Salivary Cortisol Response to ACTH Stimulation Is a Reliable Alternative to Serum Cortisol in Evaluating Hypoadrenalism.

CONTEXT: The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected by changes in cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. OBJECTIVES: (1) To establish the salivary cortisol response to ACTH stimulation in healthy volunteers and patients with altered CBG concentrations; (2) to evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism (SH-patients). DESIGN: A 250 µg ACTH stimulation test was undertaken in 139 healthy volunteers, 24 women taking an estradiol-containing oral contraceptive pill (OCP-females), 10 patients with low serum protein concentration (LP-patients), and 30 SH-patients. Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. Mean and LRL of the 30-minute salivary cortisol response (mean-1.96 standard deviation) were derived from log-transformed concentrations. The LRL was applied as a diagnostic cut-off in SH-patients, with comparison to the serum response. RESULTS: Mean CBG concentrations (range) were 58 (42-81) mg/L, 64 (43-95) mg/L, 41 (28-60) mg/L, and 116 (84-159) mg/L in males, females, LP-patients, and OCP-females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 (2.5th-97.5th percentile 10.3-36.2) nmol/L in healthy volunteers. Corresponding values were not different in OCP-females [19.7 (9.5-41.2) nmol/L; P = .59] or LP-patients [19.0 (7.7-46.9) nmol/L; P = .97]. Overall diagnostic agreement between salivary and serum responses in SH-patients was 79%. CONCLUSION: Salivary cortisol response to ACTH stimulation offers a reliable alternative to serum and may be especially useful in conditions of altered CBG concentration.

Radiomic analysis in contrast-enhanced mammography using a multivendor data set: accuracy of models according to segmentation techniques.

OBJECTIVE: Radiomic analysis of contrast-enhanced mammographic (CEM) images is an emerging field. The aims of this study were to build classification models to distinguish benign and malignant lesions using a multivendor data set and compare segmentation techniques. METHODS: CEM images were acquired using Hologic and GE equipment. Textural features were extracted using MaZda analysis software. Lesions were segmented with freehand region of interest (ROI) and ellipsoid_ROI. Benign/Malignant classification models were built using extracted textural features. Subset analysis according to ROI and mammographic view was performed. RESULTS: 269 enhancing mass lesions (238 patients) were included. Oversampling mitigated benign/malignant imbalance. Diagnostic accuracy of all models was high (>0.9). Segmentation with ellipsoid_ROI produced a more accurate model than with FH_ROI, accuracy:0.947 vs 0.914, AUC:0.974 vs 0.86, p < 0.05. Regarding mammographic view all models were highly accurate (0.947-0.955) with no difference in AUC (0.985-0.987). The CC-view model had the greatest specificity:0.962, the MLO-view and CC + MLO view models had higher sensitivity:0.954, p < 0.05. CONCLUSIONS: Accurate radiomics models can be built using a real-life multivendor data set segmentation with ellipsoid-ROI produces the highest level of accuracy. The marginal increase in accuracy using both mammographic views, may not justify the increased workload. ADVANCES IN KNOWLEDGE: Radiomic modelling can be successfully applied to a multivendor CEM data set, ellipsoid_ROI is an accurate segmentation technique and it may be unnecessary to segment both CEM views. These results will help further developments aimed at producing a widely accessible radiomics model for clinical use.

Spatial representation by ramping activity of neurons in the retrohippocampal cortex.

