Barriers and enablers to screening, management and referral of sleep disorders in patients attending cardiac rehabilitation: A qualitative descriptive study.

AIMS: To examine healthcare professional's knowledge about assessment and management of sleep disorders for cardiac patients and to describe the barriers to screening and management in cardiac rehabilitation settings. DESIGN: A qualitative descriptive study. Data were collected via semi-structured interviews. METHODS: In March 2022, a total of seven focus groups and two interviews were conducted with healthcare professionals who currently work in cardiac rehabilitation settings. Participants included 17 healthcare professionals who had undertaken cardiac rehabilitation training within the past 5 years. The study adheres to the consolidated criteria for reporting qualitative research guidelines. An inductive thematic analysis approach was utilized. RESULTS: Six themes and 20 sub-themes were identified. Non-validated approaches to identify sleep disorders (such as asking questions) were often used in preference to validated instruments. However, participants reported positive attitudes regarding screening tools provided they did not adversely affect the therapeutic relationship with patients and benefit to patients could be demonstrated. Participants indicated minimal training in sleep issues, and limited knowledge of professional guidelines and recommended that more patient educational materials are needed. CONCLUSION: Introduction of screening for sleep disorders in cardiac rehabilitation settings requires consideration of resources, the therapeutic relationship with patients and the demonstrated clinical benefit of extra screening. Awareness and familiarity of professional guidelines may improve confidence for nurses in the management of sleep disorders for patients with cardiac illness. IMPACTS: The findings from this study address healthcare professionals' concerns regarding introduction of screening for sleep disorders for patients with cardiovascular disease. The results indicate concern for therapeutic relationships and patient management and have implications for nursing in settings such as cardiac rehabilitation and post-cardiac event counselling. REPORTING METHOD: Adherence to COREQ guidelines was maintained. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution as this study explored health professionals' experiences only.

Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.

Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of "sickness", that has knock-on effects to the blood-brain barrier, brain-spinal barrier, blood-cerebrospinal fluid barrier, neuro-axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof-of-concept study to link for the first time late non-CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO-binding PET tracer [11 C]-PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non-CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non-central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral-to-centralized inflammatory response in non-CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms.

Development of a short form of the Cardiac Distress Inventory.

BACKGROUND: Cardiac distress may be viewed as a persistent negative emotional state that spans multiple psychosocial domains and challenges a patient's capacity to cope with living with their heart condition. The Cardiac Distress Inventory (CDI) is a disease-specific clinical assessment tool that captures the complexity of this distress. In busy settings such as primary care, cardiac rehabilitation, and counselling services, however, there is a need to administer briefer tools to aid in identification and screening. The aim of the present study was to develop a short, valid screening version of the CDI. METHODS: A total of 405 participants reporting an acute coronary event in the previous 12 months was recruited from three hospitals, through social media and by direct enrolment on the study website. Participants completed an online survey which included the full version of the CDI and general distress measures including the Kessler K6, Patient Health Questionnaire-4, and Emotion Thermometers. Relationship of the CDI with these instruments, Rasch analysis model fit and clinical expertise were all used to select items for the short form (CDI-SF). Construct validity and receiver operating characteristics in relation to the Kessler K6 were examined. RESULTS: The final 12 item CDI-SF exhibited excellent internal consistency indicative of unidimensionality and good convergent and discriminant validity in comparison to clinical status measures, all indicative of good construct validity. Using the K6 validated cutoff of ≥ 18 as the reference variable, the CDI-SF had a very high Area Under the Curve (AUC) (AUC = 0.913 (95% CI: 0.88 to 0.94). A CDI-SF score of ≥ 13 was found to indicate general cardiac distress which may warrant further investigation using the original CDI. CONCLUSION: The psychometric findings detailed here indicate that the CDI-SF provides a brief psychometrically sound screening measure indicative of general cardiac distress, that can be used in both clinical and research settings.

Prophylactic gabapentin during head and neck cancer therapy: a systematic review and meta-analysis.

PURPOSE: This review was designed to compile the currently available evidence on the prophylactic use of gabapentin in the head and neck cancer patient population. METHODS: A systematic search was conducted of PubMed, Web of Science, and Google Scholar to identify articles related to the use of prophylactic gabapentin in patients undergoing head and neck cancer therapy. Candidate studies were screened for inclusion and a subsequent bias assessment was conducted by multiple reviewers. Meta-analysis was conducted in cases in which the studies used compatible outcome measures. RESULTS: Ten studies were identified that met the inclusion criteria and were assessed for bias. Among the four small studies that examined pain prevention, 2 were positive and 2 were inconclusive. Three of the four studies examiniRDng opioid use noted less need for opioids in the treatment arm. Meta-analysis of the pertinent studies showed no difference in feeding tube placement (RD = 0.64%, 95%CI: (- 25.8%, 27.1%), p = 0.962) but substantially less weight loss among those in the treatment arm (p = 0.047). CONCLUSION: Prophylactic gabapentin appears to be a promising treatment option for preventing pain, reducing opioids, and reducing weight loss in patients undergoing head and neck cancer therapy. However, the studies on the treatment to date are small and several have a substantial risk of bias.

