Impact Treatment Success Research Articles

Effect of missed clinic visits on treatment outcomes among people with tuberculosis: a quasi-experimental study utilizing instrumental variable analysis

ObjectivesMissed clinic visits disrupt the continuity of care and potentially impact tuberculosis (TB) treatment outcomes negatively. We evaluated the effect of missed clinic visits on mortality and treatment success among people with bacteriologically confirmed pulmonary TB in rural eastern Uganda. MethodsUsing routine TB clinic data, we designed a quasi-experimental study and used instrumental variable analysis to estimate a cause-effect. The exposure was one or more missed clinic visit(s), the instrumental variable was patient residence in the same sub-county as the TB clinic, and the outcomes were mortality and treatment success. We performed a two-stage least squares logistic regression for causal analysis and reported the odds ratio (OR) and 95% confidence interval (CI). ResultsOf 762 participants with similar baseline characteristics, 186 (24.4%) missed ≥1 clinic visit(s), 342 (44.9%) resided in the same sub-county as the TB clinic, 61 (8.0%) had died, and 687 (90.2%) were successfully treated for TB. Missed clinic visits increased mortality (OR 2.88, 95% CI 1.36-6.13) and reduced TB treatment success (OR 0.41, 95% CI 0.20-0.82). ConclusionsMissed clinic visits increase mortality and negatively impact treatment success among people with TB. The reasons for missed clinic visits should be identified and tackled through context-specific measures.

Clinical homologous recombination repair gene reversion analysis identifies mechanisms of resistance to PARP inhibitors and platinum‐chemotherapy

AbstractIdentifying mechanisms underlying cancer resistance to therapy is vital for advancing treatment strategies. Pathogenic mutations of homologous recombination repair (HRR) genes are known biomarkers for platinum (Pt)‐based chemotherapy and poly ADP ribose polymerase inhibitors (PARPi) effectiveness. Yet, the dynamics of HRR reversion mutations, which may herald therapy resistance, are not fully elucidated. Addressing this gap, our study analyzed secondary HRR gene mutations in a comprehensive pan‐cancer data set of approximately 13,000 patients who underwent targeted next‐generation sequencing. We identified a subset of patients harboring secondary mutations, which were further categorized into three tiers based on their nature, and occur in the presence of a primary pathogenic mutation, notably in BRCA1, BRCA2, PALB2, and RAD51D genes. Here we show that secondary BRCA2 mutations, indicative of adaptive resistance, emerge post‐Pt/Olaparib treatment. This challenges the prevailing notion that pathogenic HRR mutations uniformly predict therapeutic sensitivity, highlighting a nuanced genetic interplay that impacts treatment success. This investigation enriches our understanding of cancer's adaptive mechanisms against therapy, suggesting a pivotal shift towards more personalized, dynamic treatment strategies. It underscores the imperative of adapting to cancer's genetic evolution, aiming for a step ahead in the ongoing battle against this disease.

ARTICLE REVIEW: THE TREATMENT PROBLEM AND ADVERSE DRUG REACTIONS IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS

Multidrug-resistant tuberculosis (MDR-TB) is the resistance of Mycobacterium tuberculosis to at least two tuberculosis (TB) drugs, rifampicin and isoniazid. The disease requires a long treatment duration with several second-line drugs. This leads to a globally low success rate of approximately 56% for MDR-TB treatment. Studies have reported that adverse drug reactions (ADRs) contribute to high rates of non-compliance, treatment discontinuation, and failure. This narrative review aimed to provide information about MDR-TB treatment modalities, various ADRs, challenges encountered in MDR-TB treatment, and instances of ADRs that can impact treatment success. This narrative review study was conducted by searching for scientific information from the primary electronic databases PubMed and Google Scholar, covering 2012-2022. Based on the literature search results, 14 studies were identified, demonstrating challenges in TB and MDR-TB treatment, along with 6 ADRs that can influence treatment success in MDR-TB patients. ADRs during MDR-TB treatment can affect patients’ physical, mental, and social well-being as well as their beliefs and behaviors related to treatment. Comprehensive support from families, communities, and healthcare providers is essential to assist patients in addressing treatment challenges and adverse ADRs. Rapid identification and strategies for monitoring and managing treatment challenges and ADRs can improve compliance and success of MDR-TB treatment. Keywords: Adverse Drug Reactions, Drug Side Effects, Multi Drug-Resistant Tuberculosis (MDR-TB), Treatment Success

