POLQ seals post-replicative ssDNA gaps to maintain genome stability in BRCA-deficient cancer cells.

POLQ is a key effector of DSB repair by microhomology-mediated end-joining (MMEJ) and is overexpressed in many cancers. POLQ inhibitors confer synthetic lethality in HR and Shieldin-deficient cancer cells, which has been proposed to reflect a critical dependence on the DSB repair pathway by MMEJ. Whether POLQ also operates independent of MMEJ remains unexplored. Here, we show that POLQ-deficient cells accumulate post-replicative ssDNA gaps upon BRCA1/2 loss or PARP inhibitor treatment. Biochemically, cooperation between POLQ helicase and polymerase activities promotes RPA displacement and ssDNA-gap fill-in, respectively. POLQ is also capable of microhomology-mediated gap skipping (MMGS), which generates deletions during gap repair that resemble the genomic scars prevalent in POLQ overexpressing cancers. Our findings implicate POLQ in mutagenic post-replicative gap sealing, which could drive genome evolution in cancer and whose loss places a critical dependency on HR for gap protection and repair and cellular viability.

Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps.

Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, preclinical and clinical research with PARPi has revealed multiple resistance mechanisms, highlighting the need for identification of novel functional biomarkers and combination treatment strategies. Functional genetic screens performed in cells and organoids that acquired resistance to PARPi by loss of 53BP1 identified loss of LIG3 as an enhancer of PARPi toxicity in BRCA1-deficient cells. Enhancement of PARPi toxicity by LIG3 depletion is dependent on BRCA1 deficiency but independent of the loss of 53BP1 pathway. Mechanistically, we show that LIG3 loss promotes formation of MRE11-mediated post-replicative ssDNA gaps in BRCA1-deficient and BRCA1/53BP1 double-deficient cells exposed to PARPi, leading to an accumulation of chromosomal abnormalities. LIG3 depletion also enhances efficacy of PARPi against BRCA1-deficient mammary tumors in mice, suggesting LIG3 as a potential therapeutic target.

Quantitative, titratable and high-throughput reporter assays to measure DNA double strand break repair activity in cells.

Repair of DNA damage is essential for the maintenance of genome stability and cell viability. DNA double strand breaks (DSBs) constitute a toxic class of DNA lesion and multiple cellular pathways exist to mediate their repair. Robust and titratable assays of cellular DSB repair (DSBR) are important to functionally interrogate the integrity and efficiency of these mechanisms in disease models as well as in response to genetic or pharmacological perturbations. Several variants of DSBR reporters are available, however these are often limited by throughput or restricted to specific cellular models. Here, we describe the generation and validation of a suite of extrachromosomal reporter assays that can efficiently measure the major DSBR pathways of homologous recombination (HR), classical nonhomologous end joining (cNHEJ), microhomology-mediated end joining (MMEJ) and single strand annealing (SSA). We demonstrate that these assays can be adapted to a high-throughput screening format and that they are sensitive to pharmacological modulation, thus providing mechanistic and quantitative insights into compound potency, selectivity, and on-target specificity. We propose that these reporter assays can serve as tools to dissect the interplay of DSBR pathway networks in cells and will have broad implications for studies of DSBR mechanisms in basic research and drug discovery.

A case-based narrative review of pregnancy-associated atypical hemolytic uremic syndrome/complement-mediated thrombotic microangiopathy.

