Patient-reported Adverse Events Research Articles

OC-0440: Proton Therapy Reduces Patient-Reported Adverse Events: A Neural Network for Large-Volume Practice

OC-0440: Proton Therapy Reduces Patient-Reported Adverse Events: A Neural Network for Large-Volume Practice

Digital Health Applications for Pharmacogenetic Clinical Trials.

Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is increasingly being used in clinical trials, and an important field that could potentially benefit from incorporating DH into trial design is pharmacogenetics. Prospective pharmacogenetic trials typically compare a standard care arm to a pharmacogenetic-guided therapeutic arm. These trials often require large sample sizes, are challenging to recruit into, lack patient diversity, and can have complicated workflows to deliver therapeutic interventions to both investigators and patients. Importantly, the use of DH technologies could mitigate these challenges and improve pharmacogenetic trial design and operation. Some DH use cases include (1) automatic electronic health record-based patient screening and recruitment; (2) interactive websites for participant engagement; (3) home- and tele-health visits for patient convenience (e.g., samples for lab tests, physical exams, medication administration); (4) healthcare apps to collect patient-reported outcomes, adverse events and concomitant medications, and to deliver therapeutic information to patients; and (5) wearable devices to collect vital signs, electrocardiograms, sleep quality, and other discrete clinical variables. Given that pharmacogenetic trials are inherently challenging to conduct, future pharmacogenetic utility studies should consider implementing DH technologies and trial methodologies into their design and operation.

Artificial Neural Networks Utilizing Standardly Collected Electronic Healthcare Data Provide Clinically Interpretable Predictions Of Patient-Reported Adverse Events For Breast Cancer

We instituted a prospective registry to capture patient-reported clinical outcomes in a large radiation oncology practice. Herein, we evaluate the predictive power of artificial neural networks (ANN) for adverse events (AEs) assessed by the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAETM) for breast cancer patients. PRO-CTCAE questionnaires were administered at baseline, end-of-treatment, 3, 6, 12 months, then annually. Eligible patients received treatment with curative intent for primary breast cancer. Patient-reported treatment-related symptomatic AEs are defined as a score of “Severe/Frequent” or “Very Severe/Constantly” for any PRO-CTCAE item worse than baseline. ANN algorithms were trained on a blend of synthesized and original data and utilized to predict patient-reported AEs with local interpretable model-agnostic explanations (LIME) used to provide clinical interpretability. Two-hundred and eighty-six (286) patients with a median follow-up of 2.3 years (range, 0.4–3.9) were included for analysis. Patient and tumor characteristics included: 65% ECOG 0, median body mass index (BMI) 27.3 (range, 16.4 – 53.8), 50% pT1, 20% pT2, 6% pT3, 62% pN0, 81% ER+, 76% PR+, and 11% HER2+. Treatment characteristics included: median RT dose 40.05 Gy (range, 21.9–50.4 Gy), 65% treated with hypofractionation, 42% received a boost (median 10 Gy, range 5.4–14 Gy), 84% treated with photons, 16% treated with proton beam therapy, 73% underwent lumpectomy, and 42% received chemotherapy. Baseline-adjusted patient-reported AE rates of “Severe/Frequent” or worse were 33.2%, while “Very Severe/Constantly” was 7.4%. Patients reporting “Severe” or worse AEs were accurately predicted 74.5% (95% CI: 72%, 76%) utilizing the ANN model. LIME demonstrated that patients with: prior lumpectomy or mastectomy, baseline ECOG ≥ 2, lobular histology, and higher dose were at higher risk for developing a “Severe” or worse PRO-CTCAE score greater than their respective pre-RT score. This analysis of standard-of-care, electronically collected healthcare data from a large prospective registry demonstrates that artificial neural networks provide accurate and clinically interpretable predictions of patient-reported AEs. Knowledge of these contributing factors and predictions of patient-reported complications may provide helpful insights to patients being treated for breast cancer.

Clinically Interpretable Predictions of Patient-Reported Adverse Events (PRO-CTCAE) for Prostate Cancer Utilizing Artificial Neural Networks

Patient reported toxicities (PROs) correlate clinically with patient adverse events. We evaluate the predictive power of artificial neural networks (ANN) using clinical, treatment and dosimetric data (DVH), to predict adverse events (AEs) assessed by the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAETM) in prostate cancer patients. From 2016-2018, 252 patients were treated with curative intent radiotherapy (RT) for localized prostate cancer in our prospective IRB approved registry. PRO-CTCAE questionnaires were administered at baseline, end-of-treatment, 3, 6, 12 months, then annually. Patients were curatively treated for primary prostate cancer and completed baseline and at least one post-RT questionnaire. Patient-reported treatment-related AEs are defined as a “Severe/Frequent” or “Very Severe/Constantly” for any PRO-CTCAE (prostate specific or overall quality-of-life) item that is worse than baseline. We synthesized artificial data from the original data, and then tested it for interval validity and external consistency with the original data set. ANN algorithms were constructed utilizing clinical, treatment, and DVH data to predict patient-reported AEs with local interpretable model-agnostic explanations (LIME) to provide clinical interpretability. Median follow-up was 20 months (range: 2.5–40 months) with a median pre-RT PSA of 6.12 (1.3–129), 6.6% non-white, median T Stage T1c (T1b–T3b), median Gleason Score of 7 (3+4, range 6-10), and 99% N0. The median prescribed dose was 70 Gy (38–79.2) in 5 to 44 fractions. Standard fractionation (1.8-2Gy) was used in 120 patients (48.2%), moderate hypofractionation (2-3 Gy) in 87 patients (35.1%), and extreme hypofractionation (>6Gy) in 42 patients (16.7%). Baseline-adjusted patient-reported AE rates of “Severe” or worse were 38%, while “Very Severe” was 19%. Patients reporting “Severe” or worse were accurately predicted 68.4% (95% CI: 66.6%, 69.3%) by the ANN model. LIME demonstrated that patients with: Non-white race, higher number of biopsy cores taken, higher pre-RT PSA, higher CTV volume, higher baseline ECOG, and BED V51 Gy > 14.376% were at higher risk for developing a “Severe” or worse PRO-CTCAE score greater than their respective pre-RT score. Employing clinical, treatment and DVH data, ANN can predict patient reported toxicities with high validity and confidence. We have shown here that we can not only predict changes in PRO-CTCAE for prostate cancer patients, but also predict with narrow confidence intervals patients at high risk to develop patient reported toxicity months in advance of the event.

