Common Reason For Exclusion Research Articles

Abstract 4137986: Evaluation of an AI-Based Clinical Trial Screening Method Through a Randomized Controlled Implementation Study

Background: Clinical trial screening is labor-intensive, time-consuming, and error prone. We have developed RECTIFIER, an AI-based clinical trial screening tool, to enhance the efficiency and accuracy of patient recruitment. This study aims to evaluate RECTIFIER's effectiveness compared to manual screening in a randomized implementation study. Methods: This study was designed as an implementation study as part of an active heart failure trial named COPILOT-HF (NCT05734690). Potential eligible patients were identified via a structured electronic medical record query and randomized to be screened for clinical trial eligibility either by RECTIFIER or manually by clinical staff. The outcome measures included the number of patients contacted, and the number of patients reached for clinical trial enrollment. Data was collected over a period of 3 months. Results: A total of 3834 patients were included in the study, with 1919 patients randomized to the RECTIFIER group and 1915 patients to the manual screening group (Figure). Study staff could manually screen only 1367 patients at the end of the 3-month period. RECTIFIER identified more eligible patients compared to manual screening (833[43.4%] vs. 284[14.8%], p<0.001). The most common reason for exclusion was absence of symptomatic heart failure in both groups (287 in RECTIFIER 304 in manual screening). Screening via RECTIFIER also led to a higher contact rate, with 455 patients being contacted compared to 216 in the manual group (23.7% vs. 11.3%, p<0.001). The percentage of patients who could be reached for an enrollment call was also higher in the RECTIFIER group, with 330 patients responding versus 164 in the manual group (17.2% vs. 8.6%, p<0.001). Conclusion: Screening via RECTIFIER significantly outperformed manual screening in identifying eligible patients, contacting them, and eliciting responses. These results suggest that integrating AI into clinical trial recruitment processes can enhance efficiency and effectiveness, potentially leading to increased patient participation in clinical trials. Future studies with sufficient power should assess recruitment endpoints and explore scalability.

Projected Annual Lecanemab Treatment Eligibility in an Irish Regional Specialist Memory Clinic.

The advent of Disease Modifying Therapies (DMTs) for the treatment of Alzheimer's Disease (AD) has the potential to transform the lives of those with early AD. Timely identification of eligible patients is needed to ensure treatments are delivered during a narrow window of therapeutic opportunity. Appropriate clinical service design will hinge on improved understanding of future demands, thus there is a pressing need to investigate patient eligibility in real world clinical cohorts. The primary aim of this study is to assess the eligibility by appropriate use criteria (AUC) for lecanemab therapy in a real-world, undifferentiated clinical patient cohort attending a Regional Specialist Memory Clinic (RSMC), with the secondary aims of determining the proportion of patients with biomarker positive Alzheimer's Disease (AD) who would be eligible for lecanemab therapy by AUC. Clinical trial eligibility criteria were also applied to both groups and discrepancies that exist between eligibility rates explored. A retrospective cohort study of all new patients attending a RSMC from 1st January 2022 to 31st December 2022 was conducted. Data collected included demographic details, outcomes of diagnostic assessments and comorbidities. MRI images, where indicated, were reviewed. Amyloid positivity was defined as either Amyloid and Tau positive (A+T+) or Amyloid positive with a positive P-Tau/Ab42 ratio on cerebrospinal fluid (CSF) testing. Appropriate use criteria (AUC) and clinical trial criteria for lecanemab were applied. Proportion of eligible patients was calculated. Eleven (5.9%) of 188 new patient attenders were eligible (average age 66.7years [SD 8.9], 63.6% female) by AUC, with 26.2% of patients with biomarker positive Alzheimer's Disease eligible for lecanemab therapy. The most common reason for exclusion was a lack of biomarker confirmation of AD pathology followed by cognitive ineligibility (based on defined cognitive testing cut-offs) at the time of referral and/or initial assessment. Only 40.4% of patients had CSF testing for AD biomarkers while almost 20% of the patients with biomarker positive AD were excluded due to lack of a screening MRI in the previous 12months. In this study, the potential eligibility rate by AUC of the entire patient cohort (5.9%) was limited by the small proportion of patients who had CSF testing for AD biomarkers. So while disease-modification with Lecanemab is a welcome therapeutic advance, although only a small proportion of people currently attending specialist services will be eligible. Successful delivery of DMTs will require significant resource allocation and optimisation of referral pathways to facilitate early identification of potentially eligible patients.

