Development of a Simple Scoring System for Predicting Discharge Safety from the Medical ICU to Low-Acuity Wards: The Role of the Sequential Organ Failure Assessment Score, Albumin, and Red Blood Cell Distribution Width.

Despite advancements in artificial intelligence-based decision-making, transitioning patients from intensive care units (ICUs) to low-acuity wards is challenging, especially in resource-limited settings. This study aimed to develop a simple scoring system to predict ICU discharge safety. We retrospectively analyzed patients admitted to a tertiary hospital's medical ICU (MICU) between July 2016 and December 2021. This period was divided into two phases for model development and validation. We identified risk factors associated with unexpected death within 14 days of MICU discharge and developed a predictive scoring system that incorporated these factors. We verified the system's performance using validation data. In the development cohort, 522 patients were discharged from the MICU, and 42 (8.04%) died unexpectedly. In multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.13-1.41), red blood cell distribution width (RDW) (OR 1.20, 95% CI 1.07-1.36), and albumin (OR 0.37, 95% CI 0.16-0.84) were predictors of unexpected death. Each variable was assigned a weighted point in the scoring system, and the area under the curve (AUC) was 0.788 (95% CI 0.714-0.855). The scoring system was performed using an AUC of 0.738 (95% CI 0.653-0.822) in the validation cohort of 343 patients with 9.62% of unexpected deaths. When a cut-off of 0.032 was applied, a sensitivity and a specificity of 81.8% and 55.2%, respectively, were achieved. This simple bedside predictive score for ICU discharge uses the SOFA score, albumin level, and RDW to aid in timely decision-making and optimize critical care facility allocation in resource-limited settings.

Automatic Assessment of Upper Extremity Function and Mobile Application for Self-Administered Stroke Rehabilitation.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

Prognostic value of MRI volumetric parameters in non-small cell lung cancer patients after immune checkpoint inhibitor therapy: comparison with response assessment criteria.

BACKGROUND: Accurate response parameters are important for patients with brain metastasis (BM) undergoing clinical trials using immunotherapy, considering poorly defined enhancement and variable responses. This study investigated MRI-based surrogate endpoints for patients with BM receiving immunotherapy. METHODS: Sixty-three non-small cell lung cancer patients with BM who received immune checkpoint inhibitors and underwent MRI were included. Tumor diameters were measured using a modification of the RECIST 1.1 (mRECIST), RANO-BM, and iRANO adjusted for BM (iRANO-BM). Tumor volumes were segmented on 3D contrast-enhanced T1-weighted imaging. Differences between the sum of the longest diameter (SLD) or total tumor volume at baseline and the corresponding measurement at time of the best overall response were calculated as "changes in SLDs" (for each set of criteria) and "change in volumetry," respectively. Overall response rate (ORR), progressive disease (PD) assignment, and progression-free survival (PFS) were compared among the criteria. The prediction of overall survival (OS) was compared between diameter-based and volumetric change using Cox proportional hazards regression analysis. RESULTS: The mRECIST showed higher ORR (30.1% vs. both 17.5%) and PD assignment (34.9% vs. 25.4% [RANO-BM] and 19% [iRANO-BM]). The iRANO-BM had a longer median PFS (13.7 months) than RANO-BM (9.53 months) and mRECIST (7.73 months, P = 0.003). The change in volumetry was a significant predictor of OS (HR = 5.87, 95% CI: 1.46-23.64, P = 0.013). None of the changes in SLDs, as determined by RANO-BM or iRANO-BM, were significant predictors of OS, except for the mRECIST, which exhibited a weak association with OS. CONCLUSION: Quantitative volume measurement may be an accurate surrogate endpoint for OS in patients with BM undergoing immunotherapy, especially considering the challenges of multiplicity and the heterogeneity of sub-centimeter size responses.

Biomarker-Based Assessment Model for Detecting Sepsis: A Retrospective Cohort Study.

