Low-Dose vs Standard-Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated With Fondaparinux: The FUTURA/OASIS-8 Randomized Trial.

JAMA. 2010 Aug 31;

Authors: , Steg PG, Jolly SS, Mehta SR, Afzal R, Xavier D, Rupprecht HJ, López-Sendón JL, Budaj A, Diaz R, Avezum A, Widimsky P, Rao SV, Chrolavicius S, Meeks B, Joyner C, Pogue J, Yusuf S

CONTEXT: The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain. OBJECTIVE: To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010. INTERVENTIONS: Patients received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT). MAIN OUTCOME MEASURES: Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30. RESULTS: The primary outcome occurred in 4.7% of those in the low-dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were not different but the rates of minor bleeding were lower with 0.7% in the low-dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P = .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs 3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for death, myocardial infarction, or target vessel revascularization it was 4.5% for the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98-2.53; P = .06). Catheter thrombus rates were very low (0.5% in the low-dose group and 0.1% in the standard-dose group, P = .15). CONCLUSION: Low-dose compared with standard-dose unfractionated heparin did not reduce major peri-PCI bleeding and vascular access-site complications. Trial Registration clinicaltrials.gov Identifier: NCT00790907.

PMID: 20805623 [PubMed - as supplied by publisher]

Anemia and blood transfusion and outcome on the intensive care unit.

Crit Care. 2010 May 25;14(1):438

Authors: Müller MC, Juffermans NP

ABSTRACT: The observation of Sakr and colleagues that transfusion may be beneficial in certain subgroups of intensive care unit (ICU) patients 1 is interesting, since large observational studies demonstrate that transfusion is independently associated with an increased risk of death 2. Also, a systematic review showed that the benefits of transfusion in the ICU do not outweigh the risks 3. Sakr and colleagues ascribe their discrepant results to the fact that transfused blood was leukoreduced. Of the 17 randomized controlled trials on the association of nonleukoreduced blood with mortality, however, a benefit of leukoreduction was found only in cardiac surgery patients 4. A meta-analysis confirmed that available evidence does not justify universal leukoreduction 5.Given the increased risk of nosocomial infection, multiple organ failure and acute respiratory distress syndrome, an explanation of a beneficial effect from transfusion in anemic critically ill patients is tempting. We propose that the results of this study may be related to the indication of transfusion, this being active bleeding and not correction of anemia associated with critical illness. Hereby, transfusion may have prevented adverse events due to postoperative bleeding, explaining the survival benefit. The fact that 76% of patients were referred from the operating/recovery room and that the median length of ICU stay was only 1 day may support this hypothesis. Based on numerous reports on the association of transfusion with adverse outcome, a liberal transfusion strategy in critically ill anemic patients in the absence of acute bleeding should not be advocated.

PMID: 20804562 [PubMed - as supplied by publisher]

EFNS guideline on the management of status epilepticus in adults.

Eur J Neurol. 2010 Mar;17(3):348-55

Authors: Meierkord H, Boon P, Engelsen B, Göcke K, Shorvon S, Tinuper P, Holtkamp M,

The objective of the current article was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005 and in the current updated version all pertinent publications from January 2005 to January 2009. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear, we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4-8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE. However, if it turns out to be refractory, further non-anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics. In subtle SE, in most patients, i.v. anaesthesia is required.

PMID: 20050893 [PubMed - indexed for MEDLINE]

Primary care summary of the British Thoracic Society Guidelines for the management of community acquired pneumonia in adults: 2009 update. Endorsed by the Royal College of General Practitioners and the Primary Care Respiratory Society UK.

