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In his book What is Life? Erwin Schrödinger coined the term 'code-script', thought by some to be the first published suggestion of a hereditary code and perhaps a forerunner of the genetic code. The etymology of 'code' suggests three meanings relevant to 'code-script which we distinguish as 'cipher-code', 'word-code' and 'rule-code'. Cipher-codes and word-codes entail translation of one set of characters into another. The genetic code comprises not one but two cipher-codes: the first is the DNA 'base-pairing cipher'; the second is the 'nucleotide-amino-acid cipher', which involves the translation of DNA base sequences into amino-acid sequences. We suggest that Schrödinger's code-script is a form of 'rule-code', a set of rules that, like the 'highway code' or 'penal code', requires no translation of a message. Schrödinger first relates his code-script to chromosomal genes made of protein. Ignorant of its properties, however, he later abandons 'protein' and adopts in its place a hypothetical, isomeric 'aperiodic solid' whose atoms he imagines rearranged in countless different conformations, which together are responsible for the patterns of ontogenetic development. In an attempt to explain the large number of combinations required, Schrödinger referred to the Morse code (a cipher) but in doing so unwittingly misled readers into believing that he intended a cipher-code resembling the genetic code. We argue that the modern equivalent of Schrödinger's code-script is a rule-code of organismal development based largely on the synthesis, folding, properties and interactions of numerous proteins, each performing a specific task.

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The notions of 'the Darwinian revolution' and of 'the scientific Revolution' are no longer unproblematic; so this paper does not construe its task as relating these two items to each other. There can be big-picture and long-run history even when that task is declined. Such history has to be done pluralistically. Relating Darwin's science to Newton's science is one kind of historiographical challenge; relating Darwin's science to seventeenth-century finance capitalism is another kind. Relating Darwin's science to long-run traditions and transitions is a different kind of task from relating his science to the immediate short-run contexts.

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When socio-economic contexts are sought for Darwin's science, it is customary to turn to the Industrial Revolution. However, important issues about the long run of England's capitalisms can only be recognised by taking a wider view than Industrial Revolution historiographies tend to engage. The role of land and finance capitalisms in the development of the empire is one such issue. If we historians of Darwin's science allow ourselves a distinction between land and finance capitalisms on the one hand and industrial capitalism on the other; and if we ask with which side of this divide were Darwin and his theory of branching descent by natural selection aligned, then reflection on leading features of that theory, including its Malthusian elements, suggests that the answer is often and largely, though not exclusively: on the land side. The case of Wallace, socialist opponent of land capitalism, may not be as anomalous for this suggestion as one might at first think. Social and economic historians have reached no settled consensuses on the long-run of England's capitalisms. We historians of Darwin's science would do well to import some of these unsettled states of discussion into our own work over the years to come.

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The incidence of human immunodeficiency virus type 1 (HIV-1) infection among opiate users was determined in a retrospective cohort of 436 patients with multiple admissions to the only inpatient drug treatment program in northern Thailand between October 1993 and September 1995. During 323.4 person-years of follow-up, 60 patients presenting for detoxification acquired HIV-1 infection, for a crude incidence rate of 18.6 per 100 person-years (95% confidence interval 14.4-23.9). All seroconverters were male. HIV-1 incidence varied by the current route of drug administration: 31.3 per 100 person-years for injectors and 2.8 per 100 person-years for noninjectors (smoking and ingestion). Significant differences were found by ethnicity: HIV-1 incidence was 29.3 per 100 person-years for Thai lowlanders and 8.5 per 100 person-years for hill tribes. Multivariate relative risk estimates showed that injecting opiates (vs. use by other routes), being unmarried, being under age 40 years, being a Thai lowlander, having a primary and secondary education, and being employed in the business sector were each independently associated with human immunodeficiency virus seroconversion. This HIV-1 incidence rate is double that reported for Bangkok and suggests that prevention and control programs for drug users need to be expanded throughout Thailand. Improved availability of more-effective treatment regimens and increased access to sterile injection equipment are needed to confront the HIV-1 epidemic among opiate users in northern Thailand.

