Category: Nevin Manimala

Nat Commun. 2021 Jun 11;12(1):3559. doi: 10.1038/s41467-021-23711-x.

ABSTRACT

Various large-area growth methods for two-dimensional transition metal dichalcogenides have been developed recently for future electronic and photonic applications. However, they have not yet been employed for synthesizing active pixel image sensors. Here, we report on an active pixel image sensor array with a bilayer MoS₂ film prepared via a two-step large-area growth method. The active pixel of image sensor is composed of 2D MoS₂ switching transistors and 2D MoS₂ phototransistors. The maximum photoresponsivity (R_ph) of the bilayer MoS₂ phototransistors in an 8 × 8 active pixel image sensor array is statistically measured as high as 119.16 A W^-1. With the aid of computational modeling, we find that the main mechanism for the high R_ph of the bilayer MoS₂ phototransistor is a photo-gating effect by the holes trapped at subgap states. The image-sensing characteristics of the bilayer MoS₂ active pixel image sensor array are successfully investigated using light stencil projection.

PMID:34117235 | DOI:10.1038/s41467-021-23711-x

Clin J Sport Med. 2021 Jun 9. doi: 10.1097/JSM.0000000000000950. Online ahead of print.

ABSTRACT

OBJECTIVE: Hemarthrosis after knee trauma often indicates serious joint injury. Few studies have evaluated agreement between clinical examination and findings from magnetic resonance imaging (MRI). We aimed to describe the agreement between acute clinical examination and subacute MRI findings after acute knee trauma with hemarthrosis and the importance of the subspecialty of the examiner.

DESIGN: Longitudinal cohort study. Agreement with MRI findings was evaluated by logistic regression.

SETTING: Helsingborg hospital.

PATIENTS: Thousand one hundred forty-five consecutive patients with hemarthrosis after knee trauma.

INTERVENTIONS: Clinical examination and MRI.

MAIN OUTCOME MEASURES: agreement between clinical examination and findings from MRI. We considered the radiologist’s report as the gold standard.

RESULTS: Median time (25th, 75th percentile) from injury to clinical examination was 2 (1, 7) days, and from injury to imaging was 8 (5, 15) days. The overall sensitivity and specificity of clinical examination versus MRI for major ligament injury or lateral patella dislocation (LPD) were 70% [95% confidence interval 67-73) and 66% (61-72), respectively. Orthopedic subspecialist knee had the highest agreement with anterior cruciate ligament rupture (adjusted odds ratios were 1.7 (95% confidence interval 1.2-2.3), 1.9 (1.2-3.0) and 5.9 (3.7-9.5) for orthopedic trainees, orthopedic subspecialists other, and orthopedic subspecialist knee, respectively]. For other ligament injuries and LPD, we did not find statistically significant differences.

CONCLUSIONS: Clinical diagnosis after acute knee injury is relatively unreliable versus MRI findings even when performed by orthopedic specialists. However, the agreement is improved when the examination is performed by an orthopedic knee subspecialist.

PMID:34117155 | DOI:10.1097/JSM.0000000000000950

Comput Inform Nurs. 2021 Jun 11. doi: 10.1097/CIN.0000000000000785. Online ahead of print.

ABSTRACT

Nurses have experienced unintended consequences and workarounds associated with health information technology implementation. However, examination of this occurrence is rare. This study aimed to examine the unintended consequences and workarounds produced by the implementation of electronic medical record systems in clinical nursing practice. A total of 143 nurses participated in a survey using statistically tested instruments. The data were analyzed using descriptive statistics and a nonparametric test. The descriptive data were analyzed by meaning. The participants experienced unintended consequences and workarounds related to electronic medical record implementation at moderate or high levels based on the responses to questions scored on 5-point Likert scales. The unintended consequences were closely associated with workarounds. The degree of experience with unintended consequences and the use of workarounds differed significantly according to the level of education, job position, and years in nursing practice. The nursing examples of unintended consequences and workarounds were organized into four categories of unintended consequences. By presenting unintended consequences and workarounds together, this study enhances the understanding of the problems encountered in EMR implementation and the action of nurses. Nurses’ needs should be considered as an important resource in developing, redesigning, or purchasing and implementing health information technology in healthcare settings.

