Incidence of pulmonary toxicity in bleomycin-containing regimens for testicular cancer with and without the use of growth factor.

INTRODUCTION: The concurrent use of bleomycin and granulocyte colony-stimulating factors (G-CSFs) has historically been debated as a risk factor for bleomycin-induced pulmonary toxicity in patients with both testicular cancer and Hodgkin's lymphoma. The purpose of this study is to evaluate the incidence of pulmonary toxicity in patients with testicular cancer who were treated with bleomycin and pegfilgrastim concurrently. METHODS: This is a retrospective study that includes male patients over the age of 18 years old diagnosed with testicular cancer who received bleomycin-containing chemotherapy regimens with and without the use of G-CSF agents. RESULTS: There were a total of 33 patients identified as receiving bleomycin, with 30 of those patients having received concurrent G-CSF therapy. Of the patients who received G-CSF therapy, 11 patients (36.6%) experienced pulmonary toxicity leading to discontinuation of bleomycin or changes in chemotherapy regimens altogether. CONCLUSION: There were no major differences in patient demographics or risk factors between those who received G-CSF and developed pulmonary toxicity and those who received G-CSF but did not develop pulmonary toxicity. Further studies are needed in order to fully assess the risk of pulmonary toxicity with this chemotherapy regimen.

Implementation of a medication delivery service for ambulatory oncology infusion patients.

OBJECTIVE: Patients receiving infusions for the treatment of cancer are commonly prescribed supportive care medications which are filled through retail pharmacies. The initial phase of the COVID-19 pandemic created hurdles for patients to receive supportive care medications due to concerns related to exposure risk. Meds-to-Chemo Chairs (M2CC) was created allowing an onsite retail pharmacy to dispense and hand-deliver supportive care prescriptions to patients in the infusion suite. The purpose of this study was to assess the value of this program. DATA SOURCES: The volume of prescriptions dispensed through the M2CC service, as well as the financial impact, was tracked through the prescription software system used by the onsite retail pharmacy dispensing and delivering the medications. DATA SUMMARY: Through the first 2.5 years of the program, M2CC has delivered over 13,000 prescriptions with an estimated gross revenue of $3.5 million. CONCLUSIONS: The M2CC medication delivery program has proved to be highly successful and feasible.

Correlation Between Trough Level of Abiraterone and Prostate-Specific Antigen (PSA) Response in Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND Prostate cancer growth is primarily driven by testosterone and 5a-dihydrotestosterone. Abiraterone is an irreversible inhibitor of CYP17, and CYP17 inhibition is a required step in testosterone biosynthesis. Previous studies have shown that abiraterone trough levels are predictive of prostate-specific antigen (PSA) response in metastatic castrate-resistant prostate cancer (mCRPC). It has not been demonstrated if this association exists for patients with metastatic hormone-sensitive prostate cancer (mHSPC). In this study, we aimed to explore the correlation and association between abiraterone trough levels and PSA levels in patients with mHSPC. MATERIAL AND METHODS This was a single-center, prospective, observational study of patients with mHSPC being treated with abiraterone acetate (AA) 1000 mg once daily. Abiraterone trough levels (22-26 h after drug administration) were drawn at 1, 3, and 7 months after treatment initiation. RESULTS Thirteen patients with mHSPC were enrolled, and complete pharmacokinetic data were available for 8 patients. The mean trough levels at 1 month, 3 months, and 7 months were 34.49 ng/mL (3.36-240.46), 13.82 ng/mL (2.91-29.96), and 15.7 ng/mL (3.58-26.86), respectively. The correlation between the 1-month abiraterone trough level and 1-month PSA level was 0.29 (P=0.38), between 3-month abiraterone trough and 3-month PSA was -0.61 (P=0.08), and between 7-month abiraterone trough and 7-month PSA was -0.31 (P=0.54). CONCLUSIONS This study demonstrated a trend toward a negative correlation between 3-month abiraterone trough levels and PSA levels, but the correlation was not statistically significant. A study with a larger prospective sample size is needed to validate these findings.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

PURPOSE: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. EXPERIMENTAL DESIGN: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. RESULTS: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). CONCLUSION: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

Use of Cystatin C to Assess Immunotherapy Toxicity in a Patient With Melanoma.

