Haemoptysis as a late presentation of aneurysm leakage after aortic coarctation repair: the case for vigilant lifelong radiology surveillance?
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OBJECTIVE: The aim of this study was to compare the cosmetic appearance and related complications of selected skin lacerations closed by traditional suture technique with that of the dynamic sliding loop suture technique. DESIGN: Prospective, randomised clinical trial. SETTING: A district general hospital. PARTICIPANTS: Thirty seven eligible patients aged between 16 and 60 years with skin lacerations (no deeper than superficial fascia) to the limbs, trunk, and neck (excluding face and scalp) and with no associated neurovascular or tendon injuries were recruited into the trial. The exclusion criteria used included immunocompromised patients (diabetics, malignancy, renal failure, corticosteroid treatment), primary dermatological conditions (psoriasis, eczema), keloid prone or susceptible patients, and wounds judged unsuitable for primary closure. INTERVENTION: Skin lacerations were randomly allocated to have closure by either the traditional method or by use of the dynamic sliding loop suture method. The trial had ethical approval of the hospital ethics committee and all participants were fully informed of the trial both verbally and by an information leaflet. Written informed consent was obtained before starting the study. MAIN OUTCOME MEASURE: The cosmetic appearance of photographs of wounds immediately after suture removal and at three months were assessed by a general surgeon and an orthopaedic surgeon blinded to the technique used. The 10 point visual analogue cosmesis scale was used for scoring the appearance of the wounds. SECONDARY OUTCOME MEASURE: The presence of wound closure related complications such as infection, dehiscence, suture slippage, wound edge submergence, skin edge necrosis, and haematoma formation were noted and recorded on follow up visits. RESULTS: A total of 37 patients participated in the trial over a period of 18 months. Seventeen patients underwent suture by the traditional technique and 20 by the dynamic sliding loop suture technique. Four patients (all from the traditional group) were lost to follow up and not included in the study. Most wounds healed uneventfully although there was one case of wound infection in each group. Four patients had ligature slippage (three from the dynamic suture and one from the traditional group). Two patients had evidence of skin edge necrosis both from the traditional technique group. A comparison of the healed wounds by two independent assessors blinded to the technique used showed no statistically significant difference observed between the two types of intervention (Wilcoxon matched paired test p>0.05) immediately after suture removal or at three months. Although there was no statistically demonstrable difference, the comparative paired absolute visual analogue scores seemed to consistently show higher values for the sliding loop technique. CONCLUSION: The cosmetic appearance of wounds sutured using the dynamic sliding loop suture technique in this study were not statistically shown to be superior to those sutured using the traditional suture technique although absolute visual analogue scores consistently showed higher values for the sliding loop technique. The significance of this is unclear and may warrant a much larger trial to see if it is a trend that a larger population of participants can help to support or refute with regard to the superiority of this new technique.
BACKGROUND: The relationship between changes in intracranial pressure and incidence of subclinical seizures in patients requiring neurological intensive care is not fully understood. The aim of this study was to investigate if acute increases in intracranial pressure were accompanied by subclinical seizures. METHODS: We prospectively studied 17 intensive care patients (11 male, aged 3-66 yr) who were selected from 85 patients requiring intracranial pressure measurement. Patients were selected to have a 30 min, 16-channel electroencephalogram (EEG) recorded when intracranial pressure remained increased despite preliminary treatments. RESULTS: Diagnoses included head injury, intracranial haemorrhage, subarachnoid haemorrhage and sagittal sinus thrombosis. All patients had at least one acute episode of intracranial pressure increase. Pressures ranged from 90 to 440 mm H(2)O. Encephalopathic features (delta/theta rhythms and burst suppression) were noted on all EEGs. No seizure activity was recorded. CONCLUSIONS: We conclude from this pilot study that seizures are an uncommon cause of acute raised intracranial pressure. To determine whether raised intracranial pressure causes seizures, long-term monitoring in a large cohort of intensive care patients would be necessary, studying patients with similar diagnoses and ages.
