In their landmark publication, the authors were fundamentally preoccupied with the notion that:“The central idea of early disease detec-tion and treatment is essentially simple. However, the path to its successful achievement (on the one hand, bring-ing to treatment those with previously undetected disease, and, on the other, avoiding harm to those persons not in need of treatment) is far from simple though sometimes it may appear de-ceptively easy.”For this reason, Wilson and Jungner at-tempted to define screening criteria to guide the selection of conditions that would be suitable for screening, based, among other factors, on the capacity to detect the condition at an early stage and the availability of an acceptable treatment (Box 1). They considered these criteria “especially important when case-finding is carried out by a public health agency, where the pitfalls may be more numerous than when screening is performed by a personal physician”.Just as forty years ago, Wilson and Jungner wrote their treatise amidst a great deal of controversy surrounding the early detection of disease, there are now similar debates with respect to genetic screening. A growing number of diseases can now be detected in the pre-clinical stage, and even in the pre-pathological stage, using molecular and non-molecular diagnostic techniques.Large-scale screening for genetic conditions began around the time of the Wilson and Jungner publication. There was newborn screening for inborn errors of metabolism such as phenylketonuria, later followed by prenatal screening for Down syndrome and neural tube defects using ultrasound and biochemical mark-ers. Once individual disease genes started to be identified using novel molecular techniques, pilot screening programmes were established for several rare genetic conditions such as Tay Sachs disease and cystic fibrosis. With the advances in genetic technology, the rate at which new disease genes are being identified is out-pacing the ability of professionals and

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Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years

Objective To evaluate the effect of oral decontamination on the incidence of ventilator associated pneumonia and mortality in mechanically ventilated adults. Design Systematic review and meta-analysis. Data sources Medline, Embase, CINAHL, the Cochrane Library, trials registers, reference lists, conference proceedings, and investigators in the specialty. Review methods Two independent reviewers screened studiesforinclusion,assessedtrialquality,andextracted data. Eligible trials were randomised controlled trials enrolling mechanically ventilated adults that compared the effects of daily oral application of antibiotics or antiseptics with no prophylaxis. Results11trialstotalling3242patientsmettheinclusion criteria. Among four trials with 1098 patients, oral application of antibiotics did not significantly reduce the incidence of ventilator associated pneumonia (relative risk 0.69, 95% confidence interval 0.41 to 1.18). In seven trials with 2144 patients, however, oral application of antiseptics significantly reduced the incidence of ventilator associated pneumonia (0.56, 0.39 to 0.81). When the results of the 11 trials were pooled, rates of ventilator associated pneumonia were lower among patients receiving either method of oral decontamination (0.61, 0.45 to 0.82). Mortality was not influenced by prophylaxis with either antibiotics (0.94, 0.73 to 1.21) or antiseptics (0.96, 0.69 to 1.33) nor was duration of mechanical ventilation or stay in the intensive care unit. Conclusions Oral decontamination of mechanically ventilated adults using antiseptics is associated with a lower risk of ventilator associated pneumonia. Neither antiseptic nor antibiotic oral decontamination reduced mortality or duration of mechanical ventilation or stay in the intensive care unit.

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Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and

Objective To evaluate the effect of oral decontamination on the incidence of ventilator associated pneumonia and mortality in mechanically ventilated adults. Design Systematic review and meta-analysis. Data sources Medline, Embase, CINAHL, the Cochrane Library, trials registers, reference lists, conference proceedings, and investigators in the specialty. Review methods Two independent reviewers screened studies for inclusion, assessed trial quality, and extracted data. Eligible trials were randomised controlled trials enrolling mechanically ventilated adults that compared the effects of daily oral application of antibiotics or antiseptics with no prophylaxis. Results 11 trials totalling 3242 patients met the inclusion criteria. Among four trials with 1098 patients, oral application of antibiotics did not significantly reduce the incidence of ventilator associated pneumonia (relative risk 0.69, 95% confidence interval 0.41 to 1.18). In seven trials with 2144 patients, however, oral application of antiseptics significantly reduced the incidence of ventilator associated pneumonia (0.56, 0.39 to 0.81). When the results of the 11 trials were pooled, rates of ventilator associated pneumonia were lower among patients receiving either method of oral decontamination (0.61, 0.45 to 0.82). Mortality was not influenced by prophylaxis with either antibiotics (0.94, 0.73 to 1.21) or antiseptics (0.96, 0.69 to 1.33) nor was duration of mechanical ventilation or stay in the intensive care unit. Conclusions Oral decontamination of mechanically ventilated adults using antiseptics is associated with a lower risk of ventilator associated pneumonia. Neither antiseptic nor antibiotic oral decontamination reduced mortality or duration of mechanical ventilation or stay in the intensive care unit.