The advent of immunotherapy has improved outcomes of patients in a number of cancers.1 While immunotherapy helps the immune system recognize malignant cells, it also can lead to adverse effects that mimic autoimmune diseases including, but not limited to, rash, colitis, pneumonitis, and nephritis. Diagnosis of immunotherapy related nephritis is based on serum creatinine trends, which can be falsely elevated in the setting of high muscle mass. Cystatin C is an adjunctive kidney biomarker that can estimate glomerular filtration rate independent of muscle mass. We present a case where the use of cystatin C avoided unnecessary therapy interruption in a young, athletic man being treated with nivolumab for melanoma. Further research is needed to define the role cystatin C in monitoring kidney function during immunotherapy.

DYSPHAGIA OCCURRENCE IN COVID-19-POSITIVE PATIENTS IN TWO HOSPITALS IN BRAZIL.

BACKGROUND: COVID-19 comprises a respiratory infection resulting from contamination by SARS-CoV-2, with acute respiratory failure being one of its main characteristics, leading to a high frequency of orotracheal intubation (OTI), which in turn increases the risk for dysphagia. Since this can lead to pulmonary impairment, knowing the real occurrence of dysphagia in part of the Brazilian population and its associations allows early and effective clinical management of the multidisciplinary team in relation to patients. OBJECTIVE: To verify the occurrence of dysphagia in COVID-19-positive adult patients in two Brazilian reference hospitals in the care of the pandemic. METHODS: This was a prospective, longitudinal observational study carried out in two private hospitals in Brazil, both references in the care of patients with coronavirus isolation. Data were initially collected by consulting the medical records of each patient. Information was collected regarding sex, age, previous diseases, COVID-19 testing, and the OTI period. After data collection, the clinical speech-language assessment of swallowing for each patient was carried out using the adapted Gugging Swallowing Screen (GUSS), the ASHA NOMS and the Functional Oral Intake Scale (FOIS). RESULTS: A total of 129 participants were evaluated, with a mean age of 72 years. According to the GUSS scale, 9.3% of the patients presented normal/functional swallowing, while 90.7% presented dysphagia, with mild dysphagia in 17.05%, moderate dysphagia in 33.33%, and severe dysphagia in 37.98%. As for the results of the ASHA NOMS, the majority (36.5%) of the patients were at level 1, which represents the patient who is not able to receive his or her food supply orally, having the need to use tube feedings. This is in line with the results observed with the FOIS scale, whereby most patients (42.1%) were classified as Level I, when food intake occurs exclusively through feeding tubes, with no oral supply. Of the 129 participants, 59% of them required OTI. When comparing the time of OTI and the severity of dysphagia, there was a statistically significant difference, with more severe dysphagia, the longer the patient remained intubated. CONCLUSION: There is a high incidence of oropharyngeal dysphagia in patients with COVID-19, with increased severity during longer periods of OTI.

Evaluation of Fall and Fracture Risk Among Men With Prostate Cancer Treated With Androgen Receptor Inhibitors: A Systematic Review and Meta-analysis.

Importance: A high incidence of fall and fracture in a subset of patients treated with androgen receptor inhibitors (ARIs) has been reported, although the relative risk (RR) of fall and fracture for patients who receive ARI treatment is unknown. Objective: To evaluate whether treatment with ARIs is associated with an elevated relative risk for fall and fracture in patients with prostate cancer. Data Sources: Cochrane, Scopus, and MedlinePlus databases were searched from inception through August 2019. Study Selection: Randomized clinical trials comparing patients with prostate cancer treated with any ARI or placebo were included. Data Extraction and Synthesis: Two independent reviewers used a standardized data extraction and quality assessment form. A mixed effects model was used to estimate the effects of ARI on relative risk, with included studies treated as random effects and study groups treated as fixed effects in the pooled analysis. Sample size for each study was used to weight the mixed model. Statistical analysis was performed from August to October 2019. Main Outcomes and Measures: The primary outcome was RR of fall and fractures for patients receiving ARI treatment. Results: Eleven studies met this study's inclusion criteria. The total population was 11 382 men (median [range] age: 72 [43-97] years), with 6536 in the ARI group and 4846 in the control group. Participants in the ARI group could have received enzalutamide, apalutamide, or darolutamide in combination with androgen deprivation therapy or other enzalutamide combinations; patients in the control group could have received placebo, bicalutamide, or abiraterone. The reported incidence of fall was 525 falls (8%) in the ARI group and 221 falls (5%) in the control group. The incidence of fracture was 242 fractures (4%) in the ARI group and 107 fractures (2%) in the control group. Use of an ARI was associated with an increased risk of falls and fractures: all-grade falls (RR, 1.8; 95% CI, 1.42-2.24; P < .001); grade 3 or greater fall (RR, 1.6; 95% CI, 1.27-2.08; P < .001); all-grade fracture (RR, 1.59; 95% CI, 1.35-1.89; P < .001), and likely grade 3 or greater fracture (RR, 1.71; 95% CI, 1.12-2.63; P = .01). Conclusions and Relevance: Use of ARI was associated with an increase in falls and fractures in patients with prostate cancer as assessed by a retrospective systematic review and meta-analysis. Further studies are warranted to identify and understand potential mechanisms and develop strategies to decrease falls and fractures associated with ARI use.