Prim Care Respir J. 2010 Mar;19(1):21-7

Authors: Levy ML, Le Jeune I, Woodhead MA, Macfarlaned JT, Lim WS,

INTRODUCTION: The identification and management of adults presenting with pneumonia is a major challenge for primary care health professionals. This paper summarises the key recommendations of the British Thoracic Society (BTS) Guidelines for the management of Community Acquired Pneumonia (CAP) in adults. METHOD: Systematic electronic database searches were conducted in order to identify potentially relevant studies that might inform guideline recommendations. Generic study appraisal checklists and an evidence grading from A+ to D were used to indicate the strength of the evidence upon which recommendations were made. CONCLUSIONS: This paper provides definitions, key messages, and recommendations for handling the uncertainty surrounding the clinical diagnosis, assessing severity, management, and follow-up of patients with CAP in the community setting. Diagnosis and decision on hospital referral in primary care is based on clinical judgement and the CRB-65 score. Unlike some other respiratory infections (e.g. acute bronchitis) an antibiotic is always indicated when a clinical diagnosis of pneumonia is made. Timing of initial review will be determined by disease severity. When there is a delay in symptom or radiographic resolution beyond six weeks, the main concern is whether the CAP was a complication of an underlying condition such as lung cancer.

PMID: 20157684 [PubMed - indexed for MEDLINE]

Inpatient length of stay: a finite mixture modeling analysis.

Eur J Health Econ. 2010 Apr;11(2):119-26

Authors: Singh CH, Ladusingh L

Length of stay (LOS) in hospital for inpatient treatment is a measure of crucial recovery time. Using nationwide data on inpatient healthcare in India, a three-component finite mixture negative binomial model was found to provide a reasonable fit to the heterogeneous LOS distribution. Associated risk factors for short-stay, medium-stay and long-stay subgroups were identified from the respective negative binomial components. In addition, significant heterogeneities within each group were also found.

PMID: 19430985 [PubMed - indexed for MEDLINE]

Intensive glucose control in the management of diabetes mellitus and inpatient hyperglycemia.

Am J Health Syst Pharm. 2010 May 15;67(10):798-805

Authors: Shogbon AO, Levy SB

PURPOSE: The current evidence on intensive glycemic control in the inpatient and outpatient settings and its implications to practice are reviewed. SUMMARY: Poor glycemic control in patients with diabetes is associated with microvascular and macrovascular complications. Various clinical trials involving patients with type 1 and type 2 diabetes have revealed the benefits of intensive glycemic control in delaying the onset and progression of microvascular complications of diabetes. However, while long-term epidemiologic trials and a meta-analysis have shown a benefit of intensive glycemic control in reducing the incidence of macrovascular complications, recent clinical trials have not found similar benefits. The American Diabetes Association (ADA), American College of Endocrinology (ACE), and American Association of Clinical Endocrinologists recommend intensive control of glycosylated hemoglobin and plasma glucose at specified goals. Hyperglycemia in the inpatient setting is associated with increased morbidity and mortality. ACE and ADA recommend the use of an i.v. insulin infusion in critically ill inpatients with hyperglycemia. In noncritically ill inpatients, basal and bolus doses of insulin are recommended. The use of sliding-scale insulin as the sole therapy for inpatient hyperglycemia is discouraged. However, caution must be exercised to ensure a balance between controlling hyperglycemia and reducing the risk of hypoglycemia. CONCLUSION: While intensive glycemic control is known to prevent or delay the occurrence of microvascular complications of diabetes, macrovascular benefits are still uncertain. Current evidence suggests that intensive glycemic control should be initiated as soon as possible after diagnosis of type 1 or type 2 diabetes in order to maximize potential long-term macrovascular benefits. Inpatient hyperglycemia should be managed appropriately to reduce morbidity and mortality, with great care taken to avoid and appropriately treat hypoglycemia.

PMID: 20479101 [PubMed - indexed for MEDLINE]

[Hospital medicine]

Rev Med Chil. 2009 Oct;137(10):1385-7

Authors: Berkovits A, Aizman A, Eymin G, Rojas L

Hospital medicine was created over 10 years ago aiming to provide an integral care to hospitalized patients. Hospital specialists are physicians mainly devoted to the global care of hospitalized patients. Their professional functions include patient care, teaching, clinical research and managing activities. The main difference with other specialties is their exclusive dedication to hospital work. The impact of this specialty on patient care has been demonstrated by a significant reduction in the hospitalization days and costs and higher level of patient satisfaction. In clinical hospitals, the presence of tutors during the complete working day, has resulted in better pre and postgraduate teaching activities and a higher availability of supervisors for trainees. Four years ago, hospital medicine was established as a discipline at the Clinical Hospital of Pontificia Universidad Católica de Chile. In this period, these specialists became essential for student training and an integral part of the faculty staff.