Changes in Prostate-Specific Patient-Reported Adverse Events (PRO-CTCAE) Prior to Clinical Visit Significantly Predicts Clinician Reported Adverse Events (CTCAE) in Prostate Cancer Patients

Patient reported toxicity is believed to be more sensitive and be found earlier than physician “clinical” reported toxicity (C-AE). We analyzed prostate cancer patients treated with radiotherapy (RT) in an IRB approved prospective registry in a single institution to determine the effectiveness of utilizing patient reported toxicity (PRO-CTCAE) to predict future clinical grade ≥2 adverse events. From 2016-2018, 294 patients were treated with curative intent PBT for localized prostate cancer in our prospective IRB approved registry and completed at least two PRO-CTCAE surveys. PRO-CTCAE score of 2 correlates to ‘moderate’ symptom burden, while a score of 3 correlates to a ‘severe’ symptom burden and they were matched to their corresponding C-AE. To determine predictability every C-AE ≥2 was scored and we determined if patient toxicity was reported within the last 4-weeks and was considered the prognostic toxicity (P-AE). The patient’s reported status prior to the P-AE was used as reference (REF). Paired t-tests were used to show differences between P-AE and REF scores, with one-sample t-tests utilized to determine the magnitude of the P-AE and REF score individually. Median follow-up was 18 months (range: 0.5–40 months) with a median pre-RT PSA of 6.10 (0.1–129), median T Stage T1c (T0–T3b), median Gleason Score of 7 (3+4, range: 6-10), and 99% N0. The median prescribed dose was 70 Gy (38 – 79.2) in 5 to 44 fractions. Grade ≥2 AE (C-AE) were seen in 192 patients (65%). 26 (14%) patients had a P-AE within 1 week of the C-AE; 36 (19%) patients within 2 weeks; 66 (34%) within 4 weeks. For all patients with REF surveys within 4 weeks, the average (95% CI) prostate-specific PRO-CTCAE score was 1.5 (1.3–1.7) demonstrating that prior to the P-AE score patients experience significantly less than ‘moderate’ burden (p< 0.0001). The average P-AE score was significantly greater than ‘moderate’ within 1, 2, or 4 weeks of the AE was 2.53 (2.3-2.8), 2.50 (2.3-2.8), 2.41 (2.0-2.6), respectively (all p<0.001). Therefore, all P-AE scores, predicting CTCAE Grade 2+ are significantly greater than ‘moderate’ burden; however, the further you go from the AE date the lower the P-AE score. There is a significant increase from REF to P-AE; with an average difference of 0.83 (95% CI: 0.4 – 1.3, p<0.001) for 1 week, 1.0 (95% CI: 0.7 – 1.3, p<0.0001) for 2 week, 0.97 (95% CI: 0.7 – 1.2, p<0.0001) for 4 weeks. For prostate cancer patients treated with curative intent, obtaining and understanding patient-reported outcomes through PRO-CTCAE can provide significant clinical impact on the identification and treatment of clinician reported adverse events through C-AE. The implementation of PRO-CTCAE could therefore be utilized as a prognostic tool to predict AEs when patients are unable to be physically present for clinical assessment.

Patient-Reported Adverse Events of Radiopharmaceuticals: A Prospective Study of 1002 Patients.

IntroductionAdverse events of radiopharmaceuticals may be underreported or remain undetected. Patients can provide information about these adverse events to enable healthcare professionals to detect, understand, and manage them more efficiently.ObjectiveIn this study, we aimed to (a) determine the type, causality, and frequency of patient-reported adverse events of radiopharmaceuticals and to (b) assess the onset, outcome, and follow-up of these adverse events from the patient’s perspective.MethodsWe performed a prospective cohort study of 1002 patients who underwent a nuclear medicine examination. Using a validated questionnaire, we collected patient-reported information on adverse events that occurred immediately after administration of the radiopharmaceutical as well as those that occurred later. Adverse events were analysed, coded and assessed for causality by two independent researchers.ResultsA total of 187 (18.7%) patients reported 379 adverse events. Most patient-reported adverse events of radiopharmaceuticals belonged to the ‘general disorder and administration site conditions’ (42.0%) and ‘nervous system disorders’ (16.9%) system organ classes. Of the patient-reported adverse events, 43.0% were possibly or probably causally related to radiopharmaceuticals. We found the frequency of patient-reported adverse drug reactions to diagnostic radiopharmaceuticals to be 2.8%. No important medical events were related to the administrations of diagnostic radiopharmaceuticals. Most adverse events (80.0%) occurred shortly after administration of the radiopharmaceutical and were resolved within a few hours. Some events (20.0%) emerged after patients had left the nuclear medicine department, took longer to resolve, and sometimes prompted the patient to consult a healthcare professional.ConclusionAdverse reactions to diagnostic radiopharmaceuticals can occur, and the frequency reported by patients was found to be 2.8%, which is higher than reported in the existing literature. We hope that the results of this study increase awareness of these adverse reactions among patients and healthcare professionals.Electronic supplementary materialThe online version of this article (10.1007/s40264-020-01006-2) contains supplementary material, which is available to authorized users.