PIP: The incidence of HIV-1 infection among opiate users was assessed in a retrospective cohort of 436 patients with multiple admissions to the only inpatient drug treatment program in northern Thailand between October 1993 and September 1995. During 323.4 person-years of follow-up, 60 patients presenting for detoxification acquired HIV-1 infection, for a crude incidence rate of 18.6/100 person-years. All seroconverters were male. HIV-1 incidence varied by the current route of drug administration: 31.3/100 person-years for injectors and 2.8/100 person-years among those who smoked or ingested the drug. HIV-1 incidence was 29.3/100 person-years for Thai lowlanders and 8.5/100 person-years for hill tribes. Multivariate analysis found that injecting opiates, being unmarried, being under age 40 years, being a Thai lowlander, having a primary and secondary education, and being employed in the business sector were each independently associated with HIV seroconversion. The HIV-1 incidence rate in this population is double that reported for Bangkok. As such, HIV prevention and control programs for drug users need to be expanded throughout Thailand. Moreover, improved availability of more effective treatment regimens and increased access to sterile injection equipment are needed to confront the HIV-1 epidemic among opiate users in northern Thailand.

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Characterizing the epidemiology of HIV-1 infection in Northern Thai opiate users is important in developing control strategies in this ethnically diverse and culturally distinct region. A cross-sectional survey of drug users first admitted between 1993 and 1995 at the Northern Drug Dependence Treatment Center, Mae Rim, Thailand, was conducted. Patients (n = 4197) were interviewed at intake about their history of drug use when they provided serum specimens for HIV-1 antibody testing. The HIV-1 prevalence was 18.6%, with men having a fourfold higher prevalence than women. Wide diversity in HIV-1 prevalence was seen by ethnicity; the HIV-1 prevalence among Thai lowlanders was four times greater than that among ethnic minorities (hill tribes). Differences in HIV-1 prevalence were the result of differences in opiate use; hill tribes frequently smoked or ingested opium, whereas Thai lowlanders injected heroin. The high HIV-1 prevalence suggests that preventive interventions for risk reduction are urgently needed in these populations. Education about the risks of injection drug use (IDU) as well as information concerning needle disinfection and expansion of drug treatment are required to reduce the risk of HIV-1 transmission associated with sharing injection equipment. Further, increasing sources of sterile needles should be considered for active users, especially for those in more remote settings.

PIP: A cross-sectional survey of 4197 men and women admitted to the Northern Drug Dependence Treatment Center in Mae Rim, Thailand, in 1993-95 was conducted to characterize the epidemiology of HIV-1 infection in Northern Thai opiate users. Overall HIV prevalence was 18.6%, with men having a more than 4-fold higher prevalence than women (20.0% and 5.9%, respectively). HIV prevalence was also 4 times greater among Thai lowlanders (29.4%) than hill tribes (9.1%). Interviews revealed that, while lowlanders were most likely to inject heroin, hill tribes more frequently smoked or ingested opium. Overall, heroin users were nine times more likely to be HIV-infected than those who used opium (36.3% and 4.0%, respectively). These findings suggest that cultural differences in patterns of drug use produce different HIV prevalences among ethnic groups in Northern Thailand. Multivariate regression analysis of HIV risk factors, after adjustment for drug of choice and route of administration, found significantly reduced risks for married and cohabitating persons, civil servants, and students and significantly elevated risks for those with only a primary education or employed in agriculture or business. Education about the risks of injection drug use, as well as information on needle disinfection and expanded sources for sterile needles, is needed, especially in Thailand's more remote settings.

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Measuring quality of life and assessing technologies are both increasingly prominent in health care systems. This growth has accompanied growing concern over aging populations and health care expenditure growth. Nevertheless, there appears to be unrealized potential for synergy between quality of life research and technology assessment. In this paper, we consider the roles and challenges facing quality of life research in three domains: research-particularly clinical trials of therapeutics; clinical situations and policy-making. We then examine the potential for synergy in these domains and conclude that expanding collaboration will strengthen both fields and intensify their impact in research, clinical practice and policy-making.

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Setting priorities and selecting topics are important steps in guidelines development, but they have received relatively little attention to date. Responses from a survey of guidelines stakeholders in Canada suggest that the health burden of a clinical condition on the population is an important factor in priority setting. Economic considerations, cast as either costs of treatment to the health care system or the economic burden of illness to society, are given varying importance by different stakeholder groups. Drawing on the literature and the survey results, the authors propose a framework for priority setting. Important issues requiring consideration include the role of public and community participation, the need for and appropriate emphasis on quantitative data regarding current practice and its variation, and mechanisms to link guidelines to health-policy development and management of the health care system.

