The experience of effort in ADHD: a scoping review.

Background: Mental effort plays a critical role in regulating cognition. However, the experience of mental effort may differ for individuals with Attention-Deficit/Hyperactivity Disorder (ADHD), a disorder for which sustained mental effort 'avoidance' or 'dislike' is a criterion in the DSM. We conducted a scoping review to characterize the literature on the experiences of effort in ADHD. Methods: This systematic scoping review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews and Joanna Briggs Methodology. PsycINFO (OVID), PsycINFO (ProQuest) and PubMed were searched for studies published in English before February 14, 2023. Studies must have included an ADHD population or a measure of ADHD symptomatology, in addition to a self-report measure of the experience of effort or the use of an effort preference paradigm. Two researchers reviewed all abstracts, and one researcher reviewed full-text articles. Results: Only 12 studies met the inclusion criteria. Several gaps and inconsistencies in the research were identified in terms of method, definitions of effort, measurements of ADHD, and sample characteristics. Moreover, the pattern of results on the experience of effort was mixed. Conclusion: Despite its diagnostic and conceptual significance, the experience of mental effort in ADHD is not well studied. Critical gaps were identified in the existing literature. A three-facet conceptualization of effort is proposed-specifically, task-elicited effort, volitionally exerted effort, and the affect associated with engaging in effort - to guide future explorations of the experience of effort in ADHD.

Strength of female mate preferences in temperature manipulation study supports the signal reliability hypothesis.

Both sexually selected traits and mate preferences for these traits can be context dependent, yet how variation in preferred traits could select for context dependent preferences has rarely been examined. The signal reliability hypothesis predicts that mate preferences vary across contexts (e.g., environments) in relation to the reliability of the information preferred traits provide in those contexts. Extensive variation in copy number of mc4r B alleles on the Y-chromosome that associates with male size in Xiphophorus multilineatus allowed us to use a split-sibling design to determine if male size is more likely to provide information about male genotype (i.e., dam) when males were reared in a warm as compared to a cold environment. We then examined strength of preference for male size by females reared in the same two environments. We found that males were larger in the cold environment, but male size was more variable across dams in the warm environment, and therefore male size would be a more reliable indicator of dam (i.e., genetics) in the warm environment. Females reared in the warm environment had stronger mate preferences based on male size than cold reared females, with a significant influence of dam on strength of preference. Therefore, strength of female preference for male size was influenced by the temperature in which they were reared, with the direction of the difference across treatments supporting the signal reliability hypothesis. Understanding how the reliability of male traits can select for contextual variation in the strength of the female mate preferences will further our discovery of adaptive mate preferences. For example, a relationship between the strength of a female's mate preference and their growth rates was detected in the context where females had a preference based on male size, supporting a hypothesis from previous work with this species of disassortative mating in relation to growth rates to mitigate a documented growth-mortality tradeoff.

Barriers and facilitators to engaging with a digital self-management programme for painful distal upper limb musculoskeletal disorders: A qualitative exploratory study.