Neurons in the retrohippocampal cortices play crucial roles in spatial memory. Many retrohippocampal neurons have firing fields that are selectively active at specific locations, with memory for rewarded locations associated with reorganization of these firing fields. Whether this is the sole strategy for representing spatial memories is unclear. Here, we demonstrate that during a spatial memory task retrohippocampal neurons encode location through ramping activity that extends across segments of a linear track approaching and following a reward, with the rewarded location represented by offsets or switches in the slope of the ramping activity. Ramping representations could be maintained independently of trial outcome and cues marking the reward location, indicating that they result from recall of the track structure. When recorded in an open arena, neurons that generated ramping activity during the spatial memory task were more numerous than grid or border cells, with a majority showing spatial firing that did not meet criteria for classification as grid or border representations. Encoding of rewarded locations through offsets and switches in the slope of ramping activity also emerged in recurrent neural network models trained to solve a similar spatial memory task. Impaired performance of model networks following disruption of outputs from ramping neurons is consistent with this coding strategy supporting navigation to recalled locations of behavioral significance. Our results suggest that encoding of learned spaces by retrohippocampal networks employs both discrete firing fields and continuous ramping representations. We hypothesize that retrohippocampal ramping activity mediates readout of learned models for goal-directed navigation.

The geographic distribution of private health insurance in Australia in 2001.

BACKGROUND: Private health insurance has been a major focus of Commonwealth Government health policy for the last decade. Over this period, the Howard government introduced a number of policy changes which impacted on the take up of private health insurance. The most expensive of these was the introduction of the private health insurance rebate in 1997, which had an estimated cost of $3 billion per annum. METHODS: This article uses information on the geographic distribution of the population with private health insurance cover to identify associations between rates of private health insurance cover and socioeconomic status. The geographic analysis is repeated with survey data on expenditure on private health insurance, to provide an estimate of the rebate flowing to different socioeconomic groups. RESULTS: The analysis highlights the strong association between high rates of private health insurance cover and high socioeconomic status and shows the substantial transfer of funds, under the private health insurance rebate, to those living in areas of highest socioeconomic status, compared with those in areas of lower socioeconomic status, and in particular those in the most disadvantaged areas. The article also provides estimates of private health insurance cover by federal electorate, emphasising the substantial gaps in cover between Liberal Party and Australian Labor Party seats. CONCLUSION: The article concludes by discussing implications of the uneven distribution of private health insurance cover across Australia for policy formation. In particular, the study shows that the prevalence of private health insurance is unevenly distributed across Australia, with marked differences in prevalence in rural and urban areas, and substantial differences by socioeconomic status. Policy formation needs to take this into account. Evaluating the potential impact of changes in private health insurance requires more nuanced consideration than has been implied in the rhetoric about private health insurance over the last decade.

Stellate Cells in the Medial Entorhinal Cortex Are Required for Spatial Learning.

Spatial learning requires estimates of location that may be obtained by path integration or from positional cues. Grid and other spatial firing patterns of neurons in the superficial medial entorhinal cortex (MEC) suggest roles in behavioral estimation of location. However, distinguishing the contributions of path integration and cue-based signals to spatial behaviors is challenging, and the roles of identified MEC neurons are unclear. We use virtual reality to dissociate linear path integration from other strategies for behavioral estimation of location. We find that mice learn to path integrate using motor-related self-motion signals, with accuracy that decreases steeply as a function of distance. We show that inactivation of stellate cells in superficial MEC impairs spatial learning in virtual reality and in a real world object location recognition task. Our results quantify contributions of path integration to behavior and corroborate key predictions of models in which stellate cells contribute to location estimation.

Serum thyroglobulin in the monitoring of differentiated thyroid cancer.

Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement. The limitations of Tg immunoassay are well described and include potential interference from TgAb. For the majority of patients with DTC who are TgAb-negative, Tg measurement remains the most useful method of follow-up. For the TgAb-positive minority, interference and the possibility of producing erroneous results is a concern. Some assays are less badly affected than others and laboratories are advised to choose their assays carefully. Laboratories have sought to identify interferences using measurement of TgAb, lack of concordance between RIAs and immunometric assays and recovery of added Tg. More recently LC-MSMS assays to quantify Tg have been developed. They are not currently as sensitive as Tg immunoassays and it is likely these assays will, like immunoassays, be limited by Tg heterogeneity and standardization issues, although initial evaluations indicate that they may have value in the clinical setting as a second line test in antibody-positive DTC patients in whom Tg is unmeasurable by immunoassay.

