Lessons learned with Bone Health TeleECHO: making treatment decisions when guidelines conflict.

Clinical practice guidelines provide helpful information for managing patients with metabolic bone disease. Good guidelines are based on the best available medical evidence; however, guidelines from different societies can conflict. Additionally, it is not possible for a guideline to anticipate the vast variability of circumstances, comorbidities, previous medical experiences, cultural differences, and preferences in real-world patients. Bone Health TeleECHO is a strategy for sharing knowledge on the care of patients with skeletal diseases through ongoing interactive videoconferences. We report three cases based on those presented at Bone Health TeleECHO, where, through discussion, treatment outside of commonly used guidelines was ultimately recommended. Guidelines developed by different organizations may provide "evidence-based" or "informed" recommendations which do not account for the variability of clinical circumstances encountered in the care of individual patients. This highlights the importance of Bone Health TeleECHO, where healthcare professionals can share knowledge, individualize treatment decisions, and improve patient care.Learning objectives At the end of this activity participants should be able to:• Distinguish between the onset and off of bisphosphonates versus other medications used in the prevention and treatment of osteoporosis and how this affects choice of a "drug holiday."• Understand the limitations of clinical practices guidelines in the care of an individual patient and how interactive video conferencing can assist with decision making.• Recognize that patients treated with glucocorticoids at high risk for fracture can benefit from more aggressive interventions for osteoporosis.

Sleepless and desynchronized: Impaired inter trial phase coherence of steady-state potentials following sleep deprivation.

Sleep loss has detrimental effects on cognitive and emotional functioning. These impairments have been associated with alterations in EEG measures of power spectrum and event-related potentials, however the impact of sleep loss on inter trial phase coherence (ITPC), a measure of phase consistency over experimental trials, remains mostly unknown. ITPC is thought to reflect the ability of the neural response to temporally synchronize with relevant events, thus optimizing information processing. In the current study we investigated the effects of sleep deprivation on information processing by evaluating the phase consistency of steady-state visual evoked potentials (ssVEPs) as well as amplitude-based measures of ssVEPs, obtained from a group of 18 healthy individuals following 24 h of total sleep deprivation and after a night of habitual sleep. An ssVEP task was utilized, which included the presentation of dots flickering at 7.5 Hz, along with a cognitive-emotional task. Our results show that ITPC is significantly reduced under sleep deprivation relative to habitual sleep. Interestingly, decreased ITPC under sleep deprivation was associated with decreased behavioral performance in the psychomotor vigilance task (PVT), a validated measure of reduced vigilance following a lack of sleep. The results suggest that the capability of the brain to synchronize with rhythmic stimuli is disrupted without sleep. Thus, decreased ITPC may represent an objective and mechanistic measure of sleep loss, allowing future work to study the relation between brain-world synchrony and the specific functional impairments associated with sleep deprivation.

In-vitro investigation of the hemodynamic responses of the cerebral, coronary and renal circulations with a rotary blood pump installed in the descending aorta.

This study investigates the hemodynamic responses of the cardiovascular system when a rotary blood pump is operating in the descending aorta, with a focus on the cerebral, coronary and renal autoregulation, using our in-house cardiovascular emulator. Several improvements have been made from our previous studies. A novel coronary system was developed to replicate the native coronary perfusion. Three pinch valves actuated by stepper motors were used to simulate the regional autoregulation systems of the native cerebral, coronary and renal circulations. A rotary pump was installed in the descending aorta, in series with the heart, and the hemodynamic responses of the cardiovascular system were investigated with a focus on cerebral, coronary and renal circulation over a wide range of pump rotor speeds. Experiments were performed twice, once with the autoregulation systems active and once with the autoregulation systems inactive, to reflect that there will be some impairment of autoregulatory systems in a patient with heart failure. It was shown that by increasing the rotor speed to 3000 rpm, the cardiac output was improved from 2.9 to 4.1 L/min as a result of an afterload reduction induced by the pressure drop upstream of the pump. The magnitudes of changes in perfusion in the cerebral, coronary and renal circulations were recorded with regional autoregulation systems active and inactive.

Does a 'direct' transfer protocol reduce time to coronary angiography for patients with non-ST-elevation acute coronary syndromes? A prospective observational study.

OBJECTIVE: National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography. METHODS: This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay. RESULTS: Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission. CONCLUSIONS: The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS.

Effect of abiraterone acetate on fatigue in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy.

