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PubMed2026

Integrating Next-Generation Sequencing into von Willebrand Disease Diagnostics: Insights from the PCM-EVW-ES Multicenter Project.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by quantitative or qualitative defects in von Willebrand factor (VWF). Diagnosis is challenging and requires integrating bleeding history, VWF antigen and activity measurements, FVIII assays, and specialized phenotyping. Genetic testing is increasingly recognized as a key component. Here, we review current concepts in VWD diagnostics and highlight the Spanish Clinical and Molecular Profile of von Willebrand Disease (PCM-EVW-ES) project as a model for genomics-enabled precision medicine. PCM-EVW-ES is a multicenter initiative involving 48 hospitals, centralized phenotypic testing, and next-generation sequencing of the VWF coding region, enabling definitive classification in 730 individuals with VWD to date. Harmonized recruitment criteria and standardized workflows improve subtype assignment, uncover complex genotypes, refine genotype-phenotype correlations, and facilitate the identification of asymptomatic carriers. The PCM-EVW-ES variant spectrum highlights recurrent disease-causing variants in Spain and underscores the value of coordinated national registries for variant curation. Building on these data, we propose a diagnostic algorithm in which bleeding assessment and first-line VWF/FVIII assays, combined with, early VWF molecular testing increases diagnostic accuracy and guides targeted second-line investigations to confirm and refine VWD subtype classification. We also outline persisting challenges, including the interpretation of variants of uncertain significance and patients without identifiable pathogenic VWF variants, and future directions integrating third-generation sequencing, expanded gene panels, functional studies, and artificial-intelligence-driven multiomic approaches. Together, these advances illustrate how robust multicenter studies can bridge the gap between complex diagnostics and clinical practice in VWD.

Humans↗

PubMed2006

Competition or collaboration--the tensions within the purchaser provider relationship in nurse education.

AIMS: To explore the nature of the relationship between purchasers and providers from the perspectives of the key individuals involved in healthcare education in the late 1990s. To discuss the lessons that can be learned for nursing from their experiences. BACKGROUND: Although the findings illustrate experiences of individuals at a specific time, the issues that arise have implications for contemporary health care, as contract use is increasing and, with the introduction of foundation trusts, contracts may replace Service Level Agreements. METHOD: The design was qualitative and the methods used were policy analysis and interviews. Interviews were conducted with a national, purposive sample of 70 participants. RESULTS: The key finding was the amount of variation in effectiveness of relationships. Many purchasers and providers formed strong partnerships but a number had fraught relationships--a situation perceived as detrimental to productive working. A significant issue for current healthcare was the reasons why relationships worked well in some institutions and were ineffective in others. CONCLUSIONS: There are a number of key lessons that can be learned about the nature of the relationship between purchasers and providers and applied to contemporary health care. Notably: .the value of clear policy aims; .the importance of context and history in shaping the relationship; .the necessity of ensuring that individuals involved have the ability and commitment to make the relationship work; .the need to view the contracting relationship as a dynamic 'project' that must be worked on; .the value of sharing good practice.

Attitude of Health Personnel↗

PubMed1996

Introduction: the many faces of aging: challenges for the future.

In coming decades, the United States will see a major demographic shift as the largest birth cohort in our history approaches its older years; by the year 2030, it has been projected that approximately one-third of the population will be aged 65 or older. Yet the national debate on how we plan to accommodate our aging society is in considerable turmoil. This symposium offers the insights of several leaders in the fields of social work and aging regarding the profound economic, political, and moral implications of the projected changes in society. While medical and technological advances promise greater independence and higher quality of life for some, there is a disturbing trend of economic inequality for future elders. It is expected that the "baby boom" generation will not only bring about major policy changes, but will redefine aging and the search for meaning in what Charles Fahey has termed the "third age." It is certain that the societal values we hold and our commitment to the well-being of our older population today will have a profound impact on what the future holds for old and young alike.

Aged↗

PubMed1989

Value of assessment of ploidy in rectal cancers.

