Utility of 30 and 60 minute cortisol samples after high-dose synthetic ACTH-1-24 injection in the diagnosis of adrenal insufficiency

BACKGROUND: In clinical practise the high dose ACTH stimulation test (HDT) is frequently used in the assessment of adrenal insufficiency (AI). However, there is uncertainty regarding optimal time-points and number of blood samplings. The present study compared the utility of a single cortisol value taken either 30 or 60 minutes after ACTH stimulation with the traditional interpretation of the HDT. METHODS: Retrospective analysis of 73 HDT performed at a single tertiary endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes after intravenous administration of 250 µg synthetic ACTH1-24. Adrenal insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l. RESULTS: There were twenty patients (27.4%) who showed an insufficient rise in serum cortisol using traditional HDT criteria and were diagnosed to suffer from AI. There were ten individuals who showed insufficient cortisol values after 30 minutes, rising to sufficient levels at 60 minutes. All patients revealing an insufficient cortisol response result after 60 minutes also had an insufficient result after 30 minutes. The cortisol value taken after 30 minutes did not add incremental diagnostic value in any of the cases under investigation compared with the 60 minutes' sample. CONCLUSIONS: Based on the findings of the present analysis the utility of a cortisol measurement 30 minutes after high dose ACTH injection was low and did not add incremental diagnostic value to a single measurement after 60 minutes.

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study

STUDY OBJECTIVE: The objective of this study was to investigate the impact of two different socioeconomic status (SES) measures on child and adolescent self reported health related quality of life (HRQoL). The European KIDSCREEN project aims at simultaneous developing, testing, and implementing a generic HRQoL instrument. DESIGN AND SETTING: The pilot version of the questionnaire was applied in school surveys to students from 8 to 18 years of age, as well as to their parents, together with such determinants of health status as two SES indicators, the parental educational status and the number of material goods in the family (FAS, family affluence scale). PARTICIPANTS: Students from seven European countries: 754 children (39.8%; mean: 9.8 years), and 1142 adolescents (60.2 %; mean: 14.1 years), as well as their respective parents. MAIN RESULTS: In children, a higher parental educational status was found to have a significant positive impact on the KIDSCREEN dimensions: physical wellbeing, psychological wellbeing, moods and emotions, bullying and perceived financial resources. Increased risk of low HRQoL was detected for adolescents in connection with their physical wellbeing. Family wealth plays a part for children's physical wellbeing, parent relations and home life, and perceived financial resources. For adolescents, family wealth furthermore predicts HRQoL on all KIDSCREEN dimensions. CONCLUSIONS: There is evidence to suggest that exposure to low parental educational status may result in a decreased HRQoL in childhood, whereas reduced access to material (and thereby social) resources may lead to a lower HRQoL especially in adolescence.

Sex differences in cryptogenic stroke with patent foramen ovale

BACKGROUND: Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. METHODS: One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. RESULTS: The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. CONCLUSION: Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.

Predictors of health care professionals' attitudes towards involvement in safety-relevant behaviours

BACKGROUND Patients can make valuable contributions towards promoting the safety of their health care. Health care professionals (HCPs) could play an important role in encouraging patient involvement in safety-relevant behaviours. However, to date factors that determine HCPs' attitudes towards patient participation in this area remain largely unexplored. OBJECTIVE To investigate predictors of HCPs' attitudes towards patient involvement in safety-relevant behaviours. DESIGN A 22-item cross-sectional fractional factorial survey that assessed HCPs' attitudes towards patient involvement in relation to two error scenarios relating to hand hygiene and medication safety. SETTING Four hospitals in London PARTICIPANTS   Two hundred sixteen HCPs (116 doctors; 100 nurses) aged between 21 and 60 years (mean: 32): 129 female. OUTCOME MEASURES Approval of patient's behaviour, HCP response to the patient, anticipated effects on the patient-HCP relationship, support for being asked as a HCP, affective rating response to the vignettes. RESULTS HCPs elicited more favourable attitudes towards patients intervening about a medication error than about hand sanitation. Across vignettes and error scenarios, the strongest predictors of attitudes were how the patient intervened and how the HCP responded to the patient's behaviour. With regard to HCP characteristics, doctors viewed patients intervening less favourably than nurses. CONCLUSIONS HCPs perceive patients intervening about a potential error less favourably if the patient's behaviour is confrontational in nature or if the HCP responds to the patient intervening in a discouraging manner. In particular, if a HCP responds negatively to the patient (irrespective of whether an error actually occurred), this is perceived as having negative effects on the HCP-patient relationship.