OBJECTIVE: The objective of this study was to better understand neutropenia induced by standard dose chemotherapy and to verify if there are any hematological parameters for defining the phase and possibly the duration of neutropenia. METHODS: The kinetics of large unstained cells (LUCs) and lymphocytes was evaluated in 324 blood counts of 56 chemotherapy cycles through the use of a Technicon H2 or an ADVIA 120 hematology analyzer. Blood samples collected during the neutropenia phase were also studied by flow cytometry using a large panel of monoclonal antibodies. Parametric and nonparametric statistics were employed to compare the different variables analyzed. A linear regression between each variable before and after nadir and a simple linear correlation among the same variables in the neutropenic and recovery phase were performed. RESULTS: The percentage of LUCs reaches the higher value at nadir and the difference between the mean value of prenadir and nadir is statistically significant (P <.01). The number of LUCs increases during the pre and postnadir phase. Lymphocytes number appears stable in the prenadir phase. The MPXI index increases in the prenadir phase and falls at nadir and this difference is statistically significant(P <.01). LUCs are correlated with blasts and CD34+ cells in the pre and postnadir phase, with CD3+/CD4+ cells in the prenadir phase, and with CD2+/CD56+ in the postnadir phase. CONCLUSIONS: Our data have shown that the estimation of both percentage of LUCs and MPXI can predict the neutropenia phase and orient for its duration. The lymphocyte number may be regarded as a parameter of risk of fever after day 5 of chemotherapy and the number of blood CD34+ cells may be predicted by LUC count.
There has been recent interest in developing a health technology assessment (HTA) function in Estonia. A group of individuals knowledgeable about HTA in Canada, Germany, Romania and Spain, along with representatives of the University of Tartu, Estonia, was convened by the Institute of Health Economics in Edmonton, Canada, to consider options for such a function. In a one-day workshop strengths, weaknesses, opportunities and threats (SWOT) analyses of HTA were conducted, first at a 'global' level, and then of the Estonian situation. The 'global' SWOT analysis yielded a large number of items that pertain to institutionalized HTA in a generic sense, i.e. not based on any individual HTA agency. The 'Estonian' SWOT yielded a subset of items, which pertain to development of HTA in that country. Ten actionable steps were then developed on the basis of this subset, which could be used to initiate the creation of an HTA body in Estonia.
Bifrontal decompressive craniectomy has been used on an ad hoc basis for the treatment of post-traumatic intracranial hypertension for more than thirty years. In this observational study we report the clinical outcome and physiological effects of the procedure in a series of 26 patients with refractory intracranial hypertension treated on a protocol driven basis. Bifrontal decompressive craniectomy was associated with significant reductions in mean ICP from 37.5 to 18.1 mmHg (p = 0.003). In addition, craniectomy reduced the amplitude of ICP waves (p < 0.02) and increased compensatory reserve (p < 0.05). A favourable outcome was achieved in 69% of patients; 8% were severely disabled and 23% died. We conclude that this study provides pathophysiological evidence that bifrontal decompressive craniectomy significantly reduces posttraumatic intracranial hypertension and improves pressure dynamics. Our results support the continued use of bifrontal decompressive craniectomy in selected patients after head injury.
INTRODUCTION: Sonography has found a role in the evaluation of patients with abdominal injury. However, the accuracy of sonography as performed by non-radiologists remains controversial. This study aims to determine the accuracy of focused abdominal sonography for trauma when performed by surgeons. MATERIALS AND METHOD: Over a 1-year period, 48 patients with abdominal injury were initially evaluated for free intraperitoneal fluid by sonography. These tests were performed by 2 surgeons who had received instructions and performed a minimum of 30 examinations. Sonographic findings were then compared with other diagnostic modalities including computed tomography (CT) scan, diagnostic peritoneal lavage and exploratory laparotomy. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for sonography were found to be 0.86, 0.92, 0.89, 0.90 and 0.89, respectively. Although not specifically sought for, 2 cases of solid organ injury and 1 haemothorax, which were missed in initial examinations and X-rays, were detected on sonography. CONCLUSION: In conclusion, our initial experience suggests that local surgeons can perform a focused sonographic examination for trauma with acceptable accuracy. Although sonography lacks the sensitivity of diagnostic peritoneal lavage and the accuracy of CT scan, the diagnostic algorithm for abdominal trauma should include sonography as a screening test.