Automated dispensing cabinets and their impact on the rate of omitted and delayed doses: A systematic review

Use of automated dispensing cabinets (ADCs) is increasing in hospital settings. ADCs bring various potential benefits, among which are improvements to patient safety and reduction of medication errors. A core function of ADCs is to prevent medication stock outs by triggering an order when stock is reaching low levels. A quantifiable patient safety measure is the occurrence of omitted or delayed doses, which can range in severity from being negligible, to potentially fatal. The purpose of this review is to identify and synthesise the existing evidence regarding the impact of ADCs situated in secondary and tertiary care inpatient settings, on the rate of omitted and delayed doses as a specific subsection of medication errors. In April 2024 searches were conducted in Embase, PubMed and CINAHL, with additional articles discovered through citation searching and from colleagues. A total of 375 articles were returned from the search. Nine articles met the inclusion criteria. The most common reason for exclusion was due to lack of relevance. The included papers were focused on centres which had implemented six or fewer ADCs. The studies mostly presented findings which suggest ADCs have a positive impact on the rate of omitted or delayed doses, although crucially only two papers correlated missed doses due to unavailability of medications The studies highlighted other factors which should be considered prior to the implementation of ADCs. Factors included staffing requirement, type of stock held in the cabinets, and interoperability with other systems. Studies only reported omitted or missed doses, none reported results on delayed doses. It is widely accepted that ADCs can prevent medication unavailability but there is a paucity of evidence linking the improved availability of medications through the utilisation of ADCs with the perceived impact on missed or delayed doses. Further multi-centre studies are needed to determine this causality.

Behavior Change Approaches in Digital Technology-Based Physical Rehabilitation Interventions Following Stroke: Scoping Review.

Digital health technologies (DHTs) are increasingly used in physical stroke rehabilitation to support individuals in successfully engaging with the frequent, intensive, and lengthy activities required to optimize recovery. Despite this, little is known about behavior change within these interventions. This scoping review aimed to identify if and how behavior change approaches (ie, theories, models, frameworks, and techniques to influence behavior) are incorporated within physical stroke rehabilitation interventions that include a DHT. Databases (Embase, MEDLINE, PsycINFO, CINAHL, Cochrane Library, and AMED) were searched using keywords relating to behavior change, DHT, physical rehabilitation, and stroke. The results were independently screened by 2 reviewers. Sources were included if they reported a completed primary research study in which a behavior change approach could be identified within a physical stroke rehabilitation intervention that included a DHT. Data, including the study design, DHT used, and behavior change approaches, were charted. Specific behavior change techniques were coded to the behavior change technique taxonomy version 1 (BCTTv1). From a total of 1973 identified sources, 103 (5%) studies were included for data charting. The most common reason for exclusion at full-text screening was the absence of an explicit approach to behavior change (165/245, 67%). Almost half (45/103, 44%) of the included studies were described as pilot or feasibility studies. Virtual reality was the most frequently identified DHT type (58/103, 56%), and almost two-thirds (65/103, 63%) of studies focused on upper limb rehabilitation. Only a limited number of studies (18/103, 17%) included a theory, model, or framework for behavior change. The most frequently used BCTTv1 clusters were feedback and monitoring (88/103, 85%), reward and threat (56/103, 54%), goals and planning (33/103, 32%), and shaping knowledge (33/103, 32%). Relationships between feedback and monitoring and reward and threat were identified using a relationship map, with prominent use of both of these clusters in interventions that included virtual reality. Despite an assumption that DHTs can promote engagement in rehabilitation, this scoping review demonstrates that very few studies of physical stroke rehabilitation that include a DHT overtly used any form of behavior change approach. From those studies that did consider behavior change, most did not report a robust underpinning theory. Future development and research need to explicitly articulate how including DHTs within an intervention may support the behavior change required for optimal engagement in physical rehabilitation following stroke, as well as establish their effectiveness. This understanding is likely to support the realization of the transformative potential of DHTs in stroke rehabilitation.