Optimal Workflow and Process-Based Performance Measures for Endovascular Therapy in Acute Ischemic Stroke: Analysis of the Solitaire FR Thrombectomy for Acute Revascularization Study.

BACKGROUND AND PURPOSE We report on workflow and process-based performance measures and their effect on clinical outcome in Solitaire FR Thrombectomy for Acute Revascularization (STAR), a multicenter, prospective, single-arm study of Solitaire FR thrombectomy in large vessel anterior circulation stroke patients. METHODS Two hundred two patients were enrolled across 14 centers in Europe, Canada, and Australia. The following time intervals were measured: stroke onset to hospital arrival, hospital arrival to baseline imaging, baseline imaging to groin puncture, groin puncture to first stent deployment, and first stent deployment to reperfusion. Effects of time of day, general anesthesia use, and multimodal imaging on workflow were evaluated. Patient characteristics and workflow processes associated with prolonged interval times and good clinical outcome (90-day modified Rankin score, 0-2) were analyzed. RESULTS Median times were onset of stroke to hospital arrival, 123 minutes (interquartile range, 163 minutes); hospital arrival to thrombolysis in cerebral infarction (TICI) 2b/3 or final digital subtraction angiography, 133 minutes (interquartile range, 99 minutes); and baseline imaging to groin puncture, 86 minutes (interquartile range, 24 minutes). Time from baseline imaging to puncture was prolonged in patients receiving intravenous tissue-type plasminogen activator (32-minute mean delay) and when magnetic resonance-based imaging at baseline was used (18-minute mean delay). Extracranial carotid disease delayed puncture to first stent deployment time on average by 25 minutes. For each 1-hour increase in stroke onset to final digital subtraction angiography (or TICI 2b/3) time, odds of good clinical outcome decreased by 38%. CONCLUSIONS Interval times in the STAR study reflect current intra-arterial therapy for patients with acute ischemic stroke. Improving workflow metrics can further improve clinical outcome. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT01327989.

Expectations and effects of a single yoga session on pain perception

BACKGROUND Several studies show yoga may benefit chronic pain management. We investigated the effect of a single yoga session on the perception of pain, measured by a standardized pain provocation test in healthy yoga participants while also comparing pain perception to participants' own expectations. MATERIALS AND METHODS Ninety yoga participants were recruited at hatha yoga schools in Switzerland. Pain perception was measured with a standardized algometric pain provocation test; i.e., a calibrated peg was applied for 10 seconds after which the participant rated pain intensity on a 0-10 numerical rating scale. The test was applied to the middle finger, ear lobe, and second toe before and after a 60-minute yoga session. RESULTS Sixty out of 90 (66.7%) yoga participants expected a reduced pain perception after the yoga session. However, 36 (40%) participants actually experienced less pain after compared to before the yoga session. But overall, pain perception statistically did not significantly change from before to after the yoga session at any of the three body locations assessed. The expectations and also the previous yoga experience did not significantly influence the participants' pain perception. CONCLUSIONS Regardless of the high positive expectations on the influence of yoga on pain, a single yoga session does not significantly influence pain perception induced by a pain provocation test. Hypoalgesic effects of yoga should be explained otherwise.

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Evaluation of the isoflurane-sparing effects of lidocaine infusion during umbilical surgery in calves

OBJECTIVE: To evaluate the isoflurane-sparing effects of lidocaine administered by constant rate infusion (CRI) during umbilical surgery in calves. STUDY DESIGN: Randomized 'blinded' prospective clinical study. ANIMALS: Thirty calves (mean 4.7 +/- SD 2.5 weeks old) undergoing umbilical surgery. METHODS: After premedication with xylazine (0.1 mg kg(-1) , IM), anaesthesia was induced with ketamine (4 mg kg(-1) , IV) and maintained with isoflurane in O(2) administered through a circle breathing system. The calves were assigned randomly to receive a bolus of 2 mg kg(-1) lidocaine IV after induction of anaesthesia, followed by CRI of 50 mug kg(-1) minute(-1) (group L, n=15) or a bolus and CRI of 0.9% sodium chloride (NaCl, group S, n=15). End-tidal isoflurane was adjusted to achieve adequate depth of anaesthesia. Heart rate, direct arterial blood pressure and body temperature were measured intraoperatively. Groups were compared by t- tests, anova or Mann-Whitney rank sum test as appropriate. RESULTS: The end-tidal concentration of isoflurane (median, IQR) was significantly lower in group L [1.0% (0.94-1.1)] compared to group S [1.2% (1.1-1.5)], indicating a 16.7% reduction in anaesthetic requirement during lidocaine CRI. Cardiopulmonary parameters and recovery times did not differ significantly between groups. CONCLUSION AND CLINICAL RELEVANCE: Lidocaine CRI may be used as a supplement to inhalation anaesthesia during umbilical surgery in calves in countries where such a protocol would be within the legal requirements for veterinary use in food animals. This study did not show any measurable benefit to the calves other than a reduction in isoflurane requirement.

