Financial hardship associated with catastrophic out-of-pocket spending tied to primary care services in low- and lower-middle-income countries: findings from a modeling study.

BACKGROUND: Financial risk protection (FRP) is a key component of universal health coverage (UHC): all individuals must be able to obtain the health services they need without experiencing financial hardship. In many low-income and lower-middle-income countries, however, the health system fails to provide sufficient protection against high out-of-pocket (OOP) spending on health services. In 2018, OOP health spending comprised approximately 40% of current health expenditures in low-income and lower-middle-income countries. METHODS: We model the household risk of catastrophic health expenditures (CHE), conditional on having a given disease or condition-defined as OOP health spending that exceeds a threshold percentage (10, 25, or 40%) of annual income-for 29 health services across 13 disease categories (e.g., diarrheal diseases, cardiovascular diseases) in 34 low-income and lower-middle-income countries. Health services were included in the analysis if delivered at the primary care level and part of the Disease Control Priorities, 3rd edition "highest priority package." Data were compiled from several publicly available sources, including national health accounts, household surveys, and the published literature. A risk of CHE, conditional on having disease, was modeled as depending on usage, captured through utilization indicators; affordability, captured via the level of public financing and OOP health service unit costs; and income. RESULTS: Across all countries, diseases, and health services, the risk of CHE (conditional on having a disease) would be concentrated among poorer quintiles (6.8% risk in quintile 1 vs. 1.3% in quintile 5 using a 10% CHE threshold). The risk of CHE would be higher for a few disease areas, including cardiovascular disease and mental/behavioral disorders (7.8% and 9.8% using a 10% CHE threshold), while lower risks of CHE were observed for lower cost services. CONCLUSIONS: Insufficient FRP stands as a major barrier to achieving UHC, and risk of CHE is a major problem for health systems in low-income and lower-middle-income countries. Beyond its threat to the financial stability of households, CHE may also lead to worse health outcomes, especially among the poorest for whom both ill health and financial risk are most severe. Modeling the risk of CHE associated with specific disease areas and services can help policymakers set progressive health sector priorities. Decision-makers could explicitly include FRP as a criterion for consideration when assessing the health interventions for inclusion in national essential benefit packages.

Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients.

BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.

3.6 mW Active-Electrode ECG/ETI Sensor System Using Wideband Low-Noise Instrumentation Amplifier and High Impedance Balanced Current Driver.

An active electrode (AE) and back-end (BE) integrated system for enhanced electrocardiogram (ECG)/electrode-tissue impedance (ETI) measurement is proposed. The AE consists of a balanced current driver and a preamplifier. To increase the output impedance, the current driver uses a matched current source and sink, which operates under negative feedback. To increase the linear input range, a new source degeneration method is proposed. The preamplifier is realized using a capacitively-coupled instrumentation amplifier (CCIA) with a ripple-reduction loop (RRL). Compared to the traditional Miller compensation, active frequency feedback compensation (AFFC) achieves bandwidth extension using the reduced size of the compensation capacitor. The BE performs three types of signal sensing: ECG, band power (BP), and impedance (IMP) data. The BP channel is used to detect the Q-, R-, and S-wave (QRS) complex in the ECG signal. The IMP channel measures the resistance and reactance of the electrode-tissue. The integrated circuits for the ECG/ETI system are realized in the 180 nm CMOS process and occupy a 1.26 mm2 area. The measured results show that the current driver supplies a relatively high current (>600 µApp) and achieves a high output impedance (1 MΩ at 500 kHz). The ETI system can detect resistance and capacitance in the ranges of 10 mΩ-3 kΩ and 100 nF-100 µF, respectively. The ECG/ETI system consumes 3.6 mW using a single 1.8 V supply.

A Compact and Efficient Boost Converter in a 28 nm CMOS with 90 mV Self-Startup and Maximum Output Voltage Tracking ZCS for Thermoelectric Energy Harvesting.

