Restoring microvascular circulation with diagnostic ultrasound and contrast agent: Rationale and Design of the REDUCE trial.

OBJECTIVES: This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure. BACKGROUND: More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear. METHODS: The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of two treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for six months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total. CONCLUSIONS: This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.

The steadily growing problem of lentigo maligna and lentigo maligna melanoma in Australia: Population-based data on diagnosis and management.

BACKGROUND/OBJECTIVES: There are limited population-based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population. METHODS: Prospective collection of incidence and clinician-reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12-months in 2006-2007. RESULTS: The estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non-LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non-LM MIS (P = 0.001). CONCLUSIONS: In this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required.

Follow-Up Recommendations after Diagnosis of Primary Cutaneous Melanoma: A Population-Based Study in New South Wales, Australia.

BACKGROUND: Follow-up practices after diagnosis and treatment of primary cutaneous melanoma vary considerably. We aimed to determine factors associated with recommendations for follow-up setting, frequency, skin surveillance, and concordance with clinical guidelines. METHODS: The population-based Melanoma Patterns of Care study documented clinicians' recommendations for follow-up for 2148 patients diagnosed with primary cutaneous melanoma over a 12-month period (2006/2007) in New South Wales, Australia. Multivariate log binomial regression models adjusted for patient and lesion characteristics were used to examine factors associated with follow-up practices. RESULTS: Of 2158 melanomas, Breslow thickness was < 1 mm for 57% and ≥ 1 mm for 30%, while in situ melanomas accounted for 13%. Follow-up was recommended for 2063 patients (96%). On multivariate analysis, factors associated with a recommendation for follow-up at a specialist center were Breslow thickness ≥ 1 mm [prevalence ratio (PR) 1.05, 95% confidence interval (CI) 1.01-1.09] and initial treatment at a specialist center (PR 1.12, 95% CI 1.08-1.16). Longer follow-up intervals of > 3 months were more likely to be recommended for females, less likely for people living in rural compared with urban areas, and less likely for thicker (≥ 1 mm) melanomas compared with in situ melanomas. Skin self-examination was encouraged in 84% of consultations and was less likely to be recommended for patients ≥ 70 years (PR 0.88, 95% CI 0.84-0.93) and for those with thicker (≥ 1 mm) melanomas (PR 0.92, 95% CI 0.86-0.99). Only 1% of patients were referred for psychological care. CONCLUSIONS: Follow-up recommendations were generally consistent with Australian national guidelines for management of melanoma, however some variations could be targeted to improve patient outcomes.

Poor Adherence to National Clinical Management Guidelines: A Population-Based, Cross-Sectional Study of the Surgical Management of Melanoma in New South Wales, Australia.

BACKGROUND: Standardization of the clinical management of melanoma through the formulation of national guidelines, based on interpretation of the existing evidence and consensus expert opinion, seeks to improve quality of care; however, adherence to national guidelines has not been well studied. METHODS: A population-based, cross-sectional study of the clinical management of all patients with newly notified primary melanomas in the state of New South Wales, Australia, during 2006/2007 was conducted using cancer registry identification and questionnaires completed by treating physicians. RESULTS: Surgical margin guidelines were adhered to in 35% of cases; 45% were over treated and 21% were undertreated. Factors independently associated with non-concordance on multivariate analysis were lower Breslow thickness, lower socio-economic status of the physician's practice location, older physician age, lower physician caseload, and physicians who biopsied the lesion and then referred for definitive management. Complications were not related to over- or under-treatment on multivariate analysis (p = 0.72). Sentinel lymph node biopsy was performed in 17% of patients with invasive melanoma, with the main determinant for selection being a Breslow thickness >0.75 mm. CONCLUSIONS: The low level of concordance with national guidelines for surgical management of melanoma resulted in overtreatment of many patients. However, a fifth of patients were undertreated, which is likely to have resulted in increased locoregional recurrence rates. The better concordance achieved by physicians treating >30 melanomas per year suggests that a minimum caseload threshold for physicians treating melanoma patients would be desirable. High guideline concordance will ensure patients receive optimal care and minimize morbidity and health service costs.

Diagnosis and clinical management of melanoma patients at higher risk of a new primary melanoma: A population-based study in New South Wales, Australia.

BACKGROUND/OBJECTIVES: To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. METHODS: The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). RESULTS: Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. CONCLUSIONS: Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk.

A Systematic Review of Scaling Left Atrial Size: Are Alternative Indexation Methods Required for an Increasingly Obese Population?

