Outcomes of long-term von Willebrand factor prophylaxis use in von Willebrand disease: A systematic literature review.

BACKGROUND: Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long-term prophylaxis. AIM: Systematically summarize the evidence on the clinical outcomes of secondary long-term prophylaxis in patients with VWD and severe recurrent bleedings. METHODS: We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long-term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non-Randomized Studies of interventions (ROBINS-I) tool to assess the quality of the included studies. We conducted random-effects meta-analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR], .24; 95% confidence interval [CI], .17-.35; low certainty evidence), and of epistaxis (RR, .38; 95%CI, .21-.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI .12-59.57; low certainty). Evidence from four before-and-after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR .34; 95%CI, .25-.46; very low certainty evidence). CONCLUSION: VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits.

Exploring the Evolving Scope of Neoadjuvant Immunotherapy in NSCLC.

While lung cancer remains the leading cause of cancer death worldwide, lung cancer mortality has notably decreased in the past decade. Immunotherapy with immune checkpoint inhibitors have played a noteworthy role in contributing to this improved survival, particularly for patients with non-small cell lung cancer (NSCLC). However, until now the benefits have primarily been seen in patients with advanced or metastatic disease. Several recent early phase and ongoing phase III trials have been assessing whether the treatment benefit of immunotherapy in NSCLC can extend to the neoadjuvant setting for resectable diseases. In this comprehensive narrative review, we evaluate the most recent efficacy and safety data from these studies. We also outline questions that will need to be further examined to legitimate neoadjuvant immunotherapy's role in NSCLC treatment, including the best surrogate marker of response, the incorporation of liquid biopsy for disease monitoring, the ability to be combined with other treatment modalities, the need for further adjuvant therapy, and potential future treatment combinations.

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients.

Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature.

von Willebrand disease (VWD) disproportionately affects women because of the potential for heavy menstrual bleeding (HMB), delivery complications, and postpartum hemorrhage (PPH). To systematically synthesize the evidence regarding first-line management of HMB, treatment of women requiring or desiring neuraxial analgesia, and management of PPH. We searched Medline and EMBASE through October 2019 for randomized trials, comparative observational studies, and case series comparing the effects of desmopressin, hormonal therapy, and tranexamic acid (TxA) on HMB; comparing different von Willebrand factor (VWF) levels in women with VWD who were undergoing labor and receiving neuraxial anesthesia; and measuring the effects of TxA on PPH. We conducted duplicate study selection, data abstraction, and appraisal of risk of bias. Whenever possible, we conducted meta-analyses. We assessed the quality of the evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We included 1 randomized trial, 3 comparative observational studies, and 10 case series. Moderate-certainty evidence showed that desmopressin resulted in a smaller reduction of menstrual blood loss (difference in mean change from baseline, 41.6 [95% confidence interval, 16.6-63.6] points in a pictorial blood assessment chart score) as compared with TxA. There was very-low-certainty evidence about how first-line treatments compare against each other, the effects of different VWF levels in women receiving neuraxial anesthesia, and the effects of postpartum administration of TxA. Most of the evidence relevant to the gynecologic and obstetric management of women with VWD addressed by most guidelines is very low quality. Future studies that address research priorities will be key when updating such guidelines.

Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of >0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures.

Hospitalization at the end of life in patients with multiple myeloma.

BACKGROUND: Despite advances in treatment, multiple myeloma (MM) remains incurable and results in significant morbidity and mortality. Further research investigating where MM patients die and characterization of end-of-life hospitalizations is needed. METHODS: We utilized the National Inpatient Sample (NIS) to explore the hospitalization burden of MM patients at the end of their lives. RESULTS: The percent of patients dying in the hospital as a percent of overall MM deaths ranged from 54% in 2002 to 41.4% in 2017 (p < 0.01). Blood transfusions were received in 32.7% of these hospitalizations and infections were present in 47.8% of patients. Palliative care and/or hospice consultations ranged from 5.3% in 2002 to 31.4% in 2017 (p < 0.01). CONCLUSION: Our study demonstrates that patients with MM dying in the hospital have a significant requirement for blood transfusions and have a high infection burden. We also show that palliative care and hospice involvement at the end of life has increased over time but remains low, and that ultimately, inpatient mortality has decreased over time, but MM patients die in the hospital at a higher rate than the general population.

