Overdose deaths before and during the COVID-19 pandemic in a US county.

Introduction: Globally, overdose deaths increased near the beginning of the COVID-19 pandemic, which created availability and access barriers to addiction and social services. Especially in times of a crisis like a pandemic, local exposures, service availability and access, and system responses have major influence on people who use drugs. For policy makers to be effective, an understanding at the local level is needed. Methods: This retrospective epidemiologic study from 2019 through 2021 compares immediate and 20-months changes in overdose deaths from the pandemic start to 16 months before its arrival in Pinellas County, FL We examine toxicologic death records of 1,701 overdoses to identify relations with interdiction, and service delivery. Results: There was an immediate 49% increase (95% CI 23-82%, p < 0.0001) in overdose deaths in the first month following the first COVID deaths. Immediate increases were found for deaths involving alcohol (171%), heroin (108%), fentanyl (78%), amphetamines (55%), and cocaine (45%). Overdose deaths remained 27% higher (CI 4-55%, p = 0.015) than before the pandemic through 2021.Abrupt service reductions occurred when the pandemic began: in-clinic methadone treatment dropped by two-thirds, counseling by 38%, opioid seizures by 29%, and drug arrests by 56%. Emergency transport for overdose and naloxone distributions increased at the pandemic onset (12%, 93%, respectively) and remained higher through 2021 (15%, 377%,). Regression results indicate that lower drug seizures predicted higher overdoses, and increased 911 transports predicted higher overdoses. The proportion of excess overdose deaths to excess non-COVID deaths after the pandemic relative to the year before was 0.28 in Pinellas County, larger than 75% of other US counties. Conclusions: Service and interdiction interruptions likely contributed to overdose death increases during the pandemic. Relaxing restrictions on medical treatment for opioid addiction and public health interventions could have immediate and long-lasting effects when a major disruption, such as a pandemic, occurs. County level data dashboards comprised of overdose toxicology, and interdiction and service data, can help explain changes in overdose deaths. As a next step in predicting which policies and practices will best reduce local overdoses, we propose using simulation modeling with agent-based models to examine complex interacting systems.

Normalization of Prevention Principles and Practices to Reduce Substance Use Disorders Through an Integrated Dissemination and Implementation Framework.

Major research breakthroughs over the past 30 years in the field of substance use prevention have served to: (1) enhance understanding of pharmacological effects on the central and peripheral nervous systems and the health and social consequences of use of psychoactive substances, particularly for children and adolescents; (2) delineate the processes that increase vulnerability to or protect from initiation of substance use and progression to substance use disorders (SUDs) and, based on this understanding, (3) develop effective strategies and practices to prevent the initiation and escalation of substance use. The challenge we now face as a field is to "normalize" what we have learned from this research so that it is incorporated into the work of those involved in supporting, planning, and delivering prevention programming to populations around the world, is integrated into health and social service systems, and helps to shape public policies. But we wish to go further, to incorporate these effective prevention practices into everyday life and the mind-sets of the public, particularly parents and educators. This paper reviews the advances that have been made in the field of prevention and presents a framework and recommendations to achieve these objectives generated during several meetings of prevention and implementation science researchers sponsored by the International Consortium of Universities for Drug Demand Reduction (ICUDDR) that guides a roadmap to achieve "normalization."

Strengthening systems of care for people with or at risk for HIV, HCV and opioid use disorder: a call for enhanced data collection.