There are increasing demands for the Internet of Things (IoT), wearable electronics, and medical implants. Wearable devices provide various important daily applications by monitoring real-life human activities. They demand low-cost autonomous operation in a miniaturized form factor, which is challenging to realize using a rechargeable battery. One promising energy source is thermoelectric generators (TEGs), considered the only way to generate a small amount of electric power for the autonomous operation of wearable devices. In this work, we propose a compact and efficient converter system for energy harvesting from TEGs. The system consists of an 83.7% efficient boost converter and a 90 mV self-startup, sharing a single inductor. Innovated techniques are applied to adaptive maximum power point tracking (A-MPPT) and indirect zero current switching (I-ZCS) controllers for efficient operation. The startup circuit is realized using a gain-boosted tri-state buffer, which achieves 69.8% improved gain at the input VIN = 200 mV compared to the conventional approach. To extract the maximum power, we use an A-MPPT controller based on a simple capacitive divider, achieving 95.2% tracking efficiency. To address the challenge of realizing accurate voltage or current sensors, we propose an I-ZCS controller based on a new concept of maximum output voltage tracking (MOVT). The integrated circuit (IC) is fabricated using a 28 nm CMOS in a compact chip area of 0.03 mm2. The compact size, which has not been obtained with previous designs, is suitable for wearable device applications. Measured results show successful startup operation at an ultralow input, VIN = 90 mV. A peak conversion efficiency of 85.9% is achieved for the output of 1.07 mW.

An 11.8-fJ/Conversion-Step Noise Shaping SAR ADC with Embedded Passive Gain for Energy-Efficient IoT Sensors.

Herein, we present a noise shaping successive-approximation-register (SAR) analog-to-digital converter (ADC) with an embedded passive gain multiplication technique. The noise shaping moves the in-band quantization noise from the signal band to out-of-band for improved signal-to-noise ratio (SNR). The proposed approach tackles the drawback of the previous active noise shaping (increased power and extra noise) and passive noise shaping (limited noise suppression and signal loss). Both noise shaping and gain multiplication are realized on-chip in an energy-efficient manner without an opamp. This approach uses only capacitors and switches in the finite impulse response (FIR) and infinite impulse response (IIR) filters. A comparator suppressing kickback noise is presented to handle the tradeoff between noise suppression and the filter capacitor size. The energy-efficient merged-capacitor switching (MCS) technique is effectively combined with rail-to-rail swing comparator and thermometer-coded capacitor array, which reduces the settling error in the digital to analog converter (DAC). The process-induced mismatch effect in the capacitive DAC is investigated using a behavioral model of the ADC. Additionally, we propose dynamic element matching (DEM) for the thermometer-coded capacitor array. The ADC is fabricated using a 0.18 µm CMOS process in an area of 0.26 mm2. Consuming 4.1 µW, the ADC achieves a signal-to-noise and distortion ratio (SNDR) of 66.5 dB and a spurious-free dynamic range (SFDR) of 79.1 dB. The figure-of-merit (FoM) of the ADC is 11.8 fJ/conversion-step.

A 12-b Subranging SAR ADC Using Detect-and-Skip Switching and Mismatch Calibration for Biopotential Sensing Applications.

This paper presents a 12-b successive approximation register (SAR) analog-to-digital converter (ADC) for biopotential sensing applications. To reduce the digital-to-analog converter (DAC) switching energy of the high-resolution ADC, we combine merged-capacitor-switching (MCS) and detect-and-skip (DAS) methods, successfully embedded in the subranging structure. The proposed method saves 96.7% of switching energy compared to the conventional method. Without an extra burden on the realization of the calibration circuit, we achieve mismatch calibration by reusing the on-chip DAC. The mismatch data are processed in the digital domain to compensate for the nonlinearity caused by the DAC mismatch. The ADC is realized using a 0.18 µm CMOS process with a core area of 0.7 mm2. At the sampling rate fS = 9 kS/s, the ADC achieves a signal-to-noise ratio and distortion (SINAD) of 67.4 dB. The proposed calibration technique improves the spurious-free dynamic range (SFDR) by 7.2 dB, resulting in 73.5 dB. At an increased fS = 200 kS/s, the ADC achieves a SINAD of 65.9 dB and an SFDR of 68.8 dB with a figure-of-merit (FoM) of 13.2 fJ/conversion-step.

