The Sexual Offences (NI) Order 2008 implications for nurses

This article outlines the changes to the definition of sexual offences in Northern Ireland following the implementation of the Sexual offences Northern Ireland Order 2008 in 2009, and its implications for nurses working with sexually active children in a range of clinical settings. The paper outlines the key changes for practice and addresses the needs of children in three different age groups with emphasis on children aged 13-15 years, and reviews mandatory reporting, the differences between the rights of children to consent and confidentiality, developmental sexual experimentation and sexual health promotion. It reviews related policy and guidance and makes clear the differences between sexual abuse and exploitation, and experimentation. It seeks to advise the Safeguarding Committee of the Department of Health Northern Ireland on how best to support nurses working with sexually active children and when this activity should be discussed with line managers and safeguarding specialists or referred to the safeguarding authorities.

Legalizing physician-assisted suicide and/or euthanasia: Pragmatic implications

Objective: Despite the availability of palliative care in many countries, legalization of euthanasia and physician-assisted suicide (EAS) continues to be debated-particularly around ethical and legal issues-and the surrounding controversy shows no signs of abating. Responding to EAS requests is considered one of the most difficult healthcare responsibilities. In the present paper, we highlight some of the less frequently discussed practical implications for palliative care provision if EAS were to be legalized. Our aim was not to take an explicit anti-EAS stance or expand on findings from systematic reviews or philosophical and ethico-legal treatises, but rather to offer clinical perspectives and the potential pragmatic implications of legalized EAS for palliative care provision, patients and families, healthcare professionals, and the broader community.

Method: We provide insights from our multidisciplinary clinical experience, coupled with those from various jurisdictions where EAS is, or has been, legalized.

Results: We believe that these issues, many of which are encountered at the bedside, must be considered in detail so that the pragmatic implications of EAS can be comprehensively considered.

Significance of Results: Increased resources and effort must be directed toward training, research, community engagement, and ensuring adequate resourcing for palliative care before further consideration is given to allocating resources for legalizing euthanasia and physician-assisted suicide.

High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination

BACKGROUND: Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement.

METHODS: A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis.

RESULTS: In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations.

CONCLUSIONS: The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.

A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking

Objectives: To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. 

Methods: The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed-days and per 100 bed-days/age-adjusted comorbidity score. 

Results: Results showed that antibiotic use had significant positive relationships with the sum of age-adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. 

Conclusions: The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects. 

Characterization of NKR+ T-cell subsets in human bone marrow:implications for immunosurveillance of neoplasia

In addition to hematopoietic progenitors, human bone marrow contains mature T/NK lymphocytes. Valpha24Vbeta11 NKT-cells, a subset of NK receptor+ (NKR+) T-cells in humans, are rare in bone marrow, suggesting the presence of other NKR+ T-cells which may contribute to tumor surveillance. NKR+/- T-cells were examined in blood (PB), and bone marrow from donors (DM) and patients with active hematopoietic malignancy (PM), or in remission (PR). T-cells in PR & PM were enriched for CD56+ and CD57+ subsets, compared to DM. All marrow NKR+/- T-cell subsets were more activated than PB. PM and, surprisingly, PR marrow contained more activated cells than DM. CD8+ cells were significantly increased in all patient marrows and there was evidence of the formation of an effector/memory pool in malignant marrow. These data suggest that NKR+ T-cell enrichment in human bone marrow that has been exposed to neoplastic transformation is compatible with a role in localized tumor surveillance/eradication.

Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

Implications of aligning full registration of doctors with medical school graduation:a qualitative study of stakeholder perspectives

OBJECTIVES: The Shape of Training report recommended that full registration is aligned with medical school graduation. As part of a General Medical Council-funded study about the preparedness for practice of UK medical graduates, we explored UK stakeholders' views about this proposal using qualitative interviews (30 group and 87 individual interviews) and Framework Analysis.