BACKGROUND: The syndemic between opioid use disorder (OUD), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) results in excessive burdens on the healthcare system. Integrating these siloed systems of care is critical to address all three conditions adequately. In this implementation project, we assessed the data capacity of the health system to measure a cascade of care (COC) across HIV, HCV and OUD services in five states to help guide public health planning. MATERIALS AND METHODS: Data for this study were gathered from publicly available datasets and reports from government (SAMSHA, CMS, HRSA and CDC) sites. We created, where possible, COCs for HIV, HCV, and OUD spanning population estimate, diagnosis, treatment initiation, treatment retention, and patient outcomes for each of five states in the study. RESULTS: The process of data collection showed that baseline COCs examining the intersections of OUD, HIV, and HCV cannot be produced and that there are missing data in all states examined. Collection of specific data points is not consistent across all states. States are better at reporting HIV cascades due to federal requirements. Only gross estimates could be made for OUD cascades in all states because data are separated by payer source, leaving no central point of data collection from all sources. Data for HCV were not publicly available. CONCLUSION: It is difficult to assess the strategies needed or the progress made towards increasing treatment access and decreasing the burden of disease without the ability to construct an accurate baseline. Using integrated COCs with relevant benchmarks can not only guide public health planning, but also provide meaningful targets for intervention.KEY MESSAGESWhile HIV COCs are available for most states at least annually, they are not disaggregated for populations with co-occurring OUD or HCV.Data to calculate HCV COC are not available and data to calculate OUD COC are partially available, but only for specific payers.States do not have systems in place to measure the scope of the syndemic or to identify targets for quality improvement activities.

Opioid use disorder Cascade of care framework design: A roadmap.

Unintentional overdose deaths, most involving opioids, have eclipsed all other causes of US deaths for individuals less than 50 years of age. An estimated 2.4 to 5 million individuals have opioid use disorder (OUD) yet a minority receive treatment in a given year. Medications for OUD (MOUD) are the gold standard treatment for OUD however early dropout remains a major challenge for improving clinical outcomes. A Cascade of Care (CoC) framework, first popularized as a public health accountability strategy to stem the spread of HIV, has been adapted specifically for OUD. The CoC framework has been promoted by the NIH and several states and jurisdictions for organizing quality improvement efforts through clinical, policy, and administrative levers to improve OUD treatment initiation and retention. This roadmap details CoC design domains based on available data and potential linkages as individual state agencies and health systems typically rely on limited datasets subject to diverse legal and regulatory requirements constraining options for evaluations. Both graphical decision trees and catalogued studies are provided to help guide efforts by state agencies and health systems to improve data collection and monitoring efforts under the OUD CoC framework.

Rapid adaptation during the COVID crisis: Challenges experienced in delivering service to those with Opioid Use Disorders.

Background: Adaptation is an accepted part of implementing evidence-based practices. COVID-19 presented a unique opportunity to examine adaptation in evolving contexts. Delivering service to people with opioid use disorder during the pandemic required significant adaptation due to revised regulations and limited service access. This report evaluated changes to addiction medication services caused by the pandemic, challenges encountered in rapidly adapting service delivery, and initial impressions of which changes might be sustainable over time. Methods: Qualitatively-evaluated structured interviews (N = 20) were conducted in late 2020 with key informants in Pinellas County (FL) to assess the pandemic's impact. Interviewees represented a cross-section of the professional groups including direct SUD/HIV service providers, and sheriff's office, Department of Health, and regional clinical program administrative staff. The interview questions examined significant changes necessitated by the pandemic, challenges encountered in adapting to this evolving context, and considerations for sustained change. Results: The most significant changes to service delivery identified were rapid adaptation to a telehealth format, and modifying service consistent with SAMHSA guidance, to allow for 'take-home' doses of methadone. Limitations imposed by access to technology, and the retraining of staff and patients to give and receive service differently were the most common themes identified as challenging adaptation efforts. Respondents saw shifts towards telehealth as most likely to being sustained. Conclusions: COVID-19 provided an unprecedented opportunity to examine adaptation in a fast-paced, dynamic, and evolving context. Adaptations identified will only be sustained through multisystem collaboration and validation. Results suggest that additional components could be added to implementation frameworks to assess rapid adaptation during unplanned events, such as access to additional resources or local decision-making that impacts service delivery. Findings will also be integrated with quantitative data to help inform local policy decisions. Plain Language Summary: Adaptation is an accepted part of implementing evidencebased practices. COVID-19 presented a unique opportunity to examine rapid adaptation necessitated within evolving contexts. Delivering services to people with opioid use disorder required significant adaptation due to changing regulations and limited access to lifesaving services. This study examined changes in service delivery due to the pandemic, challenges encountered in rapid adaptation, and initial impressions of which changes might be sustainable over time. Qualitatively-evaluated structured interviews were conducted with a cross-section of professional groups (direct substance use disorder (SUD) and human immunodeficiency virus (HIV) service providers, and sheriff's office, Department of Health, and clinical program administrative staff) in Pinellas County (FL). The most significant changes to service delivery were rapid adaptation to a telehealth format and increased allowance for 'takehome' doses of methadone medication. Limitations imposed by access to technology, as well as the education of and staff and patients were the most common themes identified as challenges. Respondents saw shifts towards telehealth as most likely to be sustained. COVID-19 provided an unprecedented opportunity to examine adaptation in a fast-paced, dynamic, and evolving context. Adaptations will only be sustained through multisystem collaboration and validation. Findings suggest that additional components could be added to implementation frameworks to assess rapid adaptation during unplanned events, such as access to additional resources or local decision-making that impacts service delivery.

