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[This corrects the article DOI: 10.1017/ash.2022.189.].

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Data is incredibly significant in today's digital age because data represents facts and numbers from our regular life transactions. Data is no longer arriving in a static form; it is now arriving in a streaming fashion. Data streams are the arrival of limitless, continuous, and rapid data. The healthcare industry is a major generator of data streams. Processing data streams is extremely complex due to factors such as volume, pace, and variety. Data stream classification is difficult owing to idea drift. Concept drift occurs in supervised learning when the statistical properties of the target variable that the model predicts change unexpectedly. We focused on solving various forms of concept drift problems in healthcare data streams in this research, and we outlined the existing statistical and machine learning methodologies for dealing with concept drift. It also emphasizes the use of deep learning algorithms for concept drift detection and describes the various healthcare datasets utilized for concept drift detection in data stream categorization.

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PURPOSE: Although local control is an important issue for longer-term survivors of spinal metastases treated with conventional external beam radiation therapy (EBRT), the literature on radiographic local failure (LF) in these patients is sparse. To inform clinical decision-making, we evaluated rates, consequences, and predictors of radiographic LF in patients with spinal metastases managed with palliative conventional EBRT alone. METHODS AND MATERIALS: We retrospectively reviewed 296 patients with spinal metastases who received palliative EBRT at a single institution (2006-2013). Radiographic LF was defined as radiologic progression within the treatment field, with death considered a competing risk. Kaplan-Meier, cumulative incidence, and Cox regression analyses determined overall survival estimates, LF rates, and predictors of LF, respectively. RESULTS: There were 182 patients with follow-up computed tomography or magnetic resonance imaging; median overall survival for these patients was 7.7 months. Patients received a median of 30 Gy in 10 fractions to a median of 4 vertebral bodies. Overall, 74 of 182 patients (40.7%) experienced LF. The 6-, 12-, and 18-month LF rates were 26.5%, 33.1%, and 36.5%, respectively, while corresponding rates of death were 24.3%, 38.1%, and 45.9%. Median time to LF was 3.8 months. Of those with LF, 51.4% had new compression fractures, 39.2% were admitted for pain control, and 35.1% received reirradiation; median time from radiation therapy (RT) to each of these events was 3.0, 5.7, and 9.2 months, respectively. Independent predictors of LF included single-fraction RT (8 Gy) (hazard ratio [HR], 2.592; 95% confidence interval [CI], 1.437-4.675; P = .002), lung histology (HR, 3.568; 95% CI, 1.532-8.309; P = .003), and kidney histology (HR, 4.937; 95% CI, 1.529-15.935; P = .008). CONCLUSIONS: Patients experienced a >30% rate of radiographic LF by 1 year after EBRT. Single-fraction RT and lung or kidney histology predicted LF. Given the high rates of LF for patients with favorable prognosis, assessing the risk of death versus LF is important for clinical decision-making.

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BACKGROUND: Acute right ventricular (RV) failure is challenging to treat and mechanical circulatory support devices are limited. The TandemHeart ProtekDuo (THPD; TandemLife) is a novel percutaneous RV assist device that can provide 4.0 liters per minute of blood flow through venovenous extracorporeal life support. It allows venous drainage from the right atrium and reinfusion of blood into the main pulmonary artery via internal jugular vein access. We aim to provide real-world insight into disease characteristics resulting in the use of THPD for mechanical support and enhance knowledge of best practice regarding clinical management weaning and removal/exit strategies. METHODS: We retrospectively collected data of consecutive patients who received a THPD device at our center for acute RV failure between August 2015 and February 2018. RESULTS: Eleven patients were diagnosed with acute RV failure and required placement of THPD. The hospital length of stay ranged from 12 to 223 days. The average length of support ranged from 11 to 154 days. We observed complications such as stroke (18.2%), sepsis (63.6%), massive gastrointestinal bleed (45.5%), and heparin-induced thrombocytopenia (54.5%). These patients received on average 85 units of blood products. Survival was 82% at 30 days and 72% at 180 days. Six of the patients were successfully weaned from the THPD devices and 1 patient required venovenous extracorporeal life support. CONCLUSIONS: This real-world experience, despite high morbidity, continues to suggest benefits of THPD for patients with severe acute RV failure.