Antibiotic Overuse at Discharge in Hospitalized Patients with Bacteriuria or Treated for Pneumonia: A Multihospital Study

Background: Nearly half of hospitalized patients with bacteriuria or treated for pneumonia receive unnecessary antibiotics (noninfectious or nonbacterial syndrome such as asymptomatic bacteriuria), excess duration (antibiotics prescribed for longer than necessary), or avoidable fluoroquinolones (safer alternative available) at hospital discharge.1–3 However, whether antibiotic overuse at discharge varies between hospitals or is associated with patient outcomes remains unknown. Methods: From July 2017 to December 2018, trained abstractors at 46 Michigan hospitals collected detailed data on a sample of adult, non–intensive care, hospitalized patients with bacteriuria (positive urine culture with or without symptoms) or treated for community-acquired pneumonia (CAP; includes those with the disease formerly known as healthcare-associated pneumonia [HCAP]). Antibiotic prescriptions at discharge were assessed for antibiotic overuse using a previously described, guideline-based hierarchical algorithm.3 Here, we report the proportion of patients discharged with antibiotic overuse by the hospital. We also assessed hospital-level correlation (using Pearson’s correlation coefficient) between antibiotic overuse at discharge for patients with bacteriuria and patients treated for CAP. Finally, we assessed the association of antibiotic overuse at discharge with patient outcomes (mortality, readmission, emergency department visit, and antibiotic-associated adverse events) at 30 days using logit generalized estimating equations adjusted for patient characteristics and probability of treatment. Results: Of 17,081 patients (7,207 with bacteriuria; 9,874 treated for pneumonia), nearly half (42.2%) had antibiotic overuse at discharge (36.3% bacteriuria and 51.1% pneumonia). The percentage of patients discharged with antibiotic overuse varied 5-fold among hospitals from 14.7% (95% CI, 8.0%–25.3%) to 74.3% (95% CI, 64.2%–83.8%). Hospital rates of antibiotic overuse at discharge were strongly correlated between bacteriuria and CAP (Pearson’s correlation coefficient, 0.76; P ≤ .001) (Fig. 1). In adjusted analyses, antibiotic overuse at discharge was not associated with death, readmission, emergency department visit, or Clostridioides difficile infection. However, each day of overuse was associated with a 5% increase in the odds of patient-reported antibiotic-associated adverse events after discharge (Fig. 2). Conclusions: Antibiotic overuse at discharge was common, varied widely between hospitals, and was associated with patient harm. Furthermore, antibiotic overuse at discharge was strongly correlated between 2 disparate diseases, suggesting that prescribing culture or discharge processes—rather than disease-specific factors—contribute to overprescribing at discharge. Thus, discharge stewardship may be needed to target multiple diseases.Funding: This study was supported by the Society for Healthcare Epidemiology of America and by Blue Cross Blue Shield of Michigan and Blue Care Network.Disclosures: Valerie M. Vaughn reports contracted research for Blue Cross and Blue Shield of Michigan, the Department of VA, the NIH, the SHEA, and the APIC. She also reports receipt of funds from the Gordon and Betty Moore Foundation Speaker’s Bureau, the CDC, the Pew Research Trust, Sepsis Alliance, and the Hospital and Health System Association of Pennsylvania.

Effect of Short-term Integrated Palliative Care on Patient-Reported Outcomes Among Patients Severely Affected With Long-term Neurological Conditions

