Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

Emotion/cognition-coupling in word recognition memory of depressive patients: an event-related potential study

Depressive patients show deficits in memory functions. However, the underlying mechanisms remain unclear. Experiments with a special emphasis on the link between emotion and cognition appear challenging. The aim of this study is to investigate the influence of the emotional content of words on memory in non-medicated depressive patients (n=11) compared with a control group (n=11) utilizing event-related brain potentials (ERPs). In a continuous word recognition paradigm brain responses to repeated items are characterized by more positive waveforms of ERPs. This recognition effect ('old/new effect') has been shown to be sensitive to parameters relevant for memory processing. For the purpose of this ERP experiment visually presented words were classified into three different categories of emotional content. The ERPs for the correctly detected 'old' (repeated) words showed an increased positivity beginning approximately 250 ms post-stimulus, concurring with a good recognition performance. In addition, old/new effect and behavioral data were sensitive to words' different emotional connotations in the control group. In contrast, the depressive patients performed worse and showed no significant old/new effect. Nevertheless, their recognition performance was also enhanced by the emotional content. Furthermore, a differential effect of the emotional content on frontal ERPs was found between groups. In contrast to the control group, a reduced old/new effect indicates a reduced working memory capacity in the moderately depressed patients. This is suggested to be partially due to changes of the emotion/cognition coupling related to ruminations with preferably negative emotional connotation. However, the emotional content also affects recognition performance in the depressive patients.     

Testing and implementing signal impact analysis in a regulatory setting: results of a pilot study.

BACKGROUND AND AIM: Statistical signal detection methods such as proportional reporting ratios (PRRs) detect many drug safety signals when applied to databases of spontaneous suspected adverse drug reactions (ADRs). Impact analysis is a tool that was developed as an aid to prioritisation of such signals. This paper describes a pilot project whereby impact analysis was simultaneously introduced into practice in a regulatory setting and tested in comparison with the existing approach. METHODS: Impact analysis was run on signals detected during a 26-week period from the UK Adverse Drug Reactions On-line Information Tracking (ADROIT) database of spontaneous ADRs that met minimum criteria (PRR>or=3.0, chi2>or=4.0 and >or=3 reported cases) and related to established drugs (i.e. those that have been available for at least 2 years and no longer carry the 'black triangle' symbol). The current method of signal prioritisation (i.e. the collective judgement at a weekly meeting) was initially performed without knowledge of the findings of impact analysis. Subsequently, the meeting was presented with the findings and, where appropriate, given the opportunity to reconsider the judgement made. The categories arising from the two methods were compared and the ultimate action recorded. Inter-observer variation between scientists performing impact analysis was also assessed. RESULTS: Eighty-six separate signals were analysed by impact analysis, of which 5% were categorised as high priority (A), 14% as requiring further information (B), 31% as low priority (C) and 50% as no action required (D). In general, the new method tended to give a higher level of priority to signals than the existing approach. Overall, there was 59% agreement between the impact analysis and the collective judgement at the meetings (kappa statistic=0.30). There was slightly greater agreement between impact analysis and the final action taken (kappa statistic=0.39), indicating that the findings of an impact analysis had an influence on the outcome. Assessment of inter-observer variation demonstrated that the method is repeatable (kappa statistic for overall category=0.77). Almost 70% of those who participated in the pilot study believed that impact analysis represented an improvement in how signals were prioritised. CONCLUSIONS: Impact analysis is a repeatable method of signal prioritisation that tended to give a higher level of priority to signals than the standard approach and which had an influence on the ultimate outcome.     

Attitudes towards HPV testing: a qualitative study of beliefs among Indian,Pakistani, African-Caribbean and white British women in the UK

This study examined attitudes to human papillomavirus (HPV) testing among a purposively selected sample of women from four ethnic groups: white British, African Caribbean, Pakistani and Indian. The design was qualitative, using focus group discussion to elicit women's attitudes towards HPV testing in the context of cervical cancer prevention. The findings indicate that although some women welcomed the possible introduction of HPV testing, they were not fully aware of the sexually transmitted nature of cervical cancer and expressed anxiety, confusion and stigma about HPV as a sexually transmitted infection. The term 'wart virus', often used by medical professionals to describe high-risk HPV to women, appeared to exacerbate stigma and confusion. Testing positive for HPV raised concerns about women's sexual relationships in terms of trust, fidelity, blame and protection, particularly for women in long-term monogamous relationships. Participation in HPV testing also had the potential to communicate messages of distrust, infidelity and promiscuity to women's partners, family and community. Concern about the current lack of available information about HPV was clearly expressed and public education about HPV was seen as necessary for the whole community, not only women. The management of HPV within cervical screening raises important questions about informed participation. Our findings suggest that HPV testing has the potential to cause psychosocial harm to women and their partners and families.     

Partnerships: survey respondents’ perceptions of inter-professional collaboration to address alcohol-related harms in England

Tackling alcohol-related harms crosses agency and professional boundaries, requiring collaboration between health, criminal justice, education and social welfare institutions. It is a key component of most multi-component programmes in the United States, Australia and Europe. Partnership working, already embedded in service delivery structures, is a core mechanism for delivery of the new UK Government Alcohol Strategy. This article reports findings from a study of alcohol partnerships across England. The findings are based on a mix of open discussion interviews with key informants and on semi-structured telephone interviews with 90 professionals with roles in local alcohol partnerships. Interviewees reported the challenges of working within a complex network of interlinked partnerships, often within hierarchies under an umbrella partnership, some of them having a formal duty of partnership. The new alcohol strategy has emerged at a time of extensive reorganisation within health, social care and criminal justice structures. Further development of a partnership model for policy implementation would benefit from consideration of the incompatibility arising from required collaboration and from tensions between institutional and professional cultures. A clearer analysis of which aspects of partnership working provide ‘added value’ is needed.