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A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

BackgroundGammaKnife (GK) and CyberKnife (CK) have been the mainstay stereotactic radiosurgery (SRS) solution for multiple brain metastases (MBM) for several years. Recent technological advancement has seen an increase in single-isocentre C-arm linac-based SRS. This systematic review focuses on dosimetric and geometric insights into contemporary MBM SRS and thereby establish if linac-based SRS has matured to match the mainstay SRS delivery systems.MethodsThe PubMed, Web of Science and Scopus databases were interrogated which yielded 891 relevant articles that narrowed to 20 articles after removing duplicates and applying the inclusion and exclusion criteria. Primary studies which reported the use of SRS for treatment of MBM SRS and reported the technical aspects including dosimetry were included. The review was limited to English language publications from January 2015 to August 2023. Only full-length papers were included in the final analysis. Opinion papers, commentary pieces, letters to the editor, abstracts, conference proceedings and editorials were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The reporting of conformity indices (CI) and gradient indices, V12Gy, monitor units and the impact of translational and rotational shifts were extracted and analysed.ResultsThe single-isocentre technique for MBM dominated recent SRS studies and the most studied delivery platforms were Varian. The C-arm linac-based SRS plan quality and normal brain tissue sparing was comparable to GK and CK and in some cases better. The most used nominal beam energy was 6FFF, and optimised couch and collimator angles could reduce mean normal brain dose by 11.3%. Reduction in volume of the healthy brain receiving a certain dose was dependent on the number and size of the metastases and the relative geometric location. GK and CK required 4.5-8.4 times treatment time compared with linac-based SRS. Rotational shifts caused larger changes in CI in C-arm linac-based single-isocentre SRS.ConclusionC-arm linac-based SRS produced comparable MBM plan quality and the delivery is notably shorter compared to GK and CK SRS.

Previous research has indicated the suitability of behavioural activation (BA) as an intervention for reducing depression in older adults. However, little research has investigated the potential of BA to increase active engagement and well-being in older adults. The current pilot study sought to investigate the usefulness and acceptability of BA to promote well-being in a group of non-clinical older adults. Participants (N = 18) aged between 65 and 86 (M = 77.82, SD = 5.59) who were retired and living independently in the community were provided a 6-week BA program predominantly delivered online. Treatment retention, self-ratings, and participants' compliance to treatment principles indicate preliminary feasibility for the use of BA as an approach for increasing active engagement in older adult populations. Participants also provided feedback on their experiences with the program post-intervention via individual structured interviews. Thematic analysis of these data revealed that participants found the program to be beneficial in terms of increased self-awareness and social engagement, and provided several recommendations for improving acceptability of the program and workbook. The unexpected events relating to the first wave of the novel coronavirus (COVID-19) led to necessary adaptations to delivery modalities, and provided the researchers with an opportunity to investigate the use of a structured well-being program on a high-risk population during a pandemic. Our findings support the proposition that BA is a suitable intervention for increasing engagement and well-being in older adults, provide insight into adapting programs for older adults, and suggest next steps for testing intervention efficacy.

BackgroundLow social participation is a potentially modifiable risk factor for cognitive deterioration in the general population and related to lower quality of life (QoL). We aimed to find out whether social participation is linked to cognitive deterioration and QoL for people with borderline intellectual functioning and mild intellectual disability.MethodWe used data from the National Child Development Study, consisting of people born during one week in 1958, to compare midlife social participation in people with mild intellectual disability, borderline intellectual functioning, and without intellectual impairment. We defined social participation as 1. confiding/emotional support from the closest person and social network contact frequency at age 44, and 2. confiding relationships with anyone at age 50. We then assessed the extent to which social participation mediated the association between childhood intellectual functioning and cognition and QoL at age 50.Results14,094 participants completed cognitive tests at age 11. People with borderline intellectual functioning and mild intellectual disability had more social contact with relatives and confiding/emotional support from their closest person, but fewer social contacts with friends and confiding relationships with anyone than those without intellectual disability. Having a confiding relationship partially mediated the association at age 50 between IQ and cognition (6.4%) and QoL (27.4%) for people with borderline intellectual functioning.ConclusionWe found adults with intellectual disability have positive family relationships but fewer other relationships. Even at the age of 50, confiding relationships may protect cognition for people with borderline intellectual functioning and are important for QoL.

ObjectivesSocial prescribing is an approach that enables the referral of patients to non-clinical support and places a focus on holistic care. This study explored views of community pharmacists regarding social prescribing in pharmacies.Study designA qualitative phenomenological approach was used.MethodsA convenience sample of eleven community pharmacists from Northern England were recruited via social media (Twitter, Facebook) and took part in a semi-structured, one-to-one qualitative interviews that asked about their knowledge of social prescribing, the advantages of community pharmacist involvement and any barriers they predicted to its implementation. Interviews were transcribed verbatim and thematically analysed.ResultsThe sample included largely male pharmacists (63.3%) with less than five years' experience (45.5%) and included pharmacists working as employees (63.6%), locums (27.3%) and owners (9%) in both chain (36%) and independent stores (54.5%). The main findings indicate an enthusiasm for but limited understanding of social prescribing. Factors which appeared to influence involvement were training requirements and time available to complete an additional service in busy pharmacies. Opportunities centred on the broader pharmacy team's role to optimise health outcomes.ConclusionsThe findings indicate pharmacists may be an underused resource due to a poor understanding of the full scale and scope of social prescribing beyond health promotion, lifestyle interventions. Further work is needed to explore the transferability of the findings to the broader pharmacy workforce to understand how social prescribing can be positioned within pharmacy practice.

