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[Current situation and future of gastric cancer screening examinations: from the viewpoint of gastric X-ray screening].

In Japan, screening examinations for gastric cancer have been conducted for 50 years because of the high prevalence of this type of cancer. Gastric X-ray screening examinations have contributed to the detection early gastric cancer. In 2001, Hisamichi et al. reported that X-ray examination is a valid technique in gastric cancer screening. However, they indicated that problems in the uncertainty of accuracy and the risk of radiation exposure at a young age. On the other hand, endoscopic screening examination, pepsinogen-method and H. pylori method are not acceptable because of incident risk. Our future goals are to improve the precision of gastric X-ray examinations in cancer screening nationwide and to advocate for annual gastric screening examinations in higher risk groups. As a result, it is hoped that gastric cancer X-ray screening examinations can contribute to preventive medicine.

Antibodies, Bacterial↗

[A population survey on a mass screening program for gastric cancer. 1. Population characteristics related to examination rates for the screening program].

The types of examination received for gastric cancer during the past 3 years have been surveyed by a self-administered questionnaire among residents of a small town near Kitakyushu City. Among 3660 surveyed, 2205 subjects who completed the questionnaire are analyzed in this study. Examination rates of mass screening for males were higher than those for females. Males in their forties and fifties and females in their forties through sixties have higher examination rates than other age groups. Higher examination rates were seen in public officials and employees who have opportunities to receive the screening program at work site. On the other hand, among people without a job and housewives who have opportunities to receive a screening program offered only by the town hall, examination rates of the mass screening program were low. More people with a family history of cancer death were examined than those without a similar family history. There was no difference in the examination rates by the mass screening program between the people who took care of their health and those who did not. In order to raise examination rates for the mass screening program, it is essential to improve the systems of this program which can be easily accepted, and to educate residents in order to stimulate motivation for screening.

Adult↗

Routine meconium screening versus drug screening per physician order: detecting the true incidence of drug-exposed infants.

National statistics indicate that 11% of newborns are exposed to drugs of abuse in utero (Chasnoff, Burns, Schnoll, & Burns, 1985). From July through November of 1993, 0.2% (1/583) of infants in our hospital screened positive for exposure to drugs of abuse in utero, by blood and urine screens collected per physician's order. During the same 4 months in 1995, 0.2% (1/574) screened positive. In contrast, from July through November 1994, all newborns born at our institution were screened for in utero drug exposure using meconium samples; approximately 4.5% (22/493) were positive. Meconium screening of all infants, not just those per physician order, produced a dramatic increase in positive drug results. Of great concern in this study was that only two of the 22 mothers identified as having drug-screen positive babies during the 1994 meconium screening agreed to use rehabilitative services. This highlights the necessity of intervention through early educational programs stressing prevention.

Female↗

Testing an instrument to screen for fibromyalgia syndrome in general population studies: the London Fibromyalgia Epidemiology Study Screening Questionnaire.

OBJECTIVE: To develop and test an instrument to screen for fibromyalgia syndrome (FM) in general population surveys. METHODS: We designed a questionnaire with 4 pain and 2 fatigue items. A positive screen was defined 2 ways: (1) positive responses to all 4 items on pain, and (2) positive responses to all pain and fatigue items. Sensitivity was tested in the clinic on 31 outpatients with FM, specificity on 30 outpatients with rheumatoid arthritis (RA) and 30 healthy controls. Test-retest reliability (TRR) was estimated in a community survey of 672 noninstitutionalized adults. Positive predictive value (PPV) was estimated as part of a community survey of 3395 noninstitutionalized adults, in which 100 cases of FM were confirmed by examination. RESULTS: For pain criteria alone sensitivity was 100% (95% confidence intervals 90.3%, 100%); in patients with RA specificity was 53.3% (35.4%, 71.2%). For the pain plus fatigue criteria, sensitivity was 93.5% (83.8%, 100%), and specificity in patients with RA 80% (65.7%, 94.3%). In nonpatient controls, specificity was 100% (89.3%, 100%) using either definition of a positive screen. For those initially screening negative, TRR was 100% (93.2%, 100%) using either definition. For positive screens, TRR was 95.0% (88.8%, 100%) for the pain criteria alone, and 81.0% (69.1%, 92.8%) for the combined criteria. PPV was 56.8% (53.0%, 60.6%) using the pain criteria alone, and 70.6% (CI 55.3%, 85.9%) using the combined criteria. CONCLUSION: The instrument appears to be useful in screening for FM in general population surveys of noninstitutionalized adults. Confirmation of FM among those who screen positive requires a personal interview to reestablish pain duration and distribution, and an examination for tender points.

