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P J Helms

Publications and source records attributed to P J Helms.

At least 19 recordsLinked to original sources
PubMed2006

A prospective questionnaire assessment of attitudes and experiences of off label prescribing among hospital based paediatricians.

OBJECTIVE: To assess current attitudes of hospital based paediatricians to off label prescribing, and the performance of clinical trials in children. DESIGN: A prospective, questionnaire based study. SETTING: 257 hospital based consultants and specialist registrars in paediatric practice in Scotland during 2003-2004. RESULTS: A 25 item questionnaire was sent to 257 hospital based paediatricians and 151 (59%) were returned completed. Over 90% of responders were familiar with the concept of, and knowingly prescribed, off label drugs; 55% of responders stated that such prescribing disadvantaged children, and 47% expressed concerns about the efficacy of off label medicines. Although 70% of responders expressed concerns about safety, only 17% had observed an adverse event, and 47% a treatment failure, while 69% did not obtain informed consent or tell parents they were prescribing off label, and 67% did not inform the family's general practitioner. Many respondents did not believe it was necessary to carry out clinical trials in children for new (46%) or generic (64%) medicines. However, 52% of respondents stated that they would be willing to undertake clinical studies and recruit their own patients (61%) or children (73%) to take part in such studies. CONCLUSIONS: Among Scottish paediatricians there is concern about off label prescribing, although the majority do not consider it necessary to inform parents or GP colleagues. The need for clinical trials in children was recognised but there was a less than wholehearted acceptance of the need for such studies, at variance with the current drive to promote clinical trials in this age group.

Attitude of Health Personnel↗
PubMed2005

Adolescent use of the combined oral contraceptive pill: a retrospective observational study.

AIMS: To determine the extent of combined oral contraceptive use by girls aged 10-16 years in Scotland. METHODS: Assessment of combined oral contraceptive prescribing in 35 414 girls for the year 1 November 1999-31 October 2000 from data retrieved from 161 primary care practices taking part in the Scottish Programme for Improving Clinical Effectiveness in Primary Care, and from national aggregated data from family planning clinics. RESULTS: During the study period the oral contraceptive pill (OCP) was prescribed by a primary care physician to 1531 girls (4.3%) aged 10-16 years. The age specific prevalence rates per 1000 girls registered with their family doctor rose from 0.9/1000 girls aged 12 years or younger, to 6.9, 30, 86.3, and 174.8/1000 for girls aged 13, 14, 15, and 16 years respectively. The overall prevalence of combined oral contraceptive prescribing by primary care physicians was 43.2/1000 girls aged 10-16 years. A further 1765 girls aged 13-16 years obtained a prescription for the OCP from a Scottish family planning clinic, giving an overall prevalence rate for family planning clinic prescribing of 8.0/1000 girls aged 10-16 years. Despite reportedly high levels of sexual activity and teenage pregnancy in this age group, these results confirm that OCP use is relatively low. CONCLUSIONS: The UK has the highest rate of teenage pregnancy in Western Europe, but despite the medical and social concerns about the sexual health of teenagers, the level of oral contraceptive use in this young age group remains low.

Adolescent↗
PubMed2005

Preferential transmission and association of the -403 G --> A promoter RANTES polymorphism with atopic asthma.

Asthma is a complex inherited disease. The study was undertaken to identify the association of RANTES promoter polymorphisms with atopy and asthma using family-based association tests (FBATs) and generation-specific case-control analyses. We identified 154 nuclear families (453 individuals) in whom we established RANTES promoter status using the RFLP-PCR method. Of the two known promoter polymorphisms -403G/A and -28C/G, only the former appeared with a clinically relevant frequency. A total of 61 families were eligible for assessment of transmission of the allele with asthma and atopy by the pedigree disequilibrium test (PDT). Overall, allele frequency for -403A was 38.3% and 84 of 89 (94.3%) alleles were transmitted with physician diagnosed asthma (PDA) (P=0.001). All 89 children with atopy received the mutant allele, which was more than expected following Mendelian Laws of transmission (P=0.0001). In 303 unrelated parents, significant associations of the mutant allele were for atopy with or without asthma (P=0.001). In 150 unrelated children, significant associations were for atopy alone (P=0.001) and asthma (P=0.001). No associations were found for bronchial hyper-responsiveness (BHR). The -403 G --> A is transmitted with atopy and atopic asthma, although its contribution appears to relate more to atopy than asthma and BHR.