IntroductionThere have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening.MethodsBetween August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma.ResultsOf the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants.ConclusionUse of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

BackgroundDengue is a mosquito-borne disease caused by four distinct, closely related dengue viruses (DENV). Global dengue incidence has markedly increased in the past decades. The World Health Organization reported that cases increased from 505,430 in 2000 to 5.2 million in 2019. Similarly, the total dengue cases in Malaysia increased from 7,103 in 2000 to a peak of 130,101 in 2019. Knowledge, attitude, and practice (KAP) remain the most effective dengue prevention and control tools. Furthermore, school-based health education is key to enhancing knowledge and raising awareness of the seriousness of dengue among schoolchildren and transferring knowledge and practice from classrooms to homes. Thus, it is necessary to plan an integrated module for the primary prevention of dengue infection, specifically among schoolchildren.AimsThe present study intends to develop, implement, and evaluate the effectiveness of a theory-based integrated dengue education and learning (iDEAL) module in improving the KAP, environmental cleanliness index, and dengue index among schoolchildren in Selangor and Kuala Lumpur.MethodsThis study is a single-blinded, cluster randomised controlled trial to be conducted from 1 September 2023 to 31 August 2025. The study will involve 20 primary and 20 secondary schools in Selangor and Kuala Lumpur. The 1600 participants will be randomly allocated to intervention and control groups based on selected clusters to avoid contamination. A cluster is a comparable school that fulfils the inclusion and exclusion criteria. The intervention group will receive the iDEAL module, while the control group will receive standard education. The iDEAL module will be developed following a systematic procedure and delivered in-person by trained researchers to the participants. The outcome will be measured using validated, self-administered questionnaires at baseline (T0), immediately (T1), one month (T2), and three months (T3) post-intervention to measure the intervention module effectiveness. The data will be analysed using IBM Statistical Package for Social Science (SPSS) version 28 and descriptive and inferential statistics. Within-group changes over time will be compared using one-way repeated measure analysis of variance for continuous and normally distributed variables. Within-group analysis of categorical data will use Cochran's Q test. The main effect and interaction between and within the intervention and control groups at T0, T1, T2, and T3 will be tested using the generalised linear mixed model (GLMM). Hypothetically, the KAP, environmental cleanliness index, and dengue index among the intervention group will be significantly improved compared to the control group. The hypothesis will be tested using a significance level with a p-value of 0.05 and a confidence interval of 95%.ConclusionsThe study protocol outlines developing and testing an iDEAL module for schoolchildren in Selangor and Kuala Lumpur, with no socio-demographic differences expected. The intervention aims to improve KAP, environmental cleanliness index, and dengue index, potentially reducing dengue risk. Results could inform public health policies, emphasizing school-based interventions' importance in combating diseases like dengue.

Annually, about 300 million surgeries lead to significant intraoperative adverse events (iAEs), impacting patients and surgeons. Their full extent is underestimated due to flawed assessment and reporting methods. Inconsistent adoption of new grading systems and a lack of standardization, along with litigation concerns, contribute to underreporting. Only half of relevant journals provide guidelines on reporting these events, with a lack of standards in surgical literature. To address these issues, the Intraoperative Complications Assessment and Reporting with Universal Standard (ICARUS) Global Surgical Collaboration was established in 2022. The initiative involves conducting global surveys and a Delphi consensus to understand the barriers for poor reporting of iAEs, validate shared criteria for reporting, define iAEs according to surgical procedures, evaluate the existing grading systems' reliability, and identify strategies for enhancing the collection, reporting, and management of iAEs. Invitation to participate are extended to all the surgical specialties, interventional cardiology, interventional radiology, OR Staffs and anesthesiology. This effort represents an essential step towards improved patient safety and the well-being of healthcare professionals in the surgical field.

The COVID-19 pandemic caused far-reaching societal changes, including significant educational impacts affecting over 1.6 billion pupils and 100 million education practitioners globally. Senior school leaders were at the forefront and were exposed to particularly high demands during a period of "crisis leadership". This occupation were already reporting high work-related stress and large numbers leaving the profession preceding COVID-19. This cross-sectional descriptive study through the international COVID-Health Literacy network aimed to examine the well-being and work-related stress of senior school leaders (n = 323) in Wales (n = 172) and Northern Ireland (n = 151) during COVID-19 (2021-2022). Findings suggest that senior school leaders reported high workloads (54.22±11.30 hours/week), low well-being (65.2% n = 202, mean WHO-5 40.85±21.57), depressive symptoms (WHO-5 34.8% n = 108) and high work-related stress (PSS-10: 29.91±4.92). High exhaustion (BAT: high/very high 89.0% n = 285) and specific psychosomatic complaints (experiencing muscle pain 48.2% n = 151) were also reported, and females had statistically higher outcomes in these areas. School leaders were engaging in self-endangering working behaviours; 74.7% (n = 239) gave up leisure activities in favour of work and 63.4% (n = 202) sacrificed sufficient sleep, which was statistically higher for females. These findings are concerning given that the UK is currently experiencing a "crisis" in educational leadership against a backdrop of pandemic-related pressures. Senior leaders' high attrition rates further exacerbate this, proving costly to educational systems and placing additional financial and other pressures on educational settings and policy response. This has implications for senior leaders and pupil-level outcomes including health, well-being and educational attainment, requiring urgent tailored and targeted support from the education and health sectors. This is particularly pertinent for Wales and Northern Ireland as devolved nations in the UK, who are both implementing or contemplating major education system level reforms, including new statutory national curricula, requiring significant leadership, engagement and ownership from the education profession.

IntroductionEarly in the COVID-19 pandemic, Canadian primary care practices rapidly adapted to provide care virtually. Most family physicians lacked prior training or expertise with virtual care. In the absence of formal guidance, they made individual decisions about in-person versus remote care based on clinical judgement, their longitudinal relationships with patients, and personal risk assessments. Our objective was to explore Canadian family physicians' perspectives on the strengths and limitations of virtual care implementation for their patient populations during the COVID-19 pandemic and implications for the integration of virtual care into broader primary care practice.MethodsWe conducted semi-structured qualitative interviews with family physicians working in four Canadian jurisdictions (Vancouver Coastal health region, British Columbia; Southwestern Ontario; the province of Nova Scotia; and Eastern Health region, Newfoundland and Labrador). We analyzed interview data using a structured applied thematic approach.ResultsWe interviewed 68 family physicians and identified four distinct themes during our analysis related to experiences with and perspectives on virtual care: (1) changes in access to primary care; (2) quality and efficacy of care provided virtually; (3) patient and provider comfort with virtual modalities; and (4) necessary supports for virtual care moving forward.ConclusionsThe move to virtual care enhanced access to care for select patients and was helpful for family physicians to better manage their panels. However, virtual care also created access challenges for some patients (e.g., people who are underhoused or living in areas without good phone or internet access) and for some types of care (e.g., care that required access to medical devices). Family physicians are optimistic about the ongoing integration of virtual care into broader primary care delivery, but guidance, regulations, and infrastructure investments are needed to ensure equitable access and to maximize quality of care.