SETTING: Four UK study sites, one in each country.Save

PARTICIPANTS: 185 individuals from eight stakeholder groups: (1) foundation year 1 (F1) doctors (n=34); (2) fully registered trainee doctors (n=33); (3) clinical educators (n=32); (4) undergraduate/postgraduate Deans, and Foundation Programme Directors (n=30); (5) other healthcare professionals (n=13); (6) employers (n=7); (7) policy and government (n=11); (8) patient and public representatives (n=25).

RESULTS: We identified four main themes: (1) The F1 year as a safety net: patients were protected by close trainee supervision and 'sign off' to prevent errors; trainees were provided with a safe environment for learning on the job; (2) Implications for undergraduate medical education: if the proposal was accepted, a 'radical review' of undergraduate curricula would be needed; undergraduate education might need to be longer; (3) Implications for F1 work practice: steps to protect healthcare team integration and ensure that F1 doctors stay within competency limits would be required; (4) Financial, structural and political implications: there would be cost implications for trainees; clarification of responsibilities between undergraduate and postgraduate medical education would be needed. Typically, each theme comprised arguments for and against the proposal.

CONCLUSIONS: A policy change to align the timing of full registration with graduation would require considerable planning and preliminary work. These findings will inform policymakers' decision-making. Regardless of the decision, medical students should take on greater responsibility for patient care as undergraduates, assessment methods in clinical practice and professionalism domains need development, and good practice in postgraduate supervision and support must be shared.

Clinical Application of Poly(ADP-Ribose) Polymerase Inhibitors in High-Grade Serous Ovarian Cancer

: High-grade serous ovarian cancer is characterized by genomic instability, with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Given the action of poly(ADP-ribose) polymerase (PARP) inhibitors in targeting tumors with deficiencies in this repair pathway by loss of BRCA1/2, ovarian tumors could be an attractive population for clinical application of this therapy. PARP inhibitors have moved into clinical practice in the past few years, with approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past 2 years. The U.S. FDA approval of olaparib applies to fourth line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval to olaparib maintenance in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. In order to widen the ovarian cancer patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. Additionally, a better understanding of the toxicity profile is needed if PARP inhibitors are to be used in the curative, rather than the palliative, setting. We reviewed the development of PARP inhibitors in phase I-III clinical trials, including combination trials of PARP inhibitors and chemotherapy/antiangiogenics, the approval for these agents, the mechanisms of resistance, and the outstanding issues, including the development of biomarkers and the rate of long-term hematologic toxicities with these agents.

IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib has recently received approval from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) likely to be approved in the near future. However, the patient population with potential benefit from PARP inhibitors is likely wider than that of germline BRCA mutation-associated disease, and biomarkers are in development to enable the selection of patients with the potential for clinical benefit from these agents. Questions remain regarding the toxicities of PARP inhibitors, limiting the use of these agents in the prophylactic or adjuvant setting until more information is available. The indications for olaparib as indicated by the FDA and EMA are reviewed.

Assessing and Reporting the Adverse Effects of Antipsychotic Medication: A Systematic Review of Clinical Studies, and Prospective, Retrospective, and Cross-Sectional Research

Objective: Adverse effects (AEs) of antipsychotic medication have important implications for patients and prescribers in terms of wellbeing, treatment adherence and quality of life. This review summarises strategies for collecting and reporting AE data across a representative literature sample to ascertain their rigour and comprehensiveness. Methods: A PsycINFO search, following PRISMA Statement guidelines, was conducted in English-language journals (1980–July 2014) using the following search string: (antipsychotic* OR neuroleptic*) AND (subjective effect OR subjective experience OR subjective response OR subjective mental alterations OR subjective tolerability OR subjective wellbeing OR patient perspective OR self-rated effects OR adverse effects OR side-effects). Of 7,825 articles, 384 were retained that reported quantified results for AEs of typical or atypical antipsychotics amongst transdiagnostic adult, adolescent, and child populations. Information extracted included: types of AEs reported; how AEs were assessed; assessment duration; assessment of the global impact of antipsychotic consumption on wellbeing; and conflict of interest due to industry sponsorship. Results: Neurological, metabolic, and sedation-related cognitive effects were reported most systematically relative to affective, anticholinergic, autonomic, cutaneous, hormonal, miscellaneous, and non-sedative cognitive effects. The impact of AEs on patient wellbeing was poorly assessed. Cross-sectional and prospective research designs yielded more comprehensive data about AE severity and prevalence than clinical or observational retrospective studies. 3 Conclusions: AE detection and classification can be improved through the use of standardised assessment instruments and consideration of subjective patient impact. Observational research can supplement information from clinical trials to improve the ecological validity of AE data.

