Minimal Clinically Important Difference (MCID) for the Short Musculoskeletal Function Assessment (SMFA) in Severe Lower Extremity Trauma: Pooled Data from 7 Multicenter, Prospective Clinical Trials.

BACKGROUND: The Short Musculoskeletal Function Assessment (SMFA) is a well validated, widely used patient-reported outcome (PRO) measure for orthopaedic patients. Despite its widespread use and acceptance, this measure does not have an agreed upon minimal clinically important difference (MCID). The purpose of the present study was to create distributional MCIDs with use of a large cohort of research participants with severe lower extremity fractures. METHODS: Three distributional approaches were used to calculate MCIDs for the Dysfunction and Bother Indices of the SMFA as well as all its domains: (1) half of the standard deviation (one-half SD), (2) twice the standard error of measurement (2SEM), and (3) minimal detectable change (MDC). In addition to evaluating by patient characteristics and the timing of assessment, we reviewed these calculations across several injury groups likely to affect functional outcomes. RESULTS: A total of 4,298 SMFA assessments were collected from 3,185 patients who had undergone surgical treatment of traumatic injuries of the lower extremity at 60 Level-I trauma centers across 7 multicenter, prospective clinical studies. Depending on the statistical approach used, the MCID associated with the overall sample ranged from 7.7 to 10.7 for the SMFA Dysfunction Index and from 11.0 to 16.8 for the SMFA Bother Index. For the Dysfunction Index, the variability across the scores was small (<5%) within the sex and age subgroups but was modest (12% to 18%) across subgroups related to assessment timing. CONCLUSIONS: A defensible MCID can be found between 7 and 11 points for the Dysfunction Index and between 11 and 17 points for the Bother Index. The precise choice of MCID may depend on the preferred statistical approach and the population under study. While differences exist between MCID values based on the calculation method, values were consistent across the categories of the various subgroups presented. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Safer-use strategies in the context of harm-reduction treatment for people experiencing homelessness and alcohol use disorder.

BACKGROUND: Two, randomized controlled trials found harm-reduction treatment for AUD (HaRT-A) improves alcohol outcomes for adults experiencing homelessness. HaRT-A, which neither requires nor precludes abstinence, entails tracking alcohol-related harm, harm-reduction goals, and safer-use strategies. This secondary dual study qualitatively describes this last component, safer-use strategies, and their quantitative association with treatment outcomes. METHODS: Participants were people who experienced homelessness and AUD and were enrolled in the active HaRT-A treatment arms in 2 randomized control trials (Trial 1 N = 86; Trial 2 N = 208). Trial 1was a 2-arm study with randomization to HaRT-A or services as usual. Trial 2 was a 4-arm study combining HaRT-A and extended release naltrexone. In HaRT-A sessions, participants received a list of 3 categories of safer-use strategies (i.e., buffering alcohol's effects on the body, changing the manner of drinking to be safer and healthier, and reducing alcohol use). Mixed methods were used to qualitatively describe safer-use strategies implemented and quantitatively test their association with alcohol outcomes (i.e., peak quantity, frequency, alcohol-related harm). RESULTS: In Trial 1, but not Trial 2, participants committed to more safer-use strategies across time, which was associated with reductions in alcohol frequency over the past 30 days. In both trials, participants committing to reducing alcohol consumption drank on a quarter fewer days overall, and in Trial 2, experienced 15 % less alcohol-related harm. In Trial 1, participants who committed to changing the manner of drinking were heavier drinkers overall, and although they showed significant reductions in alcohol-related harm, their reduction rate was slower than for participants who selected other strategies. In Trial 2, strategies to buffer alcohol's effects were associated with a monthly 14 % decrease of alcohol-related harm. CONCLUSION: This study replicated prior findings that people experiencing homelessness and AUD regularly adopt strategies to reduce alcohol-related harm. The implementation of safer-use strategies was favorably associated with alcohol outcomes, but specific associations differed by trial and outcome. Discussion of safer-use strategies appears helpful; however, further research is needed to firmly establish how this HaRT-A component works.

A pilot study of virtual Harm Reduction Talking Circles for American Indian and Alaska Native adults with alcohol use disorder.

