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Biomedical subjects

J J Deeks

Publications and source records attributed to J J Deeks.

At least 19 recordsLinked to original sources
PubMed2001

Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells.

BACKGROUND: Identification of individuals latently infected with Mycobacterium tuberculosis is an important part of tuberculosis control. The current method, the tuberculin skin test (TST), has poor specificity because of the antigenic cross-reactivity of purified protein derivative (PPD) with M bovis BCG vaccine and environmental mycobacteria. ESAT-6 is a secreted antigen that is highly specific for M tuberculosis complex, but is absent from M bovis BCG. With an enzyme-linked immunospot (ELISPOT) assay for interferon gamma, we have identified ESAT-6-specific T cells as an accurate marker of M tuberculosis infection. METHODS: We did a prospective, masked study of 50 healthy contacts, with varying but well defined degrees of exposure to M tuberculosis, who attended an urban contact-tracing clinic. We assessed and compared the efficacy of our assay and TST for detection of symptomless infected individuals by correlation of test results with the degree of exposure to an infectious index case. FINDINGS: The ESAT-6 ELISPOT assay results had a strong positive relation with increasing intensity of exposure (odds ratio=9.0 per unit increase in level of exposure [95% CI 2.6--31.6], p=0.001), whereas TST results had a weaker relation with exposure (1.9 [1.0--3.5], p=0.05). By contrast, ELISPOT results were not correlated with BCG vaccination status (p=0.7), whereas TST results were significantly more likely to be positive in BCG-vaccinated contacts (12.1 [1.3--115.7], p=0.03). INTERPRETATION: This new antigen-specific T cell-based assay could allow more accurate identification of symptom-free individuals recently exposed to M tuberculosis, and thereby help to improve tuberculosis control.

Adult↗
PubMed2001

Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis.

CONTEXT: Second-trimester prenatal ultrasound is widely used in an attempt to detect Down syndrome in fetuses, but the accuracy of this method is unknown. OBJECTIVE: To determine the accuracy of second-trimester ultrasound in detecting Down syndrome in fetuses. DATA SOURCES: English-language articles published between 1980 and February 1999 identified through MEDLINE and manual searches. STUDY SELECTION: Studies were included if they recorded second-trimester findings of ultrasonographic markers, chromosomal abnormalities, and clinical outcomes for a well-described sample of women. A total of 56 articles describing 1930 fetuses with Down syndrome and 130 365 unaffected fetuses were included. DATA EXTRACTION: Articles were independently reviewed, selected, and abstracted by 2 reviewers. Discrepancies in data abstraction were resolved by consensus with a third reviewer. Overall estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated for the following markers: choroid plexus cyst, thickened nuchal fold, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, and humeral and femoral shortening. Results were stratified by whether markers were identified in isolation or in conjunction with fetal structural malformations. DATA SYNTHESIS: When ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each was low (range, 1%-16%), and most fetuses with such markers had normal outcomes. A thickened nuchal fold was the most accurate marker for discriminating between unaffected and affected fetuses and was associated with an approximately 17-fold increased risk of Down syndrome. If a thickened nuchal fold is used to screen for Down syndrome, 15 893 average-risk women or 6818 high-risk women would need to be screened for each case of Down syndrome identified. For each of the other 6 markers, when observed without associated structural malformations, the marker had marginal impact on the risk of Down syndrome. Because the markers were detected in only a small number of affected fetuses, the likelihood of Down syndrome did not decrease substantially after normal examination findings (none of the negative likelihood ratios were significant). CONCLUSIONS: A thickened nuchal fold in the second trimester may be useful in distinguishing unaffected fetuses from those with Down syndrome, but the overall sensitivity of this finding is too low for it to be a practical screening test for Down syndrome. When observed without associated structural malformations, the remaining ultrasonographic markers could not discriminate well between unaffected fetuses and those with Down syndrome. Using these markers as a basis for deciding to offer amniocentesis will result in more fetal losses than cases of Down syndrome detected, and will lead to a decrease in the prenatal detection of fetuses with Down syndrome.

Down Syndrome↗
PubMed2001

Suicide in doctors: a study of risk according to gender, seniority and specialty in medical practitioners in England and Wales, 1979-1995.