Atypical hemolytic uremic syndrome is a complement-mediated thrombotic microangiopathy caused by uncontrolled activation of the alternative complement pathway in the setting of autoantibodies to or rare pathogenic genetic variants in complement proteins. Pregnancy may serve as a trigger and unmask atypical hemolytic uremic syndrome/complement-mediated thrombotic microangiopathy (aHUS/CM-TMA), which has severe, life-threatening consequences. It can be difficult to diagnose aHUS/CM-TMA in pregnancy due to overlapping clinical features with other thrombotic microangiopathy syndromes including hypertensive disorders of pregnancy. However, the distinction among thrombotic microangiopathy etiologies in pregnancy is important because each syndrome has specific disease management and treatment. In this narrative review, we discuss 2 cases to illustrate the diagnostic challenges and evolving approach in the management of pregnancy-associated aHUS/CM-TMA. The first case involves a 30-year-old woman presenting in the first trimester who was diagnosed with aHUS/CM-TMA and treated with eculizumab from 19 weeks' gestation. Genetic testing revealed a likely pathogenic variant in CFI. She successfully delivered a healthy infant at 30 weeks' gestation. In the second case, a 22-year-old woman developed severe postpartum HELLP syndrome, requiring hemodialysis. Her condition improved with supportive management, yet investigations assessing for aHUS/CM-TMA remained abnormal 6 months postpartum consistent with persistent complement activation but negative genetic testing. Through detailed case discussion describing tests assessing for placental health, fetal anatomy, complement activation, autoantibodies to complement regulatory proteins, and genetic testing for aHUS/CM-TMA, we describe how these results aided in the clinical diagnosis of pregnancy-associated aHUS/CM-TMA and assisted in guiding patient management, including the use of anticomplement therapy.

Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women.

Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman's reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.

Assessing cardiovascular disease risk in women with a history of hypertensive disorders of pregnancy: A guidance paper for studies using administrative data.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality, and their association with increased cardiovascular disease (CVD) risk represents a major public health concern. However, assessing CVD risk in women with a history of these conditions presents unique challenges, especially when studies are carried out using routinely collected data. OBJECTIVES: To summarise and describe key challenges related to the design and conduct of administrative studies assessing CVD risk in women with a history of HDP and provide concrete recommendations for addressing them in future research. METHODS: This is a methodological guidance paper. RESULTS: Several conceptual and methodological factors related to the data-generating mechanism and study conceptualisation, design/data management and analysis, as well as the interpretation and reporting of study findings should be considered and addressed when designing and carrying out administrative studies on this topic. Researchers should develop an a priori conceptual framework within which the research question is articulated, important study variables are identified and their interrelationships are carefully considered. CONCLUSIONS: To advance our understanding of CVD risk in women with a history of HDP, future studies should carefully consider and address the conceptual and methodological considerations outlined in this guidance paper. In highlighting these challenges, and providing specific recommendations for how to address them, our goal is to improve the quality of research carried out on this topic.

Evaluation of a Question Prompt List About Cardiovascular Disease Risk and Prevention After Hypertensive Pregnancy: A Pilot Study.

INTRODUCTION: The aim of this study was to pilot test a question prompt list (QPL) about cardiovascular disease (CVD) risk reduction after hypertensive pregnancy (HDP). METHODS: In a prospective cohort study of adult women who had HDP given the QPL before and surveyed after a physician visit, we assessed perceived person-centred care, self-efficacy for self-management, perceived self-management and QPL feasibility. RESULTS: Twenty-three women participated: 57% of diverse ethno-cultural groups, 65% < 40 years of age and 48% immigrants. Most scored high for person-centred care (mean 4.1 ± 0.2/5); and moderately for self-efficacy (mean 7.4 ± 0.6/10) and self-management (mean 3.1 ± 0.3/5). Most appreciated QPL design and reported QPL benefits: helped them to prepare for the visit and know what to ask; increased confidence to ask questions, knowledge of the link between HDP and CVD and lifestyle behaviours to reduce CVD risk. Most reported that physicians were receptive to discussing QPL questions. CONCLUSION: Women appreciated the QPL and knowledge about self-management was high but self-efficacy for or perceived self-management was moderate. It appears feasible to share a QPL with ethno-culturally diverse women who can share it with physicians to facilitate discussions about post-pregnancy HDP-related CVD risk. PATIENT OR PUBLIC CONTRIBUTION: This study involved women who experienced HDP and engaged ethno-culturally diverse women with lived experience of HDP as study advisors in all stages of the research.

Antenatal Glycemic Management and Postpartum Cardiovascular Disease Risk Screening.

