Financial hardship among patients suffering from neglected tropical diseases: A systematic review and meta-analysis of global literature.

INTRODUCTION: Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. METHODS: We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I2 statistic. RESULTS: Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0-11.0%), dengue (12.5%), and lymphatic filariasis (0.0-23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9-99.3%) and visceral leishmaniasis (24.6-91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65-80%, n = 2, I2 = 0.00%). Costs of visceral leishmaniasis impoverished 20-26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare. CONCLUSION: NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors.

A nationwide analysis of the treatment patterns, survival, and medical costs in Korean patients with relapsed or refractory diffuse large B-cell lymphoma.

Background: Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to treatment or experience relapse after initial therapy. Unfortunately, treatment options for older patients and those who experience relapse or become refractory to hematopoietic stem cell transplantation (HSCT) are limited. This nationwide population-based study aimed to identify treatment patterns, survival times, and treatment costs in patients with relapsed/refractory DLBCL (R/R DLBCL). Materials and methods: Between 2011 and 2020, data on patients with R/R DLBCL were retrieved from the Korean Health Insurance Review & Assessment Service, encompassing the entire population. We identified the treatment patterns for each treatment line using a Sankey diagram and calculated the median time to the subsequent treatment in line. Median overall and progression-free survival times were estimated using the Kaplan-Meier survival curves. Finally, the medical costs incurred during DLBCL treatment were calculated for each treatment line and the costs related to HSCT were summarized at the episode level. Results: A total of 864 patients with R/R DLBCL who received second-line treatment were identified, and a regimen of ifosfamide, carboplatin, and etoposide (ICE) was administered the most. Among them, 353 were refractory or relapsed cases that were treated with third-line treatments. The median times for second-line to third-line, third-line to fourth-line, fourth-line to fifth-line, and fifth-line to sixth-line treatment failures gradually decreased (3.93, 2.86, 1.81, and 1.38 months, respectively). The median overall survival time was 8.90 and 4.73 months following the second-line and third-line treatments, respectively. In the third-line treatment setting, the patients did not show a significant difference in survival time after HSCT. The median medical cost was $39,491 across all treatment lines including the cost of HSCT which was $22,054. Conclusion: The treatment patterns in patients with R/R DLBCL, especially at third-line treatments and thereafter, were complicated, and their prognosis was poor despite the high medical costs. Novel and effective treatment options are expected to improve the prognosis and alleviate the economic burden of patients with R/R DLBCL.

Equity-Informative Economic Evaluations of Vaccines: A Systematic Literature Review.

The Immunization Agenda 2030 prioritizes the populations without access to vaccines. Health equity has been increasingly incorporated into economic evaluations of vaccines to foster equitable access. Robust and standardized methods are needed to evaluate the health equity impact of vaccination programs to ensure monitoring and effective addressing of inequities. However, methods currently in place vary and potentially affect the application of findings to inform policy decision-making. We performed a systematic review by searching PubMed, Embase, Econlit, and the CEA Registry up to 15 December 2022 to identify equity-informative economic evaluations of vaccines. Twenty-one studies were included that performed health equity impact analysis to estimate the distributional impact of vaccines, such as deaths averted and financial risk protection, across equity-relevant subgroups. These studies showed that the introduction of vaccines or improved vaccination coverage resulted in fewer deaths and higher financial risk benefits in subpopulations with higher disease burdens and lower vaccination coverage-particularly poorer income groups and those living in rural areas. In conclusion, methods to incorporate equity have been evolving progressively. Vaccination programs can enhance equity if their design and implementation address existing inequities in order to provide equitable vaccination coverage and achieve health equity.

CT-based preoperative risk assessment of prolonged urine leak in patients undergoing partial nephrectomy.

