Kate Hey

Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch.

Polymorphisms in the dopamine D2 receptor (DRD2 C/T and DRD2 A/G) and in dopamine beta hydroxylase (DBH A/G) have been implicated in modulation of smoking and other reward-seeking behaviours. We hypothesized that these alleles would predict the outcome of nicotine patch therapy for smoking cessation. In 1991-93, we performed a randomized controlled trial of the nicotine patch on 1686 heavy smokers (> or = 15 cigarettes/day). In 1999-2000, we contacted 1532 of the 1612 subjects still available; 767 (50%) completed a questionnaire and gave a blood sample. In the 755 cases in which DNA was successfully genotyped, we examined associations between the polymorphisms in DRD2 and DBH, and smoking cessation. At 1 week, the patch was more effective for smokers with DRD2 CT/TT genotype [patch/placebo odds ratio (OR) 2.8, 95% confidence interval (CI) 1.7-4.6] than with CC (OR 1.4, 0.9-2.1; P for difference in ORs 0.04). Smokers with both DRD2 CT/TT and DBH GA/AA genotypes had an OR of 3.6 (2.0-6.5) compared to 1.4 (1.0-2.1) for others (P = 0.01). At 12 weeks, the ORs for these genotypic groups were 3.6 (1.7-7.8) and 1.4 (0.9-2.3), respectively (P = 0.04). There was no association between patch effectiveness and DRD2 exon 8. Short-term effectiveness of the nicotine patch may be related to dopamine beta-hydroxylase and dopamine D2 receptor genotype. Our results support the need for further investigation into personalized therapies for smoking cessation based on individual genotype.

Bromocriptine use is associated with decreased smoking rates.

Dopaminergic transmission in the central nervous system is thought to underlie addictive behaviours, including smoking. One effective smoking cessation drug, bupropion, enhances dopaminergic transmission; conversely, antipsychotic drugs, which are dopamine antagonists, are associated with increased smoking. Thus we hypothesized that subfertile women treated with the potent dopamine agonist bromocriptine might smoke less as a consequence of their treatment. Among 4608 subfertile women those conceiving on bromocriptine were half as likely to smoke as those taking other drugs or those conceiving without medication (p < 0.0001). This observation supports the role of dopamine in nicotine addiction, and suggests that bromocriptine‐like drugs could be used effectively by pregnant women to aid cessation.

INFERTILITY TREATMENT AND MULTIPLE BIRTH RATES IN BRITAIN, 1938–94

Trends in multiple birth rates are thought to have been substantially affected by subfertility treatments in the last 25 years, but there are few quantitative assessments of this. This paper examines trends in twin and higher multiple birth rates separately in Scotland, England and Wales and compares their course with corresponding multiple birth rates in the Oxford Record Linkage Study area, where the proportions following subfertility treatment are documented. National data on prescriptions for subfertility treatments reinforce the view that they have had a major effect on the trends, and currently perhaps 60% of triplet and higher order births and 15% of twins follow their use in Britain.

Clinical guidelines and hospital discharges of children with acute urinary tract infections

