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Objective: To evaluate the difference in proportion of patients receiving antimicrobials within one hour of sepsis recognition at sepsis-related Medical Emergency Team (MET) calls, without or with a sepsis-credentialed pharmacist. Design: Retrospective pre and post-intervention study. Setting: Single centre tertiary referral hospital. Participants: Patients admitted to the General Medicine Unit who had a sepsis-related MET call 24 hrs per day, and all other units from 17:00-08:00 hrs from August 2019 to Jan 2020 in the pre-intervention cohort and Aug 2020 to Jan 2021 for the post-intervention cohort. Interventions: Pharmacists attended MET calls to assist selection of antimicrobials, collaboratively prescribe with the medical officers, ensure supply, provide advice on dosing calculations, reconstitution, and administration. The pre-intervention cohort (Aug 2019-Jan 2020) did not have credentialed pharmacists' involvement at MET calls. Outcome Measures: Proportion of patients who received antimicrobials within one hours of MET call. Results: There were 97 sepsis-related MET calls in the pre-intervention cohort and 110 sepsis-related MET calls in the post-intervention cohort. A significantly higher proportion of patients received antimicrobials within one hour with pharmacist involvement, compared to control (81.3% vs 59.7%, P  = .0006). A reduction in median time to antimicrobial administration (43 min vs 54 min, P  = .017) was observed. Conclusion: Sepsis-related MET calls with pharmacist involvement experienced a greater proportion of patients receiving antimicrobials within one hour of sepsis recognition, and a reduction in median time to antimicrobial administration. These results provide support for routine pharmacist involvement at MET calls to assist patients receiving medications in a timely and efficient manner., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study explores the experiences of nurses that provide 'complex', generalist healthcare in hospital settings. Complex care is described as care for patients experiencing acute issues additional to multimorbidity, ageing or psychosocial complexity. Nurses are the largest professional group of frontline healthcare workers and patients experiencing chronic conditions are overrepresented in acute care settings. Research exploring nurses' experiences of hospital-based complex care is limited, however. This study aims to add to what is known currently. Four 'complex care' nurses undertook in-depth semistructured interviews and their narratives were analysed using the conceptual framework of complex adaptive phenomenology. Two overarching themes constituting the 'essence' of complex care nursing were identified: Contextual factors and attribute/value-based elements. Creating meaningful patient outcomes and feeling part of a team were experienced as fulfilling, whereas time constraints, institutional settings and systemic barriers to comprehensive caregiving diminished the experience of providing complex care. Overall, work meaning presented as a dynamic phenomenon, shaped by personal and professional values, local settings and systemic factors. It is recommended that more expansive research be undertaken to explore the experience of complex care for nurses. Such knowledge can contribute to initiatives that draw a skilled, effective and engaged hospital-based complex care nursing workforce., (© 2024 The Authors. Nursing Inquiry published by John Wiley & Sons Ltd.)

Background: The COVID-19 pandemic created systemic challenges in patient care delivery., Aim: To evaluate the impact on pharmacist activities during pharmacist participation in ward rounds via telehealth, compared to physical attendance., Method: A single-centre, retrospective cohort study conducted from 18th Aug through 26th Oct 2020. Patients admitted to COVID and non-COVID general medical teams were included. Pharmacists attended ward rounds via telehealth for COVID teams; physical attendance continued for non-COVID teams. Telehealth involved pharmacists interacting with clinicians and patients virtually via videoconferencing whilst stationed remotely on the ward. Routine clinical pharmacy activities during telehealth ward rounds were compared to those during face-to-face ward rounds using comparative statistics., Results: Among the 1230 patients included (762 COVID, 468 non-COVID), pharmacist participation in telehealth ward rounds demonstrated significantly more documented activities compared with face-to-face rounds (mean 6.7 vs 4.9 per patient per day, p < 0.001). The telehealth cohort exhibited a higher number of orders placed via pharmacy-partnered medication charting (3.0 vs 2.4 per patient per day, p < 0.001), medication orders verified (2.3 vs 1.1, p < 0.001), and documented pharmacy notes (0.6 vs 0.2, p < 0.001). No significant difference was observed in medication requests processed (0.4 vs 0.4, p = 738), whilst non-COVID patients had more discharge prescription items generated (0.3 vs 0.7, p < 0.001)., Conclusion: Pharmacist involvement in medical ward rounds via telehealth enabled the ongoing provision of advanced clinical pharmacy services to inpatients in isolation rooms during the COVID-19 pandemic. This approach resulted in a greater number of pharmacy activities during telehealth ward rounds compared to standard in-person attendance., (© 2024. Crown.)