PMID:34117159 | DOI:10.1097/CIN.0000000000000785

Am J Med Qual. 2021 Jun 10. doi: 10.1097/01.JMQ.0000735504.65700.25. Online ahead of print.

ABSTRACT

Family history screening to identify individuals at increased risk for hereditary cancers could be a powerful strategy to prevent cancer but is used inconsistently in primary care. The objective was to improve identification of women with at-risk family histories using a point-of-care family history screening tool administered on an electronic tablet device during well-woman appointments. A total of 288 women were invited to participate and 136 women (47.2%) completed the electronic family history screening tool. Significantly more women were identified and referred to the genetics department with the electronic family history screening tool than the standard-of-care paper questionnaire (11.8% versus 0.8%, P < 0.001). There were no statistically significant differences in the proportion of referred women who were evaluated by the genetic counselors, and no pathogenic variants were found with either family history screening method. Implementing innovative self-reporting tools may improve inherited cancer risk detection.

PMID:34117164 | DOI:10.1097/01.JMQ.0000735504.65700.25

J Immunother Cancer. 2021 Jun;9(6):e002194. doi: 10.1136/jitc-2020-002194.

ABSTRACT

BACKGROUND: Metastatic human epidermal growth receptor II (HER2) negative breast cancer remains incurable. Our phase I study showed that anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) may be effective against HER2-tumors. This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor positive (HR+) and triple negative breast cancer (TNBC) as immune consolidation after chemotherapy. The primary objective of this study was to increase the traditional median time to progression after failure of first-line therapy of 2-4 months with the secondary endpoints of increasing overall survival (OS) and immune responses.

METHODS: HER2- metastatic breast cancer (MBC) patients received 3 weekly infusions of HER2 BATs and a boost after 12 weeks.

RESULTS: This phase II study included 24 HER2-HR+ and 8 TNBC patients who received a mean of 3.75 and 2.4 lines of prior chemotherapy, respectively. Eight of 32 evaluable patients were stable at 4 months after the first infusion. There were no dose limiting toxicities. Tumor markers decreased in 13 of 23 (56.5%) patients who had tumor markers. The median OS was 13.1 (95% CI 8.6 to 17.4), 15.2 (95% CI 8.6 to 19.8), and 12.3 (95% CI 2.1 to 17.8) months for the entire group, HER2-HR+, and TNBC patients, respectively. Median OS for patients with chemotherapy-sensitive and chemotherapy-resistant disease after chemotherapy was 14.6 (9.6-21.8) and 8.6 (3.3-17.3) months, respectively. There were statistically significant increases in interferon-γ immunospots, Th₁ cytokines, Th₂ cytokines, and chemokines after HER2 BATs infusions.

CONCLUSIONS: In heavily pretreated HER2-patients, immune consolidation with HER2 BATs after chemotherapy appears to increase the proportion of patients who were stable at 4 months and the median OS for both groups as well as increased adaptive and innate antitumor responses. Future studies combining HER2 BATs with checkpoint inhibitors or other immunomodulators may improve clinical outcomes.

PMID:34117114 | DOI:10.1136/jitc-2020-002194

Am J Ther. 2021 Jun 2. doi: 10.1097/MJT.0000000000001388. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have shown that cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of fluvoxamine, the activity of which is highly dependent, inter alia, on the polymorphism of the gene encoding it. The objective of our study was to investigate the effect of 1846G>A polymorphism of the CYP2D6 gene on the efficacy and safety of fluvoxamine, using findings on CYP2D6 enzymatic activity and on CYP2D6 expression level in patients with depressive disorders comorbid with alcohol use disorder.

STUDY QUESTION: Efficacy and safety of fluvoxamine depend on the polymorphism of CYP2D6 gene in patients with major depressive disorder.

STUDY DESIGN: Our study enrolled 96 male patients with depressive disorders comorbid with alcohol use disorder. Patients were examined on days 1, 9, and 16 of fluvoxamine therapy.

MEASURES AND OUTCOMES: Treatment efficacy was evaluated using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6-hydroxy-1,2,3,4-tetrahydro-β-carboline/pinoline ratio).

