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Khalid S Khan

Publications and source records attributed to Khalid S Khan.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of treatment effects between animal experiments and clinical trials: systematic review.

OBJECTIVE: To examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review. DATA SOURCES: Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. STUDY SELECTION: Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome. RESULTS: Corticosteroids did not show any benefit in clinical trials of treatment for head injury but did show a benefit in animal models (pooled odds ratio for adverse functional outcome 0.58, 95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in clinical trials but the data were inconclusive in animal models. Thrombolysis improved outcome in patients with ischaemic stroke. In animal models, tissue plasminogen activator reduced infarct volume by 24% (95% confidence interval 20% to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was associated with a worse outcome in patients with ischaemic stroke. In animal models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced respiratory distress and mortality in neonates whereas in animal models respiratory distress was reduced but the effect on mortality was inconclusive (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased bone mineral density in patients with osteoporosis. In animal models the bisphosphonate alendronate increased bone mineral density compared with placebo by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8% to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% (-1.4% to 4.7%). CONCLUSIONS: Discordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.

Animal Experimentation↗
PubMed2006

A hierarchy of effective teaching and learning to acquire competence in evidenced-based medicine.

BACKGROUND: A variety of methods exists for teaching and learning evidence-based medicine (EBM). However, there is much debate about the effectiveness of various EBM teaching and learning activities, resulting in a lack of consensus as to what methods constitute the best educational practice. There is a need for a clear hierarchy of educational activities to effectively impart and acquire competence in EBM skills. This paper develops such a hierarchy based on current empirical and theoretical evidence. DISCUSSION: EBM requires that health care decisions be based on the best available valid and relevant evidence. To achieve this, teachers delivering EBM curricula need to inculcate amongst learners the skills to gain, assess, apply, integrate and communicate new knowledge in clinical decision-making. Empirical and theoretical evidence suggests that there is a hierarchy of teaching and learning activities in terms of their educational effectiveness: Level 1, interactive and clinically integrated activities; Level 2(a), interactive but classroom based activities; Level 2(b), didactic but clinically integrated activities; and Level 3, didactic, classroom or standalone teaching. SUMMARY: All health care professionals need to understand and implement the principles of EBM to improve care of their patients. Interactive and clinically integrated teaching and learning activities provide the basis for the best educational practice in this field.

Competency-Based Education↗
PubMed2006

Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy.

BACKGROUND: Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 x 2 tables. DISCUSSION: The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia.

Journal Article↗
PubMed2006

WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity.

BACKGROUND: Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates. METHODS: We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies. RESULTS: There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%. CONCLUSION: There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.

Chronic Disease↗
PubMed2006

Progesterone for the prevention of preterm birth: a critical evaluation of evidence.

A systematic review of the literature identified nine randomised trials that evaluated the effects of progestational agents in the prevention of preterm delivery. These studies were of variable quality. Meta-analyses showed reductions in delivery rates before 37 weeks (OR 0.42, 95% CI 0.31-0.57) and 34 weeks (OR 0.51, 95% CI 0.34-0.77) as well as in respiratory distress syndrome (OR 0.55, 95% CI 0.31-0.96) with progestational agents. A cumulative meta-analysis showed that the treatment benefit for the outcome of delivery before 37 weeks exceeded the conventional level of statistical significance in 1975 (p<0.01); by 1985, the p-value was <0.001, and by 2003, it was <0.0001. Another cumulative meta-analysis in which the studies were added to the pooled analysis by decreasing quality score showed significant benefit even when the analysis was limited to just the highest quality trials (OR 0.47, 95% CI 0.33, 0.66, p<0.0001). An exploration of the applicability of the effects across various baseline risks using a L'abbe plot found that the benefit was consistent across a range of risks. A comprehensive review of both trial and observational data on harm did not show any demonstrable evidence of harm to mother and baby. Women at high risk of preterm birth should be recommended progestational agent therapy.

Female↗
PubMed2006

Quality of health information for cervical cancer treatment on the internet.

