CELPI: trial protocol for a randomised controlled trial of a Carer End of Life Planning Intervention in people dying with dementia.

BACKGROUND: Dementia is a leading cause of death in developed nations. Despite an often distressing and symptom laden end of life, there are systematic barriers to accessing palliative care in older people dying of dementia. Evidence exists that 70% of people living with severe dementia attend an emergency department (ED) in their last year of life. The aim of this trial is to test whether a Carer End of Life Planning Intervention (CELPI), co-designed by consumers, clinicians and content specialists, improves access to end of life care for older people with severe dementia, using an ED visit as a catalyst for recognising unmet needs and specialist palliative care referral where indicated. METHODS: A randomised controlled trial (RCT) enrolling at six EDs across three states in Australia will be conducted, enrolling four hundred and forty dyads comprising a person with severe dementia aged ≥ 65 years, and their primary carer. Participants will be randomly allocated to CELPI or the control group. CELPI incorporates a structured carer needs assessment and referral to specialist palliative care services where indicated by patient symptom burden and needs assessment. The primary outcome measure is death of the person with dementia in the carer-nominated preferred location. Secondary outcomes include carer reported quality of life of the person dying of dementia, hospital bed day occupancy in the last 12 months of life, and carer stress. An economic evaluation from the perspective of a health funder will be conducted. DISCUSSION: CELPI seeks to support carers and provide optimal end of life care for the person dying of dementia. This trial will provide high level evidence as to the clinical and cost effectiveness of this intervention. TRIAL REGISTRATION: ACTRN12622000611729 registered 22/04/2022.

Association between pelvic inflammatory disease, infertility, ectopic pregnancy and the development of ovarian serous borderline tumor, mucinous borderline tumor and low-grade serous carcinoma.

OBJECTIVE: Risk factors for ovarian borderline tumors and low-grade serous carcinoma (LGSC) are poorly understood. The aim of this study was to examine the association between infertility, pelvic inflammatory disease (PID), endometriosis, ectopic pregnancy, hysterectomy, tubal ligation and parity and the risk of serous borderline tumor (SBT), mucinous borderline tumor (MBT) and LGSC. METHODS: This was a population-based cohort study using linked administrative and hospital data. Participants were 441,382 women born between 1945 and 1975 who had been admitted to hospital in Western Australia between 1 January 1980 and 30 June 2014. We used Cox regression to estimate hazard ratios (HRs). RESULTS: We observed an increased rate of SBT associated with infertility, PID and ectopic pregnancy (HRs and 95% CIs were, respectively, 1.98 (1.20-3.26); 1.95 (1.22-3.10) and 2.44 (1.20-4.96)). We did not detect an association between any of the factors under study and the rate of MBT. A diagnosis of PID was associated with an increased rate of LGSC (HR 2.90, 95% CI 1.21-6.94). CONCLUSIONS: The association with PID supports the hypothesis that inflammatory processes within the upper gynaecological tract and/or peritoneum may predispose to the development of SBT and LGSC.

Risk of persistent or recurrent cervical neoplasia in patients with 'pure' adenocarcinoma-in-situ (AIS) or mixed AIS and high-grade cervical squamous neoplasia (cervical intra-epithelial neoplasia grades 2 and 3 (CIN 2/3)): a population-based study.

OBJECTIVE: To compare outcomes of patients with pure adenocarcinoma-in-situ (AIS) and mixed AIS/CIN 2/3 lesions including the incidence of AIS persistence, recurrence and progression to adenocarcinoma. DESIGN: Retrospective cohort study. SETTING: Statewide population in Western Australia. POPULATION: Women diagnosed with AIS between 2001 and 2012. METHODS: We conducted a retrospective, population-based cohort study. MAIN OUTCOME MEASURES: De-identified linked data were utilised to ascertain the association between patient age at excisional treatment, margin status, lesion type, lesion size, and risk of persistent AIS (defined as the presence of AIS <12 months from treatment), recurrent AIS (≥12 months post-treatment), and adenocarcinoma. RESULTS: 636 patients were eligible for analysis. The mean age was 32.3 years and median follow-up interval was 2.5 years. Within the study cohort, 266 patients (41.8%) had pure AIS and 370 (58.2%) had mixed AIS/CIN 2/3. Overall, 47 patients (7.4%) had AIS persistence/recurrence and 12 (1.9%) had adenocarcinoma. Factors associated with persistence/recurrence were pure AIS (hazard ratio (HR) 2.3; 95%CI 1.28-3.94; P = 0.005), age >30 years (HR 2.1; 95%CI 1.16-3.81; P = 0.015), positive endocervical margins (HR 5.8; 95%CI 3.05-10.92; P = <0.001) and AIS lesions >8 mm (HR 2.5; 95%CI 1.00-6.20; P = 0.049). A histologically positive AIS ectocervical margin was not associated with persistence/recurrence. CONCLUSION: In this study, pure AIS was associated with greater risk of persistence/recurrence than was mixed AIS/CIN 2/3. AIS lesions >8 mm and positive endocervical margins were significant predictors for persistent or recurrent disease. TWEETABLE ABSTRACT: Pure cervical adenocarcinoma-in-situ (AIS) may have greater risk of recurrence than AIS co-existing with CIN 2/3.

