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Biomedical subjects

K G Nicholson

Publications and source records attributed to K G Nicholson.

At least 19 recordsLinked to original sources
PubMed2005

The cost-effectiveness of influenza vaccination of healthy adults 50-64 years of age.

Influenza can cause significant morbidity and mortality. Influenza vaccination is an effective and safe strategy in the prevention of influenza. Currently the National Health Service (NHS) vaccinates 'at-risk' individuals only. This definition includes everyone over 65 years of age but excludes individuals 50-64 years of age unless they have an additional risk factor, such as underlying heart disease or lung disease. In order to examine the cost-effectiveness of an extension of the vaccination policy to include this age group we constructed an economic model to estimate the costs and benefits of vaccination from both a health service and a societal perspective. Data to populate the model was obtained from the literature and the outcome measure used was the quality adjusted life year (QALY). Influenza vaccination prevented an estimated 4508 cases (95% CI: 2431-7606) per 100,000 vaccinees per influenza season for a net cost to the NHS of pound653,221 (95% CI: 354,575-1,072,257). The net cost increased to pound1,139,069 (95% CI 27,052-2,030,473) when non-NHS costs were included and the estimated cost-per-QALY were pound6174 and pound10,766 for NHS and all costs respectively. Extension of the current immunisation policy has the potential to generate a significant health benefit at a comparatively low cost.

Cost-Benefit Analysis↗
PubMed2004

Detection of anti-H5 responses in human sera by HI using horse erythrocytes following MF59-adjuvanted influenza A/Duck/Singapore/97 vaccine.

Haemagglutination-inhibition (HI) tests are a simple method used to assess immune responses to influenza haemagglutinin. However, HI tests are insensitive at detection of antibody responses to avian haemagglutinin after vaccination or natural infection, even in the presence of high titres of neutralising antibody or virus isolation. Avian influenza viruses preferentially bind to sialic acid receptors that contain N-acetylneuraminic acid alpha2,3-galactose (alpha2,3Gal) linkages while human viruses preferentially bind to those containing N-acetylneuraminic acid alpha2,6-galactose (alpha2,6Gal) linkages. By using horse erythrocytes in the HI test and thereby increasing the proportion of alpha2,3Gal linkages available for binding, we are able to demonstrate improved detection of antibody to avian H5 in human sera following vaccination with MF59-adjuvanted A/Duck/Singapore/97 surface antigen vaccine. This modified HI test was more sensitive in detection of anti-H5 antibody evoked by revaccination of primed subjects and may be useful in assessing potential avian HA vaccine candidates.

Adjuvants, Immunologic↗
PubMed2003

Sialic acid receptor specificity on erythrocytes affects detection of antibody to avian influenza haemagglutinin.

Haemagglutination-inhibition tests (HI) are used to detect increases in influenza antibody in serum. However, they are relatively insensitive for the detection of human antibody responses to avian haemagglutinin, even in the presence of high titres of neutralising antibody after confirmed infection or vaccination. Human influenza viruses bind preferentially sialic acid containing N-acetylneuraminic acid alpha2,6-galactose (SAalpha2,6Gal) linkages while avian and equine viruses bind preferentially those containing N-acetylneuraminic acid alpha2,3-galactose (SAalpha2,3Gal) linkages. Increasing the proportion of SAalpha2,3Gal linkages on the erythrocytes used, by enzymatic modification or change of species, improves the ability of erythrocytes to bind to avian influenza strains and thereby improves the sensitivity of detection of antibody to avian and equine HA in a range of mammalian and human sera using HI tests.

Animals↗
PubMed2002

Experience with the clinical development of influenza vaccines for potential pandemics.