Accuracy of GE digital breast tomosynthesis vs supplementary mammographic views for diagnosis of screen-detected soft-tissue breast lesions.

OBJECTIVE: To compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment of soft-tissue mammographic abnormalities. METHODS: Women recalled for further assessment of soft-tissue abnormalities were recruited and received standard supplementary views (typically spot compression views) and two-view GE DBT. The added value of DBT in the assessment process was determined by analysing data collected prospectively by radiologists working up the cases. Following anonymization of cases, there was also a retrospective multireader review. The readers first read bilateral standard two-view digital mammography (DM) together with the supplementary mammographic views and gave a combined score for suspicion of malignancy on a five-point scale. The same readers then read bilateral standard two-view DM together with two-view DBT. Pathology data were obtained. Differences were assessed using receiver operating characteristic analysis. RESULTS: The study population was 342 lesions in 322 patients. The final diagnosis was malignant in 113 cases (33%) and benign/normal in 229 cases (67%). In the prospective analysis, the performance of two-view DM plus DBT was at least equivalent to the performance of two-view DM and standard mammographic supplementary views-the area under the curve (AUC) was 0.946 and 0.922, respectively, which did not reach statistical significance. Similar results were obtained for the retrospective review-AUC was 0.900 (DBT) and 0.873 (supplementary views), which did not reach statistical significance. CONCLUSION: The accuracy of GE DBT in the assessment of screen detected soft-tissue abnormalities is equivalent to the use of standard supplementary mammographic views. ADVANCES IN KNOWLEDGE: The vast majority of evidence relating to the use of DBT has been gathered from research using Hologic equipment. This study provides evidence for the use of the commercially available GE DBT system demonstrating that it is at least equivalent to supplementary mammographic views in the assessment of soft-tissue screen-detected abnormalities.

Thyroglobulin in differentiated thyroid cancer.

Identification of differentiated thyroid cancer (DTC) is becoming increasingly common. Patients usually have an excellent prognosis. Most undergo total thyroidectomy, radioiodine ablation and treatment with suppressive doses of levothyroxine. Patients require long term follow-up which includes measurement of serum thyroglobulin (Tg). Interpretation of serum Tg requires knowledge of the concurrent thyroid stimulating hormone (TSH) concentration, as secretion is TSH dependant, and an awareness of the limitations of the methods used to measure it. These limitations include the heterogeneity of Tg in serum, the ability of assays to recognise forms of Tg secreted by a tumour, assay biases and not least the potential for interference in immunoassays for Tg from endogenous thyroglobulin antibodies (TgAbs) in patient serum. This review considers what the clinician wants to know and how Tg results can be interpreted in light of an awareness of assay limitations.

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy.

Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal ß-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of ß-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.

Adherence among rural HIV-infected patients in the deep south: a comparison between single-tablet and multi-tablet once-daily regimens.

BACKGROUND: Once-daily (QD), combination antiretroviral therapy (ART) can impact the willingness and ability of patients to take medications as directed. The impact of antiretroviral (ARV) drug adherence influenced by single-tablet (STR) versus multi-tablet regimens (MTR) among patients enrolled in the AIDS Drug Assistance Program (ADAP) in a rural environment has not yet been assessed. MATERIAL AND METHODS: A retrospective chart review evaluated adherence and outcomes in adult HIV-infected patients enrolled in the ADAP at 2 ambulatory clinics in the Southeast, taking either a QD STR (efavirenz [EFV]/emtricitabine/tenofovir [TDF]) or a QD protease inhibitor (PI)-based, MTR (atazanavir [ATV], ritonavir [RTV], and emtricitabine/TDF) by evaluating pharmacy refill records, patient self-reported adherence, and virologic response. RESULTS: A total of 389 patient records were analyzed (STR, n = 165 versus MTR, n = 224). There were more males, a higher percentage of treatment-naive patients, and more patients with a baseline CD4 count of >200 cells/mm(3) in the MTR group. Based on refill records, more patients on MTR were >90% adherent (61.6% versus 51.5%, P = .047). In a multivariable analysis, being treatment experienced was a negative predictor (odds ratio [OR] = 0.48, 0.29-0.78) for adherence. Regimen choice was not associated with adherence. More patients taking MTR were virologically suppressed at the end of the observation period. Regardless of the regimen, being >90% adherent was a significant predictor of virologic suppression (OR = 3.51, 1.98-6.23). CONCLUSION: Treatment-experienced patients enrolled in ADAP are less likely to be adherent. A QD PI-based MTR may result in comparable adherence to an STR in a rural HIV-infected population.

