Patient and Clinician Experiences with the Implementation of Telemedicine and Related Adaptations in Office-Based Buprenorphine Treatment During the COVID-19 Pandemic: A Qualitative Study.

Background: Deaths from opioid overdose have increased dramatically in the past decade, representing an epidemic in the United States. For individuals with opioid use disorder (OUD), agonist medications such as methadone and buprenorphine reduce opioid-related morbidity and mortality. Historically, the provision of buprenorphine treatment in office-based settings has relied on frequent in-person contact, likely influencing patients' access to and retention in care. In response to the COVID-19 pandemic, providers of office-based buprenorphine treatment rapidly adapted their care processes, increasingly relying on telemedicine visits. To date, relatively few prior studies have combined patient and clinician perspectives to examine the implementation of telemedicine and related care adaptations, particularly in safety-net settings. Methods: Qualitative methods were used to explore clinician and patient experiences with telemedicine in an office-based buprenorphine treatment clinic affiliated with an urban safety-net hospital. From this clinic, we interviewed 25 patients and 16 clinicians (including prescribers and non-prescribers) to understand how telemedicine impacted treatment quality and engagement in care, as well as preferences for using telemedicine moving forward. Results: Five themes regarding the implementation of telemedicine and other COVID-19-related care adaptations arose from patient and clinician perspectives: 1) telemedicine integration precipitated openness to more flexibility in care practices, 2) concerns regarding telemedicine-related adaptations centered around safety and accountability, 3) telemedicine encounters required rapport and trust between patients and clinicians to facilitate open communication, 4) safety-net patient populations experienced unique challenges when using telemedicine, particularly in terms of the technology required and the need for privacy, and 5) there is an important role for telemedicine in office-based buprenorphine treatment moving forward, primarily through its use in hybrid models of care. Conclusions: Telemedicine implementation within office-based buprenorphine treatment has the potential to improve patients' engagement in care; however, our findings emphasize the need for tailored approaches to implementing telemedicine in office-based buprenorphine treatment, particularly within safety-net settings. Overall, this study supports the maintenance of changes to policy and practice that facilitate the use of telemedicine in office-based buprenorphine treatment beyond the COVID-19 public health emergency.

Development and validation of a predictive model for febrile seizures.

Febrile seizures (FS) are the most prevalent type of seizures in children. Existing predictive models for FS exhibit limited predictive ability. To build a better-performing predictive model, a retrospective analysis study was conducted on febrile children who visited the Children's Hospital of Shanghai from July 2020 to March 2021. These children were divided into training set (n = 1453), internal validation set (n = 623) and external validation set (n = 778). The variables included demographic data and complete blood counts (CBCs). The least absolute shrinkage and selection operator (LASSO) method was used to select the predictors of FS. Multivariate logistic regression analysis was used to develop a predictive model. The coefficients derived from the multivariate logistic regression were used to construct a nomogram that predicts the probability of FS. The calibration plot, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate model performance. Results showed that the AUC of the predictive model in the training set was 0.884 (95% CI 0.861 to 0.908, p < 0.001) and C-statistic of the nomogram was 0.884. The AUC of internal validation set was 0.883 (95% CI 0.844 to 0.922, p < 0.001), and the AUC of external validation set was 0.858 (95% CI 0.820 to 0.896, p < 0.001). In conclusion, the FS predictive model constructed based on CBCs in this study exhibits good predictive ability and has clinical application value.

Pertuzumab plus high-dose trastuzumab for HER2-positive breast cancer with brain metastases: PATRICIA final efficacy data.

The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy. Primary analysis confirmed CNS objective response rate (ORR) was 11% (95% confidence interval [CI]: 3-25); clinical benefit rate (CBR) was 68% (4 months) and 51% (6 months). We report final efficacy data after a further 21-months of follow-up, updated safety, survival, and patient-reported outcomes (PROs). Patients received standard-dose pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Primary endpoint: confirmed ORR (CNS) per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary endpoints were response duration, CBR, progression-free survival (PFS), overall survival (OS), safety, and PROs. By clinical cut-off, 39 patients had completed or discontinued treatment. Confirmed ORR (CNS) was 11% (95% CI: 3.0-25.4). Median CNS-PFS was 4.6 months (95% CI: 4.0-8.9), as was median CNS-PFS or systemic PFS (95% CI: 4.0-8.9); median OS was 27.2 months (95% CI: 16.1-not reached). CBR in the CNS was 51% (19 patients, 95% CI: 34.4-68.1) at 6 months. Two patients remained on treatment until study closure, achieving stable disease for 4.1 and 4.8 years. Treatment-related grade 3/4 adverse events occurred in 7.7% of patients. Patients with confirmed partial response or stable disease (≥4 months) in the CNS had stable PROs over time. Pertuzumab plus high-dose trastuzumab represents a reasonable non-chemotherapeutic treatment option for selected patients with HER2-positive MBC with CNS metastases.

