Cost-effectiveness of point-of-care C-Reactive Protein test compared to current clinical practice as an intervention to improve antibiotic prescription in malaria-negative patients in Afghanistan.

BACKGROUND: Antimicrobial resistance (AMR) is a global health problem requiring a reduction in inappropriate antibiotic prescribing. Point-of-Care C-Reactive Protein (POCCRP) tests could distinguish between bacterial and non-bacterial causes of fever in malaria-negative patients and thus reduce inappropriate antibiotic prescribing. However, the cost-effectiveness of POCCRP testing is unclear in low-income settings. METHODS: A decision tree model was used to estimate cost-effectiveness of POCCRP versus current clinical practice at primary healthcare facilities in Afghanistan. Data were analysed from healthcare delivery and societal perspectives. Costs were reported in 2019 USD. Effectiveness was measured as correctly treated febrile malaria-negative patient. Cost, effectiveness and diagnostic accuracy parameters were obtained from primary data from a cost-effectiveness study on malaria rapid diagnostic tests in Afghanistan and supplemented with POCCRP-specific data sourced from the literature. Incremental cost-effectiveness ratios (ICERs) reported the additional cost per additional correctly treated febrile malaria-negative patient over a 28-day time horizon. Univariate and probabilistic sensitivity analyses examined the impact of uncertainty of parameter inputs. Scenario analysis included economic cost of AMR per antibiotic prescription. RESULTS: The model predicts that POCCRP intervention would result in 137 fewer antibiotic prescriptions (6%) with a 12% reduction (279 prescriptions) in inappropriate prescriptions compared to current clinical practice. ICERs were $14.33 (healthcare delivery), $11.40 (societal), and $9.78 (scenario analysis) per additional correctly treated case. CONCLUSIONS: POCCRP tests could improve antibiotic prescribing among malaria-negative patients in Afghanistan. Cost-effectiveness depends in part on willingness to pay for reductions in inappropriate antibiotic prescribing that will only have modest impact on immediate clinical outcomes but may have long-term benefits in reducing overuse of antibiotics. A reduction in the overuse of antibiotics is needed and POCCRP tests may add to other interventions in achieving this aim. Assessment of willingness to pay among policy makers and donors and undertaking operational trials will help determine cost-effectiveness and assist decision making.

Cost Analysis of Emergency Department Criteria for Evaluation of Febrile Infants Ages 29 to 90 Days.

OBJECTIVE: To compare the medical costs associated with risk stratification criteria used to evaluate febrile infants 29-90 days of age. STUDY DESIGN: A cost analysis study was conducted evaluating the Boston, Rochester, Philadelphia, Step-by-Step, and PECARN criteria. The percentage of infants considered low risk and rates of missed infections were obtained from published literature. Emergency department costs were estimated from the Centers for Medicare and Medicaid Services. The Health Care Cost and Utilization Project databases were used to estimate the number of infants ages 29-90 days presenting with fever annually and costs for admissions related to missed infections. A probabilistic Markov model with a Dirichlet prior was used to estimate the transition probability distributions for each outcome, and a gamma distribution was used to model costs. A Markov simulation estimated the distribution of expected annual costs per infant and total annual costs. RESULTS: For low-risk infants, the mean cost per infant for the criteria were Rochester: $1050 (IQR $1004-$1092), Philadelphia: $1416 (IQR, $1365-$1465), Boston: $1460 (IQR, $1411-$1506), Step-by-Step $942 (IQR, $899-$981), and PECARN $1004 (IQR, $956-$1050). An estimated 18 522 febrile 1- to 3-month-old infants present annually and estimated total mean costs for their care by criteria were: Rochester, $127.3 million (IQR, $126.1-$128.5); Philadelphia, $129.9 million (IQR, $128.7-$131.1); Boston, $128.7 million (IQR, $127.5-$129.9); Step-by-Step, $ 126.6 million (IQR, $125.4-$127.8); and PECARN, $125.8 million (IQR, $124.6-$127). CONCLUSIONS: The Rochester, Step-by-step, and PECARN criteria are the least costly when evaluating infants 29-90 days of age with a fever.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

The impact of global budgeting in Taiwan on inpatients with unexplained fever.

Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan.The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000-2001 were recruited; their 2000-2001 and 2004-2005 data were considered baseline and postintervention data, respectively.Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ±â€Š0.35 days and 5.29 ±â€Š0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ±â€ŠNT$97.43, NT$3249.90 ±â€ŠNT$1108.27, NT$421.03 ±â€ŠNT$100.03, and NT$13,866.77 ±â€ŠNT$2,114.95 before GB system implementation to NT$2224.34 ±â€ŠNT$238.36, NT$4272.31 ±â€ŠNT$1466.90, NT$2217.03 ±â€ŠNT$672.20, and NT$22,856.41 ±â€ŠNT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ±â€Š2.7% and 8.3% ±â€Š2.4% before implementation to 6.3% ±â€Š2.2% and 4.0% ±â€Š1.7% after implementation.GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.

The cost of diagnostic uncertainty: a prospective economic analysis of febrile children attending an NHS emergency department.

BACKGROUND: Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial causes, necessitating a cautious approach. This may result in extended periods of observation, additional radiography, and the precautionary use of antibiotics (ABs) prior to evidence of bacterial foci. This study examines resource use, service costs, and health outcomes. METHODS: We studied an all-year prospective, comprehensive, and representative cohort of 6518 febrile children (aged < 16 years), attending Alder Hey Children's Hospital, an NHS-affiliated paediatric care provider in the North West of England, over a 1-year period. Performing a time-driven and activity-based micro-costing, we estimated the economic impact of managing paediatric febrile illness, with focus on nurse/clinician time, investigations, radiography, and inpatient stay. Using bootstrapped generalised linear modelling (GLM, gamma, log), we identified the patient and healthcare provider characteristics associated with increased resource use, applying retrospective case-note identification to determine rates of potentially avoidable AB prescribing. RESULTS: Infants aged less than 3 months incurred significantly higher resource use than any other age group, at £1000.28 [95% CI £82.39-£2993.37] per child, (p < 0.001), while lesser experienced doctors exhibited 3.2-fold [95% CI 2.0-5.1-fold] higher resource use than consultants (p < 0.001). Approximately 32.4% of febrile children received antibiotics, and 7.1% were diagnosed with bacterial infections. Children with viral illnesses for whom antibiotic prescription was potentially avoidable incurred 9.9-fold [95% CI 6.5-13.2-fold] cost increases compared to those not receiving antibiotics, equal to an additional £1352.10 per child, predominantly resulting from a 53.9-h increase in observation and inpatient stay (57.1 vs. 3.2 h). Bootstrapped GLM suggested that infants aged below 3 months and those prompting a respiratory rate 'red flag', treatment by lesser experienced doctors, and Manchester Triage System (MTS) yellow or higher were statistically significant predictors of higher resource use in 100% of bootstrap simulations. CONCLUSION: The economic impact of diagnostic uncertainty when managing paediatric febrile illness is significant, and the precautionary use of antibiotics is strongly associated with increased costs. The use of ED resources is highest among infants (aged less than 3 months) and those infants managed by lesser experienced doctors, independent of clinical severity. Diagnostic advances which could increase confidence to withhold antibiotics may yield considerable efficiency gains in these groups, where the perceived risks of failing to identify potentially life-threatening bacterial infections are greatest.

Admit Versus Discharge-A Cost Analysis of Infants 29 to 60 Days Old With Febrile Urinary Tract Infection at Low Risk for Bacteremia.

