The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

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Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration

Efforts to reduce global cancer disparities begin with an understanding of geographic patterns in cancer incidence, mortality, and prevalence. Using the GLOBOCAN (2002) and Cancer Incidence in Five Continents databases, we describe overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world. For the eight most common malignancies-cancers of lung, breast, colon and rectum, stomach, prostate, liver, cervix, and esophagus-the most important risk factors, cancer prevention and control measures are briefly reviewed. In 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide; nearly 25 million persons were living with cancer. Among the eight most common cancers, global disparities in cancer incidence, mortality, and prevalence are evident, likely due to complex interactions of nonmodifiable (ie, genetic susceptibility and aging) and modifiable risk factors (ie, tobacco, infectious agents, diet, and physical activity). Indeed, when risk factors among populations are intertwined with differences in individual behaviors, cultural beliefs and practices, socioeconomic conditions, and health care systems, global cancer disparities are inevitable. For the eight most common cancers, priorities for reducing cancer disparities are discussed.

Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the World

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies, and cross-sectional studies, and 4 are specific to each of the 3 study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors, and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, 1 or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (www.strobe-statement.org) should be helpful resources to improve reporting of observational research.

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Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration

1described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific community and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite alterations on cell-free DNA (cfDNA) were shown in cancer patients 4

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Cell-free nucleic acids as biomarkers in cancer patients

Neonatal End-of-Life Decision Making

and risk of glioma in five North European countries. Int J Cancer 2007;120:1769–75. 17 StataCorp. Stata Statistical Software: Release 9.0. Texas, Stata Corporation: College Station, 2005. 18 Ahlbom A, Green A, Kheifets L, Savitz D, Swerdlow A; ICNIRP (International Committee for Non-Ionizing Radiation Protection) Standing Committee on Epidemiology. Epidemiology of health effects of radiofrequency exposure. Environ Health Perspect 2004;112:1741–54. 19 Lahkola A, Tokola K, Auvinen A. Meta-analysis of mobile phone use and intracranial tumors. Scand J Work Environ Health 2006;32:171–77. 20 Lahkola A, Salminen T, Auvinen A. Selection bias due to differential participation in a case-control study of mobile phone use and brain tumors. Ann Epidemiol 2005;15: 321–25. 21 Inskip PD, Tarone RE, Hatch EE et al. Sociodemographic indicators and risk of brain tumors. Int J Epidemiol 2003;32:225–33. 22 Rohringer M, Sutherland GR, Louw DF, Sima AA. Incidence and clinicopathological features of meningioma. J Neurosurg 1989;71:665–72. 23 DeMonte F, Marmor E, Al-Mefty O. Meningiomas. In: Kaye A, Laws ER, Jr (eds). Brain Tumors: An Encyclopedic Approach. New York: Churchill Livingstone, 2001. 24 Parslow RC, Hepworth SJ, McKinney PA. Recall of past use of mobile phone handsets. Radiat Prot Dosimetry 2003;106:233–40. 25 Samkange-Zeeb F, Berg G, Blettner M. Validation of selfreported cellular phone use. J Expo Anal Environ Epidemiol 2004;14:245–48. 26 Berg G, Schutz J, Zamkange-Zeeb F, Blettner M. Assessment of radiofrequency exposure from cellular telephone daily use in an epidemiological study: German validation study of the international case-control study of cancers of the brain – INTERPHONE study. J Expo Anal Environ Epidemiol 2005;15:217–24. 27 Vrijheid M, Cardis E, Armstrong BK et al. Validation of short term recall of mobile phone use for the Interphone study. Occup Environ Med 2006;63:237–43. 28 Armstrong BG. Effect of measurement error on epidemiological studies of environmental and occupational exposures. Occup Environ Med 1998;55:651–56. 29 Dreyer NA, Loughlin JE, Rothman KJ. Cause-specific mortality in cellular telephone users. JAMA 1999;282:1814–16.

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Commentary: Observational studies may conceal a weakly elevated risk under the appearance of consistently reduced risks

The current decade has witnessed an increasing interest in the diet-cancer issue as a central one for public health. Notwithstanding a substantial amount of epidemiological investigations, firm evidence of carcinogenicity exists only for alcoholic beverages with respect to cancers at several sites, and for aflatoxin with respect to liver cancer; also, the relation is established between diet related excess of energy intake, as translated into obesity, and cancer of endometrium and gallbladder. For a number of other dietary factors the evidence for a causal or protective role still remains at a presumptive level (e.g. intake of fresh vegetables and fruits with respect to cancers at several sites), or is still frankly open to debate (e.g. fat with respect to breast and colon cancer). Methodological inadequacies in past studies have been identified and clearer results should derive in the coming decade from epidemiological investigations substantially improved in methodology, particularly from the longterm prospective studies as now planned by the International Agency for Research on Cancer. Fortunately for cancer prevention, such dietary advice as can be derived from the highly incomplete and unsatisfactory knowledge on the role of dietary factors on cancer, turns out to be in broad agreement with the advice aimed at preventing other major diseases such as ischaemic heart disease and hypertension. This allows the issuing of a set of simple but important ‘prudent diet’ recommendations.

The diet and cancer hypothesis: current trends.

Re: "Occupational cancer: Where now where next?".

Negotiations on the European Union's fifth framework programme of research are at a critical juncture. Within the next few weeks discussions between the council of ministers and the European parliament will determine the direction of collaborative multinational research in Europe over the next five years. Funds for the life sciences programme, which includes health, are likely to amount to 2-2.5 billion ecu. The programme will be based on “key actions” proposed by the European Commission. These currently include food and health, vaccines, health and the environment, biotechnology, and aging.1 How funds will be apportioned is yet to be decided, …

Rodolfo Saracci

Papers

Neonatal End-of-Life Decision Making

Commentary: Observational studies may conceal a weakly elevated risk under the appearance of consistently reduced risks

The diet and cancer hypothesis: current trends.

Re: "Occupational cancer: Where now where next?".

Europe's health research: getting the right balance.