Oral candidiasis in a specialist palliative care unit: assessment, diagnosis, management.

OBJECTIVES: To evaluate current clinical practices of assessment, diagnosis and management of oral candidiasis in a specialist palliative care unit to improve patient outcomes through compliance with the Australian Commission on Safety and Quality in Health Care Antimicrobial Stewardship Clinical Care Standard. METHODS: A clinical audit cycle: review of 100 patient records preceded an educational intervention delivered over 4 weeks to clinical stakeholders, followed by a review of an additional 100 records. RESULTS: Eleven patients in each cohort had oral candidiasis. A statistically significant improvement in documented rates of oral examination (33% to 51%, p=0.015) and appropriate microbiological testing (0% to 63.6%, p=0.004) was achieved. Documentation of oral symptoms and prescribing practices were unchanged. CONCLUSIONS: Meaningful changes in practice relating to oral assessment and diagnosis of oral candidiasis are possible. Future iterations of the audit cycle may benefit from multimodal interventions to encourage further practice change.

Opioid Use Disorder Treatments: An Evidence Map.

BACKGROUND: Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions. AIM: Our aim was to publish an interactive summary of all peer-reviewed interventional and observational trials assessing the treatment of OUD and common clinical outcomes. METHODS: PubMed, Embase, PsycInfo, Cochrane Central Register of Clinical Trials, and Web of Science were queried using multiple OUD-related MESH terms, without date limitations, for English-language publications. Inclusions were human subjects, treatment of OUD, OUD patient or community-level outcomes, and systematic reviews of OUD interventions. Exclusions were laboratory studies, reviews, and case reports. Two reviewers independently scanned abstracts for inclusion before coding eligible full-text articles by pre-specified filters: research design, study population, study setting, intervention, outcomes, sample size, study duration, geographical region, and funding sources. RESULTS: The OUD Evidence Map (https://med.nyu.edu/research/lee-lab/research/opioid-use-disorder-treatment-evidence-map) identified and assessed 12,933 relevant abstracts through 2020. We excluded 9455 abstracts and full text reviewed 2839 manuscripts; 888 were excluded, 1591 were included in the final evidence map. The most studied OUD interventions were methadone (n = 754 studies), buprenorphine (n = 499), and naltrexone (n = 134). The most common outcomes were heroin/opioid use (n = 708), treatment retention (n = 557), and non-opioid drug use (n = 368). Clear gaps included a wider array of opioid agonists for treatment, digital behavioral interventions, studies of OUD treatments in criminal justice settings, and overdose as a clinical outcome. CONCLUSION: This OUD Evidence Map highlights the importance of pharmacologic interventions for OUD and reductions in opioid use. Future iterations will update results annually and scan policy-level interventions.

The physical and developmental outcomes of children whose mothers are substance abusers: Analysis of associated factors and the impact of early intervention.

Background/objectives: Maternal illicit drug use is associated with negative physical and developmental outcomes for their born children. We aim to find out the incidence of different developmental problems in a cohort of Chinese children born to drug-abusing mothers, compare the physical health and developmental outcomes of the subjects recruited in the Integrated Program to the Comprehensive Child Development Service (CCDS), and to study the potential factors on their associations. Methods: A retrospective longitudinal cohort study with frequent clinical assessments of the children's physical and developmental outcomes in a HKSAR's regional hospital from birth until 5 years old. 123 Children in Integrated Program were compared with 214 children in CCDS between 1 January 2008 and 28 February 2019. Cox regression analysis was performed to determine the possible factors associated with the developmental outcomes. Results: Developmental delay was detected in 129 children (38.9%). CCDS group has significantly higher incidence of cognitive delay (p = < 0.001), language delay (p = < 0.001), motor delay (p = < 0.001), social delay (p = 0.002), and global delay (p = 0.002). On Cox multivariable regression analysis, integrated program (HRadj 0.53, 95% C. I. 0.34-0.84), social support (HRadj 0.45, 95% C.I. 0.25-0.80), and maternal abstinence from drug use up to 2-year post-delivery (HRadj 0.62, 95% C.I. 0.40-0.95) were significant protective factors, while male gender (HRadj 1.73, 95% C.I. 1.18-2.54) was a significant risk factor. Conclusion: CCDS achieves early engagement of drug-abusing expectant mothers during pregnancy, and an early integrated program with multidisciplinary collaboration was an independent factor in improving the developmental outcomes of these vulnerable children.

