An International, Multidisciplinary Consensus Set of Patient-Centered Outcome Measures for Substance-Related and Addictive Disorders.

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience (n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

Comparative Risk of Injury with Concurrent Use of Opioids and Skeletal Muscle Relaxants.

Concurrent use of skeletal muscle relaxants (SMRs) and opioids has been linked to an increased risk of injury. However, it remains unclear whether the injury risks differ by specific SMR when combined with opioids. We conducted nine retrospective cohort studies within a US Medicaid population. Each cohort consisted exclusively of person-time exposed to both an SMR and one of the three most dispensed opioids-hydrocodone, oxycodone, and tramadol. Opioid users were further divided into three cohorts based on the initiation order of SMRs and opioids-synchronically triggered, opioid-triggered, and SMR-triggered. Within each cohort, we used Cox proportional hazard models to compare the injury rates for different SMRs compared to methocarbamol, adjusting for covariates. We identified 349,543, 139,458, and 218,967 concurrent users of SMRs with hydrocodone, oxycodone, and tramadol, respectively. In the oxycodone-SMR-triggered cohort, the adjusted hazard ratios (HRs) were 1.86 (95% CI, 1.23-2.82) for carisoprodol and 1.73 (1.09-2.73) for tizanidine. In the tramadol-synchronically triggered cohort, the adjusted HRs were 0.69 (0.49-0.97) for metaxalone and 0.62 (0.42-0.90) for tizanidine. In the tramadol-SMR-triggered cohort, the adjusted HRs were 1.51 (1.01-2.26) for baclofen and 1.48 (1.03-2.11) for cyclobenzaprine. All other HRs were statistically nonsignificant. In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol.

Disparate impact of the COVID-19 pandemic on delays in colorectal cancer treatment: A National Cancer Database study.

BACKGROUND: Timely treatment for patients with colorectal cancer may have been disrupted by the COVID-19 pandemic. We evaluated the impact of the pandemic on delays to treatment with surgery or systemic therapy for patients with colorectal cancer and delineated factors predictive of delayed treatment. METHODS: Using the National Cancer Database, patients diagnosed with colorectal cancer were categorized by year of diagnosis as COVID-19 era (2020) versus pre-COVID-19 (2018-2019). Categorical variables were compared by χ2 analysis. Multivariate logistic regression was used to assess odds ratios for delayed time to surgery or chemoimmunotherapy, defined as >60 days. RESULTS: In total, 50,689 patients colorectal cancer were diagnosed patients who were pre-COVID-19 vs 21,331 within the COVID-19-era. Patients diagnosed with COVID-19 had a higher stage at diagnosis. There were no differences in the proportion of delayed time to surgery for patients diagnosed in 2020, but patients who were tested for COVID-19 had increased proportions of delayed time to surgery (P < .0001). In multivariate analysis, Black race (P = .0026) and uninsured/underinsured status (P = .0017) were associated with delayed time to surgery. Diagnosis during COVID-19 did not increase delayed time to chemoimmunotherapy, regardless of COVID-19 testing or positivity; however, delays were seen for Black (P < .0001), Hispanic (P < .0001), and uninsured/underinsured patients (P < .0001). CONCLUSION: Although the pandemic did not delay treatment for colorectal cancer overall, vulnerable and underserved populations were disproportionately affected by delays to all forms of therapy. The difference in colorectal cancer outcomes in the coming years as a result of delays in treatment may be significant for these patients.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

INTRODUCTION: Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. RESULTS: A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). CONCLUSION: At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Impact of the COVID-19 Pandemic on Delays to Breast Cancer Surgery: Ripples or Waves?

