was told no, that the epoxy had to have been covered within a day or two or else another epoxy coat had to be sprayed.
I'm not planning on leaving the car sit for ages after I strip and epoxy, just that I'm not sure how long I'll have to get it done. Could very well become an epoxy and sit till the fall season project.
Oh well, thanks to all again. Really admire the hard work you people put in and the results you share with the rest of us.
On a different topic, hope you don't mind. I bought a few Durablock sanding blocks at a swapmeet this past weekend. One of the blocks is a pretty decent length, like 24". What paper can I/should I use on this and where can I buy it?
Not sure of the question.
After sandblasting I epoxy, the whole car, two coats.
Then say the next night I'm doing the quarter after all body work is done I spray a coat of epoxy and it stays like that until the whole car is ready for 2K primer.
I scuff the epoxy with 180 by hand and apply the primer, block and re-prime as many times as necessary.
When done with primer I do spray another coat of epoxy as my final sealer coat before basing.
Perhaps overkill but that is how I do it and I hope I clarified for your question?
Barry, as you said above, 2 weeks later, you've got the whole body done and sealed with epoxy, ready for primer....wouldn't you have to spray epoxy again before the primer? That's what I've read and it confuses me that I couldn't just scuff and prime.
Being new to this I too thought it was overwhelming. But like the guys said just take on one section, door, fender at a time and see it thru completion. You will be amazed at how fast it goes if you are diligent in staying on your project. Good luck and let us know how it goes. (One of my fenders had 9 rust out places I had to make patch panels for..but it is so much fun and fulfilling.)
Lots of good advice given.
Even though I travel a lot if your efficient and organized you can still do a complete frame off in a years time.
The biggest thing is do one thing at a time so you don't get overwhelmed.
When the body work starts I will work on the one panel that night until i have that panel in epoxy over any filler.
Where people make a mistake is running to his fender to fix something and back to this door etc. Next thing you know in the four hours of work that night you have nothing done.
The next night I will do a door until done.
If you think about it in a two week period with 2-4 hours a night you can have the whole body done and sealed with epoxy and ready for primmer.
Only time I work on multiple panels is when painting the undersides and I will do the doors, hood, deck lid all at once so can paint at the same time.
After visiting the Good Guys event in Del Mar, CA back in early April I decided that I would spruce up my '29 Highboy for my 'local' Good Guys event in Jacksonville at the end of May thinking I had tons of time! This included rebuilding/painting the front, rewiring the car and rebuilding the engine. All of this was done in my home garage completely solo.
After stripping the front end to the bare rails and removing the firewall, floor and drivetrain I realized the job was bigger than I had ever imagined.
So, I focused on completely finishing one thing at a time; rails, engine, trans, wiring, floor, firewall etc.
It is 90% back together and I am on track for the show in 3 weeks but there were times when I thought I would never do it.
Considering I ONLY attacked the front of the car I can't believe how much work it was. Now that it will be back on the road soon I will do the rest of the bodywork one panel at a time once the temperature drops again in the winter.
I am VERY glad I did it but and I learnt a hell of a lot doing it.
I know what I did is not the pure bodywork project you are undertaking but the effort required just even to get the firewall to the condition you see was incredible. The masking for the checkerboard pattern alone took almost 2 hours! I have a new understanding as to why bodyshops charge what they do for GOOD work!
I think you need to estimate how long it takes, double it and then ensure you have a TON of patience to do it right and not rush it. There can be a temption, at least with me, to say "oh, that should be fine" knowing there are still blemishes that will show once it is finished. Self discipline in making sure each step was completed prior to moving on was critical to the final finish.
I am a complete beginner who never held a spray gun until 3 weeks ago and I am pretty pleased with the outcome. The main things that I see that impacted the final outcome are:
- use the right tools. if you don't have them borrow/buy them
- use the right grit! really important
- the old credo of 90% prep, 10% paint application is right.
- follow the tech sheets for paint, the only time I had a problem and had to redo a part was when I rushed the times
- you need a spotless envrionment which to be fair I didnt have but I was pretty lucky.
- patience, patience, patience!!! getting a good finish takes a long time!
- Dont panic. even if you get a seemingly bad finish (orange peel etc) it can usually be rectified, get input from others who know.
- Use the internet: forums like this provided me with TONS of info from people who know, I also used it to research paint specs/flash times etc.
Good luck and let us see your results!
