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Biomedical subjects

M Egger

Publications and source records attributed to M Egger.

At least 37 records · Page 2Linked to original sources
PubMed2002

Do all men attending departments of genitourinary medicine need to be screened for non-gonococcal urethritis?

We investigated the influence of symptoms and signs on the detection of Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum organisms (ureaplasmas) in men with non-gonococcal urethritis (NGU). Two hundred and forty-two men attending the Jefferiss Wing at St Mary's Hospital for a sexual health assessment were evaluated, of whom 169 had NGU. Urethral inflammation was diagnosed if there were either > or =5 polymorphonuclear leucocytes (PMNLs) per high-power field (HPF) in five or more microscope fields of a Gram-stained urethral smear, or > or =10 PMNLs per HPF in five or more fields of a Gram-stained thread from 15-20 mL of a first-passed urine (FPU) specimen. C. trachomatis was diagnosed by direct immunofluoresence, M. genitalium by a polymerase chain reaction assay and ureaplasmas by culture. On multivariate analysis, to control for potential confounding by age, ethnicity, sexual lifestyle and co-infection, an urethral discharge remained significantly associated with the detection of C. trachomatis and M. genitalium in men with acute urethritis [OR 12.3, 95% CI (2.39-63.5) and OR 35.2, 95% CI (3.9-319.6), respectively], but dysuria or penile irritation did not. The detection of ureaplasmas was not associated with any clinical feature. In addition, on multivariate analysis men with NGU who were either symptomatic or had an observable discharge were more likely to have C. trachomatis or M. genitalium detected [(OR 6.92, 95% CI 1.41-33.9) and (OR 5.18, 95% CI 0.99-27.1), respectively], but not ureaplasmas (OR 1.19, 95% CI 0.33-4.35). The findings suggest that in men with acute NGU, symptoms or signs, and in particular a urethral discharge, are associated with the detection of C. trachomatis and M. genitalium, but not ureaplasmas. Currently, there is no precise answer to the question of whether all men attending a GUM clinic need to be screened for NGU, but if clinically asymptomatic NGU is found not to be associated with a sexually transmitted pathogen, the UK clinical guidelines requiring the preparation of a urethral smear from such men would need to be revised.

Chlamydia Infections↗
PubMed2001

Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study.

The prevalence, clinical presentation, and risk factors for hyperlactatemia among patients receiving antiretroviral therapy was determined during a 1-month period for patients in the Swiss HIV Cohort Study. Overall, 73 (8.3%) of 880 patients presented an increase in serum lactate of >1.1 times the upper normal limit (UNL). For 9 patients (1%), lactate elevation was moderate or severe (>2.2 times the UNL). Patients who presented with hyperlactatemia were more likely to be receiving stavudine with or without didanosine (odds ratio, 2.7; 95% confidence interval, 1.5-4.8), as compared with patients who received zidovudine-based regimens. The risk increased with increasing time receiving stavudine with or without didanosine. The association between hyperlactatemia and stavudine with or without didanosine was not biased by these medications being more recently available and, therefore, being given preferentially to patients who had prolonged use of nucleoside analog reverse-transcriptase inhibitors. Hyperlactatemia was associated with lipoatrophy, hyperlipidemia, and hyperglycemia. Age, sex, or stage of infection with human immunodeficiency virus were not predictive of hyperlactatemia. Determination of lactate levels may prove useful in the screening for mitochondrial toxicity.

Acidosis, Lactic↗
PubMed2001

Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials.

