Pharmacologic management of refractory depression.

OBJECTIVE: To review published clinical trials of the pharmacologic management of refractory depression. DATA SOURCES: MEDLINE was searched for relevant articles published from 1983 to 1990. The bibliographies of review articles were searched for additional references. Studies of nonpharmacologic treatments, such as electroconvulsive therapy, were not included. STUDY SELECTION: Eleven studies were found that did not contain obvious digressions from several methodologic assessment criteria (adapted from the McMaster guidelines for the evaluation of clinical trials). Further scrutiny by a nonblind reviewer resulted in the selection of four reports that were considered acceptable. An assessment by a second reviewer, blind as to author, results and journal name, confirmed this judgement. DATA EXTRACTION: Data describing response to the treatments were extracted by a single (nonblind) reviewer. Post-hoc power estimates and 95% confidence intervals were calculated whenever possible. DATA SYNTHESIS: The efficacy of augmenting an antidepressant regimen with lithium carbonate, triiodothyronine or reserpine was not supported by findings from the clinical trials reviewed. However, many trials with negative results lacked adequate statistical power to exclude the possibility of the drug''s efficacy. The use of a monoamine oxidase inhibitor was supported by the one study that met the review''s methodologic criteria. However, this study was not conducted under double-blind conditions. CONCLUSION: The generally recommended strategies for the pharmacologic treatment of refractory depression are not supported by methodologically sound studies.     

Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal

OBJECTIVE: To analyse the evidence for the efficacy and potential harmful effects of benzodiazepines compared with other therapies in the treatment of acute alcohol withdrawal. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1997 that described randomized controlled trials (RCTs) of benzodiazepines in the treatment of acute alcohol withdrawal. Key words included "benzodiazepines" (exploded) and "randomized controlled trial." Bibliographies of relevant articles were reviewed for additional RCTs, and manufacturers of benzodiazepines were asked to submit additional RCT reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were RCTs involving patients experiencing acute alcohol withdrawal and comparing a benzodiazepine available in Canada with placebo or an active control drug. Of the original 23 trials identified, 11 met these criteria, representing a total of 1286 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analysis of benefit (therapeutic success within 2 days) showed that benzodiazepines were superior to placebo (common odds ratio [OR] 3.28, 95% confidence interval [CI] 1.30-8.28). Data on comparisons between benzodiazepines and other drugs, including beta-blockers, carbamazepine and clonidine, could not be pooled, but none of the alternative drugs was found to be clearly more beneficial than the benzodiazepines. The meta-analysis of harm revealed no significant difference between benzodiazepines and alternative drugs in terms of adverse events (common OR 0.67, 95% CI 0.34-1.32) or dropout rates (common OR 0.68, 95% CI 0.47-0.97). INTERPRETATION: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal.     

Meta-analysis of benzodiazepine use in the treatment of insomnia

OBJECTIVE: To systematically review the benefits and risks associated with the use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1998 that described randomized controlled trials of benzodiazepines for the treatment of insomnia. Key words included "benzodiazepines" (exploded), "randomized controlled trial" and "insomnia." Bibliographies of relevant articles were reviewed for additional studies and manufacturers of benzodiazepines were asked to submit additional randomized controlled trial reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were randomized controlled trials involving patients with insomnia and compared a benzodiazepine with placebo or another active agent. Of the 89 trials originally identified, 45 met our criteria, representing a total of 2672 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records indicated that, when compared with placebo, benzodiazepines decreased sleep latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7 to 9.2) and significantly increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep latency; those randomized to benzodiazepine treatment estimated a sleep latency decrease of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving benzodiazepine treatment reported adverse effects, especially daytime drowsiness and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to 2.4), dropout rates for the benzodiazepine and placebo groups were similar. Cognitive function decline including memory impairment was reported in several of the studies. Zopiclone was not found to be superior to benzodiazepines on any of the outcome measures examined. INTERPRETATION: The use of benzodiazepines in the treatment of insomnia is associated with an increase in sleep duration, but this is countered by a number of adverse effects. Additional studies evaluating the efficacy of nonpharmacological interventions would be valuable.     