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Mutations in hepatocyte nuclear factor (HNF)1A gene cause the most common form of Maturity-onset diabetes of the young (MODY), a monogenic subtype of diabetes mellitus. Functional characterization of mutant proteins reveals that mutations may disrupt DNA binding capacity, transactivation ability and nuclear localization of HNF1A depending on the position of the mutation. Previously identified Arg271Trp and Ser345Tyr mutations in HNF1A were found to be defective in nuclear localization. Arg271 residue resides in a region similar to classical nuclear localization signal (NLS) motif, while Ser345 does not. Importin α family members recognize NLS motifs on cargo proteins and subsequently translocate them into nucleus. Here, we first investigated the nuclear localization mechanism of wild type HNF1A protein. For this purpose, we analyzed the interaction of HNF1A with three mouse homolog importin α proteins (KPNA2, KPNA4 and KPNA6) by co-immunoprecipitation assay and molecular docking simulation. Hereby, KPNA6 was identified as the main import receptor, which is responsible for the transport of HNF1A into the nucleus. Immunolocalization studies in mouse pancreatic cells (Min6) also confirmed the co-localization of HNF1A and KPNA6 in the cytoplasm. Secondly, the interaction between KPNA6 and mutant HNF1A proteins (Arg271Trp and Ser345Tyr) was assessed. Co-immunoprecipitation studies revealed a reduced interaction compared to wild type HNF1A. Our study demonstrated for the first time that HNF1A transcription factor is recognized and transported by importin/karyopherin import family, and mutations in NLS motifs may disrupt the interaction leading to nuclear localization abnormalities and MODY phenotype.

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OBJECTIVES: To investigate the prognostic impact of primary tumor-specific growth rate (TSGR) on treatment outcomes after definitive radiation therapy (RT) for nonoropharyngeal squamous cell carcinoma (non-OPSCC). METHODS: The diagnostic tumor and nodal volumes of 39 non-OPSCC patients were contoured and compared to corresponding RT planning scan volumes to determine TSGR. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were evaluated according to the Kaplan-Meier method; and hazard ratios (HR) were estimated using Cox regression. Based on the 75th percentile TSGR of 2.18%, we stratified patients into a high TSGR group (≥ 2.18% per day) and low TSGR group (< 2.18% per day). RESULTS: The median follow-up was 22 months (range: 1-86 months) and median time between diagnostic and simulation computed tomography scans was 22 days (range: 7-170 days). Median RT dose was 70 Gy (range: 60-79.2 Gy). Based on the 75th percentile TSGR, OS at median follow-up was 50.0% for the high TSGR group compared to 92.5% for the low TSGR group (HR [95% confidence interval (CI)] = 2.12[1.16-11.42], P = 0.018). There was a trend toward worse DFS at median follow-up for the high versus low TSGR groups, at 55.6% and 82.3%, respectively (HR [95% CI] = 2.29[0.82-6.38], P = 0.103). CONCLUSION: Our study contributes to growing literature on TSGR as a temporal biomarker in patients with non-OPSCC. Patients with high TSGR ≥2.18% per day have significantly worse OS compared to those with TSGR below this threshold. Efforts to address treatment initiation delays may benefit patients with particularly aggressive and rapidly growing tumors. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2378-2384, 2020.

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Objective: We describe characteristics of patient and treatment recommendations from a spinal tumor board at one institution, including representation from palliative care. Background: The impact of prospective multidisciplinary input for patients with spinal tumors is poorly understood despite their increasing complexity. Methods: We retrospectively reviewed 622 cases sequentially discussed at a weekly spinal tumor board, and abstracted patient and treatment information from the medical record and meeting minutes. Results: From April 2017 to February 2019, 622 cases representing 438 unique patients were discussed. The median age was 62 years (range 21-92). Most patients had spinal tumors originating from metastases (91.78%), including breast (14.3%), nonsmall cell lung cancer (13.4%), prostate (10.9%), and renal cell cancer (8.8%), and the remainder had primary central nervous system (4.3%) or benign tumors (3.9%). Sixty-five percent of patients were alive at last follow-up. Conventional external beam radiotherapy was the most common treatment recommendation (33.8%) followed by surgery (26.2%), stereotactic body radiation therapy (17.8%), imaging follow-up (16.6%), and vertebroplasty (15.9%). Palliative care was the primary treatment recommended for 4.5%, and no therapy recommended for 4.0%. Treatment recommendation involved two modalities for 29% of cases, and three in 1.3% of cases. In four cases, biopsy to confirm pathology changed management due to unexpected findings of osteomyelitis, hematopoiesis, or new diagnosis of plasmacytoma. Conclusions: Multidisciplinary input is integral to the optimal care of spinal tumor patients. The high risk of death highlights the need to prioritize modalities that optimize quality of life in the context of a patient's individual prognosis.

