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WHO Expert Consultation on rabies.

More than 99% of all human rabies deaths occur in the developing world, and although effective and economical control measures are available, the disease has not been brought under control throughout most of the affected countries. Given that a major factor in the low level of commitment to rabies control is a lack of accurate data on the true public health impact of the disease, this report of a WHO Expert Consultation begins by providing new data on the estimated burden of the disease and its distribution in the world. It also reviews recent progress in the classification of rabies viruses, rabies pathogenesis and diagnosis, rabies pre- and post-exposure prophylaxis, the management of rabies patients, and canine as well as wildlife rabies prevention and control. Considering the emergence of new lyssaviruses and changes in animal and human rabies epidemiology observed on different continents, the definition of a rabies-free country or area has been revised to assist public health authorities in better assessing the risk of human rabies resulting from contact with animals. Measures aiming at preventing the spread of rabies through the international transfer of animals, mainly with regard to pets, are discussed as well as the new systems in place within and outside WHO to share rabies data and information. As certain tools currently used in rabies prevention and control, such as biologicals, tests for intra vitam and postmortem diagnosis, vaccines and immunoglobulin quality control, need improvement, the report ends by outlining the priorities for basic research, as well as those for operational research for sustainable canine rabies control, including dog population management schemes complying with animal welfare principles. Such operational research is necessary for removing or alleviating the main constraints to rabies control in dogs, as these are the source of most human rabies cases worldwide.

Animals↗

Shared antigenic determinants between human hemopoietic cells and nervous tissues and tumors.

A panel of nine monoclonal antibodies raised against human hemopoietic cells was used for immunohistological labeling of frozen sections of human nervous tissues and tumors. Three antibodies showed a remarkably consistent labeling pattern when tested on 18 samples of normal or reactive tissue, on 31 neurogenic and 17 non-neurogenic tumors in an indirect immunofluorescence technique. VIM C6, an antibody recognizing cells of the granulocyte series, showed surface labeling of normal and reactive glial cells and of all types of glioma regardless of the grade of malignancy. VIT 13, an antibody recognizing activated T-cells, labeled the processes of normal, reactive, and neoplastic glia in a manner very similar to but not identical with glial fibrillary acidic protein (GFAP). VIB C5, an antibody recognizing B cells and granulocytes, showed surface labeling restricted to malignant cells (malignant gliomas and primitive neuroectodermal tumors) and fetal brain, thus recognizing, within the nervous system, an oncofetal antigen. Due to this operational specificity within the nervous system, some of the antibodies described here might have a role as diagnostic markers for CNS tumors. This study confirms and expands previous data that sharing of antigenic determinants by hemopoietic cells and nervous tissue or neurogenic tumors is common. However, the significance of such cross-recognition is still obscure. It is tempting to speculate that cross-reacting auto-antibodies might contribute to tissue damage in some immune-mediated neurologic diseases (myasthenia gravis, multiple sclerosis, CNS involvement in systemic lupus erythematosus) or to impairment of immunoregulation in multiple sclerosis or glioma patients. Furthermore, sharing of surface determinants might be responsible for the dual tissue tropism of some viruses, including the lymphotrophic virus (HTLV) in the encephalopathy of the acquired immune deficiency syndrome (AIDS).

Antibodies, Monoclonal↗

Differences in cancer mortality trends between four neighboring north-eastern areas and Italy, 1970-1990.

