A harm reduction model to assess the impact of new treatments for pain over standard of care among patients with osteoarthritis

Abstract Background and study aims Bowel preparation for colonoscopy is frequently inadequate in hospitalized patients. We explored the impact of specific verbal instructions on the quality of inpatients bowel preparation and factors associated with preparation failure. Patients and methods Randomized (1:1), two strata (mobilized vs. bedridden; 3:2) trial of consecutive inpatients from four tertiary centers, who received either specific, verbal instructions or the standard of care (SOC) ward instructions about bowel preparation. The rate of adequate bowel preparation (Boston Bowel Preparation Score [BBPS] ≥ 6, no segment < 2) comprised the primary endpoint. Mean BBPS score, good (BBPS score ≥ 7, no segment score < 2) and excellent (BBPS = 9) were among secondary endpoints. Results We randomized 300 inpatients (180 mobile) aged 71.7 ± 15.1 years in the intervention (49.7 %) and SOC (50.3 %) groups, respectively. Overall, more patients in the intervention group achieved adequate bowel preparation, but this difference did not reach statistical significance neither in the intention-to-treat [90/149 (60.4 %) vs. 82/151 (54.3 %); P = 0.29] nor in the per-protocol analysis [90/129 (69.8 %) vs. 82/132 (62.1 %); P = 0.19]. Overall BBPS score did not differ statistical significantly in the two groups, but the provision of specific verbal instructions was associated with significant higher rates of good (58.1 % vs. 43.2 %; P = 0.02) and excellent (31.8 % vs. 16.7 %; P = 0.004) bowel preparation compared to the SOC group. Administration of same-day bowel preparation and patient American Society of Anesthesiologists score > 2 were identified as risk factors for inadequate bowel preparation. Conclusions Provision of specific verbal instructions did not increase the rate of adequate bowel preparation in a population of mobilized and bedridden hospitalized patients.

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Beyond Microsatellite Instability: Evolving Strategies Integrating Immunotherapy for Microsatellite Stable Colorectal Cancer

Current Treatment Options in Oncology ◽

10.1007/s11864-021-00870-z ◽

2021 ◽

Vol 22 (8) ◽

Author(s):

Federica Pecci ◽

Luca Cantini ◽

Alessandro Bittoni ◽

Edoardo Lenci ◽

Alessio Lupi ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Mismatch Repair ◽

Cancer Progression ◽

Checkpoint Inhibitors ◽

Tnm Classification ◽

Standard Of Care ◽

First Line Therapy ◽

Combination Strategies ◽

The Impact

Opinion statementAdvanced colorectal cancer (CRC) is a heterogeneous disease, characterized by several subtypes with distinctive genetic and epigenetic patterns. During the last years, immune checkpoint inhibitors (ICIs) have revamped the standard of care of several tumors such as non-small cell lung cancer and melanoma, highlighting the role of immune cells in tumor microenvironment (TME) and their impact on cancer progression and treatment efficacy. An “immunoscore,” based on the percentage of two lymphocyte populations both at tumor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite stable (MSS) CRC. This group includes roughly 95% of all advanced CRC, and standard chemotherapy, in addition to anti-EGFR or anti-angiogenesis drugs, still represents first treatment choice. Hopefully, deeper understanding of CRC immune landscape and of the impact of specific genetic and epigenetic alterations on tumor immunogenicity might lead to the development of new drug combination strategies to overcome ICIs resistance in pMMR CRC, thus paving the way for immunotherapy even in this subgroup.

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Implementation of a Rapid Phenotypic Susceptibility Platform for Gram-Negative Bloodstream Infections With Paired Antimicrobial Stewardship Intervention: Is the Juice Worth the Squeeze?

Clinical Infectious Diseases ◽

10.1093/cid/ciab126 ◽

2021 ◽

Author(s):

Evan D Robinson ◽

Allison M Stilwell ◽

April E Attai ◽

Lindsay E Donohue ◽

Megan D Shah ◽

...