BACKGROUND: Adherence to current recommendations for optimal time from diagnosis to treatment for patients with breast cancer may have been disrupted by the COVID-19 pandemic. This study aimed to evaluate the impact of the pandemic on time to surgery or systemic treatment with chemotherapy or immunotherapy for patients diagnosed with breast cancer. METHODS: Using the National Cancer Database, patients diagnosed with breast cancer in 2020 were compared to those diagnosed from 2018-2019 (Pre-COVID). Sub-analyses were performed for patients who were tested for COVID-19 and those who had a positive result in 2020. Multivariate logistic regression was used assess odds ratios for delayed time to surgery (DTS, defined as > 90 days) or systemic therapy (defined as > 120 days). RESULTS: In total, 230,997 patients were diagnosed with breast cancer in 2018 and 2019 compared to 102,065 in 2020. Of the 2020 cohort, 47,659 (46.7%) received COVID-19 testing; of which, 3,158 (6.6%) resulted positive. A larger proportion of COVID-tested or COVID-positive patients had higher stage at diagnosis. DTS was more likely for patients who were diagnosed in 2020, uninsured or underinsured, non-white, Hispanic, less educated, or age < 70 years. Similar factors were predictive of delay to systemic therapy (less age < 70 years); however, diagnosis in 2020 was not. CONCLUSION: The COVID-19 pandemic was associated with significant DTS for breast cancer but spared time to systemic therapy. Delays disproportionately impacted vulnerable and underserved patient populations. The true clinical effects of these delays may yet be realized for breast cancer patients.

A majority of trauma-related deep venous thromboses resolve prior to discharge.

Post-traumatic DVTs present unique challenges in patient populations with specific high-risk injury patterns. Duplex ultrasound (US) can be used to assess evolution of DVTs and may guide treatment for high-risk patients. We hypothesized that many DVTs resolve during the initial admission. Weekly duplex US are ordered on all trauma inpatients regardless of prior DVT at our facility. We reviewed US and outcomes data on all patients with lower extremity DVTs at our Level I trauma center from January 2012-December 2021. 392 patients were diagnosed with lower extremity DVT by US. 261 (67%) patients received follow-up US with a mean time to repeat US of 6 days. Of these, 91 (35%) patients experienced DVT resolution prior to the first follow-up US, and 141 (54%) patients experienced resolution prior to discharge. Mean time to resolution was 10 days. Over 50% of DVTs resolve before discharge and are detected by US. Further studies and post-discharge follow-up are needed to determine if patients with resolved DVTs can be managed without therapeutic anticoagulation.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

The impact of social risk factors on the presentation, treatment and survival of patients with hepatocellular carcinoma at an urban, academic safety-net hospital.

BACKGROUND: Vulnerable populations have worse hepatocellular carcinoma (HCC) outcomes. We sought to understand if this could be mitigated at a safety-net hospital. METHODS: A retrospective chart review of HCC patients was conducted (2007-2018). Stage at presentation, intervention and systemic therapy were analyzed (Chi-square for categorical variables and Wilcoxon tests for continuous variables) and median survival calculated by Kaplan-Meier method. RESULTS: 388 HCC patients were identified. Sociodemographic factors were similar for stage at presentation, except insurance status (diagnosis at earlier stages for commercial insurance and later stages for safety-net/no insurance). Higher education level and origin of mainland US increased intervention rates for all stages. Early-stage disease patients had no differences in receipt of intervention or therapy. Late-stage disease patients with higher education level had increased intervention rates. Median survival was not impacted by any sociodemographic factor. CONCLUSION: Urban safety-net hospitals with a focus on vulnerable patient populations provide equitable outcomes and can serve as a model to address inequities in HCC management.

Combined High-Volume Common Complex Cancer Operations Safeguard Long-Term Survival in a Low-Volume Individual Cancer Operation Setting.