Positive Role of Delta Neutrophil Index (DNI) as a Prodiagnostic Marker in Cecal Ligation and Puncture (CLP)-Induced Sepsis Murine Model.

Sepsis is an emergent infectious disease and a leading cause of death despite immediate intervention. While Delta neutrophil index (DNI) and myeloperoxidase (MPO) are known as a prodiagnostic marker of sepsis, the preclinical evidence of the best marker of sepsis is unclear. For this, using a well-designed cecal ligation and puncture (CLP)-induced sepsis mouse model, we comparatively measured the level and cost-effectiveness of sepsis biomarkers such as DNI, myeloperoxidase (MPO), procalcitonin (PCT), and tumor necrosis factor-alpha (TNF-α). First, we found that the optimal time point for early detection is at 6 h, 24 h post-CLP. Strikingly, the peak level and fold change of DNI was revealed at 24 h, further showing the best fold change as compared with other biomarker levels. Given the fold change at 6, 24 h, PCT was next to DNI. Third, a cost-effectiveness survey showed that DNI was the best, with PCT next. Further, DNI level was moderate positively associated with PCT (ρ = 0.697, p = 0.012) and TNF-α (ρ = 0.599, p = 0.040). Collectively, these data indicate that DNI in CLP-induced sepsis mice is as effective as the existent inflammatory biomarkers such as MPO, PCT and TNF-α to predict the prognosis of sepsis. This might have clinically important implications that DNI is cost effective, thus quickly and rationally applying to diverse types of imminent sepsis regardless of species. This might be the first report on the validity of DNI in preclinical CLP-induced murine sepsis.

Association between depression and antibiotic use: analysis of population-based National Health Insurance claims data.

BACKGROUND: Frequent exposure to antibiotic treatments may increase the risk of antibiotic resistance, which may threaten the effectiveness of future antibiotic treatments. Thus, it is important to identify the preventable risks in terms of antibiotic use. This study assessed the association between major depressive disorder (MDD) and antibiotic use by comparing the likelihood and extent of antibiotic use between patients with and without MDD. METHODS: This retrospective cross-sectional study utilized the National Patients Sample data from the 2017 Health Insurance Review and Assessment Service. We analyzed 16,950 patients with MDD, defined as those with at least two claims records stating a primary diagnosis of MDD (International Classification of Diseases, 10th revision codes F32-33) and 67,800 patients without MDD (1:4 propensity-score matched control group). Antibiotic use was compared between the patients with and without MDD based on three variables: the presence of antibiotic prescriptions, total prescription days of antibiotics per year, and total medication costs of antibiotics per year. RESULTS: The adjusted odds ratio obtained by multivariate regression analysis for the presence of prescription of antibiotics was 1.31 (95% confidence interval [CI]: 1.25-1.36). In the negative binomial model, the number of prescription days was 1.25 times (95% CI: 1.23-1.28) higher in patients with MDD than in those without MDD. Generalized linear model analysis showed a 1.39-fold (95% CI: 1.36-1.43) higher cost of antibiotic prescription in patients with MDD than in those without MDD. CONCLUSIONS: Our results suggest a potential association between MDD and the prescription of antibiotics, implying that patients with MDD are relatively vulnerable to infections. It is important to prevent as well as closely monitor the occurrence of infections when managing patients with MDD.

Analyzing factors associated with decisional stage of adopting breast cancer screening among Korean American women using precaution adoption process model.

Background: Korean American (KA) women have experienced higher prevalence and lower survival rates of breast cancer (BC) than other ethnic groups in the United States. However, BC screening rates for KA women remain significantly lower than the national target (81.1%) specified by Healthy People 2020. Few studies have explained how the decision to adopt BC screening occurs and progresses and what factors contribute to this decision among KA women. This study used Weinstein's Precaution Adoption Process Model (PAPM) as a theoretical framework to examine characteristics and factors associated with the decisional stage of mammography adoption.Methods: A cross-sectional self-report survey was administered among KA women (N = 308) ages 50-80 from the Atlanta metropolitan area. A total of 281 KA women completed the survey, answering questions about socio-demographics, health-related information, mammography history, doctor recommendation, BC screening knowledge, self-efficacy for BC screening, decisional balance scores on attitudes and beliefs pertaining to mammography, and the seven-stage PAPM.Results: KA women reported a low rate of mammography uptake with about 24% and 35% of the participants undergoing mammography within the last year and two years, respectively. KA women in stages 5 (decided yes), 6 (action), and 7 (maintenance) were likely to have increased screening-related knowledge, positive decisional balance, and regular medical check-up compared to those in stages 1 (unaware), 2 (unengaged), and 3 (deciding).Conclusion: This study highlights important factors that could potentially facilitate BC screening among KA women in Georgia. The findings also provide implications for interventions and practice for increasing mammography screening among medically underserved populations.

