The Australian Health Care Homes trial: quality of care and patient outcomes. A propensity score-matched cohort study.

OBJECTIVE: To assess the impact of the Health Care Homes (HCH) primary health care initiative on quality of care and patient outcomes. DESIGN, SETTING: Quasi-experimental, matched cohort study; analysis of general practice data extracts and linked administrative data from ten Australian primary health networks, 1 October 2017 - 30 June 2021. PARTICIPANTS: People with chronic health conditions (practice data extracts: 9811; linked administrative data: 10 682) enrolled in the HCH 1 October 2017 - 30 June 2019; comparison groups of patients receiving usual care (1:1 propensity score-matched). INTERVENTION: Participants were involved in shared care planning, provided enhanced access to team care, and encouraged to seek chronic condition care at the HCH practice where they were enrolled. Participating practices received bundled payments based on clinical risk tier. MAIN OUTCOME MEASURES: Access to care, processes of care, diabetes-related outcomes, hospital service use, risk of death. RESULTS: During the first twelve months after enrolment, the mean numbers of general practitioner encounters (rate ratio, 1.14; 95% confidence interval [CI], 1.11-1.17) and Medicare Benefits Schedule claims for allied health services (rate ratio, 1.28; 95% CI, 1.24-1.33) were higher for the HCH than the usual care group. Annual influenza vaccinations (relative risk, 1.20; 95% CI, 1.17-1.22) and measurements of blood pressure (relative risk, 1.09; 95% CI, 1.08-1.11), blood lipids (relative risk, 1.19; 95% CI, 1.16-1.21), glycated haemoglobin (relative risk, 1.06; 95% CI, 1.03-1.08), and kidney function (relative risk, 1.13; 95% CI, 1.11-1.15) were more likely in the HCH than the usual care group during the twelve months after enrolment. Similar rate ratios and relative risks applied in the second year. The numbers of emergency department presentations (rate ratio, 1.09; 95% CI, 1.02-1.18) and emergency admissions (rate ratio, 1.13; 95% CI, 1.04-1.22) were higher for the HCH group during the first year; other differences in hospital use were not statistically significant. Differences in glycaemic and blood pressure control in people with diabetes in the second year were not statistically significant. By 30 June 2021, 689 people in the HCH group (6.5%) and 646 in the usual care group (6.1%) had died (hazard ratio, 1.07; 95% CI, 0.96-1.20). CONCLUSIONS: The HCH program was associated with greater access to care and improved processes of care for people with chronic diseases, but not changes in diabetes-related outcomes, most measures of hospital use, or risk of death.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Transcriptomic analysis reveals myometrial topologically associated domains linked to the onset of human term labour.

Changes in cell phenotype are thought to occur through the expression of groups of co-regulated genes within topologically associated domains (TADs). In this paper, we allocate genes expressed within the myometrium of the human uterus during the onset of term labour into TADs. Transformation of the myometrial cells of the uterus into a contractile phenotype during term human labour is the result of a complex interaction of different epigenomic and genomic layers. Recent work suggests that the transcription factor (TF) RELA lies at the top of this regulatory network. Using deep RNA sequencing (RNAseq) analysis of myometrial samples (n = 16) obtained at term from women undergoing caesarean section prior to or after the onset of labour, we have identified evidence for how other gene expression regulatory elements interact with TFs in the labour phenotype transition. Gene set enrichment analysis of our RNAseq data identified three modules of enriched genes (M1, M2 and M3), which in gene ontology studies are linked to matrix degradation, smooth muscle and immune gene signatures, respectively. These genes were predominantly located within chromosomal TADs suggesting co-regulation of expression. Our transcriptomic analysis also identified significant differences in the expression of long non-coding RNAs (lncRNA), microRNAs (miRNA) and TFs that were predicted to target genes within the TADs. Additionally, network analysis revealed 15 new lncRNA (MCM3AP-AS1, TUG1, MIR29B2CHG, HCG18, LINC00963, KCNQ1OT1, NEAT1, HELLPAR, SNHG16, NUTM2B-AS1, MALAT1, PSMA3-AS1, GABPB1-AS1, NORAD and NKILA) and 4 miRNA (mir-145, mir-223, mir-let-7a and mir-132) as top gene hubs with three TFs (NFKB1, RELA and ESR1) as master regulators. Together, these factors are likely to be involved in co-regulatory networks driving a myometrial transformation to generate an estrogen-sensitive phenotype. We conclude that lncRNA and miRNA targeting the estrogen receptor 1 and nuclear factor kappa B pathways play a key role in the initiation of human labour. For the first time, we perform an integrative analysis to present a multi-level genomic signature made of mRNA, non-coding RNA and TFs in the myometrium for spontaneous term labour.

