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Biomedical subjects

G Byrnes

Publications and source records attributed to G Byrnes.

16 recordsLinked to original sources

Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Surgery is considered the treatment of choice for patients with resectable stage I and II (and some patients with stage IIIA) non-small cell lung cancer (NSCLC), but there have been no previously published systematic reviews. METHODS: A systematic review and meta-analysis of randomised controlled trials was conducted to determine whether surgical resection improves disease specific mortality in patients with stages I-IIIA NSCLC compared with non-surgical treatment, and to compare the efficacy of different surgical approaches. RESULTS: Eleven trials were included. No studies had untreated control groups. In a pooled analysis of three trials, 4 year survival was superior in patients undergoing resection with stage I-IIIA NSCLC who had complete mediastinal lymph node dissection compared with lymph node sampling (hazard ratio estimated at 0.78 (95% CI 0.65 to 0.93)). Another trial reported an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small study reported a survival advantage among patients with stage IIIA NSCLC treated with chemotherapy followed by surgery compared with chemotherapy followed by radiotherapy. No other trials reported significant improvements in survival after surgery compared with non-surgical treatment. CONCLUSION: It is difficult to draw conclusions about the efficacy of surgery for locoregional NSCLC because of the small number of participants studied and methodological weaknesses of the trials. However, current evidence suggests that complete mediastinal lymph node dissection is associated with improved survival compared with node sampling in patients with stage I-IIIA NSCLC undergoing resection.

Carcinoma, Non-Small-Cell Lung↗

Surgery for early stage non-small cell lung cancer.

BACKGROUND: Surgical resection (usually lobectomy) is considered the treatment of choice for individuals with stage I and II non-small cell lung cancer (NSCLC) and for some patients with resectable stage IIIA NSCLC. However much of the evidence supporting surgery is observational. OBJECTIVES: To determine whether, in patients with early stage non-small cell lung cancer, surgical resection of cancer improves disease-specific and all-cause mortality compared with no treatment, radiotherapy or chemotherapy. To compare the effectiveness of different surgical approaches (e.g. lobectomy versus limited resection) in improving disease-specific or all-cause mortality in patients with early stage lung cancer. SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE (1966 to December 2003)), bibliographies, handsearching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing surgery alone (or in combination with other therapy) with non-surgical therapy and randomised trials comparing different surgical approaches. DATA COLLECTION AND ANALYSIS: A pooled hazard ratio was calculated where possible. Tests for statistical heterogeneity were performed. MAIN RESULTS: Eleven trials were included with a total of 1910 subjects. There were no studies with an untreated control group. In a pooled analysis of three trials, four-year survival was superior in patients with resectable stage I to IIIA NSCLC who underwent resection and complete mediastinal lymph node dissection compared with those undergoing resection and lymph node sampling, the hazard ratio was estimated to be 0.78 (95% CI 0.65-0.93, P = 0.005). A further trial found an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small trial found a survival advantage in favour of chemotherapy followed by surgery compared to chemotherapy followed by radiotherapy in patients with stage IIIA NSCLC. However none of the other trials included in the review demonstrated a significant improvement in survival in patients treated with surgery compared with non surgical therapy. Several of the included trials had potential methodological weaknesses. AUTHORS' CONCLUSIONS: Conclusions about the efficacy of surgery for local and loco-regional NSCLC are limited by the small number of participants studied to date and potential methodological weaknesses of trials. Current evidence suggests that lung cancer resection combined with complete mediastinal lymph node dissection is associated with a small to modest improvement in survival compared with lung cancer resection combined with systematic sampling of mediastinal nodes in patients with stage I to IIIA NSCLC.

Carcinoma, Non-Small-Cell Lung↗

Screening for lung cancer.

BACKGROUND: While population based screening for lung cancer has not been adopted by most countries, it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography are effective in reducing mortality from lung cancer. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000) ), bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effects model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Adult↗

Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation.

