US Clinical Research Articles

Paper 30: Superior Improvements in Knee Pain and Function with a Novel Synthetic Medial Meniscus Replacement Prosthesis Compared to Non-surgical Care in Subjects with Knee Pain Following Partial Meniscectomy: Three-year Results from Two Prospective US Clinical Trials

Objectives:Results from 2 FDA-regulated clinical trials demonstrate superiority of a synthetic medial meniscus prosthesis to non-surgical care in treating persistent or recurrent knee pain following previous partial meniscectomy.Arthroscopic partial meniscectomy (APM) is the most common surgical treatment for symptomatic, irreparable meniscal tears that do not improve with non-surgical care. For many patients, APM is associated with improvements in knee pain and function, but a subset of patients report persistent or recurrent knee pain 1-2 years after APM surgery. Current treatment options for post-APM knee pain are limited, especially for patients considered too young for knee replacement. The polymeric medial meniscus prosthesis (NUsurfaceâ, Active Implants, Memphis TN) mimics the biomechanical function of the natural medial meniscus and provides relief from pain and improved function in subjects with knee pain following APM. The meniscus prosthesis met the primary endpoint of superiority over non-surgical care at 2 years. The current hypothesis was that investigational subjects maintained superior improvements in knee-related pain, function, and quality of life, compared to non-surgical subjects, through 3 years of follow-up.Methods:242 subjects (176 investigational, 66 control) treated in 2 prospective, concurrent clinical trials in the U.S., and pooled for analysis: a randomized controlled superiority trial (RCT) comparing the investigational device (investigational group) to non-surgical care (control), and a single-arm, prosthesis-only trial. Subjects had persistent knee pain and one or more previous partial meniscectomies at least 6 months before trial entry. Subject follow-up visits at 1.5 months, 6 months, 1, 2 and 3 year. Patient-reported knee pain, function, and quality of life were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Treatment cessation was defined as any investigational subject who discontinued the per-protocol treatment by permanent prosthesis removal, or control subjects undergoing any surgical procedure on the index knee. Investigational subjects who underwent subsequent surgical procedures on index knees (e.g. prosthesis exchange) remained in the trial. The investigational and control cohorts analyzed were compared at each time point using a two tailed t-test. All baseline cohort comparisons of demographics were not statistically different (p>0.05).Results:The magnitude of improvement from baseline to 3 years was statistically superior in the investigational cohort, compared to the control cohort for all 6 KOOS subscales (Figure 1), including the primary outcomes of KOOS Overall and KOOS Pain (Figure 1A, B). Improvement in KOOS Overall and KOOS Pain for the investigational and control cohorts at 3 years were 26.4 vs 10.4 points, and 26.9 vs 15.4 points, respectively (Figure 1). These data show a statistically significant improvement, exceeding a clinically meaningful improvement of ≥20 points versus controls as early as 6 months (20.0 vs 9.2 pts), continuing through the 3-year timepoint. Controls experienced a 35% decline in KOOS Overall improvement between the 2-year and 3-year timepoint (15.9 vs 10.4). Accountability of patients not available or yet reaching the 3-year follow-up time period are reflected in Table 1. Treatment cessation through 3 years was 31% greater in the control cohort than the investigational cohort (15.0% vs. 19.6%).Conclusions:Three-year results demonstrate statistically superior relief from post-APM knee pain and function compared to non-surgical care alone. At 3 years, the magnitude of change from baseline to 3 years significantly favored the investigational device compared to control treatments. Investigational subjects discontinued treatment at a far lower rate compared to control subjects. Investigational subjects who underwent a device exchange or repositioning procedure were able to continue therapy benefit with the medial meniscus prosthesis. In all KOOS subscales, the investigational subjects experienced superior improvements and outcomes at 3 years compared to non-surgical care subjects.Figure 1.Magnitude of improvement in KOOS Overall (A), Pain (B), Symptoms (C), Activities of Daily Living (ADL; D), Sports and Recreation (E), and Quality of Life (QOL; F) from baseline (BL) to each follow-up time point.Table 1.Numbers are patients available to complete the KOOS questionnaire; Numbers in parentheses are percentages of the baseline population.

Development of a WeChat-based Mobile Messaging Smoking Cessation Intervention for Chinese Immigrant Smokers: Qualitative Interview Study.