OBJECTIVE: To determine whether a period of starvation (nil by mouth) after gastrointestinal surgery is beneficial in terms of specific outcomes. DESIGN: Systematic review and meta-analysis of randomised controlled trials comparing any type of enteral feeding started within 24 hours after surgery with nil by mouth management in elective gastrointestinal surgery. Three electronic databases (PubMed, Embase, and the Cochrane controlled trials register) were searched, reference lists checked, and letters requesting details of unpublished trials and data sent to pharmaceutical companies and authors of previous trials. MAIN OUTCOME MEASURES: Anastomotic dehiscence, infection of any type, wound infection, pneumonia, intra-abdominal abscess, length of hospital stay, and mortality. RESULTS: Eleven studies with 837 patients met the inclusion criteria. In six studies patients in the intervention group were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98, P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84, 0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal abscess, and mortality, but these failed to reach significance (P>0.10). The risk of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046). CONCLUSIONS: There seems to be no clear advantage to keeping patients nil by mouth after elective gastrointestinal resection. Early feeding may be of benefit. An adequately powered trial is required to confirm or refute the benefits seen in small trials.

Anastomosis, Surgical↗
PubMed2001

Value of flow diagrams in reports of randomized controlled trials.

CONTEXT: Diagrams of the flow of participants through a clinical trial are recommended in the Consolidated Standards for Reporting of Trials (CONSORT) statement, but it is unclear whether such flow diagrams improve the quality of trial reports. OBJECTIVE: To examine the information contributed by flow diagrams and the completeness of reporting overall in reports of randomized controlled trials (RCTs) published in 5 general and internal medicine journals. DESIGN AND SETTING: Analysis of 270 reports of RCTs published in 1998 in the Annals of Internal Medicine (AIM; n = 19), BMJ (n = 42), JAMA (n = 45), The Lancet (n = 81), and The New England Journal of Medicine (NEJM; n = 83). MAIN OUTCOME MEASURES: Proportion of reports that included a flow diagram, information provided in flow diagrams, and completeness of reporting about flow of participants overall in flow diagrams or text. RESULTS: A total of 139 reports (51.5%) of RCTs included a flow diagram, but this varied widely among journals (AIM, 21.0%; BMJ, 38.1%; JAMA, 80.0%; The Lancet, 93.8%; and NEJM, 8.4%). Diagrams generally provided useful information, but only 73 (52.5%) included the number of participants who received allocated interventions and only 32 (23.0%) included the number of participants included in the analysis. In logistic regression analysis, overall completeness of reporting about flow of study participants was associated with publication of a flow diagram. CONCLUSIONS: Flow diagrams are associated with improved quality of reporting of randomized controlled trials. However, the structure of current flow diagrams is less than ideal. We propose a revised flow diagram that includes all important counts through the stages of parallel group trials.

Algorithms↗
PubMed2001

The revised CONSORT statement for reporting randomized trials: explanation and elaboration.

Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards. A group of scientists and editors developed the CONSORT (Con solidated S tandards o f R eporting T rials) statement to improve the quality of reporting of RCTs. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have adopted the CONSORT statement. The CONSORT statement facilitates critical appraisal and interpretation of RCTs by providing guidance to authors about how to improve the reporting of their trials. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the CONSORT statement. The meaning and rationale for each checklist item are presented. For most items, at least one published example of good reporting and, where possible, references to relevant empirical studies are provided. Several examples of flow diagrams are included. The CONSORT statement, this explanatory and elaboration document, and the associated Web site ( http://www.consort-statement.org ) should be helpful resources to improve reporting of randomized trials. Throughout the text, terms marked with an asterisk are defined at end of text.

Algorithms↗
PubMed2001

Role of Mycoplasma genitalium and Ureaplasma urealyticum in acute and chronic nongonococcal urethritis.