The ever-increasing prevalence of chronic conditions over the last half century has gradually altered the demographic of patients admitted to acute care settings; environments traditionally associated with episodic care rather than chronic and complex healthcare. In consequence, the lifeworld of the hospital medical doctor often entails healthcare for a complex, multi-morbid, patient cohort. This paper examines the experience of providing complex healthcare in the pressurised and fast-paced acute care setting. Four medical doctors from two metropolitan health services were interviewed and their data were analysed using a combinatorial framework of phenomenology and complexity theory. The horizon of complex care revealed itself as dynamic, expansive, immersive, and relational, entailing a specialised kind of practice that is now common in acute care settings. Yet this practice has made inroads largely without heralding the unique nature and potential of its ground. Herein lies opportunity for complex care clinicians to expand notions of health and illness, and to shape research, practice, and system design, for a future in which care for health complexity is optimised, irrespective of care settings., (© 2024. The Author(s).)

Increasingly, complexity science concepts are informing health care design and practice. The present paper describes the implementation of early complexity science principles in a Complex Care Program with the aim of strengthening the provision of integrated care. Grounded in cybernetic network theory, Stafford Beers Viable Systems Model [1] provided the guiding principles for the programs redesign. The Viable Systems Model with its broadly applicable principles [1], is now the conceptual model of information management in the program. Beers framework has enabled a relatively small number of clinicians to coordinate care for a large cohort of patients with significant clinical complexity, and a multitude of providers, in the community setting., Competing Interests: The authors have no competing interests to declare., (Copyright: 2021 The Author(s).)

Introduction: The population is ageing, with increasing health and supportive care needs. For older people, complex chronic health conditions and frailty can lead to a cascade of repeated hospitalisations and further decline. Existing solutions are fragmented and not person centred. The proposed Being Your Best programme integrates care across hospital and community settings to address symptoms of frailty., Methods and Analysis: A multicentre pragmatic mixed methods study aiming to recruit 80 community-dwelling patients aged ≥65 years recently discharged from hospital. Being Your Best is a codesigned 6-month programme that provides referral and linkage with existing services comprising four modules to prevent or mitigate symptoms of physical, nutritional, cognitive and social frailty. Feasibility will be assessed in terms of recruitment, acceptability of the intervention to participants and level of retention in the programme. Changes in frailty (Modified Reported Edmonton Frail Scale), cognition (Mini-Mental State Examination), functional ability (Barthel and Lawton), loneliness (University of California Los Angeles Loneliness Scale-3 items) and nutrition (Malnutrition Screening Tool) will also be measured at 6 and 12 months., Ethics and Dissemination: The study has received approval from Monash Health Human Research Ethics Committee (RES-19-0000904L). Results will be disseminated through peer-reviewed journals, conference and seminar presentations., Trial Registration Number: ACTRN12620000533998; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Victorian Emergency Minimum Dataset (VEMD) collects administrative and clinical data for all presentations to Victorian public ED. The present study aimed to examine the level of agreement between the VEMD data and the medical record for a sample of patients coded as having acute cardiovascular conditions (acute coronary syndrome, stroke and transient ischaemic attack [TIA]) and unspecified chest pain in the VEMD., Methods: Six months of data provided to the VEMD from a large metropolitan hospital was obtained, and a random sample of 10% of cases (n = 310) were selected for review. Data for eight VEMD items were compared for concordance to data recorded in the ED medical record., Results: Complete concordance between the VEMD and medical records for all eight items was observed only for 101 (33%) presentations. Overall, the least concordant variables were those with a high number of coding options: usual type of accommodation (76%), referral pattern (84%) and primary diagnosis (85%). The concordance of the VEMD primary diagnosis varied when examined as individual codes (range 75%-100%) and when combined (acute coronary syndrome = 94%, stroke or TIA = 85% and chest pain unspecified = 75%). The level of agreement for some items improved when VEMD codings were combined., Conclusion: When compared to the medical record, our data suggest there is likely variation in the accuracy of some VEMD items, and suggests a larger prospective validation of the VEMD is warranted. For researchers using existing VEMD data, combining of some codes may be necessary., (© 2019 Australasian College for Emergency Medicine.)

Objective: This study compared the prevalence of homelessness in consecutive patients presenting to a metropolitan hospital ED measured via a prospective housing screen with the prevalence of homelessness determined via retrospective audit of hospital data. Factors that altered the odds of patients being homeless and service outcomes that differed were examined for screened patients., Methods: All patients presenting to the ED during a 7 day period in 2017 were invited to complete a housing screen. A retrospective audit of all ED presentations during the same period also occurred. Demographic (e.g. age, gender), clinical (e.g. reason for presentation, ED presentation history) and arrival mode (e.g. time, how arrived) predictors of homeless status were examined alongside care outcomes (e.g. ED length of stay, admission and 28 day re-presentation)., Results: Of 1208 presenting patients, 504 were prospectively screened and 7.9% were homeless. This compared with 0.8% of ED presentations coded as homeless in the Victorian Emergency Minimum Dataset and 2.3% of the 704 non-screened patients identified as homeless using Victorian Emergency Minimum Dataset Usual Accommodation alongside primary diagnosis and registration address. Within the screened sample, homeless patients were more likely to be male, arrive by emergency ambulance/with police, have a psychosocial diagnosis, and be frequent presenters. Re-presentation within 28 days occurred for 43% of homeless and 15% of not-homeless patients., Conclusions: Hospital ED administrative data substantially under-recognises the prevalence of homelessness in presenting patients. Standardised use of brief housing screens could improve identification of and provision of support to this often highly vulnerable population., (© 2019 Australasian College for Emergency Medicine.)