Unpacking analyses relying on area-based data: are the assumptions supportable?

BACKGROUND: In the absence in the major Australian administrative health record collections of a direct measure of the socioeconomic status of the individual about whom the event is recorded, analysis of the association between the health status, use of health services and socioeconomic status of the population relies an area-based measure of socioeconomic status.This paper explores the reliability of the area of address (at the levels typically available in administrative data collections) as a proxy measure for socioeconomic disadvantage. The Western Australian Data Linkage System was used to show the extent to which hospital inpatient separation rates for residents of Perth vary by socioeconomic status of area of residence, when calculated at various levels of aggregation of area, from smallest (Census Collection District) to largest (postcode areas and Statistical Local Areas). Results are also provided of the reliability, over time, of the address as a measure of socioeconomic status. RESULTS: There is a strong association between the socioeconomic status of the usual address of hospital inpatients at the smallest level in Perth, and weaker associations when the data are aggregated to larger areas. The analysis also shows that a higher proportion of people from the most disadvantaged areas are admitted to hospital than from the most well-off areas (13% more), and that these areas have more separations overall (47% more), as a result of larger numbers of multiple admissions.Of people admitted to hospital more than once in a five year period, four out of five had not moved address by the time of their second episode. Of those who moved, the most movement was within, or between, areas of similar socioeconomic status, with people from the most well off areas being the least likely to have moved. CONCLUSION: Postcode level and SLA level data provide a reliable, although understated, indication of socioeconomic disadvantage of area. The majority of Perth residents admitted to hospital in Western Australia had the same address when admitted again within five years. Of those who moved address, the majority had moved within, or between, areas of similar socioeconomic status.Access to data about individuals from the Western Australian Data Linkage System shows that more people from disadvantaged areas are admitted to a hospital, and that they have more episodes of hospitalisation. Were data to be available across Australia on a similar basis, it would be possible to undertake research of greater policy-relevance than is currently possible with the existing separations-based national database.

The socioeconomic gradient and chronic illness and associated risk factors in Australia.

OBJECTIVE: To examine the prevalence of major chronic diseases and their risk factors in different socioeconomic groups in the Australian population, in order to highlight the need for public policy initiatives to reduce socioeconomic inequalities in health. METHODS: Data were provided by the Australian Bureau of Statistics (ABS) from the 2001 National Health Survey (NHS) for selected chronic diseases and associated risk factors. Conditions selected were those, which form the National Health Priority Area (NHPA) conditions (other than injury, which has not been included in this paper, with its focus on chronic disease); plus other 'serious' chronic conditions, in line with the classification developed by Mathers; and for which sufficient cases were available for analysis by socioeconomic status. Indirectly age-standardised prevalence rates were calculated by broad age group for Australia and for five groups of socioeconomic status; rate ratios were calculated to show variations in prevalence between these groups. RESULTS: Significant socioeconomic inequalities were evident for many of the major chronic diseases; the largest was for diabetes mellitus (at ages 25 to 64 years); and for many diseases, there was also a strong, continuous socioeconomic gradient in the rates.Circulatory system diseases (in particular, hypertensive disease) and digestive system diseases also exhibited a strong differential in the 25 to 64 year age group.In the 65 years and over age group, the strongest inequalities were evident for mental and behavioural problems, diabetes (with a continuous socioeconomic gradient in rates) and respiratory system diseases.A number of risk factors for chronic diseases, namely self-reported smoking, alcohol misuse, physical inactivity and excess weight showed a striking association with socioeconomic status, in particular for people who were smokers and those who did not exercise. CONCLUSION: This analysis shows that the prevalence of chronic disease varies across the socioeconomic gradient for a number of specific diseases, as well as for important disease risk factors. Therefore, any policy interventions to address the impact of chronic disease, at a population level, need to take into account these socioeconomic inequalities.

