To test or to not test: A retrospective cross-sectional study on potentially inappropriate use of pathology testing in South Australian hospitals.

OBJECTIVES: To measure rates of potentially inappropriate pathology testing in the hospital setting. METHODS: Retrospective cross-sectional study in hospital setting from July 2021 to December 2021. We examined 3 potentially inappropriate uses: overordering, selection errors, and unnecessary repeat testing. Overordering included vitamin D and lipids (rarely required in acute hospital care). Selection error was the ratio of iron studies to standalone ferritin requests. Unnecessary repeats included any repeat vitamin D, lipids, iron, or ferritin in an episode of care or C-reactive protein (CRP) repeated within 3 days and N-terminal pro-brain natriuretic peptide (NT-proBNP) within 7 days and repeated previously abnormal CRP and NT-proBNP tests. Costs of inappropriate tests were estimated using the Australian Medicare Benefits Schedules. RESULTS: Among 55,904 test requests, 15% (n = 8120) were potentially inappropriate. Vitamin D was frequently ordered (n = 4498), as were lipids (n = 2872). Ratio of iron studies to standalone ferritin was 36. Of 19,233 repeat CRPs, 36% (n = 6947) were within 3 days and 62% (n = 179) of repeat NT-proBNPs were within 7 days of the first test. For initially abnormal tests, 89% of CRPs and 97% of NT-proBNPs remained abnormal. Inappropriate test costs accounted for 12% to 30% of costs. CONCLUSIONS: Frequent potential inappropriate use and selection of pathology tests was observed in South Australian hospitals.

Trends in surgery, hospital admissions and imaging for pituitary adenomas in Australia.

PURPOSE: There is a paucity of epidemiological information on treatment and imaging of pituitary adenomas in Australia. METHODS: Australian data on pituitary surgery, hospital admissions for pituitary adenomas, and pituitary imaging on patients 15 years and over were obtained from administrative databases between 2000/2001 and 2014/2015. Changes over time and by age and sex were assessed. RESULTS: In 2014/15 there were 37.7 pituitary procedures/million population, corresponding to a 35.4% (p < 0.05) increase over the 2000/2001 rate. Overall, most (87.2%) procedures were partial excisions of pituitary gland via transsphenoidal surgery (TSS). Admissions for acromegaly increased from 7.1/million in 2000/2001 to 17.2/million in 2003/2004 and then decreased to 6.5/million in 2014/2015. The average age-adjusted rate of pituitary imaging over the study period was 689.6/million/year, which increased significantly (p < 0.05). There was a significant increase in pituitary MRIs (p < 0.05) and a significant decline in pituitary CTs (p < 0.05). Surgical procedure rates were correlated with the pituitary imaging rates (r = 0.62, p < 0.05). CONCLUSION: Pituitary surgery rates increased between 2000/2001 and 2014/2015. The most common procedure was partial excision of the pituitary gland via TSS. Admissions for pituitary neoplasms increased over the study while admissions for acromegaly rose to their highest rate in 2003/2004 and then decreased. There was a substantial increase in the rate of pituitary imaging, which may have resulted in increased detection of pituitary incidentalomas. The underlying reasons for the increased rate of pituitary surgery, and the non-sustained increased rate of admissions for acromegaly are unclear and warrant further investigation.

Vasculogenic hyperprolactinemia: severe prolactin excess in association with internal carotid artery aneurysms.

