The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023.

"It's like your days are empty and yet there's life all around": A mixed methods, multi-site study exploring boredom during and following homelessness.

PURPOSE: To identify experiences of boredom and associations with psychosocial well-being during and following homelessness. METHODS: Using a convergent, mixed-methods explanatory design, we conducted quantitative interviews with 164 participants) (n = 102 unhoused; n = 62 housed following homelessness) using a 92-item protocol involving demographic components and seven standardized measures of psychosocial well-being. A sub-sample (n = 32) was approached to participate in qualitative interviews. Data were analyzed by group (unhoused; housed). Quantitative data were analyzed using descriptive statistics designed to generate insights into boredom, meaningful activity engagement, and their associations with psychosocial well-being during and following homelessness. Qualitative data were analyzed using thematic analysis. Quantitative and qualitative findings were integrated at the stage of discussion. RESULTS: Quantitative analyses revealed small to moderate correlations between boredom and increased hopelessness (rs = .376, p < .01), increased drug use (rs = .194, p < .05), and lowered mental well-being (rs = -.366, p < .01). There were no statistically significant differences between unhoused and housed participants on any standardized measures. Hierarchical regression analyses revealed that housing status was not a significant predictor of boredom or meaningful activity engagement (p>.05). Qualitative interviews revealed profound boredom during and following homelessness imposing negative influences on mental well-being and driving substance use. CONCLUSIONS: Boredom and meaningful activity are important outcomes that require focused attention in services designed to support individuals during and following homelessness. Attention to this construct in future research, practice, and policy has the potential to support the well-being of individuals who experience homelessness, and to contribute to efforts aimed at homelessness prevention.

Effectiveness of Interventions for Meaningful Activity Participation in Homelessness: A Systematic Review.

Background. Meaningful activity participation has been identified as a key outcome of services designed to support individuals during and following homelessness. Little is known about the effectiveness of interventions for promoting this outcome. Purpose. To identify the range and effectiveness of interventions on promoting meaningful activity participation among persons with experiences of homelessness. Method. We conducted a systematic review using the Joanna Briggs Institute methodology following PRISMA guidelines including a critical appraisal and narrative synthesis. Findings. Of 12,343 titles and abstracts screened, we included 12 studies. The authors of the included studies primarily used standardized measures of meaningful activity engagement. Critical appraisal scores ranged from 50.0 to 77.8. The most common interventions evaluated in the included studies were psychosocial interventions (n = 6; 50.0%), followed by case management and housing support interventions (n = 4; 33.3%) and Housing First (n = 2; 16.7%). While several interventions demonstrated effectiveness in promoting meaningful activity participation including psychosocial and case management interventions, Housing First, Critical Time Intervention, and a peer support intervention were found to be ineffective for promoting engagement in meaningful activity. Conclusion. Few intervention studies have been conducted that demonstrate effectiveness for promoting participation in meaningful activity for individuals during and following homelessness. Occupational therapy researchers and practitioners can build on existing evidence by developing and evaluating novel approaches by co-designing interventions in collaboration with persons with experiences of homelessness and service providers.

Reversion of breast epithelial polarity alterations caused by obesity.

Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.

Meaningful Activity, Psychosocial Wellbeing, and Poverty During COVID-19: A Longitudinal Study.

Background: Only a few studies have explored experiences of meaningful activity and associations with psychosocial wellbeing during COVID-19. None reflect a Canadian context or focus on persons living in poverty. Purpose: To identify experiences and associations between meaningful activity and psychosocial wellbeing for persons living in poverty during the first year of COVID-19. Method: We delivered a quantitative survey at three time points during the first year of the pandemic supplemented by qualitative interviews at Time(T) 1 and 1 year later at T3. Findings: One hundred and eight participants completed T1 surveys, and 27 participated in qualitative interviews. Several statistically significant correlations between indices of meaningful activity engagement and psychosocial wellbeing were identified across T1-T3. Meaningful activity decreased from T1-T3 [X2 (2, n = 49) = 9.110, p < .05], with a significant decline from T2-T3 (z = -3.375, p < .001). In T1 qualitative interviews, participants indicated that physical distancing exacerbated exclusion from meaningful activities early in the pandemic. At T3 (1 year later), they described how classist and ableist physical distancing policies layered additional burdens on daily life. Implications: Meaningful activity engagement and psychosocial wellbeing are closely associated and need to be accounted for in the development of pandemic policies that affect persons living in low income. Occupational therapists have a key role in pandemic recovery.