Indoor light energy harvesting for battery-powered sensors using small photovoltaic modules.

As interest in Internet-of-Things (IoT) devices like wireless sensors increases, research efforts have focused on finding ways for these sensors to self-harvest energy from the environment in which they are installed. Photovoltaic (PV) cells or mini-modules are an intuitive choice for harvesting indoor ambient light, even under low light conditions, and using it for battery charging and powering of these devices. Characterizations of battery charging, for small rechargeable batteries from low charge to full charge, have been investigated using PV mini-modules of equal area. We present battery charging results using three different PV technologies, monocrystalline silicon (c-Si), gallium-indium-phosphide (GaInP) and gallium-arsenide (GaAs) under a warm color temperature (3000 K) LED lighting at an illuminance of 1000 lx. Battery charging times are shortest for the more efficient GAInP and GaAs mini-modules whose spectral response are a better match to the LED test source, which contains mostly visible photons, and longest for the less efficient Si cells. As a demonstration, a wireless temperature sensor mote was attached to the charging circuit and operated to determine its power consumption in relation to the available charging power. The mote's maximum power draw was less than the charging power from the least efficient c-Si mini-module. Our findings affirm the feasibility of utilizing PV under typical indoor lighting conditions to power IoT devices.

Reconciling LED and monochromator-based measurements of spectral responsivity in solar cells.

Irradiance spectral responsivity is an important measurement characteristic for a solar cell and has served as a primary reference cell calibration parameter for a growing number of national laboratories in recent years. This paper discusses the process by which a packaged reference cell is calibrated using the power spectral responsivity from a monochromator-based measurement coupled with discrete irradiance responsivity measurements from a light-emitting diode (LED) array source to uniformly illuminate the cell. To accurately transfer the responsivity from a calibrated detector cell to a fully packaged reference cell, differences in the measurements of power and irradiance responsivities due to the two separate lighting sources must be reconciled. The spectral effects of using LEDs, as well as other physical packaging effects, are discussed in detail, and a comprehensive treatment of the uncertainty components from both approaches is presented.

Utility of Routine Surveillance Imaging for Hodgkin Disease following Autologous Transplant: Experiences from a Single Institution.

BACKGROUND: Surveillance scans performed after autologous stem cell transplant (auto-HCT) for patients with Hodgkin disease (HD) have no proven survival benefit. METHODS: We studied survival differences among patients with HD after auto-HCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. RESULTS: Among the 98 patients with HD that underwent auto-HCT from 2000 to 2014 at our institution, 30 relapsed, of which 21 were detected radiologically and 9 clinically. There were no statistically significant differences in patient characteristics between the 2 groups. The median time to progression was 118 days for the clinical cohort and 284 days for the radiological cohort (p = 0.05). Median overall survival (OS) was 728 days for the clinical cohort, and was not reached for the radiological cohort (p = 0.02). DISCUSSION: In our review, most patients with HD after auto-HCT were diagnosed radiologically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Routine scanning may not be necessary in the majority of patients with HD following auto-HCT.

Utility of routine surveillance imaging for diffuse large B-cell lymphoma post autologous transplant: A single center experience.

Surveillance scans after autologous stem cell transplant (auto-HCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post auto-HCT whose recurrences were detected clinically versus with routine surveillance imaging. Among the 139 patients with RR DLBCL that underwent auto-HCT from 2000 to 2014 at our institution, 37 relapsed: 21 clinical and 16 radiological. The median time to progression was 167 days for the clinical cohort and 565 days for the radiological cohort (p = 0.03), and median overall survival (OS) was 587 days and not reached, respectively (p = 0.006). Most patients with relapsed DLBCL after auto-HCT were diagnosed clinically and were likely to be detected earlier and have a shorter OS. Relapse in patients with aggressive disease will likely be detected when clinically apparent, and the outcome of these patients is independent of the way the relapse is diagnosed. Thus, universal scanning after auto-HCT appears to have little benefit.

