Prior cancer and risk of monoclonal gammopathy of undetermined significance: a population-based study in Iceland and Sweden.

There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with a higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore constitute a target population for MGUS screening. This two-part study is the first study to evaluate a relationship between MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio=1.10; 95% confidence interval: 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer was associated with progression of MGUS, except for myeloid malignancies which were associated with a lower risk of progression (hazard ratio=0.37; 95% confidence interval: 0.16-0.89; P=0.028). Our findings indicate that a prior cancer is not a significant etiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.

Demonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV.

BACKGROUND: Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables. OBJECTIVE: To examine LA-ART in a population of PWH that includes those with viremia. DESIGN: Observational cohort study. SETTING: Urban academic safety-net HIV clinic. PATIENTS: Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use. INTERVENTION: Demonstration project of long-acting injectable CAB-RPV. MEASUREMENTS: Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data. RESULTS: Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks. LIMITATION: Single-site study. CONCLUSION: This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed. PRIMARY FUNDING SOURCE: National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable Human Immunodeficiency Virus (HIV) Viremia in an Urban HIV Clinic.

BACKGROUND: Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART. METHODS: Ward 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. RESULTS: Between June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days. CONCLUSIONS: This small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.

[Training of Icelandic rural doctors in managing trauma and acute illness].

INTRODUCTION: Rural medicine is in many ways different from urban primary care. In addition to providing primary care for a population, the rural doctor is tasked with the initial evaluation and stabilization of all emergencies usually managed by an Emergency Department in urban areas. The goal of this study was to assess rural doctors' in Iceland attendance of courses in Emergency Medicine (EM), how rural doctors grade their own ability to respond to emergencies and evaluate their Continuous Medical Education (CME) within the field of EM. MATERIALS AND METHODS: In this descriptive cross-sectional study, all rural general practitioners (GP) in Iceland with at least two years of experience post foundation training and who practiced at least a quarter of every year outside the capital area were surveyed using an electronic questionnaire. T-test and qi-square test were used for analysis and significance determined if p<0.05. RESULTS: The survey was sent to 84 doctors with 47 (56%) completing the survey. Over 90% of the participants reported having completed a course in Advanced Life Support (ALS) but only 18% had completed a course in prehospital EM specifically designed for this group of doctors. Over half of the participants considered themselves to have good training to perform 7 out of 11 surveyed emergency procedures. Over 40% of participants considered it necessary to improve their CME in 7 out of 10 categories of EM. The majority of rural GPs considered shortage of doctors in the rural environment a significant factor limiting their CME. CONCLUSIONS: The majority of rural doctors in Iceland consider themselves to have a good training to provide initial EM care in their community. Efforts to improve their training in this field of medicine should focus on scene safety and working in the prehospital setting, pediatrics, labor and deliveries and gynecological emergencies. Rural doctors need to have access to appropriate EM training courses.

Impact of Multicomponent Support Strategies on Human Immunodeficiency Virus Virologic Suppression Rates During Coronavirus Disease 2019: An Interrupted Time Series Analysis.

BACKGROUND: After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. METHODS: We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. RESULTS: Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5). CONCLUSIONS: The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

Examining the Impact of the Golden Compass Clinical Care Program for Older People with HIV: A Qualitative Study.

The combined burden of geriatric conditions, comorbidities, and HIV requires a model of HIV care that offers a comprehensive clinical approach with people 50 years or older with HIV. Golden Compass is an outpatient, multidisciplinary HIV-geriatrics program with an onsite HIV geriatrician, cardiologist, pharmacist, and social worker, offering specialist referrals, care navigation, and classes on improving functional status and cognition. Participants (13 patients and 11 primary care providers) were recruited using a non-probability sampling method to participate in semi-structured interviews on the perceived impact of Golden Compass on care delivered to older people with HIV. Interviews were transcribed verbatim and framework analysis used to analyze the transcripts. The perceived impacts of Golden Compass by patients and providers were organized by the Compass points (Northern: Heart and Mind, Eastern: Bones and Strength, Southern: Navigation and Network, Western: Dental, Hearing, and Vision). Overall, patients valued the focus on functional health and whole-person care, leading to greater trust in the ability of providers. Providers gained new skills through the geriatrics, cardiology and/or pharmacist consultations. The HIV-geriatrics specialty approach of Golden Compass improved functional ability and quality of life for older adults with HIV. Few integrated care programs for older people with HIV have been evaluated. This study adds to the limited literature demonstrating high patient and provider satisfaction with a HIV-care model that incorporated principles of geriatric medicine emphasizing a comprehensive approach to sustaining functional ability and improving quality of life.

Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliacea.

Chemical investigation of the marine bryozoan Flustra foliacea collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W (1-7) and flustraminols C-H (8-13), and two new imidazole alkaloids, flustrimidazoles A and B (14 and 15), together with 12 previously described compounds (16-27). Their structures were established by detailed spectroscopic analysis using 1D and 2D NMR and HRESIMS. Structure 2 was verified by calculations of the 13C and 1H NMR chemical shifts using density functional theory. The relative and absolute configurations of the new compounds were elucidated on the basis of coupling constant analysis, NOESY, [α]D, and ECD spectroscopic data, in addition to chemical derivatization. The compounds were tested for in vitro anti-inflammatory activity using a dendritic cell model. Eight compounds (1, 3, 5, 13, 16, 18, 26, and 27) decreased dendritic cell secretion of the pro-inflammatory cytokine IL-12p40, and two compounds (4 and 14) increased secretion of the anti-inflammatory cytokine IL-10. Deformylflustrabromine B (27) showed the most potent anti-inflammatory effect (IC50 2.9 µM). These results demonstrate that F. foliacea from Iceland expresses a broad range of brominated alkaloids, many without structural precedents. The potent anti-inflammatory activity in vitro of metabolite 27 warrants further investigations into its potential as a lead for inflammation-related diseases.

Evaluating an Innovative eLearning Pain Education Interprofessional Resource: A Pre-Post Study.

Objective: The challenges of moving the pain education agenda forward are significant worldwide, and resources, including online, are needed to help educators in curriculum development. Online resources are available but with insufficient evaluation in the context of prelicensure pain education. Therefore, this pre-post study examined the impact of an innovative eLearning model: the Pain Education Interprofessional Resource (PEIR) on usability, pain knowledge, beliefs, and understanding of pain assessment skills including empathy. Methods: Participants were students (N = 96) recruited from seven prelicensure health sciences programs at the University of Toronto. They worked through three multifaceted modules, developed by an interprofessional team, that followed a patient with acute to persistent postsurgical pain up to one year. Module objectives, content, and assessment were based on International Association for the Study of Pain Pain Curricula domains and related pain core competencies. Multimedia interactive components focused on pain mechanisms and key pain care issues. Outcome measures included previously validated tools; data were analyzed in SPSS. Online exercises provided concurrent individual feedback throughout all modules. Results: The completion rate for modules and online assessments was 100%. Overall usability scores (SD) were strong 4.27/5 (0.56). On average, pain knowledge scores increased 20% (P < 0.001). The Pain Assessment Skills Tool was sensitive to differences in student and expert pain assessment evaluation ratings and was useful as a tool to deliver formative feedback while engaged in interactive eLearning about pain assessment. Conclusions: PEIR is an effective eLearning program with high student ratings for educational design and usability that significantly improved pain knowledge and understanding of collaborative care.

The Pain Interprofessional Curriculum Design Model.

Objective: Although the University of Toronto Centre for the Study of Pain has successfully implemented an Interfaculty Pain Curriculum since 2002, we have never formalized the process in a design model. Therefore, our primary aim was to develop a model that provided an overview of dynamic, interrelated elements that have been important in our experience. A secondary purpose was to use the model to frame an interactive workshop for attendees interested in developing their own pain curricula. Methods: The faculties from Dentistry, Medicine, Nursing, Occupational Therapy, Pharmacy, and Physical Therapy met to develop the model components. Discussion focused on patient-centered pain assessment and management in an interprofessional context, with pain content being based on the International Association for the Study of Pain-Interprofessional Pain Curriculum domains and related core pain competencies. Profession-specific requirements were also considered, including regulatory/course requirements, level of students involved, type of course delivery, and pedagogic strategies. Results: The resulting Pain Interprofessional Curriculum Design Model includes components that are dynamic, competency-based, collaborative, and interrelated. Key questions important to developing curricular components guide the process. The Model framed two design workshops with very positive responses from international and national attendees. Conclusions: The Pain Interprofessional Curriculum Design Model is based on established pain curricula and related competencies that are relevant to all health science students at the prelicensure (entry-to-practice) level. The model has been developed from our experience, and the components resonated with workshop attendees from other regions. This Model provides a basis for future interventions in curriculum design and evaluation.