BACKGROUND: The internet has become a frequently used and powerful tool for patients seeking medical information. This information may not undergo the same quality consideration as the peer-review criteria for publication of information in a journal. The aim of this study is to assess the quality of internet sites providing information on the treatment of cervical cancer, with comparisons between the quality assessments made by an educated lay person and an expert in the field. METHODS: A search of the World Wide Web was made by a lay person to identify sites containing information on the treatment of cervical cancer. The credibility and accuracy of these sites was assessed using predefined criteria based on 'Criteria for Assessing the Quality of Health Information on the Internet' and accepted guidelines for the treatment of cervical cancer. The assessment was made independently and in duplicate by the lay reviewer and medical expert in order to allow comparison. RESULTS: 46 relevant websites were assessed. Only one site contained all the credibility and accuracy criteria, with a further website containing all the credibility criteria. The majority of sites, 38/46, were deemed easy to navigate. The agreement between lay person and expert was good with only 6 items in total changed by the expert. CONCLUSION: This study clearly shows there is wide variation in quality of websites available to patients on the treatment of cervical cancer. Further research and consideration is needed on the effects of website information on gynaecological cancer patients and how steps can be made to insure the posting of good quality information.

Journal Article↗
PubMed2006

The architecture of evidence-based gynaecology.

Modern evidence-based medicine (EBM) and its predecessor 'Medecin d'Observation' both emphasise that potential advances in healthcare must be researched and proven to do more good than harm using the principles of clinical epidemiology before they are incorporated into medical practice. EBM is considered an important advance in improving clinical care in gynaecology but EBM skills have traditionally not been covered in undergraduate or postgraduate education. Therefore there is a perceived need to compile texts on various aspects of gynaecological practice using EBM principles. This is what these two issues of the Best Practice series hope to achieve. The various chapters will provide readers with clinical advice generated from critically appraised information that has been identified as addressing relevant questions.

Decision Making↗
PubMed2006

WHO analysis of causes of maternal death: a systematic review.

BACKGROUND: The reduction of maternal deaths is a key international development goal. Evidence-based health policies and programmes aiming to reduce maternal deaths need reliable and valid information. We undertook a systematic review to determine the distribution of causes of maternal deaths. METHODS: We selected datasets using prespecified criteria, and recorded dataset characteristics, methodological features, and causes of maternal deaths. All analyses were restricted to datasets representative of populations. We analysed joint causes of maternal deaths from datasets reporting at least four major causes (haemorrhage, hypertensive disorders, sepsis, abortion, obstructed labour, ectopic pregnancy, embolism). We examined datasets reporting individual causes of death to investigate the heterogeneity due to methodological features and geographical region and the contribution of haemorrhage, hypertensive disorders, abortion, and sepsis as causes of maternal death at the country level. FINDINGS: 34 datasets (35,197 maternal deaths) were included in the primary analysis. We recorded wide regional variation in the causes of maternal deaths. Haemorrhage was the leading cause of death in Africa (point estimate 33.9%, range 13.3-43.6; eight datasets, 4508 deaths) and in Asia (30.8%, 5.9-48.5; 11,16 089). In Latin America and the Caribbean, hypertensive disorders were responsible for the most deaths (25.7%, 7.9-52.4; ten, 11,777). Abortion deaths were the highest in Latin America and the Caribbean (12%), which can be as high as 30% of all deaths in some countries in this region. Deaths due to sepsis were higher in Africa (odds ratio 2.71), Asia (1.91), and Latin America and the Caribbean (2.06) than in developed countries. INTERPRETATION: Haemorrhage and hypertensive disorders are major contributors to maternal deaths in developing countries. These data should inform evidence-based reproductive health-care policies and programmes at regional and national levels. Capacity-strengthening efforts to improve the quality of burden-of-disease studies will further validate future estimates.

Abortion, Induced↗
PubMed2006

Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research.

BACKGROUND: Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. METHODS: We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996-2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. RESULTS: Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. CONCLUSION: There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research.

Animal Experimentation↗
PubMed2006

Is general inpatient obstetrics and gynaecology evidence-based? A survey of practice with critical review of methodological issues.

BACKGROUND: To examine the rates of evidence-supported care provided in an obstetrics-gynaecology unit. METHODS: The main diagnosis-intervention set was established for a sample of 325 consecutive inpatient admissions in 1998-99 in a prospective study in a UK tertiary care centre. A comprehensive literature search was conducted to obtain the evidence supporting the intervention categorised according to the following hierarchy: Grade A, care supported by evidence from randomised controlled trials; Grade B, care supported by evidence from controlled observational studies and convincing non-randomised evidence; and Grade C, care without substantial research evidence. RESULTS: Of the 325 admissions, in 135 (42%) the quality of care was based on Grade A evidence, in 157 (48%) it was based on Grade B evidence, and in 33 (10%) it was based on Grade C evidence. The patterns of care were not different amongst patients sampled in 1998 and 1999. CONCLUSION: A significant majority (90%) of obstetric and gynaecological care was found to be supported by substantial research evidence.