Polypharmacy in Palliative Care for Advanced Heart Failure: The PAL-HF Experience.

BACKGROUND: Palliative care (PC) in advanced heart failure (HF) aims to improve symptoms and quality of life (QOL), in part through medication management. The impact of PC on polypharmacy (>5 medications) remains unknown. METHODS AND RESULTS: We explored patterns of polypharmacy in the Palliative Care in HF (PAL-HF) randomized controlled trial of standard care vs interdisciplinary PC in advanced HF (N = 150). We describe differences in medication counts between arms at 2, 6, 12, and 24 weeks for HF (12 classes) and PC (6 classes) medications. General linear mixed models were used to evaluate associations between treatment arm and polypharmacy over time. The median age of the patients was 72 years (interquartile range 62-80 years), 47% were female, and 41% were Black. Overall, 48% had ischemic etiology, and 55% had an ejection fraction of 40% or less. Polypharmacy was present at baseline in 100% of patients. HF and PC medication counts increased in both arms, with no significant differences in counts by drug class at any time point between arms. CONCLUSIONS: In a trial of patients with advanced HF considered eligible for PC, polypharmacy was universal at baseline and increased during follow-up with no effect of the palliative intervention on medication counts relative to standard care.

Protecting patients and staff in residential treatment centers during exposure to COVID-19: commentary.

BACKGROUND: The COVID-19 pandemic has created a crisis in access to addiction treatment. Programs with residential components have been particularly impacted as they try to keep infection from spreading in facilities and contributing to further community spread of the virus. This crisis highlights the ongoing daily trade-offs that organizations must weigh as they balance the risks and benefits of individual patients with those of the group of patients, staff and the community they serve. MAIN BODY: The COVID-19 pandemic has forced provider organizations to make individual facility level decisions about how to manage patients who are COVID-19 positive while protecting other patients, staff and the community. While guidance documents from federal, state, and trade groups aimed to support such decision making, they often lagged pandemic dynamics, and provided too little detail to translate into front line decision making. In the context of incomplete knowledge to make informed decisions, we present a way to integrate guidelines and local data into the decision process and discuss the ethical dilemmas faced by provider organizations in preventing infections and responding to COVID positive patients or staff. CONCLUSION AND COMMENTARY: Provider organizations need decision support on managing the risk of COVID-19 positive patients in their milieu. While useful, guidance documents may not be capable of providing support with the nuance that local data and simulation modeling may be able to provide.

A randomized clinical trial of smartphone self-managed recovery support services.

