Ethical issues with newborn screening in the genomics era.

Continued technological advances have made the prospect of routine whole-genome sequencing (WGS) imminent. To date, much of the discussion about WGS has focused on its application and use in clinical medicine. Relatively little attention has been paid to the potential integration of WGS into newborn screening programs. Given the structure and scope of these programs, it is possible that the early applications of WGS will occur in state-run newborn screening programs. Assessment of the pressing ethical issues currently facing the newborn screening community will provide insight into the challenges that lie ahead in the genomics era.

Is there a benefit to a routine preoperative screening of infectivity for HIV, hepatitis B and C virus before elective orthopaedic operations?

PURPOSE: Before elective operations, particularly orthopaedic surgery, national guidelines in Germany recommend testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) to reduce the risk of transmission of the virus through a needlestick or cutting injury. Such testing is expensive. The number of new and unknown diagnoses of viral infections that can be detected by routine screening has not yet been evaluated. METHODS: The aim of our department of orthopaedic surgery is to screen every adult patient listed for an operation for HBV, HCV and HIV. We retrospectively analysed the number of operations in this single centre from 2001 to 2010, correlated this number with the total number of screens and calculated the number of newly diagnosed infections. An additional cost:benefit ratio was calculated. RESULTS: A total of 20,869 operations were performed by the department between 2001 and 2010. After exclusion of all interventions in children and all patients who had multiple operations, 15,482 patients remained. Test results were found for 10,011 of these patients during this period (screening rate 65 %). Of those screened, in only four cases (0.4 ‰) was a previously unknown infection detected. CONCLUSIONS: Two-thirds of the patients included in our study actually underwent screening; this rate was lower than expected. The incidence of newly detected infections was low, putting the benefit of a routine preoperative screening for HBV, HCV and HIV into question. From an economic point of view the low detection rate is a strong argument in favour of omitting routine preoperative screening. Screening only those patients with risk factors may be as safe as screening every patient and would help reduce costs.

Is there evidence for mandating electrocardiogram as part of the pre-participation examination?

The risk of sudden cardiac death may be increased up to 2.8 times in competitive athletes compared with nonathletes. The majority of sudden cardiac death cases are caused by an underlying abnormality that potentially may be identified on cardiovascular screening, depending on the specific abnormality and the content of the cardiovascular screening applied. Indeed, today, cardiac screening is universally recommended by the cardiac societies [European Society of Cardiology (ESC) and American Heart Association (AHA)] and required by the sporting bodies [Fédération Internationale de Football Association (FIFA) and Union of European Football Associations (UEFA)]. Pre-participation examination is by consensus understood to include personal history and physical examination; controversy exists regarding the usefulness and appropriateness of screening using resting 12-lead electrocardiogram (ECG), with an apparent transatlantic difference. The ESC recommends screening consisting of personal history, physical examination, and 12-lead resting ECG, whereas recommendations from the AHA includes only personal history and physical examination. There is firm scientific ground to state that the sensitivity of screening with ECG is vastly superior to, and the cost-effectiveness significantly better than, screening without ECG. Cardiac screening of elite athletes with personal history, physical examination, and ECG is cost-effective also in comparison with other well-accepted procedures of modern health care, such as dialysis and implantable cardiac defibrillators. Newly published recommendations for the interpretation of the ECG in athletes (ESC) and future studies on ECGs in athletes of different ethnicity, gender, and age may further increase the specificity of ECG in cardiac screening, refining the screening procedure and lowering the costs for additional follow-up testing. Cardiac screening without ECG is not cost-effective and may be only marginally better than no screening at all and at a considerable higher cost. The difficulties in feasibility and liability issues for recommending ECGs in some countries need to be acknowledged but must be dealt with within those countries/systems. On ethical grounds, the reasons (logistical, legal, economic) for not screening individual athletes should be clearly stated. Alas, the current evidence, as presented here, suggests that the ECG should be mandatory in pre-participation screening of athletes.

Costs of cannabis testing compliance: Assessing mandatory testing in the California cannabis market.