Adult↗

Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group.

BACKGROUND: Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening. The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated. The authors describe a cluster-randomized, controlled oral cancer screening trial in southern India and its early results. METHODS: Apparently healthy subjects age 35 years or older in 13 clusters called panchayaths were randomized to either an intervention group (n = 7) or a control group (n = 6). Subjects in the intervention group will receive 3 rounds of screening consisting of oral visual inspection by trained health workers at 3-year intervals. The first round of screening was carried out between October 1995 and May 1998. Participants were visited in their homes and interviewed for sociodemographic details, tobacco-smoking and alcohol-drinking habits, and personal medical history. Those with tobacco or alcohol habits were advised to stop those habits. Subjects in the intervention group were offered screening, and those with lesions suggestive of oral leukoplakia, submucous fibrosis, or oral cancer were referred for examination by physicians. Confirmed leukoplakias were excised whenever possible, others were kept on follow-up, and those with confirmed oral cancers were referred for treatment. Data on oral cancer incidence, stage distribution, survival, and mortality in the study groups are obtained by record linkage with the Trivandrum population-based cancer registry and municipal death registration systems. RESULTS: There were 59,894 eligible subjects in the intervention group and 54,707 in the control group; 31.4% of the former group reported no tobacco or alcohol habits, compared with 44.1% of the latter. The distribution of age, education, occupation, income, and socioeconomic status were similar in the two groups. Of 3585 subjects in the intervention group referred, 52.4% were examined by physicians; 36 subjects with oral cancers and 1310 with oral precancers were diagnosed. Of the 63 oral cancers recorded in the cancer registry, 47 were in the intervention group and 16 were in the control group, yielding incidence rates of 56.1 and 20.3 per 100,000 person-years in the intervention and control groups, respectively. The program sensitivity for detection of oral cancer was 76.6% and the specificity 76.2%; the positive predictive value was 1.0% for oral cancer. In the intervention group, 72.3% of the cases were in Stages I-II, as opposed to 12.5% in the control group. The 3-year case fatality rates were 14.9% (7 of 47 patients) in the intervention group and 56.3% (9 of 16 patients) in the control group. CONCLUSIONS: Though compliance with referral for confirmatory examination in the first round was lower than the 70% anticipated, intermediate end points, such as stage at diagnosis and case fatality, indicate that the trial is making fairly satisfactory progress.

Adult↗

Development and standardization of a new telephonic cognitive screening test: the Minnesota Cognitive Acuity Screen (MCAS).

OBJECTIVE: The aim of this study was to determine the validity and reliability of a telephonically administered cognitive screening battery, consisting of nine brief tests (orientation, attention, delayed word recall, comprehension, repetition, naming, computation, judgment, and verbal fluency), to distinguish between patients with dementia and healthy control subjects. BACKGROUND: Existing telephonic screening instruments do not take full advantage of strategies that might increase precision. METHODS: A total of 228 elderly individuals received a telephone assessment of cognitive function (99 mildly to moderately demented nursing home residents with an established diagnosis of dementia residing in 1 of 12 nursing facilities, and 129 community-dwelling elderly individuals who were independently screened to verify normal cognitive function). RESULTS: Nurses and psychologists experienced in telephonic test administration typically completed the screening with each subject in less than 20 minutes. At the 100% sensitivity level, the test battery had a specificity of 87%. The post hoc optimal cut-score of the discriminant analysis yielded a sensitivity of 97.5% and a specificity of 98.5%. The split-half reliability of the test battery was 0.91. The more powerfully predictive subtests were orientation, delayed word recall, verbal fluency, computation, and judgment. CONCLUSIONS: This telephonic screening instrument appears to have promise to distinguish, with high precision, healthy elderly individuals from those individuals with cognitive impairment. The Minnesota Cognitive Acuity Screen (MCAS) should undergo further study in unselected elderly populations to better understand its value as a screening tool.

Age Distribution↗

International cooperation in neonatal screening: technical training course for newborn and infant screening.

