Palifermin for oral mucositis after intensive therapy for hematologic cancers

BACKGROUND: Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. METHODS: This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 microg per kilogram of body weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation. RESULTS: The incidence of oral mucositis of World Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P\u3c0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless of the occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P\u3c0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P\u3c0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P\u3c0.001), the use of opioid analgesics (median, 212 mg of morphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P\u3c0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P\u3c0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient. CONCLUSIONS: Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers

Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers

BACKGROUND Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability ofpalifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. METHODS This double-blind study compared the effect ofpalifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 μg per kilogram ofbody weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation. RESULTS The incidence oforal mucositis of World Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P<0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless ofthe occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P<0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P<0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P<0.001), the use ofopioid analgesics (median, 212 mg ofmorphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P<0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P<0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient CONCLUSIONS Palifermin reduced the duration and severity oforal mucositis after intensive chemotherapy and radiotherapy for hematologic cancers

Progressive Drug Policies and the Impacts of Supply-Side Control

For over a century the international community has widely accepted a policy of universal drug prohibition. However, an increasing number of countries have been willing to experiment with progressive drug policies as the shortcomings of strict prohibition become more clear. This thesis is a study of the structures of drug laws in four countries – the Netherlands, Portugal, the United States, and Mexico – and their economic, public health, and human rights outcomes. The policies range in restrictiveness from the decriminalization of all drugs in Portugal to complete criminalization in Mexico. This thesis focuses on cannabis and heroin, two drugs which differ markedly in their risk for addiction and acute harm. A wide range of sources in the drug policy literature was analyzed. Evidence suggests that progressive policies in Portugal and the Netherlands have not significantly increased drug use and have led to numerous favorable public health outcomes. States in America that have legalized marijuana face many legal and economic challenges, and they should be observed closely as their policies develop further. Strict supply-control enforcement in Mexico has, on the other hand, led to an extreme upsurge in violent crime. These results suggest that in the future policymakers should drastically reallocate resources from ineffective supply-side strategies and pursue proven policies centered on public health and the protection of human rights

Search for A = 60 fragments from neutron-induced fission with accelerator mass spectrometry

Abstract The high sensitivity of the accelerator mass spectrometry (AMS) method has been utilized to measure the extremely low yields for super asymmetric neutron-induced fission of uranium. From a high level radioactive waste concentrate (HAWC) of the reprocessing plant WAK in Karlsruhe, Germany, iron has been chemically extracted and investigated by means of AMS for possible 60 Fe from nuclear fission. The fission yield is masked due to the competing 60 Fe production via double neutron capture on 58 Fe. Therefore, only an upper limit for the A = 60 fission chain yield of 1 × 10 −8 % could be determined. To estimate this branch, the cross section for the 59 Fe(n, γ ) 60 Fe reaction has been measured to (6.0 ± 1.3) barn

Establishing an objective biomarker for corneal cystinosis using a threshold‐based Spectral domain optical coherence tomography imaging algorithm

Purpose: The purpose of the present study was to establish a semi-automated threshold-based image segmentation algorithm to detect and objectively quantify corneal cystine crystal deposition in ocular cystinosis with anterior segment optical coherence tomography (AS-OCT). Methods: This prospective, observational, comparative study included 88 eyes of 45 patients from the German Cystinosis Registry Study as well as 68 eyes of 35 healthy control subjects. All eyes were imaged with AS-OCT (Cirrus HD-OCT 5000, Carl Zeiss Meditec AG, Jena, Germany). As an initial step, B-scan images were subjectively analysed for typical changes in morphology in comparison to healthy controls. Based on the experience gained, an objective semi-automated B-scan image segmentation algorithm was developed using a grey scale value-based threshold method to automatically quantify corneal crystals. Results: On AS-OCT B-scans, corneal crystals appeared as hyperreflective deposits within the corneal stroma. The crystals were distributed either in all stromal layers (43 eyes, 49%) or confined to the anterior (23 eyes, 26%) or posterior stroma (22 eyes, 25%), respectively. The novel automatic B-scan image segmentation algorithm was most efficient in delineating corneal crystals at higher grey scale thresholds (e.g. 226 of a maximum of 255). Significant differences in suprathreshold grey scale pixels were observable between cystinosis patients and healthy controls (p < 0.001). In addition, the algorithm was able to detect an age-dependent depth distribution profile of crystal deposition. Conclusion: Objective quantification of corneal cystine crystal deposition is feasible with AS-OCT and can serve as a novel biomarker for ocular disease control and topical treatment monitoring