Emergency responses for clinical deterioration within and beyond 24 hours of emergency admission: Patient outcomes and ICU implications

Introduction: The National Emergency Access Target was implemented to ensure 90% of patients leave emergency departments (EDs) within 4h. The impact of time driven performance on the number of physiologically unstable ward-based patients is unknown. An increase in clinical deterioration episodes potentially leading to adverse events will have resource implications for intensive care units (ICUs).
Objectives: To compare the characteristics and outcomes of patients who required an emergency response for clinical deterioration (cardiac arrest team or rapid response system activation) within and beyond 24 h of emergency admission to general medical and surgical units.
Methods: A retrospective exploratory design was used. The study site was a 365 bed urban hospital in Melbourne. Emergency responses for clinical deterioration during 2012 were examined.
Results: Of 819 emergency responses for clinical deterioration, 587 patients were admitted via ED. The median time to first responsewas59h, 28.4% of patients required this <24 h after admission. One in eight patients required ICU admission. Comparison of patients requiring a response within and beyond 24h of admission showed no significant differences in age, gender, waiting times, ED length of stay or in-hospital mortality rates. Patients in whom first emergency response occurred <24h after admission were less likely to be admitted to ICU immediately following the emergency response (7.6% vs 13.9%, p-0.039), less likely to have recurrent emergency responses during their hospitalisation (9.7% vs 34.0%, p<0.001), and had shorter median hospital length of stay (7 vs 11 days, p<0.001).
Conclusions: Considerable ICU resources were utilised given one in eight patients required ICU admission following emergency response, and patients admitted via the ED constituted 55% of all rapid response system activations. Exploring potential antecedents to clinical deterioration in this cohort may assist in establishing risk management strategies to reduce utilisation of ICU resources.

Evaluation of a filmed clinical scenario as a teaching resource for an introductory pharmacology unit for undergraduate health students: A pilot study.

BACKGROUND: Simulation is frequently being used as a learning and teaching resource for both undergraduate and postgraduate students, however reporting of the effectiveness of simulation particularly within the pharmacology context is scant. OBJECTIVES: The aim of this pilot study was to evaluate a filmed simulated pharmacological clinical scenario as a teaching resource in an undergraduate pharmacological unit. DESIGN: Pilot cross-sectional quantitative survey. SETTING: An Australian university. PARTICIPANTS: 32 undergraduate students completing a healthcare degree including nursing, midwifery, clinical science, health science, naturopathy, and osteopathy. METHODS: As a part of an undergraduate online pharmacology unit, students were required to watch a filmed simulated pharmacological clinical scenario. To evaluate student learning, a measurement instrument developed from Bloom's cognitive domains (knowledge, comprehension, application, analysis, synthesis and evaluation) was employed to assess pharmacological knowledge conceptualisation and knowledge application within the following fields: medication errors; medication adverse effects; medication interactions; and, general pharmacology. RESULTS: The majority of participants were enrolled in an undergraduate nursing or midwifery programme (72%). Results demonstrated that the majority of nursing and midwifery students (56.52%) found the teaching resource complementary or more useful compared to a lecture although less so compared to a tutorial. Students' self-assessment of learning according to Bloom's cognitive domains indicated that the filmed scenario was a valuable learning tool. Analysis of variance indicated that health science students reported higher levels of learning compared to midwifery and nursing. CONCLUSION: Students' self-report of the learning benefits of a filmed simulated clinical scenario as a teaching resource suggest enhanced critical thinking skills and knowledge conceptualisation regarding pharmacology, in addition to being useful and complementary to other teaching and learning methods.

An adjunctive antidepressant nutraceutical combination in treating major depression: study protocol and clinical considerations