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Inappropriate choices and durations of therapy for urinary tract infections (UTI) are a common and widespread problem. In this qualitative study, we sought to understand why primary care providers (PCPs) choose certain antibiotics or durations of treatment and the sources of information they rely upon to guide antibiotic-prescribing decisions. We conducted semi-structured interviews with 18 PCPs in two family medicine clinics focused on antibiotic-prescribing decisions for UTIs. Our interview guide focused on awareness and familiarity with guidelines (knowledge), acceptance and outcome expectancy (attitudes), and external barriers. We followed a six-phase approach to thematic analysis, finding that many PCPs believe that fluoroquinolones achieve more a rapid and effective control of UTI symptoms than trimethoprim-sulfamethoxazole or nitrofurantoin. Most providers were unfamiliar with fosfomycin as a possible first-line agent for the treatment of acute cystitis. PCPs may be misled by advanced patient age, diabetes, and recurrent UTIs to make inappropriate choices for the treatment of acute cystitis. For support in clinical decision making, few providers relied on guidelines, preferring instead to have decision support embedded in the electronic medical record. Knowing the PCPs' knowledge gaps and preferred sources of information will guide the development of a primary care-specific antibiotic stewardship intervention for acute cystitis.

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High harmonics from laser-ablated plumes are mostly generated from ionic species. We demonstrate that with ultrashort infrared (∼1.82 µm) driving lasers, high harmonics from laser-ablated manganese are predominantly generated from neutral atoms, a transition metal atom with an ionization potential of 7.4 eV. Our results open the possibility to advance laser-ablation technique to study the dynamics of neutral atoms of low ionization potential. Moreover, as manganese contains giant autoionizing resonance, intense and broadband high harmonics have been demonstrated from this resonance at energies from 49 to 53 eV. This opens the possibility to generate intense attosecond pulses directly from the giant resonances, as well as to study these resonances using high-harmonic spectroscopy.

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Physicochemical properties of titanium dioxide nanoparticles (TiO2 NPs) can be tuned by doping with metals or nonmetals. Copper (Cu) doping improved the photocatalytic behavior of TiO2 NPs that can be applied in various fields such as environmental remediation and nanomedicine. However, interaction of Cu-doped TiO2 NPs with human cells is scarce. This study was designed to explore the role of Cu doping in cytotoxic response of TiO2 NPs in human lung epithelial (A549) cells. Characterization data demonstrated the presence of both TiO2 and Cu in Cu-doped TiO2 NPs with high-quality lattice fringes without any distortion. The size of Cu-doped TiO2 NPs (24 nm) was lower than pure TiO2 NPs (30 nm). Biological results showed that both pure and Cu-doped TiO2 NPs induced cytotoxicity and oxidative stress in a dose-dependent manner. Low mitochondrial membrane potential and higher caspase-3 enzyme (apoptotic markers) activity were also observed in A549 cells exposed to pure and Cu-doped TiO2 NPs. We further observed that cytotoxicity caused by Cu-doped TiO2 NPs was higher than pure TiO2 NPs. Moreover, antioxidant N-acetyl cysteine effectively prevented the reactive oxygen species generation, glutathione depletion, and cell viability reduction caused by Cu-doped TiO2 NPs. This is the first report showing that Cu-doped TiO2 NPs induced cytotoxicity and oxidative stress in A549 cells. This study warranted further research to explore the role of Cu doping in toxicity mechanisms of TiO2 NPs.