Most U.S. states that have regulated and taxed cannabis have imposed some form of mandatory safety testing requirements. In California, the country's largest and oldest legal cannabis market, mandatory testing was first enforced by state regulators in July 2018, and additional mandatory tests were introduced at the end of 2018. All cannabis must be tested and labeled as certified by a state-licensed cannabis testing laboratory before it can be legally marketed in California. Every batch that is sold by licensed retailers must be tested for more than 100 contaminants, including 66 pesticides with tolerance levels lower than the levels allowable for any other agricultural product in California. This paper estimates the costs of compliance with mandatory cannabis testing laws and regulations, using California's testing regime as a case study. We use state government data, data collected from testing laboratories, and data collected from lab equipment suppliers to run a set of Monte Carlo simulations and estimate the cost per pound of compliance with California's new cannabis testing regulations. We find that cost per pound is highly sensitive to average batch size and testing failure rates. We present results under a variety of different assumptions about batch size and failure rates. We also find that under realistic assumptions, the loss of cannabis that must be destroyed if a batch fails testing accounts for a larger share of total testing costs than does the cost of the lab tests. Using our best estimates of average batch size (8 pounds) and failure rate (4%) in the 2019 California market, we estimate testing cost at $136 per pound of dried cannabis flower, or about 10 percent of the reported average wholesale price of legal cannabis in the state. Our findings explain effects of the testing standards on the cost of supplying legal licensed cannabis, in California, other U.S. states, and foreign jurisdictions with similar testing regimes.

Optimal HIV testing and earlier care: the way forward in Europe.

The articles in this supplement were developed from a recent pan-European conference entitled 'HIV in Europe 2007: Working together for optimal testing and earlier care', which took place on 26-27 November in Brussels, Belgium. The conference, organized by a multidisciplinary group of experts representing advocacy, clinical and policy areas of the HIV field, was convened in an effort to gain a common understanding on the role of HIV testing and counselling in optimizing diagnosis and the need for earlier care. Key topics discussed at the conference and described in the following articles include: current barriers to HIV testing across Europe, trends in the epidemiology of HIV in the region, problems associated with undiagnosed infection and the psychosocial barriers impacting on testing. The supplement also provides a summary of the World Health Organization's recommendations for HIV testing in Europe and an outline of an indicator disease-guided approach to HIV testing proposed by a committee of experts from the European AIDS Clinical Society (EACS). We hope that consideration of the issues discussed in this supplement will help to shift the HIV field closer towards our ultimate goal: provision of optimal HIV testing and earlier care across the whole of the European region.

Lessons from state mandates of preventive cancer screenings.

We use the 1997-2008 Medical Expenditure Panel Survey (MEPS) and variation in the timing of state mandates for coverage of colorectal, cervical, and prostate cancer screenings to investigate the behavioral and financial effects of mandates on privately insured adults. We find that state mandates did not result in increased rates of cancer screening. However, coverage of preventive care, whether mandated or not, moves the cost of care from the consumer's out-of-pocket expense to the premium, resulting in a cross-subsidy of users of the service by non-users. While some cross-subsidies are intentional, others may be unintentional. We find that users of cancer screening have higher levels of income and education, while non-users tend to be racial minorities, lack a usual source of care, and live in communities with fewer physicians per capita. These results suggest that coverage of preventive care may transfer resources from more advantaged individuals to less advantaged individuals.

HIV screening of surgeons and dentists: a cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of human immunodeficiency virus (HIV) screening strategies of surgeons and dentists. DESIGN: We constructed a model to project costs and HIV transmissions prevented over 15 years for four screening scenarios: 1) one-time voluntary screening, 2) one-time mandatory screening, 3) annual voluntary screening, and 4) annual mandatory screening. One-time screening occurs only in the first year of the program; annual screening occurs once each year. Under mandatory screening, all practitioners are tested and risks of practitioner-to-patient transmission are eliminated for all practitioners testing positive. Voluntary screening assumes 90% of HIV-positive and 50% of HIV-negative practitioners are tested, and risks of transmission in the clinical setting are eliminated for 90% of HIV-positive surgeons and dentists. All costs and benefits are discounted at 5% per annum over 15 years. RESULTS: Using "best-case" scenario assumptions, we find for surgeons that a one-time voluntary screening program would be most cost-effective, at $899,336 for every HIV transmission prevented. For dentists, the one-time voluntary program also is the most cost-effective, at $139,571 per transmission prevented. Annual mandatory programs were least cost-effective for both surgeons and dentists, at $63.3 million and $2.2 million per transmission prevented, respectively. CONCLUSIONS: HIV screening of surgeons and dentists ranks among the more expensive medical lifesaving programs, even using liberal assumptions about program effectiveness. Frequency of screening and whether testing is mandatory or voluntary dramatically affect cost per transmission prevented; these features should be considered carefully in designing specific HIV screening programs.