2805. Extended-Infusion versus Intermittent-Infusion Piperacillin/tazobactam for High Minimum Inhibitory Concentration Pseudomonas aeruginosa Infections

Abstract Background Extended-infusion (EI) piperacillin/tazobactam, compared to intermittent-infusion (II) piperacillin/tazobactam, has been associated with improved clinical outcomes for both critically ill and febrile neutropenic patients. However, there is a paucity of data on whether these clinical benefits apply to broader populations. Infections involving high minimum inhibitory concentration (MIC) Pseudomonas aeruginosa represent an additional group where optimization of pharmacokinetic parameters may impact treatment success. Methods Medical records of adults who received II or EI piperacillin/tazobactam for pneumonia and/or bacteremia caused by Pseudomonas aeruginosa with MIC 8 or 16 mcg/mL were reviewed. The primary outcome was 30-day all-cause mortality. Hospital and/or intensive care unit (ICU) length of stay (LOS) and recurrence of infection were also recorded. Additionally, an escalation of care composite was assessed by need for new ICU transfer, new vasopressor start, new mechanical ventilation, or rescue antibiotic therapy change. Finally, a safety outcome of acute kidney injury (AKI) was recorded. Results A total of 69 patients were included, 31 in the II group and 38 in the EI group. Bacteremia was detected in 19.4% and 23.7% of the II and EI groups, respectively (p = 0.66). Baseline demographics and characteristics of treatment were similar between groups. The most common dosing regimens were 3.375 g IV every 6 hours over 30 minutes and 3.375 g IV every 8 hours over 4 hours. 30-day mortality was 32.3% in the II group and 39.5% in the EI group (p = 0.54). Similarly, hospital LOS (19 versus 15 days, p = 0.27) and ICU LOS (23 versus 15 days, p = 0.15), as well as recurrence (29.4% versus 23.5%, p = 1) and therapy escalation (38.7% versus 47.4%, p = 0.47), were not significantly different between groups. 43.5% of patients in the II group and 40.6% of patients in the EI group developed AKI (p = 0.83). Conclusion The present study found no significant difference in outcomes between piperacillin/tazobactam infusion strategies. However, the small sample size and complex patient factors may have limited the comparison. Disclosures Dustin R. Carr, PharmD, BCPS, BCIDP, Merck: Advisor/Consultant Thomas L. Walsh, MD, Accelerate Diagnostics: Advisor/Consultant Derek N. Bremmer, PharmD, BCIDP, Thermo Fisher Scientific: Advisor/Consultant

Psychosocial and medical factors associated with intrathecal baclofen pump explants: A case series.

The goal of this retrospective chart review study was to explore factors that contributed to consideration of or actual pump explantation in pediatric patients with intrathecal baclofen (ITB) pumps. Medical records of 30 patients with ITB pumps were reviewed. Quantitative data, including demographic, clinical, psychosocial, and service utilization variables were culled from the records. Qualitative data were collected from clinic visit notes, pump-related follow-up phone calls, and any pump-related emergency room visits. Of those reviewed, six underwent ITB pump explantation, and two considered explantation. Factors contributing to pump explantation or consideration of explantation included the following: postoperative infection, pump malfunction, non-adherence, anxiety/behavioral factors impacting the patient's tolerance of the pump, distance to the medical provider, frequency of required pump refill appointments, lack or perceived lack of intrathecal baclofen effect, and difficulty transitioning to adult care providers. Due to the complex care regimen associated with ITB pumps and various psychosocial and logistical factors that impact treatment success, a standardized multidisciplinary pre-implantation education, screening, and assessment process should be developed. Such a process would ensure that patients/families receive appropriate education, including proactively identifying treatment barriers and potential complications, possibly minimizing dissatisfaction with treatment and the need for explantation.

