The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes: a cohort and nested case-control study.

OBJECTIVE: To obtain evidence of the effects of metformin and statins on the incidence of ovarian cancer in women with type 2 diabetes (T2D). DESIGN: A retrospective cohort study and nested case-control study. SETTING: The data were obtained from a diabetes database (FinDM) combining information from several nationwide registers. POPULATION: A cohort of 137 643 women over 40 years old and diagnosed with T2D during 1996-2011 in Finland. METHODS: In full cohort analysis Poisson regression was used to estimate the hazard ratios (HR) in relation to ever use of metformin, insulin other oral anti-diabetic medication or statins. In the nested case-control analysis 20 controls were matched to each case of ovarian cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different medications. The estimates were adjusted for age and duration of T2D. MAIN OUTCOME MEASURE: Incidence of ovarian cancer. RESULTS: In all, 303 women were diagnosed with ovarian cancer during the follow up. Compared with other forms of oral anti-diabetic medication, metformin (HR 1.02, 95% CI: 0.72-1.45) was not found to be associated with the incidence of ovarian cancer. Neither was there evidence for statins to affect the incidence (HR 0.99, 95% CI: 0.78-1.25). In nested case-control analysis the results were essentially similar. CONCLUSIONS: No evidence of an association between the use of metformin or statins and the incidence of ovarian cancer in women with T2D was found. TWEETABLE ABSTRACT: No evidence found for metformin or statins reducing the incidence of ovarian cancer.

Cause-specific mortality in endometrioid endometrial cancer patients with type 2 diabetes using metformin or other types of antidiabetic medication.

AIM: To obtain further evidence of the association between metformin or other types of antidiabetic medication (ADM) and mortality from endometrial cancer (EC) and other causes of death in patients with endometrioid EC and type 2 diabetes (T2D). MATERIALS AND METHODS: A retrospective cohort of women with existing T2D and diagnosed with endometrioid EC from 1998 to 2011, obtained from a nationwide diabetes database (FinDM), were included in the study. Cumulative mortality from EC and that from other causes was described by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models, and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of ADM during the three-year period preceding EC diagnosis. RESULTS: From the FinDM cohort we identified 1215 women diagnosed with endometrioid EC, of whom 19% were metformin users, 12% were users of other types of oral antidiabetic medication, 25% used other types of oral antidiabetic medication plus metformin, 26% used insulin and 14% had no antidiabetic medication. Mortality from EC was not found to be different in women using metformin (HR 0.89, 95% Cl 0.52-1.54) but mortality from other causes was lower (HR 0.52, 95% Cl 0.31-0.88) compared with women using other types of oral ADM. CONCLUSIONS: Our findings are inconclusive as to the possible effect of metformin on the prognosis of endometrioid EC in women with T2D. However, use of metformin may reduce mortality from other causes.

HIV research productivity and structural factors associated with HIV research output in European Union countries: a bibliometric analysis.

OBJECTIVES: To assess HIV/AIDS research productivity in the 27 countries of the European Union (EU), and the structural level factors associated with levels of HIV/AIDS research productivity. METHODS: A bibliometric analysis was conducted with systematic search methods used to locate HIV/AIDS research publications (period of 1 January 2002 to 31 December 2011; search databases: MEDLINE (Ovid, PubMed), EMBASE, ISI-Thomson Web of Science; no language restrictions). The publication rate (number of HIV/AIDS research publications per million population in 10 years) and the rate of articles published in HIV/AIDS journals and selected journals with moderate to very high (IF ≥3) 5-year impact factors were used as markers for HIV research productivity. A negative binomial regression model was fitted to assess the impact of structural level factors (sociodemographic, health, HIV prevalence and research/development indicators) associated with the variation in HIV research productivity. RESULTS: The total numbers of HIV/AIDS research publications in 2002-2011 by country ranged from 7 to 9128 (median 319). The median publication rate (per million population in 10 years) was 45 (range 5-150) for all publications. Across all countries, 16% of the HIV/AIDS research was published in HIV/AIDS journals and 7% in selected journals with IF ≥3. Indicators describing economic (gross domestic product), demographic (size of the population) and epidemiological (HIV prevalence) conditions as well as overall scientific activity (total research output) in a country were positively associated with HIV research productivity. CONCLUSIONS: HIV research productivity varies noticeably across EU countries, and this variation is associated with recognisable structural factors.

Predictive factors for quality of life after tonsillectomy among adults with recurrent pharyngitis: a prospective cohort study.