Slow-Breathing Curriculum for Stress Reduction in High School Students: Lessons Learned From a Feasibility Pilot.

Purpose: Nearly one in three US adolescents meet the criteria for anxiety, an issue that has worsened with the COVID-19 pandemic. We developed a video-based slow diaphragmatic breathing stress-reduction curriculum for high school students and evaluated its feasibility, tolerability, and preliminary effectiveness. Methods: This cluster-randomized feasibility pilot compared 5-min slow diaphragmatic breathing for 5 weeks with treatment-as-usual control among four 12th-grade public high school classes. Students individually participated after school during COVID-19-related hybrid teaching, with slow diaphragmatic breathing three times/week and breath science education once/week. Feasibility was based on completion of breathing exercises, breath science education, and preliminary effectiveness assessments, and ease/tolerability was based on qualitative assessments. Preliminary effectiveness was measured with the State-Trait Anxiety Inventory (STAI) and a timed-exhale carbon dioxide tolerance test (CO2TT) of physiological stress response. Descriptive statistics and repeated analysis of variance were performed to quantify and compare outcomes between time periods. Human subjects research approval was granted through Western IRB-Copernicus Group (WCG IRB) [ClinicalTrials.gov, Identifier: NCT05266833.]. Results: Forty-three students consented to participate. Breath practice compliance ranged from 29 to 83% across classes and weeks, and decreased on average over the 5 weeks. Compliance with the breath science videos ranged from 43 to 86%, and that with the weekly STAI-State and CO2TT measures varied from 36 to 86%. Compliance with ease/tolerability assessments ranged from 0 to 60%. Preliminary effectiveness assessments' compliance varied across classes from 83 to 89% during baseline, and 29 to 72% at follow-up. The curriculum was rated as somewhat-to-definitely useful/beneficial, and definitely-to-very easy/tolerable. Students reported enjoying the diaphragmatic breathing, CO2TT, and breath science education; some found the extended exhales challenging and the curriculum and assessments time-consuming. Preliminary effectiveness analyses indicated no significant changes in STAI or CO2TT from baseline to followup or from before to after breathing exercises (p > 0.05 for all). Conclusions: Implementation of this 5-week slow breathing curriculum was feasible and tolerable to this cohort. Compliance, tolerability, and effectiveness may be improved with in-class participation. Future research on simple and accessible slow-breathing exercises is warranted to address today's adolescent stress-management crisis. Trial Registration: ClinicalTrials.gov, Identifier: NCT05266833.

Advances in Hemophilia A Management.

Hemophilia A is an inherited insufficiency of Factor VIII (FVIII), one of the critical clotting factors. The gold standard for the management of moderate-to-severe hemophilia A is prophylaxis using regular replacement therapy with clotting factor concentrates. Compared with conventional treatment, extended half-life products reduce the burden of frequent factor replacement injections. Of note, up to 30% of patients with hemophilia A receiving prophylactic factor infusions develop "inhibitors," neutralizing anti-FVIII autoantibodies. Therapeutic options for patients with hemophilia A and inhibitors include the immune tolerance induction (ie, eradication of inhibitors) and the management of acute bleeds with bypassing agents and/or emicizumab. Emicizumab is a biphasic monoclonal antibody mimicking activated FVIII, approved for patients with hemophilia A with/without inhibitors. Gene therapy is an emerging therapy for hemophilia A, essentially curing patients with hemophilia A or transforming them to a milder phenotype by establishing continuous endogenous expression of FVIII after one-time treatment.

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study.

Importance: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, Setting, and Participants: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. Main Outcomes and Measures: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results: The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance: In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

Perceptions and experiences toward extended-release buprenorphine among persons leaving jail with opioid use disorders before and during COVID-19: an in-depth qualitative study.