BACKGROUND: Ninety percent of infants 29 to 60 days old presenting to the emergency department with fever and urinary tract infection are admitted due to fear of concomitant bacteremia. Many of these infants are at low risk for bacteremia and can be safely discharged with no heightened risk of adverse events. This study sought to estimate the potential savings from outpatient management of low-risk infants. METHODS: A comparative cost analysis was performed using bacteremia probability estimates from a previously published prediction model. We estimated costs using a national pediatric database coupled with retrospective chart review of infants who presented to our emergency department between 2011 and 2015. RESULTS: The relative cost savings for the discharge strategy were $80,333 ($19,127 vs $99,460; 80% savings) for each patient with bacteremia and $257,073 per 100 patients overall. Similar savings were found for charges-$304,949 ($71,421 vs $376,371; 80%) for each patient with bacteremia and $975,838 per 100 patients. Our institutional reimbursements provided an estimated savings of $148,924 ($73,280 vs. $222,204; 67%) and $476,533 per 100 patients overall. CONCLUSIONS: The relative cost savings from discharging rather than admitting low-risk infants with febrile urinary tract infection were significant, even accounting for expenditures associated with the return emergency room visit of initially discharged bacteremic patients. These savings are achievable without an increase in adverse events. Similar outcomes were demonstrated for hospital charges and reimbursements, further strengthening these results. This study emphasizes how risk stratification in clinical decision-making can lead to substantial cost savings without compromising patient outcomes.

Cost-benefit analysis of introducing next-generation sequencing (metagenomic) pathogen testing in the setting of pyrexia of unknown origin.

Pyrexia of unknown origin (PUO) is defined as a temperature of >38.3°C that lasts for >3 weeks, where no cause can be found despite appropriate investigation. Existing protocols for the work-up of PUO can be extensive and costly, motivating the application of recent advances in molecular diagnostics to pathogen testing. There have been many reports describing various analytical methods and performance of metagenomic pathogen testing in clinical samples but the economics of it has been less well studied. This study pragmatically evaluates the feasibility of introducing metagenomic testing in this setting by assessing the relative cost of clinically-relevant strategies employing this investigative tool under various cost and performance scenarios using Singapore as a demonstration case, and assessing the price and performance benchmarks, which would need to be achieved for metagenomic testing to be potentially considered financially viable relative to the current diagnostic standard. This study has some important limitations: we examined only impact of introducing the metagenomic test to the overall diagnostic cost and excluded costs associated with hospitalization and makes assumptions about the performance of the routine diagnostic tests, limiting the cost of metagenomic test, and the lack of further work-up after positive pathogen detection by the metagenomic test. However, these assumptions were necessary to keep the model within reasonable limits. In spite of these, the simplified presentation lends itself to the illustration of the key insights of our paper. In general, we find the use of metagenomic testing as second-line investigation is effectively dominated, and that use of metagenomic testing at first-line would typically require higher rates of detection or lower cost than currently available in order to be justifiable purely as a cost-saving measure. We conclude that current conditions do not warrant a widespread rush to deploy metagenomic testing to resolve any and all uncertainty, but rather as a front-line technology that should be used in specific contexts, as a supplement to rather than a replacement for careful clinical judgement.

Pre-hospital ambulance care of patients following a suspected seizure: A cross sectional study.

PURPOSE: We aimed to investigate the characteristics of patients presenting to the ambulance service with suspected seizures, the costs of managing these patients and the factors which predicted transport to hospital. METHODS: We employed a cross-sectional design using routine clinical data from a UK regional ambulance service. Logistic regression was used to identify predictors of transport to hospital from ambulance response times, demographics, clinical (physiological) findings and treatments. RESULTS: There were 177,715 emergency incidents recorded in 2011/12 of which 2.9% (5139/177,715) were classified as seizures by ambulance call handlers and 2.7% (4884/177,715) by paramedics on the scene. Suspected seizures were the seventh most common call type. The annual cost of managing these incidents was £890,148. Clinical and physiological variables were normal for most patients. 59.3% (2894/4884) of patients were transported to hospital. 1/4884 (0.02%) patient died. Administration of diazepam, insertion of an airway and pyrexia perfectly predicted transport to hospital, tachycardia had a modest association, but other variables were only weak predictors of transport to hospital. CONCLUSIONS: This study shows that most patients after a suspected seizure are not acutely unwell but nevertheless most patients are transported to hospital. Further research is required to determine which factors are important in decisions to transport to hospital and to create evidence-based tools to help paramedics identify patients who could be safely managed without transport to hospital.

Safety and cost benefit of an ambulatory program for patients with low-risk neutropenic fever at an Australian centre.