The concept of the quick sequential organ failure assessment (qSOFA) simplifies sepsis detection, and the next SOFA should be analyzed subsequently to diagnose sepsis. However, it does not include the concept of suspected infection. Thus, we simply developed a biomarker-based assessment model for detecting sepsis (BADS). We retrospectively reviewed the electronic health records of patients admitted to the intensive care unit (ICU) of a 2000-bed university tertiary referral hospital in South Korea. A total of 989 patients were enrolled, with 77.4% (n = 765) of them having sepsis. The patients were divided into a ratio of 8:2 and assigned to a training and a validation set. We used logistic regression analysis and the Hosmer-Lemeshow test to derive the BADS and assess the model. BADS was developed by analyzing the variables and then assigning weights to the selected variables: mean arterial pressure, shock index, lactate, and procalcitonin. The area under the curve was 0.754, 0.615, 0.763, and 0.668 for BADS, qSOFA, SOFA, and acute physiology and chronic health evaluation (APACHE) II, respectively, showing that BADS is not inferior in sepsis prediction compared with SOFA. BADS could be a simple scoring method to detect sepsis in critically ill patients quickly at the bedside.

RoBANS 2: A Revised Risk of Bias Assessment Tool for Nonrandomized Studies of Interventions.

Assessment of the risk of bias is an essential component of any systematic review. This is true for both nonrandomized studies and randomized trials, which are the main study designs of systematic reviews. The Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) was developed in 2013 and has gained wide usage as a risk-of-bias assessment tool for nonrandomized studies. Four risk-of-bias assessment experts revised it by reviewing existing assessment tools and user surveys. The main modifications included additional domains of selection and detection bias susceptible to nonrandomized studies of interventions, a more detailed consideration of the comparability of participants, and more reliable and valid outcome measurements. A psychometric assessment of the revised RoBANS (RoBANS 2) revealed acceptable inter-rater reliability (weighted kappa, 0.25 to 0.49) and construct validity in which intervention effects of studies with an unclear or high risk of bias were overestimated. The RoBANS 2 has acceptable feasibility, fair-to-moderate reliability, and construct validity. It provides a comprehensive framework for allowing authors to assess and understand the plausible risk of bias in nonrandomized studies of interventions.

Artificial intelligence (AI)-based decision support improves reproducibility of tumor response assessment in neuro-oncology: An international multi-reader study.

BACKGROUND: To assess whether artificial intelligence (AI)-based decision support allows more reproducible and standardized assessment of treatment response on MRI in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden using the Response Assessment in Neuro-Oncology (RANO) criteria. METHODS: A series of 30 patients (15 lower-grade gliomas, 15 glioblastoma) with availability of consecutive MRI scans was selected. The time to progression (TTP) on MRI was separately evaluated for each patient by 15 investigators over two rounds. In the first round the TTP was evaluated based on the RANO criteria, whereas in the second round the TTP was evaluated by incorporating additional information from AI-enhanced MRI sequences depicting the longitudinal changes in tumor volumes. The agreement of the TTP measurements between investigators was evaluated using concordance correlation coefficients (CCC) with confidence intervals (CI) and P-values obtained using bootstrap resampling. RESULTS: The CCC of TTP-measurements between investigators was 0.77 (95% CI = 0.69,0.88) with RANO alone and increased to 0.91 (95% CI = 0.82,0.95) with AI-based decision support (P = .005). This effect was significantly greater (P = .008) for patients with lower-grade gliomas (CCC = 0.70 [95% CI = 0.56,0.85] without vs. 0.90 [95% CI = 0.76,0.95] with AI-based decision support) as compared to glioblastoma (CCC = 0.83 [95% CI = 0.75,0.92] without vs. 0.86 [95% CI = 0.78,0.93] with AI-based decision support). Investigators with less years of experience judged the AI-based decision as more helpful (P = .02). CONCLUSIONS: AI-based decision support has the potential to yield more reproducible and standardized assessment of treatment response in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden, particularly in patients with lower-grade gliomas. A fully-functional version of this AI-based processing pipeline is provided as open-source (https://github.com/NeuroAI-HD/HD-GLIO-XNAT).

