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Background and Objectives: Ketamine is increasingly being utilized in the management of acute pain in the emergency department (ED), including for older adults, a population at increased risk of adverse effects from medications. We aimed to compare the safety and analgesic effects of high-dose (≥0.3mg/kg) to low-dose (<0.3mg/kg) intravenous (IV) ketamine among older ED patients., Methods: Multi-center, retrospective cohort study of adults ≥60years who received IV ketamine for pain between 2018 and 2021. The primary outcome was pain improvement as measured by the Numerical Rating Scale (NRS) pain score within 60min after administration. Secondary outcomes included adverse effects (early discontinuation, nausea, rescue benzodiazepines and intubation) and the need for rescue analgesia. Linear regression was used to assess the association between the change in NRS pain scores and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid., Results: A total of 130 older adults received ketamine as an analgesic (37 high-dose, 93 low-dose). Median age was 69.2years, 52 % were women, 40 % had a history of substance use disorder. Prior to ketamine, 76 % received alternate analgesics and 23 % antiemetics. Baseline mean pain score was lower in the high-dose group (6.7 vs. 8.3, difference -1.7 [95 % CI -2.6 to -0.7], p = 0.013). Change in NRS pain scores were similar between the high-dose and low-dose groups (-2.4 [95 % CI -3.6 to -1.3] vs -1.6 [95 % CI -2.2 to -0.9], p = 0.27). After adjustment for baseline pain score, the high-dose group had a larger reduction in pain scores (-1.3 [95 % CI -2.6 to -0.1], p = 0.042) and percent change of pain (-23.8 % [95 % CI -42.1 % to -5.4 %], p = 0.012). There was no significant difference in rates of rescue analgesia (35.1 % vs. 44.1 %, p = 0.35) or early discontinuation (29.7 % vs. 32.3 %, p = 0.78). Rates of adverse effects were similar., Conclusion: High-dose and low-dose ketamine reduced pain scores in older adults. High-dose ketamine led to a greater reduction in pain scores, and there was no observed difference in adverse effects or the need for rescue analgesia. One-third needed discontinuation of ketamine in both groups., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration., Methods: In part 2, participants received natalizumab (Tysabri ® ) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire., Results: A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified "requires less time in the clinic" as the reason for the SC preference., Conclusion: In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration., Clinicaltrials: GOV: NCT03689972. INFOGRAPHIC., (© 2024. The Author(s).)

Excipients are often the major component of the formulation that critically affect the dosage form, manufacturing process, product performance, stability and safety. They exert different roles and functions in a dosage form. Selecting excipients with appropriate safety and tolerability is a major hurdle in paediatric formulation development. The suitability of a particular excipient will be dependent on the context of its use with regard to the paediatric age range, acute versus chronic use, and clinical risk-benefit of the disease, active and excipient. Scientists are encouraged to apply the principle of risk-benefit to assess the suitability of excipients to the specific paediatric population. Indicative list of parameters that should be taken into consideration and hierarchy of information sources when assessing the excipients risks is provided by regulatory agencies. However, the approach to be taken and details of how the risk evaluation should be undertaken are lacking. There is a need for a systematic approach to selection of excipients and assessment of the risk of excipient exposure. The Paediatric Excipients Risk Assessment (PERA) framework developed and proposed in this paper provides a structured, systematic decision-making framework via customizable tools and processes that can help to improve the transparency and communications on the selection and justification of use of excipients in a paediatric formulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Importance: Clinicians are a key component of preexposure prophylaxis (PrEP) care. Yet, no prior studies have quantitatively investigated how PrEP adherence differs by clinician specialty., Objective: To understand the association between prescribing clinician specialty and patients not picking up (reversal/abandonment) their initial PrEP prescription., Design, Setting, and Participants: This cross-sectional study of patients who were 18 years or older used pharmacy claims data from 2015 to 2019 on new insurer-approved PrEP prescriptions that were matched with clinician data from the US National Plan and Provider Enumeration System. Data were analyzed from January to May 2022., Main Outcomes and Measures: Clinician specialties included primary care practitioners (PCPs), infectious disease (ID), or other specialties. Reversal was defined as a patient not picking up their insurer-approved initial PrEP prescription. Abandonment was defined as a patient who reversed and still did not pick their prescription within 365 days., Results: Of the 37 003 patients, 4439 (12%) were female and 32 564 (88%) were male, and 77% were aged 25 to 54 years. A total of 24 604 (67%) received prescriptions from PCPs, 3571 (10%) from ID specialists, and 8828 (24%) from other specialty clinicians. The prevalence of reversals for patients of PCPs, ID specialists, and other specialty clinicians was 18%, 18%, and 25%, respectively, and for abandonments was 12%, 12%, and 20%, respectively. After adjusting for confounding, logistic regression models showed that, compared with patients who were prescribed PrEP by a PCP, patients prescribed PrEP by ID specialists had 10% lower odds of reversals (odds ratio [OR], 0.90; 95% CI, 0.81-0.99) and 12% lower odds of abandonment (OR, 0.88; 95% CI, 0.78-0.98), while patients prescribed by other clinicians had 33% higher odds of reversals (OR, 1.33; 95% CI, 1.25-1.41) and 54% higher odds of abandonment (OR, 1.54; 95% CI, 1.44-1.65)., Conclusion: The results of this cross-sectional study suggest that PCPs do most of the new PrEP prescribing and are a critical entry point for patients. PrEP adherence differs by clinician specialties, likely due to the populations served by them. Future studies to test interventions that provide adherence support and education are needed.

Purpose: To identify and examine subgroups of people with spinal cord injury (SCI) with different patterns of lived experience, and examine hidden impairments and disability among functionally independent and ambulant people., Materials and Methods: Latent profile analysis of population-based data from the Australian arm of the International Spinal Cord Injury (InSCI) Community survey ( n  = 1579)., Results: Latent subgroups reflected levels of functional independence and extent of problems with health, activity/participation, environmental barriers, and self-efficacy. Quality of life (QoL), psychological profiles, and activity/participation were often as good or better in participants who reported lower ( vs. higher) functional independence alongside comparable burden of health problems and environmental barriers. QoL, mental health, and vitality reflected self-efficacy and problem burdens more closely than functional independence. Ambulant participants reported a substantial burden of underlying, potentially hidden impairments, with QoL and mental health similar to wheelchair users., Conclusion: Hidden disability among more independent and/or ambulant people with SCI can affect well-being substantially. Early and ongoing access to support, rehabilitation, and SCI specialist services is important irrespective of cause, type, severity of injury, and level of functional independence. Improved access to SCI expertise and equity of care would help to improve early recognition and management of hidden disability., Trial Registration: Not applicable.

