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A frailty model is a random effects model for time variables, where the random effect (the frailty) has a multiplicative effect on the hazard. It can be used for univariate (independent) failure times, i.e. to describe the influence of unobserved covariates in a proportional hazards model. More interesting, however, is to consider multivariate (dependent) failure times generated as conditionally independent times given the frailty. This approach can be used both for survival times for individuals, like twins or family members, and for repeated events for the same individual. The standard assumption is to use a gamma distribution for the frailty, but this is a restriction that implies that the dependence is most important for late events. More generally, the distribution can be stable, inverse Gaussian, or follow a power variance function exponential family. Theoretically, large differences are seen between the choices. In practice, using the largest model makes it possible to allow for more general dependence structures, without making the formulas too complicated.

In the participating centers with a multidisciplinary team, only one third of the patients had an HbA1c level of < 8%.

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OBJECTIVE -It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families.RESEARCH DESIGN AND METHODS -The study involved 2,101 adolescents, aged 10 -18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA 1c was analyzed centrally (normal range 4.4 -6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires.RESULTS -Mean HbA 1c was 8.7% (range 4.8 -17.4). Lower HbA 1c was associated with lower impact (P Ͻ 0.0001), fewer worries (P Ͻ 0.05), greater satisfaction (P Ͻ 0.0001), and better health perception (P Ͻ 0.0001) for adolescents. Girls showed increased worries (P Ͻ 0.01), less satisfaction, and poorer health perception (P Ͻ 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P Ͻ 0.0001).Patients from ethnic minorities had poorer scores for impact (P Ͻ 0.0001), worries (P Ͻ 0.05), and health perception (P Ͻ 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores.CONCLUSIONS -In a multiple regression model, lower HbA 1c was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

OBJECTIVETo find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment.RESEARCH DESIGN AND METHODSA total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function.RESULTSBy multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient −0.21, P < 0.001) and insulin dose (−0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose–adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg−1 · 24 h−1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months.CONCLUSIONSA new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions.

Objective: To study trends in multiple pregnancies not explained by changes in maternal age and parity patterns. Design: Trends in population based figures for multiple pregnancies in Denmark studied from complete national records on parity history and vital status. Population: 497 979 Danish women and 803 019 pregnancies, 1980-94. Main outcome measures: National rates of multiple pregnancies, infant mortality, and stillbirths controlled for maternal age and parity. Special emphasis on primiparous women >30 years of age, who are most likely to undergo fertility treatment. Results:The national incidence of multiple pregnancies increased 1.7-fold during 1980-94, the increase primarily in 1989-94 and almost exclusively in primiparous women aged >30 years, for whom the adjusted population based twinning rate increased 2.7-fold and the triplet rate 9.1-fold. During 1989-94, the adjusted yearly increase in multiple pregnancies for these women was 19% (95% confidence interval 16% to 21%) and in dizygotic twin pregnancies 25% (21% to 28%). The proportion of multiple births among infant deaths in primiparous women >30 years increased from 11.5% to 26.9% during the study period. The total infant mortality, however, did not increase for these women because of a simultaneous significant decrease in infant mortality among singletons. Conclusions: A relatively small group of women has drastically changed the overall national rates of multiple pregnancies. The introduction of new treatments to enhance fertility has probably caused these changes and has also affected the otherwise decreasing trend in infant mortality. Consequently, the resources, both economical and otherwise, associated with these treatments go well beyond those invested in specific fertility enhancing treatments.

Severe hypoglycaemia remains a significant clinical problem in type 1 diabetes. The rate of severe hypoglycaemia and the influence of risk markers are very sensitive to selection and differences in rates between centres or studies seem to disappear after correction for differences in clinical characteristics. Smoking is a novel overall risk marker of severe hypoglycaemia.