Amyotrophic lateral sclerosis (ALS) has been linked to overactivity of the protein kinase RNA-like ER kinase (PERK) branch of the unfolded protein response (UPR) pathway, both in ALS patients and mouse models. However, attempts to pharmacologically modulate PERK for therapeutic benefit have yielded inconsistent and often conflicting results. This study sought to address these discrepancies by comprehensively evaluating three commonly used, CNS-penetrant, PERK modulators (GSK2606414, salubrinal, and Sephin1) in the same experimental models, with the goal of assessing the viability of targeting the PERK pathway as a therapeutic strategy for ALS. To achieve this goal, a tunicamycin-challenge assay was developed using wild-type mice to monitor changes in liver UPR gene expression in response to PERK pathway modulation. Subsequently, multiple dosing regimens of each PERK modulator were tested in standardized, well-powered, gender-matched, and litter-matched survival efficacy studies using the SOD1G93A mouse model of ALS. The alpha-2-adrenergic receptor agonist clonidine was also tested to elucidate the results obtained from the Sephin1, and of the previously reported guanabenz studies, by comparing the effects of presence or absence of α-2 agonism. The results revealed that targeting PERK may not be an ideal approach for ALS treatment. Inhibiting PERK with GSK2606414 or activating it with salubrinal did not confer therapeutic benefits. While Sephin1 showed some promising therapeutic effects, it appears that these outcomes were mediated through PERK-independent mechanisms. Clonidine also produced some favorable therapeutic effects, which were unexpected and not linked to the UPR. In conclusion, this study highlights the challenges of pharmacologically targeting PERK for therapeutic purposes in the SOD1G93A mouse model and suggests that exploring other targets within, and outside, the UPR may be more promising avenues for ALS treatment.

Partisan animosity has been on the rise in America. Partisan animosity involves blame, wherein political partisans blame outparty members for their beliefs and actions. Here, we examine whether a historicist thinking intervention-drawn from research on blame mitigation-can reduce partisan animosity. The intervention consisted of three components: (1) a narrative about the idiosyncratic development of one political opponent paired with (2) a message about how unique life experiences shape everyone's political beliefs and (3) a suggestion that outparty members can be changed by future formative experiences. Experiments 1 and 2 showed that the intervention reduced cold feelings-measured via Feeling Thermometer-towards the outparty for both Democrats and Republicans. Experiments 3 and 4 focused on more specific emotional changes. Experiment 3 showed that, for Democrats, the intervention increased compassion. Experiment 4 showed that, for Republicans, the intervention reduced disgust, disapproval, anger, and contempt, but had no impact on compassion. For Democrats, but not for Republicans, reductions in animosity were mediated by reduced perceptions of control of self-formation, the mediator identified in prior work on historicist thinking and blame mitigation.

INTRODUCTION: Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients. METHODS: A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary). DISCUSSION: This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention.

Host-associated microbiomes can play important roles in the ecology and evolution of their insect hosts, but bacterial diversity in many insect groups remains poorly understood. Here we examine the relationship between host environment, host traits, and microbial diversity in three species in the ground beetle family (Coleoptera: Carabidae), a group of roughly 40,000 species that synthesize a wide diversity of defensive compounds. This study used 16S amplicon sequencing to profile three species that are phylogenetically distantly related, trophically distinct, and whose defensive chemical secretions differ: Anisodactylus similis LeConte, 1851, Pterostichus serripes (LeConte, 1875), and Brachinus elongatulus Chaudoir, 1876. Wild-caught beetles were compared to individuals maintained in the lab for two weeks on carnivorous, herbivorous, or starvation diets (n = 3 beetles for each species-diet combination). Metagenomic samples from two highly active tissue types-guts, and pygidial gland secretory cells (which produce defensive compounds)-were processed and sequenced separately from those of the remaining body. Bacterial composition and diversity of these ground beetles were largely resilient to controlled changes to host diet. Different tissues within the same beetle harbor unique microbial communities, and secretory cells in particular were remarkably similar across species. We also found that these three carabid species have patterns of microbial diversity similar to those previously found in carabid beetles. These results provide a baseline for future studies of the role of microbes in the diversification of carabids.

Atomic Force Microscopy was utilized to study the morphology of Gag, ΨRNA, and their binding complexes with lipids in a solution environment with 0.1Å vertical and 1nm lateral resolution. TARpolyA RNA was used as a RNA control. The lipid used was phospha-tidylinositol-(4,5)-bisphosphate (PI(4,5)P2). The morphology of specific complexes Gag-ΨRNA, Gag-TARpolyA RNA, Gag-PI(4,5)P2 and PI(4,5)P2-ΨRNA-Gag were studied. They were imaged on either positively or negatively charged mica substrates depending on the net charges carried. Gag and its complexes consist of monomers, dimers and tetramers, which was confirmed by gel electrophoresis. The addition of specific ΨRNA to Gag is found to increase Gag multimerization. Non-specific TARpolyA RNA was found not to lead to an increase in Gag multimerization. The addition PI(4,5)P2 to Gag increases Gag multimerization, but to a lesser extent than ΨRNA. When both ΨRNA and PI(4,5)P2 are present Gag undergoes comformational changes and an even higher degree of multimerization.

