'Integrating Ethics and Equity with Economics and Effectiveness for newborn screening in the genomic age: A qualitative study protocol of stakeholder perspectives.

BACKGROUND: Newborn bloodspot screening is a well-established population health initiative that detects serious, childhood-onset, treatable conditions to improve health outcomes. With genomic technologies advancing rapidly, many countries are actively discussing the introduction of genomic assays into newborn screening programs. While adding genomic testing to Australia's newborn screening program could improve outcomes for infants and families, it must be considered against potential harms, ethical, legal, equity and social implications, and economic and health system impacts. We must ask not only 'can' we use genomics to screen newborns?' but 'should we'?' and 'how much should health systems invest in genomic newborn screening?'. METHODS: This study will use qualitative methods to explore understanding, priorities, concerns and expectations of genomic newborn screening among parents/carers, health professionals/scientists, and health policy makers across Australia. In-depth, semi-structured interviews will be held with 30-40 parents/carers recruited via hospital and community settings, 15-20 health professionals/scientists, and 10-15 health policy makers. Data will be analysed using inductive content analysis. The Sydney Children's Hospital Network Human Research Ethics Committee approved this study protocol [2023/ETH02371]. The Standards for Reporting Qualitative Research will guide study planning, conduct and reporting. DISCUSSION: Few studies have engaged a diverse range of stakeholders to explore the implications of genomics in newborn screening in a culturally and genetically diverse population, nor in a health system underpinned by universal health care. As the first study within a multi-part research program, findings will be used to generate new knowledge on the risks and benefits and importance of ethical, legal, social and equity implications of genomic newborn screening from the perspective of key stakeholders. As such it will be the foundation on which child and family centered criteria can be developed to inform health technology assessments and drive efficient and effective policy decision-making on the implementation of genomics in newborn screening.

Characterization of the Cynomolgus Macaque Model of Marburg Virus Disease and Assessment of Timing for Therapeutic Treatment Testing.

Marburg virus (MARV) causes severe disease and high mortality in humans. The objective of this study was to characterize disease manifestations and pathogenesis in cynomolgus macaques exposed to MARV. The results of this natural history study may be used to identify features of MARV disease useful in defining the ideal treatment initiation time for subsequent evaluations of investigational therapeutics using this model. Twelve cynomolgus macaques were exposed to a target dose of 1000 plaque-forming units MARV by the intramuscular route, and six control animals were mock-exposed. The primary endpoint of this study was survival to Day 28 post-inoculation (PI). Anesthesia events were minimized with the use of central venous catheters for periodic blood collection, and temperature and activity were continuously monitored by telemetry. All mock-exposed animals remained healthy for the duration of the study. All 12 MARV-exposed animals (100%) became infected, developed illness, and succumbed on Days 8-10 PI. On Day 4 PI, 11 of the 12 MARV-exposed animals had statistically significant temperature elevations over baseline. Clinically observable signs of MARV disease first appeared on Day 5 PI, when 6 of the 12 animals exhibited reduced responsiveness. Ultimately, systemic inflammation, coagulopathy, and direct cytopathic effects of MARV all contributed to multiorgan dysfunction, organ failure, and death or euthanasia of all MARV-exposed animals. Manifestations of MARV disease, including fever, systemic viremia, lymphocytolysis, coagulopathy, and hepatocellular damage, could be used as triggers for initiation of treatment in future therapeutic efficacy studies.

The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants-a multi-site prospective cohort study.

BACKGROUND: Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer. METHODS: This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken. RESULTS: Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing. CONCLUSIONS: These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.

What could health technology assessment learn from living clinical practice guidelines?