3‐month melatonin supplementation to reduce brain oxidative stress and improve sleep in mild cognitive impairment: a randomised controlled feasibility trial

AbstractBackgroundMelatonin has multiple proposed therapeutic benefits including antioxidant properties, circadian rhythm synchronisation and sleep promotion. Since these areas are also recognised risk factors for dementia, melatonin has been hypothesised to slow cognitive decline in older adults.MethodParticipants with Mild Cognitive Impairment (MCI) were recruited from the community for a 12‐week randomised placebo‐controlled parallel, feasibility trial of 25mg oral melatonin daily. Primary outcomes were feasibility, acceptability, and tolerability. Secondary outcomes were brain oxidative stress, cognition, mood, and sleep at 12 weeks.ResultForty participants were randomised to receive melatonin or placebo. Feasibility, determined by the percentage of people who met inclusion and exclusion criteria and could potentially join the study, was 42/389, 11%. The most common reason for exclusion was age. Acceptability, the number of people who agreed to be randomised as a fraction of all potential participants, was 40/42, 95%. Adherence to the intervention and completion of the main secondary outcome (oxidative stress) was over the pre‐defined 80% threshold for all participants and reported safety outcomes were balanced between groups. The current protocol was feasible and acceptable as we reached our target of 40 participants between 60‐80 years of age with MCI. All participants were able to complete all aspects of the trial, including online visits and assessments.ConclusionThis is promising for future trials which should conduct the study with a higher sample size and longer duration to yield necessary efficacy data.

C3+ and C3- Warm Autoimmune Hemolytic Anemias: A Comparison of Clinical Characteristics and Treatment Outcomes

Background: Warm autoimmune hemolytic anemia (WAIHA) is mostly IgG mediated (IgG+C3-), which may at times fix complement (IgG+C3+). Whether the clinical outcome of complement-fixing (C3+) WAIHA is different from that of non-complement fixing (C3-) WAIHA remains unclear. The goal of this retrospective study was to describe and compare the clinical characteristics and treatment outcomes of patients with C3+ and C3- WAIHA. Methods: We included adult WAIHA patients seen at our institution from 2001-2023 who met all of the following criteria: A) age >18 years; B) direct antiglobulin test [DAT] IgG+ + C3+ with no cold agglutinin; and C) biochemical evidence of hemolysis. Response to treatment was based on the international consensus criteria: complete (CR; normal Hb or Hb ≥12 g/dL, with resolution of hemolysis); partial (PR; Hb >10 but <12 g/dL or Hgb >12 g/dL without resolution of hemolysis); or no response (neither CR nor PR). 223 WAIHA patients were found, and 132 patients were ultimately included. The most common reason for exclusion was a lack of complete DAT that included C3 testing. Results: There were 59 patients with C3- WAIHA and 73 patients with C3+ WAIHA, reflecting 44.7% and 55.3% of total patients respectively. Pertinent demographic, clinical, and treatment information are shown in Table 1. Slightly over half (52.3%) were males and the mean age (SD) was 63.9 years (18.1). Concomitant lymphoproliferative disease was present in 34.1% of the patients. The 3 most common treatments were steroids (97%), rituximab (66.7%), and splenectomy (18.2%). The median follow-up from diagnosis was 20.0 months (range, 1.0-251.8 months), and 14.4% of patients had died at the time of this analysis with no difference between the groups (P=0.82). There was no significant difference in the demographic composition, clinical findings, and treatment received in both groups. The number of treatments received were similar between C3- and C3+ WAIHA groups (Table 1). After first line of treatment, response was achieved in 86.4% and 94.4% of the C3- and C3+ groups (P=0.12), respectively. Additionally, 62.7% of the C3- group and 80.8% of the C3+ group were in PR or CR by their most recent CBC (P=0.02). 33.9% and 43.8% of the C3- and C3+ groups relapsed at least once (P=0.25). In those who relapsed, there was an average of 2.6 relapse events in the C3- WAIHA group compared to 1.8 relapse events in the C3+ WAIHA group (P=0.03). However, there was no difference in time to first relapse between the groups (P=0.51), shown in Figure 1. Conclusion: There have been retrospective descriptions of multiple AIHA subtypes and response rates to different therapies; however, this is one of the first studies to our knowledge to focus specifically on outcomes between complement subgroups. In our large group of patients with C3- and C3+ WAIHA, the clinical presentation, treatments utilized, and response to treatment were similar. Our data suggest that C3- and C3+ WAIHA can be approached and treated similarly.