How to treat with gynecological cancers during COVID-19 pandemic: A review

The COVID-19 pandemic has created difficulties in managing gynecological malignancies, leading to limitations on routine visits, reduced face-to-face appointments, postponements of surgeries and interventions, and necessary adjustments to treatment strategies. Hospitals have been overwhelmed with COVID-19 cases, making resource allocation a focal point. The pandemic significantly impacted the mental well-being of women with gynecological cancers, leading to heightened anxiety, worries about treatment delays, and increased stress, depression, and fear. Strategies to support mental health, such as telehealth-based mental health services offering online therapy and support groups, have proven beneficial. Additionally, incorporating mindfulness techniques and meditation practices into daily routines could assist patients in coping with stress and anxiety, ultimately fostering emotional resilience. The COVID-19 pandemic has complicated the traditional approach to prioritizing cancer treatment based on cancer stage. Certain gynecological cancers and their treatments can weaken patients' immune systems, making them more susceptible to severe COVID-19 complications. Advanced-stage and aggressively growing cancers pose a particular risk, as postponing treatment due to COVID-19 concerns could lead to disease progression and impact treatment success and patient survival. The urgency of therapeutic decisions during the pandemic is influenced by cancer stage and aggressiveness, with advanced and rapidly progressing cancers requiring prompt intervention. Patient age and overall health status also play crucial roles, as younger patients with strong immune systems may tolerate treatment delays better than older patients with underlying health conditions. COVID-19 outbreak has undeniably disrupted traditional approaches to managing gynecological malignancies, but it has also spurred creativity and adaptation. Treatment decisions for gynecological cancer patients must consider age, overall health, and cancer stage. By embracing telemedicine, using risk assessment models, and prioritizing collaborative patient management, a more resilient and patient-centered healthcare system can be developed to address current and future pandemic challenges.

Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India

Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. To evaluate changes in antifungal resistance over time. Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001). This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world. ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.

An investigation comparing primary and secondary substance cravings between mental health and substance use disorder program inpatients

Background: Mental illness symptoms can trigger substance use cravings, which are strongly associated with relapse. Aim: Our study examines differences in substances craved among adults entering inpatient mental health (MH) and substance use disorder (SUD) treatment programs in 2018. Method: Our sample includes 2,486 adults; 1,686 adults admitted to MH programs and 800 adults admitted to SUD programs. We conducted chi-square tests and Fisher’s exact tests to determine group differences, with a Bonferroni correction to adjust the alpha for multiple tests. Results: We found that patients programmed to SUD services more often reported alcohol (39.99 vs. 49.63%; x2 (1, N = 2,488) =20.56, p&lt;0.001) and opioid (8. 00% vs. 35.88%; x2 (1, N = 2,488) =299.48, p &lt; 0.001) cravings. Patients programmed to MH primary more often reported cannabis (16. 35% vs. 1.00%; x2 (1, N=2,488) =299.48, p&lt;0.001), stimulants (10.25% vs. 6.13%; x2(1, N =2,488) = 11.36, p &lt; 0.001), and “other substances” cravings (21.45% vs. 3.25; x2 (2, N = 2,488) =136.52, p &lt;0.001). Both groups mostly did not report secondary cravings. Conclusions: Because cravings can negatively impact treatment success of patients with co-occurring disorders, cravings should be assessed upon admission to mental health or SUD inpatient treatment.