We have previously characterized a truncated isoform of the C. elegans insulin-like receptor, DAF-2B, which retains the ligand binding domain but cannot transduce a signal due to the absence of the intracellular signaling domain. DAF-2B modifies insulin / insulin-like growth factor signaling-dependent processes, such as dauer formation and lifespan, by sequestering insulin-like peptides (ILP) and preventing signaling through full length DAF-2 receptors. Here we show that DAF-2B is also important for starvation resistance, as genetic loss of daf-2b reduces survival in arrested first stage larvae (L1). Under fed conditions, we observe daf-2b splicing capacity in both the intestine and the hypodermis, but in starved L1s this becomes predominantly hypodermal. Using a novel splicing reporter system, we observe an increase in the ratio of truncated to full length insulin receptor splicing capacity in starved L1 larvae compared with fed, that may indicate a decrease in whole body insulin responsiveness. Consistent with this, overexpression of DAF-2B from the hypodermis, but not the intestine, confers increased survival to L1 animals under starvation conditions. Our findings demonstrate that the truncated insulin receptor DAF-2B is involved in the response to L1 starvation and promotes survival when expressed from the hypodermis.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

The blameworthiness of an offender is often discussed in groups. Yet, the research literature overwhelmingly examines individuals assessing blameworthiness in isolation. To address this gap in the literature, the present study examines group deliberations about blameworthiness, with a particular focus on how group deliberations impact utilization of mitigating information about an offender's unfortunate life history. Participants from introductory psychology courses at a U.S. university were placed in groups of two or three and each group also included a confederate who followed a script. Groups were randomly assigned to one of four conditions. In one condition (deed only), groups learned only about the offender's heinous crimes. In the three remaining conditions, participants also received a historicist narrative regarding how the offender's unfortunate history deformed his moral character. These conditions differed in terms of the confederate's arguments: Neutral arguments, arguments to ignore the narrative, or arguments to give great weight to the narrative. Results showed that the historicist narrative was particularly effective at reducing outrage and increasing compassion when the confederate argued for its utilization. The reduction in outrage mediated a reduction in spiteful punitiveness toward the offender. Interestingly, the confederate who urged fellow deliberators to ignore the historicist narrative had no impact on outrage or compassion. We also examined mediation of the impact of historicist narratives on outrage and compassion. We found that when the confederate remained neutral the impact of historicist narratives on outrage and compassion was mediated via diminished perceptions of the offender's control of self-formation. This mirrors what is typically found in prior work focused on individual judgments. In contrast, when the confederate argued that great weight should be given to the narrative, reductions in outrage were mediated via diminished perceptions of offender freedom of action. This pattern of mediation is not typically found but has been found in one previous study where participants received social encouragement to mitigate blame. Results are discussed in terms of how social influence might alter the inferences draw from historicist narratives. Suggestions for future research on social influence in the context of blame are presented.

BackgroundLarge observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting.MethodsWe conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir.ResultsThere were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths.InterpretationNirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.

BackgroundMental health impacts of the COVID-19 pandemic have not been felt equally within populations. Parents with children living at home were early on identified as a population at heightened mental health risk, with concerns about the potential long-term impacts of the pandemic on parents' mental health, family functioning, and children's well-being. This study investigates impacts of the pandemic on parents' psychological distress, contextual sources of distress, and associations with family functioning nearly two years into the pandemic.Methods and findingsData were drawn from a national cross-sectional survey of adults living in Canada in November and December 2021 that was representative by age, gender, household income, and region. Parents with children < 18 years old living at home (N = 553) reported their experiences of psychological distress, pandemic-related stressors, coping mechanisms, and family functioning (changes in parent-child interactions, children's anxiety). Chi-square tests, logistic regression, and linear regression analyses examined sociodemographic inequities in parents' levels of psychological distress, sources and mitigating mechanisms of distress, and associations between psychological distress and family functioning. Nearly two years into the pandemic, parents with children at home reported nearly double pre-pandemic population estimates of moderate to severe psychological distress. Psychological distress was more frequently reported among parents with pre-existing mental health conditions, disabilities, and financial stressors. Parents with greater psychological distress reported increases in negative parent-child interactions due to the pandemic and higher anxiety among their children.ConclusionsThis study identifies sustained negative impacts of the pandemic on parents' mental health and family functioning in Canada nearly two years into the pandemic, despite high vaccine uptake and declining infection rates. Disparities in financial stress, social support structures, and pre-existing mental health were identified as underlying sources of psychological distress. These results highlight that meaningful responses to promote mental health among parents and families must address social and structural inequities.

IntroductionWe aimed to investigate ethnic differences in the associations of potentially modifiable risk factors with dementia.MethodsWe used anonymised data from English electronic primary care records for adults aged 65 and older between 1997 and 2018. We used Cox regression to investigate main effects for each risk factor and interaction effects between each risk factor and ethnicity.ResultsWe included 865,674 people with 8,479,973 person years of follow up. Hypertension, dyslipidaemia, obesity and diabetes were more common in people from minority ethnic groups than White people. The impact of hypertension, obesity, diabetes, low HDL and sleep disorders on dementia risk was increased in South Asian people compared to White people. The impact of hypertension was greater in Black compared to White people.DiscussionDementia prevention efforts should be targeted towards people from minority ethnic groups and tailored to risk factors of particular importance.