One hundred fourteen heterosexual men with acute nongonococcal urethritis (NGU) and 64 patients without NGU were studied. We determined that Chlamydia trachomatis and Mycoplasma genitalium were strongly associated with acute NGU after controlling, by means of multivariate analysis, for age, race, sexual lifestyle, and coinfection (odds ratio [OR], 13.0, 95% confidence interval [CI], 2.6-64.5; and OR, 17.9, 95% CI, 2.0-160, respectively). Eighty-six men with acute NGU reattended at least once 10-92 days after treatment; 59 (69%) of these 86 men had urethritis. Seven men had M. genitalium detected during 10-92 days of follow-up, and all had urethritis. Ureaplasmas were not associated with acute NGU in multivariate analysis, but their detection was associated with the presence of urethritis during follow-up (P=.014). Ureaplasmas or M. genitalium were associated with both chronic NGU, which was defined as urethritis that occurred 30-92 days after the commencement of treatment (P=.028), and chronic NGU with symptoms or signs (P=.005).

Acute Disease↗
PubMed2001

Discontinuation of primary prophylaxis in HIV-infected patients at high risk of Pneumocystis carinii pneumonia: prospective multicentre study.

OBJECTIVES: To assess the safety of discontinuation of primary prophylaxis in HIV-infected patients on antiretroviral combination therapy at high risk of developing Pneumocystis carinii pneumonia. DESIGN: Prospective multicentre study. PATIENTS AND METHODS: The incidence of P. carinii pneumonia after discontinuation of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral combination therapy who experienced an increase in their CD4 cell count to at least 200 x 10(6)/l and 14% of total lymphocytes; the study population included 191 patients with a history of CD4 cell counts below 100 x 10(6)/l (245 person-years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person-years). RESULTS: There was one case of Pneumocystis pneumonia, an incidence of 0.18 per 100 person-years [95% confidence interval (CI), 0.005--1.0 per 100 person-years]. No case was diagnosed in groups with low nadir CD4 cell counts (95% CI, 0--1.2 per 100 person-years) or detectable plasma HIV RNA (95% CI, 0--1.4 per 100 person-years). CONCLUSIONS: Discontinuation of primary prophylaxis against Pneumocystis pneumonia is safe in patients who have responded with a sustained increase in their CD4 cell count to antiretroviral combination therapy, irrespective of the CD4 cell count nadir and the viral load at the time of stopping prophylaxis.

Adult↗
PubMed2001

Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis.

Asymmetry in funnel plots may indicate publication bias in meta-analysis, but the shape of the plot in the absence of bias depends on the choice of axes. We evaluated standard error, precision (inverse of standard error), variance, inverse of variance, sample size and log sample size (vertical axis) and log odds ratio, log risk ratio and risk difference (horizontal axis). Standard error is likely to be the best choice for the vertical axis: the expected shape in the absence of bias corresponds to a symmetrical funnel, straight lines to indicate 95% confidence intervals can be included and the plot emphasises smaller studies which are more prone to bias. Precision or inverse of variance is useful when comparing meta-analyses of small trials with subsequent large trials. The use of sample size or log sample size is problematic because the expected shape of the plot in the absence of bias is unpredictable. We found similar evidence for asymmetry and between trial variation in a sample of 78 published meta-analyses whether odds ratios or risk ratios were used on the horizontal axis. Different conclusions were reached for risk differences and this was related to increased between-trial variation. We conclude that funnel plots of meta-analyses should generally use standard error as the measure of study size and ratio measures of treatment effect.

Data Interpretation, Statistical↗
PubMed2001

Helicobacter sp. flexispira bacteremia in an immunocompetent young adult.

A young immunocompetent patient was admitted for a febrile illness with malaise, arthralgias, painful leg swelling, and polyserositis. Shortly prior to becoming ill, the patient had traveled to the Northern African desert. The symptoms disappeared during treatment with antibiotics (doxycycline and ceftriaxone) but recurred twice after stopping therapy. A motile gram-negative fusiform rod was isolated from a blood culture taken on the first admission. Analysis of the 16S rRNA gene of the blood culture isolate revealed close similarity with Helicobacter sp. flexispira taxon 8 (99.9% identity), a species that was previously reported as "Flexispira rappini." This is the first reported case of a recurrent Helicobacter sp. flexispira bacteremia in an adult, immunocompetent patient.