A "living" approach to clinical practice guidelines is when the identification, appraisal and synthesis of evidence is maintained and repeated at an agreed frequency, with a clear process for when and how new evidence is to be incorporated. The value of a living approach to guidelines was emphasised during the COVID-19 pandemic when health professionals and policymakers needed to make decisions regarding patient care in the context of a nascent but rapidly evolving evidence base. In this perspective, we draw on our recent experience developing Australian and international living guidelines and reflect on the feasibility of applying living guideline methods and processes to a lifecycle approach to health technology assessment (HTA). We believe the opportunities and challenges of adopting a living approach in HTA fall into five key themes: identification, appraisal and synthesis of evidence; optimising the frequency of updates; embedding ongoing multi-stakeholder engagement; linking the emergence of new evidence to reimbursement; and system capacity to support a living approach. We acknowledge that the suitability of specific living approaches to HTA will be heavily influenced by the type of health technology, its intended use in the health system, local reimbursement pathways, and other policy settings. But we believe that the methods and processes applied successfully to guideline development to manage evidentiary uncertainty could be applied in the context of HTA and reimbursement decision-making to help manage similar sources of uncertainty.

Stakeholder preferences for attributes of digital health technologies to consider in health service funding.

OBJECTIVES: Health service providers are currently making decisions on the public funding of digital health technologies (DHTs) for managing chronic diseases with limited understanding of stakeholder preferences for DHT attributes. This study aims to understand the community, patient/carer, and health professionals' preferences to help inform a prioritized list of evaluation criteria. METHODS: An online best-worst scaling survey was conducted in Australia, New Zealand, Canada, and the United Kingdom to ascertain the relative importance of twenty-four DHT attributes among stakeholder groups using an efficient incomplete block design. The attributes were identified from a systematic review of DHT evaluation frameworks for consideration in a health technology assessment. Results were analyzed with multinomial models by stakeholder group and latent class. RESULTS: A total of 1,251 participants completed the survey (576 general community members, 543 patients/carers, and 132 health professionals). Twelve attributes achieved a preference score above 50 percent in the stakeholder group model, predominantly related to safety but also covering technical features, effectiveness, ethics, and economics. Results from the latent class model supported this prioritization. Overall, connectedness with the patient's healthcare team seemed the most important; with "Helps health professionals respond quickly when changes in patient care are needed" as the most highly prioritized of all attributes. CONCLUSIONS: It is proposed that these prioritized twelve attributes be considered in all evaluations of DHTs that manage chronic disease, supplemented with a limited number of attributes that reflect the specific perspective of funders, such as equity of access, cost, and system-level implementation considerations.

Economic evaluations of fall prevention exercise programs: a systematic review.

OBJECTIVE: To investigate cost-effectiveness and costs of fall prevention exercise programmes for older adults. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Web of Science, Scopus, National Institute for Health Research Economic Evaluation Database, Health Technology Assessment database, Tufts Cost-Effectiveness Analysis Registry, Research Papers in Economics and EconLit (inception to May 2022). ELIGIBILITY CRITERIA FOR STUDY SELECTION: Economic evaluations (trial-based or model-based) and costing studies investigating fall prevention exercise programmes versus no intervention or usual care for older adults living in the community or care facilities, and reporting incremental cost-effectiveness ratio (ICER) for fall-related outcomes or quality-adjusted life years (QALY, expressed as cost/QALY) and/or intervention costs. RESULTS: 31 studies were included. For community-dwelling older adults (21 economic evaluations, 6 costing studies), results ranged from more effective and less costly (dominant) interventions up to an ICER of US$279 802/QALY gained and US$11 986/fall prevented (US$ in 2020). Assuming an arbitrary willingness-to-pay threshold (US$100 000/QALY), most results (17/24) were considered cost-effective (moderate certainty). The greatest value for money (lower ICER/QALY gained and fall prevented) appeared to accrue for older adults and those with high fall risk, but unsupervised exercise appeared to offer poor value for money (higher ICER/QALY). For care facilities (two economic evaluations, two costing studies), ICERs ranged from dominant (low certainty) to US$35/fall prevented (moderate certainty). Overall, intervention costs varied and were poorly reported. CONCLUSIONS: Most economic evaluations investigated fall prevention exercise programmes for older adults living in the community. There is moderate certainty evidence that fall prevention exercise programmes are likely to be cost-effective. The evidence for older adults living in care facilities is more limited but promising. PROSPERO REGISTRATION NUMBER: PROSPERO 2020 CRD42020178023.