BackgroundPeriorbital and orbital cellulitis are inflammatory conditions of the eye that can be difficult to distinguish using clinical examination alone. Computer tomography (CT) scans are often used to differentiate these two infections and to evaluate for complications. Orbital ultrasound (US) could be used as a diagnostic tool to supplement or replace CT scans as the main diagnostic modality. No prior systematic review has evaluated the diagnostic test accuracy (DTA) of ultrasound compared to cross-sectional imaging.ObjectiveTo conduct a systematic review of studies evaluating the DTA of orbital ultrasound compared with cross-sectional imaging, to diagnose orbital cellulitis.MethodsMEDLINE, EMBASE, CENTRAL, and Web of Science were searched from inception to August 10, 2022. All study types were included that enrolled patients of any age with suspected or diagnosed orbital cellulitis who underwent ultrasound and a diagnostic reference standard (i.e., CT or magnetic resonance imaging [MRI]). Two authors screened titles/abstracts for inclusion, extracted data, and assessed the risk of bias.ResultsOf the 3548 studies identified, 20 were included: 3 cohort studies and 17 case reports/series. None of the cohort studies directly compared the diagnostic accuracy of ultrasound with CT or MRI, and all had high risk of bias. Among the 46 participants, diagnostic findings were interpretable in 18 (39%) cases which reported 100% accuracy. We were unable to calculate sensitivity and specificity due to limited data. In the descriptive analysis of the case reports, ultrasound was able to diagnose orbital cellulitis in most (n = 21/23) cases.ConclusionFew studies have evaluated the diagnostic accuracy of orbital ultrasound for orbital cellulitis. The limited evidence based on low quality studies suggests that ultrasound may provide helpful diagnostic information to differentiate orbital inflammation. Future research should focus studies to determine the accuracy of orbital US and potentially reduce unnecessary exposure to radiation.

Poria cocos (PC) is a medicinal herb frequently used in weight-loss clinical trials, however the mechanisms by which its compounds target orexigenic receptors including the neuropeptide Y1 receptor (Y1R) remain largely unknown. This study aimed to screen PC compounds for favourable pharmacokinetics profiles and examine their molecular mechanisms targeting Y1R. Forty-three PC compounds were systematically sought from pharmacological databases and docked with Y1R (PDB: 5ZBQ). By comparing the relative binding affinities, pharmacokinetics and toxicity profiles, we hypothesised that compounds designated PC1 3,4-Dihydroxybenzoic acid, PC8 Vanillic acid, PC40 1-(alpha-L-Ribofuranosyl)uracil, could be potential antagonists as they contact major residues Asn283 and Asp287, similar to various potent Y1R antagonists. In addition, PC21 Poricoic acid B, PC22 Poricoic acid G and PC43 16alpha,25-Dihydroxy-24-methylene-3,4-secolanosta-4(28),7,9(11)-triene-3,21-dioic acid, contacting Asn299, Asp104 and Asp200 proximal to the extracellular surface could also interfere with agonist binding by stabilising the extracellular loop (ECL) 2 of Y1R in a closed position. Owing to their selective interaction with Phe302, an important residue in binding of selective Y1R antagonists, PC12 beta-Amyrin acetate, PC26 3-Epidehydrotumulosic acid and PC27 Cerevisterol were proposed as putative antagonists. Following the consensus approach, PC12 beta-Amyrin acetate, PC26 3-Epidehydrotumulosic acid and PC27 Cerevisterol were identified as candidate compounds due to their high affinities (-12.2, -11.0 and -10.8 kcal, respectively), high drug-likeness and low toxicity profiles. Trajectory analyses and energy contributions of PC12-Y1R complex further confirmed their structural stability and favourable binding free energies, highlighting the feasibility and possible development of PC12 beta-Amyrin acetate as a future Y1R inhibitor.

BackgroundMobile applications and technology (e.g., stroboscopic glasses) are increasingly being used to deliver combined visual and cognitive (termed visuo-cognitive) training that replaces standard pen and paper-based interventions. These 'technological visuo-cognitive training' (TVT) interventions could help address the complex problems associated with visuo-cognitive dysfunction in people with long term neurological conditions such as Parkinson's disease. As data emerges to support the effectiveness of these technologies, patient perspectives offer an insight into how novel TVT is received by people living with long term neurological conditions.ObjectiveTo explore experiences of people with Parkinson's in using technology as part of a home-based visuo-cognitive training programme compared to traditional approaches to rehabilitation.MethodsEight people with Parkinson's who took part in a pilot randomised cross-over trial, investigating the efficacy and feasibility of TVT compared to standard care, were interviewed to explore their experiences of each arm of the training they received. Integration of Normalisation Process Theory (NPT) into the analysis enabled examination of the potential to embed novel TVT into a home-based rehabilitation intervention for people with Parkinson's disease.ResultsThree key themes emerged from the thematic analysis as factors influencing the implementation potential of TVT for people with Parkinson's disease: perceived value of technology, perceived ease of use and support mechanisms. Further examination of the data through the lens of NPT revealed that the implantation and embedding of novel technology was dependent on positive user experience, individual disease manifestation and engagement with a professional.ConclusionsOur findings provide insights into the challenges of engaging with technology-based interventions while living with a progressive and fluctuating disease. When implementing technology-based interventions for people with Parkinson's, we recommend that patients and clinicians collaborate to determine whether the technology fits the capacity, preference, and treatment needs of the individual patient.

IntroductionCompanionship in antenatal care is important for facilitating positive parental experiences. During the COVID-19 pandemic, restrictions on partner attendance at fetal ultrasound scans were introduced nationally to minimise transmission of the virus. This study aimed to explore the effect of these restrictions on maternal and paternal experiences of pregnancy scans and evaluate their potential effect on parent-fetal bonding.MethodsA UK-wide, anonymous cross-sectional survey was completed by new and expectant parents (n = 714) who had, or were awaiting a pregnancy scan during the COVID-19 pandemic. The CORE-10 and an adapted version of the Prenatal Attachment Inventory were used to evaluate psychological distress and prenatal bonding. Additional survey questions captured parental experiences of scans. Separate statistical and thematic analyses of the data were undertaken. A joint display matrix was used to facilitate integration of quantitative and qualitative claims to generate a comprehensive interpretation of study findings.FindingsWhen fathers did not attend the scan, feelings of excitement and satisfaction were significantly reduced (pConclusionRestrictions on partner attendance at scans during the COVID-19 pandemic had a negative effect on parental experiences of antenatal imaging. Provision of parent-centred care, which is inclusive of partners, is essential for improved parental experiences.