Does dietary fat cause a dose dependent glycemic response in youth with type 1 diabetes?

OBJECTIVE: To determine the glycemic impact of dietary fat alone consumed without prandial insulin in individuals with T1D. RESEARCH DESIGN AND METHODS: Thirty participants with T1D (aged 8-18 years) consumed a test drink with either 20 g glucose or 1, 13, 26, 39, 51 g of fat with negligible carbohydrate/protein on 6 consecutive evenings, in a randomized order without insulin. Continuous glucose monitoring was used to measure glucose levels for 8 h postprandially. Primary outcome was mean glycemic excursion at each 30 min interval for each test condition. Generalized linear mixed models with a random effect for people with diabetes were used to test for an increase in blood glucose excursion with increasing quantity of fat. RESULTS: Glycemic excursions after 20 g glucose were higher than after fat drinks over the first 2 h (p < 0.05). Glycemic excursion for the fat drinks demonstrated a dose response, statistically significant from 4 h (p = 0.026), such that increasing loads of fat caused a proportionally larger increase in glycemic excursion, remaining statistically significant until 8 h (p < 0.05). Overall, for every 10 g fat added to the drink, glucose concentrations rose by a mean of 0.28 mmol L-1 from 330 min (95% CI 0.15 to 0.39, p < 0.001). CONCLUSIONS: Fat ingested without other macronutrients increases glucose excursions from 4 to 8 h after ingestion, in a dose dependent manner. These observations may impact on insulin dosing for high-fat foods in individuals with T1D.

Do outcomes of cognitive-behaviour therapy for co-occurring alcohol misuse and depression differ for participants with symptoms of posttraumatic stress?

BACKGROUND: Although post-traumatic stress disorder (PTSD) often co-occurs with depression and alcohol use disorder (AUD), treatment settings may not screen for PTSD symptoms. AIMS: To explore the effects of PTSD symptoms in participants seeking treatment for depression and alcohol misuse by capitalising on the DAISI (Depression and Alcohol Integrated and Single focussed Interventions) project. METHODS: Participants (N = 220) with current depressive symptoms and alcohol misuse were recruited from the DAISI project, a randomised controlled trial with four treatment arms. PTSD symptoms were assessed at baseline by the Posttraumatic Stress Diagnostic Scale and again at the 3-month assessment. RESULTS: McNemars t-test assessed for changes in PTSD symptom severity and PTSD symptom clusters at the 3-month assessment. Repeated measures multivariate analysis of variance assessed for changes in PTSD symptoms, by DAISI treatment allocation. At the 3-month assessment, participants with PTSD reported significant reductions in PTSD symptoms (except intrusion) and a lower rate of PTSD, and responded better to integrated depression-alcohol misuse CBT than to the alcohol/depression single-focussed or brief interventions. CONCLUSION: Integrated depression and alcohol misuse CBT may be effective for PTSD symptoms, but intrusions may need to be addressed specifically.

Home ward bound: features of hospital in the home use by major Australian hospitals, 2011-2017.