Lipophilic fractions from the marine sponge Halichondria sitiens decrease secretion of pro-inflammatory cytokines by dendritic cells and decrease their ability to induce a Th1 type response by allogeneic CD4+ T cells.

CONTEXT: Halichondria (Halichondriidae) marine sponges contain components possessing various biological activities, but immunomodulation is not among the ones reported. OBJECTIVE: This study evaluated the immunomodulatory effects of fractions/compounds from Halichondria sitiens Schmidt. MATERIALS AND METHODS: Crude dichloromethane/methanol extracts of H. sitiens were subjected to various chromatographic techniques to obtain fractions/compounds with immunomodulatory activity, using bioassay-guided isolation. The effects of the fractions/compounds were determined by measuring secretion of cytokines and expression of surface molecules by dendritic cells (DCs) and their ability to stimulate and modify cytokine secretion by allogeneic CD4+ T cells. The bioactive fractions were chemically analyzed to identify the immunomodulatory constituents by 1D, 2D NMR, and HRMS data. RESULTS: Several lipophilic fractions from H. sitiens at 10 µg/mL decreased secretion of the pro-inflammatory cytokines IL-12p40 and IL-6 by the DCs, with maximum inhibition being 64% and 25%, respectively. In addition, fractions B3b3F and B3b3J decreased the ability of DCs to induce T cell secretion of IFN-γ. Fraction B3b3 induced morphological changes in DCs, characterized by extreme elongation of dendrites and cell clustering. Chemical screening revealed the presence of glycerides and some minor unknown constituents in the biologically active fractions. One new glyceride, 2,3-dihydroxypropyl 2-methylhexadecanoate (1), was isolated from one fraction and two known compounds, 3-[(1-methoxyhexadecyl)oxy]propane-1,2-diol (2) and monoheptadecanoin (3), were identified in another, but none of them had immunomodulatory activity. DISCUSSION AND CONCLUSIONS: These results demonstrate that several lipophilic fractions from H. sitiens have anti-inflammatory effects on DCs and decrease their ability to induce a Th1 type immune response.

Identifying Implementation Determinants and Strategies for Long-Acting Injectable Cabotegravir-Rilpivirine in People With HIV Who Are Virally Unsuppressed.

BACKGROUND: Early evidence suggests long-acting injectable cabotegravir and rilpivirine (LA-CAB/RPV) may be beneficial for people with HIV (PWH) who are unable to attain viral suppression (VS) on oral therapy. Limited guidance exists on implementation strategies for this population. SETTING: Ward 86, a clinic serving publicly insured PWH in San Francisco. METHODS: We describe multilevel determinants of and strategies for LA-CAB/RPV implementation for PWH without VS, using the Consolidated Framework for Implementation Research. To assess patient and provider-level determinants, we drew on pre-implementation qualitative data. To assess inner and outer context determinants, we undertook a structured mapping process. RESULTS: Key patient-level determinants included perceived ability to adhere to injections despite oral adherence difficulties and care engagement challenges posed by unmet subsistence needs; strategies to address these determinants included a direct-to-inject approach, small financial incentives, and designated drop-in days. Provider-level determinants included lack of time to obtain LA-CAB/RPV, assess injection response, and follow-up late injections; strategies included centralizing eligibility review with the clinic pharmacist, a pharmacy technician to handle procurement and monitoring, regular multidisciplinary review of patients, and development of a clinic protocol. Ward 86 did not experience many outer context barriers because of rapid and unconstrained inclusion of LA-CAB/RPV on local formularies and ability of its affiliated hospital pharmacy to stock the medication. CONCLUSIONS: Multilevel strategies to support LA-CAB/RPV implementation for PWH without VS are required, which may necessitate additional resources in some settings to implement safely and effectively. Advocacy to eliminate outer-context barriers, including prior authorizations and specialty pharmacy restrictions, is needed.

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Background: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. Methods: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. Results: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. Conclusions: In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Pragmatic randomized trial of a pre-visit intervention to improve the quality of telemedicine visits for vulnerable patients living with HIV.