OBJECTIVES: This study aims to evaluate the cardiovascular disease (CVD) risk profiles of patients referred to the Maternal Health Clinic (MHC) with a history of gestational diabetes mellitus (GDM). METHODS: Eligible patients had their MHC appointment at 6 months postpartum between November 2011 and May 2022 and experienced GDM in their most recent pregnancy. Included participants were then divided into subgroups comparing methods of glycemic control: diet-controlled GDM and insulin-controlled GDM. Additionally, the MHC recruited 47 patients who have not experienced a complication in pregnancy to act as a comparator group in research studies. Demographics, medical and pregnancy history, and CVD risk scores were compared between the 3 groups. RESULTS: In total, 344 patients with GDM were included in the analysis; 165 were insulin-controlled and 179 diet-controlled. When measuring the median 30-year Framingham risk score based on both BMI and lipids, there was a significant stepwise increase seen from the unexposed group, the diet-controlled GDM, and the insulin-controlled groups, respectively (all P < 0.05). The presence of metabolic syndrome showed a stepwise increase in prevalence when comparing the unexposed group, diet-exposure group, and the insulin-exposure group, respectively (16.7%; 21.5%-44.8%, P < 0.05). CONCLUSIONS: Our findings reinforce the prevalence of maternal CVD risk among GDM-diagnosed patients in the postpartum period and the necessity for screening. More specifically, our findings show how CVD risk may differ based on required interventions for glycemic control throughout pregnancy. Future research should aim to compare a more diverse patient population to optimise the generalizability of glycemic control-specific CVD outcomes.

Ten-Year Review of the Postpartum Maternal Health Clinic at the Kingston Health Sciences Centre.

OBJECTIVES: The postpartum Maternal Health Clinic (MHC) sees patients who have experienced pregnancy complications identified as pregnancy-related cardiovascular disease (CVD) risk indicators (hypertensive disorders of pregnancy, gestational diabetes, placental abruption, idiopathic preterm delivery, and intrauterine growth restriction) at 6 months postpartum for CVD risk screening. This project aimed to summarise the past 10 years of the MHC and identify trends in patient characteristics, patient CVD risk assessments, and clinic attendance over time. METHODS: Patients included in this study have experienced 1 or more pregnancy-related CVD risk indicator(s) and have delivered between April 2011 and April 2021. MHC patient data and the Better Outcomes Registry Network database were utilised to compare eligible and participating patient data during clinically significant time periods. RESULTS: The clinic has seen 1030 patients in the last 10 years and their characteristics have remained largely consistent. However, there has been an increase in the proportion of patients seen because of a hypertensive disorder and an increase in the proportion of patients with obesity, abnormal total cholesterol, and elevated fasting glucose. Additionally, CVD risk scores and the prevalence of metabolic syndrome have remained consistent over the years. Regarding the clinic's outreach, patient eligibility for the MHC has been increasing while attendance has been decreasing over time. CONCLUSIONS: Overall, there remains a need to screen these patients for CVD risk and counsel them on risk reduction. There is also an opportunity to increase patient recruitment to improve attendance and to address the increased need for CVD risk screening and counselling in the community.

Reconsidering Routine Repeat Group and Screens During Pregnancy-Personalizing Pregnancy Care.

The group and screen (G&S) are performed in early pregnancy to identify clinically significant antibodies (CSA) that may necessitate fetal monitoring for hemolysis/anemia or affect RhIg eligibility. Guidelines vary, including differences between RhD-positive and negative patients, but typically, the G&S is repeated at 28 weeks, and sometimes pre-delivery. We reviewed data showing a low risk (0.01%-0.43%) of detecting a new CSA in late gestation (late alloimmunization) and the risk of late alloimmunization causing severe hemolysis/anemia is even lower at <0.01%. Routinely repeating a G&S at 28 weeks and delivery may not be necessary for healthy, low-risk pregnancies.

A network analysis of self-compassion and burnout in a sample of nurses.

