Response rates,duration of response,and dose response effects in phase I studies of antineoplastics

Summary Over a period of 14 years, 7,960 patients were treated in 228 phase I trials. In these patients, there were 75 complete and 432 partial responses for an overall objective response rate of 6%. Complete responses lasted a median of six months (range 1–18), while partial responses lasted a median of three months (range 1–17). Of note is that no drug has made it to the market which has not had a response in phase I trials. Responses were noted in very diverse histologic types of tumors. Although there were responses at doses which were as low as 3–5% of the recommended dose for phase II trials, the majority of responses did occur at 80–120% of the dose recommended for phase II trials. Although the response rate in phase I trials is indeed low, responses do occur. This response rate information should help the clinician provide facts for the patient considering a phase I trial with new anticancer agents. These findings also emphasize that although phase I trials are characteristically dose-finding studies, if no responses are noted in phase I studies, it is unlikely the drug will be used routinely in the clinic.     

The effect of pre-admission education on domiciliary recovery following laparoscopic cholecystectomy.

OBJECTIVES: The objectives of this randomised controlled study were to determine if pre-admission patient education affects post-operative pain levels, domiciliary self-care capacity and patient recall following a laparoscopic cholecystectomy (LC). Participants were randomised to receive the standard preadmission program (SP) or an individualised, education intervention (El). DESIGN: A pre-operative questionnaire was administered in the pre-admission clinic to determine participants' knowledge of LC and post-operative management. Telephone follow-up and post-operative questionnaire were conducted approximately 14 days post discharge. SETTING: Preadmission clinic of a Sydney, Australia, tertiary referral hospital. SAMPLE: Ninety-three elective LC patients. RESULTS: EI participants experienced lower pain levels and had significantly greater recall of provided information. However, no significant differences were found between the control and intervention groups for domiciliary self-care. CONCLUSION: Pre-admission education intervention helps reduce post-operative pain levels following LC and significantly increases patients' knowledge of self-care and complication management.     

Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

Nicotine dependence and withdrawal in alcoholic and nonalcoholic ever-smokers

We compared nicotine dependence and withdrawal in male alcoholic and control ever-smokers, controlling for relevant demographic and clinical variables. Alcoholics were more likely to meet criteria for moderate or severe nicotine dependence and endorse more nicotine dependence symptoms. Symptoms reported more frequently by alcoholics included: (a) using nicotine in larger amounts or over a longer time than intended; (b) continued use despite problems caused or exacerbated by nicotine; (c) marked tolerance; and (d) experiencing characteristic nicotine withdrawal symptoms. Alcoholics also smoked more heavily. Other than “headaches,” and “decreased heart rate,” alcoholics consistently endorsed nicotine withdrawal symptoms at a higher rate. After controlling for demographic and clinical variables and level of nicotine dependence, only “feel depressed” differed significantly between groups. Our research supports previous findings suggesting that nicotine dependence is more severe in those with a history of alcohol dependence. As a result, alcoholics may experience greater discomfort from nicotine withdrawal upon smoking cessation.     

Patterns of Cocaine Use Among Cocaine-Dependent Outpatients

The authors systematically evaluated the frequency patterns of cocaine use in 85 cocaine-dependent outpatients and found four patterns of use: continuous (27%), intermittent patterned (35%), intermittent nonpatterned (25%), and occasional (13%). Few subjects reported consistent cycling between binges and crashes. There were no significant differences in patterns of use associated with gender, race, educational level, route of administration, or recency of heroin use. Continuous users and occasional users were older than intermittent users. Because different contingencies may control patterned vs. nonpatterned cocaine use, pattern of use may have implications for treatment, even in individuals reporting similar amounts of cocaine use.     

Development of the Massachusetts School Nurse Research Network (MASNRN): A Practice-Based Research Network to improve the quality of school nursing practice.

When school nurses embrace evidence-based practice (EBP), higher-quality care is provided to students, their families, and the larger community. Despite this, school nursing has been slow to embrace EBP. Practice-Based Research Networks (PBRNs), which capitalize on the combined strengths of clinicians and researchers to study clinical questions, are one approach to overcoming barriers towards advancing evidence-based practice (EBP) in school nursing. This article will briefly review EBP and PBRNs. The development of Massachusetts School Nurse Research Network (MASNRN), a PBRN designed to investigate health issues common across schools and to validate school nursing practice, will then be described. Details regarding MASNRN's mission, governance, communications systems, staffing, and network maintenance and funding will be explicated. MASNRN can serve as a model for PBRN development within the broader school nursing community.