Impact Of False-positive Results Research Articles

Psychosocial Impact of False-Positive Newborn Screening Results: A Scoping Review.

Psychosocial consequences of false-positive results following newborn bloodspot screening have been identified as a potential risk to this highly successful public health initiative. A scoping review was undertaken in October 2023 underpinned by the Arksey and O'Malley framework. Twenty-four papers were included in the review, many of which focused on cystic fibrosis. The results indicated that impact of false-positive results is variable; some studies suggest false-positive results have the potential to result in negative sequelae including increased stress and changes in parental perceptions of their child, while others suggest these impacts are transient and, in some instances, may even lead to positive outcomes. Further evidence is needed to ensure the representation of other conditions included in newborn bloodspot screening and to support strategies to overcome potential negative sequela.

The clinical and economic benefits associated with novel multi-cancer early detection tests: conference highlights from the 2022 ISPOR Annual Meeting.

Cancer remains the second leading cause of death in the United States despite decades of treatment advances. While death rates have fallen for breast, cervical, and colorectal cancers, all of which have population-based screening options, rates remain high for the majority of malignancies, with most diagnosed in the later stages. In addition, adherence to screening recommendations in the United States is low, with high rates of false-positive results. Multi-cancer early detection (MCED) tests detect early cancer signals from as many as 50 or more neoplasms using cell-free DNA and other circulating analytes in blood. They may be more accessible and easier to disseminate than organ-specific tests. However, the impact on cancer-related deaths remains unclear. Other unanswered questions include cost-effectiveness, the impact of false-positive results on patients and costs, the overdiagnosis of more indolent cancers, uptake among patients and clinicians, and the need for protocols covering their use. Research and development of blood-based MCED tests continue.

The impact of false positive COVID-19 results in an area of low prevalence

False negative results in COVID-19 testing are well recognised and frequently discussed. False positive results, while less common and less frequently discussed, still have several adverse implications, including potential exposure of a non-infected person to the virus in a cohorted area. Although false positive results are proportionally greater in low prevalence settings, the consequences are significant at all times and potentially of greater significance in high-prevalence settings. We evaluated COVID-19 results in one area during a period of low prevalence. The consequences of these results are discussed and implications for these results in both high and low prevalence settings are considered. We also provide recommendations to minimise the risk and impact of false-positive results.

The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study.

BackgroundThere is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants.MethodsThe cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use.ResultsWe identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life.ConclusionsThe higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

Audit of antenatal screening for syphilis and HIV in migrant and refugee women on the Thai-Myanmar border: a descriptive study

The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in the same population and reassess the trends in HIV rates. From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border. Seroprevalence for HIV 0.47% (95% CI 0.30-0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL≥1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (>75% were < 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors. As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies.

Audit of antenatal screening for syphilis and HIV in migrant and refugee women on the Thai-Myanmar border: a descriptive study

Objective: The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in the same population and reassess the trends in HIV rates.Methods: From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border.Results: Seroprevalence for HIV 0.47% (95% CI 0.30-0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL≥1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (>75% were < 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors.Conclusion: As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies.

Screening for prevention and early diagnosis of cancer.

The poor outcomes for cancers diagnosed at an advanced stage have been the driver behind research into techniques to detect disease before symptoms are manifest. For cervical and colorectal cancer, detection and treatment of "precancers" can prevent the development of cancer, a form of primary prevention. For other cancers-breast, prostate, lung, and ovarian-screening is a form of secondary prevention, aiming to improve outcomes through earlier diagnosis. International and national expert organizations regularly assess the balance of benefits and harms of screening technologies, issuing clinical guidelines for population-wide implementation. Psychological research has made important contributions to this process, assessing the psychological costs and benefits of possible screening outcomes (e.g., the impact of false positive results) and public tolerance of overdiagnosis. Cervical, colorectal, and breast screening are currently recommended, and prostate, lung, and ovarian screening are under active review. Once technologies and guidelines are in place, delivery of screening is implemented according to the health care system of the country, with invitation systems and provider recommendations playing a key role. Behavioral scientists can then investigate how individuals make screening decisions, assessing the impact of knowledge, perceived cancer risk, worry, and normative beliefs about screening, and this information can be used to develop strategies to promote screening uptake. This article describes current cancer screening options, discusses behavioral research designed to reduce underscreening and minimize inequalities, and considers the issues that are being raised by informed decision making and the development of risk-stratified approaches to screening.

Low and stable rates of antenatal syphilis and HIV in migrant and refugee women on the Thai-Myanmar border: a descriptive study

Objective: The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in migrant and refugee women on the Thai Myanmar border.Methods: From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border.Results: Seroprevalence for HIV 0.47% (95% CI 0.30-0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL≥1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (&gt;75% were &lt; 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors.Conclusion: As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies.

Impact of new screening technologies: should we screen and does phenotype influence this decision?