Flow cytometry was performed on available archival material from 232 patients with rectal cancer enrolled in the National Surgical Adjuvant Breast and Bowel Project protocol R-01. Tumor ploidy was not found to be significantly related to such pathologic and clinical parameters as Dukes' stage; nodal status; nuclear or histologic grades; patient's age, sex, or overall survival rate with an average study time of 79 months. A trend was evident that patients with poor histologic grade, or those with Dukes' B and C tumors that were aneuploid fared worse than those with diploid cancers. However, measurements of survival were found to be more strongly and consistently related to such conventional prognostic parameters as tumor differentiation, Dukes' stage, and nodal status. Further, numbers of nodes with metastases (ie, 1 to 4 or 5+) more significantly discriminated Dukes' C cases than estimation of tumor ploidy. Although tumor ploidy may reflect some features of rectal cancers, their natural history and prognosis are explained better by assessment of conventional parameters used for these purposes.

Age Factors↗

PubMed1992

National psychology, national socialism, and analytical psychology: reflections on Jung and anti-semitism. Part II.

The paper is a critical study of the intellectual relations of analytical psychology and national socialism. I try to show that it was Jung's attempt to establish a psychology of nations that brought him into the same frame as Nazi anti-semitic ideology. In addition, Jung was absorbed by the question of leadership, also a pressing issue during the 1930s. Exploring these ideas as thoroughly as possible leads to a kind of reparation, for I think that post-Jungians do have reparation to make. Then it is possible to revalue Jung's overall project in more positive terms. By coupling a less simplistic methodology and a more sensitive set of values to Jung's basic intuitions about the importance of a psychology of cultural difference, analytical psychology has something to offer a depth psychology that is concerned with processes of political and social transformation.

Germany↗

PubMed1997

Prognostic indicators in medical rehabilitation of traumatic brain injury: a commentary and review.

The National Information System (NIS) project is developing consensus opinion regarding a proposed structural framework for the prognostic data to be collected as part of this proposed multicenter research effort on severe traumatic brain injury (TBI). This article provide a brief history of the process, examines challenges facing rehabilitation research in this particular area, discusses reasons for identifying prognostic data within the research context of the NIS project, and describes methodologies for use of mathematical models in predicting outcome from TBI. The literature regarding prognostic parameters in severe TBI is briefly reviewed, utilizing three broad parameter categorizations: preinjury, injury, and postinjury. The implications of this research and directions for further study within the NIS project are discussed.

Brain Injuries↗

PubMed2001

Standardization of immunoassay for CRM-related proteins in Japan: from evaluating CRM 470 to setting reference intervals.

The Japan National Institute of Health (JNIH), in close collaboration with academic societies, commercial companies, and the Japan Society of Medical Technologists, has led in the attempt to standardize plasma protein assays since the mid 1980s. Under a framework of global standardization, they used WHO primary reference materials to reduce discrepancies in values reported for proteins assayed using different systems, thus laying the foundations for a protein immunoassay standardization system in Japan. With the introduction of CRM 470 in 1993, the Japanese Committee for Clinical Laboratory Standards (JCCLS) has taken the initiative in promoting the use of the new material and bringing about the re-evaluation of all systems of quality assurance in clinical laboratories. This eventually led to the establishment of reference intervals in Japanese populations of children and adults after preparation of assigned calibrators from CRM 470 for each assay system. Here we review the history of a series of projects carried out in Japan and describe several remaining problems, through which we will attempt to evaluate the potential value of protein immunoassay standardization.

Adult↗

PubMed2003

Identification of persons at high risk for kidney disease via targeted screening: the NKF Kidney Early Evaluation Program.