Economic evaluation is a component of health technology assessment. Methods for economic evaluation began to be developed about 30 years ago. More recently, governments have encouraged the development of methodological and reporting guidelines for economic evaluation in health care with the major focus being placed on pharmaceutical products. There are two aspects of economic evaluations discussed in the present paper: the science of the techniques used and the utility of the resulting evaluations. Although activity is increasing in this area, it is still not clear how useful such 'value for money' evaluations have actually been and how much they have been used. It seems that the 'value for money' of 'value for money' evaluations of pharmaceutical products has yet to be shown.
Modifications of body composition are frequent in cancer patients. Bioelectric impedance analysis can specifically detect changes in tissue electric properties, which may be associated with outcome. We evaluated the distribution of the impedance vectors from 63 adult male patients with lung cancer, stages IIIB (33 patients) and IV (30 patients), in supportive therapy. Body weight change over the previous 6 m.o. was the same in both groups (stable/increased 36% and decreased in 62%). Patients were compared with 56 healthy subjects matched for gender, age, and body mass index (25 kg/m2). Impedance measurements (standard tetrapolar electrode placement on the hand and foot) were made with 50-kHz alternating currents. The resistance and reactance of the vector components were standardized by the height of the subjects and were plotted as resistance/reactance graphs. The impedance vector distribution was the same in patients with either stage IIIB or IV cancer. The mean vector position differed significantly between cancer patients and control subjects (Hotelling T2 test, P < 0.01) because of a reduced reactance component (i.e., a smaller phase angle) with preserved resistance component in both cancer groups. Patients with a phase angle smaller than 4.5 degrees had a significantly shorter, i.e., 18 m.o., survival. Body weight loss was not significantly associated with survival. In conclusion, impedance vectors from lung cancer patients were characterized by a reduced reactance component. The altered tissue electric properties were more predictive than weight loss of prognosis.
OBJECTIVES: Since 1988, four government-funded health technology assessment (HTA) agencies have been established in Canada. This paper is a descriptive review of reports issued by these organizations during the period from 1988 to 1998. METHODS: Publications from the national and three provincial HTA agencies in Canada were obtained and reviewed. Only the 117 assessment reports that were reported to have undergone external review were included in this analysis. Each report was classified on a standard abstraction form according to criteria such as technology type(s), assessment focus, whether a specific policy question was clearly stated and relevant decision maker(s) identified, description of search strategy and selection criteria, sources of data and assessment methods used, whether recommendations or conclusions were made, and duplication or overlap of reports. The trends in these qualities over the 10-year period were also examined. RESULTS: Therapeutic technologies have received the most attention from all four agencies, although the focus on devices, drugs, and procedures varied between agencies. The policy question under investigation was clearly identified in 82% of reports, and 71% clearly identified the decision maker toward whom the assessment was targeted. Efficacy or effectiveness was examined in 81% of reports, and costs were assessed in 65% of studies. These were the two most frequently examined aspects. Almost all assessments were descriptive literature reviews; 9% included meta-analyses and 32% had cost analyses or economic evaluations. Forty-four percent of reports had a clear description of the literature search strategy, and selection criteria were clearly specified in 38% of studies, but there was considerable variation among agencies in the level of description of these methods. Conclusions were clearly stated in 83% of the assessments' conclusions, and 13% had recommendations. When analyzed longitudinally, it is apparent that the quality of reports has improved markedly during the past decade. This was determined by examining the clarity of specifying the policy question(s) under investigation, the identification of the target audience of decision makers for the information, and by evaluating the thoroughness of the description of the methods used in the assessment. CONCLUSIONS: Canadian government agencies have contributed a considerable quantity of health technology assessments. There has been very little duplication of technologies evaluated, and the quality of the assessment reports has markedly improved during the past decade.
Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) might increase the risk of cerebral ischaemia while stabilizing the clot at the site of aneurysmal rupture, an open-label, dose-escalation safety study has been developed in collaboration with the UK Spontaneous Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid haemorrhage verified by computerized tomography scan or lumbar puncture. Safety evaluation includes clinical observation, monitoring of laboratory variables, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO2) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven 80 microg/kg single bolus (n = 2), NovoSeven 80 microg/kg single bolus followed by continuous infusion at 3.5 microg/kg per h (n = 2) or 7 microg/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcranial Doppler ultrasound and PET studies revealed no evidence of cerebral ischaemia in the first nine patients treated with NovoSeven. The last patient developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation.