"I can't remember the last time I was comfortable about being home": lived experience perspectives on thriving following homelessness.

PURPOSE: Strategies for preventing and ending homelessness are frequently measured by their effectiveness on indices of tenancy sustainment. To shift this narrative, we conducted research to identify what is needed to "thrive" following homelessness from the perspectives of persons with lived experience in Ontario, Canada. METHODS: Conducted in the context of a community-based participatory research study aimed at informing the development of intervention strategies, we interviewed 46 persons living with mental illness and/or substance use disorder [n = 25 (54.3%) unhoused; n = 21 (45.7%) housed following homelessness] using qualitative interviews. A subsample of 14 participants agreed to engage in photovoice interviews. We analysed these data abductively using thematic analysis informed by health equity and social justice. RESULTS: Participants described experiences of "living in a state of lack" following homelessness. This essence was expressed through four themes: 1) housing as part one of the journey to home; 2) finding and keeping "my people"; 3) meaningful activity as critical for thriving following homelessness; and 4) struggling to access mental health supports in the context of challenging circumstances. CONCLUSIONS: Individuals struggle to thrive following homelessness in the context of insufficient resources. There is a need to build on existing interventions to address outcomes beyond tenancy sustainment.

Effectiveness of Suicide Safety Planning Interventions: A Systematic Review Informing Occupational Therapy.

Background. Suicide safety planning (SSP) is a suicide prevention approach that involves developing a collaborative plan between a service provider such as an occupational therapist and a person who is at risk of suicide. Purpose. To synthesize effectiveness studies on SSP. Method. Using the Joanna Briggs Institute methodology, we conducted a systematic review of effectiveness studies including a: (1) title and abstract screening; (2) full-text review; (3) critical appraisal; and (4) narrative synthesis. Findings. We included 22 studies. Critical appraisal scores ranged from 38.5 to 92.3 (m = 63.7). The types of interventions included were: standard and enhanced SSP (n = 11); electronically delivered SSP (n = 5); and SSP integrated with other approaches (n = 6). Only three studies identified meaningful activity as a component of SSP. Evidence across a range of studies indicates that SSP is effective for reducing suicide behavior (SB) and ideation (SI). While some studies have demonstrated effectiveness for reducing symptoms of mental illness, promoting resilience and service use, the number of studies exploring these outcomes is currently limited. Implications. Occupational therapists support individuals expressing SI, and SSP is a necessary skill for practice.

'We stick people in a house and say okay, you're housed. The problem is solved': A qualitative study of service provider and organisational leader perspectives on thriving following homelessness.

Research aimed at identifying and evaluating approaches to homelessness has predominately focused on strategies for supporting tenancy sustainment. Fewer studies focus on strategies for enabling thriving following homelessness, and the perspectives of service providers and organisational leaders (SPOL) on this topic are rare. We conducted this study in the context of a community-based participatory research project in two cities in Ontario, Canada. This research was aimed at identifying the strengths and challenges of existing supports in enabling thriving following homelessness, followed by co-designing a novel intervention alongside persons with lived experience of homelessness (PWLEH) and SPOL. The current study presents the findings of interviews conducted in 2020-2021 with SPOL in organisations serving PWLEH. We interviewed 60 individuals including service providers (n = 38; 63.3%) and organisational leaders (n = 22; 36.7%) using semi-structured qualitative interviews. Interviews were conducted and recorded on Zoom to align with physical distancing protocols associated with the COVID-19 pandemic. Recordings were transcribed verbatim and analysed abductively informed by the lenses of social justice and health equity. The essence of our findings is represented by a quote from a research participant: 'We stick people in a house and say okay, you're housed. The problem is solved'. This essence was expressed through five themes: (1) stuck in a system that prevents thriving, (2) substance use as an important coping strategy that prevents tenancy sustainment and thriving, (3) the critical importance of targeting community integration following homelessness, (4) incorporating peer expertise as imperative and (5) people need to be afforded options in selecting housing and services following homelessness. Our findings indicate that SPOL envision possibilities of thriving following homelessness yet are embedded within a system that often prevents them from supporting individuals who are leaving homelessness to do so. Research, practice and policy implications are discussed.