Utility of a prognostic assessment tool to predict survival following surgery for brain metastases.

Brain metastases account for more than 50% of all intracranial tumors and are associated with poor outcomes. Treatment decisions in this highly heterogenous cohort remain controversial due to the myriad of treatment options available, and there is no clearly defined standard of care. The prognosis in brain metastasis patients varies widely with tumor type, extracranial disease burden and patient performance status. Decision-making regarding treatment is, therefore, tailored to each patient and their disease. This is a retrospective cohort study assessing survival outcomes following surgery for brain metastases over a 50-month period (April 1, 2014-June 30, 2018). We compared predicted survival using the diagnosis-specific Graded Prognostic Assessment (ds-GPA) with actual survival. A total of 186 patients were included in our cohort. Regression analysis demonstrated no significant correlation between actual and predicted outcome. The most common reason for exclusion was insufficient information being available to the neuro-oncology multidisciplinary team (MDT) meeting to allow GPA calculation. In this study, we demonstrate that "predicted survival" using the ds-GPA does not correlate with "actual survival" in our operated patient cohort. We also identify a shortcoming in the amount of information available at MDT in order to implement the GPA appropriately. Patient selection for aggressive therapies is crucial, and this study emphasizes the need for treatment decisions to be individualized based on patient and cancer clinical characteristics.

Safety of peripheral 3% hypertonic saline bolus administration for neurologic emergency

Background/objectiveHypertonic sodium chloride (HTS) is used for emergent treatment of acute cerebral edema and other neurologic emergencies. Central access is not commonly available in emergent situations and 3% HTS is utilized peripherally. Many studies have shown the safety of its administration at rates up to 75 mL/h, but there is a lack of data to establish the safety of peripherally administered, rapid bolus dosing in emergent situations. The objective of this study is to describe the safety of rapid, peripherally administered (≥ 250 mL/h) 3% HTS for neurologic emergencies. MethodsThis is a retrospective, cohort study including adult patients receiving 3% HTS via a peripheral IV site for elevated intracranial pressure, cerebral edema, or other neurological emergencies at a rate of at least 250 m/h between May 5, 2018 – September 30, 2021. Patients were excluded if they simultaneously received another hypertonic saline fluid. Baseline characteristics collected included HTS dose, rate and site of administration, indication for use and patient demographics. The primary safety outcome was incidence of extravasation and phlebitis within one hour of HTS administration. ResultsThere were 206 patients receiving 3% HTS who were screened, and 37 patients met inclusion criteria. The most common reason for exclusion was administration at a rate < 250 m/h. The median age was 60 (IQR 45, 72) with 51.4% being male. The most common indications for HTS were traumatic brain injury (45.9%) and intracranial hemorrhage (37.8%). The most common administration location was the emergency department (78.4%). The median IV-gauge (n = 29) was 18 (IQR 18, 20), with the most common placement site being antecubital (48.6%). The median dose of HTS was 250 mL (IQR 250, 350), with a median administration rate of 760 mL/h (IQR 500, 999). There were no episodes of extravasation or phlebitis noted. ConclusionsRapid, peripheral administration of 3% HTS boluses is a safe alternative for treatment of neurologic emergencies. Administration at rates up to 999 mL/h did not result in extravasation or phlebitis.