AIMS AND BACKGROUND: The present report combines descriptive statistics (partly never published) on four neighboring areas of north-eastern (NE) Italy [Friuli-Venezia Giulia (1970-89) and Veneto (1970-87) regions and the provinces of Trento (1970-89) and Bolzano (1971-90)], and all Italy (1970-89). The aim was to highlight potential differences in mortality trends and promote a more systematic sharing of data and methodologies. METHODS: Death certificates stratified by cause, sex, age and residence were obtained from official publications of the Italian Central Institute of Statistics. Absolute numbers of deaths from different causes, age-standardized rates (on the basis of the European standard population) and percentage of change over the examined period for both sexes were computed for each geographic area. RESULTS: Unfavorable trends were seen for neoplasms of the upper aerodigestive tract, lung, breast, colorectum, bladder, kidney and pancreas and cutaneous malignant melanoma. Increases in most of these neoplasms were more marked in the 4 NE areas than in Italy, especially with respect to cancers of the upper aerodigestive tract in both sexes and cancer of the lung and ovary in women. In Bolzano, rates of neoplasms associated with tobacco and alcohol consumption were lower and less steeply increasing than in the other NE areas, most notably Trento, therefore, contributing to produce the lowest overall cancer mortality rates of NE areas. Cancers of the stomach, uterus, and testis and Hodgkin's disease presented consistent downward trends in all examined areas. CONCLUSIONS: The analysis of mortality trends across areas is consistent with elevated and still increasing cancer rates in the 4 NE areas considered, especially for tobacco and alcohol-related neoplasms and skin melanoma. Preventive strategies, based on epidemiologic knowledge, especially against tobacco and heavy alcohol consumption, and intense intermittent sun exposure, seem to be priorities and may benefit from systematic sharing of information, expertise and intervention tools in NE Italy. At least part of the lack of cancer deaths in Bolzano must be attributable to the deaths of Bolzano residents abroad (especially in Austria) and/or to differences in coding practices. This should be elucidated in future studies.

Age Distribution↗

Health benefits offer rates: is there a nonresponse bias?

OBJECTIVE: To determine whether a nonresponse bias exists in the offer rate for health benefits in firms with fewer than 50 workers and to present a simple adjustment to correct for observed bias. DATA SOURCES: The 2003 Employer Health Benefits Survey (EHBS) conducted by the Kaiser Family Foundation and Health Research and Educational Trust, and a follow-up survey of nonrespondents to the 2003 EHBS. STUDY DESIGN: We conducted a follow-up survey to the 2003 EHBS to collect health benefits offering data from firms with fewer than 50 workers. We used McNemar's test to verify that the follow-up survey provided results comparable to the EHBS, and t-tests were used to determine nonresponse bias. We applied a simple weighting adjustment to the EHBS. DATA COLLECTION: The data for both the EHBS and the follow-up survey were collected by the same survey research firm. The EHBS interviews the person most knowledgeable about the firm's health benefits, while the follow-up survey interviews the first person who answers the telephone whether they are the most knowledgeable or not. Principal Findings. Firms with 3-9 workers were more likely to exhibit a bias than were firms with 10-24 workers and 25-49 workers. Although the calculated bias for each size category was not significant, there is sufficient evidence to warrant caution when reporting offer rates. CONCLUSIONS: Survey nonresponse in the EHBS produces an upward bias on estimates for the offer rates of small firms. Although not significant, this upward bias is because of nonresponse by small firms that do not offer health benefits. Our research is limited in that we only control for differences in the size of the firm.

Adult↗

Genetic and environmental influences on MMPI factor scales: joint model fitting to twin and adoption data.

In general, the shared family environment appears to play a negligible role in determining individual differences in personality and interests. Nevertheless, scattered reports of significant shared environmental influence on such variables appear in the literature. Using data from the Texas Adoption Project (TAP), the current study attempted to replicate twin study findings of significant shared environmental variance on four of nine Minnesota Multiphasic Personality Inventory (MMPI) factor scales (Rose, 1988). Conventional behavioral genetic analyses of the adoption data agreed in affirming a significant shared environmental influence on individual differences in Religious Orthodoxy only. Subsequent simultaneous modeling of Rose's twin data and TAP adoption data resulted in three scales (Extraversion, Inadequacy, and Religious Orthodoxy) showing significant shared environmental influence. Again, effects were most substantial for Religious Orthodoxy, where the shared environment accounted for nearly 50% of the variance. It is argued that assortative mating cannot explain this finding.

Adolescent↗

New dimensions of economic well-being among people with mental illness: evidence from Healthcare for Communities.