Role of Health Literacy in Health-Related Information-Seeking Behavior Online: Cross-sectional Study.

BACKGROUND: The internet has emerged as a main venue of health information delivery and health-related activities. However, few studies have examined how health literacy determines online health-related behavior. OBJECTIVE: The aim of this study was to investigate the current level of health-related information-seeking using the internet and how health literacy, access to technology, and sociodemographic characteristics impact health-related information-seeking behavior. METHODS: We conducted a cross-sectional study through a survey with Minnesotan adults (N=614) to examine their health literacy, access to technology, and health-related information-seeking internet use. We used multivariate regression analysis to assess the relationship between health-related information-seeking on the internet and health literacy and access to technology, controlling for sociodemographic characteristics. RESULTS: Better health literacy (ß=.35, SE 0.12) and greater access to technological devices (eg, mobile phone and computer or tablet PC; ß=.06, SE 0.19) were both associated with more health-related information-seeking behavior on the internet after adjusting for all other sociodemographic characteristics. Possession of a graduate degree (ß=.28, SE 0.07), female gender (ß=.15, SE 0.05), poor health (ß=.22, SE 0.06), participation in social groups (ß=.13, SE 0.05), and having an annual health exam (ß=.35, SE 0.12) were all associated with online health-related information-seeking. CONCLUSIONS: Our findings indicate that access to online health-related information is not uniformly distributed throughout the population, which may exacerbate disparities in health and health care. Research, policy, and practice attention are needed to address the disparities in access to health information as well as to ensure the quality of the information and improve health literacy.

Poor prognosis in patients with diffuse large B cell lymphomas with bone marrow involvement possessing chromosomal abnormalities, despite aggressive treatment.

In 27% of diffuse large B cell lymphoma (DLBCL) cases, bone marrow (BM), assessed by BM biopsy, is involved. BM involvement, an extranodal site involvement, affects the International Prognostic Index (IPI) score adversely. However, chromosomal abnormalities are neither included as a prognostic factor nor are they considered in the IPI risk classification category. We retrospectively analyzed 600 DLBCL patients at diagnosis for BM involvement (by both BM biopsy immunohistochemistry [BMI] with karyotyping and 18-fluorodeoxyglucose-positron emission tomography [FDG-PET] high uptake [BMP]). The BM-involved DLBCL patients identified by both BMI and BMP showed significantly inferior survival outcomes. Chromosomal abnormalities, especially complex karyotype (CK) of the involved BM, are related to much worse survival outcomes due to the inadequate treatment response including frontline auto-hematopoietic stem cell transplantation (HSCT). Therefore, CK population should either be considered for more aggressive treatment modalities, such as frontline allo-HSCT, or those further clinical trials are explored for alternative or novel treatment approaches. Furthermore, if the FDG-PET shows high possibility of marrow involvement, bilateral BM biopsy with cytogenetic evaluation should be incorporated into the routine workup for newly diagnosed DLBCL patients. This is to look for other markers of poor-risk factors, such as CK or further genetic mutations.

Non-myeloablative matched sibling stem cell transplantation with the optional reinforced stem cell infusion for patients with hemoglobinopathies.

