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Community-Institutional Relations↗
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Is it ethical to study what ought not to happen?
In the Democratic Republic of Congo, only an estimated 2% of all AIDS patients have access to treatment. As AIDS treatment access is scaled-up in the coming years, difficult rationing decisions will have to be made concerning who will come to gain access to this scarce medical resource. This article focuses on the position, expressed by representatives of Médecins sans Frontières (MSF), that the practice of AIDS treatment access rationing is fundamentally unethical because it conflicts with the ideal of universal treatment access and the human right to health. The conclusion is that MSF's position lacks coherence, has negative practical implications, and is unfair to governments struggling to increase patient's access to AIDS treatment in unfavorable circumstances.
Acquired Immunodeficiency Syndrome↗
Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.
One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.
Adult↗
The effects of dietary cholesterol on experimental diabetic nephropathy.
Hyperlipidaemia has been previously shown to accelerate various models of renal disease. The present study has evaluated the effects of dietary cholesterol supplementation on functional and structural aspects of experimental diabetic nephropathy. Control and streptozotocin diabetic male Sprague Dawley rats were randomized to receive a normal diet or a high cholesterol (4% cholesterol + 1% cholic acid) diet. After 32 weeks, serum lipids, glycaemic control, urinary albumin excretion and glomerular ultrastructural parameters were evaluated in the 4 groups. Diabetes was associated with increased total cholesterol and triglyceride levels. Cholesterol supplementation increased total and decreased HDL-cholesterol in control and diabetic rats. Diabetes increased albuminuria but cholesterol supplementation did not influence urinary albumin excretion. In diabetic rats, glomerular basement membrane thickness and glomerular volume were increased but cholesterol supplementation did not influence any glomerular ultrastructural parameter. In control rats, increased dietary cholesterol intake led to an increase in blood pressure and glomerular volume. In contrast to other models of renal disease, experimental diabetic nephropathy does not appear to be exacerbated by dietary cholesterol supplementation.
Albuminuria↗
Manipulation of the n-3 polyunsaturated fatty acid content of muscle and adipose tissue in lambs.
Fifty Suffolk-crossbred wether lambs, with an initial live weight of 29 +/- 2.1 kg, were allocated to one of five concentrate-based diets formulated to have a similar fatty acid content (60 g/kg DM), but containing either linseed oil (high in 18:3n-3); fish oil (high in 20:5n-3 and 22:6n-3); protected linseed and soybean (PLS; high in 18:2n-6 and 18:3n-3); fish oil and marine algae (fish/algae; high in 20:5n-3 and 22:6n-3); or PLS and algae (PLS/algae; high in 18:3n-3 and 22:6n-3). Lambs were slaughtered when they reached 40 kg. Growth performance and intake were similar (P > 0.35) among treatments. By contrast, gain:feed was higher (P < 0.05) in lambs fed the fish oil compared with the linseed oil or PLS/algae diets. Total fatty acid concentration (mg/100 g) in the neutral lipid of the longissimus muscle was not affected by treatment (P > 0.87) but was least (P < 0.05) in the phospholipid fraction in lambs fed the linseed oil diet. Lambs fed either diet containing marine algae contained the highest (P < 0.05) percentage of 22:6n-3 in the phospholipid (mean of 5.2%), 2.8-fold higher than in sheep fed the fish oil diet. In lambs fed the fish/algae diet, the percentage of 20:5n-3 was highest (P < 0.05), contributing some 8.7, 0.8, and 0.5% of the total fatty acids in the muscle phospholipid, neutral lipids, and adipose tissue, respectively. The percentage of 18:3n-3 in the phospholipid fraction of the LM was highest (P < 0.05) in lambs fed the linseed oil diet (6.9%), a value double that of sheep fed the PLS diet. By contrast, lambs fed the PLS diet had twice the percentage of 18:3n-3 in the muscle neutral lipids (3.8%) than those offered the linseed oil diet, and 5.5-fold greater than lambs fed the fish/algae treatment (P < 0.05), an effect that was similar in the adipose tissue. The percentage of 18:2n-6 was highest (P < 0.05) in lambs fed the PLS diet, where it contributed 33.7, 10.1, and 11.2% in the muscle phospholipid, neutral lipids, and adipose tissue, respectively. The highest (P < 0.05) muscle PUFA-to-saturated fatty acid (P:S) ratio was obtained in lambs fed the PLS diet (0.57), followed by the PLS/algae diet (0.46), and those fed the fish oil or linseed oil diets had the lowest ratios (0.19 and 0.26, respectively). The favorable P:S ratio of lambs fed the PLS/algae diet, in conjunction with the increased levels of 20:5n-3 and 22:6n-3, enhanced the nutritional qualities of lamb to more closely resemble what is recommended for the human diet.