INTRODUCTION: People living with a painful distal upper limb musculoskeletal disorder (DUL-MSD) often experience pain, difficulty in doing everyday tasks and a reduced quality of life. Currently, there are challenges in the treatment of DUL-MSDs, highlighting the need to develop innovative approaches to rehabilitation. A potential solution is to develop and implement a digital self-management rehabilitation programme focussing on optimising recovery, improving function and reducing pain. Before developing this programme, we aimed to identify the barriers and facilitators to using a digital health intervention (DHI) for self-management of DUL-MSDs. OBJECTIVE: This study aimed to investigate the potential barriers and facilitators to using a DHI with people living with DUL-MSDs and healthcare professionals (HCPs). METHODS: A qualitative exploratory study was carried out with purposely selected participants consisting of 15 participants with DUL-MSDs and 13 HCPs. Three focus groups (FGs) and four semistructured interviews with DUL-MSD participants and semistructured interviews with 13 HCPs were conducted. FGs and interviews were digitally recorded, transcribed and analysed using reflexive thematic analysis. RESULTS: To address challenges in the care and management of DUL-MSDs, both HCPs and people living with a DUL-MSD welcomed the development of a DHI. This study identified several barriers and facilitators that would influence engagement with a digital intervention. Findings suggest that in developing a DHI, attention needs to be paid to digital design features, usability, tailoring, personalisation and consideration of how well usual care could be replicated digitally without direct HCP involvement. CONCLUSION: The identified digital design features of importance to participants will inform the design of a digital self-management rehabilitation programme for people living with DUL-MSDs. Addressing the barriers and facilitators to engagement with a DHI is essential in ensuring its relevance and acceptability to those who will use it. PATIENT OR PUBLIC CONTRIBUTION: Patient and Public Involvement and Engagement (PPIE) was integral throughout the study. PPIE members contributed to the development and planning of this study, checked and confirmed the relevance of the findings and are involved in the dissemination plans.

Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Lifestyle Factors in Patients with Bladder Cancer: A Contemporary Picture of Tobacco Smoking, Electronic Cigarette Use, Body Mass Index, and Levels of Physical Activity.

BACKGROUND: Little is known about contemporary lifestyle choices in patients with bladder cancer (BC). These choices include carcinogenic risk factors and could affect fitness to receive treatments. OBJECTIVE: To evaluate the contemporary lifestyle choices in BC patients. DESIGN, SETTING, AND PARTICIPANTS: Self-reported surveys from participants diagnosed with BC in the previous 10 yr captured smoking patterns, e-cigarette use, physical activity using the GODIN Leisure-Time Exercise Questionnaire, long-term conditions (LTCs), relationship status, sociodemographics, and body mass index (BMI; height and weight). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Findings were compared with the general population and men with prostate cancer. RESULTS AND LIMITATIONS: Completed surveys were received from 2092 participants. Most respondents were ex-smokers (61% vs 10% current vs 29% never). The use of e-cigarettes was uncommon (9%) and at lower rates than the age-equivalent general population. Passive smoke exposure was frequent (48%). Most participants (68%) were "insufficiently active" using the GODIN criteria and less physically active than the age-equivalent general population. Most respondents (44%) were classified as overweight (BMI 25-29.99) or obese (22%, BMI >30). Lifestyle factors varied with age, sex, socioeconomic deprivation, and LTCs. Younger participants were less likely to smoke (p < 0.001), more likely to have used e-cigarettes (p < 0.001), but more likely to have had passive smoke exposure (p = 0.008). Those from less affluent areas were more likely to smoke (p < 0.001), have used e-cigarettes (p < 0.001), and have had passive smoke exposure (p = 0.02). Females were less likely to be smokers (p < 0.001) but more likely to have been exposed to passive smoke (p < 0.001). CONCLUSIONS: Persons affected by BC often have smoking exposures and high BMI, and are insufficiently active. Rates of e-cigarette use were lower than in the general population. Efforts to improve quality of life in this cohort should include wider advocation of smoking cessation, perhaps including the use of e-cigarettes, and programmes to increase exercise and reduce BMI. PATIENT SUMMARY: We looked at the lifestyle choices, such as smoking, e-cigarette use, physical activity levels, and obesity, of patients following a bladder cancer diagnosis. We conclude that this population would benefit from healthy lifestyle interventions.

Childhood Abuse and Neglect, Exposure to Domestic Violence and Sibling Violence: Profiles and Associations With Sociodemographic Variables and Mental Health Indicators.