BACKGROUND: Extended-release buprenorphine (XRB) offers a novel approach to sustained monthly treatment for people who use opioids in criminal justice settings (CJS). This study explores the experiences of adults receiving XRB as a jail-to-community treatment. METHODS AND FINDINGS: In-depth qualitative interviews were conducted among adult participants with opioid use disorder (OUD; n = 16) who were recently released from NYC jails and maintained on XRB after switching from daily sublingual buprenorphine (SLB). Interviews elaborated on the acceptability and barriers and facilitators of XRB treatment pre- and post-release. Interviews were audio recorded, transcribed, and analyzed for content related to factors influencing XRB treatment uptake and community reentry. Important themes were grouped into systems, medication, and patient-level factors. Key systems-level factors influencing initiation of XRB in jail included an alternative to perceived stigmatization and privacy concerns associated with daily in-jail SLB administration and less concerns with buprenorphine diversion. In-jail peer networks positively influenced participant adoption of XRB. XRB satisfaction was attributed to reduced in-jail clinic and medication administration visits, perceived efficacy and blockade effects upon the use of heroin/fentanyl following release, and averting the risk of criminal activities to fund opioid use. Barriers to retention included post-injection withdrawal symptoms and cravings attributed to perceived suboptimal medication dosing, injection site pain, and lack of in-jail provider information about the medication. CONCLUSION: Participants were generally favorable to XRB initiation in jail and retention post-release. Further studies are needed to address factors influencing access to XRB in criminal justice settings, including stigma, ensuring patient privacy following initiation on XRB, and patient-, provider-, and correctional staff education pertaining to XRB. Trial Registration ClinicalTrials.gov Identified: NCT03604159.

Comparison of Treatment Retention of Adults With Opioid Addiction Managed With Extended-Release Buprenorphine vs Daily Sublingual Buprenorphine-Naloxone at Time of Release From Jail.

Importance: Extended-release buprenorphine (XRB), a monthly injectable long-acting opioid use disorder (OUD) treatment, has not been studied for use in corrections facilities. Objective: To compare treatment retention following release from jail among adults receiving daily sublingual buprenorphine-naloxone (SLB) vs those receiving XRB. Design, Setting, and Participants: This open-label, randomized comparative effectiveness study included 52 incarcerated adults in New York City observed for 8 weeks postrelease between June 2019 and May 2020. Participants were soon-to-be-released volunteers from 1 men's and 1 women's jail facility who had OUDs already treated with SLB. Follow-up treatment was received at a primary care clinic in Manhattan. Data were analyzed between June 2020 and December 2020. Interventions: XRB treatment was offered prior to release and continued monthly through 8 weeks after release. SLB participants continued to receive daily directly observed in-jail SLB administration, were provided a 7-day SLB supply at jail release, and followed up at a designated clinic (or other preferred clinics). Main Outcomes and Measures: Buprenorphine treatment retention at 8 weeks postrelease. Results: A total of 52 participants were randomized 1:1 to XRB (26 participants) and SLB (26 participants). Participants had a mean (SD) age of 42.6 (10.0) years; 45 participants (87%) were men; and 40 (77%) primarily used heroin prior to incarceration. Most participants (30 [58%]) reported prior buprenorphine use; 18 (35%) reported active community buprenorphine treatment prior to jail admission. Twenty-one of 26 assigned to XRB received 1 or more XRB injection prior to release; 3 initiated XRB postrelease; and 2 did not receive XRB. Patients in the XRB arm had fewer jail medical visits compared with daily SLB medication administration (mean [SD] visits per day: XRB, 0.11 [0.03] vs SLB, 1.06 [0.08]). Community buprenorphine treatment retention at week 8 postrelease was 18 participants in the XRB group (69.2%) vs 9 in the SLB group (34.6%), and rates of opioid-negative urine tests were 72 of 130 tests in the XRB group (55.3%) and 50 of 130 tests in the SLB group (38.4%). There were no differences in rates of serious adverse events, no overdoses, and no deaths. Conclusions and Relevance: XRB was acceptable among patients currently receiving SLB, and patients had fewer in-jail clinic visits and increased community buprenorphine treatment retention when compared with standard daily SLB treatment. These results support wider use and further study of XRB as correctional and reentry OUD treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT03604159.

Use of non-prescribed buprenorphine in the criminal justice system: Perspectives of individuals recently released from incarceration.