Adipose Tissue↗
The policies of organ transplantation in Europe: issues and problems.
Transplantation has evolved from an experiment to a routinely performed procedure for a widening range of organs. Transplantation in Europe is dominated by the scarcity of organs from deceased donors leading to problems of selection criteria for recipients, of legal protection for donors and of the empowerment of agencies for allocative decisions. Although public involvement is very emotional, there has been a benign neglect in several European countries by policy makers, accepting implicitly organ transplantation leading to a variety of programs for diffusion, organization, and financing of transplantation. Non-transplanting hospitals play a key role in organ procurement and transplant centers are increasingly subject to quality assessment, whereby the issue of the relation between improved outcome at higher volumes comes to the forefront. International cooperation is critical for the development of effective transplant programs in Europe.
Europe↗
Conditional power for arbitrary survival curves to decide whether to extend a clinical trial.
This article describes a computer simulation methodology to calculate conditional power for comparing two arbitrary survival curves as an aid in deciding whether or not to extend a clinical trial. The method is a modification of that by Halpern and Brown, which computes unconditional power for comparing arbitrary survival curves at the beginning of a study. The advantage of this method is that it permits conditional power calculations for comparisons of distribution-free survival curves. Power is computed for two commonly used statistical tests, the log-rank test and Gehan's generalization of the Wilcoxon test, and for a modified Kolmogorov-Smirnov test, which is particularly sensitive to crossing survival curves. This method for estimating conditional power should be useful in the situation in which a decision must be made regarding the benefit of continuing a clinical trial. The application of this method is shown using VA Cooperative Study No. 90, "Prognosis and Outcome Following Heart Valve Replacement."
Aortic Valve↗
The Midlands Trial of Empirical Amiodarone versus Electrophysiology-guided Interventions and Implantable Cardioverter-defibrillators (MAVERIC): a multi-centre prospective randomised clinical trial on the secondary prevention of sudden cardiac death.
AIMS: MAVERIC was a randomised clinical trial designed to test the possibility of prospectively identifying patients who would benefit most from the implantable cardioverter-defibrillator (ICD) by electrophysiology (EP) study in the context of secondary prevention of sudden cardiac death (SCD) through comparing EP-guided interventions (anti-arrhythmic drugs, coronary revascularization, and ICD) against empirical amiodarone therapy. METHODS: Two hundred and fourteen survivors of sustained ventricular tachycardia (VT), ventricular fibrillation (VF) or SCD were randomized to either treatment strategy, pre-stratified for haemodynamic status at index event, and followed up for a median of 5 years. RESULTS: Of the 106 amiodarone arm patients, 89 (84%) received the drug and 5 (5%) received an ICD after crossing over. Of the 108 EP arm patients, 31 (29%) received an ICD, 46 (43%) received anti-arrhythmic drugs only (mainly amiodarone or sotalol) and 18 (17%) received coronary revascularization but no ICD. No significant differences in survival or arrhythmia recurrence existed between the two treatment arms after 6 years. However, ICD recipients had a lower mortality than non-ICD recipients, regardless of allocated treatment (hazard ratio=0.54, p=0.0391). CONCLUSIONS: Prospective selection of patients to receive the ICD by EP study did not improve survival compared with empirical amiodarone therapy among survivors of VT, VF or SCD, whereas ICD implantation improved survival regardless of allocated treatment. On this basis, routine EP study has no role in the management of such patients, who should be offered empirical ICD therapy according to the results of other secondary prevention ICD trials.
Amiodarone↗
Consequences of displaying abnormal social behaviour: avoidance and reduction of social reinforcement.
BACKGROUND: Abnormal social behaviour, which is a common feature of psychiatric disorders, is associated with rejection. A passive lack of participation or involvement has been studied as characteristic of depression but active forms of nonparticipation have received little experimental attention. This study examined the interpersonal consequences of four distinct types of social behaviour by using the role enactment method. Two of the roles portrayed abnormal social behaviour, active nonparticipant 'manic' and passive nonparticipant 'sad', and two portrayed normal social behaviour, active participant 'warm' and passive participant 'shy'. METHODS: Sixty-three normal subjects were randomly allocated to a brief dyadic social interaction with a confederate acting one of four roles. Subsequently, they rated their level of rejection of the confederate and took part in the mixed-motive game with him/her. RESULTS: The subjects were more likely to reject confederates in the abnormal social behaviour roles. This was shown on both their nonverbal behaviour and their verbal report. On the mixed-motive game, subjects gave fewer points and less cooperative and ingratiating messages to the confederates who had displayed abnormal social behaviour. LIMITATIONS: This result might only reveal the effects of first impressions of a confederate who behaves in a particular way, but not be generalised to long term acquaintanceship. CONCLUSIONS: These results extend previous findings that passive nonparticipant behaviour leads to rejection to active nonparticipant behaviour and show that the consequences of displaying such behaviour not only result in rejection but also in the reduction of social reinforcement. This might slow a patient's recovery process.
