Impact of public health strategies on the birth prevalence of cystic fibrosis in Brittany,France

Taking into account the situation of Brittany, a region of western France where cystic fibrosis (CF) is common and where a neonatal screening program was set up 14 years ago, the aim of this study was to determine the way in which the birth prevalence of CF has been influenced by the various public health strategies implemented in the region (neonatal screening, prenatal diagnosis, ultrasound examination and family testing). This study used the results of the neonatal screening program, which enabled a precise measure of the prevalence of CF at birth to be obtained. Over the same period, we collected data from prenatal diagnoses carried out in the region, first in families related to a CF child and also those made following the detection of an echogenic bowel upon routine ultrasound examination performed during pregnancy. The prevalence of CF at birth was estimated to be 1/2838 in the region over a 10-year period (1992-2001). By including the 54 CF-affected pregnancies that were terminated during these 10 years, the corrected birth prevalence of CF was 1/1972. Prenatal diagnosis was therefore responsible for a global decrease in CF prevalence at birth of 30.5%. This work constitutes the first study able to provide a precise measure of CF birth prevalence and of its evolution through the combined effects of neonatal screening, prenatal diagnosis, ultrasound examination and family testing.     

Prenatal screening for cystic fibrosis carriers: an economic evaluation.

The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical question is whether the cost of such screening is justified. Decision analysis was performed that used information about choices that pregnant women were observed to make at each stage in the Rochester prenatal carrier-screening trial. The cost of screening per CF birth voluntarily averted was estimated to be $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF child in today's dollars was estimated to be slightly>$1,000,000. Therefore, despite both the high cost of carrier testing and the relative infrequency of CF conceptions in the general population, the averted medical-care cost resulting from choices freely made are estimated to offset approximately 74%-78% of the costs of a screening program. At present, if it is assumed that a pregnancy terminated because of CF is replaced, the marginal cost for prenatal CF carrier screening is estimated to be $8,290 per quality-adjusted life-year. This value compares favorably with that of many accepted medical services. The cost of prenatal CF carrier screening could fall to equal the averted costs of CF patient care if the cost of carrier testing were to fall to $100.     

Determination of polyphenol and crude nutrient content and nutrient digestibility of dried and ensiled white and red grape pomace cultivars

The present study aimed to determine the nutrient and energy content of fresh and ensiled grape pomace (GP) from different grape varieties originating from Germany, and to estimate the feed value of dried white, dried red and ensiled white GP by calculating nutrient digestibility and the content of metabolisable energy (ME) and net energy lactation (NEL) measured in sheep as a ruminant model. GP from red cultivars had higher contents of organic matter (OM), crude protein (CP), ether extract (EE), crude fibre (CF), total phenolic contents (TPC) and ME, whereas the concentrations of ash and sugar were lower than from white cultivars. Compared with untreated GP, ensiled GP had increased concentrations of CP (+19%), ether extract (EE; +23%) and CF (+12%) and a higher ME content (+7%) and markedly decreased concentrations of sugar (?99.6%) and TPC (?48%). The concentrations of dry matter, OM and ash were not different between ensiled and fresh GP. Compared with dried GP, ensiled GP had a higher nutrient digestibility (OM, +32%; CP, +43%; CF, +46%; neutral detergent fibre [NDF], +54%; acid detergent fibre [ADF], +69%) and higher energy values (ME, +16%; NEL, +19%). The digestibility of OM, CP, EE and CF and the energy content were higher for dried red than for dried white GP, whereas the digestibility of NDF_OM and ADF_OM was lower for dried red than dried white GP. In conclusion, the results show that both red and white GP are suitable dietary sources for enrichment with TPC. Furthermore, compared with drying ensiling of GP improves the feeding value of GP and is a good possibility of preserving the seasonally produced by-product of winemaking for ruminant feeding.     

Preconception cystic fibrosis carrier couple screening: impact,understanding, and satisfaction

The impact, understanding of test-results, and satisfaction among participating couples in a preconception cystic fibrosis (CF) carrier screening project were assessed 6 months after testing. Questionnaire data were obtained from 17/18 identified carriers, 15 partners of carriers with negative test results, and 794 (73%) other participants. None of the carriers changed their reproductive plans because of their test results. Eight participants were worried about their results, including four carriers. Those who attended a general practitioner (GP) consultation for pretest education were less worried than those who attended an educational session. Seven carriers felt less healthy. Predictors of a correct understanding of test results (correct in 62% of participants) were: positive test results, high level of knowledge of CF, high level of education, attending an educational session, and previously heard of CF. All participants who reported that they were worried, all carriers, and 95% of the other participants said that they would make the same decision to be tested again. Although couples who were educated during a GP consultation were less worried, the results of the study suggest that understanding is more correct in couples attending an educational session. The results further suggest that since satisfaction with the screening was high, worries and feeling less healthy due to the test results are probably not a great burden.     