Background: Preexposure prophylaxis (PrEP) is an effective biological option for HIV prevention yet persistent disparities in PrEP uptake and retention exist among Hispanic/Latino men who have sex with men (MSM). We evaluated barriers and facilitators to PrEP care among Hispanic/Latino MSM at risk for and living with HIV., Setting: A small urban setting in the Northeastern United States., Methods: This was a mixed-methods, exploratory, sequential, qualitative and quantitative pilot study among Latino MSM at-risk and/or living with HIV across (1) semistructured qualitative interviews (N = 15) and (2) cross-sectional survey (N = 98)., Results: Participants reported a diverse range of sexual identities, HIV statuses, and PrEP statuses. Qualitative participants described feelings of isolation in both Hispanic/Latino and queer communities that made it challenging to learn about HIV prevention or PrEP from peers. Participants in the survey indicated that they would be more inclined to uptake PrEP if PrEP were offered in primary care settings (n = 61; 62.2%); there were specific LGBTQ+ affirming medical settings (n = 36; 36.7%); and/or they could meet other people who are currently on PrEP and sharing experiences online (n = 46; 46.9%) or in person (n = 38; 38.8%). Findings were organized to reflect determinants and implementation strategies that could be used to improve PrEP uptake among this population., Conclusions: This mixed-methods study identified several challenges and opportunities for increasing the reach of PrEP to Hispanic/Latino MSM. These findings should be used to inform tailored implementation strategies to promote PrEP uptake among this at-risk yet currently underserved population., Competing Interests: Dr. B.G.R. received funding in the form of a Developmental Research Award from the Providence/Boston Center for AIDS Research to conduct this project (P30AI042853). During this funding period, Dr. B.G.R. also had research funding from Gilead Sciences (IN-US-276-5463). Dr. A.H. receives royalties from Oxford University Press for books published on LGBTQ+ affirmative mental health treatment. Dr. A.H. was supported by the National Institute on Minority Health and Health Disparities (K23MD015690). Dr. T.A. was supported by the National Institute of Mental Health (K23MH124539). Dr. P.C. consults for the Rhode Island Department of Health and is the chief medical officer at Rhode Island Public Health Institute. Dr. A.N. is the executive director of the Rhode Island Public Health Institute. Michaela Maynard, NP is director of Clinical Operations at Open Door Health. No other conflicts of interest or sources of funding are reported., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Doxycycline as post-exposure prophylaxis (DoxyPEP) is a novel prevention approach which has demonstrated efficacy in preventing bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW) including people who are living with HIV and those on HIV pre-exposure prophylaxis (PrEP). We evaluated patient knowledge and interest in DoxyPEP, as well as early adopters of its use., Methods: In 2023, patients presenting for HIV and STI services at a primary care and sexual health clinic were asked about DoxyPEP knowledge, interest and use. Bivariate and multivariate analyses were used to evaluate demographics and behaviours associated with these outcomes., Results: A total of n=421 people presented for care. Of these, 314 were MSM/TGW. Fifteen percent were Black/African-American, and 21% were Hispanic/Latino. A total of 50% of MSM/TGW had heard of DoxyPEP, 49% were interested and 18% reported prior DoxyPEP use. Having a history of STI infection ever (adjusted OR (aOR) 5.95, 95% CI 2.69 to 13.13) and in the past 12 months (aOR 2.99, 95% CI 1.56 to 5.72) were both associated with DoxyPEP use. Individuals who had ever used HIV PrEP had nearly three times the odds of ever taking DoxyPEP (aOR 2.88, 95% CI 1.56 to 5.30). There was no association between the use of DoxyPEP and race, ethnicity or HIV status., Conclusions: Among MSM and TGW, there is already significant awareness, interest and use of DoxyPEP to prevent bacterial STIs. Public health efforts should focus on improving access and delivery of this STI prevention intervention to MSM and TGW., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Photobiomodulation, utilising non-ionising light in the visible and near-infrared (NIR) spectrum, has been suggested as a potential method for enhancing tissue repair, reducing inflammation and possibly mitigating cancer-therapy-associated side effects. NIR light is suggested to be absorbed intracellularly, mainly by chromophores within the mitochondria. This study examines the impact of 734 nm NIR light on cellular senescence. Cancer (MCF7 and A549) and non-cancer (MCF10A and IMR-90) cell populations were subjected to 63 mJ/cm 2 NIR-light exposure for 6 days. Senescence levels were quantified by measuring active senescence-associated beta-galactosidase. Exposure to NIR light significantly increases senescence levels in cancer (10.0%-203.2%) but not in non-cancer cells (p > 0.05). Changes in senescence were associated with significant modulation of mitochondrial homeostasis, including increased levels of reactive oxygen species (p < 0.05) and mitochondrial membrane potential (p < 0.05) post-NIR-light treatment. These results suggest that NIR light modulates cellular chemistry, arresting the proliferation of cancer cells via senescence induction while sparing non-cancer cells., (© 2024 The Author(s). Journal of Biophotonics published by Wiley‐VCH GmbH.)

Objectives: In the first year of pandemic measures, opioid-related deaths across Ontario's (ON) 34 public health units (PHUs) increased by 60%. Death rates for all seven Northern ON PHUs were above the provincial average. This study describes and compares factors surrounding opioid-related deaths before and after pandemic measures were introduced, for Northern ON compared to the rest of ON., Methods: Aggregate data were provided for Northern ON and the rest of the province by the Office of the Chief Coroner/Ontario Forensic Pathology Services. Opioid-related deaths were cohorted by date of death for the year before and after pandemic measures were introduced on March 16, 2020. Chi-square tests were used to compare between cohorts and geographies to determine significant differences for each variable, and for dichotomized levels within variables. P-values < 0.05 were considered statistically significant a priori., Results: In Northern ON, the number of opioid-related deaths approximately doubled from the pre-pandemic cohort (n = 185) to the early pandemic cohort (n = 365). Compared to the rest of ON, higher proportions of deaths occurred in Northern ON among individuals who lived and died in private residences, among women (although the majority of decedents were male) and among individuals employed in mining, quarrying, and oil and gas industries. Compared to the pre-pandemic year, in Northern ON, higher proportions of opioid-related deaths involved fentanyl and stimulants as direct contributors, and the majority involved evidence of inhaled drugs., Conclusion: Differences between the circumstances of death in Northern ON and in the rest of ON suggest opportunities to tailor interventions., (© 2024. Crown.)

Objectives: Adults with spinal cord injury (SCI) are often sedentary, increasing their risk of cardiometabolic diseases. Leisure-time Physical Activity (LTPA) is physical activity completed during recreation time for enjoyment. We aimed to quantify LTPA in people ≥45 years with SCI and to explore its relationship with participants' characteristics., Methods: This is a secondary analysis on a subset of the Australian International SCI Survey in participants ≥45 years, at least 12 months post-injury. We described levels of LTPA and used multivariable regressions to estimate the associations between participant characteristics and LTPA., Results: Of 1,281 participants (mean age: 62.7 years, mean time since injury: 18.7 years; 74% males) 44% reported no participation in LTPA. The average LTPA participation was 197 (SD 352) minutes per week (median: 50). Females (β = -62.3, 95% CI [-112.9, -11.7]), and participants with non-traumatic injuries (β = -105.2, 95% CI [-165.9, -44.6]) performed less LTPA. Time since injury was not associated with moderate-to-heavy LTPA (LR: Probability > F = 0.785)., Conclusion: LTPA promotion in the SCI population ≥45 years focusing on females and non-traumatic injuries is warranted., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Stendell, Stubbs, Rogers, Verhagen, Middleton, Davis, Arora, Marshall, Geraghty, Nunn and Quel de Oliveira.)

Recurrence rates following surgical management of chronic subdural haematoma (CSDH) range from 5 to 33 %. There is growing evidence which suggests middle meningeal artery embolisation (MMAe) may reduce recurrence rates when used as surgical adjunct or standalone treatment. In this study we described our experience of this new procedure in the our UK institution. Patients with recurrent CSDH or CSDH at high risk of recurrence were selected for MMAe on a case-by-case basis following MDT discussion. A departmental database was used to identify patients treated. 26 CSDH were embolised in 20 patients; 9 CSDH were de-novo and 17 were recurrent. 10/26 CSDH were treated with MMAe only. No procedural mortality, access site or thrombo-embolic complications occurred. One patient experienced symptomatic collection growth 12 h following MMAe and required surgical drainage. 15 (75 %) of patients were living at home at follow-up (mean 14 months). On imaging follow-up 15/18 showed CSDH volume reduction or resolution, 1/18 remained stable requiring no further treatment, 2/18 patients suffered recurrent CSDH requiring treatment. In both recurrent cases incomplete embolisation was noted on procedural imaging (posterior division of MMA not embolised). Persistent posterior MMA division filling was significantly associated with collection recurrence (p = 0.002). Our results suggest MMAe as a stand-alone or adjuvant therapy can be performed safely in a UK neuroscience setting and is associated with high rates of symptomatic CSDH size reduction or resolution in problematic CSDH that have either recurred or are prone to recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Study Design: Cross-sectional survey., Objectives: Appropriate and timely lifelong access to healthcare following a spinal cord injury (SCI) is critical, yet unmet healthcare needs in this population are common. Poor experiences with healthcare providers can be a barrier to health-seeking behaviour, and we hypothesised that there would be an association between unmet healthcare needs and care experiences. This study aimed to: (1) describe healthcare provider utilisation in the past year, unmet care needs and satisfaction with healthcare services; (2) explore the association between experiences with healthcare providers and unmet healthcare needs; and (3) explore the association between healthcare provider utilisation and participant characteristics, including unmet healthcare needs., Setting: Community., Methods: Analysis of data for 1579 Australians aged ≥ 18, who were ≥ 1-year post-SCI and living in the community. Bayesian penalised regression was used to model six binary outcomes: unmet healthcare needs; the use of general practitioners (GPs), allied health practitioners, rehabilitation specialists; medical specialists; and hospitalisations in the past 12-months., Results: Unmet needs were reported by 17% of participants, with service cost the common deterrent. There was evidence of an effect for provider experiences on unmet healthcare needs, but no evidence that unmet healthcare needs was associated with the use of GPs, allied health practitioners, and rehabilitation or medical specialists., Conclusions: Unmet healthcare needs were reported in the context of high healthcare use and large proportions of secondary conditions in a cohort with long-term SCI. Improved health access for people with SCI include better primary-secondary care collaboration is needed., (© 2024. The Author(s).)