Economic evaluation of physical activity mass media campaigns across the globe: a systematic review.

BACKGROUND: Physical activity mass media campaigns can deliver physical activity messages to many people, but it remains unclear whether they offer good value for money. We aimed to investigate the cost-effectiveness, cost-utility, and costs of physical activity mass media campaigns. METHODS: A search for economic evaluations (trial- or model-based) and costing studies of physical activity mass media campaigns was performed in six electronic databases (June/2021). The authors reviewed studies independently. A GRADE style rating was used to assess the overall certainty of each modelled economic evaluation. Results were summarised via narrative synthesis. RESULTS: Twenty-five studies (five model-based economic evaluations and 20 costing studies) were included, and all were conducted in high-income countries except for one costing study that was conducted in a middle-income country. The methods and assumptions used in the model-based analyses were highly heterogeneous and the results varied, ranging from the intervention being more effective and less costly (dominant) in two models to an incremental cost of US$130,740 (2020 base year) per QALY gained. The level of certainty of the models ranged from very low (n = 2) to low (n = 3). Overall, intervention costs were poorly reported. CONCLUSIONS: There are few economic evaluations of physical activity mass media campaigns available. The level of certainty of the models was judged to be very low to low, indicating that we have very little to little confidence that the results are reliable for decision making. Therefore, it remains unclear to what extent physical activity mass media campaigns offer good value for money. Future economic evaluations should consider selecting appropriate and comprehensive measures of campaign effectiveness, clearly report the assumptions of the models and fully explore the impact of assumptions in the results. REVIEW REGISTRATION: https://bit.ly/3tKSBZ3.

Evaluating genetic and genomic tests for heritable conditions in Australia: lessons learnt from health technology assessments.

The Medical Services Advisory Committee (MSAC) is an independent non-statutory committee established by the Australian government to provide recommendations on public reimbursement of technologies and services, other than pharmaceuticals. MSAC has established approaches for undertaking health technology assessment (HTA) of investigative services and codependent technologies. In 2016, MSAC published its clinical utility card (CUC) Proforma, an additional tool to guide assessments of genetic testing for heritable conditions. We undertook a review and narrative synthesis of information extracted from all MSAC assessments of genetic testing for heritable conditions completed since 2016, regardless of the HTA approach taken. Ten assessments met our inclusion criteria, covering a range of testing methods (from gene panels to whole-exome sequencing) and purposes (including molecular diagnosis, genetic risk assessment, identification of congenital anomaly syndromes, and carrier screening). This analysis identified a range of methodological and policy challenges such as how to incorporate patient and societal preferences for the health and non-health outcomes of genomic testing, how best to capture the concept of co-production of utility, and how to engage clinicians as referrers for genomics tests whilst at the same time ensuring equity of access to a geographically dispersed population. A further challenge related to how qualitative assessments of patient and community needs influenced the evidence thresholds against which decisions were made. These concepts should be considered for incorporation within the value assessment frameworks used by HTA agencies around the world.

Application of a health technology assessment framework to digital health technologies that manage chronic disease: a systematic review.