OBJECTIVES: This study aims to evaluate risk factors of prolonged urine leak following partial nephrectomy (PN) to identify objective imaging characteristics on preoperative CT. METHODS: A total of 865 patients who underwent PN and had preoperative CT and postoperative imaging were included. We set a twofold size-matched control group without urine leak, with all tumors located ≤ 4 mm to the collecting system to identify imaging parameters that increase the risk of urine leak other than tumor size and location. Four CT parameters that show the relationship of the tumor and collecting system, namely, curvilinear border length, protruding distance, margin at the interface, and pelvicalyceal contact, were analyzed. Multivariate logistic regression analyses were performed to identify significant predictors of urine leak. The diagnostic performance of the significant parameters was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Fifty-three of 865 patients (6.1%) demonstrated urine leak. Compared with the control group, urine leak group showed longer curvilinear border length, longer protruding distance, frequent non-smooth contact interface, and frequent direct pelvicalyceal contact (p < 0.05 for all). In the multivariate analysis, pelvicalyceal contact was the independent predictor of urine leak (OR = 2.62; 95% C.I 1.02-6.63). Combining four CT parameters, an AUC of 0.70 with a sensitivity of 58.5% and a specificity of 79.2% for identifying urine leak after PN could be obtained. CONCLUSIONS: The four CT features that describe the relationship between the tumor and collecting system might be useful for evaluating the risk of urine leak before PN. KEY POINTS: • Four CT parameters (curvilinear border length, protruding distance, margin at the interface, and pelvicalyceal contact) were significantly associated with postoperative urine leak after partial nephrectomy. • A comprehensive preoperative imaging evaluation of the relationship between the tumor and renal sinus may help in selecting the optimal surgical options and afford better patient counseling of complication risk.

Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data.

BACKGROUND: Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain. METHODS: We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses. RESULTS: Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER. CONCLUSION: We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.

Cost-Effectiveness of Tiotropium in Elderly Patients with Severe Asthma Using Real-World Data.

BACKGROUND: Tiotropium has the potential to alleviate asthmatic symptoms caused by the aging of lungs. However, few studies have focused on specific treatments for elderly patients with asthma. OBJECTIVES: To estimate the cost-effectiveness of adding tiotropium to inhaled corticosteroids and long-acting beta-agonists in elderly patients with severe asthma using real-world data. METHODS: Phase I was a retrospective cohort study using the National Health Insurance claims data to measure clinical and economic outcomes. In phase II, a Markov model was constructed to evaluate cost-effectiveness from Korean health care system perspective, based on phase I, including 2 health states, and an asthma exacerbation event. We estimated cost given in 2018 US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Subgroup analyses for patients with poorly controlled symptoms (frequent short-acting beta-agonist users; frequent exacerbators) were performed. RESULTS: In elderly patients with severe asthma, the incremental cost and effectiveness in the tiotropium group compared with the inhaled corticosteroid and long-acting beta-agonist group were $2281 and 0.038 QALYs, respectively. The incremental cost-effectiveness ratio was $60,074/QALY, indicating that the addition of tiotropium is not a cost-effective alternative. Meanwhile, 2 subgroups with poorly controlled symptoms showed that adding tiotropium is a cost-effective alternative (frequent short-acting beta-agonist users $4078/QALY; frequent exacerbators $8332/QALY). CONCLUSIONS: Tiotropium shows a higher cost-effectiveness profile when applied to elderly patients with uncontrolled symptoms. These results using real-world evidence provide information beyond the clinical outcomes reported by randomized controlled trials, providing a complementary ground in establishing the reimbursement criteria of tiotropium for elderly patients with severe asthma.

Utilization of virtual low-keV monoenergetic images generated using dual-layer spectral detector computed tomography for the assessment of peritoneal seeding from ovarian cancer.