Abstract: The rates of sexually transmitted infections (STIs) in the United States, including chlamydia and gonorrhea, are rising. Point-of-care (POC) testing could increase access to testing and treatment. This evaluation found POC STI testing to be concordant with the results of traditional laboratory testing for 100% of patients who were tested. Ninety-five percent of the patients reported being satisfied with the experience, and 66% preferred it to traditional laboratory testing. The most commonly reported reason for preferring the test was the short amount of time it took to receive results. However, insurance reimbursed less than 30% of what was billed for the POC tests. Low insurance reimbursement rates could be a barrier to implementation long-term financial sustainability of POC STI testing., Competing Interests: Conflicts of Interest and Source of Funding: None declared., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Web-based learning activities are key components of continuing medical education (CME) for health care professionals (HCPs). However, the published outcomes of web-based educational interventions for early breast cancer (EBC) are limited., Objective: This study aims to objectively assess knowledge, competence, and performance among HCPs following participation in 2 EBC-focused CME activities and to identify the remaining educational gaps., Methods: We developed 2 CME-accredited web-based educational activities addressing high-risk EBC, including integration of shared decision-making to optimize patient care (touchMDT) and stratification for early identification of high-risk patients and novel treatment strategies (touchPANEL DISCUSSION). Knowledge, competence, and performance were assessed before and after the activities against an expanded outcomes framework (levels 1-5) using self-reported questionnaires and an analysis of anonymized data extracted from patient records., Results: Six months after the launch of the activity, 7047 and 8989 HCP participants engaged with touchMDT and touchPANEL DISCUSSION, respectively. The overall satisfaction was 82% (a total score of 20.6 out of 25) for the touchMDT and 88% (a total score of 21.9 out of 25) for the touchPANEL DISCUSSION. For the evaluation of knowledge and competence (50 respondents before the activity and 50 learners after the activity), there was a significant increase in the mean number of correctly answered questions from pre- to postactivity (touchMDT: median 4.0, IQR 3.0-5.0 to median 5.5, IQR 4.0-7.0; mean 4.00, SD 1.39 to mean 5.30, SD 1.56 and touchPANEL DISCUSSION: median 4.0, IQR 4.0-5.0 to median 6.0, IQR 5.0-7.0; mean 4.32, SD 1.30 to mean 5.88, SD 1.49; both P<.001). A significant improvement in self-reported performance (50 respondents before the activity and 50 learners after the activity) was observed in a combined analysis of both activities (median 3.0, IQR 2.0-3.0 to median 4.0, IQR 3.0-5.0; mean 2.82, SD 1.08 to mean 4.16, SD 1.45; P<.001). Patient record analysis (50 respondents before the activity and 50 learners after the activity) showed that the HCPs used a range of measures to determine EBC recurrence risk and revealed no significant differences in adjuvant therapies used before and after the activity (P=.97 and P>.99 for Ki-67 <20% and Ki-67 ≥20% tumors, respectively). The remaining educational gaps included strategies for implementing shared decision-making in clinical practice and the use of genetic and biomarker testing to guide treatment selection., Conclusions: Brief, web-based CME activities on EBC were associated with an improvement in HCP knowledge, competence, and self-reported performance and can help identify unmet needs to inform the design of future CME activities., (©Michael Gnant, Khatijah Lim Abdullah, Frances Boyle, Chiun-Sheng Huang, Katie Bickford, Sola Neunie, Alexander Noble, Anne Nunn, Caroline Sproat, Nadia Harbeck, Carlos Barrios. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.03.2024.)

Life may be expressed as the flow of electrons, protons, and other ions, resulting in large potential difference. It is also highly photo-sensitive, as a large proportion of the redox capable molecules it relies on are chromophoric. It is thus suggestive that a key organelle in eukaryotes, the mitochondrion, constantly adapt their morphology as part of the homeostatic process. Studying unstained in vivo nano-scale structure in live cells is technically very challenging. One option is to study a central electron carrier in metabolism, reduced nicotinamide adenine dinucleotide (NADH), which is fluorescent and mostly located within mitochondria. Using one and two-photon absorption (340-360 nm and 730 nm, respectively), fluorescence lifetime imaging and anisotropy spectroscopy of NADH in solution and in live cells, we show that mitochondria do indeed appear to be aligned and exhibit high anisotropy (asymmetric directionality). Aqueous solution of NADH showed an anisotropy of ~ 0.20 compared to fluorescein or coumarin of < 0.1 and 0.04 in water respectively and as expected for small organic molecules. The anisotropy of NADH also increased further to 0.30 in the presence of proteins and 0.42 in glycerol (restricted environment) following two-photon excitation, suggesting more ordered structures. Two-photon NADH fluorescence imaging of Michigan Cancer Foundation-7 (MCF7) also showed strong anisotropy of 0.25 to 0.45. NADH has a quantum yield of fluorescence of 2% compared to more than 40% for photoionisation (electron generation), when exposed to light at 360 nm and below. The consequence of such highly ordered and directional NADH patterns with respect to electron ejection upon ultra-violet (UV) excitation could be very informative-especially in relation to ascertaining the extent of quantum effects in biology, including electron and photonic cascade, communication and modulation of effects such as spin and tunnelling., (© 2024. The Author(s).)

Background: Improving family engagement in juvenile justice (JJ) system behavioral health services is a high priority for JJ systems, reform organizations, and family advocacy groups across the United States. Family-driven care (FDC) is a family engagement framework used by youth-serving systems to elevate family voice and decision-making power at all levels of the organization. Key domains of a family-driven system of care include: 1) identifying and involving families in all processes, 2) informing families with accurate, understandable, and transparent information, 3) collaborating with families to make decisions and plan treatments, 4) responding to family diversity and inclusion, 5) partnering with families to make organizational decisions and policy changes, 6) providing opportunities for family peer support, 7) providing logistical support to help families overcome barriers to participation, and 8) addressing family health and functioning. FDC enhances family participation, empowerment, and decision-making power in youth services; ultimately, improving youth and family behavioral health outcomes, enhancing family-child connectedness, and reducing youth recidivism in the JJ setting., Methods: We evaluated staff-perceived adoption of the eight domains of FDC across detention and community services agencies in the state of Georgia. We collected mixed methods data involving surveys and in-depth qualitative interviews with JJ system administrators, staff, and practitioners between November 2021- July 2022. In total, 140 individuals from 61 unique JJ agencies participated in surveys; and 16 JJ key informants participated in qualitative interviews., Results: FDC domains with the highest perceived adoption across agencies included identifying and involving families, informing families, collaborative decision-making and treatment planning, and family diversity and inclusion. Other domains that had mixed or lower perceived adoption included involving families in organizational feedback and policy making, family peer support, logistical support, and family health and functioning. Adoption of FDC domains differed across staff and organizational characteristics., Conclusions: Findings from this mixed methods assessment will inform strategic planning for the scale-up of FDC strategies across JJ agencies in the state, and serve as a template for assessing strengths and weaknesses in the application of family engagement practices in systems nationally., (© 2024. The Author(s).)