BACKGROUND: In the nursing profession, the concept of self-compassion has been associated with burnout. However, to date, the fine-grained relationships between different dimensions of self-compassion and symptoms of burnout have not been investigated. Network analysis provides a new avenue for exploring the fine-grained correlation paths of two related variables. AIM: To analyse the nuanced associations between self-compassion and burnout using network analysis in a large cohort of Chinese nurses. DESIGN: A cross-sectional multi-centre survey design study. METHODS: Participants were recruited from 30 hospitals in China between April and May 2022. These nurses completed the Chinese Maslach Burnout Inventory-General Survey (C-MBI-GS) and Self-Compassion Scale-Short Form (SCS-SF). Network analysis was performed to illustrate the complex nuanced relationships between self-compassion and burnout. RESULTS: A total of 1467 nurses (age 32.2 [18-56] years; 89.9% were female) participated in the study. Nodes Mindfulness and Isolation had the highest centralities measured by strength. Nodes Mindfulness, reduced personal accomplishment and Isolation were the most negative and positive influential nodes that bridged self-compassion and burnout. There were no differences in terms of gender, age, professional title and job tenure in the structure or connectivity of the self-compassion and burnout network. CONCLUSION: Different components of self-compassion were specifically associated with different dimensions of burnout in registered nurses. Among these, Mindfulness, Isolation and Reduced personal accomplishment were the three most important components of self-compassion for burnout symptoms. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT: Understanding the intricate connections between self-compassion and burnout will allow hospital administrators to prioritize the elements of Mindfulness and Isolation within self-compassion and the dimension of Reduced personal accomplishment within burnout when designing preventative measures and interventions aimed at reducing nurse burnout.

Navigating changes: A qualitative study exploring the health-related quality of life of breast cancer survivors during the coronavirus disease 2019 pandemic.

AIMS: To explore the impact of the coronavirus disease 2019 pandemic on the health-related quality of life (HRQoL) of breast cancer survivors. DESIGN: We utilized a qualitative descriptive approach to facilitate interviews among 25 participants, all of whom are survivors of breast cancer and have received treatment in Hong Kong within the preceding 3 years. METHODS: Content analysis was performed to understand how patients' HRQoL views and experiences changed during coronavirus disease 2019 pandemic. RESULTS: The results included six themes delineating the impact of the coronavirus disease 2019 pandemic: (i) survivor sensitivities in pandemic times, (ii) coping and conditioning in pandemic times, (iii) transforming work and home dynamics in pandemic times, (iv) cognitive resilience and adaptation to the COVID-19 protective measures, (v) social resilience in pandemic times and (vi) healthcare adaptation and coping in pandemic times. CONCLUSION: This study provides insights into the experiences and challenges of breast cancer survivors during the coronavirus disease 2019 pandemic. Some survivors had new physical and psychological symptoms, including fear and anxiety, isolation, pain, lymphoedema and burnout, which potentially have long-term impact upon HRQoL. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the unique challenges faced by breast cancer survivors during the coronavirus disease 2019 pandemic, including accessing healthcare services and the impact of social isolation. Healthcare providers should consider the holistic needs of breast cancer survivors in the provision of health care and develop supportive interventions, including telehealth services and online support groups, to address these challenges and improve their HRQoL. IMPACT: Surgery aimed at treating breast cancer or reducing its risk generally influences the appearance of breast areas and donor sites. The continuing effects of these changes on body image and HRQoL are well-reported, although studies have ineffectively examined the initial experiences of women regarding their postoperative appearance, particularly during the pandemic. REPORTING METHOD: The checklist of consolidated criteria for reporting qualitative research (COREQ) was utilized. PATIENT OR PUBLIC CONTRIBUTION: A small selection on breast cancer survivors contributed to the design of this study, in particular the content of the semi-structured interviews.

Experiences and Understanding of Well-Being in Lung Transplant Recipients in China: A Phenomenological Qualitative Study.