Wellness programs: a review of the evidence

OBJECTIVE: To review studies that have examined an association between wellness programs and improvements in quality of life and to assess the strength of the scientific evidence. DATA SOURCES: A MEDLINE search was constructed with the following medical subject headings: "psychoneuroimmunology," "chronic disease" and "health promotion," "chronic disease" and "health behaviour," "relaxation techniques," "music therapy," "laughter," "anger," "mediation" and "behavioural medicine." Searches using the text words "wellness" and "wellness program" were also carried out. References from the primary articles identified in the search and contemporary writing on wellness were also considered. STUDY SELECTION: Selection was limited to randomized controlled trials or prospective studies published in English that involved human subjects and that took place between 1980 and 1996. All studies with an intervention aimed at promoting wellness and measuring outcomes were included, except studies of patients with cancer and HIV and studies of health promotion programs in the workplace. Of the 1082 references initially identified, 11 met the criteria for inclusion in the critical appraisal. DATA EXTRACTION: The following information was extracted from the 11 studies: characteristics of the study population, number of participants (and number followed to completion), length of follow-up, type of intervention, outcome measures and results. All 11 studies were assessed for the quality of their evidence. DATA SYNTHESIS: All studies reported some positive outcomes following the intervention in question, although many had limitations precluding applicability of the results to a wider population. CONCLUSIONS: Despite the suggested benefit associated with wellness programs, the evidence was inconclusive. Whether the composition of the target group or the type of intervention has a role in determining outcomes is unknown. Although trends suggest that wellness programs may be cost-effective, further research is needed for confirmation.     

The effects of clinical practice guidelines on patient outcomes in primary care: a systematic review

OBJECTIVE: To assess the evidence for the effectiveness of clinical practice guidelines (CPGs) in improving patient outcomes in primary care. DATA SOURCES: A search of the MEDLINE, HEALTHPLAN, CINAHL and FAMLI databases was conducted to identify studies published between Jan. 1, 1980, and Dec. 31, 1995, concerning the use of guidelines in primary medical care. The keywords used in the search were "clinical guidelines," "primary care," "clinical care," "intervention," "randomized controlled trial" and "effectiveness." STUDY SELECTION: Studies of the use of CPGs were selected if they involved a randomized experimental or quasi-experimental method, concerned primary care, were related to clinical care and examined patient outcomes. Of 91 trials of CPGs identified through the search, 13 met the criteria for inclusion in the critical appraisal. DATA EXTRACTION: The following data were extracted, when possible, from the 13 trials: country and setting, number of physicians, number of patients (and the proportion followed to completion), length of follow-up, study method (including random assignment method), type of intervention, medical condition treated and effect on patient outcomes (including clinical and statistical significance, with confidence intervals). DATA SYNTHESIS: The most common conditions studied were hypertension (7 studies), asthma (2 studies) and cigarette smoking (2 studies). Four of the studies followed nationally developed guidelines, and 9 used locally developed guidelines. Six studies involved computerized or automated reminder systems, whereas the others relied on small-group workshops and education sessions. Only 5 of the 13 trials (38%) produced statistically significant results. CONCLUSION: There is very little evidence that the use of CPGs improves patient outcomes in primary medical care, but most studies published to date have used older guidelines and methods, which may have been insensitive to small changes in outcomes. Research is needed to determine whether the newer, evidence-based CPGs have an effect on patient outcomes.     

Depression in elderly medical inpatients: a meta-analysis of outcomes

OBJECTIVE: To determine the prognosis of elderly medical inpatients with depression. DATA SOURCES: A MEDLINE search for relevant articles published from January 1980 to September 1996 and a search of the PSYCH INFO database for articles published from January 1984 to September 1996. The bibliographies of identified articles were searched for additional references. STUDY SELECTION: Eight reports (involving 265 patients with depression) met the following 5 inclusion criteria: original research, published in English or French, population of general medical inpatients, mean age of depressed patients 60 years and over, and affective state reported as an outcome. The validity of the studies was assessed according to the criteria for prognostic studies described by the Evidence-Based Medicine Working Group. DATA EXTRACTION: Information about the patient population, the proportion of cases detected and treated by attending physicians, the length of follow-up, the affective outcome and the prognostic factors was abstracted from each report. DATA SYNTHESIS: All of the studies had some methodologic limitations. A meta-analysis of outcomes at 3 months or less indicated that 18% of patients were well, 43% were depressed and 22% were dead. At 12 months or more, 19% were well, 29% were depressed and 53% were dead. Factors associated with worse outcomes included more severe depression, more serious physical illness and symptoms of depression before admission. CONCLUSIONS: Elderly medical inpatients who are depressed appear to have a very poor prognosis: the recovery rate among these patients is low and the mortality rate high.     