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The organizing committee of a workshop on clinical practice guidelines (CPGs) surveyed invited organizations on their attitudes and activities related to five topics to be covered during the workshop sessions: organizational roles, priority setting, guidelines implementation, guidelines evaluation and development of a network of those active in the CPG field. Organizational roles: The national specialty societies were felt to have the largest role to play; the smallest roles were assigned to consumers, who were seen to have a role mainly in priority setting, and to industry and government, both of which were seen to have primarily a funding role. Many barriers to collaboration were identified, the solutions to all of which appeared to be better communication, establishment of common principles and clear role definitions. Priority setting: There was considerable agreement on the criteria that should be used to set priorities for CPG activities: the burden of disease on population health, the state of scientific knowledge, the cost of treatment and the economic burden of disease on society were seen as important factors, whereas the costs of guidelines development and practitioner interest in guidelines development were seen as less important. Organizations were unable to give much information on how they set priorities. Guidelines implementation: Most of the organizations surveyed did not actively try to ensure the implementation of guidelines, although a considerable minority devoted resources to implementation. The 38% of organizations that implemented guidelines actively listed a wide variety of activities, including training, use of local opinion leaders, information technology, local consensus processes and counter detailing. Guidelines evaluation: Formal evaluation of guidelines was undertaken by fewer than 13% of the responding organizations. All the evaluations incorporated assessments before and after guideline implementation, and some used primary patient data. Barriers to evaluation included lack of money, time, data or expertise. CPG Network: Most of the respondents felt that all organizations and individuals interested or involved in guidelines should form the membership of the network. The three most important functions of such a network were deemed to be (a) to facilitate collaboration among those involved in the CPG process, (b) to maintain an information centre on CPGs and (c) to provide expertise to the CPG process. It was felt that the network should have some formal structure and communicate through e-mail and print media.

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Since 1971 pediatric mortality rates have decreased markedly but differently in Canada and the United States. These trends were examined in light of changes in hospital use and health care financing. Annual mortality and hospital use rates for children aged 14 years and younger were calculated. Between 1971 and 1987, all-cause mortality in Canada fell from 165 to 74 per 100,000; the American rate fell from 172 to 96 per 100,000. American hospitalization rates remained essentially constant until 1983 and then fell by 27.5%, while Canadian hospitalization rates declined throughout. In 1987 Canadian children had higher hospitalization rates, while American children had higher mortality rates. These differences may be associated with differences in health financing; the adoption of US prospective payment systems was temporally coincident with sharp declines in hospitalization rates for American children.

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While physicians are often portrayed as scientists, the defining character of medical practice is its being both science and art. Indeed, despite drawing on the ever-expanding knowledge base and range of therapies, medical practice remains fundamentally an interpersonal experience, drawing on the dynamic and rich interaction between practitioner and patient. With the goal of situating clinical practice guidelines in a broader context, we briefly explore models of medicine and the nature of clinical practice. The implications of these for guideline development and implementation are then examined as we present guidelines as an opportunity for enhancing medical practice and increasing both patient and practitioner satisfaction.

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Intraperitoneal gallstones left behind at laparoscopic cholecystectomy are not uncommon. Such stones have previously been thought to be harmless. We report three instances of delayed intra-abdominal infection and/or inflammation related to these misplaced gallstones. All three patients presented months postoperatively with vague abdominal complaints. Computed tomography revealed inflammatory foci involving intraperitoneal gallstones. All patients required percutaneous or operative drainage of the collections. Every effort should be made to locate and remove "spilled" gallstones at the time of laparoscopic cholecystectomy.

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We consider the nature of technology assessment and then briefly summarize technology assessment activities in five countries: Canada, France, the Netherlands, the United Kingdom, and the United States. Drawing from these examples, we then identify determinants of the emergence and impact of technology assessment.

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The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) was recently evaluated. We summarize the evaluation process, report, and 17 recommendations for enhancing CCOHTA's effectiveness. This paper may be useful for evaluators of agencies for technology assessment.

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In Canada, all citizens are insured for health services. Health care is a provincial responsibility. The federal role is limited to health care financing, health protection including regulation of pharmaceuticals, and environmental health. The health care system represents a balance among government direction, consumer choice, and provider autonomy. Canada has largely controlled the costs of health care by funding and management mechanisms, the most important of which is the global budget formula used to fund hospitals. This paper discusses the Canadian health care system, with particular emphasis on the province of Quebec. In 1988, the provincial government of Quebec established the first Canadian body dedicated to technology assessment. Since then, a national coordinating office and several other provincial bodies have developed. The work of these and other evaluation efforts has had a growing influence on technology management decisions, particularly those dealing with procurement of capital-intensive technologies. Expanding this influence into the realm of technology use, especially for low-cost, high-volume technologies, remains a challenge.

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