PURPOSE: Internal carotid artery (ICA) aneurysms have rarely been found in association with marked hyperprolactinemia in the absence of prolactinoma; the cause of hyperprolactinemia has never been investigated. We aimed to determine if the observed hyperprolactinemia is due to a vascular-derived or known prolactin secretagogue from the injured ICA, analogous to pregnancy-associated hyperprolactinemia putatively due to placental factors. METHODS: We conducted a case series and literature review of individuals with severe hyperprolactinemia in association with ICA aneurysms. In two affected patients at our institutions, we performed RT-PCR and ELISA of prolactin secretagogues that are produced by vascular tissue and/or upregulated in pregnancy: AGT (encoding angiotensinogen), TAC1 (encoding substance P), HDC (encoding the enzyme responsible for conversion of histidine to histamine), and prolactin-releasing hormone (PRLH). Patient blood samples were compared to pregnancy blood samples (positive controls) and middle-aged male blood samples (negative controls). RESULTS: Two men presented with serum prolactin >100-fold normal associated with cavernous ICA aneurysms and no pituitary adenoma. Aneurysm stenting in one man more than halved his serum prolactin. In both men, dopamine agonist therapy markedly reduced serum prolactin. RT-PCR and ELISA showed no differences between patients and controls in AGT, TAC1 or HDC expression or PRLH titre, respectively. Literature review revealed 11 similar cases. CONCLUSIONS: We propose the term 'vasculogenic hyperprolactinemia' to encompass the hyperprolactinemia associated with ICA aneurysms. This may be mediated by an endothelial factor capable of paracrine stimulation of lactotrophs; however, angiotensin II, substance P, histamine and PRLH appear unlikely to be causative.

Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans.

Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol, in association with pyrexia. This accords with data indicating that CBG acts a thermocouple in vivo, increasing free cortisol levels independent of elastase-driven cleavage.

Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial.

UNLABELLED: Long-term opioid therapy has been associated with low cortisol levels due to central suppression of the hypothalamic-pituitary-adrenal axis. The implications of hypocortisolism on wellbeing have not been established. Our aim was to determine whether intervention with physiologic glucocorticoid replacement therapy improves wellbeing and analgesic responses in patients with chronic non-cancer pain on long-term opioid therapy with mild cortisol deficiency. We performed a pilot randomized, double-blind, placebo-controlled crossover study of oral hydrocortisone replacement therapy in 17 patients recruited from a Pain Clinic at a single tertiary center in Adelaide, Australia. Patients were receiving long-term opioid therapy (≥ 20 mg morphine equivalents per day for ≥ 4 weeks) for chronic non-cancer pain with mild hypocortisolism, as defined by a plasma cortisol response ≤ 350 nmol/L at 60 min following a cold pressor test. The crossover intervention included 28-day treatment with either 10mg/m(2)/day of oral hydrocortisone in three divided doses or placebo. Improvement in wellbeing was assessed using Version 2 of the Short Form-36 (SF-36v2), Brief Pain Inventory-Short Form, and Addison's disease quality of life questionnaires; improvement in analgesic response was assessed using cold pressor threshold and tolerance times. Following treatment with hydrocortisone, the bodily pain (P=0.042) and vitality (P=0.013) subscales of the SF-36v2 were significantly better than scores following treatment with placebo. There was also an improvement in pain interference on general activity (P=0.035), mood (P=0.03) and work (P=0.04) following hydrocortisone compared with placebo. This is the first randomized, double-blind placebo-controlled trial of glucocorticoid replacement in opioid users with chronic non-cancer pain and mild hypocortisolism. Our data suggest that physiologic hydrocortisone replacement produces improvements in vitality and pain experiences in this cohort compared with placebo. TRIAL REGISTRATION: Therapeutic Goods Administration Clinical Trials Notification Scheme (Drugs), Trial Number 2012/0476.

Incidence and outcomes of knee and hip joint replacement in veterans and civilians.

BACKGROUND: This article describes the incidence of total knee and hip replacement, and compares post-surgery health status outcomes in veterans and civilians. METHODS: The numbers of male veterans and civilians who had a knee and/or a hip replacement in South Australia (1994-2002) were obtained. Standardized morbidity ratios, and odds ratios for age group by veteran/civilian interactions, were calculated. Presurgery and 1-year post-surgery Medical Outcomes Short Form (36) Health Survey, Knee Society and Harris hip scores were completed. Independent samples t-tests were used to compare presurgery scores. ancova models were used to determine any differences between veterans and civilians post-surgery. RESULTS: For veterans, standardized morbidity ratios were 0.987 and 0.715 for knee and hip replacements, respectively (P < 0.0001). Veterans' odds ratios for knee and hip replacements were significantly lower in the 65- to 74-year age group (P < 0.001), similar in the 75- to 84-year and above 85-year age groups for hip replacement, but significantly higher in the above 85-year age group for knee replacement (P < 0.001). Presurgery, veterans reported significantly lower scores (P < 0.003) for knee function. After knee replacement, veterans reported significantly lower Medical Outcomes Short Form (36) Health Survey scores for bodily pain, physical functioning, role - physical, role--emotional, social functioning and physical component summary (P < 0.033). Significantly lower physical functioning, role--physical and physical component summary scores (P < 0.02) were reported by veterans post-surgery for hip replacement. CONCLUSION: Veterans are delaying joint replacement. Presurgical knee function is worse in veterans. Post-surgery, the veterans are worse off in a number of health status outcomes.