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In high-order harmonic generation, resonant harmonics (RH) are sources of intense, coherent extreme-ultraviolet radiation. However, intensity enhancement of RH only occurs for a single harmonic order, making it challenging to generate short attosecond pulses. Moreover, the mechanism involved behind such RH was circumstantial, because of the lack of direct experimental proofs. Here, we demonstrate the exact quantum paths that electron follows for RH generation using tin, showing that it involves not only the autoionizing state, but also a harmonic generation from dressed-AIS that appears as two coherent satellite harmonics at frequencies ±2Ω from the RH (Ω represents laser frequency). Our observations of harmonic emission from dressed states open the possibilities of generating intense and broadband attosecond pulses, thus contributing to future applications in attosecond science, as well as the perspective of studying the femtosecond and attosecond dynamics of autoionizing states.

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We demonstrate an intense broadband terahertz (THz) source based on the interaction of relativistic-intensity femtosecond lasers with aligned copper nanorod array targets. For copper nanorod targets with a length of 5 µm, a maximum 13.8 times enhancement in the THz pulse energy (in ≤20 THz spectral range) is measured as compared to that with a thick plane copper target under the same laser conditions. A further increase in the nanorod length leads to a decrease in the THz pulse energy at medium frequencies (≤20 THz) and increase of the electromagnetic pulse energy in the high-frequency range (from 20-200 THz). For the latter, we measure a maximum energy enhancement of 28 times for the nanorod targets with a length of 60 µm. Particle-in-cell simulations reveal that THz pulses are mostly generated by coherent transition radiation of laser produced hot electrons, which are efficiently enhanced with the use of nanorod targets. Good agreement is found between the simulation and experimental results.

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Dual antiplatelet therapy (DAPT) following an acute coronary syndrome or after placement of a coronary artery stent is superior to aspirin alone for prevention of atherothrombotic events but carries an increased bleeding risk. DAPT should be continued for at least 12 months based on current guidelines. Recent randomized trials demonstrate reduced ischemic events including myocardial infarction (MI), stroke, and death with continued DAPT for up to 30 months or longer, particularly in the post-MI population. However, this clinical benefit is accompanied by an increased risk of bleeding. Additional trials show mixed safety and efficacy with duration of DAPT of less than 12 months. The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding. Patients at an increased risk of ischemic events and a lower risk of bleeding should be strongly considered for prolonged DAPT beyond the 1 year currently recommended in the practice guidelines.

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The impact of physical inactivity on heart failure (HF) mortality is unclear. We analyzed data from the HF Adherence and Retention Trial (HART) which enrolled 902 patients with New York Heart Association class II/III HF, with preserved or reduced ejection fraction, who were followed for 36 months. On the basis of mean self-reported weekly exercise duration, patients were classified into inactive (0 min/week) and active (≥1 min/week) groups and then propensity score matched according to 34 baseline covariates in 1:2 ratio. Sedentary activity was determined according to self-reported daily television screen time (<2, 2 to 4, >4 h/day). The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. There were 196 inactive patients, of whom 171 were propensity matched to 342 active patients. Physical inactivity was associated with greater risk of all-cause death (hazard ratio [HR] 2.01, confidence interval [CI] 1.47 to 3.00; p <0.001) and cardiac death (HR 2.01, CI 1.28 to 3.17; p = 0.002) but no significant difference in HF hospitalization (p = 0.548). Modest exercise (1 to 89 min/week) was associated with a significant reduction in the rate of death (p = 0.003) and cardiac death (p = 0.050). Independent of exercise duration and baseline covariates, television screen time (>4 vs <2 h/day) was associated with all-cause death (HR 1.65, CI 1.10 to 2.48; p = 0.016; incremental chi-square = 6.05; p = 0.049). In conclusion, in patients with symptomatic chronic HF, physical inactivity is associated with higher all-cause and cardiac mortality. Failure to exercise and television screen time are additive in their effects on mortality. Even modest exercise was associated with survival benefit.

