Old tech but not low tech: telephone-based treatment provision for substance use.

The future of telemedicine for substance use treatment hangs by a thread, as the United States awaits approval of proposed regulations and laws to increase care access in light of the 2022 Centers for Medicare and Medicaid Services revisions allowing for audio-only care. Telemedicine improves patient care access and outcomes. Audio-only telemedicine can be an effective and viable modality for individuals without technology resources (devices, internet services, and literacy), those with reduced telehealth service utilization (Black individuals or those with unstable housing, who are older, with low income, or with low education), and those living in rural locations. Studies suggest that telephone visits for buprenorphine treatment are well-accepted by patients and providers, making telephone visits essential in care access to reduce disparities. Telephone counseling for patients in substance use treatment is convenient, flexible, and empowering and can augment therapeutic alliances and treatment goals. Both providers and patients advocate for patient-centered hybrid care to include telephone-only treatment, which enhances service productivity and care access; reduces no-show rates, costs, and stigma; and is sustainable. Numerous solutions can expand technology access, proficiency, assimilation, and trust. Despite being "old" technology, the telephone remains an essential resource for substance use treatment.

Lived Experience of Adult Female Cancer Survivors to Discover Common Protective Resilience Factors to Cope with Cancer Experience and to Identify Potential Barriers to Resilience.

Objectives: Primary objective - Phase I: The primary objective of this study was as follows: (1) To identify common protective resilient factors that enabled the adult female cancer survivors to cope with the cancer experience. (2) To identify potential barriers to the resilience of adult female cancer survivors. Secondary objective - Phase II: The secondary objective of this study was to develop and validate a resilience tool for cancer survivorship. Material and Methods: A mixed approach using sequential exploratory design was used in the study. A qualitative approach using phenomenology design was used in the first phase followed by a quantitative approach in the second phase. In the first phase, in-depth interviews were conducted until data saturation with 14 female breast cancer survivors chosen by purposive and maximum variation sampling methods based on inclusion criteria. The researcher used Colaizzi's data analysis framework to analyse the transcripts. Findings were configured as protective resilience factors and barriers to resilience. Based on the analysis of the qualitative phase, the researcher developed a 35-item resilience tool for cancer survivorship. Content validity, criterion validity and reliability of the newly developed instrument were assessed. Results: In the qualitative phase, the mean age of the participants was 57.07 years and the mean age at diagnosis was 55.5 years. The majority 11 (78.57%) of them were homemakers. All 14 (100%) of them had undergone surgery. The majority 11 (78.57%) of them had all three modes of therapy, that is, surgery, chemotherapy and radiation therapy. The categories of themes identified are presented under two main headings, that is, protective resilience factors and barriers to resilience. The theme categories identified under protective resilience factors were personal, social, spiritual, physical, economic and psychological factors. The barriers to resilience identified were lack of awareness, medical/biological barriers, social, financial and psychological barriers. The developed resilience tool had a content validity index of 0.98, a criterion validity of 0.67, internal consistency of 0.88 and stability of 0.99 at a 95% confidence interval. Principle component analysis (PCA) was used to validate the domains. PCA of protective resilience factors (Q1-Q23) and barriers to resilience (Q24-Q35) had Eigenvalues of 7.65 and 4.49, respectively. The resilience tool for cancer survivorship was found to have good construct validity. Conclusion: The present study has identified the protective resilience factors and barriers to resilience among adult female cancer survivors. The developed resilience tool for cancer survivorship was found to have good validity and reliability. It will be useful for nurses and all other healthcare professionals to assess the resilience needs of cancer survivors and to provide need-based quality cancer care.

Major Bleeding Postadministration of Tenecteplase Versus Alteplase in Acute Ischemic Stroke.

BACKGROUND: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. OBJECTIVE: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. METHODS: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. RESULTS: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. CONCLUSIONS AND RELEVANCE: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

Uncompetitive, adduct-forming SARM1 inhibitors are neuroprotective in preclinical models of nerve injury and disease.