Prior research suggests that culturally aligned, accessible and lower-barrier interventions are well-placed to align with the needs of American Indian and Alaska Native (AI/AN) people with alcohol use disorder (AUD). Taking into account community members' suggestions and the need for physical distancing during the COVID-19 pandemic, our team developed a protocol for virtual Harm Reduction Talking Circles (HaRTC) to incorporate these points. The aims of this 8-week, single-arm pilot were to initially document feasibility, acceptability, and outcomes associated with attendance at virtual HaRTC, which integrates the accessibility of virtual connection, a lower-barrier harm-reduction approach, and a culturally aligned intervention. Participants (N = 51) were AI/AN people with AUD (current or in remission) across 41 Tribal affiliations and 25 US states. After a baseline interview, participants were invited to attend 8, weekly virtual HaRTC sessions. At the baseline, midpoint and post-test assessments, we collected data on virtual HaRTC acceptability, cultural connectedness, quality of life, and alcohol outcomes. Of the 123 people approached, 63% were interested in and consented to participation. Participants attended an average of 2.1 (SD = 2.02) virtual HaRTC sessions, with 64% of participants attending at least one. On a scale from 1 to 10, participants rated the virtual HaRTC as highly acceptable (M = 9.3, SD = 1.9), effective (M = 8.4, SD = 2.9), culturally aligned (M = 9.2, SD = 1.5), helpful (M = 8.8, SD = 1.9), and conducted in a good way (M = 9.8, SD = 0.5). Although the single-arm study design precludes causal inferences, participants evinced statistically significant decreases in days of alcohol use and alcohol-related harm over the three timepoints. Additionally, both sense of spirituality, which is a factor of cultural connectedness, and health-related quality of life increased over time as a function of the number of HaRTC sessions attended. Virtual HaRTC shows initial feasibility and acceptability as a culturally aligned intervention for AI/AN people with AUD. Future randomized controlled trials will provide a test of the efficacy of this approach.

A systematic meta-epidemiologic review on nonabstinence-inclusive interventions for substance use: inclusion of race/ethnicity and sex assigned at birth/gender.

Background: Minoritized racial/ethnic and sex assigned at birth/gender groups experience disproportionate substance-related harm. Focusing on reducing substance-related harm without requiring abstinence is a promising approach.Objectives: The purpose of this meta-epidemiologic systematic review was to examine inclusion of racial/ethnic and sex assigned at birth/gender in published studies of nonabstinence-inclusive interventions for substance use.Methods: We systematically searched databases (PubMed and PsycINFO) on May 26, 2022 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Articles were eligible for inclusion if they: 1) reported in English language, 2) had a primary goal of investigating a nonabstinence-inclusive intervention to address substance use, 3) used human subjects, and 4) only included adults aged 18 or older. Two coders screened initial articles and assessed eligibility criteria of full text articles. A third consensus rater reviewed all coding discrepancies. For the remaining full-length articles, an independent rater extracted information relevant to study goalsResults: The search strategy yielded 5,759 records. 235 included articles remained. Only 73 articles (31.1%) fully reported on both racial/ethnic and sex assigned at birth/gender, and only seven articles (3.0%) reported subgroup analyses examining treatment efficacy across minoritized groups. Nine articles (3.8%) mentioned inclusion and diversity regarding both racial/ethnic and sex assigned at birth/gender in their discussion and four articles (1.7%) broadly mentioned a lack of diversity in their limitationsConclusion: Findings highlight that little is known about nonabstinence-inclusive interventions to address substance use for individuals from minoritized racial/ethnic and sex assigned at birth/gender groups.

Does Topical Vancomycin Powder Use in Fracture Surgery Change Bacteriology and Antibiotic Susceptibilities? An Analysis of the VANCO Trial.

OBJECTIVE: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens. DESIGN: Secondary analysis of phase III, prospective, randomized clinical trial. SETTING: Thirty-six US trauma centers. PATIENT SELECTION CRITERIA: Patients who became infected after fixation of tibial plateau or pilon fracture. OUTCOME MEASURES AND COMPARISONS: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room. RESULTS: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus. CONCLUSIONS: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Commentary: Similarities and Differences Between Harm-Reduction and Substitute Addiction-- Implications for the Health Professions.