https://www.bmj.com/content/bmj/334/7599/889.full.pdf

Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis

Background Severe combined immunodeficiency (SCID) is a treatable, inherited lack of cellular and humoral immunity caused by diverse mutations in several different genes and leading to death in infancy unless immune reconstitution is provided Currently no population screening exists for SCID, but early diagnosis would improve outcome Objective Because all patients with SCID make few or no T cells, we asked whether the absence of T-cell receptor excision circles (TRECs), DNA episomes in newly formed T cells, could identify SCID regardless of genotype Methods DNA isolated from dried blood spots was assayed by real-time PCR to quantitate TRECs Control PCR was performed on a segment of the β-actin gene After pilot studies with adult and cord blood control subjects, blood from SCID patients was spotted onto filters and tested, followed by screening of actual blood spots from the Maryland Newborn Screening Program Finally, newborn blood spots were recovered and tested from 2 infants after their diagnosis of SCID Results In contrast to filters from the newborn screening program, which had a mean of 1020 TRECs in two 3-mm punches, samples from 23 infants with SCID had Conclusion TRECs are a stable analyte that can identify T-cell lymphopenia in newborn dried blood spots so that infants with SCID can receive early, life-saving treatment

Development of population-based newborn screening for severe combined immunodeficiency

Life after the thymus: CD31+ and CD31− human naive CD4+ T-cell subsets

Primary immunodeficiency (PI) diseases are a group of primarily single-gene disorders of the immune system. Approximately 100 separate PI diseases have been described, but 90% of cases. Although diverse, PI diseases share the common feature of susceptibility to infection and result in substantial morbidity and shortened life spans. Most important, prompt diagnosis and treatment can now lead to life-saving treatment and result in marked improvements in the quality and length of life for persons with PI diseases. In November 2001, a workshop was convened by CDC in Atlanta, Georgia, to discuss ways to improve health outcomes among persons with PI disease. A multidisciplinary panel of persons knowledgeable in PI diseases and public health met to identify and discuss public health strategies that can be applied to PI diseases and possibly for other genetic disorders. A systematic assessment based on the established public health framework was applied to the growing group of PI diseases, whose diverse genetic mutations span multiple components of the immune system but all lead to increased incidence and severity of infections. During the meeting, specialists in clinical immunology, public health, genetics, pediatrics, health communication, and ethics from state and federal agencies, academic centers, professional organizations, and advocacy foundations discussed the four components of the public health framework as they relate to PI diseases. These four components include 1) public health assessment (application of traditional public health methods to assess the occurrence and impact of PI diseases on communities); 2) population-based interventions (development, implementation, and evaluation of screening tests administered to newborns and clinical algorithms for early recognition of symptomatic persons to facilitate the earliest possible diagnosis and treatment for PI diseases); 3) evaluation of screening and diagnostic tools (to ensure their quality and appropriateness for identification of patients with PI diseases); and 4) communication (communication with and information dissemination to health-care providers and the public to facilitate prompt and appropriate diagnosis and intervention). The working group's deliberations focused on challenges and opportunities, priority research questions, and recommendations for future action for these four components. These recommendations, developed by workshop participants, will be useful to medical and public health professionals who are evaluating methods to increase recognition of PI diseases and other genetic disorders.

Baker Tg

Papers

Applying public health strategies to primary immunodeficiency diseases: a potential approach to genetic disorders.