DNA damage reduces heterogeneity and coherence of chromatin motions.

Chromatin motions depend on and may regulate genome functions, in particular the DNA damage response. In yeast, DNA double-strand breaks (DSBs) globally increase chromatin diffusion, whereas in higher eukaryotes the impact of DSBs on chromatin dynamics is more nuanced. We mapped the motions of chromatin microdomains in mammalian cells using diffractive optics and photoactivatable chromatin probes and found a high level of spatial heterogeneity. DNA damage reduces heterogeneity and imposes spatially defined shifts in motions: Distal to DNA breaks, chromatin motions are globally reduced, whereas chromatin retains higher mobility at break sites. These effects are driven by context-dependent changes in chromatin compaction. Photoactivated lattices of chromatin microdomains are ideal to quantify microscale coupling of chromatin motion. We measured correlation distances up to 2 µm in the cell nucleus, spanning chromosome territories, and speculate that this correlation distance between chromatin microdomains corresponds to the physical separation of A and B compartments identified in chromosome conformation capture experiments. After DNA damage, chromatin motions become less correlated, a phenomenon driven by phase separation at DSBs. Our data indicate tight spatial control of chromatin motions after genomic insults, which may facilitate repair at the break sites and prevent deleterious contacts of DSBs, thereby reducing the risk of genomic rearrangements.

Characterization and implementation of a miniature X-ray system for live cell microscopy.

The study of radiation effects on biological tissues is a diverse field of research with direct applications to improve human health, in particular in the contexts of radiation therapy and space exploration. Understanding the DNA damage response following radiation exposure, which is a key determinant for mutagenesis, requires reproducible methods for delivering known doses of ionizing radiation (IR) in a controlled environment. Multiple IR sources, including research X-ray and gamma-ray irradiators are routinely used in basic and translational research with cell and animal models. These systems are however not ideal when a high temporal resolution is needed, for example to study early DNA damage responses with live cell microscopy. Here, we characterize the dose rate and beam properties of a commercial, miniature, affordable, and versatile X-ray source (Mini-X). We describe how to use Mini-X on the stage of a fluorescence microscope to deliver high IR dose rates (up to 29 Gy/min) or lower dose rates (≤ 0.1 Gy/min) in live cell imaging experiments. This article provides a blueprint for radiation biology applications with high temporal resolution, with a step-by-step guide to implement a miniature X-ray system on an imaging platform, and the information needed to characterize the system.

Elevated leptin disrupts epithelial polarity and promotes premalignant alterations in the mammary gland.

Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in mammary glands. Here we show that mice with diet-induced obesity display mislocalization of Par3, a regulator of cellular junctional complexes defining mammary epithelial polarity. We found that epithelial polarity loss also occurs in a 3D coculture system that combines acini with human mammary adipose tissue, and establish that a paracrine effect of the tissue adipokine leptin causes loss of polarity by overactivation of the PI3K/Akt pathway. Leptin sensitizes non-neoplastic cells to proliferative stimuli, causes mitotic spindle misalignment, and expands the pool of cells with stem/progenitor characteristics, which are early steps for cancer initiation. We also found that normal breast tissue samples with high leptin/adiponectin transcript ratio characteristic of obesity have an altered distribution of apical polarity markers. This effect is associated with increased epithelial cell layers. Our results provide a molecular basis for early alterations in epithelial architecture during obesity-mediated cancer initiation.

Radial Profile Analysis of Epithelial Polarity in Breast Acini: A Tool for Primary (Breast) Cancer Prevention.