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma

AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage.

Mean 20-year followup of Bernese periacetabular osteotomy

The goal of the Bernese periacetabular osteotomy is to correct the deficient acetabular coverage in hips with developmental dysplasia to prevent secondary osteoarthrosis. We determined the 20-year survivorship of symptomatic patients treated with this procedure, determined the clinical and radiographic outcomes of the surviving hips, and identified factors predicting poor outcome. We retrospectively evaluated the first 63 patients (75 hips) who underwent periacetabular osteotomy at the institution where this technique was developed. The mean age of the patients at surgery was 29 years (range, 13-56 years), and preoperatively 24% presented with advanced grades of osteoarthritis. Four patients (five hips) were lost to followup and one patient (two hips) died. The remaining 58 patients (68 hips) were followed for a minimum of 19 years (mean, 20.4 years; range, 19-23 years) and 41 hips (60%) were preserved at last followup. The overall mean Merle d'Aubigné and Postel score decreased in comparison to the 10-year value and was similar to the preoperative score. We observed no major changes in any of the radiographic parameters during the 20-year postoperative period except the osteoarthritis score. We identified six factors predicting poor outcome: age at surgery, preoperative Merle d'Aubigné and Postel score, positive anterior impingement test, limp, osteoarthrosis grade, and the postoperative extrusion index. Periacetabular osteotomy is an effective technique for treating symptomatic developmental dysplasia of the hip and can maintain the natural hip at least 19 years in selected patients. LEVEL OF EVIDENCE: Level III, prognostic study.

Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of isoflurane in Shetland ponies using a sequence of three different supramaximal noxious stimulations at each tested concentration of isoflurane rather than a single stimulation. STUDY DESIGN: Prospective, experimental trial. ANIMALS: Seven 4-year-old, gelding Shetland ponies. METHODS: The MAC of isoflurane was determined for each pony. Three different modes of electrical stimulation were applied consecutively (2 minute intervals): two using constant voltage (90 V) on the gingiva via needle- (CVneedle) or surface-electrodes (CVsurface) and one using constant current (CC; 40 mA) via surface electrodes applied to the skin over the digital nerve. The ability to clearly interpret the responses as positive, the latency of the evoked responses and the inter-electrode resistance were recorded for each stimulus. RESULTS: Individual isoflurane MAC (%) values ranged from 0.60 to 1.17 with a mean (+/-SD) of 0.97 (+/-0.17). The responses were more clearly interpreted with CC, but did not reach statistical significance. The CVsurface mode produced responses with a longer delay. The CVneedle mode was accompanied by variable inter-electrode resistances resulting in uncontrolled stimulus intensity. At 0.9 MAC, the third stimulation induced more positive responses than the first stimulation, independent of the mode of stimulation used. CONCLUSIONS: The MAC of isoflurane in the Shetland ponies was lower than expected with considerable variability among individuals. Constant current surface electrode stimulations were the most repeatable. A summation over the sequence of three supramaximal stimulations was observed around 0.9 MAC. CLINICAL RELEVANCE: The possibility that Shetland ponies require less isoflurane than horses needs further investigation. Constant current surface-electrode stimulations were the most repeatable. Repetitive supramaximal stimuli may have evoked movements at isoflurane concentrations that provide immobility when single supramaximal stimulation was applied.