BACKGROUND: As health services increasingly make investment decisions in digital health technologies (DHTs), a DHT-specific and comprehensive health technology assessment (HTA) process is crucial in assessing value-for-money. Research in DHTs is ever-increasing, but whether it covers the content required for HTA is unknown. OBJECTIVES: To summarize current trends in primary research on DHTs that manage chronic disease at home, particularly the coverage of content recommended for DHT-specific and comprehensive HTA. METHODS: Medline, Embase, Econlit, CINAHL, and The Cochrane Library (1 January 2015 to 20 March 2020) were searched for primary research studies using keywords related to DHT and HTA domains. Studies were assessed for coverage of the most frequently recommended content to be considered in a nine domain DHT-specific HTA previously developed. RESULTS: A total of 178 DHT interventions were identified, predominantly randomized controlled trials targeting cardiovascular disease/diabetes in high- to middle-income countries. A coverage assessment of the cardiovascular and diabetes DHT studies (112) revealed less than half covered DHT-specific content in all but the health problem domain. Content common to all technologies but essential for DHTs was covered by more than half the studies in all domains except for the effectiveness and ethical analysis domains. CONCLUSIONS: Although DHT research is increasing, it is not covering all the content recommended for a DHT-specific and comprehensive HTA. The inability to conduct such an HTA may lead to health services making suboptimal investment decisions. Measures to increase the quality of trial design and reporting are required in DHT primary research.

Health technology assessment for digital technologies that manage chronic disease: a systematic review.

OBJECTIVE: A growing number of evaluation frameworks have emerged over recent years addressing the unique benefits and risk profiles of new classes of digital health technologies (DHTs). This systematic review aims to identify relevant frameworks and synthesize their recommendations into DHT-specific content to be considered when performing Health Technology Assessments (HTAs) for DHTs that manage chronic noncommunicable disease at home. METHODS: Searches were undertaken of Medline, Embase, Econlit, CINAHL, and The Cochrane Library (January 2015 to March 2020), and relevant gray literature (January 2015 to August 2020) using keywords related to HTA, evaluation frameworks, and DHTs. Included framework reference lists were searched from 2010 until 2015. The EUNetHTA HTA Core Model version 3.0 was selected as a scaffold for content evaluation. RESULTS: Forty-four frameworks were identified, mainly covering clinical effectiveness (n = 30) and safety (n = 23) issues. DHT-specific content recommended by framework authors fell within 28 of the 145 HTA Core Model issues. A further twenty-two DHT-specific issues not currently in the HTA Core Model were recommended. CONCLUSIONS: Current HTA frameworks are unlikely to be sufficient for assessing DHTs. The development of DHT-specific content for HTA frameworks is hampered by DHTs having varied benefit and risk profiles. By focusing on DHTs that actively monitor/treat chronic noncommunicable diseases at home, we have extended DHT-specific content to all nine HTA Core Model domains. We plan to develop a supplementary evaluation framework for designing research studies, undertaking HTAs, and appraising the completeness of HTAs for DHTs.

Mercury in neonatal and juvenile blacktip sharks (Carcharhinus limbatus). Part II: Effects assessment.

As apex predators, blacktip sharks (Carcharhinus limbatus) are highly susceptible to biomagnified mercury (Hg) particularly in the Gulf of Mexico (GOM), which is known to contain fishes and invertebrates with elevated Hg levels. Blacktip sharks occur in the GOM year-round and are heavily fished both commercially and recreationally, but little is known about how Hg affects the species. In this study, blood, muscle, liver, and kidney samples were collected from neonatal (n = 57) and juvenile (n = 13) blacktip sharks in Charlotte Harbor, Florida. Hg concentrations in neonates and juveniles were found to be elevated in muscle (mean ± SE = 0.59 ± 0.23 mg kg-1), liver (0.39 ± 0.29 mg kg-1), kidney (0.56 ± 0.25 mg kg-1), and blood (0.059 ± 0.041 mg kg-1) compared to other local shark species and conspecifics from other areas. Blood plasma chemistry, hematology, and liver histology were evaluated to assess the relationship between Hg and tissue damage. Plasma chemistry parameters alanine aminotransferase (ALT) and phosphorus (PHOS) were not correlated with tissue Hg or liver condition index. Hematological effects were also not correlated with tissue Hg. However, melanomacrophage presence and lipid deposition, evaluated as part of histopathological analysis, were found to exhibit a statistically significant association with concentrations of Hg in tissue and ALT levels. These results suggest that Hg exposure potentially had a negative effect on the livers of the blacktip sharks evaluated in the present study.