OBJECTIVE: To analyze the relationship between mental health and savings and compare it to the relationship between common chronic physical conditions and savings. DATA SOURCE: Healthcare for Communities, a national survey conducted in 1997/1998 with approximately 10,000 respondents. STUDY DESIGN: We used logistic regression to analyze any savings versus no savings and used ordinary least squares regression to study level of savings conditional on having any savings. PRINCIPAL FINDINGS: Individuals screening positive for any mental health disorder are less than two-thirds as likely as individuals with no mental health problems to have any savings. The percent age of savers declines with age among those with a probable mental health condition, compared to a rise with age among other individuals, including those who are chronically physically ill. CONCLUSION: The main finding is less the sizeable gap in the percentage of savers among individuals who have and do not have a mental disorder th an the strong interaction with age. Older individuals with mental health conditions are at particular risk for having no savings and are at more risk than individuals in poor physical health . Low levels of saving among older individuals with mental health problems become particularly problematic when these individuals transition into Medicare. With limited household wealth, these individuals are the group least likely to be able to afford supplemental insurance that covers medications and least likely to be able to afford the out-of-pocket costs for newer psychotropic medications.

Adult↗

The equity impacts of community financing activities in three African countries.

Although the Bamako Initiative from its very beginning was caught up in wider debates about the potential equity impact of any form of user financing, to date there has been little empirical investigation of this impact. This three-country study, undertaken in Benin, Kenya and Zambia in 1994/95, was initiated to add to the body of relevant evidence. It sought to understand not only what had been the equity impacts of community financing activities in these countries but also how they had been brought about. As a result, it investigated equity primarily through consideration of the design of these financing activities and through the perceptions of different actors, within a limited number of purposively selected geographical areas in each country, about their strengths and weaknesses. Additional data on utilization were either collected during the course of the study (Kenya) or drawn from other available studies (Benin and Zambia). Key issues considered in the studies' assessment of equity were the extent to which both relative and absolute affordability gains were achieved, as well as as an influence over both the distributional and procedural justice of the financing activities, the pattern of decision-making. Across countries there was evidence of relative affordability gains in Benin and Kenya, but Kenyan gains were not sustained over time and no such gains were identified in Zambia. In addition, no country had given attention either to the issue of absolute affordability, through the implementation of effective exemption mechanisms to protect the poorest from the burden of payment, or to the establishment of community decision-making bodies that effectively represented the interests of all groups including the poorest. Overall, therefore, although the Benin Bamako Initiative programme might be judged as successful in terms of what appear to be its own equity objectives, the other two countries' schemes had clear equity problems even in these terms. The experience across countries also highlights the unresolved question of whether equity is concerned with the greatest good for the greatest number or with promoting the interests of the most disadvantaged.

Benin↗

Eligibility for the Medicare buy-in programs, based on a survey of income and program participation simulation.