We report the outline and results of our experience with a group training course of neonatal screening for health care professionals in developing countries. Sapporo City Institute of Public Health (SCIPH) has been offered a training course on neonatal screening once a year since 1991 under the Technical Training Program of the Japan International Cooperation Agency (JICA). The aims of this training course are to enhance the participants' technical knowledge and skills, and also to deepen their understanding of the principle of neonatal screening as well as the relevant diseases. Lectures and laboratory practice on phenylketonuria (PKU), congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and neuroblastoma are included in the 3-month program. After the completion of the training, participants are expected to play a major role in establishing and expanding neonatal screening system in each of their countries. We have received a total of 67 participants from 25 countries until March 1998: 58 pediatricians; 2 gynecologists; 6 biochemists; 1 administrative officer. After they returned to their countries, 11 engaged in neonatal screening and started PKU and CH screening in their institute, city or province in Argentina, Brazil, Mexico, Peru and Thailand. We believe that these results fulfilled our objectives. Also, for follow-up, SCIPH has been giving information and consultation to the participants on requests. This international cooperation network could also benefit our present network of the International Society Screening in the future.

Developing Countries↗

Newborn screening for cystic fibrosis. The Cystic Fibrosis Neonatal Screening Study Group.

Many questions remain regarding the efficacy, risks, and costs of CF neonatal screening. The major gap in knowledge that must be closed before CF neonatal screening can be recommended generally in the United States concerns the potential long-term medical benefits of initiating treatment in early infancy. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. It is for this reason we designed a randomized, controlled investigation of CF neonatal screening and implemented this project in Wisconsin during 1985. The fact that 5 years of randomized screening and systematic evaluation of outcome measures have not yet revealed any pulmonary benefits underscores the importance of rigorous investigation to resolve the efficacy issue. In addition to the medical uncertainties, we believe that the ethical issues described herein need to be resolved; this concern pertains not only to the CF patient but also the heterozygote carrier. On the other hand, financial factors and uncertainty about the cost effectiveness of CF neonatal screening do not appear to be dominant issues according to our assessment of current data. Despite the reservations related to the benefit/risk relationship, we expect that the discovery of the CF gene should have a favorable impact on neonatal screening for the disease, as well as for management.

Cost-Benefit Analysis↗

[Mass-screening for ovarian cancer by means of transvaginal ultrasonography--study on size of ovary to select subjects requiring second screening].

Mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in Aomori Prefecture since 1989. To select appropriate candidates to receive the second screening, the size of 44 normal ovaries removed by surgery and was measured studied on 10,692 ultrasonic pictures recorded on a VTR. The results were as follows: (1) All 44 ovaries were under 40mm. (2) In 3,806 (35.6%) of 10,692 women at the first screening, their ovaries were detected by ultrasonography. This detection rate was higher in young subjects and in the luteal and menstrual phases than in others. (3) Of these ovaries, 1,303 (34.2%) were under 19mm, 1,891 (49.7%) were 20-29mm and 614 (16.1%) were over 30mm in size. (4) The second screening was performed in 472 of the 614 women, and the size of the ovaries in 83 (17.6%) of them was under 29mm. (5) The frequency of ovarian size exceeding 40mm at the second screening, was 12.5% of the 30-39mm diameter group and 48.0% of the 40-49mm group at the first screening. There was no malignant tumor in the former, but there were one pre-malignant and one malignant tumor in the latter. These results indicate that the second screening should be performed for women having ovaries over 40mm in size.

Adult↗

[Postnatal screening of renal developmental anomalies. Classical diagnostic methods, risk factors and routine screening].

During a 6 years' period (2 years of control, 2 years of risk group and 2 years of routine screening) the authors examined the effect of different diagnostical methods on the frequency of detected renal developmental anomalies. The incidence of documented renal malformations was 1.1% during the use of classical diagnostical methods, 8.3% during the application of intrauterine routine and postnatal risk group screening, and 10.3% after the introduction of postnatal routine screening in 2 years' periods. The advantage of both postnatal risk group and postnatal routine screening was that the greatest part of renal anomalies could have been diagnosed before the appearance of the symptoms of urinary infection. On the basis of effectivity of postnatal routine screening and decrease of uncertainty of postnatal risk group screening authors suggested the introduction of the postnatal routine screening as general practice under our own circumstances.

Child↗

Cervical intraepithelial neoplasia III. An estimate of screening error rates and optimal screening interval.