OBJECTIVE: To describe uptake of hospital in the home (HIH) by major Australian hospitals and the characteristics of patients and their HIH admissions; to assess change in HIH admission numbers relative to total hospital activity. DESIGN: Descriptive, retrospective study of HIH activity, analysing previously collected census data for all multi-day hospital inpatient admissions to included hospitals during the period 1 January 2011 - 31 December 2017. SETTING, PARTICIPANTS: Nineteen principal referrer hospital members of the Health Roundtable in Australia. MAIN OUTCOME MEASURES: HIH admissions by diagnosis-related group (DRG); patient and admission characteristics. RESULTS: 80 167 of 2 185 421 admissions to the 19 hospitals included HIH care, or 3.7% (95% CI, 3.6-3.7%) of all admissions. Median length of stay for admissions including HIH (7.3 days; IQR, 3.1-14 days) was longer than that for those that did not (2.7 days; IQR, 1.6-5.1 days). For HIH admissions, the proportion of men was higher (54.4% v 45.9%), the proportion of patients who died in hospital was lower (0.3% v 1.4%), and re-admission within 28 days was less frequent (2.3% v 3.6%). The 50 DRGs with greatest HIH activity encompassed 65 811 HIH admissions (82.1%), or 8.4% (95% CI, 8.4-8.5%) of all admissions in these DRGs. HIH admission numbers grew more rapidly than non-HIH admissions, but the difference was not statistically significant. CONCLUSIONS: HIH care is most frequently provided to patients requiring hospital treatment related to infections, venous thromboembolism, or post-surgical care. Its use could be expanded in clinical areas where it is currently used, and extended to others where it is not. HIH activity is growing. It should be systematically monitored and reported to allow better overview of its use and outcomes.

Nurse-Initiated Acute Stroke Care in Emergency Departments: The Triage, Treatment, and Transfer Implementation Cluster Randomized Controlled Trial.

Background and Purpose- We aimed to evaluate the effectiveness of an intervention to improve triage, treatment, and transfer for patients with acute stroke admitted to the emergency department (ED). Methods- A pragmatic, blinded, multicenter, parallel group, cluster randomized controlled trial was conducted between July 2013 and September 2016 in 26 Australian EDs with stroke units and tPA (tissue-type plasminogen activator) protocols. Hospitals, stratified by state and tPA volume, were randomized 1:1 to intervention or usual care by an independent statistician. Eligible ED patients had acute stroke <48 hours from symptom onset and were admitted to the stroke unit via ED. Our nurse-initiated T3 intervention targeted (1) Triage to Australasian Triage Scale category 1 or 2; (2) Treatment: tPA eligibility screening and appropriate administration; clinical protocols for managing fever, hyperglycemia, and swallowing; (3) prompt (<4 hours) stroke unit Transfer. It was implemented using (1) workshops to identify barriers and solutions; (2) face-to-face, online, and written education; (3) national and local clinical opinion leaders; and (4) email, telephone, and site visit follow-up. Outcomes were assessed at the patient level. Primary outcome: 90-day death or dependency (modified Rankin Scale score of ≥2); secondary outcomes: functional dependency (Barthel Index ≥95), health status (Short Form [36] Health Survey), and ED quality of care (Australasian Triage Scale; monitoring and management of tPA, fever, hyperglycemia, swallowing; prompt transfer). Intention-to-treat analysis adjusted for preintervention outcomes and ED clustering. Patients, outcome assessors, and statisticians were masked to group allocation. Results- Twenty-six EDs (13 intervention and 13 control) recruited 2242 patients (645 preintervention and 1597 postintervention). There were no statistically significant differences at follow-up for 90-day modified Rankin Scale (intervention: n=400 [53.5%]; control n=266 [48.7%]; P=0.24) or secondary outcomes. Conclusions- This evidence-based, theory-informed implementation trial, previously effective in stroke units, did not change patient outcomes or clinician behavior in the complex ED environment. Implementation trials are warranted to evaluate alternative approaches for improving ED stroke care. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: ACTRN12614000939695.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

OBJECTIVE: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. DESIGN, SETTING: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. PARTICIPANTS: Patients aged 18 years or more admitted to hospital from EDs. INTERVENTION: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. MAIN OUTCOME MEASURE: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. RESULTS: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. CONCLUSION: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials.

BACKGROUND: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. METHODS: We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group. RESULTS: Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0-1: odds ratio, 1.77; 95% confidence interval, 0.89-3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0-1: odds ratio, 2.33; 95% confidence interval, 1.13-5.94; P=0.032) than those treated with alteplase. CONCLUSIONS: Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion-defined target mismatch. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926. URL: https://www.anzctr.org.au. Unique identifier: ACTRN12608000466347.

Reducing early career general practitioners' antibiotic prescribing for respiratory tract infections: a pragmatic prospective non-randomised controlled trial.