BACKGROUND: More than 340,000 individuals were receiving renal replacement therapy in the United States at the end of 1999; this number is projected to double by the year 2010. Almost half had a primary diagnosis of diabetes mellitus particularly type 2, and more than one quarter a primary diagnosis of hypertension. Studies have demonstrated effective maneuvers to prevent or delay the rate of progression of kidney disease, and decrease morbidity and mortality. The objective of early diagnosis is early detection of asymptomatic disease at a time when intervention has a reasonable potential to have a positive impact on outcome. METHODS: In 1997, the National Kidney Foundation launched KEEP trade mark (Kidney Early Evaluation Program), a free community-based screening that targets first order relatives of persons with hypertension, diabetes or kidney disease, and those with a personal history of diabetes or hypertension. RESULTS: Of the 889 individuals screened in the pilot study, 71.4% had at least one abnormality. The program includes an educational component and referral to a physician for follow-up of abnormal values. CONCLUSIONS: Targeted screenings are an effective means of identifying persons at risk for kidney disease, and can identify individuals at risk early enough in the course of their disease to allow for effective intervention.

Early Diagnosis↗

PubMed2004

Screening for diabetes in an African-American community: the Project DIRECT experience.

AIM: To report the results of a community-based screening program associated with Project DIRECT, a multiyear diabetes mellitus prevention and control project targeting African-American residents of southeast Raleigh, NC. METHODS: Between December 1996 and June 1999, 183 screening events took place in community settings. Screening was by capillary glucose concentration. Participants with a positive screen were referred for confirmatory testing and physician follow-up. MAIN RESULTS: Risk factors for diabetes were prevalent, including ethnic minority race (88.2%), obesity (45.6%), and family history of diabetes (41.7%). In all, 197 personshad an elevated screening result; the prevalence of diabetes in the screened population that underwent follow-up testiing was 1.7%. Despite persistent tracking efforts, 28% of the persons with a high screening test received no final diagnosis CONCLUSIONS: In this community-based screening program targeted to high-risk African Americans, risk factors for diabetes were common, but new cases of undiagnosed diabetes among participants were uncommon. Intensive follow-up for persons with high screening values is necessary but difficult to achieve. Our results support national recommendations against community-based screening; opportunistic screening for diabetes in clinical settings is likely a more effective use of resources.

Adult↗

PubMed1992

Birth spacing and child mortality in a Caribbean population.

Ten independent variables were used to predict death before the first birthday for 4411 births that took place from 1878 to 1976 to 978 women of native ancestry on the island of St. Barthélemy. Significant predictors of death include the death of the mother within a year, the birth year, multiple birth, whether the preceding child also died before 1 year of age, and whether the next child was conceived before the index child was 1 year old. Unlike most prior studies, birth-spacing variables were only weakly related to death in the first year. The relative absence of contraceptive techniques to control birth spacing in the study population and the use of vital records rather than survey data distinguish this project from others and may account at least partly for the unusual findings.

Birth Intervals↗

PubMed2003

Palliative care for AIDS at a large urban teaching hospital: program description and preliminary outcomes.