The Wall Eclipsing Sign on Pulmonary Artery Computed Tomography Angiography Is Pathognomonic for Pulmonary Artery Sarcoma

Background

The objective of this study was to evaluate the imaging characteristics of pulmonary artery sarcoma (PAS) on pulmonary artery computed tomography angiography (PACTA) that can be used to differentiate between PAS and pulmonary thromboembolic diseases, including chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE).

Methods

The clinical data and imaging characteristics of 12 patients with PAS, 156 patients with CTEPH, and 426 patients with APE who were treated at Beijing Anzhen Hospital from January 2007 to August 2013 were retrospectively analyzed. All patients underwent PACTA before treatment, and the diagnoses of PAS and CTEPH were all confirmed by surgical biopsy.

Results

All 12 PAS patients were initially misdiagnosed and received inappropriate thrombolytic and/or anticoagulant therapy before they were referred for surgical intervention. The mean time from PACTA to surgical intervention was 5.5±3.7 months (range 2–11 months). On PACTA, the PAS lesion always eclipsed the wall of the pulmonary artery before infiltrating outside the pulmonary artery, which was termed the wall eclipsing sign. This sign was observed in all PAS patients but was not observed in any CTEPH or APE patients.

Conclusions

PAS is a rare neoplasm with a poor prognosis, and is easily misdiagnosed as thromboembolic disease. The wall eclipsing sign on PACTA is pathognomonic for PAS, and patients with this sign should be investigated to confirm the diagnosis and should undergo surgical intervention as soon as possible, rather than receiving thrombolytic or anticoagulant therapy.     

The impact of unemployment on health: a review of the evidence.

OBJECTIVE: To review the scientific evidence supporting an association between unemployment and adverse health outcomes and to assess the evidence on the basis of the epidemiologic criteria for causation. DATA SOURCES: MEDLINE was searched for all relevant articles with the use of the MeSH terms "unemployment," "employment," "job loss," "economy" and a range of mortality and morbidity outcomes. A secondary search was conducted for references from the primary search articles, review articles or published commentaries. Data and definitions of unemployment were drawn from Statistics Canada publications. STUDY SELECTION: Selection focused on articles published in the 1980s and 1990s. English-language reports of aggregate-level research (involving an entire population), such as time-series analyses, and studies of individual subjects, such as cross-sectional, case-control or cohort studies, were reviewed. In total, the authors reviewed 46 articles that described original studies. DATA EXTRACTION: Information was sought on the association (if any) between unemployment and health outcomes such as mortality rates, specific causes of death, incidence of physical and mental disorders and the use of health care services. Information was extracted on the nature of the association (positive or negative), measures of association (relative risk, odds ratio or standardized mortality ratio), and the direction of causation (whether unemployment caused ill health or vice versa). DATA SYNTHESIS: Most aggregate-level studies reported a positive association between national unemployment rates and rates of overall mortality and mortality due to cardiovascular disease and suicide. However, the relation between unemployment rates and motor-vehicle fatality rates may be inverse. Large, census-based cohort studies showed higher rates of overall mortality, death due to cardiovascular disease and suicide among unemployed men and women than among either employed people or the general population. Workers laid off because of factory closure have reported more symptoms and illnesses than employed people; some of these reports have been validated objectively. Unemployed people may be more likely than employed people to visit physicians, take medications or be admitted to general hospitals. A possible association between unemployment and rates of admission to psychiatric hospitals is complicated by other institutional and environmental factors. CONCLUSIONS: Evaluated on an epidemiologic basis, the evidence suggests a strong, positive association between unemployment and many adverse health outcomes. Whether unemployment causes these adverse outcomes is less straightforward, however, because there are likely many mediating and confounding factors, which may be social, economic or clinical. Many authors have suggested mechanisms of causation, but further research is needed to test these hypotheses.     

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). CONCLUSIONS: The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).     

Prognosis of delirium in elderly hospital patients.

