The clinical effectiveness and cost-effectiveness of vinorelbine for breast cancer: a systematic review and economic evaluation.
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Biomedical subjects
Publications and source records attributed to R Lewis.
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BACKGROUND: Epidemics of meningococcal disease in Africa are commonly detected too late to prevent many cases. We assessed weekly meningitis incidence as a tool to detect epidemics in time to implement mass vaccination. METHODS: Meningitis incidence for 41 subdistricts in Mali was determined from cases recorded in health centres (1989-98) and from surveillance data (1996-98). For incidence thresholds of 5 to 20 cases per 100000 inhabitants per week, we calculated sensitivity and specificity for detecting epidemics, and determined the time lapse between threshold and epidemic peak. FINDINGS: We recorded 9084 meningitis cases. Clinic-based weekly incidence of 5 and 10 cases per 100000 inhabitants detected all meningitis epidemics (sensitivity 100%, 95% CI 93-100), with median threshold-to-peak time of 5 and 3 weeks. Under-reporting reduced sensitivity: only surveillance thresholds of 5 or 7 cases per 100000 inhabitants per week detected all epidemics. Crossing the lower threshold before the 10th calendar week doubled epidemic risk relative to crossing it later (relative risk 2.1, 95% CI 1.4-3.2). At 10 cases per 100000 inhabitants per week, specificity for outbreak prediction was 88%, 95% CI 83-91). For populations under 30000, 3 to 5 cases in one or two weeks predicted epidemics with 85% to 97% specificity. INTERPRETATION: Low meningitis thresholds improve timely detection of epidemics. Ten cases per 100000 inhabitants per week in one area confirm epidemic activity in a region, with few false alarms. An alert threshold of 5 cases per 100000 inhabitants per week allows time to investigate, prepare for an epidemic, and initiate mass vaccination where appropriate. For populations under 30000, the alert threshold is two cases in a week. High quality surveillance is essential.
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This is a lightly edited version of Roger Lewis' notes for the speech he gave at the 11th International Conference on the Reduction of Drug Related Harm in Jersey in March 2000, shortly before his death. In this paper Roger Lewis argues for the need to take global and historical view of both drug markets and ways that nations try to control them. Drug markets have become globalised, influenced by changes in communication, finance, commodity and labour markets. Drug control activities are used to defend global strategic interests, amd foreign policy imperatives usually take precendence over drug policy.
Spiders (Araneae) spin high-performance silks from liquid fibroin proteins. Fibroin sequences from basal spider lineages reveal mosaics of amino acid motifs that differ radically from previously described spider silk sequences. The silk fibers of Araneae are constructed from many protein designs. Yet, the repetitive sequences of fibroins from orb-weaving spiders have been maintained, presumably by stabilizing selection, over 125 million years of evolutionary history. The retention of these conserved motifs since the Mesozoic and their convergent evolution in other structural superproteins imply that these sequences are central to understanding the exceptional mechanical properties of orb weaver silks.
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OBJECTIVES: To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). METHODS: A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire. RESULTS: Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P <0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P <0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events. CONCLUSIONS: Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.
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The purpose of this study was to analyze the outcome of elderly burn victims and to determine an instrument to predict survival in this population. Charts of three hundred and eight burn patients > or =60 yr of age who were admitted to a university-based hospital between the years of 1977-1996 were retrospectively analyzed. The mean age of the population was 71.5+/-8.6, with a male predominance (1.8 to 1, P < 0.001). The majority of the burns were secondary to flame injuries (210, 68.6%). The median body surface area (BSAB) was 13.0% with an in-hospital mortality rate of 30.2%. We demonstrated improved survival in patients aged 60-74 yr as compared to 1965-1971 national burn survival data. A similar trend could not be shown in the very old (> 75 yr of age). Only age and BSAB were related to death by multiple stepwise forward linear regression. The Baux score, which adds age and BSAB, was predictive of outcome in 87.0% of our population. In conclusion, this study reinforces the high mortality associated with burn injuries in the elderly and the superior ability of the Baux score (age + percent burn) in predicting outcome in this population.