The detection rates of grade III cervical intraepithelial neoplasia (CIN III) in women at the initial and subsequent screenings were studied in Florence for the period 1979 to 1982 to assess the optimal interval between tests and the sensitivity of the screening (cytology plus advised colposcopy in cases with slightly abnormal Papanicolaou tests). The protective interval was calculated to be about three years. No differences in the risk of developing CIN III were observed between women with only an initial screening and women rescreened within the three-year interval. Screening sensitivity was calculated according to two different models: (1) when assumed to be a constant, the sensitivity of our cytologic-colposcopic screening was 0.71, with 0.64 for cytology alone; (2) when assumed to decrease in subsequent screening rounds, the sensitivity was calculated at 0.60 (0.50 in subsequent rounds), with 0.52 for cytology alone. The benefit of an early cytologic rescreening is discussed and compared to a wider use of colposcopy, which, with lower costs, permits a good sensitivity utilizing only one round of screening.

Adolescent↗

The Papanicolaou smear as a sentinel screening test for health screening in women.

BACKGROUND: There has been evidence that, in primary care practices, health screening tests are not ordered in random fashion but instead are coupled or bundled into distinct groups. This study was performed to determine if the Papanicolaou (Pap) smear serves as a marker for other health screening tests. METHODS: The study consisted of a retrospective chart review of female patients over the age of 18 years at three rural health clinics, followed by a prospective study of patients during a 3-month period in five rural family practice clinics. The study focused on whether a Pap smear was performed and whether a breast examination, mammogram, rectal examination or stool occult blood test, or serum cholesterol testing was performed. RESULTS: In both the retrospective and prospective series, patients who received Pap smears were significantly more likely to receive breast examinations, mammograms, colorectal screening and cholesterol tests. In addition, the coupling of other screening tests with the Pap smear appeared to increase with advancing patient age, with a decline after age 70 years. In patients who did not have Pap smears, only cholesterol testing increased as patients aged. CONCLUSION: Health screening tests in women are associated with the performance of a Pap smear. Providers may use the Pap smear as a marker of whether a woman has received screening for several other medical problems. Thus, the Pap smear can be considered a "sentinel" test for health screening in women, and efforts to identify women at high risk and increase health promotion and disease prevention in this group should focus on women who have not received this test.

Adult↗

Barriers to screening among participants of a media-promoted breast cancer screening project.

Breast cancer detection and awareness projects have been implemented nationwide in an attempt to increase compliance with screening mammography. Previous studies, however, showed that the elderly, minorities, and women of lower socioeconomic status fail to respond in representative numbers. A cross-sectional analysis of 6640 participants of a Breast Cancer Detection and Awareness Project in Tampa, FL, was conducted to determine if barriers and motivations to screening differed among targeted (the elderly, minorities, women of lower socioeconomic status) and nontargeted groups. Targeted demographic groups reported far more barriers to screening and fewer motivating factors in their decision to participate in screening. This was true for the elderly, minorities, and women of lower socioeconomic status. Women in greater need of screening mammography report fewer motivations, and must overcome greater barriers to participate in media-promoted breast screening projects. Changes in the design and promotion of these screening projects must occur to prevent reverse targeting.

Breast Neoplasms↗

Decision aids for people facing health treatment or screening decisions.

