Cost effectiveness and decision analysis for national airport screening options to reduce risk of COVID-19 introduction in Uganda, 2020.

INTRODUCTION: Early during the COVID-19 outbreak, various approaches were utilized to prevent COVID-19 introductions from incoming airport travellers. However, the costs and effectiveness of airport-specific interventions have not been evaluated. METHODS: We evaluated policy options for COVID-19-specific interventions at Entebbe International Airport for costs and impact on COVID-19 case counts, we took the government payer perspective. Policy options included; (1)no screening, testing, or mandatory quarantine for any incoming traveller; (2)mandatory symptom screening for all incoming travellers with RT-PCR testing only for the symptomatic and isolation of positives; and (3)mandatory 14-day quarantine and one-time testing for all, with 10-day isolation of persons testing positive. We calculated incremental cost-effectiveness ratios (ICERs) in US$ per additional case averted. RESULTS: Expected costs per incoming traveller were $0 (Option 1), $19 (Option 2), and $766 (Option 3). ICERs per case averted were $257 for Option 2 (which averted 4,948 cases), and $10,139 for Option 3 (which averted 5,097 cases) compared with Option I. Two-week costs were $0 for Option 1, $1,271,431 Option 2, and $51,684,999 Option 3. The per-case ICER decreased with increase in prevalence. The cost-effectiveness of our interventions was modestly sensitive to the prevalence of COVID-19, diagnostic test sensitivity, and testing costs. CONCLUSION: Screening all incoming travellers, testing symptomatic persons, and isolating positives (Option 2) was the most cost-effective option. A higher COVID-19 prevalence among incoming travellers increased cost-effectiveness of airport-specific interventions. This model could be used to evaluate prevention options at the airport for COVID-19 and other infectious diseases with similar requirements for control.

Group-based Education and monitoring program delivered by community health workers to improve control of high blood pressure in island districts of lake victoria, Uganda.

BACKGROUND: Individuals living in communities with poor access to healthcare may be unaware of their high blood pressure (BP). While the use of community health workers (CHWs) can address gaps in human resources for health, CHWs in Uganda have not been used previously for BP screening and management. We report the results of an initiative to train CHWs to evaluate BP and to administer group-based education in Kalangala and Buvuma Island Districts of Lake Victoria, Uganda. METHODS: We randomly selected 42 of 212 villages. We trained CHWs based in island districts on measuring BP. CHWs visited all households in the selected villages and invited all adults ≥ 18 years to be screened for high BP. We used the World Health Organization's STEPwise tool to collect data on demographic and behavioral characteristics and BP measurements. High blood pressure was defined as systolic BP (SBP) ≥ 140 mm Hg and/or diastolic BP (DBP) ≥ 90 mm Hg over three readings. CHWs created and led fortnight support groups for individuals identified with high blood pressure at baseline. At each group meeting, CHWs re-measured BP and administered an intervention package, which included self-management and lifestyle education to participants. The paired t-test was used to compare mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after the intervention. Generalized estimating equations (GEE) were used to model longitudinal changes in BP. RESULTS: We trained 84 CHWs to measure BP and deliver the intervention package. Among 2,016 community members, 570 (28.3%) had high blood pressure; of these, 63 (11.1%) had a previous diagnosis of hypertension. The comparison of SBP and DBP before and after the intervention revealed significant reductions in mean SBP from 158mmHg (SD = 29.8) to 149 mmHg (SD = 29.8) (p < 0.001) and mean DBP from 97mmHg (SD = 14.3) to 92mmHg (p < 0.001). GEE showed decreases of -1.133 (SBP) and - 0.543 mmHg (DBP)/fortnight. CONCLUSION: High BP was common but previously undiagnosed. The CHW-led group-based self-management and education for controlling high BP was effective in the island districts in Uganda. Scaling up the intervention in other hard-to-reach districts could improve control of high BP on a large scale.

Antibias Efforts in United States Maternity Care: A Scoping Review of the Publicly Funded Health Equity Intervention Pipeline.

