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Disasters are exceptional events that cause damages on a scale that result in widespread unmet human needs that are critical and urgent. The exceptional circumstances in disasters may render established ethical norms of healthcare practice inapplicable or inappropriate. Healthcare professionals who work in disasters are faced with choices that have direct impacts on the life, death, and suffering of both disaster victims, and themselves. Some choices faced may be dilemmatic choices between competing irreconcilable moral principles. Whilst some choices reflect uncertainty as to how to realise moral precepts. In these situations, there is an appeal for guidance that is fitted to the circumstances found within disasters. Appealing to codes of professional conduct and ethics is problematic as many codes are either silent on the difficulties encountered in disasters, or overly demanding through the use of imperative language. Considering the relative weakness of published codes, universal principles of first do no harm and do good are offered as guiding principles. However, in disasters opportunities exist for harming through nondoing, creating the possibility that as aid is rendered to some, harm is occasioned to others. When considering doing good in disasters, maximising aggregate benefit is the established ethical framework employed. However, this framework’s foundational assumptions of aggregation of benefits and harms, commensurability of different ends, and the privileging of the greater number are open to critique. Thus, the principles of first do no harm and do good are problematic in disaster settings. Virtue ethics is proposed as a novel response to the difficulties faced by healthcare professionals in disasters. Virtue ethics provides an account of the healthcare professional as one who must choose with wisdom, courage and integrity in exceptional circumstances. Further, virtue ethics provides an understanding of how it is possible to act well in the tragic circumstances found within disasters.

Purpose:\ud \ud We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials.\ud \ud Experimental design:\ud \ud Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules.\ud \ud Results:\ud \ud Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma.\ud \ud Conclusions:\ud WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly.

Objective: To examine the role of acetyl-L-carnitine (ALC) in the treatment of diabetic peripheral neuropathy (DPN). Data Sources: A MEDLINE search (1966–April 2008) of the English-language literature was performed using the search terms carnitine, diabetes, nerve, and neuropathy. Studies identified were then cross-referenced for their citations. Study Selection and Data Extraction: The search was limited to clinical trials, meta-analyses, and reviews addressing the use of ALC for the treatment of DPN. Studies that included other disease states that could cause peripheral neuropathy were excluded. Two large clinical studies that used ALC for the treatment of DPN were identified. No case studies were identified. Data Synthesis: The results from 2 published clinical trials Involving 1679 subjects were included. Subjects who received at least 2 g daily of ALC showed decreases in pain scores. One study showed improvements in electrophysiologic factors such as nerve conduction velocities, while the other did not. Patients who had neuropathic pain reported reductions in pain using a visual analog scale. Nerve regeneration was documented in one trial. The supplement was well tolerated, A proprietary form of ALC was used in both studies. Conclusions: Data on treatment of DPN with ALC support its use. It should be recommended to patients early in the disease process to provide maximal benefit. Further studies should be conducted to determine the effectiveness of ALC in the treatment and prevention of the worsening symptoms of DPN.

The conference had three broad goals: first, to review the basic structure of epidemiology and demography to provide a backdrop to more-effective dialogue; second, to present research on specific areas of inquiry that have been addressed by both disciplines; and third, to discuss explicit ways of improving communication and collaboration across the disciplines.

To describe an insulin titration-by-phone service conducted by pharmacists and to discuss the effects of this service on patient care and outcomes in the first year of its existence.An academic family medicine department in which pharmacists practice in nondistributory roles, from March 2009 through March 2010.Pharmacy services within the department include a chronic disease medication therapy management clinic as well as consultation in various other primary care and specialty clinics. Fourth-year student pharmacists complete advanced pharmacy practice experiences at this site as well.Based upon a need identified by department providers (physicians and physician assistants), an insulin titration-by-phone service was implemented by two faculty pharmacists. Patients were referred into this service by their primary care provider (PCP) and were called by one of the pharmacists on a regular basis. Pharmacist recommendations for insulin dose adjustments were made based on patient reported self-monitored glucose values. PCP approved recommendations and the patient was notified of changes.Decrease in glycosylated hemoglobin (A1C ) within 9 months of referral to the service when compared with baseline.Analysis included 76 patients. The mean decrease in A1C was 1.55% (SD 2.31; P0.001). The largest decrease in A1C (1.4%) was seen in the first 3 months after referral. Seven patients achieved an A1C ≤7% ( P = 0.007). Forty-one patients had a decrease in A1C of at least 1% during the first 9 months after their referral ( P0.001).The implementation of a pharmacist-run insulin titration-by-phone service resulted in improvements in A1C that were most pronounced in the first 3 months after referral.

This study examined nonmarital fertility among never married women those who remain unmarried after the birth or who marry after the birth and married women who give birth after the end of their marriage in the US. Comparisons were made between marital and nonmarital childbearing. Data were obtained from the 1987-88 and the 1992-94 waves of the National Survey of Families and Households among 1536 women who gave birth 5 years before the first interview. 1069 women had a marital birth. 480 were unmarried. 285 women were never married in both waves. 62 were unmarried at the birth but married at the time of the interview. 133 were previously married but married at the time of the birth. 81% were reinterviewed in 1992-94. Wave II interviews included 85% of women with marital births 75% of the never-married subgroup 68% of the premarital-birth subgroup and 71% of the postmarital-birth subgroup. Findings indicate that women with marital births were more advantaged regardless of birth timing. Women with nonmarital births in Wave I who were unmarried at Wave II were the poorest socioeconomically. Unmarried mothers were as likely to work or not work as married mothers. Findings suggest that nonmarital fertility is affected by marriage status at the time of the birth life course timing and behavior after the birth.

CONTROVERSIES ABOUT how to discipline children are of concern to parents, other adults who care for children, clinicians, and policymakers. There are disparate views about some aspects of the advisability and effects of different forms of discipline and substantial variability in the amount and quality of the research that informs these opinions. To address these issues, a conference—Research on Discipline: The State of the Art, Deficits, and Implications—was sponsored by the National Institutes of Child Health and Human Development Family and Child Well-being Research Network, Chapel Hill, NC, April 25-26, 1996. The focus of the conference was on discipline research conceptualization, methodology, issues of causality, outcomes, and interventions. The aim was to review what we may conclude from previous work and to identify deficits that might be addressed in future research. Three of the papers from the conference are presented in this issue of theArchives. We highlight herein some