During normal interpandemic influenza seasons, immune responses to vaccines are quite predictable and meet the licensing criteria of the European Union (EU) Committee for Proprietary Medicinal Products (CPMP). In a pandemic situation, large sections, if not all of the community will be immunologically naïve and therefore new immunisation strategies will be needed. In 1976 and 1977 H1N1 vaccines were prepared and tested clinically. To stimulate 'protective' antibody responses, two doses of vaccine were needed in people below the age of 24 years (no previous experience of H1N1 virus), whereas one conventional dose was adequate in older people. In 1997, the highly pathogenic avian influenza H5N1 virus caused widespread concern when it infected man, with lethal effects. Due to safety concerns it was necessary to adopt new strategies for vaccine development and one such strategy was to produce vaccine from an avirulent H5N3 virus, A/Duck/Singapore-Q/F119-2/97. Clinical trials of a subunit vaccine prepared from A/Duck/Sing/97 virus revealed that even two doses of twice the normal vaccine concentration (i.e. 30 micro g haemagglutinin) were poorly immunogenic, whereas an H5N3 vaccine adjuvanted with microfluidised emulsion (MF) 59 stimulated antibody levels that complied with CPMP criteria after two half strength doses (i.e. 7.5 micro g haemagglutinin).

Clinical Trials as Topic↗
PubMed2002

Healthcare workers and their attitudes to influenza vaccination.

Despite Department of Health recommendations that healthcare workers (HCWs) receive influenza vaccination, uptake is low. Influenza vaccination has been promoted to reduce nosocomial transmission and staff absenteeism during the winter period. Our study aimed to investigate factors associated with uptake, and non-uptake, of influenza vaccination. In March 2001 we undertook a questionnaire-based cross-sectional survey of 604 hospital HCWs in Leicester and 11 occupational health nurses. Following multivariate analysis, uptake was associated with previous influenza vaccination (OR: Odds ratio 1000, 95% CI 20-3,333), age > 45 years (OR 4.45, 95% CI 1.66-11.9), and belief that influenza is a serious illness (OR 3.8, 95% CI 1.3-10.6). HCWs receive vaccination predominantly as a benefit for themselves. Campaigns should improve accessibility, target younger staff and stress the consequences of influenza infection. Simply raising awareness may not translate into increased uptake. Absenteeism was attributed to vaccine-related adverse effects by 11/83 (13%) vaccinees, resulting in 0.46 workdays lost per dose administered.

Adult↗
PubMed2001

Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza.

BACKGROUND: In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat to human beings. A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines. METHODS: 32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 microg haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination. FINDINGS: The A/Duck/SIngapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 microgram doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 microg doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus. INTERPRETATION: Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 microg haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.

Adult↗
PubMed2001

Surface cues reduce the latency to name rotated images of objects.

Jolicoeur (1985, Memory & Cognition 13 289-303) found a linear increase in the latency to name line drawings of objects rotated (0 degrees to 120 degrees) from the upright (0 degrees) in the initial trial block. This effect was much shallower in later blocks. He proposed that the initial effect may indicate that mental rotation is the default process for recognising rotated objects, and that the decrease in this effect, seen with practice, may reflect the increased use of learned orientation-invariant features. Initially, we were interested in whether object-colour associations that may be learned during the initial block, could account for the reduced latency to name rotated objects, seen in later blocks. In experiment 1 we used full-cue colour images of objects that depicted colour and other surface cues. Surprisingly, given that Jolicoeur's findings were replicated several times with line drawings, we found that even the initial linear trend in naming latency was shallow. We replicated this result in follow-up experiments. In contrast, when we used less-realistic depictions of the same objects that had fewer visual cues (ie line drawings, coloured drawings, greyscale images), the results were comparable to those of Jolicoeur. Also, the initial linear trends were steeper for these depictions than for full-cue colour images. The results suggest that, when multiple surface cues are available in the image, mental rotation may not be the default recognition process.

Adult↗
PubMed2001

Influenza: vaccination and treatment.

Few conditions exert such an enormous toll of absenteeism, suffering, medical consultations, hospitalization, death and economic loss as influenza. Patients at high risk of complications and mortality include the elderly and those with pre-existing cardiopulmonary disease. The outbreak in 1997 in Hong Kong, of avian H5N1 influenza in man, which resulted in six deaths among 18 hospitalized cases, and the recent isolation of H9N2 viruses from two children in Hong Kong, are reminders that preparation must be made for the next pandemic. Since the 1970s, efforts to control influenza have mostly focussed on the split product and surface antigen vaccines. These vaccines are of proven efficacy in healthy adults and are effective in elderly people with and without medical conditions putting them at high risk of complications and death following influenza infection. However, vaccine coverage is patchy and often low, and outbreaks of influenza are not uncommon in well-immunized residents of nursing homes. New vaccines and methods of vaccine delivery are being developed in attempts to overcome the limitations of existing vaccines. The antiviral drugs amantadine and rimantadine were developed in the 1960s, but have not been used widely due to their spectrum of activity, rapid emergence of resistance, and adverse effects associated with amantadine. The site of enzyme activity of the influenza neuraminidase is highly conserved between types, subtypes and strains of influenza and has emerged as the target of an exciting new class of antiviral agents that are effective both prophylactically and as therapy.