Cost-effectiveness of mandatory compared with voluntary screening for human immunodeficiency virus in pregnancy.

OBJECTIVE: To determine the cost-effectiveness of mandatory screening for human immunodeficiency virus (HIV) in pregnancy compared with that of voluntary screening under varying assumptions about patient behavior. METHODS: Using a health care system perspective, a decision-analysis model was constructed to estimate the outcomes and costs of the two strategies. Average and incremental cost-effectiveness ratios were calculated for each strategy. Sensitivity analyses were performed to test the effects of different values on the results of the simulation. In particular, we examined the potential effects of changes in patient behavior resulting from mandatory screening on our estimates of cost-effectiveness. RESULTS: At a prevalence of 170 per 100,000, average costs per case prevented were $255,158 and $367,998 for mandatory and voluntary screening, respectively. The incremental cost-effectiveness of mandatory compared with voluntary screening was $29,478. These values decreased as prevalence of HIV increased, or as the estimated lifetime cost of pediatric HIV infection increased: above an estimated cost for pediatric HIV of $129,250, mandatory screening was less expensive and more effective than voluntary screening. Assumptions about patient behavior affected these results: a 40% reduction in zidovudine acceptance in women identified only through mandatory screening increased the incremental cost-effectiveness to $112,434. The impact of behavior increased as the prevalence of HIV increased. CONCLUSION: Mandatory screening will prevent more cases of pediatric AIDS, but at a somewhat higher cost than voluntary screening under baseline assumptions. The cost-effectiveness of mandatory screening will be influenced by patient behavior, especially acceptance of zidovudine treatment among women who would have refused voluntary screening.

The Omega-Project--a comparison of two diagnostic strategies for risk- and cost-oriented management of dyspepsia.

OBJECTIVES: In dyspepsia few data are available from the primary care setting on how selective, risk-factor-oriented endoscopy compares with mandatory endoscopy in the diagnostic outcome and in direct and secondary costs. We studied this in a two-armed multicentre trial (omega-project) with primary care physicians. MATERIAL AND METHODS: Patients were enrolled and treated by primary care physicians and referred to a gastroenterologist for upper gastrointestinal endoscopy (UGE). Patients were enrolled in the study if they had had epigastric complaints for more than 1 month and no obvious signs or history of organic disease. In the first arm of the study endoscopy was mandatory, in the second selective, i.e. according to a predefined risk profile. Patients enrolled were treated with prokinetic drugs for 2 months. A further indication for endoscopy was non-response to treatment (reduction of the initial symptoms score by less than two-thirds) in the study with selective endoscopy and relapse within the 2-month follow-up period in both studies. The direct costs from number of consultations with the primary care physician, UGEs, number of prescriptions per patient and also absenteeism in days per week were carefully registered in both groups. RESULTS: All 172 patients of the mandatory endoscopy study and 203/656 patients enrolled in the selective endoscopy study had an UGE (125 at admission, 78 in the follow-up period). Patients were treated for 4 weeks (cisapride or domperidone) and thereafter followed for 8 weeks, at the end of the observation period the response rates were 80% and 79%, respectively. The prevalence of gastric cancers was similar in both groups (> 1%) but extrapolation from the data collected with compulsory endoscopy suggests that two-fifths of the anticipated peptic lesions remained undetected by following the selective strategy. The cost analysis revealed a 31% cost reduction with the selective strategy--in the Swiss cost system--through a reduction in the number of endoscopies by 67%. CONCLUSION: Selective UGE is cheaper and appears not to compromise the response to prokinetics; however, its diagnostic power is less than with mandatory UGE.

A survey of compliance: Medicaid's mandated blood lead screenings for children age 12-18 months in Nebraska.

