Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations.

BACKGROUND: Viral childhood infections may be involved in the multiple sclerosis (MS) pathogenesis. Following national Swedish vaccination programs, measles sharply declined in the 1970s, and measles, mumps, and rubella were virtually eliminated in cohorts born from 1981. OBJECTIVES: To examine whether the vaccination induced reduction in these infections influences the MS incidence. In addition, the public health aspect justified an early evaluation of beneficial as well as harmful effects of mass vaccinations. MATERIALS AND METHODS: From an incidence material of 534 MS patients, born 1959-1990, we selected one unvaccinated cohort and four cohorts, each corresponding to a vaccination program (MS patients = 251). RESULTS: With the ability to detect a decrease by 30-35%, and an increase by 37-48% in the MS incidence in the first three cohorts, we found no vaccination related MS incidence changes. The background MS incidence showed a significant gradual age dependent increase. CONCLUSIONS: While the present follow-up provided limited power in the last cohort, there is no evidence as yet that the radical decline in three viral infections influenced the MS incidence. However, the increasing background MS incidence of unknown cause may have concealed a reduction in MS risk associated with mass vaccinations

A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden

Background: In 2008, immigrants constituted 14% of the population of Sweden, a high-risk area for multiple sclerosis (MS). We investigated the largest Swedish immigrant populations for the prevalence of MS.Method: Data on foreign-born MS patients were retrieved from Swedish national health and population registers. We calculated observed versus expected numbers of MS patients and gender-and age-specific prevalence ratios (PR) between immigrant populations and the general population of Sweden and, where possible, of the countries of birth.Results: The 19 largest immigrant populations included 1327 MS patients. The global variation in MS prevalence was reflected in Sweden. The prevalence in immigrant populations who had moved to Sweden from countries with a lower MS risk was however higher than in their countries of birth. Notably, the MS prevalence in the population born in Iran was at least as high as in the general population of Sweden (men: PR = 1.10, 95% CI 0.81-1.46, p = 0.537, women: PR = 1.18, 95% CI 0.97-1.44, p = 0.855) and more than twice as high as in Isfahan, Iran (men: PR = 3.06 (95% CI 2.26-4.06),

High nationwide incidence of multiple sclerosis in Sweden

Over recent years increased MS incidence, primarily in women, has been reported. We recently reported an unexpectedly high MS prevalence of 189/100,000 in Sweden. In the present study we estimated the nationwide age- and gender-specific MS incidence and the sex ratio in Sweden between 2001 and 2008. MS patients were identified by linking two nationwide health data registers, and the Swedish population register. The earliest registered date of MS diagnosis was determined. By logistic regression, the probability of the date of MS diagnosis being within the incidence period, depending on age and time was estimated for a subset of patients and applied to other patients. By Poisson regression, the hazard functions for the incidence of MS diagnosis were estimated. The expected number of MS patients was 7,361.4. The incidence in the average population of 9,054,658 was 10.2 per 100,000 person-years, and 6.2 and 14.0 per 100,000 person-years for men and women, respectively. The crude female to male ratio was 2.26. No increase of incidence or change of sex ratio was observed from 2001 to 2008. In conclusion, the average MS incidence in Sweden from 2001 to 2008 was 10.2 per 100.000, which was considerably higher than previous regional Swedish estimates of 4.3-6.4. No increase of female to male ratio of MS during the study period was observed. We provide supplementary data that can be used as tools for examining excess MS risk in different study materials

A method to predict the metabolic effects of changes in insulin treatment in subgroups of a large population based patient cohort.

This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials

The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: An observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes.

AIMS: To elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance. METHODS: Continuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden. RESULTS: In 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p=0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78-2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p=0.35) and the mean risk was similar for glargine and non-glargine (p=0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p=0.037) and breast cancer (p=0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59-0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78-1.14) compared to the general population and did not change with longer diabetes duration (p=0.68 and p=0.53 respectively). CONCLUSIONS: Analysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research

Impact of short periods with worsened or improved INR control on life expectancy and QALYs in patients with atrial fibrillation