Comparison of cold knife cone biopsy and loop electrosurgical excision procedure in the management of cervical adenocarcinoma in situ: What is the gold standard?

OBJECTIVE: To compare the outcomes of patients with cervical adenocarcinoma in situ (ACIS) treated with cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for the treatment of cervical adenocarcinoma in situ (ACIS). STUDY DESIGN: This is a retrospective, population-based cohort study of Western Australian patients with ACIS diagnosed between 2001 and 2012. Outcomes included pathological margin status and the incidence of persistent or recurrent endocervical neoplasia (ACIS and adenocarcinoma) during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The study group comprised 338 patients including 107 (32%) treated initially by LEEP and 231 (68%) treated by CKC biopsy. The mean age was 33.2 years (range 18 to 76 years) and median follow-up interval was 3.6 years (range <1 year to 11.8 years). Overall, 27 (8.0%) patients had ACIS persistence/recurrence while 9 (2.7%) were diagnosed with adenocarcinoma during the follow-up and surveillance periods. No patient died of cervical cancer within the study period. There were no significant differences in the incidence of persistent and/or recurrent endocervical neoplasia according to the type of excisional procedure. Patients with positive biopsy margins were 3.4 times more likely to have disease persistence or recurrence. CONCLUSION(S): LEEP and CKC biopsy appear equally effective in the treatment of ACIS for women wishing to preserve fertility. Patients undergoing conservative management for ACIS should be closely monitored, particularly if biopsy margins are positive in initial excision specimens. Patients and their clinicians should be aware of the potential risks of residual and recurrent disease.

Detection of liver injury in IBD using transient elastography.

BACKGROUND: Up to 5% of inflammatory bowel disease (IBD) patients are thought to have clinically significant liver disease due to multifactorial causes, however, this figure may be an underestimate due to reliance on abnormal liver tests (LTs) and/or liver biopsies. AIMS: Our aim was to evaluate the prevalence of clinically significant liver disease in IBD patients as defined by an increased liver stiffness measurement (LS) ≥8kPa using transient elastography (TE). METHODS: 110 IBD patients, and 55 non-IBD control subjects, had their LS recorded using FibroScan® (EchoSense, Paris, France) by a single blinded operator trained in TE. RESULTS: 71 Crohn's disease and 39 ulcerative colitis subjects were included. All demographic variables were similar between the IBD and control groups apart from a significantly higher proportion of IBD patients who smoked (17.3% vs 3.6%, P=0.013). Seven IBD patients (6.4%) had an LS over 8 kPa and 3 had persistently elevated LS 6 months later. One patient had compensated cirrhosis. No significant differences in overall LS were observed between the IBD and control groups. Increased BMI and age, however, were independently associated with a higher LS in the IBD but not in the control group (P<0.001 and 0.010 respectively). CONCLUSION: Using TE, the prevalence of clinically significant liver disease in IBD patients is low. The association of increased BMI and age with increased LS in IBD suggests fatty liver disease being the prevailing aetiology in these patients.

Long-term survival following laparoscopic and open colectomy for colon cancer: a meta-analysis of randomized controlled trials.