Axon degeneration is an early pathological event in many neurological diseases. The identification of the nicotinamide adenine dinucleotide (NAD) hydrolase SARM1 as a central metabolic sensor and axon executioner presents an exciting opportunity to develop novel neuroprotective therapies that can prevent or halt the degenerative process, yet limited progress has been made on advancing efficacious inhibitors. We describe a class of NAD-dependent active-site SARM1 inhibitors that function by intercepting NAD hydrolysis and undergoing covalent conjugation with the reaction product adenosine diphosphate ribose (ADPR). The resulting small-molecule ADPR adducts are highly potent and confer compelling neuroprotection in preclinical models of neurological injury and disease, validating this mode of inhibition as a viable therapeutic strategy. Additionally, we show that the most potent inhibitor of CD38, a related NAD hydrolase, also functions by the same mechanism, further underscoring the broader applicability of this mechanism in developing therapies against this class of enzymes.

Barriers and poor telephone counseling experiences among patients receiving medication for opioid use disorders.

OBJECTIVE: The COVID-19 pandemic catalyzed the relaxation of regulations surrounding Medication for Opioid Use Disorders (MOUD) treatment, including a shift from in-person to telehealth counseling services adjunct to MOUD treatment. We examine how patient-level barriers impact their counseling experiences. METHODS: We examine data from n = 264 participants who completed a cross-sectional survey regarding their experiences with telephone counseling adjunct to MOUD between July to November 2020. Variables examined include: convenience and satisfaction with telephone counseling, comfort and change in relationship with counselor, and how telephone counseling helped with anxiety, depression, anger, substance use, and recovery. Participants also listed the barriers they faced when using telephone counseling. RESULTS: Thirty-one percent of the sample (n = 81) reported experiencing one or more barriers to telephone counseling. Satisfaction with counseling, perceived convenience, comfort, and beneficial effects of counseling on substance use were associated with increased odds of reporting no barriers (range of p.038 to <0.001). CONCLUSIONS: Many participants reported barriers to telehealth counseling, and these barriers were in turn associated with poorer counseling experiences. PRACTICE IMPLICATIONS: Many treatment providers plan to integrate telehealth service provision in their healthcare delivery model, but more research on patient-level barriers and its impact on treatment is needed.

Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe.

Chromosomal instability (CIN) is a hallmark of cancer that results from errors in chromosome segregation during mitosis. Targeting of CIN-associated vulnerabilities is an emerging therapeutic strategy in drug development. KIF18A, a mitotic kinesin, has been shown to play a role in maintaining bipolar spindle integrity and promotes viability of CIN cancer cells. To explore the potential of KIF18A, a series of inhibitors was identified. Optimization of an initial hit led to the discovery of analogues that could be used as chemical probes to interrogate the role of KIF18A inhibition. Compounds 23 and 24 caused significant mitotic arrest in vivo, which was sustained for 24 h. This would be followed by cell death either in mitosis or in the subsequent interphase. Furthermore, photoaffinity labeling experiments reveal that this series of inhibitors binds at the interface of KIF18A and tubulin. This study represents the first disclosure of KIF18A inhibitors with in vivo activity.

Antibiotic Prophylaxis and Incidence of Infection with External Ventricular Drains and Intra-Cranial Pressure Monitors.

Objectives: Guidelines do not recommend extended antibiotic prophylaxis for external ventricular drains (EVD) or intra-cranial pressure (ICP) monitors. The study objective was to determine if infection rates are different for patients receiving antibiotic prophylaxis for EVD or ICP monitors. Patients and Methods: This single-center retrospective cohort reviewed intensive care unit patients who had an EVD or ICP monitor placed. Patients receiving antibiotic prophylaxis were compared with those who did not receive prophylaxis. The primary end point was incidence of central nervous system (CNS) infection. Results: Overall, 228 patients were included, 120 of whom received prophylaxis and 108 who did not receive prophylaxis. The primary end point of CNS infection was not different between groups (18 [17%] vs. 23 [19%]; p = 0.6236). Conclusions: Antibiotic prophylaxis was not associated with a decreased incidence of CNS infection in patients with EVD or ICP monitors. Evaluation of antibiotic use in this patient population is warranted to prevent resistance and adverse drug effects.

Patient Experiences with the Transition to Telephone Counseling during the COVID-19 Pandemic.