BACKGROUND: We previously demonstrated the importance of combined complex surgery volume on short-term outcomes of high-risk cancer operations. This study investigates the impact of combined common complex cancer operation volume on long-term outcomes at hospitals with low cancer-specific operation volumes. PATIENTS AND METHODS: A retrospective cohort of National Cancer Data Base (2004-2019) patients undergoing surgery for hepatocellular carcinoma, non-small cell lung cancers, or pancreatic, gastric, esophageal, or rectal adenocarcinomas was utilized. Three separate cohorts were established: low-volume hospitals (LVH), mixed-volume hospitals (MVH) with low-volume individual cancer operations and high-volume total complex operations, and high-volume hospitals (HVH). Survival analyses were performed for overall, early-, and late-stage disease. RESULTS: The 5 year survival was significantly better at MVH and HVH compared with LVH, for all operations except late-stage hepatectomy (HVH survival > LVH and MVH). The 5 year survival probability was similar between MVH and HVH for operations on late-stage cancers. Early and overall survival for gastrectomy, esophagectomy, and proctectomy were equivalent between MVH and HVH. While early and overall survival for pancreatectomy were benefited by HVH over MVH, the opposite was true for lobectomy/pneumonectomy, which were benefited by MVH over HVH; however, none of these differences were likely to have an effect clinically. Only hepatectomy patients demonstrated statistical and clinical significance in 5 year survival at HVH compared with MVH for overall survival. CONCLUSIONS: MVH hospitals performing sufficient complex common cancer operations demonstrate similar long-term survival for specific high-risk cancer operations to HVH. MVH provide an adjunctive model to the centralization of complex cancer surgery, while maintaining quality and access.

Delay and Disparity in Observed vs Predicted Incidence Rate of Screenable Cancer During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic resulted in disruption of healthcare services, including cancer screenings, yet data on this are limited. We sought to compare observed and expected cancer incidence rates for screenable cancers, quantifying potential missed diagnoses. STUDY DESIGN: Lung, female breast, and colorectal cancer patients from 2010 to 2020 in the National Cancer Database were standardized to calculate annual incidence rates per 100,000. A linear regression model of 2010 through 2019 incidence rates (pre-COVID) was used to calculate predicted 2020 incidence compared with observed incidence in 2020 (COVID) with subanalyses for age, sex, race, ethnicity, and geographic region. RESULTS: In total, 1,707,395 lung, 2,200,505 breast, and 1,066,138 colorectal cancer patients were analyzed. After standardizing, the observed 2020 incidence was 66.888, 152.059, and 36.522 per 100,000 compared with the predicted 2020 incidence of 81.650, 178.124, and 44.837 per 100,000, resulting in an observed incidence decrease of -18.1%, -14.6%, and -18.6% for lung, breast, and colorectal cancer, respectively. The difference was amplified on subanalysis for lung (female, 65 or more years old, non-White, Hispanic, Northeastern and Western region), breast (65 or more years old, non-Black, Hispanic, Northeastern and Western region), and colorectal (male, less than 65 years old, non-White, Hispanic, and Western region) cancer patients. CONCLUSIONS: The reported incidence of screenable cancers significantly decreased during the COVID-19 pandemic (2020), suggesting that many patients currently harbor undiagnosed cancers. In addition to the human toll, this will further burden the healthcare system and increase future healthcare costs. It is imperative that providers empower patients to schedule cancer screenings to flatten this pending oncologic wave.

Axillary Lymph Node Dissection is Associated with Improved Survival Among Men with Invasive Breast Cancer and Sentinel Node Metastasis.

BACKGROUND: Male breast cancer (MBC) is rare, and management is extrapolated from trials that enroll only women. It is unclear whether contemporary axillary management based on data from landmark trials in women may also apply to men with breast cancer. This study aimed to compare survival in men with positive sentinel lymph nodes after sentinel lymph node biopsy (SLNB) alone versus complete axillary dissection (ALND). PATIENTS AND METHODS: Using the National Cancer Database, men with clinically node-negative, T1 and T2 breast cancer and 1-2 positive sentinel nodes who underwent SLNB or ALND were identified from 2010 to 2020. Both 1:1 propensity score matching and multivariate regression were used to identify patient and disease variables associated with ALND versus SLNB. Survival between ALND and SLNB were compared using Kaplan-Meier methods. RESULTS: A total of 1203 patients were identified: 61.1% underwent SLNB alone and 38.9% underwent ALND. Treatment in academic centers (36.1 vs. 27.7%; p < 0.0001), 2 positive lymph nodes on SLNB (32.9 vs. 17.3%, p < 0.0001) and receipt or recommendation of chemotherapy (66.5 vs. 52.2%, p < 0.0001) were associated with higher likelihood of ALND. After propensity score matching, ALND was associated with superior survival compared with SLNB (5-year overall survival of 83.8 vs. 76.0%; log-rank p = 0.0104). DISCUSSION: The results of this study suggest that among patients with early-stage MBC with limited sentinel lymph node metastasis, ALND is associated with superior survival compared with SLNB alone. These findings indicate that it may be inappropriate to extrapolate the results of the ACOSOG Z0011 and EORTC AMAROS trials to MBC.