Mercury in neonatal and juvenile blacktip sharks (Carcharhinus limbatus). Part I: exposure assessment.

Elasmobranchs are exposed to mercury (Hg) through a variety of pathways in the environment. This study assessed maternal offloading and diet-based Hg exposure for neonatal and juvenile blacktip sharks (Carcharhinus limbatus) from Charlotte Harbor located along southwest Florida's coast, a recognized Hg hotspot. Neonates (n = 57) had highest total Hg (THg) concentrations in the kidney (0.56 ± 0.26 mg kg-1; n = 38) and muscle (0.53 ± 0.17 mg kg-1; n = 57), followed by liver (0.31 ± 0.11 mg kg-1; n = 38), and blood (0.05 ± 0.033 mg kg-1; n = 57). Juveniles (n = 13) exhibited a different distribution with highest THg in the liver (0.868 ± 0.54 mg kg-1; n = 6), followed by the muscle (0.84 ± 0.28 mg kg-1; n = 13), kidney (0.55 ± 0.22 mg kg-1; n = 6), and blood (0.11 ± 0.04 mg kg-1; n = 11). The distribution of THg among tissues and liver-to-muscle ratios indicated that Hg originated primarily from maternal offloading in neonates, whereas juveniles continued to accumulate Hg through dietary exposure post-parturition. Additionally, comparisons between results of the present study and previous Florida blacktip shark surveys suggested that Hg levels have not declined in southwest Florida estuaries for over two decades.

A National Budget Impact Analysis of a Specialised Surveillance Programme for Individuals at Very High Risk of Melanoma in Australia.

BACKGROUND: Specialised surveillance using total body photography and digital dermoscopy to monitor people at very high risk of developing a second or subsequent melanoma has been reported as cost effective. OBJECTIVES: We aimed to estimate the 5-year healthcare budget impact of providing specialised surveillance for people at very high risk of subsequent melanoma from the perspective of the Australian healthcare system. METHODS: A budget impact model was constructed to assess the costs of monitoring and potential savings compared with current routine care based on identification of patients at the time of a melanoma diagnosis. We used data from a published cost-effectiveness analysis of specialised surveillance, and Cancer Registry data, to estimate the patient population and healthcare costs for 2017-2021. RESULTS: When all eligible patients, estimated at 18% of patients with melanoma diagnosed annually in Australia, received specialised surveillance rather than routine care, the cumulative 5-year cost was estimated at $93.5 million Australian dollars ($AU) ($US 64 million) for specialised surveillance compared with $AU 120.7 million ($US 82.7 million) for routine care, delivering savings of $AU 27.2 million ($US 18.6 million). With a staggered introduction of 60% of eligible patients accessing surveillance in year 1, increasing to 90% in years 4 and 5, the cumulative cost over 5 years was estimated at $AU 98.1 million ($US 67.2 million), amounting to savings of $AU 22.6 million ($US 15.5 million) compared with routine care. CONCLUSIONS: Specialised melanoma surveillance is likely to provide substantial cost savings for the Australian healthcare system.

Cost-effectiveness analysis of germ-line BRCA testing in women with breast cancer and cascade testing in family members of mutation carriers.