Background: Meaningful partnering with patients is advocated to enhance care delivery. Little is known about how this is operationalised at the point of care during hospital ward rounds, where decision-making concerning patient care frequently occurs., Objective: Describe participation of patients, with differing preferences for participation, during ward rounds in acute medical inpatient services., Methods: Naturalistic, multimethod design. Data were collected using surveys and observations of ward rounds at two hospitals in Melbourne, Australia. Using convenience sampling, a stratified sample of acute general medical patients were recruited. Prior to observation and interview, patient responses to the Control Preference Scale were used to stratify them into three groups representing diverse participation preferences: active control where the patient makes decisions; shared control where the patient prefers to make decisions jointly with clinicians; and passive control where the patient prefers clinicians make decisions., Results: Of the 52 patients observed over 133 ward rounds, 30.8% (n=16) reported an active control preference for participation in decision-making during ward rounds, 25% (n=13) expressed shared control preference and 44.2% (n=23) expressed low control preference. Patients' participation was observed in 75% (n=85) of ward rounds, but few rounds (18%, n=20) involved patient contribution to decisions about their care. Clinicians prompted patient participation in 54% of rounds; and in 15% patients initiated their own participation. Thematic analysis of qualitative observation and patient interview data revealed two themes, supporting patient capability and clinician-led opportunity , that contributed to patient participation or non-participation in ward rounds., Conclusions: Participation in ward rounds was similar for patients irrespective of control preference. This study demonstrates the need to better understand clinician roles in supporting strategies that promote patient participation in day-to-day hospital care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To systematically review the available evidence about hospital discharge communication practices and identify which practices were preferred by patients and healthcare providers, improved patient and provider satisfaction, and increased patients' understanding of their medical condition., Data Sources: OVID Medline, Web of Science, ProQuest, PubMed and CINAHL plus., Study Selection: Databases were searched for peer-reviewed, English-language papers, published to August 2016, of empirical research using quantitative or qualitative methods. Reference lists in the papers meeting inclusion criteria were searched to identify further papers., Data Extraction: Of the 3489 articles identified, 30 met inclusion criteria and were reviewed., Results of Data Synthesis: Much research to date has focused on the use of printed material and person-based discharge communication methods including verbal instructions (either in person or via telephone calls). Several studies have examined the use of information technology (IT) such as computer-generated and video-based discharge communication practices. Utilizing technology to deliver discharge information is preferred by healthcare providers and patients, and improves patients' understanding of their medical condition and discharge instructions., Conclusion: Well-designed IT solutions may improve communication, coordination and retention of information, and lead to improved outcomes for patients, their families, caregivers and primary healthcare providers as well as expediting the task for hospital staff., (© The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: This study aimed to quantify the rate of transfer of care or overstay from cellulitis management in the emergency short stay unit (ESSU) and to identify risk factors during initial assessment associated with transfer of care or overstay., Methods: A retrospective cohort study was conducted including cellulitis patients diagnosed with and admitted to the ESSU at a metropolitan adult tertiary referral centre. Data abstracted included patient demographics, comorbidities, initial investigations and initial vital signs. Transfer of care or overstay were defined as inpatient admission or a stay in ESSU >28 h, respectively., Results: Of the 451 included patients, 157 (34.8%) met the criteria for transfer of care or overstay. These criteria included admission to hospital inpatient units (115 patients, 73.2%) and patients who overstayed the ESSU time period (42 patients, 26.8%). Variables independently associated with transfer of care or overstay were obesity (adjusted odds ratio [OR] 4.33; 95% confidence interval [CI] 1.38-15.59), i.v. drug use (adjusted OR 2.15; 95% CI 1.03-4.51), white blood cell count (adjusted OR 1.09; 95% CI 1.02-1.16 per 1 × 10 9 /L increase) and C-reactive protein (adjusted OR 1.004; 95% CI 1.00-1.01 per 1 mg/L increase)., Conclusions: Transfer of care or overstay after admission to ESSU was high among patients with cellulitis. Variables independently associated with transfer of care or overstay were obesity, i.v. drug use, elevated white blood cell count and elevated C-reactive protein. Awareness of these variables can inform appropriate guidelines for ESSU admission, potentially improving patient flow and reducing length of stay in the ED and hospital., (© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Objective: To determine the prevalence of resuscitation orders and Advance Care Plans, and the relationship with Medical Emergency Team (MET) calls., Methods: A point prevalence review of patient records at five Victorian hospital services., Results: One thousand nine hundred and thirty-four patient records were reviewed, and 230 resuscitation orders and 15 Advance Care Plans found. Significantly, more resuscitation orders were found at public hospitals. Patients admitted to private hospitals were older, with shorter admissions. A further 24 orders were written following MET calls for 97 patients. Only 16% of patients aged 80+ years had a resuscitation order written within 24 hours of admission., Conclusion: Fewer resuscitation orders were written at admission for older adults than might be expected if goals of care and resuscitation outcome are considered. MET continue to have a prominent role in end-of-life care. Consideration and documentation about treatment plans are needed early in an admission to avoid burdensome and futile resuscitation events., (© 2016 AJA Inc.)