AIM: Large randomized clinical trials comparing long-term survival after laparoscopic and open colectomy for large bowel cancer show equivalence, but meaningful analysis of data by stage has not been possible due to the small numbers of patients in individual trials. The aim of this meta-analysis was to improve statistical power by combining data to enable assessment of survival for individual stages. METHOD: A systematic review and meta-analysis was conducted through a computerized search of all randomized controlled trials comparing open and laparoscopic surgery for large bowel cancer. Overall survival data were analysed and subgroup analysis was performed for cancer of Stages I-III. RESULTS: Five trials (3152 patients) were included. Overall survival was equivalent (hazard ration 0.93; 95% confidence interval 0.80-1.07). With each of the cancer stages, I-III, there was no difference in 5-year survival. There was, however, a nonsignificant trend in favour of open surgery in the subgroup analysis of Stage II patients. CONCLUSION: Laparoscopic-assisted surgery for colon cancer is equivalent to open surgery with respect to long-term survival although there may be a difference for Stage II cancer.

Earlier age of dementia onset and shorter survival times in dementia patients with diabetes.

Diabetes is a risk factor for dementia, but relatively little is known about the epidemiology of the association. A retrospective population study using Western Australian hospital inpatient, mental health outpatient, and death records was used to compare the age at index dementia record (proxy for onset age) and survival outcomes in dementia patients with and without preexisting diabetes (n = 25,006; diabetes, 17.3%). Inpatient records from 1970 determined diabetes history in this study population with incident dementia in years 1990-2005. Dementia onset and death occurred an average 2.2 years and 2.6 years earlier, respectively, in diabetic compared with nondiabetic patients. Age-specific mortality rates were increased in patients with diabetes. In an adjusted proportional hazard model, the death rate was increased with long-duration diabetes, particularly with early age onset dementia. In dementia diagnosed before age 65 years, those with a ≥15-year history of diabetes died almost twice as fast as those without diabetes (hazard ratio = 1.9, 95% confidence interval: 1.3, 2.9). These results suggest that, in patients with diabetes, dementia onset occurs on average 2 years early and survival outcomes are generally poorer. The effect of diabetes on onset, survival, and mortality is greatest when diabetes develops before middle age and after 15 years' diabetes duration. The impact of diabetes on dementia becomes progressively attenuated in older age groups.

An assessment of burn injury hospitalisations of adolescents and young adults in Western Australia, 1983-2008.

BACKGROUND: This study presents a 26-year epidemiological assessment of burn injury hospitalisations for people 15-29 years of age in Western Australia. METHODS: Linked hospital morbidity and death data for all persons hospitalised with an index burn injury in Western Australia for the period 1983-2008 were analyzed. Annual age-specific incidence rates were estimated. Poisson regression analyses were used to estimate temporal trends in hospital admissions. RESULTS: There were 6404 burn hospital admissions of which 76% were male. Males had hospitalisation rates 3.0 times that of females (95%CI: 2.8-3.2) and Aboriginal people had rates 2.3 times (95%CI: 2.1-2.5) that of non-Aboriginal persons. Hospitalisations for burn injury declined by 42% (95%CI: 35-47) for males and 21% (95%CI: 6-33) for females. Hospitalisations declined by 53% (95%CI: 35-63) for Aboriginal people, and by 35% (95%CI: 29-41) for non-Aboriginal people. Significant reductions were observed for flame and electrical burn hospitalisations. The major causes of burns in males were exposure to controlled fires and ignition of inflammable materials, with scalds the predominant cause of burn in females. CONCLUSIONS: Downward trends in burn injury hospitalisations for both males and females 15-29 years of age were observed; however, males and Aboriginal persons have significantly elevated hospitalisation rates.

Is colonoscopy still mandatory after a CT diagnosis of left-sided diverticulitis: can colorectal cancer be confidently excluded?