The Association between GP Consultations for Non-Specific Physical Symptoms in Children and Parents: A Case-Control Study

Background

Non-specific physical symptoms (NSPS) such as abdominal pain, headache and musculoskeletal pain are widespread in the community, and are common reasons for visiting a general practitioner (GP). Causes of NSPS are multifactorial, but may include parental influences.

Objective

To investigate associations between GP consultations for NSPS in parents and their children.

Methods

Matched case-control study using GP consultation data from 12 GP practices in the United Kingdom. Participants were 1328 children who consulted a GP for NSPS in 2009 (cases), 3980 controls who consulted a GP in 2009 but not for NSPS, plus parents of cases and controls (n = 8354). Primary outcome measure: child consultation status for NSPS.

Results

Maternal consultation for NSPS was associated with significantly increased odds of their child consulting for NSPS (odds ratio (OR) 1.51, 95% confidence intervals (CI) 1.33, 1.73); there was no significant association with paternal consultations (OR 0.87, 95% CI 0.71, 1.08). Each additional maternal consultation for NSPS was associated with an increase in the rate ratio for number of consultations for NSPS in the child by 1.03 (95% CI 1.01, 1.05). This overall association was clearest in maternal-child consultations for painful NSPS and for specific bodily systems including gastrointestinal, musculoskeletal and neurologic symptoms.

Conclusions

Maternal GP consultation for NSPS is associated with increased odds of GP consultations for NSPS in children. This study included a large sample of children and parents and used medical records data which is not subject to recall bias. However, analysis was based on medical records, thus the presence of NSPS not leading to consultations is unknown. Medical practitioners managing children with NSPS need to be aware of this association.     

Preconceptional cystic fibrosis carrier screening: opinions of general practitioners, gynecologists, and pediatricians in the Netherlands

Knowledge of the opinions of physicians with regard to preconceptional cystic fibrosis (CF) carrier screening and the possible factors that are associated with their opinions is important for the implementation of such a screening program. Data were obtained from a study in which genetic knowledge, opinions with regard to genetic testing and related skills were investigated. A questionnaire, developed and used by American researchers, was adapted to the Dutch health care situation, and sent to randomly selected general practitioners (GPs) (n = 200), gynecologists (GYNs) (n = 300), and pediatricians (PEDs) (n = 265). In this part of the study, their opinions with regard to genetic preconceptional CF carrier screening in different situations were assessed. The response rate for the GPs, GYNs, and PEDs was 64%, 69%, and 72%, respectively. In total, 63% of the GPs, 69% of the GYNs and 72% of the PEDs supported preconceptional CF carrier testing if a couple requested a test. Sixteen percent, 19% and 25%, respectively, were in favor of actively offering a test with 95% test sensitivity to all couples who were planning a pregnancy. A positive opinion on preconceptional CF carrier screening was associated with the following variables: "considering the test sensitivity as less important" (GPs, GYNs), "high perceived risk of having a child with CF" (GYNs), "providing genetic counselling in their own practice" (PEDs) and "reassurance when both partners test negative" (PEDs). Physicians are sympathetic toward preconceptional CF carrier screening if the couples themselves request a test. Physicians had reservations about routinely offering a CF carrier test.     

Application of DNA analysis in a population-screening program for neonatal diagnosis of cystic fibrosis (CF): comparison of screening protocols.