OBJECTIVES: To assess health-related quality of life (QoL) and clinical factors predicting it after tonsillectomy among adult patients with recurrent pharyngitis. DESIGN: Prospective cohort design. SETTING: Tertiary referral centre. PARTICIPANTS: Adults (n = 153) who underwent tonsillectomy for recurrent pharyngitis. MAIN OUTCOME MEASURES: QoL 6 months after tonsillectomy measured by the Glasgow Benefit Inventory (GBI). Factors predicting high postoperative QoL were sought using multiple linear regression analysis. RESULTS: Of the 142 patients (93% of all eligible) responding to the GBI questionnaire, 94 (66%) were female; median age was 26 years (range 14-65). GBI Total Scores varied markedly (range -19 to +69), but on average showed improvement (median +27, interquartile range 18-36), most evidently in the GBI Physical Health Score (median +83), after tonsillectomy. Among routinely recorded clinical characteristics, the number of prior pharyngitis episodes, frequent throat pain, untreated dental caries and chronically infected tonsils made up the optimal subset of factors for predicting the GBI Total Score. However, in a random sample of patients (n = 56) for whom preoperative diary-based data were also available, somewhat better predictive ability was achieved based on just two diary items: number of days with throat pain and with fever during the preceding few months (correlation coefficient, r, between observed and fitted scores improved from 0.39 to 0.55). Yet, the precision of even these predictions was still quite low. CONCLUSIONS: Adult patients with recurrent pharyngitis were on average satisfied after tonsillectomy, regardless of the aetiology of the episodes. Clinical factors rather modestly predicted which patients benefited most from the operation.

Caesarean section and allergic manifestations: insufficient evidence of association found in population-based study of children aged 1 to 4 years.

AIM: To provide evidence on the association between caesarean section and allergic manifestations in an unselected child population. METHODS: Research focused on all children aged from one to 4 years (N = 4779), born between April 2001 and March 2005 and living in the province of South Karelia, Finland. They were identified from the nationwide population register. Questionnaire data on 3181 participants were individually merged with allergy test results (skin prick tests, IgE antibodies and open food challenges) from all patient records. RESULTS: Compared with vaginal delivery, the adjusted relative incidence of positive allergy tests (with 95% confidence intervals, CI) in children born by caesarean section was 1.14 (0.79, 1.65) for food, 1.16 (0.66, 2.05) for animals, 0.94 (0.46, 1.92) for pollen and 1.19 (0.87, 1.63) for any allergens. The corresponding adjusted prevalence odds ratios (with 95% CI) of physician-diagnosed allergic manifestations were 1.15 (0.80, 1.63) for food allergy, 0.90 (0.47, 1.59) for pollen allergy or hay fever, 1.00 (0.75, 1.31) for atopic eczema, 0.96 (0.53, 1.65) for asthma and 1.08 (0.85, 1.38) for any allergic manifestation. CONCLUSION: Insufficient evidence was found in our population for any association between birth by caesarean section and allergic manifestations. Further evidence from unselected populations, with longer follow-up periods, is needed.

Avoidable deaths and random variation in patients' survival.

BACKGROUND: Random error in the numbers of avoidable deaths among cancer patients has not been considered in earlier studies. METHODS: Methods to obtain valid confidence intervals (CIs) for numbers of avoidable deaths were developed. The excess mortality rates were estimated for patients diagnosed with colon cancer in five cancer control regions in Finland during 2000-2007 using a relative survival regression model. Numbers of avoidable deaths due to colon cancer and other causes, respectively, were estimated in different scenarios. RESULTS: Altogether, 4139 and 1335 out of 10 772 patients under 90 years at diagnosis were estimated to have died due to colon cancer and other causes, respectively, during the first 5 years after diagnosis. If all the patients had shared the relative survival of the largest cancer control region to which the country capital belongs, the estimated number of avoidable deaths would have been 146 (95% CI 3-290). CONCLUSION: Random error in numbers of avoidable deaths, often substantial, can be quantified by realistic error margins, based on appropriate statistical methods.

Prevalence and associated factors of restless legs in a 57-year-old urban population in northern Finland.