The majority of invasive aspergillosis (IA) in allogeneic stem cell transplantation (SCT) occurs during the post-engraftment period. We used Cox proportional hazards regression to evaluate post-engraftment IA risk in a cohort of 217 allogeneic SCT recipients from 1991 to 1998. The aim was to quantify the effects of dose-intensity and duration of corticosteroids and other risk factors. Median duration of follow-up was 330 days. There were 19 cases of IA (overall 8.8%) with 14 post-engraftment infections. In the final model, the risk of IA was greatest within 2 weeks of high-dose corticosteroids (HR 8.5, P=0.003), with risk extending to 4 weeks with doses of 0.25-1 mg/kg/day (HR 3.1, P=0.08). Ganciclovir was associated with greatest risk (HR 13.6). Grade 3 or 4 acute GVHD (HR 5.7) and secondary neutropenia (HR=1.3) were also additive risks. In the univariate analysis, corticosteroid doses of 0.25-1.0 mg/kg/day for any duration between 2 and 10 weeks demonstrated prolonged risk for IA. Moderate doses of corticosteroids can confer an increased risk for IA for extended periods which is almost as marked as that conferred by higher doses. Knowledge of these risks may facilitate the development of targeted surveillance and prophylaxis strategies for prevention of IA.

Adolescent↗

Head lice prevalence in primary schools in Victoria, Australia.

OBJECTIVES: To determine the prevalence of and assess risk factors associated with head lice infections (pediculosis) in children from government primary schools in Victoria, Australia. METHODS: Between May and October 2001, children were selected by clustered random sampling of schools and classes, then examined for head lice using hair conditioner and a fine-toothed head lice comb. There were 1838 children screened from 16 primary schools. Risk factors evaluated included metropolitan or rural residence, school class, gender and hair length. RESULTS: Thirteen percent of children (239/1838) had an active infection (95% CI, 10.9-15.1) and 3.3% (61/1838) had an inactive infection (95% CI, 2.0-4.6). Prevalence of active pediculosis varied between schools from 0 to 28%. Our screening identified no more than one case per class in the majority of classes screened (58.5%). Females were 2.2 times more likely to have active infection than males (95% CI [1.7,2.9]) and there was no significant difference for the other risk factors investigated. CONCLUSIONS: Our study demonstrated the prevalence of head lice varied across Victoria and showed that risk factors commonly attributed to head lice infections did not hold true. Our findings support the premise that traditional ad hoc mass school-based screening may not be the best use of resources when controlling head lice. We suggest a more pragmatic community-based approach.

Adolescent↗

Phyllodes tumor of breast.

Phyllodes tumors account for 0.3%-0.5% of all the breast tumors. They are usually benign but malignant variants exist and have the potential to metastasize. Surgery is the mainstay of treatment as there is no proven benefit of adjuvant chemotherapy or radiotherapy. Wider excision with 1 cm clear margins is recommended in cases where the resection margins are involved. Simple mastectomy is recommended even for large benign tumors as there is increased likelihood of recurrence. We are presenting a case of 42 years old female with benign phyllodes tumor and a brief review of literature on the subject.

Adult↗

Screening for lung cancer: a systematic review and meta-analysis of controlled trials.

BACKGROUND: Lung cancer is a substantial public health problem in western countries. Previous studies have examined different screening strategies for lung cancer but there have been no published systematic reviews. METHODS: A systematic review of controlled trials was conducted to determine whether screening for lung cancer using regular sputum examinations or chest radiography or computed tomography (CT) reduces lung cancer mortality. The primary outcome was lung cancer mortality; secondary outcomes were lung cancer survival and all cause mortality. RESULTS: One non-randomised controlled trial and six randomised controlled trials with a total of 245 610 subjects were included in the review. In all studies the control group received some type of screening. More frequent screening with chest radiography was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23). A non-statistically significant trend to reduced mortality from lung cancer was observed when screening with chest radiography and sputum cytological examination was compared with chest radiography alone (RR 0.88, 95% CI 0.74 to 1.03). Several of the included studies had potential methodological weaknesses. Controlled studies of spiral CT scanning have not been reported. CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. Frequent chest radiography might be harmful. Further methodologically rigorous trials are required before any new screening methods are introduced into clinical practice.