Preventing cancer is vastly better than treating the disease in terms of a patient's quality of life and healthcare costs. Yet, to screen for chemopreventative drugs or evaluate interventions aimed at lowering cancer risk, quantitative readouts of risk are needed. In the breast and in other organs of epithelial origin, apical-basal polarity is key to homeostasis and is one of the first tissue characteristics lost during cancer initiation. Therefore, apical-basal polarity may be leveraged as an "architectural" determinant of cancer risk. A classic approach to quantify the localization of epithelial polarity markers is visual scoring at the microscope by trained investigators. This approach is time-intensive and limited to low throughput. To increase the speed, accuracy, and scoring volume, we developed an algorithm that essentially replaces the human eye to objectively quantify epithelial polarity in microscopy images of breast glandular units (acini). Acini in culture are identified based on a nuclear stain and the corresponding masks are divided into concentric terraces of equal width. This positional information is used to calculate radial intensity profiles (RP) of polarity markers. Profiles with a steep slope represent polarized structures, whereas more horizontal curves are indicative of non-polarized acini. To compare treatment effects, RP curves are integrated into summary values of polarity. We envision applications of this method for primary cancer prevention research with acini organoids, specifically (1) to screen for chemoprevention drugs, (2) for toxicological assessment of suspected carcinogens and pharmacological hit compounds, and (3) for personalized evaluation of cancer risk and risk-reducing interventions. The RadialProfiler algorithm developed for the MATLAB computing environment and for users without prior informatics knowledge is publicly available on the Open Science Framework (OSF).

National Center for Health Statistics Guidelines for Analysis of Trends.

Many reports present analyses of trends over time based on multiple years of data from National Center for Health Statistics (NCHS) surveys and the National Vital Statistics System (NVSS). Trend analyses of NCHS data involve analytic choices that can lead to different conclusions about the trends. This report discusses issues that should be considered when conducting a time trend analysis using NCHS data and presents guidelines for making trend analysis choices. Trend analysis issues discussed include: choosing the observed time points to include in the analysis, considerations for survey data and vital records data (record level and aggregated), a general approach for conducting trend analyses, assorted other analytic issues, and joinpoint regression. This report provides 12 guidelines for trend analyses, examples of analyses using NCHS survey and vital records data, statistical details for some analysis issues, and SAS and SUDAAN code for specification of joinpoint regression models. Several an lytic choices must be made during the course of a trend analysis, and the choices made can affect the results. This report highlights the strengths and limitations of different choices and presents guidelines for making some of these choices. While this report focuses on time trend analyses, the issues discussed and guidelines presented are applicable to trend analyses involving other ordinal and interval variables.

Mortality among US-born and immigrant Hispanics in the US: effects of nativity, duration of residence, and age at immigration.

OBJECTIVES: We examined the effects of duration of residence and age at immigration on mortality among US-born and foreign-born Hispanics aged 25 and older. METHODS: We analyzed the National Health Interview Survey-National Death Index linked files from 1997-2009 with mortality follow-up through 2011. We used Cox proportional hazard models to examine the effects of duration of US residence and age at immigration on mortality for US-born and foreign-born Hispanics, controlling for various demographic, socioeconomic and health factors. Age at immigration included 4 age groups: <18, 18-24, 25-34, and 35+ years. Duration of residence was 0-15 and >15 years. RESULTS: We observed a mortality advantage among Hispanic immigrants compared to US-born Hispanics only for those who had come to the US after age 24 regardless of how long they had lived in the US. Hispanics who immigrated as youths (<18) did not differ from US-born Hispanics on mortality despite duration of residence. CONCLUSIONS: Findings suggest that age at immigration, rather than duration of residence, drives differences in mortality between Hispanic immigrants and the US-born Hispanic population.

Use and in-hospital mortality associated with two cardiac procedures, by sex and age: national trends, 1990-2004.

This study used data from the National Hospital Discharge Survey to examine sex- and age-specific trends in use and in-hospital mortality associated with coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) among adults age forty-five and older during 1990-2004. Although use rates for PCI increased 58 percent over the study period, CABG use rates declined. In-hospital death rates declined or stayed the same even though comorbidities increased for patients who received the procedures. PCI and CABG use rates for men were at least twice those for women, although women generally had more comorbidities and higher in-hospital death rates.

