Roger Newson

Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood

Background We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring.

Paracetamol use in pregnancy and wheezing in early childhood

Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18–20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30–42 months (n=9400) and eczema at 18–30 months (n=10 216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30–42 months) were examined. Results: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20–32 weeks), but not in early pregnancy (<18–20 weeks), was associated with an increased risk of wheezing in the offspring at 30–42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30–42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. Conclusions: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.

Paracetamol sales and atopic disease in children and adults: an ecological analysis

The authors recently observed that frequent paracetamol use was positively associated with asthma and rhinitis in young adults. Therefore, an ecological analysis was performed to measure international associations between paracetamol sales and atopic disease prevalences in children and adults. Published data from the International Study of Asthma and Allergies in Childhood (ISAAC) on the prevalence of four atopic symptoms in 13-14-yr-olds (112 centres) and 67-yr-olds (66 centres) in 1994/1995, and European Community Respiratory Health Survey (ECRHS) data on the prevalence of asthma symptoms, diagnosed asthma and rhinitis (44 centres), prevalence of atopy, mean bronchial responsiveness and mean total immunoglobulin E levels (34 centres) in young adults in 1991/1992, were used. Their associations with national 1994/1995 per capita paracetamol sales were measured using linear regression. Paracetamol sales were high in English-speaking countries, and were positively associated with asthma symptoms, eczema and allergic rhinoconjunctivitis in 13-14-yr-olds, and with wheeze, diagnosed asthma, rhinitis and bronchial responsiveness in adults. The prevalence of wheeze increased by 0.52% in 13-14-yr-olds and by 0.26% in adults (p<0.0005) for each gram increase in per capita paracetamol sales. These ecological findings require cautious interpretation, but raise the possibility that variation in paracetamol usage may explain some of the variation in atopic disease prevalence between countries.

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30–42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0–6 months and 30–42 months, respectively (n=2,044), and with eczema at 18–30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.

HLA-C and guttate psoriasis

Backgroundu2002Psoriasis is a heterogeneous disease in its clinical expression. Both genetic and environmental factors are thought to contribute to the pathogenesis of the inflammatory and hyperproliferative components of the typical skin lesions. Predisposing genetic influences include associations with human leucocyte antigens (HLA) of which that with HLA‐Cw6 is the strongest. Guttate psoriasis is a specific clinical manifestation of psoriasis frequently associated with group A β‐haemolytic streptococcal throat infection.

Diagnosis and initial management of stroke and transient ischemic attack across UK health regions from 1992 to 1996: experience of a national primary care database.

Background and Purpose The aim of this study was to establish the difference in burden of cerebrovascular disease across the different health regions of the United Kingdom and to determine whether the initial management of new cases of stroke and transient ischemic attack (TIA) was uniform across the United Kingdom. Methods The General Practice Research Database (GPRD) is a national database used for epidemiological studies. This was a cohort study identifying incident cases of stroke and TIA over a 5-year study period between 1992 and 1996. The population studied was patients registered with general practitioners contributing to the GPRD across the different health regions of the United Kingdom. Outcome measures were new diagnoses of stroke and TIA, new prescriptions for antiplatelet and anticoagulant agents, and referrals made for specialist opinion. Results The age-adjusted annual incidence rate across all regions was 151 per 100000 for stroke and 190 per 100000 for TIA. There was almost a 2-fold difference in the incidence of cerebrovascular disease between the regions. The management of stroke and TIA in terms of antiplatelet prescription and of referral onward for further opinion to hospital specialists varied significantly between regions. Conclusions Reported stroke and TIA incidence on the GPRD was comparable to that of other European studies. There were striking regional differences in the incidence of disease. The primary care management, both in prescription and referral rates, varied significantly between the different regions. There was a marked underuse of antiplatelet and anticoagulant agents, and referral rates for specialists’ opinions were low.

A comparison of telemedicine with face-to-face consultations for trauma management.

We compared the accuracy of teleconsultations for minor injuries with face-to-face consultations. Two hundred patients were studied. Colour change, swelling, decreased movement, tenderness, instability, radiological examination, severity of illness, treatment and diagnosis were recorded for both telemedicine and face-to-face consultations. Colour change showed an accuracy of 97%, presence of swelling or deformity of 98%, diminution of joint movement of 95%, presence of tenderness of 97%, weight bearing and gait of 99%, and radiological diagnosis of 98%. The severity of illness or injury was overestimated in one case and underestimated in five cases. Treatment was over-prescribed in one case and under-prescribed in three cases. The final diagnosis was correct in all but the two cases in which mistakes were made in the teleradiology. Overall, there was good accuracy using teleconsultations.

Comparison of virologic, immunologic, and clinical response to five different initial protease inhibitor-containing and nevirapine-containing regimens.

