Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

Validation of the Addiction Severity Index in French-speaking alcoholic patients.

OBJECTIVE: Evaluation of a French translation of the Addiction Severity Index (ASI) in 100 (78 male) alcoholic patients. METHOD: Validity of the instrument was assessed by measuring test-retest and interrater reliability, internal consistency and convergence and discrimination between items and scales. Concurrent validity was assessed by comparing the scores from the ASI with those obtained from three other clinimetric instruments. RESULTS: Test-retest reliability of ASI scores (after a 10-day interval) was good (r = 0.63 to r = 0.95). Interrater reliability was evaluated using six video recordings of patient interviews. Severity ratings assigned by six rates were significantly different (p < .05), but 72% of the ratings assigned by those who viewed the videos were within two points of the interviewer's severity ratings. Cronbach alpha coefficient of internal consistency varied from 0.58 to 0.81 across scales. The average item-to-scale convergent validity (r value) was 0.49 (range 0.0 to 0.84) for composite scores and 0.35 (range 0.00 to 0.68) for severity ratings, whereas discriminant validity was 0.11 on average (range-0.19 to 0.46) for composite scores and 0.12 (range-0.20 to 0.52) for severity ratings. Finally, concurrent validity with the following instruments was assessed: Severity of Alcoholism Dependence Questionnaire (40% shared variance with ASI alcohol scale), Michigan Alcoholism Screening Test (2% shared variance with ASI alcohol scale) and Hamilton Depression Rating Scale (31% shared variance with ASI psychiatric scale). CONCLUSIONS: The Addiction Severity Index covers a large scope of problems encountered among alcoholics and quantifies need for treatment. This French version presents acceptable criteria of reliability and validity.

Cost-effectiveness of opportunistic versus organised mammography screening in Switzerland

BACKGROUND: Various centralised mammography screening programmes have shown to reduce breast cancer mortality at reasonable costs. However, mammography screening is not necessarily cost-effective in every situation. Opportunistic screening, the predominant screening modality in several European countries, may under certain circumstances be a cost-effective alternative. In this study, we compared the cost-effectiveness of both screening modalities in Switzerland. METHODS: Using micro-simulation modelling, we predicted the effects and costs of biennial mammography screening for 50-69 years old women between 1999 and 2020, in the Swiss female population aged 30-70 in 1999. A sensitivity analysis on the test sensitivity of opportunistic screening was performed. RESULTS: Organised mammography screening with an 80% participation rate yielded a breast cancer mortality reduction of 13%. Twenty years after the start of screening, the predicted annual breast cancer mortality was 25% lower than in a situation without screening. The 3% discounted cost-effectiveness ratio of organised mammography screening was euro11,512 per life year gained. Opportunistic screening with a similar participation rate was comparably effective, but at twice the costs: euro22,671-24,707 per life year gained. This was mainly related to the high costs of opportunistic mammography and frequent use of imaging diagnostics in combination with an opportunistic mammogram. CONCLUSION: Although data on the performance of opportunistic screening are limited, both opportunistic and organised mammography screening seem effective in reducing breast cancer mortality in Switzerland. However, for opportunistic screening to become equally cost-effective as organised screening, costs and use of additional diagnostics should be reduced.

MRSA screening by the Xpert MRSA PCR assay: pooling samples of the nose, throat, and groin increases the sensitivity of detection without increasing the laboratory costs.

The performance of the Xpert MRSA polymerase chain reaction (PCR) assay on pooled nose, groin, and throat swabs (three nylon flocked eSwabs into one tube) was compared to culture by analyzing 5,546 samples. The sensitivity [0.78, 95 % confidence interval (CI) 0.73-0.82] and specificity (0.99, 95 % CI 0.98-0.99) were similar to the results from published studies on separated nose or other specimens. Thus, the performance of the Xpert MRSA assay was not affected by pooling the three specimens into one assay, allowing a higher detection rate without increasing laboratory costs, as compared to nose samples alone.

Obesity and overweight associated with lower rates of colorectal cancer screening in Switzerland.

