Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection.

INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3. METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8 weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial's blinded phase only. RESULTS: Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week 8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week 8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p < 0.05) and mental domain (16.2 [6.0], p < 0.01) scores vs. placebo from baseline to week 8. CONCLUSION: Compared to placebo, RBL demonstrated a significantly higher treatment success in preventing further rCDI and enhanced HRQL among patients at first recurrence, establishing RBL as an effective treatment to prevent further recurrences in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03244644.

Effect of Fecal Microbiota, Live-Jslm (REBYOTA [RBL]) on Health-Related Quality of Life in Patients With Recurrent Clostridioides difficile Infection: Results From the PUNCH CD3 Clinical Trial.

Background: Recurrence of Clostridioides difficile infection (rCDI) is common, prolonging disease morbidity and leading to poor quality of life. We evaluated disease-specific health-related quality of life (HRQL) in patients with rCDI treated with fecal microbiota, live-jslm (REBYOTA [RBL]; Rebiotix) versus placebo. Methods: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific Clostridioides difficile Quality of Life Survey (Cdiff32) was administered at baseline and at weeks 1, 4, and 8. Changes in Cdiff32 total and domain (physical, mental, social) scores from baseline to week 8 were compared between RBL and placebo and for responders and nonresponders. Results: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all P < .001); RBL-treated patients showed significantly greater improvements in mental domain than those receiving placebo. In adjusted analyses, RBL-treated patients showed greater improvements than placebo in total score and physical and mental domains (all P < .05). Similar improvement in mental domain was observed among responders, while nonresponders showed numerical improvements with RBL but not placebo. Conclusions: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients. Clinical Trials Registration: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

Benefits of Autoantibody Enrichment in Early Rheumatoid Arthritis: Analysis of Efficacy Outcomes in Four Pooled Abatacept Trials.

INTRODUCTION: The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients. METHODS: Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration < 1 year, and Disease Activity Score-28 (DAS28) C-reactive protein (CRP) ≥ 3.2 at baseline; non-SPEAR otherwise. Outcomes included: American College of Rheumatology (ACR) 20/50/70 at week 24; mean change from baseline to week 24 for DAS28 (CRP), Simple Disease Activity Index (SDAI), ACR core components; DAS28 (CRP) and SDAI remission. Adjusted regression analyses among abatacept-treated patients compared SPEAR and non-SPEAR patients, and in full trial population estimating how the efficacy of abatacept versus comparators [adalimumab + methotrexate, methotrexate] was modified by SPEAR status. RESULTS: The study included 1400 SPEAR and 673 non-SPEAR patients; most were female (79.35%), white (77.38%), and with a mean age 49.26 (SD 12.86) years old. Around half with non-SPEAR were RF + and three-quarters ACPA +. Stronger improvements from baseline to week 24 were observed in almost all outcomes for abatacept-treated SPEAR versus non-SPEAR patients or versus SPEAR patients treated with comparators. Larger improvements were observed for SPEAR patients among the abatacept-treated population, and more strongly improved efficacy among SPEAR patients for abatacept than comparators. CONCLUSIONS: This analysis, including large patient numbers of early-RA abatacept trials, confirmed beneficial treatment effects of abatacept in patients with SPEAR versus non-SPEAR.

The association between patient-provider racial/ethnic concordance, working alliance, and length of treatment in behavioral health settings.

Racial/ethnic concordance between patients and providers concerning the quality of care has received interest over past decades yielding mixed results. Patients seem to prefer clinicians of their own race/ethnicity, but empirical studies have found small or inconsistent effects on the quality of care. Research on the impact of racial/ethnic concordance and treatment duration appears to suggest that racial/ethnic concordance is associated with retention and completion; however, exactly why racial/ethnic concordance improves treatment length remains unexplored. On the other side, the quality of working alliance is a well-established common factor underlying effective treatments. In this study, we examined the interaction between patient-provider racial/ethnic concordance, length of treatment in the therapeutic dyad, and working alliance as evaluated by both patients themselves and objective raters. The study included 312 patients and 74 providers from 13 community and hospital-based outpatient mental health clinics in Massachusetts. Results indicated that among racial/ethnic concordant therapeutic dyads, longer length of treatment was associated with better quality of working alliance as evaluated by objective raters. Implications for clinical practice and future research on racial/ethnic concordance studies linked to the length of treatment are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PIK3CA mutation status, progression and survival in advanced HR + /HER2- breast cancer: a meta-analysis of published clinical trials.

BACKGROUND: Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC.  METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies. RESULTS: The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I2 = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I2 = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I2 = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I2 = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726). CONCLUSIONS: Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.