Background: To identify and document the treatment experiences among patients with opioid use disorder (OUD) in the context of the rapid move from in-person to telephone counseling due to the COVID-19 pandemic. Methods: Participants (n = 237) completed a survey with open-ended questions that included the following domains: (1) satisfaction with telephone counseling, (2) perceived convenience, (3) changes to the therapeutic relationship, (4) perceived impact on substance use recovery, and (5) general feedback. Responses were coded using thematic analysis. Codes were subsequently organized into themes and subthemes (covering 98% of responses). Interrater reliability for coding of participants' responses ranged from 0.89 to 0.95. Results: Overall, patients reported that telephone counseling improved the therapeutic experience. Specifically, 74% of respondents were coded as providing responses consistently indicating "positive valency". "Positive valency" responses include: (1) feeling supported, (2) greater comfort and privacy, (3) increased access to counselors, and (4) resolved transportation barriers. Conversely, "negative valency" responses include: (1) impersonal experience and (2) reduced privacy. Conclusions: Telephone counseling presents its own set of challenges that should be investigated further to improve the quality of care and long-term patient outcomes.

Medication for Opioid Use Disorder Service Provision and Telephone Counseling: A Concurrent Mixed-Methods Approach.

Using quantitative and qualitative evidence, this study triangulates counselors' perspectives on the use of telemedicine in the context of Opioid Use Disorder (OUD) treatment. A concurrent mixed-methods design examined counselors' experiences with telephone counseling during the COVID-19 pandemic. N = 42 counselors who provided OUD counseling services completed a close-ended, quantitative survey examining their experiences in addressing clients' anxiety, depression, anger, substance use, therapeutic relationship, and substance use recovery using telephone counseling. The survey also assessed comfort, convenience, and satisfaction with telephone counseling. Counselors also completed open-ended responses examining satisfaction, convenience, relationship with patients, substance use, and general feedback with telephone counseling. The synthesis of quantitative and qualitative evidence indicated that a majority of counselors had positive experiences with using telephone counseling to provide services to clients undergoing OUD treatment. Convenience, greater access to clients, and flexibility were among the reasons cited for their positive experience. However, counselors also expressed that the telephone counseling was impersonal, and that some clients may have difficulties accessing appropriate technology for telehealth adoption. Findings suggest that further research with counselors is needed to identify the key elements of an effective integration of telephone counseling with traditional in-person treatment approaches in the post-pandemic era.

Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors.

KRASG12C has emerged as a promising target in the treatment of solid tumors. Covalent inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by this long-"undruggable" target; however clinically viable inhibitors have yet to be identified. Here, we report efforts to exploit a cryptic pocket (H95/Y96/Q99) we identified in KRASG12C to identify inhibitors suitable for clinical development. Structure-based design efforts leading to the identification of a novel quinazolinone scaffold are described, along with optimization efforts that overcame a configurational stability issue arising from restricted rotation about an axially chiral biaryl bond. Biopharmaceutical optimization of the resulting leads culminated in the identification of AMG 510, a highly potent, selective, and well-tolerated KRASG12C inhibitor currently in phase I clinical trials (NCT03600883).

Innovative Program Delivery and Determinants of Frequent Visitation to a Mobile Medical Clinic in an Urban Setting.

The Community Health Care Van (CHCV) is a mobile medical clinic (MMC) that has served vulnerable populations in New Haven, Connecticut since 1993. This study explores utilization patterns to understand if certain populations frequently rely upon non-traditional health care within a representative MMC. Patient characteristics, services used, and visitation frequency were described and compared for 8,415 unique clients making 29,728 visits. Negative binomial regression was used to model the impact of specific indicators on visitation. Clients receiving buprenorphine had the highest visitation rates, with 2.09 visits per person-year. Increased CHCV visitation was positively associated with being foreign-born (additional 3.42 visits on average, p < .001), injection drug use (additional 1.69 visits on average, p < .001) and having hypertension (additional 1.09 visits on average, p < .001). As the Affordable Care Act has increased health insurance coverage, MMCs will continue their role in assisting entry into continuous health care and offering low-threshold acute care for urban vulnerable populations.