"Substitute addiction" refers to the process of achieving abstinence or resolution of one addictive behavior and subsequently engaging in one or more additional addictive behaviors in its place. Substitute addiction, a concept in the abstinence-based recovery field for decades, is viewed as a cause for concern because resolving one addictive behavior might not fully remove harm or ensure recovery. Conversely, "harm-reduction treatment" refers to a counseling orientation that focuses on helping service users reduce substance-related harm and improve their quality of life without necessarily requiring abstinence or use reduction. Harm-reduction treatment assesses a constellation of addictive behaviors in the larger context of a person's life to holistically reduce harm in that constellation. In this commentary, we define and compare both constructs and point out their implications for addictions treatment.

Impact of Harm Reduction Treatment with or without Pharmacotherapy on Polysubstance Use among People Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: A prior randomized controlled trial showed behavioral harm reduction treatment for alcohol use disorder (AUD), or HaRT-A, was effective in improving alcohol outcomes and quality of life for people experiencing homelessness and AUD when provided with or without pharmacotherapy (ie, extended-release naltrexone). Because nearly 80% of the sample also reported baseline polysubstance use, this secondary study tested whether HaRT-A also positively impacted other substance use. METHODS: In the parent study, 308 adults with AUD and homelessness were randomized to receive HaRT-A plus intramuscular injections of 380-mg extended-release naltrexone (HaRT-A + extended-release naltrexone), HaRT-A plus placebo (HaRT-A + placebo), HaRT-A alone, or community-based services as usual (control). In this secondary study, we used random intercept models to detect changes in other substance use after exposure to any of the HaRT-A conditions. For less prevalent behaviors, outcomes included past-month use (cocaine, amphetamines/methamphetamines, opioids). For more prevalent behaviors (polysubstance, cannabis), outcomes were past-month use frequency. RESULTS: Compared with controls, participants who received HaRT-A showed significantly reduced 30-day frequency of cannabis use (incident rate ratio = 0.59, 95% CI = 0.40-0.86, P = 0.006) and polysubstance use (incident rate ratio = 0.65, 95% CI = 0.43-0.98, P = 0.040). No other significant changes were detected. CONCLUSIONS: Compared with services as usual, HaRT-A is associated with reduced cannabis and polysubstance use frequency. The benefits of HaRT-A may thus extend beyond its impact on alcohol and quality of life outcomes to positively reshape overall substance use patterns. A randomized controlled trial is needed to further investigate the efficacy of such combined pharmacobehavioral harm reduction treatment for polysubstance use.

Linear IgA Bullous Dermatosis Attributable to the Use of Spironolactone: A Case Report.

Linear IgA bullous dermatosis (LABD) is a rare, idiopathic, or drug-induced vesiculobullous disease caused by IgA autoantibodies in the basement membrane zone. An 84-year-old man was started on spironolactone two weeks before presentation for the management of hypertension and heart failure with preserved ejection fraction. He presented to our hospital for evaluation of worsening lower extremity swelling and a painful pruritic rash that started on the day preceding his presentation. On examination, he had 3+ lower extremity edema and an erythematous, painful, pruritic, bullous rash on all his extremities. He had a significantly elevated IgA level (1033 mg/dL). A lesional skin biopsy demonstrated epidermal ulceration with degenerated collagen fibers. Direct immunofluorescence of the perilesional skin showed linear IgA at the dermal-epidermal junction. The rash resolved following steroid therapy and discontinuation of spironolactone. There have been previous reports of bullous pemphigoid induced by spironolactone. To our knowledge, LABD associated with spironolactone has not previously been reported.