Patient Preferences for Attributes of Biologic Treatments in Moderate to Severe Asthma: A Discrete Choice Experiment Study.

Purpose: Multiple biologics are available for moderate to severe asthma. Given the important relationship between patient engagement in healthcare decision-making and health outcomes, patient preference is an increasingly important consideration. This study elicited patients' preferences for attributes of biologic therapies for moderate to severe asthma. Patient and Methods: A discrete choice experiment (DCE) questionnaire was designed to collect data from an existing survey panel of adults with moderate to severe asthma in the United States. Patients were asked to select their preferred hypothetical treatment from profiles with varying attributes related to efficacy, safety, and administration convenience. Conditional logit regression models were used to quantify patient preferences. Results: Of 301 eligible patients who completed the survey, the mean age was 46.7±15.1 years and 71.8% were female. Patients had asthma for 22.5±16.3 years on average, and most (97.3%) had experienced ≥1 asthma attack in the past 12 months. Among treatment attributes examined, patients most valued the absence of a black box warning for the risk of a life-threatening allergic reaction, effectiveness of reducing severe asthma exacerbations, and improvement in lung function (all p < 0.001). Home administration setting for subcutaneous injections (vs doctor's office/clinic) (p = 0.009) and ability of a biologic to treat additional chronic condition(s) (p < 0.05) were also considered important. Dosing frequency and type of injection device were not significant factors. Conclusion: Patients with moderate to severe asthma valued efficacy and safety over convenience attributes when selecting biologic treatments. Awareness of these preferences can facilitate patient-physician shared decision-making when managing moderate to severe asthma in clinical practice.

Indirect Treatment Comparison of Larotrectinib versus Entrectinib in Treating Patients with TRK Gene Fusion Cancers.

Information regarding the comparative efficacy of first-generation receptor tyrosine kinase inhibitors is limited. This matching-adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)) were used. Adults (≥18 years) across trials were matched on available baseline characteristics. Outcomes evaluated included overall response rate (ORR), complete response (CR) rate, duration of response (DoR), overall survival (OS), progression-free survival (PFS), any serious treatment-related adverse events of grade ≥ 3 (TRAEs), and TRAEs leading to treatment discontinuation. The MAIC included 74 patients from entrectinib trials and 117 and 147 patients for the larotrectinib efficacy and safety populations, respectively. Post-matching, larotrectinib was associated with a significantly longer median duration of OS than entrectinib (p < 0.05) and a numerically longer median PFS (p = 0.07). ORR was similar for both agents (p = 0.63). The CR rate was higher (p < 0.05) and the DoR was longer for larotrectinib (p < 0.05). Safety outcomes were comparable and low for both treatments. Results were consistent in sensitivity analyses. These findings suggest favorable efficacy for larotrectinib and comparable safety profiles versus entrectinib in treating tropomyosin receptor kinase fusion cancer.

Barriers to Mental Health Service Use and Predictors of Treatment Drop Out: Racial/Ethnic Variation in a Population-Based Study.

This study examines racial/ethnic differences in perceived need for mental health treatment, barriers to treatment receipt, and reasons for dropout. Data are from the Collaborative Psychiatric Epidemiology Studies, a pooled dataset from three U.S. nationally-representative adult samples. Among respondents with a 12-month psychiatric disorder who received no treatment (N = 1417), Asians and Latinos reported lower perceived need than Blacks and Whites, and Latinos reported the fewest attitudinal barriers. Among those with a 12-month disorder who dropped out of treatment, Asians and Latinos gave more reasons for dropping out. Significant interactions of race/ethnicity with other characteristics identified subpopulations with high unmet need.

Change in Patient Activation and Mental Illness Symptoms After Communication Training: A Multisite Study With a Diverse Patient Sample.

OBJECTIVE: Patient activation involves patients' ability and motivation to communicate about their health and health care. Research has demonstrated that clinician or patient interventions may improve patient activation. This study explored the degree to which clinician and patient interventions affected both patient activation and symptoms of depression and anxiety in a racially and ethnically diverse clinical sample. METHODS: Data were from a randomized clinical trial that included 312 patients and 74 clinicians from 13 Massachusetts community- and hospital-based outpatient behavioral health clinics. Patients completed measures of patient activation and depression and anxiety symptoms. Secondary data analyses were conducted to examine the effect of patient and clinician interventions (DECIDE-PA and DECIDE-PC, respectively) on depression and anxiety symptoms and patient activation. A multilevel, mixed-effects simultaneous-equation model was estimated to assess the relationship between the interventions, changes in patients' symptoms, and patient activation. RESULTS: Clinicians' greater intervention dosage (i.e., more completed DECIDE-PC training sessions) was associated with patients' decreased anxiety symptoms, but associations with patient activation or depression symptoms were not significant. The effect of clinician training dosage on anxiety symptoms was stronger when patients and clinicians were not of the same race-ethnicity. The reduction in patients' anxiety symptoms appeared to increase patient activation. CONCLUSIONS: Clinician interventions designed to boost patient-clinician communication and the therapeutic alliance may serve to lessen patients' anxiety and may ultimately improve patient activation.