BACKGROUND: The NIH protocol for non-myeloablative (NMA) conditioning allogeneic stem cell transplantation (alloSCT) with alemtuzumab and low-dose total body irradiation corrected the abnormal sickle cell disease (SCD) phenotype without the risk of graft-versus-host disease. However, alloSCT using NMA conditioning had been rarely applied to ß-thalassemia major (ß-TM) patients. METHODS: To avoid prolonged immunosuppression, we developed a two-stage strategy. Mixed donor chimerism was initially achieved using the protocol developed by the NIH protocol. Thereafter, we facilitated donor chimerism using the optional reinforced stem cell (SC) infusion in cases requiring protracted immunosuppression or experiencing impending graft failure. RESULTS: In this study, ß-TM (n = 9) and SCD (n = 4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four ß-TM, achieved stable mixed chimerism without receiving optional reinforced SC infusion. All patients that received optional reinforced infusion achieved complete (n = 4) or mixed chimerism (n = 1). The overall survival rate and event-free survival at 4 years were 91.7% (95% CI; 53.9-98.8) in both groups, with a thalassemia-free survival rate in ß-TM patients of 87.5% (95% CI; 38.7-98.1). CONCLUSION: This study is the first to report successful NMA conditioning alloSCT to achieve stable mixed chimerism correcting the abnormal hemoglobin phenotype in adult ß-TM patients.

Role of pretransplant anti-thymocyte globulin in matched sibling donor stem cell transplantation after reduced intensity conditioning for myelodysplastic syndrome.

OBJECTIVE: We investigated the role of anti-thymocyte globulin (ATG; Thymoglobulin) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) after reduced intensity conditioning (RIC) in myelodysplastic syndrome (MDS). METHODS: Forty-seven patients with 10 mg/kg ATG (ATG group; median age 53 years) and 33 without ATG (no-ATG group; median age 43, P < .0001) were compared. RESULTS: Median time to engraftment was similar. Two-year cumulative incidence of moderate-to-severe chronic graft-versus-host disease (GVHD) was significantly lower in the ATG group (15% vs 55%, P < .0001), while that of acute GVHD was similar compared with the no-ATG group. After a median follow-up of 60 months (range, 14-184), the 3-year cumulative incidences of non-relapse mortality and relapse were 9% and 21% for ATG group and 15% and 19% for no-ATG group (P = .408 and P = .717), respectively, leading to a significantly better 3-year GVHD-free and relapse-free survival (GRFS) in the ATG group (55% vs 19%, P = .006): The 3-year overall and disease-free survival were similar. Infectious complication occurred with similar frequencies in both groups. CONCLUSION: These findings suggest that ATG can be safely used to decrease moderate-to-severe chronic GVHD with improved GRFS for patients with MDS receiving MSD-HSCT in RIC setting.

A 0.6-µW Chopper Amplifier Using a Noise-Efficient DC Servo Loop and Squeezed-Inverter Stage for Power-Efficient Biopotential Sensing.

To realize an ultra-low-power and low-noise instrumentation amplifier (IA) for neural and biopotential signal sensing, we investigate two design techniques. The first technique uses a noise-efficient DC servo loop (DSL), which has been shown to be a high noise contributor. The proposed approach offers several advantages: (i) both the electrode offset and the input offset are rejected, (ii) a large capacitor is not needed in the DSL, (iii) by removing the charge dividing effect, the input-referred noise (IRN) is reduced, (iv) the noise from the DSL is further reduced by the gain of the first stage and by the transconductance ratio, and (v) the proposed DSL allows interfacing with a squeezed-inverter (SQI) stage. The proposed technique reduces the noise from the DSL to 12.5% of the overall noise. The second technique is to optimize noise performance using an SQI stage. Because the SQI stage is biased at a saturation limit of 2VDSAT, the bias current can be increased to reduce noise while maintaining low power consumption. The challenge of handling the mismatch in the SQI stage is addressed using a shared common-mode feedback (CMFB) loop, which achieves a common-mode rejection ratio (CMRR) of 105 dB. Using the proposed technique, a capacitively-coupled chopper instrumentation amplifier (CCIA) was fabricated using a 0.18-µm CMOS process. The measured result of the CCIA shows a relatively low noise density of 88 nV/rtHz and an integrated noise of 1.5 µVrms. These results correspond to a favorable noise efficiency factor (NEF) of 5.9 and a power efficiency factor (PEF) of 11.4.