BACKGROUND: Despite major advances in therapy, acquired immune deficiency syndrome (AIDS) remains an important cause of morbidity and mortality in young adult populations. As AIDS has been converted into a chronic disease, it has resulted for some patients in a more protracted course of symptomatic illness. Comprehensive care for late-stage human immunodeficiency virus (HIV) disease now involves an increasingly complex mixture of disease-specific and palliative therapies, requiring coordination and collaboration between AIDS and palliative care services. We describe the experience of developing a palliative care consultation service for patients with AIDS at a large urban teaching hospital, funded by the Health Resources and Services Administration as one of six national demonstration projects for the integration of HIV and palliative care. SETTING: An 1100-bed medical center in the Bronx, New York. The multidisciplinary consultation team included a physician, nurse practitioner, social worker, chaplain, outreach worker, psychiatrist, and ethicist. Patients were referred from inpatient AIDS services and outpatient care sites. METHODS: Patients underwent standardized assessment with clinical case review, Memorial Symptom Assessment Scale (MSAS), Mini-Mental Status Examination (MMSE), Karnofsky score, and Rapid Disability Rating Scale (RDRS). Interventions and follow-up outcomes were recorded and categorized. All deaths were analyzed and predictors of mortality were determined by bivariate and logistic regression analysis. RESULTS: Program referrals have been steady, with 132 patients followed by the consultation service from July 2000 through October 2001; 73% were referred from inpatient services (representing 12% of all AIDS inpatients admitted to the hospital during the study period); 57% of patients were male, 36% African American, 55% Hispanic; 44% had a history of injection drug use. Median baseline values included: CD4+ T-lymphocyte count = 35/mm3, HIV viral load = 53,813 copies per milliliter, Karnofsky = 40, MMSE = 0 (with a median score of 24 for those able to complete the examination); number of severe symptoms reported by MSAS = 4; 71% had one or more serious impairments in activities of daily living (ADL) by RDRS. In addition to AIDS, 20% of patients had malignancies and 13% had end-stage liver disease. Presenting problems and priority issues identified at consultation included: care decisions/goals of care (68%), pain (40%), psychosocial issues (31%), depression (23%), anxiety (19%), nausea/vomiting (14%), insomnia (13%), and patient/family/team conflict (13%); these problems were fully or partially resolved in 68-91% of cases. 63 patients died (median days enrolled = 35); leading causes of death included AIDS (38%), sepsis (19%), cancer (19%), and liver failure/cirrhosis (17%). Death was predicted only by baseline functional status (Karnofsky, MMSE, ADL impairment), and not by CD4+ count, viral load, or any AIDS-specific variables. CONCLUSION: Results suggest an important and ongoing need for palliative care services for patients with advanced HIV/AIDS, whose needs are likely to increase as AIDS evolves into more of a chronic disease. Patients were readily referred from predominantly inpatient settings, with very advanced disease; problems included a mix of medical and psychosocial issues, and were readily resolved by the consultation team in most cases. Death was predicted only by baseline functional status, not by traditional HIV disease markers. Mortality reflected both AIDS-related and non-AIDS-specific causes. Further studies are needed to identify more specific prognostic variables and to continue to improve palliative care treatment outcomes in late-stage patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Methods used to develop clinical guidelines in France. The example of common lumbosciatic syndrome.

A number of Regulatory Medical References, or criteria for quality health care, have been worked out in France by a committee of physicians' union and national health insurance agency representatives, based on clinical guidelines developed using predefined methods. For each guideline, the level of evidence was evaluated, and when this level was inadequate a strong professional consensus was sought. For common lumbosciatic syndrome, the ANDEM (Agence Nationale pour le Développment de l'Evaluation Médicale, or national agency for the development of medical evaluation) worked with a multidisciplinary study group (specialists and nonspecialists, physicians from teaching hospitals, regional hospitals and private practices, primary care practitioners and specialists) whose members were from different areas of France. A computerized and manual literature search was conducted. The project director and the study group chairperson reviewed each document using predefined criteria to evaluate the methodology and level of scientific evidence. When this level was inadequate, a strong consensus expressing an opinion accepted by the medical profession was looked for. Bold type was used to indicate data resting on very high levels of evidence. The committee of physicians' union and national health insurance agency representatives used these documents to select a number of situations for which "regulatory medical references" would be useful. Each reference was written as one or a few sentences starting by "It is inappropriate to...". The study group found that subjectivity and pragmatism significantly influence the selection of diagnostic and therapeutic strategies for common lumbosciatic syndrome. The review and discussion of the high-quality literature on this condition led the study group members to modify their opinions and facilitated the development of a consensus. The group noted the paucity of scientific data on the natural history of common lumbosciatic syndrome and on the value of drug therapy and other commonly used therapeutic modalities.

France↗

PubMed2005

[Application of the Gail method of calculating risk in the population of Valencia].

BACKGROUND: The objective of this study was to verify whether the method defined by Gail is applicable and predictive in a population of women in Valencia (Spain). POPULATION AND METHODS: Of the 685 patients diagnosed with breast cancer and attended-to in 2000-2001, 186 incident cases were identified. The variables studied were obtained from a specific questionnaire which included characteristics of reproductive history, number of biopsies and contraceptive pill consumption prior to the diagnosis. Using the model of the National Surgical Adjuvant Breast and Bowel Project (NSABP), an adaptation of the Gail model, the risk of developing breast cancer at 5 years was estimated. RESULTS: Only 40% of those women diagnosed as having breast cancer would have been identified as a high-risk patient by the Gail method. With our population group, the method detected the elderly women with a medical history of breast cancer who developed advanced stage disease. CONCLUSIONS: The Gail method does not adapt well to the study population of Valencia. It would be necessary to add other risk-factors to the Gail method so as to identify more patients in our area.