Current treatment for major depressive disorder (MDD), a prevalent and disabling mental illness, is inadequate, with two-thirds of people treated with first-line antidepressants not achieving remission. MDD is for many a chronic condition, often requiring multiple treatment attempts, thus development of additional interventions is urgently required. An emerging approach to improve non-response to antidepressants is the use of adjunctive nutraceuticals. The pathophysiology of MDD is considered to involve a range of abnormalities (monoamine impairment, neuro-endocrinological changes, reduced brain-derived neurotrophic factor, and cytokine alterations). By targeting an array of these key neurobiological pathways via specific nutraceuticals (S-adenosyl methionine; [SAMe], 5-HTP [active tryptophan], folinic acid [active folic acid], omega-3 fatty acids, and zinc), there is the potential to provide a more comprehensive therapeutic biological approach to treat depression. We are currently conducting a National Health and Medical Research Council funded study in Australia (APP1048222). The clinical trial is phase II/III, multi-site, 3-arm, 8-week, randomised, double-blind, placebo-controlled study using SAMe + folinic acid versus a combination nutraceutical (SAMe, 5-HTP, folinic acid, omega-3, and zinc) or matching placebo in 300 currently depressed participants with diagnosed MDD who are non-responsive to current antidepressants (ANZCTR, protocol number: 12613001300763). The results may provide evidence for a novel adjunctive neurobiological approach for treating depression.

Prevalence of cardiovascular and metabolic events in patients prescribed clozapine: a retrospective observational, clinical cohort study

BACKGROUND: The efficacy of clozapine for the treatment of schizophrenia has been demonstrated. However, a range of adverse events have been associated with its use. To date, there remains a paucity of data regarding the prevalence of clozapine-induced cardiovascular (CV) and parameters associated with the development of metabolic syndrome, alongside associated risk factors for their development. METHODS: An observational, clinical cohort study design of 355 clozapine patients who were enrolled in the Barwon Health Clozapine Program at Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were accessed retrospectively. Multivariate logistic regression was used to determine associations with adverse event(s). RESULTS: Older age of commencement with clozapine was consistently associated with increased risk of CV abnormalities, with the exception of tachycardia where older age was protective (Odds Ratio [OR]: 0.97; 95% Confidence Intervals [CI]: 0.95, 0.99). Males had significantly greater odds of most metabolic disturbances with the exception of being obese (BMI: ≥30 OR: 0.45; 95% CIs: 0.24, 0.85). Older age of commencement was a significantly associated variable with High- Density Lipoprotein-cholesterol (OR: 1.03; 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04; 95% CIs: 1.02, 1.07). An increase in BMI was consistently and significantly associated with all metabolic events. CONCLUSION: Male patients who are obese at any point during treatment and older at treatment commencement may be the most vulnerable to adverse CV and metabolic events. While future studies using a matched case-control design may be required to verify these findings, we recommend that treating clinicians consider these risks when assessing patient suitability to clozapine therapy.

Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.

The association between types of eating behaviour and dispositional mindfulness in adults with diabetes. Results from Diabetes MILES. The Netherlands.

Although healthy food choices are important in the management of diabetes, making dietary adaptations is often challenging. Previous research has shown that people with type 2 diabetes are less likely to benefit from dietary advice if they tend to eat in response to emotions or external cues. Since high levels of dispositional mindfulness have been associated with greater awareness of healthy dietary practices in students and in the general population, it is relevant to study the association between dispositional mindfulness and eating behaviour in people with type 1 or 2 diabetes. We analysed data from Diabetes MILES - The Netherlands, a national observational survey in which 634 adults with type 1 or 2 diabetes completed the Dutch Eating Behaviour Questionnaire (to assess restrained, external and emotional eating behaviour) and the Five Facet Mindfulness Questionnaire-Short Form (to assess dispositional mindfulness), in addition to other psychosocial measures. After controlling for potential confounders, including demographics, clinical variables and emotional distress, hierarchical linear regression analyses showed that higher levels of dispositional mindfulness were associated with eating behaviours that were more restrained (β = 0.10) and less external (β = -0.11) and emotional (β = -0.20). The mindfulness subscale 'acting with awareness' was the strongest predictor of both external and emotional eating behaviour, whereas for emotional eating, 'describing' and 'being non-judgemental' were also predictive. These findings suggest that there is an association between dispositional mindfulness and eating behaviour in adults with type 1 or 2 diabetes. Since mindfulness interventions increase levels of dispositional mindfulness, future studies could examine if these interventions are also effective in helping people with diabetes to reduce emotional or external eating behaviour, and to improve the quality of their diet.