BackgroundSmoking remains a major public health issue among Chinese immigrants. Smoking cessation programs that focus on this population are scarce and have a limited population-level impact due to their low reach. Mobile messaging interventions have the potential to reach large audiences and expand smokers’ access to smoking cessation treatment.ObjectiveThis study describes the development of a culturally and linguistically appropriate mobile messaging smoking cessation intervention for Chinese immigrant smokers delivered via WeChat, the most frequently used social media platform among Chinese people globally.MethodsThis study had 2 phases. In phase 1, we developed a mobile message library based on social cognitive theory and the US Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We culturally adapted messages from 2 social cognitive theory-based text messaging smoking cessation programs (SmokefreeTXT and Decídetexto). We also developed new messages targeting smokers who were not ready to quit smoking and novel content addressing Chinese immigrant smokers’ barriers to quitting and common misconceptions related to willpower and nicotine replacement therapy. In phase 2, we conducted in-depth interviews with 20 Chinese immigrant smokers (including 7 women) in New York City between July and August 2021. The interviews explored the participants’ smoking and quitting experiences followed by assessment of the text messages. Participants reviewed 17 text messages (6 educational messages, 3 self-efficacy messages, and 8 skill messages) via WeChat and rated to what extent the messages enhanced their motivation to quit, promoted confidence in quitting, and increased awareness about quitting strategies. The interviews sought feedback on poorly rated messages, explored participant preferences for content, length, and format, discussed their concerns with WeChat cessation intervention, and solicited recommendations for frequency and timing of messages.ResultsOverall, participants reported that the messages enhanced their motivation to quit, offered encouragement, and made them more informed about how to quit. Participants particularly liked the messages about the harms of smoking and strategies for quitting. They reported barriers to applying some of the quitting strategies, including coping with stress and staying abstinent at work. Participants expressed strong interest in the WeChat mobile messaging cessation intervention and commented on its potential to expand their access to smoking cessation treatment.ConclusionsMobile messages are well accepted by Chinese immigrant smokers. Research is needed to assess the feasibility, acceptability, and efficacy of WeChat mobile messaging smoking cessation interventions for promoting abstinence among Chinese immigrant smokers.

Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx

Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n= 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n= 141), and between CHL subgroups (C&D [n= 56] and PR [n= 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Effectiveness of a Conversational Chatbot (Dejal@bot) for the Adult Population to Quit Smoking: Pragmatic, Multicenter, Controlled, Randomized Clinical Trial in Primary Care.

BackgroundTobacco addiction is the leading cause of preventable morbidity and mortality worldwide, but only 1 in 20 cessation attempts is supervised by a health professional. The potential advantages of mobile health (mHealth) can circumvent this problem and facilitate tobacco cessation interventions for public health systems. Given its easy scalability to large populations and great potential, chatbots are a potentially useful complement to usual treatment.ObjectiveThis study aims to assess the effectiveness of an evidence-based intervention to quit smoking via a chatbot in smartphones compared with usual clinical practice in primary care.MethodsThis is a pragmatic, multicenter, controlled, and randomized clinical trial involving 34 primary health care centers within the Madrid Health Service (Spain). Smokers over the age of 18 years who attended on-site consultation and accepted help to quit tobacco were recruited by their doctor or nurse and randomly allocated to receive usual care (control group [CG]) or an evidence-based chatbot intervention (intervention group [IG]). The interventions in both arms were based on the 5A’s (ie, Ask, Advise, Assess, Assist, and Arrange) in the US Clinical Practice Guideline, which combines behavioral and pharmacological treatments and is structured in several follow-up appointments. The primary outcome was continuous abstinence from smoking that was biochemically validated after 6 months by the collaborators. The outcome analysis was blinded to allocation of patients, although participants were unblinded to group assignment. An intention-to-treat analysis, using the baseline-observation-carried-forward approach for missing data, and logistic regression models with robust estimators were employed for assessing the primary outcomes.ResultsThe trial was conducted between October 1, 2018, and March 31, 2019. The sample included 513 patients (242 in the IG and 271 in the CG), with an average age of 49.8 (SD 10.82) years and gender ratio of 59.3% (304/513) women and 40.7% (209/513) men. Of them, 232 patients (45.2%) completed the follow-up, 104/242 (42.9%) in the IG and 128/271 (47.2%) in the CG. In the intention-to-treat analysis, the biochemically validated abstinence rate at 6 months was higher in the IG (63/242, 26%) compared with that in the CG (51/271, 18.8%; odds ratio 1.52, 95% CI 1.00-2.31; P=.05). After adjusting for basal CO-oximetry and bupropion intake, no substantial changes were observed (odds ratio 1.52, 95% CI 0.99-2.33; P=.05; pseudo-R2=0.045). In the IG, 61.2% (148/242) of users accessed the chatbot, average chatbot-patient interaction time was 121 (95% CI 121.1-140.0) minutes, and average number of contacts was 45.56 (SD 36.32).ConclusionsA treatment including a chatbot for helping with tobacco cessation was more effective than usual clinical practice in primary care. However, this outcome was at the limit of statistical significance, and therefore these promising results must be interpreted with caution.Trial RegistrationClinicaltrials.gov NCT 03445507; https://tinyurl.com/mrnfcmtdInternational Registered Report Identifier (IRRID)RR2-10.1186/s12911-019-0972-z