This study aimed to compare the quality of virtual low-keV monoenergetic images vs conventional images reconstructed from dual-layer spectral detector computed tomography (SDCT) for the detection of peritoneal implants of ovarian cancer.Fifty ovarian cancer patients who underwent abdominopelvic SDCT scans were included in this retrospective study. Virtual monoenergetic images at 40 (VMI40) and 50 keV (VMI50), and two conventional images were reconstructed using filtered back projection (FBP) and iterative model reconstruction (IMR) protocols. The mean attenuation of the peritoneal implant, signal-to-noise ratio (SNR), contrast-to-noise ratio relative to ascites (CNRA) and adjacent reference tissues (e.g., bowel wall, hepatic, or splenic parenchyma [CNRB]) were calculated and compared using paired t tests. Qualitative image analysis regarding overall image quality, image noise, image blurring, lesion conspicuity, was performed by two radiologists. A subgroup analysis according to the peritoneal implant region was also conducted.VMI40 yielded significantly higher mean attenuation (183.35) of SNR and CNR values (SNR 11.69, CNRA 7.39, CNRB 2.68), compared to VMI50, IR, and FBP images (P < .001). The mean attenuation (129.65), SNR and CNR values (SNR 9.37, CNRA 5.72, CNRB 2.02) of VMI50 were also significantly higher than those of IR and FBP images (P < .001). In the subgroup analysis, all values were significantly higher on VMI40 regardless of the peritoneal implant region (P < .05). In both readers, overall image quality and image blurring showed highest score in VMI50, while image noise and lesion conspicuity showed best score in IMR and VMI40 respectively. Inter-reader agreements are moderate to almost perfect in every parameter.The low-keV VMIs improved both quantitative assessment and lesion conspicuity of peritoneal implants from ovarian cancer compared to conventional images.

Bioelectrical impedance analysis as a nutritional assessment tool in Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) patients with massive organomegaly suffer from pressure-related complications including malnutrition. In this study, we analyzed the efficacy of segmental bioelectrical impedance analysis (BIA) for objective and quantitative nutritional assessment in ADPKD patients. DESIGN AND METHODS: We conducted a cross-sectional study, to evaluate the clinical utility of segmental BIA for assessing the nutritional status of ADPKD patients. BIA measurements was assessed according to modified subjective global assessment (SGA) scores and were compared with data from a healthy population. The association between BIA measurements and the height adjusted kidney and liver volumes (htTKLV), were analyzed. SUBJECTS: A total of 288 ADPKD patients, aged ≥ 18 years old, were analyzed. MAIN OUTCOME MEASURES: Nutritional status was evaluated with SGA and segmental BIA. The htTKLV were measured in each patients using computed tomonography images. RESULTS: Higher ratios of extracellular water to total body water (ECW/TBW) in the whole-body (ECW/TBWWB), trunk (ECW/TBWTR), and lower extremities (ECW/TBWLE) and lower phase angle of lower extremities (PhALE) correlated with lower SGA scores in the ADPKD population and in both gender. The four parameters, ECW/TBWWB, ECW/TBWTR, and ECW/TBWLE of >0.38 and PhALE of <5.8 θ were associated with malnutrition in ADPKD patients. These correlations were preserved in the subgroup analysis for chronic kidney disease stages 1-3A. Compared to healthy populations' data, body fluid parameters and segmental ECW/TBW values, except for the upper extremities (ECW/TBWUE), were greater in ADPKD patients. Increased htTKLV was an independent risk factor for malnutrition in ADPKD. The highest correlation with htTKLV was observed for the ECW/TBWTR (r = 0.466), followed by ECW/TBWWB (r = 0.407), ECW/TBWLE (r = 0.385), PhALE (r = -0.279), and PhATR (r = 0.215). CONCLUSIONS: These results demonstrated that segmental BIA parameters of ECW/TBWWB, ECW/TBWTR, ECW/TBWLE and PhALE provide useful information on nutritional status including the impact of organomegaly in ADPKD.

Intravoxel incoherent motion MRI-derived parameters and T2* relaxation time for noninvasive assessment of renal fibrosis: An experimental study in a rabbit model of unilateral ureter obstruction.