BACKGROUND: Fatigue is a common, debilitating side-effect of prostate cancer and its treatment. Patient-reported fatigue was evaluated as part of COU-AA-301, a randomized, placebo-controlled, phase III trial of abiraterone acetate and prednisone versus placebo and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel chemotherapy. This is the first phase III study in advanced prostate cancer to evaluate fatigue outcomes using a validated fatigue-specific instrument. PATIENTS AND METHODS: The Brief Fatigue Inventory (BFI) questionnaire was used to measure patient-reported fatigue intensity and fatigue interference with activities of daily life. All analyses were conducted using prespecified responder definitions of clinically meaningful changes. RESULTS: A total of 797 patients were randomized to abiraterone acetate and prednisone, and 398 were randomized to placebo and prednisone. Compared with prednisone alone, in patients with clinically significant fatigue at baseline, abiraterone acetate and prednisone significantly increased the proportion of patients reporting improvement in fatigue intensity (58.1% versus 40.3%, P = 0.0001), improved fatigue interference (55.0% versus 38.0%, P = 0.0075), and accelerated improvement in fatigue intensity (median 59 days versus 194 days, P = 0.0155). CONCLUSIONS: In patients with mCRPC progressing after docetaxel chemotherapy, abiraterone acetate and prednisone yielded clinically meaningful improvements in patient-reported fatigue compared with prednisone alone.

Case fatality rates for South Asian and Caucasian patients show no difference 2.5 years after percutaneous coronary intervention.

OBJECTIVE: To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates. DESIGN: Retrospective cohort study. SETTING: A cardiology referral centre in east London. PATIENTS: 9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian. MAIN OUTCOME MEASURES: In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5 years (range 1.5-3.6 years). RESULTS: South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13 years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan-Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23). CONCLUSION: In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.

Coma as a presenting sign of Datura stramonium seed tea poisoning.

Datura stramonium is a hallucinogenic plant that causes serious poisoning. Consumption of any part of the plant may result in a severe anticholinergic reaction that may lead to toxicity and occasionally cause diagnostic difficulties. We report two patients with coma as a presenting sign of intoxication following intentional Datura seed tea ingestion and we review the leading clues for its diagnosis and treatment.

Role of non-invasive imaging in the management of coronary artery disease: an assessment of likely change over the next 10 years. A report from the British Cardiovascular Society Working Group.

Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15-20 years. However, established non-invasive testing (such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10-15 years. This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change.

The ORTHO BC-SAT--a satisfaction questionnaire for women using hormonal contraceptives.

OBJECTIVE: To assess the reliability and validity of the ORTHO Birth Control Satisfaction Assessment Tool (ORTHO BC-SAT). DESIGN: 339 women using 1 of 4 hormonal birth control methods (oral contraceptives, transdermal patch, vaginal ring, injections), completed the questionnaire 1-2 times. MATERIALS AND METHODS: The questionnaire was developed based on findings from the literature, focus groups, and interviews. Internal consistency reliability, test-retest reliability, construct validity, and known groups validity were evaluated. RESULTS: Based on variable clustering, 8 domains were identified (Ease of Use/Convenience, Compliance, Lifestyle Impact, Symptom/Side Effect Bother, Menstrual Impact, Future Fertility Concerns, Assurance/Confidence, Overall Satisfaction). Internal consistency reliability was demonstrated with Cronbach's alpha values ranging from 0.70 to 0.89. All multi-item scales reported acceptable test-retest reliability (0.79-0.87). Construct validity was demonstrated by support of a hypothesized pattern of correlations. Known groups validity was confirmed by examining scale scores of women categorized by levels of symptom bother. As expected, women with the least amount of bother reported higher scores on all satisfaction scales than those with higher bother (p < 0.0001), except on Future Fertility Concerns (p = 0.27). CONCLUSION: Our results support the reliability and validity of the ORTHO BC-SAT. It may be used in future studies to evaluate satisfaction among hormonal contraceptive users.

Recommendations on percutaneous coronary intervention for the reperfusion of acute ST elevation myocardial infarction.

Little information is currently available from the various societies of cardiology on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Since primary PCI is the main method of reperfusion in AMI in many centres, and since of all cardiac emergencies AMI represents the most urgent situation for PCI, recommendations based on scientific evidence and expert experience would be useful for centres practising primary PCI, or those looking to establish a primary PCI programme. To this aim, a task force for primary PCI in AMI was formed to develop a set of recommendations to complement and assist clinical judgment. This paper represents the product of their recommendations.

Coronary artery brachytherapy.

Coronary artery disease is the leading cause of mortality in the West with over 1.2 million angioplasties performed annually. Despite the introduction of stents, restenosis occurs in 30-40% of vessels, which until recently has only been treated effectively by coronary artery bypass surgery. Coronary artery brachytherapy appears to provide an alternative, less invasive remedy. The mechanisms of restenosis and how these are inhibited by radiation are described here. The practicalities of radiation delivery and the history of the development of intravascular radiation as an effective clinical tool are outlined. Finally, the pitfalls of the current technology and the areas in which future research must be targeted for the field to develop are discussed.

Use of a self-report constipation questionnaire with older adults in long-term care.