WT1 Measurable Residual Disease Assay in Patients With Acute Myeloid Leukemia Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation: Optimal Time Points, Thresholds, and Candidates.

The absence of relevant guidelines for Wilms tumor 1 (WT1) gene quantification as a measurable residual disease (MRD) assessment for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has limited the widespread use in practice. We investigated optimal time points, thresholds, and candidates for the bone marrow WT1 MRD assay in 425 consecutive patients with AML who underwent allo-HSCT. WT1 expression kinetics before allo-HSCT and at 1 or 3 months after allo-HSCT were determined by real-time PCR using the European LeukemiaNet (ELN) normalized method. Relapsed patients had significantly higher WT1 levels before allo-HSCT and at 3 months after allo-HSCT. The best time point for the WT1 MRD assay was before allo-HSCT by the receiver operating characteristic curve. Among various thresholds, 250 copies recommended from ELN researchers were mostly predictive of post-transplant relapse. In multivariate analysis, WT1 MRD positivity independently predicted relapse, resulting in inferior survival. In subgroup analyses, pretransplant WT1 MRD positivity was predictive of post-transplant relapse in the intermediate group, whereas WT1 MRD positivity occurred at 3 months after allo-HSCT in favorable and adverse risk groups. Among MRD-positive patients before allo-HSCT, all patients who were MRD positive at 3 months relapsed within 6 months. The WT1 MRD assay before allo-HSCT or 3 months after allo-HSCT is useful for predicting post-transplant relapse with a different significance in each risk group by time points, showing the benefit of multiple tests over time. Such monitoring is particularly available in patients with AML without specific molecular targets.

Analyzing factors enabling colorectal cancer screening adherence in Korean Americans using the Andersen's Behavioral Model of Health Services Utilization.

Purpose/objectives: Korean Americans (KAs) report suboptimal colorectal cancer (CRC) screening adherence. This study investigated factors that enable KAs to adhere to CRC screening guidelines using the Andersen's Behavioral Model of Health Services Utilization. Design: Cross-sectional survey using self-reported measures of CRC screening behaviors. Sample and methods: Purposive sampling was used to recruit 433 KAs aged 50-75 from the Atlanta metropolitan area who completed questionnaires measuring predisposing (i.e., gender, age, marital status, and educational attainment), enabling (income, health insurance, regular annual health checkups, doctor's recommendation English proficiency, CRC knowledge, self-efficacy for CRC screening, and decisional balance in CRC screening), and need (family cancer history and self-reported health status) factors associated with CRC screening. Findings: A multiple logistic regression model including all 14 predictor variables revealed that several enabling factors (i.e., income, regular annual health checkups, doctor's recommendation, self-efficacy, and decisional balance) independently predicted increased CRC screening adherence in KAs. No predisposing or need factors independently predicted CRC screening. Conclusions and implications for psychosocial providers or policy: To increase CRC screening adherence among KAs, psychosocial interventions should target on improving their self-efficacy and decisional balance regarding CRC screening, while policy interventions should focus on promoting health providers' CRC screening recommendations during routine health checkups.

Comparison of transplant-specific prognostic scoring systems in haploidentical transplantation for myelodysplastic syndrome.

OBJECTIVES: We intended to identify the predictive abilities of recently published transplant-specific prognostic scoring systems in patients with myelodysplastic syndrome (MDS) receiving haploidentical transplantation. METHODS: The outcomes of 73 patients with MDS receiving haploidentical transplantation were analyzed, according to the MTPSS, the TRI, and the CIBMTR scoring systems. RESULTS: The median age of patients at transplantation was 50 (range, 19-69) years. The IPSS-R cytogenetic risks of very good/good, intermediate, and poor/very poor were, respectively, observed in 35 (48.0%), 25 (34.2%), and 13 (17.8%) patients, including 4 (5.5%) with a monosomal karyotype. Pretransplant treatment failure and high (≥3) HCT-CI were observed in 30 (41.1%) and 35 (48.0%) patients, respectively. With survivor's median follow-up of 42.3 months, the overall survival rate at 4 years of all patients was 65.5% (95% CI, 52.4-75.9). The MTPSS (100%, 77.3%, 62.5%, and 42.0% at 4 years; P = .02) and the TRI (100%, 79.9%, 76.0%, and 17.1% at 4 years; P < .01) differentiate proportionally overall survival rates according to their 4 risk groups, whereas the CIBMTR scoring system did not (P = .17). CONCLUSIONS: Our results suggest the potential ability of the MPTSS and the TRI as prognostic tools for patients with MDS receiving haploidentical transplantation.

