Killing time for cancer cells

As the signalling pathways that control cellular proliferation and death are unravelled, a range of targets have emerged as candidates for molecular cancer therapy. For their survival, cancer cells depend on a few highly activated signalling pathways; inhibition of these pathways has a strong apoptotic effect and can lead to tumour regression. But drugs that exploit this weakness, such as imatinib, have not cured patients: withdrawal of the drug leads to disease recurrence, and sustained treatment leads to the emergence of drug-resistant clones. Can cancer be cured, or will it have to be controlled as a chronic disease?     

Marijuana use and later problems: when frequency of recent use explains age of initiation effects (and when it does not)

Tobacco, alcohol, and marijuana are among the most commonly used drugs during adolescence. Initiation of marijuana use typically peaks at age 15, with risk of initiation continuing throughout adolescence. The goal of the current study was to prospectively examine the influence of age of marijuana initiation on four outcomes: physical health, mental health, illicit drug use other than marijuana, and marijuana-use related consequences at age 18. We controlled for several important predictors of adolescent drug use and its associated consequences, including demographics, social bonding variables, personality variables, and recent use of marijuana. Baseline survey data were collected in 1984 at grade 7 and follow up surveys were conducted at grades 8, 9, 10, and 12 (N = 2079). This initiates-only sample was 47% female, 66% White, 11% African American, 13% Hispanic, 5% Asian, and 5% other race or ethnicity. Findings indicated that age of initiation predicted marijuana consequences and other illicit drug use after controlling for demographic, social, and behavioral factors. However, once frequency of recent marijuana use was included in the models, age of initiation was only associated with other illicit drug use. Both primary and secondary prevention are needed to curb marijuana use and its associated harms.     

Use of medications in Wolff-Parkinson-White syndrome

The diagnosis of Wolff-Parkinson-White syndrome is generally straightforward; however, the management may not be, and requires an understanding of the competing risks of various treatment options and that of the clinical setting in which the diagnosis is made. The symptomatic patient with Wolff-Parkinson-White has an increased risk of atrial fibrillation and a small but significant risk of sudden cardiac death. Therapy is based on reduction in symptom burden and attenuation of the risk of pre-excited atrial fibrillation. Catheter ablation is the most effective means of achieving this goal with abolition of symptoms and risk of pre-excited atrial fibrillation. Medication is often employed in the acute setting to terminate paroxysms of arrhythmia associated with the accessory pathway and reduce the subsequent burden of symptoms until ablation can be performed. An overview of the agents commonly used is provided together with recommendations.     

Validation of a nomogram for predicting disease-specific survival after an R0 resection for gastric carcinoma

BACKGROUND: A statistical model for predicting disease-specific survival in patients with gastric carcinoma, based on a single U.S. institution experience, was tested for validity in a sample of patients treated at different institutions. METHODS: The authors analysed 459 patients from the Dutch Gastric Cancer trial that compared limited (D1) with extended (D2) lymph node dissection. The discrimination ability of the nomogram with respect to 5 and 9-year disease-specific survival probabilities was superior to that of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: There was considerable heterogeneity of risk within many of the AJCC stages. Calibration plots suggested that predicted probabilities from the nomogram corresponded closely to actual disease-specific survival. The gastric carcinoma nomogram performed well when applied to patients treated in a large number of institutions. CONCLUSIONS: The nomogram provided predictions that discriminated better than the AJCC staging system, regardless of the extent of lymph node dissection. Patient counseling and adjuvant therapy decision-making should benefit from use of the nomogram.     

Intestinal parasite analysis in organic sediments collected from a 16th-century Belgian archeological site

Parasite eggs found in organic remains collected from medieval structures in Raversijde (medieval name: Walraversijde), a village on the northern coast of Belgium, are discussed. The eggs were identified as Ascaris lumbricoides and Trichuris trichiura, both human parasites. Species identification allowed elucidating the origin of the organic sediments and the structures, in this case latrines used by humans. Capillaria sp. and free-living nematode larvae were also found in the latrine. Although neither parasite burden nor prevalence rates could be measured, the abundance of human intestinal parasite eggs indicated a high infection rate in the village residents, reflecting very poor sanitation.     