Palliative care has shown benefits in reducing symptom intensity and quality of life in patients with advanced cancer. However, high-quality evidence to support palliative care policy and service developments for patients with long-term neurological conditions (LTNCs) is lacking. To determine the effectiveness of a short-term integrated palliative care (SIPC) intervention for people with LTNCs. Multicenter, phase 3, randomized clinical trial conducted from April 1, 2015, to November 30, 2017, with a last follow-up date of May 31, 2018, in 7 UK hospitals with both neurology and palliative care services. A total of 535 patients with LTNC were assessed for eligibility and 350 were randomized. Inclusion criteria were patients 18 years or older with any advanced stage of multiple sclerosis, motor neuron disease, idiopathic Parkinson disease multiple system atrophy, or progressive supranuclear palsy. Data were analyzed from November 2018 to March 2019. Patients were randomized 1:1 using minimization method to receive SIPC (intervention, n = 176) or standard care (control, n = 174). Primary outcome was change in 8 key palliative care symptoms from baseline to 12-weeks, measured by the Integrated Palliative care Outcome Scale for neurological conditions. Secondary outcomes included change in the burden of other symptoms, health-related quality of life, caregiver burden, and costs. Data were collected and analyzed blindly by intention to treat. A total of 350 patients (mean [SD] age 67 [12] years; years since diagnosis, 12 [range, 0-56]; 51% men; 49% requiring considerable assistance) with an advanced stage of LTNC were recruited, along with informal caregivers (n = 229). There were no between-group differences in primary outcome (effect size, -0.16; 95% CI, -0.37 to 0.05), any other patient-reported outcomes, adverse events, or survival. Although there was more symptom reduction in the SIPC group in relation to mean change in primary outcome, the difference between the groups was not statistically significant (-0.78; 95% CI, -1.29 to -0.26 vs -0.28; 95% CI, -0.82 to 0.26; P = .14). There was a decrease in mean health and social care costs from baseline to 12 weeks -$1367 (95% CI, -$2450 to -$282) in the SIPC group and -653 (95% CI, -$1839 to -$532) in the control group, but this difference was not statistically significant (P = .12). SIPC was perceived by patients and caregivers as building resilience, attending to function and deficits, and enabling caregivers. In this study, SIPC was not statistically significantly different from standard care for the patient-reported outcomes. However, SIPC was associated with lower cost, and in qualitative analysis was well-received by patients and caregivers, and there were no safety concerns. Further research is warranted. isrctn.org Identifier: ISRCTN18337380.

Abstract LB-362: Vaginal microbiome associated with patient-reported sexual dysfunction and physician-reported vaginal adverse events in gynecologic cancer women across radiotherapy

Abstract Background: Women with gynecological cancer (GynCa) undergoing radiation therapy (RT) are at increased risk for acute and long-term sexual dysfunction after treatment. The vaginal microbiome (VM) is the first line of defense against vaginal infection and sexually transmitted diseases. Compositions of VM between women with GynCa receiving RT and healthy women and associations between the VM and sexual dysfunction and vaginal adverse events are unknown. Methods: Using a longitudinal study design, VM, patient-reported sexual dysfunction and physician-reported vaginal adverse events data were collected from postmenopausal GynCa women receiving RT and healthy postmenopausal women. VM swabs from mid-vagina were used for DNA extraction and sequencing of the V3-V4 region of the 16S rRNA gene. Female Sexual Function Index (FSFI) was used to measure women's sexual dysfunction; the Common Terminology Criteria for Adverse Event (CTCAE) Reporting System was used to assess the severity of vaginal adverse events by physicians. All data were collected pre-RT, right after RT completion, 6- and 12-months post-RT. Group-based trajectory modeling was used to identify the sexual dysfunction trajectories. VM compositions were obtained using Qiime and associations with sexual dysfunction trajectories and vaginal adverse events were identified with univariate and multivariate analysis of variance in the R package vegan. Bacterial taxa characteristic for each trajectory group were identified using the LefSe pipeline. Results: Sixty-five patients with GynCa receiving RT and 69 healthy women participated. GynCa and healthy groups had no differences in age and race. VM communities were dominated by Lactobacillus, Prevotella, Dialister and Anaerococcus bacterial genera. We observed higher α-diversity in cancer than healthy patients, and in post-RT VMs than pre-RT. Three groups of sexual dysfunction trajectories were identified: low risk (17.4%), moderate risk (12.3%), and high risk (70.4%). Cancer and healthy women had no difference in sexual dysfunction trajectories. The VM compositions (Bray-Curtis Index) showed significant or marginal associations with vaginal pH (p=0.001), FSFI total score (p=0.001), all domains of FSFI (desire, arousal, lubrication, orgasm, pain, and satisfaction, all p&amp;lt;0.05); CTCAE of vaginal pain (p=0.054), hemorrhage (p=0.004), and inflammation (p=0.071). VM pre-RT predicted the trajectories of arousal (p=0.009), lubrication (p=0.009), and pain (p=0.043). Specific bacterial taxa were enriched in the groups of high risk sexual dysfunction (3 taxa for arousal; 12 taxa for lubrication; 3 taxa for vaginal pain) as compared to low or moderate risk groups. Peptoniphilus, Anaerococcus, and Actinotignum genera were associated with all high risk groups for arousal, lubrication, and pain. Conclusions: Significant associations between VM and sexual dysfunction and vaginal adverse events were found for women with GynCa undergoing RT. Infection-related genera such as Peptoniphilus, Anaerococcus, and Actinotignum genera were enriched in women with high risk of sexual dysfunction. Future research should explore the VM function in the sexual dysfunction and vaginal adverse events in this population. Citation Format: Jinbing Bai, Despina Tsementzi, Pretesh Patel, Joseph Shelton, Mary Dolan, Jessica Arluck, Namita Khanna, Tony Y. Eng, Konstantinos T. Konstantinidis, Deborah Watkins Bruner. Vaginal microbiome associated with patient-reported sexual dysfunction and physician-reported vaginal adverse events in gynecologic cancer women across radiotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-362.

Interventions for the management of obesity in people with bipolar disorder.