The Effect of Speaking Valves on ICU Mobility of Individuals With Tracheostomy.

BACKGROUND: Early mobilization is part of the rehabilitation process for critically ill patients and is currently considered a means of preventing ICU-acquired muscle deterioration and worsening of physical function. We sought to determine whether the use of speaking valves in tracheostomized patients would improve their mobility. We evaluated the changes in mobility performance with the use of speaking valves in tracheostomized subjects. METHODS: We performed a cohort study of a series of subjects who were tracheostomized and were being weaned from mechanical ventilation between April 2016 and May 2018. The subjects were those able to tolerate a speaking valve for a minimum of 30 min. Demographic data, comorbidities, cause of ICU admission, days in the ICU, duration of mechanical ventilation before tracheostomy, and days free from mechanical ventilation before tracheostomy were collected. Mobility status was evaluated using daily measurements of the Perme Intensive Care Unit Mobility Score. RESULTS: During the study period, 63 patients were tracheostomized. Patients with deficiencies in language (n = 2) or cognitive deficits (n = 36) and patients in exclusive palliative care (n = 7) were excluded. Eighteen subjects were enrolled in the study. The mean age of the subjects was 64.6 ± 14.2 y (55.5% were male), and the most common reason for ICU admission was pneumonia (n = 7; 38.8%). Perme scores increased from 11.3 (interquartile range 10.1-12.0) on the day before initiation of the speaking valve to 18.2 (IQR 16.2-20.1) immediately after the initiation of a speaking valve (P < .01). These changes were maintained during all periods of speaking valve use. CONCLUSIONS: The use of speaking valves in tracheostomized subjects improved mobility.

Ocorrência de disfagia em pacientes COVID-19 positivo em dois hospitais do Brasil / Dysphagia occurrence in covid-19-positive patients in two hospitals in brazil

ABSTRACT Background COVID-19 comprises a respiratory infection resulting from contamination by SARS-CoV-2, with acute respiratory failure being one of its main characteristics, leading to a high frequency of orotracheal intubation (OTI), which in turn increases the risk for dysphagia. Since this can lead to pulmonary impairment, knowing the real occurrence of dysphagia in part of the Brazilian population and its associations allows early and effective clinical management of the multidisciplinary team in relation to patients. Objective To verify the occurrence of dysphagia in COVID-19-positive adult patients in two Brazilian reference hospitals in the care of the pandemic. Methods This was a prospective, longitudinal observational study carried out in two private hospitals in Brazil, both references in the care of patients with coronavirus isolation. Data were initially collected by consulting the medical records of each patient. Information was collected regarding sex, age, previous diseases, COVID-19 testing, and the OTI period. After data collection, the clinical speech-language assessment of swallowing for each patient was carried out using the adapted Gugging Swallowing Screen (GUSS), the ASHA NOMS and the Functional Oral Intake Scale (FOIS). Results A total of 129 participants were evaluated, with a mean age of 72 years. According to the GUSS scale, 9.3% of the patients presented normal/functional swallowing, while 90.7% presented dysphagia, with mild dysphagia in 17.05%, moderate dysphagia in 33.33%, and severe dysphagia in 37.98%. As for the results of the ASHA NOMS, the majority (36.5%) of the patients were at level 1, which represents the patient who is not able to receive his or her food supply orally, having the need to use tube feedings. This is in line with the results observed with the FOIS scale, whereby most patients (42.1%) were classified as Level I, when food intake occurs exclusively through feeding tubes, with no oral supply. Of the 129 participants, 59% of them required OTI. When comparing the time of OTI and the severity of dysphagia, there was a statistically significant difference, with more severe dysphagia, the longer the patient remained intubated. Conclusion: There is a high incidence of oropharyngeal dysphagia in patients with COVID-19, with increased severity during longer periods of OTI.