Negative appraisals of insulin therapy are common among adults with Type 2 diabetes using insulin: results from diabetes MILES - Australia cross-sectional survey

AIM: To identify insulin therapy appraisals among adults with Type 2 diabetes using insulin and how negative appraisals relate to clinical, self-care and psychosocial outcomes. METHODS: Diabetes MILES - Australia 2011 was a national survey of adults with diabetes, focused on behavioural and psychosocial issues. Subgroup analyses were conducted on the responses of 273 adults with Type 2 diabetes using insulin (46% women; mean ± sd age: 59 ± 9 years; diabetes duration: 12 ± 7 years; years using insulin: 4 ± 4). They completed validated measures of insulin therapy appraisals (ITAS), depression (PHQ-9), anxiety (GAD-7), diabetes distress (PAID) and diabetes-specific self-efficacy (DES-SF). RESULTS: Insulin was perceived to be very important, and its benefits (e.g. improves health) were endorsed by most (82%). Fifty-one per cent believed that taking insulin means their diabetes has become worse; 51% that insulin causes weight gain; 39% that they have 'failed to manage' their diabetes. Those with the greatest and least 'ITAS negative' scores did not differ by diabetes duration or years using insulin, or by average number of insulin injections or blood glucose checks per day. Those with more negative insulin appraisals were significantly younger (Mean Diff. = 5 years, P < 0.001), less satisfied with recent blood glucose levels (P < 0.001, d = 0.63), had reduced diabetes-specific self-efficacy (P < 0.001, d = 0.7), and were more likely to report depressive symptoms, anxiety or diabetes distress (all P < 0.001, d = 0.65-1.1). CONCLUSIONS: Negative insulin therapy appraisals are common among adults with Type 2 diabetes using insulin, and are associated with lower general and diabetes-specific emotional well-being, reduced diabetes-specific self-efficacy and satisfaction with blood glucose.

Nursing educator perspectives of overseas qualified nurses' intercultural clinical communication: barriers, enablers and engagement strategies

AIMS AND OBJECTIVES: To understand the intercultural communication experiences and associated communication training needs of overseas qualified nurses in the Australian healthcare system from the unique perspectives of nurse educators teaching in accredited bridging programmes. BACKGROUND: Overseas qualified nurses are an integral part of the nursing workforce in migration destination countries. Communication training needs are more complex when there are cultural, ethnic and language differences between nurses, other health professionals and patients. DESIGN: A qualitative, exploratory research design using semi-structured interviews. METHODS: All (nine) organisations involved in conducting the Australian Health Practitioner Regulation Agency approved preregistration bridging programmes for overseas qualified nurses within the state of Victoria, Australia, were involved in the study. Participants were 12 nurse educators employed in these organisations. Thematic analysis was undertaken. RESULTS: Three macro themes emerged about the overseas qualified nurses' intercultural communication: (1) pre-existing barriers and enablers to intercultural communication, for example, nurses' reluctance to engage in communicative strategies that build rapport with patients, (2) transitional behaviours and impact on communication, including maintenance of perceived cultural hierarchies between health professionals and (3) development of communicative competence, including expanding one's repertoire of conversational gambits. CONCLUSIONS: The findings point to the domains and causes of communication challenges facing overseas qualified nurses in new healthcare settings as well as strategies that the nurse educators and nurses can adopt. Communication cannot be merely regarded as a skill that can be taught in a didactic programme. Comprehensive understanding is needed about the sociocultural dimensions of these nurses' orientation, which can impact on how they communicate in their new healthcare settings. RELEVANCE TO CLINICAL PRACTICE: The findings can act as triggers for discussion with overseas qualified nurses and other health professionals to raise awareness about the aspects of intercultural communication and to debate alternative viewpoints and explanations. They can also inform changes in the structure and content of the bridging programmes.

Nephrologists' management of patient medications in kidney transplantation: results of an online survey

Rationale, aims and objectives: Medication adherence is essential in kidney transplant recipients to reduce the risk of rejection and subsequent allograft loss. The aim of this study was to delineate what 'usual care' entails, in relation to medication management, for adult kidney transplant recipients. Methods: An online survey was developed to explore how nephrologists promote and assess medication adherence, the management of prescriptions, the frequency of clinic appointments and the frequency of clinical screening tests. Nephrologists from all acute kidney transplant units in Victoria, Australia, were invited to participate. Data were collected between May and June 2014. Results: Of 60 nephrologists invited to participate, 22 completed the survey (response rate of 36.6%). Respondents had a mean age of 49.1±10.1 years, with a mean of 20.1±9.9 years working in nephrology and 14 were men. Descriptive analysis of responses showed that nephrologists performed frequent screening for kidney graft dysfunction that may indicate medication non-adherence, maintained regular transplant clinic visits with patients and emphasized the importance of medication education. However, time constraints during consultations impacted on extensive patient education and the long-term medication follow-up support was often delivered by the renal transplant nurse coordinator or pharmacist. Conclusions: This study highlighted that nephrologists took an active approach in the medication management of kidney transplant recipients, which may assist with facilitating long-term graft survival. Ultimately, promoting medication adherence needs to be patient centred, involving an interdisciplinary team of nephrologists, pharmacists and renal transplant nurse coordinators, working together with the patient to establish optimal adherence.