Controlled Clinical Trials as Topic↗

Safety and pharmacokinetics of intravitreal 2-methoxyestradiol implants in normal rabbit and pharmacodynamics in a rat model of choroidal neovascularization.

Choroidal neovascularization (CNV) is the leading cause of severe vision loss associated with age-related macular degeneration. As the pathogenesis of CNV formation is better understood, mechanism-based therapies, including the use of antiangiogenesis inhibitors, have been investigated. 2-methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been shown in the chick allantoic membrane model and the corneal micropocket assay to have antiangiogenic properties. The authors sought to determine the safety and pharmacokinetics of sustained-release intravitreal 2ME2 implants in normal rabbit and their efficacy in a rat model of CNV. 2ME2 implants were constructed using two designs: implant A, a silicone-based reservoir implant for the rabnbit eye, and implant B, a microimplant matrix design for the rat eye. In vitro release rates of both implants were determined. New Zealand white (NZW) rabbits had implant A placed in the vitreous cavity of one eye and the ocular toxicity was evaluated by clinical examination, serial electroretinography (ERG), and histopathology over a 28 week period. The steady state clearance of 2ME2 in the rabbit eye was calculated from in vivo release rates divided by steady state vitreous concentrations. A CNV model in the Brown-Norway rat was performed by injecting an adenoviral vector encoding human vascular endothelial growth factor in the subretinal space. Following the injection, a 2ME2 or sham (no drug) microimplant was placed in the vitreous cavity. Animals were killed over a 3 week period and the eyes examined for CNV by histopathology. Results showed that following a short burst, the release rate of implant A followed zero-order kinetics, typical of reservoir devices, and the cumulative release of implant B was proportional to the square root of time, as expected for a matrix delivery device. The safety studies in normal rabbit showed no ocular toxicities by clinical examination, ERG, and histopathology. Pharmacokinetic evaluation in the rabbit showed mean 2ME2 vitreous levels within the therapeutic range for the inhibition of endothelial cell proliferation. The experimental rat model showed a significant reduction in CNV in eyes treated with the 2ME2 implant. In conclusion, sustained-release 2ME2 intravitreal implants, which can be designed to deliver potentially therapeutic vitreous levels of 2ME2 for an extended period of time, appeared to be safe in normal rabbit and effective in a rat model of CNV. Sustained-release 2ME2 intravitreal implants may hold promise in the treatment of recurrent CNV refractory to standard therapy.

2-Methoxyestradiol↗

Screening for lung cancer.

BACKGROUND: The effectiveness of screening for lung cancer with chest radiography, sputum cytology or spiral CT has not been established. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases, bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effect model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Adult↗

Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy.

We describe the risk factors for and the natural history and response to treatment of extramedullary (EM) relapse in 183 patients who underwent allogeneic bone marrow transplantation (alloBMT) for a variety of haematological malignancies at our institution over a 7 1/2 year period. Fifty-one patients relapsed; 15 had EM relapse either alone or in association with marrow involvement. A retrospective analysis found that the presence of chronic GVHD and a longer interval between transplant and relapse were independently associated with an increased risk of EM compared to marrow-only relapse. EM relapse was also associated with a longer post-relapse survival. Patients with EM relapse appeared to respond to cytotoxic therapy but not to DLI. EM relapse after alloBMT may be more common than previously thought and have a better prognosis than marrow-only relapse. While patients developing chronic GVHD after alloBMT have a lower overall relapse risk than those who do not, they may be more prone to delayed relapse at EM sites.

Adolescent↗

Perception of social value predicts participation in school-based research.

OBJECTIVE: To investigate factors affecting the participation of schools in a serosurvey. METHODS: A telephone interview was conducted with a representative of 80 schools (response rate 92%). The schools had been randomly selected to participate in a seroprevalence survey evaluating a measles vaccination campaign of Victorian school-aged children in 1998. RESULTS: Univariate analysis suggested that responses to the interview were not influenced by school level (primary/secondary), geographic location, funding source or participation in the seroprevalence survey. There was, however, a strong association of participation in the seroprevalence survey with the perception of value to students and the value to the community. Factor analysis identified two issues: the societal value and practical issues, which explained most of the variance in participation (pseudo R2 = 0.84). CONCLUSION: The perception of the benefits of the study strongly influenced the decision by school representatives to participate in the seroprevalence survey. IMPLICATIONS: Recruitment of schools for health-related research may be improved if the number of research projects in schools is monitored and possibly restricted, and the social value of the research is emphasised.