Interaction between glucocorticoid and adenosine A2A receptors in the hippocampus : implications for learning and memory

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2014

Respiratory and non-respiratory sinus arrhythmia: implications for heart rate variability

The quantity of blood arriving at the left side of the heart oscillates throughout the breathing cycle due to the mechanics of breathing. Neurally regulated fluctuations in the length of the heart period act to dampen oscillations of the left ventricular stroke volume entering the aorta. We have reported that stroke volume oscillations but not spectral frequency variability stroke volume measures can be used to estimate the breathing frequency. This study investigated with the same recordings whether heart period oscillations or spectral heart rate variability measures could function as estimators of breathing frequency. Continuous 270 s cardiovascular recordings were obtained from 22 healthy adult volunteers in the supine and upright postures. Breathing was recorded simultaneously. Breathing frequency and heart period oscillation frequency were calculated manually, while heart rate variability spectral maximums were obtained using heart rate variability software. These estimates were compared to the breathing frequency using the Bland–Altman agreement procedure. Estimates were required to be \±10% (95% levels of agreement). The 95% levels of agreement measures for the heart period oscillation frequency (supine: -27.7 to 52.0%, upright: -37.8 to 45.9%) and the heart rate variability spectral maximum estimates (supine: -48.7 to 26.5% and -56.4 to 62.7%, upright: -37.8 to 39.3%) exceeded 10%. Multiple heart period oscillations were observed to occur during breathing cycles. Both respiratory and non-respiratory sinus arrhythmia was observed amongst healthy adults. This observation at least partly explains why heart period parameters and heart rate variability parameters are not reliable estimators of breathing frequency. In determining the validity of spectral heart rate variability measurements we suggest that it is the position of the spectral peaks and not the breathing

Identifying the psychosexual implications of radical radiation treatment in prostate cancer

The purpose of this study was to determine whether there was any evidence of psychosexual morbidity among men who experienced radical radiation treatment for prostate cancer. With relatively little known or available retrospective data on the psychosexual implications of radical radiation treatment in men with prostate cancer, this study posited eight research questions which provided the basis for the research. Fifty men from Southern Ontario, between the ages of 52 to 78 years, were included in the study. They had been previously randomized to a clinical trial comparing radical radiation therapy by external beam radiation, or radical radiation using a combination of a temporary iridium implant plus external beam radiation, for localized or locally advanced prostate cancer. Assessment of sexual functioning, drive, attitudes, body image, and sexual satisfaction was drawn from a multidimensional approach, since psychosexuality was viewed as having an impact on biological, psychological, and sociological domains of functioning. Medical chart reviews, semi-structured interviews, demographical profiles of each participant, and the Derogatis Sexual Functioning Inventory (DSFI) were the methods used to collect data over a four-month period. Both quantitative and qualitative research methods were incorporated in the design and evaluation of the study. Frequencies, contingency analysis, Pearson's coefficient of correlation, t-tests, and ANOVA comprised the quantitative analysis. Data obtained from audio-taped interviews were analyzed qualitatively, and used for offering further insight and for facilitating the quantitative aspect of the analysis. Overall, there was sufficient evidence to suggest psychosexual morbidity among men who were treated with radiation therapy for prostate cancer. As well,there were a number of significant findings available to answer all of the posited research questions. The most significant findings were noted in post-treatment erectile ability and sexual activity. A post-treatment change in erectile ability was reported by eighty percent of men. Sixty percent of men noted a decrease in their ability to achieve an erection by reporting some morning stiffness only, penile rigidity insufficient for penetration, decreased control of erection, and loss of spontaneous erection. Other contributing factors associated with change in erectile status were: pain or altering sensation of orgasm, blood in ejaculate, pain and decreased amount of ejaculate, and penile numbness or pain. Eighty-two percent of men experienced a post-treatment change in sexual function, primarily due to the impact of decreasing erectile status. Only seven men reported that they experienced a decrease in desire mentally, whereas the vast majority did not experience any change in desire. Changes in foreplay, stress with optimal sexual positioning, and reduced spontaneity of sex, were other factors reported with the changes in sexual activity. The findings in this study broaden our understanding of what middle- to later-aged men feel and experience as they venture onward following treatment. This was the first study that evaluated available prospective data on pre-treatment erectile status and sexual activity. As well, this study was the first (with participant compliance rates of 100 percent) to have included an interview format to capture the views of such a large number of men. This study concluded with recommendations and implications for future research and practice as we move in the direction of understanding what is necessary for preserving psychosexual well being and enhancing quality of life in men treated with radiation therapy for prostate cancer.