EE185 Healthcare Resource Utilization in US Clinical Practice Among Patients with von Willebrand Disease

International guidelines recommend long-term prophylaxis for patients with von Willebrand disease (VWD) and severe/frequent bleeding, but this is not currently approved in the US. We assessed healthcare resource utilization (HRU) in patients with VWD including those eligible for prophylaxis.

P1062: A REAL-WORLD EVALUATION OF THE ASSOCIATION BETWEEN ELEVATED BLOOD COUNTS AND THROMBOTIC EVENTS IN POLYCYTHEMIA VERA: AN ANALYSIS OF DATA FROM THE REVEAL STUDY

Background: Polycythemia vera (PV) is characterized by clonal hematopoiesis leading to elevated peripheral blood counts and an increased risk of thrombotic events (TEs). Advanced age and TE history form the conventional risk model used to determine TE risk/treatment strategy. Associations between TEs and elevated hematocrit (HCT) levels exist, but associations with white blood cell (WBC) or platelet (PLT) counts have not been assessed consistently. The large, real-world, prospective Observational Study of Pts with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159) followed pts with PV treated in community or academic centers. Aims: This analysis evaluated associations between elevated blood counts and TEs in pts with PV using data from REVEAL. Methods: Eligible pts had ≥3 lab values (blood counts) post-enrollment; pts with a post-enrollment TE but no lab value <6 mo before that TE were excluded. The association between blood counts and TEs was assessed using a time-dependent covariate Cox proportional hazards model. Time to first post-enrollment TE was modeled with time censored at last known visit for pts with no TE. Each lab parameter was modeled with sex, age, disease duration, and TE history at enrollment as baseline covariates and treatment as a time-dependent covariate. Blood counts were included as binary time–dependent covariates using the following thresholds: HCT >45%, WBC >11×109/L, PLT >400×109/L. Linear interpolation was used to determine lab values between observed lab values. Alternative thresholds for WBC (<7, ≥7 to <8.5; ≥8.5 to <11, and ≥11×109/L, and >12×109/L with HCT controlled at ≤45%) and PLT counts (>600×109/L) were evaluated. Statistical significance was considered at P<0.05. Results: 2271/2510 pts were eligible (median age, 66 y [range, 22–95]; male, 54.1%). Median disease duration was 4.1 y (range, 0–56.3), 456 (20.1%) had TE history; 52.6% of pts received hydroxyurea. Of 106 pts who had TEs, 30 had arterial TEs (most commonly, transient ischemic attack [n=15]) and 76 had venous TEs (most commonly, deep vein thrombosis [n=37]). Elevated HCT levels (>45%, hazard ratio [HR]=1.84 [95% CI, 1.234–2.749], P=0.0028), WBC (>11×109/L, HR=2.35 [1.598–3.465], P<0.0001), and PLT counts (>400×109/L, HR=1.60 [1.088–2.359], P=0.0170) were each associated with increased TE risk (Table 1). WBC count ≥11×109/L is associated with the highest TE risk compared with WBC count <7×109/L (HR=2.61 [95% CI, 1.594–4.262], P<0.0001). Elevated WBC >12×109/L was significantly associated with increased risk of TE with HCT controlled at ≤45%. PLT count (>600×109/L) increased TE risk (HR=1.37 [95% CI, 0.763–2.468]) compared with PLT count ≤600×109/L, but this was not statistically significant (P>0.05). In all models, advanced age, female sex, and TE history were associated with increased TE risk. Image:Summary/Conclusion: This analysis of REVEAL, the largest real-world cohort of PV pts to date, demonstrated that elevated HCT levels (>45%), WBC (>11×109/L), and PLT counts (>400×109/L) were associated with increased TE risk. An association of elevated WBC >12×109/L with increased risk of TE was also observed when HCT was controlled, indicating that TE risk may be reduced by controlling WBC as well as HCT. These data support the need to incorporate blood count into risk stratification and treatment strategies for pts with PV in clinical practice and to move beyond the conventional risk model. Further studies to understand the causal relationship between elevated blood counts and TEs are warranted.

Anatomic Site-Specific Gonorrhea and Chlamydia Testing and Incidence Among People With HIV Engaged in Care at 4 US Clinical Centers, 2014-2018.