Objective: to profile the trajectory of, and risk factors for, functional decline in older patients in the 30 days following Emergency Department (ED) discharge., Methods: prospective cohort study of community-dwelling patients aged ≥65 years, discharged home from a metropolitan Melbourne ED, 31 July 2012 to 30 November 2013. The primary outcome was functional decline, comprising either increased dependency in personal activities of daily living (ADL) or in skills required for living independently instrumental ADL (IADL), deterioration in cognitive function, nursing home admission or death. Univariate analyses were used to select risk factors and logistic regression models constructed to predict functional decline., Results: at 30 days, 34.4% experienced functional decline; with 16.7% becoming more dependent in personal ADL, 17.5% more dependant in IADL and 18.4% suffering deterioration in cognitive function. Factors independently associated with decline were functional impairment prior to the visit in personal ADL (Odds Ratio [OR] 3.21, 95% confidence interval [CI] 2.26-4.53) or in IADL (OR 6.69, 95% CI 4.31-10.38). The relative odds were less for patients with moderately impaired cognition relative to those with normal cognition (OR 0.38, 95% CI 0.19-0.75). There was a 68% decline in the relative odds of functional decline for those with any impairment in IADL who used an aid for mobility (OR 0.32, 95% CI 0.14-0.7)., Conclusion: older people with pre-existing ADL impairment were at high risk of functional decline in the 30 days following ED presentation. This effect was largely mitigated for those who used a mobility aid. Early intervention with functional assessments and appropriate implementation of support services and mobility aids could reduce functional decline after discharge., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com)

What Is Known and Objective: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors., Methods: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process., Results: Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1)., What Is New and Conclusion: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy., (© 2016 John Wiley & Sons Ltd.)

Background: an emergency department (ED) visit is a sentinel event for an older person, with increased likelihood of adverse outcomes post-discharge including early re-presentation., Objectives: to determine factors associated with early re-presentation., Methods: prospective cohort study conducted in the ED of a large acute Melbourne tertiary hospital. Community-dwelling patients ≥65 years were interviewed including comprehensive assessment of cognitive and functional status, and mood. Logistic regression was used to identify risk factors for return within 30 days., Results: nine hundred and fifty-nine patients, median age 77 years, were recruited. One hundred and forty patients (14.6%) re-presented within 30 days, including 22 patients (2.3%) on ≥2 occasions and 75 patients (7.8%) within 7 days. Risk factors for re-presentation included depressive symptoms, cognitive impairment, co-morbidity, triaged as less urgent (ATS 4) and attendance in the previous 12 months, with a decline in risk after 85 years of age. Logistic regression identified chronic obstructive pulmonary disease (OR 1.78, 95% CI 1.02-3.11), moderate cognitive impairment (OR 2.07, 95% CI 1.09-3.90), previous ED visit (OR 2.11, 95% CI 1.43-3.12) and ATS 4 (OR 2.34, 95% CI 1.10-4.99) as independent risk factors for re-presentation. Age ≥85 years was associated with reduced risk (OR 0.81, 95% CI 0.70-0.93)., Conclusion: older discharged patients had a high rate of early re-presentation. Previously identified risk factors-increased age, living alone, functional dependence and polypharmacy-were not associated with early return in this study. It is not clear whether these inconsistencies represent a change in patient case-mix or strategies implemented to reduce re-attendance. This remains an important area for future research., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: A partnered medication review and charting model involving a pharmacist and medical officer was implemented in the Emergency Short Stay Unit and General Medicine Unit of a major tertiary hospital. The aim of the study was to describe the safety and effectiveness of partnered medication charting in this setting., Methods: A partnered medication review and charting model was developed. Credentialed pharmacists charted pre-admission medications and venous thromboembolism prophylaxis in collaboration with the admitting medical officer. The pharmacist subsequently had a clinical discussion with the treating nurse regarding the medication management plan for the patient. A prospective audit was undertaken of all patients from the initiation of the service., Results: A total of 549 patients had medications charted by a pharmacist from the 14th of November 2012 to the 30th of April 2013. A total of 4765 medications were charted by pharmacists with 7 identified errors, corresponding to an error rate of 1.47 per 1000 medications charted., Conclusions: Partnered medication review and charting by a pharmacist in the Emergency Short Stay and General Medicine unit is achievable, safe and effective. Benefits from the model extend beyond the pharmacist charting the medications, with clinical value added to the admission process through early collaboration with the medical officer. Further research is required to provide evidence to further support this collaborative model., (Copyright © 2015. Published by Elsevier Ltd.)

