Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

INTRODUCTION: Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. METHODS: This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). RESULTS: Among 93 patients selected, median age at index was 67 years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3 months (IQR 8.7-25.4 months), and median time from end of 1L therapy to 1LM initiation was 35.0 days (IQR 25.0-53.9 days). Median TTD was 9.3 months (95% CI 6.1-11.3 months). Median TTNT was 12.9 months (95% CI 11.5-19.0 months). CONCLUSIONS: This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.

Prediction of sustained remission after tyrosine kinase inhibitor discontinuation with BCR::ABL1 digital PCR in chronic myeloid leukemia patients.

Precise and reliable predictive parameters to accurately identify chronic myeloid leukemia (CML) patients who can successfully discontinue their tyrosine kinase inhibitor (TKI) treatment are lacking. One promising parameter is depth of molecular response measured by BCR::ABL1 digital PCR (dPCR). The aim of this study was to validate a previously described prediction cutoff of 0.0023%IS and to assess the value of dPCR for treatment-free remission (TFR) prediction in relation to other clinical parameters. A droplet-based dPCR assay assessed BCR::ABL1 %IS prior to TKI discontinuation. The primary endpoint was molecular recurrence (MolR) by 36 months. A total of 186 patients from Canada, Germany, and the Netherlands were included. In patients with a first TKI discontinuation attempt (n = 163), a BCR::ABL1 dPCR < and ≥0.0023%IS had a MolR probability of 33% and 70%, respectively. Patients treated less than 6 years with a BCR::ABL1 dPCR <0.0023%IS had a MolR probability of 31%. After correction for treatment duration, both high dPCR value and the use of imatinib (vs. second-generation TKI) were significantly associated with a higher risk of MolR (HR of 3.66, 95%CI 2.06-6.51, p < .001; and 2.85, 95%CI 1.25-6.46, p = .013, respectively). BCR::ABL1 dPCR was not associated with TFR outcome after second TKI discontinuation, however, with the limitation of a small number of patients analyzed (n = 23). In conclusion, BCR::ABL1 digital PCR based on the cutoff of 0.0023%IS is a valuable predictive tool to identify CML patients with a high probability of TFR success after first TKI discontinuation, including patients treated for less than 6 years.

The Effect of Rifapentine and Rifampicin on Serum Voriconazole Levels Persist for 5 Days and 7 Days or More After Discontinuation in Tuberculosis Patients with Chronic Pulmonary Aspergillosis.

Purpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine. Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses. Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (>70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine. Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.

Outcomes of patients with advanced solid tumors who discontinued immune-checkpoint inhibitors: a systematic review and meta-analysis.

Background: The outcome of patients with metastatic tumors who discontinued immune checkpoint inhibitors (ICIs) not for progressive disease (PD) has been poorly explored. We performed a meta-analysis of all studies reporting the clinical outcome of patients who discontinued ICIs for reasons other than PD. Methods: We searched PubMed, Embase and Scopus databases, from the inception of each database to December 2023, for clinical trials (randomized or not) and observational studies assessing PD-(L)1 and CTLA-4 inhibitors in patients with metastatic solid tumors who discontinued treatment for reasons other than PD. Each study had to provide swimmer plots or Kaplan-Meier survival curves enabling the reconstruction of individual patient-level data on progression-free survival (PFS) following the discontinuation of immunotherapy. The primary endpoint was PFS from the date of treatment discontinuation overall and according to tumor histotype, type of treatment and reason of discontinuation. The Combersure's method was used to estimate meta-analytical non-parametric summary survival curves assuming random effects at study level. Findings: Thirty-six studies (2180 patients) were included. The pooled median PFS (mPFS) was 24.7 months (95% CI, 18.8-30.6) and the PFS-rate at 12, 24, and 36 months was respectively 69.8% (95% CI, 63.1-77.3), 51.0% (95% CI, 43.4-59.8) and 34.0% (95% CI, 27.0-42.9). Univariable analysis showed that the mPFS was significantly longer for patients with melanoma (43.0 months), as compared with non-small cell lung cancer (NSCLC, 13.5 months) and renal cell carcinoma (RCC, 10.0 months; between-strata comparison test p-value < 0.001); for patients treated with anti-PD-(L)1 + anti-CTLA-4 as compared with anti-PD-(L)1 monotherapy (44.6 versus 19.9 months; p-value < 0.001), and in NSCLC when the reason of treatment discontinuation was elective as compared with toxicity onset (19.6 versus 4.8 months; p-value = 0.003). The multivariable analysis confirmed these differences. Interpretation: The long-term outcome of patients who stopped ICIs for reasons other than PD was substantially affected by clinicopathological features: PFS after treatment discontinuation was longer in patients with melanoma, and/or treated with anti-PD-(L)1 + anti-CTLA-4, and shorter in patients with RCC or in those patients with NSCLC who stopped treatment for toxicity onset. Funding: The Italian Ministry of University and Research (PRIN 2022Y7HHNW).