BACKGROUND: Decision aids are interventions designed to help people make specific and deliberative choices among options (including status quo) by providing (at a minimum) information on the options and outcomes relevant to a person's health status. A systematic review is needed to summarize what is known about their efficacy. OBJECTIVES: 1. To create an inventory of existing decision aids. 2. To conduct a systematic review of randomized controlled trials of decision aids aimed at improving people's decision making and outcomes. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE, EMBASE, PsycINFO, CINAHL, Aidsline, Cancerlit, the Cochrane Controlled Trials Register. In addition, individuals known to be active in the field of decision support were contacted. SELECTION CRITERIA: We screened titles and abstracts for all interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Information about the decision aids was compiled in an inventory and those evaluated in a randomized controlled trial were reviewed in detail. DATA COLLECTION AND ANALYSIS: Using Cochrane review methods, two reviewers independently screened and extracted data on several evaluation criteria. Results of randomized trials were pooled using weighted mean differences and relative risks with all data analysed using a random effects model. MAIN RESULTS: Eighty-seven decision aids were identified. Twenty-three of them had been evaluated in 24 randomized controlled trials. Among the trials comparing decision aids to usual care interventions, decision aids performed better in terms of: a) greater knowledge of options in seven of seven studies (weighted mean difference (WMD = 19 out of 100, 95% confidence interval (CI): 13,25); b) more realistic expectations in two of three studies (RR=1.48 95%CI 1.02, 2.14); c) lower decisional conflict related to feeling informed in three of three studies (WMD = -9.0 of 100 95%CI: -15, -3); d) reducing the proportion of people who were passive in decision making in three of four studies (RR = 0.63, 95% CI: 0.5, 0.8). When simpler decision aids were compared to more detailed ones, the relative improvement was significant in: a) improved knowledge in two of seven studies (WMD = 4 out of 100, 95% CI: 2, 5); b) realistic expectations in two of two studies (relative risk (RR ranged from 1.5 95%CI: 1.3,1.8); and c) decisional conflict in one of two studies (WMD= -4 95% CI -8,-0.2). There was a consistent trend for decision aids to do no better than comparison interventions in affecting: satisfaction with the decision in five of six studies, satisfaction with the decision making process in four of five studies, and anxiety in four of five studies. Decision aids had a variable effect on which screening or treatment options were selected. Exposure to decision aids relative to controls resulted in a consistent non-significant trend toward reduced preference for major surgery over conservative options by 21 to 42 per cent in five of five studies; however, they had no impact on circumcision in two of two studies. For colon and prostate cancer screening choices, the results were inconsistent. Two studies have shown no impact on persistence with chosen option and few studies have shown significant benefits on general health outcomes (two of three studies), or disease-specific health outcomes (one of four studies). REVIEWER'S CONCLUSIONS: The number of decision aids is expanding, but there is considerable overlap in some areas leaving gaps in others. Trials of decision aids indicate that they are superior to usual care interventions in improving knowledge and realistic expectations of the benefits and harms of options; reducing passivity in decision making; and lowering decisional conflict stemming from feeling uninformed. When simpler versions of decision aids are compared to more detailed aids, the differences in knowledge are marginal but there are other benefits in terms of creating realistic expectations and in reducing decisional conflict. To date, decision aids have had little effect on anxiety or satisfaction with the decision making process or satisfaction with the decision. Their effects on choices vary with the decision. The effects on persistence with chosen therapies and health outcomes require further evaluation. The essential elements in decision aids for different groups and different types of decisions need to be established. Consensus needs to be reached regarding standards for developing and evaluating decision aids.

Decision Support Techniques↗

Adherence to repeat screening flexible sigmoidoscopy in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

BACKGROUND: Acceptance of screening flexible sigmoidoscopy has been poor, in part because of providers' concerns regarding the acceptability of the procedure. In the current prospective study, the authors used adherence to repeat testing to assess the acceptability of screening flexible sigmoidoscopy. METHODS: The current study was a prospective study of a randomized clinical trial drawing volunteers from the community. Subjects included 10,164 Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants who were available for follow-up 3 years after undergoing a baseline screening flexible sigmoidoscopy examination. The authors measured adherence and identified those factors that appeared to affect adherence to repeat sigmoidoscopy. RESULTS: Overall, 18.3% of women and 10.0% of men did not undergo a repeat sigmoidoscopy. Among individuals who attended the Year-3 clinic, 10.4% of women and 5.1% of men specifically refused repeat sigmoidoscopy when it was offered (risk of refusal in women compared with men, 2.04; 95% confidence interval, 1.76-2.36). Another factor found to be associated with refusal included a technically inadequate baseline sigmoidoscopy. CONCLUSIONS: Gender and past experiences with sigmoidoscopy may impact adherence to repeat screening. Nonetheless, among research volunteers in a randomized clinical trial of screening, excellent adherence to repeat screening flexible sigmoidoscopy could be achieved.

Aged↗

Assessment of the value of reporting partial screening results in prenatal screening for Down syndrome.

Prenatal screening for Down syndrome can be performed using the first trimester Combined Test [nuchal translucency (NT), pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin (hCG) and maternal age] or the Integrated Test (for example, NT and PAPP-A in the first trimester and two or more serum markers in the second trimester, all with maternal age). We investigated the value of providing partial results when using the Combined Test or Integrated Test to identify women with a high enough risk of having an affected pregnancy based on NT and maternal age alone such that there would be little advantage in combining this information with data on the serum markers. We also assessed whether in programmes using the Integrated Test it is worthwhile reporting partial results based on risk using first trimester markers and not obtaining a second trimester blood sample. Published data based on 480 affected and 96 839 unaffected pregnancies were used for the present study. Using NT and age alone, about 0.14% of all women screened would have such a high risk that they would always remain screen-positive after the Combined Test and only 0.06% would remain screen-positive after the Integrated Test. Similarly, about 0.07% of all women screened who have a high risk based on NT, PAPP-A and age would remain screen-positive after the Integrated Test. These percentages are too small to justify reporting two risk estimates for all women, given the confusion this would generate. It is therefore not worthwhile reporting partial risk estimates in screening programmes using the Combined Test or Integrated Test.