Racial/ethnic variation in trauma-related psychopathology in the United States: a population-based study.

BACKGROUND: The prevalence of mental disorders among Black, Latino, and Asian adults is lower than among Whites. Factors that explain these differences are largely unknown. We examined whether racial/ethnic differences in exposure to traumatic events (TEs) or vulnerability to trauma-related psychopathology explained the lower rates of psychopathology among racial/ethnic minorities. METHODS: We estimated the prevalence of TE exposure and associations with onset of DSM-IV depression, anxiety and substance disorders and with lifetime post-traumatic stress disorder (PTSD) in the Collaborative Psychiatric Epidemiology Surveys, a national sample (N = 13 775) with substantial proportions of Black (35.9%), Latino (18.9%), and Asian Americans (14.9%). RESULTS: TE exposure varied across racial/ethnic groups. Asians were most likely to experience organized violence - particularly being a refugee - but had the lowest exposure to all other TEs. Blacks had the greatest exposure to participation in organized violence, sexual violence, and other TEs, Latinos had the highest exposure to physical violence, and Whites were most likely to experience accidents/injuries. Racial/ethnic minorities had lower odds ratios of depression, anxiety, and substance disorder onset relative to Whites. Neither variation in TE exposure nor vulnerability to psychopathology following TEs across racial/ethnic groups explained these differences. Vulnerability to PTSD did vary across groups, however, such that Asians were less likely and Blacks more likely to develop PTSD following TEs than Whites. CONCLUSIONS: Lower prevalence of mental disorders among racial/ethnic minorities does not appear to reflect reduced vulnerability to TEs, with the exception of PTSD among Asians. This highlights the importance of investigating other potential mechanisms underlying racial/ethnic differences in psychopathology.

Racial/ethnic differences in 12-month prevalence and persistence of mood, anxiety, and substance use disorders: Variation by nativity and socioeconomic status.

BACKGROUND: Despite equivalent or lower lifetime and past-year prevalence of mental disorder among racial/ethnic minorities compared to non-Latino Whites in the United States, evidence suggests that mental disorders are more persistent among minorities than non-Latino Whites. But, it is unclear how nativity and socioeconomic status contribute to observed racial/ethnic differences in prevalence and persistence of mood, anxiety, and substance disorders. METHOD: Data were examined from a coordinated series of four national surveys that together assessed 21,024 Asian, non-Latino Black, Latino, and non-Latino White adults between 2001 and 2003. Common DSM-IV mood, anxiety, and substance disorders were assessed using the Composite International Diagnostic Interview. Logistic regression analyses examined how several predictors (e.g., race/ethnicity, nativity, education, income) and the interactions between those predictors were associated with both 12-month disorder prevalence and 12-month prevalence among lifetime cases. For the second series of analyses, age of onset and time since onset were used as additional control variables to indirectly estimate disorder persistence. RESULTS: Non-Latino Whites demonstrated the highest unadjusted 12-month prevalence of all disorder types (p < 0.001), though differences were also observed across minority groups. In contrast, Asian, Latino, and Black adults demonstrated higher 12-month prevalence of mood disorders among lifetime cases than Whites (p < 0.001) prior to adjustments Once we introduced nativity and other relevant controls (e.g., age, sex, urbanicity), US-born Whites with at least one US-born parent demonstrated higher 12-month mood disorder prevalence than foreign-born Whites or US-born Whites with two foreign parents (OR = 0.51, 95% CI = [0.36, 0.73]); this group also demonstrated higher odds of past-year mood disorder than Asian (OR = 0.59, 95% CI = [0.42, 0.82]) and Black (OR = 0.70, 95% CI = [0.58, 0.83]) adults, but not Latino adults (OR = 0.89, 95% CI = [0.74, 1.06]). Racial/ethnic differences in 12-month mood and substance disorder prevalence were moderated by educational attainment, especially among adults without a college education. Additionally, racial/ethnic minority groups with no more than a high school education demonstrated more persistent mood and substance disorders than non-Latino Whites; these relationships reversed or disappeared at higher education levels. CONCLUSION: Nativity may be a particularly relevant consideration for diagnosing mood disorder among non-Latino Whites; additionally, lower education appears to be associated with increased relative risk of persistent mood and substance use disorders among racial/ethnic minorities compared to non-Latino Whites.