Adult↗
PubMed2001

Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives.

BACKGROUND: Subgroup analyses are common in randomised controlled trials (RCTs). There are many easily accessible guidelines on the selection and analysis of subgroups but the key messages do not seem to be universally accepted and inappropriate analyses continue to appear in the literature. This has potentially serious implications because erroneous identification of differential subgroup effects may lead to inappropriate provision or withholding of treatment. OBJECTIVES: (1) To quantify the extent to which subgroup analyses may be misleading. (2) To compare the relative merits and weaknesses of the two most common approaches to subgroup analysis: separate (subgroup-specific) analyses of treatment effect and formal statistical tests of interaction. (3) To establish what factors affect the performance of the two approaches. (4) To provide estimates of the increase in sample size required to detect differential subgroup effects. (5) To provide recommendations on the analysis and interpretation of subgroup analyses. METHODS: The performances of subgroup-specific and formal interaction tests were assessed by simulating data with no differential subgroup effects and determining the extent to which the two approaches (incorrectly) identified such an effect, and simulating data with a differential subgroup effect and determining the extent to which the two approaches were able to (correctly) identify it. Initially, data were simulated to represent the 'simplest case' of two equal-sized treatment groups and two equal-sized subgroups. Data were first simulated with no differential subgroup effect and then with a range of types and magnitudes of subgroup effect with the sample size determined by the nominal power (50-95%) for the overall treatment effect. Additional simulations were conducted to explore the individual impact of the sample size, the magnitude of the overall treatment effect, the size and number of treatment groups and subgroups and, in the case of continuous data, the variability of the data. The simulated data covered the types of outcomes most commonly used in RCTs, namely continuous (Gaussian) variables, binary outcomes and survival times. All analyses were carried out using appropriate regression models, and subgroup effects were identified on the basis of statistical significance at the 5% level. RESULTS: While there was some variation for smaller sample sizes, the results for the three types of outcome were very similar for simulations with a total sample size of greater than or equal to 200. With simulated simplest case data with no differential subgroup effects, the formal tests of interaction were significant in 5% of cases as expected, while subgroup-specific tests were less reliable and identified effects in 7-66% of cases depending on whether there was an overall treatment effect. The most common type of subgroup effect identified in this way was where the treatment effect was seen to be significant in one subgroup only. When a simulated differential subgroup effect was included, the results were dependent on the nominal power of the simulated data and the type and magnitude of the subgroup effect. However, the performance of the formal interaction test was generally superior to that of the subgroup-specific analyses, with more differential effects correctly identified. In addition, the subgroup-specific analyses often suggested the wrong type of differential effect. The ability of formal interaction tests to (correctly) identify subgroup effects improved as the size of the interaction increased relative to the overall treatment effect. When the size of the interaction was twice the overall effect or greater, the interaction tests had at least the same power as the overall treatment effect. However, power was considerably reduced for smaller interactions, which are much more likely in practice. The inflation factor required to increase the sample size to enable detection of the interaction with the same power as the overall effect varied with the size of the interaction. For an interaction of the same magnitude as the overall effect, the inflation factor was 4, and this increased dramatically to of greater than or equal to 100 for more subtle interactions of < 20% of the overall effect. Formal interaction tests were generally robust to alterations in the number and size of the treatment and subgroups and, for continuous data, the variance in the treatment groups, with the only exception being a change in the variance in one of the subgroups. In contrast, the performance of the subgroup-specific tests was affected by almost all of these factors with only a change in the number of treatment groups having no impact at all. CONCLUSIONS: While it is generally recognised that subgroup analyses can produce spurious results, the extent of the problem is almost certainly under-estimated. This is particularly true when subgroup-specific analyses are used. In addition, the increase in sample size required to identify differential subgroup effects may be substantial and the commonly used 'rule of four' may not always be sufficient, especially when interactions are relatively subtle, as is often the case. CONCLUSIONS--RECOMMENDATIONS FOR SUBGROUP ANALYSES AND THEIR INTERPRETATION: (1) Subgroup analyses should, as far as possible, be restricted to those proposed before data collection. Any subgroups chosen after this time should be clearly identified. (2) Trials should ideally be powered with subgroup analyses in mind. However, for modest interactions, this may not be feasible. (3) Subgroup-specific analyses are particularly unreliable and are affected by many factors. Subgroup analyses should always be based on formal tests of interaction although even these should be interpreted with caution. (4) The results from any subgroup analyses should not be over-interpreted. Unless there is strong supporting evidence, they are best viewed as a hypothesis-generation exercise. In particular, one should be wary of evidence suggesting that treatment is effective in one subgroup only. (5) Any apparent lack of differential effect should be regarded with caution unless the study was specifically powered with interactions in mind. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: (1) The implications of considering confidence intervals rather than p-values could be considered. (2) The same approach as in this study could be applied to contexts other than RCTs, such as observational studies and meta-analyses. (3) The scenarios used in this study could be examined more comprehensively using other statistical methods, incorporating clustering effects, considering other types of outcome variable and using other approaches, such as Bootstrapping or Bayesian methods.