Background: Inappropriate antibiotic prescription and consequent antibacterial resistance is a major threat to healthcare. Objectives: To evaluate the efficacy of a multifaceted intervention in reducing early career general practitioners' (GPs') antibiotic prescribing for upper respiratory tract infections (URTIs) and acute bronchitis/bronchiolitis. Methods: A pragmatic non-randomized trial employing a non-equivalent control group design nested within an existing cohort study of GP registrars' (trainees') clinical practice. The intervention included access to online modules (covering the rationale of current clinical guidelines recommending non-prescription of antibiotics for URTI and bronchitis/bronchiolitis, and communication skills in management of acute bronchitis) followed by a face-to-face educational session. The intervention was delivered to registrars (and their supervisors) in two of Australia's seventeen regional GP training providers (RTPs). Three other RTPs were the control group. Outcomes were proportion of registrars' URTI consultations and bronchitis/bronchiolitis consultations prescribed antibiotics. Intention-to-treat analyses employed logistic regression within a Generalised Estimating Equation framework, adjusted for relevant independent variables. The predictors of interest were time; treatment group; and an interaction term for time-by-treatment group. The P value associated with an interaction term determined statistically significant differences in antibiotic prescribing. Results: Analyses include data of 217 intervention RTPs' and 311 control RTPs' registrars. There was no significant reduction in antibiotic prescribing for URTIs. For bronchitis/bronchiolitis, a significant reduction (interaction P value = 0.024) remained true for analysis adjusted for independent variables (P value = 0.040). The adjusted absolute reduction in prescribing was 15.8% (95% CI: 4.2%-27.5%). Conclusions: A multifaceted intervention reduced antibiotic prescribing for bronchitis/bronchiolitis but not URTIs.

Mortality Reduction for Fever, Hyperglycemia, and Swallowing Nurse-Initiated Stroke Intervention: QASC Trial (Quality in Acute Stroke Care) Follow-Up.

BACKGROUND AND PURPOSE: Implementation of nurse-initiated protocols to manage fever, hyperglycemia, and swallowing dysfunction decreased death and disability 90 days poststroke in the QASC trial (Quality in Acute Stroke Care) conducted in 19 Australian acute stroke units (2005-2010). We now examine long-term all-cause mortality. METHODS: Mortality was ascertained using Australia's National Death Index. Cox proportional hazards regression compared time to death adjusting for correlation within stroke units using the cluster sandwich (Huber-White estimator) method. Primary analyses included treatment group only unadjusted for covariates. Secondary analysis adjusted for age, sex, marital status, education, and stroke severity using multiple imputation for missing covariates. RESULTS: One thousand and seventy-six participants (intervention n=600; control n=476) were followed for a median of 4.1 years (minimum 0.3 to maximum 70 months), of whom 264 (24.5%) had died. Baseline demographic and clinical characteristics were generally well balanced by group. The QASC intervention group had improved long-term survival (>20%), but this was only statistically significant in adjusted analyses (unadjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.58-1.07; P=0.13; adjusted HR, 0.77; 95% CI, 0.59-0.99; P=0.045). Older age (75-84 years; HR, 4.9; 95% CI, 2.8-8.7; P<0.001) and increasing stroke severity (HR, 1.5; 95% CI, 1.3-1.9; P<0.001) were associated with increased mortality, while being married (HR, 0.70; 95% CI, 0.49-0.99; P=0.042) was associated with increased likelihood of survival. Cardiovascular disease (including stroke) was listed either as the primary or secondary cause of death in 80% (211/264) of all deaths. CONCLUSIONS: Our results demonstrate the potential long-term and sustained benefit of nurse-initiated multidisciplinary protocols for management of fever, hyperglycemia, and swallowing dysfunction. These protocols should be a routine part of acute stroke care. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000563369.

Too good to treat? ischemic stroke patients with small computed tomography perfusion lesions may not benefit from thrombolysis.