BACKGROUND: It is routine practice to perform colonoscopy as a follow-up after an attack of diverticulitis, with the main aim to exclude any underlying malignancy. PURPOSE: This study aimed to determine whether colonoscopy is necessary and what additional information is gained from this procedure. DESIGN: This is a study of a retrospective cohort. SETTINGS AND PATIENTS: From January 2003 to June 2009, patients in whom left-sided diverticulitis was diagnosed on CT scan were matched with colonoscopy reports within 1 year from the date of CT by the use of radiology and endoscopy databases. Patients who had colonoscopy within 1 year before the CT scan were excluded. The Western Australian Cancer Registry was cross-referenced to identify patients who subsequently received diagnoses of cancers for whom colonoscopy reports were unavailable. MAIN OUTCOME MEASURES: The main outcome measures were the number of patients in whom colorectal cancers were diagnosed and other incidental findings, eg, polyps, colitis, and stricture. RESULTS: Left-sided diverticulitis was diagnosed in 1088 patients on CT scan, whereas follow-up colonoscopy reports were available for 319 patients. Eighty-two (26%) patients had incidental findings of polyps (9 polyps >1 cm), and 9 patients (2.8%) received diagnoses of colorectal cancers on colonoscopy. After cross-referencing with the cancer registry, the overall prevalence of colorectal cancer among the cohort within 1 year of CT scan was 2.1% (23 cases). The odds of a diagnosis of colorectal cancer were 6.7 times (95% CI 2.4-18.7) in patients with an abscess reported on CT, 4 times (95% CI 1.1-14.9) in patients with local perforation, and 18 times (95% CI 5.1-63.7) in patients with fistula compared with patients with uncomplicated diverticulitis. LIMITATIONS: This study was limited by the unavailability of data for private/interstate hospitals, and the relatively small number of cancer cases reduced the statistical power of the study. CONCLUSIONS: We recommend routine colonoscopy after an attack of presumed left-sided diverticulitis in patients who have not had recent colonic luminal evaluation. The rate of occult carcinoma is substantial in this patient population, in particular, when abscess, local perforation, and fistula are observed.

Morbidity outcomes of 78,577 hysterectomies for benign reasons over 23 years.

OBJECTIVE: To investigate the association of the method of hysterectomy for benign reasons with morbidity outcomes in Western Australia after taking other demographic, social and health-related factors into account. DESIGN: Population-based retrospective observational study. SETTING: All hospitals in Western Australia where hysterectomies were performed from 1981 to 2003. POPULATION: All women aged 20 years or older who underwent a hysterectomy for benign reasons. METHOD: Logistic and zero-truncated negative binomial regression analysis of record-linked administrative health data. MAIN OUTCOME MEASURES: Relative odds of experiencing complications during the hysterectomy admission or readmission and relative length of stay in hospital by type of hysterectomy. RESULTS: There were 78,577 hysterectomies performed for benign reasons from 1981 to 2003. Procedure-related haemorrhage (2.4%) was the most commonly recorded complication, followed by genitourinary disorders (1.9%), infection (1.6%) and urinary tract infections (1.6%). Vaginal hysterectomy was associated with reduced odds of infection and haemorrhage compared with abdominal procedures during the hysterectomy admission. Readmission rates increased from 5.4% in 1981-84 to 7.2% in 2000-03 as average length of stay decreased by 53% over the same time period. Women who underwent laparoscopically assisted vaginal hysterectomies and vaginal hysterectomies had increased odds of readmission for haemorrhage and genitourinary disorders compared with abdominal hysterectomy. Young age, increasing number of co-morbid conditions and having a complication at hysterectomy admission were also associated with increased odds of readmission. CONCLUSION: These findings identify women at risk of readmission following hysterectomy and highlight an opportunity to modify early discharge and patient follow-up practices to reduce this risk.

WITHDRAWN: Support for carers of people with Alzheimer's type dementia.