Validity of 12-month falls recall in community-dwelling older women participating in a clinical trial

Objectives. To compare 12-month falls recall with falls reported prospectively on daily falls calendars in a clinical trial of women aged ≥70 years. Methods. 2,096 community-dwelling women at high risk of falls and/or fracture completed a daily falls calendar and standardised interviews when falls were recorded, for 12 months. Data were compared to a 12-month falls recall question that categorised falls status as “no falls,” “a few times,” “several,” and “regular” falls. Results. 898 (43%) participants reported a fall on daily falls calendars of whom 692 (77%) recalled fall(s) at 12 months. Participants who did not recall a fall were older (median 79.3 years versus 77.8 years, ). Smaller proportions of fallers who sustained an injury or accessed health care failed to recall a fall (all ). Among participants who recalled “no fall,” 85% reported zero falls on daily calendars. Few women selected falls categories of “several times” or “regular” (4.1% and 0.4%, resp.) and the sensitivity of these categories was low (30% to 33%). Simply categorising participants into fallers or nonfallers had 77% sensitivity and 94% specificity. Conclusion. For studies where intensive ascertainment of falls is not feasible, 12-month falls recall questions with fewer responses may be an acceptable alternative.

Restorative care for palliative patients: a retrospective clinical audit of outcomes for patients admitted to an inpatient palliative care unit

BACKGROUND: Restorative care in palliative care is a subset of rehabilitation that aims to improve quality of life through restoration or maintenance of physical functions. Outcomes for restorative care programmes delivered by palliative care units have not adequately been assessed. OBJECTIVES: The objectives are to examine the outcomes of a restorative care programme in an inpatient palliative care unit, including discharge destination, performance status changes and length of stay. METHODS: Retrospective clinical audit of consecutive patients admitted to Calvary Health Care Bethlehem in Melbourne, Australia, principally for restorative care from July 2010 to December 2011. RESULTS: 79 admissions met inclusion criteria. Mean age was 76.5 years (SD=11.14) and 43 (54%) were men. 75 (95%) patients had a malignant diagnosis; of these, the majority had lung cancer (24%). 16 patients (20%) were discharged home, 51 (65%) died and 12 (15%) were transferred. Of the patients discharged home, only 6 (38% of those discharged home) improved their performance status. Those discharged home had a significantly shorter length of stay (17 days compared to 39 days; p<0.05). Patients discharged home also had significantly better Australia-modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups-Activities of Daily Living (RUG-ADL) scores on admission than others (both p<0.05). CONCLUSIONS: The majority of patients referred for restorative care died during admission, with only a minority discharged home. Patients discharged most commonly experienced maintenance and not improvement in performance status. A successful discharge home following restorative care was associated with a shorter length of stay. Implications and recommendations for successful restorative care will be discussed.