Adult↗

Prenatal screening for group B Streptococcus. I. Impact of antepartum screening on antenatal prophylaxis and intrapartum care.

OBJECTIVE: Our purpose was to evaluate current obstetric practice regarding screening and prophylaxis for group B Streptococcus and to evaluate the impact of screening on antepartum and intrapartum care. STUDY DESIGN: A total of 1232 members of the Society of Perinatal Obstetricians were asked to indicate their practices regarding screening for group B Streptococcus. Respondents were then asked their practices regarding antepartum and intrapartum prophylaxis on the basis of screening cultures, prior antimicrobial treatment, and other risk factors for neonatal sepsis. RESULTS: Of the 925 respondents (75.1%), 30.8% performed routine screening in all pregnancies: first prenatal visit (42.3%), 26 to 28 weeks (41.3%), and 34 to 38 weeks (22.1%). In addition, 65.9% would screen patients only under high-risk situations. Although 70.5% sample multiple sites, respondents were inconsistent regarding the sites from which cultures are obtained: distal vagina (64.2%), cervix (53.9%), proximal vagina (40.0%), anal canal (38.5%), and urethra (4.3%). A total of 34.7% of respondents would treat the patient at the time of a positive culture. Knowledge of maternal group B Streptococcus carriage would significantly alter intrapartum prophylaxis in low-risk (60.3% vs 0.5%) and various high-risk populations (74.0% to 98.4% vs 11.3% to 55.0%). However, no consensus as to optimal practice was identified. CONCLUSIONS: This survey demonstrates significant inconsistencies in screening and prophylaxis for group B Streptococcus by specialists in maternal-fetal medicine. In addition, it reveals that the recommendations of The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics are not routinely followed by these specialists. Knowledge of group B Streptococcus carriage significantly increases antepartum and intrapartum treatment regardless of the presence of other risk factors for neonatal sepsis. The impact of this practice on neonatal therapy warrants further evaluation.

Amoxicillin↗

Cost-effectiveness of alternative cascade screening strategies for familial hypercholesterolemia with realistic cascade screening acceptance rates and use of novel treatment.

BACKGROUND AND AIMS: Cascade screening (CS) for familial hypercholesterolemia (FH) has been found to be cost-effective in many published studies. However, most existing studies (i) ignored or overstated first-degree relative (FDR) participation rate (as 60-100 %), (ii) did not consider novel and expensive therapies, e.g. PCSK9 inhibitors (PCSK9i), and (iii) were conducted outside of Asia. This study, conducted in Singapore, where FDR participation rate is about 25 % among probands who have known pathogenic variants, aims to identify drivers of cost-effectiveness of CS protocols for FH. METHODS: Four CS protocols, which vary in the application of genetic tests, were examined using a hybrid decision tree-Markov model. Sensitivity analyses were conducted to identify drivers of cost-effectiveness. RESULTS: Cascade acceptance rates are key drivers of cost-effectiveness. Other drivers include age of proband, prevalence of FH among probands, health-related quality of life loss with cardiovascular disease, timeliness of starting treatment post-screening, treatment effectiveness, cost of PCSK9i and discount rate for cost and QALY. With cascade acceptance rates observed in Singapore, among various screening protocols examined, probabilities of being cost-effective ranged from 86 % to 95 % when no access to PCSK9i and ranged from 75 % to 98 % when PCSK9i are provided. The most cost-effective protocol differs depending on cascade acceptance rates and whether PCSK9i is provided. CONCLUSION: For better cost-effectiveness of CS for FH, health systems need to look for ways to improve proband's willingness to share contact of their relatives and relatives' willingness to be screened and to lower the cost of novel treatment. Other ways to improve cost-effectiveness include to select age groups for proband screening, improve screening detection rate among probands, and start timely treatment post-screening.

Humans↗