High-risk Members Research Articles

Study of the RET gene and his implication in thyroid cancer: Morocco case family

Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant inherited cancer syndrome that affects multiple tissues derived from the neural crest. Inheritance of MTC is related to the presence of specific mutations in the RET proto-oncogene. Almost all mutations in MEN 2A involve one of the cysteines in the extracellular domain of the RET receptor. The objective of the present study was the biochemical and molecular characterization of the first Moroccan clinically established MEN 2A patient and at-risk family members. This is a study on a family presented with MTC referred to our institute in 2004. Peripheral blood leukocyte DNA samples were isolated and amplified by polymerase chain reaction followed by restriction enzyme analysis and DNA sequencing. We identified a heterozygous germ line missense mutation at codon 634 of exon 11 in the RET gene that causes a cysteine to arginine amino acid substitution in the DNA of the proband; this mutation was not found in the DNA of the parents or relatives. The detection of mutated MEN 2A gene carriers enables us to differentiate high-risk members from those who bear the wild-type gene. Occasionally, application of RET proto-oncogene testing may lead to the detection of unexpected de novo mutation that could be transmitted to children.

Resectability rate of hepatocellular carcinoma in rural southern Africans.

The purpose of this analysis was to ascertain the resectability rate of symptomatic hepatocellular carcinoma in rural southern African black males. All 224 such patients proven to have hepatocellular carcinoma in a single hospital were included in the study. Of 205 patients undergoing a complete diagnostic work-up, 134 [65.3 per cent) were judged on clinical criteria to be inoperable, 23 (11.2 per cent) had pulmonary or osseous metastases, and 38 (18.5 per cent) proved on hepatic imaging and 5 (2.4 per cent) on hepatic arteriography to have an irresectable tumour. Thus, only five (2.4 per cent) of these patients proceeded to laparotomy. Another 7 patients who did not have an arteriogram, 9 with surgical emergencies, and 2 mistakenly believed to have an amoebic hepatic abscess also underwent laparotomy. Only 2 patients (0.9 per cent of 223) proved to have a resectable tumour. The extremely low resectability rate reinforces the urgent need for a surveillance programme to detect early tumours in high-risk members of this population.

PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation

Parkinson's disease may arise from multiple aetiologies, including genetic mutations that are for the most part uncommon. We describe here the positron emission tomography (PET) findings in clinically affected and asymptomatic, high-risk members of two autosomal dominantly inherited Parkinson's disease kindreds with recently described mutations at the PARK8 locus, in a novel gene encoding a leucine-rich repeat kinase (LRRK2). Affected family members have L-dopa-responsive parkinsonism with loss of dopaminergic nigral neurons and pleomorphic subcellular pathology. Fifteen family members underwent PET using: 18F-6-fluoro-L-dopa (18F-dopa) to assess dopamine (DA) synthesis and storage, 11C-(+/-)-dihydrotetrabenazine (11C-DTBZ) for the vesicular monoamine transporter, and 11C-d-threo-methylphenidate (11C-MP) for the membrane dopamine transporter (DAT). Measurements were compared with normal (n = 33) and sporadic Parkinson's disease (sPD) (n = 67) control groups. Four clinically affected members had findings similar to sPD, with impaired presynaptic DA function affecting the putamen more than the caudate. In two affected members, D2 dopamine receptor binding was intact. Two asymptomatic mutation carriers had abnormal DAT binding with another two developing such abnormalities over 4 years of follow-up. In these individuals, 18F-dopa uptake remained normal, although two of them also displayed abnormal 11C-DTBZ binding. Our study demonstrates that the in vivo neurochemical phenotype of LRRK2 mutations is indistinguishable from that of sPD, despite the pathological heterogeneity of the condition. Furthermore, we suggest that compensatory changes including downregulation of the DAT and upregulation of decarboxylase activity may delay the onset of parkinsonian symptoms.