Journal Article↗
PubMed2006

Mapping the theories of preeclampsia: the need for systematic reviews of mechanisms of the disease.

Preeclampsia, a major cause of morbidity in pregnancy, is still a disease of unknown cause, despite considerable research in recent times. We believe that progress in understanding the disorder would be enhanced if the systematic review methodology, similar to that used to assess data from clinical trials, is applied to studies that investigate the many theories advanced to explain its cause. This article discusses the need for and a frame work of such an endeavor. The systematic review approach helps to determine where research should be focused, to prioritize the use of resources, to understand, and then hopefully to conquer a disease that still kills mothers and infants each year, worldwide.

Female↗
PubMed2006

Accuracy of serum uric acid determination in predicting pre-eclampsia: a systematic review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early prediction of pre-eclampsia may be used to target high-risk women for effective preventative treatments. Hyperuricemia is associated with pre-eclampsia and it has been tested in early pregnancy for its ability to predict the later onset of the disease. OBJECTIVE: To systematically review the accuracy of determining serum uric acid before the 25th gestational week in predicting pre-eclampsia. METHODS: We searched Medline, Embase, Cochrane Library, Medion, bibliographies of review articles and eligible primary studies, and contacted experts in the field. Language restrictions were not applied. Reviewers working independently selected studies, extracted data and assessed validity according to eight criteria. Sensitivities and specificities were plotted in a Receiver Operating Characteristic plot. RESULTS: We identified five primary articles, with a total of 572 women, including 44 who developed pre-eclampsia. Study populations differed clinically, with incidences ranging from 3.4% to 40.1%. Sensitivity ranged from 0.0% to 55.6% and specificity ranged from 76.9% to 94.9%. Clinical heterogeneity and poor reporting precluded sensible pooling of data. In particular, consecutive entry of eligible women, blind assessment of the reference standard, and treatment to prevent pre-eclampsia were poorly reported. CONCLUSION: Contrary to previous reviews, we conclude that there is currently insufficient evidence to draw firm conclusions about the accuracy of serum uric acid determination in predicting pre-eclampsia.

Female↗
PubMed2006

Rapid tests for group B Streptococcus colonization in laboring women: a systematic review.

OBJECTIVES: We set out to determine the accuracy and rapidity of various intrapartum group B Streptococcus (GBS) colonization tests. STUDY DESIGN: We performed a systematic review of test-accuracy studies, which were identified without language restriction from Medline and Cochrane databases; bibliographies of known primary and review articles; and contact with authors, experts, and manufacturers. Studies were selected if they tested pregnant women intrapartum for GBS colonization and confirmed by "gold-standard" laboratory cultures. Two reviewers independently selected studies and extracted data on their characteristics, quality, and results. Accuracy data were used to form 2 x 2 contingency tables. Heterogeneity was assessed, and LRs for positive and negative test results were pooled in subgroups of studies of various tests. RESULTS: There were 29 test-accuracy studies in 15,691 women, evaluating 6 different tests: polymerase chain reaction (PCR), optical immunoassay (OIA), DNA hybridization, enzyme immunoassay, latex agglutination, and Islam starch medium tests. The methodologic quality of the studies was generally poor. The most accurate was the real-time PCR test, but it was less rapid than OIA test. Real-time PCR took 40 minutes to complete, whereas the OIA took 30 minutes. CONCLUSIONS: Real-time PCR and OIA are candidates for rapid near patient intrapartum GBS testing to determine the need for antibiotic prophylaxis to prevent neonatal GBS disease. Before implementation in practice, a robust technology assessment of their accuracy, acceptability, and cost-effectiveness is required.

Adult↗
PubMed2005

The accuracy of maternal anthropometry measurements as predictor for spontaneous preterm birth--a systematic review.