BackgroundThe incidence of Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) is increasing in the United States; however, there are limited data on anatomic site–specific GC/CT among people with HIV (PWH).MethodsWe reviewed records of all PWH in care between January 1, 2014, and November 16, 2018, at 4 sites in the CFAR Network of Integrated Clinical Systems Cohort (CNICS; n = 8455). We calculated anatomic site–specific GC/CT testing and incidence rates and used Cox proportional hazards models modified for recurrent events to examine sociodemographic and clinical predictors of GC/CT testing and incidence at urogenital, rectal, and pharyngeal sites. We also calculated site-specific number needed to test (NNT) to detect a positive GC/CT test.ResultsOf 8455 PWH, 2460 (29.1%) had at least yearly GC/CT testing at any anatomic site. The rates of urogenital, rectal, and pharyngeal GC were 1.7 (95% CI, 1.6–1.9), 3.2 (95% CI, 3.0–3.5), and 2.7 (95% CI, 2.5–2.9) infections per 100 person-years, respectively. The rates of urogenital, rectal, and pharyngeal CT were 1.9 (95% CI, 1.7–2.1), 4.3 (95% CI, 4.0–4.5), and 0.9 (95% CI, 0.8–1.0) infections per 100 person-years, respectively. PWH 16–39 years old experienced greater GC/CT rates at all anatomic sites, while men who have sex with men experienced greater rates of extragenital infections. NNTs for urogenital, rectal, and pharyngeal GC/CT were 20 (95% CI, 19–21), 5 (95% CI, 5–5), and 9 (95% CI, 8–9), respectively.ConclusionsMany PWH are not tested annually for GC/CT, and rates of GC/CT infection, particularly rates of extragenital infections, are high. We identified groups of PWH who may benefit from increased site-specific GC/CT testing.

69-OR: Implementing Autonomous AI in a Federally Qualified Health Center (FQHC) for the Detection of Diabetic Retinopathy Improves Access to Care: A Pre–Post Comparison in the Southeastern U.S.

Diabetic retinopathy (DR) and diabetic macular edema (DME) are debilitating complications of diabetes; however, patients in the most vulnerable populations often face barriers in accessing recommended ocular exams, leading to major health inequity. These barriers are especially true for FQHCs, as they serve the most under resourced and underserved populations. More recently, rigorously validated, FDA cleared, autonomous AI for the detection of DR and DME has been considered as an alternative to deployed remote reading networks. We examined the impact of autonomous AI compared to remote reading on patient access and clinical workflow efficiency, measured as number of steps by the operator. During 90 days in mid-2021, at two FQHC clinics in the southeastern US, autonomous AI was provided in place of a remote reading network. All steps were completed at the point-of-care: qualified patients with diabetes were identified in the electronic health record (EHR) , diagnosed by the autonomous AI output, provided results at time of the exam, and referred to specialists where appropriate. After 90 days, 1patients with diabetes underwent autonomous AI diagnostic testing, and 30/1patients with diabetes (28.6%) were identified by the AI as having signs of vision threatening DR or DME. Testing was accomplished with fewer steps as compared to exams completed with a remote reading network at the same clinics. We conclude that implementing autonomous AI point-of-care testing for the identification of DR and DME in an FQHC setting improved workflow efficiency and patient access compared to remote reading, demonstrating a potential to address health inequities in underserved and vulnerable populations. Disclosure J.Goldstein: Employee; Digital Diagnostics. D.Weitzman: Employee; Digital Diagnostics. M.D.Abràmoff: Advisory Panel; NovaGo Therapeutics AG, Board Member; Digital Diagnostics, Consultant; Digital Diagnostics, Speaker's Bureau; AbbVie Inc., Stock/Shareholder; Digital Diagnostics.

Efficacy of smartphone applications for smoking cessation in heavy-drinking adults: Secondary analysis of the iCanQuit randomized trial