Bipolar disorder is one of the most common serious mental illnesses, affecting approximately 60 million people worldwide. Characterised by extreme alterations in mood, cognition, and behaviour, bipolar disorder can have a significant negative impact on the functioning and quality of life of the affected individual. Compared with the general population, the prevalence of comorbid obesity is significantly higher in bipolar disorder. Approximately 68% of treatment seeking bipolar patients are overweight or obese. Clinicians are aware that obesity has the potential to contribute to other physical health conditions in people with bipolar disorder, including diabetes, hypertension, metabolic syndrome, cardiovascular disease, and coronary heart disease. Cardiovascular disease is the leading cause of premature death in bipolar disorder, happening a decade or more earlier than in the general population. Contributing factors include illness-related factors (mood-related factors, i.e. mania or depression), treatment-related factors (weight implications and other side effects of medications), and lifestyle factors (physical inactivity, poor diet, smoking, substance abuse). Approaches to the management of obesity in individuals with bipolar disorder are diverse and include non-pharmacological interventions (i.e. dietary, exercise, behavioural, or multi-component), pharmacological interventions (i.e. weight loss drugs or medication switching), and bariatric surgery. To assess the effectiveness of interventions for the management of obesity in people with bipolar disorder. We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) and the Cochrane Central Register for Controlled Trials (CENTRAL) to February 2019. We ran additional searches via Ovid databases including MEDLINE, Embase, and PsycInfo to May 2020. We searched the World Health Organization (WHO) trials portal (International Clinical Trials Registry Platform (ICTRP)) and ClinicalTrials.gov. We also checked the reference lists of all papers brought to full-text stage and all relevant systematic reviews. Randomised controlled trials (RCTs), randomised at the level of the individual or cluster, and cross-over designs of interventions for management of obesity, in which at least 80% of study participants had a clinical diagnosis of bipolar disorder and comorbid obesity (body mass index (BMI) ≥ 30 kg/m²), were eligible for inclusion. No exclusions were based on type of bipolar disorder, stage of illness, age, or gender. We included non-pharmacological interventions comprising dietary, exercise, behavioural, and multi-component interventions; pharmacological interventions consisting of weight loss medications and medication switching interventions; and surgical interventions such as gastric bypass, gastric bands, biliopancreatic diversion, and vertical banded gastroplasty. Comparators included the following approaches: dietary intervention versus inactive comparator; exercise intervention versus inactive comparator; behavioural intervention versus inactive comparator; multi-component lifestyle intervention versus inactive comparator; medication switching intervention versus inactive comparator; weight loss medication intervention versus inactive comparator; and surgical intervention versus inactive comparator. Primary outcomes of interest were changes in body mass, patient-reported adverse events, and quality of life. Four review authors were involved in the process of selecting studies. Two review authors independently screened the titles and abstracts of studies identified in the search. Studies brought to the full-text stage were then screened by another two review authors working independently. However, none of the full-text studies met the inclusion criteria. Had we included studies, we would have assessed their methodological quality by using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions. We intended to combine dichotomous data using risk ratios (RRs), and continuous data using mean differences (MDs). For each outcome, we intended to calculate overall effect size with 95% confidence intervals (CIs). None of the studies that were screened met the inclusion criteria. None of the studies that were assessed met the inclusion criteria of this review. Therefore we were unable to determine the effectiveness of interventions for the management of obesity in individuals with bipolar disorder. Given the extent and impact of the problem and the absence of evidence, this review highlights the need for research in this area. We suggest the need for RCTs that will focus only on populations with bipolar disorder and comorbid obesity. We identified several ongoing studies that may be included in the update of this review.

The Association of Preoperative Opioid Usage With Patient-Reported Outcomes, Adverse Events, and Return to Work After Lumbar Fusion: Analysis From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

It is important to delineate the relationship between opioid use and spine surgery outcomes. To determine the association between preoperative opioid usage and postoperative adverse events, patient satisfaction, return to work, and improvement in Oswestry Disability Index (ODI) in patients undergoing lumbar fusion procedures by using 2-yr data from a prospective spine registry. Preoperative opioid chronicity from 8693 lumbar fusion patients was defined as opioid-naïve (no usage), new users (<6 wk), short-term users (6 wk-3 mo), intermediate-term users (3-6 mo), and chronic users (>6 mo). Multivariate generalized estimating equation models were constructed. All comparisons were to opioid-naïve patients. Chronic opioid users showed less satisfaction with their procedure at 90 d (Relative Risk (RR) 0.95, P=.001), 1 yr (RR 0.89, P=.001), and 2 yr (RR 0.89, P=.005). New opioid users were more likely to show improvement in ODI at 90 d (RR 1.25, P<.001), 1 yr (RR 1.17, P<.001), and 2 yr (RR 1.19, P=.002). Short-term opioid users were more likely to show ODI improvement at 90 d (RR 1.25, P<.001). Chronic opioid users were less likely to show ODI improvement at 90 d (RR 0.90, P=.004), 1 yr (RR 0.85, P<.001), and 2 yr (RR 0.80, P=.003). Chronic opioid users were less likely to return to work at 90 d (RR 0.80, P<.001). In lumbar fusion patients and when compared to opioid-naïve patients, new opioid users were more likely and chronic opioid users less likely to have improved ODI scores 2 yr after surgery. Chronic opioid users are less likely to be satisfied with their procedure 2 yr after surgery and less likely to return to work at 90 d. Preoperative opioid counseling is advised.

An intergroup collaboration for advanced stage classical Hodgkin lymphoma (cHL) in adolescents and young adults (AYA): SWOG S1826.