Buprenorphine, an effective treatment for opioid use disorder (OUD), remains underutilized in many U.S. jails and prisons. However, use of non-prescribed (i.e., diverted) buprenorphine has been reported in these settings. The current study examined non-prescribed buprenorphine use experiences in correctional and community contexts. The study conducted face-to-face interviews with 300 adults with OUD/opioid misuse and recent incarceration, recruited in Baltimore, MD, and New York, NY (n = 150 each). Illicit/non-prescribed opioid use during incarceration was reported by 63% of participants; 39% reported non-prescribed buprenorphine. Non-prescribed buprenorphine was considered the most widely available opioid in jails/prisons in both states (81% reported "very" or "somewhat" easy to get). The average price of non-prescribed buprenorphine in jail/prison was ~10× higher than in the community (p < 0.001). Participants were more likely to endorse getting high/mood alteration as reasons for using non-prescribed buprenorphine during incarceration, but tended to ascribe therapeutic motives to use in the community (e.g., self-treatment; p < 0.001). Multivariable logistic regression analyses showed that different individual-level characteristics were associated with history of non-prescribed buprenorphine use during incarceration and in the community. Use of non-prescribed buprenorphine during incarceration was associated with younger age (p = 0.006) and longer incarceration history (p < 0.001), while use of non-prescribed buprenorphine in the community was associated with MD recruitment site (p = 0.001), not being married (p < 0.001), prior buprenorphine treatment experience (p < 0.001), and housing situation (p = 0.01). These findings suggest that different dynamics and demand characteristics underlie the use of non-prescribed buprenorphine in community and incarceration contexts, with implications for efforts to expand OUD treatment in correctional settings.

Pertuzumab Plus High-Dose Trastuzumab in Patients With Progressive Brain Metastases and HER2-Positive Metastatic Breast Cancer: Primary Analysis of a Phase II Study.

PURPOSE: Effective therapies are needed for the treatment of patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) with brain metastases. A trastuzumab radioisotope has been shown to localize in brain metastases of patients with HER2-positive MBC, and intracranial xenograft models have demonstrated a dose-dependent response to trastuzumab. METHODS: In the phase II PATRICIA study (ClinicalTrials.gov identifier: NCT02536339), patients with HER2-positive MBC with CNS metastases and CNS progression despite prior radiotherapy received pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. The primary end point was confirmed objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary end points included duration of response, clinical benefit rate (complete response plus partial response plus stable disease ≥ 4 or ≥ 6 months) in the CNS, and safety. RESULTS: Thirty-nine patients were treated for a median (range) of 4.5 (0.3-37.3) months at clinical cutoff. Thirty-seven patients discontinued treatment, most commonly because of CNS progression (n = 27); two remained on treatment. CNS ORR was 11% (95% CI, 3 to 25), with four partial responses (median duration of response, 4.6 months). Clinical benefit rate at 4 months and 6 months was 68% and 51%, respectively. Two patients permanently discontinued study treatment because of adverse events (left ventricular dysfunction [treatment-related] and seizure, both grade 3). No grade 5 adverse events were reported. No new safety signals emerged with either agent. CONCLUSION: Although the CNS ORR was modest, 68% of patients experienced clinical benefit, and two patients had ongoing stable intracranial and extracranial disease for > 2 years. High-dose trastuzumab for HER2-positive CNS metastases may warrant further study.

Long-acting buprenorphine vs. naltrexone opioid treatments in CJS-involved adults (EXIT-CJS).

The EXIT-CJS (N = 1005) multisite open-label randomized controlled trial will compare retention and effectiveness of extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) to treat opioid use disorder (OUD) among criminal justice system (CJS)-involved adults in six U.S. locales (New Jersey, New York City, Delaware, Oregon, Connecticut, and New Hampshire). With a pragmatic, noninferiority design, this study hypothesizes that XR-B (n = 335) will be noninferior to XR-NTX (n = 335) in retention-in-study-medication treatment (the primary outcome), self-reported opioid use, opioid-positive urine samples, opioid overdose events, and CJS recidivism. In addition, persons with OUD not eligible or interested in the RCT will be recruited into an enhanced treatment as usual arm (n = 335) to examine usual care outcomes in a quasi-experimental observational cohort.

Recurrence rates in patients with HER2+ breast cancer who achieved a pathological complete response after neoadjuvant pertuzumab plus trastuzumab followed by adjuvant trastuzumab: a real-world evidence study.