Keyword(s):

Median Time ◽

Antimicrobial Stewardship ◽

A Priori ◽

Bloodstream Infections ◽

Standard Of Care ◽

Post Intervention ◽

Gram Negative ◽

Stewardship Program ◽

Days Of Therapy ◽

The Impact

Abstract Background Implementation of the Accelerate PhenoTM Gram-negative platform (RDT) paired with antimicrobial stewardship program (ASP) intervention projects to improve time to institutional-preferred antimicrobial therapy (IPT) for Gram-negative bacilli (GNB) bloodstream infections (BSIs). However, few data describe the impact of discrepant RDT results from standard of care (SOC) methods on antimicrobial prescribing. Methods A single-center, pre-/post-intervention study of consecutive, nonduplicate blood cultures for adult inpatients with GNB BSI following combined RDT + ASP intervention was performed. The primary outcome was time to IPT. An a priori definition of IPT was utilized to limit bias and to allow for an assessment of the impact of discrepant RDT results with the SOC reference standard. Results Five hundred fourteen patients (PRE 264; POST 250) were included. Median time to antimicrobial susceptibility testing (AST) results decreased 29.4 hours (P < .001) post-intervention, and median time to IPT was reduced by 21.2 hours (P < .001). Utilization (days of therapy [DOTs]/1000 days present) of broad-spectrum agents decreased (PRE 655.2 vs POST 585.8; P = .043) and narrow-spectrum beta-lactams increased (69.1 vs 141.7; P < .001). Discrepant results occurred in 69/250 (28%) post-intervention episodes, resulting in incorrect ASP recommendations in 10/69 (14%). No differences in clinical outcomes were observed. Conclusions While implementation of a phenotypic RDT + ASP can improve time to IPT, close coordination with Clinical Microbiology and continued ASP follow up are needed to optimize therapy. Although uncommon, the potential for erroneous ASP recommendations to de-escalate to inactive therapy following RDT results warrants further investigation.

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Challenges in Treating Tardive Dyskinesia: Assessing the Impact of Virtual Medical Education

CNS Spectrums ◽

10.1017/s1092852920002667 ◽

2021 ◽

Vol 26 (2) ◽

pp. 165-165

Author(s):

Amanda Glazar ◽

Cecilia Peterson ◽

Michael Lemon ◽

Chirag Shah ◽

Prakash Masand

Keyword(s):

Medical Education ◽

Tardive Dyskinesia ◽

Treatment Options ◽

Respiratory Muscles ◽

Educational Activity ◽

Activity Participation ◽

Chi Square ◽

Practice Performance ◽

New Treatments ◽

The Impact

AbstractIntroductionTardive Dyskinesia (TD) refers to abnormal, involuntary, choreoathetoid movements of the tongue, lips, face, trunk, and extremities and is associated with long-term exposure to dopamine-blocking agents, such as antipsychotic medications. Once established, these movements usually persist. The movements are disfiguring and can bring unwanted attention to affected individuals. When severe, especially if the respiratory muscles are affected, the movements can be disabling, limit activity, and reduce quality of life. The prevalence is 7.2% in individuals on newer antipsychotics who have never been exposed to older neuroleptics. Until recently, there were no effective treatments for TD. In recent years, many new treatments have been investigated for the treatment of TD, including valbenazine, deutetrabenazine, and branched chain amino acids. Valbenazine first, followed by deutetrabenazine are FDA approved to treat TD. A virtual broadcast was developed to assess the ability of continuing medical education (CME) to improve awareness of the recognition and treatment of TD among psychiatrists.MethodsThe virtual broadcast (May 9, 2020) consisted of a two-hour, live-streamed discussion between two expert faculty. Impact of the educational activity was assessed by comparing psychiatrists’ responses to four identical questions presented before and directly after activity participation. A follow-up survey was sent to all participants six-weeks post-activity to measure performance in practice changes. A chi-square test was used to identify significant differences between pre- and post-assessment responses. Cohen’s d was used to calculate the effect size of the virtual broadcast.ResultsActivity participation resulted in a noticeable educational effect among psychiatrists (n=621; d=6.12, P<.001). The following areas showed significant (P<0.05) pre- vs post-educational improvements: recognition of movements in patients with TD, rate of TD in SGA exposed patients, treatment options for TD (on and off-label), and treatment of TD using VMAT inhibitors. Additionally, 54% of psychiatrists reported a change in practice performance as a result of the education received in the activity, including utilization of a standard scale to evaluate movement disorders and educate patients and family members about potential for TD, how to recognize symptoms, and when to treat.ConclusionsThe results indicated that a CME-certified two-hour virtual broadcast was effective at improving knowledge among psychiatrists for the recognition and treatment of TD. This knowledge also resulted in positive changes in practice performance post-activity. Future education should continue to address best practices in the diagnosis, treatment and management of patients with TD, as there remains an increased need for tailored CME among psychiatrists.FundingNeurocrine Biosciences, Inc.