V05-07 INITIAL EXPERIENCE WITH REAL-TIME DETECTION OF KIDNEY STONE COMPOSITION USING ARTIFICIAL INTELLIGENCE, MACHINE LEARNING, AND SMARTPHONE TECHNOLOGY

INTRODUCTION AND OBJECTIVE:Kidney stone composition is becoming increasingly important in treatment algorithms as the composition/hardness of stones impacts treatment success. Artificial intelligen...

A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer

Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of treatment timing using a novel mathematical model of irinotecan cellular pharmacokinetics and –dynamics linked to a representation of the core clock and predict treatment toxicity in a colorectal cancer (CRC) cellular model. The mathematical model is fitted to three different scenarios: mouse liver, where the drug metabolism mainly occurs, and two human colorectal cancer cell lines representing an in vitro experimental system for human colorectal cancer progression. Our model successfully recapitulates quantitative circadian datasets of mRNA and protein expression together with timing-dependent irinotecan cytotoxicity data. The model also discriminates time-dependent toxicity between the different cells, suggesting that treatment can be optimized according to their cellular clock. Our results show that the time-dependent degradation of the protein mediating irinotecan activation, as well as an oscillation in the death rate may play an important role in the circadian variations of drug toxicity. In the future, this model can be used to support personalized treatment scheduling by predicting optimal drug timing based on the patient’s gene expression profile.

4499 A look at motivation and income level for families in obesity treatment

OBJECTIVES/GOALS: An evidence-based approach for childhood obesity is family-based treatment (FBT). Research supports that motivation and income level may impact treatment success; however, the relationship between the two is understudied. Therefore, the objective of this study was to examine whether motivation for beginning FBT is associated with income levels. METHODS/STUDY POPULATION: 459 parent and child dyads from the PLAN (Pediatric, Learning, Activity, Nutrition) with Families multisite study were included in this study. PLAN consists of FBT through personalized health coaching over the course of two years, focusing on nutrition, physical activity, and parenting skills. Parent and child also attend height and weight assessments every 6 months in the study. Outcomes of the study include weight change and mastery of behavioral skills. Motivation and income level were provided by self-report at the beginning of the study. Motivation was based on a scale from 1-10 (1 = no motivation, 10 = high motivation). Income levels were grouped into one of three broader categories- low income ($80,000/year). RESULTS/ANTICIPATED RESULTS: The mean level of motivation for the parent was 8.76 and for the child was 7.87. There was a significant difference in the mean level of motivation for the child and parent, t = 7.73, p = &lt; .001. Post-hoc multiple comparisons using Tukey’s HSD test indicated that children in the high-income group had lower levels of motivation (M = 7.29, SD = 2.07) compared to children in the middle (M = 8.18) and low (M = 8.70) income groups. Level of motivation did not differ for children in the middle and low-income groups. Finally, parent motivation level did not differ significantly by income group. While there were significant differences between parent and child motivation levels, the motivation remained high for both groups. DISCUSSION/SIGNIFICANCE OF IMPACT: The data suggests a significant difference in mean child motivation and income level. Child’s high motivation may be from the idea of participating in something new, a rare opportunity for low-income children. To improve the implementation and efficacy of FBT, further study into the relationship between motivation and income level should be done.

Effect of force direction and tooth angulation during traction of palatally impacted canines: A finite element analysis

Treatment of a palatally impacted canine (PIC) is associated with demanding anchorage control, increased treatment duration, and undesirable side effects. Accurate PIC localization and force application impact treatment success. The objective of this research was to determine the stresses on the PIC when subjected to initial force activation in various directions (buccal, vertical, and distal) and relative to impaction severity. Thirty PICs from 21 scans underwent finite element modeling. A prototype 3D model was reconstructed and segmented into its anatomic components. Each PIC was precisely positioned in the prototype model according to impaction position. Stresses in response to a (1.0N) force in the distal, vertical, and buccal directions were evaluated at different levels of the root (apical, middle, and cervical). Distal and buccal forces yielded higher stress (6.64 and 6.41kPa, respectively) than the vertical force (5.97kPa) on the total PIC root and the apical and cervical root levels, but not at midroot. Statistically significant differences between severity groups were found mostly at the apical level among all force directions, except between distal and buccal forces in the higher severity group. In this group, stress was greatest at the cervical level with the buccal force significantly different from the stresses generated by either the distal or the vertical force. Vertical forces generated the lowest stresses. Differentially distributed stresses over the root reflected an initial tipping movement. Greater cervical stresses from the buccal force indicate resistance to movement, suggesting treatment initiation with vertical and distal forces over buccal forces, particularly with severely inclined canines.