B-type natriuretic peptide for diagnosis and treatment of congestive heart failure

BACKGROUND Prognostic classification of congestive heart failure (CHF) is difficult and only possible with the help of additional diagnostic tools. B-type natriuretic peptide (BNP) has been used as a diagnostic and prognostic marker for patients (pts) with CHF. In this study, the clinical value of BNP for stratification and treatment of pts with CHF was evaluated. PATIENTS AND METHODS 33 out-pts with CHF (age 57 +/- 12 years) were included. Left-ventricular (LV) ejection fraction (EF) was 27 +/- 8% (mean +/- SD) and NYHA-class 2.4 +/- 0.7. Following parameters were measured: BNP and sodium from blood samples, exercise performance from 6-minute walking test (6MWT, meters) (n = 18), LV end-diastolic diameter (LVEDD) and LV mass (LVM) from 2D-echocardiography (n = 33), as well as LV end-diastolic pressure (LVEDP, n = 23) and systemic vascular resistance (SVR, n = 20) from heart-catheterisation. Ten pts were hospitalised in the preceding 6 months because of worsening CHF or for optimisation of medical therapy. BNP was measured at the beginning and end of the hospital-stay. Follow-up was for 1 year. RESULTS Pts with a high NYHA-class had a higher BNP (pg/ml) than those with a low NYHA- class: NYHA I 51 +/- 20, II 281 +/- 223, III 562+/-346 and IV 1061 +/- 126 pg/ml (p = 0.002). BNP correlated with LVEDP (r = 0.50, p <0.02), SVR (r =0.49, p <0.03) and inversely with 6MWT (r =-0.60, p <0.009), LVEF (r = -0.49, p <0.004) and sodium (r = -0.36, p = 0.04). In the hospitalised pts, mean BNP (pg/ml) was 881 +/- 695 at admission,and 532 +/- 435 at discharge (n.s.). Decrease in BNPduring hospitalisation paralleled weight-loss and was significantly greater in patients with >1000 pg/ml BNP at admission (n = 5) as compared to the 5 patients with BNP <1000 (p <0.03). Patients with an adverse event during 1-year follow-up had significantly higher BNP both at steady-state (603 +/-359 pg/ml) and at time of decompensation than patients with a favourable outcome (227 +/- 218 pg/ml,p <0.001). CONCLUSIONS BNP correlates well with the clinical severity of CHF (NYHA-class) and is directly related to filling pressure (LVEDP), LV function(LVEF) and exercise performance (6 MWT). Furthermore, BNP has prognostic impact with regard to adverse clinical events.

Anaesthesia with medetomidine, midazolam and ketamine in six gorillas after premedication with oral zuclopenthixol dihydrochloride

OBJECTIVE To evaluate the effects of medetomidine, midazolam and ketamine (MMK) in captive gorillas after premedication with oral zuclopenthixol. STUDY DESIGN Case series. ANIMALS Six gorillas, two males and four females, aged 9-52 years and weighing 63-155 kg. METHODS The gorillas were given zuclopenthixol dihydrochloride 0.2 ± 0.05 mg kg(-1) per os twice daily for 3 days for premedication. On the day of anaesthesia the dose of zuclopenthixol was increased to 0.27 mg kg(-1) and given once early in the morning. Anaesthesia was induced with medetomidine 0.04 ± 0.004 mg kg(-1) , midazolam 0.048 ± 0.003 mg kg(-1) and ketamine 4.9 ± 0.4 mg kg(-1) intramuscularly (IM). Upon recumbency, the trachea was intubated and anaesthesia was maintained on 1-2% isoflurane in oxygen. Physiological parameters were monitored every 10 minutes and arterial blood gas analysis was performed once 30-50 minutes after initial darting. At the end of the procedure, 42-115 minutes after initial darting, immobilisation was antagonized with atipamezole 0.21 ± 0.03 mg kg(-1) and sarmazenil 5 ± 0.4 μg kg(-1) IM. RESULTS Recumbency was reached within 10 minutes in five out of six animals. One animal required two additional darts before intubation was feasible. Heart rate ranged from 60 to 85 beats minute(-1) , respiratory rate from 17 to 46 breaths minute(-1) and temperature from 36.9 to 38.3 °C. No spontaneous recoveries were observed and anaesthetic level was stable. Blood gas analyses revealed mild respiratory acidosis, and mean PaO(2) was 24.87 ± 17.16 kPa (187 ± 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was smooth and gorillas were sitting within 25 minutes. CONCLUSION AND CLINICAL RELEVANCE The drug combination proved to be effective in anaesthetizing captive gorillas of various ages and both sexes, with minimal cardio-respiratory changes.

Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function.

INTRODUCTION: The objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis. METHODS: Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP). RESULTS: MAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003). CONCLUSIONS: The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.