Abstract In order to evaluate the effect of the introduction of recent similar guidelines on the treatment of acute urinary tract infection (UTI) in children, and possible changes in its epidemiology, we analyzed the records of hospital discharge for acute UTI under the age of 15 years in England and Wales between 1979 and 1993 and in Finland between 1978 and 1994. Cases were defined by the ICD9 diagnostic codes 590.1 (acute pyelonephritis) and 599.0 (UTI, site not specified) for males and females according to three age groups (0–4, 5–9, and 10–14 years). We also compared the registry data on kidney transplants due to end-stage renal disease caused by recurrent pyelonephritis in the United Kingdom and Finland. In England the rate of attack of symptomatic UTI per 1,000 girls under 15 years increased from 0.74 (95% confidence interval 0.71–0.76) in 1987 to 1.32 (1.29–1.35) in 1993 (P<0.001, test for trend). The respective figures for Finnish girls were 1.74 (1.62–1.86) in 1987 and 1.62 (1.51–1.74) in 1993 (P=0.72). In English boys, the increase in the attack rate was from 0.38 (0.36–0.40) in 1987 to 0.70 (0.68–0.73) in 1993 (P<0.001). In Finnish boys the respective figures were 0.74 (0.66–0.82) in 1987 and 0.88 (0.80–0.97) in 1993 (P<0.02). The observed increases in the attack rates of UTI most probably relate to increased referral of acute UTI patients to hospitals for the recommended imaging studies rather than changing occurrence. Publication of guidelines for treatment of UTI in children, consolidating more-general awareness, may have contributed to this. The mean annual numbers of kidney transplants in the United Kingdom and Finland during 1989–1995 due to end-stage renal disease caused by pyelonephritis were of similar magnitude, i.e., 1.9 (1.6–2.3) transplants per million inhabitants in the United Kingdom and 2.8 (1.5–4.7) transplants per million inhabitants in Finland. The decreasing trend in these figures in both countries, although statistically significant only in the United Kingdom (P<0.05, test for trend), suggests improved long-term outcome of these patients induced by better diagnosis and treatment of pyelonephritis and the diseases related to it, such as congenital malformations. According to our data, valid clinical guidelines are effective in changing clinical practice.

Childhood cancer incidence in a cohort of twin babies

We studied childhood cancer incidence in a population-based twin cohort using record linkage to the National Registry of Childhood Tumours. After correcting for mortality, an incidence deficit was observed (Standardized Incidence Ratio (SIR) 79; 95% Confidence Interval (CI) 39–120). Pooled analysis with data from published cohort studies indicates a similar significant incidence reduction (SIR 81, 95% CI 67–96). Further studies are warranted.

Zyban for smoking cessation in a general practice setting: the response to an invitation to make a quit attempt.

The objective of this study was to assess the feasibility and success of Zyban as part of a moderately supported smoking cessation programme within UK general practice. Treatment was offered to 479 moderately dependent smokers (smoking 15 or more cigarettes per day) who had never used Zyban, and who had taken part in a previous NRT trial (the PATCH study). Main outcome measures were point prevalence and continuous abstinence from smoking at 6 and at 12 months. Two hundred and forty were excluded because of medical reasons or prescribing contraindication. Of the remainder (n  = 239) only 54 (23%) made an active quit attempt. Thirty percent (16/54) were abstinent at six months, and 22% (12/54) at 12 months (biochemically validated point prevalence rates). Age, socio‐economic status, nicotine dependence, and genetic profile appeared to have little impact on success rates, but male quit‐attempters were significantly more successful than female (40% vs. 10% at 12 months, p  < 0.05). In conclusion, a real‐world smoking cessation programme using Zyban with moderate support within a general practice setting may achieve satisfactory quit rates without widening existing disparities in cessation.

Does cigarette smoking increase time to conception

Data are reported on the relationship between cigarette smoking and other health-related behaviours and time to conception in a population-based sample of women who acted as a control group in a case-control study of twinning. Women who continued to smoke close to the time of conception took significantly longer to become pregnant than women who never smoked or stopped smoking before the year during which they attempted to conceive. A hierarchical regression analysis performed on time-to-conception data in women who continued to smoke in the year before conception provided weak evidence for a dose-response relationship between time to conception and number of cigarettes smoked per day. No significant relationships were found between time to conception and other health-related behaviours.

Pregnancy Outcome among Twins Conceived after Subfertility Treatment Compared with Natural Twins: A Population-based Study

Pregnancy outcome and characteristics of women who conceive following subfertility treatment remains a subject of great interest. We analyzed these variables among 199 women who delivered a registerable twin birth compared with 1773 women who delivered a naturally conceived twin birth in a population-based obstetric cohort drawn from around Oxford, England. Treatment was restricted to conceptions involving simple ovulation induction only. Treated mothers were of significantly higher social class and older, more likely to deliver girls and to be delivered by cesarean section, and significantly less likely to be smokers at the time of antenatal booking and to have delivered previous pregnancies. Pregnancy outcome was similar between the two groups for most measures, with the exception of birthweight which was lower in treated twins, though not significantly so. Overall the results are reassuring with respect to outcome in twin pregnancies following simple ovulation induction.