BACKGROUND: Research has highlighted the problems for carers of people with dementia. These include the effective loss of companionship and support of a life partner, social isolation and complex financial, legal and social decision making. The burden of caring is financially, emotionally and physically significant. Studies of the effects of ways of supporting carers and reducing the burden of caring often examine a range of outcomes. Probably because of these characteristics, no formal overview of this area of service provision has been undertaken. Moreover, the term 'intervention' in relation to caregivers of people with Alzheimer's disease is open to wide variations in interpretation at the level of service provision. Interventions range from the application of 'hi-tech' computer technology for socially isolated carers, to the formation of specialist support groups and respite services. OBJECTIVES: The objective of this review is to provide an assessment of the effectiveness of health and/or social interventions designed to help support the carers of people with Alzheimer's-type dementias. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched using the terms 'carer*' and 'caregiv*'. See the Cochrane Dementia & Cognitive Impairment group's details for the full search strategy. SELECTION CRITERIA: All randomised trials in which primary carers of people with Alzheimer's disease are allocated to either intervention or non-intervention/control groups and where the intervention was provided by healthcare and/or social services. DATA COLLECTION AND ANALYSIS: Data was extracted by both reviewers and was found to be unsuitable for quantitative synthesis. A qualitative overview is presented and structured according to the comparisons used in the review. Weighted Mean Differences (weighted by sample size) for each outcome and its subcategories are also presented. MAIN RESULTS: The results of the review are inconclusive. No evidence was found for the following comparison interventions:1) individualised service assessment and planning versus conventional support2) technology-based carer networking (via computers or telephones) versus conventional support3) carer-education/training versus conventional support4) multi-faceted/dimensional strategies (such as specialised carer assessment and training) versus conventional supportWhilst the overview suggests little or no evidence that interventions to support caregivers of people with Alzheimer's disease are of quantifiable benefit, the poor quality and small sample sizes of the studies, as well as the diversity of interventions examined and outcomes reported, mean that this conclusion cannot be put forward without the need for caution, particularly as some of the studies put forward qualitative evidence which contradicts this conclusion. AUTHORS' CONCLUSIONS: With the limited nature of the research evidence in mind, it is not possible to recommend either wholesale investment in caregiver support programmes or withdrawal of the same. With the addition of further studies in future updates of this review, expected in early 1999, this presently inconclusive picture may become clearer.A number of conclusions relating to future areas of research can be put forward with more conviction. Specifically,1) Future trials need to examine interventions included in the existing knowledge base on Alzheimer's carer-supportive interventions.2) Outcome measures used should mirror those in similar studies.3) Outcome measures need to be clinically and 'lay' relevant.4) Trials need to be of longer duration given the 7-10 years median life expectancy of people with Alzheimer's Disease.5) Sample sizes need to be increased and calculated properly given the likelihood of a moderate intervention effect (if any).7) Blinding at the outcome assessment stage needs to be a part of future basic trial designs if bias is to be avoided.8) If reviews are to have their power increased then quality of reporting results needs to be improved.

A systematic review of the effectiveness and cost-effectiveness of different models of community-based respite care for frail older people and their carers.

OBJECTIVES: To review the evidence for different models of community-based respite care for frail older people and their carers, where the participant group included older people with frailty, disability, cancer or dementia. Where data permitted, subgroups of carers and care recipients, for whom respite care is particularly effective or cost-effective, were to be identified. DATA SOURCES: Major databases were searched from 1980 to March 2005. Ongoing and recently completed research databases were searched in July 2005. REVIEW METHODS: Data from relevant studies were extracted and quality assessed. The possible effects of study quality on the effectiveness data and review findings were discussed. Where sufficient clinically and statistically similar data were available, data were pooled using appropriate statistical techniques. RESULTS: Twenty-two primary studies were included. Most of the evidence came from North America, with a minority of effectiveness and economic studies based in the UK. Types of service studied included day care, host family, in-home, institutional and video respite. Effectiveness evidence suggests that the consequences of respite upon carers and care recipients are generally small, with better controlled studies finding modest benefits only for certain subgroups. However, many studies report high levels of carer satisfaction. No reliable evidence was found that respite can delay entry to residential care or that respite adversely affects care recipients. Randomisation validity in the included randomised studies was sometimes unclear. Studies reported many different outcome measures, and all of the quasi-experimental and uncontrolled studies had methodological weaknesses. The descriptions of the studies did not provide sufficient detail of the methods of data collection or analysis, and the studies failed to describe adequately the groups of study participants. In some studies, only evidence to support respite care services was presented, rather than a balanced view of the services. Only five economic evaluations of respite care services were found, all of which compared day care with usual care and only one study was undertaken in the UK. Day care tended to be associated with higher costs and either similar or a slight increase in benefits, relative to usual care. The economic evaluations were based on two randomised and three quasi-experimental studies, all of which were included in the effectiveness analysis. The majority of studies assessed health and social service use and cost, but inadequate reporting limits the potential for exploring applicability to the UK setting. No study included generic health-related quality of life measures, making cost-effectiveness comparisons with other healthcare programmes difficult. One study used sensitivity analysis to explore the robustness of the findings. CONCLUSIONS: The literature review provides some evidence that respite for carers of frail elderly people may have a small positive effect upon carers in terms of burden and mental or physical health. Carers were generally very satisfied with respite. No reliable evidence was found that respite either benefits or adversely affects care recipients, or that it delays entry to residential care. Economic evidence suggests that day care is at least as costly as usual care. Pilot studies are needed to inform full-scale studies of respite in the UK.