BACKGROUND: Left atrial (LA) size indexed to body surface area (BSA) is a clinically important marker of cardiovascular prognosis. However, indexation using a scaling variable such as BSA has inherent flaws, particularly in an obese population. The aim of this study was to determine whether alternative indexation methods may more accurately scale for LA size. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to execute a structured search of medical databases, to identify articles discussing alternative methods of LA indexation in echocardiography. Articles that stratified indexed LA size by obesity class were also included. Two independent reviewers identified relevant articles and extracted baseline characteristics, alternative indexation methods, scaling variables, obesity class characteristics, and correlation coefficients. RESULTS: A total of 3,804 articles were found in the database search after removing duplicates. After abstract and full-text screening, 13 relevant articles were identified. Twelve studies used alternative methods of LA indexation, of which nine reported allometric indices. Seven of the included studies reported LA size by obesity class, of which six reported alternative indices. Correlation coefficients plotted for indexed LA size against absolute measured LA size showed that allometric indices (specifically to height) were more likely to maintain proportionality to body size compared with isometric indices such as BSA. Allometric indices were less likely to overcorrect for body size compared with isometric indices. CONCLUSIONS: Compared with isometric indexation to BSA, allometric indexation (specifically to height) improves scaling of LA volumes to maintain proportionality and avoid overcorrection for body size.

Association Between Melanoma Detected During Routine Skin Checks and Mortality.

IMPORTANCE: Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces mortality. OBJECTIVE: To assess melanoma-specific and all-cause mortality associated with melanomas detected through routine skin checks, incidentally or patient detected. A secondary aim was to examine patient, sociodemographic, and clinicopathologic factors associated with different modes of melanoma detection. DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, cohort study included patients in New South Wales, Australia, who were diagnosed with melanoma over 1 year from October 23, 2006, to October 22, 2007, in the Melanoma Patterns of Care Study and followed up until 2018 (mean [SD] length of follow-up, 11.9 [0.3] years) by using linked mortality and cancer registry data. All patients who had invasive melanomas recorded at the cancer registry were eligible for the study, but the number of in situ melanomas was capped. The treating doctors recorded details of melanoma detection and patient and clinical characteristics in a baseline questionnaire. Histopathologic variables were obtained from pathology reports. Of 3932 recorded melanomas, data were available and analyzed for 2452 (62%; 1 per patient) with primary in situ (n = 291) or invasive (n = 2161) cutaneous melanoma. Data were analyzed from March 2020 to January 2021. MAIN OUTCOMES AND MEASURES: Melanoma-specific mortality and all-cause mortality. RESULTS: A total of 2452 patients were included in the analyses. The median age at diagnosis was 65 years (range, 16-98 years), and 1502 patients (61%) were men. A total of 858 patients (35%) had their melanoma detected during a routine skin check, 1148 (47%) self-detected their melanoma, 293 (12%) had their melanoma discovered incidentally when checking another skin lesion, and 153 (6%) reported "other" presentation. Routine skin-check detection of invasive melanomas was associated with 59% lower melanoma-specific mortality (subhazard ratio, 0.41; 95% CI, 0.28-0.60; P < .001) and 36% lower all-cause mortality (hazard ratio, 0.64; 95% CI, 0.54-0.76; P < .001), adjusted for age and sex, compared with patient-detected melanomas. After adjusting for prognostic factors including ulceration and mitotic rate, the associations were 0.68 (95% CI, 0.44-1.03; P = .13), and 0.75 (95% CI, 0.63-0.90; P = .006), respectively. Factors associated with higher odds of routine skin-check melanoma detection included being male (female vs male, odds ratio [OR], 0.73; 95% CI, 0.60-0.89; P = .003), having previous melanoma (vs none, OR, 2.36; 95% CI, 1.77-3.15; P < .001), having many moles (vs not, OR, 1.39; 95% CI, 1.10-1.77; P = .02), being 50 years or older (eg, 50-59 years vs <40 years, OR, 2.89; 95% CI, 1.92-4.34; P < .001), and living in nonremote areas (eg, remote or very remote vs major cities, OR, 0.23; 95% CI, 0.05-1.04; P = .003). CONCLUSIONS AND RELEVANCE: In this cohort study, melanomas diagnosed through routine skin checks were associated with significantly lower all-cause mortality, but not melanoma-specific mortality, after adjustment for patient, sociodemographic, and clinicopathologic factors.

Quality of histopathological reporting on melanoma and influence of use of a synoptic template.

AIMS: To evaluate the quality of histopathological reporting for melanoma in a whole population, to assess the influence on quality of the use of a synoptic template and thus to provide an evidence base to guide improvement in reporting melanoma pathology. METHODS AND RESULTS: Histopathology reports of all primary invasive melanomas notified to the New South Wales Central Cancer Registry between October 2006 and October 2007 (n = 3784) were reviewed. A detailed audit of histopathology reports for consecutively diagnosed primary invasive melanoma over 6 months (n = 2082) was performed to assess the quality of each report based on compliance with the 2008 Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand. Only half of the initial excision specimen reports included the essential components necessary to stage a melanoma patient according to the 2002 American Joint Committee on Cancer/International Union Against Cancer melanoma staging system. Report format was strongly correlated with completeness and validity of reporting: reports in a synoptic format, with or without a descriptive component, achieved the highest quality levels. CONCLUSIONS: Even in a population with a high incidence of melanoma, concordance of pathology reports with current guidelines was comparatively low. Wider adoption of synoptic reporting is likely to increase report quality.