Adolescent↗
Peers and partners: working together to strengthen preceptorship in mental health nursing.
The Sussex Education Consortium commissioned a development project to identify the education and training needs of community mental health nurses (CMHNs). The project also afforded an opportunity to examine the CMHNs' perception of their role of preceptor with pre-registration diploma nursing (PRDN) students following the mental health branch. Utilizing a 'responsive evaluation' methodology, stakeholders' views were captured. As a consequence of the issues and concerns raised, the Consortium commissioned a second project, following a similar methodolgy, to explore preceptorship in greater depth. This paper reports stakeholders' views on preceptorship arrangements expressed in semi-structured interviews, focused group discussions and other fora during the two projects. Preceptor preparation and support arrangements did not meet the needs of preceptors. Many preceptors felt their role was neither valued nor acknowledged. The link lecturer role was perceived as important by preceptors; but lecturers were often unable to meet the expectations placed upon them. The volume of students and allocation arrangements caused problems for placement areas. Finding time to carry out the roles of the preceptor was a challenge for practitioners. Recommendations for improving preceptorship are discussed and developments described, illustrating how locally commissioned research may influence both education and practice in mental health nursing.
Cooperative Behavior↗
Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: a randomized, controlled trial.
BACKGROUND: Endoscopy with the patient under sedation with propofol requires careful monitoring of patient consciousness and vital signs to achieve the desired hypnotic effect without overdosage. Because level of consciousness is difficult to judge by clinical observation alone, electroencephalogram monitoring has been used to guide general anesthesia. METHODS: Eighty consecutive patients (mean [SD] age 62 [14] years) undergoing ERCP for various indications were randomly allocated to 2 groups. In group A (n = 40), propofol sedation was guided by conventional monitoring (heart rate, blood pressure, oxygen saturation, electrocardiogram), whereas electroencephalogram monitoring was performed but not displayed to the physician who administered the drug. In group B (n = 40), electroencephalogram monitoring was displayed online and used to guide propofol administration to maintain a preselected sedation level. Procedure-related parameters, recovery time, and quality (postanesthesia recovery score), as well as patient cooperation and tolerance for the procedure (visual analog scale) were prospectively assessed. RESULTS: The groups were comparable with regard to demographic, clinical, and procedure-related parameters. Mean propofol dose was significantly lower in group B than in group A (respectively, 290 [158] mg vs. 374 [166] mg; p = 0.02). The mean decrease in arterial blood pressure was significantly lower in group B than in group A (respectively, 11 [6] mm Hg vs. 14 [7] mm Hg; p < 0.05). Clinically relevant changes in vital signs to below critical values were observed in both groups, albeit infrequently. Efficacy of sedation was also rated similar in both groups, whereas mean recovery time was significantly faster in group B than in group A (respectively, 16 [7] minutes vs. 20 [8] minutes; p = 0.02). Accordingly, the recovery score tended to be better in group B compared with group A (respectively, 8.4 [1.0] points vs. 8.0 [0.9] points; p = 0.06). The predefined target level of sedation was maintained during 75% of the procedure time in group B but in only 58% of the time in group A (p < 0.05), and deeper sedation levels were achieved significantly more often in group B patients compared with group A patients (p < 0.05). CONCLUSION: Electroencephalogram monitoring enables more effective titration of propofol dosage for sedation during endoscopy and is, therefore, associated with faster patient recovery.
Adult↗
Comparison of two skin care regimes for incontinence.
It is estimated that 30% of nursing home residents may be faecally incontinent, with those figures rising to 60% for patients in long-stay hospitals (Royal College of Physicians, 1995). Maintaining skin integrity for these patients can be complex. With little clinical information to support carers, choosing a skin care regime that maintains skin integrity for this high-risk group can be difficult. This study aims to compare two recognized skin care regimes, used in the cleansing of patients' skin following an episode of incontinence, and their impact on patients' skin integrity. A total of 93 patients were recruited to the trial from five care of the elderly or dependent service providers. The subjects were randomly allocated to either group A (soap and water; n = 49), or group B (Clinisan (Vernacare); n = 44). Initially, 33 patients in both groups started with healthy skin. However, the results of the final assessment identified only 17 subjects in group A remaining healthy, compared with 27 in group B.