OBJECTIVE: The objective of this study was to develop an instrument that will assist in evaluating the methodological quality of drug utilization reviews (DURs) and studies of prescribing appropriateness. DESIGN: An expert committee followed accepted steps for developing and testing new instruments. Consultations on content, face validity, and scoring of items were solicited from external experts. Seven raters tested an initial version; subsequently, a refined instrument was designed. The Edmonton Quality Assessment Tool for Drug Utilization Reviews (EQUATDUR-2) evaluates 3 domains: sample selection (1 item), data collection (1 item), and data analysis (3 items). Sixteen raters tested EQUATDUR-2 on a random sample of DURs. MEASURES: The study measures were reliability-using random effects interclass correlation coefficients for ratings by individual raters (ICC2,1) and the mean of ratings (ICC2,k)-and variability between DUR quality levels and rater groups. RESULTS: There were significant differences in methodological quality (P <0.001) and in mean scores comparing low-, moderate-, and high-quality DURs. Nonmethodologists' ratings exhibited significant variability (P = 0.03) and tended to be higher. Agreement varied for individual items (ICC2,1, 0.22 to 0.44; ICC2,k, 0.81 to 0.91) and for mean summary ratings (ICC2,1, 0.42 [95% CI, 0.28 to 0.61]; ICC2,k, 0.92 [95% CI, 0.86 to 0.96]). The average time to rate each DUR was 10.0 minutes (95% CI, 9.2 to 10.9). CONCLUSIONS: EQUATDUR-2 is a succinct, self-administered instrument with evidence of validity and reliability. We recommend that > or =2 raters independently assess each DUR and resolve disagreements by consensus. EQUATDUR-2 will help clinicians and decision makers to evaluate the quality of DUR studies and provide a framework for enhancing rigor in the design, conduct, and reporting of DURs.
Drug utilization review (DUR) is a tool for monitoring the appropriateness of physicians' prescribing patterns. The present systematic overview was undertaken to determine the extent of appropriate use of oral quinolones, cephalosporins, and macrolides in nonacute-care settings in North America reported in published DUR studies. Potentially relevant DURs conducted since 1987 were retrieved from an electronic search of 6 databases (augmented by manual searches of bibliographies of appropriate articles) and from personal communications with local experts. Independent reviewers applied objective criteria to select the DURs for inclusion. Quality assessments were performed by 4 independent reviewers using the Edmonton Quality Assessment Tool for Drug Utilization Reviews, an instrument developed to assess the potential for systematic bias in a DUR. Data from the studies included were abstracted independently by 2 reviewers using a standard data-collection form. Twelve of 587 (2.0%) articles met the inclusion criteria. Eight studies targeted the appropriateness of prescriptions for ciprofloxacin (appropriateness range, 5% to 95%), 3 included cephalosporins (range, 0% to 100%), and 2 examined erythromycin (40%). There were 2 primary reasons for a rating of inappropriate: (1) the prescription was not first-line therapy, or (2) there was insufficient documentation in the patient record. The designation inappropriate did not mean that the drug did not benefit the patient. Of the 4 intervention-based DURs, 1 study showed a significant improvement in appropriate use. Because of heterogeneity in study design, delivery of interventions, and outcome assessment, a pooled estimate of effect was not derived. Four studies estimated the cost of inappropriate prescribing to the institutional study site, which ranged from $20,500 to $173,359 annually; however, these estimates cannot be generalized because of various limitations. When the 12 studies were assessed for methodologic quality, 1 study was rated as high, 7 as moderate, and 4 as low. Levels of prescribing appropriateness reported in the DUR literature should be interpreted cautiously. The DUR studies included in this review varied greatly in the methodologic rigor applied to sample selection, standardized data collection, application of standardized screening criteria, and validated data analysis.
The purpose of this article is to report on the results of a workshop that introduced evidence-based decision-making techniques to Board members of regional health authorities in Alberta. results and conclusions: The workshop demonstrated that it is possible to design a process for the incorporation of evidence in administrative decision-making. The participants demonstrated that they were able to apply scientific evidence in administrative decision making and that the decisions taken were reasonably consistent. Also, in the absence of evidence, values took precedence in the decision-making process and the decisions taken were less consistent.