Extended-release Naltrexone Is Not Linked to Hepatotoxicity in Adults Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: The use of extended-release naltrexone (XR-NTX) as treatment for alcohol use disorder (AUD) has been limited by a prior black box warning for hepatotoxicity. We performed a secondary analysis of data from a randomized clinical trial to compare serum liver enzyme levels for those randomized to XR-NTX versus placebo. METHODS: The parent study aimed to test the efficacy of combined pharmacobehavioral harm-reduction treatment in improving alcohol and quality-of-life outcomes for adults experiencing homelessness and AUD. We compared the 2 arms that received intramuscular injections of either 380 mg XR-NTX (n = 74) or placebo (n = 77). Outcomes included ( a ) liver enzyme levels and ( b ) liver enzyme values categorized as normal (<1× upper limit of normal [ULN]), elevated (1-3× ULN), or high (>3× ULN). We performed multinomial logistic regression and negative binomial generalized estimating equations modeling to assess the effects of treatment group and the time × treatment group interaction on liver enzyme outcomes. RESULTS: The mean age was 47.9 ± 9.9 years, and the mean baseline alcohol consumption was 23.2 ± 14.0 drinks per day. There were no significant differences in the development of liver enzyme elevations 1 to 3× ULN or more than 3× ULN (all P s > 0.25) or in the change in liver enzyme values (all P s > 0.41) between the placebo and the XR-NTX groups over the treatment course. CONCLUSIONS: In our study of adults experiencing homelessness and AUD, receipt of XR-NTX was not associated with hepatotoxicity. These findings support the use of XR-NTX to treat AUD even in patients who are drinking heavily and physiologically dependent on alcohol.

Oncolytic BHV-1 Is Sufficient to Induce Immunogenic Cell Death and Synergizes with Low-Dose Chemotherapy to Dampen Immunosuppressive T Regulatory Cells.

Immunogenic cell death (ICD) can switch immunologically "cold" tumors "hot", making them sensitive to immune checkpoint inhibitor (ICI) therapy. Many therapeutic platforms combine multiple modalities such as oncolytic viruses (OVs) and low-dose chemotherapy to induce ICD and improve prognostic outcomes. We previously detailed many unique properties of oncolytic bovine herpesvirus type 1 (oBHV) that suggest widespread clinical utility. Here, we show for the first time, the ability of oBHV monotherapy to induce bona fide ICD and tumor-specific activation of circulating CD8+ T cells in a syngeneic murine model of melanoma. The addition of low-dose mitomycin C (MMC) was necessary to fully synergize with ICI through early recruitment of CD8+ T cells and reduced infiltration of highly suppressive PD-1+ Tregs. Cytokine and gene expression analyses within treated tumors suggest that the addition of MMC to oBHV therapy shifts the immune response from predominantly anti-viral, as evidenced by a high level of interferon-stimulated genes, to one that stimulates myeloid cells, antigen presentation and adaptive processes. Collectively, these data provide mechanistic insights into how oBHV-mediated therapy modalities overcome immune suppressive tumor microenvironments to enable the efficacy of ICI therapy.

Differential Cellular Sensing of Fusion from within and Fusion from without during Virus Infection.

The physical entry of virus particles into cells triggers an innate immune response that is dependent on both calcium and nucleic acid sensors, with particles containing RNA or DNA genomes detected by RNA or DNA sensors, respectively. While membrane fusion in the absence of viral nucleic acid causes an innate immune response that is dependent on calcium, the involvement of nucleic acid sensors is poorly understood. Here, we used lipoplexes containing purified reovirus p14 fusion protein as a model of exogenous or fusion from without and a cell line expressing inducible p14 protein as a model of endogenous or fusion from within to examine cellular membrane fusion sensing events. We show that the cellular response to membrane fusion in both models is dependent on calcium, IRF3 and IFN. The method of sensing fusion, however, differs between fusion from without and fusion from within. Exogenous p14 lipoplexes are detected by RIG-I-like RNA sensors, whereas fusion by endogenous p14 requires both RIG-I and STING to trigger an IFN response. The source of nucleic acid that is sensed appears to be cellular in origin. Future studies will investigate the source of endogenous nucleic acids recognized following membrane fusion events.

The Statewide Epidemiology of Mucormycosis Among Trauma Patients in Florida.