Reasons for ineligibility for clinical trials of patients with medication-resistant epilepsy.

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for exclusion. Among 212 patients with medication-resistant epilepsy, 144 and 28 patients met the criteria for focal or generalized onset epilepsy, respectively. Overall, 9.4% (n = 20) patients were eligible for trials (19 focal onset and one generalized onset). Most patients were excluded from the study due to insufficient seizure frequency (58% of focal onset, 55% of generalized onset). A small proportion of patients with medication-resistant epilepsy were eligible for trials based on common selection criteria. These eligible patients may not be representative of the general population of patients with medication-resistant epilepsy. Insufficient seizure frequency was the most common reason for exclusion.

85. The neurology stability epidural compression assessment: a new score to establish the need for surgery in spinal metastases

85. The neurology stability epidural compression assessment: a new score to establish the need for surgery in spinal metastases

Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan.

The design and baseline data of the PRECISION study, which evaluates the effect of the dual endothelin receptor antagonist aprocitentan on blood pressure (BP) in patients with resistant hypertension (RHT) are presented. The study is a blinded, randomized, parallel‐group Phase 3 study and its three‐part design assesses the short‐term and sustained long‐term effects of aprocitentan on BP. Results are expected in 2022.Patients with uncontrolled BP (measured as unattended automated office BP) despite the use of three or more antihypertensive medications for at least 1 year were screened. They were switched to a single‐tablet triple fixed combination antihypertensive therapy for at least 4 weeks before entering a single‐blind placebo run‐in period. The 4‐week placebo run‐in period further excluded placebo responders. The randomization period consisted of three sequential parts: (1) a 4‐week double‐blind part with aprocitentan 12.5 mg, 25 mg, or placebo (1:1:1 ratio); (2) a 32‐week single‐blind part with aprocitentan 25 mg; and (3) a 12‐week randomized withdrawal part with aprocitentan 25 mg or placebo (1:1 ratio). The purpose was to demonstrate the BP lowering effect of aprocitentan in RHT (Part 1) and the persistence of this effect (Parts 2 and 3).Out of 1965 screened patients, 730 were randomized resulting in an overall inclusion failure rate of 62.8%. The most common reason for exclusion (44.4% of all screened patients) was failure to meet the BP inclusion criteria. These results underline the high proportion of pseudoresistant hypertension among patients referred for RHT.

Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome.

BackgroundInhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States.MethodsThis was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression–Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio.ResultsThirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I.ConclusionIn patients hospitalized with COVID-19 and mild-to-moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit–risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.

Baseline data of a sequential multiple assignment randomized trial (STEP study).

Research has shown that preventative intervention in individuals at ultra-high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectiveness of (1) support and problem solving, (2) cognitive-behavioural case management and (3) antidepressant medication with an embedded fast-fail option of (4) omega-3 fatty acids or low-dose antipsychotic medication. This paper presents the recruitment flow and baseline clinical characteristics of the sample. STEP is a sequential multiple assignment randomized trial. We present the baseline demographics, clinical characteristics and acceptability and feasibility of this treatment approach as indicated by the flow of participants from first contact up until enrolment into the trial. Recruitment took place between April 2016 and January 2019. Of 1343, help-seeking young people who were considered for participation, 402 participants were not eligible and 599 declined/disengaged, resulting in a total of 342 participants enrolled in the study. The most common reason for exclusion was an active prescription of antidepressant medication. Eighty-five percent of the enrolled sample had a non-psychotic DSM-5 diagnosis and symptomatic/functional measures showed a moderate level of clinical severity and functional impairment. The present study demonstrates the acceptability and participant's general positive appraisal of sequential treatment. It also shows, in line with other trials in UHR individuals, a significant level of psychiatric morbidity and impairment, demonstrating the clear need for care in this group and that treatment is appropriate.