IntroductionEfficacious smoking cessation treatments are needed for heavy-drinking adults who often have difficulty quitting smoking. In a secondary analysis of a parent randomized controlled trial, we explored the efficacy of an Acceptance and Commitment Therapy (ACT)-based smartphone application (iCanQuit) versus a US Clinical Practice Guidelines (USCPG)-based smartphone application (QuitGuide) for smoking cessation among heavy-drinking participants (4 + drinks/day for women; 5 + drinks/day for men). MethodsParticipants were randomized to receive iCanQuit (n = 188) or QuitGuide (n = 160) for 12-months. Smoking cessation outcomes were measured at 3, 6 and 12-months. The primary outcome was self-reported complete-case 30-day point prevalence abstinence (PPA) at 12-months. Secondary outcomes were 7-day PPA at all timepoints; prolonged abstinence; and cessation of all nicotine-containing products at 12-months. Multiple imputation and missing-as-smoking analyses were also conducted. Exploratory outcomes were cessation of both smoking and heavy drinking and change in alcohol use (drinks/day) at 12-months. Treatment engagement and satisfaction and change in ACT-based processes were compared between arms. ResultsRetention rate was 85% at 12-months and did not differ by arm. At 12-months, iCanQuit participants had nearly double the odds of smoking cessation compared to QuitGuide (complete-case 30-day PPA = 24% vs. 15%; OR = 1.87 95% CI: 1.03, 3.42). Findings were similar for the multiple imputation and missing-as-smoking outcomes at 12-months. Combined cessation of smoking and heavy drinking, and alcohol use at 12-months did not differ by arm. iCanQuit was significantly more engaging and satisfying than QuitGuide. Increased acceptance of thoughts about smoking mediated the effect of treatment on cessation of heavy drinking at 12-months. ConclusionsThe iCanQuit smartphone application was more efficacious and engaging for smoking cessation among heavy-drinking adults than a USCPG-based smartphone application.

Clinic- and Community-Based SARS-CoV-2 Testing Among People Experiencing Homelessness in the United States, March-November 2020.

Objective:SARS-CoV-2 testing is a critical component of preventing the spread of COVID-19. In the United States, people experiencing homelessness (PEH) have accessed testing at health clinics, such as those provided through Health Care for the Homeless (HCH) clinics or through community-based testing events at homeless service sites or encampments. We describe data on SARS-CoV-2 testing among PEH in US clinic- and community-based settings from March through November 2020.Methods:We conducted a descriptive analysis of data from HCH clinics and community testing events. We used a standardized survey to request data from HCH clinics. We developed and made publicly available an online data entry portal to collect data from community-based organizations that provided testing for PEH. We assessed positivity rates across clinics and community service sites serving PEH and used generalized linear mixed models to account for clustering.Results:Thirty-seven HCH clinics reported providing 280 410 tests; 3.2% (n = 8880) had positive results (range, 1.6%-4.9%). By race, positivity rates were highest among people who identified as >1 race (11.6%; P < .001). During the reporting period, 22 states reported 287 community testing events and 14 116 tests; 7.1% (n = 1004) had positive results. Among facility types, day shelters (380 of 2697; 14.1%) and inpatient drug/alcohol rehabilitation facilities (32 of 251; 12.7%) reported the highest positivity rates.Conclusions:While HCH clinic data provided results for a larger number of patients, community-based testing data showed higher positivity rates. Clinic data demonstrated racial disparities in positivity. Community-based testing data provided information about SARS-CoV-2 transmission settings. Although these data provide information about testing, standard surveillance systems are needed to better understand the incidence of disease among PEH.

Patient perspectives on symptoms, health-related quality of life, and treatment experience associated with relapsed/refractory multiple myeloma

PurposeThis study aimed to better understand the patient perspective and treatment experience of relapsed and/or refractory multiple myeloma (RRMM).MethodsThis qualitative study enrolled adult RRMM patients from 6 US clinics who had ≥ 3 months of life expectancy, ≤ 6 prior lines of therapy, and ≥ 1 treatment regimen with a proteasome inhibitor and immunomodulator, or a CD38 monoclonal antibody or an alkylating agent, and a steroid. In-person semi-structured qualitative interviews were conducted to capture concepts that were relevant and important to patients. Topics included RRMM symptoms and impacts and the mode of administration, frequency, duration, convenience, side effects, and overall experience with RRMM treatment.ResultsA total of 22 patients completed interviews. At enrollment, 59.1% of participants were using regimens containing dexamethasone, 36.4% daratumumab, 27.3% carfilzomib, and 18.2% lenalidomide. More participants had experience using intravenous or injectable therapy alone (40.9%) than oral therapy alone (18.2%). Back pain and fatigue were the most frequently reported symptoms (40.9% each); 27.3% reported no symptoms. Most participants reported physical function limitations (86.4%), emotional impacts (77.3%), MM-related activity limitations (72.7%), and sleep disturbances (63.6%). Most participants perceived treatment effectiveness based on physician-explained clinical signs (68.2%) and symptom relief (40.9%). Participants experienced gastrointestinal adverse events (59.1%), fatigue (59.1%), sleep disturbances (31.8%), and allergic reactions (31.8%) with treatment. Key elements of treatment burden included the duration of a typical treatment day (68.2%), treatment interfering with daily activities (54.5%), and infusion duration (50.0%).ConclusionsThese results provide treatment experience–related data to further understand RRMM treatment burden and better inform treatment decision-making.