Due to the accelerating climate change, it is crucial to understand how plants adapt to rapid environmental changes. Such adaptation may be mediated by epigenetic mechanisms like DNA methylation, which could heritably alter phenotypes without changing the DNA sequence, especially across clonal generations. However, we are still missing robust evidence of the adaptive potential of DNA methylation in wild clonal populations. Here, we studied genetic, epigenetic and transcriptomic variation of Fragaria vesca, a predominantly clonally reproducing herb. We examined samples from 21 natural populations across three climatically distinct geographic regions, as well as clones of the same individuals grown in a common garden. We found that epigenetic variation was partly associated with climate of origin, particularly in non-CG contexts. Importantly, a large proportion of this variation was heritable across clonal generations. Additionally, a subset of these epigenetic changes affected the expression of genes mainly involved in plant growth and responses to pathogen and abiotic stress. These findings highlight the potential influence of epigenetic changes on phenotypic traits. Our findings indicate that variation in DNA methylation, which can be environmentally inducible and heritable, may enable clonal plant populations to adjust to their environmental conditions even in the absence of genetic adaptation., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Background: Stage 1 of the STREAM trial demonstrated that the 9 month (Short) regimen developed in Bangladesh was non-inferior to the 20 month (Long) 2011 World Health Organization recommended regimen. We assess the association between HIV infection and radiographic manifestations of tuberculosis and factors associated with time to culture conversion in Stage 1 of the STREAM trial., Methods: Reading of chest radiographs was undertaken independently by two clinicians, and films with discordant reading were read by a third reader. Recording of abnormal opacity of the lung parenchyma included location (right upper, right lower, left upper, and left lower) and extent of disease (minimal, moderately-advanced, and far advanced). Time to culture conversion was defined as the number of days from initiation of treatment to the first of two consecutive negative culture results, and compared using the log-rank test, stratified by country. Cox proportional hazards models, stratified by country and adjusted for HIV status, were used to identify factors associated with culture conversion., Results: Of the 364 participants, all but one had an abnormal chest X-ray: 347 (95%) had opacities over upper lung fields, 318 (87%) had opacities over lower lung fields, 124 (34%) had far advanced pulmonary involvement, and 281 (77%) had cavitation. There was no significant association between HIV and locations of lung parenchymal opacities, extent of opacities, the presence of cavitation, and location of cavitation. Participants infected with HIV were significantly less likely to have the highest positivity grade (3+) of sputum culture (p = 0.035) as compared to participants not infected with HIV. Cavitation was significantly associated with high smear positivity grades (p < 0.001) and high culture positivity grades (p = 0.004) among all participants. Co-infection with HIV was associated with a shorter time to culture conversion (hazard ratio 1.59, 95% CI 1.05-2.40)., Conclusions: Radiographic manifestations of tuberculosis among the HIV-infected in the era of anti-retroviral therapy may not differ from that among those who were not infected with HIV. Radiographic manifestations were not consistently associated with time to culture conversion, perhaps indicating that the Short regimen is sufficiently powerful in achieving sputum conversion across the spectrum of radiographic pulmonary involvements., Trial Registration: ISRCTN ISRCTN78372190. Registered 14/10/2010. The date of first registration 10/02/2016., (© 2024. The Author(s).)

Background: In patients with spinal cord injuries (SCIs), infections continue to be a leading cause of morbidity, mortality and hospital admission., Objectives: This study evaluated the long-term impact of a weekly, multidisciplinary Spinal/Antimicrobial Stewardship (AMS) meeting for acute-care SCI inpatients, on antimicrobial prescribing over 3 years., Methods: A retrospective, longitudinal, pre-post comparison of antimicrobial prescribing was conducted at our tertiary hospital in Melbourne. Antimicrobial prescribing was audited in 6 month blocks pre- (25 April 2017 to 24 October 2017), immediately post- (27 March 2018 to 25 September 2018) and 3 years post-implementation (2 March 2021 to 31 August 2021). Antimicrobial orders for patients admitted under the spinal unit at the meeting time were included., Results: The number of SCI patients prescribed an antimicrobial at the time of the weekly meeting decreased by 40% at 3 years post-implementation [incidence rate ratio (IRR) 0.63; 95% CI 0.51-0.79; P ≤ 0.001]. The overall number of antimicrobial orders decreased by over 22% at 3 years post-implementation (IRR 0.78; 95% CI 0.61-1.00; P  = 0.052). A shorter antimicrobial order duration in the 3 year post-implementation period was observed (-28%; 95% CI -39% to -15%; P ≤ 0.001). This was most noticeable in IV orders at 3 years (-36%; 95% CI -51% to -16%; P  = 0.001), and was also observed for oral orders at 3 years (-25%; 95% CI -38% to -10%; P  = 0.003). Antimicrobial course duration (days) decreased for multiple indications: skin and soft tissue infections (-43%; 95% CI -67% to -1%; P  = 0.045), pulmonary infections (-45%; 95% CI -67% to -9%; P  = 0.022) and urinary infections (-31%; 95% CI -47% to -9%; P  = 0.009). Ninety-day mortality rates were not impacted., Conclusions: This study showed that consistent, collaborative meetings between the Spinal and AMS teams can reduce antimicrobial exposure for acute-care SCI patients without adversely impacting 90 day mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Intimate partner violence (IPV) can constraint Black women's ability to prioritize and access Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP) services. Recent research has called for the development of trauma-informed PrEP implementation programs to improve the delivery of PrEP to Black cisgender women; however, many PrEP-prescribing settings do not reflect this recommendation. The current study sought to identify key components to develop a trauma-informed PrEP implementation program for Black cisgender women and clinical staff. We conducted focus groups with PrEP-eligible Black cisgender women (February-June 2019), and semi-structured interviews with clinical staff offering HIV prevention and treatment services (October-November 2020) in community healthcare clinics in Mississippi. Seven themes were identified as needed to facilitate integration of trauma-informed approaches into existing PrEP programs, including defining intimate partner violence (IPV), appropriate IPV screening and response, HIV prevention in abusive relationships, staff training needs, and creating supportive clinic environments. PrEP-eligible Black women and clinical staff generally agreed on how to best operationalize IPV screening and response, the importance of trauma-informed staff training, and the need for Black women-specific informational campaigns. However, Black women highlighted the need for providers to discuss HIV prevention in controlling relationships, and to respond to IPV disclosure. HIV pre-exposure prophylaxis has yet to achieve the potential impact observed in trials. Ultimately, realizing the HIV prevention potential of PrEP in the US necessitates centering the perspectives of Black cisgender women and staff to better integrate trauma-informed approaches., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Objectives: The purpose of this study was to develop and establish reliability and validity of a virtual performance measure (VPM) score that encompassed 10 videos in patients with osteoarthritis of the knee joint. Patients' experience and satisfaction were documented., Design: Forty videos were chosen for 10 functional tasks, with four videos showing increasing difficulty for each task. Patients were requested to choose the video that best reflected their own situation. Clinical and radiological findings and self-report and performance measures were completed., Results: Data of 100 patients, 70 (70%) females, mean age: 65 ​± ​9 were examined. The Cronbach's alpha coefficient that examined internal consistency of the VPM score was 0.92. The intraclass correlation value of 0.82 was obtained for test-retest reliability. Factor analysis showed three distinct domains. There was moderate correlations between the VPM score and the self-report and actual performance measures ranging from r ​= ​0.46 to 0.66. The VPM summated score of 10 activities was able to differentiate between candidates and non-candidates for knee arthroplasty, with the area under the curve value of 0.90 indicating excellent predictive validity. The overall patient experience and satisfaction was positive with 67% of participants feeling that virtual care could have an impact on minimizing physical presence in the clinic or hospital., Conclusions: The VPM is a reliable and valid outcome measure in patients with osteoarthritis of the knee joint. This digital tool has the potential to transform osteoarthritis care by providing a valid remote measurement of real-life functional limitations and reduce the burden of time consuming in-person tests., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s).)