Studies in this laboratory are designed to determine the effects of vasoconstrictor agents on the erectile response in rats. We have previously demonstrated that the vasoconstrictor effect of endothelin-1 (ET-1) is sharply reduced by erection and by nitric oxide (NO) administration. The present study was performed to determine if vasoconstriction, resulting from alpha-adrenergic stimulation, is altered by erection and NO. During continuous monitoring of corpus cavernosum pressure (CCP) and mean arterial pressure (MAP), erection was induced by electrical stimulation of the autonomic ganglion for the innervation of the penis. When the alpha-adrenergic agonist methoxamine (METH, 10 microg/kg) was injected before erection (ie, into the non-erect penis), the subsequent erectile response (CCP/MAP) was significantly reduced from 0.68+/-0.03 before METH to 0.34+/-0.08 after METH. Injection of METH into the erect penis (ie, during erection) reduced the vasoconstrictor action of METH; CCP/MAP was 0.74+/-0.02 before METH and 0.55+/-0.05 after METH (P<0.05). The vasoconstrictor action of METH was slightly reduced when given in conjunction with NOR-1, a NO donor drug; CCP/MAP was 0.70+/-0.05 before METH, 0.55+/-0.09 after METH but this change was not significant. These results demonstrate that the response to alpha-adrenergic stimulation is attenuated during erection in response to ganglionic stimulation. Furthermore, it appears that NO, produced during erection, may serve to override agonist-induced vasoconstriction. These results support our hypothesis that NO acts to directly stimulate relaxation of cavernous smooth muscle and to inhibit the vasoconstrictor actions of agents like ET-1 and alpha-adrenergic agonists including norepinephrine.
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To evaluate the antihypertensive effects of lisinopril, a renally excreted angiotensin-converting enzyme inhibitor, we assessed supervised administration of the drug after hemodialysis (HD) three times weekly. Blood pressure (BP) was assessed by interdialytic 44-hour ambulatory BP (ABP) monitoring, and endocrine responses were assessed by plasma renin activity (PRA) before and after dialysis. Lisinopril dose was titrated at biweekly intervals. If this was not effective after full titration (lisinopril to 40 mg three times weekly), ultrafiltration was added to reduce dry weight. The primary outcome variable was change in BP from the end of the run-in period to the end of the study. No change in mean ABP was noted during run-in. However, mean 44-hour ABP decreased from 149 +/- 14 (SD)/84 +/- 9 to 127 +/- 16/73 +/- 9 mm Hg, a decrease of 22/11 mm Hg (P < 0.001) at final evaluation. Of 11 patients who completed the trial, only 2 patients had systolic hypertension (>/=135 mm Hg) and 1 patient had diastolic hypertension (>/=85 mm Hg) at the final visit. Four patients were administered 10 mg of lisinopril; 5 patients, 20 mg; and 2 patients, 40 mg; only 1 of these patients required ultrafiltration therapy. There was a persistent antihypertensive effect over 44 hours. BP reduction was achieved without an increase in intradialytic symptomatic or asymptomatic hypotensive episodes. PRA increased in response to dialysis, as well as lisinopril. In conclusion, supervised lisinopril therapy is effective in controlling hypertension in chronic HD patients. This may be related to blockade of angiotensin II generation by kidneys despite the loss of excretory function.
A self-reported behaviour survey using an anonymous critical incident based questionnaire was administered by trained interviewers in 1998. Five hundred and thirty-one homosexual and bisexual men were recruited from gay bars, clubs, cafes, a sauna and 'cruising ground' in central Edinburgh. The use of alcohol and recreational drugs and details of sexual activity over the preceding three months and at the last sexual encounter were recorded. Unsafe sex was defined as anal sex without the use of a condom with a partner of unknown or different HIV status. Safer sex was defined as all other types of sex, including anal sex with a condom and anal sex without a condom with a partner whose HIV status was known to be the same. Of the questionnaires completed, 506 were suitable for analysis; 29 men (6.1%) reported anal sex with a partner of unknown or different HIV status without a condom ('unsafe sex') during their last sexual encounter. A total of 53 men (10.5%) could recall an episode of unsafe sex within the last three months. Men who had used marijuana or inhaled nitrites ('poppers') less than two hours before sex, or whose sexual partners had done so, were more likely to have unsafe sex than those who had not. Although alcohol use was more likely before sex with casual partners, the use of alcohol less than 2 hours before sex was not associated with sex being unsafe.