Context: The effectiveness of different protease inhibitors (PIs) and non‐nucleoside reverse transcriptase inhibitors outside the setting of clinical trials has not been well described. Objectives: To compare five different PI‐ and nevirapine (NVP)‐containing regimens on virologic, immunologic, and clinical outcomes and treatment discontinuation. Design and Setting: Observational cohort study based on an HIV clinic in London. Patients: A total of 690 patients who received either saquinavir hard gel (SQV HG) (n = 183), indinavir (IDV) (n = 189), nelfinavir (NFV) (n = 109), ritonavir (RTV) (n = 42), ritonavir with saquinavir hard gel (RTV/SQV HG) (n = 45), or NVP (n = 122) as part of an initial PI‐ or NVP‐containing treatment regimen between November 1994 and December 1998. A total of 351 (51%) patients had prior exposure to nucleoside reverse transcriptase inhibitors (NRTIs). Main Outcome Measures: The main outcome measures were virologic undetectability, subsequent virologic rebound, CD4 cell count rise, development of AIDS, and treatment discontinuation. All analyses were stratified for year of initiation of the PIor NVP‐containing regimen. Results: Overall, 63% of patients attained an undetectable viral load (VL) within 6 months of starting their PI or NVP regimen. The adjusted relative hazard (95% confidence interval [CI]) for an undetectable VL relative to SQV HG was (in rank order): 2.77 (CI: 1.84‐4.17) for NFV, 2.54 (CI: 1.81‐3.57) for IDV, 2.43 (CI: 1.52‐3.87) for RTV, 2.08 (CI: 1.28‐3.37) for RTV/SQV HG, and 1.96 (CI: 1.35‐2.85) for NVP. Forty‐nine percent of patients experienced VL rebound within 12 months of initial attainment of undetectability, but relative to SQV HG, this did not differ significantly across the different PI and NVP regimens. The CD4 cell count response and rate of AIDS events were also similar across the different regimens. No independent predictors of VL undetectability were identified, but prior NRTI exposure was associated with VL rebound, and a lower baseline VL and CD4 cell count were associated with a reduced CD4 count response. The frequency (95% CI) of treatment discontinuation differed across the regimens; at 6 months, it was lowest for NFV (18% [CI: 13%‐24%]), IDV (25% [CI: 22%‐29%]), and NVP (28% [CI: 22%‐34%]) and highest for RTV (41% [CI: 31%‐52%]) and SQV HG (52% [CI: 48%‐57%]). Conclusions: Although PI‐ and NVP‐containing regimens were similar in their CD4 cell count response and rates of subsequent VL rebound, differences were observed in time to VL undetectability and discontinuation rates relative to SQV HG. SQV HG was consistently inferior to the other PIs and NVP. The use of NFV and IDV was associated with the highest rates of undetectability, and together with NVP, the lowest rates of discontinuation.

How do teleconsultations for remote trauma management change over a period of time

We obtained follow-up information about the new patients seen at a minor accident and treatment service (MATS) staffed by emergency nurse practitioners (ENPs). A previous study, of 150 teleconsultations in a six-month period starting in April 1996, was used for comparison. In the present series, 150 teleconsultations occurring in a four-month period starting in April 1999 were studied; the patients constituted 5.6% of the 2658 new attenders or 3.8% of the 3936 total attenders. In comparison with the study three years before, falling teleconsultation rates were partly offset by increasing numbers of attenders and an extension of the ENPs’ roles and skills. Teleconsultation rates rose when the number of consultant-run clinics was curtailed and ENP-run clinics replaced some of them. Eligibility to request and report more radiographs reduced the need for teleconsultations, and subsequently teleconsultations for help with interpretation of radiographs fell as the ENPs became more experienced. Specialty residents trusted ENP judgement and accepted telephoned direct admission of cases to their wards. Fewer teleconsultations were required for soft-tissue injuries. Telemedicine is an excellent educational tool.

Level of diagnostic confidence and accuracy in teleradiology for minor injuries work

The National Council State Boards of Nursing (NCSBN) approved an interstate compact on 9 January 1998 which allows nurses to hold a licence in their state of residency and practise physically or electronically in any state that has signed the compact. Utah was the first to adopt the compact, on 14 March 1998. There were proposals in several other states to adopt it during 1999. Senator Kent Conrad of North Dakota introduced the Comprehensive Telehealth Act on 13 April 1999. This bill builds on the version of the Comprehensive Telehealth Act that was passed by Congress under the Balanced Budget Act of August 1997. The Act provides for revision and clarification of current Medicare reimbursement for telehealth services. The Health Insurance Portability and Accountability Act was signed into law by President Clinton on 21 August 1996. One key principle of this Act is privacy legislation to protect the confidentiality of individually identifiable health information and institute security standards for electronic health data. The deadline for Congress to enact privacy protections for this legislation was 21 August 1999. Congress did not meet this deadline so the Secretary of Health and Human Services is currently drafting a privacy notice of proposed rule making (NPRM) that will be published later this year in the Federal Register. Level of diagnostic confidence and accuracy in teleradiology for minor injuries work