We compare two protocols for newborn screening for cystic fibrosis (CF). The first uses the immunoreactive trypsinogen (IRT) assay with a cutoff of > or = 180 ng/ml and a sweat test to identify CF patients. The second uses the IRT assay with a 100 ng/ml cutoff in conjunction with direct analysis for the delta F508 CF transmembrane conductance regulator (CFTR) mutation in a two-tiered (i.e., IRT/DNA) protocol, followed by a sweat test. We screened 220,865 newborns from Wisconsin for CF, using the IRT protocol identifying 369 infants with an elevated IRT, of whom 46 were found to have CF. Another 7 CF patients were identified who had a false-negative IRT level. The CF incidence in the white population was 1 in 3,431 (carrier incidence of 1 in 30). The IRT protocol had a sensitivity of 87% and a positive predictive value of 12.5%. We subsequently used the IRT/DNA protocol to screen 21,258 infants. Of 518 infants with an IRT level > or = 100 ng/ml, 24 carried at least one copy of the delta F508 CFTR mutation, and 4 of these infants were found to have CF, yielding a positive predictive value for this protocol of 16.7%. Direct comparison of the positive predictive value of the two protocols is not valid, because of the different populations screened. However, had the IRT protocol been used on the IRT/DNA cohort, 50 infants, including the 4 with CF, would have received sweat tests, yielding a positive predictive value of 8%. Because of the small sample size, this positive predictive value is not significantly different from that obtained for the IRT/DNA test. However, from a practical point of view the IRT/DNA approach does decrease considerably the number of sweat tests that must be undertaken. The number of false positives for the IRT protocol (46 in 21,258) is increased significantly compared with that for the IRT/DNA approach (20 in 21,258; P < .001). The incidence of delta F508 carriers detected in cohorts with an elevated IRT level was increased compared with the incidence in the general population. The direct costs for the IRT/DNA approach (100 ng/ml) were $11,374 per CF patient detected, compared with $10,187 per CF patient detected for the IRT protocol. Therefore, we conclude that the IRT/DNA approach to CF newborn screening decreases the number of false-positive subjects contacted, without a significant increase in cost.     

Weather impacts on respiratory infections in Athens, Greece

In this study the contribution of meteorological parameters to the total variability of respiratory infections (RI) is analysed. For this purpose, data on the daily numbers of general practitioner (GP) consultations for RI during the year 2002 were used. This dataset has been compiled by the Local Health Service in the surroundings of Athens, Greece (Acharnes city). The meteorological data obtained by the Meteorological Station of the National Observatory of Athens comprise daily values of mean, maximum, and minimum air temperature, air temperature range, relative humidity, absolute humidity, sunshine, surface atmospheric pressure, wind speed, as well as day-to-day changes of these parameters. Furthermore, the following biometeorological parameters and thermal indices were also evaluated: mean radiant temperature (T _mrt), predicted mean vote (PMV), physiologically equivalent temperature (PET) and standard effective temperature (SET*) as well as their day-to-day changes. First, the relationship between every meteorological-biometeorological parameter and consultations for RI was examined by applying the Pearson Chi-Square Test (χ ²) to the data of the 25 compiled contingency tables. In the second stage, the application of generalised linear models (GLM) with Poisson distribution to the data revealed how much the weather variability leads to statistically important changes in consultations for RI. The results of this study contribute to the evidence that there is an association between weather conditions and the number of GP consultations for RI. More specifically, the influence of air temperature and absolute humidity on consultations on the same day is weaker than the lag effect (∼2 weeks) related to cold existence and absolute humidity, while a strong wind during the preceding 3 days drives a peak in GP consultations.     

The plant growth-promoting fungus Penicillium simplicissimum GP17-2 induces resistance in Arabidopsis thaliana by activation of multiple defense signals

Arabidopsis thaliana grown in soil amended with barley grain inocula of Penicillium simplicissimum GP17-2 or receiving root treatment with its culture filtrate (CF) exhibited clear resistance to Pseudomonas syringae pv. tomato DC3000 (Pst). To assess the contribution of different defense pathways, Arabidopsis genotypes implicated in salicylic acid (SA) signaling expressing the NahG transgene or carrying disruption in NPR1 (npr1), jasmonic acid (JA) signaling (jar1) and ethylene (ET) signaling (ein2) were tested. All genotypes screened were protected by GP17-2 or its CF. However, the level of protection was significantly lower in NahG and npr1 plants than it was in similarly treated wild-type plants, indicating that the SA signaling pathway makes a minor contribution to the GP17-2-mediated resistance and is insufficient for a full response. Examination of local and systemic gene expression revealed that GP17-2 and its CF modulate the expression of genes involved in both the SA and JA/ET signaling pathways. Subsequent challenge of GP17-2-colonized plants with Pst was accompanied by direct activation of SA-inducible PR-2 and PR-5 genes as well as potentiated expression of the JA-inducible Vsp gene. In contrast, CF-treated plants infected with Pst exhibited elevated expression of most defense-related genes (PR-1, PR-2, PR-5, PDF1.2 and Hel) studied. Moreover, an initial elevation of SA responses was followed by late induction of JA responses during Pst infection of induced systemic resistance (ISR)-expressing plants. In conclusion, we hypothesize the involvement of multiple defense mechanisms leading to an ISR of Arabidopsis by GP17-2.     