OBJECTIVE: Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regardless of thrombolysis administration. METHODS: We used a prospectively collected cohort of acute ischemic stroke patients being assessed for treatment with IV-alteplase, who had CTP before a treatment decision. Volumetric CTP was retrospectively analyded to identify patients with a small perfusion lesion (<15ml in volume). The primary analysis was excellent 3-month outcome in patients with a small perfusion lesion who were treated with alteplase compared to those who were not treated. RESULTS: Of 1526 patients, 366 had a perfusion lesion <15ml and were clinically eligible for alteplase (212 being treated and 154 not treated). Median acute National Institutes of Health Stroke Scale score was 8 in each group. Of the 366 patients with a small perfusion lesion, 227 (62%) were modified Rankin Scale (mRS) 0 to 1 at day 90. Alteplase-treated patients were less likely to achieve 90-day mRS 0 to 1 (57%) than untreated patients (69%; relative risk [RR] = 0.83; 95% confidence interval [CI], 0.71-0.97; p = 0.022) and did not have different rates of mRS 0 to 2 (72% treated patients vs 77% untreated; RR, 0.93; 95% CI, 0.82-1.95; p = 0.23). INTERPRETATION: This large observational cohort suggests that a portion of ischemic stroke patients clinically eligible for alteplase therapy with a small perfusion lesion have a good natural history and may not benefit from treatment. Ann Neurol 2016;80:286-293.

Perfusion computed tomography to assist decision making for stroke thrombolysis.

The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.

Attitudes to Alzheimer's disease testing of Australian general practice patients: a cross-sectional questionnaire-based study.

OBJECTIVE: In view of proposed screening for presymptomatic Alzheimer's disease (AD) with advanced imaging, and blood and cerebral spinal fluid analysis, we aimed to establish levels, and associations, of acceptance of AD testing modalities by general practice patients. METHODS: A cross-sectional questionnaire-based study of consecutive patients (aged 50 years and over) of general practices of an Australian practice-based research network was used. The questionnaire elicited demographic data and attitudes to screening for other diseases and included the screening acceptance domain of the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) instrument. This assesses receptivity to modalities of testing for AD: short questionnaire, blood test, cerebral imaging, and annual physician examination. Reflecting speculation of possible future AD diagnostic methods, an item regarding testing cerebral spinal fluid was also included. Associations of PRISM-PC scores were analyzed with multiple linear regression. RESULTS: Of 489 participants (response rate 87%), 66.2% would like to know if they had AD. Participants were more accepting of testing modalities that were noninvasive or familiar (questionnaire, physician's examination, and blood test) as opposed to cerebral imaging or lumbar puncture. Attitudes to AD testing are influenced by a positive attitude to disease screening in general. Patients with a self-perceived higher risk of AD were less accepting of testing, as were participants with an educational level of junior high school (10 school years) or less. CONCLUSIONS: This study demonstrates that a majority of patients would like to know if they have AD. Acceptability of testing modalities, however, varies. Noninvasive, familiar methods are more acceptable.

A pilot, multisite, randomized controlled trial of a self-directed coping skills training intervention for couples facing prostate cancer: accrual, retention, and data collection issues.

PURPOSE: To examine the acceptability of the methods used to evaluate Coping-Together, one of the first self-directed coping skill intervention for couples facing cancer, and to collect preliminary efficacy data. METHODS: Forty-two couples, randomized to a minimal ethical care (MEC) condition or to Coping-Together, completed a survey at baseline and 2 months after, a cost diary, and a process evaluation phone interview. RESULTS: One hundred seventy patients were referred to the study. However, 57 couples did not meet all eligibility criteria, and 51 refused study participation. On average, two to three couples were randomized per month, and on average it took 26 days to enrol a couple in the study. Two couples withdrew from MEC, none from Coping-Together. Only 44 % of the cost diaries were completed, and 55 % of patients and 60 % of partners found the surveys too long, and this despite the follow-up survey being five pages shorter than the baseline one. Trends in favor of Coping-Together were noted for both patients and their partners. CONCLUSIONS: This study identified the challenges of conducting dyadic research, and a number of suggestions were put forward for future studies, including to question whether distress screening was necessary and what kind of control group might be more appropriate in future studies.

Predictors of health-related quality of life in community-dwelling stroke survivors: a cohort study.

