Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program

Background: There is on-going controversy in relation to the efficacy of naltrexone used for the treatment of heroin addiction, and the important covariates of that success. We were also interested to review our experience with two depot forms of implantable naltrexone. Methods: A retrospective review of patients' charts was undertaken, patients were recalled by telephone and by letter, and urine drug screen samples were collected. Opiate free success (OFS) was the parameter of interest. Three groups were defined. The first two were treated in the previous 12 months and comprised "implant" and "tablet" patients. A third group was "historical" comprising those treated orally in the preceding 12 months. Results: There were 102, 113 and 161 patients in each group respectively. Groups were matched for age, sex, and dose of heroin used, but not financial status or social support. The overall follow-up rate was 82%. The Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment variables were independently associated with treatment retention. In a Cox proportional hazard multivariate model social support, the number of detoxification episodes, post-treatment employment, the use of multiple implant episodes and spiritual belief were significantly related to OFS. Conclusion: Consistent with the voluminous international literature clinically useful retention rates can be achieved with naltrexone, which may be improved by implants and particularly serial implants, repeat detoxification, meticulous clinical follow-up, and social support. As depot formulations of naltrexone become increasingly available such results can guide their clinical deployment, improve treatment outcomes, and enlarge the policy options for an exciting non-addictive pharmacotherapy for opiate addiction

A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer

Gemcitabine (GEM)-based chemotherapy is regarded as the standard treatment of pancreatic adenocarcinoma, but yields a very limited disease control. Very few studies have investigated salvage chemotherapy after failure of GEM or GEM-containing chemotherapy and preclinical studies attempting to widen the therapeutic armamentarium, not including GEM, are warranted. MIA PaCa2, CFPAC-1 and Capan-1 pancreatic cancer cell lines were treated with GEM, fluouracil (5-FU), docetaxel (DCT), oxaliplatin (OXP), irinotecan (CPT-11), pemetrexed (PMX) and raltitrexed (RTX) as single agent. Pemetrexed, inducing apoptosis with IC50s under the Cmax in the three lines tested, appeared the most effective drug as single agent. Based on these results, schedule- and concentration-dependent drug interactions (assessed using the combination index) of PMX/GEM, PMX/DCT and PMX–CPT-11 were evaluated. The combinatory study clearly indicated the PMX and CPT-11 combination as the most active against pancreatic cancer. To confirm the efficacy of PMX–CPT-11 combination, we extended the study to a panel of 10 pancreatic cancer cell lines using clinically relevant concentrations (PMX 10 μM; CPT-11 1 μm). In eight of 10 lines, the PMX–CPT-11 treatment significantly reduced cell recovery and increased both the subG1 and caspase 3/7 fraction. After a 5-day wash out period, an increased fraction of subG1 and caspase3/7 persisted in PMX–CPT-11-pretreated cell lines and a significant reduction in the clonogenicity capacity was evident. Finally, in vivo, the PMX/CPT-11 combination showed the ability to inhibit xenograft tumours growth as second-line therapy after GEM treatment. The PMX and CPT-11 combination displays a strong schedule-independent synergistic cytotoxic activity against pancreatic cancer, providing experimental basis for its clinical testing as salvage chemotherapy in pancreatic cancer patients

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

Dry matter intake and body condition score gain of dairy cows offered kale and grass

An outdoor grazing study conducted with 45 pregnant, dry dairy cows for 47 days during the winter period measured dry matter (DM) utilisation, DM intake, forage disappearance, body condition score (BCS) and liveweight (LW) of cows fed 11 (K11) or 14 (K14) kg of kale DM per day or 11 (G11) kg DM Italian ryegrass per cow per day. Cows were offered 3 kg DM barley straw/cow/day at 0800 h and their daily forage allowance at 0900 h. Within 6 hours of being offered a fresh forage allocation, cows had consumed more than 86% of their apparent daily DM intake with cumulative DM intake of 10.4, 10.5 and 7.3 kg DM/cow for K11, K14 and G11, respectively. Daily percentage DM utilisation averaged over the 47 days of the trial was higher for K11 (96%) and K14 (88%) than for G11 (70%), leading to higher apparent daily DM intake for K14 (12.1 kg) and K11 (10.5 kg) than for G11 (7.9 kg DM). Liveweight and BCS gain during the 47 days were higher for K14 (45.4 kg LW and 0.3 BCS units) and G11 (46.8 kg LW and 0.3 BCS units) than for K11 (30.1 kg LW and 0.2 BCS units). This study indicates that compared with offering the common industry allowance of 11 kg kale DM/cow/day, increasing the allowance to 14 kg kale DM/cow/day or offering grass at 11 kg DM/cow/day may lead to higher BCS and LW gain, although all regimes failed to meet expectations of cows gaining 0.5 BCS units during the winter feeding period. © 2014 The Royal Society of New Zealand

An Argumentation Based Approach to Risk Assessment.