Measuring grip strength in normal adults: reference ranges and a comparison of electronic and hydraulic instruments.

PURPOSE: To determine reference ranges for peak, average, and final adult grip strength over 10 seconds by using an electronic dynamometer, and to compare results from hydraulic and electronic dynamometers. METHODS: The hand-grip strengths of 476 healthy adult subjects were tested using the electronic (Grippit; AB Detektor, Goteborg, Sweden) and hydraulic (Jamar; Smith and Nephew, Memphis, TN) dynamometers. RESULTS: Age- and gender-specific reference ranges for the Jamar and Grippit dynamometers are presented. Bland-Altman analysis of the differences between the results obtained using the 2 instruments revealed a bias (mean difference) of 22 N (Jamar - Grippit) and limits of agreement of -86 to 129 N (mean +/- 2 SD), which indicates that grip measurements may vary by up to 215 N between instruments. CONCLUSIONS: The study yielded population reference ranges of peak, average, and final strength over a 10-second grip assessment using an electronic dynamometer. Results from the Grippit and Jamar dynamometers are similar; however, the dynamometers cannot be interchanged. The Grippit provides information about endurance and fatigue of grip over 10 seconds, showing differences between right- and left-dominant adults.

Metacarpophalangeal arthroplasty from the patient's perspective.

The results of metacarpophalangeal (MCP) arthroplasty have been measured by objective measures and, to a lesser extent, subjective measures. The aim of this study was to understand patients' goals for MCP arthroplasty and the changes that occurred for them after surgery. Twenty of 24 patients reported that their MCP arthroplasty was successful because their function, pain, or hand appearance improved after the surgery. Functional changes related to how an activity was performed rather than new abilities being enabled by the surgery. There are many qualities to changes in pain and function, which closed-ended questions would not capture. Patients may not have attempted all normal activities within the first four postoperative months; therefore, functional outcomes must be measured after four months. Concurrent surgical, pharmaceutical, and therapy interventions also change patients' function, making the exact effects of the MCP arthroplasty unclear.

Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways.

Transforming growth factor (TGF)-beta promotes breast cancer metastasis to bone. To determine whether the osteolytic factor parathyroid hormone-related protein (PTHrP) is the primary mediator of the tumor response to TGF-beta, mice were inoculated with MDA-MB-231 breast cancer cells expressing a constitutively active TGF-beta type I receptor. Treatment of the mice with a PTHrP-neutralizing antibody greatly decreased osteolytic bone metastases. There were fewer osteoclasts and significantly decreased tumor area in the antibody-treated mice. TGF-beta can signal through both Smad and mitogen-activated protein (MAP) kinase pathways. Stable transfection of wild-type Smad2, Smad3, or Smad4 increased TGF-beta-stimulated PTHrP secretion, whereas dominant-negative Smad2, Smad3, or Smad4 only partially reduced TGF-beta-stimulated PTHrP secretion. When the cells were treated with a variety of protein kinases inhibitors, only specific inhibitors of the p38 MAP kinase pathway significantly reduced both basal and TGF-beta-stimulated PTHrP production. The combination of Smad dominant-negative blockade and p38 MAP kinase inhibition resulted in complete inhibition of TGF-beta-stimulated PTHrP production. Furthermore, TGF-beta treatment of MDA-MB-231 cells resulted in a rapid phosphorylation of p38 MAP kinase. Thus, the p38 MAP kinase pathway appears to be a major component of Smad-independent signaling by TGF-beta and may provide a new molecular target for anti-osteolytic therapy.