Research indicates substantial overlap between child abuse and neglect (CAN), exposure to domestic violence and sibling abuse, with multiple victimisation experiences conferring greater risk for adverse mental health outcomes than does exposure to a single subtype. The application of latent class analysis (LCA) to child maltreatment has gained momentum, but it remains the case that few studies have incorporated a comprehensive range of subtypes, meaning that real-life patterns in victimisation experiences cannot be accurately modelled. Based on self-report data from an ethnically diverse sample (N = 2813) of 10-17 year olds in the United Kingdom, the current study used LCA to model constellations among nine types of maltreatment in the home (physical, emotional and sexual abuse; physical and emotional neglect; exposure to physical and verbal domestic violence, or a drug-related threat; and sibling violence). A four-class solution comprising of a low victimisation class (59.3% of participants), an emotional abuse and neglect class (19.0%), a high verbal domestic violence class (10.5%) and a maltreatment and domestic violence class (11.2%) provided the best fit for the data. Associations with sociodemographic variables were examined, revealing differences in the composition of the classes. Compared to the low victimisation class, participants in the verbal domestic violence class, emotional abuse and neglect class and especially the maltreatment and domestic violence class, reported higher symptoms of anxiety and depression and an increased likelihood of non-suicidal self-injury, suicide ideation and suicide attempt. The findings carry important implications for understanding patterns of child maltreatment, and the implications for preventative strategies and support services are discussed.

Stability of health-related quality of life and morbidity burden from 18 months after diagnosis of prostate cancer: results of a UK-wide population-based outcome cohort.

OBJECTIVE: To evaluate the dynamic nature of self-reported health-related quality of life (HRQL) and morbidity burden in men diagnosed with prostate cancer, we performed a follow-up study of the Life After Prostate Cancer Diagnosis (LAPCD) study cohort 12 months after initial survey. METHODS: The LAPCD study collected information from 35,823 men across the UK who were 18-42 months post-diagnosis of prostate cancer. Men who were still alive 12 months later were resurveyed. Generic HRQL (EQ-5D-5L plus self-assessed health rating) and prostate cancer-specific outcomes (EPIC-26) were assessed. Treatment(s) received was self-reported. Previously defined clinically meaningful differences were used to evaluate changes in outcomes over time. RESULTS: A total of 28,450 men across all disease stages completed follow-up surveys (85.8% response). Of the 21,700 included in this study, 89.7% reported no additional treatments since the first survey. This group experienced stable urinary and bowel outcomes, with good function for most men at both time points. On-going poor (but stable) urinary issues were associated with previous surgery. Sexual function scores remained low (mean: 26.8/100). Self-assessed health ratings were stable over time. The largest declines in HRQL and functional outcomes were experienced by men reporting their first active treatment between surveys. DISCUSSION: The results suggest stability of HRQL and most specific morbidities by 18-42 months for men who report no further treatment in the subsequent 12 months. This is reassuring for those with good function and HRQL but re-enforces the need for early intervention and support for men who experience poor outcomes.

Profiles of abuse and neglect and the association with mental health indicators among a large sample of boys and girls from India.

BACKGROUND: Child abuse and neglect (CAN) is a major public health concern, but limited data are available on the occurrence, co-occurrence, and correlates of these phenomena outside Western societies. OBJECTIVES: The first aim of this study was to establish the prevalence of CAN across two settings (inside and outside the home) among children and adolescents in Mumbai, India. Another aim was to use latent class analysis (LCA) to identify meaningful profiles of maltreatment, and to examine how class membership is associated with mental wellbeing. PARTICIPANTS AND SETTING: Self-report data was collected from males (n = 4454; Mage = 12.77 years) and females (n = 3850; Mage = 12.87) at secondary schools. RESULTS: Four latent classes of maltreatment were identified among males, including 'low victimisation' (50.4% of participants), 'intra-familial non-sexual abuse' (34.6%), 'intra- and extra- familial non-sexual abuse' (10.2%), and 'poly-victimisation' (4.8%). Among females, three latent classes were identified including, 'low victimisation' (68.1%), 'intra-familial non-sexual abuse' (28.8%), and 'poly-victimisation' (3.0%). Compared to the 'low victimisation' class, children in the abuse classes demonstrated higher levels of anxiety and depression and increased odds of self-injurious thoughts and behaviours. These associations were augmented for girls relative to boys. CONCLUSION: There were very few maltreated children who were subjected to just one form of CAN and experiencing co-occurring patterns of abuse and neglect was associated with indicators of poor mental health, especially among girls. These findings highlight the complexity of the situation and will inform policy makers, health professionals and school counsellors.