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OBJECTIVES: This study sought to evaluate the impact of sodium restriction on heart failure (HF) outcomes. BACKGROUND: Although sodium restriction is advised for patients with HF, data on sodium restriction and HF outcomes are inconsistent. METHODS: We analyzed data from the multihospital HF Adherence and Retention Trial, which enrolled 902 New York Heart Association functional class II/III HF patients and followed them up for a median of 36 months. Sodium intake was serially assessed by a food frequency questionnaire. Based on the mean daily sodium intake prior to the first event of death or HF hospitalization, patients were classified into sodium restricted (<2,500 mg/d) and unrestricted (≥2,500 mg/d) groups. Study groups were propensity score matched according to plausible baseline confounders. The primary outcome was a composite of death or HF hospitalization. The secondary outcomes were cardiac death and HF hospitalization. RESULTS: Sodium intake data were available for 833 subjects (145 sodium restricted, 688 sodium unrestricted), of whom 260 were propensity matched into sodium restricted (n = 130) and sodium unrestricted (n = 130) groups. Sodium restriction was associated with significantly higher risk of death or HF hospitalization (42.3% vs. 26.2%; hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.21 to 2.84; p = 0.004), derived from an increase in the rate of HF hospitalization (32.3% vs. 20.0%; HR: 1.82; 95% CI: 1.11 to 2.96; p = 0.015) and a nonsignificant increase in the rate of cardiac death (HR: 1.62; 95% CI: 0.70 to 3.73; p = 0.257) and all-cause mortality (p = 0.074). Exploratory subgroup analyses suggested that sodium restriction was associated with increased risk of death or HF hospitalization in patients not receiving angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (HR: 5.78; 95% CI: 1.93 to 17.27; p = 0.002). CONCLUSIONS: In symptomatic patients with chronic HF, sodium restriction may have a detrimental impact on outcome. A randomized clinical trial is needed to definitively address the role of sodium restriction in HF management. (A Self-management Intervention for Mild to Moderate Heart Failure [HART]; NCT00018005).

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BACKGROUND: The impact of health insurance carrier and socioeconomic status (SES) on the adherence to appropriate use criteria (AUC) for radionuclide myocardial perfusion imaging (MPI) is unknown. HYPOTHESIS: Health insurance carrier's prior authorization and patient's SES impact adherence to AUC for MPI in a fee-for-service setting. METHODS: We conducted a prospective cohort study of 1511 consecutive patients who underwent outpatient MPI in a multi-site, office-based, fee-for-service setting. The patients were stratified according to the 2009 AUC into appropriate/uncertain appropriateness and inappropriate use groups. Insurance status was categorized as Medicare (does not require prior authorization) vs commercial (requires prior authorization). Socioeconomic status was determined by the median household income in the ZIP code of residence. RESULTS: The proportion of patients with Medicare was 33% vs 67% with commercial insurance. The rate of inappropriate use was higher among patients with commercial insurance vs Medicare (55% vs 24%; P < 0.001); this difference was not significant after adjusting for confounders known to impact AUC determination (odds ratio: 1.06, 95% confidence interval: 0.62-1.82, P = 0.82). The mean annual household income in the residential areas of patients with inappropriate use as compared to those with appropriate/uncertain use was $72 000 ± 21 000 vs $68 000 ± 20 000, respectively (P < 0.001). After adjusting for covariates known to impact AUC determination, SES (top vs bottom quartile income area) was not independently predictive of inappropriate MPI use (odds ratio: 0.9, 95% confidence interval: 0.53-1.52, P = 0.69). CONCLUSIONS: Insurance carriers prior authorization and SES do not seem to play a significant role in determining physicians adherence to AUC for MPI.