Aim: The EMA defines acceptability as "the overall ability and willingness of the patient to use, and their caregiver to administer, the medicine as intended" [1]. This paper seeks to outline issues of acceptability in relation to injectable therapy, namely intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration routes, and to lay a foundation to identify a minimum set of data that would satisfy Regulatory Authorities when discussing the acceptability of an injectable product. In addition, it will alert drug product developers to other factors that might contribute to good practice, alternative administration strategies and overall adherence to achieve successful treatment. Whilst the term 'parenteral' means "outside the intestine" [2,3] and so potentially covers a range of administration routes including intranasal and percutaneous administration, this review focuses on IV, IM and SC administration by injection. The use of indwelling canulae or catheters to reduce venepuncture and facilitate prolonged treatment is common and may impact acceptability [4]. This may be influenced by information provided by the manufacturer but is not always in their direct control. Other injectable products suitable for routes such as intradermal, intra-articular, intraosseous and intrathecal, share the requirement to be acceptable but are not specifically covered in this paper [2,5]., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cervical spinal cord injury (SCI) usually results in severe, long-term disability. Early therapeutic hypothermia (33-34°C) has been used to improve outcomes in preclinical studies, but previous clinical studies have commenced cooling after arrival at hospital. The objective of the study is to determine the feasibility and safety of early therapeutic hypothermia initiated by paramedics and maintained for up to 24 hours in hospital in patients with SCI. This is a pilot clinical study. The study was undertaken at Ambulance Victoria and The Alfred Hospital, Victoria, Australia. A total of 17 consecutive patients with suspected acute traumatic cervical SCI were enrolled. Patients with suspected cervical SCI were administered a bolus (up to 20 mL/kg) intravenous (IV) cold (4°C) normal saline in the prehospital phase of care. After hospital admission and spinal imaging, further cooling used IV catheter temperature control or surface cooling. Major complications and long-term outcomes were compared with historical controls admitted to the same center before the study. A decrease in core temperature of 1.1°C was achieved during prehospital care and the target temperature was achieved in 6 hours with mechanical temperature management devices in the hospital. There were no major safety concerns. Patients with motor complete SCI who underwent early decompressive surgery had a favorable rate of partial spinal cord recovery compared with historical controls. Therapeutic hypothermia induced using bolus, large-volume, ice-cold saline prehospital and maintained for 24 hours using mechanical devices appears to be feasible and safe in patients with SCI. Larger trials need to be undertaken to determine whether prehospital cooling combined with early decompressive surgery improves outcomes in patients with complete cervical SCI. Australian and New Zealand Clinical Trials Registry (ACTRN12616001086459).

River catchments worldwide are heavily fragmented by anthropogenic barriers, reducing their longitudinal connectivity and contributing to the decline of migratory fish populations. Direct impacts of individual barriers on migratory fish are well-established, but barrier impacts on onward migration are poorly understood, despite their relevance to evidence-based, catchment-scale, management of threatened species. This study investigated the upstream spawning migration of 352 acoustic tagged river lamprey (Lampetra fluviatilis), translocated upstream of two key barriers (R2: n = 60 & 59; R3: n = 59 & 52) compared to a control group (R1: n = 61 & 59), across two contrasting (dry and wet, n = 180 and 172) years in the River Yorkshire Ouse, England, to reveal the impact of barriers on the onward migration of upstream migrating fish. Release further upstream increased the degree of catchment penetration, with median distance upstream of R1 56.1% and 68.6% greater for lamprey released at R2 and R3 respectively. Median delays at the two downstream-most main river barriers by the control group were 23.8 and 5.4 days (2018/19) and 9.3 and 11.4 days (2019/20). However, impacts of delay were only observed on the time to reach spawning habitat, time to reach final assumed spawning location and speed of movement in one upper catchment tributary during 2019/20 whilst they were only observed on time to reach spawning habitat during 2018/19 and on assumed spawning location distance during 2019/20 in the other. Ultimately, limited impacts of delay at barriers on onward fish migration post-passage were observed but median catchment penetration was increased with consecutive release upstream. This study demonstrated the importance of a true understanding of barrier impacts to inform catchment-wide planning, evidence vital for management worldwide. Although the findings of this study do support the use of trap and transport as a measure to remediate barrier impacts on migration, fish passage engineering improvements or barrier removal, at structures shown to be the most inhibiting to fish migration should be considered the best and most sustainable option to improve barrier passage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pressure ulcers (PU) are a common yet debilitating injury within the spinal cord injury (SCI) population. This retrospective data analysis is intended to identify the contributing factors, review the current management protocol, and risk of recurrence of PU in SCI patients at Victoria's state referral centre for traumatic spinal cord injuries., Methods: A retrospective audit of the medical records of SCI patients with pressure ulcers was conducted for the period of January 2016 to August 2021. Patients aged 18 years and older who presented for surgical management of their PU were included in the study., Results: Among the 93 patients who met the inclusion criteria, there were a total of 195 surgeries for 129 PU. Ninety-seven percent were classified as grade of 3 or 4 and 53% had osteomyelitis on presentation. 58% were either current smokers or ex-smokers, and 19% were diabetic. Debridement alone was the most common type of surgical management (58%), followed by flap reconstruction (25%). Those who underwent flap reconstruction were admitted for 71 days longer, on average. 41% of the surgeries were associated with a post-operative complication, with the most prominent being an infection at 26%. Of the 129 PU, 11% recurred at least 4 months post initial presentation., Conclusion: There are a multitude of a factors that impact prevalence, surgical complications, and recurrence of PU. This study provides insight into these factors to review our current practices and optimize surgical outcomes in the management of PU in the SCI population., (© 2023 Royal Australasian College of Surgeons.)

Background: Human papillomavirus (HPV) vaccination is the most effective biomedical intervention for HPV infections. HPV vaccination rate among sexually active young adults is largely unknown., Methods: Patients aged 18-26 years, who attended the Rhode Island Sexually Transmitted Infections Clinic between 2013-2018, were included in the study. We extracted demographics, behavioral characteristics, and HPV vaccination status from electronic medical records. Exploratory logistic regressions were conducted to identify factors associated with vaccination status., Results: Among 2729 eligible individuals, the median age was 23 years (interquartile range: 22-25). Only 8.1% of males and 24.8% of females received at least one dose of HPV vaccine. Females were 144% (crude odds ratio [cOR]: 2.44, 95% confidence interval [CI]: 2.03, 2.94) more likely to receive at least one dose of HPV vaccine than males. Being Black/African American (B/AA) or Hispanic/Latino (H/L) was associated with a 21% (cOR: 0.79, 95% CI: 0.62, 1.00) and 34% (cOR: 0.66, 95% CI: 0.53, 0.81) decrease in the odds of vaccination, respectively., Conclusions: HPV vaccination rate was low among sexually active young adults. Gender and racial/ethnic disparities existed in HPV vaccination. Interventions are needed to promote HPV vaccination among sexually active young adults, especially B/AA and H/L communities.

Study Design: Cross-sectional survey., Objectives: To describe design and methods of Australian arm of International Spinal Cord Injury (Aus-InSCI) community survey, reporting on participation rates, potential non-response bias and cohort characteristics., Setting: Survey of community-dwelling people with SCI at least 12 months post-injury, recruited between March 2018 and January 2019, from state-wide SCI services, a government insurance agency and not-for-profit consumer organisations across four Australian states., Methods: The Aus-InSCI survey combined data for people with SCI from nine custodians, using secure data-linkage processes, to create a population-based, anonymised dataset. The Aus-InSCI questionnaire comprised 193 questions. Eligibility, response status and participation rates were calculated. Descriptive statistics depict participant characteristics. Logistic regression models were developed for probability of participation, and inverse probability weights generated to assess potential non-response bias., Results: 1579 adults with SCI were recruited, a cooperation rate of 29.4%. Participants were predominantly male (73%), with 50% married. Mean age was 57 years (range 19-94) and average time post-injury 17 years (range 1-73). Paraplegia (61%) and incomplete lesions (68%) were most common. Males were more likely than females to have traumatic injuries (p < 0.0001) and complete lesions (p = 0.0002), and younger age-groups were more likely to have traumatic injuries and tetraplegia (p < 0.0001). Potential non-response bias evaluated using selected outcomes was found to be negligible in the Aus-InSCI cohort., Conclusions: The Aus-InSCI survey made efforts to maximise coverage, avoid recruitment bias and address non-response bias. The distributed, linked and coded (re-identifiable at each custodian level) 'virtual quasi-registry' data model supports systematic cross-sectional and longitudinal research., (© 2022. Crown.)

