Premature Treatment Discontinuation Research Articles

Cardio-oncology: chances and challenges.

Cardio-oncology is an emerging field that aims to ensure optimal cancer treatment while minimising cardiovascular toxicity. The management of cardiovascular toxicity is critical because it can lead to premature discontinuation of treatment, increasing the risk of cancer recurrence and mortality. The 2022 European Society of Cardiology guidelines were a milestone in advocating a patient-centred, multidisciplinary approach. Key components include risk stratification and a standardised criterion for adverse events, incorporating definitions from the International Cardio-Oncology Society. Effective risk stratification, supported by imaging and biomarkers, helps to anticipate cardiovascular problems and implement preventive measures. Future research should focus on understanding mechanisms, developing preventive strategies and implementing personalised medicine. Education and reducing disparities in care are essential to advance cardio-oncology and improve patient outcomes.

Efficacy and safety of co-trimoxazole in device-related bone and joint infections: a CRIOGO multicentre case-control study.

Co-trimoxazole could be an alternative antibiotic to treat device-related bone and joint infection (BJI) but there are few published data about its efficacy and safety in this complex scenario to treat infection. The objective was to compare the outcome of patients with device-related BJI treated with an antibiotic regimen including co-trimoxazole versus a regimen without co-trimoxazole. This multicentre case-control study included consecutive adult patients diagnosed with device-related BJI. Each patient receiving co-trimoxazole was included in the co-trimoxazole group and was matched with two control patients, with stratification on microbial aetiology and age. The primary outcome was composite and defined by death or treatment failure during the follow-up. In this study, 150 patients were included, 50 in the co-trimoxazole group and 100 in the control group. The rate of reaching the primary endpoint was 18% in the co-trimoxazole group (9/50 cases) versus 21% in the control group (21/100) (P = 0.66). Co-trimoxazole use was not associated with an unfavourable outcome in the multivariate analysis (adjusted OR 0.8, 95% CI 0.31-2.06, P = 0.64). Although no significant difference was observed in premature discontinuation of treatment due to an adverse event between both groups (14 versus 12%, P = 0.73), treatment-related adverse events were significantly more frequently reported in patients of the co-trimoxazole group than the control group [34% (17/50) versus 18% (18/100), P = 0.03]. Co-trimoxazole appears to be an effective alternative for the treatment of BJI, even when it occurs on a device, but the safety profile requires close monitoring of adverse effects.

Attention Deficit Hyperactivity Disorder: A Risk Factor for Premature Discontinuation of Inpatient Opioid Withdrawal Treatment.

Background: Substance use disorders present a tremendous challenge within contemporary healthcare systems. Specifically, in the domain of opioid use disorders (OUDs), several foundational elements are crucial for the efficacious management of afflicted individuals. Regrettably, the premature discontinuation of inpatient opioid withdrawal treatment is a prevalent phenomenon. This study aims to elucidate the prevalence of the premature termination of inpatient opioid withdrawal treatment among patients with comorbid ADHD. Methods: We conducted a comprehensive assessment of all participants currently undergoing inpatient opioid withdrawal treatment. Our assessment protocol included the administration of the ADHD Self-Report Scale (ADHD-SR) and the Wender Utah Rating Scale (WURS-k). Additionally, participants who met the thresholds on one or both questionnaires underwent further evaluation using the Diagnostic Interview for ADHD in Adults (DIVA-2.0). Results: The prevalence of individuals diagnosed with ADHD within the studied cohort was determined to be 29.3%. Among the subset of participants identified as ADHD-positive, a notable 54.5% prematurely ceased therapy. In contrast, among those identified as ADHD-negative, the premature discontinuation rate was substantially lower at 28.3%. Conclusions: In summary, the impact of ADHD as a comorbid condition on the efficacy of inpatient opioid withdrawal treatment has been underscored. By identifying comorbid ADHD early in the treatment process, tailored therapeutic approaches may help to maximize the effectiveness of interventions and may improve patient outcomes. This underscores the importance of proactive screening for ADHD as a psychiatric comorbidity in optimizing the management of individuals undergoing inpatient opioid withdrawal treatment.

Family engagement in a behavioral parenting intervention: A randomized comparison of telehealth versus office-based treatment formats.