Race/ethnicity, nativity, and lifetime risk of mental disorders in US adults.

PURPOSE: There has been no comprehensive examination of how race/ethnicity and nativity intersect in explaining differences in lifetime prevalence of mental disorders among Asian, Black, Latino, and White adults. This study aims to estimate racial/ethnic differences in lifetime risk of mental disorders and examine how group differences vary by nativity. METHODS: Survival models were used to estimate racial/ethnic and nativity differences in lifetime risk of DSM-IV anxiety, mood, and substance use disorders in a nationally representative sample of over 20,000 respondents to four US surveys. RESULTS: Asians had the lowest lifetime prevalence of mental disorders (23.5%), followed by Blacks (37.0%), Latinos (38.8%), and Whites (45.6%). Asians and Blacks had lower lifetime risk than Whites for all disorders even after adjusting for nativity; Latinos and Whites had similar risk after adjusting for nativity. Risk of disorder onset was lowest for foreign-born respondents in years before migration. There were significant race/ethnicity and nativity interactions for mood and substance use disorders. Odds of mood disorder onset were higher for Whites with at least one US-born parent. Odds of substance use disorder onset among Asians were higher for US-born respondents; for Latinos, they were higher for those with at least one US-born parent. CONCLUSIONS: Parental foreign-born nativity is associated with a low risk of mental disorders, but not uniformly across racial/ethnic groups or disorders. Exposure to the US context may be associated with greater mental disorder risk for Latinos and Whites particularly. Investigations of cultural processes, including among Whites, are needed to understand group differences.

Effectiveness of the DECIDE Interventions on Shared Decision Making and Perceived Quality of Care in Behavioral Health With Multicultural Patients: A Randomized Clinical Trial.

Importance: Few randomized clinical trials have been conducted with ethnic/racial minorities to improve shared decision making (SDM) and quality of care. Objective: To test the effectiveness of patient and clinician interventions to improve SDM and quality of care among an ethnically/racially diverse sample. Design, Setting, and Participants: This cross-level 2 × 2 randomized clinical trial included clinicians at level 2 and patients (nested within clinicians) at level 1 from 13 Massachusetts behavioral health clinics. Clinicians and patients were randomly selected at each site in a 1:1 ratio for each 2-person block. Clinicians were recruited starting September 1, 2013; patients, starting November 3, 2013. Final data were collected on September 30, 2016. Data were analyzed based on intention to treat. Interventions: The clinician intervention consisted of a workshop and as many as 6 coaching telephone calls to promote communication and therapeutic alliance to improve SDM. The 3-session patient intervention sought to improve SDM and quality of care. Main Outcomes and Measures: The SDM was assessed by a blinded coder based on clinical recordings, patient perception of SDM and quality of care, and clinician perception of SDM. Results: Of 312 randomized patients, 212 (67.9%) were female and 100 (32.1%) were male; mean (SD) age was 44.0 (15.0) years. Of 74 randomized clinicians, 56 (75.7%) were female and 18 (4.3%) were male; mean (SD) age was 39.8 (12.5) years. Patient-clinician pairs were assigned to 1 of the following 4 design arms: patient and clinician in the control condition (n = 72), patient in intervention and clinician in the control condition (n = 68), patient in the control condition and clinician in intervention (n = 83), or patient and clinician in intervention (n = 89). All pairs underwent analysis. The clinician intervention significantly increased SDM as rated by blinded coders using the 12-item Observing Patient Involvement in Shared Decision Making instrument (b = 4.52; SE = 2.17; P = .04; Cohen d = 0.29) but not as assessed by clinician or patient. More clinician coaching sessions (dosage) were significantly associated with increased SDM as rated by blinded coders (b = 12.01; SE = 3.72; P = .001; Cohen d = 0.78). The patient intervention significantly increased patient-perceived quality of care (b = 2.27; SE = 1.16; P = .05; Cohen d = 0.19). There was a significant interaction between patient and clinician dosage (b = 7.40; SE = 3.56; P = .04; Cohen d = 0.62), with the greatest benefit when both obtained the recommended dosage. Conclusions and Relevance: The clinician intervention could improve SDM with minority populations, and the patient intervention could augment patient-reported quality of care. Trial Registration: clinicaltrials.gov Identifier: NCT01947283.