Empathy and Emotion Processing in Mild Head Injury and Sub-clinical Psychopathy

The current study sought to investigate the nature of empathic responding and emotion processing in persons who have experienced Mild Head Injury (MHI) and how this relationship between empathetic responding and head injury status may differ in those with higher psychopathic characteristics (i.e., subclinical psychopathy). One-hundred university students (36% reporting having a previous MHI) completed an Emotional Processing Task (EPT) using images of neutral and negative valence (IAPS, 2008) designed to evoke empathy; physiological responses were recorded. Additionally, participants completed measures of cognitive competence and various individual differences (empathy - QCAE; Reniers, 2011; Psychopathy - SRP-III, Williams, Paulhus & Hare, 2007) and demographics questionnaires. MHI was found to be associated with lower affective empathy and physiological reactivity (pulse rate) while viewing images irrespective of valence, reflecting a pattern of generalized underarousal. The empathic deficits observed correlated with the individual’s severity of injury such that the greater number of injury characteristics and symptoms endorsed by a subject, the more dampened the affective and cognitive empathy reactions to stimuli and the lower his/her physiological reactivity. Importantly, psychopathy interacted with head injury status such that the effects of psychopathy were significant only for individuals indicating a MHI. This group, i.e., MHI subjects who scored higher on psychopathy, displayed the greatest compromise in empathic responding. Interestingly, the Callous Affect component of psychopathy was found to account for the empathic and emotion processing deficits observed for individuals who report a MHI; in contrast, the Interpersonal Manipulation component emerged as a better predictor of empathic and emotion deficits observed in the No MHI group. These different patterns may indicate the involvement of different underlying processes in the manifestation of empathic deficits associated with head injury or subclinical psychopathy. It also highlights the importance of assessing for prior head injury in populations with higher psychopathic characteristics due to the possible combined/enhanced influences. The results of this study have important social implications for persons who have experienced a concussion or limited neural trauma since even subtle injury to the head may be sufficient to produce dampened emotion processing, thereby impacting one’s social interactions and engagement (i.e., at risk for social isolation or altered interpersonal success). Individuals who experience MHI in conjunction with certain personality profiles (e.g., higher psychopathic characteristics) may be particularly at risk for being less capable of empathic compassion and socially-acceptable pragmatics and, as a result, may not be responsive to another person’s emotional well-being.

Frailty, an Emerging Research and Clinical Paradigm: Issues and Controversies

Ne pas citer. Version pour diffusion uniquement. Citer l'article une fois publié. / Not to be cited. For distribution only. Cite article once published.