The need for better communication and collaboration between health technology assessment agencies led to the formation of an International Network of Agencies for Health Technology Assessment (INAHTA). The network now comprises 27 agencies and has been successful in improving exchange of information and in undertaking joint health technology assessment projects. Issues for the future include possible changes to criteria for membership and identification of resources for more extensive programs.
We have assessed the use of cetrorelix, a gonadotrophin releasing hormone (GnRH) antagonist, in conjunction with clomiphene citrate and gonadotrophin in 31 in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) cycles for 25 difficult responders. Group I included 18 poor responders (24 cycles) with no live birth in 23 previous IVF cycles with GnRH agonists. Group II included seven patients (seven cycles) with polycystic ovaries. Thirteen previous IVF/GIFT cycles with GnRH agonists had resulted in one live birth and three of these patients had developed ovarian hyperstimulation syndrome (OHSS). The treatment protocol involved a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections from cycle day 2. Cetrorelix 0.25 mg/day was started when the leading follicle reached 14 mm. The outcome in both groups was favourable compared to previous treatment with GnRH agonists. In group I the abandoned cycle rate was 29 versus 57% (P = 0.06). More oocytes were produced (6.4 versus 4.7 oocytes/cycle) at a lower dose of follicle-stimulating hormone (FSH) (709 versus 1163 IU/oocyte; P = 0.08) and two live births resulted (11.8%). In group II fewer oocytes were produced (10.2 versus 14.5 oocytes/cycle), using a lower dose of gonadotrophin (170 versus 189 IU/oocyte) and resulted in one ongoing pregnancy. No patients experienced OHSS. This report is preliminary and a further controlled randomized study is required.
The first edition of the Guidelines for Economic Evaluation of Pharmaceuticals: Canada was published in November 1994. At that time, the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) was assigned the task of maintaining and regularly updating the Canadian Guidelines. Since their introduction, a great deal of experience has been gained with the practical application of the guidelines. Their role has also evolved over time, from being a framework for pharmacoeconomic research to the point where a wide variety of decision-makers use economic evaluations based on the principles set out in the guidelines as a means of facilitating their formulary decisions. In addition, methodologies in certain areas (and the body of related research literature in general) have developed considerably over time. Given these changes in the science and the experience gained, CCOHTA convened a multi-disciplinary committee to address the need for revisions to the guidelines. The underlying principles of the review process were to keep the guidance nature of the document, to focus on the needs of 'doers' (so as to meet the information needs of 'users') and to provide information and advice in areas of controversy, with sound direction in areas of general agreement. The purpose of this review is three-fold: (i) to outline the process which lead to the revision of the Canadian Guidelines; (ii) to describe the major changes made to the second edition of this document; and (iii) to consider the 'next steps' as they relate to the impact of such guidelines and the measurement of outcomes related to economic assessments of pharmaceuticals in general.
OBJECTIVE: To assess the goals, strategic focus, structure, capabilities, activities and effectiveness of health economics (HE) departments in the Canadian pharmaceutical industry, to examine how these have evolved, and the implications of HE in the future of the pharmaceutical industry. DESIGN AND INTERVENTIONS: A mixture of telephone and face-to-face interviews with members of the HE unit (survey 1) and the chief executive officers (CEOs) [survey 2] of the top 21 Canadian pharmaceutical companies was undertaken in 1997. MAIN OUTCOME MEASURES AND RESULTS: 17 out of 21 companies responded to the first survey, and 12 of the 17 CEOs responded to our second survey. The goals of the HE department in most of the pharmaceutical companies have evolved from supporting efforts to gain reimbursement on government drug plans to include pricing, promotion, internal decision-making and other activities. Members of the HE department perceive their work to be valuable to the company. The CEOs felt that the true value of HE data is not adequately understood by formulary reviewers and, therefore, HE data may be an impediment to market access. CONCLUSIONS: The purpose of the HE department is to demonstrate the value of the company's product to provincial government insurers. However, pharmaceutical companies are having difficulty justifying the importance of the HE department because of inconsistencies in the interpretation of economic evaluations by healthcare payers.