High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy.

BACKGROUND AND AIMS: Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation. METHODS: Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off-treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE-B score was calculated for the purposes of model validation. RESULTS: HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p = .001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE-B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off-treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss. CONCLUSIONS: High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation.

The safety of orthokeratology contact lens wear in slowing the axial elongation of the eye in children.

PURPOSE: To evaluate the safety of orthokeratology contact lens wear in slowing the axial elongation of the eye in myopic children. METHODS: Safety data from three prospective studies, which evaluated the use of orthokeratology for slowing myopia progression in children in comparison to a parallel control group of single-vision spectacle lens wearers over a 2-year period, were pooled together for analysis. The primary and secondary safety endpoints are the comparisons of adverse events and slit-lamp findings grades ≥ 2 between orthokeratology and control groups, respectively. RESULTS: Collectively, data from 125 orthokeratology and 118 control subjects were analyzed in this study. Of these, 101 (81 %) and 88 (75 %) orthokeratology and control subjects completed the 2-year follow-up period, respectively. Nineteen orthokeratology subjects experienced 28 adverse events, of which 6 were significant, whereas just one adverse event was found in the control group; this difference was statistically significant (p < 0.001). Most adverse events found in the orthokeratology group were corneal in nature, primarily corneal abrasion/staining, accounting for around 40 % of all adverse events. Of the 28 adverse events, only 18 (3 significant) are likely to be contact lens-related, leading to incidence rates of total and device-related adverse events per 100 patient years of lens wear (95 % confidence intervals) of 13.1 (9.2-18.2) and 8.4 (5.4-10.7), respectively. No significant differences were found between groups in the total number of silt-lamps findings with grades ≥ 2 (p > 0.05). CONCLUSION: Around 13% of eyes wearing overnight orthokeratology contact lenses are likely to experience an adverse event over one year of lens wear, with this figure being lower when considering device-related adverse events alone. No serious adverse events were found, with most being non-significant. These results inform eye care practitioners on the safety of orthokeratology lenses when prescribed for slowing myopia progression to myopic children.

Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis.

Introduction: Limited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs). Methods: We conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis. Results: A total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1-2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI. Conclusions: Patients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.

Oral Preexposure Prophylaxis Uptake and Discontinuation in the HIV Vaccine Trials Network 704/HIV Prevention Trials Network 085 Study: Implications for Biomedical Human Immunodeficiency Virus Prevention Trials.

Background: HIV Vaccine Trials Network (HVTN) 704/085, a placebo-controlled clinical trial assessing the efficacy of VRC01 broadly neutralizing antibody infusion for HIV prevention, offered oral preexposure prophylaxis (PrEP) as the standard of prevention at no cost to participants. Methods: We characterized features of- identified factors associated with- PrEP initiation and discontinuation, and the effects of PrEP initiation on HIV incidence. Results: Of 2221 participants, 31.8% initiated oral PrEP during study follow-up, with the highest proportion of PrEP initiations in Brazil (83.2%) and the United States (US) (54.2%). Prior PrEP use was associated with PrEP initiation (hazard ratio [HR], 2.22 [95% confidence interval {CI}, 1.25-3.95]). Participants from Switzerland (HR, 0.5 [95% CI, .3-1.0]) and Peru (HR, 0.08 [95% CI, .06-.1]) had lower likelihood of PrEP initiation compared to the US, while participants from Brazil had higher likelihood (HR, 2.6 [95% CI, 2.0-3.3]). In the US, PrEP initiation was lower in areas with higher unmet need for PrEP (HR, 0.9 per 5 units [95% CI, 0.8-1.0]). PrEP initiators had 58% less risk of acquiring HIV than PrEP noninitiators. Among PrEP initiators, 34.4% discontinued PrEP during study follow-up. Brazil had 63% less likelihood of PrEP discontinuation than the US (HR, 0.37 [95% CI, .22-.60]). Conclusions: When included as standard of prevention in HVTN 704/085, oral PrEP utilization patterns mirrored those observed in real-life settings. Variable effects of oral PrEP on HIV outcomes in clinical trials may be expected based on regional differences in oral PrEP use.