PMID: 20011948 [PubMed - indexed for MEDLINE]

Hospitalist time usage and cyclicality: Opportunities to improve efficiency.

J Hosp Med. 2010 Jul;5(6):329-34

Authors: Kim CS, Lovejoy W, Paulsen M, Chang R, Flanders SA

BACKGROUND:: Academic medical centers (AMCs) have a constrained resident work force. Many AMCs have increased the use of nonresident service hospitalists to manage continued growth in clinical volume. To optimize their time in the hospital, it is important to understand hospitalists' work flow. DESIGN:: We performed a time-motion study of hospitalists carrying the admission pager throughout the 3 types of shifts we have at our hospital (day shift, swing shift, and night shift). SETTING:: Tertiary academic medical center in the Midwest. RESULTS:: Hospitalists spend about 15% of their time on direct patient care, and two-thirds of their time on indirect patient care. Of the indirect activities, communication and documentation dominate. Travel demands make up over 7% of a hospitalists' time. There are spikes in indirect patient care, followed closely by spikes in direct patient care, at shift changes. CONCLUSIONS:: At our AMC, indirect patient care activities accounted for the majority of the admitting hospitalists' time spent in the hospital, with documentation and communication dominating this time. Travel takes a significant fraction of hospitalists' time. There is also a cyclical nature to activities performed throughout the day, which can cause patient delays and impose variability on support services. There is a need for both service-specific and systemic improvements for AMCs to efficiently manage further growth in their inpatient volume. Journal of Hospital Medicine 2010;5:329-334. (c) 2010 Society of Hospital Medicine.

PMID: 20803670 [PubMed - in process]

The impact of fragmentation of hospitalist care on length of stay.

J Hosp Med. 2010 Jul;5(6):335-8

Authors: Epstein K, Juarez E, Epstein A, Loya K, Singer A

BACKGROUND:: Different hospitalist staffing models provide different levels of inpatient continuity of care, which may impact length of stay (LOS). OBJECTIVE:: To determine if fragmentation of care (FOC) by hospitalist physicians is associated with LOS. DESIGN:: Concurrent control study. SETTING:: Hospitalist practices managed by IPC The Hospitalist Company. PATIENTS:: A total of 10,977 patients admitted for diagnosis-related group (DRG) of 89 pneumonia with complications or comorbidities (PNA) or a DRG of 127 heart failure and shock (HF) between December 2006 and November 2007. MEASUREMENTS:: FOC was defined as the percentage of care given by hospitalists other than the hospitalist who saw the patient the majority of the stay. Negative binomial regression was performed on DRG 89 and DRG 127 patients with LOS as the dependent variable. We adjusted for gender, age, severity of illness (SOI) scores, risk of mortality (ROM) scores, and number of secondary diagnoses, and admission day of the week. RESULTS:: A 10% increase in fragmentation was associated with an increase of 0.39 days (P < 0.0001) in the LOS for pneumonia, and an increase of 0.30 days (P < 0.0001) in LOS for heart failure. CONCLUSIONS:: As FOC increased for pneumonia and heart failure, the LOS increased significantly. Methods to reduce fragmentation should be explored, while more research is needed to identify the source of the relationship between FOC and LOS. Journal of Hospital Medicine 2010;5:335-338. (c) 2010 Society of Hospital Medicine.

PMID: 20803671 [PubMed - in process]

Comparing academic and community-based hospitalists.