Identifying future repeat danger from sexual offenders against children: A focus on those convicted and those strongly suspected of such crime

This study provides a 14 – 16-year criminological follow-up, to the end of 2003, of all those convicted or strongly suspected of committing sexual offences against children in one English county, Lancashire, between 1987 and 1989 (inclusive). The main analysis focuses on 124 males (40%) convicted compared with 188 males (60%) strongly suspected but not convicted. The age and sex of the victims and the relationship between offender and victim show no significant association with conviction status, but the former group tend to be older. Of the 103 convicted adult males, 20% were reconvicted for a sexual offence, whereas of the 116 adult males strongly suspected but not convicted, 9% had a subsequent conviction for a sexual offence. However, the difference is largely explained by their predicted risk scores. The risk assessment tool used, Static-99, is shown to be remarkably effective in identifying high-risk members of the two groups. The 93 convicted and strongly suspected males in the total sample aged under 18 tend to offend against acquaintances (54%), and target a female victim (69%) and a younger (5 – 7 years) age group of children (48%). The convicted young males had a higher rate of subsequent sex convictions (14.3%) than those suspected but not convicted (1.4%). The policy implications of the findings are addressed.

Reducing eating disorder risk factors in sorority members: A randomized trial

Although sororities are often perceived as contributing to eating-disordered behavior, limited research has investigated eating disorders in sorority members. The purpose of this study was to investigate the utility of a highly interactive cognitive dissonance prevention program in reducing empirically supported risk factors in sorority members. Members (N = 149) were randomized to the highly interactive intervention, a more passive intervention, or wait-list. Results indicated that both interventions reduced dietary restraint, body dissatisfaction, and eating disorder pathology. Only the highly interactive group reduced thin-ideal internalization as compared to wait-list. Exploratory analyses also indicated that interventions were beneficial to both lower- and higher-risk members. Taken together, results suggest that sororities are a viable population to target in the prevention of eating disorders.

Ensuring quality of highest-risk population care management in a teleworking environment.

Abstract Disease management (DM) has been shown to improve the care process and health outcomes for individuals with particu-lar chronic conditions, but what about people who struggle with several chronic conditions and are at greatest risk for imminent hospitalization? Even the most effective DM initiatives do not always reach health plan members with maximum risks and impending costs. Single-condition DM programs may not always fully address the multiple medical and psychosocial issues prevalent among highest-risk members.

Ensuring quality of highest-risk population care management in a teleworking environment

Disease management (DM) has been shown to improve the care process and health outcomes for individuals with particu-lar chronic conditions, but what about people who struggle with several chronic conditions and are at greatest risk for imminent hospitalization? Even the most effective DM initiatives do not always reach health plan members with maximum risks and impending costs. Single-condition DM programs may not always fully address the multiple medical and psychosocial issues prevalent among highest-risk members.

Colorectal cancer screening

Colorectal cancer occurs throughout the world. Little is known about the etiology of this disease, however, adequate data exist to recommend secondary prevention with mass screening of average risk asymptomatic people age 50 or over. Three randomized controlled trials of a guaiac test for fecal occult blood involving over 250,000 participants found significant reductions in colorectal cancer mortality from both annual and biennial screening. Results from observational studies are consistent with the results from the randomized trials. Therefore, a screening recommendation for a fecal occult blood testing can be justified based on the overwhelming scientific evidence. A compelling argument can be made to use an immunochemical rather than guaiac test, since data suggests that immunochemical tests may be more sensitive and more specific than guaiac tests. Colorectal cancer mortality reductions of at least 33% can be attained with annual fecal occult blood testing. Biennial screening will result in reductions of at least 15 to 20%. There is insufficient evidence to justify either flexible sigmoidoscopy or colonoscopy for mass screening of an average-risk asymptotic population. However, there is justification for colonoscopic evaluation of high-risk members of the population.

Cost-Effectiveness of a Targeted Disinfection Program in Household Kitchens To Prevent Foodborne Illnesses in the United States, Canada, and the United Kingdom

Foodborne illnesses impose a substantial economic and quality-of-life burden on society by way of acute morbidity and chronic sequelae. We developed an economic model to evaluate the potential cost-effectiveness of a disinfection program that targets high-risk food preparation activities in household kitchens. For the United States, Canada, and the United Kingdom, we used published literature and expert opinion to estimate the cost of the program (excluding the educational component); the number of cases of Salmonella, Campylobacter, and Escherichia coli O157:H7 infections prevented; and the economic and quality-of-life outcomes. In our primary analysis, the model estimated that approximately 80,000 infections could be prevented annually in U.S. households, resulting in $138 million in direct medical cost savings (e.g., physician office visits and hospitalizations avoided), 15,845 quality-adjusted life-years (QALYs) gained, $788 million in program costs, and a favorable cost-effectiveness ratio of $41,021/QALY gained. Results were similar for households in Canada and the United Kingdom (Can $21,950/QALY gained and £86,341/QALY gained, respectively). When we evaluated implementing the program only in U.S. households with high-risk members (those less than 5 years of age, greater than 65 years of age, or immunocompromised), the cost-effectiveness ratio was more favorable ($10,163/QALY gained). Results were similar for high-risk households in Canada and the United Kingdom (Can$1,915/QALY gained and £28,158/QALY gained, respectively). Implementing a targeted disinfection program in household kitchens in the United States, Canada, and the United Kingdom appears to be a cost-effective strategy, falling within the range generally considered to warrant adoption and diffusion (<$100,000/QALY gained).

