Project description:Cytomegalovirus (CMV) infection is now the commonest congenital form of infective neurological handicap, recognized by the Institute of Medicine as the leading priority for the developed world in congenital infection. In the absence of an effective vaccine, universal screening for CMV in pregnancy has been proposed, in order that primary infection could be diagnosed and- potentially- the burden of disability due to congenital CMV prevented.Universal screening for CMV to identify seronegative women at the beginning of pregnancy could potentially reduce the burden of congenital CMV in one of three ways. The risk of acquiring the infection during pregnancy has been shown to be reduced by institution of simple hygiene measures (primary prevention). Among women who seroconvert during pregnancy, CMV hyperimmune globulin (CMV HIG) shows promise in reducing the risk of perinatal transmission (secondary prevention), and CMV HIG and/ or antivirals may be effective in reducing the risk of clinical sequelae among those known to be infected (tertiary prevention). The reports from these studies have re-ignited interest in universal screening for CMV, but against the potential benefit of these exciting therapies needs to be weighed the challenges associated with the implementation of any universal screening in pregnancy. These include; the optimal test, and timing of screening, to maximize detection; an approach to the management of equivocal results, and the cost effectiveness of the proposed screening program. In this article, we provide an overview of current knowledge and ongoing trials in the prevention, diagnosis and management of congenital CMV. Recognising that CMV screening is already being offered to many patients on an ad hoc basis, we also provide a management algorithm to guide clinicians and assist in counseling patients.We suggest that- on the basis of current data- the criteria necessary to recommend universal screening for CMV are not yet met, but this position is likely to change if trials currently underway confirm that CMV HIG and/ or antivirals are effective in reducing the burden of congenital CMV disease.

Project description:ImportanceThe nationwide fecal immunochemical test-based screening program has influenced surgical care for patients with colorectal cancer (CRC) in the Netherlands, although these implications have not been studied in much detail so far.ObjectiveTo compare surgical outcomes of patients diagnosed as having CRC through the fecal immunochemical test-based screening program (screen detected) and patients with non-screen-detected CRC.Design, setting, and participantsThis was a population-based comparative cohort study using the Dutch ColoRectal Audit and analyzed all Dutch hospitals performing CRC resections. Patients who underwent elective resection for CRC between January 2011 to December 2016 were included.InterventionsColorectal cancer surgery.Main outcomes and measuresPostoperative nonsurgical complications, postoperative surgical complications, postoperative 30-day or in-hospital mortality, and complicated course (postoperative complication resulting in a hospital stay >14 days and/or a reintervention and/or mortality). A risk-stratified comparison was made for different postoperative outcomes based on screening status (screen detected vs not screen detected), cancer stage (I-IV), and for cancer stage I to III also on age (aged ≤70 years and >70 years) and American Society of Anesthesiologists score (I-II and III-IV). To determine any residual case-mix-corrected differences in outcomes between patients with screen-detected and non-screen-detected cancer, univariable and multivariable logistic regression analyses were performed.ResultsIn total, 36 242 patients with colon cancer and 17 416 patients with rectal cancer were included for analysis. Compared with patients with non-screen-detected CRC, screen-detected patients were younger (mean [SD] age, 68 [5] vs 70 [11] years), more often men (3777 [60%] vs 13 506 [57%]), and had lower American Society of Anesthesiologists score (American Society of Anesthesiologists score III+: 838 [13%] vs 5529 [23%]). Patients with stage I to III colon cancer who were screen detected had a significantly lower mortality and complicated course rate compared with non-screen-detected patients. For patients with rectal cancer, only a significant difference was found in mortality rate in patients with a cancer stage IV disease, which was higher in the screen-detected group. Compared with non-screen-detected colon cancer, an independent association was found for screen-detected colon cancer on nonsurgical complications (adjusted odds ratio, 0.81; 95% CI, 0.73-0.91), surgical complications (adjusted odds ratio, 0.80; 95% CI, 0.72-0.89), and complicated course (adjusted odds ratio, 0.80; 95% CI, 0.71-0.90). Screen-detected rectal cancer had significantly higher odds on mortality.Conclusions and relevancePostoperative outcomes were significantly better for patients with colon cancer referred through the fecal immunochemical test-based screening program compared with non-screen-detected patients. These differences were not found in patients with rectal cancer. The outcomes of patients with screen-detected colon cancer were still better after an extensive case-mix correction, implying additional underlying factors favoring patients referred for surgery through the screening program.

Project description:BackgroundAsymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling.MethodsA probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters.ResultsFor the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Years, 28,052 Euros), these results indicate that PAD screening and treatment is a dominant strategy. The cost effectiveness acceptability curves show 88% probability of PAD screening being cost effective at the Willingness To Pay (WTP) threshold of 40000 Euros. In a scenario analysis using clopidogrel as an alternative anti-platelet drug, PAD screening strategy remained dominant.ConclusionThis decision analysis suggests that targeted ABI screening and consequent secondary prevention of cardiovascular events using low dose aspirin or clopidogrel in the identified patients is a cost-effective strategy. Implementation of targeted PAD screening and subsequent treatment in primary care practices and in public health programs is likely to improve the societal health and to save health care costs by reducing catastrophic cardiovascular events.

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