Data Interpretation, Statistical↗
PubMed2000

L-type Ca2+ current as the predominant pathway of Ca2+ entry during I(Na) activation in beta-stimulated cardiac myocytes.

In the present study Ca2+ entry via different voltage-dependent membrane channels was examined with a fluorescent Ca2+ indicator before and after beta-adrenergic stimulation. To clearly distinguish between Ca2+ influx and Ca2+ release from the sarcoplasmic reticulum the Ca2+ store was blocked with 0.1 microM thapsigargin and 10 microM ryanodine. Omitting Na+ from the pipette filling solution minimized Ca2+ entry via Na+-Ca2+ exchange. Individual guinea-pig ventricular myocytes were voltage clamped in the whole-cell configuration of the patch-clamp technique and different membrane currents were activated using specific voltage protocols. The intracellular Ca2+ concentration was simultaneously recorded with a laser-scanning confocal microscope using fluo-3 as a Ca2+ indicator. Ca2+ entry pathways were discriminated using pharmacological blockers under control conditions and during beta-adrenergic stimulation with 1 microM isoproterenol (isoprenaline) in the bathing solution or 100 microM cAMP in the patch-clamp pipette. Isoproterenol or cAMP potentiated the Ca2+ influx signals recorded during L-type Ca2+ current activation but, more interestingly, also during Na+ current (INa) activation. The Ca2+ influx signal arising from L-type Ca2+ current activation was usually blocked by 50 microM Cd2+. However, the Ca2+ influx signal elicited by the Na+ current activation protocol was only curtailed to 56.4 +/- 28.2 % by 100 microM Ni2+ but was reduced to 17.9 +/- 15.1 % by 50 microM Cd2+ and consistently eliminated by 5 mM Ni2+. The pronounced Cd2+ and moderate Ni2+ sensitivity of the Ca2+ influx signals suggested that the predominant source of Ca2+ influx during the Na+ current activation - before and during beta-adrenergic stimulation - was a spurious activation of the L-type Ca2+ current, presumably due to voltage escape during Na+ current activation. Calculations based on the relationship between Ca2+ current and fluorescence change revealed that, on average, we could reliably detect rapid Ca2+ concentration changes as small as 5.4 +/- 0.7 nM. Thus, we can estimate an upper limit for the Ca2+ permeability of the phosphorylated TTX-sensitive Na+ channels which is less than 0.04:1 for Ca2+ ions flowing through Na+ channels via the proposed 'slip-mode' Ca2+ conductance. Therefore the slip-mode Ca2+ conductance of Na+ channels does not contribute noticeably to the Ca2+ signals observed in our experiments.

Adrenergic beta-Agonists↗