Patient acceptability of larval therapy for leg ulcer treatment: a randomised survey to inform the sample size calculation of a randomised trial.

BACKGROUND: A trial was commissioned to evaluate the effectiveness of larval therapy to debride and heal sloughy and necrotic venous leg ulcers. Larval therapy in the trial was to be delivered in either loose or bagged form. Researchers were concerned that resistance to larval therapy may threaten the feasibility of the trial. Additionally there was concern that the use of larval therapy may require a larger effect size in time to healing than originally proposed by the investigators. METHODS: To formally evaluate patient preferences a survey using two randomly allocated, nurse administered questionnaires was undertaken. Patients were randomised to receive one of the two following questionnaires (i) preferences between loose larvae and standard treatment (hydrogel) or (ii) patient preferences between bagged larvae and standard therapy (hydrogel). The study was undertaken in a Vascular Clinic, in an Outpatients Department of a large teaching hospital in the North of England. The sample consisted of 35 people aged 18 years and above with at least one leg ulcer of venous or mixed (venous and arterial) aetiology. RESULTS: Approximately 25% of participants would not consider the use of larval therapy as an acceptable treatment option for leg ulcers, regardless of the method of containment. For the patients that would consider the use of larval therapy, different preferences in healing times required to use the therapy were observed depending upon the method of containment. The median response of those participants questioned about bagged larvae found that they would be willing to use this therapy even if they were equally able to achieve healing with the use of hydrogel by 20 weeks. For those participants questioned about the use of loose larvae complete healing would have to have taken place over 17 weeks for them to choose larvae as their preferred option rather than hydrogel. This difference was not significant (p = 0.075). CONCLUSION: We found no evidence of widespread resistance to the utilisation of larval therapy from patients regardless of the method of larval therapy containment. These methods have the potential to inform sample size calculations where there are concerns of patient acceptability.

Persistent high rates of hysterectomy in Western Australia: a population-based study of 83 000 procedures over 23 years.

OBJECTIVE: To investigate incidence trends and demographic, social and health factors associated with the rate of hysterectomy and morbidity outcomes in Western Australia and compare these with international studies. DESIGN: Population-based retrospective cohort study. SETTING: All hospitals in Western Australia where hysterectomies were performed from 1981 to 2003. POPULATION: All women aged 20 years or older who underwent a hysterectomy. METHODS: Statistical analysis of record-linked administrative health data. MAIN OUTCOME MEASURES: Rates, rate ratios and odds ratios for incidence measures and length of stay in hospital and odds ratios for morbidity measures. RESULTS: The age-standardised rate of hysterectomy adjusted for the underlying prevalence of hysterectomy decreased 23% from 6.6 per 1000 woman-years (95% CI 6.4-6.9) in 1981 to 4.8 per 1000 woman-years (95% CI 4.6-4.9) in 2003. Lifetime risk of hysterectomy was estimated as 35%. In 2003, 40% of hysterectomies were abdominal. The rate of hysterectomy to treat menstrual disorders fell from 4 per 1000 woman-years in 1981 to 1 per 1000 woman-years in 1993 and has since stabilised. Low socio-economic status, having only public health insurance, nonindigenous status and living in rural or remote areas were associated with increased risk of having a hysterectomy for menstrual disorders. Indigenous women had higher rates of hysterectomy to treat gynaecological cancers compared with nonindigenous women, particularly in rural areas. The odds of a serious complication were 20% lower for vaginal hysterectomies compared with abdominal procedures. CONCLUSION: Western Australia has one of the highest hysterectomy rates in the world, although proportionally, significantly fewer abdominal hysterectomies are performed than in most countries.

Pressure relieving support surfaces: a randomised evaluation.