BACKGROUND: Neutropenic fever (NF) is a common complication of cancer chemotherapy. Patients at low risk of medical complications from NF can be identified using a validated risk assessment and managed in an outpatient setting. This is a new model of care for Australia. This study described the implementation of a sustainable ambulatory program for NF at a tertiary cancer centre over a 12-month period. METHODS: Peter MacCallum Cancer Centre introduced an ambulatory care program in 2014, which identified low-risk NF patients, promoted early de-escalation to oral antibiotics, and early discharge to a nurse-led ambulatory program. Patients prospectively enrolled in the ambulatory program were compared with a historical-matched cohort of patients from 2011 for analysis. Patient demographics, clinical variables (cancer type, recent chemotherapy, treatment intent, site of presentation) and outcomes were collected and compared. Total cost of inpatient admissions was determined from diagnosis-related group (DRG) codes and applied to both the prospective and historical cohorts to allow comparisons. RESULTS: Twenty-five patients were managed in the first year of this program with a reduction in hospital median length of stay from 4.0 to 1.1 days and admission cost from Australian dollars ($AUD) 8580 to $AUD2360 compared to the historical cohort. Offsetting salary costs, the ambulatory program had a net cost benefit of $AUD 71895. Readmission for fever was infrequent (8.0%), and no deaths were reported. CONCLUSION: Of relevance to hospitals providing cancer care, feasibility, safety, and cost benefits of an ambulatory program for low-risk NF patients have been demonstrated.

Body Temperature after EMS Transport: Association with Traumatic Brain Injury Outcomes.

INTRODUCTION: Low body temperatures following prehospital transport are associated with poor outcomes in patients with traumatic brain injury (TBI). However, a minimal amount is known about potential associations across a range of temperatures obtained immediately after prehospital transport. Furthermore, a minimal amount is known about the influence of body temperature on non-mortality outcomes. The purpose of this study was to assess the correlation between temperatures obtained immediately following prehospital transport and TBI outcomes across the entire range of temperatures. METHODS: This retrospective observational study included all moderate/severe TBI cases (CDC Barell Matrix Type 1) in the pre-implementation cohort of the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH/NINDS: 1R01NS071049). Cases were compared across four cohorts of initial trauma center temperature (ITCT): <35.0°C [Very Low Temperature (VLT)]; 35.0-35.9°C [Low Temperature (LT)]; 36.0-37.9°C [Normal Temperature (NT)]; and ≥38.0°C [Elevated Temperature (ET)]. Multivariable analysis was performed adjusting for injury severity score, age, sex, race, ethnicity, blunt/penetrating trauma, and payment source. Adjusted odds ratios (aORs) with 95% confidence intervals (CI) for mortality were calculated. To evaluate non-mortality outcomes, deaths were excluded and the adjusted median increase in hospital length of stay (LOS), ICU LOS and total hospital charges were calculated for each ITCT group and compared to the NT group. RESULTS: 22,925 cases were identified and cases with interfacility transfer (7361, 32%), no EMS transport (1213, 5%), missing ITCT (2083, 9%), or missing demographic data (391, 2%) were excluded. Within this study cohort the aORs for death (compared to the NT group) were 2.41 (CI: 1.83-3.17) for VLT, 1.62 (CI: 1.37-1.93) for LT, and 1.86 (CI: 1.52-3.00) for ET. Similarly, trauma center (TC) LOS, ICU LOS, and total TC charges increased in all temperature groups when compared to NT. CONCLUSION: In this large, statewide study of major TBI, both ETs and LTs immediately following prehospital transport were independently associated with higher mortality and with increased TC LOS, ICU LOS, and total TC charges. Further study is needed to identify the causes of abnormal body temperature during the prehospital interval and if in-field measures to prevent temperature variations might improve outcomes.

Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States, 2012.