Twenty years of traditional and complementary medicine regulation and its impact in Malaysia: achievements and policy lessons.

BACKGROUND: Many countries are trying to integrate traditional and complementary medicine (T&CM) into their health care systems. However, it is not easy to integrate T&CM within a given health care system. This study aims to draw policy outcomes and lessons from the case of Malaysia, which has been making efforts for over 20 years to integrate various types of T&CM into the national health care system (NHS). METHODS: Documents were searched in major databases and websites using words such as Malaysia and T&CM, and additional documents were secured using snowballing techniques. Data were classified and organized according to the World Health Organization health systems framework. RESULTS: Malaysia has focused on managing the safety and quality of T&CM, and to that end it has been institutionalized by enacting specialized laws rather than by applying existing medical law directly. Malaysia was able to institutionalize T&CM by adopting a step-by-step approach that considered the appropriateness of administrative policies and measures. CONCLUSIONS: Malaysia's experiences in implementing its T&CM policies will raise practical implications for countries struggling to integrate their existing T&CM into the NHS and utilize it for universal health coverage.

Refinement of response assessment in neuro-oncology (RANO) using non-enhancing lesion type and contrast enhancement evolution pattern in IDH wild-type glioblastomas.

BACKGROUND: Updated response assessment in neuro-oncology (RANO) does not consider peritumoral non-enhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma. METHODS: This retrospective study enrolled 86 patients with IDH wild-type glioblastoma who underwent consecutive MRI examinations before and after concurrent chemoradiotherapy (CCRT). NEL was classified as edema- or tumor-dominant type on pre-CCRT MRI. CE evolution was categorized into 4 patterns based on post-operative residual CE (measurable vs. non-measurable) and CE volume change (same criteria with RANO) during CCRT. Multivariable logistic regression, including clinical parameters, NEL type, and CE evolution pattern, was used to analyze pseudoprogression rate. TTP and OS according to NEL type and CE evolution pattern was analyzed by the Kaplan-Meier method. RESULTS: Pseudoprogression rate was significantly lower (chi-square test, P = .047) and TTP was significantly shorter (hazard ratio [HR] = 2.03, P = .005) for tumor-dominant type than edema-dominant type of NEL. NEL type was the only predictive marker of pseudoprogression on multivariate analysis (odds ratio = 0.26, P = .046). Among CE evolution patterns, TTP and OS was shortest in patients with residual CE compared with those exhibiting new CE (HR = 4.33, P < 0.001 and HR = 3.71, P = .009, respectively). In edema-dominant NEL type, both TTP and OS was stratified by CE evolution pattern (log-rank, P = .001), whereas it was not in tumor-dominant NEL. CONCLUSIONS: NEL type improves prediction of pseudoprogression and, together with CE evolution pattern, further stratifies TTP and OS in patients with IDH wild-type glioblastoma and may become a helpful biomarker for refining RANO.

The Association Between Health Changes and Cessation of Alcohol Consumption.