AIM: To explore lung transplant recipients' perceptions of well-being when they are facing uncertain health outcomes, including identifying the factors to enhance well-being. DESIGN: A qualitative descriptive study. METHODS: A purposive sample of 11 lung transplantation recipients who were hospitalised in the Department of Organ Transplantation of a tertiary university hospital was recruited in China. A descriptive qualitative study using thematic analysis of semistructured interviews. Themes were organised within a PERMA model. Colaizzi's qualitative analysis was used to analyse the data. RESULTS: Five major themes and 11 categories were generated: (1) mindset shift [optimism and hope and living in the moment]; (2) meaning in life [self-care, priority change and value realisation]; (3) health benefits [improved health and behavioural changes]; (4) perceived support [support from family, the health care team and others]; (5) unmet support needs. CONCLUSION: Lung transplant recipients could perceive well-being from five aspects that caused significantly favourable transformation across a variety of aspects in patients' lives. These findings may support nursing staff when caring for this patient group, making them aware of multifaceted nature of well-being. They could offer insight into potential pathways for the development of nurse-led tailored interventions, based on specific elements of PERMA model. IMPACT: This work adds to a growing body of knowledge about well-being amongst lung transplant patients. These findings may support nursing staff when caring for this patient group, making them aware of multifaceted nature of well-being and illustrating factors that promote positive well-being in this group, based on specific elements of PERMA model. REPORTING METHOD: This study followed the Consolidated Criteria for Reporting Qualitative Research checklist. PATIENT OR PUBLIC CONTRIBUTION: Two lung transplant recipients were involved in the early phases of this study. They helped in formulating the interview outline.

Generic Nonadditivity of Quantum Capacity in Simple Channels.

Determining capacities of quantum channels is a fundamental question in quantum information theory. Despite having rigorous coding theorems quantifying the flow of information across quantum channels, their capacities are poorly understood due to superadditivity effects. Studying these phenomena is important for deepening our understanding of quantum information, yet simple and clean examples of superadditive channels are scarce. Here we study a family of channels called platypus channels. Its simplest member, a qutrit channel, is shown to display superadditivity of coherent information when used jointly with a variety of qubit channels. Higher-dimensional family members display superadditivity of quantum capacity together with an erasure channel. Subject to the "spin-alignment conjecture" introduced in our companion paper [F. Leditzky, D. Leung, V. Siddhu, G. Smith, and J. A. Smolin, The platypus of the quantum channel zoo, IEEE Transactions on Information Theory (IEEE, 2023), 10.1109/TIT.2023.3245985], our results on superadditivity of quantum capacity extend to lower-dimensional channels as well as larger parameter ranges. In particular, superadditivity occurs between two weakly additive channels each with large capacity on their own, in stark contrast to previous results. Remarkably, a single, novel transmission strategy achieves superadditivity in all examples. Our results show that superadditivity is much more prevalent than previously thought. It can occur across a wide variety of channels, even when both participating channels have large quantum capacity.

Targeting ATR in Cancer Medicine.

As a key component of the DNA Damage Response, the Ataxia telangiectasia and Rad3-related (ATR) protein is a promising druggable target that is currently widely evaluated in phase I-II-III clinical trials as monotherapy and in combinations with other rational antitumor agents, including immunotherapy, DNA repair inhibitors, chemo- and radiotherapy. Ongoing clinical studies for this drug class must address the optimization of the therapeutic window to limit overlapping toxicities and refine the target population that will most likely benefit from ATR inhibition. With advances in the development of personalized treatment strategies for patients with advanced solid tumors, many ongoing ATR inhibitor trials have been recruiting patients based on their germline and somatic molecular alterations, rather than relying solely on specific tumor subtypes. Although a spectrum of molecular alterations have already been identified as potential predictive biomarkers of response that may sensitize to ATR inhibition, these biomarkers must be analytically validated and feasible to measure robustly to allow for successful integration into the clinic. While several ATR inhibitors in development are poised to address a clinically unmet need, no ATR inhibitor has yet received FDA-approval. This chapter details the underlying rationale for targeting ATR and summarizes the current preclinical and clinical landscape of ATR inhibitors currently in evaluation, as their regulatory approval potentially lies close in sight.

Study protocol for the sheMATTERS study (iMproving cArdiovascular healTh in new moThERS): a randomized behavioral trial assessing the effect of a self-efficacy enhancing breastfeeding intervention on postpartum blood pressure and breastfeeding continuation in women with hypertensive disorders of pregnancy.