Impact of Early COVID-19 Waves on Cardiac Rehabilitation Delivery in Australia: A National Survey.

BACKGROUND: The novel coronavirus disease of 2019 (COVID-19) pandemic significantly disrupted health care, especially outpatient services such as cardiac rehabilitation (CR). We investigated the impact of early COVID-19 waves on the delivery of Australian CR programs, comparing this time period with usual practice prior to the pandemic (2019) and current practice (2021) once the early waves had subsided. Specifically, we aimed to understand how the delivery of programs during COVID-19 compared to usual practice. METHODS: An anonymous online cross-sectional survey of Australian CR program staff was conducted, comprising three sections: program and respondent characteristics, COVID-19 impact on program delivery, and barriers to, and enablers of, program delivery. Respondents were asked to consider three key timepoints: 1) Pre-COVID-19 (i.e. usual practice in 2019), 2) Early COVID-19 waves (March-December 2020), and 3) Currently, at time of survey completion post early COVID-19 waves (May-July 2021). RESULTS: Of the 314 Australian CR programs, 115 responses were received, of which 105 had complete data, representing a 33% response rate. All states and territories were represented. During early COVID-19 waves programs had periods of closure (40%) or reduced delivery (70%). The majority of programs reported decreased CR referrals (51.5%) and decreased participation (77.5%). The two core components of CR-exercise and education-were significantly impacted during early COVID-19 waves, affecting both the number and duration of sessions provided. Exercise session duration did not return to pre-pandemic levels (53.5 min compared to 57.7 min, p=0.02). The majority of respondents (77%) reported their CR program was inferior in quality to pre-pandemic and more organisational support was required across information technology, staffing, administration and staff emotional and social support. CONCLUSION: Australian CR programs underwent significant change during the early COVID-19 waves, consistent with international CR reports. Fewer patients were referred and attended CR and those who did attend received a lower dose of exercise and education. It will be important to continue to monitor the long-term impacts of the COVID-19 pandemic to ensure CR programs return to pre-pandemic functioning and continue to deliver services in line with best practice and evidence-based recommendations.

Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies.

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

The cardiac distress inventory: A new measure of psychosocial distress associated with an acute cardiac event.

BACKGROUND: Many challenges are posed by the experience of a heart attack or heart surgery which can be characterised as 'cardiac distress'. It spans multiple psychosocial domains incorporating patients' responses to physical, affective, cognitive, behavioural and social symptoms and experiences related to their cardiac event and their recovery. Although some measures of the psychological and emotional impacts of a cardiac event exist, none provides a comprehensive assessment of cardiac distress. To address this gap, the study aimed to develop a Cardiac Distress Inventory (CDI) using best practice in instrument design. METHOD: An item pool was generated through analysis of cognate measures, mostly in relation to other health conditions and through focus group and individual review by a multidisciplinary development team, cardiac patients, and end-users including cardiac rehabilitation co-ordinators. The resulting 144 items were reduced through further reviews to 74 for testing. The testing was carried out with 405 people recruited from three hospitals, through social media and by direct enrolment on the study website. A two-stage psychometric evaluation of the 74 items used exploratory factor analysis to extract the factors followed by Rasch analysis to confirm dimensionality within factors. RESULTS: Psychometric analysis resulted in the identification of 55 items comprising eight subscales, to form the CDI. The subscales assess fear and uncertainty, disconnection and hopelessness, changes to roles and relationships, overwhelm and depletion, cognitive challenges, physical challenges, health system challenges, and death concerns. Validation against the Kessler 6 supports the criterion validity of the CDI. CONCLUSION: The CDI reflects a nuanced understanding of cardiac distress and should prove to be a useful clinical assessment tool, as well as a research instrument. Individual subscales or the complete CDI could be used to assess or monitor specific areas of distress in clinical practice. Development of a short form screening version for use in primary care, cardiac rehabilitation and counselling services is warranted.

AKI in Hospitalized Patients with COVID-19.

BACKGROUND: Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described. METHODS: This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. RESULTS: Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. CONCLUSIONS: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.

Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict progression of diabetic kidney disease.

AIM: Predicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX™) combining electronic health records (EHR) and biomarkers. METHODS: This is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for predicting a composite outcome of eGFR decline of ≥5 ml/min per year, ≥40% sustained decline, or kidney failure within 5 years. RESULTS: In 1146 patients, the median age was 63 years, 51% were female, the baseline eGFR was 54 ml min-1 [1.73 m]-2, the urine albumin to creatinine ratio (uACR) was 6.9 mg/mmol, follow-up was 4.3 years and 21% had the composite endpoint. On cross-validation in derivation (n = 686), KidneyIntelX had an AUC of 0.77 (95% CI 0.74, 0.79). In validation (n = 460), the AUC was 0.77 (95% CI 0.76, 0.79). By comparison, the AUC for the clinical model was 0.62 (95% CI 0.61, 0.63) in derivation and 0.61 (95% CI 0.60, 0.63) in validation. Using derivation cut-offs, KidneyIntelX stratified 46%, 37% and 17% of the validation cohort into low-, intermediate- and high-risk groups for the composite kidney endpoint, respectively. The PPV for progressive decline in kidney function in the high-risk group was 61% for KidneyIntelX vs 40% for the highest risk strata by KDIGO categorisation (p < 0.001). Only 10% of those scored as low risk by KidneyIntelX experienced progression (i.e., NPV of 90%). The NRIevent for the high-risk group was 41% (p < 0.05). CONCLUSIONS: KidneyIntelX improved prediction of kidney outcomes over KDIGO and clinical models in individuals with early stages of DKD.

Advanced pneumatic compression for treatment of lymphedema of the head and neck: a randomized wait-list controlled trial.

PURPOSE: Lymphedema associated with head and neck cancer (HNC) therapy causes adverse clinical outcomes. Standard treatment includes professionally administered complete decongestive therapy (CDT). Cost and availability of trained therapists are known barriers to therapy. Advanced pneumatic compression devices (APCD) may address these issues. A randomized, wait-list controlled trial was undertaken to evaluate an APCD in post-treatment HNC patients with lymphedema. MATERIAL AND METHODS: Eligible patients had completed treatment for HNC, were disease free, and had lymphedema at enrollment. Participants were randomized to wait-list lymphedema self-management (standard of care) or lymphedema self-management plus the use of the APCD bid. Safety (CTCAE V4.0) and feasibility were primary endpoints; secondary endpoints included efficacy measure by objective examination and patient reported outcomes (symptoms, quality of life, function), adherence barriers, and satisfaction. Assessments were conducted at baseline and weeks 4 and 8. RESULTS: Forty-nine patients were enrolled (wait-list n = 25; intervention n = 24). In total, forty-three patients completed the study. No device-related Serious Adverse Events were reported. Most patients used the APCD once per day, instead of the prescribed twice per day, citing time related factors as barriers to use. APCD use was associated with significant improvement in perceived ability to control lymphedema (p = 0.003) and visible external swelling (front view p < 0.001, right view p = 0.004, left p = 0.005), as well as less reported pain. CONCLUSION: This trial supports the safety and feasibility of the APCD for the treatment of secondary lymphedema in head and neck cancer patients. In addition, preliminary data supports efficacy.

Identification of the blue light intensity administered to one eye required to suppress bovine plasma melatonin and investigation into effects on milk production in grazing dairy cows.