AIMS: To assess whether health changes affect cessation of alcohol consumption and to compare the health status of former drinkers and abstainers. METHODS: Cohort data from 9001 Korean participants aged 40-69 years old were analyzed. Alcohol consumption was assessed every 2 years for 10 years. Participant age, sex, marital status, education level, employment status, smoking, chronic disease, perceived health and changes in these variables were analyzed to identify factors associated with quitting alcohol drinking. The number of diseases and perceived health of former drinkers and people who at baseline were lifetime abstainers were compared. RESULTS: Among 4037 drinkers at baseline, 673 (16.7%) were classed as quitters and 3364 (83.3%) were classed as non-quitters. Sex, age and worsened perception of health were significantly associated with cessation of drinking. Women and individuals >60 years were more likely to cease drinking. There was a significant association between disease onset or treatment and alcohol cessation for cancer cases, but not for cardiovascular disease or chronic disease cases. There was no significant difference in number of diseases or perceived health between former drinkers and people who at baseline were lifetime abstainers. CONCLUSIONS: The effect of disease onset or treatment on alcohol consumption cessation depended on disease type. Former drinkers did not show significantly worse health than people who at baseline were lifetime abstainers. Further studies of alcohol consumption and its effects on health are needed to consider disease occurrence and changes in alcohol consumption. SHORT SUMMARY: Disease onset or treatment significantly affected alcohol consumption cessation for cancer cases, but not for cardiovascular disease or other chronic disease cases. There was no significant difference in health status between former drinkers and lifetime abstainers.

Assessment of Measurement Repeatability and Reliability With Virtual Touch Tissue Quantification Imaging in Cervical Lymphadenopathy.

OBJECTIVES: The purpose of this study was to prospectively assess the repeatability and reliability of 2 measurements of cervical lymphadenopathy using Virtual Touch tissue quantification (VTQ) imaging (Siemens Medical Solutions, Mountain View, CA) and to analyze the factors affecting the reliability of the measurements, including pathologic findings, lesion size and location, and shear wave velocities (SWVs). METHODS: In this Institutional Review Board-approved prospective study, 92 patients underwent conventional sonography and 2 VTQ measurements by acoustic radiation force impulse imaging in a single session. The repeatability and reliability of the SWV measurement was determined by using an average coefficient of variation (standard deviation/mean) and intraclass correlation coefficient (ICC), respectively. By comparing ICCs with a 95% confidence interval, the effects of pathologic findings, depth, size, SWV, and distance from the carotid artery on reliability were assessed. RESULTS: The mean age of the 92 patients included in the study was 51 years (range, 14-77 years). The average coefficient of variation was 19.4%. The overall reliability of the 2 measurements was excellent (ICC, 0.837), but ICCs were significantly decreased in lymph nodes in a superficial location (<1 cm) and those with a low SWV (<1.8 m/s). No significant effect was found on reliability in relation to pathologic findings, lesion size, or distance from the carotid artery to the lymph nodes. CONCLUSIONS: For SWV measurement by VTQ imaging, the repeatability was 19.4%, and reliability was excellent. However, caution is warranted in the use of VTQ imaging for superficial soft cervical lymph nodes, as both a superficial location and a soft composition tend to be characterized by low reliability of SWV findings.

Understanding, benefits and difficulties of home medicines review - patients' perspectives.

BACKGROUND: The home medicines review (HMR) is an important tool for promoting a model of patient-centred care. This article seeks pa-tients' perspectives on understanding, and perceived benefits and difficulties of HMRs. METHODS: A qualitative study based on semi-structured interviews of adult participants who completed an HMR was undertaken in Black-town, a growing, multicultural suburb in Western Sydney. The medical centre is a large general practice offering comprehensive, integrated care. Fifteen participants consented to be interviewed. There was even representation of men and women, and the majority had completed high school. RESULTS: Three major areas were explored: understanding and expectation of an HMR, perceived patient benefits and difficulties. DISCUSSION: The HMR has the potential to be a useful tool in patients' management of their medications. There are clear benefits when per-formed well. However, we have identified areas of limitations in effectiveness, which present opportunities for strengthening the HMR process. Training of doctors and pharmacists may be needed to ensure better patient outcomes.

Pseudoprogression in Patients with Glioblastoma: Assessment by Using Volume-weighted Voxel-based Multiparametric Clustering of MR Imaging Data in an Independent Test Set.