Aged↗
[The comparative study of the ultra-light anaesthesia between N(2)O inhalation and propofol intravenous in tooth extraction]
OBJECTIVE:To study the effect of N(2)O inhalation and propofol intravenous anaesthesia in tooth extraction. METHODS: 40 dental outpatients with the extraction of the mandibular wisdom tooth,ASAI,were randomly allocated to two groups:N(2)O group with the age of 20-36 years old and propofol group with the age of 21-35 years old.All cases undergoing dental extraction were given ultra-light anaesthesia as an adjunct local anaesthesia. RESULTS: The two groups were gained various levels of sedation,there were no significant difference among BP,HR,RR,SPO(2) before,in,and after the operation.Dental treatment could be carried out in cooperating conditin throughout the whole procedure.There was a certain extent of amnesia postoperation,the incidence of postoperative side effects was low,the recovery time was gained within 30 minutes. CONCLUSION: The analgesic effects of N(2)O group were superior to the propofol group.
Journal Article↗
Reproductive conflict in social insects: male production by workers in a slave-making ant.
In insect societies, workers cooperate but may also pursue their individual interests, such as laying viable male eggs. The case of obligatory slave-making ants is of particular interest because workers do not engage in maintenance activities and foraging. Therefore, worker egg laying is expected to be less detrimental for colony efficiency than in related, nonparasitic species. Furthermore, as slave-making workers usually do not perform brood care and thus might have little power in manipulating sex allocation, they might be more strongly selected to increase their direct fitness by producing their own sons than workers in nonparasitic species. In this study we investigated worker reproduction in four natural colonies of the slave-making ant Polyergus rufescens, using highly variable microsatellite markers. Our results show that workers produce up to 100% of the males. This study thus presents the first direct evidence of an almost complete takeover of male reproduction by workers in ants.
Animals↗
The effects of individual and nursing-unit characteristics on willingness to adopt an innovation. A multilevel analysis.
In this study, the authors investigate the effects of efficacy and cooperativeness on willingness to adopt an innovation at the individual and nursing-unit levels. The results of a field report showed that efficacy was significantly associated with willingness to adopt an innovation at both the individual and nursing-unit levels, whereas cooperativeness was significant only at the individual level. These results suggest that examining innovation adoption at multiple levels provides more valid information than does examining it at a single level.
Adult↗
Identification of amplified and expressed genes in breast cancer by comparative hybridization onto microarrays of randomly selected cDNA clones.
Microarray analysis using sets of known human genes provides a powerful platform for identifying candidate oncogenes involved in DNA amplification events but suffers from the disadvantage that information can be gained only on genes that have been preselected for inclusion on the array. To address this issue, we have performed comparative genome hybridization (CGH) and expression analyses on microarrays of clones, randomly selected from a cDNA library, prepared from a cancer containing the DNA amplicon under investigation. Application of this approach to the BT474 breast carcinoma cell line, which contains amplicons at 20q13, 17q11-21, and 17q22-23, identified 50 amplified and expressed genes, including genes from these regions previously proposed as candidate oncogenes. When considered together with data from microarray expression profiles and Northern analyses, we were able to propose five genes as new candidate oncogenes where amplification in breast cancer cell lines was consistently associated with higher levels of RNA expression. These included the HB01 histone acetyl transferase gene at 17q22-23 and the TRAP100 gene, which encodes a thyroid hormone receptor-associated protein coactivator, at 17q11-21. The results demonstrate the utility of this microarray-based CGH approach in hunting for candidate oncogenes within DNA amplicons.
Breast Neoplasms↗
Analgesic efficacy of an ibuprofen-codeine combination.
Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given, under double-blind, randomized conditions, a single dose of either codeine 60 mg, aspirin 650 mg, ibuprofen 400 mg, aspirin 650 mg + codeine 60 mg, ibuprofen 400 mg + codeine 60 mg, or placebo. A total of 249 subjects were included in the statistical analysis. On a report form, subjects recorded pain intensity, pain relief, and side effects hourly for four hours. They also gave an overall impression at the end of the observation period. Analysis of variance and pairwise contrasts were used to analyze the data. For the sum of pain intensity differences, the total of the hourly pain relief scores, and overall impression, there was a significant analgesic effect for codeine, aspirin, and ibuprofen and no significant interaction when they were used in combination. Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination. The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter, but it was not statistically superior to ibuprofen alone. The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model. There was no notable difference in the frequency or intensity of side effects among the treatment groups, and no subject had to withdraw due to an adverse effect. This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination. Codeine added a small amount of additional analgesia when used in combination with ibuprofen.
Adolescent↗