In the week following the onset of the 2009 heatwave in Melbourne, Australia, The Alfred Hospital observed a significant increase in total hospital admissions (adjusted incidence rate ratio (IRR) 1.11, P = 0.046), emergency department presentations (IRR 1.15, P < 0.01) and general medical admissions (IRR 1.81, P < 0.01). Under the general medical unit there was a rise in the number of deaths (IRR 3.9, P < 0.01), and patients with a broad range of disorders, particularly of the endocrine/metabolic (IRR 2.2, P < 0.01), circulatory (IRR 1.9, P < 0.01) and genitourinary (IRR 2.6, P < 0.01) systems., (© 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.)

Background: A perceived risk of time-limited emergency department (ED) assessment of patients is inadequate workup leading to inappropriate disposition. The aim of this study was to examine the association of time to disposition plan (TDP) on ED length of stay (LOS) and correlate this to mortality., Methods: A retrospective review of data collected from ED information systems at three hospitals was conducted between June 2008 and October 2009. Included patients were admitted to a general medical unit. Patients were excluded if admitted to intensive care, coronary care, a cardiac monitored bed or required surgery in first 24 h or had an expected LOS of <48 h. Multivariate regression analysis was used to identify independent associations with mortality., Results: A total of 10,107 patient episodes was analysed, of which 6768 patients (67.0%) had an ED LOS of ≥8 h. There was significant effect modification by ED LOS in the association of TDP and mortality. In the setting of longer ED LOS, a TDP of <4 h was associated with significantly higher mortality (OR 1.57, 95% CI: 1.28-1.92, P < 0.001), corrected for age, gender and triage category. This association was not significant when ED LOS was <8 h (OR 0.88, 95% CI: 0.60-1.27, P = 0.49)., Conclusions: In the setting of prolonged ED LOS, completing ED assessment and management within 4 h of presentation was associated with significantly higher mortality. Further prospective studies are required to understand the relationship between rapid decision making in the ED and patient safety., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Background: Insulin is a high-risk medicine which may cause significant patient harm or death when given incorrectly. A 10-fold error in administered insulin dose commonly occurs when the abbreviation 'u' is used for 'units' and subsequently misinterpreted as a 'zero.', Method: A multidisciplinary working party was convened and mapped insulin prescribing, dispensing and administration. All inpatient orders above 25 units for short-acting insulin and 50 units for other insulin require validation by an additional source. Educational strategies to support adherence to the guideline and product-labelling alerts were developed., Results: Implementation occurred in August 2008 across the three hospital sites. In 90 weeks after implementation, there were 150 patients identified in which 200 high doses of insulin were prescribed (>25 units for short-acting insulin and 50 units for other insulin). There were eight instances where high doses of insulin were prescribed in error but were detected and rectified through the new validation process. There were 12 dosing errors that occurred, including two 10-fold dosing errors. In contrast, seven major errors resulting in excessive insulin administration were identified over a 2-year period prior to the introduction of the insulin high-dose validation system., Conclusion: A structured validation process was successful in reducing incorrect prescription and administration of high-dose insulin and has reduced the risk of associated fatalities or significant patient harm. Consideration should be given to adopting this process in any setting where insulin is prescribed and administered.

At common law no legal duty exists to rescue. This article examines the common law position and whether NSW case of Lowns v Woods 1996 ATR 81-376 creates a new duty to rescue. Recent legislation in some states provides protection from litigation to those who assist in emergencies providing they act in good faith and without gross negligence. The implications for midwives who act as good Samaritans are discussed.

This article examines the right of pregnant women to determine what will happen to their own bodies and whether their right to autonomy is absolute when refusing treatment which may be consider in their best interests and/or their fetuses'. A theoretical framework is used supported by relevant legal cases to argue that in some instance the rights of women to refuse treatment, most notably caesarean section have been overridden in favour of the fetus. The conclusion from the legal cases is that despite the consequences a woman's rights should not be overridden in favour of the fetus.

Should health professionals act legally or ethically in the delivery of health care presuming it is impossible to do both? There is a tendency by some to take the position that to act ethically is more important in the provision of health care and to ignore or at least minimise any legal consequences that may arise. At the same time the law may ignore ethical principles claiming the legal position is more important. This article argues that while law and ethics are both important in the delivery of health care the law as the final arbitrator takes precedence.

In most trials, at least 50% of patients with Graves' disease treated with antithyroid drugs (ATD) relapse after achieving euthyroidism. At present, there are no definitive prognostic parameters available early in treatment to indicate those likely to achieve long-term remission. Because thyrotropin receptor antibodies (TRAb) are specific for Graves' disease, the possibility that their rate of change early in treatment (0 to 6 months) might be such an indicator was explored. TRAb were measured both as thyrotropin binding inhibitory immunoglobulins (TBII) and as thyroid-stimulating antibodies (TSAb) in 85 patients with untreated Graves' disease at 6-month intervals throughout their ATD treatment. The patients in the study were treated for a minimum period of 12 months and were categorized retrospectively into two groups depending on whether or not they remained in remission after ATD treatment. Remission was deemed as reached in patients who remained euthyroid for a minimum period of 15 months after cessation of ATD. The mean initial TBII and TSAb values in the nonremission group were significantly higher than in the remission group (p < 0.001 for both parameters). The rates of fall in mean TBII levels were similar for each group in the first 6 months of treatment, but while they continued to fall in the remission group over the next 6 to 12 months, mean values for the nonremission group plateaued and failed to fall to control levels within that period. These results indicate that changes in TRAb levels, measured either as TBII or TSAb, occur more rapidly in the second 6 months of treatment in patients who ultimately achieve remission than those who do not. If TBII fall to control levels by 12 months, the patient has at least a 70% chance of ultimately achieving remission with ATD treatment alone.