INTRODUCTION: The COVID-19 pandemic has required a shift of many routine primary care visits to telemedicine, potentially widening disparities in care access among vulnerable populations. In a publicly-funded HIV clinic, we aimed to evaluate a pre-visit phone-based planning intervention to address anticipated barriers to telemedicine. METHODS: We conducted a pragmatic randomized controlled trial of patients scheduled for a phone-based HIV primary care visit at the Ward 86 HIV clinic in San Francisco from 15 April to 15 May 2020. Once reached by phone, patients were randomized to either have a structured pre-visit planning intervention to address barriers to an upcoming telemedicine visit versus a standard reminder call. The primary outcome was telemedicine visit attendance. RESULTS: Of 476 scheduled telemedicine visits, 280 patients were reached by a pre-visit call to offer enrollment. Patients were less likely to be reached if virally unsuppressed (odds ratio (OR) 0.11, 95% confidence intervals (CI) 0.03-0.48), CD4 < 200 (OR 0.24, 95% CI 0.07-0.85), or were homeless (OR 0.24, 95% CI 0.07-0.87). There was no difference between intervention and control in scheduled visit attendance (83% v. 78%, OR 1.38, 95% CI 0.67-2.81). CONCLUSIONS: A structured phone-based planning call to address barriers to telemedicine in a public HIV clinic was less likely to reach patients with poorly-controlled HIV and patients experiencing homelessness, suggesting additional interventions may be needed in this population to ensure access to telemedicine-based care. Among patients reachable by phone, telemedicine visit attendance was high and not improved with a structured pre-visit intervention, suggesting that standard reminders may be adequate in this population.

Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study.

Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG.

Prevalence of smoldering multiple myeloma based on nationwide screening.

Smoldering multiple myeloma (SMM) is an asymptomatic precursor to multiple myeloma. Here we define the epidemiological characteristics of SMM in the general population in Iceland. The iStopMM study (ClinicalTrials.gov ID: NCT03327597 ) is a nationwide screening study for multiple myeloma precursors where all residents in Iceland 40 years or older were invited to participate. SMM was defined as 10-60% bone marrow plasma cells and/or monoclonal (M) protein concentration ≥3 g dl-1, in the absence of myeloma-defining events. Of the 80,759 who gave informed consent to participate, 75,422 (93%) were screened. The prevalence of SMM in the total population was 0.53% (95% confidence interval (CI) = 0.49-0.57%) in individuals 40 years or older. In men and women, the prevalence of SMM was 0.67% (95% CI = 0.62-0.73%) and 0.39% (95% CI = 0.35-0.43%), respectively; it increased with age in both sexes. For the 193 individuals with SMM, median age was 70 years (range 44-92 years) and 60% were males. The mean M protein concentration of individuals with SMM was 0.62 g dl-1 (range 0.01-3.5 g dl-1) and 73% had 11-20% bone marrow plasma cell infiltration. The high prevalence of SMM has implications for future treatment policies in multiple myeloma as the evidence supporting treatment initiation at the SMM stage is emerging.

Determining hemodilution in diagnostic bone marrow aspirated samples in plasma cell disorders by next-generation flow cytometry: Proposal for a bone marrow quality index.

Hemodilution of bone marrow (BM) aspirates is a limitation of multiparameter flow cytometry (MFC) in plasma cell disorders. There is a need for a validated approach for assessing sample quality and the distribution of non-plasma cell BM populations by MFC could provide a solution. We evaluated BM-associated cell populations, assessed by next-generation flow cytometry (NGF) and white blood cell (WBC) count in 351 BM aspirated samples from 219 participants with plasma cell disorders in the Iceland Screens, Treats, or Prevents MM study (iStopMM), as markers of hemodilution by their discriminatory ability between first and (generally more hemodiluted) second pull BM aspirated samples. The most discriminating markers were used to derive a novel BM quality index (BMQI). Nucleated red blood cells and myeloid precursors provided the greatest discriminatory ability between first vs second pull samples (area under the curve (AUC): 0.87 and 0.85, respectively), significantly better than B cell precursors (AUC = 0.64; p < 0.001), mast cells (AUC = 0.65; p < 0.001), and the BM WBC count (AUC = 0.77; p < 0.05). We generated a novel BMQI that is intrinsic to current NGF protocols, for evaluating quality of diagnostic BM samples and suggest the use of a BMQI scoring system for interpreting results and guiding appropriate actions.