Adult↗

PubMed2001

Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiative's Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer.

OBJECTIVE: To assist women and their physicians in making decisions regarding the prevention of breast cancer with tamoxifen and raloxifene. EVIDENCE: Systematic review of English-language literature published from 1966 to August 2000 retrieved from MEDLINE, HealthSTAR, Current Contents and Cochrane Library. VALUES: The strength of evidence was evaluated using the methods of the Canadian Task Force on Preventive Health Care and the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. RECOMMENDATIONS: Women at low or normal risk of breast cancer (Gail risk assessment index < 1.66% at 5 years): There is fair evidence to recommend against the use of tamoxifen to reduce the risk of breast cancer in women at low or normal risk of the disease (grade D recommendation). Women at higher risk of breast cancer (Gail index > or = 1.66% at 5 years): Evidence supports counselling women at high risk on the potential benefits and harms of breast cancer prevention with tamoxifen (grade B recommendation). The cutoff for defining high risk is arbitrary, but the National Surgical Adjuvant Breast and Bowel Project P-1 Study included women with a 5-year projected risk of at least 1.66% according to the Gail index, and the average risk of patients entered in the trial was 3.2%. Examples of high-risk clinical situations are 2 first-degree relatives with breast cancer, a history of lobular carcinoma in situ or a history of atypical hyperplasia. As the risk of breast cancer increases above 5% and the benefits outweigh the harms, a woman may choose to take tamoxifen. The duration of tamoxifen use in such situations is 5 years based on the results from trials of tamoxifen involving women with early breast cancer. If a woman raises concerns or has already been evaluated and is calculated to be at high risk, then individuals experienced and skilled in counselling may discuss the potential benefits and harms of tamoxifen use. Important additional issues: Prevention of breast cancer with raloxifene: Current evidence does not support recommending chemoprevention of breast cancer with raloxifene outside of a clinical trial setting. Screening using the Gail risk assessment index: This index was the main eligibility criterion for enrolling women in the one study that showed potential benefit from chemoprevention. However, it has not been evaluated for use as a routine screening or case-finding instrument; validation of the index is required. Overall, current evidence does not support a shift to its routine use in physicians' offices for screening or case finding. However, when a woman or her physician is concerned about the woman's increased risk of breast cancer, the index can be a useful tool in deciding whether to pursue an in-depth discussion of the potential benefits and harms of chemoprevention. Hence, the approach to identifying women at higher risk who warrant counselling and shared decision-making will vary across practices. (The risk assessment index is available online at http://bcra.nci.nih.gov/brc/). [A patient version of these guidelines appears in Appendix 2.] VALIDATION: The authors' original text was revised by both the Canadian Task Force on Preventive Health Care and the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. The final document reflects a consensus of these contributors. SPONSOR: Health Canada. COMPLETION DATE: February 2001.

Adult↗

PubMed1995

Populations with constant immigration.

"We consider a Leslie-type model of a one-sex (female) population of natives with constant immigration. The fertility and mortality schedule of the natives may be below or above replacement level. Immigrants retain their fertility and mortality, their children adopt the fertility and mortality of the natives. It is shown how this model may be written in a homogeneous form (without additive term) with a Leslie-type matrix. Reproductive values of individuals in each age group are discussed in terms of a left eigenvector of this matrix. The homogeneous form of our projection model permits the transformation into a Markov chain with transient and recurrent states. The Markov chain is the basis for the definition of genealogies, which incorporate immigration. It is shown that genealogies describe the life histories of individuals in a population with immigration. We calculate absorption times of the Markov chain and relate them to genealogies. This extends the theory originally designed for closed populations to populations with immigration." (SUMMARY IN FRE)

Demography↗

PubMed2000

Evaluation of a pilot standard questionnaire for the enhanced surveillance of sporadic cases of suspected food poisoning.