Validity of the Faces Anxiety Scale for the assessment of state anxiety in intensive care patients not receiving mechanical ventilation.

OBJECTIVES: Anxiety is a commonly reported discomfort in critically ill patients in the intensive care unit (ICU) but is rarely assessed routinely in a systematic manner. The main aim of this study was to assess criterion validity of the Faces Anxiety Scale in relation to the State-Anxiety Inventory (SAI) in intensive care patients able to respond verbally to the items in the SAI of the Spielberger State-Trait Anxiety Inventory. It also reports on the severity of anxiety in intensive care patients not receiving mechanical ventilation. METHODS: Nonventilated intensive care patients (n=100) self-reported anxiety levels on the Faces Anxiety Scale and on the SAI, administered in random order. Validity was examined using Spearman's rho. RESULTS: Patients had a mean age of 59.8 years and 65% were male; were in ICU for mainly cardiovascular, respiratory, and neurological diagnoses; and had median length of stay of 2.1 days. The correlation between the two scales was .70 (P<.0005), indicating good criterion validity. Patients reported low to moderate levels of anxiety on both the Faces Anxiety Scale and the Spielberger SAI. CONCLUSION: The Faces Anxiety Scale is a valid single-item, self-report measure of state anxiety in intensive care patients that is easy to administer and imposes minimal respondent burden. It has the potential to be a useful instrument for the assessment of state anxiety by clinicians and for research into the reduction of anxiety in this vulnerable population.

Clinical Features Associated With Individuals at Higher Risk of Melanoma: A Population-Based Study.

Importance: The identification of a subgroup at higher risk of melanoma may assist in early diagnosis. Objective: To characterize melanoma patients and the clinical features associated with their melanomas according to patient risk factors: many nevi, history of previous melanoma, and family history of melanoma, to assist with improving the identification and treatment of a higher-risk subgroup. Design, Setting, and Participants: The Melanoma Patterns of Care study was a population-based observational study of physicians' reported treatment of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 conducted in New South Wales. Our analysis of these data took place from 2015 to 2016. Main Outcomes and Measures: Age at diagnosis and body site of melanoma. Results: Of the 2727 patients with melanoma included, 1052 (39%) were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi. Compared with patients with melanoma who were at lower risk (ie, without any of these risk factors), the higher-risk group had a younger mean age at diagnosis (62 vs 65 years, P < .001), but this differed by risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P < .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57% vs 42%, P < .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P = .003). Conclusions and Relevance: These findings suggest that a person's risk factor status could be used to tailor surveillance programs and education about skin self-examination.

The health and social effects of drinking water-based infusions of kava: a review of the evidence.

ISSUES: To review the evidence on the health and social effects of drinking kava; a water-based infusion of the roots of the kava plant. APPROACH: Included all empirical studies of the effects of kava published 1987-2008 reporting health and social outcomes. Evidence appraised on study design (level of evidence) and standard epidemiological criteria for causality. KEY FINDINGS: Causality indicated: scaly skin rash, weight loss, raised Gamma Glutamyl Transpeptidase liver enzyme levels, nausea, loss of appetite or indigestion; Association indicated but causality unclear: red sore eyes, impotence or loss of sexual drive, self-reported poor health, raised cholesterol, and loss of time and money, low motivation and 'slow/lazy' days following use, reduced alcohol consumption and related violence; Association hypothesised: fits or seizures, Melioidosis, Ischaemic Heart Disease, protective effects for cancer; No association indicated: cognitive performance; No association suggested: cognitive impairment, liver toxicity or permanent liver damage, other pneumonia; No association hypothesised: hallucinations. IMPLICATIONS: The health and social implications of chronic kava drinking can be significant for individuals and communities, although most effects of even heavy consumption appear to be reversible when consumption is stopped. CONCLUSION: An Australia-wide ban on commercial importation of kava has been in place since mid-2007, but there is no published literature to date on the impact of the ban.

Principles of recruitment and retention in clinical trials.

Efficient and effective recruitment and retention of participants is the largest single component of the study workload and forms an essential component in the conduct of clinical trials. In this paper, we present five principles to guide the processes of both recruitment and retention. These principles include the selection of an appropriate population to adequately answer the research question, followed by the establishment of a sampling process that accurately represents that population. Creation of systematic and effective recruitment mechanisms should be supported by implementation of follow-up mechanisms that promote participant retention. Finally, all activities related to recruitment and retention must be conducted within the framework of ethics and privacy regulations. Adherence to these principles will assist the researcher in achieving the goals of the study within the available resources.