Adolescent↗
PubMed2004

Assessment of airway function in young children with asthma: comparison of spirometry, interrupter technique, and tidal flow by inductance plethsmography.

The assessment of airway function in young children requires adaptation of techniques designed for adults and/or application of techniques that do not require complex respiratory maneuvers. We sought to assess two methods of measuring airway function: time to peak expiratory flows as a ratio of expiratory time (T(PTEF)/T(E)), derived from respiratory inductance plethysmography, and total respiratory resistance by the interrupter technique (Rint), both obtained during quiet tidal breathing. Both techniques were referenced to FEV1 and flow at 50% expired volume (FEF50) from conventional spirometry in 30 children aged 4-8 years (median age, 6.9; range, 4.5-8.5 years) with a physician diagnosis of asthma and who were able to perform FEV1 with a repeatability of at least 8%. T(PTEF)/T(E) and Rint were performed in random order followed by spirometry, in order to reduce the possible effects of pulmonary stretch on tidal breathing measures. Coefficients of variation (CV) and mean absolute change/baseline standard deviation were derived for each measurement. Baseline FEV1 did not correlate significantly with T(PTEF)/T(E) (r = 0.025), but did correlate with Rint (r = 0.737, P < 0.001); respective relationships for change after bronchodilator were r = 0.09 (ns) and r = 0.64 (P < 0.001). FEF50 also correlated significantly with Rint (R = 0.769, P < 0.001) but not with T(PTEF)/T(E). FEV1 and FEF50 both increased postbronchodilator, with respective mean changes of 11.4% and 28% (P < 0.001), while Rint decreased by 24.3% (P < 0.001). No significant changes were noted for T(PTEF)/T(E). T(PTEF)/T(E) derived from inductance plethysmography does not detect mild airway obstruction or modest changes in airway caliber following bronchodilator in young children with asthma. The interrupter technique may have a role in assessing baseline airway function and response to therapy in children unable to perform reliable spirometry, and/or when the investigator wishes to avoid the possible influence of forced maneuvers on airway tone.

Age Factors↗
PubMed2004

Eosinophil activation and cysteinyl leukotriene production in infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: It has been suggested that acute infantile bronchiolitis associated with respiratory syncytial virus (RSV) may share some pathogenic features with atopic asthma in that virus-specific IgE is produced and cysteinyl leukotrienes (cLTs) and eosinophil cationic protein (ECP) have been detected in airway secretions. ECP is a specific marker of eosinophil activation although leukotrienes can be released from a variety of cells including mast cells, eosinophils and monocytes. OBJECTIVE: To test the association between eosinophil activation and cysteinyl leukotriene production in the upper airway secretions of infants with RSV positive (RSV+ve) bronchiolitis. METHODS: Nasal lavage samples were performed in 78 infants (0.0-11.5 months) admitted to hospital with RSV+ve bronchiolitis soon after admission (0-48 h). Leukotriene C4 (LTC4) was assayed by enzyme immunoassay (EIA) and eosinophil cationic protein (ECP) by fluoroimmunoassay (FIA). RESULTS: LTC4 was detectable in 51 and ECP in 57 of 78 samples with a significant positive relationship between LTC4 and ECP (r=0.557, P<0.001). CONCLUSION: In the majority of our subjects with RSV+ve bronchiolitis ECP and LTC4 were detectable in upper airway secretions and were significantly associated with each other. In this clinical setting much of the detected LTC4 within upper airway secretions is likely to originate from the eosinophil, an observation that may have implications for clinical management and for delineation of the underlying mechanisms associated with this illness.

Blood Proteins↗
PubMed2004

Higher incidence of SIDS at weekends, especially in younger infants.

BACKGROUND: An increased incidence of sudden infant death syndrome (SIDS) at weekends has been previously noted, although it has not been found in all studies. Where a weekend effect has been found it is most prominent on Sundays. AIM: To identify the magnitude of this effect in British data before and after the fall in prevalence associated with the "back to sleep" campaign. METHODS: Aggregated data from England Wales, Scotland, and Northern Ireland for the years 1986-98 during which there were 12,762 deaths from SIDS were examined. RESULTS: Comparing the periods before (1986-90) and after (1993-98) the fall in incidence associated with the "back to sleep" campaign, the percentage of infants dying at the weekend in the later period (32.24%) was slightly greater than for the earlier period (31.30%), although this difference was not statistically significant. In both periods the observed weekend incidences were significantly higher than the expected weekend percentage of 28.6%. Although the proportion of infants aged < or =4 months and > or =5 months at death did not change between the two periods, the weekend effect was more marked in the younger infants, particularly in the 1993-98 period. There was no consistent Saturday effect. In 1993-98 deaths appeared to be more evenly distributed throughout the week for infants > or =5 months. CONCLUSION: The excess of SIDS at weekends still appears to be present despite the overall fall in prevalence associated with the "back to sleep" campaign. Increased risks at weekends might have implications for support to high risk families.