Quality of Life After Bladder Cancer: A Cross-sectional Survey of Patient-reported Outcomes.

BACKGROUND: Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC). OBJECTIVE: To determine this, we undertook a cross-sectional survey covering 10% of the English population. DESIGN, SETTING, AND PARTICIPANTS: Participants 1-10 yr from diagnosis were identified through national cancer registration data. INTERVENTION: A postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generic HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24. RESULTS AND LIMITATIONS: A total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non-muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr [67% {95% confidence interval or CI: 61-74}] vs 85+ yr [84% {95% CI: 81-89}], p = 0.016) and long-term conditions (no conditions [53% {95% CI: 48-58}] vs more than four conditions [94% {95% CI: 90-97}], p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 [95% CI: 16-25]) than those aged 85+ yr (6.8 [4.5-9.2], p < 0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% [95% CI: 66-72]) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% [95% CI: 48-53], all p < 0.05). CONCLUSIONS: HRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers. PATIENT SUMMARY: Patients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.

Prevalence and correlates of non-suicidal self-injury, suicidal ideation, and suicide attempt among children and adolescents: Findings from Uganda and Jamaica.

BACKGROUND: Youth non-suicidal self-injury (NSSI) and suicide are major public health concerns, but limited data are available on the prevalence and correlates of these problems in developing countries. The aim of this study is to describe experiences of three suicidal phenomena (NSSI, suicidal ideation [SI], and suicide attempt [SA]) among children and adolescents from two developing countries. We also examine how depression, anxiety, sleep problems, child maltreatment, and other socio-demographic variables associate with the risk of NSSI only, SI only, SA only, and co-occurring NSSI/SI/SA. METHODS: We conducted a population-based cross-sectional study of school-based Ugandan and Jamaican children and adolescents. Participants were 11,518 (52.4% female) Ugandan and 7,182 (60.8% female) Jamaican youths aged 9-17 years. RESULTS: The estimated lifetime prevalence of NSSI, SI, and SA was 25.5%, 25.6%, and 12.8% respectively among Ugandan boys and 23.2%, 32.5%, and 15.3% respectively among Ugandan girls. As for the Jamaican sample, the estimated lifetime prevalence of NSSI, SI, and SA was 21%, 27.7%, and 11.9% respectively among boys and 32.6%, 48.6%, and 24.7% respectively among girls. The odds of experiencing SI only, SA only, and co-occurring NSSI/SI/SA were significantly elevated among participants with mild, moderate, and severe depression in both countries. LIMITATIONS: The current study relied on retrospective data. CONCLUSIONS: This study found that suicidal phenomena are common among youths from Uganda and Jamaica, with rates substantially higher than among youths from high-income countries. The risk of suicidal phenomena was especially high among youths with severe depression.

Life and bladder cancer: protocol for a longitudinal and cross-sectional patient-reported outcomes study of Yorkshire (UK) patients.

INTRODUCTION: Little is known about the impact of bladder cancer (BC) and its treatments on health-related quality of life (HRQL). To date, most work has been small in scale or restricted to subsets of patients. Life and bladder cancer is a cross-sectional and longitudinal study collecting patient-reported outcomes within two distinct cohorts. METHODS AND ANALYSIS: A longitudinal study will collect patient-reported outcomes at 3-monthly intervals from newly diagnosed patients. Eligible cases will be identified by recruiting hospitals and surveyed at baseline, 6, 9 and 12 months postdiagnosis to explore changes in outcomes over time. A separate cross-sectional cohort of patients diagnosed within the last 10 years across Yorkshire will be identified through cancer registration systems and surveyed once to explore longer-term HRQL in BC survivors. A comprehensive patient-reported outcome measure (PROM) has been developed using generic, cancer-specific and BC-specific instruments. The study will provide evidence about how useful these PROMs are in measuring BC patient HRQL. The outcome data will be linked with administrative health data (eg, treatment information from hospital data). ETHICS AND DISSEMINATION: The study has received the following approvals: Yorkshire and the Humber-South Yorkshire Research Ethics Committee (17/YH/0095), Health Research Authority Confidentiality Advisory Group (17/CAG/0054). Results will be made available to patients, funders, NHS Trusts, Clinical Commissioning Groups, Strategic Clinical Networks and other researchers.