RESUMO Contexto A COVID-19 compreende uma infecção respiratória decorrente da contaminação pelo vírus SARS-CoV-2, sendo a insuficiência respiratória aguda uma de suas principais características, levando a uma alta frequência de intubação orotraqueal (IOT), que por sua vez aumenta o risco para a disfagia. Uma vez que esta pode levar ao comprometimento pulmonar, conhecer a real ocorrência de disfagia em parte da população brasileira e suas associações permite o manejo clínico precoce e eficaz da equipe multidisciplinar em relação aos pacientes. Objetivo: Verificar a ocorrência de disfagia em pacientes adultos positivos para COVID-19 em dois hospitais brasileiros, referências no atendimento à pandemia. Métodos: Trata-se de um estudo prospectivo, observacional longitudinal, realizado em dois hospitais privados no Brasil, ambos referências no atendimento de pacientes com isolamento por coronavírus. Inicialmente os dados foram levantados por meio de consulta aos prontuários de cada paciente. Foram também coletadas informações sobre sexo, idade, doenças anteriores, teste de COVID-19 e período de IOT. Após a coleta de dados, foi realizada a avaliação fonoaudiológica clínica da deglutição de cada paciente por meio do Gugging Swallowing Screen (GUSS) adaptado, do ASHA NOMS e da Functional Oral Intake Scale (FOIS). Resultados Foram avaliados 129 participantes, com média de idade de 72 anos. De acordo com a escala GUSS, 9,3% dos pacientes apresentaram deglutição normal/funcional, enquanto 90,7% apresentaram disfagia, sendo esta de grau leve em 17,05%, moderado em 33,33% e grave em 37,98%. Quanto aos resultados do ASHA NOMS, a maioria (36,5%) dos pacientes encontrava-se no nível 1, que representa o paciente que não consegue receber alimentação por via oral, tendo a necessidade do uso de alimentação por sonda. Esse dado está de acordo com os resultados observados com a escala FOIS, em que a maioria dos pacientes (42,1%) foi classificada como nível I, quando a ingestão de alimentos ocorre exclusivamente por sondas, sem oferta por via oral. Dos 129 participantes, 59% deles necessitaram de IOT. Ao comparar o tempo de IOT e a gravidade da disfagia, encontrou-se diferença estatisticamente significante, sendo que quanto mais grave a disfagia, maior o tempo que o paciente permaneceu intubado. Conclusão Existe alta incidência de disfagia orofaríngea em pacientes com COVID-19, com maior gravidade durante períodos mais longos de IOT.

Association between neurological injury and the severity of oropharyngeal dysphagia after stroke.

PURPOSE: To associate the degree of biomechanical impairment in the swallowing process with the severity (National Institute of Health Stroke Scale - NIHSS) and type of neurological injury in patients post stroke. METHODS: A cross-sectional, descriptive study conducted with 42 patients (22 females), aged 65.7 years on average diagnosed with stroke. All patients underwent clinical neurological evaluation and application of the NIHSS in the first 48 hours after stroke. The swallowing function was evaluated using the Functional Oral Intake Scale (FOIS) and the Protocol for the Investigation of Oropharyngeal Dysphagia in Adults. The Fisher's Exact Probability Test was used to assess the correlation between the degree of swallowing impairment and the severity (NIHSS score) and type of stroke. The study results were statistically analyzed at 5% significance level (p≤0.05). RESULTS: 92.9% of the patients presented ischemic stroke; 59.5% presented impairment of the anterior cerebral circulation. Statistically significant correlation was found between the neurological scale (NIHSS) scores and the swallowing impairment scale (p=0.016). CONCLUSION: An association between stroke severity and oropharyngeal dysphagia severity was observed. A high proportion of patients with ischemic stroke with circulation affected in the anterior cerebral region presented severe oropharyngeal dysphagia. No statistically significant correlation was observed between the FOIS scale and stroke severity.