Metabolic power (net energy consumed while walking per unit time) is, on average, two-to-three times greater in children with cerebral palsy (CP) than their typically developing peers, contributing to greater physical fatigue, lower levels of physical activity and greater risk of cardiovascular disease. The goal of this study was to identify the causal effects of clinical factors that may contribute to high metabolic power demand in children with CP. We included children who 1) visited Gillette Children's Specialty Healthcare for a quantitative gait assessment after the year 2000, 2) were formally diagnosed with CP, 3) were classified as level I-III under the Gross Motor Function Classification System and 4) were 18 years old or younger. We created a structural causal model that specified the assumed relationships of a child's gait pattern (i.e., gait deviation index, GDI) and common impairments (i.e., dynamic and selective motor control, strength, and spasticity) with metabolic power. We estimated causal effects using Bayesian additive regression trees, adjusting for factors identified by the causal model. There were 2157 children who met our criteria. We found that a child's gait pattern, as summarized by the GDI, affected metabolic power approximately twice as much as the next largest contributor. Selective motor control, dynamic motor control, and spasticity had the next largest effects. Among the factors we considered, strength had the smallest effect on metabolic power. Our results suggest that children with CP may benefit more from treatments that improve their gait pattern and motor control than treatments that improve spasticity or strength.

BackgroundOver a third of pregnant women (around 250,000) each year in the United Kingdom have experienced trauma such as domestic abuse, childhood trauma or sexual assault. These experiences can have a long-term impact on women's mental and physical health. This global qualitative evidence synthesis explores the views of women and maternity care professionals on routine discussion of previous trauma in the perinatal period.MethodsSystematic database searches (MEDLINE, EMBASE, CINAHL Plus, APA PsycINFO and Global Index Medicus) were conducted in July 2021 and updated in April 2022. The quality of each study was assessed using the Critical Appraisal Skills Programme. We thematically synthesised the data and assessed confidence in findings using GRADE-CERQual.ResultsWe included 25 papers, from five countries, published between 2001 and 2022. All the studies were conducted in high-income countries; therefore findings cannot be applied to low- or middle-income countries. Confidence in most of the review findings was moderate or high. The findings are presented in six themes. These themes described how women and clinicians felt trauma discussions were valuable and worthwhile, provided there was adequate time and appropriate referral pathways. However, women often found being asked about previous trauma to be unexpected and intrusive, and women with limited English faced additional challenges. Many pregnant women were unaware of the extent of the trauma they have suffered, or its impact on their lives. Before disclosing trauma, women needed to have a trusting relationship with a clinician; even so, some women chose not to share their histories. Hearing trauma disclosures could be distressing for clinicians.ConclusionDiscussions of previous trauma should be undertaken when women want to have the discussion, when there is time to understand and respond to the needs and concerns of each individual, and when there are effective resources available for follow up if needed. Continuity of carer should be considered a key feature of routine trauma discussion, as many women will not disclose their histories to a stranger. All women should be provided with information about the impact of trauma and how to independently access support in the event of non-disclosures. Care providers need support to carry out these discussions.

BackgroundOne of the 'best buys' for preventing Non-Communicable Diseases (NCDs) is to reduce tobacco use. The synergy scenario of NCDs with tobacco use necessitates converging interventions under two vertical programs to address co-morbidities and other collateral benefits. The current study was undertaken with an objective to ascertain the feasibility of integrating a tobacco cessation package into NCD clinics, especially from the perspective of healthcare providers, along with potential drivers and barriers impacting its implementation.MethodsA disease-specific, patient-centric, and culturally-sensitive tobacco cessation intervention package was developed (published elsewhere) for the Health Care Providers (HCPs) and patients attending the NCD clinics of Punjab, India. The HCPs received training on how to deliver the package. Between January to April 2020, we conducted a total of 45 in-depth interviews [medical officers (n = 12), counselors (n = 13), program officers (n = 10), and nurses (n = 10)] within the trained cohort across various districts of Punjab until no new information emerged. The interview data wereanalyzed deductively based on six focus areas concerning feasibility studies (acceptability, demand, adaptation, practicality, implementation, and integration) using the 7- step Framework method of qualitative analysis and put under preset themes.ResultsThe respondent's Mean ± SD age was 39.2± 9.2 years, and years of service in the current position were 5.5 ± 3.7 years. The study participants emphasized the role of HCPs in cessation support (theme: appropriateness and suitability), use of motivational interviewing, 5A's & 5R's protocol learned during the training & tailoring the cessation advice (theme: actual use of intervention activities); preferred face-to-face counseling using regional images, metaphors, language, case vignettes in package (theme: the extent of delivery to intended participants). Besides, they also highlighted various roadblocks and facilitators during implementation at four levels, viz. HCP, facility, patient, and community (theme: barriers and favorable factors); suggested various adaptations to keep the HCPs motivated along with the development of integrated standard operating procedures (SOPs), digitalization of the intervention package, involvement of grassroots level workers (theme: modifications required); the establishment of an inter-programmatic referral system, and a strong politico-administrative commitment (theme: integrational perspectives).ConclusionThe findings suggest that implementing a tobacco cessation intervention package through the existing NCD clinics is feasible, and it forges synergies to obtain mutual benefits. Therefore, an integrated approach at the primary & secondary levels needs to be adopted to strengthen the existing healthcare systems.