1. Recommendations and decisions concerning treatment should primarily be based on the absolute evaluation of risk and risk reduction and not on calculation of a relative risk situation. 2. The therapeutic benefit in women at low risk should be balanced against possible physical and psychic side effects and submitted to a cost/benefit analysis. 3. The fact that coronary heart disease is rare in young women must not at all be reason for a less consequent treatment and prevention in women with established coronary heart disease.

The release of secretory phospholipase A2 (sPLA2) into the mammalian circulation may contribute to the development of hemorrhagic and inflammatory diseases. sPLA2 has previously been shown to alter the behavior of platelets, leukocytes, and endothelial cells, although the molecular basis for these cellular effects has not been established. Our studies indicate that the inhibition of platelet aggregation by snake, bee venom, and pancreatic sPLA2 is dependent on a plasma cofactor. This cofactor resides within the lipoprotein fraction of plasma, with 54%, 31%, and 11% of the activity present in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions, respectively. Delipidation of HDL and LDL was associated with the complete loss of platelet-inhibitory activity. Incubation of purified sPLA2 with the HDL fraction of plasma resulted in the time-dependent generation of lysophosphatidylcholine (lysoPC). The formation of lysoPC correlated with the inhibition of platelet aggregation. Purified lysoPC (10 to 100 micrograms/mL) inhibited platelet aggregation and dense granule release induced by thrombin (0.05 U/mL), collagen (1 micrograms/mL), ionophore A23187 (2 mumol/L), ADP (12.5 mumol/L), and adrenaline (3.2 mumol/L). The inhibition of platelet aggregation by lysoPC was dose-dependent and correlated with decreased fibrinogen binding to glycoprotein IIb-IIIa. Our studies indicate that the enzymatic generation of lysoPC from plasma lipoproteins is essential for the sPLA2-mediated inhibition of platelet activation in the presence of albumin. These results raise the possibility that the toxic effects of circulating sPLA2 may be due in part to the generation of the bioactive lysophospholipid, lysoPC.

Cardiovascular disease remains the major cause of death for postmenopausal women in Western societies. The majority of epidemiological studies indicate that postmenopausal oestrogen replacement therapy is associated with a 50% reduction in the risk of cardiovascular disease, with much of the reduction being mediated by changes in the plasma concentration of cholesterol within high and low density lipoproteins. In addition to favourably influencing the plasma concentration of lipoproteins, oestrogens also influence the complex metabolism of lipoproteins in the arterial wall, helping to impede the formation of the atherosclerotic plaque. Whilst oestrogens alter endothelial function, vascular reactivity and fibrinolysis, these changes are also seen with reduction of LDL cholesterol and may partly reflect the altered concentration of plasma lipoproteins induced by oestrogens. Oral oestrogens have substantially greater favourable effects on LDL and HDL cholesterol than their transdermal counterparts but also result in greater hypertriglyceridaemia. Most progestogens antagonize the beneficial effects of oestrogens on lipoproteins in a dose-dependent manner; however, cyclical use of low doses of progestogens with an oral oestrogen generally retains a net beneficial effect. Lipoprotein levels fluctuate during cyclical therapy, the most adverse changes being noted at the end of the progestogen phase. Lipoprotein concentrations are constant during continuous combined regimens which have the potential for more prolonged exposure to an adverse progestational effect. Despite adverse effects on the lipoprotein profile, animal studies suggest that progestogens do not substantially reverse the beneficial effects of oestrogens on the development of atherosclerosis. Finally, oestrogen therapy may be useful in the management of postmenopausal women with hyperlipidaemia, and also in the secondary prevention of clinical sequelae in women with established atherosclerosis.