STUDY OBJECTIVE: To investigate the suicide risk of doctors in England and Wales, according to gender, seniority and specialty. DESIGN: Retrospective cohort study. Suicide rates calculated by gender, age, specialty, seniority and time period. Standardised mortality ratios calculated for suicide (1991-1995), adjusted for age and sex. SETTING: England and Wales. SUBJECTS: Doctors in the National Health Service who died by suicide between 1979 and 1995, identified by death certificates. Population at risk based on Department of Health manpower data. MAIN RESULTS: Two hundred and twenty three medical practitioners in the National Health Service who died by suicide or undetermined cause were identified. The annual suicide rates in male and female doctors were 19.2 and 18.8 per 100 000 respectively. The suicide rate in female doctors was higher than in the general population (SMR 201.8; 95% CI 99.7, 303.9), whereas the rate in male doctors was less than that of the general population (SMR 66.8; 95% CI 46.6, 87.0). The difference between the mortality ratios of the female and male doctors was statistically significant (p=0.01), although the absolute suicide risk was similar in the two genders. There were significant differences between specialties (p=0.0001), with anaesthetists, community health doctors, general practitioners and psychiatrists having significantly increased rates compared with doctors in general hospital medicine. There were no differences with regard to seniority and time period. CONCLUSIONS: There is an increased risk of suicide in female doctors, but male doctors seem to be at less risk than men in the general population. The excess risk of suicide in female doctors highlights the need to tackle stress and mental health problems in doctors more effectively. The risk requires particular monitoring in the light of the very large increase in the numbers of women entering medicine.

Adult↗
PubMed2000

Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom.

CONTEXT: The schedule for Haemophilus influenzae type b (Hib) vaccination of infants in the United Kingdom consists of 3 doses given at 2, 3, and 4 months of age. Many countries include a fourth dose (booster) of Hib vaccine in the second year of life on the basis of declining Hib antibody concentrations after the primary series. Few data are available to show that this fourth dose is actually necessary. OBJECTIVE: To evaluate long-term clinical protection against Hib disease and Hib antibody concentrations following primary Hib vaccination without a booster dose. DESIGN, SETTING, AND SUBJECTS: Clinical protection study conducted between October 1992 and March 1999 in the United Kingdom, in which children developing invasive Hib disease despite vaccination in infancy with 3 doses of Hib conjugate vaccine were reported by pediatricians through an active, prospective, national survey. Separate antibody studies were conducted among 2 cohorts of children (n = 153 and n = 107) vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccine and followed up to 43 and 72 months of age. MAIN OUTCOME MEASURES: Age-specific vaccine effectiveness, derived from the observed number of true vaccine failures after 3 Hib vaccine doses compared with the number of cases expected based on the age-specific rates of invasive Hib disease obtained prior to the introduction of Hib vaccines; and proportion of children in the 2 cohorts with Hib antibody concentrations of less than 0.15 and less than 1.0 microg/mL. RESULTS: Ninety-six true vaccine failures occurring after 3 vaccine doses were detected. During the study period, an estimated 4,368,200 infants in the United Kingdom received 3 doses of vaccine; therefore, the vaccine failure rate was 2.2 per 100,000 vaccinees (95% confidence interval, 1.8-2.7 per 100,000). Although vaccine effectiveness declined significantly after the first year of life (P<.001), it remained high until the sixth year of life (99.4% in children aged 5-11 months vs 97.3% in those aged 12-71 months). The proportion of cohorts 1 and 2 with anti-PRP antibody levels of less than 0.15 microg/mL increased between 12 and 72 months of age (6% at 12 months, 8% at 43 months, and 32% at 72 months; chi(2)(1) = 18.25; P<.001 for trend). CONCLUSIONS: Our results suggest that anti-PRP antibody levels and clinical protection against Hib disease wane over time after Hib vaccination at 2, 3, and 4 months of age without a booster dose at 2 years of age. The decline in clinical protection is minimal, however, suggesting that a booster dose of Hib vaccine following infant vaccination is not essential. JAMA. 2000;284:2334-2340.

Antibodies, Bacterial↗
PubMed2000

Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial.