Electrocautery ablation of anal high-grade squamous intraepithelial lesions: Effectiveness and key factors associated with outcomes.

Electrocautery ablation (EA) is a common treatment modality for patients with anal high-grade squamous intraepithelial lesions (HSILs), but to the authors' knowledge its effectiveness has been understudied. The objective of the current study was to determine ablation outcomes and to identify clinicopathological factors associated with postablation disease recurrence. A total of 330 people living with HIV with de novo intra-anal HSIL who were treated with EA from 2009 to 2016 were studied retrospectively. Using long-term, surveillance high-resolution anoscopy biopsy data, treatment failures were classified as local recurrence (HSIL noted at the treated site at the time of surveillance) or overall recurrence (HSIL noted at treated or untreated sites). The associations between these outcomes and clinical factors were analyzed using Cox proportional hazards models. Approximately 88% of participants were men who have sex with men. The median age of study participants was 45.5years (range, 35-51years) and approximately 49% had multiple index HSILs (range, 2-6 index HSILs). At a median of 12.2months postablation (range, 6.3-20.9months postablation), approximately 45% of participants had developed local recurrence whereas 60% had developed overall recurrence. Current cigarette smoking, HIV viremia (HIV-1 RNA ≥100copies/mL), and multiple index HSILs were found to be predictive of local recurrence. Overall recurrence was more common in current smokers and those with multiple index lesions. In multivariable models that included human papillomavirus (HPV) genotypes, baseline and persistent infections with HPV-16 and/or HPV-18 were found to be significantly associated with both local and overall recurrence. EA is an effective treatment modality for anal HSIL in people living with HIV, but rates of disease recurrence are substantial. Multiple index HSILs, HIV viremia, current cigarette smoking, and both baseline and persistent infection with HPV-16 and/or HPV-18 appear to negatively impact treatment success. Ongoing surveillance is imperative to capture recurrence early and improve long-term treatment outcomes.

434. Concurrent Gonococcal Infections with Differing Susceptibility Results from the Enhanced Gonococcal Isolate Surveillance Project (eGISP)

BackgroundConcurrent gonococcal infections could impact treatment success in cases of anatomic site-specific strains with different antimicrobial susceptibilities; however, little is known about same-patient differences in susceptibility as most antibiotic resistance surveillance is based on only male urethral isolates.MethodsIn August 2017, the enhanced Gonococcal Isolate Surveillance Project (eGISP) began collecting male and female genital and extragenital gonococcal isolates from patients in 12 STD clinics. Minimum Inhibitory Concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, gentamicin, cefixime, ceftriaxone and azithromycin were determined by agar dilution. We identified patients with isolates from multiple anatomic sites of infection collected during the same clinic visit. Isolate sets were categorized as pairs or triplets based on the number of culture positive anatomic sites. We identified same-patient isolate sets with differing MICs (≥2 dilution difference) for each antibiotic, and identified if the difference affected susceptibility categorization. All isolates in a set were tested in the same batch run by the same laboratory.ResultsFrom August 2017-February 2019, 280 isolates were collected from 135 patients, representing 136 isolate sets (128 pairs and 8 triplets); one patient contributed 2 isolate sets. Of the 136 isolate sets, the majority (72; 53%) were grouped as genital and pharyngeal isolates (Table 1). Overall, 33 isolate sets (24%) had differing MICs for ≥1 antibiotic and 21 sets (15%) for ≥2 antibiotics. Across all anatomical site combinations, differing MICs were most common for ciprofloxacin (10.3%), penicillin (9.6%) and azithromycin (9.6%). Only 18 isolate sets (13%) demonstrated differing MICs where an isolate was considered susceptible and another was considered resistant or reduced-susceptible.ConclusionAmong persons with concurrent gonococcal infections, MICs can vary by ≥2 dilutions between sites and may change susceptibility interpretation. Variation by the anatomic site can result from initial infection with multiple strains or differential development of resistance after infection. Continued surveillance of multi-site infections could help understand resistance development and inform patient management. Disclosures All authors: No reported disclosures.