RESULTS: Our study revealed the statistically significant results for the treatment efficacy evaluation [the Hamilton Depression Rating Scale scores at the end of the treatment course: (GG) 2.0 (1.0-4.0) and (GA) 5.0 (4.0-7.0), P < 0.001]. Analysis of the results of the pharmacotranscriptomic part of the study did not show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 26.9 (15.0-32.2), (GA) 31.8 (22.7-33.7), P = 0.247. In addition, we evaluated the relationship between the CYP2D6 enzymatic activity (as evaluated by 6-hydroxy-1,2,3,4-tetrahydro-β-carboline/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.243, P = 0.017.

CONCLUSIONS: The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of fluvoxamine was demonstrated in a group of 96 patients with depressive disorders comorbid with alcohol use disorder.

PMID:34117140 | DOI:10.1097/MJT.0000000000001388

Clin J Sport Med. 2021 Jun 9. doi: 10.1097/JSM.0000000000000949. Online ahead of print.

ABSTRACT

OBJECTIVES: To identify risk factors that predict gradual onset running-related injuries (GORRIs) in ultramarathon runners entering a mass community-based event.

DESIGN: Descriptive cross-sectional study.

SETTING: Two Oceans 56 km ultramarathon 2012 to 2015.

PARTICIPANTS: Race entrants (n = 42 003) completed a compulsory pre-race medical history questionnaire; 29 585 (70.4%) of entrants consented.

DEPENDENT/OUTCOME VARIABLE: A history of GORRIs in the past 12 months among race entrants.

MAIN OUTCOME MEASURES: In a multi-variate model, runner demographics, training variables (years of recreational running, weekly running distance, training running speed), history of chronic disease (composite score), and history of allergies were included as factors predicting GORRIs. Prevalence (%) and prevalence ratios (PR, 95% CIs) are reported.

RESULTS: The lifetime prevalence of GORRIs in ultramarathon runners was 24.4%. Independent factors predicting GORRIs were: higher chronic disease composite score (PR = 2.05 times increase risk for every 2 additional chronic diseases; P < 0.0001), history of allergies (PR = 1.66; P < 0.0001), increased years of recreational running (PR = 1.07 times increased risk for every 5 year increase in running; P < 0.0001), lower average weekly running distance (PR = 0.98 times decreased risk for every 15 km increase weekly running distance; P < 0.0001), and slower average training running speed (PR = 0.96 times decreased risk for every km/h increase in training running speed; P < 0.0001).

CONCLUSIONS: Novel risk factors predicting GORRIs are increased number of chronic diseases and a history of allergies. These factors, together with training variables (years of recreational running, weekly running distance, and training running speed) can be targeted to develop and implement injury prevention, treatment, and rehabilitation interventions in ultramarathon runners.

PMID:34117154 | DOI:10.1097/JSM.0000000000000949

Clin J Am Soc Nephrol. 2021 Jun;16(6):880-888. doi: 10.2215/CJN.19611220. Epub 2021 Jun 11.

ABSTRACT

BACKGROUND AND OBJECTIVES: Despite the increasing prioritization of the promotion of patient activation in nephrology, its applicability to people with CKD is not well established. Before the Patient Activation Measure is universally adopted for use in CKD, it is important to critically evaluate this measure. The aim of this study was to describe the psychometric properties of the Patient Activation Measure in CKD.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A survey containing the 13-item Patient Activation Measure was completed by 942 patients with CKD, not treated with dialysis. Data quality was assessed by mean, item response, missing values, floor and ceiling effects, internal consistency (Cronbach’s alpha and average interitem correlation), and item-rest correlations. Rasch modeling was used to assess item performance and scaling (item statistics, person and item reliability, rating scale diagnostics, factorial test of residuals, and differential item functioning).

RESULTS: The item response was high, with a small number of missing values (<1%). Floor effect was small (range 1%-5%), but the ceiling effect was above 15% for nine items (range 15%-38%). The Patient Activation Measure demonstrated good internal consistency overall (Cronbach α=0.925, and average interitem correlation 0.502). The difficulty of the Patient Activation Measure items ranged from -0.90 to 0.86. Differential item functioning was found for disease type (item 3) and age (item 12). The person separation index was 9.48 and item separation index was 3.21.

CONCLUSIONS: The 13-item Patient Activation Measure appears to be a suitably reliable and valid instrument for assessing patient activation in CKD. In the absence of a kidney-specific instrument, our results support the 13-item Patient Activation Measure as a promising measure to assess activation in those with CKD, although consideration for several items is warranted. The high ceiling effect may be a problem when using the 13-item Patient Activation Measure to measure changes over time.