Study Design: Cross-sectional population-based survey for the Australian cohort of the International Spinal Cord Injury (InSCI) Community Survey., Objectives: To differentiate subgroups of people with spinal cord injury (SCI) who self-report good and poor overall quality of life (QoL) using domains of the International Classification of Functioning (ICF), and to evaluate how these factors contribute to QoL when considered together, while controlling confounders., Setting: Australian survey data from four state-wide SCI services, one government insurance agency, and three not-for-profit consumer organisations., Methods: Explanatory factors for QoL were compared between participants reporting poor vs. good QoL. Path models estimated total, direct and mediated contributions from each explanatory factor to QoL ratings after accounting for confounders., Results: Most participants (62%) reported good or very good QoL, 12% reported poor or very poor QoL. When explanatory factors were considered together, the strongest total effects on QoL involved social integration (+0.36 SDs), subjective social position (+0.29), secondary health condition burden (-0.28), activity/participation problem burden (-0.26), day-to-day assistance (-0.26), mental health (+0.18), pain (-0.16), self-efficacy (+0.15), vitality (+0.14) and environmental barriers (-0.11). Effects of social integration, mental health, vitality, self-efficacy, pain and activity/participation problems were partly or wholly direct., Conclusion: Opportunities to improve QoL in people with SCI exist at every level of the health system. Virtually all aspects of the ICF framework make a substantive difference to QoL outcomes. Social and psychological factors and ability to complete desired activities have key direct effects and influence effects of secondary health condition burden and environmental barriers., (© 2022. The Author(s).)

Background: From March 2020 to January 2021, Newfoundland and Labrador experienced 408 coronavirus disease 2019 (COVID-19) cases (incidence 78 per 100,000). In February and March 2021, a community outbreak of the B.1.1.7 (Alpha) variant occurred in the Eastern Regional Health Authority. This article describes the epidemiology of this variant of concern outbreak, identifies settings that likely contributed to spread and informs recommendations for public health measures (PHMs)., Methods: Provincial surveillance data were linked with case interview data and a school class roster. Descriptive epidemiological methods were used to characterize the outbreak. Secondary attack rates (SAR) were calculated for households and classrooms., Results: This outbreak involved 577 laboratory-confirmed and 38 probable cases. Whole genome sequencing determined cases were B.1.1.7. The median age was 31 years and the highest proportion of cases were in the 15 to 19-year age group (29%); 293 (51%) were female and 140 (24%) were asymptomatic upon identification. Early cases were linked to a high school, sports activities, a restaurant and social gatherings. As the outbreak progressed, cases were associated with household transmission, a daycare, healthcare settings and a workplace. The unadjusted SAR estimate among laboratory-confirmed cases was 24.4% for households and 19.3% for classroom exposures. When adjusted for other potential exposures, SAR estimates were 19.9% for households and 11.3% for classrooms., Conclusion: This outbreak demonstrated how B.1.1.7 spread rapidly through a community with previously low COVID-19 transmission and few preventative PHMs in place. Implementation and compliance with school and community-based PHMs is critical for preventing transmission during outbreaks., Competing Interests: Competing interests LG is a member of study teams that received funding from Roche Diagnostics and Seegene Inc. No other competing interests were declared.

Transgender and gender-diverse (TGD) people are disproportionately impacted by incarceration, interpersonal violence, HIV and other sexually transmitted infections, substance use disorders, and suicidality. Little is known about successful approaches to improve health outcomes for TGD individuals impacted by incarceration. We review the barriers to providing gender-affirming clinical care in correctional systems in the United States, identify key knowledge gaps regarding the provision of gender-affirming care to incarcerated TGD populations, and highlight necessary steps to improve the health and safety of this highly vulnerable population. We also describe the components of a gender-affirming care model implemented in a state correctional facility, including support from correctional administrators, identifying a gender-affirming care provider, standardizing clinical care protocols, and adapting clinical services to TGD population needs. Similar models should be employed elsewhere to improve health outcomes for TGD populations during incarceration and on release.

Objectives: This study described leisure-time physical activity (LTPA) for people in Australia with spinal cord injury (SCI) and whether certain sociodemographic and psychosocial variables might be associated with LTPA uptake and guidelines adherence. Methods: The Physical Activity Scale for Individuals with a Physical Disability was used to measure the intensity and volume of LTPA of 1,579 individuals with SCI. Summary statistics were calculated for LTPA guidelines adherence. Analyses included regression modelling. Results: Of the 1,579 participants, 58% performed LTPA and 13% adhered to recommended guidelines for weekly LTPA. There was an association with being an "exerciser" based on the time since injury (OR = 1.02 [95% 1.01-1.03]), a traumatic injury (OR = 1.53 [95% CI 1.13-2.08]) and a higher self-rating of health (OR = 1.10 [95% CI 0.95-1.27]). Where LTPA guidelines were met, adherence was most related to a traumatic injury (OR = 1.75 [95% CI 1.02-3.02]) and being unemployed (OR = 1.53 [95% CI 1.03-2.25]). Conclusion: Of those who performed LTPA with SCI, one in four met population-specific LTPA guidelines. Sociodemographic variables were moderately associated with being an "exerciser" or LTPA "guideline-adherent.", Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2022 Watson, Arora, Middleton, Quel de Oliveira, Heard, Nunn, Geraghty, Marshall and Davis.)

Purpose: The aim of this study was to explore older adults' experiences of and approaches to managing their long-term health and mobility after traumatic injury., Methods: A longitudinal qualitative study was undertaken with older adults following traumatic injury in Victoria, Australia. Fifteen participants (≥65 years) were interviewed at three years post-injury ( n  = 15), and re-interviewed at four ( n  = 14) and five years ( n  = 12) post-injury. Using a framework approach, a longitudinal thematic analysis was performed., Results: Older age at the time of injury was identified by participants as a key factor influencing their recovery. Many participants reported actively attempting to regain their strength and fitness in the first five years following injury. However, their age, injury impacts, other health conditions, and weight gain made it difficult to achieve recovery goals. Many older adults reported a decline in their physical function over time. While these experiences and persistent disability constrained or changed the quality of social relationships, community participation, and independence, several participants described adapting to their functional limitations, and managing their secondary conditions over time., Conclusion: In our cohort, the intertwined combination of ageing, injury, and comorbid conditions negatively affected health and mobility, reinforcing the need for preventative strategies.Implications for rehabilitationOlder adults recovering from traumatic injury may benefit from specialised care pathways that offer long-term and tailored therapies, with programs and services specific to their needs and goals.An integrated service approach by injury insurers, health care, primary care, disability, and aged care could more clearly identify and effectively address the individual needs and goals of older adults with complex conditions.Health and social services that work with people with injuries to develop personalised coping strategies can reduce anxiety related to uncertainty about the future, promote well-being, and support participation in valued activities.

Study Design: Cross-sectional survey., Objectives: To identify common problems across key domains of functioning, health and wellbeing, as well as evaluate self-reported quality of life (QoL) by people with SCI, examining differences by age, gender, injury characteristics and level of mobility., Setting: Data from four state-wide SCI clinical services, one government insurance agency and three not-for-profit consumer organisations., Methods: Participants were 18 years or over with SCI and at least 12 months post-injury, recruited between Mar'18 and Jan'19. The Aus-InSCI questionnaire comprised 193 questions, including socio-demographics, SCI characteristics, body functions and structures, activities and participation, environmental and personal factors, and appraisal of health and well-being. General linear model was used to examine differences in functioning and QoL., Results: Participants (mean age 57 years, range 19-94 years) with tetraplegia and/or complete injuries had more health problems, activity/participation problems and environmental barriers. However, self-rated overall QoL did not differ for injury level or completeness. Participants with more recent injuries exhibited lower independence levels, more mental health problems and poorer satisfaction with self and their living conditions. Major activity/participation problems related to intimate relationships and accessing public transportation. Less than half of the working age population were engaged in paid work. The top two environmental barriers frequently related to accessing public places or homes and unfavourable climatic conditions., Conclusions: This large, comprehensive community survey draws a detailed picture of the lived experience of people with SCI in Australia, identifying priority needs, gaps in services and barriers to achieving a full and satisfying life., (© 2022. Crown.)