Nonlinearity measurements of solar cells with an LED-based combinatorial flux addition method.

We present a light emitting diode (LED)-based system utilizing a combinatorial flux addition method to investigate the nonlinear relationship in solar cells between the output current of the cell and the incident irradiance level. The magnitude of the light flux is controlled by the supplied currents to two LEDs (or two sets of them) in a combinatorial fashion. The signals measured from the cell are arranged within a related overdetermined linear system of equations derived from an appropriately chosen Nth degree polynomial representing the relationship between the measured signals and the incident fluxes. The flux values and the polynomial coefficients are then solved for by linear least squares to obtain the best fit. The technique can be applied to any solar cell, under either monochromatic or broadband spectrum. For the unscaled solution, no reference detectors or prior calibrations of the light flux are required. However, if at least one calibrated irradiance value is known, then the entire curve can be scaled to an appropriate spectral responsivity value. Using this technique, a large number of data points can be obtained in a relatively short time scale over a large signal range.

Spectral dependence of carrier lifetimes in silicon for photovoltaic applications.

Charge carrier lifetimes in photovoltaic-grade silicon wafers were measured by a spectral-dependent, quasi-steady-state photoconductance technique. Narrow bandwidth light emitting diodes (LEDs) were used to excite excess charge carriers within the material, and the effective lifetimes of these carriers were measured as a function of wavelength and intensity. The dependence of the effective lifetime on the excitation wavelength was then analyzed within the context of an analytical model relating effective lifetime to the bulk lifetime and surface recombination velocity of the material. The agreement between the model and the experimental data provides validation for this technique to be used at various stages of the solar cell production line to investigate the quality of the passivation layers and the bulk properties of the material.

Large-area irradiance-mode spectral response measurements of solar cells by a light-emitting, diode-based integrating sphere source.

An irradiance-mode absolute differential spectral response (SR) measurement system based on a light emitting diode (LED) array is described. The LEDs are coupled to an integrating sphere whose output irradiance is uniform to better than 2% over an area of 160 mm by 160 mm. SR measurements of solar cells when subject to diffuse irradiation, as provided by the integrating sphere, are compared with collimated irradiance SR measurements. Issues originating from the differences in angular response of the reference versus the test cells are also investigated. The SR curves of large-area cells with dimensions of up to 155 mm are measured and then used to calculate the cell's short circuit current (I(sc)), if illuminated by a defined solar spectrum. The resulting values of I(sc) agree well with the values obtained from secondary measurements.

Absolute spectral responsivity measurements of solar cells by a hybrid optical technique.

An irradiance mode, absolute differential spectral response measurement system for solar cells is presented. The system is based on combining the monochromator-based approach of determining the power mode spectral responsivity of cells with an LED-based measurement to construct a curve representing the light-overfilled absolute spectral response of the entire cell. This curve can be used to predict the short-circuit current (I(sc)) of the cell under the AM 1.5 standard reference spectrum. The measurement system is SI-traceable via detectors with primary calibrations linked to the NIST absolute cryogenic radiometer. An uncertainty analysis of the methodology places the relative uncertainty of the calculated I(sc) at better than ±0.8%.

Versatile light-emitting-diode-based spectral response measurement system for photovoltaic device characterization.

An absolute differential spectral response measurement system for solar cells is presented. The system couples an array of light emitting diodes with an optical waveguide to provide large area illumination. Two unique yet complementary measurement methods were developed and tested with the same measurement apparatus. Good agreement was observed between the two methods based on testing of a variety of solar cells. The first method is a lock-in technique that can be performed over a broad pulse frequency range. The second method is based on synchronous multifrequency optical excitation and electrical detection. An innovative scheme for providing light bias during each measurement method is discussed.