PURPOSE: To validate a volume-weighted voxel-based multiparametric clustering (VVMC) method for magnetic resonance imaging data that is designed to differentiate between pseudoprogression and early tumor progression (ETP) in patients with glioblastoma in an independent test set. MATERIALS AND METHODS: This retrospective study was approved by the local institutional review board, with waiver of the need to obtain informed consent. The study patients were grouped chronologically into a training set (108 patients) and a test set (54 patients). The reference standard was pathologic findings or subsequent clinical-radiologic study results. By using the optimal cutoff determined in the training set, the diagnostic performance of VVMC was subsequently tested in the test set and was compared with that of single-parameter measurements (apparent diffusion coefficient [ADC], normalized cerebral blood volume [nCBV], and initial area under the time-signal intensity curve). RESULTS: Interreader agreement was highest for VVMC (intraclass correlation coefficient, 0.87-0.89). Receiver operating characteristic curve analysis revealed that VVMC performed the best as a classifier, although statistical significance was not demonstrated with respect to the nCBV in the training set. In the test set, the diagnostic accuracy of VVMC was higher than that of any single-parameter measurements, but this trend reached significance only for the ADC. When the entire population was considered, VVMC had significantly better diagnostic accuracy than did any single parameter (P = .003-.046 for reader 1; P = .002-.016 for reader 2). Results of fivefold cross validation confirmed the trends in both the training set and the test set. CONCLUSION: VVMC is a superior and more reproducible imaging biomarker than single-parameter measurements for differentiating between pseudoprogression and ETP in patients with glioblastoma. Online supplemental material is available for this article.

Results of tuberculosis contact investigation in congregate settings in Korea, 2013.

OBJECTIVES: This study aimed to check the status of the contact investigation in congregate settings to eradicate tuberculosis (TB) in the Republic of Korea. METHODS: The "Integrated System for Disease and Public Health Management" is used for care and follow-up for patients and contacts of TB. We downloaded data for contact investigations conducted from January to December 2013. RESULTS: A total of 1,200 contact investigations in congregate settings were carried out by 25 field investigators in 2013. We performed the status of contact investigation, TB, and LTBI rate by age, accept rate of LTBI treatment, and complete rate of LTBI treatment during 2013. A total of 1,547 index TB patients, 149,166 contacts, and 259 additional TB patients were found through the investigation. Kindergartens showed the highest LTBI rate, 19.8%, among educational facilities. The second highest was in elementary schools and the subtotal LTBI rate of educational facilities was 7.8%. Social welfare/correctional facilities and workplaces showed relatively high LTBI rates of 23.8% and 23.6%, respectively. By age, individuals >35 years showed the highest LTBI rate, followed by those aged 0-4 years, 30-34 years, and 5-9 years, with rates of 18.1%, 16.4%, and 15.4% respectively. When comparing the tuberculin skin test (TST) positive conversion ratio by facility, middle school and high school were relatively high compared to the others. The accept rate of LTBI treatment in the workplace was lowest at 63% and the complete rate in elementary schools was lowest at 76.5%. CONCLUSION: TB contact investigation is considered as a meaningful strategy for preventing TB outbreaks in congregate settings and decreasing the prevalence of TB in young people. Results of this study could be used to establish the LTBI management policy.

Routine HIV screening in Portugal: clinical impact and cost-effectiveness.

OBJECTIVE: To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening. DESIGN: We used Portuguese national clinical and economic data to conduct a model-based assessment. METHODS: We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/µL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness. RESULTS: One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively. CONCLUSIONS: One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal's challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings.

Cost-effectiveness of World Health Organization 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe.