OBJECTIVES: Mucormycosis is a rare angioinvasive infection caused by filamentous fungi with a high lethality among the immunocompromised. In healthy people, the innate immune system is sufficient to prevent infection. The exception to this is deep tissue exposure seen during trauma. The purpose of this study is to evaluate the epidemiology of mucormycosis using a statewide population-based data set. METHODS: This is a retrospective cohort study of all hospital admissions for mucormycosis within the state of Florida from 1997 through the beginning of 2020. A distribution map was created to evaluate for geographic variation. Botanical growth zones, based on plant hardiness, used by state environmental agencies and landscapers were also used to detect possible patterns based on climate conditions throughout Florida. A multivariable regression analysis was performed to account for confounders and limit bias. RESULTS: A total of 1190 patients were identified for mucormycosis infection. Only 86 of these patients were admitted for trauma. Cutaneous infections were more prevalent among trauma patients while non-trauma patients had more pulmonary infections (P = .04). Trauma patients with infection tended to be younger and less likely to suffer from comorbidities such as immunosuppression (36% vs 46%, P = .07) and diabetes (22.1% vs 47.1%, P ≤ .0001) as compared to their non-trauma counterparts. Mortality was similar with 17.8% for non-trauma patients and 15.1% for traumatized patients (AOR .80 [.42, 1.52]). Length of stay was longer for trauma patients (37.3 vs 23.0, P < .0001). Infections were less prominent in plant hardiness Zone 9 and Zone 10 as compared to Zone 8 (AOR .71 [.61, .82]; AOR .54 [.46, .64], respectively). CONCLUSION: Trauma patients who develop infection from mucormycosis are at high risk of death despite being a younger and healthier population. Mucormycosis infections were primarily soft tissue based among trauma patients. These infections are more prevalent in colder regions within Florida.

Measurement invariance and other psychometric properties of the Short Inventory of Problems (SIP-2R) across racial groups in adults experiencing homelessness and alcohol use disorder.

OBJECTIVE: People experiencing homelessness are disproportionately impacted by alcohol-related harm. Racially minoritized groups are disproportionately represented in the homeless population and are likewise disproportionately impacted by alcohol-related harm. Most alcohol outcome measures have not been adequately psychometrically studied in this marginalized population and across racial groups. This study documents psychometric properties, including measurement invariance, reliability, and convergent validity, of a measure of alcohol-related harm, the Short Inventory of Problems (SIP-2R), across Black, North American Indigenous (NAI), and White adults experiencing homelessness and alcohol use disorder (AUD). METHOD: Adults experiencing homelessness and AUD who had participated in one of two randomized controlled trials of harm-reduction treatment (N = 493; NAI = 205, Black = 125, and White = 163) were included in this psychometric study of the 15-item SIP-2R. RESULTS: Multigroup confirmatory factor analysis (MGCFA) indicated that a model comprising one general alcohol-related harm factor overarching five factors, showed close fit and partial scalar invariance, χ²(329, N = 493) = 624.902, p < .001, comparative fit index (CFI) = .966, root-mean-square error of approximation (RMSEA) = .074, 90% CI [.066, .083], standardized root-mean-square residual (SRMR) = .063, confirming acceptable measurement equivalence across racial groups. The SIP-2R showed internal consistency (α = .94, ω = .95) and convergent validity, that is, positive correlation between the total SIP-2R score and the number of drinks consumed the heaviest drinking day, ρ(490) = .30, p < .001. CONCLUSION: This study provided support for the internal consistency, convergent validity, and cross-group measurement equivalence of the SIP-2R for NAI, Black, and White adults experiencing homelessness with AUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is the main reason for poor outcomes after lung transplantation (LTx). We and others have recently identified B cells as major contributors to BOS after LTx. The extent of B cell heterogeneity and the relative contributions of B cell subpopulations to BOS, however, remain unclear. Here, we provide a comprehensive analysis of cell population changes and their gene expression patterns during chronic rejection after orthotopic LTx in mice. Of 11 major cell types, Mzb1-expressing plasma cells (PCs) were the most prominently increased population in BOS lungs. These findings were validated in 2 different cohorts of human BOS after LTx. A Bhlhe41, Cxcr3, and Itgb1 triple-positive B cell subset, also expressing classical markers of the innate-like B-1 B cell population, served as the progenitor pool for Mzb1+ PCs. This subset accounted for the increase in IgG2c production within BOS lung grafts. A genetic lack of Igs decreased BOS severity after LTx. In summary, we provide a detailed analysis of cell population changes during BOS. IgG+ PCs and their progenitors - an innate B cell subpopulation - are the major source of local Ab production and a significant contributor to BOS after LTx.