Previous reports have produced conflicting views of the effects of lipoprotein lipase (LPL) on the particle size distribution of high density lipoproteins (HDL). In this study we have investigated the changes in particle size of HDL promoted by the interaction of LPL, the cholesteryl ester transfer protein (CETP) and very low density lipoproteins (VLDL). When the plasma fraction of d less than 1.21 g/ml (containing all lipoprotein fractions) was incubated for 24 h with bovine milk LPL alone or with CETP alone, there was relatively little change in the particle size distribution of HDL. When both LPL and CETP were added to the lipoprotein mixture, there was a substantial reduction in the particle size of HDL. This reduction in HDL particle size was found to be a direct function of the concentration of CETP. It was also influenced by the concentrations of VLDL and LPL, although in these cases the relationships were complex. When mixtures of the plasma fraction of d = 1.006-1.21 g/ml (this fraction includes low density lipoproteins and HDL but not VLDL) were supplemented with both LPL and CETP and incubated in the presence of varying concentrations of added VLDL, there was a progressive increase in the conversion of HDL into very small HDL particles of radius 3.7 nm as the concentration of VLDL triacylglycerol increased up to about 400 nmol/nml. However, further increases in the concentration of VLDL were accompanied by a progressive reduction in the formation of small HDL particles until, at higher VLDL concentrations, the effect was all but abolished. There was a similar enhancement in the formation of small HDL when LPL was added at low but not at high concentrations. These findings are consistent with the existence of two opposing processes. On the one hand there is likely to be a synergism between CETP and the non-esterified fatty acids (NEFA) released by LPL; this will favour a reduction in HDL particle size. On the other hand, the transfer of lipolysis products from VLDL to HDL may mask any such particle size reduction. The fact that the reduction in HDL particle size promoted by LPL, CETP and VLDL was found to be all but abolished by adding fatty acid-poor albumin to the incubation mixture is consistent with the proposition that NEFA are involved in the process. It also suggests, however, that the phenomenon may have little if any physiological significance.

The effects of lipid transfers and hepatic lipase (HL) on the concentration, composition, particle size distribution and morphology of high density lipoproteins (HDL) have been investigated. Human plasma supplemented with additional very low density lipoproteins (VLDL), cholesteryl ester transfer protein (CETP) and HL has been incubated at 37 degrees C for up to 8 h. The HDL became depleted of cholesteryl esters and reduced in particle size. Within 2 h of such incubation they had also lost about 30% of their apo A-I. However, with extension of the incubations beyond 2 h, the apo A-I returned progressively to the HDL fraction until, after 8 h, the concentration of apo A-I in HDL was identical to that in non-incubated samples. This return of apo A-I to the HDL density range was accompanied by a progressive appearance in electron micrographs of discoidal HDL particles. Thus, the depletion of the core lipid content and the reduction in particle size of HDL promoted by lipid transfers and HL activity in vitro is accompanied by a shedding of apo A-I which forms the nucleus of new discoidal HDL particles. The potential physiological importance of such a process is considerable.

Studies have been performed to investigate a possible mechanism to account for the low concentrations of apolipoproteins A-I (apo A-I) in subjects with hypertriglyceridemia. Incubation of human plasma in vitro with canine hepatic lipase resulted in the hydrolysis of approximately half the triglyceride in the high density lipoproteins (HDLs), but little change in the concentrations of other HDL constituents. However, when the plasma was supplemented with cholesteryl ester transfer protein and very low density lipoproteins to enrich the HDL with triglyceride, hepatic lipase promoted not only a significant reduction in HDL triglyceride acquired by the lipid transfer process but also an enhanced transfer of cholesteryl esters out of the particles. These changes were accompanied by a marked loss of apo A-I from HDL, which was demonstrated independently by ultracentrifugation, size-exclusion chromatography, and gradient gel-immunoblot analysis. The apo A-I lost from HDL was recovered in the "lipoprotein-free" fraction of plasma. The results of these studies indicate that primary reductions in the concentration of HDL core lipids in vitro are accompanied by a secondary loss of apo A-I from HDL. While recognizing the need for caution in any extrapolation from observations made in vitro to what may occur in vivo, these studies are nevertheless consistent with a proposition that the low concentration of apo A-I in subjects with hypertriglyceridemia is secondary to the reduced concentration of HDL core lipids in such subjects.

Purified human cholesteryl ester transfer protein (CETP) has been found, under certain conditions, to promote changes to the particle size distribution of high-density lipoproteins (HDL) which are comparable to those attributed to a putative HDL conversion factor. When preparations of either the conversion factor or CETP are incubated with HDL3 in the presence of very-low-density lipoproteins (VLDL) or low-density lipoproteins (LDL), the HDL3 are converted to very small particles. The possibility that the conversion factor may be identical to CETP was supported by two observations: (1) CETP was found to be the main protein constituent of preparations of the conversion factor and (2) an antibody to CETP not only abolished the cholesteryl ester transfer activity of the conversion factor preparations but also inhibited changes to HDL particle size. In additional studies, the changes to HDL particle size promoted by purified CETP were inhibited by the presence of fatty-acid-free bovine serum albumin; by contrast, albumin had no effect on the cholesteryl ester transfer activity of the CETP. The possibility that albumin may inhibit changes to HDL particle size by removing unesterified fatty acids from either the lipoproteins or CETP was tested by adding exogenous unesterified fatty acids to the incubations. In incubations of HDL with either VLDL or LDL, sodium oleate had no effect on HDL particle size. However, when CETP was also present in the incubation mixtures the capacity of CETP to reduce the particle size of HDL was greatly enhanced by the addition of sodium oleate. It is concluded that the changes in HDL particle size which were previously attributed to an HDL conversion factor can be explained in terms of the interacting effects of CETP and unesterified fatty acids.