Medicare buy-in programs are designed to reduce out-of-pocket expenses of beneficiaries with modest income and assets. This article provides estimates of the size of the Medicare beneficiary population eligible for the Qualified Medicare Beneficiary (QMB) program, the Specified Low-Income Medicare Beneficiary (SLMB) program, and the Qualified Individual-1 (QI-1) program. The buy-in programs use the same resource limits (twice those used in the Supplemental Security Income (SSI) program) but different thresholds for determining income eligibility. The QMB program uses 100 percent of the poverty line as the cutoff, QI-1 covers persons above 120 percent but at or below 135 percent of the poverty line, and the SLMB program is in between. Making informed judgments about the rate of participation in the buy-in programs and the need for outreach requires an accurate estimate of the size of the eligible population. If that population is underestimated, policymakers might come to unduly optimistic conclusions about current buy-in participation. In contrast, an overestimate may make current participation seem too low. If policymakers react to an upwardly biased estimate of the eligible population by increasing outreach, they are bound to be disappointed by the results of that effort. Estimates of the eligible population from past studies of the QMB and SLMB programs range from 5.1 million to 9.1 million. In the absence of new information, it is difficult to judge the accuracy of those estimates because the methodologies had substantial shortcomings that might bias the results. The most common shortcomings include the lack of high-quality, monthly income data and the lack of information on assets from the same data file that was used to estimate participation and income eligibility for Medicare. The current study uses the most recently available (as of August 2000) Survey of Income and Program Participation (SIPP) file that is matched to the Social Security Administration's (SSA's) administrative records. The data file covers 1995 information. Estimates were also obtained using 1991 data to assess the sensitivity of eligibility estimates to the year chosen. The SIPP has several major advantages over other data sources because it contains relevant, high-quality information on both income and assets for establishing financial eligibility for the buy-in programs. First, the SIPP collects detailed and conceptually appropriate information on monthly, rather than annual, income and therefore has more complete information about income than do other surveys. As a result, SIPP-based estimates of poverty are substantially lower than estimates based on the Current Population Survey. Second, the SIPP also collects information on assets at the individual level. Thus, the survey provides enough detail to measure the major income and asset exclusions directly. Finally, the SIPP data are matched to SSA administrative records: Medicare eligibility can therefore be accurately measured, and self-reported data on Social Security and SSI benefits can be replaced with more accurate monthly information. Our 1995 simulation estimates that approximately 4.8 million persons in the U.S. noninstitutionalized population were eligible for the QMB program and an additional 1.6 million for the SLMB program. The total--roughly 6.5 million--is within the range of estimates from past studies but is closer to the lower end, suggesting that the eligible population is smaller than was previously believed. When the estimated QI-1 eligible population of 0.9 million is added, the total for the three buy-in programs is 7.4 million. Because the QI-1 program did not exist in 1995, only the estimated 6.5 million QMBs and SLMBs would actually have been eligible to receive benefits. The 7.4 million figure represents the 1995 Medicare beneficiaries who would be eligible for buy-in under program rules for 2000. Adjusting that number to account for increases in the Medicare population between 1995 and 1999 yields an estimated eligible population of 7.8 million in 1999. Compared with other elderly Medicare recipients, eligible elderly QMBs and SLMBs have poorer health, more functional limitations, and higher rates of health care use. Thus, not only are their income resources relatively limited, but their need for potentially expensive medical care is also greater. Similar differences were not found in health, functional limitations, and health care use among disabled participants in the QMB and SLMB programs. Our estimates imply that about 2.5 million noninstitutionalized individuals were eligible for but not enrolled in the QMB and SLMB programs in 1999. That finding suggests that fewer eligibles may be available for targeting by outreach efforts than was previously believed. Outreach may be more difficult than it would be with a larger eligible population. (ABSTRACT TRUNCATED)

Adolescent↗

Population cancer screening.

Controlled trials to evaluate mass screening programs for cancer detection have been singularly lacking. High cost, lack of medical manpower, and low yield have contributed to this problem. A new program in cancer detection (CANSCREEN) has been developed jointly by The Fox Chase Cancer Center in Philadelphia and the Preventive Medicine Institute in New York City. This program attempts to provide a quality cancer-detection examination with increased cost effectiveness. Features include: 1) a self-administered questionnaire on medical history, symptoms, and risk factors; 2) nonphysican examiners; 3) risk-facotr analysis with a predetermined decision logic to determine type and periodicity of examination; and 4) primary intervention (health education). This collaborative program between two institutions in two cities demonstrates the feasibility of introducing similar programs elsewhere. A data base shared by cooperating centers permits information on all patients to be used for evaluation of new techniques, end results, etc. A randomized controlled trial has been designed to evaluate the effectiveness and efficiency of the questionnaire alone and of the questionnaire and examination.

Breast Neoplasms↗

Ethical issues concerning genetic testing and screening in public health.