Objective: To explore the association between sociodemographic, health, functional independence, and environmental variables with engagement in paid work for people with spinal cord injury (SCI)., Design: Self-reported, cross-sectional Australian data from a large international SCI survey., Setting: Community-based., Participants: 1189 working-age people with SCI (18-67 years) or aged >67 years and engaged in paid employment. Respondents were community based and at least 1 year after injury., Interventions: Not applicable., Main Outcome Measures: Employment and work integration variables. Bayesian penalized regression was used to determine associations between 23 predictor variables and engagement in paid work., Results: Most participants (87%) were employed pre-injury, with 39% in paid employment at the time of the survey. Participants who attained a master's/doctoral degree (odds ratio [OR]=3.01; 95% credible interval [CrI], 1.63, 5.44) and those married (OR=1.68; 95% CrI, 1.13, 2.49) were more likely to be engaged in paid work. Women (OR=0.55; 95% CrI, 0.37, 0.81), people receiving a disability pension (OR=0.17; 95% CrI, 0.13, 0.24), and older participants (OR=0.75; 95% CrI, 0.63, 0.90) were less likely to be in paid work. Working participants identified hardships including problems completing their work (60%) and accessing the workplace (32%), as well as unmet needs relating to assistive devices required for completing their work (50%)., Conclusions: Findings from the current study can assist in directing resources to subgroups within the SCI population who need greater assistance or intervention related to employment outcomes, including through vocational rehabilitation services/programs. Unmet needs and workplace issues expressed by employed individuals identify gaps in work integration and satisfaction that could affect employment sustainability that need to be addressed., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: STREAM (Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) Stage 1 was a randomised trial of a Short (9-month) regimen for rifampicin-resistant TB (RR-TB). QT or QTcF prolongation ≥500 ms occurred in 31 (11%) of 282 Short regimen participants. The frequent ECG monitoring employed might be challenging for treatment programmes. This analysis aimed to determine whether those at higher risk of severe QT prolongation could be identified early for more targeted monitoring. METHODS: Data from the first month of treatment were used to investigate whether participants were at risk of developing QT/QTcF ≥500 ms. QTcF increases from baseline at different time points were examined. Absolute QTcF measurements were categorised in 5 ms increments at each time-point. The most discriminating time points and QTcF cut-offs were combined to optimise sensitivity and specificity. RESULTS: Absolute QTcF values were more discriminating than magnitude of increase from baseline. More participants who developed QT/QTcF ≥500 ms had a QTcF of respectively ≥425 ms and ≥430 ms at 4 h and Week 3 ( P < 0.05) than those who did not. By combining QTcF values ≥425 ms at 4 h and ≥430 ms at Week 3, we identified high-risk participants with 97% sensitivity and 99% negative predictive value. CONCLUSION: Reduced ECG monitoring may be possible for many Short regimen participants.

Natural plant populations often harbour substantial heritable variation in DNA methylation. However, a thorough understanding of the genetic and environmental drivers of this epigenetic variation requires large-scale and high-resolution data, which currently exist only for a few model species. Here, we studied 207 lines of the annual weed Thlaspi arvense (field pennycress), collected across a large latitudinal gradient in Europe and propagated in a common environment. By screening for variation in DNA sequence and DNA methylation using whole-genome (bisulfite) sequencing, we found significant epigenetic population structure across Europe. Average levels of DNA methylation were strongly context-dependent, with highest DNA methylation in CG context, particularly in transposable elements and in intergenic regions. Residual DNA methylation variation within all contexts was associated with genetic variants, which often co-localized with annotated methylation machinery genes but also with new candidates. Variation in DNA methylation was also significantly associated with climate of origin, with methylation levels being lower in colder regions and in more variable climates. Finally, we used variance decomposition to assess genetic versus environmental associations with differentially methylated regions (DMRs). We found that while genetic variation was generally the strongest predictor of DMRs, the strength of environmental associations increased from CG to CHG and CHH, with climate-of-origin as the strongest predictor in about one third of the CHH DMRs. In summary, our data show that natural epigenetic variation in Thlaspi arvense is significantly associated with both DNA sequence and environment of origin, and that the relative importance of the two factors strongly depends on the sequence context of DNA methylation. T. arvense is an emerging biofuel and winter cover crop; our results may hence be relevant for breeding efforts and agricultural practices in the context of rapidly changing environmental conditions., Competing Interests: The authors have declared that no competing interests exist.

Whole-genome bisulfite sequencing (WGBS) is the standard method for profiling DNA methylation at single-nucleotide resolution. Different tools have been developed to extract differentially methylated regions (DMRs), often built upon assumptions from mammalian data. Here, we present MethylScore, a pipeline to analyse WGBS data and to account for the substantially more complex and variable nature of plant DNA methylation. MethylScore uses an unsupervised machine learning approach to segment the genome by classification into states of high and low methylation. It processes data from genomic alignments to DMR output and is designed to be usable by novice and expert users alike. We show how MethylScore can identify DMRs from hundreds of samples and how its data-driven approach can stratify associated samples without prior information. We identify DMRs in the A. thaliana 1,001 Genomes dataset to unveil known and unknown genotype-epigenotype associations ., Competing Interests: The authors declare the following competing interests: J.H. is currently an employee of Computomics GmbH. S.J.S. is currently the CEO of and holds shares in Computomics GmbH. D.W. hold shares in Computomics GmbH. A.N. is currently an employee of ecSEQ Bioinformatics GmbH. D.L. is currently the CEO of and holds shares in ecSEQ Bioinformatics GmbH., (© The Author(s) 2022.)

HIV incidence among African American (AA) young men who have sex with men (YMSM) has remained stable even though they made up the largest number of new HIV diagnoses among men who have sex with men (MSM) in 2017. HIV spreads at increased rates in dense sexual networks. Identifying the location of risk behaviors "activity spaces" could inform geographically circumscribed HIV prevention interventions. Utilizing the modified social ecological model we completed five semi-structured focus groups incorporating a modified social mapping technique, based on Singer et al.'s approach. Participants included 27 AA YMSM. Focus groups explored how and where HIV transmission happens in Jackson, Mississippi. Result themes included: 1) location of sexual behaviors, 2) knowledge of geographic hotspots of HIV infection in Jackson, and 3) traveling to meet partners: at home and away. HIV transmission or "activity spaces" may be occurring outside identified HIV hot spots. Mixed geospatial and qualitative methods offered a comprehensive assessment of where HIV transmission occurs, and suggests that geographically circumscribed interventions may need to focus on where individuals living with HIV reside and in specific geographic locations where they engage in behaviors that raise their HIV acquisition risks.

Background: Black cisgender women in the U.S. South bear a disproportionate burden of HIV compared to cisgender women in other racial and ethnic groups and in any other part of the US. Critical to decreasing new HIV infections is the improved delivery of pre-exposure prophylaxis (PrEP) for Black cisgender women as it remains underutilized in 2021. Informed by intersectionality, the study sought to characterize the sociostructural influences on Black cisgender women's deliberations about PrEP within the context of interlocking systems of oppression including racism, sexism, and classism., Methods: Six focus groups were conducted with 37 Black women residing in Jackson, Mississippi. This sample was purposively recruited to include Black cisgender women who were eligible for PrEP but had never received a PrEP prescription., Results: Six themes were identified as concerns during PrEP deliberation among Black women: 1) limited PrEP awareness, 2) low perceived HIV risk, 3) concerns about side effects, 4) concerns about costs, 5) limited marketing, and 6) distrust in the healthcare system. Three themes were identified as facilitators during PrEP deliberations: 1) women's empowerment and advocacy, 2) need for increased PrEP-specific education, and 3) the positive influence of PrEP-engaged women's testimonials. Black women shared a limited awareness of PrEP exacerbated by the lack of Black women-specific marketing. Opportunities to support Black women-specific social marketing could increase awareness and knowledge regarding PrEP's benefits and costs. Black women also shared their concerns about discrimination in healthcare and distrust, but they felt that these barriers may be addressed by patient testimonials from PrEP-engaged Black women, empowerment strategies, and directly addressing provider biases., Conclusions: An effective response to PrEP implementation among Black women in the South requires developing programs to center the needs of Black women and carry out active strategies that prioritize peer advocacy while reinforcing positive and mitigating negative influences from broader social and historical contexts., (© 2022. The Author(s).)

Background: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings., Methods: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence., Results: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief)., Discussion: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health., (© 2022. The Author(s).)