Clinical and Epidemiological Characteristics of Stenotrophomonas maltophilia Associated Lower Respiratory Tract Infections in Qatar: A Retrospective Study.

BackgroundStenotrophomonas maltophilia is a rapidly emerging nosocomial pathogen with intrinsic or acquired resistance mechanisms to several antibiotic classes. It can cause life-threatening opportunistic pneumonia, particularly among hospitalized patients. Incidence of infections by S. maltophilia has been reported as 0.07-0.4% of hospital discharges, but its mortality is 20 -60%. This is the first study from Qatar indexing the clinical and epidemiological characteristics and antibiotic susceptibility of S. maltophilia.Materials and methodsThis retrospective descriptive epidemiological study was conducted in 6 tertiary care hospitals under Hamad Medical Corporation in Doha, Qatar, analyzing inpatient respiratory isolates of S. maltophilia during 2016-17. Out-patients, children below 14 years, and non-respiratory samples except blood cultures in patients with pneumonia were excluded. Clinical records were reviewed to identify possible risk factors. Infection and colonization were identified using the Centers for Disease Control and Prevention (CDC) algorithm for clinically defined pneumonia and statistically analyzed using the chi-square test and Pearson's correlation.ResultsS. maltophilia was isolated from 2.07% (317/15312) of all respiratory samples received in the microbiology lab during our study period. Three hundred seventeen patients studied had a mean age of 60 ± 20 years, and 68% were men. Most of the isolates were from sputum (179), followed by tracheal aspirate (82) and bronchoscopy (42). Fourteen blood culture samples from patients diagnosed with pneumonia were also included. 67% were hospitalized for more than two weeks, 39.1% were on mechanical ventilators, and 88% had received a broad-spectrum antibiotic before the event. 29.1% were deemed to have an infection and 70.9% colonization. Incidence of infection in those with Charlson’s Co-morbidity Index (CCI) ≥ 3 was 36.5% compared to 24.2% in those with CCI < 3 (Relative Risk (RR)=1.52; 95% CI: 1.04,2.18; p=0.01). Patients with recent chemotherapy, immunosuppressant, or steroid use had a significantly higher infection risk than those without (69.2% v/s 23.3% RR=2.96; 95% CI:2.2,3.9; p<0.005). The most common symptoms in patients with infection were fever (96%) and expectoration (61.9%). The most common radiological finding was lobar consolidation (71.6%). Mean CRP and procalcitonin were 106.5±15.5 mg/l and 12.3 ± 14 ng/ml. Overall mortality was 16.3%. Patients on mechanical ventilator with IBMP-10 score ≥ 2 had 22.8% mortality compared to 5.7% in those with score < 2 (RR=3.9;95%CI:0.9,16.6; p<0.015). As per The US Clinical and Laboratory Standards Institute (CSLI) breakpoint values, Trimethoprim-Sulfamethoxazole (TMP-SMX) showed the highest sensitivity (97.8%), followed by levofloxacin (71.6%). 0.3% of samples were pan-drug resistant.ConclusionsS. maltophilia is a frequent nosocomial colonizer, but it can cause nosocomial pneumonia in almost one-third of cases, specifically in immunocompromised and patients with CCI ≥ 3 with a high risk of mortality due to ventilator-associated pneumonia (VAP) in those with IBMP-10 ≥ 2. Prolonged hospital stay is a risk factor for colonization by S. maltophilia, while recent chemotherapy, immunosuppressant, or steroid use are risk factors for hospital-acquired pneumonia due to S. maltophilia. TMP-SMX and levofloxacin are the only reliable agents for monotherapy of respiratory infections due to S. maltophilia in Qatar.

Greater Adherence and Persistence with Injectable Dulaglutide Compared with Injectable Semaglutide at 1-Year Follow-up: Data from US Clinical Practice