OBJECTIVES: To determine differences between alternating pressure overlays and alternating pressure replacement mattresses with respect to the development of new pressure ulcers, healing of existing pressure ulcers, patient acceptability and cost-effectiveness of the different pressure-relieving surfaces. Also to investigate the specific additional impact of pressure ulcers on patients' well-being. DESIGN: A multicentre, randomised, controlled, open, fixed sample, parallel-group trial with equal randomisation was undertaken. The trial used remote, concealed allocation and intention-to-treat (ITT) analysis. The main trial design was supplemented with a qualitative study involving a purposive sample of 20-30 patients who developed pressure ulcers, to assess the impact of the pressure ulcers on their well-being. In addition, a focus group interview was carried out with clinical research nurses, who participated in the PRESSURE (Pressure RElieving Support SUrfaces: a Randomised Evaluation) Trial, to explore the experiences of their role and observations of pressure area care. SETTING: The study took place in 11 hospital-based research centres within six NHS trusts in England. PARTICIPANTS: Acute and elective patients aged 55 years or older and admitted to vascular, orthopaedic, medical or care of the elderly wards in the previous 24 hours were investigated. INTERVENTIONS: Patients were randomised to either an alternating pressure overlay or an alternating pressure mattress replacement, with mattress specifications clearly defined to enable the inclusion of centres using products from different manufacturers, and to exclude hybrid mattress systems (which either combine foam or constant low pressure with alternating pressure in one mattress, or can be used as either an overlay or a replacement mattress). MAIN OUTCOME MEASURES: Development of a new pressure ulcer (grade < or =2, i.e. partial-thickness wound involving epidermis/dermis only) on any skin site. Also healing of existing pressures ulcers, patient acceptability and cost-effectiveness. RESULTS: In total, 6155 patients were assessed for eligibility to the trial and 1972 were randomised: 990 to the alternating pressure overlay (989 after one postrandomisation exclusion) and 982 to the alternating pressure mattress replacement. ITT analysis found no statistically significant difference in the proportions of patients developing a new pressure ulcer of grade 2 or above [10.7% overlay patients, 10.3% mattress replacement patients, a difference of 0.4%, 95% confidence interval (CI) -2.3 to 3.1%, p = 0.75]. When logistic regression analysis was used to adjust for minimisation factors and prespecified baseline covariates, there was no difference between the mattresses with respect to the odds of ulceration (odds ratio 0.94, 95% CI 0.68 to 1.29). There was no evidence of a difference between the mattress groups with respect to time to healing (p = 0.86). The Kaplan-Meier estimate of the median time to healing was 20 days for each intervention. More patients allocated overlays requested mattress changes due to dissatisfaction (23.3%) than mattress replacement patients (18.9%, p = 0.02) and more than one-third of patients reporting difficulties associated with movement in bed and getting into or out of bed. There is a higher probability (64%) that alternating mattress replacements are cost-saving; they were associated with lower overall costs (74.50 pounds sterling per patient on average, mainly due to reduced length of stay) and greater benefits (a delay in time to ulceration of 10.64 days on average). Patients' accounts highlighted that the development of a pressure ulcer could be pivotal in the trajectory from illness to recovery, by preventing full recovery or causing varied impacts on their quality of life. CONCLUSIONS: There is no difference between alternating pressure mattress replacements and overlays in terms of the proportion of patients developing new pressure ulcers; however, alternating pressure mattress replacements are more likely to be cost-saving. The results suggest that when renewing alternating pressure surfaces or ordering equipment within a rental contract, mattress replacements should be specified; however, overlays are acceptable if no replacement mattress is available. Similarly, patient preferences can be supported, without any great increase in risk, if individual patients request an overlay rather than a replacement mattress. Further research could include a randomised controlled trial comparing alternating pressure mattress replacements and high-specification foam mattresses in patients at moderate to high risk; an accurate costing study to understand better how much pressure ulcers cost health and social services in the UK; and trials in higher risk groups of patients. Also future trials should measure time to ulceration as the primary end-point, since this is more informative economically and possibly also from a patient and clinical perspective.

Economic evaluation of a nursing-led intermediate care unit.

OBJECTIVES: The aim of this paper is to examine the costs of introducing a nursing-led ward program together with examining the impact this may have on patients' outcomes. METHODS: The study had a sample size of 177 patients with a mean age of 77, and randomized to either a treatment group (care on a nursing-led ward, n = 97) or a control group (standard care usually on a consultant-led acute ward, n = 80). Resource use data including length of stay, tests and investigations performed, and multidisciplinary involvement in care were collected. RESULTS: There were no significant differences in outcome between the two groups. The inpatient costs for the treatment group were significantly higher, due to the longer length of stay in this group. However, the postdischarge costs were significantly lower for the treatment group. CONCLUSIONS: The provision of nursing-led intermediate care units has been proposed as a solution to inappropriate use of acute medical wards by patients who require additional nursing rather than medical care. Whether the treatment group is ultimately cost-additive is dependent on how long reductions in postdischarge resource use are maintained.