Partnering With Patients to Improve Care: The Value of Patient and Family Advisory Councils.

Increasingly, healthcare organizations are adopting patient and family advisory councils as a key strategy to create a culture grounded in patient- and family-centered principles and improve the patient experience. In the 1st of a 3-part series, the chief nurse executive and the director of patient- and family-centered care at a Magnet®-designated academic medical center discuss how a stronger patient voice can lead to better care and improved clinical outcomes. The authors examine ways in which the Magnet culture helped drive change and offer tips to establish a successful patient and family advisory council.

Ligand-Controlled Diastereoselective 1,3-Dipolar Cycloadditions of Azomethine Ylides with Methacrylonitrile.

Copper-catalyzed reactions of glycine ester arylimines and methacrylonitrile provide selective access to either the endo or exo pyrrolidine cycloadducts. DFT calculations have elucidated the origins of ligand-controlled diastereoselectivity.

Tricyclic Analogues of Epidithiodioxopiperazine Alkaloids with Promising In Vitro and In Vivo Antitumor Activity.

Epipolythiodioxopiperazine (ETP) alkaloids are structurally elaborate alkaloids that show potent antitumor activity. However, their high toxicity and demonstrated interactions with various biological receptors compromises their therapeutic potential. In an effort to mitigate these disadvantages, a short stereocontrolled construction of tricyclic analogues of epidithiodioxopiperazine alkaloids was developed. Evaluation of a small library of such structures against two invasive cancer cell lines defined initial structure-activity relationships (SAR), which identified 1,4-dioxohexahydro-6H-3,8a-epidithiopyrrolo[1,2-a]pyrazine 3c and related structures as particularly promising antitumor agents. ETP alkaloid analogue 3c exhibits low nanomolar activity against both solid and blood tumors in vitro. In addition, 3c significantly suppresses tumor growth in mouse xenograft models of melanoma and lung cancer, without obvious signs of toxicity, following either intraperitoneal (IP) or oral administration. The short synthesis of molecules in this series will enable future mechanistic and translational studies of these structurally novel and highly promising clinical antitumor candidates.

Patient-Centered Care and the Mediator's Skills.

Bioethics mediation training offers knowledge and skills valuable for clinical ethics consultants who are engaged in high conflict situations. Furthermore, clinicians with this training can support organizational efforts to create a culture that is centered on the values, needs, and care preferences of patients and their families, rather than on those of the clinician or organization. Patient-centeredness is a hallmark of quality and an essential component for patients' safety. Clinicians with mediation training have the communication skills to address the myriad needs of patients and their loved ones, needs that are challenging to meet in inpatient hospital settings. The author illustrates principles of mediation such as validating patients' emotions, revealing the interests of all stakeholders, and shaping a shared solution to demonstrate how these skills have broad applicability in patient care settings.

Mandate for care.

MUCH HAS been written on the need to move to a more patient- and family-centred system of healthcare delivery. Recognised steps that nursing staff can take to design patient-centred care delivery models include, for example, unrestricted visiting for family members, hourly rounding and having open medical record policies.

Latent tuberculosis infection screening in foreign-born populations: a successful mobile clinic outreach model.

OBJECTIVES: We evaluated the efficacy of a mobile medical clinic (MMC) screening program for detecting latent tuberculosis infection (LTBI) and active tuberculosis. METHODS: A LTBI screening program in a MMC in New Haven, Connecticut, used medical surveys to examine risk factors and tuberculin skin test (TST) screening eligibility. We assessed clinically relevant correlates of total (prevalent; n = 4650) and newly diagnosed (incident; n = 4159) LTBI from 2003 to 2011. RESULTS: Among 8322 individuals, 4159 (55.6%) met TST screening eligibility criteria, of which 1325 (31.9%) had TST assessed. Similar to LTBI prevalence (16.8%; 779 of 4650), newly diagnosed LTBI (25.6%; 339 of 1325) was independently correlated with being foreign-born (adjusted odds ratio [AOR] = 8.49; 95% confidence interval [CI] = 5.54, 13.02), Hispanic (AOR = 3.12; 95% CI = 1.88, 5.20), Black (AOR = 2.16; 95% CI = 1.31, 3.55), employed (AOR = 1.61; 95% CI = 1.14, 2.28), and of increased age (AOR = 1.04; 95% CI = 1.02, 1.05). Unstable housing (AOR = 4.95; 95% CI = 3.43, 7.14) and marijuana use (AOR = 1.57; 95% CI = 1.05, 2.37) were significantly correlated with incident LTBI, and being male, heroin use, interpersonal violence, employment, not having health insurance, and not completing high school were significantly correlated with prevalent LTBI. CONCLUSIONS: Screening for TST in MMCs successfully identifies high-risk foreign-born, Hispanic, working, and uninsured populations and innovatively identifies LTBI in urban settings.