Cannabis flower odour is an important aspect of product quality as it impacts the sensory experience when administered, which can affect therapeutic outcomes in paediatric patient populations who may reject unpalatable products. However, the cannabis industry has a reputation for having products with inconsistent odour descriptions and misattributed strain names due to the costly and laborious nature of sensory testing. Herein, we evaluate the potential of using odour vector modelling for predicting the odour intensity of cannabis products. Odour vector modelling is proposed as a process for transforming routinely produced volatile profiles into odour intensity (OI) profiles which are hypothesised to be more informative to the overall product odour (sensory descriptor; SD). However, the calculation of OI requires compound odour detection thresholds (ODT), which are not available for many of the compounds present in natural volatile profiles. Accordingly, to apply the odour vector modelling process to cannabis, a QSPR statistical model was first produced to predict ODT from physicochemical properties. The model presented herein was produced by polynomial regression with 10-fold cross-validation from 1,274 median ODT values to produce a model with R2 = 0.6892 and a 10-fold R2 = 0.6484. This model was then applied to terpenes which lacked experimentally determined ODT values to facilitate vector modelling of cannabis OI profiles. Logistic regression and k-means unsupervised cluster analysis was applied to both the raw terpene data and the transformed OI profiles to predict the SD of 265 cannabis samples and the accuracy of the predictions across the two datasets was compared. Out of the 13 SD categories modelled, OI profiles performed equally well or better than the volatile profiles for 11 of the SD, and across all SD the OI data was on average 21.9% more accurate (p = 0.031). The work herein is the first example of the application of odour vector modelling to complex volatile profiles of natural products and demonstrates the utility of OI profiles for the prediction of cannabis odour. These findings advance both the understanding of the odour modelling process which has previously only been applied to simple mixtures, and the cannabis industry which can utilise this process for more accurate prediction of cannabis odour and thereby reduce unpleasant patient experiences.

Employees with mental health problems often struggle to remain in employment. During the COVID-19 pandemic, these employees face multiple additional stressors, which are likely to worsen their mental health and work productivity. Currently, it is unclear how to best support employees with mental health problems (and their managers) to improve wellbeing and productivity. We aim to develop a new intervention (MENTOR) that will jointly involve employees, managers, and a new professional (mental health employment liaison worker, MHELW), to help employees who are still at work with a mental health condition and currently receiving professional support for their mental health. A feasibility pilot study will then be undertaken to examine the feasibility and acceptability of the intervention from the perspective of employees and line managers. The study involves a feasibility randomised controlled study comparing outcomes of participants randomised to receive the intervention (MENTOR) with wait-list controls. Participants allocated to the waitlist control group will receive the intervention after three months. We aim to randomise 56 employee-manager pairs recruited from multiple organisations in the Midlands region of England. An intervention including 10 sessions for employees and managers (3 individual sessions and 4 joint sessions) will be delivered over 12 weeks by trained MHELWs. Primary outcomes include measures of feasibility and acceptability of the intervention and work productivity. Secondary outcomes include mental health outcomes. Qualitative interviews will be undertaken with a purposively selected sub-sample of employees and line managers at three-month post-intervention assessment. To our knowledge, this will be the first trial with a joint employee-manager intervention delivered by MHELWs. Anticipated challenges are dual-level consent (employees and managers), participants' attrition, and recruitment strategies. If the intervention and trial processes are shown to be feasible and acceptable, the outcomes from this study will inform future randomised controlled trials. Trial registration: This trial is pre-registered with the ISRCTN registry, registration number: ISRCTN79256498. Protocol version: 3.0_March_2023. https://www.isrctn.com/ISRCTN79256498.

BackgroundCrystal methamphetamine ('ice') use is a large and growing worldwide problem, yet few research studies have explored the impact of crystal methamphetamine use on affected friends and family members. We explored the experiences and narratives of family members and friends of people who use methamphetamine to inform the development of a Family and Friend Support Program.MethodsThis paper reports on a subset of findings from a mixed method study, which sought to better understand the experiences of family members and friends of people who use methamphetamine. Participants were recruited via Facebook advertising and asked to complete a survey outlining their experiences. At the end of the survey, participants were invited to be interviewed by a clinical psychologist on the research team, to discuss their experiences in greater depth; seventeen people agreed to be interviewed. This paper is based on a qualitative thematic analysis of these interviews using Braun and Clarke's 6-stage approach to identify key areas of concern for friends and family members of people who use methamphetamine.ResultsThrough thematic analysis, five key themes were developed, namely: (1) loss, (2) stigma, (3) support (or lack thereof), (4) ways of coping, and (5) the value in sharing personal experiences. The results of this study revealed the profound sadness, frustration and loss friends and family members experienced when caring for a loved one who uses methamphetamine. This loss was further complicated by societal stigma surrounding the use of methamphetamine, which often extended to friends and family members themselves. Since experiences of grief and loss were interwoven across the three themes, concepts of ambiguous loss, disenfranchised grief, and narrative constructivist approaches to understanding loss, were applied to the discussion of results.ConclusionThis study provides a more complete picture of family and caregiver experiences when caring for a loved one using methamphetamine, which may further help inform the design of intervention programs. Implications for future research and practice with this population are considered.

BackgroundAfrican American and Hispanic populations have been affected disproportionately by COVID-19. Reasons are multifactorial and include social and structural determinants of health. During the onset and height of the pandemic, evidence suggested decreased access to SARS CoV-2 testing. In 2020, the National Institutes of Health launched the Rapid Acceleration of Diagnostics (RADx)- Underserved Populations initiative to improve SARS CoV-2 testing in underserved communities. In this study, we explored attitudes, experiences, and barriers to SARS CoV-2 testing and vaccination among New York City public housing residents.MethodsBetween December 2020 and March 2021, we conducted 9 virtual focus groups among 36 low-income minority residents living in New York City public housing.ResultsAmong residents reporting a prior SARS CoV-2 test, main reasons for testing were to prepare for a medical procedure or because of a high-risk exposure. Barriers to testing included fear of discomfort from the nasal swab, fear of exposure to COVID-19 while traveling to get tested, concerns about the consequences of testing positive and the belief that testing was not necessary. Residents reported a mistrust of information sources and the health care system in general; they depended more on "word of mouth" for information. The major barrier to vaccination was lack of trust in vaccine safety. Residents endorsed more convenient testing, onsite testing at residential buildings, and home self-test kits. Residents also emphasized the need for language-concordant information sharing and for information to come from "people who look like [them] and come from the same background as [them]".ConclusionsBarriers to SARS CoV-2 testing and vaccination centered on themes of a lack of accurate information, fear, mistrust, safety, and convenience. Resident-endorsed strategies to increase testing include making testing easier to access either through home or onsite testing locations. Education and information sharing by trusted members of the community are important tools to combat misinformation and build trust.