J Hosp Med. 2010 Jul;5(6):349-52

Authors: Malkenson D, Siegal EM, Leff JA, Weber R, Struck R

In 2006, hospitalist programs were formally introduced at both an academic and community hospital in the same city providing an opportunity to study the similarities and differences in workflows in these two settings. The data were collected using a time-flow methodology allowing the two workflows to be compared quantitatively. The results showed that the hospitalists in the two settings devoted similar proportions of their workday to the task categories studied. Most of the time was spent providing indirect patient care followed by direct patient care, travel, personal, and other. However, after adjusting for patient volumes, the data revealed that academic hospitalists spent significantly more time per patient providing indirect patient care (Academic: 54.7 +/- 11.1 min/patient, Community: 41.9 +/- 9.8 min/patient, p < 0.001). Additionally, we found that nearly half of the hospitalists' time at both settings was spent multitasking. Although we found subtle workflow differences between the academic and community programs, their similarities were more striking as well as greater than their differences. We attribute these small differences to the higher case mix index at the academic program as well greater complexity and additional communication hand-offs inherent to a tertiary academic medical center. It appears that hospitalists, irrespective of their work environment, spend far more time documenting, communicating and coordinating care than they do at the bedside raising the question, is this is a necessary feature of the hospitalist care model or should hospitalists restructure their workflow to improve outcomes? Journal of Hospital Medicine 2010;5:349-352. (c) 2010 Society of Hospital Medicine.

PMID: 20803674 [PubMed - in process]

A model of a hospitalist role in the care of admitted patients in the emergency department.

J Hosp Med. 2010 Jul;5(6):360-4

Authors: Briones A, Markoff B, Kathuria N, Jagoda A, Baumlin K, Hill S, Mumm L, Jervis R, Dunn A

PMID: 20803676 [PubMed - in process]

Management of patients undergoing anticoagulant treatment. Results from a large, multicentre, prospective, case-control study.

Thromb Haemost. 2010 Aug 30;104(5)

Authors: Bacci C, Maglione M, Favero L, Perini A, Di Lenarda R, Berengo M, Zanon E

Following favourable results from a previous study, a large, multicentre, prospective, case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure. In the warfarin-treated group, the oral anticoagulant regimen was maintained unchanged, such that the patients had an International Normalised Ratio ranging between 1.8 and 4, and local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes saturated with tranexamic acid) were adopted. All the procedures were performed in an outpatient setting. Seven bleeding complications occurred in the OAT group and four in the control group; the difference in the number of bleeding events between the two groups was not statistically significant (OR=1.754; 95% CI 0.510 - 6.034; p=0.3727). No post-operative late bleeds requiring hospitalisation and/or blood transfusions were recorded, and the adjunctive local haemostatic measures were adequate to stop the bleeding. The results of our protocol applied in this large, multicenter study show that dental extractions can be performed easily and safely in anticoagulated outpatients without any modification of the ongoing anticoagulant therapy, thus minimising costs and reducing discomfort for patients.

PMID: 20806110 [PubMed - as supplied by publisher]

ESWL for difficult bile duct stones: A 15-year single centre experience.

World J Gastroenterol. 2010 Sep 7;16(33):4159-63

Authors: Muratori R, Azzaroli F, Buonfiglioli F, Alessandrelli F, Cecinato P, Mazzella G, Roda E

AIM: To evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) for the management of refractory bile duct cholelithiasis in a third level referral centre. METHODS: The clinical records of all patients treated with a second generation electromagnetic lithotripter (Lithostar Plus, SIEMENS) from October 1990 to April 2005 were evaluated. All patients were monitored during the procedure and antibiotics were administered in case of cholangitis. The chi(2) test and logistic regression analysis were performed as appropriate. RESULTS: Two hundred and fourteen patients (102 males, 112 females; mean age 74.8 +/- 0.84 years - single stone 97, multiple stones 117) underwent ESWL. The mean number of sessions and shock waves were 3.5 +/- 0.13 and 3477.06 +/- 66.17, respectively. The maximum stone size was 5 cm. Complete stone clearance was achieved in 192 (89.7%) patients. Of the remaining patients 15 required surgery, 2 a palliative stent and in 5 patients stone fragmentation led to effective bile drainage with clinical resolution despite incomplete clearance. Age, sex and stone characteristics were not related to treatment outcome. Major complications occurred in two patients (haemobilia and rectal bleeding) and minor complications in 25 (3 vomiting, 22 arrhythmias). No procedure-related deaths occurred. CONCLUSION: ESWL is a safe and effective technique for clearance of refractory bile duct stones.