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COVD-25. THE PARADOXICAL EFFECTS OF COVID-19 ON CANCER CARE IN THE NEURO-ONCOLOGY SETTING

Neuro-Oncology ◽

10.1093/neuonc/noaa215.106 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii26-ii26

Author(s):

Nicole Cort ◽

Alex Broom ◽

Katherine Kenny ◽

Alexander Page ◽

Jennifer Durling ◽

...

Keyword(s):

Cancer Care ◽

Standard Of Care ◽

Adult Brain ◽

Evidence Based ◽

Negative Consequences ◽

Traditional Practice ◽

Delivery Of Care ◽

Paradoxical Effects ◽

Oncology Care ◽

The Impact

Abstract COVID-19 has caused ongoing interruptions to healthcare systems worldwide, shifting care to virtual platforms, and placing significant economic and logistical burdens on clinical practice. The pandemic has created uncertainty in delivering the standard of care, both in areas of cancer diagnosis and treatment, especially within neuro-oncology. Due to the pandemic, care and operational planning goals have shifted to infection prevention, modifying recommendations to decrease viral transmission and increasing telemedicine use, potentially creating a burden on implementing evidence-based medicine. These dynamics have since begun to redefine traditional practice and research regimens, impacting the comprehensive care that cancer patients can and should receive; and the enduring consequences for the delivery of healthcare. The impact of COVID-19 on oncology practice and trials might endure well beyond the short- to mid-term of the active pandemic. Therefore, these shifts must be accompanied by improved training and awareness, enhanced infrastructure, and evidence-based support to harness the positives and offset the potential negative consequences of the impacts of COVID-19 on cancer care. To address these paradoxical effects, we will conduct iterative, qualitative (face-to-face/video conference) interviews with neuro-oncology clinical and research professionals and adult brain tumor patients receiving care during the pandemic. We will capture unique aspects of oncology care: the lived, subjective, situated, and contingent accounts of patients and medical professionals, especially during a pandemic. We will also specifically compare the impact of telehealth during the pandemic on delivery of care to complex neuro-oncology patients. A summary of this in-depth, qualitative approach will result in a sophisticated understanding of neuro-oncology care on the frontline at a time of crisis, as experienced during a pandemic, to articulate best practices for future implementation.

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STEM-24. RADIATION-INDUCED EXTRACELLULAR VESICLE (EV) RELEASE OF miR-603 PROMOTES IGF1-MEDIATED STEM CALL STATE IN GLIOBLASTOMAS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.841 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii201-ii201

Author(s):

Valya Ramakrishnan ◽

Beibei Xu ◽

Johnny Akers ◽

Thien Nguyen ◽

Jun Ma ◽

...

Keyword(s):

Recipient Cell ◽

Alkylating Agents ◽

Acquired Resistance ◽

Standard Of Care ◽

Extracellular Vesicle ◽

Cross Resistance ◽

Dna Damages ◽

Care Treatment ◽

Standard Of Care Treatment ◽

The Impact

Abstract INTRODUCTION Release of exosomes and extracellular vesicles (EV) by glioblastomas plays key roles in modulating the tumor microenvironment and therapeutic response. Studies to date have largely focused on the impact of EV and exosomes on the recipient cell. Here, we demonstrate that EV-mediated export of a master-regulatory miRNA has fate-determining impacts on the cell releasing the EVs. METHODS microRNA (miRNA) profiling was performed using clinical glioblastoma specimens from the same patients derived pre- and post-standard of care treatment. Mechanism mediating altered miRNA homeostasis were assessed. RESULTS While the levels of nearly all miRNAs remained unchanged after standard-of-care treatment, decreased levels of few, select miRNAs were observed, including miR-603. In response to ionizing radiation (IR), but not temozolomide (TMZ), glioblastoma cell lines exhibited a time-dependent decrease in miR-603 levels. While miR-603 biogenesis and degradation remained unchanged after IR, IR induced an increase in EV-mediated export of miR-603. Profiling of miR-603 targets revealed that miR-603 repressed the insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), genes required to maintain the cancer stem cell (CSC) state, as well as MGMT, the gene encoding a DNA repair protein that detoxifies temozolomide (TMZ) induced DNA damages. IR induced export of miR-603 de-repress IGF1/IGF1R to promote radiation resistance and de-repress MGMT to promote cross-resistance to TMZ and CCNU. Ectopic miR-603 expression overwhelmed cellular capacity for miR-603 export and synergized with the tumoricidal effects of IR and temozolomide (TMZ). CONCLUSIONS Radiation stimulated EV-mediated export of miR-603 to facilitate acquired resistance to IR and cross-resistance to DNA alkylating agents.