CONTEXT: Neisseria meningitidis is a common cause of meningitis and septicemia in infants worldwide. Whether a meningococcal C conjugate vaccine protects infants against the serogroup C strain is unknown. OBJECTIVES: To determine whether a meningococcal C conjugate vaccine is safe and immunogenic and induces immunologic memory in infants. DESIGN: Single-center, double-blind, randomized controlled trial in 1995 and 1996. SETTING: Community, Oxfordshire, England. PARTICIPANTS: One hundred eighty-two healthy infants. INTERVENTIONS: Participants were randomly assigned to receive vaccination with 0. 5-mL doses of 1 of 2 lots of meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or a hepatitis B control vaccine (group 3; n=62), administered with routine immunizations at 2, 3, and 4 months of age. Approximately half of each group received meningococcal C conjugate vaccine and half received plain meningococcal polysaccharide vaccine (MPS) at 12 months of age. MAIN OUTCOME MEASURES: Serum antibodies to meningococcal C polysaccharide, assayed by enzyme-linked immunosorbent assay, and serum bactericidal activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and systemic reactions, recorded for 6 days after each vaccination, compared by intervention group. RESULTS: Meningococcal C conjugate vaccine was well tolerated. After 3 doses, children in groups 1 and 2 achieved significantly higher meningococcal C IgG geometric mean concentrations (21 and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and 420, respectively, vs 4.1; P<. 001) than controls. At 12 months, antibody concentrations had decreased in all groups but remained significantly higher in children vaccinated with meningococcal C conjugate vaccine (SBA, 24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001). Following vaccination with MPS at 12 months of age, SBA in the meningococcal C conjugate vaccine group was significantly higher than in controls (SBA, 789 vs 4.5; P<.001). CONCLUSIONS: Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age. JAMA. 2000;283:2795-2801

Analysis of Variance↗
PubMed2000

The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. CARE-COAD1 Group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease.

CONTEXT: The accuracy of the clinical examination in detecting obstructive airway disease (OAD) is largely unknown because of a paucity of methodologically rigorous studies. OBJECTIVE: To determine the accuracy of patient history, wheezing, laryngeal height, and laryngeal descent in the diagnosis of OAD. DESIGN: Comparison study conducted from November 3, 1998, to December 4, 1998, evaluating 4 clinical examination elements for diagnosis of OAD vs the gold standard of forced expiratory volume in 1 second (FEV1) and FEV1-forced vital capacity (FVC) ratio less than the fifth percentile (adjusted for patient height, age, and sex). SETTING: Twenty-five sites, including primary care and referral practices, in 14 countries. PARTICIPANTS: A total of 309 consecutive patients were recruited (mean age, 56 years; 43% female), 76 (25%) with known chronic OAD, 114 (37%) with suspected chronic OAD, and 119 (39%) with neither known nor suspected OAD. MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios (LRs) for each of the 4 elements of the clinical examination compared with the gold standard. RESULTS: Mean FEV1 and FVC values were 2.1 L/s and 2.9 L; 52% had an FEV1 and FEV1-FVC ratio less than the fifth percentile. The LR for wheezing was 2.7 (95% confidence interval [CI], 1.7-4.2) and was not statistically significant in the multivariate model. The LR for laryngeal descent ranged from 0.9 (95% CI, 0.5-1.4) to 1.2 (95% CI, 0.4-3.4), depending on the cut point chosen, and did not enter the multivariate model. Only 4 of the history or physical examination elements we tested were significantly associated with the diagnosis of OAD on multivariate analysis: smoking for more than 40 pack-years (LR, 8.3), self-reported history of chronic OAD (LR, 7.3), maximum laryngeal height of 4 cm [corrected] or less (LR, 2.8), and age at least 45 years (LR, 1.3). Patients having all 4 findings had an LR of 220 (ruling in OAD); those with none had an LR of 0.13 (ruling out OAD). The area under the receiver operating characteristic curve for the model incorporating these 4 factors was 0.86. CONCLUSIONS: Further research is needed to validate our model, but in the meantime, our data suggest that less emphasis should be placed on the presence of individual symptoms or signs (such as wheezing or laryngeal descent) in the diagnosis of OAD.