The Impact of the COVID-19 Pandemic on Hepatocellular Carcinoma Time to Treatment Initiation: A National Cancer Database Study.

BACKGROUND: The COVID-19 pandemic strained oncologic care access and delivery, yet little is known about how it impacted hepatocellular carcinoma (HCC) management. Our study sought to evaluate the annual effect of the COVID-19 pandemic on time to treatment initiation (TTI) for HCC. METHODS: The National Cancer Database was queried for patients diagnosed with clinical stages I-IV HCC (2017-2020). Patients were categorized based on their year of diagnosis as "Pre-COVID" (2017-2019) and "COVID" (2020). TTI based on stage and type of treatment first received was compared by the Mann-Whitney U test. A logistic regression model was used to evaluate factors of increased TTI and treatment delay (> 90 days). RESULTS: In total, 18,673 patients were diagnosed during Pre-COVID, whereas 5249 were diagnosed during COVID. Median TTI for any first-line treatment modality was slightly shorter during the COVID year compared with Pre-COVID (49 vs. 51 days; p < 0.0001), notably in time to ablation (52 vs. 55 days; p = 0.0238), systemic therapy (42 vs. 47 days; p < 0.0001), and radiation (60 vs. 62 days; p = 0.0177), but not surgery (41 vs. 41 days; p = 0.6887). In a multivariate analysis, patients of Black race, Hispanic ethnicity, and uninsured/Medicaid/Other Government insurance status were associated with increased TTI by factors of 1.057 (95% CI: 1.022-1.093; p = 0.0013), 1.045 (95% CI: 1.010-1.081; p = 0.0104), and 1.088 (95% CI: 1.053-1.123; p < 0.0001), respectively. Similarly, these patient populations were associated with delayed treatment times. CONCLUSIONS: For patients diagnosed during COVID, TTI for HCC, while statistically significant, had no clinically significant differences. However, vulnerable patients were more likely to have increased TTI.

Antidepressant drug-drug-drug interactions associated with unintentional traumatic injury: Screening for signals in real-world data.

Antidepressants are associated with traumatic injury and are widely used with other medications. It remains unknown how drug-drug-drug interactions (3DIs) between antidepressants and two other drugs may impact potential injury risks associated with antidepressants. We aimed to generate hypotheses regarding antidepressant 3DI signals associated with elevated injury rates. Using 2000-2020 Optum's de-identified Clinformatics Data Mart, we performed a self-controlled case series study for each drug triad consisting of an antidepressant + codispensed drug (base-pair) with a candidate interacting medication (precipitant). We included persons aged greater than or equal to 16 years who (1) experienced an injury and (2) used a candidate precipitant, during base-pair therapy. We compared injury rates during observation time exposed to the drug triad versus the base-pair only, adjusting for time-varying covariates. We calculated adjusted rate ratios (RRs) using conditional Poisson regression and accounted for multiple comparisons via semi-Bayes shrinkage. Among 147,747 eligible antidepressant users with an injury, we studied 120,714 antidepressant triads, of which 334 (0.3%) were positively associated with elevated injury rates and thus considered potential 3DI signals. Adjusted RRs for signals ranged from 1.31 (1.04-1.65) for sertraline + levothyroxine with tramadol (vs. without tramadol) to 6.60 (3.23-13.46) for escitalopram + simvastatin with aripiprazole (vs. without aripiprazole). Nearly half of the signals (137, 41.0%) had adjusted RRs greater than or equal to 2, suggesting strong associations with injury. The identified signals may represent antidepressant 3DIs of potential clinical concern and warrant future etiologic studies to test these hypotheses.