Age Factors↗
PubMed2004

Seasonality of type 1 diabetes mellitus in children and its modification by weekends and holidays: retrospective observational study.

BACKGROUND: Diagnoses of type 1 insulin dependent diabetes mellitus are generally more common in winter, although this seasonal pattern has not been observed in children of preschool age (0-4 years) or in all countries. AIMS: To confirm the persistence of seasonality and the influence of age, holidays, and weekends. METHODS: We extracted data on date of birth, date of presentation, age, and sex of children diagnosed with diabetes and registered with the Scottish Study Group for the Care of Diabetes in the Young. Cosinor analysis was applied to monthly and mid-monthly data. Two sample Z tests were used to compare the epochs 1984-1992 and 1993-2001. RESULTS: Some 4517 children between 0 and 14 years of age (2407 male and 2110 female) presented with IDDM between 1 January 1984 and 31 December 2001. Seasonality was evident in children above 4 years of age with amplitudes of 19.5-25.7% and peaks between mid December and mid January. Presentation was strongly influenced by weekends and holiday periods, with reduced presentations in December compared with November and January, and with the lowest presentations in July (the main Scottish holiday month). Using mid-month to mid-month data did not change the overall seasonality but did improve the fits for cosinor analysis. Mondays and Fridays were the most common days for presentation. CONCLUSION: Initial presentation of IDDM in Scotland follows a stable seasonal pattern in all but the youngest children with lower rates of presentation in holiday periods and at weekends for all age groups.

Adolescent↗
PubMed2003

Association of CCR5Delta32 with reduced risk of childhood but not adult asthma.

BACKGROUND: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5Delta32 mutation on asthma and allergy in the transition from childhood to adulthood. METHODS: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5Delta32 status was also characterised and the association with childhood and adulthood symptoms determined. RESULTS: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5Delta32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% CI 0.14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the same population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5Delta32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status. CONCLUSIONS: In a population with a high allelic frequency for the CCR5Delta32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

Adult↗
PubMed2002

Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data.

BACKGROUND: The recent rise in the prevalence of immune-mediated diseases has been attributed to environmental factors such as a lack of microbial challenge, or dietary change, that deviate the overall balance between mutually antagonistic subsets of T helper (Th) cells. OBJECTIVE: An alternative proposal is that recent environmental changes have resulted in an immune system that is more likely to produce both Th1 and Th2 responses against benign antigens. The prediction of this hypothesis, that Th1 and Th2-mediated diseases are not mutually exclusive, and may be positively associated, is tested here in a whole population. METHODS: Data from General Practices participating in the Scottish Continuous Morbidity Recording (CMR) project were used to determine the coincidence of the major Th2-mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1-mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and psoriasis. We also identified the prescription rates of inhaled therapy for asthma in patients with Th1-mediated disease. RESULTS: There was a significant increase in the risk of presenting with a Th1-mediated autoimmune condition in patients with a history of allergic disease (standardized prevalence ratio (95% confidence interval) 1.28 (1.18-1.37)). Likewise, the standardized prevalence ratios of presenting with either eczema (1.67 (1.48-1.87)) or allergic rhinitis (1.22 (1.02-1.44)) were significantly increased in subjects with a history of Th1-mediated disease. There was a particularly strong association between current psoriasis and current eczema (standardized prevalence ratio ofpsoriasis in subjects with eczema 2.88, 95% confidence interval (CI) 2.38-3.45). There was also a significant increase in prescriptions for inhaled asthma therapy in patients with Th1 disease. CONCLUSION: It is concluded that Th1- and Th2-mediated diseases are significantly associated in a large General Practice population. This finding supports the proposal that autoimmune and atopic diseases share risk factors that increase the propensity of the immune system to generate both Th1- and Th2-mediated inappropriate responses to non-pathological antigens.