Case report of a child bearing a novel deleterious splicing variant in PIGT.

RATIONALE: Trio family-based whole exome sequencing (WES) is a powerful tool in the diagnosis of rare neurodevelopmental diseases, even in patients with the unclear diagnosis. There have been previous reports of variants in the phosphatidylinositol glycan anchor biosynthesis class T (PIGT) gene associated with multiple congenital anomalies, with a total of 14 affected individuals across 8 families. PATIENT CONCERNS: An 18-month-old boy of Greek ancestry presented with global developmental delay, generalized tonic-clonic seizures, hypotonia, renal cysts, esotropia, bilateral undescended testes, bilateral vesicoureteric reflux, marked cardiac dextroposition, bilateral talipes equinovarus, and dysmorphic features. DIAGNOSIS: WES revealed 2 compound heterozygous variants in the PIGT gene, c.[494-2A>G]; [547A>C]/p.[Asp122Glyfs*35]; [Thr183Pro]. The splicing mutation was demonstrated to lead to the skipping of exon 4. INTERVENTIONS: Seizures, infections, and other main symptoms were treated. OUTCOMES: The patient died at 2 years of age before the molecular diagnosis was achieved. Genetic counseling has been offered to the family. LESSONS: Most of the clinical features of the patient are in agreement with the previously described PIGT cases corroborating the usefulness of WES as a diagnostic tool.

Evaluating patient-reported outcome measures (PROMs) for bladder cancer: a systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist.

Patient-reported outcome measures (PROMs) are important tools used to understand patient-focused outcomes from care. Various PROMs have been developed for patients with bladder cancer (BC), although the disease's heterogeneity makes selection difficult. Accurate measurement of health-related quality of life (HRQL) can only be achieved if the PROM chosen is 'fit for purpose' (i.e. psychometrically sound). Systematic reviews of psychometric properties are useful for selecting the best PROM for a specific purpose. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) developed a checklist to improve the selection of health measurement instruments as part of a review process. Our aims were to undertake a systematic review, using the COSMIN criteria, to assess the quality of studies that report the psychometric properties of PROMs used with people with BC and determine the psychometric quality of these PROMs. An electronic search of seven databases including PubMed, MEDLINE and EMBASE (PROSPERO reference CRD42016051974) was undertaken to identify English language publications, published between January 1990 and September 2017 that evaluated psychometric properties of PROMs used in BC research. Two researchers independently screened abstracts and selected full-text papers. Studies were rated on methodological quality using the COSMIN checklist. Overall, 4663 records were screened and 23 studies, reporting outcomes in 3568 patients, were evaluated using the COSMIN checklist. Most PROMs had limited information reported about their psychometric properties. Studies reporting on the Bladder Cancer Index (BCI) and Functional Assessment of Cancer Therapy Vanderbilt Cystectomy Index (FACT-VCI) provided the most detail and these PROMs could be evaluated on the most COSMIN properties. Based on the available evidence, no existing PROM stands out as the most appropriate to measure HRQL in BC populations. This is due to two factors; (i) the heterogeneity of BC and its treatments (ii) no PROM was evaluated on all COSMIN measurement properties due to a lack of validation studies. We suggest future evaluation of generic, cancer generic and BC-specific PROMs to better understand their application with BC populations and propose strategies to help clinicians and researchers.

Health-related quality of life after treatment for bladder cancer in England.