Despite effective treatment options, many families-especially those from marginalized backgrounds-lack access to quality care for their children's behavioral difficulties. Since the COVID-19 pandemic, telehealth has become a prominent format for the delivery of outpatient services, with potential to increase access to quality care. Although telehealth-delivered parenting interventions are associated with positive clinical outcomes, limited research has examined whether telehealth formats improve treatment engagement relative to office-based care. The present study is the first controlled comparison of engagement across office-based parent-child interaction therapy (PCIT) and internet-delivered PCIT (iPCIT). Children ages 3-5 years, and their caregiver(s) (N = 40) participated in a randomized trial comparing iPCIT to office-based PCIT in the treatment of behavioral problems. Analyses examined the effects of treatment format on engagement (i.e., missed sessions, premature treatment discontinuation, homework completion, therapeutic alliance, and treatment satisfaction). Logistic and linear regressions further explored whether treatment format moderated the effects of common predictors of treatment engagement (i.e., family economic means, racial/ethnic background, caregiver stress). iPCIT improved attendance rates relative to office-based PCIT, especially for families from minoritized racial/ethnic backgrounds. At the same time, among families with relatively higher levels of caregiver stress, office-based PCIT was associated with lower dropout rates and improved treatment alliance and satisfaction, relative to iPCIT. This study provides the first experimental support that telehealth formats can improve treatment attendance in behavioral parenting interventions. Findings highlight nuances in treatment engagement across treatment formats that reveal limits to the extent telehealth transcends engagement concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multiple-target Therapy for Posttransplant Focal Segmental Glomerulosclerosis.

There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results. This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients. Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis. In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.

Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies.

Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.

Results of the Phase II of Epirchop Study, Evaluating the Efficacy of Tazemetostat in Combination with R-CHOP in Elderly Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL): A Lysa Study

Introduction: Tazemetostat (TAZ) is a selective oral EZH2 inhibitor with a favorable safety profile and activity in pts with either EZH2wild type or mutant B-cell NHL. In the phase I part of Epi-RCHOP study, we reported that R-CHOP plus TAZ (Taz-RCHOP) was well tolerated with safety and PK results comparable to R-CHOP alone, and the RP2D of TAZ in combination with RCHOP was consistent with TAZ monotherapy (800mg BID). We report here the efficacy results of the phase II TAZ R-CHOP study (Epi-RCHOP, NCT02889523), in pts 60-80y with newly diagnosed DLBCL. Methods: Pts received 6 R-CHOP every 21 days in combination with continuous TAZ at 800 mg BID, plus 2 cycles of TAZ and R (cycle 7 and 8). Prophylaxis with G-CSF, valaciclovir and trimethoprim sulfamethoxazole were strongly recommended. Primary endpoint was PET-based complete metabolic response rate (CR, Lugano 2014) at end of study treatment (EOT, i.e 8 cycles or at time of