BACKGROUND: Impaired health-related quality of life (HRQoL) post stroke is common, though prevalence estimates vary considerably. Few longitudinal studies explore post-stroke patterns of HRQoL and factors contributing to their change over time. Accurately identifying HRQoL after stroke is essential to understanding the extent of stroke effects. OBJECTIVES: This study aimed to assess change in levels of, and identify independent predictors of, HRQoL over the first 12-months post-stroke. METHODS: Design. A prospective cohort study. SETTING AND PARTICIPANTS: Community-dwelling stroke survivors in metropolitan Newcastle, New South Wales (NSW), Australia. Consecutively recruited stroke patients (n = 134) participated in face-to-face interviews at baseline, 3, 6, 9 and 12 months. OUTCOME MEASURE: HRQoL (measured using the Assessment Quality-of-life).Independent measures. Physical and psycho-social functioning, including depression and anxiety (measured via Hospital Anxiety and Depression Scale), disability (Modified Rankin Scale), social support (Multi-dimensional Scale Perceived Social Support) and community participation (Adelaide Activities Profile). ANALYSES: A linear mixed model was used to establish the predictors of, change in HRQoL over time. RESULTS: On multivariable analysis, HRQOL did not change significantly with time post-stroke. Higher HRQoL scores were independently associated with higher baseline HRQoL (P = 0.03), younger age (P = 0.006), lower disability (P = 0.003), greater community participation (P ≤ 0.001) and no history of depression (P = 0.03). CONCLUSION: These results contribute to an understanding of HRQoL in the first year post-stroke. Community participation and stroke-related disability are potentially modifiable risk factors affecting post-stroke HRQoL. Interventions aimed at addressing participation and disability post-stroke should be developed and tested.

Dietary pattern transitions, and the associations with BMI, waist circumference, weight and hypertension in a 7-year follow-up among the older Chinese population: a longitudinal study.

BACKGROUND: Few studies explored the effects of nutritional changes on body mass index (BMI), weight (Wt), waist circumference (WC) and hypertension, especially for the older Chinese population. METHODS: By using China Health and Nutrition Survey 2004-2011 waves, a total of 6348 observations aged ≥ 60 were involved in the study. The number of participants dropped from 2197 in 2004, to 1763 in 2006, 1303 in 2009, and 1085 in 2011. Dietary information was obtained from participants using 24 hour-recall over three consecutive days. Height, Wt, WC, systolic and diastolic blood pressure were also measured in each survey year. The dietary pattern was derived by exploratory factor analysis using principal component analysis methods. Linear Mixed Models were used to investigate associations of dietary patterns with BMI, Wt and WC. Generalized Estimating Equation models were used to assess the associations between dietary patterns and hypertension. RESULTS: Over time, older people's diets were shifting towards a modern dietary pattern (high intake of dairy, fruit, cakes and fast food). Traditional and modern dietary patterns had distinct associations with BMI, Wt and WC. Participants with a diet in the highest quartile for traditional composition had a ß (difference in mean) of -0.23 (95 % CI: -0.44; -0.02) for BMI decrease, ß of -0.90 (95 % CI: -1.42; -0.37) for Wt decrease; and ß of -1.57 (95 % CI: -2.32; -0.83) for WC decrease. However, participants with a diet in the highest quartile for modern diet had a ß of 0.29 (95 % CI: 0.12; 0.47) for BMI increase; ß of 1.02 (95 % CI: 0.58; 1.46) for Wt increase; and ß of 1.44 (95 % CI: 0.78; 2.10) for Wt increase. No significant associations were found between dietary patterns and hypertension. CONCLUSIONS: We elucidate the associations between dietary pattern and change in BMI, Wt, WC and hypertension in a 7-year follow-up study. The strong association between favourable body composition and traditional diet, compared with an increase in BMI, WC and Wt with modern diet suggests that there is an urgent need to develop age-specific dietary guideline for older Chinese people.

Changing the Antibiotic Prescribing of general practice registrars: the ChAP study protocol for a prospective controlled study of a multimodal educational intervention.