Addition of a c-myc epitope tag within the VEGF protein does not affect in vitro biological activity.

The overexpression of vascular endothelial growth factor (VEGF) has been strongly implicated in diseases involving neovascularization. VEGF exists in as many as six different isoforms, each showing a unique pattern of tissue distribution and activity. To investigate the effect of individual VEGF isoform overexpression in neovascular disease models, we inserted c-myc epitope tags into the three VEGF isoforms expressed in retinal pigment epithelial cells, VEGF121, VEGF165, and VEGF189. We found that the 12-amino acid insertion between the receptor binding and heparin binding domains did not affect VEGF transcription, translation, or secretion. In addition, VEGF isoforms containing the c-myc epitope tag were able to stimulate endothelial cell proliferation as efficiently as non-tagged VEGF isoforms and they could be individually identified by Western blotting and immunocytochemistry using the c-myc epitope specific monoclonal antibody 9E10.

Defining the nursing contribution to patient outcome: lessons from a review of the literature examining nursing outcomes, skill mix and changing roles.

A review of the evidence to define the nursing contribution to patient outcome is presented. The review relies on work related to nursing sensitive outcomes, skill mix and changing roles. Methodological difficulties associated with these studies are highlighted. Areas requiring further research are discussed. It is suggested that experimental evidence is not always appropriate, when attempting to describe nursing activity. The authors advocate that new methodologies, in particular practitioner-centred research, are needed to unpack the nature of nursing.

Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization.

Vascular endothelial growth factor (VEGF) has been strongly implicated in the development of choroidal neovascularization found in age-related macular degeneration. Normally expressed in low levels, this study investigates whether the overexpression of VEGF in the retinal pigment epithelium is sufficient to cause choroidal neovascularization in the rat retina. A recombinant adenovirus vector expressing the rat VEGF(164) cDNA (AdCMV.VEGF) was constructed and injected into the subretinal space. The development of neovascularization was followed by fluorescein angiography, which indicates microvascular hyperpermeability of existing and/or newly forming blood vessels, and histology. VEGF mRNA was found to be overexpressed by retinal pigment epithelial cells and resulted in leaky blood vessels at 10 days postinjection, which was maintained for up to 31 days postinjection. By 80 days postinjection, new blood vessels had originated from the choriocapillaris, grown through the Bruch's membrane to the subretinal space, and disrupted the retinal pigment epithelium. This ultimately led to the formation of choroidal neovascular membranes and the death of overlying photoreceptor cells. By controlling the amount of virus delivered to the subretinal space, we were able to influence the severity and extent of the resulting choroidal neovascularization. These results show that even temporary overexpression of VEGF in retinal pigment epithelial cells is sufficient to induce choroidal neovascularization in the rat eye.

The effectiveness of intermediate care in a nursing-led in-patient unit.

In order to assess the potential for a nursing-led in-patient unit (NLIU) to substitute for a period of care in the acute hospital environment and promote recovery before discharge, a randomised controlled trial was conducted. The setting was an acute inner London hospital trust, part of the UK's national health service. Of patients referred to a NLIU from acute wards, 80 were randomly assigned to usual care (remain in normal hospital system) and 97 to the NLIU (nursing-led care with no routine medical involvement). Patients were identified as medically stable but in need of additional nursing intervention by referring medical staff prior to full nursing assessment of suitability. Outcomes compared included functional dependence (Barthel Index), discharge destination and length of hospital stay. Inputs from nursing, paramedical and medical staff were measured. There was no significant difference in functional independence at discharge (p0.05). Patients undergoing usual care stayed in hospital for less time (mean difference 18 days, p<0.01) but the same number of patients were in hospital 90 days after recruitment (23% NLIU, 24% usual care p0.05) due to re-admissions. The model of care implemented differed considerably from that described in the literature with the NLIU having significantly fewer qualified nurses (RNs). Although the anticipated benefits of the NLIU were not demonstrated, the study does not conclude that the model should be rejected. Factors driving length of stay need to be further investigated, as does the possibility of post-discharge benefits. The NLIU does offer some potential to substitute for acute care but also appears to substitute for a period of primary care.