Junmei Miao Jonasson

BACKGROUND: In epidemiological studies researchers use logistic regression as an analytical tool to study the association of a binary outcome to a set of possible exposures. METHODS: Using a simulation study we illustrate how the analytically derived bias of odds ratios modelling in logistic regression varies as a function of the sample size. RESULTS: Logistic regression overestimates odds ratios in studies with small to moderate samples size. The small sample size induced bias is a systematic one, bias away from null. Regression coefficient estimates shifts away from zero, odds ratios from one. CONCLUSION: If several small studies are pooled without consideration of the bias introduced by the inherent mathematical properties of the logistic regression model, researchers may be mislead to erroneous interpretation of the results.

OBJECTIVE: To evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function. DESIGN: Observational study between July 2004 and December 2010, mean follow-up 3.9 years. SETTING: Hospital outpatient clinics and primary care in Sweden. PARTICIPANTS: 51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin. MAIN OUTCOME MEASURES: Risks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression. RESULTS: Compared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45-60 ml/min/1.73 m(2), and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30-45 ml/min/1.73 m(2). CONCLUSIONS: Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.

RACOMIP is a population‐based, randomized trial of the effectiveness and cost‐effectiveness of different interventions aimed at increasing participation in a well‐run cervical cancer screening program in western Sweden. In this article, we report results from one intervention, offering non‐attendees a high‐risk human papillomavirus (HPV) self‐test. Comparison was made with standard screening invitation routine or standard routine plus a telephone call. Women (8,800), aged 30–62, were randomly selected among women without a registered Pap smear in the two latest screening rounds. These women were randomized 1:5:5 to one of three arms: 800 were offered a high‐risk HPV self‐test, 4,000 were randomized to a telephone call (reported previously) and 4,000 constituted a control group (standard screening invitation routine). Results were based on intention to treat analysis and cost‐effectiveness was calculated as marginal cost per cancer case prevented. The endpoint was the frequency of testing. The total response rate in the self‐testing arm was 24.5%, significantly higher than in the telephone arm (18%, RR 1.36, 95% CI 1.19–1.57) and the control group (10.6%, RR 2.33, 95% CI 2.00–2.71). All nine women who tested positive for high‐risk HPV attended for a cervical smear and colposcopy. From the health‐care sector perspective, the intervention will most likely lead to no additional cost. Offering a self‐test for HPV as an alternative to Pap smears increases participation among long‐term non‐attendees. Offering various screening options can be a successful method for increasing participation in this group.

OBJECTIVE: The purpose of this study was to assess fertility in women with type 1 diabetes and the risk of congenital malformations in their offspring. RESEARCH DESIGN AND METHODS: This was a register-based cohort study in Sweden. All 5,978 women hospitalized for type 1 diabetes at age <or=16 years identified in the Swedish Inpatient Register during 1965-2004 were followed until the end of 2004 through linkage to nationwide registers. A standardized fertility ratio (SFR), the ratio of observed to expected number of live births, with 95% CIs, was used to express the relative fertility rate. The proportion of newborns with congenital malformations was compared with that of the general population. RESULTS: We observed 4,013 live births (SFR 0.80 [95% CI 0.77-0.82]). The SFRs for those who had retinopathy, nephropathy, neuropathy, or cardiovascular complications were 0.63, 0.54, 0.50, and 0.34, respectively. Stratified analyses by year of first hospitalization showed that the reduced fertility was confined to women first hospitalized before 1985, but the presence of complications was associated with subfertility in all calendar-year strata. The proportions of newborns with congenital malformations decreased from 11.7% during 1973-1984 to 6.9% during 1995-2004 but were consistently higher than the corresponding figures for the general population. CONCLUSIONS: Women with type 1 diabetes have reduced fertility, but it appears that normalization has occurred among women with uncomplicated disease and an onset in the past 20 years. Our results suggest that the stricter metabolic control exercised in the past 20 years may have helped prevent subfertility. However, although the risk of congenital malformations has decreased, it is still higher than that for the general population.