This study examines the effectiveness of smartphone-based ecological momentary interventions (EMI) and assessments (EMA), delivered separately and combined, to provide recovery support following substance use disorder (SUD) treatment engagement. We recruited adults (N = 401) from SUD treatment programs in Chicago and, after engagement for at least two sessions, nights, or medication dosages, we randomly assigned them to one of four conditions that lasted 6 months: (1) EMI only, (2) EMA only, (3) both EMI and EMA, and (4) control condition of neither EMI nor EMA. EMIs provided support for recovery through applications on the phone or links to other resources; EMAs were delivered randomly 5 times per day asking participants to indicate recent substance use and situational risk and protective factors. The primary dependent variable was days of abstinence in the 6 months following study intake. Rates of EMI and EMA utilization indicated high compliance, although EMI use decreased over time. There was a small direct effect of time across conditions (F(2,734) = 4.33, p = .014, Cohen's f = 0.11) and a small direct effect of time-by-EMI use (F(2,734) = 4.85, p = .009, f = 0.11) on days of abstinence. There was no significant direct effect of time-by-EMAs nor interaction effect of time-by-EMI-by-EMA. However, secondary path model analyses showed a small but significant indirect effect of EMA on abstinence via EMI use. Stepwise modeling identified a simplified model based on the proportion of weeks using ≥1 EMI and the EMI to listen to music, which predicted 7.2% of the variance in days of abstinence (F(2,195,) = 7.56, p < .001). Combined delivery of EMI and EMA shows potential for increasing abstinence above and beyond the effect of SUD treatment engagement and for addressing the limited national capacity for recovery support.

Treatment with Human Amniotic Suspension Allograft Improves Tendon Healing in a Rat Model of Collagenase-Induced Tendinopathy.

Treatment of tendon injuries is challenging, with neither conservative nor surgical approaches providing full recovery. Placental-derived tissues represent a promising tool for the treatment of tendon injuries. In this study, human amniotic suspension allograft (ASA) was investigated in a pre-clinical model of Achilles tendinopathy. Collagenase type I was injected in the right hind limb of Sprague Dawley rats to induce disease. Contralateral tendons were either left untreated or injected with saline as controls. Seven days following induction, tendons were injected with saline, ASA, or left untreated. Rats were sacrificed 14 and 28 days post-treatment. Histological and biomechanical analysis of tendons was completed. Fourteen days after ASA injection, improved fiber alignment and reduced cell density demonstrated improvement in degenerated tendons. Twenty-eight days post-treatment, tendons in all treatment groups showed fewer signs of degeneration, which is consistent with normal tendon healing. No statistically significant differences in histological or biomechanical analyses were observed between treatment groups at 28 days independent of the treatment they received. In this study, ASA treatment was safe, well-tolerated, and resulted in a widespread improvement of the tissue. The results of this study provide preliminary insights regarding the potential use of ASA for the treatment of Achilles tendinopathy.

Developing an opioid use disorder treatment cascade: A review of quality measures.

BACKGROUND: Despite increasing opioid overdose mortality, problems persist in the availability and quality of treatment for opioid use disorder (OUD). Three FDA-approved medications (methadone, buprenorphine, and naltrexone) have high quality evidence supporting their use, but most individuals with OUD do not receive them and many experience relapse following care episodes. Developing and organizing quality measures under a unified framework such as a Cascade of Care could improve system level practice and treatment outcomes. In this context, a review was performed of existing quality measures relevant to the treatment of OUD and the literature assessing the utility of these measures in community practice. METHODS: Systematic searches of two national quality measure clearinghouses (National Quality Forum and Agency for Healthcare Research and Quality) were performed for measures that can be applied to the treatment of OUD. Measures were categorized as structural, process, or outcome measures. Second stage searches were then performed within Ovid/Medline focused on published studies investigating the feasibility, reliability, and validity of identified measures, predictors of their satisfaction, and related clinical outcomes. RESULTS: Seven quality measures were identified that are applicable to the treatment of OUD. All seven were process measures that assess patterns of service delivery. One recently approved measure addresses retention in medication-assisted treatment for patients with OUD. Twenty-nine published studies were identified that evaluate the quality measures, primarily focused on initiation and engagement in care for addiction treatment generally. Most measures and related studies do not specifically incorporate the evidence base for the treatment of OUD or assess patient level outcomes such as overdose. CONCLUSION: Despite considerable progress, gaps exist in quality measures for OUD treatment. Development of a unified quality measurement framework such as an OUD Treatment Cascade will require further elaboration and refinement of existing measures across populations and settings. Such a framework could form the basis for applying strategies at clinical, organizational, and policy levels to expand access to quality care and reduce opioid-related mortality.