BACKGROUND: STREAM (Standardised Treatment Regimens of Anti-tuberculosis drugs for Multidrug-Resistant Tuberculosis) Stage 1 demonstrated non-inferior efficacy of a short regimen for rifampicin-resistant TB (RR-TB) compared to a long regimen as recommended by the WHO. The present paper analyses factors associated with a definite or probable failure or relapse (FoR) event in participants receiving the Short regimen. METHODS: This analysis is restricted to 253 participants allocated to the Short regimen and is based on the protocol-defined modified intention to treat (mITT) population. Multivariable Cox regression models were built using backwards elimination with an exit probability of P = 0.157, equivalent to the Akaike Information Criterion, to identify factors independently associated with a definite or probable FoR event. RESULTS: Four baseline factors were identified as being significantly associated with the risk of definite or probable FoR (male sex, a heavily positive baseline smear grade, HIV co-infection and the presence of costophrenic obliteration). There was evidence of association of culture positivity at Week 8 and FoR in a second model and Week 16 smear positivity, presence of diabetes and of smoking in a third model. CONCLUSION: The factors associated with FoR outcomes identified in this analysis should be considered when determining the optimal shortened treatment regimen.

Several reduced-representation bisulfite sequencing methods have been developed in recent years to determine cytosine methylation de novo in nonmodel species. Here, we present epiGBS2, a laboratory protocol based on epiGBS with a revised and user-friendly bioinformatics pipeline for a wide range of species with or without a reference genome. epiGBS2 is cost- and time-efficient and the computational workflow is designed in a user-friendly and reproducible manner. The library protocol allows a flexible choice of restriction enzymes and a double digest. The bioinformatics pipeline was integrated in the Snakemake workflow management system, which makes the pipeline easy to execute and modular, and parameter settings for important computational steps flexible. We implemented bismark for alignment and methylation analysis and we preprocessed alignment files by double masking to enable single nucleotide polymorphism calling with Freebayes (epiFreebayes). The performance of several critical steps in epiGBS2 was evaluated against baseline data sets from Arabidopsis thaliana and great tit (Parus major), which confirmed its overall good performance. We provide a detailed description of the laboratory protocol and an extensive manual of the bioinformatics pipeline, which is publicly accessible on github (https://github.com/nioo-knaw/epiGBS2) and zenodo (https://doi.org/10.5281/zenodo.4764652)., (© 2022 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Background: Calling germline SNP variants from bisulfite-converted sequencing data poses a challenge for conventional software, which have no inherent capability to dissociate true polymorphisms from artificial mutations induced by the chemical treatment. Nevertheless, SNP data is desirable both for genotyping and to understand the DNA methylome in the context of the genetic background. The confounding effect of bisulfite conversion however can be conceptually resolved by observing differences in allele counts on a per-strand basis, whereby artificial mutations are reflected by non-complementary base pairs., Results: Herein, we present a computational pre-processing approach for adapting sequence alignment data, thus indirectly enabling downstream analysis on a per-strand basis using conventional variant calling software such as GATK or Freebayes. In comparison to specialised tools, the method represents a marked improvement in precision-sensitivity based on high-quality, published benchmark datasets for both human and model plant variants., Conclusion: The presented "double-masking" procedure represents an open source, easy-to-use method to facilitate accurate variant calling using conventional software, thus negating any dependency on specialised tools and mitigating the need to generate additional, conventional sequencing libraries alongside bisulfite sequencing experiments. The method is available at https://github.com/bio15anu/revelio and an implementation with Freebayes is available at https://github.com/EpiDiverse/SNP., (© 2022. The Author(s).)

Results from the STREAM stage 1 trial showed that a 9-month regimen for patients with rifampicin-resistant tuberculosis was non-inferior to the 20-month regimen recommended by the 2011 WHO treatment guidelines. Similar levels of severe adverse events were reported on both regimens suggesting the need for further research to optimise treatment. Stage 2 of STREAM evaluates two additional short-course regimens, both of which include bedaquiline. Throughout stage 2 of STREAM, new drug choices and a rapidly changing treatment landscape have necessitated changes to the trial's design to ensure it remains ethical and relevant. This paper describes changes to the trial design to ensure that stage 2 continues to answer important questions. These changes include the early closure to recruitment of two trial arms and an adjustment to the definition of the primary endpoint. If the STREAM experimental regimens are shown to be non-inferior or superior to the stage 1 study regimen, this would represent an important contribution to evidence about potentially more tolerable and more efficacious MDR-TB regimens, and a welcome advance for patients with rifampicin-resistant tuberculosis and tuberculosis control programmes globally.Trial registration: ISRCTN ISRCTN18148631 . Registered 10 February 2016., (© 2022. The Author(s).)

Among close contacts of patients with invasive group A streptococcal (iGAS) infection, the benefits and harms of chemoprophylaxis are uncertain. We conducted a systematic review of studies that reported on persons who, after being exposed to a case of laboratory-confirmed or probable iGAS, received any antibiotic prophylaxis for the prevention of GAS infection or carriage. Thirty-seven studies including 26 outbreak investigations and 11 case series or reports were included with predominantly descriptive information that suggested that antibiotic prophylaxis may be effective in preventing GAS infection or GAS carriage, with very few serious adverse events. However, current available evidence is scant (with limited information on contacts of iGAS cases) and largely based on studies with weak design and small sample size. Therefore, definitive conclusions on effectiveness of antibiotic prophylaxis cannot be drawn. Well designed prospective studies are required to establish the benefit-harm profile of antibiotic prophylaxis for secondary prevention of GAS disease among close contacts of iGAS cases., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Thlaspi arvense (field pennycress) is being domesticated as a winter annual oilseed crop capable of improving ecosystems and intensifying agricultural productivity without increasing land use. It is a selfing diploid with a short life cycle and is amenable to genetic manipulations, making it an accessible field-based model species for genetics and epigenetics. The availability of a high-quality reference genome is vital for understanding pennycress physiology and for clarifying its evolutionary history within the Brassicaceae. Here, we present a chromosome-level genome assembly of var. MN106-Ref with improved gene annotation and use it to investigate gene structure differences between two accessions (MN108 and Spring32-10) that are highly amenable to genetic transformation. We describe non-coding RNAs, pseudogenes and transposable elements, and highlight tissue-specific expression and methylation patterns. Resequencing of forty wild accessions provided insights into genome-wide genetic variation, and QTL regions were identified for a seedling colour phenotype. Altogether, these data will serve as a tool for pennycress improvement in general and for translational research across the Brassicaceae., (© 2022 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

HIV pre-exposure prophylaxis (PrEP) remains underutilized in the U.S. Since greater than 85% of PrEP prescriptions are filled at commercial pharmacies, pharmacists are uniquely positioned to increase PrEP use. This scoping review explores pharmacy-based initiatives to increase PrEP use. We searched PubMed, PsycINFO, CINAHL, and Scopus for peer-reviewed studies on pharmacist-led interventions to increase PrEP use or pharmacy-based PrEP initiatives. Forty-nine articles were included in this review. Overall, studies demonstrated that patients expressed strong support for pharmacist prescription of PrEP. Three intervention designs compared changes in PrEP initiation or knowledge pre- and post-intervention. Commentary/review studies recommended PrEP training for pharmacists, policy changes to support pharmacist screening for HIV and PrEP prescription, and telemedicine to increase prescriptions. Pharmacists could play key roles in improving PrEP use in the U.S. Studies that assess improvements in PrEP use after interventions such as PrEP prescription, PrEP-specific training, and adherence monitoring by pharmacists are needed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Food on the Move is an ongoing mobile produce market program in Rhode Island whose operations evolved from previous mobile market programs evaluated by 2 research studies: (1) one on Fresh to You, a prospective cohort study evaluating markets at community sites serving low-income families; and (2) one on Live Well, Viva Bien, a cluster randomized controlled trial evaluating markets and complementary nutrition interventions at public housing sites. The 2 studies spanned more than a decade and demonstrated the effect of mobile produce markets on access to, affordability of, and consumption of fruit and vegetables in low-income communities in Rhode Island. When grant funding ended in 2016, academic and community partners continued the mobile market program as Food on the Move. The Rhode Island Public Health Institute adopted the program model and developed a business plan to maximize market efficiency. To address price as a barrier to buying fruit and vegetables, the Institute implemented an innovative incentive program for purchases made with Supplemental Nutrition Assistance Program (SNAP) benefits, funded by a federal Food Insecurity Nutrition Incentive grant program. In 2018, Food on the Move sold more than $160 000 in produce at 335 markets, more than $50 000 of which came from these SNAP incentive programs. For sustained change in communities, researchers and community partners need examples of how to translate findings from research trials into public health practice. Food on the Move serves as a case study for the successful transition of community-focused research into a sustainable and scalable evidence-based program.