1297. Azithromycin vs Beta Lactams in Acute Exacerbations of COPD

BackgroundBacterial infections cause approximately 50% of Acute Exacerbations of COPD (AECOPD). Current guidelines recommend a wide range of antibiotics, but evidence comparing agents is limited. The purpose of this study is to compare the effectiveness of azithromycin to beta lactams in the treatment of hospitalized patients with AECOPD.MethodsA multicenter, retrospective, observational study of adult patients admitted with AECOPD who received at least two consecutive days of either a beta lactam or azithromycin were included. The primary endpoint was treatment failure which is a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, requirement of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days. Secondary endpoints included each individual component of the composite endpoint and length of stay.ResultsOf 11,395 patients screened, 595 met the inclusion criteria (428 were treated with azithromycin and 167 patients were treated with a beta lactam). The most common reason for exclusion was the receipt of both azithromycin and beta-lactam in 9857 patients. The patients were similar except the azithromycin group was more likely to be African-American and less likely to have failed an outpatient antibiotic. Treatment failure rate was 19.6% in the azithromycin group and 32.3% in the beta lactam group (P=0.001). Patients in the beta lactam group were more likely to experience in-hospital mortality (P=0.023), require a new antibiotic during admission (P< 0.001), and were more likely to be readmitted within 30 days of discharge due to AECOPD (P=0.032). Length of stay was significantly shorter in the azithromycin group compared to the beta lactam group. There were no statistically significant differences in the rates of adverse events among both groups.ConclusionTreatment failure rate and length of stay were significantly higher in the beta lactam group compared to the azithromycin group. However, there were no differences in the side effect profile among both groups. Further studies should be performed to confirm these findings.Disclosures All Authors: No reported disclosures

Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.

Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus

BackgroundMen who have sex with men (MSM) are at high risk for human papillomavirus (HPV)–related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied.MethodsTwo hundred and sixty MSMLWH aged 18–26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24.ResultsAmong 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type–associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18–associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events.Conclusions18–26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type–associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Eyes that Do Not Meet the Eligibility Criteria of Clinical Trials on Age-Related Macular Degeneration: Proportion of the Real-World Patient Population and Reasons for Exclusion.

Background To evaluate the proportion of eyes that do not meet the eligibility criteria of clinical trials on neovascular age-related macular degeneration (AMD) and the reasons for exclusion. Methods This retrospective, observational study included 512 eyes of 463 patients diagnosed with treatment-naïve neovascular AMD. The proportion of eyes that did not meet the eligibility criteria of the Vascular Endothelial Growth Factor Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies were evaluated. The two most common reasons for exclusion were also evaluated in each subtype of neovascular AMD (typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), and type 3 neovascularization). Results Among the 512 eyes, 229 (44.7%) did not meet the eligibility criteria. In all the included eyes, the most common reasons for exclusion were good or poor visual acuity (169 eyes, 33.0%), followed by the presence of subretinal hemorrhage (47 eyes, 9.5%). Moreover, good or poor visual acuity was the most common reason for exclusion in all three subtypes of neovascular AMD. The second most common reason was a fovea-involving scar or fibrosis in typical neovascular AMD, subretinal hemorrhage in PCV, and other vascular diseases affecting the retina in type 3 neovascularization. Conclusions Among the included cases, 44.7% did not meet the eligibility criteria for VIEW study, suggesting that the conclusion derived from clinical trials may not directly reflect the real-world outcomes. Additionally, the reasons for ineligibility differed among the different subtypes of neovascular AMD.