Reliable quantitative risk assessment requires the use of meaningful statistical data and well validated models for their interpretation. In certain domains neither the data nor the validated models are available. Nevertheless, there may still be a requirement to generate a meaningful characterisation of risk, presented in a form which reflects the reliability and accuracy of the data available. One such domain is the assessment of the potential carcinogenic risk in chemical compounds, and there are many others. Work is described which is underway to provide a sound framework for the qualitative assessment of risk using a computer model of "argumentation". This work is being applied to the development of computer-based support for the assessment of carcinogenic risk. 1. Introduction This paper describes work which is under way to develop sound qualitative methods for risk assessment. A specific focus of this work is the development of a computer-based assistant for the assessment of ..

The effects of feeding cut plantain and perennial ryegrass-white clover pasture on dairy heifer feed and water intake, apparent nutrient digestibility and nitrogen excretion in urine

Urinary nitrogen concentration (UNcc) and urinary N excretion (UN) are directly associated with the nitrogen (N) leaching potential of soil and greenhouse gas emissions from grazing ruminants’ urine patches. This study was carried out to examine the effects of feeding cut plantain (PL) and perennial ryegrass-white clover pasture (PW) on dairy heifer feed and water intake, apparent nutrient digestibility and N excretion in urine. Twelve Jersey-Friesian heifers aged 9–10 months with an average body weight of 200 ± 18.8 kg (mean ± standard deviation (SD)) and breeding worth of NZ$162 ± 16.9 (mean ± SD) were randomly allocated to one of two treatments (six heifers per treatment): PW and PL. No difference was observed in dry matter intake (P = 0.117) and N intake (P = 0.370) between PW- and PL-fed heifers. The dry matter digestibility and digestible organic matter in the dry matter were similar between PL- and PW-fed heifers (P > 0.05). Heifers consuming PL had lower UNcc and UN than those consuming PW (P < 0.01). Estimated urine volume and total water intake were higher for PL-fed heifers than those fed PW (P < 0.01). Further, in comparison with PW-fed heifers, PL-fed heifers had lower plasma urea N (P < 0.001) and tended to have lower plasma δ¹⁵N – feed δ¹⁵N (P = 0.086). The findings suggest that feeding PL to dairy heifers may reduce UNcc and UN in comparison with those on conventional pastures; therefore it provides an opportunity to mitigate on-farm N pollution

Radiation induced angiosarcoma of the breast: outcomes from a retrospective case series.

Background Radiation induced angiosarcoma (RIAS) of the breast is a rare and aggressive complication of radiotherapy. Due to the rarity of this disease, much of the evidence for its management is based on case reports or small retrospective series. We sought to describe the management and outcomes of RIAS in a large single-institution series.Methods All patients diagnosed with RIAS between January 2000 and January 2014 were identified from an institutional database.Results A total of 49 patients were identified. Median age at diagnosis was 72 years (range 51-93). Median time from completion of radiotherapy to diagnosis of RIAS was 7.5 years. Median tumour size at presentation was 5.0 cm (1.5-19.0). The majority of patients presented with localised disease (47, 95.9%). Of these, 35 (74.5%) were suitable for surgery and underwent surgery with curative intent. Twelve patients presented with localised irresectable disease. Of these, 7 received systemic chemotherapy, with a sufficient response to facilitate surgery in 3 patients. Following potentially curative surgery, 2-year local recurrence-free was 55.2%. Survival was significantly prolonged in patients presenting with resectable disease (2-year overall survival 71.1% vs 33.3%, p 5 cm was prognostic of distant metastases-free survival and overall survival.Conclusion RIAS are rare, aggressive soft-tissue lesions with limited treatment options and high-rates of both local and systemic relapse