Risk factors and clinical outcomes of breakthrough yeast bloodstream infections in patients with hematological malignancies in the era of newer antifungal agents.

Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls (P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.

A Cyclic Vernier Two-Step TDC for High Input Range Time-of-Flight Sensor Using Startup Time Correction Technique.

Herein, we present a low-power cyclic Vernier two-step time-to-digital converter (TDC) that achieves a wide input range with good linearity. Since traditional approaches require a large area or high power to achieve an input range >300 ns, we solve this problem by proposing a simple yet efficient TDC suitable for time-of-flight (TOF) sensors. In previous studies using the cyclic structure, the effect of startup time on the linearity of the TDC is not described. Thus, the achievable linearity has been limited when the TDC is used for applications requiring a high input range. We solve this problem by using a simple yet effective technique to compensate. The proposed technique is realized using (1) digitally-controlled oscillators (DCOs) that have dual frequency control and matched startup time; (2) an alignment detector that performs startup time correction by proper timing control; and (3) a fully symmetric arbiter that precisely detects the instant of edge alignment. To achieve a fine resolution for the cyclic Vernier TDC, we design two closely-matched DCOs with dual frequency control. The alignment detector performs the critical task of cancelling startup time via timing control. The detector is delay-compensated by using a dummy to provide matched loading for the two DCOs. To enhance the detection speed under low power, a current-reuse approach is employed for the arbiter. The TDC is fabricated using a 0.18 µm complementary metal⁻oxide⁻semiconductor (CMOS) process in a compact chip area of 0.028 mm². Measured results show a dynamic range of 355 ns and a resolution of 377 ps. When the result is applied for TOF sensing, it corresponds to a distance range of 53.2 m and a resolution of 5.65 cm. Over a relatively large input range, good linearity is achieved, which is indicated by a DNL of 0.28 LSBrms and an INL of 0.96 LSBrms. The result corresponds to root mean square (RMS) error distance of 5.42 cm. The result is achieved by consuming a relatively low power of 0.65 mW.

A 1.15 µW 200 kS/s 10-b Monotonic SAR ADC Using Dual On-Chip Calibrations and Accuracy Enhancement Techniques.

Herein, we present an energy efficient successive-approximation-register (SAR) analog-to-digital converter (ADC) featuring on-chip dual calibration and various accuracy-enhancement techniques. The dual calibration technique is realized in an energy and area-efficient manner for comparator offset calibration (COC) and digital-to-analog converter (DAC) capacitor mismatch calibration. The calibration of common-mode (CM) dependent comparator offset is performed without using separate circuit blocks by reusing the DAC for generating calibration signals. The calibration of the DAC mismatch is efficiently performed by reusing the comparator for delay-based mismatch detection. For accuracy enhancement, we propose new circuit techniques for a comparator, a sampling switch, and a DAC capacitor. An improved dynamic latched comparator is proposed with kick-back suppression and CM dependent offset calibration. An accuracy-enhanced bootstrap sampling switch suppresses the leakage-induced error <180 µV and the sampling error <150 µV. The energy-efficient monotonic switching technique is effectively combined with thermometer coding, which reduces the settling error in the DAC. The ADC is realized using a 0.18 µm complementary metal⁻oxide⁻semiconductor (CMOS) process in an area of 0.28 mm². At the sampling rate fS = 9 kS/s, the proposed ADC achieves a signal-to-noise and distortion ratio (SNDR) of 55.5 dB and a spurious-free dynamic range (SFDR) of 70.6 dB. The proposed dual calibration technique improves the SFDR by 12.7 dB. Consuming 1.15 µW at fS = 200 kS/s, the ADC achieves an SNDR of 55.9 dB and an SFDR of 60.3 dB with a figure-of-merit of 11.4 fJ/conversion-step.