permanent treatment discontinuation) (data cut-off was January 30, 2023). Sample size calculation was made with the expectation of an increase of 10% in CR, with an H0 hypothesis of 70% and an H1 assumption of 80%, leading to a theorical sample size of 122 pts, assuming a drop out of 5%. The efficacy set correspond to pts who signed an informed consent and received at least one dose of TAZ. Pts without response assessment (no matter the reason) were considered non-responders. Key secondary objectives were progression free and overall survival. A sensitivity analysis was performed excluding pts who withdrawn their consent (N=112). Analyses were conducted using SAS® version 9.3. Results: From July 31, 2020 to July 18, 2022, 122 pts were enrolled in 27 LYSA centers. Median age was 70 years (60-80), 57% were female, 12% had an ECOG-PS2+, 70.5% a stage IV disease and 19.7% stage III, 66% elevated LDH, 73.8% an IPI of 3-5. Mutational profile was available for 76 pts, of whom 10 (13%) had an EZH2 mutations and 26 (34%) and EZB profile as assessed with LymphGen classifier. One hundred pts (82%) received 8 cycles and 22 had a premature treatment discontinuation (PTD), 12 (9.8%) during the first 2 cycles and 10 (8.2%) between cycle 3 and 8. Reasons for PTD were: consent withdrawal (N=10, including 7 during cycle 1 & 2), adverse events (AE, N=6, including 2 treatment related), death (N=2, both due to septic shock), protocol deviation (N=2), progressive disease (N=1) or physician decision (N=1). Overall, the median percentage of TAZ dose received was 98.4% (mean 77.2%, Q1: 61%; Q3: 100%), and AE led to TAZ interruption in 4.1%, discontinuation in 2.8% and dose reduction in 2.4% of the cases. Mean time between cycles was 21.5 days. In oct 2020, after the inclusion of 22 pts, recommendation to cap vincristine at 1mg was done, due to an excess of constipation. At end of treatment or PTD, 92/122 pts (75.4%, IC95: 66.8-82.8%) achieved CR, 8 (6.6%) PR, 5 (4.1%) had a PD, 2 (1.6%) had died (septic shock) and 15 (12.3%) were not evaluated and considered as non-responders. The primary objective was not met in this efficacy set, with a CR of 75.4% (lower than the H1 at 80%). The sensitivity analysis, excluding the 10 pts that withdrawn their consent (all non-evaluated), showed a CR rate of 82.1% (92/112, IC95: 73.8-88.7%) and PR rate of 7.1%. After a median follow-up of 18.5 months (Range = [0.2; 28.1]), 17/122 pts had a relapse/progression (13.9%) and 12 had died: 4 due to lymphoma, 3 to COVID-19, 4 to AE (2 septic shock, 1 acute myeloid leukemia and 1 heart failure), 1 unknown cause (in CMR). The estimated 18m PFS and OS were 77.7% (IC95: 67.5-85.1%) and 88.8% (IC95: 79.9-93.9%) respectively. Most frequent AE were: neutropenia (53%), anemia (51%), nausea (47%), asthenia (42%), peripheral neuropathy (37%), gastro-intestinal hypomotility (35%), weight loss (28%), vomiting (24%), thrombocytopenia (24%). AE of grade 3 or more occurred in 73% of the pts and were mainly hematological AE with neutropenia (48%, including 6% of febrile neutropenia), anemia (23%), thrombocytopenia (17%) and gastro-intestinal disorder (overall 10.7%). Red blood cell and platelets transfusions were administered in 31% and 11.5% of the pts respectively. Conclusion: R-CHOP plus TAZ is doable. Efficacy results in this trial conducted during the COVID pandemic in a particularly challenging population, suggest that the combination warrant further investigation including correlative studies with molecular subclassification that will be presented.