TPS8067 Background: Treatment for pediatric cHL varies considerably from that in adult cHL. Hence there are gaps in risk prediction and optimal therapy for de-novo advanced stage disease across the adolescent and young adult (AYA) age spectrum. Early access to novel agents for AYA could be facilitated via collaboration with adult research groups through the U.S. National Cancer Institute’s National Clinical Trials Network (NCTN). The PD-1 inhibitor Nivolumab (Nivo) has safety and efficacy in relapsed and refractory disease in children and adults, but has not been evaluated in de-novo disease to date. Methods: North American cooperative group lymphoma chairs, Cancer Therapy Evaluation Program (CTEP) representatives and patient advocates met to establish consensus on the comparison arms and study design, based on recent historical approaches across adult and pediatric groups. Study champions were identified across North American cooperative groups and include expertise in imaging, radiation oncology, biology and patient-reported outcomes. A therapeutic study was designed with the primary aim being to compare progression-free survival with novel targeted agents in advanced stage cHL. S1826 (NCT03907488), led by SWOG Cancer Research Network, opened to accrual in July 2019. Eligibility criteria include age &gt; 12 years, and Stage III or IV cHL. Patients are randomized (1:1) to 6 cycles of either Nivo-Adriamycin, Vinblastine, Dacarbazine (AVD) or Brentuximab vedotin (Bv)-AVD. Enrollment is stratified by age, baseline International Prognostic Score, and provider intent to use involved site radiation therapy (ISRT). Protocol-prescribed ISRT is response-adapted, based on end of therapy imaging. The primary endpoint is a comparison of progression-free survival between arms. Secondary clinical endpoints include comparison of: overall survival, metabolic response at the end of therapy, physician-reported adverse events, patient-reported adverse events, and health-related quality of life (overall, and specific to fatigue and neuropathy). This unique intergroup collaboration demonstrates the process and the feasibility of consensus study designs toward early adoption of targeted therapies and harmonization of treatment approaches for AYA populations. Clinical trial information: NCT03907488 .

Distribution and frequency of patient-reported symptomatic adverse events at a comprehensive cancer center.

e19117 Background: Systematic review of electronic patient reported outcomes (ePRO) has been shown to improve quality of life and overall survival in clinical trial. We previously demonstrated feasibility of ePRO across Dana-Farber Cancer Institute (DFCI). We sought to examine the distribution and frequency of first symptomatic adverse events (SAEs) among ePRO responders in ambulatory oncology practice. Methods: The ePRO tool uses the validated NCI developed Patient Reported Outcomes – Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument to assess attributes of 15 core SAEs (fatigue, insomnia, general pain, decreased appetite, nausea, vomiting, constipation, diarrhea, shortness of breath, numbness and tingling, rash, concentration, fever, anxiety, sadness) selected by clinician stakeholders and deployed via any internet-enabled device once every 7 days. Responses are viewable in the EHR, scored 0 to 3 using an algorithm, with scores of 3 highlighted to indicate severe grade SAEs. Results: We examined the distribution and frequency of the first 5183 unique ePRO reports for unselected patients seen in the medical, radiation and surgical oncology outpatient clinics of four pilot multidisciplinary clinics (Breast, Genitourinary, Gastrointestinal and Head and Neck) between September 2018-December 2019. Twenty one percent of eligible patients responded to ePRO (5183 of 26,084). Most respondents were female (59%), Caucasian (89%), and age 50-69 years (56% compared to 16% age &lt;50 years, 28% age ≥70; range 19-98 years). The frequency of grade 3 SAEs was pain (10%), fatigue (6%), insomnia (4%), constipation (3%), numbness and tingling/concentration/anxiety/decreased appetite (2%), diarrhea/shortness of breath/sadness (1%), and rash/fever/nausea/vomiting (none) (Table). Conclusions: We observed a consistent distribution of SAEs across cancer types, age and sex. The most frequently reported SAEs are those clinicians struggle to treat with medications - pain, fatigue, insomnia and anxiety. Research to develop effective strategies to address this constellation of SAEs should be prioritized. [Table: see text]

Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis.

Objective: To synthesize the best evidence surrounding the efficacy of cannabinoids for acute pain in the clinical setting based on subjective pain scores and observed adverse effects. Design: Systematic review with meta-analysis. Data Sources: PubMed, Embase, Cochrane Databases, and Google Scholar. Eligibility Criteria: English-language randomized-controlled clinical trials comparing cannabinoids with placebo in patients with acute pain. Data Extraction and Synthesis: Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of three reviewers. Data were pooled through meta-analysis and stratified by route of administration. Primary Outcomes and Measures: Patient-reported pain and adverse events (AEs). Results: Six trials (678 participants) were included examining oral (5 trials) and intramuscular (1 trial) cannabinoids. Overall, there was a small but statistically significant treatment effect favoring the use of cannabinoids over placebo (-0.90, 95% confidence interval [CI] -1.69 to -0.1, i 2=65%, p=0.03). When stratified by route of administration, intramuscular cannabinoids were found to have a significant reduction in pain relative to placebo (-2.98, 95% CI -4.09 to -1.87, i 2=0%, p<0.0001). No difference in effect was observed between oral cannabinoids and placebo (-0.21, 95% CI -0.64 to 0.22, i 2=3%, p=0.34). Serious AEs were rare, and similar across the cannabinoid (14/374, 3.7%) and placebo groups (8/304, 2.6%). Conclusions: There is low-quality evidence indicating that cannabinoids may be a safe alternative for a small but significant reduction in subjective pain score when treating acute pain, with intramuscular administration resulting in a greater reduction relative to oral. Higher quality, long-term randomized-controlled trials examining whether there may be a role for cannabinoids in treating acute pain are required.