PURPOSE: The Patient Assessment of Constipation (PAC), a symptom and quality-of-life inventory, was developed among community-dwelling adults under age 65. The purpose of this study was to evaluate the feasibility and validity of an interview format of the PAC for older adults residing in long-term care. DESIGN AND METHODS: The PAC was administered to 24 nursing home residents aged 65 and older. Cognitive interviewing methods were used to evaluate subjects' understanding and interpretation of PAC items. RESULTS: The PAC interview required an average of 11 min, 15 s, to complete. Administration modifications for this population included rereading Likert anchor points and the stem question for each item. Subject item interpretation was generally accurate, as was interpretation of Likert anchors. IMPLICATIONS: The PAC is easily administered and well understood by older adult residents in long-term care and provides a brief method for obtaining constipation-specific symptom and quality-of-life data from this population.

Symptoms associated with gastroesophageal reflux disease: development of a questionnaire for use in clinical trials.

UNLABELLED: Many persons who suffer from GERD report additional symptoms, e.g., chest pain, dyspepsia, dysphagia, that are often not measured in clinical trials even though they may be distressing to the GERD sufferer. The primary goal of this study was to develop and assess the psychometric characteristics of a new GERD symptom scale measuring frequency, severity, and distress. The GERD Symptom Assessment Scale (GSAS) was administered to a sample of 169 GERD sufferers at baseline and two weeks. Internal consistency, construct validity, and test-retest reliability were assessed. Responsiveness was evaluated using clinical trial data assessing drug efficacy. RESULTS: Internal consistency was >0.80 for the symptom severity and distress scales. All three scales showed stability over two weeks (ICC >0.70). Both validity hypotheses were supported. Comparison of effect sizes showed the GSAS is sensitive to changes in severity of symptoms. In conclusion, the GSAS is a reliable, valid, and responsive measure of GERD symptoms.

An intracranial aspergilloma with low signal on T2-weighted images corresponding to iron accumulation.

We present a case of cerebral aspergillosis in an immunocompetent patient. The MRI signal characteristics were compared with the histologic findings. Irregular low-signal zones were demonstrated between the wall of the abscess and the central necrosis on T2-weighted images; the pathology specimen revealed concentrated iron in these transitional zones but no hemosiderin. Iron is an essential element for the growth of fungal hyphae. The low-signal zones may represent the areas where there was active proliferation of aspergillus, and the unique location of the low signal may be a helpful imaging characteristic for the diagnosis of an aspergillus abscess.

Suitability of the Cordis Stabilizer marker guide wire for quantitative coronary angiography calibration: an in vitro and in vivo study.

Catheters usually are used for calibration purposes in quantitative coronary angiography (QCA). The systematic and random errors in these calibration factors (CFs) are dependent on the size and quality of the catheters and limited by out-of-plane magnification (OPM). Theoretically, a guide wire with evenly spaced marker bands would solve many of these potential problems. For this reason, we tested the Cordis Stabilizer marker wire, featuring 10 radiopaque platinum marker bands 15 mm apart, in in vitro and in vivo studies. To assess the effect of foreshortening, wires were positioned in a tube phantom; a centimeter grid was used as the gold standard. Radiographic images were acquired at 5-inch and 7-inch image-intensifier sizes, 512(2) and 1,024(2) matrix sizes and angulations from 0 degrees to 70 degrees in steps of 10 degrees. It was concluded that the relative errors in CFs are less than 7% if the foreshortening angles remain less than 20 degrees. In DICOM images of 15 patients, 65 measurements were taken after calibration on an 8F catheter and on a guide wire positioned in the coronary lesion. In all but two cases, the wire CFs were larger than the catheter CFs (relative difference, 24.7 +/- 19.6%). The measurements were divided into four groups: (I) no apparent OPM or foreshortening (n = 7), (II) only OPM (n = 4), (III) only foreshortening (n = 10), and (IV) the combination of both (n = 44). In group I (no OPM or foreshortening) the QCA results were similar using the guide wire or catheter as the calibration device (relative CF difference, 2.9% only). In group III the diameters were overestimated using the guide wire (obstruction diameter difference, 0.22 +/- 0.11 mm; reference diameter difference, 0.35 +/- 0.06 mm). For only OPM (group II) and the combination of OPM and foreshortening (group IV), the lesion length was underestimated on average by 2.4 mm using the catheter instead of the guide wire. In conclusion, if accurate assessment of the lesion length is important, the marker wire should be used for calibration purposes. For vessel diameter measurements, the conventional catheter calibration approach is the method of choice.

Angiographic and clinical one-year follow-up of the Cordis tantalum coil stent in a multicenter international study demonstrating improved restenosis rates when compared to pooled PTCA and BENESTENT-I data: the European Antiplatelet Stent Investigation (EASI).

The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow-up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 +/- 0.28 mm preprocedure to 2.93 +/- 0.34 mm poststenting and at 6 months was 1.99 +/- 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months.