Screening for colorectal cancer (CRC) is associated with reduced CRC mortality, but low screening rates have been reported in several settings. The aim of the study was to assess predictors of low CRC screening in Switzerland. A retrospective cohort of a random sample of 940 patients aged 50-80 years followed for 2 years from four Swiss University primary care settings was used. Patients with illegal residency status and a history of CRC or colorectal polyps were excluded. We abstracted sociodemographic data of patients and physicians, patient health status, and indicators derived from RAND's Quality Assessment Tools from medical charts. We defined CRC screening as colonoscopy in the last 10 years, flexible sigmoidoscopy in the last 5 years, or fecal occult blood testing in the last 2 years. We used bivariate and multivariate logistic regression analyses. Of 940 patients (mean age 63.9 years, 42.7% women), 316 (33.6%) had undergone CRC screening. In multivariate analysis, birthplace in a country outside of Western Europe and North America [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.45-0.97], male sex of the physician in charge (OR 0.67, 95% CI 0.50-0.91), BMI 25.0-29.9 kg/m (OR 0.66, CI 0.46-0.96) and at least 30.0 kg/m (OR 0.61, CI 0.40-0.90) were associated with lower CRC screening rates. Obesity, overweight, birthplace outside of Western Europe and North America, and male sex of the physician in charge were associated with lower CRC screening rates in Swiss University primary care settings. Physician perception of obesity and its impact on their recommendation for CRC screening might be a target for further research.

Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia.

Background Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2). Methods Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study), and group 2, patients without ADAMTSL2 mutations (n=19). Results The main discriminating features were facial dysmorphism and tip-toe walking, which were almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness, and radiographic features. Conclusions It is concluded that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.

Incidence of invasive cervical cancer in the Swiss canton of Vaud, and a note on screening.

Age adjusted incidence rates (World standard) from invasive cervical cancer in the Swiss canton of Vaud decreased from 17.7/100,000 in 1968-70 to 9.9/100,000 in 1983-85. The decline was substantial in younger middle age, but no appreciable trend was observed in women over 70. This is consistent with available interview based information on the pattern of cervical screening in the Swiss population. Although there was no organised screening programme in Switzerland, over 80% of women aged 20-44 and 65% of those aged 45-64 reported one or more screening smears over the previous 3 years, compared to only 22% of women aged 65 or over. In the last calendar period, there was an apparent increase in the incidence of invasive cervical cancer (from 2.5 to 6.1/100,000) in women aged 25-29. Although based on small absolute numbers, this is in agreement with incidence and mortality data from other countries, and may therefore confirm a change in risk factor exposure in younger women.

Impact and cost of a 2-week community-based screening and awareness program for diabetes and cardiovascular risk factors in a Swiss canton.

BACKGROUND: Community-based diabetes screening programs can help sensitize the population and identify new cases. However, the impact of such programs is rarely assessed in high-income countries, where concurrent health information and screening opportunities are common place. INTERVENTION AND METHODS: A 2-week screening and awareness campaign was organized as part of a new diabetes program in the canton of Vaud (population of 697,000) in Switzerland. Screening was performed without appointment in 190 out of 244 pharmacies in the canton at the subsidized cost of 10 Swiss Francs per participant. Screening included questions on risk behaviors, measurement of body mass index, blood pressure, blood cholesterol, random blood glucose (RBG), and A1c if RBG was >/=7.0 mmol/L. A mass media campaign promoting physical activity and a healthy diet was channeled through several media, eg, 165 spots on radio, billboards in 250 public places, flyers in 360 public transport vehicles, and a dozen articles in several newspapers. A telephone survey in a representative sample of the population of the canton was performed after the campaign to evaluate the program. RESULTS: A total of 4222 participants (0.76% of all persons aged >/=18 years) underwent the screening program (median age: 53 years, 63% females). Among participants not treated for diabetes, 3.7% had RBG >/= 7.8 mmol/L and 1.8% had both RBG >/= 7.0 mmol/L and A1c >/= 6.5. Untreated blood pressure >/=140/90 mmHg and/or untreated cholesterol >/=5.2 mmol/L were found in 50.5% of participants. One or several treated or untreated modifiable risk factors were found in 78% of participants. The telephone survey showed that 53% of all adults in the canton were sensitized by the campaign. Excluding fees paid by the participants, the program incurred a cost of CHF 330,600. CONCLUSION: A community-based screening program had low efficiency for detecting new cases of diabetes, but it identified large numbers of persons with elevated other cardiovascular risk factors. Our findings suggest the convenience of A1c for mass screening of diabetes, the usefulness of extending diabetes screening to other cardiovascular risk factors, and the importance of a robust background communication campaign.