PURPOSE: To evaluate the cost-effectiveness of BRCA testing in women with breast cancer, and cascade testing in family members of BRCA mutation carriers. METHODS: A cost-effectiveness analysis was conducted using a cohort Markov model from a health-payer perspective. The model estimated the long-term benefits and costs of testing women with breast cancer who had at least a 10% pretest BRCA mutation probability, and the cascade testing of first- and second-degree relatives of women who test positive. RESULTS: Compared with no testing, BRCA testing of affected women resulted in an incremental cost per quality-adjusted life-year (QALY) gained of AU$18,900 (incremental cost AU$1,880; incremental QALY gain 0.10) with reductions of 0.04 breast and 0.01 ovarian cancer events. Testing affected women and cascade testing of family members resulted in an incremental cost per QALY gained of AU$9,500 compared with testing affected women only (incremental cost AU$665; incremental QALY gain 0.07) with additional reductions of 0.06 breast and 0.01 ovarian cancer events. CONCLUSION: BRCA testing in women with breast cancer is cost-effective and is associated with reduced risk of cancer and improved survival. Extending testing to cover family members of affected women who test positive improves cost-effectiveness beyond restricting testing to affected women only.

Euthanasia assessment in ebola virus infected nonhuman primates.

Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts.

Breastfeeding practices among the Old Order Mennonites in Ontario, Canada: a multiple methods study.

BACKGROUND: The Old Order Mennonites (OOM) of rural Ontario have a lifestyle that is very distinct from the rest of Canada. Breastfeeding practices among this community have not been described previously. OBJECTIVES: This study aimed to estimate the prevalence of exclusive breastfeeding (EBF) at 2, 4, and 6 months; to compare the prevalence of EBF among OOM and Canadian women; to investigate factors associated with EBF at 6 months; and to gain qualitative insight into the breastfeeding practices of OOM women. METHODS: Data on maternal characteristics, delivery factors, and infant feeding methods at birth and at 2, 4, and 6 months were obtained from medical records at the Elmira Medical Centre for all births to OOM women between January 2006 and December 2011. Semi-structured interviews were carried out with 2 lactation consultants working at the Elmira Medical Centre. RESULTS: Complete breastfeeding data were available for 195 of 225 OOM women (77.4%). The majority of OOM women initiated breastfeeding (87.9%); 81.4% continued to breastfeed exclusively at 2 months, 74.0% to 4 months, and 36.8% to 6 months. Women who had a homebirth (12.3%) had 2.6-fold higher odds of EBF at 6 months (odds ratio, 2.59; 95% confidence interval, 1.03-6.53) compared with women who delivered in a hospital. Cultural and religious influences and community support were suggested as reasons for the relatively high prevalence of EBF. CONCLUSION: Breastfeeding rates among OOM women are consistently higher in the first 6 months of life compared to the general Canadian population. Homebirth independently predicted increased odds of EBF at 6 months.

The epidemiology and cost of surgical site infections in Korea: a systematic review.

PURPOSE: To conduct a systematic literature review of the epidemiological and economic burden of surgical site infection (SSI) in Korea. METHODS: A search of the EMBASE, Medline and KoreaMed databases for English and Korean language publications was conducted. Searches for epidemiological and economic studies were conducted separately and limited to 1995 to 2010 to ensure the pertinence of the data. RESULTS: Twenty-six studies were included. The overall incidence of SSI in Korea was 2.0 to 9.7%. The National Nosocomial Infections Surveillance risk index was positively correlated with the risk of developing an SSI. Specific risk factors for SSI, identified through multivariate analyses included; diabetes, antibiotic prophylaxis and wound classification. SSIs were associated with increased hospitalisation cost, with each episode of SSI estimated to cost about an additional ₩2,000,000. A substantial portion of the increased cost was attributed to hospital room costs and the need for additional medication. Studies also found that post-operative stays for patients with SSIs were 5 to 20 days longer, while two studies reported that following cardiac surgery, patients with SSIs spent an additional 5 to 11 days in the intensive care unit, compared to patients without SSIs. CONCLUSION: Data from the included studies demonstrate that SSI represents a significant clinical and economic burden in Korea. Consequently, the identification of high-risk patient populations and the development of strategies aimed at reducing SSI may lead to cost-savings for the healthcare system.