HUMAN HEALTH SIGNIFICANCE OF ORGANOCHLORINE AND MERCURY CONTAMINANTS IN JAPANESE WHALE MEAT

The concentrations of total mercury, polychlorinated biphenyls (PCBs), and organochlorine pesticides ( DDT, dieldrin, hexachlorobenzene [HCB], and HCH) were determined in 61 whale meat products (bacon, blubber, red meat, liver, intestine, and tongue) purchased from retail outlets across Japan. Mean (range) concentrations of contaminants in all samples were: total mercury 4.17 (0.01-204); PCB 1.14 (0-8.94); DDT 0.98 (0-7.46); dieldrin 0.07 (0-0.35); HCB 0.06 (0-0.22); and HCH 0.07 (0-0.19) g/g (wet weight). The data were used to calculate estimated daily intakes (EDIs) of contaminants at two hypothetical levels of whale meat consumption. These EDIs were compared with FAO/WHO "tolerable daily intake" (TDI) values for each chemical. EDIs calculated for higher levels of whale meat consumption were in some cases exceptionally high and for many products exceeded FAO/ WHO-TDIs for total mercury, PCBs, and dieldrin, with exceedance factor values (EDI/TDI) for total mercury, PCBs, and dieldrin reaching maxima of 175, 5.36, and 2.1, respectively. For sensitive consumers and those with high-level consumption (e.g., whaling communities), exposure to mercury and to a lesser extent PCBs from certain whale blubber and bacon and striped dolphin liver products could lead to chronic health effects. The Japanese community should therefore exercise a precautionary approach to the consumption of such foods in excess, particularly by high-risk members of the population.

Genetik des malignen Melanoms der Haut - Aktueller Wissensstand und klinische Anwendungen -

In malignant melanoma as in many other malignancies the process of tumorigenesis and tumor progression appears to result from the accumulation of multiple genetic lesions. Linkage analyses in melanoma families gave evidence for at least three predisposing genes. Besides an infrequently altered CDK4 gene two other still unknown genes may be located in the bands 1p36 and 9p21. Recent data indicate that the p16 (CDKN2) tumor suppressor gene may be involved in very early stages of melanoma progression. It has been shown that an association with particular variants of the Melanocortin-1 Receptor gene modifies and increases melanoma risk. An inactivation of genes not yet identified on 6q, 10q and 10p seems to be involved in later progression stages. However, these genetic alterations could not be associated with clinically defined stages of melanoma progression such as radial growth (RGP) or vertical growth phase (VGP). Paralleling findings in other malignancies loss of genetic material of chromosome bands 1p36 and 11q23-25 as well as gain of bands of chromosome 7 seem to be associated with the capability to metastasize. These findings have already been applied to identify high risk members of melanoma families. In near future molecular data might provide prognostic information in patients with sporadic melanoma.

When Should Programs for Teen Parents and Babies Begin? Longitudinal Evaluation of a Teen Parents and Babies Program

Confirmed child abuse and neglect rates were assessed for a group of 204 low-income, low-education adolescent mothers several years after identification of the teens either as low-risk or as high risk/low-support and eligible for 18 to 27 months of home-visitation by trained child development specialists. Three groups were studied: Low-risk Contrast Group, High-risk Program Graduates, and a Dropout Comparison Group—the last group being formed unintentionally when some participants dropped out of the high risk program. The major finding of this study is that acceptance of high-risk mothers into program prior to the infant's birth made a significant difference in preventing later child abuse/neglect. Child abuse/neglect rates and subsequent parity rates were not different between high-risk program graduates and low-risk contrast group members. Both of these groups differed significantly on these two rates with the Dropout Comparison Group. However, due to the unknown nature of this comparison group, more research is needed to understand this finding. Program costs were significantly lower than county foster care costs for children placed because of child abuse. Thus, prenatal initiation of program for high-risk pregnant adolescents may provide a cost-effective boost for family mental health and prevent child abuse and neglect by at-risk families.