Carrier screening for cystic fibrosis in a prenatal setting

Maternal prenatal cystic fibrosis (CF) screening was offered from September, 1997, to April, 1999, at the Ghent University Hospital, to couples undergoing prenatal diagnosis (amniocentesis) for reasons not related to CF. Fifteen minutes were devoted to explaining CF, CF screening, and the study protocol. The purpose was to assess the short- and long-term knowledge of CF, the attitude towards carrier screening, and carriership. A total of 314 couples entered the pilot study; 13 female CF carriers were identified. None of their partners carried an identifiable mutation. Our survey results show that information about CF and CF screening can be given effectively as part of antenatal care because most couples recalled important medical and genetic issues, valued the genetic test for CF, and seemed to cope well with the results. Risk estimates and actual numbers were more difficult to process and recall. From the small number of couples in which the woman alone was found to be a carrier, there was little or no evidence of marked distress.     

The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

Background

Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts.

Methods and Findings

We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses.

Conclusions

Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be tailored to countries using local epidemiologic and programmatic data.     

Acceptability of carrier screening for cystic fibrosis during pregnancy in a German population

A pilot project offering voluntary heterozygote screening for the F508 mutation causing cystic fibrosis (CF) to 638 pregnant women attending two antenatal clinics in the eastern part of Berlin was carried out from 1990–1993. Participation was invited using an information leaflet and inclusion in the study was conditional on written informed consent. Of those invited to participate, only one refused to be tested, on the grounds of non-acceptance of prenatal diagnosis. Eighteen pregnant women were identified as carriers of the F508 mutation. All of them and their male partners accepted counselling in which the genetics of CF, its prognosis and treatment were explained, with emphasis on the meaning of heterozygosity, the fact that carriers are healthy, and the risk of an affected fetus when only one parent is identified as a heterozygote. All partners agreed to be tested for the F508 R553X and G551D mutations and a second counselling session was carried out after this test result was available. No problems were observed during initial testing but, as in other studies, we found considerable anxiety on being given the result in all couples where the woman tested positive; this was reduced substantially by counselling and when the partner tested negative. All probands found to be carriers stated that they found screening acceptable. In contrast to the cautious statement by the German Berufsverband Medizinische Genetik and the hostile reaction from a representative of the CF self-support organisation towards community-based heterozygote screening for CF, this study shows that CF screening is generally acceptable in this German population and that it is actively taken up by most pregnant women when offered.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

PCR-based screening for cystic fibrosis carrier mutations in an ethnically diverse pregnant population.

As the most common lethal autosomal recessive disorder in North America, cystic fibrosis (CF) is an obvious candidate for general population carrier screening. Although the identification of the causative gene has made detection of asymptomatic carriers possible, the extreme heterogeneity of its mutations has limited the sensitivity of the available DNA screening tests and has called into question their utility when they are applied to patients with no family history of the disease. The purpose of this study was to determine the technical feasibility, patient acceptance and understanding, and psychosocial impact of large-scale CF carrier screening in an ethnically diverse pregnant population. A total of 4,739 pregnant women attending prenatal clinics located in both an academic medical center and a large HMO were invited in person to participate. Of this group, 3,543 received CF instruction and assessments of knowledge and mood, and 3,192 underwent DNA testing for the six most common CF mutations, by means of a noninvasive PCR-based reverse-dot-blot method. Overall participation rates (ranging from 53% at the HMO to 77% at the academic center) and consent rates for DNA testing after CF instruction (>98%) exceeded those of most other American studies. The PCR-based screening method worked efficiently on large numbers of samples, and 55 carriers and one at-risk couple were identified. Understanding of residual risk, anxiety levels, and overall satisfaction with the program were acceptable across all ethnic groups. Our strategy of approaching a motivated pregnant population in person with a rapid and noninvasive testing method may provide a practical model for developing a larger CF screening program targeting appropriate high-risk groups at the national level, and may also serve as a paradigm for population-based screening of other genetically heterogeneous disorders in the future.     