The early detection offered by newborn screening for phenylketonuria clearly demonstrates the benefits for patients with inherited metabolic disorders of well organised screening programmes. It is therefore perhaps surprising that 20years after the introduction of electrospray MS/MS methods to support expanded newborn screening that considerable international variation in practice, not linked to economic factors, exists. It is likely that the commonly used criteria to assess the suitability of a disorder for screening need to be re-appraised as they apply to rare disorders. In addition, national differences in the pattern of policy making may influence the strategy adopted and these different approaches need to be scrutinised more closely. Despite this contextual variation a number of real issues do need to be addressed as the range of conditions included in screening programmes continues to increase. These include the need for well organised outcome studies based upon agreed case definitions and comparable treatment regimens; the need for appropriate information for parents to support them before and during the screening odyssey; an improved understanding of the impact of false positive results and in particular a clearer understanding of the way in which some of the problems resulting from false positive results can be avoided or ameliorated; the challenge offered by mild or atypical screen positive cases and the consequent design of proportionate treatment options. A thorough understanding of the genetic, biochemical and clinical features of screen positive cases supported by effective international outcome studies is required to optimise both screening and treatment strategies.

Screening for depression in medical research: ethical challenges and recommendations

BackgroundDue to the important role of depression in major illnesses, screening measures for depression are commonly used in medical research. The protocol for managing participants with positive screens is unclear and raises ethical concerns. The aim of this article is to identify and critically discuss the ethical issues that arise when a positive screen for depression is detected, and offer some guidance on managing these issues.DiscussionDeciding on whether to report positive screens to healthcare practitioners is both an ethical and a pragmatic dilemma. Evidence suggests that reporting positive depression screens should only be considered in the context of collaborative care. Possible adverse effects, such as the impact of false-positive results, potentially inappropriate labelling, and potentially inappropriate treatment also need to be considered. If possible, the psychometric properties of the selected screening measure should be determined in the target population, and a threshold for depression that minimises the rate of false-positive results should be chosen. It should be clearly communicated to practitioners that screening scores are not diagnostic for depression, and they should be informed about the diagnostic accuracy of the measure. Research participants need to be made aware of the consequences of the detection of high scores on screening measures, and to be fully informed about the implications of the research protocol.SummaryFurther research is needed and the experiences of researchers, participants, and practitioners need to be collated before the value of reporting positive screens for depression can be ascertained. In developing research protocols, the ethical challenges highlighted should be considered. Participants must be agreeable to the agreed protocol and efforts should be made to minimise potentially adverse effects.

Putting a value on the avoidance of false positive results when screening for inherited metabolic disease in the newborn

Despite the increase in the number of inherited metabolic diseases that can be detected at birth using a single dried blood spot sample, the impact of false positive results on parents remains a concern. We used an economic approach - the contingent valuation method - which asks parents to give their maximum willingness to pay for an extension in a screening programme and the degree to which the potential for false positive results diminishes their valuations. 160 parents of a child or children under the age of 16years were surveyed and given descriptions of the current screening programme in the UK, an extended programme and an extended programme with no false positives. 148 (92.5%) respondents said they would accept the screen for the five extra conditions in an expanded screening programme whilst 10 (6.3%) said they would not and two were unsure. When asked to indicate if they would choose to be screened under an expanded screening programme with no false positive results, 152 (95%) said they would, five (3.1%) said they would not, two were unsure, and there was one non-response. 151 (94.4%) said they preferred the hypothetical test with no false-positives. The mean willingness to pay for the expanded programme was £178 compared to £219 for the hypothetical expanded programme without false positives (p > 0.05). The results suggest that there is widespread parental support for extended screening in the UK and that the number of false-positives is a relatively small issue.

Risk of sports: do we need a pre-participation screening for competitive and leisure athletes?

Sudden cardiac arrest is most often the first clinical manifestation of an underlying cardiovascular disease and usually occurs in previously asymptomatic athletes. The risk benefit ratio of physical exercise differs between young competitive athletes and middle-age/senior individuals engaged in leisure-time sports activity. Competitive sports are associated with an increase in the risk of sudden cardiovascular death (SCD) in susceptible adolescents and young adults with underlying cardiovascular disorders. In middle-age/older individuals, physical activity can be regarded as a 'two-edged sword': vigorous exertion increases the incidence of acute coronary events in those who did not exercise regularly, whereas habitual physical activity reduces the overall risk of myocardial infarction and SCD. Although cardiovascular pre-participation evaluation offers the potential to identify athletes with life-threatening cardiovascular abnormalities before onset of symptoms and may reduce their risk of SCD, there is a significant debate among cardiologists about efficacy, impact of false-positive results and cost-effectiveness of routine screening. This review presents an appraisal of the available data and criticisms concerning screening programmes aimed to prevent SCD of either young competitive athletes or older individuals engaged in leisure-time sports activity.

Preparticipation Screening of Young Competitive Athletes for Cardiovascular Disorders

The beneficial effects of regular physical exercise on cardiovascular morbidity and mortality are well documented. In rare cases, however, athletes with cardiovascular abnormalities are at increased risk of exercise-related sudden cardiac death (SCD). Paradoxically, most SCDs can be attributed to cardiovascular abnormalities that can be identified during an athlete's life. Such abnormalities can be minimized by several therapeutic strategies, including insertion of an implantable cardioverter-defibrillator. Based on these considerations, the medical and sporting governing bodies recommend preparticipation cardiovascular screening (PPS) in young competitive athletes (aged ≤ 35 years) to identify potentially fatal cardiovascular disorders. However, PPS is associated with several controversies related to the efficacy, cost-effectiveness, and impact of false-positive results. This article aims to provide a detailed overview of the issues concerning PPS based on current evidence.