Patient-Specific Precision Injury Signatures to Optimize Orthopaedic Interventions in Multiply Injured Patients (PRECISE STUDY).

SUMMARY: Optimal timing and procedure selection that define staged treatment strategies can affect outcomes dramatically and remain an area of major debate in the treatment of multiply injured orthopaedic trauma patients. Decisions regarding timing and choice of orthopaedic procedure(s) are currently based on the physiologic condition of the patient, resource availability, and the expected magnitude of the intervention. Surgical decision-making algorithms rarely rely on precision-type data that account for demographics, magnitude of injury, and the physiologic/immunologic response to injury on a patient-specific basis. This study is a multicenter prospective investigation that will work toward developing a precision medicine approach to managing multiply injured patients by incorporating patient-specific indices that quantify (1) mechanical tissue damage volume; (2) cumulative hypoperfusion; (3) immunologic response; and (4) demographics. These indices will formulate a precision injury signature, unique to each patient, which will be explored for correspondence to outcomes and response to surgical interventions. The impact of the timing and magnitude of initial and staged surgical interventions on patient-specific physiologic and immunologic responses will be evaluated and described. The primary goal of the study will be the development of data-driven models that will inform clinical decision-making tools that can be used to predict outcomes and guide intervention decisions.

Streamlining Trauma Research Evaluation With Advanced Measurement (STREAM) Study: Implementation of the PROMIS Toolbox Within an Orthopaedic Trauma Clinical Trials Consortium.

LEVEL OF EVIDENCE: Prognostic Level II.

Dual study describing patient-driven harm reduction goal-setting among people experiencing homelessness and alcohol use disorder.

Two recent randomized controlled efficacy trials showed that harm-reduction treatment for alcohol use disorder (AUD)-or patient-driven treatment that does not require abstinence and instead supports decreased alcohol-related harm and improved quality of life (QoL)-is efficacious for adults experiencing homelessness and AUD. The present study provides qualitative and quantitative analysis of one component of harm-reduction treatment, participants' harm-reduction goal-setting, within these two trials. Aims of this secondary, dual-trial study (Trial 1 N = 208, Trial 2 N = 86) were to describe participant-generated harm-reduction goals and determine whether aspects of harm-reduction goal-setting predict treatment outcomes. Across both trials, qualitative findings indicated improving QoL, meeting basic needs, improving physical and mental health, and changing drinking behavior were participants' top four goals. Only 2%-6% of goals centered on attaining alcohol abstinence. Regarding quantitative findings, Trial 1 showed statistically significant increases in goals generation over the course of treatment, while proportion of achieved goals stayed constant. In Trial 2, number of goals generated remained constant, while proportion of goals achieved increased. Trial 2 findings showed greater goal generation over time was associated with better physical health-related QoL, and drinking-related goals predicted improved alcohol outcomes. Overall, this secondary, dual-trial study suggests patient-driven goal-setting in harm-reduction treatment is feasible: Participants generated diverse, personalized, and clinically relevant goals. This study built on positive efficacy trial findings, indicating participants' generation of goals was associated with improved treatment outcomes. More research is needed to further understand more nuanced relationships between harm-reduction goal-setting and treatment outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Definitions of Frailty in Qualitative Research: A Qualitative Systematic Review.

The purpose of this qualitative systematic review was to examine how frailty was conceptually and operationally defined for participant inclusion in qualitative research focused on the lived experience of frailty in community-living frail older adults. Search of six electronic databases, 1994-2019, yielded 25 studies. Data collection involved extracting the definition of frailty from the study aim, background, literature review, methods, and sampling strategy in each research study. Quality appraisal indicated that 13 studies (52%) demonstrated potential researcher bias based on insufficient information about participant recruitment, sampling, and relationship between the researcher and participant. Content analysis and concept mapping were applied for data synthesis. Although frailty was generally defined as a multidimensional, biopsychosocial construct with loss of resilience and vulnerability to adverse outcomes, most studies defined the study population based on older age and physical impairments derived from subjective assessment by the researcher, a healthcare professional, or a family member. However, 13 studies (52%) used objective or performance-based quantitative measures to classify participant frailty. There was no consistency across studies in standardized measures or objective assessment of frailty. Synthesis of the findings yielded four themes: Time, Vulnerability, Loss, and Relationships. The predominance of older age and physical limitations as defining characteristics of frailty raises questions about whether participants were frail, since many older adults at advanced age and with physical limitations are not frail. Lack of clear criteria to classify frailty and reliance on subjective assessment introduces the risk for bias, threatens the validity and interpretation of findings, and hinders transferability of findings to other contexts. Clear frailty inclusion and exclusion criteria and a standardized approach in the reporting of how frailty is conceptually and operationally defined in study abstracts and the methodology used is necessary to facilitate dissemination and development of metasynthesis studies that aggregate qualitative research findings that can be used to inform future research and applications in clinical practice to improve healthcare.