IntroductionTrue penicillin allergy is rare and is commonly incorrectly reported. In fact, less than five percent of patients who report a penicillin allergy will have a currently active clinically-significant IgE- or T-cell-mediated hypersensitivity when appropriately tested. Penicillin is the agent of choice for intrapartum antibiotic prophylaxis to reduce the risk of group B streptococcus early-onset disease in the newborn. Inaccurate penicillin allergy status may lead to inappropriate antibiotic use, as most alternative drugs are more expensive and broader spectrum than penicillin. Penicillin allergy testing has been found to be safe in pregnancy and cost-effective in other patient populations.ObjectiveTo evaluate the cost-effectiveness of penicillin allergy testing and appropriate antibiotic treatment (test then treat strategy) compared to usual care among pregnant women.MethodsWe developed a decision tree to evaluate the cost of providing appropriate care via a test then treat strategy for pregnant women who report a penicillin allergy, compared to usual care.ResultsUsing the test then treat strategy the additional cost to ensure appropriate care for all pregnant women who report a penicillin allergy, was $1122.38 per person. Adopting a test then treat strategy increased the number of appropriate antibiotic use from 7,843/10,000 to 10,000/10,000 simulations.ConclusionOur results show that a test then treat strategy for pregnant women who report a penicillin allergy is a good-value intervention.

Background: GammaKnife (GK) and CyberKnife (CK) have been the mainstay stereotactic radiosurgery (SRS) solution for multiple brain metastases (MBM) for several years. Recent technological advancement has seen an increase in single-isocentre C-arm linac-based SRS. This systematic review focuses on dosimetric and geometric insights into contemporary MBM SRS and thereby establish if linac-based SRS has matured to match the mainstay SRS delivery systems. Methods: The PubMed, Web of Science and Scopus databases were interrogated which yielded 891 relevant articles that narrowed to 20 articles after removing duplicates and applying the inclusion and exclusion criteria. Primary studies which reported the use of SRS for treatment of MBM SRS and reported the technical aspects including dosimetry were included. The review was limited to English language publications from January 2015 to August 2023. Only full-length papers were included in the final analysis. Opinion papers, commentary pieces, letters to the editor, abstracts, conference proceedings and editorials were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The reporting of conformity indices (CI) and gradient indices, V12Gy, monitor units and the impact of translational and rotational shifts were extracted and analysed. Results: The single-isocentre technique for MBM dominated recent SRS studies and the most studied delivery platforms were Varian. The C-arm linac-based SRS plan quality and normal brain tissue sparing was comparable to GK and CK and in some cases better. The most used nominal beam energy was 6FFF, and optimised couch and collimator angles could reduce mean normal brain dose by 11.3%. Reduction in volume of the healthy brain receiving a certain dose was dependent on the number and size of the metastases and the relative geometric location. GK and CK required 4.5–8.4 times treatment time compared with linac-based SRS. Rotational shifts caused larger changes in CI in C-arm linac-based single-isocentre SRS. Conclusion: C-arm linac-based SRS produced comparable MBM plan quality and the delivery is notably shorter compared to GK and CK SRS. [ABSTRACT FROM AUTHOR]

Evidence from in vitro and animal models has identified the pulmonary toxicity of flavors in electronic cigarettes (ECIGs); however, less is known from epidemiological studies about the effects of flavors in the respiratory health. This study examined the longitudinal association between exposure to ECIGs flavors and nocturnal dry cough among ECIGs users. A secondary analysis of data from the Population Assessment of Tobacco and Health Study (2014–2019) was conducted. The study population included adults who provided information (n = 18,925) for a total of 38,638 observations. Weighted-incidence estimates and weighted- generalized estimating equation models were performed to assess unadjusted and adjusted associations. The weighted incidence proportion (WIP) of nocturnal dry cough was significantly higher among current (WIP:16.6%; 95%CI 10.5, 21.2) and former fruit flavored ECIGs users (WIP:16.6%; 95%CI 11.3, 21.9) as compared to non-ECIGs users (WIP:11.1%; 95%CI 10.6, 11.6). Current ECIGs users of fruit flavors showed 40% higher risk of reporting cough than non-ECIGs users (aRR:1.40, 95%CI 1.01, 1.94). Former ECIGs users of multiple flavors and other flavors had 300% and 66% higher risk to develop cough, respectively (aRR:3.33, 95%CI 1.51, 7.34 and aRR:1.66, 95%CI 1.0.9, 2.51), relative to non-ECIGs users. We observed a significantly higher risk of developing nocturnal dry cough in the past 12 months in current and former ECIGs users of fruit flavors and in former ECIGs users of multiple flavors. To the extent that cough may serve as an early indicator of respiratory inflammation and potential disease risk, the association between ECIGs use and cough raises potential concerns. [ABSTRACT FROM AUTHOR]

Previous research has indicated the suitability of behavioural activation (BA) as an intervention for reducing depression in older adults. However, little research has investigated the potential of BA to increase active engagement and well-being in older adults. The current pilot study sought to investigate the usefulness and acceptability of BA to promote well-being in a group of non-clinical older adults. Participants (N = 18) aged between 65 and 86 (M = 77.82, SD = 5.59) who were retired and living independently in the community were provided a 6-week BA program predominantly delivered online. Treatment retention, self-ratings, and participants' compliance to treatment principles indicate preliminary feasibility for the use of BA as an approach for increasing active engagement in older adult populations. Participants also provided feedback on their experiences with the program post-intervention via individual structured interviews. Thematic analysis of these data revealed that participants found the program to be beneficial in terms of increased self-awareness and social engagement, and provided several recommendations for improving acceptability of the program and workbook. The unexpected events relating to the first wave of the novel coronavirus (COVID-19) led to necessary adaptations to delivery modalities, and provided the researchers with an opportunity to investigate the use of a structured well-being program on a high-risk population during a pandemic. Our findings support the proposition that BA is a suitable intervention for increasing engagement and well-being in older adults, provide insight into adapting programs for older adults, and suggest next steps for testing intervention efficacy. [ABSTRACT FROM AUTHOR]