Role of Cardiac CT in Pre-Procedure Planning for Transcatheter Mitral Valve Replacement

ObjectivesThis study sought to evaluate cardiac computed tomography (CCT) findings and their clinical impact among patients being considered for transcatheter mitral valve replacement (TMVR). BackgroundCCT is used to evaluate whether patients are candidates for TMVR, but limited data exist on the yield of such tests. MethodsPatients referred for pre-procedural CCT for TMVR planning in the context of failing mitral bioprosthetic valves, annuloplasty rings, and severe native valve disease with annular calcification were included in this study. CCT findings were analyzed to evaluate for suitability for TMVR. In the subset of patients who underwent TMVR, echocardiographic and procedural characteristics were recorded. ResultsAmong 80 patients who underwent pre-procedural CCT, the mean age was 71.8 ± 11.4 years, 60% were women, and the mean Society of Thoracic Surgeon score was 9.4 ± 6.7. Most cases were referred for valve-in-native annular calcification planning (n = 43), followed by valve-in-valve (n = 29), and valve-in-ring procedures (n = 8). A total of 51 (64%) patients did not undergo TMVR, 37 of whom had high-risk features identified on CCT. The most common reason for exclusion was related to large annular size, followed by heightened risk of left ventricular outflow tract (LVOT) obstruction. Among 29 patients (36%) who underwent TMVR, the 30-day mortality rate was 17%. Five patients experienced LVOT obstruction, 4 of whom were predicted by CCT. Following TMVR, 5 patients had at least moderate peri-valvular regurgitation. ConclusionsA minority of patients referred for TMVR planning ultimately undergo the procedure. CCT identifies unsuitable anatomy and leads to exclusion in a significant number of cases.

Thromboelastography is a Marker for Clinically Significant Progressive Hemorrhagic Injury in Severe Traumatic Brain Injury.

Coagulopathy in traumatic brain injury (TBI) is associated with increased risk of poor outcomes, but accurate prediction of clinically significant progressive hemorrhagic injury (PHI) in patients with severe TBI remains a challenge. Thromboelastography (TEG) is a real-time test of whole blood coagulation that provides dynamic information about global hemostasis. This study aimed to identify differences in TEG values between patients with severe TBI who did or did not experience clinically significant PHI. This was a single-center retrospective cohort study of adult patients with severe TBI. Patients were eligible for inclusion if initial Glasgow coma scale (GCS) was ≤ 8 and baseline head computed tomography (CT) imaging and TEG were available. Exclusion criteria included receipt of hemostatic agents prior to TEG. PHI was defined as bleeding expansion on CT within 24h associated with 2-point drop in GCS, neurosurgical intervention, or mortality within 24h. The primary endpoint was TEG value differences between patients with and without PHI. Secondary endpoints included differences in conventional coagulation tests (CCTs) between groups. Of the 526 patients evaluated, 141 met inclusion criteria. The most common reason for exclusion was lack of baseline TEG and receipt of reversal product prior to TEG. Sixty-four patients experienced PHI in the first 24h after presentation. K time (2.03min vs. 1.33min, P = 0.035) and alpha angle (65° vs. 69°, P = 0.015) were found to be significantly different in patients experiencing PHI. R time (5.25min vs. 4.71min), maximum amplitude (61mm vs. 63mm), and clot lysis at 30min after maximum clot strength (3.5% vs. 1.7%) were not significantly different between groups. Of the CCTs, only activated partial thromboplastin time (30.3s vs. 27.6s, P = 0.014) was found to be different in patients with PHI. Prolonged K time and narrower alpha angle were found to be associated with developing clinically significant PHI in patients with severe TBI. Despite differences detected in alpha angle, median values in both groups were within normal reference ranges. These abnormalities may reflect pathologic hypoactivity of fibrinogen, and further study is warranted to evaluate TEG-guided cryoprecipitate administration in this patient population.