A national survey of local authorities, carried out in 1997, investigated how they dealt with sporadic cases of suspected food poisoning. A standard questionnaire for recording routine follow up information was then designed and piloted for three months in 30 local authorities in England. The questionnaire captured information on clinical and demographic details and exposure histories such as contact with animals, recreational exposure to water, and travel but was less successful at capturing information on domestic catering practices and food consumption. A successful surveillance questionnaire must be designed carefully to gather essential data without overburdening investigating officers.

England↗

PubMed1999

Rinderpest: a case study of animal health emergency management.

The history of rinderpest and control of the disease in Africa and Asia is reviewed briefly. The present distribution of rinderpest virus in relation to its phylogenetic lineages is presented. Rinderpest-free countries bordering rinderpest-infected countries are considered to be under permanent threat of a transboundary rinderpest incursion and therefore face continuous and serious emergency situations. The nature of these emergencies in relation to the remaining foci of the three lineages is described. It is argued that the Global Rinderpest Eradication Programme (GREP) eradication strategies now need to focus on the use of epidemiological studies to define foci of infection and guide targeted, pulsed vaccination campaigns rather than broad, routine vaccination. The emergency posed by the re-emergence of African lineage 2 virus in East Africa and the challenge of mild rinderpest is explored in some detail as a phenomenon which may be more widespread than has been assumed. Points at which the future of GREP is threatened are illustrated and means of removing some of the dangers are suggested. The lessons which need to be learnt from the experience of the Indian National Project on Rinderpest Eradication and the Pan-African Rinderpest Campaign are discussed, including the value of strengthening surveillance systems in accordance with the Office International des Epizooties Pathway and how to cope with the problem associated with cryptic foci of rinderpest persistence--perhaps the greatest challenge facing GREP. The value of vaccine buffer zones is considered in detail and the authors conclude that unless those zones are of considerable depth and are well maintained, they are unlikely to prevent dissemination of the virus. The role of emergency preparedness planning in preventing the spread of rinderpest is discussed, with the understanding that effective surveillance, as a component of emergency preparedness planning, is safer than vaccination as a means of ensuring that the disease does not re-enter or penetrate a population. The swift initiation of a programme for the eradication of rinderpest from Pakistan is seen as the key issue in dealing with the Asian lineage rinderpest emergency. Development and implementation of strategies with the benefit of experience gained in Africa and India could provide a rapid resolution of the emergency.

Africa↗

PubMed2005

Prostate-specific antigen screening in a high-risk population: lessons from the community and how they relate to large-scale population-based studies.

OBJECTIVES: To estimate the incidence of prostate cancer among African-American men and Caribbean immigrants to the United States, to assess the applicability of large-scale prostate screening trials to a community screening program, and to recruit unscreened men. METHODS: African-American and Caribbean-American men were targeted with a community-based prostate cancer screening program in Jamaica, New York. Serum prostate-specific antigen determination and digital rectal examination were used to determine abnormal findings. The incidence of an abnormal screening examination was used to project the incidence of prostate cancer, which was compared with that in other reported trials. RESULTS: The projected incidence of prostate cancer among African-Americans and Caribbean-Americans older than 50 years was 8% and 7%, respectively, similar to that reported in other trials of African-American men. The projected incidence of prostate cancer in Caribbean-American men aged 40 to 49 years was 1%, the same as the high rate reported among Caribbean men. As in other trials, a family history of prostate cancer and age were strong predictors of abnormal findings. Of the recruited men older than 50 years, 58% had never been screened compared with 42% nationally. CONCLUSIONS: Large population-based screening trials have identified ethnic groups at high risk of prostate cancer. This trial detected high rates of abnormal screening findings by targeting ethnicity. The incidence of an abnormal examination was high in Caribbean-American men younger than 50 years old. Finally, this trial successfully recruited underscreened men.

Adult↗