Relationship between rheumatoid arthritis disease severity, health-related utility, and resource use in Australian patients: A cross-sectional, multicenter study.

OBJECTIVES: This research explores the relationship between rheumatoid arthritis (RA) severity measures, clinical characteristics, and patient preference-based health-related quality of life (ie, utility) in Australian RA patients. A secondary objective was to investigate the relationship between a range of disease severity measures, clinical characteristics, and the cost of RA-related resource use. METHODS: This was a cross-sectional, multicenter study of consecutive patients with RA aged > or =18 years attending routine clinical appointments. Patients completed a questionnaire comprising general demographic, resource use, and disease-specific questions; the RA-specific Health Assessment Questionnaire (HAQ); and 2 multiattribute preference-based quality-of-life (utility) instruments, the Health Utilities Index Mark 3 (HUI3) and the EuroQol 5 Dimensions (EQ-5D). A second questionnaire was completed by the patient's rheumatologist, with questions on key clinical data pertinent to RA, including the number and location of tender joints and swollen joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, current and previous treatments, and details of important comorbid conditions. Data on RA-specific resource use were also collected, including health-professional visits (eg, general practitioner, specialist, nurse, occupational therapist, paid caregivers), hospital admissions, surgery, and RA-associated home modifications. Spearman nonparametric correlation, simple linear, multiple, and stepwise regression analyses were used to explore the relationship between utility scores (HUI3 and EQ-5D) and variables including HAQ, RA-related resource use, and key demographic, physical, and biochemical measures. RESULTS: A total of 170 patients were recruited from 4 centers in Australia. Consistent with the epidemiology of RA, the ratio of women to men was approximately 3:1 (126 vs 44, respectively). Male and female patients were of similar age (mean [SD], 59.2 [12.9] and 58.9 [12.2] years, respectively). Time since diagnosis of RA was significantly shorter for men than for women (mean difference, -4.52 years; 95% CI, -8.65 to -0.38; P = 0.03). Of all the disease severity measures and clinical characteristics investigated, patients' HAQ scores predicted their utility most closely (for HUI3, R(2) = 0.626, P < 0.001; for EQ-5D, R(2) = 0.403, P < 0.001). The Disease Activity Score 28 severity index provided the next best relationship with a patient's utility; however, its explanatory power was poor (for HUI3, R(2) = 0.085, P < 0.001; for EQ-5D, R(2) = 0.042, P = 0.008). ESR, CRP, and, RA-affected joint counts had negligible explanatory power for patient utility. In analyses of the relationship between a range of key variables and the direct costs associated with RA, the HAQ score explained 22% of the variability in log costs (P < 0.001). CONCLUSION: This study found that of all the disease severity measures and clinical characteristics investigated, patients' HAQ scores predicted their utility most closely.

An assessment of health status among medical research volunteers who served in the Project Whitecoat program at Fort Detrick, Maryland.

Between 1954 and 1973, more than 2000 men entering military service as conscientious objectors participated in Project Whitecoat as medical research volunteers for the Army's biological warfare defense program. An assessment of self-reported, current health status among 358 "exposed" individuals and 164 unexposed control subjects found no conclusive evidence that receipt of investigational agents was related to adverse health outcomes. No differences in current overall health, current exercise levels, self-reported symptoms, and self-reported medical conditions were seen between the study groups. Possible associations were seen between exposure to antibiotics or other biological agents and self-reported asthma (13.0% vs. 2.4%, relative risk [RR] = 6.00, 95% confidence interval [CI] = 1.03-34.90, p = 0.050), as well as between receipt of tularemia vaccine(s) and self-reported asthma (13.3% vs. 2.4%, RR = 6.15, 95% CI = 1.03-36.70, p = 0.049) and increased frequency/severity of headaches (35.6% vs. 18.3%, RR = 2.46, 95% CI = 0.99-6.15, p = 0.074). However, the size of the population under study was insufficient to assert with confidence that these statistical associations are real.