Accumulated pre-switch resistance to more recently introduced one-pill-once-a-day antiretroviral regimens impacts HIV-1 virologic outcome

BackgroundOne-pill-once-a-day regimens (OPODs) appeal to providers and patients. The impact of resistance to OPODs in routine clinical care is important yet unclear, particularly in treatment-experienced patients. ObjectivesWe hypothesized that resistance to any OPOD component impacts treatment success and that historical, vs. most recent, resistance better predicts it. Study designIn the largest RI HIV Center, we identified all patients starting/switching to Complera/Stribild, evaluated their 12-month viral load (VL) suppression, and examined the impact of demographic, clinical and laboratory data on it, focusing on recent-only vs. accumulated significant resistance, defined as low-, intermediate- or high-level predicted resistance to any OPOD component. Associations with outcomes were evaluated using Fisher exact and Wilcoxon rank sum tests. Hypotheses were tested using logistic regression. ResultsOf 1624 patients, 224 started/switched to Complera or Stribild, mean age 44 years, 8 years post-diagnosis, CD4 468 cells/μL; 183 treatment-experienced (140 with genotypes; 61% suppressed at switch). Significant OPOD-associated resistance was in 30% by recent-only genotypes, and 38% by all genotypes. 12-month VL suppression was in 83% of treatment-experienced participants: 96% of suppressed at switch, associated with older age, higher CD4, fewer prior genotypes, less accumulated resistance, and better adherence; and 61% of unsuppressed at switch, associated with better adherence. Accumulated resistance independently predicted 12-month failure, better than most-recent resistance only. Conclusion12-month VL suppression with Complera/Stribild was high, suggesting that OPODs remain options even for experienced patients. Clinicians should consider resistance history before switching to OPODs and continue to focus on improving adherence.

Predictive Factors of De Novo Overactive Bladder After Artificial Urinary Sphincter Implantation in Men With Postprostatectomy Incontinence

To investigate the rates and predictive factors associated with the development of de novo overactive bladder (OAB) and to assess the effects of de novo OAB on surgical outcomes after an artificial urinary sphincter (AUS). We performed a retrospective review of 132 patients with postprostatectomy incontinence who underwent AUS surgery. Urodynamic studies were performed during preoperative visits in all patients, and patients with OAB or neurogenic bladder were excluded. We assessed the development of de novo OAB based on patient symptoms. Treatment success was defined as no need for pads, and social continence was defined as the need for ≤1pad per day at the end of the follow-up. A multivariate analysis was performed using a logistic regression model to assess predictors of de novo OAB. The rate of development of de novo OAB after surgery was 37.5%. The treatment success rate was significantly higher in the no-OAB group (72.4%) than in the de novo OAB group (55.4%) (P = .038). A low preoperative cystometric capacity of less than 300 mL (odds ratio 5.27, confidence interval 1.02-27.28; P = .048) and pelvic irradiation (odds ratio 3.18, confidence interval 1.01-10.03; P = .049) were predictive factors of de novo OAB after AUS surgery. De novo OAB occurs commonly after AUS surgery, and the presence of de novo OAB adversely impacts treatment success. Low preoperative cystometric capacity of less than 300 mL and pelvic irradiation predict the occurrence of de novo OAB after AUS implantation.