Beyond the initial indicators: lessons from the OECD Health Care Quality Indicators Project and the US National Healthcare Quality Report.

UNLABELLED: Interest in comparative quality measurement and evaluation has grown considerably over the past two decades because of factors such as the recognition of widespread variation in clinical practice, the increased availability of evidence about medical effectiveness, and increasing concern about the cost and quality of health care. This article describes and contrasts two current efforts to develop health performance reporting systems: one, an international initiative-the Health Care Quality Indicator (HCQI) Project, sponsored by the Organization for Economic Cooperation and Development (OECD); and the other, a national project-the National Healthcare Quality Report (NHQR), sponsored by the US Agency for Healthcare Quality and Research. There are a number of lessons learned from a comparison of the two efforts that are relevant for the future of each project and for other indicator-based reporting efforts in quality of health care. These lessons are discussed in the article and include: Conceptual frameworks should be established to guide the selection of indicators. Choices should be made early on in the process to focus on a wide range of clinical conditions or to report on a few priority areas. METHODS: should be developed to add and subtract indicators while maintaining a stable set of indicators to track over time. Resources should be allocated to communication strategies and how best to present data results to diverse audiences. Mechanisms should be put in place to maintain project momentum.

Measurement challenges in developing the national healthcare quality report and the national healthcare disparities report.

OBJECTIVES: The objective of this study was to describe 2 measurement challenges faced in the development of the National Healthcare Quality Report (NHQR) and the National Healthcare Disparities Report (NHDR): the use of federal data on race and ethnicity and the selection of measures of socioeconomic status (SES). METHODS: Over 30 federal and nonfederal data systems were examined to identify measures of race, ethnicity, and SES and to evaluate the characteristics and relative quality of the data. RESULTS: The availability and quality of data on race, ethnicity, and SES vary by factors such as the type of data (population or establishment based-survey, administrative/claims data, or vital statistics), the source of information (self, proxy, other, or some combination), and the transition to new federal standards. No single measure of SES could be identified, so a mix of measures is presented, including income, education, and expected source of payment (ESOP). Income relative to federal poverty level was used as the preferred SES measure from person-based surveys. Selected analyses linking hospital discharge data to annual median household income from US census data were presented for data derived from administrative data systems. Educational attainment was the variable used for examining SES using data from the Vital Statistics System. CONCLUSIONS: The first NHQR and NHDR maximized the presentation of data by accommodating the variation among data systems while at the same time imposing some standardization in the coding and classification of data on race, ethnicity, and SES.

Heart disease and prevention: race and age differences in heart disease prevention, treatment, and mortality.

OBJECTIVE: The objective of this study was to analyze race and age differences in the distribution of health promotion and cardiovascular screening tests, and the prevalence of serious heart disease and cardiovascular mortality in the United States. DATA SOURCES/STUDY POPULATION: Data are from 7 federal datasets represented in the first National Healthcare Quality Report and the National Healthcare Disparities Report, and include surveys, administrative and vital statistics data systems. The study analyzes blacks and whites. MEASURES: Counseling on diet and nutrition, exercise, and tobacco during an outpatient visit indicate the availability of health promotion services, and screening for high blood pressure and cholesterol represent preventive services. Hospitalizations for heart-related conditions and use of certain cardiac procedures identify serious heart disease. Deaths from coronary artery disease and stroke are the heart-related mortality measures. PRINCIPAL FINDINGS: Counseling and education services tend to occur more on outpatient visits by individuals aged 45 to 64 years than in younger age groups. Screening rates among individuals aged 45 to 64 years of approximately 90% for hypertension and 80% for high cholesterol suggest progress in early detection of cardiac risk factors. However, blacks aged 45 to 64 years are 5.6 times more likely than their white counterparts to be hospitalized for hypertension, approximately one third less likely to receive a cardiac procedure, and almost twice as likely to die of coronary heart disease. CONCLUSIONS: Although findings indicate few racial differences in health promotion services in ambulatory care or screening for cardiac risk factors, the prevalence of serious cardiovascular disease, use of cardiac procedures, and heart-related mortality suggest continuing racial disparities in heart disease.