Human plasma lipoproteins or human whole plasma have been incubated in vitro with canine hepatic lipase (HL) and bovine milk lipoprotein lipase (LPL) to determine the effects of lipases on the particle size distribution of HDL. Confirming previous reports, HL preferentially hydrolysed high density lipoprotein (HDL) triacylglycerol while LPL hydrolysed predominantly very low density lipoprotein (VLDL) triacylglycerol; however, neither lipase altered HDL particle size unless both VLDL and cholesteryl ester transfer protein (CETP) were present. Under these conditions HL promoted marked reduction in HDL particle size in a process dependent on the concentration of VLDL triacylglycerol while LPL was virtually without effect. When both LPL and HL were included in the same incubation, however, LPL prevented the effects of HL. These results are consistent with a proposition that HL has a direct effect on HDL particle size in a process which is dependent on concurrent lipid transfers between HDL and VLDL and that LPL reduces the effect of HL by reducing the concentration of VLDL triacylglycerol.

Studies have been performed to determine the involvement of very-low-density lipoproteins (VLDL), cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) in the formation of very small HDL particles. Human whole plasma has been incubated for 6 h at 37 degrees C in the absence and in the presence of various additions. There was minimal formation of very small HDL in incubations of non-supplemented plasma or in plasma supplemented with either VLDL, CETP or HL alone; nor were small HDL prominent after incubating plasma supplemented with mixtures of VLDL plus CETP, VLDL plus HL or CETP plus HL. By contrast, when plasma was supplemented with a mixture containing all three of VLDL, CETP and HL, incubation resulted in an almost total conversion of the HDL fraction into very small particles of radius 3.7 nm. The appearance of these very small HDL was independent of activity of lecithin: cholesterol acyltransferase. It was, however, dependent on both duration of incubation and on the concentrations of the added VLDL, CETP and HL. The effects of these incubations was also assessed in terms of changes to the concentration and distribution of lipid constituents across the lipoprotein spectrum. It was found that not only did lipid transfers and HL exhibit a marked synergism in promoting a reduction in HDL particle size but also that HL, although deficient in intrinsic transfer activity, enhanced the CETP-mediated transfers of cholesteryl esters from HDL to other lipoprotein fractions.

We studied the acute effect of standard therapeutic doses of oral frusemide on indices of thyroid function in 34 hospital in-patients with congestive cardiac failure. A transient decrease in total T4, elevation in the T3 resin uptake and consequent increase in the free T4 index (FT4I) were seen 2-5 h after ingestion of frusemide at a chronic morning dosage of 80, 120 or 250 mg. The FT4I pre-vs post-frusemide values after 250 mg of drug were 109 +/- 12 vs 129 +/- 18 (P less than 0.05) after 120 mg 92 +/- 14 vs 119 +/- 12 (P less than 0.01), and after 80 mg 102 +/- 6 vs 112 +/- 4 (P less than 0.01) (mean +/- SEM). Similar increases in apparent free T4 measured by an analogue tracer assay (free T4 RIA sol, Henning, Berlin) were seen after frusemide. In a time course study, the major change in the T3 uptake 120 min after frusemide ingestion correlated with the change in serum frusemide concentration. When frusemide was added to serum in vitro its influence was greatest in methods that involved least dilution of serum. In two of the patients difficulty in clinical assessment of thyroid status was compounded by the effect of oral frusemide on FT4I. We conclude that oral frusemide may influence biochemical assessments of thyroid function in patients with congestive cardiac failure. It is necessary to consider the time interval between ingestion of high doses of oral frusemide and blood sampling in evaluating such results.

In order to assess the value of thyroid function testing during amiodarone therapy, we reviewed all available tests in 128 patients treated with this drug. Nine patients (7.0%) developed biochemical hyperthyroidism with elevation of both free thyroxine index (FT4I) and free triiodothyronine index (FT3I) and marked suppression of serum thyroid stimulating hormone (TSH) after 1-46 months of therapy; six of these nine patients had clear clinical evidence of thyroid overactivity. Where serial tests were available before development of hyperthyroidism, this complication developed suddenly, despite previously stable normal indices of thyroid function, and could not be predicted by currently-available biochemical tests such as T4, T3, sensitive TSH, thyroglobulin or sex hormone binding globulin (SHBG) assays. Clinical features such as unexplained weight loss, proximal myopathy, exacerbation of arrhythmia, or heat intolerance appear to be the key to prompt diagnosis of this complication. Hyperthyroxinemia without T3 excess was found in 32.8% of patients without progression to true hyperthyroidism. Serum TSH remained detectable by sensitive assay in 17 out of 18 patients with amiodarone-induced euthyroid hyperthyroxinemia and was significantly higher than in patients with equivalent hyperthyroxinemia due to thyroxine therapy. Serial levels of SHBG were higher in patients with true hyperthyroidism than in those with euthyroid hyperthyroxinemia. The effect of combined treatment with propylthiouracil (800 mg/day) and potassium perchlorate (800 mg/day) was evaluated in five of the six clinically hyperthyroid patients. Biochemical euthyroidism was achieved after 7-19 weeks, a response slower than previously reported, indicating that this drug combination does not result uniformly in prompt resolution of amiodarone-induced hyperthyroidism.