The 'marks' you see on the firewall below are reflections from the engine. The finish is pretty much flawless thanks to the guys on this forum and at autobody101.com
|Centerline said a lot of what I would of and all the guys gave you some good advice. It can seem overwhelming. When I worked on my bonny and a mustang for someone else, I was laid off from work at the time, but even still, it was very time consuming and a lot of work to get done. There are always commitments that take you away from getting work done. I pretty much work a panel or two at a time. I like to get all the bodywork on the outside done and primed and blocked and to the point of just needing a final sand before paint, then I work on prepping the jambs, and try to shoot all the parts off together if possible, but I don't really see a problem if you do only one at a time. But if there is any amount of work that has to be done inside doors or jambs, then I do that as I am working my way around the car. To do a good job, you will probably need to remove those parts to prep and paint. I like to remove the door hinges and parts like that, and sandblast them and epoxy seal and paint. Much easier to do that then trying to sand some parts. It really isn't all that much work to scuff up the epoxy primer. Much easier then if parts sitting in baremetal start rusting, and will give you the opportunity to concentrate on one area at a time and perfect it before moving on. Most basecoats have a fairly long time window. So a lot of times I will get the car all in basecoat and covered. Since I usually wetsand the base with around 1000-1500 to smooth a little an denib I'll do that after its set an hour or so, or the next day. Then I only have to spray on a coat or two of base and a few coats of clear that day. Just set a weekend aside when you get to the point of paint, or take a vacation day and make it a longer weekend so you can take your time getting it in paint. Things normally go better if you take your time and don't rush the painting and allow enough flash time. I was rushing to get a hood painted after work and had nothing but problems. When I walked away for a day, and came back and took my time, things worked out. Would have ended up being done a lot quicker if I would have not rushed the first time.
Thanks for the replies.
One of my biggest concerns, too, has to do with how I'd manage to paint the underside of the hood and the doorjams. I'd really like all surfaces to be covered and can't see how that would be done with the doors and hood attached. The front part of the door, inside where the hinge is, seems it would be particularly difficult.
At any rate, thanks again. You've given good advice. Now to figure out which fork do I use for the elephant and which is for the salad?
Definately do the project in stages. Work a few panels at a time to keep it managable. Trying to work everywhere around the car at one time will just lead to major stress and sloppy work. There's no time limit when you're after good results. Work a few panels at a time and get them to the first stage of primer surfacer then set them aside and work on two other panels. Keep rotating your focus on the parts untill they are in the final stage of primer, then final sand and paint. Yes, it takes days and days- lots of days to do the job right. My last complete inside and out top to bottom body restoration took over 400 hours.
When all the parts are final sanded and ready for paint your plan has finally come together and the light can be seen at the end of the tunnel. Be persistant and progress will show.
It is very time consuming, just look how long I have been working on my project . A guy once told me how to attack a project when it is at the point of overwhelming you.. He said "how do you eat an elephant?" I said WHAT? He said one bite at a time. Made sense to me.
Strip the car and then spray epoxy. Take your time doing the bondo and any other repair work and if you need to spray epoxy over some areas that have been worked again all you have to do is scuff the epoxy first. After you spray the primer/filler do all your sanding and get it straight. Then you can spray your top coat. You should have no problems with the time between the primer filler and top coats since you'll sand the primer/filler anyway. The only time problem you might run into would be if you were using a sealer over the primer. There usually is a time limit to spray the top coat if a sealer is used. If that time limit is exceeded you will normally have to scuff the sealer before top coating.
When all else fails check the "P" (product sheets) for all the info you'll need.
HOW do you guys do it?
I'm trying to get my plan together, to do a complete paint, including trunk, undersides of hood and decklid, doorjams, etc... and all this after doing repair of a number of rustouts and dings and dents.
With time restrictions/painting windows for when to spray epoxy followed by primer/filler, sealer, base coat and clear...........it's mind boggling to me an individual can get it all done per spec sheets and proper applications/methods!
Seems you'd have to be unemployed or take vacation to have a chance and let's not forget all the other things going on in one's life.
Can anyone give me a clue how to get 'er done?
getting areas on my car done, a little at a time, strip and epoxy, work around the car, then have to respray epoxy again, then primer/filler, work out defects, take days and days to get it straight, wouldn't the time be gone to properly spray the base? having 2K over the epoxy, how long would I have before shooting or is the time unlimited if I scuff the 2K later?
Sorry for being so long winded and obviously confused.
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text: iOS 4 brings many improvements to the Mail app for iPhone and iPod touch. The main enhancements include unified inbox, organize messages by threads, open attachments in third-party apps and more. If you use Gmail account on your device then you might have noticed that after iOS 4 upgrade when you try to swipe to delete an email when accessing … Read More


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'Sabres spokesman Mike Gilbert says there are only 15,000 tickets still unsold for the season and some of those are on hold for sponsors, visiting teams, and players. The remaining tickets are primarily single seats and for late season games.'
Sabres Games Selling Out
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