PURPOSE: Neutropenia and subsequent infections are life-threatening treatment-related toxicities of chemotherapy. Among patients with cancer, hospitalizations related to neutropenic complications result in substantial medical costs, morbidity, and mortality. Previous estimates for the cost of cancer-related neutropenia hospitalizations are based on older and limited data. This study provides nationally representative estimates of the cost of cancer-related neutropenia hospitalizations. METHODS: We examined data from the 2012 National Inpatient Sample and Kids' Inpatient Database. Hospitalizations for cancer-related neutropenia were defined as those with a primary or secondary diagnosis of cancer and a diagnosis of neutropenia or a fever of unknown origin. We examined characteristics of cancer-related neutropenia hospitalizations among children (age < 18 years) and adults (age ≥ 18 years). Adjusted predicted margins were used to estimate length of stay and cost per stay. RESULTS: There were 91,560 and 16,859 cancer-related neutropenia hospitalizations among adults and children, respectively. Total cost of cancer-related neutropenia hospitalizations was $2.3 billion for adults and $439 million for children. Cancer-related neutropenia hospitalizations accounted for 5.2% of all cancer-related hospitalizations and 8.3% of all cancer-related hospitalization costs. For adults, the mean length of stay for cancer-related neutropenia hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay. For children, the mean length of stay for cancer-related neutropenia hospitalizations was 8.5 days, with a mean hospital cost of $26,000 per stay. CONCLUSION: We found the costs of cancer-related neutropenia hospitalizations to be substantially high. Efforts to prevent and minimize neutropenia-related complications among patients with cancer may decrease hospitalizations and associated costs.

Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions.

BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTRs) are characterized by a post-transfusion temperature rise (of ≥ 1°C, to ≥ 38°C) or chills/rigors unrelated to the underlying condition. FNHTRs are provoked by inflammatory cytokines in the product or by host antileukocyte antibodies against residual donor leukocytes. FNHTRs are among the most commonly reported transfusion disturbances and are generally deemed nonserious events. However, their impact on patients and hospitals may be underestimated. STUDY DESIGN AND METHODS: A search through two hemovigilance databases identified all known possible-to-definite FNHTRs over 3 years (2013-2015) at four academic hospitals using prestorage leukoreduced components. FNHTRs were assessed for frequency by product (red blood cells [RBCs], platelets [PLTs], intravenous immunoglobulin), diagnostics (bedside, chest imaging, serology, microbiology), and management (medications, disposition change). The definition of FNHTR was derived from Canada's Transfusion-Transmitted Injuries Surveillance System. RESULTS: For 437 FNHTRs, the overall per-product rate across all sites was 0.24%, or 0.17% with RBCs alone and 0.25% with PLTs alone. One-third of patients had significant fevers (≥ 39.0°C or a rise by ≥ 2.0°C). Approximately one-quarter underwent chest imaging within 48 hours, and 79% had blood cultures. A hospital admission directly attributable to the FNHTR, to exclude other causes of fever, occurred in 15% of FNHTR outpatients. CONCLUSION: An analysis of FNHTRs reveals a substantial burden of postreaction clinical activity in addition to the disturbance itself. Efforts to avoid this adverse event may save resources, reduce patient distress, and encourage compliance with more restrictive transfusion strategies.

Routine Workup of Postoperative Pyrexia Following Total Joint Arthroplasty Is Only Necessary in Select Circumstances.

BACKGROUND: It is unclear when routine workup of postoperative pyrexia (POP) following total joint arthroplasty (TJA) should be performed. METHODS: A retrospective electronic database search was conducted on 25,558 consecutive patients undergoing primary or revision TJA between June 2001 and June 2013. We identified patient demographics, procedure type, characteristics of feverish patients, and febrile complications. The estimated costs for chest x-ray (CXR), urinalysis, urine culture, and blood culture were investigated. RESULTS: POP occurred in 46% of TJAs. A total of 11,589 separate workups were performed in 90.5% of POP patients, of which 2.4% were positive. Urinalysis, urine culture, blood culture, and CXR were positive in 38.7%, 9.5%, 7.0%, and 0.2%, respectively. Febrile complications occurred in 4.5% and the infectious complications rate was 2.0%. The positive rate of fever workups was significantly higher in patients with the first POP occurring after postoperative day 3, POP > 102°F, multiple fever spikes, and patients undergoing revision TJA. Multivariate logistic regression revealed that the time of first POP, the maximum temperature, multiple fever spikes, and revision TJA were independent predictors of febrile complications. The estimated cost for 11,319 negative workups in patients with POP was $4,636,976.80, with CXR costing $4,613,182.00. CONCLUSION: Selective workup of POP following TJA should be performed in patients with higher temperatures, fever occurring after postoperative day 3, those with multiple fever spikes, and those undergoing revision TJA. CXR with an extremely low positive rate should not routinely be ordered.