Content Analysis of Health Concerns among Housing First Residents with a History of Alcohol Use Disorder.

Previous research has utilized survey and administrative data to document health problems among Housing First (HF) residents; however, little is known about residents' personal perspectives on their health. The purpose of this study was to utilize conventional content analysis to analyze health-related concerns among HF residents with histories of alcohol use disorder. Between June and December 2013, we interviewed 44 adults who had histories of chronic homelessness and alcohol use disorder and were residing in single-site HF in Seattle, Washington. Responses centered on five primary topics: alcohol-related harm, perceived health vulnerability, concern for fellow residents' health, end of life, and health and safety promotion. HF residents experience complex alcohol-exacerbated health difficulties and existing health services may not meet the needs of those whose health is particularly compromised. Considering that HF facilitates aging in place, end-of-life care and grief counseling should be integrated into HF services.

Combining behavioral harm-reduction treatment and extended-release naltrexone for people experiencing homelessness and alcohol use disorder in the USA: a randomised clinical trial.

BACKGROUND: The rate of alcohol-related mortality in people experiencing homelessness and alcohol use disorder is high and necessitates accessible and effective treatment for alcohol use disorder. However, typical abstinence-based treatments do not optimally engage this population. Recent studies have shown that harm-reduction treatment, which does not require abstinence, but instead aims to incrementally reduce alcohol-related harm and improve health-related quality of life, is acceptable to and effective for this population. The aim of this study was to test the efficacy of combined pharmacological and behavioural harm-reduction treatment for alcohol use disorder (HaRT-A) in people experiencing homelessness and alcohol use disorder. METHODS: This randomised clinical trial was done at three community-based service sites (low-barrier shelters and housing programmes) in Seattle (WA, USA). Eligible participants were adults (aged 21-65 years) who met the DSM-IV-TR criteria for alcohol use disorder and who experienced homelessness in the past year. Participants were randomly assigned (1:1:1:1) by permuted block randomisation, stratified by site, to receive either HaRT-A plus intramuscular injections of 380 mg extended-release naltrexone (XR-NTX; HaRT-A plus XR-NTX group); HaRT-A plus placebo injection (HaRT-A plus placebo group); HaRT-A alone (HaRT-A alone group); or community-based supportive services as usual (services-as-usual control group). Patients assigned to receive HaRT-A attended sessions at baseline (week 0) and in weeks 1, 4, 8, and 12. XR-NTX and placebo injections were administered in weeks 0, 4, and 8. During the study, participants, interventionists, and investigators were masked to group assignment in the two injection arms. All participants were invited to follow-up assessments at weeks 4, 8, 12, 24, and 36. The primary outcomes were self-reported alcohol use quantity (ie, alcohol quantity consumed on peak drinking occasion, as measured with the Alcohol Quantity Use Assessment questionnaire) and frequency (measured with the Addiction Severity Index), alcohol-related harm (measured with the Short Inventory of Problems-2R questionnaire), and physical and mental health-related quality of life (measured with the Short Form-12 survey). Using piecewise growth modelling and an intention-to-treat model, we compared the effects of the three active treatment groups with the services-as-usual control group, and the HaRT-A plus XR-NTX group with the HaRT-A plus placebo group, over the 12-week treatment course and during the 24 weeks following treatment withdrawal. Safety analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT01932801. FINDINGS: Between Oct 14, 2013, and Nov 30, 2017, 417 individuals experiencing homelessness and alcohol use disorder were screened, of whom 308 were eligible and randomly assigned to the HaRT-A plus XR-NTX group (n=74), the HaRT-A plus placebo group (n=78), the