Immunosuppressives discontinuation after renal response in lupus nephritis: predictors of flares, time to withdrawal and long-term outcomes.

OBJECTIVES: The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients. METHODS: Data from 137 inception cohort LN patients were analyzed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models. RESULTS: IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) (OR : 1.07, p= 0.046) and higher SLEDAI-2K at tapering initiation (OR : 2.57, p= 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (≥2/3 of follow-up) (OR : 0.28, p= 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR : 1.70, p= 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% eGFR decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, p< 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (ß-coef=-19.8, p= 0.014). CONCLUSION: Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavorable long-term outcomes. Earlier IS D/C is feasible in membranous LN.

Favorable clinical course after discontinuation of omalizumab treatment in patients with allergic severe asthma: A real-world clinical practice.

The success rate of omalizumab discontinuation is 50-75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3-12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status.

Drug survival and risk factors for ADHD medication discontinuation in adults: A Danish Nationwide Registry-based cohort study.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) medication has proven effective for treating ADHD in adults, nonetheless previous studies have shown high rates of medication discontinuation. OBJECTIVE: To assess drug survival and identify risk factors associated with discontinuation of ADHD medication. METHODS: A nationwide registry-based cohort study in Danish adults who redeemed a prescription for ADHD medication for the first time between 2010 and 2015. All patients were followed for 5 years from the first redeemed prescription. Discontinuation was defined as a gap of 12 months between redemptions. Logistic regression analysis with odds ratio (OR) and Kaplan Meier analysis were used to examine risk factors (sex, age, socioeconomic status, substance use disorders, and comorbidities) associated with discontinuation. RESULTS: Twenty three thousand nine-hundred and sixteen patients with ADHD were identified. The 5-year overall drug survival was 29% in women vs. 23.5% in men. The risk of medication discontinuation was significantly higher in men compared to women, OR 1.26 (95% CI 1.19-1.34, p < 0.001). Adults aged 31-50 years had a significantly decreased risk of medication discontinuation compared to adults aged 18-30 years, OR 0.57 (95% CI 0.53-0.61, p < 0.001). Switching ADHD medication two times or three times or more significantly decreased the risk of discontinuation; OR 0.53 (95% CI 0.49-0.56, p < 0.001) and OR 0.26 (95% CI 0.23-0.30, p < 0.001), respectively. Substance use disorders and certain comorbidities were associated with medication discontinuation. Eating disorders, OR 0.71 (95% CI 0.64-0.78, p < 0.001), intellectual disabilities, OR 0.65 (95% CI 0.59-0.73, p < 0.001) and sleep disorders, OR 0.42 (95% CI 0.37-0.49, p < 0.001) were associated with continuation of ADHD medication. CONCLUSIONS: The 5-year overall drug survival was longer in women compared to men. Women with ADHD; adults aged 31-50; and patients with comorbid eating disorder; intellectual disability; sleep disorder and medication switching were individually associated with continuation of ADHD medication. Various factors were associated with medication discontinuation. Discontinuation should be acknowledged as a common phenomenon in patients with ADHD and calls for increased attention from the treatment responsible prescriber or team. Moreover, our findings suggest that timely, frequent medication switching, or temporary regimens may indeed represent optimal management strategies for a significant proportion of the ADHD population.

Long-term effects of benzodiazepine discontinuation among older adults: potential improvements on depressive symptoms.

OBJECTIVES: To examine how change in benzodiazepine (BZD) use is linked to changes in depressive symptoms intensity, worry intensity, and sleep quality over 16 months. METHOD: Data come from a larger randomised controlled trial (RCT) named the 'Programme d'Aide du Succès au SEvrage (PASSE-60+)' study (NCT02281175). Seventy-three participants age 60 years and older took part in a 4-month discontinuation programme and were assessed four times over 16 months. Change in BZD use was defined as the difference in reported mg/day between two assessments. Control variables were RCT discontinuation group; BZD use at T1; and either depressive symptoms, worry intensity, or sleep quality at T1. Hierarchical multiple regressions were used to analyse data. RESULTS: In the short term, right after the discontinuation programme, sleep quality worsened with lower BZD use. This link was no longer significant at the 3- and 12-month follow-up. In the long term, depressive symptoms lowered with lower BZD use. No change was found in worry intensity in relation to BZD use at all measurement times. CONCLUSION: Discontinuation may improve depressive symptoms. Our study also questions the long-term effectiveness of BZD use, since long-term discontinuation was not linked with change in worry intensity and sleep quality.