Successful Organizational Strategies to Sustain Use of A-CHESS: A Mobile Intervention for Individuals With Alcohol Use Disorders.

BACKGROUND: Mobile health (mHealth) services are growing in importance in health care research with the advancement of wireless networks, tablets, and mobile phone technologies. These technologies offer a wide range of applications that cover the spectrum of health care delivery. Although preliminary experiments in mHealth demonstrate promising results, more robust real-world evidence is needed for widespread adoption and sustainment of these technologies. OBJECTIVE: Our aim was to identify the problems/challenges associated with sustained use of an mHealth addiction recovery support app and to determine strategies used by agencies that successfully sustained client use of A-CHESS. METHODS: Qualitative inquiry assessed staff perceptions about organizational attributes and strategies associated with sustained use of the mobile app, A-CHESS. A total of 73 interviews of clinicians and administrators were conducted. The initial interviews (n=36) occurred at the implementation of A-CHESS. Follow-up interviews (n=37) occurred approximately 12 and 24 months later. A coding scheme was developed and Multiuser NVivo was used to manage and analyze the blinded interview data. RESULTS: Successful strategies used by treatment providers to sustain A-CHESS included (1) strong leadership support, (2) use of client feedback reports to follow up on non-engaged clients, (3) identify passionate staff and incorporate A-CHESS discussions in weekly meetings, (4) develop A-CHESS guidelines related to client use, (5) establish internal work groups to engage clients, and (6) establish a financial strategy to sustain A-CHESS use. The study also identified attributes of A-CHESS that enhanced as well as inhibited its sustainability. CONCLUSIONS: Mobile apps can play an important role in health care delivery. However, providers will need to develop strategies for engaging both staff and patients in ongoing use of the apps. They will also need to rework business processes to accommodate the changes in communication frequency and style, learn to use app data for decision making, and identify financing mechanisms for supporting these changes.

It's Your Game-Tech: Toward Sexual Health in the Digital Age.

Adolescent sexually transmitted infection (STI) and birth rates indicate a need for effective middle school HIV/STI, and pregnancy prevention curricula to delay, or mitigate consequences of, early sexual activity. Individual and organizational barriers to adoption, implementation, and maintenance, however, can hamper dissemination of evidence-based sexual health curricula, adversely impacting fidelity and reach. Internet-based approaches may help mitigate these barriers. This paper describes the development and feasibility testing of It's Your Game (IYG)-Tech, a stand-alone 13-lesson Internet-based sexual health life-skills curriculum adapted from an existing effective sexual health curriculum-It's Your Game… Keep it Real (IYG). IYG-Tech development adaptation steps were to: 1) Select a suitable effective program and gather the original program materials; 2) Develop "proof of concept" lessons and test usability and impact; 3) Develop the program design document describing the core content, scope, and methods and strategies; and 4) produce the new program. Lab- and school-based tests with middle school students demonstrated high ratings on usability parameters and immediate impact on selected psychosocial factors related to sexual behavior-perceptions of friends' beliefs, reasons for not having sex, condom use self-efficacy, abstinence intentions, negotiating with others to protect personal rules, and improved knowledge about what constitutes healthy relationships (all p < .05). Youth rated IYG-Tech is favorably compared to other learning channels (>76.2% agreement) and rated the lessons as helpful in making healthy choices, selecting personal rules, detecting challenges to those rules, and protecting personal rules through negotiation and refusal skills (89.5% - 100%). Further efficacy testing is indicated for IYG-Tech as a potential strategy to deliver effective HIV/STI, and pregnancy prevention to middle school youth.