PURPOSE: To evaluate the association of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) MRI-derived parameters, and T2* relaxation time with histopathological changes observed during renal fibrogenesis in a rabbit model of unilateral ureter obstruction (UUO). METHODS: Twenty New Zealand White rabbits underwent baseline MRI followed by surgery (sham or UUO) and then follow-up MRI at postoperative day (POD) 0, 3, 7, and 14. Hematoxylin and eosin and Masson's trichrome staining was performed to evaluate cell density and area of fibrosis. Spearman rank correlation and Pearson correlation tests and one-way analysis of variance were used for statistical analyses. RESULTS: There was a continuous increase in the area of fibrosis and cell density: rho = 0.900 (95% confidence interval [CI] = 0.760, 0.960; p < 0.0001) and 0.904 (95% CI = 0.769, 0.962; p < 0.0001), respectively. There was a tendency for all MRI variables to decrease at POD 3 and partly recover at POD 7. ADC, D, f, and T2* relaxation time showed significant correlation with area of fibrosis and cell density (r = -0.5177 and -0.6962, -0.5395 and -0.7851, -0.7168 and -0.7902, and -0.6808 and -0.7212, respectively; p = 0.0052-0.0481) while D* did not (p = 0.1997 and 0.7853, respectively). CONCLUSIONS: ADC, IVIM MRI-derived parameters, and T2* relaxation time were significantly associated with the area of fibrosis and cell density during renal fibrogenesis in a rabbit model of UUO. After validation in future studies, MRI may have potential for noninvasive assessment modality of renal fibrosis.

Assessment of deep myometrial invasion of endometrial cancer on MRI: added value of second-opinion interpretations by radiologists subspecialized in gynaecologic oncology.

OBJECTIVE: To investigate the added value of secondary reports issued by radiologists subspecializing in gynaecologic imaging for determining deep myometrial invasion of endometrial cancer on MRI. METHODS: Initial (from referring institutions) and secondary (by subspecialized radiologists) interpretations of MRI of 55 patients with endometrial cancer were retrospectively reviewed. A radiologist blinded to clinicopathological information assessed both reports for the presence of deep myometrial invasion. Reference standard was based on hysterectomy specimens. Kappa coefficients (k) were used to measure their concordance. McNemar testing and receiver operating characteristic (ROC) analysis was used to compare sensitivities, specificities and areas under the curves (AUCs). RESULTS: Deep myometrial invasion was present in 25 (45.5 %) patients. Among 27.3 % (15/55; k = 0.458) patients with discrepant results, secondary interpretations were correct in 10 (66.7 %) cases. Sensitivity was higher in secondary than in initial reports (76.0 % vs. 48.0 %, p = 0.039) while no significant difference was seen in specificity (70.0 % vs. 76.7 %, p = 0.668). At ROC analysis, there was a tendency for higher AUCs in secondary reports (0.785 vs 0.669, p = 0.096). CONCLUSION: Secondary readings of MRI by subspecialized gynaecologic oncologic radiologists may provide incremental value in determining deep myometrial invasion of endometrial cancer. KEY POINTS: • Deep myometrial invasion is an important prognostic factor in endometrial cancer. • Assessment of deep myometrial invasion is often discrepant between initial and secondary reports. • Secondary reports showed higher sensitivity and accuracy. • Secondary review of MRI may provide incremental value in endometrial cancer patients.

Shear wave elastography assessment in the prostate: an intraobserver reproducibility study.