Safety and efficacy of inhaled interferon-β1a (SNG001) in adults with mild-to-moderate COVID-19: a randomized, controlled, phase II trial

With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need. Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n=110) or blinded pooled placebo (n=110) between February 10 and August 18,2021. The proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n=1; 1%) compared with placebo (n=7; 6%), representing an 86% relative risk reduction (p=0.07). There were no deaths in either arm. In this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia. The ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis

Background The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population. Methods A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier’s ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations. Results The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: −0.98; 95% CI: −1.28, −0.69, p-value: < 0.0001; I2: 100%), systolic (WMD: −3.73; 95% CI: −5.42, −2.04, p-value: <0.0001; I2: 100%) and diastolic blood pressures (WMD: −0.66; 95% CI: −1.02, −0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: −3.17; 95% CI: −3.84, −2.49, p-value: <0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: <0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments. Conclusions In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin.

Corticosteroids as graft-versus-host disease prophylaxis for allogeneic hematopoietic cell transplant recipients with calcineurin inhibitor intolerance

Background aimsAlthough calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance. MethodsThis retrospective single-center study included consecutive adult patients with hematologic malignancies who underwent myeloablative peripheral blood allogeneic HCT with anti-thymocyte globulin, CNI, and methotrexate GVHD prophylaxis in Alberta, Canada. Multivariable competing-risks regression was used to compare cumulative incidences of GVHD, relapse, and non-relapse mortality between recipients of corticosteroid versus continuous CNI prophylaxis, and multivariable Cox proportional hazards regression was applied to compare overall survival, relapse-free survival (RFS) and moderate-to-severe chronic GVHD and RFS. ResultsAmong 509 allogeneic HCT recipients, 58 (11%) patients developed CNI intolerance and were switched to corticosteroid prophylaxis at median 28 days (range 1-53) after HCT. Compared with patients who received continuous CNI prophylaxis, recipients of corticosteroid prophylaxis had significantly greater cumulative incidences of grade 2-4 acute GVHD (subhazard ratio [SHR] 1.74, 95% confidence interval [CI] 1.08–2.80, P = 0.024), grade 3–4 acute GVHD (SHR 3.22, 95% CI 1.55–6.72, P = 0.002), and GVHD-related non-relapse mortality (SHR 3.07, 95% CI 1.54–6.12, P = 0.001). There were no significant differences in moderate-to-severe chronic GVHD (SHR 0.84, 95% CI 0.43–1.63, P = 0.60) or relapse (SHR 0.92, 95% CI 0.53–1.62, P = 0.78), but corticosteroid prophylaxis was associated with significantly inferior overall survival (hazard ratio [HR] 1.77, 95% CI 1.20–2.61, P = 0.004), RFS (HR 1.54, 95% CI 1.06–2.25, P = 0.024), and chronic GVHD and RFS (HR 1.46, 95% CI 1.04–2.05, P = 0.029). ConclusionsAllogeneic HCT recipients with CNI intolerance are at increased risks of acute GVHD and poor outcomes despite institution of corticosteroid prophylaxis following premature CNI discontinuation. Alternative GVHD prophylaxis strategies are needed for this high-risk population.

Real-world outcomes in advanced melanoma patients treated with first-line nivolumab plus ipilimumab.

e21552 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, has dramatically changed the treatment paradigm for melanoma in recent years. The aim of this study was to analyze treatment patterns, treatment response, survival, safety, and healthcare resource utilization with this first-line combination therapy in patients (pts) with advanced melanoma under real-world conditions. Methods: This retrospective analysis included pts with stage 3 unresectable and stage 4 melanoma treated 01/2021-06/2022 with NIVO+IPI at 6 centers in Poland according to uniform criteria. Pts received up to 4 cycles of IPI 3 mg/kg + NIVO 1 mg/kg Q3W followed by maintenance NIVO (240 mg Q2W or 480 mg Q4W) until disease progression, unacceptable toxicity or at the request of the patient or physician. Kaplan-Meier estimator and Log-rank test were used in survival analysis. Results: A total of 291 adults were identified. The median age was 53 years, 42.5% of pts were female, 47% were BRAF-mutated, and 24% of pts received prior adjuvant treatment. At baseline, 19.5% of pts had stage III disease, 14.1% stage M1a, 13.7% stage M1b, 30.1% stage M1c and 23% had M1d disease. Median follow-up time was 11.9 months. The median number of cycles of NIVO+IPI administered was 3, with 47.9% of pts completing 4 cycles. Maintenance NIVO was continued in 52.7% pts who discontinued the combination therapy due to toxicity. Median progression-free survival (mPFS) was 9.8 months (95% CI 6.9–13.4). The longest mPFS was observed in pts with stage M1a (15 months; 95%Cl 3.1–NA) and the shortest in stage M1d pts (5 months; 95%CI 2.8–NA). We observed a statistically significant longer mPFS in pts who continued NIVO monotherapy after discontinuation of combination therapy due to toxicity (13 months, 95% Cl 10.4–NA) compared to those who discontinued immunotherapy (7.1 months, 95% Cl 3.4 –12; p &lt; 0.0001). Median overall survival (OS) was not achieved, with an OS rate of 70% at 12 months (95%Cl 64–76). The objective response rate (ORR) was 39%, with 7.8% of pts achieving a complete response. For pts who received prior adjuvant therapy, the ORR was 24.2%. Treatment-related adverse events (TRAEs) of any grade were observed in 97% of pts and grade 3/4 TRAEs occurred in 29.6% of pts. The most common TRAEs were liver toxicity, colitis, hyperthyroidism, hypothyroidism, and hypopituitarism; the treatment-related hospitalization rate was 23.8% and the median length of hospital stay was 9 days. Conclusions: This real-world study confirms the high efficacy of NIVO+IPI in real-world settings with grade 3/4 toxicity lower than observed in clinical trials. Maintenance of NIVO despite early toxicity during combination treatment appears to have a beneficial effect on patient survival. Therefore, it is extremely important to carefully monitor pts for toxicity, as early intervention helps to avoid severe toxicity and premature discontinuation of treatment.