OBJECTIVE: To determine the prognosis of delirium in elderly patients. DATA SOURCES: MEDLINE was searched for relevant articles published from January 1980 to March 1992. The bibliographies of identified articles were searched for additional references. STUDY SELECTION: Eight reports (involving 573 patients with delirium) met the following inclusion criteria: original research, published in English or French, prospective study design, diagnosis based on acute deterioration in mental state, sample of at least 20 patients, patients aged 60 years or over and follow-up of at least 1 week. The validity of the studies was independently assessed according to the criteria for prognostic studies established by McMaster University, Hamilton, Ont. No study met all the criteria. DATA EXTRACTION: Information about the patient sample, length of follow-up and results was systematically abstracted from each report and tabulated. DATA SYNTHESIS: A meta-analysis of the outcomes indicated that elderly patients with delirium had a mean length of stay of 20.7 days. One month after admission 46.5% were in institutions, and 14.2% had died; only 54.9% had improved mentally. Six months after admission 43.2% were in institutions. Compared with unmatched control subjects they had longer hospital stays, higher mortality rates at 1 month and higher rates of institutional care at 1 and 6 months. The presence of severe physical illness or dementia may have been related to some outcomes. CONCLUSIONS: Delirium in the elderly appears to have a poor prognosis. However, this finding may have been confounded by the presence of concomitant dementia or severe physical illness. Future studies must pay attention to methods and design, particularly the composition of study populations and the control of extraneous prognostic factors.     

Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement.

OBJECTIVE: To compare the efficacy and cost-effectiveness of enoxaparin, a low-molecular-weight heparin derivative, with that of low-dose warfarin in the prevention of deep-vein thrombosis (DVT) after total hip replacement. DATA SOURCES: English-language articles on enoxaparin and warfarin prophylaxis is patients undergoing total hip replacement published from January 1982 to December 1992. STUDY SELECTION: Four trials of enoxaparin (involving 567 patients) and six trials of warfarin (involving 630) met the following criteria: randomized controlled trial, prophylaxis started no later than 24 hours after surgery and continued for at least 7 days, warfarin dose monitored and adjusted appropriately, enoxaparin dosage 30 mg twice daily, and DVT confirmed by bilateral venography. DATA EXTRACTION: Rates of DVT, cost of prophylaxis, diagnosis and treatment per patient, rate of pulmonary embolism (PE), number of deaths and incremental cost-effectiveness (cost per life-year gained). DATA SYNTHESIS: The pooled rate of DVT was 13.6% with enoxaparin (95% confidence interval [CI] 10.9% to 16.3%) and 20.6% with warfarin (95% CI 17.4% to 23.8%). At a cost of $19.55 per day for enoxaparin the total cost per patient, including prophylaxis and management of DVT, exceeded that per patient receiving warfarin by about $121. For every 10,000 patients treated the use of enoxaparin will prevent 47 cases of DVT, 3 cases of PE and 4 deaths. Thus, the estimated incremental cost-effectiveness of enoxaparin is $29 120 per life-year gained. CONCLUSION: On the basis of current Canadian cost-effectiveness guidelines the results of this study would be considered moderate to strong evidence to adopt enoxaparin prophylaxis against DVT after total hip replacement. However, because of the limited data the estimates are uncertain. Future trials should compare enoxaparin and warfarin and incorporate a prospective economic appraisal.     

Effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal infection: results of a meta-analysis.

OBJECTIVE: To determine the effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal (GBS) infection in neonates of women whose birth canals are colonized by group B streptococci. DATA SOURCES: Articles published between 1966 and 1992 identified from MEDLINE, EMBASE, the Science Citation Index and the Oxford Perinatal Database; the bibliographies of primary studies, textbooks and review articles and published abstracts from major conferences and symposia. DATA SELECTION: Studies were selected if four criteria were met: (a) the target population was intrapartum women and neonates, (b) the intervention was penicillin prophylaxis, (c) invasive early-onset GBS infection was an outcome measure, and (d) the studies were controlled trials or cohort studies. Seven primary studies were identified, four of which were randomized controlled trials. DATA EXTRACTION: Explicit methodologic criteria were used by two of the authors to assess independently the study quality; one of the reviewers was blind as to author, institution and journal. The baseline characteristics of the population, intervention and outcome were summarized twice and checked for accuracy by two of the authors. DATA SYNTHESIS: Five of the studies showed a trend toward a beneficial effect of penicillin prophylaxis, and two showed a statistically significant effect. The pooled odds ratio indicated a 30-fold reduction (95% confidence interval 0.0013 to 0.17) in the incidence of early-onset GBS infection with intrapartum penicillin prophylaxis. Subgroup analyses did not change these results. The magnitude of improvement observed did not differ between women with prenatal risk factors (premature rupture of the membranes and premature labour) and those without these risk factors. CONCLUSIONS: There is accumulative evidence that intrapartum penicillin prophylaxis is effective in preventing early-onset GBS infection. Such therapy is beneficial to women whose birth canals are colonized with group B streptococci. Further studies are needed to determine the optimum timing and method of detecting vaginal colonization during pregnancy.     