PURPOSE: To assess the intraobserver reproducibility of shear wave elastography (SWE) in the prostate. MATERIALS AND METHODS: This study was institutional review board approved with waiver of informed consent. Eighty men (mean age, 66.2±9.2years) with suspected prostate cancer underwent SWE. Young modulus (kPa) was measured at 24 locations in the prostate (superficial and deep locations in paramedian and lateral aspects at the base, mid-gland, and apex levels). The intraobserver reproducibility of two repeated measurements was determined using intraclass correlation coefficients (ICC) and was compared among measurement location, prostate volume, age, and prostate-specific antigen level. RESULTS: The overall intraobserver reproducibility was excellent (ICC=0.876). In addition, intraobserver reproducibility was excellent for all specified subgroups according to location, prostate volume, and clinical variables (ICC=0.826-0.917). With regard to location, SWE measurements showed substantially higher ICC values in the mid-gland than in the base and apex, in the paramedian prostate than in the lateral prostate, and in superficial locations than in deeper locations. No substantial differences in ICC values were observed according to the prostate volume and clinical variables. CONCLUSION: Intraobserver reproducibility of SWE measurements in the prostate gland was excellent. There was variability in the intraobserver reproducibility according to location within the prostate, and the operator should be aware of this and take extra caution when performing SWE in these areas.

First-trimester screening for Down syndrome; the role of nasal bone assessment in the Korean population.

OBJECTIVES: The aim of this study was to evaluate the role of nasal bone assessment in first-trimester screening for Down syndrome (DS) in the Korean population. METHODS: From July 2004 to March 2006, we prospectively evaluated the fetal nasal bones at 11-14 weeks' gestation in the Korean population. RESULTS: A successful evaluation was possible in 6490 of 6787 fetuses (95.6%). Absent, hypoechoic, and short nasal bones were seen in 4 (26.7%), 4 (26.7%), and 1 (6.7%) of 15 fetuses with DS, respectively, whereas in 5 (0.1%), 11 (0.2%), and 246 (3.8%) of 6456 normal fetuses. The incidence of absent and hypoechoic nasal bone showed significant differences between normal fetuses and fetuses with DS (P < 0.0005, both). Screening for DS using an absent or hypoechoic nasal bone resulted in a sensitivity of 53.3%, a specificity of 99.8%, a positive likelihood ratio of 215.2, and a negative likelihood ratio of 0.5. CONCLUSION: Our study showed that nasal bone abnormality at 11-14 weeks of gestation had a high association with DS in the Korean population. This suggests that nasal bone assessment can be used to supplement the current first-trimester screening for DS in the Korean population.

Quantitative assessment of fetal bowel echogenicity: comparison of harmonic, compound, and fundamental sonographic images.

PURPOSE: The aims of this study were to assess normal fetal bowel echogenicity quantitatively and to compare the levels of bowel echogenicity observed with the use of 3 different sonographic image-processing techniques-harmonic plus compound imaging, harmonic imaging alone, and fundamental imaging-and 2 different broadband transducers. METHODS: Women with normal singleton second-trimester fetuses underwent sonographic scanning with both a 2-5-MHz and a 4-7-MHz transducer. The use of the 3 imaging techniques and the 2 transducers resulted in 6 types of images: 2-5-HC (harmonic plus compound images), 2-5-H (harmonic images), and 2-5-F (fundamental images), and 4-7-HC, 4-7-H, and 4-7-F images. The relative echogenicities (brightness) of the fetal bowel and iliac bone were measured, and bowel echogenicity ratios (bowel echogenicity/iliac bone echogenicity x 100) were calculated using graphics software. The resulting data were analyzed to evaluate differences in echogenicity ratios between the 6 types of images. RESULTS: We examined 37 fetuses during the study period. The bowel echogenicity ratios were highest on the images obtained with harmonic and compound-imaging techniques (2-5-HC, 84.7 +/- 23.4%; 4-7-HC, 98.5 +/- 36.4%). The bowel echogenicity ratio for the 2-5-HC images was significantly higher than those for the 2-5-H and the 2-5-F images (p < 0.01 and p < 0.001, respectively), and those for the 4-7-HC and 4-7-H images were higher than that for the 4-7-F images (p < 0.01 for both comparisons). CONCLUSIONS: A sonographic finding of echogenic fetal bowel should be interpreted cautiously because the use of special image-processing techniques can artificially enhance the apparent level of echogenicity of the bowel. We recommend rescanning without the use of those techniques if the fetal bowel appears to have an increased level of echogenicity.