BACKGROUND: Individuals with hypertensive disorders of pregnancy (HDP) have an elevated lifetime risk of chronic hypertension, metabolic syndrome, and premature cardiovascular disease. Because breastfeeding duration and exclusivity have been associated in observational studies with improved cardiovascular health, optimizing breastfeeding in those with HDP might be an unrealized cardio-prevention approach, in particular because individuals with HDP have more breastfeeding challenges. Breastfeeding supportive interventions targeting one's breastfeeding self-efficacy have been shown to improve breastfeeding rates. METHODS: We designed an open-label, multi-center 1:1 randomized behavioral trial to test whether a previously validated self-efficacy enhancing breastfeeding intervention can improve breastfeeding duration and/or exclusivity, and lower postpartum blood pressure at 12 months. Randomization is computer-generated and stratified by site (four hospitals in Montreal, Quebec and one hospital in Kingston, Ontario; all in Canada). Included are breastfeeding participants with HDP (chronic/gestational hypertension or preeclampsia) who delivered a live singleton infant at > 34 weeks, speak English or French, and have no contraindications to breastfeeding. Informed and written consent is obtained at hospitalization for delivery or a re-admission with hypertension within 1 week of discharge. Participants assigned to the intervention group receive a breastfeeding self-efficacy-based intervention delivered by a trained lactation consultant in hospital, with continued reactive/proactive support by phone or text message for up to 6 months postpartum. Regardless of group assignment, participants are followed for self-reported outcomes, automated office blood pressure, and home blood pressure at several time points with end of follow-up at 12 months. DISCUSSION: This study will assess whether an intensive nurse-led behavioral intervention can improve breastfeeding rates and, in turn, postpartum blood pressure - an early marker for atherosclerotic cardiovascular disease. If effective, this form of enhanced breastfeeding support, along with closer BP and metabolic surveillance, can be implemented broadly in individuals lactating after HDP. TRIAL REGISTRATION: ClinicalTrials.gov, # NCT04580927 , registered on Oct 9, 2020.

Quality of life profiles and its association with predictors amongst Chinese older adults in nursing homes: a latent profile analysis.

BACKGROUND: Recently developments in the field of positive psychology have provided new perspectives for understanding the connection between individual variation in Quality of life (QoL) and positive aspects of human potential, strengths, and resources, commanding increasing attention. This study aimed to examine self-reported quality of life (QoL) profiles and the association of QoL profiles with positive psychosocial characteristics in Chinese older adults. METHODS: A convenient sample of 354 older adults in nursing homes was recruited from Guangdong Province, China, between November 2020 and January 2021. Latent Profile Analysis (LPA) was conducted to explore QoL profiles using the four WHOQOL-BREF domains as input variables. Multinomial logistic regression was performed to explore the association between latent profiles and predictors. RESULTS: LPA identified three latent QoL profiles: "low QoL with poor psychological health" (18.1%), "moderate QoL" (46.0%) and "high QoL" (35.9%). Frequency of weekly activity, optimism, gratitude, and social support were associated with the increased likelihood of belonging to the moderate-to-high QoL classes. Furthermore, Class 2 (moderate QoL group, reference) was compared with Class3 (high QoL group), higher frequency of weekly physical activity and spending more time on physical activity exhibited higher odds of belonging to high QoL class. CONCLUSION: Using the domains of the WHOQOL-BREF scale, the QoL profiles Chinese older adults can be identified. We found that psychosocial variables and demographic characteristic, including lower level of optimism and gratitude, lack of social support, low frequency of physical activity, and shorter activity duration time, heighten the risk for lower levels of QoL. Identifying classification may help focus on those at elevated risk for poor QoL and for developing tailored QoL improvement programs.

Dementia literacy in an ageing world.