Health Care Provider Factors Associated with Patient-Reported Adverse Events and Harm

Patients can provide valuable information missing from traditional sources of safety data, thus adding new insights about factors that lead to preventable harm. In this study, researchers determined associations between patient-reported contributory factors and patient-reported harms experienced after an adverse event (AE). A secondary analysis was conducted of a national sample of patient-reported AEs (surgical, medication, diagnostic, and hospital-acquired infection) gathered through an online questionnaire between January 2010 and February 2016. Generalized logit multivariable regression was used to assess the association between patient-reported contributory factors and patient-reported harms (grouped as nonphysical harm only, physical harm only, physical harm and emotional or financial harm, and all three harms) and adjusted for patient and AE characteristics. One third of patients (32.6%) reported experiencing all three harms, 27.3% reported physical harms and one additional harm, 25.5% reported physical harms only, and 14.7% reported nonphysical harms only. Patients reporting all three harms were 2.5 times more likely to have filed a report with a responsible authority (95% confidence interval [CI] = 1.23-5.01) and 3.3 times more likely to have also experienced a surgical complication (95% CI = 1.42-7.51). Odds of reporting problems related to communication between clinician and patients/families or clinician-related behavioral issues was 13% higher in those experiencing all three harm types (95% CI = 1.07-1.19). Patients' experiences are important to identify safety issues and reduce harm and should be included in patient safety measurement and improvement activities. These findings underscore the need for policy and practice changes to identify, address, and support harmed patients.

Missed Care from the Patient's Perspective - A Scoping Review.

Missed care, defined as any aspect of patient care that is omitted or delayed, is receiving increasing attention. It is primarily caused by the imbalance between patients’ nursing care needs and the resources available, making it an ethical issue that challenges nurses’ professional and moral values. In this scoping review, conducted using the five-stage approach by Arksey and O’Malley, our aim is to analyze the patients’ perspective to missed care, as the topic has been mainly examined from nurses’ perspective. The search was conducted in April 2019 in PubMed, CINAHL, PsycINFO, Web of Science, ProQuest and Philosophers Index databases using the following terms: omitted care, unfinished nursing care, care undone, care unfinished, missed care, care left undone, task undone and implicit rationing with no time limitation. The English-language studies where missed care was examined in the nursing context and had patients as informants on patient-reported missed care or patients’ perceptions on nurse-reported missed care were selected for the review. Thirteen studies were included and analyzed with thematic content analysis. Twelve studies were quantitative in nature. Patients were able to report missed care, and mostly reported missed basic care, followed by missed communication with staff and problems with timeliness when they had to wait to get the help they needed. In statistical analysis, missed care was associated with patient-reported adverse events and patients’ perceptions of staffing adequacy, and in patients’ perception, it was mainly caused by lack of staff and insufficient experience. Furthermore, patients’ health status, as opposed to gender, predicted missed care. The results concerning patients’ age and education level were conflicting. Patients are able to identify missed care. However, further research is needed to examine patient-perceived missed care as well as to examine how patients identify missed care, and to get a clear definition of missed care.

Patient-Reported Adverse Events of Radiopharmaceuticals: Development and Validation of a Questionnaire.

IntroductionRadiopharmaceuticals may cause adverse events. Knowledge about adverse events from a patient’s perspective could help healthcare professionals to detect, understand, and manage adverse events more efficiently when using radiopharmaceuticals. Researchers need a validated questionnaire that can be used in patients to assess adverse events with radiopharmaceuticals.ObjectiveThe aim of this study was to develop, validate the content of, and perform initial testing of a questionnaire assessing patient-reported adverse events of radiopharmaceuticals.MethodsBased on existing literature, six professionals drafted and evaluated a first version of the questionnaire. Further content validation was performed using cognitive interviews with six patients undergoing a nuclear medicine examination. After adaptations, the questionnaire was developed into a web-based questionnaire. One hundred patients undergoing nuclear examination tested this version, and the results were used to assess its acceptability and evaluate reported adverse events.ResultsQuestions and answer options were revised in the initial questionnaire to improve clarity. In addition, some questions were removed. The final version consisted of 18 questions. In the test phase, the acceptability of the questionnaire was demonstrated (e.g. 79% of the patients who received the questionnaire completed it, and the median time to complete the questionnaire was 12 min for patients who reported an adverse event). Of the 100 patients (53% men, median age 64 years), 12 reported a total of 22 adverse events. One of these adverse events had a high causal association.ConclusionAfter validation and testing, the developed questionnaire to study patient-reported adverse events of radiopharmaceuticals is a suitable and valid instrument which can be used in future research.Electronic supplementary materialThe online version of this article (10.1007/s40264-019-00895-2) contains supplementary material, which is available to authorized users.

Safety and Efficacy of Cultured/Noncultured Mesenchymal Stromal Cells without Concurrent Surgery for Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials.