PurposeGreater medication adherence and persistence have been associated with improved glycemic control in patients with type 2 diabetes mellitus. This study compared adherence, persistence, and treatment patterns among patients naïve to glucagon-like peptide 1 receptor agonists initiating once-weekly injectable treatment with dulaglutide versus semaglutide over 6-month (6M) and 12-month (12M) follow-up periods. MethodsThis retrospective, observational cohort study used administrative claims data from three IBM MarketScan research databases. Data from adult patients with type 2 diabetes newly initiating treatment with dulaglutide or semaglutide between January 2018 and January 2020 (index date was defined as the earliest fill date), without evidence of glucagon-like peptide 1 receptor agonist use in the 6M baseline period, and with continuous enrollment in the 6M baseline and 6M or 12M follow-up period were included. Dulaglutide initiators were propensity score–matched, in a 1:1 ratio, to semaglutide initiators in each 6M and 12M follow-up cohort (26,284 and 13,837 pairs, respectively). FindingsIn the matched cohorts, baseline characteristics were balanced; the mean age was 53 years, and 50% of patients were women. Compared to semaglutide initiators, dulaglutide initiators were more adherent (6M, 63.4% vs 47.8%; 12M, 54.4% vs 43.3%; both, P < 0.0001), more persistent on therapy (6M, 72% vs 62%, 12M, 55.5% vs 45.3%, both, P < 0.001), and had more mean days of persistence (6M, 145 vs 132, 12M, 254.3 vs 220.7; both, P < 0.001). ImplicationsAt both 6M and 12M follow-up, dulaglutide initiators had significantly greater adherence and greater persistence compared with matched semaglutide initiators.

Adherence to contemporary antiretroviral treatment regimens and impact on immunological and virologic outcomes in a US healthcare system

Only a few recent reports have examined longitudinal adherence patterns in US clinics and its impact on immunological and virological outcomes among large cohorts initiating contemporary antiretroviral therapy (ART) in US clinics. We followed all persons with HIV (PLWH) in a California clinic population initiating ART between 2010 and 2017. We estimated longitudinal adherence for each PLWH by calculating the medication possession ratio within multiple 6-month intervals using pharmacy refill records. During the study, 2315 PWLH were followed for a median time of 210.8 weeks and only 179 (7.7%) were lost-to-follow-up. The mean adherence was 84.9%. Age (Hazard Ratio (HR): (95% confidence interval): 1.25 (1.20-1.31) per 10-year increase) and Black race (HR: 0.62 (0.53-0.73) vs. White) were associated with adherence in the cohort. A 10% percent increase in adherence increased the odds of being virally suppressed by 37% (OR and 95% CI: 1.37 [1.33-1.41]) and was associated with an increase in mean CD4 count by 8.54 cells/ul in the next 6-month interval (p-value <0.0001). Our study shows that despite large improvements in retention in care, demographic disparities in adherence to ART persist. Adherence was lower among younger patients and black patients. Our study confirmed the strong association between adherence to ART and viral suppression but could only establish a weak association between adherence and CD4 count. These findings reaffirm the importance of adherence and retention in care and further highlight the need for tailored patient-centered HIV Care Models as a strategy to improve PLWH's outcomes.

Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry.

Introduction There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis. Methods We systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of phase II and III trials were identified. The collateral information was gathered via a PubMed search and press releases. Results Nine compounds were identified. AXS-05 (a combination of dextromethorphan and bupropion) and ansofaxine hydrochloride showed a positive result over placebo in a phase III study for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, facial injection of botulinum toxin A, prasterone, and casopitant demonstrated at least one positive result in phase II trials. Ayahuasca showed a greater response rate than placebo at week one, indicating the rapid antidepressant effect. Discussion These new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed.

HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer...

Opioid Epidemic: Diagnosed, Started on Treatment?

In the March 2021 issue of the journal Pharmacoepidemiology Drug Safety, an article by K. Bykov et al. was published, which contains an analysis of the use of opioid and non-opioid analgesics in US clinics in the period 20072017. According to the authors, the frequency of use of drugs in this group does not tend to decrease, despite the previously announced opioid epidemic in the USA. In Russia, the problem of the emergence of opioid dependence due to the perioperative use of drugs of this group is of little relevance. The existing legal restrictions on the prescription of opioid analgesics minimize this risk. But these same limitations make the idea of opioid-free analgesia very attractive in our country.

Type 2 Diabetes Self-Management Variables and Predictors.

Guided by the Self and Family-Management framework, relationships between diabetes distress, self-efficacy, resilience and outcomes of A1c, quality of life and health status were explored. A cross-sectional descriptive design was used. Seventy eight individuals were enrolled from US clinics. Data were analyzed to test for associations, main effects and interactions and predictors of self-management. Results indicated low diabetes distress (M = 20.53), high self-efficacy (M = 7.32), moderate resilience (M = 80.27), and mean A1c 7.35%/56.88 mmol/mol. Seventy six percent of participants scored above the mental health norm, and 46% scored above the physical health norm. The average weighted quality of life score was -1.74. Diabetes distress was negatively associated with self-efficacy, resilience, physical health, mental health, and quality of life. Self-efficacy was positively associated with resilience, physical health, and quality of life. Resilience was positively associated with physical health, mental health and quality of life. Positive associations were found between quality of life, and physical and mental health. No associations were found between A1c and variables in the study. Multiple significant interactions were found with A1c, mental health and quality of life outcomes. Terms in the model included treatment regimen, years since diagnosis, provider collaboration, and history of diabetes self-management education. Distress was a significant predictor of health status and quality of life. The results confirm self-management facilitators self-efficacy and resilience and barrier diabetes distress and their relationships with outcomes in the framework. This study contributes to the understanding of the emotional aspect of diabetes. Continuing this work will allow researchers to better understand self-management, support self-management efforts and better outcomes.