De-escalation and Discontinuation of Disease-Modifying Therapies in Multiple Sclerosis.

PURPOSE OF REVIEW: Long-term use of multiple sclerosis (MS) disease-modifying therapies (DMTs) is standard practice to prevent accumulation of disability. Immunosenescence and other age-related changes lead to an altered risk-benefit ratio for older patients on DMTs. This article reviews recent research on the topic of de-escalation and discontinuation of MS DMTs. RECENT FINDINGS: Observational and interventional studies have shed light on what happens to patients who de-escalate or discontinue DMTs and the factors, such as age, treatment type, and presence of recent disease activity, that influence outcomes. Though many questions remain, recent findings have been valuable for the development of an evidence-based approach to making de-escalation and discontinuation decisions in MS.

Toxicity-Induced Discontinuation of Immune Checkpoint Inhibitors in Metastatic Urothelial Cancer: 6-Year Experience from a Specialized Uro-Oncology Center.

Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but there are emerging data about a positive correlation between emergence of severe irAEs and therapeutic cancer responses. In this study, a retrospective analysis of patients treated for urothelial carcinoma (UC) with ICI-based immunotherapy was conducted. irAEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAEs) and radiological responses according to the Response Evaluation Criteria In Solid Tumors (RECISTs). Out of 108 patients with metastatic urothelial cancer that underwent immunotherapy, 11 experienced a severe irAE that required permanent discontinuation of ICI therapy. The most frequent irAEs leading to discontinuation were hepatitis (n = 4), pneumonitis (n = 2), and gastritis or colitis (n = 2). Prior to discontinuation (R1), the radiological best response was complete remission (CR) in three patients, partial response (PR) in six, and stable disease (SD) in wo patients. After the discontinuation of ICI therapy (R2), the best responses were CR in six, PR in three, and SD in two patients. Following discontinuation, the majority of these patients showed a sustained treatment response, despite not receiving any cancer-specific treatment. The median time of response after discontinuation of ICI therapy was 26.0 (5.2-55.8) months. We propose accurate counseling and close follow-ups of patients following their discontinuation of ICI therapy due to irAEs, as responses can be durable and deep, and many patients do not require immediate subsequent therapies, even in urothelial cancer. More data are required to find predictors of the length of response to appropriately counsel patients.

Validation of prediction model for successful discontinuation of continuous renal replacement therapy: a multicenter cohort study.

BACKGROUND: Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. METHODS: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. RESULTS: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71-0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and highscore groups, respectively. The model performance was good in four cohorts (AUROC, 0.73-0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. CONCLUSION: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

'Matters-of-concern' associated with discontinuation of long-acting injectable buprenorphine: Findings from a longitudinal qualitative study.

BACKGROUND: Discontinuation of medications such as methadone and buprenorphine amongst patients receiving opioid agonist treatment (OAT) is an international phenomenon. Recent developments in OAT medication include depot-injections of buprenorphine. Circumstances underlying discontinuation of these new formulations of medication are not fully understood from a qualitative perspective. METHODS: Data derive from a longitudinal qualitative study of patients' experience of long-acting injectable buprenorphine (LAIB), involving semi-structured telephone-interviews held at six-points in time. The relevant dataset for this article consists of 44 interview transcripts, generated from 8 participants who were each affected by discontinuation of LAIB prescriptions (during the first 12-months of treatment). Analyses sought to identify circumstances associated with LAIB discontinuation and data were further situated within a framework of 'evidence making intervention' and associated 'matters-of-concern'. Matters-of-concern relate to the ways in which an intervention is 'made' and constructed through engagement and practice, from the perspective of the recipient. FINDINGS: In this study, participants experienced either 'discontinuation of LAIB prescriptions by treatment services' or patient-led 'opt-out' from treatment. Matters-of-concern underlying the former were associated with late attendance for scheduled appointments, non-prescribed substance use or receiving a custodial sentence. Matters-of-concern relating to patient-initiated discontinuation were associated with personal circumstances that affected treatment motivation, side-effects (of buprenorphine), a preference to resume heroin use, or because individual treatment goals had been achieved. CONCLUSION: The assorted matters-of-concern that influence discontinuation of LAIB demonstrate that such OAT is complex and multi-faceted, is neither fixed nor stable, and does not generate universally shared outcome. Experiences of LAIB discontinuation are shaped by a wide range of social, temporal and treatment-related effects that include disconnected therapeutic alliance between patient and treatment providers. In order to maximise the benefits of LAIB it is necessary to develop meaningful therapeutic alliances (notwithstanding policy boundaries) to enable exploration of matters-of-concern during treatment.