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The World Health Organization has estimated that air pollution is responsible for 1.4 % of all deaths and 0.8 % of disability-adjusted life years. NOIDA, located at the National Capital Region, India, was declared as one of the critically air-polluted areas by the Central Pollution Control Board of the Government of India. Studies on the relationship of reduction in lung functions of residents living in areas with higher concentrations of particulate matter (PM) in ambient air were inconclusive since the subjects of most of the studies are hospital admission cases. Very few studies, including one from India, have shown the relationship of PM concentration and its effects of lung functions in the same location. Hence, a cross-sectional study was undertaken to study the effect of particulate matter concentration in ambient air on the lung functions of residents living in a critically air-polluted area in India. PM concentrations in ambient air (PM(1,) PM(2.5)) were monitored at residential locations and identified locations with higher (NOIDA) and lower concentrations (Gurgaon). Lung function tests (FEV(1), PEFR) were conducted using a spirometer in 757 residents. Both air monitoring and lung function tests were conducted on the same day. Significant negative linear relationship exists between higher concentrations of PM(1) with reduced FEV(1) and increased concentrations of PM(2.5) with reduced PEFR and FEV(1). The study shows that reductions in lung functions (PEFR and FEV(1)) can be attributed to higher particulate matter concentrations in ambient air. Decline in airflow obstruction in subjects exposed to high PM concentrations can be attributed to the fibrogenic response and associated airway wall remodeling. The study suggests the intervention of policy makers and stake holders to take necessary steps to reduce the emissions of PM concentrations, especially PM(1,) PM(2.5), which can lead to serious respiratory health concerns in residents.

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OBJECTIVE: Bicalutamide is approved as an adjuvant to primary treatments (radical prostatectomy or radiotherapy) or as monotherapy in men with locally advanced, nonmetastatic prostate cancer (pca). However, this treatment induces gynecomastia in most patients, which often results in treatment discontinuation. Optimal therapy for these breast events is not known so far. We undertook a meta-analysis to assess the efficacy of various treatment options for bicalutamide-induced gynecomastia. METHODS: The medline, cancerlit, and Cochrane library databases were searched and the Google search engine was used to identify prospective and retrospective controlled studies published in English from January 2000 to December 2010 comparing prophylactic or curative treatment options with a control group (no treatment) for pca patients who developed bicalutamide-induced gynecomastia. Radiotherapy-induced cardiotoxicity was also evaluated. RESULTS: The search identified nine controlled trials with a total patient population of 1573. Pooled results from prophylactic trials showed a significant reduction of gynecomastia in pca patients treated with prophylactic tamoxifen 20 mg daily (odds ratio: 0.06; 95% confidence interval: 0.05 to 0.09; p = 0.09), and pooled results from treatment trials showed a significant response of gynecomastia to definitive radiotherapy (odds ratio: 0.06; 95% confidence interval: 0.01 to 0.24; p < 0.0001). Aromatase inhibitors and weekly tamoxifen were not found to be effective as prophylactic and curative options. For the radiotherapy, skin-to-heart distance was found to be an important risk factor for cardiotoxicity (p = 0.006). A funnel plot of the meta-analysis showed significant heterogeneity (Egger test p < 0.00001) because of low sample size. CONCLUSIONS: Our meta-analysis suggests using prophylactic tamoxifen 20 mg daily as the first-line preventive measure and radiotherapy as the first-line treatment option for bicalutamide-induced gynecomastia. Aromatase inhibitors and weekly tamoxifen are not recommended.

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BACKGROUND: While results of clinical trials are used to impact practice among patients with ischemic stroke, very little information is available regarding proportion and characteristics of patients recruited in clinical trials in general practice. METHODS: We performed this analysis to provide an audit of recruitment in clinical trials among patients with acute ischemic stroke using data from the University Healthsystems Consortium benchmarking project. A review of 40 consecutive ischemic stroke cases meeting inclusion criteria and discharge within a 6-month period was conducted in 32 hospitals. RESULTS: A total of 1256 patients (mean age 67 years, range 18--99 years) were included. A total of 77 (6%) patients were recruited in clinical trials; 33 and 14 patients recruited in drug or device trials, respectively. In the multivariate analysis, age under 80 years (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.0--4.9), white or African-American race as compared with others (OR 2.5, 95% CI 0.98--6.6), evaluation by a neurologist or stroke team (OR 14.8, 95% CI 2.0--108), the use of intravenous thrombolysis (OR 8.4, 95% CI 4.9--14.4), and history of hypertension (OR 1.9, 95% CI 1.0--3.4) were associated with recruitment in clinical trials. There was no relationship between patient's gender and recruitment in clinical trials. The rate of intracranial hemorrhage (6% vs 2%, p<0.05) and progression of stroke (12% vs 3%, p<0.05) were higher among those recruited in clinical trials. CONCLUSIONS: Patients recruited in clinical trials appear to have different characteristics from those who are not recruited limiting the generalizability of results from current trials.