Inherited Pancreatic Cancer: Surveillance and Treatment Strategies for Affected Families

Background: Nearly 10% of pancreatic cancers are hereditary in origin, and in some individuals, the risk of pancreatic cancer approaches 50%. A number of defined syndromes can predispose families to pancreatic cancer, although many of the mechanisms that result in familial pancreatic cancers are unknown. This article reviews current knowledge regarding familial pancreatic cancers and highlights the rationale for screening and surveillance. Methods for screening and surveillance of these high-risk individuals are described that allow the detection of pancreatic dysplasia, the precursor to pancreatic cancer. We also describe a single-center experience with the management and surveillance of familial pancreatic cancer kindreds. Methods: Thirty-five patients from 13 familial pancreatic cancer kindreds underwent screening and/or surveillance. Endoscopic ultrasound (EUS) is the initial test of choice. Endoscopic retrograde cholangiopancreatography (ERCP) is reserved for symptomatic individuals or to investigate abnormal findings on EUS. In the proper clinical setting, patients with abnormal findings on both EUS and ERCP are candidates for total pancreatectomy. Results: Twelve of 35 patients were noted to have abnormal findings on EUS and ERCP. All of these individuals underwent pancreatectomy, 10 total and 2 partial. The patients who underwent partial pancreatectomy are currently awaiting resection of the pancreatic remnant. Histopathologic examination of all 12 specimens demonstrated pancreatic dysplasia (the precursor lesion to pancreatic cancer). These specimens had no evidence of pancreatic cancer; nor were any of the resected pancreata normal. Follow-up of the 35 high-risk patients at present varies from 1 to 48 months, and none of the patients under surveillance have developed pancreatic cancer. Conclusion: The screening and surveillance of high-risk members of familial pancreatic cancer kindreds using EUS and ERCP is an effective method for identifying individuals with pancreatic dysplasia prior to the onset of invasive pancreatic cancer. The surveillance needs to be performed by a team of specialists who have experience in dealing with pancreatic cancer and its precursors.

A Statistical Analysis of Mandatory Pooling across Health Insurers

Risk-adjusted capitation payments from a central fund to competing health insurers or health plans form an essential feature of market-oriented healthcare reforms in many countries. If these premium-replacing payments do not adequately reflect risk, it may lead to solvency problems for plans with relatively many high-risk members and to selection against such individuals. Mandatory pooling across insurers may alleviate both problems by making the market as a whole financially responsible for high-cost or high-risk individuals. To finance the pool, every insurer would be obliged to pay, for each of its members, a uniform contribution that would depend on the projected size of the pool. The statistical analysis indicates that mandatory pooling may substantially mitigate solvency and selection problems while retaining incentives for efficiency and cost containment.

Evaluation of a counselling protocol for predictive genetic testing for hereditary non-polyposis colorectal cancer

OBJECTIVESTo evaluate the feasibility of a reduced counselling programme for predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) in terms of counsellees' opinions on the extent and significance of...

Predictive genetic testing for hereditary non-polyposis colorectal cancer: Uptake and long-term satisfaction

The aim of this prospective study was to assess the uptake of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) and its associations with sociodemographic and other factors, and long-term satisfaction with taking the test. The test was offered to all high-risk members (n = 446) of 36 Finnish HNPCC families in which the mutation was known. The procedure comprised an educational counselling session, a period for reflection, and a test disclosure session. Data were collected by questionnaires sent before the educational counselling and 1 month and 1 year after the test disclosure. Of those eligible, 85% (n = 381) completed the first questionnaire study. Non-participation was more common among men living alone who had not participated in the clinical cancer surveillance programme. Of the 347 subjects who attended counselling, 334 (75% of all subjects) were actually tested. After logistic-regression analysis, the only significant factor predicting test acceptance proved to be employment status: those employed were more likely than others to accept the test (odds ratio = 2.25; 95% confidence intervals, 1.09 to 4.6 1). At follow-up, over 90% of the subjects were fully satisfied with the decision to take the test. In conclusion, acceptance of the test was considerably higher than in previously reported studies. We attribute this to our careful face-to-face individualized counselling, our health care system, and to attitudes of the Finnish population, which are generally favourable towards health care and disease prevention.