Early Molecular Response (EMR) with Frontline Treatment Is a Significant Predictor of Long-Term BCR-ABL Transcript Levels in Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia (CML) in Chronic Phase

▪Background: An emerging goal of tyrosine kinase inhibitor (TKI) therapy for patients with CML is to achieve sustained deep molecular response. Several factors, such as efficacy and tolerability of therapy and patient or disease characteristics, may impact treatment success. In this study, the correlation between specified prognostic factors and predicted molecular response levels after 1 year of treatment with nilotinib (NIL) 300 mg twice daily or imatinib (IM) 400 mg once daily was evaluated.Methods: Datafrom the ENESTnd trial comparing frontline treatment with NIL vs IM, in which BCR-ABL1 transcript levels were assessed every 3 months by real-time quantitative polymerase chain reaction on the International Scale (IS), were used to develop a statistical regression model to predict the BCR-ABL1IS category of a patient at any time point after 1 year of therapy. Potential predictors investigated were treatment, EMR status (BCR-ABL1IS ≤ 10% at 3 months), gender, age, Sokal risk score, BCR-ABL1IS categories from the previous 2 assessments, and the proportion of previous BCR-ABL1IS observations at or below MR4. BCR-ABL1IS transcript levels for patients in the NIL and IM arms of ENESTnd were stratified into 5 clinically relevant categories: ≤ 0.0032% (MR4.5), > 0.0032% to ≤ 0.01% (MR4), > 0.01% to ≤ 0.1%, > 0.1% to ≤ 10%, and > 10%. The model was specified to be a second-order Markov chain (to accommodate previous BCR-ABL1IS transcript levels) with ordinal prediction values (for ordered BCR-ABL1IS categorical outcomes).Results: Overall, 522 patients (NIL, n = 258; IM, n = 264) were included in the model, which contributed 5950 usable observations of BCR-ABL1IS transcript levels with corresponding values from the 2 prior assessments. Achievement of EMR (P = .0007), proportion of previous BCR-ABL1IS observations at or below MR4 (P < .0001), and BCR-ABL1IS categories from the previous 2 assessments (both P< .0001) were significant predictors of BCR-ABL1IS category at any time after 1 year of treatment. In our model, neither Sokal risk score nor type of therapy was a significant predictor of BCR-ABL1IS category due to their high correlations with other factors included in the model and which are measured on treatment. For example, more patients in the NIL arm than in the IM arm achieved EMR (91% vs 67%, respectively), which accounted for a lack of model statistical significance for treatment type. Model predictions had good agreement with the observed trial data (Figure).Conclusion: Patients with CML who achieve EMR after initiating frontline TKI therapy have improved long-term treatment responses and survival outcomes. Our model also demonstrates that achievement of EMR is significantly associated with BCR-ABL1IS transcript levels after 1 year. These results add to the growing body of evidence that early response to TKI treatment should be carefully considered to ensure optimal long-term treatment success. [Display omitted] DisclosuresSaglio:Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis Pharmaceutical Corporation: Consultancy, Honoraria. Snedecor:Pharmerit International: Employment, Other: Institution received payment to conduct this study. Ji:Novartis Pharmaceuticals: Research Funding. Tai:Pharmerit International: Employment. Ray:Novartis Pharmaceutical Corporation/Rutgers University: Other: I am currently a fellow with Rutgers University, conducting my "field" experience at Novartis.. Mendelson:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Buchbinder:Novartis Pharmaceutical Corporation: Employment, Equity Ownership. Edrich:Novartis Pharma AG: Employment. Mahon:Novartis: Consultancy, Honoraria; Pfizer: Consultancy; ARIAD: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria.