tPA regulates pulmonary vascular activity through NMDA receptors

Tissue-type plasminogen activator (tPA) is a potent fibrinolytic enzyme used to treat acute coronary artery obstruction. However, tPA has shown limited utility in other disorders caused by thrombotic vascular occlusion, such as pulmonary embolism. We found that tPA caused dose-dependent effects on the contractility of pulmonary arterial rings that may affect its effectiveness as a thrombolytic agent. At low concentrations (1 nM), tPA stimulated pulmonary vascular contraction in response to phenylephrine, whereas at higher concentrations (20 nM) tPA inhibited pulmonary arterial contractility and promoted pulmonary vascular permeability through an interaction between its "docking site" and N-methyl d-aspartate receptor type 1 (NMDA-R1) expressed by pulmonary arteries. A hexapeptide derived from plasminogen activator inhibitor type 1 that blocked the docking site of tPA, but not its catalytic activity, inhibited its interaction with NMDA-R1, abolished inhibition of pulmonary artery contractility, attenuated vascular permeability, and facilitated fibrinolysis in a murine model of pulmonary embolism. Similar outcomes were seen using a tPA variant that lacks the docking site but retains catalytic activity. These data suggest that it is feasible to attenuate the deleterious extrafibrinolytic effects of tPA and improve its benefit:risk profile in the management of pulmonary embolism.     

Translating guidelines into practice: a systematic review of theoretic concepts,practical experience and research evidence in the adoption of clinical practice guidelines

OBJECTIVE: To recommend effective strategies for implementing clinical practice guidelines (CPGs). DATA SOURCES: The Research and Development Resource Base in Continuing Medical Education, maintained by the University of Toronto, was searched, as was MEDLINE from January 1990 to June 1996, inclusive, with the use of the MeSH heading "practice guidelines" and relevant text words. STUDY SELECTION: Studies of CPG implementation strategies and reviews of such studies were selected. Randomized controlled trials and trials that objectively measured physicians'' performance or health care outcomes were emphasized. DATA EXTRACTION: Articles were reviewed to determine the effect of various factors on the adoption of guidelines. DATA SYNTHESIS: The articles showed that CPG dissemination or implementation processes have mixed results. Variables that affect the adoption of guidelines include qualities of the guidelines, characteristics of the health care professional, characteristics of the practice setting, incentives, regulation and patient factors. Specific strategies fell into 2 categories: primary strategies involving mailing or publication of the actual guidelines and secondary interventional strategies to reinforce the guidelines. The interventions were shown to be weak (didactic, traditional continuing medical education and mailings), moderately effective (audit and feedback, especially concurrent, targeted to specific providers and delivered by peers or opinion leaders) and relatively strong (reminder systems, academic detailing and multiple interventions). CONCLUSIONS: The evidence shows serious deficiencies in the adoption of CPGs in practice. Future implementation strategies must overcome this failure through an understanding of the forces and variables influencing practice and through the use of methods that are practice- and community-based rather than didactic.     

Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.

OBJECTIVE--To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients. DESIGN--Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically. SETTING--53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another. RESULTS--Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy v 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% v 0.9%; 2P = 0.0001). There was a slight but non-significant excess of deaths from other causes (1.0% v 0.7%), which made the difference in total mortality nonsignificant, though still favourable (1.2% v 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone. The proportional reduction in the odds of suffering a deep venous thrombosis was roughly the same in patients having general surgery, traumatic orthopaedic surgery, and elective orthopaedic surgery (and in medical patients who were at increased risk of thromboembolism). For pulmonary embolism the numbers affected were smaller, but again the reductions were highly significant both in general surgery (16 (0.5%) v 58 (1.7%) pulmonary emboli; 2P < 0.0001) and in orthopaedic surgery (28 (2.7%) v 63 (6.1%) pulmonary emboli; 2P < 0.0002). CONCLUSION--It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy--either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin)--should be considered.     