Rôles physiopathologiques du complément dans le syndrome coronarien aigu et implications thérapeutiques

Les efforts investis pour diminuer les risques de développer un infarctus du myocarde sont nombreux. Aujourd’hui les médecins prennent connaissance des divers facteurs de risque connus prédisposant aux syndromes coronariens aigus (SCA) dans le but de prendre en charge les patients «à risque» [1]. Bien que le suivi rigoureux et le contrôle de certains facteurs de risque modifiables aient permis une meilleure gestion des cas de SCA, les cas d’infarctus persistent de manière encore trop fréquente dans le monde. Puisque d’importantes études ont démontré que les SCA pouvaient survenir sans même la présence des facteurs de risque conventionnels [2, 3], les chercheurs se sont penchés sur un autre mécanisme potentiellement responsable de l’avènement des SCA : l’inflammation. L’inflammation joue un rôle prépondérant dans l’initiation, la progression et les complications de l’athérosclérose [4, 5] mais aussi dans les situations post-infarctus [6, 7]. Au cours des dernières années, le contrôle du processus inflammatoire est devenu une cible de choix dans la prévention et le traitement des SCA. Cependant, malgré les efforts investis, aucun de ces traitements ne s’est avéré pleinement efficace dans l’atteinte du but ultime visé par une diminution de l’inflammation : la diminution de la mortalité. Le complément est un système complexe reconnu principalement pour son rôle primordial dans l’immunité [2]. Cependant, lorsqu’il est activé de manière inappropriée ou excessive, il peut être à l’origine de nombreux dommages cellulaires caractéristiques de plusieurs pathologies inflammatoires dont font partie les complications de l’athérosclérose et des événements post-infarctus. Le travail effectué dans le cadre de mon doctorat vise à établir les rôles physiopathologiques du complément dans les interactions de l’axe thrombose-inflammation caractéristiques des SCA dans le but ultime d’identifier des cibles thérapeutiques permettant le développement de nouvelles approches pour la prévention et le traitement de ces pathologies. Les principaux résultats obtenus durant mon cursus suggèrent d’abord que la voie alterne du complément peut représenter une cible thérapeutique de choix dans les maladies coronariennes aiguës puisque l’activation terminale du complément semble y être principalement causée par l’activation du cette voie. De faibles niveaux sériques de MBL (mannan-binding lectin) et une activation terminale négligeable du complément caractérisent plutôt la maladie coronarienne stable. En comparant l’activité relative de chacune des voies du complément chez des cohortes de patients traités ou non par un anticorps spécifique à la protéine C5 du complément (pexelizumab), un second volet démontre quant à lui qu’une inhibition de l’activation du C5 n’a pas d’effet bénéfique majeur sur l’inhibition de la formation du complexe sC5b-9 ou sur les événements cliniques subséquents. Par conséquent, nous avons exploré, à l’aide d’un modèle in vitro, les raisons de l’inefficacité du traitement. Les résultats révèlent que le blocage du C5 avec le pexelizumab inhibe la production de l’anaphylatoxine pro-inflammatoire C5a et du complexe terminal du complément sans toutefois avoir d’effet sur l’apoptose des cellules endothéliales produites induite par le sérum des patients atteints de STEMI. Finalement, une autre section stipule que l’atorvastatine diminue l’activation du complément induite par les plaquettes sanguines chez des patients hypercholestérolémiques, mettant en évidence l’importance du rôle de cette statine dans la réduction des effets délétères de l’activation du système du complément médié par les plaquettes. Ensemble, l’étude du rôle spécifique des différentes voies d’activation du complément dans des contextes pathologiques variés, l’analyse des effets d’une inhibition spécifique de la protéine C5 du complément dans la progression des SCA et la mise en évidence des interactions entre l’activation du complément et les plaquettes activées ont contribué au développement d’une meilleure connaissance des rôles physiopathologiques du complément dans la progression de la maladie coronarienne.