AIMS: This discursive article aims to capture and explore the most pertinent nursing aspects of dementia literacy (DL). BACKGROUND: Older people constitute a rapidly increasing proportion of the global population, experiencing higher risk of developing chronic disease, including dementia. It is important that older adults receive and understand reliable health-related information, as age-related changes may affect the level of health literacy in an older person. It has been suggested that older adults may have poorer health literacy than younger adults, associated with poorer health outcomes. Health literacy, how people receive, interpret and act on health information, play a significant role in dementia-related disorders, both as a possible predicter of onset of dementia and as a potential modifier of cognitive decline. Dementia literacy constitutes one aspect of health literacy in relation to nursing care, related to knowledge of dementia-related disorders and approaches towards older people with dementia. DESIGN: This discursive article explores the importance of DL for the nursing profession, including dementia-related assessment, education and interventions. METHOD: This article is informed by analysis of relevant descriptive and empirical literature and policy documents related to DL, an increasingly important aspect of dementia-related nursing care. Valid assessment tools that can accurately assess aspects an individuals' DL are examined; these have the potential to help nurses detect dementia-related symptoms. With early detection and prevention of dementia, older people may have better chance of benefiting from evolving treatment options. CONCLUSION: Greater attention needs to be given to the issue of DL in older people, especially in terms of nursing assessment and care. Globally, increased DL-related education is urgently required to improve knowledge of this concept; this includes public awareness initiatives to better understanding this chronic condition. IMPLICATION NURSING PRACTICE: Enhancing DL has the potential to empower older people to have greater access to healthcare services and to make more informed decisions about their health care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution, as this is a discursive article.

Addressing the dauntingness of formulation: The value of considering empathy as "grasping".

AIMS AND OBJECTIVES: To explore the value of using Karl Jaspers' lived experience concept of 'grasping' in remediating the reported dauntingness of formulation. CONCLUSIONS: Formulation can be construed as both the process and explication of understanding why a patient is presenting in a particular way. In an automatic process of abduction, 'feeling into' the mind of the other, hypotheses are posted to consciousness with little mental effort as meaningful connections are grasped. Subsequent more deliberative reasoning is synthesised continuously and with surprisingly little mental effort into the best explanation(s). Karl Jaspers' introduction to Psychiatry of the concepts involved, empathy and understanding, and his aim of making their use more scientific established the ongoing, often fierce debate about the ontology of Psychiatry; empirical versus interpretive. Trainees must resolve this for themselves in explicating a formulation, risking exposure of their prejudices. Jaspers' emphasis on the lived experience of empathic understanding that psychiatrists bring to their work found him often using the term 'grasp' rather than 'empathise'. 'Grasping' seems to convey more vividly and meaningfully the role that empathy plays in the initial ascertainment of mood and the subsequent hypothesis discovery, testing and synthesis.

A retrospective observational research study to describe the real-world use of bosutinib in patients with chronic myeloid leukemia in the United Kingdom and the Netherlands.

OBJECTIVES: To describe the real-world effectiveness and safety of bosutinib in patients with chronic myeloid leukemia (CML). METHODS: This was a multi-center, retrospective, non-interventional chart review study conducted in 10 hospitals in the United Kingdom and the Netherlands. RESULTS: Eighty-seven patients were included. Bosutinib was the third-line tyrosine kinase inhibitor (TKI) in 33 (38%) and fourth-line in 44 (51%) patients. Median treatment duration was 15.6 months. Among 84 patients in chronic phase (CP) at baseline, 26 (31%) switched to bosutinib due to resistance and 57 (68%) due to intolerance to prior TKIs. Cumulative complete cytogenetic and major molecular response rates in CP patients were 67% and 55%, respectively. After a median follow-up of 21.5 months, nine (11%) patients in CP died; estimated overall survival rates at 1 and 2 years postbosutinib initiation were 95% and 91%, respectively. Overall, 33/87 (38%) patients discontinued bosutinib due to either lack of efficacy/disease progression (17%), adverse events (14%), death (2%), or other reasons (5%). Eighty-two (94%) patients experienced ≥1 adverse event possibly related to bosutinib, most commonly diarrhea (52%). CONCLUSIONS: Bosutinib used in routine clinical practice in heavily pretreated patients with CML is an effective treatment for patients in CP and is generally tolerable.