BACKGROUND: In 2010, the World Health Organization (WHO) released revised guidelines for prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). We projected clinical impacts, costs, and cost-effectiveness of WHO-recommended PMTCT strategies in Zimbabwe. METHODS: We used Zimbabwean data in a validated computer model to simulate a cohort of pregnant, HIV-infected women (mean age, 24 years; mean CD4 count, 451 cells/µL; subsequent 18 months of breastfeeding). We simulated guideline-concordant care for 4 PMTCT regimens: single-dose nevirapine (sdNVP); WHO-recommended Option A, WHO-recommended Option B, and Option B+ (lifelong maternal 3-drug antiretroviral therapy regardless of CD4). Outcomes included maternal and infant life expectancy (LE) and lifetime healthcare costs (2008 US dollars [USD]). Incremental cost-effectiveness ratios (ICERs, in USD per year of life saved [YLS]) were calculated from combined (maternal + infant) discounted costs and LE. RESULTS: Replacing sdNVP with Option A increased combined maternal and infant LE from 36.97 to 37.89 years and would reduce lifetime costs from $5760 to $5710 per mother-infant pair. Compared with Option A, Option B further improved LE (38.32 years), and saved money within 4 years after delivery ($5630 per mother-infant pair). Option B+ (LE, 39.04 years; lifetime cost, $6620 per mother-infant pair) improved maternal and infant health, with an ICER of $1370 per YLS compared with Option B. CONCLUSIONS: Replacing sdNVP with Option A or Option B will improve maternal and infant outcomes and save money; Option B increases health benefits and decreases costs compared with Option A. Option B+ further improves maternal outcomes, with an ICER (compared with Option B) similar to many current HIV-related healthcare interventions.

The cost-effectiveness of pre-exposure prophylaxis for HIV infection in South African women.

BACKGROUND: Recent trials report the short-term efficacy of tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection. PrEP's long-term impact on patient outcomes, population-level transmission, and cost-effectiveness remains unknown. METHODS: We linked data from recent trials to a computer model of HIV acquisition, screening, and care to project lifetime HIV risk, life expectancy (LE), costs, and cost-effectiveness, using 2 PrEP-related strategies among heterosexual South African women: (1) women receiving no PrEP and (2) women not receiving PrEP (a tenofovir-based vaginal microbicide). We used a South African clinical cohort and published data to estimate population demographic characteristics, age-adjusted incidence of HIV infection, and HIV natural history and treatment parameters. Baseline PrEP efficacy (percentage reduction in HIV transmission) was 39% at a monthly cost of $5 per woman. Alternative parameter values were examined in sensitivity analyses. RESULTS: Among South African women, PrEP reduced mean lifetime HIV risk from 40% to 27% and increased population discounted (undiscounted) LE from 22.51 (41.66) to 23.48 (44.48) years. Lifetime costs of care increased from $7280 to $9890 per woman, resulting in an incremental cost-effectiveness ratio of $2700/year of life saved, and may, under optimistic assumptions, achieve cost savings. Under baseline HIV infection incidence assumptions, PrEP was not cost saving, even assuming an efficacy >60% and a cost <$1. At an HIV infection incidence of 9.1%/year, PrEP achieved cost savings at efficacies ≥50%. CONCLUSIONS: PrEP in South African women is very cost-effective by South African standards, conferring excellent value under virtually all plausible data scenarios. Although optimistic assumptions would be required to achieve cost savings, these represent important benchmarks for future PrEP study design.

Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions.

Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings.

Cost-effectiveness of laboratory monitoring in sub-Saharan Africa: a review of the current literature.

As the global community evaluates the unprecedented investment in the scale-up of human immunodeficiency virus (HIV) therapy and considers future investments in HIV care, it is crucial to identify those HIV interventions that maximize the benefit realized from each dollar spent. The use of laboratory monitoring assays--CD4 cell count and HIV RNA level--in decisions about when to initiate and switch antiretroviral therapy may offer substantial clinical benefit, but their economic value remains controversial. Cost-effectiveness analysis can be used to evaluate the value for money of strategies for HIV care, including alternative approaches to laboratory monitoring. Five published cost-effectiveness analyses address the question of CD4 cell count and HIV RNA level monitoring for HIV-infected patients in Africa, with differing conclusions. We describe the use of cost-effectiveness analysis in resource-limited settings and review the cost-effectiveness literature with regard to monitoring the CD4 cell count and HIV RNA level in Africa, highlighting some of the most critical issues in this debate.