Minimum qualifications for clinical pharmacy practice faculty.

The American College of Clinical Pharmacy 2013 Educational Affairs Committee was charged with developing recommendations for the minimum qualifications required for clinical pharmacy practice faculty in United States colleges and schools of pharmacy with respect to education, postgraduate training, board certification, and other experiences. From a review of the literature, the committee recommends that clinical pharmacy practice faculty possess the following minimum qualifications, noting that, for some positions, additional qualifications may be necessary. Clinical pharmacy practice faculty should possess the Doctor of Pharmacy degree from an Accreditation Council for Pharmacy Education­accredited institution. In addition, faculty should have completed a postgraduate year one (PGY1) residency or possess at least 3 years of direct patient care experience. Faculty who practice in identified areas of pharmacotherapy specialization, as identified by American Society of Health-System Pharmacists postgraduate year two (PGY2) residency guidelines, should have completed a PGY2 residency in that area of specialty practice. Alternatively, faculty should have completed a minimum of a PGY1 residency and 1 additional year of practice, with at least 50% of time spent in their area of specialization, which is documented in a portfolio, or 4 years of direct patient care in their area of specialization, which is documented in a portfolio. Fellowship training or a graduate degree (e.g., Ph.D.) should be required for research-intensive clinical faculty positions. All faculty should obtain structured teaching experience during or after postgraduate training, preferably through a formal teaching certificate program or through activities documented in a teaching portfolio. A baseline record of scholarship should be obtained before hire as clinical pharmacy practice faculty through exposure in postgraduate programs or previous employment. Faculty should be board certified before hire or attain board certification within 2 years of hire through the Board of Pharmacy Specialties (BPS) or, if appropriate for the practice area, through a nonBPS-certifying agency. If no certification exists in the area of specialty, the faculty member should develop a portfolio with evidence of excellence in clinical practice, teaching, and scholarship.

Intussusception mimicking rectal prolapse.

We report a 10-week-old boy with a prolapsing colocolic intussusception mimicking rectal prolapse. Rectal prolapse of ileocolic intussusception has been well-described, but colocolic intussusception presenting as rectal prolapse is unique.

A comparison of the cycling performance of cyclists and triathletes.

The aim of this study was to compare the cycling performance of cyclists and triathletes. Each week for 3 weeks, and on different days, 25 highly trained male cyclists and 18 highly trained male triathletes performed: (1) an incremental exercise test on a cycle ergometer for the determination of peak oxygen consumption (VO2peak), peak power output and the first and second ventilatory thresholds, followed 15 min later by a sprint to volitional fatigue at 150% of peak power output; (2) a cycle to exhaustion test at the VO2peak power output; and (3) a 40-km cycle time-trial. There were no differences in VO2peak, peak power output, time to volitional fatigue at 150% of peak power output or time to exhaustion at VO2peak power output between the two groups. However, the cyclists had a significantly faster time to complete the 40-km time-trial (56:18 +/- 2:31 min:s; mean +/- s) than the triathletes (58:57 +/- 3:06 min:s; P < 0.01), which could be partially explained (r = 0.34-0.51; P < 0.05) by a significantly higher first (3.32 +/- 0.36 vs 3.08 +/- 0.36 l x min(-1)) and second ventilatory threshold (4.05 +/- 0.36 vs 3.81 +/- 0.29 l x min(-1); both P < 0.05) in the cyclists compared with the triathletes. In conclusion, cyclists may be able to perform better than triathletes in cycling time-trial events because they have higher first and second ventilatory thresholds.