Antibias training is increasingly identified as a strategy to reduce maternal health disparities. Evidence to guide this work is limited. We conducted a community-guided scoping review to characterize new antibias research. Four of 508 projects met our criteria: US-based, publicly funded, initiated from January 1, 2018 to June 30, 2022, and featuring an intervention to reduce bias or racism in maternal health care providers. Training was embedded in multicomponent interventions in 3 projects, limiting its evaluation as a stand-alone intervention. Major public funders have sponsored few projects to advance antibias training research in maternal health. More support is needed to develop a rigorous and scalable evidence base.

Improving the effectiveness of Field Epidemiology Training Programs: characteristics that facilitated effective response to the COVID-19 pandemic in Uganda.

BACKGROUND: The global need for well-trained field epidemiologists has been underscored in the last decade in multiple pandemics, the most recent being COVID-19. Field Epidemiology Training Programs (FETPs) are in-service training programs that improve country capacities to respond to public health emergencies across different levels of the health system. Best practices for FETP implementation have been described previously. The Uganda Public Health Fellowship Program (PHFP), or Advanced-FETP in Uganda, is a two-year fellowship in field epidemiology funded by the U.S. Centers for Disease Control and situated in the Uganda National Institute of Public Health (UNIPH). We describe how specific attributes of the Uganda PHFP that are aligned with best practices enabled substantial contributions to the COVID-19 response in Uganda. METHODS: We describe the PHFP in Uganda and review examples of how specific program characteristics facilitate integration with Ministry of Health needs and foster a strong response, using COVID-19 pandemic response activities as examples. We describe PHFP activities and outputs before and during the COVID-19 response and offer expert opinions about the impact of the program set-up on these outputs. RESULTS: Unlike nearly all other Advanced FETPs in Africa, PHFP is delinked from an academic degree-granting program and enrolls only post-Master's-degree fellows. This enables full-time, uninterrupted commitment of academically-trained fellows to public health response. Uganda's PHFP has strong partner support in country, sufficient technical support from program staff, Ministry of Health (MoH), CDC, and partners, and full-time dedicated directorship from a well-respected MoH staff member. The PHFP is physically co-located inside the UNIPH with the emergency operations center (EOC), which provides a direct path for health alerts to be investigated by fellows. It has recognized value within the MoH, which integrates graduates into key MoH and partner positions. During February 2020-September 2021, PHFP fellows and graduates completed 67 major COVID-related projects. PHFP activities during the COVID-19 response were specifically requested by the MoH or by partners, or generated de novo by the program, and were supervised by all partners. CONCLUSION: Specific attributes of the PHFP enable effective service to the Ministry of Health in Uganda. Among the most important is the enrollment of post-graduate fellows, which leads to a high level of utilization of the program fellows by the Ministry of Health to fulfill real-time needs. Strong leadership and sufficient technical support permitted meaningful program outputs during COVID-19 pandemic response. Ensuring the inclusion of similar characteristics when implementing FETPs elsewhere may allow them to achieve a high level of impact.

Uganda Public Health Fellowship Program's Contributions to the National HIV and TB Programs, 2015-2020.

Despite remarkable progress in controlling HIV and TB, Uganda is one of the 30 high-burden TB/HIV countries. Approximately 53,000 Ugandans had a new HIV diagnosis in 2019, and approximately 88,000 Ugandans had a TB diagnosis in 2020. Fellows in the Uganda Public Health Fellowship Program (UPHFP) work directly with the Ministry of Health AIDS and TB Control Programs, the U.S. Centers for Disease Control and Prevention, UPHFP supervisors, and implementing partners to investigate and evaluate HIV-related and TB-related issues. These activities have contributed to the Uganda HIV and TB programs. UPHFP fellows complete projects in 7 competency domains, including outbreak investigations, surveillance evaluations, and data quality improvement. Priority HIV/AIDS/TB information gaps/topics are identified in consultation with key stakeholders, and fellows complete projects to guide program improvements and policy decisions. During 2015-2020, UPHFP fellows implemented 127 HIV and TB projects covering key program areas in AIDS and TB control programs, including care and treatment (16 projects), TB/HIV (18), prevention of mother-to-child HIV transmission (24), key and priority populations (9), pre-exposure and post-exposure prophylaxis (7), adolescent girls and young women (6), service delivery (13), and diagnosis of TB including drug-resistant TB and TB in high-risk groups (32). These projects have helped improve retention, quality of care, and treatment outcomes for people living with HIV, HIV and TB coinfected patients, and TB patients. They have also contributed to the decrease in pediatric TB and infant HIV positivity rates and improved service delivery for key populations. UPHFP results were disseminated to relevant stakeholders such as government departments, implementing partners, districts, and the general community and guided decision making. UPHFP has significantly improved HIV and TB control in Uganda. Other countries with similar programs could benefit from this approach and utilize program fellows to support HIV and TB control.