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Community intervention for child tuberculosis active contact investigation and management: study protocol for a parallel cluster randomized controlled trial

Trials ◽

10.1186/s13063-021-05124-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Anca Vasiliu ◽

Sabrina Eymard-Duvernay ◽

Boris Tchounga ◽

Daniel Atwine ◽

Elisabete de Carvalho ◽

...

Keyword(s):

Controlled Trial ◽

Standard Of Care ◽

Preventive Therapy ◽

Community Based ◽

Randomized Controlled ◽

Eligible Child ◽

Contact Investigation ◽

Cluster Randomized ◽

The Impact ◽

Index Cases

Abstract Background There are major gaps in the management of pediatric tuberculosis (TB) contact investigation for rapid identification of active tuberculosis and initiation of preventive therapy. This study aims to evaluate the impact of a community-based intervention as compared to facility-based model for the management of children in contact with bacteriologically confirmed pulmonary TB adults in low-resource high-burden settings. Methods/design This multicenter parallel open-label cluster randomized controlled trial is composed of three phases: I, baseline phase in which retrospective data are collected, quality of data recording in facility registers is checked, and expected acceptability and feasibility of the intervention is assessed; II, intervention phase with enrolment of index cases and contact cases in either facility- or community-based models; and III, explanatory phase including endpoint data analysis, cost-effectiveness analysis, and post-intervention acceptability assessment by healthcare providers and beneficiaries. The study uses both quantitative and qualitative analysis methods. The community-based intervention includes identification and screening of all household contacts, referral of contacts with TB-suggestive symptoms to the facility for investigation, and household initiation of preventive therapy with follow-up of eligible child contacts by community healthcare workers, i.e., all young (< 5 years) child contacts or older (5–14 years) child contacts living with HIV, and with no evidence of TB disease. Twenty clusters representing TB diagnostic and treatment facilities with their catchment areas are randomized in a 1:1 ratio to either the community-based intervention arm or the facility-based standard of care arm in Cameroon and Uganda. Randomization was stratified by country and constrained on the number of index cases per cluster. The primary endpoint is the proportion of eligible child contacts who initiate and complete the preventive therapy. The sample size is of 1500 child contacts to identify a 10% difference between the arms with the assumption that 60% of children will complete the preventive therapy in the standard of care arm. Discussion This study will provide evidence of the impact of a community-based intervention on household child contact screening and management of TB preventive therapy in order to improve care and prevention of childhood TB in low-resource high-burden settings. Trial registration ClinicalTrials.gov NCT03832023. Registered on 6 February 2019

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Preclinical activity of cobimetinib alone or in combination with chemotherapy and targeted therapies in renal cell carcinoma

Future Oncology ◽

10.2217/fon-2021-0256 ◽

2021 ◽

Author(s):

Lichen Zhang ◽

Deqiong Xie ◽

Yonghua Lei ◽

Aoli Na ◽

Lei Zhu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Mapk Pathway ◽

Standard Of Care ◽

Underlying Mechanism ◽

Mek Inhibitor ◽

Tumor Formation ◽

Pathway Inhibition ◽

New Treatments

Background: The poor outcome of advanced renal cell carcinoma (RCC) necessitates new treatments. Cobimetinib is a MEK inhibitor and approved for the treatment of melanoma. This work investigated the efficacy of cobimetinib alone and in combination with anti-RCC drugs. Methods: Proliferation and apoptosis assays were performed, and combination index was analyzed on RCC cell lines (CaKi-2, 786-O, A-704, ACHN and A489) and xenograft models. Immunoblotting analysis was conducted to investigate the MAPK pathway. Results: Cobimetinib was active against RCC cells, with IC50 at 0.006–0.8μM, and acted synergistically with standard-of-care therapy. Cobimetinib at nontoxic doses prevented tumor formation, inhibited tumor growth and enhanced efficacy of 5-fluorouracil, sorafenib and sunitinib via suppressing Raf/MEK/ERK, leading to MAPK pathway inhibition. Conclusion: Our findings demonstrate the potent anti-RCC activity of cobimetinib and its synergism with RCC standard-of-care drugs, and confirm the underlying mechanism of the action of cobimetinib.