Adolescent↗

Choroidal neovascularization in the rat induced by adenovirus mediated expression of vascular endothelial growth factor.

PURPOSE: To determine the effects of an adenovirus vector encoding vascular endothelial growth factor(165) (Ad.VEGF) delivered to the subretinal space in the rat. METHODS: An E1-deleted adenoviral vector encoding VEGF was injected into the subretinal space of Long-Evans rats. Immunohistochemistry identified VEGF expression. Histopathologic changes in the retina were determined by light and electron microscopy, immunohistochemistry, fluorescein angiography, and examination of wholemounts of choroid and retina. RESULTS: Increased expression of VEGF only in the retinal pigment epithelium (RPE) was detected after Ad.VEGF injection. Histopathology of these eyes revealed minimal subretinal exudation at 1 week followed by the appearance of vascular structures in the subretinal space by week 2, which persisted up to 4 weeks. Shortening of photoreceptor outer segments and reduction of the outer nuclear layer were present overlying areas of neovascularization. Fluorescein angiography of animals injected with fluorescein-dextran revealed a deep complex of new vessels. Choroidal flatmounts showed new vessel formation, verified by detection of endothelial cells via immunohistochemistry, arising from the choroid with absence of change in the overlying retinal vasculature. Electron microscopy confirmed the presence of sub-RPE endothelial cells and pericytes and the loss of integrity of Bruch's membrane, and serial sectioning demonstrated choroidal vascular growth through Bruch's membrane. CONCLUSIONS: These results support the hypothesis that overexpression of VEGF from RPE cells is capable of inducing choroidal neovascularization in the rat and provide a framework for further examining angiogenic processes in the RPE-choroid complex.

Adenoviruses, Human↗

Crisis calls and lunar cycles: a twenty-year review.

12 studies are reviewed that have examined the relationships among crisis calls to police stations, poison centers, and crisis intervention centers and the synodic lunar cycle. On the basis of the studies considered it is concluded that no good foundation exists for the belief that lunar phase is related to the frequency of crisis calls. In addition, there is no evidence whatsoever for the contention that calls of a more emotional or "out-of-control" nature occur more often at the full moon.

Crisis Intervention↗

Diagnostic yield of gastroscopy in a general surgical unit.

Gastroscopy is the gold standard for investigating upper gastrointestinal complaints. Open access gastroscopy has advantages, but may not always be feasible in a small unit. Our 2-consultant general surgical unit provides gastroscopy on demand for medical and surgical patients. We audited the 499 gastroscopies carried out in our unit in 1997 to assess yield and diagnostic trends. The overall diagnostic yield of 69 per cent was comparable with published data from centres in Ireland and overseas. Diagnostic yield in our series was significantly lower for medical patients (59 per cent) than for surgical patients (72 per cent) (p < 0.05). Yield also varied considerably according to indication for referral. Patients referred with anaemia had a low yield (41 per cent). The indications associated with high yields were haematemesis (95 per cent), dysphagia (91 per cent), and persistent vomiting (85 per cent).

Adolescent↗

The injury potential of Fogarty balloon catheters.

The problem of arterial injury following embolectomy using a balloon catheter is reviewed. Three illustrative clinical cases are presented. The cause of the arterial injury in these cases was due to rupture of the vessel. The hypotheses were that either the vessel was ruptured by direct penetration or bursting by overdistension of the balloon. The linear appearances of the arterial tear in two patients and a false aneurysm in the third suggested that bursting was the correct explanation. Laboratory investigation was carried out on animals and human cadavers and these confirmed that arterial injury and bursting can be caused by over-distension of the balloon catheter. If the maker's recommendations are strictly adhered to; that is, the balloon should not be over-inflated and the correct volume of fluid used then rupture of the artery is unlikely by occur.

Aged↗