Evaluation of a New Field Epidemiology Training Program Intermediate Course to Strengthen Public Health Workforce Capacity in Tanzania.

OBJECTIVES: Sub-Saharan Africa faces a shortage of skilled epidemiologists to prevent, detect, and respond to health threats. Tanzania has implemented one of the first Centers for Disease Control and Prevention Field Epidemiology Training Program (FETP) Intermediate courses in Africa. This course aims to strengthen health workforce capacity in surveillance system assessment, outbreak investigation, and evaluation, prioritizing HIV control. We conducted an outcome evaluation of this new course. METHODS: We used a pre/post evaluation design using data from 4 cohorts of trainees who took the FETP Intermediate course from 2017 to 2020. We conducted knowledge assessments before and after each cohort and combined those results. Outcomes included knowledge and self-rated competency and trends in integrated disease surveillance and response (IDSR) data. We collected data through tests, field assignments, exit interviews, and data audits. We compared the mean change in pre-/posttest scores using linear regression and 95% CIs. We used content analysis to summarize exit interviews. RESULTS: Fifty-three FETP trainees from 10 regions enrolled in the FETP Intermediate course, and 52 (99.0%) completed the course. We found substantial increases in mean knowledge (44.0 to 68.0 points) and self-rated competency (4.14 to 4.43) scores before and after the course. Trainees evaluated 52 surveillance systems and 52 district HIV care programs, and 39 (75.0%) trainees participated in outbreak investigations. From before to after cohort 1, timeliness and completeness of IDSR reports increased from 4.2% to 52.1% and from 27.4% to 76.5%, respectively. Course strengths were quality of instruction, individualized mentoring, and practical skills gained. Challenges were mentor availability, limited time for data analysis practice, and balancing work and field assignments. CONCLUSIONS: The Tanzania FETP Intermediate course substantially improved trainee knowledge and helped to improve local data quality and reporting. This course is a promising model to strengthen subnational capacity to prevent, detect, and respond to public health threats in Africa.

Stunting: an overlooked problem in Myanmar - an economic evaluation.

OBJECTIVES: Stunting increases a child's susceptibility to diseases, increases mortality, and is associated over long term with reduced cognitive abilities, educational achievement, and productivity. We aimed to assess the most effective public health nutritional intervention to reduce stunting in Myanmar. METHODS: We searched the literature and developed a conceptual framework for interventions known to reduce stunting. We focused on the highest impact and most feasible interventions to reduce stunting in Myanmar, described policies to implement them, and compared their costs and projected effect on stunting using data-based decision trees. We estimated costs from the government perspective and calculated total projected cases of stunting prevented and cost per case prevented (cost-effectiveness). All interventions were compared to projected cases of stunting resulting from the current situation (e.g., no additional interventions). RESULTS: Three new policy options were identified. Operational feasibility for all three options ranged from medium to high. Compared to the current situation, two were similarly cost-effective, at an additional USD 598 and USD 667 per case of stunting averted. The third option was much less cost-effective, at an additional USD 27,741 per case averted. However, if donor agencies were to expand their support in option three to the entire country, the prevalence of 22.5 percent would be reached by 2025 at an additional USD 667 per case averted. CONCLUSIONS: A policy option involving immediate expansion of the current implementation of proven nutrition-specific interventions is feasible. It would have the highest impact on stunting and would approach the WHO 2025 target.

Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome.

Context: Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia, including surreptitious insulin administration. No standardized treatment regimen exists. Objectives: To evaluate an analytic approach to IAS and responses to different treatments. Design and Setting: Observational study in the UK Severe Insulin Resistance Service. Patients: Six patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA). Main Outcome Measures: Glycemia, plasma insulin, and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using ELISA and RIA, and IA were further characterized using radioligand binding studies. Results: All patients were diagnosed with IAS (five IgG, one IgA) based on a high insulin/C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. One patient was managed conservatively, four were treated with diazoxide without sustained benefit, and four were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis. Conclusions: IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin/C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response.

NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of 'reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution.

NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of 'reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution.

Volume perception: Disparity extraction and depth representation in complex three-dimensional environments.

Our sensitivity to binocular disparity is exquisite under the best conditions, typically in uncluttered scenes with few small objects. Yet binocular vision can deliver a very strong impression of depth for complex, cluttered scenes with lots of objects and overlaps. How good is disparity processing under these conditions? Here we explored a novel task: depth volume perception, to study how a global representation of depth is obtained using binocular disparity information. We found that the human visual system is sensitive to depth volume but that the volume perceived is dependent on the local and global arrangement of scene content. We also show how a model of early disparity extraction and combination can account for some of the biases found. Our work shows that the visual system is not able to correctly represent and interpret disparity for all locations in a complex three-dimensional scene.

Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam.

BACKGROUND: An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm(3) for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam. METHODS: Serum samples were collected and stored during 2009-2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm(3) were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines. RESULTS: Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm(3) were available for CrAg testing. Median CD4 count was 40 (range 0-99) cells/mm(3). Nine (4%; 95% CI 2-7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3-11%) than in North Vietnam (2%; 95% CI 0-6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively. CONCLUSION: CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.

A strategy to increase adoption of locally-produced, ceramic cookstoves in rural Kenyan households.

BACKGROUND: Exposure to household air pollutants released during cooking has been linked to numerous adverse health outcomes among residents of rural areas in low-income countries. Improved cookstoves are one of few available interventions, but achieving equity in cookstove access has been challenging. Therefore, innovative approaches are needed. To evaluate a project designed to motivate adoption of locally-produced, ceramic cookstoves (upesi jiko) in an impoverished, rural African population, we assessed the perceived benefits of the cookstoves (in monetary and time-savings terms), the rate of cookstove adoption, and the equity of adoption. METHODS: The project was conducted in 60 rural Kenyan villages in 2008 and 2009. Baseline (n = 1250) and follow-up (n = 293) surveys and a stove-tracking database were analyzed. RESULTS: At baseline, nearly all respondents used wood (95%) and firepits (99%) for cooking; 98% desired smoke reductions. Households with upesi jiko subsequently spent <100 Kenyan Shillings/week on firewood more often (40%) than households without upesi jiko (20%) (p = 0.0002). There were no significant differences in the presence of children <2 years of age in households using upesi jiko (48%) or three-stone stoves (49%) (p = 0.88); children 2-5 years of age were less common in households using upesi jiko versus three-stone stoves (46% and 69%, respectively) (p = 0.0001). Vendors installed 1,124 upesi jiko in 757 multi-family households in 18 months; 68% of these transactions involved incentives for vendors and purchasers. Relatively few (<10%) upesi jiko were installed in households of women in the youngest age quartile (<22 years) or among households in the poorest quintile. CONCLUSIONS: Our strategy of training of local vendors, appropriate incentives, and product integration effectively accelerated cookstove adoption into a large number of households. The strategy also created opportunities to reinforce health messages and promote cookstoves sales and installation. However, the project's overall success was diminished by inequitable and incomplete adoption by households with the lowest socioeconomic status and young children present. Additional evaluations of similar strategies will be needed to determine whether our strategy can be applied equitably elsewhere, and whether reductions in fuel use, household air pollution, and the incidence of respiratory diseases will follow adoption of improved cookstoves.

Methadone as social control: institutionalized stigma and the prospect of recovery.