The Relationship between Poverty and Healthcare Seeking among Patients Hospitalized with Acute Febrile Illnesses in Chittagong, Bangladesh.

Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0 °C and symptoms of up to 14 days' duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative's multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)-5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare.

Modelling the Impact and Cost-Effectiveness of Biomarker Tests as Compared with Pathogen-Specific Diagnostics in the Management of Undifferentiated Fever in Remote Tropical Settings.

BACKGROUND: Malaria accounts for a small fraction of febrile cases in increasingly large areas of the malaria endemic world. Point-of-care tests to improve the management of non-malarial fevers appropriate for primary care are few, consisting of either diagnostic tests for specific pathogens or testing for biomarkers of host response that indicate whether antibiotics might be required. The impact and cost-effectiveness of these approaches are relatively unexplored and methods to do so are not well-developed. METHODS: We model the ability of dengue and scrub typhus rapid tests to inform antibiotic treatment, as compared with testing for elevated C-Reactive Protein (CRP), a biomarker of host-inflammation. Using data on causes of fever in rural Laos, we estimate the proportion of outpatients that would be correctly classified as requiring an antibiotic and the likely cost-effectiveness of the approaches. RESULTS: Use of either pathogen-specific test slightly increased the proportion of patients correctly classified as requiring antibiotics. CRP testing was consistently superior to the pathogen-specific tests, despite heterogeneity in causes of fever. All testing strategies are likely to result in higher average costs, but only the scrub typhus and CRP tests are likely to be cost-effective when considering direct health benefits, with median cost per disability adjusted life year averted of approximately $48 USD and $94 USD, respectively. CONCLUSIONS: Testing for viral infections is unlikely to be cost-effective when considering only direct health benefits to patients. Testing for prevalent bacterial pathogens can be cost-effective, having the benefit of informing not only whether treatment is required, but also as to the most appropriate antibiotic; this advantage, however, varies widely in response to heterogeneity in causes of fever. Testing for biomarkers of host inflammation is likely to be consistently cost-effective despite high heterogeneity, and can also offer substantial reductions in over-use of antimicrobials in viral infections.

Cost and Predictors of Care-Seeking Behaviors Among Caregivers of Febrile Children-Uganda, 2009.

Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs--both financial and nonfinancial--remain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary.

Accuracy of commercially available c-reactive protein rapid tests in the context of undifferentiated fevers in rural Laos.

BACKGROUND: C-Reactive Protein (CRP) has been shown to be an accurate biomarker for discriminating bacterial from viral infections in febrile patients in Southeast Asia. Here we investigate the accuracy of existing rapid qualitative and semi-quantitative tests as compared with a quantitative reference test to assess their potential for use in remote tropical settings. METHODS: Blood samples were obtained from consecutive patients recruited to a prospective fever study at three sites in rural Laos. At each site, one of three rapid qualitative or semi-quantitative tests was performed, as well as a corresponding quantitative NycoCard Reader II as a reference test. We estimate the sensitivity and specificity of the three tests against a threshold of 10 mg/L and kappa values for the agreement of the two semi-quantitative tests with the results of the reference test. RESULTS: All three tests showed high sensitivity, specificity and kappa values as compared with the NycoCard Reader II. With a threshold of 10 mg/L the sensitivity of the tests ranged from 87-98 % and the specificity from 91-98 %. The weighted kappa values for the semi-quantitative tests were 0.7 and 0.8. CONCLUSION: The use of CRP rapid tests could offer an inexpensive and effective approach to improve the targeting of antibiotics in remote settings where health facilities are basic and laboratories are absent. This study demonstrates that accurate CRP rapid tests are commercially available; evaluations of their clinical impact and cost-effectiveness at point of care is warranted.