BACKGROUND: To determine the frequency of Medicaid mandated blood lead level (BLL) screening compliance rates by clinical site. METHODS: Retrospective chart review for evidence of BLLs. Data analyses were conducted using frequencies, percentages & chi-square. RESULTS: The overall incidence of documented BLLs was 78.9% with one clinic demonstrating 100% BLLs while the others had 72%. Screening rates differed significantly by clinical site (X2 = 18.460, df = 3, p < 0.001). CONCLUSION: Although universal blood lead screening is mandated, there were missed opportunities to obtain BLLs in 21.1% of the records reviewed. Only one clinic had 100% documentation of BLLs when children on Medicaid were seen between the ages of 12-18 months.

Snafu in Texas prenatal testing to remain on the books.

AIDS: The 1997-98 session of the Texas Legislature closed without the passing of several HIV-related bills. In particular, a 1995 law that requires healthcare providers to test pregnant women and provide HIV counseling during prenatal care was allowed to stand. The law is flawed because it requires testing for sexually transmitted diseases at birth. An HIV test administered at birth may be too late to prevent perinatal transmission. A proposed law would have limited the mandate for HIV testing to the woman's prenatal care. A bill that would have established nonprofit dental clinics specializing in HIV care did not clear the State Senate.^ieng

House panel to draft bill mandating testing of newborns.

AIDS: The Ryan White CARE Act reauthorization bill may be at a standstill. Republican Tom Coburn has argued that all newborns should be tested to protect the health of the infants and alert the mother to seek medical care. He has sought to amend the Ryan White reauthorization measure to mandate HIV testing. The American Medical Association, the National Governors Association, and the Association of State and Territorial Health Officials joined AIDS groups in opposing Coburn's proposal. They contend that the most effective means of protecting babies is through testing and medical intervention during pregnancy. Leaders of the House Commerce Committee agreed that the Ryan White funding would not be used to pay for the cost of testing. It would cost about forty dollars to test each of the nation's four million newborns each year, though most mothers presumably would be covered under private insurance or Medicaid.^ieng

Senate favors promoting voluntary tests for pregnant women.

AIDS: Senator Nancy Landon Kassebaum, R-Kans., has proposed legislation that would implement the Centers for Disease Control and Prevention (CDC) recommendations for universal counseling and voluntary HIV-antibody testing of pregnant women. The proposal was tacked onto the Ryan White CARE Act reauthorization bill. Under the Senator's plan, jurisdictions with a high HIV-seroprevalence rate among child-bearing women would qualify for Federal funds to promote counseling and testing. This plan is an alternative to legislation sponsored by Reps. Tom Coburn, R-Okla., and Gary Ackerman, D-NY, that would require mandatory testing of all newborns whose mothers had not been tested during pregnancy. Opponents of mandatory testing of pregnant women state that it would drive women away from important prenatal care. Coburn and Ackerman hope to amend the Ryan White reauthorization bill to force testing of all newborns. The Congressmen believe the bill will prevail in the House and be voted down in the Senate.^ieng

Mandatory ECG screening of athletes: is this question now resolved?

European and North American cardiologists have long debated the need for mandatory ECG screening of athletes in order to prevent sudden cardiac death. European investigators have recently adduced new evidence, which they believe supports the need for such screening. They note a decrease of sudden cardiac deaths among Italian athletes following the introduction of mandatory screening in that country, clearer definitions of resting ECG abnormalities in athletes, new and more encouraging calculations of cost/benefit ratios and direct comparisons of clinical examination alone against clinical examination plus ECG screening. Nevertheless, it seems that critical criteria for the success of any screening procedure (a substantial prevalence of the problem, coupled with an adequate test sensitivity and specificity) have yet to be satisfied. Very few athletes are liable to sudden cardiac death, only a few of those who are vulnerable will be identified by ECG screening, and even if all potential cases could be detected, restriction of their physical activity would be unlikely to have a major influence on their prognosis. At the same time, a requirement of mandatory testing would discourage engagement in physical activity, and would impose substantial direct costs on the community. Moreover, the large number of false positive test results could have important and undesirable consequences for both indirect medical costs and the overall health of competitors. ECG screening might become more effective if it could be focused on a smaller sub-group of vulnerable athletes, or if the problem of false positive tests could be addressed through an increase of test specificity. However, on the basis of current information, it would seem better to direct efforts in preventive medicine to more common causes of premature death in the young adult.