Adult↗
PubMed2000

Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group.

BACKGROUND: Use of some antiviral drugs for influenza infection is limited by potential rapid emergence of resistance. We studied the efficacy and safety of oseltamivir, the oral prodrug of the neuraminidase inhibitor GS4071, in adults with naturally acquired laboratory-confirmed influenza. METHODS: We did a randomised controlled trial of 726 previously healthy non-immunised adults with febrile influenza-like illness of up to 36 h duration. Patients were assigned oral oseltamivir 75 mg (n=243), oseltamivir 150 mg (n=245), or placebo (n=238) twice daily for 5 days. We assessed recovery by questionnaire and temperature recordings. The primary endpoint was time to resolution of illness in influenza-infected patients. FINDINGS: 475 (66%) patients had confirmed infection. Duration of illness was significantly shorter by 29 h (25% reduction, median duration 87.4 h [95% CI 73.3-104.7], p=0.02) with oseltamivir 75 mg and by 35 h (30%, 81.8 h [68.2-100.0], p=0.01) with oseltamivir 150 mg than with placebo (116.5 h [101.5-137.8]). The effect of oseltamivir was apparent within 24 h of the start of treatment. In patients treated within 24 h of symptom onset, symptoms were alleviated 43 h (37% reduction) and 47 h (40%) earlier with oseltamivir 75 mg and 150 mg, respectively, compared with placebo (75 mg 74.5 h [68.2-98.0], p=0.02; 150 mg 70.7 h [54.0-89.4], p=0.01; placebo 117.5 h [103.0-143.8]). Oseltamivir was associated with lower [corrected] symptom scores, less viral shedding, and improved health, activity, and sleep quality, and was well tolerated. INTERPRETATION: Oseltamivir was effective and well tolerated in the treatment of natural influenza infection in adults. The efficacy, tolerability, and ease of administration warrant further investigation in children, elderly patients, and at-risk patients.

Acetamides↗
PubMed1999

Cytomegalovirus viraemia has poor predictive value for the development of cytomegalovirus disease in patients with advanced HIV-infection.

OBJECTIVE: Cytomegalovirus (CMV) continues to be one of the most important opportunistic infections associated with human immunodeficiency virus (HIV) infection. This study investigated the value of CMV-viraemia in predicting the development of clinical CMV disease in patients with advanced HIV infection. METHODS: This was a prospective observational study performed over a 2-year period between 1994-96 in the Department of Infection and Tropical Medicine at Leicester Royal Infirmary. Adult HIV-positive patients attending a hospital clinic were included if they were CMV-seropositive with CD4 counts < or =50 cells/mm3. Subjects were seen at approximately 6-weekly intervals in the clinic and were reviewed by an experienced ophthalmologist. Serum for CMV PCR was taken and stored at regular intervals and qualitative and quantitative PCR was performed at the end of the study period. The value of PCR in predicting the development of CMV disease was then assessed. RESULTS: Twenty-six patients were followed up during the study period and 77 evaluable specimens were analysed for CMV PCR. Twenty-three (30%) samples were positive and 54 negative. Seven (27%) patients developed CMV disease (five retinitis alone, and two with retinitis and oesophagitis) during the study period. Viraemia was often intermittent and there was no significant difference in the proportions of patients with positive or negative tests who subsequently developed CMV disease. The sensitivity, specificity, positive and negative predictive values of the qualitative PCR were 71%, 47%, 33% and 82% respectively and 57%, 74%, 44% and 82% respectively for the quantitative PCR (>10(3) copies/ml). CONCLUSIONS: The results from this study, which was performed before the introduction of protease inhibitors, found that cytomegalovirus PCR was of limited clinical value in predicting the patients at greatest risk of developing CMV-disease and provided little useful prognostic information.

AIDS-Related Opportunistic Infections↗
PubMed1999

Influenza A among community-dwelling elderly persons in Leicestershire during winter 1993-4; cigarette smoking as a risk factor and the efficacy of influenza vaccination.