Immediate Versus Delayed Treatment Does Not Influence Long-term Outcomes After Radiation Therapy for Vestibular Schwannoma

Purpose/Objective(s): Observation after detection is now frequently selected as a primary management option for vestibular schwannoma (VS). It is uncertain whether this approach affects patient outcomes. It is possible that patients treated at time of progression are at an increased risk of treatment failure compared to patients treated at the time of initial detection, even among patients who may not have progressed for many years without treatment. In this study, we explore whether the decision for early or delayed treatment impacts treatment success among patients treated with hypofractionated stereotactic radiation therapy (HSRT). Materials/Methods: A retrospective review of 432 VS patients treated with HSRT regimens of 25Gy in 5 fractions or 12-15Gy in 1 fraction was performed. Patients were stratified as: (1) Early (nZ291, 67.4%), patients treated at time of initial presentation and (2) Delayed (nZ141, 32.6%), patients with radiological and/or clinical progression during a period of observation. Continuous data are summarized using median (interquartile range) and categorical data via frequency (percentage). Outcomes were measured from the date of treatment. Results: The median follow-up was 73.3 (48.7-102.9) months in the early group and 61.5 (41.0-88.7) months in the Delayed group. Baseline demographics and median baseline tumor volume (BTV) between the two groups were similar, except for older age at treatment (P 0.05). No significant differences were observed between groups with regards to median tumor volume at last follow-up, treatment failure requiring salvage microsurgery, or rate of clinical/radiological progression after treatment. Of note, a greater reduction in baseline tumor volume was observed in the Delayed group (median: -41.1%, IQR: -66.7% 9.4%) compared to the Early group (median: -32.5%, IQR: -66.7% 11.0%); however, this finding was not significant (P>0.05). Salvage microsurgery was required in 11 (3.8%) patients in the early group and 3 (2.1%) patients in the Delayed group. Ultimately, radiation therapy was equally successful in most patients in both groups (Early: nZ280, 96.2% vs Delayed: nZ138, 97.9%, PZ0.6). Conclusion: We report no difference in treatment failure rates among VS patients treated at time of initial detection versus those treated at time of progression. These data suggest that delaying RT-related toxicity by postponing RT until progression may be a reasonable approach. Author Disclosure: E.W. Sankey: None. A.E. Marciscano: None. I. Jusue-Torres: Research Grant; Salisbury Family Foundation. A. Liu: None. H.W. Francis: None. M. Lim: None. K.J. Redmond: Research Grant; Elekta Ab oligometastases research consortium. D. Rigamonti: Research Grant; Nicholl Family Foundation, Salisbury Family Foundation. L.R. Kleinberg: None.

Hepatitis C virus-HIV-coinfected patients and liver transplantation.

To review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients. The prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required. Liver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.

Programmatic treatment outcomes in HIV-infected and uninfected drug-resistant TB patients in Khayelitsha, South Africa.

South Africa has high burdens of HIV, TB and drug-resistant TB (DR-TB, rifampicin-resistance). Treatment outcome data for HIV-infected versus uninfected patients is limited. We assessed the impact of HIV and other factors on DR-TB treatment success, time to culture conversion, loss-from-treatment and overall mortality after second-line treatment initiation. A retrospective cohort analysis was conducted for patients initiated on DR-TB treatment from 2008 to 2012, within a community-based, decentralised programme in Khayelitsha, South Africa. Among 853 confirmed DR-TB patients initiating second-line treatment, 605 (70.9%) were HIV infected. HIV status did not impact on time to sputum culture conversion nor did it impact treatment success; 48.1% (259/539) and 45.9% (100/218), respectively (p=0.59). In a multivariate model, HIV was not associated with treatment success. Death during treatment was higher among HIV-infected patients, but overall mortality was not significantly higher. HIV-infected patients with CD4 <=100 cells/ml were significantly more likely to die after starting treatment. Response to DR-TB treatment did not differ with HIV infection in a programmatic setting with access to antiretroviral treatment (ART). Earlier ART initiation at a primary care level could reduce mortality among HIV-infected patients presenting with low CD4 counts.