Evaluation of multiple myeloma measurable residual disease by high sensitivity flow cytometry: An international harmonized approach for data analysis.

BACKGROUND: Multiple myeloma (MM) measurable residual disease (MRD) evaluated by flow cytometry is a surrogate for progression-free and overall survival in clinical trials. However, analysis and reporting between centers lack uniformity. We designed and evaluated a consensus protocol for MM MRD analysis to reduce inter-laboratory variation in MM MRD reporting. METHODS: Seventeen participants from 13 countries performed blinded analysis of the same eight de-identified flow cytometry files from patients with/without MRD using their own method (Stage 1). A consensus gating protocol was then designed following survey and discussions, and the data re-analyzed for MRD and other bone marrow cells (Stage 2). Inter-laboratory variation using the consensus strategy was reassessed for another 10 cases and compared with earlier results (Stage 3). RESULTS: In Stage 1, participants agreed on MRD+/MRD- status 89% and 68% of the time respectively. Inter-observer variation was high for total numbers of analyzed cells, total and normal plasma cells (PCs), limit of detection, lower limit of quantification, and enumeration of cell populations that determine sample adequacy. The identification of abnormal PCs remained relatively consistent. By consensus method, average agreement on MRD- status improved to 74%. Better consistency enumerating all parameters among operators resulted in near-unanimous agreement on sample adequacy. CONCLUSION: Uniform flow cytometry data analysis substantially reduced inter-laboratory variation in reporting multiple components of the MM MRD assay. Adoption of a harmonized approach would meet an important need for conformity in reporting MM MRD for clinical trials, and wider acceptance of MM MRD as a surrogate clinical endpoint.

Viral suppression during COVID-19 among people with HIV experiencing homelessness in a low-barrier clinic-based program.

Coronavirus disease-2019 (COVID-19) threatens to further worsen HIV outcomes among people experiencing homelessness. We conducted an interrupted time-series analysis of care engagement and viral suppression among unhoused individuals in the 'POP-UP' low-barrier, high-intensity HIV primary care program during COVID-19. Among 85 patients, care engagement and viral suppression did not decrease in the 5 months following implementation of San Francisco's 'shelter-in-place' ordinance. Low-barrier, in-person HIV care for homeless individuals may be important for maintaining HIV outcomes during COVID-19.

Evaluation of the POP-UP programme: a multicomponent model of care for people living with HIV with homelessness or unstable housing.

OBJECTIVE: Homelessness is the greatest risk factor for HIV viremia in San Francisco. Innovative care models for people with HIV (PWH) with homelessness or unstable housing (HUH) are needed to address this inequity. We developed a novel low-barrier clinic-based program for PWH-HUH in an urban safety-net clinic ('POP-UP') and report outcomes on care engagement and viral suppression. DESIGN: A prospective cohort study. SETTING: San Francisco General Hospital HIV Clinic (Ward 86). PARTICIPANTS: We enrolled PWH who are HUH, viraemic and for whom usual care is not working (at least one missed primary care appointment and at least two drop-in visits at Ward 86 in the last year). INTERVENTION: POP-UP provides drop-in comprehensive primary care, housing assistance and case management, financial incentives and patient navigation with frequent contact. MAIN OUTCOME MEASURES: We describe uptake of eligible patients into POP-UP, and cumulative incidence of antiretroviral therapy (ART) initiation, return to care and virologic suppression 6 months post-enrolment, estimated via Kaplan--Meier. RESULTS: Out of 192 referred patients, 152 were eligible, and 75 enrolled. All 75 were off ART and viraemic; 100% had a substance use disorder; and 77% had a mental health diagnosis. Over three-quarters restarted ART within 7 days of enrolment, and 91% returned for follow-up within 90 days. The cumulative incidence of viral suppression at 6 months was 55% (95% confidence interval 43-68). CONCLUSION: A novel care model for PWH-HUH demonstrates early success in engaging viraemic patients in care and improving viral suppression. Low-barrier, high-contact primary care programmes offering comprehensive services and incentives may improve outcomes for this vulnerable population.

Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.

Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.