In a prospective study of community-dwelling people 60-90 years of age, we examined the coverage of influenza vaccine during 1992-3 and 1993-4, the efficacy of vaccination in reducing serologically-confirmed clinical episodes of influenza A during 1993, and the effect of cigarette smoking. During 1992 and 1993, influenza vaccine was given to 106/215 (49%) and 120/204 (59%) people with risk conditions, and 84/225 (37%) and 103/235 (44%) without risk conditions. Influenza vaccination and general practitioner consultations during 1992 were independent predictors of vaccination in 1993, but current smoking was a negative predictor. Of 209 unimmunized people, 8/35 (23%) smokers had clinical influenza as compared with 11/174 (6%) non-smokers (OR 4.4, 95% CI 1.6 to 11.9). Of 371 non-smokers, 1/197 (0.5%) vaccinees had influenza as compared with 11/174 (6%) non-vaccinees (OR 0.075, 95% CI 0.587 to 0.009). No cases of influenza occurred among 21 current smokers who were vaccinated.

Aged↗
PubMed1998

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma.

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.

Adult↗
PubMed1997

Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden.

OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home. DESIGN: Prospective surveillance of elderly people. INTERVENTION: None. SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age. MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.

Aged↗
PubMed1997

Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group.

BACKGROUND: The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases. These viral enzymes are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, zanamivir has potent antiviral effects. We assessed the therapeutic activity of zanamivir in adults with acute influenza. METHODS: We conducted separate randomized, double-blind studies in 38 centers in North America and 32 centers in Europe during the influenza season of 1994-1995. A total of 417 adults with influenza-like illness of < or =48 hours' duration were randomly assigned to one of three treatments: 6.4 mg of zanamivir by intranasal spray plus 10 mg by inhalation, 10 mg of zanamivir by inhalation plus placebo spray, or placebo by both routes. Treatments were self-administered twice daily for five days. RESULTS: Of 262 patients with confirmed influenza-virus infection (63 percent of all patients), the median length of time to the alleviation of all major symptoms was one day shorter (four days vs. five days) in the 88 patients given inhaled and intranasal zanamivir (P=0.02) and the 85 patients given inhaled zanamivir alone (P=0.05) than in the 89 patients given placebo. Among the infected patients who were febrile at enrollment and among those who began treatment within 30 hours after the onset of symptoms, the median time to the alleviation of major symptoms was four days in both zanamivir groups and seven days in the placebo group (P< or =0.01). Viral titers of nasal washings in the group given inhaled and intranasal zanamivir were significantly lower than those in the placebo group. The topically administered zanamivir was well tolerated. CONCLUSIONS: In adults with influenza A or B virus infections, direct administration of a selective neuraminidase inhibitor, zanamivir, to the respiratory tract is safe and reduces symptoms if begun early.

Administration, Inhalation↗
PubMed1997

Outpatient parenteral antimicrobial therapy: experience in a large teaching hospital.

OBJECTIVE: to determine the practicality of treatment of infectious conditions requiring prolonged parenteral antimicrobial therapy. METHOD: review of all patients admitted to a Regional Infectious Diseases (ID) Unit who received outpatient parenteral therapy over a 12-month period. The study identified the conditions suitable for outpatient therapy, the organization of treatment and the complications and financial implications of the service. RESULTS: fifteen patients (age range 32-81) received outpatient parenteral antimicrobial therapy during the period of the study. Five patients were HIV-positive and were treated for cytomegalovirus retinitis or severe recurrent candida infection with self-administration of drugs through a Hickman line. HIV-negative patients were treated for osteomyelitis, deep-seated abscesses and subacute bacterial endocarditis. Eight of the 10 HIV-negative patients were given ceftriaxone once daily. The organization and delivery of outpatient drug therapy depended on the nature of the underlying infection and the availability of community services. Outpatient therapy was associated with considerable financial savings, and no serious adverse events were recorded. CONCLUSION: outpatient parenteral treatment is a reasonable option for a relatively small number of patients, representing less than 2% of patients admitted to the ID Unit over the time course of the study. Patients suitable for outpatient treatment have a stable medical condition and require prolonged antimicrobial therapy.

AIDS-Related Opportunistic Infections↗