Nucleic acid-based aptamers: applications, development and clinical trials

Short single-stranded oligonucleotides called aptamers, often termed as chemical antibodies, have been developed as powerful alternatives to traditional antibodies with respect to their obvious advantages like high specificity and affinity, longer shelf-life, easier manufacturing protocol, freedom to introduce chemical modifications for further improvement, etc. Reiterative selection process of aptamers over 10-15 cycles starting from a large initial pool of random nucleotide sequences renders them with high binding affinity, thereby making them extremely specific for their targets. Aptamer-based detection systems are well investigated and likely to displace primitive detection systems. Aptamer chimeras (combination of aptamers with another aptamer or biomacromolecule or chemical moiety) have the potential activity of both the parent molecules, and thus hold the capability to perform diverse functions at the same time. Owing to their extremely high specificity and lack of immunogenicity or pathogenicity, a number of other aptamers have recently entered clinical trials and have garnered favorable attention from pharmaceutical companies. Promising results from the clinical trials provide new hope to change the conventional style of therapy. Aptamers have attained high therapeutic relevance in a short time as compared to synthetic drugs and/or other modes of therapy. This review follows the various trends in aptamer technology including production, selection, modifications and success in clinical fields. It focusses largely on the various applications of aptamers which mainly depend upon their selection procedures. The review also sheds light on various modifications and chimerizations that have been implemented in order to improve the stability and functioning of the aptamers, including introduction of locked nucleic acids (LNAs). The application of various aptamers in detection systems has been discussed elaborately in order to stress on their role as efficient diagnostic agents. The key aspect of this review is focused on success of aptamers on the basis of their performance in clinical trials for various diseases.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process

BACKGROUND: The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. METHODS: The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. RESULTS: Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. CONCLUSIONS: Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Validation of the Italian version of the Yale-Brown Obsessive Compulsive Scale-Second Edition (Y-BOCS-II) in a clinical sample

OBJECTIVE: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most widely accepted measure of obsessive-compulsive disorder (OCD) symptom severity. Recently, the scale has been revised into a second edition (Y-BOCS-II) in order to improve its measurement properties. The present study aimed to evaluate the psychometric properties of the Italian version of the Y-BOCS-II Severity Scale (SS) in a large clinical sample. METHOD: The original version of the Y-BOCS-II was translated into Italian, which involved forward and back-translation procedures. The Italian Y-BOCS-II-SS was administered to one hundred twenty-five treatment-seeking adults with OCD, together with the original Y-BOCS-SS and a battery of self-report measures assessing OCD symptom severity and depressive and anxious symptomology. The factor structure, internal consistency, temporal stability, and construct validity were investigated on the whole sample, while inter-rater and test-retest reliability were assessed on a subsample of participants. RESULTS: Factor analyses revealed a two-factor structure different from those of the original scale, comprising (1) symptom severity; and (2) interference from symptoms. Internal consistency, test-retest reliability over a 2-week period and inter-rater reliability were satisfactory. The Y-BOCS-II-SS also showed excellent construct validity (and better than the Y-BOCS-SS), with good convergent and discriminant validity when assessed against other OCD symptom measures and measures of depression, anxiety and worry. CONCLUSIONS: These findings suggest that the Italian version of the Y-BOCS-II-SS retains the adequate psychometric properties of the original and that it can be confidently used as an assessment tool of OCD symptoms in both clinical and research settings.

Clinical review criteria and medical emergency teams: evaluating a two-tier rapid response system

OBJECTIVES: To assess the prevalence of patients fulfilling clinical review criteria (CRC), to determine activation rates for CRC assessments, to compare baseline characteristics and outcomes of patients who fulfilled CRC with patients who did not, and to identify the documented nursing actions in response to CRC values. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study using a retrospective medical record audit, in a universityaffiliated, tertiary referral hospital with a two-tier rapid response system in Melbourne, Australia. We used a convenience sample of hospital inpatients on general medical, surgical and specialist service wards admitted during a 24-hour period in 2013. MAIN OUTCOME MEASURES: Medical emergency team (MET) or code blue activation, unplanned intensive care unit admissions, hospital length of stay and inhospital mortality. For patients who fulfilled CRC or MET criteria during the 24- hour period, the specific criteria fulfilled, escalation treatments and outcomes were collected. RESULTS: Of the sample (N = 422), 81 patients (19%) fulfilled CRC on 109 occasions. From 109 CRC events, 66 patients (81%) had at least one observation fulfilling CRC, and 15 patients (18%) met CRC on multiple occasions. The documented escalation rate was 58 of 109 events (53%). The number of patients who fulfilled CRC and subsequent MET call activation criteria within 24 hours was significantly greater than the number who did not meet CRC (P < 0.001). CONCLUSIONS: About one in five patients reached CRC during the study period; these patients were about four times more likely to also fulfil MET call criteria. Contrary to hospital policy, escalation was not documented for about half the patients meeting CRC values. Despite the clarity of escalation procedures on the graphic observation chart, escalation remains an ongoing problem. Further research is needed on the impact on patient outcomes over time and to understand factors influencing staff response.