Discontinuation of maintenance peritoneal dialysis in children-A 10-year review from a single center in a low resource setting.

INTRODUCTION: In South Africa, only children considered eligible for transplantation are offered dialysis as bridge to kidney transplantation. Maintenance peritoneal dialysis (PD) is preferred and has several advantages over hemodialysis (HD). While awaiting transplantation, PD may be discontinued due to permanent transfer to HD or death while on PD, of which the occurrence and burden is not known in our setting. We investigated the rate of discontinuation of maintenance PD, and associated factors among children awaiting a kidney transplant under challenging socio-economic circumstances in a low resource setting. METHODS: Single center retrospective analysis of children receiving maintenance PD. Outcomes included the proportion of children who discontinued PD before transplantation, associated factors and timing of discontinuation, and the proportion transplanted. Time to discontinuation or transplantation was displayed using a Kaplan-Meier curve. RESULTS: Sixty-seven children who received maintenance automated PD as initial dialysis modality were identified from the kidney transplant waiting list between January 2009 and December 2018. Complete data was available for 52 of the 67 children. Four children had prior failed kidney transplants. The median age was 11 years (interquartile range 6.0, 13.1). Overall, 17/52 (32.7%) children discontinued PD, with 13 (25%) transfers to HD and 4 deaths (7.7%), whereas 29/52 (55.8%) received a kidney transplant. Three of the deaths were PD related. Six children remained on maintenance PD at the end of the study period. Over a half of our patients discontinued PD by 12 months, and 80% by 30 months. Most PD discontinuations were associated with peritonitis. CONCLUSIONS: The proportion discontinuing PD was high, highlighting the need to optimize measures to improve retention rates, especially through prevention of peritonitis.

High SARS-CoV-2 infection rate in children unvaccinated with COVID-19 vaccine in Changzhou, China, shortly after lifting zero-COVID-19 policy in December 2022.

BACKGROUND: China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. METHODS: From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). RESULTS: Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively. CONCLUSION: Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.

Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Discontinuation of Palliative Brain Radiotherapy in Patients with Brain Metastases: A Case-Control Study.

Background: Discontinuation of radiotherapy is rarely discussed in the scientific literature. The goal of this study was, therefore, to estimate the frequency of and reasons for treatment discontinuations in patients receiving radiotherapy for brain metastases from solid tumors and to identify factors predicting said discontinuations. Methods: All patients treated for brain metastases from solid tumors between 2010 and 2020 at our institution were retrospectively reviewed. In addition to collecting relevant patient characteristics, the Recursive Partitioning Analysis (RPA) and disease-specific Graded Prognostic Assessment (GPA) groups for each patient were calculated to assess the performance of these scores in predicting treatment discontinuations. Results: Out of 468 patients who underwent cranial radiotherapy, 35 treatments (7.5%) were discontinued. The most frequent reason was clinical deterioration, which was documented in 26 (74.3%) of discontinued treatments. Patients whose radiotherapy was discontinued had, on average, more leptomeningeal disease (20.0% vs. 12.6%), worse ECOG performance status (mean ECOG performance status 1.86 vs. 1.39), and more uncontrolled extracranial metastases (85.3% vs. 70.8%). The frequencies of treatment discontinuation increased with worse prognosis and differed significantly across RPA groups (p = 0.037) but not across GPA groups (p = 0.612). Conclusions: Treatment discontinuation occurred in 7.5% of cases, mostly due to clinical deterioration. Poor performance status, as well as more advanced disease and, in turn, poor prognosis, were associated with higher discontinuation rates.