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Biomedical subjects

Anthony Harnden

Publications and source records attributed to Anthony Harnden.

16 recordsLinked to original sources

Whooping cough in school age children with persistent cough: prospective cohort study in primary care.

OBJECTIVE: To estimate the proportion of school age children with a persistent cough who have evidence of a recent Bordetella pertussis infection. DESIGN: Prospective cohort study (October 2001 to March 2005). SETTING: General practices in Oxfordshire, England. PARTICIPANTS: 172 children aged 5-16 years who presented to their general practitioner with a cough lasting 14 days or more who consented to have a blood test. MAIN OUTCOME MEASURES: Serological evidence of a recent Bordetella pertussis infection; symptoms at presentation; duration and severity of cough; sleep disturbance (parents and child). RESULTS: 64 (37.2%, 95% confidence interval 30.0% to 44.4%) children had serological evidence of a recent Bordetella pertussis infection; 55 (85.9%) of these children had been fully immunised. At presentation, children with whooping cough were more likely than others to have whooping (odds ratio 2.85, 95% confidence interval 1.39 to 5.82), vomiting (4.35, 2.04 to 9.25), and sputum production (2.39, 1.14 to 5.02). Children with whooping cough were also more likely to still be coughing two months after the start of their illness (85% v 48%; P = 0.001), continue to have more than five coughing episodes a day (P = 0.049), and cause sleep disturbance for their parents (P = 0.003). CONCLUSIONS: For school age children presenting to primary care with a cough lasting two weeks or more, a diagnosis of whooping cough should be considered even if the child has been immunised. Making a secure diagnosis of whooping cough may prevent inappropriate investigations and treatment.

Adolescent↗

Parenteral penicillin for children with meningococcal disease before hospital admission: case-control study.

OBJECTIVE: To explore the impact on mortality and morbidity of parenteral penicillin given to children before admission to hospital with suspected meningococcal disease. DESIGN: Retrospective comparison of fatal and non-fatal cases. SETTING: England, Wales, and Northern Ireland; December 1997 to February 1999. PARTICIPANTS: 158 children aged 0-16 years (26 died, 132 survived) in whom a general practitioner had made the diagnosis of meningococcal disease before hospital admission. RESULTS: Administration of parenteral penicillin by general practitioners was associated with increased odds ratios for death (7.4, 95% confidence interval 1.5 to 37.7) and complications in survivors (5.0, 1.7 to 15.0). Children who received penicillin had more severe disease on admission (median Glasgow meningococcal septicaemia prognostic score (GMSPS) 6.5 v 4.0, P = 0.002). Severity on admission did not differ significantly with time taken to reach hospital. CONCLUSIONS: Children who were given parenteral penicillin by a general practitioner had more severe disease on reaching hospital than those who were not given penicillin before admission. The association with poor outcome may be because children who are more severely ill are being given penicillin before admission.

Adolescent↗

Clinical recognition of meningococcal disease in children and adolescents.

BACKGROUND: Meningococcal disease is a rapidly progressive childhood infection of global importance. To our knowledge, no systematic quantitative research exists into the occurrence of symptoms before admission to hospital. METHODS: Data were obtained from questionnaires answered by parents and from primary-care records for the course of illness before admission to hospital in 448 children (103 fatal, 345 non-fatal), aged 16 years or younger, with meningococcal disease. In 373 cases, diagnosis was confirmed with microbiological techniques. The rest of the children were included because they had a purpuric rash, and either meningitis or evidence of septicaemic shock. Results were standardised to UK case-fatality rates. FINDINGS: The time-window for clinical diagnosis was narrow. Most children had only non-specific symptoms in the first 4-6 h, but were close to death by 24 h. Only 165 (51%) children were sent to hospital after the first consultation. The classic features of haemorrhagic rash, meningism, and impaired consciousness developed late (median onset 13-22 h). By contrast, 72% of children had early symptoms of sepsis (leg pains, cold hands and feet, abnormal skin colour) that first developed at a median time of 8 h, much earlier than the median time to hospital admission of 19 h. INTERPRETATION: Classic clinical features of meningococcal disease appear late in the illness. Recognising early symptoms of sepsis could increase the proportion of children identified by primary-care clinicians and shorten the time to hospital admission. The framework within which meningococcal disease is diagnosed should be changed to emphasise identification of these early symptoms by parents and clinicians.

Adolescent↗

Detection of anti-pertussis toxin IgG in oral fluids for use in diagnosis and surveillance of Bordetella pertussis infection in children and young adults.

Bordetella pertussis infection is being increasingly recognized as a cause of prolonged, distressing cough (without whooping symptoms) in children and young adults. Diagnosis of infection in this population is important for treatment and surveillance purposes, and may also prove useful in reducing transmission to unvaccinated babies, for whom disease can be fatal. Serum IgG titres against pertussis toxin (PT) are routinely used as a marker of recent or persisting B. pertussis infection. However, collection of serum from young children is difficult, and compliance amongst these subjects to give samples is low. To circumvent these problems, an IgG-capture ELISA capable of detecting anti-PT IgG in oral fluid was devised. The assay was evaluated by comparison to a serum ELISA, using 187 matched serum and oral fluid samples from children (aged 5-16 years) with a history of prolonged coughing, whose serum anti-PT titre had already been determined (69 seropositive, 118 seronegative). The results showed that, using a cutoff of 70 arbitrary units (AU), the oral fluid assay detected seropositive subjects with a sensitivity of 79.7% [95% confidence interval (CI) 68.3-88.4] and a specificity of 96.6% (95% CI 91.5-99.1). Thus, oral fluid titres of >or=70 AU would possess a positive predictive value of 76.2-93.2% for pertussis amongst children with chronic coughs when used as a surrogate for the serum ELISA (assuming disease prevalence of 12-37%). This oral fluid ELISA will greatly assist in the convenience of B. pertussis disease diagnosis and surveillance.