Label-free cytotoxicity screening assay by digital holographic microscopy

Abstract We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screening compatible application, we automatized a digital holographic microscope for image acquisition of cells using commercially available 96-well plates. Data generated through both label-free DHM imaging and fluorescence-based methods were in good agreement for cell viability identification and a Z'-factor close to 0.9 was determined, validating the robustness of DHM assay for phenotypic screening. Further, an excellent correlation was obtained between experimental cytotoxicity dose-response curves and known IC values for different toxic compounds. For comparable results, DHM has the major advantages of being label free and close to an order of magnitude faster than automated standard fluorescence microscopy.

L'assurance de qualité en dépistage organise du cancer du sein [Quality assurance in organized screening of breast cancer]

Quality assurance is an essential process which should be applied for any organised breast cancer screening program since mammography it the only test available for an early diagnosis. It should also assess the quality of diagnostic and treatment processes in order to ascertain that the quality of the screening program would not be altered by the procedures which take place after the screening. Quality assurance must be applied to each component of the screening process: equipment, radiographers (technicians) as well as radiologists. It is a multidisciplinary approach following a well defined protocol, which should be supervised by a coordination unit, the Breast Cancer Screening Foundation in Canton of Vaud. Performances of the Vaud program show clearly at what extend multiple reading method improves the quality of screening. It seems that there is no inconvenient to involve radiologists who wish to participate without any selection to the reading process provided that there is in place a team of 2nd and 3rd readers who benefit of an appropriate training and experience.

Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression.

Humans differ substantially with respect to susceptibility to human immunodeficiency virus type 1 (HIV-1). We evaluated variants of nine host genes participating in the viral life cycle for their role in modulating HIV-1 infection. Alleles were assessed ex vivo for their impact on viral replication in purified CD4 T cells from healthy blood donors (n = 128). Thereafter, candidate alleles were assessed in vivo in a cohort of HIV-1-infected individuals (n = 851) not receiving potent antiretroviral therapy. As a benchmark test, we tested 12 previously reported host genetic variants influencing HIV-1 infection as well as single nucleotide polymorphisms in the nine candidate genes. This led to the proposition of three alleles of PML, TSG101, and PPIA as potentially associated with differences in progression of HIV-1 disease. In a model considering the combined effects of new and previously reported gene variants, we estimated that their effect might be responsible for lengthening or shortening by up to 2.8 years the period from 500 CD4 T cells/mul to <200 CD4 T cells/mul.

Prevalence of positive tuberculosis skin tests during 5 years of screening in a Swiss remand prison

BACKGROUND: Tuberculosis (TB) screening in prisons is recommended, but the appropriate methods remain controversial. Studies evaluating screening in remand prisons arc scarce. METHOD: Between 1997 and 2001, voluntary screening based on the tuberculin skin test (TST) was offered to all prisoners on entry into the largest remand prison in Switzerland. Prisoners with positive results underwent chest X-rays. We analysed this information collected in an anonymous database. RESULTS: A total of 4890 prisoners entered the prison and were eligible for screening; 3779 (77.3%) had TST performed on average 9 days after arrival: 46.9% were positive (induration >= 10 mm). Positive TST rates were similar over the 5 years. Women were more likely to have a negative TST (60.4%) than men (47.7%; P < 0.001, Pearson's chi(2) 16.5). Positive TSTs varied according to the prisoner's country of origin (64% for sub-Saharan Africa, 57% for Eastern Europe, 56% for North Africa, 51% for Asia and 34% for North and West Europe). CONCLUSION: The percentage of TST-positive subjects was high, and most did not receive preventive treatment for latent TB. The usefulness of systematic TST for all prisoners on entry is limited, as diagnosis of TB disease usually remains the priority in prisons. Keywords