Wearable inertial sensors for gait analysis in adults with osteoarthritis – a scoping review

Purpose: While there is no cure for OA, lower limb biomechanical data collected during walking can provide valuable information on the etiology, progression, and treatment of this disease. Unfortunately, these conventional systems can be expensive and time-consuming, which make them inaccessible to many clinicians. Fortunately, the advent of wearable inertial sensors has provided an accessible and affordable alternative to conventional optical gait analysis systems. This growing area of research has demonstrated the immense potential of these devices, but the literature remains fragmented across the broad field of OA biomechanics. Therefore, in conducting this scoping review we aimed to summarize the growing body of literature using wearable inertial sensors for gait analysis in OA. Specifically, our objective was to identify biomechanical outcomes and applications of wearable inertial sensors for assessing walking gait in adults diagnosed with lower limb OA. We aimed to highlight the quality and types of research prominent in this field, with a focus on biomechanical outcomes and important gaps to be addressed in future research. Methods: We searched six databases using predetermined search terms which highlighted the broad areas of inertial sensors, gait, and osteoarthritis on June 9, 2020. Specifically, our criteria aimed to include studies which used inertial sensors (i.e., accelerometers, gyroscopes, and/or magnetometers) for walking gait analysis in adults diagnosed with lower limb OA (e.g., hip, knee, or ankle). Studies which only examined outcomes not related to an assessment of walking gait patterns (e.g., daily step count, physical activity, energy expenditure) were not considered. Two authors independently conducted title and abstract reviews, followed by full-text screening. Study quality was also assessed by two independent reviewers. Data were extracted from included studies in areas such as study design, osteoarthritis sample, protocols, and inertial sensor outcomes. Results: Search and Screening Results. Our search strategy identified a total of 561 articles and 376 articles after duplicate removal. A total of 107 articles were passed to full-text screening which were further reduced to 72 studies included in our scoping review. The PRISMA flow diagram presented in Figure 1 documents all exclusions at the full-text level. The most common reason for exclusion at the full-text level was “no biomechanical outcomes”, which was generally the result of studies measuring only physical activity or step count data. Osteoarthritis Sample and Protocols. The gait of 2,159 adults with OA were examined using wearable inertial sensors across the 72 studies. The most common location of OA studied was the knee (n=46), followed by the hip (n=22), and the ankle (n=7). The most common placement of sensors was the back/pelvis/torso (n=41), followed closely by the shank (n=40), foot (n=31), thigh (n=27), and head/neck (n=5). The most common study design was found to be cross-sectional (n=44), with most examining differences in gait between OA and controls (n=34). There were 21 studies that utilized some type of longitudinal design, with most examining the effect of surgery (n=17) and 4 examining other interventions (e.g., exercise, gait retraining). Figure 2 illustrates the number of included studies published each year, grouped by study design. Inertial Sensor Outcomes. Mean ST parameters were the most common outcome as they were presented in 45 studies. The variability and symmetry of ST parameters were each presented in 14 studies. The second most common outcome was segment orientation or joint angles, measured in 33 studies. Linear acceleration magnitudes were the third most common and appeared in 22 studies, with estimates of variability or symmetry components surrounding these outcomes present in 10 studies. Figure 3 provides a visual representation of gait outcomes by sensor locations. Conclusions: Wearable inertial sensors provide an accessible and affordable tool to support our understanding and treatment of OA through gait analyses. We identified 72 studies which have utilized wearable inertial sensors to assess OA gait. Overall, these studies measured a wide range of outcomes from mean ST parameters to the KAM and more. Similarly, the patient populations, study designs, and sensor protocols varied greatly between studies. Two-thirds of these studies were published in the past five years (Figure 1) and we predict that 2019 may be an inflection point whereafter remarkable growth will occur in this area for years to come. While mean ST parameters remain the most assessed outcomes in OA, recent work has highlighted inertial sensors ability to measure more advanced outcomes such as knee joint angle, KAM, and impact accelerations, as well as a variety of variability and symmetry measures. Nevertheless, there remains a need for more longitudinal study designs, patient-specific models, free-living assessments, and a push for “Code Reuse” to maximize the unique capabilities of these devices and ultimately improve how we diagnose and treat this debilitating disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)