Female↗
PubMed2000

Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. The gamma-aminobutyric acid (GABA) agonist drugs have been trialed as a treatment for TD, but these drugs have intense sedative properties and can possibly exacerbate psychotic symptoms. OBJECTIVES: To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) in people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1998), The Cochrane Library CENTRAL (1998), Cochrane Schizophrenia Group's Register of Trials (1998), EMBASE (1980-1998), LILACS (1982-1996), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. First authors of each included trial were contacted. SELECTION CRITERIA: The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of GABA agonist drugs to placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the odds ratio (OR) and its 95% confidence interval (CI) or the weighted mean difference with 95% CI were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Eight studies were able to be included. Results were equivocal, showing only a tendency for clinical improvement for those using GABA agonist drugs but, when analysis of any improvement (rather than clinical improvement) was performed, a significant reduction was noted in the GABA group (OR 0.36 CI 0.15-0.85). This suggests that for every 10 people treated with GABA drugs one person would benefit with a reduction in TD symptoms. People using the interventions had more confusion (OR 7.4 CI 1.3-40.9) and sedation (OR 3.0 CI 1.2-7.6). The numbers of people needed to treat to cause one extra person to experience these side effects were three and six, respectively. Tendency for more deterioration of the TD symptoms (OR 1.72 CI 0. 54-5.5), deterioration of the mental state (OR 3.07 CI 0.78-12.05), and to drop out before the end of the trial (OR 2.05 CI 0.8-5.21) were also observed in those using GABA agonists. REVIEWER'S CONCLUSIONS: No clear statement about the efficacy of GABA agonist drugs could be provided. From the combined data, GABA agonist drugs tend to be associated with some degree of improvement in TD symptoms, but also with side effects such as confusion and sedation and a deterioration of the person's mental state.

Antipsychotic Agents↗
PubMed2000

Amantadine and rimantadine for preventing and treating influenza A in adults.

OBJECTIVES: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their properties and concerns about possible adverse effects. The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects. MAIN RESULTS: Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%) Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system adverse and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWER'S CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine.

Adult↗
PubMed2000

Vaccines for preventing influenza in healthy adults.

OBJECTIVES: To identify, retrieve and assess all studies evaluating the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. SEARCH STRATEGY: MEDLINE was searched using the strategy of the Cochrane Acute Respiratory Infections Group. The bibliography of retrieved articles, the Cochrane Controlled Trials Register (CCTR), and EMBASE (1990 to 1997) were also searched. Handsearch of the journal Vaccine from its first issue to the end of 1997 (Jefferson and Jefferson, 1996; Jefferson, 1998). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. DATA COLLECTION AND ANALYSIS: Both clinically defined cases and serologically confirmed cases of influenza were considered as outcomes according to the authors' definitions. Time off work, complication and hospitalisation rates were considered, together with adverse effects. Vaccine schedules were analysed including one component matching the recommended vaccine (WHO or government recommendations) for the year of the study, and whether they matched the circulating viral subtypes. MAIN RESULTS: The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza A by 48% (95% confidence interval 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 68% (95% confidence interval 49% to 79%). The vaccines were less effective in reducing clinical influenza cases, with efficacies of 13% and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days for each influenza episode (95% confidence interval 0.1 to 0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. REVIEWER'S CONCLUSIONS: Influenza vaccines are effective in reducing serologically confirmed cases of influenza A. However, they are not as effective in reducing cases of clinical influenza. The use of WHO recommended vaccines appears to enhance their effectiveness in practice.

Adult↗
PubMed1999

Effects of a drug overdose in a television drama on presentations to hospital for self poisoning: time series and questionnaire study.

OBJECTIVES: To determine whether a serious paracetamol overdose in the medical television drama Casualty altered the incidence and nature of general hospital presentations for deliberate self poisoning. DESIGN: Interrupted time series analysis of presentations for self poisoning at accident and emergency departments during three week periods before and after the broadcast. Questionnaire responses collected from self poisoning patients during the same periods. SETTING: 49 accident and emergency departments and psychiatric services in United Kingdom collected incidence data; 25 services collected questionnaire data. SUBJECTS: 4403 self poisoning patients; questionnaires completed for 1047. MAIN OUTCOME MEASURES: Change in presentation rates for self poisoning in the three weeks after the broadcast compared with the three weeks before, use of paracetamol and other drugs for self poisoning, and the nature of overdoses in viewers of the broadcast compared with non-viewers. RESULTS: Presentations for self poisoning increased by 17% (95% confidence interval 7% to 28%) in the week after the broadcast and by 9% (0 to 19%) in the second week. Increases in paracetamol overdoses were more marked than increases in non-paracetamol overdoses. Thirty two patients who presented in the week after the broadcast and were interviewed had seen the episode-20% said that it had influenced their decision to take an overdose, and 17% said it had influenced their choice of drug. The use of paracetamol for overdose doubled among viewers of Casualty after the episode (rise of 106%; 28% to 232%). CONCLUSIONS: Broadcast of popular television dramas depicting self poisoning may have a short term influence in terms of increases in hospital presentation for overdose and changes in the choice of drug taken. This raises serious questions about the advisability of the media portraying suicidal behaviour.

Acetaminophen↗