A note on testing in Aalen's additive hazards regression models

Aalen's additive hazards regression model is a useful alternative to the proportional hazards model for censored data regression. When used to compare treatments this approach leads to weighted comparisons of the crude estimate of the hazard rate of each group as compared to a baseline group. This is contrasted to the weighted log rank test from the proportional hazards model which compares each treatment's rate to the pooled rate. We show in this brief note that Aalen's suggestion for weights in this test leads to inconsistent tests in the sense that the test statistic depends on which group we pick for a baseline group. We show that 'consistent' tests are obtained by using common weight functions for all comparisons and we make some suggestions.     

Health information-seeking behaviour in adolescence: the place of the internet

The internet is one of a range of health information sources available to adolescents. It is recognised that young people have difficulties accessing traditional health services; in theory, the internet offers them confidential and convenient access to an unprecedented level of information about a diverse range of subjects. This could redress adolescents' state of relative health 'information poverty', compared to adults. This paper seeks to explore United Kingdom (UK) and United States (US) adolescents' perceptions and experiences of using the internet to find information about health and medicines, in the context of the other health information sources that are available to them. The study involved a series of 26 single-gender focus groups with 157 English-speaking students aged 11-19 years from the UK and the US. Many students reported that the internet was their primary general information source. Information sources were defined during analysis in terms of previous experience of the source, saliency of the available information, and credibility of the source (defined in terms of expertise, trustworthiness and empathy). Most focus group participants had extensive personal experience with the internet and some information providers therein (notably search engines). Internet health information was regarded generally as salient. Its saliency was increased through active searching and personalisation. Perceived credibility of the internet varied because expertise and trustworthiness were sometimes difficult to determine, and empathy could be facilitated through online communities but the individual could control disclosure. The internet combines positive features of traditional lay and professional, personal and impersonal sources. Although it is unlikely to supplant the role of trusted peers and adults, the internet has found an important place among adolescents' repertory of health information sources.     

Managing panic disorder in general practice

BACKGROUND: Panic disorder (PD) is common in the community and contributes to significant distress and decreased quality of life for people who suffer from it. Most people with PD will present in the first instance to their general practitioner or hospital emergency department for assistance, often with a focus on somatic symptoms and concerns. OBJECTIVE: This article aims to assist the GP to manage this group of patients by providing an outline of aetiology, approaches to assessment, and common management strategies. DISCUSSION Although GPs have an important role to play in ruling out any causal organic basis for panic symptoms, the diagnosis of PD can usually be made as a positive diagnosis on the basis of careful history taking. Thorough and empathic education is a vital step in management. The prognosis for PD can be improved by lifestyle changes, specific psychological techniques, and the judicious use of pharmacotherapy.     

Using quantitative methods to improve the diagnostic workup for abdominal pain in children

Introduction

The differential diagnosis of abdominal pain in children can be challenging. We applied quantitative decision-making methods to this process and sought to determine if their use provided measurable benefit.

Methods

After obtaining institutional review board approval, we recorded key elements of the history, physical examination, laboratory, and imaging evaluations along with the cost and the time spent in the emergency department (ED) for children presenting with abdominal pain. Initially, data were collected (group 1, n = 1366 patients) and then presented to the ED pediatricians. For subsequent patients, ED physicians received a sheet specific to that patient's age and sex reporting the most common diagnoses and the elements of the evaluation that had proven most useful (group 2, n = 624 patients). We compared the difference in length of stay and costs before and after intervention, between study groups, by age groups, and separately by sex using a 2-factor analysis of variance.

Results

The diagnostic workup cost less in boys aged 2 to 12 years after the intervention. In boys and girls older than 12 years, the cost trended lower.

Discussion

This study demonstrates that ED physicians equipped with specific information were able to complete their diagnostic evaluation of children presenting with abdominal pain at a lower cost.