Long-day photoperiod is known to positively affect milk production in confinement dairy systems, and it has been hypothesized that pineal melatonin (MT) secretion plays a substantial role in this process. Specialized mammalian photoreceptors that regulate MT secretion are optimally stimulated by short wavelength blue light. We investigated the blue light intensity administered to one eye required to suppress MT secretion in nonlactating dairy cows, and subsequently examined effects on milk production in grazing dairy cows. Following a 14-d light-dark 8:16 h environmental conditioning period, 5 nonlactating Holstein-Friesian cows were exposed to treatments of <1, 70, 125, 175, and 225 lx for 8 additional hours using a 5 × 5 Latin square design. Light was administered via headpieces fitted with light-emitting diodes emitting blue light (465 nm) to the right eye. All cows were then exposed to a light-dark 16:8 h cycle for one night via the indoor lighting system (>200 lx white light). Plasma samples collected at regular intervals were assayed for MT. A dose-dependent effect of light treatment on mean circulating MT concentrations (and 95% CI) was observed [9.4 (7.2, 12.3), 5.0 (3.8, 6.6), 4.4 (3.3, 5.7), 3.3 (2.5, 4.3) and 1.7 (1.3, 2.3) pg/mL for treatments of 0, 70, 125, 175, and 225 lx, respectively. Only the 225 lx treatment acutely suppressed plasma melatonin concentration to levels similar to the light-dark 16:8 h treatment [1.9 (1.4, 2.5) pg/mL]. Forty spring-calving cows were blocked on parity, calving date and Economic Breeding Index for milk production and assigned to the control treatment or blue light to a single eye (LT) treatment from calving through 32 wk of lactation. The cows assigned to LT treatment were fitted with headpieces providing 225 lx of blue light to the right eye from 1700 until 0000 h. Mean milk production (and 95% CI) during 32 wk of lactation was not affected by treatment [20.3 (19.3, 21.3) vs. 20.9 (19.8, 22.0) kg/d, control and LT, respectively]. Within multiparous cows, a treatment by week interaction was detected, whereby LT treatment increased milk production during the first 12 wk of lactation [25.8 (24.3, 27.3) vs. 28.0 (26.5, 29.5) kg/d; +8.5%], but had no effect thereafter. Treatment did not affect plasma insulin-like growth factor 1. We identified the blue light intensity to one eye required to acutely suppress MT concentrations. Transient favorable effects on milk production were observed in multiparous cows. It remains unclear how single-eye blue light treatment affects galactopoiesis in grazing dairy cows, and further research is needed to explore whether this modality of light delivery represents a useful means to aid productivity in pasture-based dairy systems.

How Does Mental Health Impact Women's Heart Health?

From adolescence until old age, women are more vulnerable to common mental disorders (CMDs; depression and anxiety) than men at all stages of the life course. By middle age, women who have clinical depression are at twice the risk of having an incident cardiovascular disease (CVD) than those without. This has important implications for the way we prevent, identify and treat both CMDs and coronary heart disease in women. In this paper, we discuss the various genetic, biological, ethnic/racial, and psychological pathways by which women's vulnerability to CMDs elevate their CVD risk and recovery from a cardiac event. We review the evidence from trials that have, to date, failed to show that treating depression can reduce or delay the onset or recurrence of CVD events, especially for female patients. We discuss the value of lifestyle-based therapies for treating depression, to which women may be more responsive, and finish by discussing how population-based approaches including risk factor assessment could be tailored to consider these factors.

Health-Care Professionals Perceived Barriers to Effective Cancer Pain Management in the Home Hospice Setting: Is Dying at Home Really Best?

Hospice health-care professionals (HCP) evaluate and manage cancer pain in patient homes. This study explores HCP's perceptions of barriers that affect pain management for home hospice cancer patients. A convenience sample of 20 experienced hospice HCP were recruited from a regional hospice agency. Data were collected through two focus groups using semistructured interviews and analyzed using a constant comparative approach to generate themes. An unexpected finding revealed patient's religious and cultural beliefs about suffering and family caregiver's beliefs that patients deserve to suffer due to past actions are barriers to pain management in home hospice. Hospice HCP can identify patients at risk for suffering at the end of life. Interventions targeting spiritual suffering and needs are needed. Home hospice HCP have an ethical obligation to address undue suffering through family's withholding of necessary pain medications and should consider alternative placement when home is not suitable for a peaceful death.

Genome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis.

Donor-recipient (D-R) differences at human leukocyte antigen (HLA) loci are currently incorporated into organ sharing, allocation and immunosuppression decisions. However, while acute rejection episodes have substantially diminished, progressive histologic damage occurs in allografts and improved long-term survival remains an unrealized goal among kidney recipients. Here we tested the hypothesis that non-HLA dependent, genome-wide D-R genetic differences could contribute to unchecked alloimmunity with histologic and functional consequences, culminating in long-term allograft failure. Genome-wide single nucleotide polymorphism (SNP) array data, excluding the HLA region, was utilized from 385 transplants to study the role of D-R differences upon serial histology and allograft survival. ADMIXTURE analysis was performed to quantitatively estimate ancestry in each D-R pair and PLINK was used to estimate the proportion of genome-shared identity-by-descent (pIBD) between D-R pairs. Subsequently, quantitative measures of recipient ancestry based on non-HLA SNPs was associated with death-censored allograft survival in adjusted Cox models. In D-R pairs of similar ancestry, pIBD was significantly associated with allograft survival independent of HLA mismatches in 224 transplants. Surprisingly, pIBD and recipient ancestry were not associated with clinical or subclinical rejection at any time post-transplant. Significantly, in multivariable analysis, pIBD inversely correlated with vascular intimal fibrosis in 160 biopsies obtained less than one year which in turn was significantly associated with allograft survival. Thus, our novel data show that non-HLA D-R differences associate with early vascular intimal fibrosis and allograft survival.