Genetic testing (predictive analysis that determines genetic alterations in individuals for clinical purposes) and screening (programs that identify persons within a subpopulation who may be at a higher risk for a genetic disease or condition) are increasingly utilized to promote and improve the public's health. The proliferate use of genetic testing and screening may improve public health outcomes, but it also implicates significant ethical, legal, and social concerns. Within the context of conflicting ethical values from the individual and public health perspectives, individual values such as informed consent and privacy and discrimination protections must be respected. Legal and ethical attempts to exceptionalize genetic tests and information (as compared to other health information) to protect privacy and prevent discrimination are well intended, but can also be unjust and impractical. Respect for individual ethical rights has limits. Principles of public health ethics justify voluntary genetic testing and screening and sharing of data for population-based health purposes. Thus, individual rights should not always trump the use of genetic tests or screening programs (or information derived therefrom) for legitimate public health purposes.

Bioethics↗

Terbinafine-induced hepatic failure requiring liver transplantation.

Drug-induced liver disease accounts for about 50% of acute or subacute liver failure in the United States. United Network of Organ Sharing (UNOS) data suggest 8%-20% of liver transplantation in this country per year is for fulminant liver failure due to drugs. Even though the most common medication implicated in acute liver injury is acetaminophen (75%), there are numerous other drugs that are responsible for acute and chronic liver injury. A variety of antifungal medications are known to cause a wide range of liver injury from a mild hepatocellular-cholestatic injury pattern to acute/subacute liver failure. Terbinafine is one of the antifungals that have been associated with such liver injuries. We report a case of terbinafine-induced severe liver failure requiring liver transplantation.

Acetaminophen↗

Prediction of disulfide connectivity from protein sequences.

The difficulties in predicting disulfide connectivity from protein sequences lie in the nonlocal properties of the disulfide bridges that involve cysteine pairs at large sequence separation. Though some progress has been recently made in the prediction of disulfide connectivity, the current methods predict less than half of the disulfide patterns for the data set sharing less than 30% sequence identity. In this report, we use the support vector machines based on sequence features such as the coupling between the local sequence environments of cysteine pair, the cysteines sequence separations, and the global sequence descriptor, such as amino acid content. Our approach is able to predict 55% of the disulfide patterns of proteins with two to five disulfide bridges, which is 11-26% higher than other methods in the literature.

Cysteine↗

Cross-reactivity between human hemopoietic cells and brain tumors as defined by monoclonal antibodies.

A battery of 24 monoclonal antibodies raised against human hemopoietic cells was tested in an indirect immunofluorescence technique on frozen sections of a variety of human neurogenic and non-neurogenic tumors. Twelve antibodies demonstrated some type of labeling of neurogenic tumors, frequently in patterns characteristic for benign and/or malignant gliomas and/or primitive neuroectodermal tumors (PNETs). Although also some cross-reactivity occurred in non-neurogenic tumors, the apparent operational specificity of some of our antibodies within the nervous system promises some aid in neuropathological tumor diagnosis; this was also demonstrated by combined use of some antibodies on smear preparations in which diagnosis by conventional stains was uncertain. This study confirms and expands previous data that sharing of antigenic determinants by hemopoietic cells and nervous system tumors is common. The significance of these cross-reactivities is at present a matter of speculation; cross-reacting autoantibodies might interfere with immune regulation in tumor patients, and an immune response might be initiated when glioma cells bearing Ia antigens present tumor-associated antigens to T cells.

Adolescent↗

Use of homology domains in sequence similarity detection.

We have found the detection of homology domains using a nonlinear similarity score and the DD algorithm to be a useful approach for identifying similarity between sequences and evaluating potential homology. There are several reasons for the success of the method. (i) Homology domains are identified by a rigorous method that guarantees they will be locally optimal. (ii) The relative significance of different homology domains can be directly compared using the nonlinear similarity score. (iii) Different cost matrices can be used in the calculation of the similarity score. (iv) Relatively long sequences can be compared in a single pass as storage requirements are proportional to the shorter of the two sequences being compared. (v) The method has proved to be very sensitive in practice. (vi) The boundaries of authentic regions of homology are accurately identified. (vii) The information required to define a homology domain (its location, size, similarity score, etc.) can be stored in a compact data structure, facilitating the sharing of homology domain data among different software tools. (viii) The method can be applied to similarity searches of the nucleotide and protein sequence data banks. These properties make the identification of homology domains for studying sequence similarity a useful companion to other accepted methods, such as dynamic programming based analyses.