Community Care Management: Advanced Practice Nurses as Care Managers

A group of advanced practice nurses partnered with a major insurer in the design and implementation of a care coordination model for high-risk older adults. This article will discuss the process of such an undertaking, highlighting the successes and barriers encountered. The key elements of this program included early identification and regular reassessment of each member's acuity level; fostering close partnerships between individual or teams of APRNs and groups of physicians; and uninterrupted clinical management of high-risk members across the health care continuum. This model was designed to achieve the following outcomes: to support the physician management of high-risk, chronic individuals; to increase or maintain the health of members; and to reduce health care costs. Outcome studies have demonstrated a substantial net savings by decreasing acute care admissions by 54%, reducing hospital days by 42%, and trimming primary care physicians' and specialists' visit costs by 37%. There was a 33% reduction in the overall costs of health care for members enrolled in this program. Physicians and members both rated their satisfaction with the APRN-based model of care as very high.

Community Care Management Across the Continuum: Study Results From a Medicare Health Maintenance Plan

A large national health plan piloting a community care management (CCM) model for its high-risk, chronically ill, Medicare population has demonstrated a significant reduction in overall medical costs for its participants. The key elements include: the proactive identification and risk stratification of members; assignment of advanced practice nurses to physicians with high-volume high-risk members; and ongoing clinical management across the continuum, establishing a continuous relationship with the member. The results are derived from a retrospective study comparing 6 months of claim data prior to the member entering CCM, with 6 months of claim data while participants received community, care management. Members in the pilot study experienced both a 42% reduction in institutional days and a 53% reduction in admissions to acute care settings. In addition, physician and specialists fees were reduced by 37%. This resulted in a 6-month net savings of $3,602 per participant. To be extremely conservative, the savings were reduced by 50% to reflect the possible impact of regression to the mean. Even accounting for this, the program's projected cost savings are $1,801 per participant in 6 months. The total projected savings for community care managed members in a fully implemented program divided by the entire enrolled population of 27,000 is $6.60 per member per month (PM/PM). The results of this study of care management across the continuum signal a new approach for medical management at a time when health care and the needs of the population are changing.

DNA repair proficiency: a potential marker for identification of high risk members in breast cancer families

Breast cancer is the single largest cancer and causes the high rate of cancer mortality among women. A positive family history of breast cancer is recognized as one of the major risk factors for this disease. The present study evaluates bleomycin (BLM)-induced chromosome sensitivity analysis in breast cancer families which provides indirectly a measure of the DNA repair defect of each person. BLM sensitivity assay on cultured lymphocytes of 36 familial breast cancer patients, their 85 first or second degree female relatives, 36 sporadic breast cancer patients and 40 age- and sex-matched controls (without any family history of cancer) were carried out to measure interindividual variation in their DNA repair capacity through mutagen-induced chromosome sensitivity analysis. Fifty percent of familial breast cancer patients and seven unaffected relatives showed hypersensitivity. Compared to hyposensitive relatives these seven subjects may be considered as high risk individuals.

Synthetic-peptide-based enzyme-linked immunosorbent assay for screening human serum or plasma for antibodies to human immunodeficiency virus type 1 and type 2.

A synthetic-peptide-based enzyme-linked immunosorbent assay (EIA) capable of screening for antibodies to both human immunodeficiency virus type 1 (HIV-1) and HIV-2 has been developed for use in blood banks and diagnostic laboratories. Microtiter wells are coated with two synthetic peptides, one corresponding to the highly conserved envelope region of HIV-1 and another corresponding to the conserved envelope region of HIV-2. Overall, sensitivity was 100% in 303 individuals diagnosed with AIDS and 96 individuals diagnosed with AIDS-related complex, 14.8% in a study of 500 high-risk group members, 99.9% in 600 EIA repeatedly reactive (RR)-HIV-1 Western blot (WB)-positive repository specimens, and 100% for 222 geographically diverse HIV-1 specimens and 216 confirmed HIV-2-positive specimens evaluated. The specificity was determined to be 99.72% for a total of 13,004 serum and plasma samples from random volunteer donors evaluated across five blood banks. Forty donors who were found to be EIA RR-WB indeterminate but nonreactive on the United Biomedical, Inc., test (UBI HIV 1/2 EIA) were prospectively followed as an additional measure of specificity. None of the 40 low-risk cases evolved into a positive WB pattern at follow-up. The sensitivity and specificity of this new assay are comparable to those of other Food and Drug Administration-licensed HIV-1 and HIV-1-HIV-2 assays that are currently available in the United States. The UBI HIV 1/2 EIA affords laboratories another choice in the detection of antibodies for HIV-1 and HIV-2 with a test based on an alternative antigen format.