Promoting new practices to increase access to and retention in addiction treatment: an analysis of five communication channels.

Addiction treatment programs adopt evidence-based practices slowly, in part because adopting a new practice is a process, not an event. Using different communication channels may have a different effect at different points in the process. This paper reports the effectiveness of five communication channels in getting substance abuse treatment programs to adopt new business practices. In this study, national trade media coverage produced the greatest interest among programs and the greatest number of decisions to adopt. Conference presentations produced fewer decisions to adopt than national media, but were the most effective channel when compared to the number of programs they reached. Peers were the greatest influence in moving clinic staff from the decision to adopt to implementation. These findings give preliminary evidence for using different communication channels at different times during an effort to promote the adoption of best practices.

Industrial Ziegler-type hydrogenation catalysts made from Co(neodecanoate)2 or Ni(2-ethylhexanoate)2 and AlEt3: evidence for nanoclusters and sub-nanocluster or larger Ziegler-nanocluster based catalysis.

Ziegler-type hydrogenation catalysts are important for industrial processes, namely, the large-scale selective hydrogenation of styrenic block copolymers. Ziegler-type hydrogenation catalysts are composed of a group 8-10 transition metal precatalyst plus an alkylaluminum cocatalyst (and they are not the same as Ziegler-Natta polymerization catalysts). However, for ∼50 years two unsettled issues central to Ziegler-type hydrogenation catalysis are the nature of the metal species present after catalyst synthesis, and whether the species primarily responsible for catalytic hydrogenation activity are homogeneous (e.g., monometallic complexes) or heterogeneous (e.g., Ziegler nanoclusters defined as metal nanoclusters made from combination of Ziegler-type hydrogenation catalyst precursors). A critical review of the existing literature (Alley et al. J. Mol. Catal. A: Chem. 2010, 315, 1-27) and a recently published study using an Ir model system (Alley et al. Inorg. Chem. 2010, 49, 8131-8147) help to guide the present investigation of Ziegler-type hydrogenation catalysts made from the industrially favored precursors Co(neodecanoate)(2) or Ni(2-ethylhexanoate)(2), plus AlEt(3). The approach and methods used herein parallel those used in the study of the Ir model system. Specifically, a combination of Z-contrast scanning transmission electron microscopy (STEM), matrix assisted laser desorption ionization mass spectrometry (MALDI MS), and X-ray absorption fine structure (XAFS) spectroscopy are used to characterize the transition metal species both before and after hydrogenation. Kinetic studies including Hg(0) poisoning experiments are utilized to test which species are the most active catalysts. The main findings are that, both before and after catalytic cyclohexene hydrogenation, the species present comprise a broad distribution of metal cluster sizes from subnanometer to nanometer scale particles, with estimated mean cluster diameters of about 1 nm for both Co and Ni. The XAFS results also imply that the catalyst solutions are a mixture of the metal clusters described above, plus unreduced metal ions. The kinetics-based Hg(0) poisoning evidence suggests that Co and Ni Ziegler nanoclusters (i.e., M(≥4)) are the most active Ziegler-type hydrogenation catalysts in these industrial systems. Overall, the novelty and primary conclusions of this study are as follows: (i) this study examines Co- and Ni-based catalysts made from the actual industrial precursor materials, catalysts that are notoriously problematic regarding their characterization; (ii) the Z-contrast STEM results reported herein represent, to our knowledge, the best microscopic analysis of the industrial Co and Ni Ziegler-type hydrogenation catalysts; (iii) this study is the first explicit application of an established method, using multiple analytical methods and kinetics-based studies, for distinguishing homogeneous from heterogeneous catalysis in these Ziegler-type systems; and (iv) this study parallels the successful study of an Ir model Ziegler catalyst system, thereby benefiting from a comparison to those previously unavailable findings, although the greater M-M bond energy, and tendency to agglomerate, of Ir versus Ni or Co are important differences to be noted. Overall, the main result of this work is that it provides the leading hypothesis going forward to try to refute in future work, namely, that sub, M(≥4) to larger, M(n) Ziegler nanoclusters are the dominant, industrial, Co- and Ni- plus AlR(3) catalysts in Ziegler-type hydrogenation systems.