Analysis of pathological complete response (PCR) and impact of modifiable risk factors on the premature discontinuation of pertuzumab use in early stage HER-2 breast cancer: A retrospective single-institutional study.

e12627 Background: In patients with HER-2 positive breast cancer, Pertuzumab in combination with Trastuzumab forms a potent Anti HER-2 regimen. Randomized clinical trials have concluded that addition of Pertuzumab to Trastuzumab and Chemotherapy leads to improved rates of Pathological Complete Response and also improved Invasive-disease-free survival rates in early stage HER-2 positive breast cancer. Pertuzumab is frequently associated with treatment limiting diarrhea and other adverse effects. In this study, we report our experience with the use of Pertuzumab in early stage HER-2 breast cancer. We analyzed the adverse events, PCR rates for those patients who had premature discontinuation of treatment versus those who had successful treatment completion, and modifiable risk factors that may have affected completion of treatment. Methods: We conducted an IRB approved, retrospective study, analyzing the use of Pertuzumab at our institution for early stage (Stage I-III), HER-2 positive female and male breast cancer patients seen from June 2018 to June 2022. Data were obtained from our Institutional Cancer Registry. Results: One hundred and eighteen (118) patient charts were reviewed. Sixty Five (55.08%) patients received Pertuzumab. Of the patients who received Pertuzumab, 61 (93.85%) received it in the Neoadjuvant setting. Thirty Eight (58.46%) patients completed the treatment and 27 (41.5%) patients had premature treatment discontinuation due to adverse effects. The rate of PCR in patient who completed the prescribed treatment course was 55.56%, and 51.85% for those who did not (p value 0.77). Among the patients in whom treatment was discontinued, diarrhea (51%), followed by rash (11.11%) were the main adverse effects. Almost 66% of non-smokers completed treatment as compared to 48% of smokers (p value 0.15). Patients with a normal BMI had a treatment completion rate of 76% compared to obese or overweight patients who had a rate of 52% (p value 0.08). Conclusions: Our retrospective study showed that there was a high premature discontinuation rate of the use of Pertuzumab. This is due to adverse effects, diarrhea being the most notable. However, the PCR rate difference was not statistically significant (55.56 vs 51.85, P value 0.77) in patients who completed treatment versus those who did not. There was a positive trend observed that non-smokers and non-obese patients were more likely to complete treatment with Pertuzumab. Although it was observed that premature discontinuation of Pertuzumab did not significantly impact PCR, further studies are required to validate this observation.

Acceptance and Commitment Therapy as an Adjunct or Alternative Treatment to Cognitive Behavioral Therapy for Insomnia.

Although cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment of insomnia, difficulties exist with adherence to recommendations and premature discontinuation of treatment does occur. The current article aims to review existing research on acceptance and commitment therapy (ACT)-based interventions, demonstrate differences and similarities between ACT for insomnia and CBT-I, and describe treatment components and mechanisms of ACT that can be used to treat insomnia disorder.

Medication adherence in the treatment of depression

IntroductionDepression is predicted to become one of the major sources of disease burden worldwide, leading to numerous adverse consequences that complicate the daily rhythm of life. Non-adherence is a serious issue in patients suffering from depression. Premature discontinuation of treatment is repeatedly encountered in depression, bringing on to increased disease severity, greater number of relapses, more hospitalizations and decreased remission rates. Given the impact of medication non-adherence among patients with depressive disorders, it is important to recognize factors associated with non-adherence and find ways to influence them.ObjectivesOur objective was to find out the frequency, as well as potential differences in self-reported psychological distress of medical adherence in patients diagnosed with major depressive disorder.MethodsSample consisted 83 patients (Mage = 45.4, SD = 14.8, 76% were female, 24% were male) with major depressive disorder (MDD) hospitalized at the Clinical Department of Crisis and Affective Disorders. After the informed consent of patients, the following assessment tools were administered: A socio-demographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.-6), Depression Anxiety Stress Scales (DASS-21), and The Morisky Medication Adherence Scale (MMAS-8).ResultsThirty-three (39.8%) patients were considered non-adherent (MMAS-8 adherence score &lt; 6) while 45 (54.2%) had moderate adherence (MMAS-8 adherence score &lt; 8) and 5 (6%) high adherence (MMAS-8 adherence score = 8) to their medication respectively. Negative associations were found between medication adherence and self-reported levels of depression (r = -0.30, p &lt; 0.01), anxiety (r = -0.29. p &lt; 0.01) and stress (r = -0.31, p &lt; 0.01). One-way ANOVA yielded significant variation on the self-reported anxiety subscale of the DASS-21 questionnaire among adherence groups of patients with MMD (F (2,80) = 3.73, p &lt; 0.05, η2 = 0.26). A post hoc Tuckey test showed that the non-adherent and moderate adherent groups of patients significantly differ on the level of experienced anxiety; the high adherence group was not significantly different from other two groups. Results indicate that the non-adherent group generally experiences more symptoms of anxiety than the moderate adherent group.ConclusionsPatients with major depressive disorder show significant non-adherence to medical treatment. More research is needed in this direction, as well as the development of recommendations and strategies to improve the level of adherence in this group of patients.Disclosure of InterestNone Declared