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Lessons Learned Over More than 500 Stroke Thrombectomies Using ADAPT With Increasing Aspiration Catheter Size

Neurosurgery ◽

10.1093/neuros/nyy444 ◽

2018 ◽

Cited By ~ 13

Author(s):

Ali Alawieh ◽

A Rano Chatterjee ◽

Jan Vargas ◽

M Imran Chaudry ◽

Jonathan Lena ◽

...

Keyword(s):

South Carolina ◽

Standard Of Care ◽

Multivariate Regression Analysis ◽

Lessons Learned ◽

Stent Retriever ◽

Complication Rates ◽

Procedure Time ◽

University Of South Carolina ◽

Endovascular Thrombectomy ◽

The Impact

Abstract BACKGROUND Endovascular thrombectomy is currently the standard of care for acute ischemic stroke (AIS). Although earlier trials on endovascular thrombectomy were performed using stent retrievers, recently completed the contact aspiration vs stent retriever for successful revascularization (ASTER) and a comparison of direct aspiration versus stent retriever as a first approach (COMPASS) trials have shown the noninferiority of direct aspiration. OBJECTIVE To report the largest experience with ADAPT thrombectomy and compare the impact of advancement in reperfusion catheter technologies on outcomes. METHODS We reviewed a retrospective database of AIS patients who underwent ADAPT thrombectomy between January 2013 and November 2017 at the Medical University of South Carolina. Demographics and baseline characteristics, technical variables, and radiological and clinical outcomes were reviewed. RESULTS Among 510 patients (mean age: 67.7, 50.6% females), successful recanalization at first pass was achieved in 61.8%, and with aspiration only in 77.5%. Mean procedure time was 27.4 min, and the rate of good outcomes (mRS 0-2) at 90 d was 42.9%. The rate of recanalization with aspiration only was significantly higher, and procedure time was significantly lower in patients treated with larger catheters (ACE 064 and ACE 068) compared to smaller catheters (5 MAX and ACE, P < .05). There were no differences in complication rates or postoperative parenchymal hemorrhage across groups (P > .05); however, use of ACE 068 was an independent predictor of good outcomes at 90 d on multivariate regression analysis (odds ratio = 1.6, P < .05). CONCLUSION Refinement of ADAPT thrombectomy by incorporating reperfusion catheters with higher inner diameters and thus higher aspiration forces is associated with better outcomes, shorter procedure times, and lower likelihood of using additional devices without impacting complication rates.

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Improving indicators of tuberculosis program cascades by leveraging HIV program strategies

Public Health Action ◽

10.5588/pha.19.0049 ◽

2019 ◽

Vol 9 (4) ◽

pp. 191-195

Author(s):

S. C. Meribe ◽

E. Harausz ◽

I. Lawal ◽

A. Ogundeji ◽

C. Mbanefo ◽

...

Keyword(s):

Standard Of Care ◽

Rank Test ◽

Military Hospitals ◽

Us Army ◽

Signed Rank ◽

Before And After ◽

Army Medical Research ◽

Signed Rank Test ◽

The Impact ◽

Number Of Individuals

Background: To improve rates of human immunodeficiency virus (HIV) case detection and treatment, the Nigerian Ministry of Defense Health Implementation Program and the US Army Medical Research Directorate-Africa/Nigeria introduced a HIV standard of care (SOC) package. Given the integration of tuberculosis (TB) and HIV programs and evolving policies, we evaluated the impact of this strategy on TB program indicators.Methods: Routine, de-identified program data from 27 Nigerian military hospitals were analyzed. Using Wilcoxon signed-rank test, bivariate analyses were performed to compare data from 12 months before and after implementation of the SOC package.Results: Our data showed improvements post-implementation as follows: the number of individuals receiving antiretroviral therapy (ART) screened for TB increased from 14 530 to 29 467 (P < 0.001); the number of individuals with presumptive TB identified increased from 803 to 1800 (P < 0.001); the number of ART clients bacteriologically tested for TB increased from 746 to 1717 (P < 0.001); and the number of ART clients treated for TB increased from 152 to 282 (P < 0.001). Newly registered or relapsed TB cases increased from 436 to 906 (P < 0.001), the number of TB cases with known HIV status increased from 437 to 837 (P < 0.001), the number of TB-HIV co-infected cases increased from 182 to 301 (P = 0.006), and the number of TB-HIV co-infected clients who started ART increased from 101 to 176 (P = 0.003).Conclusion: The implementation of the updated HIV SOC package led to the improvement in key TB diagnosis and treatment indicators. When emulated, this could help improve the performance of other TB programs in countries other than Nigeria.

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