It is common to encounter correlated multiple outcomes measured on the same subject in various research fields. In developmental toxicity studies, presence of malformed pups and fetal weight are measured on the pregnant dams exposed to different levels of a toxic substance. Joint analysis of such two outcomes can result in more efficient inferences than separate models for each outcome. Most methods for joint modeling assume a normal distribution as random effects. However, in developmental toxicity studies, the response distributions may change irregularly in location and shape as the level of toxic substance changes, which may not be captured by a normal random effects model. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint model for binary and continuous outcomes. In our model, we incorporate a skewed logit model for the binary outcome to allow the response distributions to have flexibly in both symmetric and asymmetric shapes on the toxic levels. We apply our proposed method to data from a developmental toxicity study of diethylhexyl phthalate.
World Agriculture faces daunting challenges in feeding the growing population today. Reduction in arable land extent due to numerous reasons threatens achievement of food and nutritional security. Under this back ground, agricultural use of acidic soils, which account for approximately 40 % of the world arable lands is of utmost important. However, due to aluminum (Al) toxicity and low available phosphorous (P) content, crop production in acidic soils is restricted. Citrus, in this context, gains worldwide recognition as a crop adapted to harsh environments. The present paper reviewed Al toxicity and possible toxicity alleviation tactics in citrus. As reported for many other crops, inhibition of root elongation, photosynthesis and growth is experienced in citrus also due to Al toxicity. Focusing at toxicity alleviation, interaction between boron (B) and Al as well as phosphorus and Al has been discussed intensively. Al toxicity in citrus could be alleviated by P through increasing immobilization of Al in roots and P level in shoots rather than through increasing organic acid secretion, which has been widely reported in other crops. Boron-induced changes in Al speciation and/or sub-cellular compartmentation has also been suggested in amelioration of root inhibition in citrus. Despite the species-dependent manner of response to Al toxicity, many commercially important citrus species can be grown successfully in acidic soils, provided toxicity alleviation Agro-biological tactics such as addition of phosphorous fertilizers are used properly.
Cervical cancer is one of the most common gynecological cancers in Iranian women. This study was initiated to assess whether the combination of paclitaxel and cisplatin with radiation might feasible for these patients. The aim was to assess tumor response and toxicity of weekly cisplatin and paclitaxel along with radiotherapy in the treatment of cervical cancer. Women with primary untreated squamous cell carcinoma of the cervix with FIGO stages IB2 to IIIB were treated with weekly injections of cisplatin 30 mg/m2 and paclitaxel 35 mg/m2 for 5-6 weeks along with radiotherapy. A total of 25 patients were enrolled in this study who completed the intended treatment. Disease was assessed prior to treatment by pelvic examination and contrast enhanced MRI of the abdomen and pelvis. Response was assessed 1 month after completion of treatment by physical examination and 3 months after also by MRI.Toxicity was assessed and was graded using RTOG grading. There was a complete response rate of 84% after 3 months. The major toxicity was grade 1 and 2 anemia (92%). The mean duration of treatment was 58 days. In conclusion, combination chemotherapy with cisplatin and paclitaxel along with radiotherapy in patients with locally advanced squamous cell carcinoma of cervixwas well tolerated, in contrast to other studies, but it seems that there was no increase in tumor response and progression free survival with this treatment regimen.
Background: This systemic analysis was conducted to evaluate the efficacy and safety of an ifosfamide-containing regimen in treating patients with osteosarcoma. Methods: Clinical studies evaluating the efficacy and safety of Ifosfamide-containing regimen on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: When ifosfamide-containing regimens were evaluated, 4 clinical studies which including 134 patients with osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 44.8% (60/134) in ifosfamide-containing regimens. Major adverse effects were neutropenia, leukopenia, and fatigue inIfosfamide-containing regimens; No treatment related death occurred in cantharidin combined regimens. Conclusion: This systemic analysis suggests that ifosfamide-containing regimens are associated with good response rate and acceptable toxicity in treating patients with osteosarcoma, but this result should be confirmed by randomized clinical trials.
Background: Fluorouracil-based regimens have been widely accepted and recommended in the guidelines for treating patients with early or advanced staged colon cancer, although results are controversial. Here we performed a systemic analysis to evaluate the impact of S-1 based regimens on response and survival of patients with colon cancer. Methods: Clinical studies evaluating the impact of S-1 based regimens on response and survival of patients with colon cancer were identified using a predefined search strategy. Summary response rates (RRs) to treatment were calculated. Results: Six clinical studies which including 227 patients with advanced colorectal cancer were considered eligible for inclusion. Two studies were conducted using combination of S-1 and Oxaliplatin, and four studies featured S-1 and irinotecan. Systemic analysis showed that, in all patients, pooled RRs was 43.17%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. No treatment related death occurred. Conclusion: This systemic analysis suggests that S-1 based regimens, both with oxaliplatin or irinotean are associated with acceptable response and toxicity in patients with colon cancer.