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial

Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. French Ministry of Health.

Hepatitis C Virus Elimination in Methadone-treated Patients: Implementation of Hepatology Clinic in a Methadone Treatment Program.

Patient ignorance and bureaucratic obstacles prevent initiation of hepatitis C virus (HCV) treatment in patients participating in methadone treatment program. Despite high safety and efficacy of currently available oral medications, the rate of patient-initiated treatment remains low. We evaluated the impact of an interventional program on treatment success rate and factors associated with treatment engagement. An intervention performed from 2018 to 2020 included an on-site Fibroscan and hepatologist evaluation, anti-viral HCV treatment initiation, and close support and follow-up by a dedicated team. Demographic and medical data were collected and comparison between patients who completed vs. patients who did not complete HCV treatment was done. Fifty-nine out of 74 HCV polymerase chain reaction-positive patients (79.7%) were willing and capable of undergoing on-site hepatologist and Fibroscan evaluations. Twelve (25%) of the participants had cirrhosis, 2 of whom were decompensated. Fifty of the 57 patients that got an anti-viral medication prescription (87%) initiated the treatment. Premature treatment discontinuation was rare (3 patients), intention-to-treat sustain virologic response (SVR) rate was 81% and per-protocol SVR rate was 97%. The rate of treatment initiation during the intervention was significantly higher than the patients' self-initiation rate (44 vs 12 patients). The main factors associated with successful completion of the care cascade was full abstinence from street drugs for 6 months before treatment initiation. Installing a hepatology clinic in an methadone treatment program center was associated with a 3-fold increase in the HCV treatment, with high adherence to treatment levels, and a high SVR rate. The main factor associated with low engagement to treatment was ongoing street drug use.

Predictors of Treatment Completion in an Inpatient Substance Use Treatment Service in India.

Treatment completion is associated with a better outcome in substance use disorders. We examined the rates of treatment completion and its predictors in patients admitted to specialized addiction treatment settings over a 13-year period. Ours was a retrospective cohort study. We included consecutive 2850 patients admitted to the inpatient treatment between January 2007 and December 2019. We divided the patients into 2 groups: completed versus premature discontinuation of treatment. The predictor variables were based on previous research, clinical experience, and availability of the digital record. The number of patients who completed and discontinued treatments was 1873 (72.6%) and 707 (27.4%), respectively. The inpatient treatment discontinuation rate varied widely during the study period (18% in 2007 and 41% in 2012). The average rate of treatment discontinuation was 27%. The change-point analysis showed 5 statistically significant change points in the years 2008, 2010, 2012, 2014, and 2016. Patients who were prescribed medications for alcohol and opioid dependence and those who were on opioid agonist treatment had 4.7 and 6.3 higher odds of completing inpatient treatment than those who were not on medication. Patients with physical and psychiatric comorbidities had higher odds of treatment completion. Patients with a primary diagnosis of opioid dependence had lower odds of treatment completion than those with alcohol dependence. The rates of discontinuation may vary with concurrent changes in the treatment policies. Awareness of the risk factors and policy measures that may improve treatment completion must aid in informed decision making.