PURPOSE: This study assessed real-world risk of invasive disease recurrence (IDR) and associated factors in patients with human epidermal growth factor receptor-2 positive (HER2+) early breast cancer (BC) with pathological complete responses (pCR) after neoadjuvant pertuzumab plus trastuzumab (nPT) plus chemotherapy, followed by adjuvant trastuzumab (aT). METHODS: Patients with HER2+ BC with pCR after nPT from 2013 to 2015 who received aT were identified in the US Oncology Network and followed until IDR or censoring. Kaplan-Meier and Cox regression methods were used to assess invasive disease-free survival (iDFS) and correlation between iDFS and patient characteristics. RESULTS: A total of 217 pCR patients' charts were reviewed; median age was 52 years. Most had stage IIA or IIB disease (62%), Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1 (84%), tumor size > 2 cm (75%), positive nodes (N+, 62%) and negative estrogen and progesterone receptor (ER- and PR-) expression (52%). Four-year iDFS rates were 90.0% overall (95% CI 84.6%, 93.6%), 86.2% for the N+ cohort and 96.0% for the N- cohort. Cox regression suggested that age, body mass index, ECOG PS, N+ status, stage T3 or T4, and ER+ or PR+ status were risk factors for IDR but were not statistically significant. CONCLUSIONS: Consistent with previous studies, this real-world study observed that patients with HER2+ BC showing pCR with nPT remain at risk for IDR, especially with node-positive disease at diagnosis. Alternatives to adjuvant trastuzumab alone, including combined trastuzumab and pertuzumab, should be considered to improve outcomes for initially N+ patients showing pCR with nPT.

Exploring nonprescribed use of buprenorphine in the criminal justice system through qualitative interviews among individuals recently released from incarceration.

BACKGROUND: Buprenorphine treatment remains unavailable in many jails and prisons, but use of nonprescribed (i.e., diverted) buprenorphine has been reported in these settings. The purpose of this analysis is to explore the experiences and motivations behind the use of diverted buprenorphine among recently incarcerated individuals. METHODS: Adults with opioid misuse who were recently released from jail or prison (n= 26; 58% male) completed semi-structured qualitative interviews as part of a study focused on buprenorphine diversion in the criminal justice system. Qualitative interviews explored participants' incarceration experiences and opioid use background, knowledge of buprenorphine and other substance use in jails/prisons, personal use of buprenorphine while incarcerated, reasons for using buprenorphine while incarcerated, and knowledge of how buprenorphine is brought into and acquired in jails/prisons. The study recorded and transcribed interviews, and analyzed the narratives for content related to these predetermined thematic areas. RESULTS: Key themes emerging from the interviews surrounding buprenorphine diversion during incarceration included: 1) the perceived high prevalence of diverted buprenorphine in jail/prison settings, 2) how the perception of prevalence is related to buprenorphine sublingual film formulation, 3) adaptive routes of administration related to the high cost of diverted buprenorphine, and 4) reasons individuals who are incarcerated use diverted buprenorphine (to achieve euphoric effects and cope with confinement, in contrast to using for self-treatment/withdrawal management as is done in the community). CONCLUSION: Participants reported widespread availability of diverted buprenorphine in criminal justice facilities, and characterized reasons for its use specific to these contexts. More research is needed to determine the impact of expanding buprenorphine treatment in jails and prisons on inmates' use of diverted buprenorphine, and future research should explore these intersections as treatment initiation opportunities.

Disentangling the Effects of Exposure to Maternal Substance Misuse and Physical Abuse and Neglect on Child Behavioral Problems.

There is inconsistent evidence on the association between prenatal substance exposure and child behavioral problems. Children affected by maternal substance misuse are vulnerable to physical abuse and neglect. Few studies have examined factors contributing to internalizing and externalizing problems in these children. This study, with a focus on children with prenatal substance exposure, investigated whether family characteristics (the duration of maternal substance misuse postpartum or the existence of a sibling) moderated the association between adverse exposure (physical abuse or neglect) and behavior (internalizing or externalizing problems). We recruited 54 Hong Kong Chinese mothers with registered records of substance misuse during pregnancy and their children (2-9 years). Mothers completed questionnaires on drug use patterns during pregnancy and postpartum, abusive and neglectful parenting behaviors in the preceding year, and children's current behavioral problems. Moderated regression analyses tested whether abusive and neglectful parenting behavior interacted with family characteristics to affect child behavioral problems. The existence of a sibling moderated the relationship between neglect experience and internalizing problems, with a positive relationship observed only among single children (adjusted B [95% confidence interval] = 3.70 [0.98, 6.41], p = .012). The duration of maternal substance misuse postpartum moderated the relationship between physical abuse experience and externalizing problems, with a positive relationship observed only among children of mothers abusing substances beyond the child's infancy period (adjusted B [95% confidence interval] = 6.86 [2.34, 11.38], p = .008). The results show that the impact of physical abuse and neglect experiences depend on the type of behavior assessed and family and child characteristics. Positive sibling relationship and early detoxification in the mother can foster healthy behavioral development for children exposed prenatally to maternal substance misuse.