Background: This systematic analysis was conducted to evaluate the efficacy and safety of cantharidin combined with chemotherapy in treating Chinese patients with metastatic colorectal cancer. Methods: Clinical studies evaluating the efficacy and safety of cantharidin combined with chemotherapy on response and safety for Chinese patients with colorectal cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated.Results: When cantharidin combined with chemotherapy, 4 clinical studies which included 155 patients with advanced colorectal cancer were considered eligible for inclusion. The systematic analysis suggested that, in all patients, pooled RR was 46.5% (72/155) in cantharidin combined regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia with cantharidin combined treatment; no treatment related deaths occurred. Conclusion: This systematic analysis suggests that cantharidin combined regimens are associated with high response rate and accepted toxicity in treating Chinese patients with metastatic colorectal cancer suggesting that randomized clinical trials are now warranted.
Studies of oxaliplatin, 5-fluorouracil and leucovorin in pretreated metastatic colorectal cancer showed that oxaliplatin dose intensity is important prognostic factor for objective response rates and progression-free-survival (PFS). To evaluate response rates, PFS and toxicity according to oxaliplatin dose intensity, we retrospectively analyzed data from patients with metastatic colorectal cancer received oxaliplatin,5-fluorouracil, leucovorin regimens. Sixty-three patients were reviewed in this study, 42 patients received low dose intensity oxaliplatin (LDI: $\leq85\;mg/m^2/2wks$) and 21 patients high dose intensity oxaliplatin (HDI: $>85\;mg/m^2/2wks$). Objective responses occurred in 10 $(47.7\%)$ HDI patients and 9 $(21.4\%)$ LDI patients (p = 0.014). Median PFS was 24.7 weeks in HDI group, with $45.1\%$ of HDI patients progression free at 6 months, and 20.5 weeks in LDI group, with $33.5\%$ of LDI patients progression free at 6 months (p = 0.344). Increased oxaliplatin dose intensity was not associated with neutropenia, thrombocytopenia, neuropathy, nausea and vomiting. This study showed that oxaliplatin dose intensification significantly improves objective response rate in pretreated metastatic colorectal cancer without increasing severe toxicity.
Kim Hunjung;Cho Young Kap;Kim Chulsu;Kim Woo Chul;Lee Sukho;Loh J K
Radiation Oncology Journal
/
v.17
no.2
/
pp.113-119
/
1999
Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.
Tank mixing application of pesticides has been used to reduce labor and to control wide spectrum of pests, but it may cause significant pesticide poisoning on human and animals due to carelessness. The toxic response of pesticides for the tank mixtures and mixtures was investigated to determine acute toxicity and enzymatic change using experimental animals. Acute oral toxicity and acute dermal toxicity were tested by RDA test guideline. The $LD_{50}$ was calculated by probit analysis method and cholinesterase was measured with automatic analyzer. The toxicities were generally higher than estimated toxicities in tank mixing and mixture. Serum cholinesterase activity was inhibited more than expected at the dose levels of 1/5, 1/10 and 1/20 of $LD_{50}$. Therefore, the results of this study showed that acute toxicity caused by the pesticide mixtures should be considered before the tank mixing method is applied.
Aquatic ecotoxicity of bisphenol A, a well-known endocrine disrupter in mammals, was studied using laboratory-reared Daphnia magna as a test organism. The static acute 48 h $EC_{50}$ of bisphenol A for daphnid neonates(<24 hold) was 12.9 mg/l and 110 h $LC_{50}$ values of bisphenol A for daphnid embryos of different ages after deposition into the brood chamber increase with ages in the range of 1.55 mg/l-8.91 mg/l. Also, 48 h $EC_{50}s$ generally increase with daphnid's ages in the range of 12.9 mg/l-19.8 mg/l. In the acute toxicity tests using mature daphnids, the lethal response and immobility all showed good concentration-response relationship with exposure concentration and exposure time, showing little difference between lethality and immobility. These results clarify that acute toxicity tests, using daphnid and its embryo, could also be useful tools easily available for the assessment of ecotoxicity of various harmful chemicals.
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