Optimal swab processing recovery method for detection of bioterrorism-related Francisella tularensis by real-time PCR

Francisella tularensis, the etiological agent of tularemia, is regarded as a potential bioterrorism agent. The advent of bioterrorism has heightened awareness of the need for validated methods for processing environmental samples. In this study we determined the optimal method for processing environmental swabs for the recovery and subsequent detection of F. tularensis by the use of real-time PCR assays. Four swab processing recovery methods were compared: heat, sonication, vortexing, and the Swab Extraction Tube System (SETS). These methods were evaluated using cotton, foam, polyester and rayon swabs spiked with six pathogenic strains of F. tularensis. Real-time PCR analysis using a multi-target 5′nuclease assay for F. tularensis showed that the use of the SETS method resulted in the best limit of detection when evaluated using multiple strains of F. tularensis. We demonstrated also that the efficiency of F. tularensis recovery from swab specimens was not equivalent for all swab processing methodologies and, thus, that this variable can affect real-time PCR assay sensitivity. The effectiveness of the SETS method was independent of the automated DNA extraction method and real-time PCR platforms used. In conclusion, diagnostic laboratories can now potentially incorporate the SETS method into specimen processing protocols for the rapid and efficient detection of F. tularensis by real-time PCR during laboratory bioterrorism-related investigations.     

Neonatal Screening for Cystic Fibrosis: Addition of Molecular Diagnostics to Increase Specificity

Newborn screening for cystic fibrosis (CF) has been carried out on approximately 106,000 neonates in western Pennsylvania since 1987 using the immunoreactive trypsinogen (IRT) assay on dried filter paper blood specimens (DBS). Molecular analysis utilizing a duplicate DBS from the same sample was implemented in November 1989 for newborns having elevated IRT levels. DNA is amplified directly from the DBS and the amplified products are tested for the delta F508 deletion and several common exon 11 mutations. Substituting dUTP for dTTP in the PCR reaction and an initial treatment with uracil N-glycosylase (UNG) virtually eliminates PCR carryover contamination. The number of confirmed cases of CF is 20, giving an estimated incidence of 1:5287 in the western Pennsylvania population. Eight of the CF patients are homozygous and 12 are compound heterozygotes for the delta F508 deletion and a second mutation. Two of the compound heterozygotes carry the G551D mutation and one has the R553X mutation. Twenty-one additional neonates that are heterozygous for the delta F508 mutation are normal carriers for CF. In approximately 55% of the cases, molecular analysis of the CF gene confirmed the diagnosis of CF prior to sweat testing. The incorporation of molecular analysis into our CF screening program increases the specificity of the screening strategy and has the potential to decrease the false positive and sweat test referral rate, reduce parental anxiety, and bring CF infants to the attention of physicians more rapidly.     

Budget Impact Analysis of Switching to Digital Mammography in a Population-Based Breast Cancer Screening Program: A Discrete Event Simulation Model

Objective

To assess the budgetary impact of switching from screen-film mammography to full-field digital mammography in a population-based breast cancer screening program.

Methods

A discrete-event simulation model was built to reproduce the breast cancer screening process (biennial mammographic screening of women aged 50 to 69 years) combined with the natural history of breast cancer. The simulation started with 100,000 women and, during a 20-year simulation horizon, new women were dynamically entered according to the aging of the Spanish population. Data on screening were obtained from Spanish breast cancer screening programs. Data on the natural history of breast cancer were based on US data adapted to our population. A budget impact analysis comparing digital with screen-film screening mammography was performed in a sample of 2,000 simulation runs. A sensitivity analysis was performed for crucial screening-related parameters. Distinct scenarios for recall and detection rates were compared.

Results

Statistically significant savings were found for overall costs, treatment costs and the costs of additional tests in the long term. The overall cost saving was 1,115,857€ (95%CI from 932,147 to 1,299,567) in the 10^th year and 2,866,124€ (95%CI from 2,492,610 to 3,239,638) in the 20^th year, representing 4.5% and 8.1% of the overall cost associated with screen-film mammography. The sensitivity analysis showed net savings in the long term.

Conclusions

Switching to digital mammography in a population-based breast cancer screening program saves long-term budget expense, in addition to providing technical advantages. Our results were consistent across distinct scenarios representing the different results obtained in European breast cancer screening programs.     