Comparison of Drug Resistance of Bile Isolated Bacteria in Nanjing from 2017 to 2020

Background: Analyzed pathogenic bacteria isolated from bile samples of patients with biliary tract infection and their drug resistance in the first Affiliated Hospital of Nanjing Medical University from 2017 to 2020, so as to provide evidence for the treatment of biliary tract infection. Methods: Clinical strains isolated from bile specimens of patients suspected of biliary infection in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2020 were collected, The drug susceptibility criteria are based on the standards published by the National Standardization Committee of the US Clinical Laboratories. WHONET 5.6 software was used to analyze the distribution of pathogens and drug resistance. Results: From January 2017 to December 2020, a total of 2006 strains of bile pathogenic bacteria were cultured and identified. There were 1253 cases of gram-negative bacilli, 638 cases of gram-positive cocci, 98 cases of fungi, and 17 cases of Gram-positive bacilli. The top five pathogens of Gram negative bacilli were Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii. The top five pathogens of gram positive cocci were Enterococcus faecium, Enterococcus faecalis, Enterococcus gallinarum, Enterococcus faecalis and Staphylococcus epidermidis. the resistance rate of Escherichia coli to ampicillin, ampicillin / sulbactam, cefotetan, ceftazidime, ceftriaxone,cefepime, itronam, compound trimethoprim decreased, the resistance rate of Klebsiella pneumoniae to gentamicin, levofloxacin decreased, the resistance rate of Enterobacter cloacae to ciprofloxacin, levofloxacin decreased. the resistance rate of Pseudomonas aeruginosa to ceftazidime, cefepime, gentamicin decreased. the resistance rate of Acinetobacter baumannii to ceftazidime, ciprofloxacin decreased. the resistance rate of Enterococcus faecium to penicillin G, high concentration streptomycin, erythromycin decreased. Conclusions: Enterogenic pathogens were the main pathogens in China. Such as Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis and Enterococcus faecalis; Nosocomial infection pathogens. For example, Pseudomonas aeruginosa and Acinetobacter also need to be paid attention to. Clinicians should improve their awareness of microbiological examination and provide more reliable pathogenic evidence for the selection of clinical antibiotic.

Higher Rates of Persistence and Adherence in Patients with Type 2 Diabetes Initiating Once-Weekly vs Daily Injectable Glucagon-Like Peptide-1 Receptor Agonists in US Clinical Practice (STAY Study).

IntroductionReducing dosing frequency may lower treatment burden and improve persistence and adherence. This retrospective, observational study assessed persistence and adherence in patients with type 2 diabetes (T2D) initiating once-weekly or daily injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice.MethodsThe study used data from adults (≥ 18 years) with T2D who were included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre-index and ≥ 365 days post-index, were GLP-1 RA and insulin naïve at first claim (index date) for once-weekly or daily injectable GLP-1 RAs (follow-up: index date + 365 days), and were propensity score (PS) matched 1:1 by baseline characteristics. Persistence, defined as the stay time, was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Adherence was defined as a proportion of days covered of 0.8 or greater. To assess whether patients with more advanced disease would benefit from long-acting treatments, patients were matched to the baseline characteristics of basal insulin initiators using inverse probability of treatment weighting (IPTW).ResultsThe PS-matched cohorts (n = 784 each) had similar baseline characteristics. Once-weekly regimens were associated with significantly higher persistence than daily treatments (median stay time: 333 vs 269 days; hazard ratio 0.80 [95% confidence interval 0.71, 0.90]; p < 0.01) and with significantly higher adherence than daily regimens at 6 months and 12 months (p < 0.01 for both). Mean glycated haemoglobin reductions were greater with once-weekly than with daily treatment at 6 months (– 1.1% vs – 0.9%; p < 0.01) and 12 months (– 0.9% vs – 0.7%; p = not significant); adherent patients experienced greater reductions than those with poor adherence. Results were similar in the IPTW-matched analysis.ConclusionIn US clinical practice, once-weekly injectable treatments are associated with better persistence and adherence than daily regimens over 1 year. Once-weekly regimens may also benefit patients with more advanced T2D.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01189-6.