BACKGROUND: Little is known about quality of life after bladder cancer treatment. This common cancer is managed using treatments that can affect urinary, sexual and bowel function. METHODS: To understand quality of life and inform future care, the Department of Health (England) surveyed adults surviving bladder cancer 1-5 years after diagnosis. Questions related to disease status, co-existing conditions, generic health (EQ-5D), cancer-generic (Social Difficulties Inventory) and cancer-specific outcomes (Functional Assessment of Cancer Therapy-Bladder). RESULTS: In total, 673 (54%) patients responded; including 500 (74%) men and 539 (80%) with co-existing conditions. Most respondents received endoscopic treatment (60%), while 92 (14%) and 99 (15%) received radical cystectomy or radiotherapy, respectively. Questionnaire completion rates varied (51-97%). Treatment groups reported ≥1 problem using EQ-5D generic domains (59-74%). Usual activities was the most common concern. Urinary frequency was common after endoscopy (34-37%) and radiotherapy (44-50%). Certain populations were more likely to report generic, cancer-generic and cancer-specific problems; notably those with co-existing long-term conditions and those treated with radiotherapy. CONCLUSION: The study demonstrates the importance of assessing patient-reported outcomes in this population. There is a need for larger, more in-depth studies to fully understand the challenges patients with bladder cancer face.

A qualitative study of patients' feedback about Outpatient Parenteral Antimicrobial Therapy (OPAT) services in Northern England: implications for service improvement.

OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation is patchy and a variety of service models are in use. The slow uptake in the UK and Europe is due to a number of clinical, financial and logistical issues, including concern about patient safety. The measurement of patient experience data is commonly used to inform commissioning decisions, but these focus on functional aspects of services and fail to examine the relational aspects of care. This qualitative study examines patients' experiences of OPAT. DESIGN: In-depth, semistructured interviews. SETTING: Purposive sample of OPAT patients recruited from four acute National Health Service (NHS) Trusts in Northern England. These NHS Trusts between them represented both well-established and recently set-up services running nurse at home, hospital outpatient and/or self-administration models. PARTICIPANTS: We undertook 28 semistructured interviews and one focus group (n=4). RESULTS: Despite good patient outcomes, experiences were coloured by patients' personal situation and material circumstances. Many found looking after themselves at home more difficult than they expected, while others continued to work despite their infection. Expensive car parking, late running services and the inconvenience of waiting in for the nurse to arrive frustrated patients, while efficient services, staffed by nurses with the specialist skills needed to manage intravenous treatment had the opposite effect. Many patients felt a local, general practitioner or community health centre based service would resolve many of the practical difficulties that made OPAT inconvenient. Patients could find OPAT anxiety provoking but this could be ameliorated by staff taking the time to reassure patients and provide tailored information. CONCLUSION: Services configurations must accommodate the diversity of the local population. Poor communication can leave patients lacking the confidence needed to be a competent collaborator in their own care and affect their perceptions of the service.

Inhibition of poly-ADP ribose polymerase enzyme activity prevents hyperglycemia-induced impairment of angiogenesis during wound healing.

We previously reported a zebrafish model of type I diabetes mellitus (DM) that can be used to study the hyperglycemic (HG) and metabolic memory (MM) states within the same fish. Clinically, MM is defined as the persistence of diabetic complications even after glycemic control is pharmacologically achieved. In our zebrafish model, MM occurs following ß-cell regeneration, which returns fish to euglycemia. During HG, fish acquire tissue deficits reflective of the complications seen in patients with DM and these deficits persist after fish return to euglycemia (MM). The unifying mechanism for the induction of diabetic complications involves a cascade of events that is initiated by the HG stimulation of poly-ADP ribose polymerase enzyme (Parp) activity. Additionally, recent evidence shows that the HG induction of Parp activity stimulates changes in epigenetic mechanisms that correlate with the MM state and the persistence of complications. Here we report that wound-induced angiogenesis is impaired in DM and remains impaired when fish return to a euglycemic state. Additionally, inhibition of Parp activity prevented the HG-induced wound angiogenesis deficiency observed. This approach can identify molecular targets that will provide potential new avenues for therapeutic discovery as angiogenesis imbalances are associated with all HG-damaged tissues.