HaRT-A alone group (n=79), or the services-as-usual control group (n=77). Compared with the services-as-usual control group, the HaRT-A plus XR-NTX group showed significant improvements from baseline to 12 weeks post-treatment across four of the five primary outcomes: peak alcohol quantity (linear B -0·48 [95% CI -0·79 to -0·18] p=0·010; full model Cohen's d=-0·68), alcohol frequency (linear B -4·42 [-8·09 to -0·76], p=0·047; full model Cohen's d=-0·16), alcohol-related harm (linear B -2·22 [-3·39 to -1·06], p=0·002; full model Cohen's d=-0·56), and physical health-related quality of life (linear B 0·66 [0·23 to 1·10], p=0·012; full model Cohen's d=0·43). Compared with the services-as-usual control group, the HaRT-A plus placebo group showed significant improvements in three of the five primary outcomes: peak alcohol quantity (linear B -0·41 [95% CI -0·67 to -0·15] p=0·010; full model Cohen's d=-0·23), alcohol frequency (linear B -5·95 [-9·72 to -2·19], p=0·009; full model Cohen's d=-0·13), and physical health-related quality of life (linear B 0·53 [0·09 to 0·98], p=0·050; full model Cohen's d=0·35). Compared with the services-as-usual control group, the HaRT-A alone group showed significant improvements in two of the five primary outcomes: alcohol-related harm (linear B -1·58 [95% CI -2·73 to -0·42] p=0·025; full model Cohen's d=-0·40) and physical health-related quality of life (linear B 0·63 [0·18 to 1·07], p=0·020; full model Cohen's d=0·41). After treatment discontinuation at 12 weeks, the active treatment groups plateaued, whereas the services-as-usual group showed improvements. Thus, during the post-treatment period (weeks 12 to 36), the services-as-usual control group showed greater reductions in alcohol-related harm compared with both the HaRT-A plus XR-NTX group (linear B 0·96 [0·24 to 1·67], p=0·028; full model Cohen's d=0·24) and the HaRT-A alone group (linear B 1·02 [0·35 to 1·70], p=0·013; full model Cohen's d=0·26). During the post-treatment period, the services-as-usual control group significantly improved on mental health-related quality of life compared with the HaRT-A alone group (linear B -0·46 [-0·79 to -0·12], p=0·024; full model Cohen's d=-0·28), and on physical health-related quality of life compared with the HaRT-A plus XR-NTX group (linear B -0·42 [-0·67 to -0·17], p=0·006; full model Cohen's d=-0·27), the HaRT-A plus placebo group (linear B -0·42 [-0·69 to -0·15], p=0·009; full model Cohen's d=-0·27), and the HaRT-A alone group (linear B -0·47 [-0·72 to -0·22], p=0·002; full model Cohen's d=-0·31). For all other primary outcomes, there were no significant linear differences between the services-as-usual and active treatment groups. When comparing the HaRT-A plus placebo group with the HaRT-A plus XR-NTX group, there were no significant differences for any of the primary outcomes. Missing data analysis indicated that participants were more likely to drop out in the services-as-usual control group than in the active treatment groups; however, primary outcome findings were found to be robust to attrition. Participants in the HaRT-A plus XR-NTX, HaRT-A plus placebo, and HaRT-A alone groups were not more likely to experience adverse events than those in the services-as-usual control group. INTERPRETATION: Compared with existing services, combined pharmacological and behavioural harm-reduction treatment resulted in decreased alcohol use and alcohol-related harm and improved physical health-related quality of life during the 12-week treatment period for people experiencing homelessness and alcohol use disorder. Although not as consistent, there were also positive findings for behavioural harm-reduction treatment alone. Considering the non-significant differences between participants receiving HaRT-A plus placebo and HaRT-A plus XR-NTX, the combined pharmacological and behavioural treatment effect cannot be attributed to XR-NTX alone. Future studies are needed to further investigate the relative contributions of the pharmacological and behavioural components of harm-reduction treatment for alcohol use disorder, and to ascertain whether a maintenance treatment approach could extend these positive outcome trajectories. FUNDING: National Institute on Alcohol Abuse and Alcoholism.