Adolescent↗
PubMed2001

Normal values for phrenic nerve latency in children.

Data derived from detailed studies of normal phrenic nerve latency in a large group of children are presented. They highlight the major differences between the three previously published studies of normal children. Phrenic nerve latency shows a curvilinear relationship with age, averaging 6.0 ms at 0-6 months, falling to 4.8 ms between 1 and 2 years, then rising to 6.3 ms between 10 and 18 years of age. These data represent the largest published study on normal phrenic nerve latency in children.

Adolescent↗
PubMed2001

Genetic/environmental determinants of adult chronic obstructive pulmonary disease and possible links with childhood wheezing.

Epidemiological evidence and similarities in underlying inflammatory mechanisms suggest that childhood respiratory conditions and adult onset chronic obstructive pulmonary disease (COPD) may have a common aetiology. The prevalence of COPD in the UK has been estimated to be 10% in males and 11% in females, and like asthma, is thought to have a polygenic contribution with a complex interplay between genetic and environmental factors. The only proven genetic factor so far identified in its pathogenesis is alpha1-antitrypsin deficiency, although this accounts for less than 1% of individuals with disease. Environmental exposures are significant but the observation that only 15% of smokers develop COPD and only some young children exposed in utero develop recurrent wheezing points to as yet undefined contributory genetic factors. The similarity in response to medication also suggests some features in common and a central question must be whether those adults who develop COPD had transient viral-associated wheeze (VAW) or non-specific bronchial hyperresponsiveness (BHR) in childhood? Similarities between some of the childhood wheezing syndromes and adult onset COPD invites a re-examination of possible links between the two conditions.

Adolescent↗
PubMed2001

Guest editorial.

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Adolescent↗
PubMed2001

Parents' quality of life and respiratory symptoms in young children with mild wheeze. EASE Study Group.

The Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), measures the impact of child asthma symptoms on family activity (CGAct) and parental anxiety (CGEmot). It has not been validated for families of children <7 yrs, with wheezing illness. This study assessed the sensitivity of the PACQLQ to symptom change in 62 preschool children with wheezing illness. The median age of children was 3 yrs (range 0.8-6 yrs). At entry and 3-month follow-up, parents recorded child respiratory symptoms in a 1-month diary and completed the PACQLQ. On average, children in the study had 7 symptomatic days per month. On entry, mothers < or = 30 yrs had worse scores than those > 30 (p < 0.02), and mothers in less affluent socioeconomic groups had worse scores than those in higher groups (p = 0.05). Change in symptom scores and symptom free days between entry and follow-up was associated with change in PACQLQ scores (r = 0.54-0.57, p <0.001). Thirty-three parents had absolute change in PACQLQ of <0.5 over three months (which has been previously defined as not being clinically significant). Compared to parents with higher PACQLQ change, parents with PACQLQ scores <0.5, did not differ in frequency of child symptoms or in social-demographic factors, but had better quality of life scores on entry to the study (p<0.01). It is concluded that the Paediatric Asthma Caregiver's Quality of Life Questionnaire is sensitive to group measures of child symptom change over 3 months, among preschool children, and this supports its use as an outcome measure in clinical trials. The absolute impact of child symptoms on parent quality of life varies among parents.

Adult↗
PubMed2001

Issues in pediatric asthma.

Different wheezing syndromes can carry the diagnostic label of "asthma," especially in very young children, and an accurate differential diagnosis is essential for improving outcomes. Because presenting symptoms are similar, making a rapid, accurate differential diagnosis is often daunting. Asthma can, eventually, be distinguished from other wheezing disorders based on differences in symptomatology, pathophysiology, and disease evolution. Once diagnosed, inhaled corticosteroids (ICS) remain the cornerstone of treatment in persistent pediatric asthma. Compelling evidence supports the benefits of these agents in reducing asthma-related morbidity and mortality and in preventing airway remodeling. As a result, ICS use in young children with asthma has grown substantially in recent years. Questions are being raised about the appropriateness of early and long-term use of ICS in young children, and whether ICS are overused in this population. Because of the challenges faced by clinicians in differentiating asthma from the other childhood wheezing disorders often present in young children, it may be best to delay the use of regular ICS therapy until a definitive diagnosis can be established. Alternatives to ICS (such as the leukotriene receptor antagonists) should also be considered to avoid the growth-suppressing potential of steroids in the management of mild asthma.

Adrenal Cortex Hormones↗