PMID: 20806432 [PubMed - in process]

Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

Thromb Haemost. 2010 Aug 30;104(5)

Authors: Di Nisio M, Ferrante N, De Tursi M, Iacobelli S, Cuccurullo F, Büller HR, Feragalli B, Porreca E

While the association between cancer and symptomatic venous thromboembolism (VTE) is well established, the incidence and risk factors for incidental VTE in cancer patients remain unclear. The medical records of 1,921 consecutive cancer patients starting chemotherapy from January 2003 up to March 2009 were identified. Patients with a positive history of VTE were excluded. Pre-existing signs of VTE, kind and stage of malignancy, first and subsequent lines of chemotherapy, and all follow-up computed tomography (CT) scans were analysed. The primary outcome was incidental VTE. Overall, there were 101 (5.3%) VTE, 62 (3.2%) incidental and 39 (2.0%) symptomatic during a median of eight months (range 3-72). The incidence on CT scans was 0.58% (95%CI: 0.44-0.74). Incidental VTE included 24 pulmonary embolism, 28 deep venous thrombosis of the extremities, and 10 thromboses of the cava or splanchnic veins. Half of the incidental VTE occurred in the first 3-6 months of chemotherapy with a relatively higher incidence in gynecological and lung cancers. The presence of metastases, high leukocyte count, and platin-based chemotherapy increased the risk up to three-fold. All patients with incidental VTE regardless the location received half to full therapeutic doses of low-molecular-weight heparin for a minimum of three months. In summary, incidental VTE is a relative common finding in patients with solid tumours, especially in the first months of chemotherapy. Further research is needed to understand the natural history of incidental thrombosis in order to develop adequate management guidelines.

PMID: 20806119 [PubMed - as supplied by publisher]

Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial.

Lancet. 2010 Aug 27;

Authors: Böhm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L,

BACKGROUND: Raised resting heart rate is a marker of cardiovascular risk. We postulated that heart rate is also a risk factor for cardiovascular events in heart failure. In the SHIFT trial, patients with chronic heart failure were treated with the selective heart-rate-lowering agent ivabradine. We aimed to test our hypothesis by investigating the association between heart rate and events in this patient population. METHODS: We analysed cardiovascular outcomes in the placebo (n=3264) and ivabradine groups (n=3241) of this randomised trial, divided by quintiles of baseline heart rate in the placebo group. The primary composite endpoint was cardiovascular death or hospital admission for worsening heart failure. In the ivabradine group, heart rate achieved at 28 days was also analysed in relation to subsequent outcomes. Analysis adjusted to change in heart rate was used to study heart-rate reduction as mechanism for risk reduction by ivabradine directly. FINDINGS: In the placebo group, patients with the highest heart rates (>/=87 beats per min [bpm], n=682, 286 events) were at more than two-fold higher risk for the primary composite endpoint than were patients with the lowest heart rates (70 to <72 bpm, n=461, 92 events; hazard ratio [HR] 2.34, 95% CI 1.84-2.98, p<0.0001). Risk of primary composite endpoint events increased by 3% with every beat increase from baseline heart rate and 16% for every 5-bpm increase. In the ivabradine group, there was a direct association between heart rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart rates lower than 60 bpm at 28 days on treatment had fewer primary composite endpoint events during the study (n=1192; event rate 17.4%, 95% CI 15.3-19.6) than did patients with higher heart rates. The effect of ivabradine is accounted for by heart-rate reduction, as shown by the neutralisation of the treatment effect after adjustment for change of heart rate at 28 days (HR 0.95, 0.85-1.06, p=0.352). INTERPRETATION: Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure. FUNDING: Servier, France.

PMID: 20801495 [PubMed - as supplied by publisher]