Methadone maintenance treatment (MMT) is an intervention used to treat opioid (heroin) dependence. Several investigators have found that MMT is effective in reducing heroin use and other behaviors; however, a disproportionate number of MMT clients leave treatment prematurely. Moreover, MMT outcome variables are often limited in terms of their measurement. Utilizing an integrated theoretical framework of social control and stigma, we focused on the experiences of methadone maintenance from the perspective of clients. We pooled interview data from four qualitative studies in two jurisdictions and found linkages between social control and institutional stigma that serve to reinforce "addict" identities, expose undeserving customers to the public gaze, and encourage clients to be passive recipients of treatment. We discuss the implications for recovery and suggest recommendations for change.

Optimal integration of shading and binocular disparity for depth perception.

We explore the relative utility of shape from shading and binocular disparity for depth perception. Ray-traced images either featured a smooth surface illuminated from above (shading-only) or were defined by small dots (disparity-only). Observers judged which of a pair of smoothly curved convex objects had most depth. The shading cue was around half as reliable as the rich disparity information for depth discrimination. Shading- and disparity-defined cues where combined by placing dots in the stimulus image, superimposed upon the shaded surface, resulting in veridical shading and binocular disparity. Independently varying the depth delivered by each channel allowed creation of conflicting disparity-defined and shading-defined depth. We manipulated the reliability of the disparity information by adding disparity noise. As noise levels in the disparity channel were increased, perceived depths and variances shifted toward those of the now more reliable shading cue. Several different models of cue combination were applied to the data. Perceived depths and variances were well predicted by a classic maximum likelihood estimator (MLE) model of cue integration, for all but one observer. We discuss the extent to which MLE is the most parsimonious model to account for observer performance.

Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia (PCP).

BACKGROUND: Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. METHODS AND FINDINGS: We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options. CONCLUSIONS: For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.

Pharmacogenomic testing to prevent aminoglycoside-induced hearing loss in cystic fibrosis patients: potential impact on clinical, patient, and economic outcomes.

BACKGROUND: Aminoglycosides are commonly used in cystic fibrosis patients to treat Pseudomonas aeruginosa respiratory infections. Aminoglycoside-induced hearing loss may occur in 1%-15% of patients with cystic fibrosis, ranging from mild to severe. Recently, a genetic test to identify patients with a mitochondrial mutation (A1555G) that may predispose patients to this adverse event has become available. Although the A1555G variant is very rare, it seems to confer a high risk of severe hearing loss in patients exposed to aminoglycosides. OBJECTIVE: The objective was to evaluate the potential clinical, patient, and economic outcomes associated with the use of A1555G testing in a cystic fibrosis population, and explore data gaps and uncertainty in its clinical implementation. METHODS: We developed a decision-analytic model to evaluate a hypothetical cohort of patients with cystic fibrosis from a societal perspective. Clinical and economic data were derived primarily from a critical literature review. The incidence of aminoglycoside-induced severe hearing loss, quality-adjusted life-years, and total health care costs were evaluated. Sensitivity analyses were conducted to evaluate uncertainty in our results. RESULTS: In the base-case analysis, A1555G testing decreased the risk of severe aminoglycoside-induced hearing loss by 0.12% in the cystic fibrosis population. The discounted incremental cost per quality-adjusted life-years gained was $79,300, but varied widely from $33,000 to testing being dominated by the no testing strategy (higher costs and lower quality-adjusted life-years with testing) in sensitivity analyses. If avoidance of aminoglycosides in patients testing positive leads to an absolute increase in the lifetime risk of death from Pseudomonas infection of 0.8% or greater, A1555G testing would lead to a decrease in quality-adjusted life-years. CONCLUSIONS: The results of our analysis suggest that there are significant data gaps and uncertainty in the outcomes with A1555G testing, but it is not likely cost-effective, and could lead to worse patient outcomes due to avoidance of first-line therapy in the >95% of patients who are false-positives. Additional research is needed before pharmacogenetic testing for the A1555G mitochondrial mutation can be recommended, even in a population with a high likelihood of exposure to aminoglycosides.