Economic costs of fever to households in the middle belt of Ghana.

BACKGROUND: Malaria is one of the main health problems in the sub-Saharan Africa accounting for approximately 198 million morbidity and close to 600,000 mortality cases. Households incur out-of-pocket expenditure for treatment and lose income as a result of not being able to work or care for family members. The main objective of this survey was to assess the economic cost of treating malaria and/or fever with the new ACT to households in the Kintampo districts of Ghana where a health and demographic surveillance systems (KHDSS) are set up to document population dynamics. METHODS: The study was a cross-sectional survey conducted from October 2009 to July 2011 using community members' accessed using KHDSS population in the Kintampo area. An estimated sample size of 4226 was randomly selected from the active members of the KHDSS. A structured questionnaire was administered to the selected populates who reported of fever within the last 2 weeks prior to the visit. Data was collected on treatment-seeking behaviour, direct and indirect costs of malaria from the patient perspective. RESULTS: Of the 4226 households selected, 947 households with 1222 household members had fever out of which 92 % sought treatment outside home; 55 % of these were females. 31.6 % of these patients sought care from chemical shops. A mean amount of GHS 4.2 (US$2.76) and GHS 18.0 (US$11.84) were incurred by households as direct and indirect cost respectively. On average a household incurred a total cost of GHS 22.2 (US$14.61) per patient per episode. Total economic cost was lowest for those in the highest quintile and highest for those in the middle quintile. CONCLUSION: The total cost of treating fever/malaria episode is relatively high in the study area considering the poverty levels in Ghana. The NHIS has positively influenced health-seeking behaviours and reduced the financial burden of seeking care for those that are insured.

The burden of bacteremia and invasive diseases in children aged less than five years with fever in Italy.

BACKGROUND: Invasive diseases (ID) caused by Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis are a major public health problem worldwide. Comprehensive data on the burden of bacteremia and ID in Italy, including data based on molecular techniques, are needed. METHODS: We conducted a prospective, multi-centre, hospital-based study (GSK study identifier: 111334) to assess the burden of bacteremia and ID among children less than five years old with a fever of 39 °C or greater. Study participation involved a single medical examination, collection of blood for polymerase chain reaction (PCR) and blood culture, and collection of an oropharyngeal swab for colonization analysis by PCR. RESULTS: Between May 2008 and June 2009, 4536 patients were screened, 944 were selected and 920 were enrolled in the study. There were 225 clinical diagnoses of ID, 9.8 % (22) of which were bacteremic. A diagnosis of sepsis was made for 38 cases, 5.3 % (2) of which were bacteremic. Among the 629 non-ID diagnoses, 1.6 % (10) were bacteremic. Among the 34 bacteremic cases, the most common diagnoses were community-acquired pneumonia (15/34), pleural effusion (4/34) and meningitis (4/34). S. pneumoniae was the most frequently detected bacteria among bacteremic cases (29/34) followed by H. influenzae (3/34). Ninety percent (27/30) of bacteremic patients with oropharyngeal swab results were colonized with the studied bacterial pathogens compared to 46.1 % (402/872) of non-bacteremic cases (p < 0.001). PCV7 (7-valent pneumococcal conjugate vaccine) vaccination was reported for 55.9 % (19/34) of bacteremic cases. S. pneumoniae serotypes were non-vaccine serotypes in children who had been vaccinated. Mean duration of hospitalization was longer for bacteremic cases versus non-bacteremic cases (13.6 versus 5.8 days). CONCLUSIONS: These results confirm that S. pneumoniae is one of the pathogens frequently responsible for invasive disease.

The Present and Future of Low-Cost Diagnostics: A new class of portable, easy-to-use products is increasing access to health care around the world, yet challenges remain.

Imagine you?re in a rural health clinic in a Kenyan village. A child comes in with a fever. It could be any one of a number of life-threatening infectious diseases. There?s no refrigeration, no access to sophisticated laboratory equipment, and no highly trained personnel. How do you go about diagnosing and treating this child?