Animals↗

Public attitudes to charging for some National Health Service services.

This report describes the views of members of the public to proposals to charge for a given list of NHS services for which no charges are currently made. The questions were part of a survey conducted in Cardiff in 1986. The majority of respondents would agree with the suggested charges being levied. This agreement spanned all sections of society. Despite the majority in favour, the sample was divided with a third of respondents being strongly for nearly all the charges and a quarter being strongly against all or all but one of the charges. Most respondents to the survey are judging each charge as a separate issue rather than indicating either approval or disapproval for all cases. If charges for services were to be introduced there could be majority agreement but each charge would have to be considered as a separate issue.

Adult↗

A home health record for children with chronic health conditions.

A Home Health Record was developed to assist parents in organizing health care information about their children who have disabilities or chronic health conditions. This record serves as a health summary to be used during travel, periods of respite care, and by grown children as they become independent health care consumers. It is intended to facilitate parent and professional collaboration, support family-centered care, and improve communication between professionals. Parents are encouraged to carry the record with them to all of their child's medical appointments to document pertinent information and to share health data with professionals.

Child↗

TERMTrial--terminology-based documentation systems for cooperative clinical trials.

Within cooperative groups of multi-center clinical trials a standardized documentation is a prerequisite for communication and sharing of data. Standardizing documentation systems means standardizing the underlying terminology. The management and consistent application of terminology systems is a difficult and fault-prone task, which should be supported by appropriate software tools. Today, documentation systems for clinical trials are often implemented as so-called Remote-Data-Entry-Systems (RDE-systems). Although there are many commercial systems, which support the development of RDE-systems there is none offering a comprehensive terminological support. Therefore, we developed the software system TERMTrial which consists of a component for the definition and management of terminology systems for cooperative groups of clinical trials and two components for the terminology-based automatic generation of trial databases and terminology-based interactive design of electronic case report forms (eCRFs). TERMTrial combines the advantages of remote data entry with a comprehensive terminological control.

Clinical Trials as Topic↗

Averting iatrogenic hypoglycemia through glucose prediction in clinical practice: progress towards a new procedure in diabetes.

BACKGROUND: Hypoglycemia is a risk factor common to all insulin therapy. The hypothesis is that efforts to reduce or prevent this adverse side effect may fail because providers generally lack the resources to predict not only future blood glucose levels but also future risks of hypoglycemia. This lack has been remedied. A controlled study was undertaken to test the hypothesis. METHODS: Twenty-two insulin dependent subjects suffering more than one (1) episode/week of hypoglycemia with similar insulin regimens, similar diabetes education and similar self-management training participated in this study. For all subjects, a remote monitoring resource (registry and database) was used to capture daily SMBG and afford a return path for provider interventions and decision support. Identical telemedical methods were used which differed only for the provider either by the presence (prediction group) or by the absence (control group) of an on-screen, visual display of predicted glycemia and predicted risks of hypoglycemia. The study lasted 2 months. RESULTS: Over an average of 41 days from baseline to follow up and while using the glycemic prediction resource, providers intervened more effectively in the prediction group reducing rates of hypoglycemia nine-fold (P<0.0001) and insulin therapy by just -9 U/day (P<0.01). Mean pre-meal glycemia was not compromised. Over 61 days from baseline to final follow up but without glycemic predictions in the control group, providers' interventions were less effective and resulted in no net changes in rates of hypoglycemia, daily insulin therapy, or mean pre-meal glycemia. CONCLUSIONS: Given knowledge of future glycemia and future risks of hypoglycemia, providers in clinical practice can now avert iatrogenic hypoglycemia in less than 2 months. A shared diabetes data center furnishing remote data capture and decision support is fundamental to the implementation of this as a new clinical procedure in diabetes.

Adolescent↗