利伐沙班用于急性肺栓塞的抗凝效果及对血清Hcy、BNP、TnI与D-D水平的影响

目的:探讨利伐沙班用于急性肺栓塞的抗凝效果及对血清脑钠肽(Brain natriuretic peptide,BNP)、肌钙蛋白I (Troponin I,TnI)、D-二聚体(D-Dimer,D-D)、同型半胱氨酸(homocysteine,Hcy)水平的影响。方法:选择2014年2月至2017年12月在我院进行治疗的(高)中危组急性肺栓塞患者106例,并将其随机分为观察组和对照组。对照组皮下注射低分子肝素钙搭配华法林治疗,观察组予以利伐沙班治疗,观察和比较两组患者的临床疗效、治疗前后血清BNP、TnI、D-D、Hcy水平的变化及不良反应的发生情况。结果:治疗后,观察组患者总有效率为94.37%,显著高于对照组(42.10%,P0.05);观察组患者血清BNP、TnI、D-D、Hcy及肺动脉收缩压水平均显著低于对照组(P0.05),而动脉收缩压、动脉血氧分压水平较对照组水平显著升高(P0.05)。结论:利伐沙班应用于治疗急性肺栓塞的抗凝效果显著优于低分子肝素钙搭配华法林治疗,其可有效降低患者血清BNP、TnI、D-D、Hcy水平以及肺动脉收缩压。     

Should we pay the patient? Review of financial incentives to enhance patient compliance.

OBJECTIVE: To determine whether financial incentives increase patients'' compliance with healthcare treatments. DATA SOURCES: Systematic literature review of computer databases--Medline, Embase, PsychLit, EconLit, and the Cochrane Database of Clinical Trials. In addition, the reference list of each retrieved article was reviewed and relevant citations retrieved. STUDY SELECTION: Only randomised trials with quantitative data concerning the effect, of financial incentives (cash, vouchers, lottery tickets, or gifts) on compliance with medication, medical advice, or medical appointments were included in the review. Eleven papers were identified as meeting the selection criteria. DATA EXTRACTION: Data on study populations, interventions, and outcomes were extracted and analysed using odds ratios and the number of patients needed to be treated to improve compliance by one patient. RESULTS: 10 of the 11 studies showed improvements in patient compliance with the use of financial incentives. CONCLUSIONS: Financial incentives can improve patient compliance.     

Aspirin Compared to Low Intensity Anticoagulation in Patients with Non-Valvular Atrial Fibrillation. A Systematic Review and Meta-Analysis

Background

Despite its lack of efficacy, aspirin is commonly used for stroke prevention in atrial fibrillation. Since prior studies have suggested a benefit of low-intensity anticoagulation over aspirin in the prevention of vascular events, the aim of this systematic review was to compare the outcomes of patients with non-valvular atrial fibrillation treated with low-intensity anticoagulation with Vitamin K antagonists or aspirin.

Methods

We conducted a systematic review searching Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, from 1946 to October 14^th, 2015. Randomized controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a low-intensity anticoagulation compared to patients treated with aspirin. The primary outcome was a combination of ischemic stroke or systemic embolism. The random-effects model odds ratio was used as the outcome measure.

Results

Our initial search identified 6309relevant articles of which three satisfied our inclusion criteria and were included. Compared to low-intensity anticoagulation, aspirin alone did not reduce the incidence of ischemic stroke or systemic embolism OR 0.94 (95% CI 0.57–1.56), major bleeding OR 1.06 (95% CI 0.42–2.62) or vascular death OR 1.04 (95% CI 0.61–1.75). The use of aspirin was associated with a significant increase in all-cause mortality OR 1.66 (95% CI 1.12–2.48).

Conclusion

In patients with non-valvular atrial fibrillation, aspirin provides no benefits over low-intensity anticoagulation. Furthermore, the use of aspirin appears to be associated with an increased risk in all-cause mortality. Our study provides more evidence against the use aspirin in patients with non-valvular atrial fibrillation.     

急性右下肢深静脉血栓的临床治疗分析

目的:探讨右下肢深静脉血栓的临床治疗方法。方法:对我院2015年6月-2017年6月收治的63例右下肢深静脉血栓形成患者进行回顾性分析,从小腿周径差、彩超检查及造影3方面对疗效进行评价,并统计导管接触溶栓后患者复查肺部增强CT情况。结果:63例患者中,57例进行导管接触溶栓+下腔静脉滤器,6例进行导管接触溶栓+下腔静脉滤器+肺动脉碎栓、溶栓。治疗后,患者小腿周径差较治疗前明显降低,差异具有统计学意义(P0.05)。患者显效26例,有效28例,好转8例,无效1例,临床治愈率为85.7%。63例下腔静脉滤器,取出60例,3例留置为永久性滤器。新增肺栓塞12例,无致死性肺栓塞发生。结论:导管接触溶栓对右下肢深静脉血栓的治疗效果较好,但导管接溶栓时有较高肺栓塞发生率,应积极放置下腔静脉滤器。