Iridium Ziegler-type hydrogenation catalysts made from [(1,5-COD)Ir(mu-O2C8H15)](2) and AlEt3: spectroscopic and kinetic evidence for the Ir(n) species present and for nanoparticles as the fastest catalyst.

Ziegler-type hydrogenation catalysts, those made from a group 8-10 transition metal precatalyst and an AlR(3) cocatalyst, are often used for large scale industrial polymer hydrogenation; note that Ziegler-type hydrogenation catalysts are not the same as Ziegler-Natta polymerization catalysts. A review of prior studies of Ziegler-type hydrogenation catalysts (Alley et al. J. Mol. Catal. A: Chem. 2010, 315, 1-27) reveals that a approximately 50 year old problem is identifying the metal species present before, during, and after Ziegler-type hydrogenation catalysis, and which species are the kinetically best, fastest catalysts--that is, which species are the true hydrogenation catalysts. Also of significant interest is whether what we have termed "Ziegler nanoclusters" are present and what their relative catalytic activity is. Reported herein is the characterization of an Ir Ziegler-type hydrogenation catalyst, a valuable model (vide infra) for the Co-based industrial Ziegler-type hydrogenation catalyst, made from the crystallographically characterized [(1,5-COD)Ir(mu-O(2)C(8)H(15))](2) precatalyst plus AlEt(3). Characterization of this Ir model system is accomplished before and after catalysis using a battery of physical methods including Z-contrast scanning transmission electron microscopy (STEM), high resolution (HR)TEM, and X-ray absorption fine structure (XAFS) spectroscopy. Kinetic studies plus Hg(0) poisoning experiments are then employed to probe which species are the fastest catalysts. The main findings herein are that (i) a combination of the catalyst precursors [(1,5-COD)Ir(mu-O(2)C(8)H(15))](2) and AlEt(3) gives catalytically active solutions containing a broad distribution of Ir(n) species ranging from monometallic Ir complexes to nanometer scale, noncrystalline Ir(n) nanoclusters (up to Ir(approximately 100) by Z-contrast STEM) with the estimated mean Ir species being 0.5-0.7 nm, Ir(approximately 4-15) clusters considering the similar, but not identical results from the different analytical methods; furthermore, (ii) the mean Ir(n) species are practically the same regardless of the Al/Ir ratio employed, suggesting that the observed changes in catalytic activity at different Al/Ir ratios are primarily the result of changes in the form or function of the Al-derived component (and not due to significant AlEt(3)-induced changes in initial Ir(n) nuclearity). However (iii), during hydrogenation, a shift in the population of Ir species toward roughly 1.0-1.6 nm, fcc Ir(0)(approximately 40-150), Ziegler nanoclusters occurs with, significantly, (iv) a concomitant increase in catalytic activity. Importantly, and although catalysis by discrete subnanometer Ir species is not ruled out by this study, (v) the increases in activity with increased nanocluster size, plus Hg(0) poisoning studies, provide the best evidence to date that the approximately 1.0-1.6 nm, fcc Ir(0)(approximately 40-150), heterogeneous Ziegler nanoclusters are the fastest catalysts in this industrially related catalytic hydrogenation system (and in the simplest, Ockham's Razor interpretation of the data). In addition, (vi) Ziegler nanoclusters are confirmed to be an unusual, hydrocarbon-soluble, highly coordinatively unsaturated, Lewis-acid containing, and highly catalytically active type of nanocluster for use in other catalytic applications and other areas.