424.9: Real-World Treatment Patterns and Outcomes For Cytomegalovirus Infection and Disease in Hematopoietic Stem Cell Transplant Recipients in Selected Countries Outside of North America and Europe: A Systematic Review

Background: There is a paucity of real-world data on treatments used for cytomegalovirus (CMV) in hematopoietic stem cell transplant (HSCT) recipients, which differ across countries, outside of developed markets. To address this knowledge gap, a systematic review was conducted to evaluate current treatment patterns for CMV infection and disease following HSCT in selected countries outside of North America and Europe and describe related outcomes. Methods: Information sources (search period: 01 Jan. 2011 – 21 Jul. 2021) included indexed literature (Ovid® MEDLINE and Embase, Cochrane Database of Systematic Reviews and World Health Organization database Global Index Medicus), conference abstracts, pragmatic searches of the grey literature and snowballing of references lists of retained studies. Observational studies of interest included HSCT recipients (any age) who developed CMV infection or disease in 15 selected countries in Asia-Pacific, Latin America, Russia, and the Middle East. Outcomes of interest were treatment patterns for CMV infection and CMV disease, proportion of patients (pts) with resistant and refractory CMV including definitions, treatment-related outcomes and adverse events (AEs). The protocol was registered in PROSPERO (CRD42020205559). Results: Out of 25 retained studies (33 to 475 pts), most included allogeneic HSCT recipients (n=21, 84.0%) and adult pts (n=20, 80.0%). In HSCT recipients, pre-emptive therapy with intravenous ganciclovir (IV GCV) and/or valganciclovir (VGCV) is the conventional first-line (1L) approach for CMV infection prevention, with a median treatment duration of 14-24 days (5 studies). GCV IV was also the conventional treatment for CMV disease (5 studies), with treatment lasting 12-30 days (3 studies). Neutropenia was observed in 30.0% and 39.8% pts treated with GCV and, in 3 studies, neutropenia, myelosuppression, and nephrotoxicity led to GCV discontinuation, respectively, in 13.6%, 10.0%, and 2.3% of pts. In 3 studies, up to 10.0% of pts had second-line (2L) treatment with foscarnet, due to GCV-related myelosuppression. The reported proportion of pts with resistant CMV (definition not specified) ranged between 0% and 7.7% (5 studies; Figure 1). These pts received foscarnet or cidofovir as 2L therapy for a mean duration of 14 days (no data on AEs reported). In 3 studies, estimates of refractory CMV were 2.9%, 13.0%, and 49.4% (latter estimate reported in 39 pts, of whom 56.0% had recurrent CMV). Conclusion: In selected countries outside of North America and Europe, conventional therapeutic options for pre-emptive and treatment of CMV infection and CMV disease following HSCT were IV GCV and VGCV. However, premature treatment discontinuation occurred in up to 1 in 8 pts, highlighting an unmet need with current standard of care. Real-world outcomes in pts with refractory CMV (with or without resistance) were scarce and warrants further investigation in this patient population, including therapeutic management.This review was funded by Takeda International AG – Singapore Branch. S-YC has served as a consultant for Takeda Pharmaceutical, and has received research support and payment for lectures from Merck Sharp & Dohme, Pfizer and Gilead. WD has no conflicts of interest to disclose. CMM has received honoraria from Takeda and MSD (advisory board, speaker, educational events, meetings). IS is an employee of Takeda Pharmaceuticals India Pvt Ltd. AS and DD are employees of Takeda International AG – Singapore Branch and hold stock options. MS has received grants from F2G, Gilead, Merck and personal fees from Gilead, Pfizer, Takeda and Roche for work outside of this research. Literature retrieval, analysis and medical writing support were provided by Aurore Bergamasco, Camille Goyer, and Yola Moride of Yolarx Consultants and funded by Takeda International AG – Singapore Branch.

Handling Informative Premature Treatment or Study Discontinuation for Assessing Between-Group Differences in a Comparative Oncology Trial

This decision analytical model study examines premature treatment discontinuation in clinical trials for patients with advanced renal cell carcinoma.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

BackgroundCognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options.Methods and designThe Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects—and their putative determinants—are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine.DiscussionThis study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol.Clinical trial registrationEudraCT 2014-003385-24.