Use of biomarkers to improve immunosuppressive drug development and outcomes in renal organ transplantation: A meeting report.

On September 27-28, 2018 the Food and Drug Administration (FDA) and the Critical Path Institute's Transplant Therapeutics Consortium convened a public workshop titled "Evidence-Based Treatment Decisions in Transplantation: The Right Dose & Regimen for the Right Patient/Individualized Treatment." The workshop facilitated cooperative engagement of transplant community stakeholders, including pharmaceutical industry, academic researchers, clinicians, patients, and regulators to discuss methods to advance the development of novel immunosuppressive drugs for use in solid organ transplantation. Day 1 focused on the utility of biomarkers in drug development, with considerations for seeking regulatory endorsement for use in clinical trials. Biomarkers add value to drug development by improving patient selection criteria, safety monitoring, endpoint selection, and more. Regulatory endorsement through the FDA Biomarker Qualification Program encourages the use of biomarkers in drug development by instilling confidence and consistency in biomarker interpretation across trials. Public-private partnerships or consortia allow stakeholders to share expertise, resources, and data in pursuit of biomarker qualification. Biomarkers relevant to pretransplant risk assessment, early posttransplant care, and assessment of immune response, immunosuppressive drug efficacy, and graft function as discussed on day 1 of the workshop are described.

COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

Machine Learning to Predict Mortality and Critical Events in a Cohort of Patients With COVID-19 in New York City: Model Development and Validation.

BACKGROUND: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking. OBJECTIVE: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. METHODS: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions. RESULTS: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. CONCLUSIONS: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes.

A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection.

BACKGROUND: In kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies. METHODS: We examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort. RESULTS: Study participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss. CONCLUSIONS: Our targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients.

The linguistic validation process of the Vanderbilt Head and Neck Symptom Survey - Italian Version (VHNSS-IT).

PURPOSE: To linguistically validate the Italian translation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), there is a patient-reported outcome measure to screen for symptoms in the head and neck cancer (HNC) patients population. The goal was to ensure conceptually equivalence with the original version and maintain clarity, ease of use and understanding. METHODS: We conducted a multi-step linguistic process (forward translation, backward translation and patient testing) to generate and validate an Italian translation of the VHNSS. RESULTS: Two intermediate Italian versions were created: The first Italian version was derived from a reconciliation of the three forward translations, and the second Italian version was derived from changes in the first version after the backward translation step. All investigators involved actively discussed possible solutions to produce a translated instrument that maintained a reading and comprehension level accessible by most respondents, without altering the meaning and content of the original source. During the patient testing step, only two patients reported problems with items comprehension and the rate of comprehension problems per single item was lower than expected. This phase allowed patients to give suggestion in order to make items clearer and easier to understand: 43% of patients proposed a revision of the survey during the face-to-face interview, and most of these suggestions were retained. CONCLUSIONS: A valid multi-step process leads to the creation of the final version of the VHNSS-IT, a suitable instrument to screen for symptoms in the Italian HNC patients population and an official measurement tool that can be used in cooperative research group.

A pilot study on the Vanderbilt head and neck symptom survey Italian version (VHNSS-IT) to test its feasibility and utility in routine clinical practice.

PURPOSE: Patient-reported outcome measures can be useful to assess symptoms in head and neck cancer (HNC) patients treated with radio-chemotherapy. This is a pilot study on the VHNSS-IT (the Italian version of the Vanderbilt head and neck symptom survey) performed to assess both the feasibility and utility of its administration in clinical practice. METHODS: The outcomes analyzed were feasibility to recruit patients, feasibility to complete the questionnaire, feasibility to review the questionnaire, utility perceived by clinicians, distribution of patient's answers reflecting symptom's intensity. RESULTS: Among the 38 patients enrolled, 37 completed the VHNSS-IT (refusal rate 2.6%). Median time of completion was 6'57″. Time of completion was influenced by age (p = 0.002), grade of education (p = 0.023) and employment status (p = 0.004). Time after the start of the radiotherapy course (< 6 months vs. > 6 months) and surgery (yes vs. no) influenced symptoms' intensity. Median time for review was 2'15″. Time burden was perceived to be acceptable for all clinicians; they all also found the questionnaire easy to use. Rates of global perceived utility and future intention to use the questionnaire were 100%. CONCLUSIONS: The VHNSS-IT has demonstrated to be a useful measurement of symptoms' burden for patients with HNC. The survey can be easily completed during the clinic routine without interfering with doctors' visits schedule, and it can help healthcare providers to identify symptoms that require referral, education or intervention.