Desempenho da alimentação oral em recém-nascidos prematuros estimulados pela técnica treino de deglutição / Oral feeding performance in premature infants stimulated by swallowing technical training

RESUMO Introdução A prematuridade pode afetar o desenvolvimento adequado do recém-nascido. Objetivo Avaliar o desempenho para a alimentação via oral em recém-nascidos prematuros, estimulados pela técnica treino de deglutição. Métodos A pesquisa ocorreu em uma unidade de terapia intensiva neonatal, no período de março a agosto de 2015. Trata-se de um estudo Quase Experimento de Série Temporal com 14 recém-nascidos pré-termo (RNPT), com idade gestacional corrigida entre 30-36 semanas. Foi aplicado o protocolo de avaliação da prontidão do prematuro para início da alimentação oral (pré e pós-treino de deglutição). O treino de deglutição ocorreu uma vez ao dia e, em média, durante seis dias consecutivos. Resultados Verificou-se melhora pós-estimulação, comparando-se os dados do protocolo pré-intervenção e pós-intervenção. Quanto aos níveis de habilidades de alimentação por via oral, 50% dos prematuros foram classificados como nível 4. A alimentação via oral foi iniciada, em média, 1 dia após o término do treino de deglutição; a sonda alimentar foi retirada em, aproximadamente, 7 dias após o início da via oral. Houve associação inversa limítrofe entre melhora no escore de prontidão e tempo de transição da via alternativa para a via oral total e associação inversa entre melhora no escore de prontidão e idade gestacional corrigida. Conclusão A intervenção com treino de deglutição possibilitou melhora na habilidade de alimentação em 50% da amostra, com início da alimentação via oral e obtenção da alimentação exclusiva via oral em um curto período de tempo, com prontidão para via oral em idades gestacionais precoces.

ABSTRACT Introduction Prematurity can affect proper development of a newborn. Purpose To evaluate performance of oral feeding in preterm infants stimulated by the swallowing training technique. Methods The study was conducted in a neonatal intensive care unit from March to August 2015. The study was developed as a Times Series Quasi Experiment with 14 preterm newborns (PTNB) with corrected gestational age between 30-36 weeks. The readiness to feed orally protocol for preterm infants (pre and post-swallowing training) was applied. Swallowing exercises were conducted once a day and on average for six consecutive days. Results Improvement post-stimulation was observed, comparing the pre-intervention and post-intervention protocol data. Regarding oral feeding skills, 50% of preterm infants were classified as level 4. Oral feeding commenced, on average, 1 day after the end of swallowing training; the gastric tube was removed approximately 7 days after beginning oral feeding. There was a borderline inverse relationship between improvement in the readiness score and transition time from tube to full oral feeding and an inverse relationship between improvement in the readiness score and corrected gestational age. Conclusion The intervention with swallowing training made it possible to improve feeding skills in 50% of the sample population, starting oral feeding and obtaining exclusive oral feeding in a short period of time, with oral readiness at early gestational ages.

Association between neurological injury and the severity of oropharyngeal dysphagia after stroke

ABSTRACT Purpose To associate the degree of biomechanical impairment in the swallowing process with the severity (National Institute of Health Stroke Scale – NIHSS) and type of neurological injury in patients post stroke. Methods A cross-sectional, descriptive study conducted with 42 patients (22 females), aged 65.7 years on average diagnosed with stroke. All patients underwent clinical neurological evaluation and application of the NIHSS in the first 48 hours after stroke. The swallowing function was evaluated using the Functional Oral Intake Scale (FOIS) and the Protocol for the Investigation of Oropharyngeal Dysphagia in Adults. The Fisher’s Exact Probability Test was used to assess the correlation between the degree of swallowing impairment and the severity (NIHSS score) and type of stroke. The study results were statistically analyzed at 5% significance level (p≤0.05). Results 92.9% of the patients presented ischemic stroke; 59.5% presented impairment of the anterior cerebral circulation. Statistically significant correlation was found between the neurological scale (NIHSS) scores and the swallowing impairment scale (p=0.016). Conclusion An association between stroke severity and oropharyngeal dysphagia severity was observed. A high proportion of patients with ischemic stroke with circulation affected in the anterior cerebral region presented severe oropharyngeal dysphagia. No statistically significant correlation was observed between the FOIS scale and stroke severity.