The quantity of studies investigating mesenchymal stromal cells (MSCs) for knee osteoarthritis (OA) treatment is not restricted, unlike the amount of randomized controlled trials (RCTs) that can be found in the literature. MSCs demonstrate a promising potential for safe pain relief of OA, yet indeterminate conclusions prevail due to heterogeneous reporting and study design. By evaluating PubMed and ScienceDirect for RCTs that describe patient-reported outcome measures (PROMs) and adverse events (AEs), we investigate safety and efficacy of MSCs for knee OA unaccompanied by adjuvant surgical intervention. This systematic review is performed in alignment with preferred reported items for systematic reviews and meta-analyses guidelines. In addition to PROMs and AEs, we review included studies for stromal cell variants, follow-up, and imaging modalities, reporting our results in tables and text. Twelve studies that ranged from 1 wk to 4 yr and examined 428 patients and 856 knees met inclusion criteria. Six studies (50%) evaluated bone marrow MSCs, five (42%) evaluated adipose-derived MSCs, and one (8%) evaluated umbilical cord MSCs. All studies reported significant PROM improvement. Mean improvements in the visual analog scale and Western Ontario and McMaster Universities Arthritis Index, ranging from 0 to 40 and 10 to 32 points, respectively, were observed. Of 343 total patients, 135 (39%) experienced AEs. Whereas most AEs involved self-limiting knee swelling and pain, only three (0.8%) were severe enough to require overnight hospitalization. MSCs without adjuvant surgery offer a safe and efficacious conservative treatment option in knee OA patients by alleviating and decreasing pain for up to 12 mo. However, study limitations and contradictory findings require more evidence regarding cartilage repair.

The use of intra-operative tranexamic acid in shoulder surgery: Protocol for a systematic review and meta-analysis

IntroductionBlood loss is an important consideration in all types of shoulder surgery. Excessive bleeding is associated with increased morbidity. Tranexamic acid (TXA) is an antifibrinolytic agent. It has been demonstrated to be effective in reducing blood loss across multiple surgical specialties. The aim of this systematic review and meta-analysis is to review the literature evaluating clinical outcomes associated with the use of TXA in shoulder surgery. MethodsThe study protocol was designed and registered prospectively on PROSPERO (International prospective register for systematic reviews). Literature search will include the MEDLINE, EMBASE, PsycINFO, and Cochrane Library databases. Randomised controlled trials (RCTs) evaluating the use of TXA against placebo, in all types of shoulder surgery, will be included. Our primary outcome is total blood loss (ml). Secondary outcomes include patient-reported outcome measures (PROMs), adverse events, and number of blood transfusions required. Risk of bias will be assessed within each study using The Cochrane Risk of Bias Tool 2.0 and the Jadad score. Inconsistency and bias across included studies will be assessed statistically. Data from comparable outcomes will be pooled and analysed quantitatively or descriptively as appropriate. Ethics and disseminationNo ethical clearances required for this study. This systematic review and meta-analysis will be published in a peer-reviewed journal. It will be presented a various national and international conferences.

Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis

Background:For patients with chronic, non-cancer pain, traditional pain-relieving medications include opioids, which have shown benefits but are associated with increased risks of addiction and adverse effects. Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of randomized clinical trials in recent years; therefore, a systematic review of the evidence was warranted.Objective:To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic, non-cancer-related pain.Design:Systematic review with meta-analysis.Data sources:Medline, Embase, CINAHL, SCOPUS, Google Scholar, and Cochrane Databases.Eligibility criteria:English language randomized clinical trials of cannabinoids for the treatment of chronic, non-cancer-related pain.Data extraction and synthesis:Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of 6 reviewers. Data were pooled through meta-analysis with different durations of treatment (2 weeks, 2 months, 6 months) and stratified by route of administration (smoked, oromucosal, oral), conditions, and type of cannabinoids.Main outcomes and measures:Patient-reported pain and adverse events (AEs).Results:Thirty-six trials (4006 participants) were included, examining smoked cannabis (4 trials), oromucosal cannabis sprays (14 trials), and oral cannabinoids (18 trials). Compared with placebo, cannabinoids showed a significant reduction in pain which was greatest with treatment duration of 2 to 8 weeks (weighted mean difference on a 0-10 pain visual analogue scale −0.68, 95% confidence interval [CI], −0.96 to −0.40, I2 = 8%, P < .00001; n = 16 trials). When stratified by route of administration, pain condition, and type of cannabinoids, oral cannabinoids had a larger reduction in pain compared with placebo relative to oromucosal and smoked formulations but the difference was not significant (P[interaction] > .05 in all the 3 durations of treatment); cannabinoids had a smaller reduction in pain due to multiple sclerosis compared with placebo relative to other neuropathic pain (P[interaction] = .05) within 2 weeks and the difference was not significant relative to pain due to rheumatic arthritis; nabilone had a greater reduction in pain compared with placebo relative to other types of cannabinoids longer than 2 weeks of treatment but the difference was not significant (P[interaction] > .05). Serious AEs were rare, and similar across the cannabinoid (74 out of 2176, 3.4%) and placebo groups (53 out of 1640, 3.2%). There was an increased risk of non-serious AEs with cannabinoids compared with placebo.Conclusions:There was moderate evidence to support cannabinoids in treating chronic, non-cancer pain at 2 weeks. Similar results were observed at later time points, but the confidence in effect is low. There is little evidence that cannabinoids increase the risk of experiencing serious AEs, although non-serious AEs may be common in the short-term period following use.