The University of Louisville currently maintains a database of work histories and exposure rankings for chemicals used in the production of polyvinyl chloride from the plant where the original angiosarcoma cases were identified. A 6-point ranking scale was used to characterize worker exposure to vinyl chloride by year, building, and job. Since this is ordinal data, non-parametric statistics have been used to evaluate exposure factors in case-control studies. Rank order analysis of vinyl chloride exposure and angiosarcoma shows a strong statistical association. In contrast, the method shows no association between vinyl chloride exposure and brain cancer. Exposure ranking is a reasonable alternative to estimation of actual dose. Rank order analysis allows for a rapid assessment of exposure-disease associations for case control studies.
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OBJECTIVES: To determine factors associated with angular malalignment of femoral shaft fractures treated with intramedullary nails and to determine differences in the incidence of angular malalignment based on fracture location, fracture comminution, and method of treatment (i.e., antegrade or retrograde). DESIGN: Retrospective. SETTING: Level I trauma center. PATIENTS: Three hundred sixty patients with 374 femoral shaft fractures were identified from a prospectively obtained orthopaedic trauma database. Complete sets of immediate postoperative anteroposterior and lateral radiographs were available for 355 (95 percent) of the 374 fractures. INTERVENTION: Patients were treated with antegrade (183 cases) or retrograde (174 cases) intramedullary femoral nailing. MAIN OUTCOME MEASURE: Goniometric measurements were made on all immediate postoperative radiographs to determine the coronal plane and sagittal plane angular alignments. A multiple linear regression statistical analysis was used to determine factors associated with increasing angular malalignment. The incidence of malalignment was determined using more than 5 degrees of deformity in any plane as the definition of malalignment. RESULTS: Proximal fracture location, distal fracture location, and unstable fracture pattern were associated with increasing fracture angulation (p < 0.001). Fracture location in the middle third, stable fracture pattern, method of treatment (i.e., antegrade or retrograde), and nail diameter were not associated with increasing fracture angulation (p > 0.05). The incidence of malalignment was 9 percent for the entire group of patients, 30 percent when the fracture was of the proximal third of the femoral shaft, 2 percent when the fracture was of the middle third, and 10 percent when the fracture was of the distal third. The incidence of malreduction was 7 percent for patients with stable fracture patterns and 12 percent for those with unstable fracture patterns. CONCLUSIONS: Patients with fractures of the proximal third of the femoral shaft treated with intramedullary nails are at highest risk for malalignment. Proximal fracture location, distal fracture location, and unstable fracture pattern are associated with increasing fracture angulation.
OBJECTIVE: The increasingly dominant performance of smaller-sized female gymnasts and increased magnitude of training beginning at an early age have prompted public and medical concerns, especially from an auxological perspective. The objective of this review is to determine if gymnastics training inhibits growth of females. DATA SOURCES: An extensive research of MedLine (PubMed interface) along with cross-referencing was conducted using the Text and MeSH words "gymnastics" in combination with "growth," "maturation," "body height," "body weight," and "growth plate." Our analysis is limited to English articles only. STUDY SELECTION: All published studies that included data related to the research questions were included. MAIN RESULTS: Although data from three historical cohort studies indicate that female gymnasts are short even before they begin training, clinical reports and cohort studies do suggest that some female gymnasts experience attenuated growth during training followed by catch-up growth during periods of reduced training or retirement. There is conflicting evidence whether the "catch-up" is complete. There were no studies reporting prevalence or incidence of inadequate growth. Three cohort studies provide evidence of reduced growth but training was not partitioned from other confounding factors in the gymnastics environment. Although there is a paucity of studies examining the link of dietary practices with diminished growth in female gymnasts, a review of related dietary literature indicates the potential for insufficient energy and nutrient intake among female gymnasts. CONCLUSIONS: Elite level or heavily involved female gymnasts may experience attenuated growth during their years of training and competition followed by catch-up growth during reduced training schedules or the months following retirement. However, a cause-effect relation between gymnastics training and inadequate growth of females has not been demonstrated.