OBJECTIVE: To assess the accuracy with which antenatal maternal anthropometric measurements predict the risk spontaneous preterm birth. STUDY DESIGN: (1) DATA SOURCES: Studies were identified without language restrictions from MEDLINE, EMBASE, PASCAL, BIOSIS, the Cochrane Library, MEDION, National Research Register, SCISEARCH and Conference Papers, and manual searching of bibliographies of known primary and review articles, and contact with authors. (2) STUDY SELECTION AND DATA EXTRACTION: Studies were selected if they used antenatal maternal anthropometric features (pre-pregnancy weight, maternal pregnancy weight gain and maternal height) to predict spontaneous preterm birth. Two reviewers independently selected studies and extracted data on their characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables of the maternal anthropometric test results with spontaneous preterm birth as the reference standard. (3) DATA SYNTHESIS: Heterogeneity assessments were carried out to aid the decision regarding pooling of the accuracy results. Likelihood ratios for positive (LR+) and negative (LR-) test results were calculated, and summary estimates were produced in absence of heterogeneity of the accuracy results. RESULTS: There were eight primary accuracy articles that met the selection criteria, which included a total of 122,647 asymptomatic women. There were six studies on pre-pregnancy weight where five measured the body mass index (BMI) and one used an arbitrary measure. There were four studies on the adequacy of pregnancy weight gain and two studies on maternal height as a predictor for the risk of preterm birth. One article contributed three studies, while two articles provided two studies each. The commonest reference standard used was birth before 37 weeks' gestation. None of the studies fulfilled the ideal test accuracy study criteria. There was heterogeneity in the accuracy results of pre-pregnancy BMI but not in the adequacy of weight gain. All three maternal anthropometric features were poor predictors of preterm labour. Pre-pregnancy BMI is a poor predictor of preterm birth before 37 weeks' gestation (LR+ that ranged from 0.96 (95% confidence interval (CI) 0.66-1.40) to 1.75 (95% CI 1.33-2.31)) as are the adequacy of pregnancy weight gain (summary LR+ of 1.81, 95% CI 1.45-2.30) and short maternal height (LR+ of 1.79 (95% CI 1.27-2.52). CONCLUSION: Routine antenatal maternal anthropometric measurements are not useful in predicting the risk of preterm birth before 37 weeks' gestation. Further studies should address their use in combination with other test but need to use a more clinically appropriate reference standard of preterm birth, such as birth before 32-34 weeks' gestation, and improve on the quality of study design.

Anthropometry↗
PubMed2005

Systematic reviews of diagnostic tests: a guide to methods and application.

This chapter describes the basic steps in a systematic review to evaluate test accuracy, and the threats to validity of reviews inherent in each step. First, the problems to be addressed are specified in the form of well-structured questions (Step 1). This is a key step, as all other aspects of the review follow directly from the questions. Second, thorough literature searches are conducted to identify potentially relevant studies that shed light on the questions (Step 2). This is one essential feature that makes a review systematic. Third, the quality of the selected studies is assessed (Step 3). Fourth, the evidence concerning study characteristics and results is summarized, and differences between studies are explored (Step 4). When feasible and appropriate, meta-analysis helps in collating results. Finally, inferences and recommendations for practice are generated from interpretation and exploration of clinical relevance of the findings (Step 5). These steps are illustrated using a published review concerning the cervicovaginal fetal fibronectin test.

Decision Making↗
PubMed2005

Mapping the theories of preeclampsia: the role of homocysteine.

OBJECTIVE: We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preeclampsia. DATA SOURCES: We searched MEDLINE, EMBASE, BIOSIS, SciSearch, and bibliographies of primary and review articles, and we contacted experts. METHODS OF STUDY SELECTION: Of the 25 relevant primary articles, 8 studies measured total serum homocysteine concentrations before the clinical onset of preeclampsia (1,876 women), whereas 17 measured it afterward (1,773 women). Meta-analytic techniques were used to examine consistency, strength, temporality, dose-response, and plausibility of the disease mechanisms implicating folate, vitamin B(6), vitamin B(12), genetic polymorphisms, oxidative stress, and endothelial dysfunction in the pathway linking hyperhomocysteinemia to preeclampsia. TABULATION, INTEGRATION, AND RESULTS: Overall, there were higher serum homocysteine concentrations among pregnant women with preeclampsia than among those with uncomplicated pregnancies, but the results were heterogeneous (P = .12; I(2) = 38.8%). Among studies with temporality, the size of association was smaller than that among those without (weighted mean difference 0.68 mumol/L versus 3.36 mumol/L; P < .006). There was no dose-response relationship between homocysteine concentration and severity of preeclampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B(12) deficiency and genetic polymorphisms) were not found to be plausible, but markers of oxidative stress and endothelial dysfunction were higher in hyperhomocysteinemia. CONCLUSION: Homocysteine concentrations are slightly increased in normotensive pregnancies that later develop preeclampsia and are considerably increased once preeclampsia is established. However, because of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature.

Adult↗