Adolescent↗

Why do general practitioners prescribe antibiotics for acute infective conjunctivitis in children? Qualitative interviews with GPs and a questionnaire survey of parents and teachers.

BACKGROUND: Acute infective conjunctivitis in children is a common presentation in primary care. Treatment is usually with antibiotics and prescribing may be affected by non-clinical factors. AIMS: To investigate the non-clinical determinants of the management of acute infective conjunctivitis in children. DESIGN: Qualitative interviews with GPs and a questionnaire survey of parents of children with acute infective conjunctivitis and teachers. SETTING: GPs in Sheffield and Berkshire and parents of children with acute infective conjunctivitis and schools in Oxfordshire. METHODS: Semi-structured telephone interviews of 39 GPs. Questionnaire survey of 326 parents of children enrolled into a trial of acute infective conjunctivitis treatment. Questionnaire survey of 223 nurseries and primary schools in Oxfordshire. RESULTS: All three groups agreed that acute infective conjunctivitis was a mild condition. Parents were certain about the benefits of antibiotic treatment and sought early consultations with their GP in a desire to get their child back to school. GPs sometimes collude with a parent's request to prescribe to enable school attendance. Despite this 54.2% (95%CI 48.5-59.8%) children missed a mean of 1.85 days from school and 28.6% of parents (95%CI 23.5-33.7%) missed a mean of 1.5 days off work. CONCLUSION: Social factors, including the need for children to attend day care or school and parents to go to work, contribute to the decision to prescribe antibiotics for children with acute infective conjunctivitis. Understanding these issues and changing school policies in line with national guidance may reduce pressure on GPs to prescribe for this condition.

Adult↗

Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled trial.

CONTEXT: The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority. OBJECTIVE: To determine the safety and immunogenicity of a combination 9-valent pneumococcal-group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months. DESIGN, SETTING, AND PARTICIPANTS: Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months. INTERVENTION: Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine). MAIN OUTCOME MEASURES: Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions. RESULTS: MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] microg/mL vs 3.36 [95% CI, 2.57-4.39] microg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] microg/mL vs 1.47 [95% CI, 1.28-1.69] microg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 microg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group. CONCLUSIONS: Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.

Antibodies, Bacterial↗

Kawasaki disease: what is the epidemiology telling us about the etiology?

Kawasaki disease (KD) is an important and common inflammatory vasculitis of early childhood with a striking predilection for the coronary arteries. It is the predominant cause of paediatric acquired heart disease in developed countries. Despite 40 years of research, the aetiology of KD remains unknown and consequently there is no diagnostic test and treatment is non-specific and sub-optimal. The consensus is that KD is due to one or more widely distributed infectious agent(s), which evoke an abnormal immunological response in genetically susceptible individuals. The epidemiology of KD has been extensively investigated in many populations and provides much of the supporting evidence for the consensus regarding etiology. These epidemiological data are reviewed here, in the context of the etiopathogenesis. It is suggested that these data provide additional clues regarding the cause of KD and may account for some of the continuing controversies in the field.

Air Pollutants↗

Morbilliform rash.

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Child, Preschool↗

Chloramphenicol treatment for acute infective conjunctivitis in children in primary care: a randomised double-blind placebo-controlled trial.

BACKGROUND: One in eight schoolchildren have an episode of acute infective conjunctivitis every year. Standard clinical practice is to prescribe a topical antibiotic, although the evidence to support this practice is scarce. We undertook a randomised double-blind trial to compare the effectiveness of chloramphenicol eye drops with placebo in children with infective conjunctivitis in primary care. METHODS: Our study included 326 children aged 6 months to 12 years with a clinical diagnosis of conjunctivitis who were recruited from 12 general medical practices in the UK. We assigned 163 children to receive chloramphenicol eye drops and 163 to receive placebo eye drops. Eye swabs were taken for bacterial and viral analysis. The primary outcome was clinical cure at day 7, which was assessed from diaries completed by parents. All children were followed up for 6 weeks to identify relapse. Survival statistics were used for comparison, and analysis was by intention to treat. FINDINGS: Nine children were lost to follow-up (one in chloramphenicol group; eight in placebo group). Clinical cure by day 7 occurred in 128 (83%) of 155 children with placebo compared with 140 (86%) of 162 with chloramphenicol (risk difference 3.8%, 95% CI -4.1% to 11.8%). Seven (4%) children with chloramphenicol and five (3%) with placebo had further conjunctivitis episodes within 6 weeks (1.2%, -2.9% to 5.3%). Adverse events were rare and evenly distributed between each group. INTERPRETATION: Most children presenting with acute infective conjunctivitis in primary care will get better by themselves and do not need treatment with an antibiotic.

Acute Disease↗