An assay for lateral line regeneration in adult zebrafish.

Due to the clinical importance of hearing and balance disorders in man, model organisms such as the zebrafish have been used to study lateral line development and regeneration. The zebrafish is particularly attractive for such studies because of its rapid development time and its high regenerative capacity. To date, zebrafish studies of lateral line regeneration have mainly utilized fish of the embryonic and larval stages because of the lower number of neuromasts at these stages. This has made quantitative analysis of lateral line regeneration/and or development easier in the earlier developmental stages. Because many zebrafish models of neurological and non-neurological diseases are studied in the adult fish and not in the embryo/larvae, we focused on developing a quantitative lateral line regenerative assay in adult zebrafish so that an assay was available that could be applied to current adult zebrafish disease models. Building on previous studies by Van Trump et al. that described procedures for ablation of hair cells in adult Mexican blind cave fish and zebrafish (Danio rerio), our assay was designed to allow quantitative comparison between control and experimental groups. This was accomplished by developing a regenerative neuromast standard curve based on the percent of neuromast reappearance over a 24 hr time period following gentamicin-induced necrosis of hair cells in a defined region of the lateral line. The assay was also designed to allow extension of the analysis to the individual hair cell level when a higher level of resolution is required.

Parp inhibition prevents ten-eleven translocase enzyme activation and hyperglycemia-induced DNA demethylation.

Studies from human cells, rats, and zebrafish have documented that hyperglycemia (HG) induces the demethylation of specific cytosines throughout the genome. We previously documented that a subset of these changes become permanent and may provide, in part, a mechanism for the persistence of complications referred to as the metabolic memory phenomenon. In this report, we present studies aimed at elucidating the molecular machinery that is responsible for the HG-induced DNA demethylation observed. To this end, RNA expression and enzymatic activity assays indicate that the ten-eleven translocation (Tet) family of enzymes are activated by HG. Furthermore, through the detection of intermediates generated via conversion of 5-methyl-cytosine back to the unmethylated form, the data were consistent with the use of the Tet-dependent iterative oxidation pathway. In addition, evidence is provided that the activity of the poly(ADP-ribose) polymerase (Parp) enzyme is required for activation of Tet activity because the use of a Parp inhibitor prevented demethylation of specific loci and the accumulation of Tet-induced intermediates. Remarkably, this inhibition was accompanied by a complete restoration of the tissue regeneration deficit that is also induced by HG. The ultimate goal of this work is to provide potential new avenues for therapeutic discovery.

Identifying priorities for patient-centered outcomes research for serious mental illness.

OBJECTIVE: The purpose of this project was to engage a diverse group of stakeholders (N=38) to help establish priorities to guide patient-centered outcomes research (PCOR) in serious mental illness. METHODS: Three meetings, two Web-based and one on site, were held to generate and prioritize an initial list of topics. Topics were then sorted and organized into common themes. RESULTS: About 140 topics were identified and sorted into 21 main themes, ranked by priority. Three of the top four themes focused on how research was conducted, particularly the need to develop consensus measurement and outcomes definitions; improving infrastructure for research, longitudinal studies, and new data sets and investigators; and developing PCOR methodology. Stakeholders also identified a need to focus on service delivery, treatment settings, and structure of the delivery of care. CONCLUSIONS: Engagement by a broad group of stakeholders in a transparent process resulted in the identification of priority areas for PCOR. Stakeholders clearly indicated a need to fundamentally change how research on serious mental illness is conducted and a critical need for the development of methodology and infrastructure. Most current PCOR has been focused on relatively short-term outcomes, but real world, long-term studies providing guidance for treatment over the lifetime of a serious mental illness are needed.