Latent tuberculosis infection: screening and treatment in an urban setting.

Despite its benefit for treating active tuberculosis, directly observed therapy (DOT) for latent tuberculosis infection (LTBI) has been largely understudied among challenging inner city populations. Utilizing questionnaire data from a comprehensive mobile healthcare clinic in New Haven, CT from 2003 to July 2011, a total of 2,523 completed tuberculin skin tests (TSTs) resulted in 356 new LTBIs. Multivariate logistic regression correlated covariates of the two outcomes (a) initiation of isoniazid preventative therapy (IPT) and (b) completion of 9 months of IPT. Of the 357 newly positive TSTs, 86.3 % (n = 308) completed screening chest radiographs (CXRs): 90.3 % (n = 278) were normal, and 0.3 % (n = 1) had active tuberculosis. Of those completing CXR screening, 44.0 % (n = 135) agreed to IPT: 69.6 % (n = 94) selected DOT, and 30.4 % (n = 41) selected self-administered therapy (SAT). Initiating IPT was correlated with undocumented status (AOR = 3.43; p < 0.001) and being born in a country of highest and third highest tuberculosis prevalence (AOR = 14.09; p = 0.017 and AOR = 2.25; p = 0.005, respectively). Those selecting DOT were more likely to be Hispanic (83.0 vs 53.7 %; p < 0.0001), undocumented (57.4 vs 41.5 %; p = 0.012), employed (p < 0.0001), uninsured (p = 0.014), and have stable housing (p = 0.002), no prior cocaine or crack use (p = 0.013) and no recent incarceration (p = 0.001). Completing 9 months of IPT was correlated with no recent incarceration (AOR 5.95; p = 0.036) and younger age (AOR 1.03; p = 0.031). SAT and DOT participants did not significantly differ for IPT duration (6.54 vs 5.68 months; p = 0.216) nor 9-month completion (59.8 vs 46.3 %; p = 0.155). In an urban mobile healthcare sample, screening completion for LTBI was high with nearly half initiating IPT. Undocumented, Hispanic immigrants from high prevalence tuberculosis countries were more likely to self-select DOT at the mobile outreach clinic, potentially because of more culturally, linguistically, and logistically accessible services and self-selection optimization phenomena. Within a diverse, urban environment, DOT and SAT IPT models for LTBI treatment resulted in similar outcomes, yet outcomes were hampered by differential measurement bias between DOT and SAT participants.

Synthesis of cyclopentenimines from N-allyl ynamides via a tandem aza-Claisen rearrangement-carbocyclization sequence.

We describe here details of our investigations into Pd-catalyzed and thermal aza-Claisen-carbocyclizations of N-allyl ynamides to prepare a variety of α,ß-unsaturated cyclopentenimines. The nature of the ynamide electron-withdrawing group and ß-substituent plays critical roles in the success of this tandem cascade. With N-sulfonyl ynamides, the use of palladium catalysis is required, as facile 1,3-sulfonyl shifts dominate under thermal conditions. However, since no analogous 1,3-phosphoryl shift is operational, N-phosphoryl ynamides could be used to prepare similar cyclopentenimines under thermal conditions through zwitter ionic intermediates that undergo N-promoted H-shifts. Alternatively, by employing ynamides bearing tethered carbon nucleophiles, the zwitter ionic intermediates could be intercepted, giving rise rapidly to more complex fused bi- and tricyclic scaffolds.