Introduction: Warfarin-treated patients with poor international normalized ratio (INR) control, measured with time in therapeutic range (TTR) or the standard deviation of transformed INR (SDTINR), have an increased risk for clinical events. To what extent only a short period with an altered INR control may influence outcomes remains unknown. This study assessed the impact of transient periods of worsened or improved INR control on life expectancy and quality-adjusted life years (QALYs) among warfarin-treated patients with atrial fibrillation (AF) using both metrics. Materials and methods: Warfarin-treated patients with AF, registered in the patient record system Journalia during years 1985-2000, were included. Information on all-cause mortality was collected from the Cause of Death Register. Hypothetical scenarios where patients were assumed to have a transiently altered INR control during 30 days were modeled statistically using hazard functions, and the impact on remaining life expectancy and QALYs was assessed. Results: When using SDTINR, a 70-year old man within the 20th best INR control percentile was estimated to lose 7.4 days of life or 0.0100 QALYs from a 30-day long worsened INR control to that of an average 70-year old male patient. Correspondingly, 4.0 days of life or 0.0059 QALYs would be gained if a 70-year old man within the 20th worst INR control percentile would have an average INR control during 30 days. The magnitudes were smaller when TTR was used to determine INR control. Conclusions: Even short periods of an altered INR control is expected to have impact on life expectancy and QALYs among patients with AF

Experience and predictors of symptoms, distress and health-related quality of life over time in postmenopausal women with recurrent breast cancer.

The purpose of this study was to explore the symptom experience and predictors of distress and quality of life over time in women with recurrent breast cancer. Fifty-six women completed questionnaires at the diagnosis of recurrence, 1 month, 3 and 6 months after recurrence. A majority of women reported multiple, concurrent and distressing symptoms such as lack of energy, difficulty sleeping, pain, worry and problems with sexual interest or activity during the recurrent breast cancer trajectory. The highest level of symptom burden and distress and decreased quality of life was reported 3 months after recurrence. Although distress declined and quality of life improved over time, patients reported persistent symptoms. Of the patients at increased risk of vulnerability to distress were women who experienced multiple and concurrent symptoms. Other risk factors were co-morbidity, prehistory of anxiety and depression and progressive or terminal disease. Fatigue, pain and depression explained 68-72% of the variance in distress. Distress explained 44-46% of the variance in quality of life. These findings suggest that symptoms are important contributors to the distress experience, and that distress has a severe impact on quality of life. The care of women with recurrent breast cancer must be based upon the awareness of critical factors that exacerbate the vulnerability to distress throughout the disease trajectory

Variability of INR and its relationship with mortality, stroke, bleeding and hospitalisations in patients with atrial fibrillation.

BACKGROUND - RATIONALE FOR STUDY: Atrial fibrillation is associated with an increased risk of stroke and mortality which is reduced by treatment with Warfarin. The most commonly used tool to assess the effectiveness of warfarin therapy is the time in therapeutic Range (TTR) of International Normalised Ratio (INR) 2.0-3.0. Our aim was to study whether INR variability, as assessed by the standard deviation of transformed INR (SDT(INR)) is more prognostically important than the TTR. METHODS AND RESULTS: We studied 19,180 patients with atrial fibrillation on warfarin therapy to evaluate the association of TTR and that of SDT(INR) with all-cause mortality, stroke, bleeding and hospitalisation. The SDT(INR) was more prognostically important than the TTR. One standard deviation (SD) higher of SDT(INR) had a hazard ratio (HR) of 1.59 (95% CI 1.52-1.66) of mortality compared with 1.18 (95% CI 1.13-1.24) for one SD lower of TTR. For the other 3 events the HR was also higher for the SDT(INR) than for the TTR (stroke 1.30 (95% CI 1.22-1.39) vs. 1.06 (95% CI 1.00-1.13), bleeding 1.27 (95% CI 1.20-1.35) vs. 1.07 (95% CI 1.01-1.14) , hospitalisation 1.47 (95% CI 1.45-1.49) vs. 1.13 (95% CI 1.10-1.15). When both metrics were included in the same analysis only the SDT(INR) was of significant predictive value. CONCLUSIONS: The SDT(INR) is a better predictor of mortality, stroke, bleeding and hospitalisation than the TTR in patients with atrial fibrillation receiving warfarin therapy

The transverse section of the fetus urinary bladder is circular and, for volume estimation, an appropriate longitudinal section is sufficient

PurposeThe purpose was to investigate the transverse shape of the fetal urinary bladder.MethodsUsing 3D ultrasound, an appropriate longitudinal image of fetal urinary bladders was chosen. Perpendicular sections were examined and the transverse bladder image with a minimum of shadows was selected, documented and transferred to a PC. The contour of the transverse bladder image was marked manually and recorded electronically. The mean of radii distances from the centre pixel to each border pixel outlining this bladder image was calculated for each fetus.ResultsIn the material comprising 20 fetuses, the range of mean radii was 2.6–18.4 mm and the SD 0.4 mm. The mean wall thickness of the bladders was 2.7 mm and the distance represented by one pixel for different selected depths was 0.3 mm on average.ConclusionsIn view of the current technical limitations, an aberration from the circular shape may not be discernible. For this reason, the transverse shape of the fetal urinary bladder can be regarded as a circle. This means that, for bladder volume estimation, only an appropriate longitudinal section is necessary