PMID:34117081 | DOI:10.2215/CJN.19611220

Clin J Am Soc Nephrol. 2021 Jun;16(6):908-915. doi: 10.2215/CJN.16871020. Epub 2021 Jun 11.

ABSTRACT

BACKGROUND AND OBJECTIVES: On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78±22 ml/min per 1.73 m²) who were at high risk of rapid progression were categorized by body mass index (BMI; calculated using nonkidney weight) as normal weight (18.5-24.9 kg/m²; n=670), overweight (25.0-29.9 kg/m²; n=429), or obese (≥30 kg/m²; n=213). Linear and multinomial logistic regression models were used to determine the association of baseline overweight and obesity with change in total kidney volume (TKV) over the 3-year study period.

RESULTS: In fully adjusted models, higher BMI was associated with greater annual percent change in TKV (difference of 1.20 [95% confidence interval (95% CI), 0.85 to 1.55] per five-unit higher BMI). Overweight and obesity were associated with higher odds of annual percent change in TKV of ≥7% versus <5% (overweight: odds ratio, 2.04 [95% CI, 1.45 to 2.87]; obese: odds ratio, 4.31 [95% CI, 2.83 to 6.57] versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of -0.95 [95% CI, -2.32 to 0.40] ml/min per 1.73 m² per year per five-unit higher BMI). The three-way interaction (treatment×time×BMI group) was not statistically significant in linear mixed models with an outcome of TKV (log-transformed estimated coefficient comparing the treatment effect for overweight versus normal weight: 0.56% [95% CI, -0.70% to 1.84%] per year; P=0.38; obese versus normal weight: 0.07% [95% CI, -1.47% to 1.63%] per year; P=0.93) or eGFR (estimated coefficient comparing overweight versus normal weight: -0.07 [95% CI, -0.95 to 0.82] ml/min per 1.73 m² per year; P=0.88; obese versus normal weight: 0.22 [95% CI, -0.93 to 1.36] ml/min per 1.73 m² per year; P=0.71).

CONCLUSIONS: Overweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4, NCT00428948.

PMID:34117082 | DOI:10.2215/CJN.16871020

Clin J Am Soc Nephrol. 2021 Jun;16(6):862-869. doi: 10.2215/CJN.18841220. Epub 2021 Jun 11.

ABSTRACT

BACKGROUND AND OBJECTIVES: AKI is associated with poor short- and long-term outcomes. Questions remain about the frequency and timing of AKI, and whether AKI is a cause of death in extremely low gestational age neonates.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Kidney Disease Study examines the kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo Neuroprotection study, a randomized, placebo-controlled trial of recombinant human erythropoietin. We included 900 of 941 patients enrolled in Preterm Epo Neuroprotection. Baseline characteristics were compared by primary exposure (severe AKI versus none/stage 1 AKI) using unadjusted logistic regression models. Cox regression models estimated the relationship between severe AKI and death after adjustment for potential confounders. Time-dependent AKI was modeled as a binary outcome and a categorical variable by stage of AKI. We fit Cox models using time-dependent AKI status lagged by <7 days before death. Landmark analyses examined the relationship of death with development of severe AKI.

RESULTS: Severe AKI occurred in 168 of 900 (19%, 95% confidence interval, 17% to 20%) neonates, and stage 3 AKI occurred in 60 (7%, 95% confidence interval, 5% to 8%). Stage 3 AKI occurring 7 days before death (hazard ratio, 3.88; 95% confidence interval, 1.26 to 11.96), intraventricular hemorrhage (hazard ratio, 2.01; 95% confidence interval, 1.01 to 3.99) and sepsis (hazard ratio, 2.85; 95% confidence interval, 1.12 to 7.22) were all independently associated with death. Severe AKI occurring 7 days before death (hazard ratio, 2.21; 95% confidence interval, 0.92 to 5.26) was associated with death but not statistically significant. In a landmark analysis, after adjusting for potential confounders, late (after day 14 and before day 28) severe AKI was strongly associated with higher hazard of death (hazard ratio, 4.57; 95% confidence interval, 1.82 to 11.5).

CONCLUSIONS: Severe AKI occurs frequently in extremely low gestational age neonates. Stage 3 AKI is associated with mortality, and this association is present 7 days before death.

PMID:34117080 | DOI:10.2215/CJN.18841220