Prevalence of cystic fibrosis mutations in Israeli Jews

The aim of this study was to evaluate the screening policies of cystic fibrosis (CF) in the Jewish population. The prevalence of mutations that account for CF in Israel have been defined in the past by determining the frequency of CF mutations in affected individuals. This study is a population-based study and is, therefore, different from previous patient-based studies. We found that the CF mutations D1152H, W1089X, and 405 + IG-->A were present in some ethnic groups in which no CF patients carrying these mutations were reported. These facts necessitate a reevaluation of the screening policy regarding the ethnic groups in Israel. We studied 9,430 healthy Jewish Israeli individuals of 36 countries of origin. The prevalence of CF mutations was 1:19, 1:19, 1:28, and 1:42 for the Ashkenazi, Sephardi, North African, and Eastern Jews, respectively. CF mutations were identified in 374 (4.0%) individuals. These included 173 (46.3%) carriers of the W1282X mutation; 110 (29.4%) found to carry delF508; 23 (6.1%) who carried G542X; 22 (5.9%) who carried 3849 + 10Kb (C-->T; 20 (5.3%) who carried D1152H; 10 (2.7%) who carried N1303K; 11 (2.9%) who carried 405 + IG-->A; 4 (1.1%) who carried W1089X; and one (0.3%) who carried S549R. No carriers were detected for the 1717-1G-->A, G85E, and T360K mutations, which were tested for in 7,383, 1,558, and 41 individuals, respectively.     

A PCR assay for the detection of Campylobacter jejuni and Campylobacter coli in water

A PCR assay has been developed for the detection of Campylobacter jejuni and Camp. coli in water samples. The sample is filtered through a membrane which is subjected to sonication to release the impacted cells. After removal of the filter from the cell suspension and a freeze/thaw cell lysis step, a semi-nested PCR is carried out on the filtrate using the primers CF02, CF03 and CF04 ( Camp. jejuni fla and flaB gene sequences). Incorporation of a sonication stage allows removal of the filter membrane since they have been shown to inhibit the PCR. In experiments with spiked water samples (20 ml) a theoretical sensitivity of 10–20 Campylobacter cells ml^-1 was achieved. Using a sample volume of 100 ml this sensitivity can be increased to approximately 2 Campylobacter cells ml^-1.     

Population-based screening for colorectal cancer using an immunochemical faecal occult blood test: A comparison of two invitation strategies

Background: To date, there is no screening programme for colorectal cancer (CRC) in Flanders, Belgium. However, The European Code Against Cancer (2003) recommends a population-based approach for CRC screening. This study aimed to obtain information about potential participation rates for a population-based screening programme for CRC in Flanders, and to compare two invitation strategies. Methods: In 2009, a trial programme for CRC screening was set up in three Flemish areas for all average-risk people aged 50-74 years, using an immunochemical faecal occult blood test (iFOBT) with a cut-off value set at 75ng/ml of haemoglobin. The faecal sampling set was sent at random by post (mail group) or provided by the general practitioner (GP group). Results: In total, 19,542 people were invited to participate. Of these, 8229 provided a faecal sample, resulting in an overall participation rate of 42.1%. Participation by mail and through the GP was 52.3% (95% CI, 51.3-53.2) and 27.7% (95% CI, 26.7-28.6), respectively. The difference of 24.6% was statistically significant (95% CI, 23.3-25.9, p<0.001). Before the reminder letter was sent and the other invitation strategy was offered, the overall participation rate was 26.5% (n=5176); 36.4% (95% CI, 35.5-37.4) for the mail group and 16.6% (95% CI, 15.8-17.3) for the GP group. The odds of participating in CRC screening was almost three times higher for people invited by mail as opposed to people invited through a GP (OR=2.96, 95% CI, 2.78-3.14, p<0.001). Women were more likely to participate in CRC screening than men (OR=1.22, 95% CI, 1.15-1.30, p<0.001). In addition, we found that inhabitants from residential (OR=1.98, 95% CI, 1.85-2.11) and rural (OR=2.90, 95% CI, 2.66-3.16) areas were more likely to participate than those in urban areas. Of the 8229 people who submitted a faecal sample, 435 (5.3%) had a positive iFOBT, and of those, CRC was diagnosed in 18 (5.7%) individuals. Compliance for follow-up colonoscopy was 72.9%, and did not differ between the mail (72.4%, 95% CI, 67.5-77.3) and GP groups (74.3, 95% CI, 66.2-82.5). Conclusion: Inviting people for CRC screening by means of a direct-mail invitation, and including a faecal sampling set (iFOBT), results in much higher participation rates than inviting people through the GP.