The role of interferons in the treatment of osteosarcoma

Interferons, a group of cytokines with antiangiogenic, direct antitumour and immunostimulating properties, have shown significant activity against osteosarcoma in vitro and in xenograft models. They have also been used in osteosarcoma clinical trials as a single adjuvant to surgery, with an apparent increase in relapse‐free survival. In the ongoing EURAMOS 1 clinical trial, interferon α‐2b is evaluated as an adjuvant treatment in osteosarcoma. This article reviews the rationale for the use of interferon in cancer with special reference to the treatment of osteosarcoma, including all published data of clinical efficacy in this disease. Pediatr Blood Cancer 2010;54:350–354. © 2009 Wiley‐Liss, Inc.     

Do Internet interventions for consumers cause more harm than good? A systematic review

Objective  To systematically review the effect of consumer use of online health information on decision-making, attitudes, knowledge, satisfaction and health outcomes and utilization.
Search strategy  Electronic databases searched included the Cochrane Controlled Trials Register, MEDLINE, PREMEDLINE (to 14 March 2001), CINAHL, Australian Medical Index, Health and Society, National Institutes of Health Clinical Trials Database and CenterWatch.
Inclusion criteria  All post-1995 comparative studies (including controlled studies, before and after studies, and interrupted time series analyses) of Internet users vs. non-Internet users and other communications mediums, and Internet characteristics such as e-mail vs. other communication mediums, were included. Outcomes included consumer decision-making, attitudes, knowledge, satisfaction and measurable changes in health status or health utilization.
Data extraction and synthesis  One reviewer screened all papers then two reviewers independently assessed studies against the selection criteria and any discrepancies were resolved by discussion with a third reviewer. No attempt was made to combine the data for further statistical analysis.
Main results  We identified 10 comparative studies. Studies evaluated the effectiveness of using the Internet to deliver a smoking cessation programme, cardiac and nutrition educational programmes, behavioural interventions for headache and weight loss, and pharmacy and augmentative services. All studies showed some positive effects on health outcomes, although the methodological quality of many studies was poor.
Conclusions  Despite widespread consumer Internet use to obtain health-care information, there is almost a complete lack of evidence of any effects this may have on health outcomes.     

Muscarinic stimulation of prostanoid synthesis by the isolated rat trachea: calcium dependency and effect of cortisol and cigarette smoke

Tracheal prostanoid synthesis was stimulated by parasympathomimetics: arecoline greater than carbachol = methacholine greater than acetylcholine much greater than arecaidine. McNA343, dimethyl phenyl piperazinium (DMPP), nicotine, potassium and isoprenaline were without effect. Prostanoid synthesis was also stimulated by Ca2+ ionophore A23187 and arachidonic acid (AA). Carbachol-stimulated prostanoid synthesis was inhibited by cholinergic antagonists (atropine greater than ipratropium bromide much greater than gallamine greater than pirenzepine); adrenaline and isoprenaline were without effect. Carbachol-stimulated prostanoid synthesis was also inhibited by the Ca2+-channel blockers, nifedipine, diethylstilboestrol and TMB-8. Hydrocortisone and betamethasone inhibited carbachol- and A23187-stimulated, but not AA-stimulated, prostanoid synthesis following an 18 h tissue culture. Cigarette smoke extracts had a biphasic effect on carbachol-, A23187- and AA-stimulated prostanoid synthesis (potentiation at low concentrations, inhibition at high concentrations of extracts). These data demonstrate (1) that rat tracheal prostanoid synthesis is stimulable by activation of muscarine receptor-linked Ca2+ mobilisation, and (2) that tracheal prostanoid synthesis may be involved in secretion of mucus, the disruption of which by cigarette smoking may be related to the pathophysiology of airway disease.     

Cancer curriculum in the Asia–Pacific: Opportunities and challenges in the age of globalization

With the rising incidence and prevalence of cancer in Asia–Pacific, the need for adequate cancer education of medical graduates in the region has become particularly urgent. There are 769 medical schools across the Asia–Pacific region in 33 countries serving over 60% of the world population in very diverse socioeconomic environments. This paper discusses some of the challenges for medical education in the Asia–Pacific in light of increasing globalization of health care, including the need to develop global standards in the area of diverse resources and health care priorities. It also points out emerging opportunities including online learning, telemedicine and collaborative educational initiatives across the region.     

Building it up and taking it down: the regulation of vertebrate ciliogenesis.

Primary cilia project from the surface of most vertebrate cells, and function in sensation and signaling during both development and adult tissue homeostasis. Mounting evidence links ciliary defects with a wide variety of diseases, underscoring the importance of understanding how these dynamic organelles are assembled and maintained. However, despite their physiological and clinical relevance, the logic and machinery that regulate ciliogenesis remain largely enigmatic. Here, we summarize emerging data that connect the assembly and disassembly of the primary cilium to cell cycle progression and we examine how determinants of cell architecture, including the planar cell polarity pathway, may regulate ciliogenesis. Additionally, identification of the genes underlying diverse ciliopathies in human patients is shedding light on the regulation of the formation of this complex organelle.     

Instrumental variables II: instrumental variable application—in 25 variations,the physician prescribing preference generally was strong and reduced covariate imbalance

ObjectiveAn instrumental variable (IV) is an unconfounded proxy for a study exposure that can be used to estimate a causal effect in the presence of unmeasured confounding. To provide reliably consistent estimates of effect, IVs should be both valid and reasonably strong. Physician prescribing preference (PPP) is an IV that uses variation in doctors' prescribing to predict drug treatment. As reduction in covariate imbalance may suggest increased IV validity, we sought to examine the covariate balance and instrument strength in 25 formulations of the PPP IV in two cohort studies.Study Design and SettingWe applied the PPP IV to assess antipsychotic medication (APM) use and subsequent death among two cohorts of elderly patients. We varied the measurement of PPP, plus performed cohort restriction and stratification. We modeled risk differences with two-stage least square regression. First-stage partial r² values characterized the strength of the instrument. The Mahalanobis distance summarized balance across multiple covariates.ResultsPartial r² ranged from 0.028 to 0.099. PPP generally alleviated imbalances in nonpsychiatry-related patient characteristics, and the overall imbalance was reduced by an average of 36% (±40%) over the two cohorts.ConclusionIn our study setting, most of the 25 formulations of the PPP IV were strong IVs and resulted in a strong reduction of imbalance in many variations. The association between strength and imbalance was mixed.