BACKGROUND: Australian General Practitioners (GPs) are generous prescribers of antibiotics, prompting concerns including increasing antimicrobial resistance in the community. Recent data show that GPs in vocational training have prescribing patterns comparable with the high prescribing rate of their established GP supervisors. Evidence-based guidelines consistently advise that antibiotics are not indicated for uncomplicated upper respiratory tract infections (URTI) and are rarely indicated for acute bronchitis. A number of interventions have been trialled to promote rational antibiotic prescribing by established GPs (with variable effectiveness), but the impact of such interventions in a training setting is unclear. We hypothesise that intervening while early-career GPs are still developing their practice patterns and prescribing habits will result in better adherence to evidence-based guidelines as manifested by lower antibiotic prescribing rates for URTIs and acute bronchitis. METHODS/DESIGN: The intervention consists of two online modules, a face-to-face workshop for GP trainees, a face-to-face workshop for their supervisors and encouragement for the trainee-supervisor dyad to include a case-based discussion of evidence-based antibiotic prescribing in their weekly one-on-one teaching meetings. We will use a non-randomised, non-equivalent control group design to assess the impact on antibiotic prescribing for acute upper respiratory infections and acute bronchitis by GP trainees in vocational training. DISCUSSION: Early-career GPs who are still developing their clinical practice and prescribing habits are an underutilized target-group for interventions to curb the growth of antimicrobial resistance in the community. Interventions that are embedded into existing training programs or are linked to continuing professional development have potential to increase the impact of existing interventions at limited additional cost. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614001209684 (registered 17/11/2014).

A Home- and Community-Based Physical Activity Program Can Improve the Cardiorespiratory Fitness and Walking Capacity of Stroke Survivors.

BACKGROUND: The cardiorespiratory fitness of stroke survivors is low. Center-based exercise programs that include an aerobic component have been shown to improve poststroke cardiorespiratory fitness. This pilot study aims to determine the feasibility, safety, and preliminary efficacy of an individually tailored home- and community-based exercise program to improve cardiorespiratory fitness and walking capacity in stroke survivors. METHODS: Independently ambulant, community-dwelling stroke survivors were recruited. The control (n = 10) and intervention (n = 10) groups both received usual care. In addition the intervention group undertook a 12-week, individually tailored, home- and community-based exercise program, including once-weekly telephone or e-mail support. Assessments were conducted at baseline and at 12 weeks. Feasibility was determined by retention and program participation, and safety by adverse events. Efficacy measures included change in cardiorespiratory fitness (peak oxygen consumption [VO2peak]) and distance walked during the Six-Minute Walk Test (6MWT). Analysis of covariance was used for data analysis. RESULTS: All participants completed the study with no adverse events. All intervention participants reported undertaking their prescribed program. VO2peak improved more in the intervention group (1.17 ± .29 L/min to 1.35 ± .33 L/min) than the control group (1.24 ± .23 L/min to 1.24 ± .33 L/min, between-group difference = .18 L/min, 95% confidence interval [CI]: .01-.36). Distance walked improved more in the intervention group (427 ± 123 m to 494 ± 67m) compared to the control group (456 ± 101m to 470 ± 106m, between-group difference = 45 m, 95% CI: .3-90). CONCLUSIONS: Our individually tailored approach with once-weekly telephone or e-mail support was feasible and effective in selected stroke survivors. The 16% greater improvement in VO2peak during the 6MWT achieved in the intervention versus control group is comparable to improvements attained in supervised, center-based programs.

A randomized trial of tenecteplase versus alteplase for acute ischemic stroke.

BACKGROUND: Intravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent. METHODS: In this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale on which higher scores indicate more severe neurologic deficits). RESULTS: The three treatment groups each comprised 25 patients. The mean (±SD) NIHSS score at baseline for all patients was 14.4±2.6, and the time to treatment was 2.9±0.8 hours. Together, the two tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P<0.001) at 24 hours than the alteplase group. There were no significant between-group differences in intracranial bleeding or other serious adverse events. The higher dose of tenecteplase (0.25 mg per kilogram) was superior to the lower dose and to alteplase for all efficacy outcomes, including absence of serious disability at 90 days (in 72% of patients, vs. 40% with alteplase; P=0.02). CONCLUSIONS: Tenecteplase was associated with significantly better reperfusion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging. (Funded by the Australian National Health and Medical Research Council; Australia New Zealand Clinical Trials Registry number, ACTRN12608000466347.).