OBJECTIVE: We examined the prevalence and associated factors of restless legs syndrome (RLS) in a 57-year-old unselected urban population in northern Finland. METHODS: A health survey was conducted in 2002 that targeted persons born in 1945 and residing in the city of Oulu on 31 December, 2001. Their history of RLS, coronary heart disease (CHD), daytime sleepiness, depressive symptoms and snoring was assessed by means of questionnaires. RESULTS: Altogether 995 of 1332 eligible subjects (74%) participated (556 women, 439 men). The overall prevalence of RLS > or = 1 per week was 20% in women and 15% in men. In the fitted multiple logistic regression model, RLS was found to be associated with female gender (OR 1.64, 95% CI 0.98-2.72), CHD (OR 2.92, 95% CI 1.18-7.23), daytime sleepiness (OR 2.12, 95% CI 1.32-3.41), moderately elevated (31-45) or high (46-65) Zung sum scores (OR 1.95, 95% CI 1.09-3.48 and OR 3.67, 95% CI 1.71-7.90, respectively), antidepressant medication (OR 2.10, 95% CI 1.06-4.19) and arthropathy (OR 1.69, 95% CI 1.04-2.72). Insufficient evidence was found of an association between RLS and type 2 diabetes or impaired glucose regulation. CONCLUSIONS: Restless legs syndrome is fairly common in subjects aged 57 years. A particularly strong positive association was observed between RLS and depressive symptoms and CHD.

Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer.

Squamous cell carcinoma (SCC) of the tongue is the most common cancer in the oral cavity and has a high mortality rate. A total of 90 mobile tongue SCC samples were analysed for Bryne's malignancy scores, microvascular density, and thickness of the SCC sections. In addition, the staining pattern of cyclooxygenase-2, alphavbeta6 integrin, the laminin-5 gamma2-chain, and matrix metalloproteinases (MMPs) -2, -7, -8, -9, -20, and -28 were analysed. The expression of MMP-8 (collagenase-2) was positively associated with improved survival of the patients and the tendency was particularly prominent in females. No sufficient evidence for a correlation with the clinical outcome was found for any other immunohistological marker. To test the protective role of MMP-8 in tongue carcinogenesis, MMP-8 knockout mice were used. MMP-8 deficient female mice developed tongue SCCs at a significantly higher incidence than wild-type mice exposed to carcinogen 4-Nitroquinoline-N-oxide. Consistently, oestrogen-induced MMP-8 expression in cultured HSC-3 tongue carcinoma cells, and MMP-8 cleaved oestrogen receptor (ER) alpha and beta. According to these data, we propose that, contrary to the role of most proteases produced by human carcinomas, MMP-8 has a protective, probably oestrogen-related role in the growth of mobile tongue SCCs.

An occupational health intervention programme for workers at high risk for sickness absence. Cost effectiveness analysis based on a randomised controlled trial.

OBJECTIVES: To determine whether, from a healthcare perspective, a specific occupational health intervention is cost effective in reducing sickness absence when compared with usual care in occupational health in workers with high risk of sickness absence. METHODS: Economic evaluation alongside a randomised controlled trial. 418 workers with high risk of sickness absence from one corporation were randomised to intervention (n = 209) or to usual care (n = 209). The subjects in the intervention group were invited to occupational health service for a consultation. The intervention included, if appropriate, a referral to specialist treatment. Register data of sickness absence were available for 384 subjects and questionnaire data on healthcare costs from 272 subjects. Missing direct total cost data were imputed using a two-part regression model. Primary outcome measures were sickness absence days and direct healthcare costs up to 12 months after randomisation. Cost effectiveness (CE) was expressed as an incremental CE ratio, CE plane and CE acceptability curve with both available direct total cost data and missing total cost data imputed. RESULTS: After one year, the mean of sickness absence was 30 days in the usual care group (n = 192) and 11 days less (95% CI 1 to 20 days) in the intervention group (n = 192). Among the employees with available cost data, the mean days of sickness absence were 22 and 24, and the mean total cost euro974 and euro1049 in the intervention group (n = 134) and in the usual care group (n = 138), respectively. The intervention turned out to be dominant-both cost saving and more effective than usual occupational health care. The saving was euro43 per sickness absence day avoided with available direct total cost data, and euro17 with missing total cost data imputed. CONCLUSIONS: One year follow-up data show that occupational health intervention for workers with high risk of sickness absence is a cost effective use of healthcare resources.

The effectiveness of two occupational health intervention programmes in reducing sickness absence among employees at risk. Two randomised controlled trials.

OBJECTIVES: To evaluate the effectiveness of two occupational health intervention programmes, both compared with usual care. METHODS: Based on a health survey, 1341 employees (88% males) in construction, service and maintenance work were classified into three groups: "low risk" (n = 386), "intermediate risk" (n = 537) and "high risk" (n = 418) of sickness absence. Two separate randomised trials were performed in the groups "high risk" and "intermediate risk", respectively. Those high risk subjects that were allocated to the intervention group (n = 209) were invited to occupational health service for a consultation. The intervention included, if appropriate, a referral to specialist treatment. Among the intermediate risk employees those in the intervention group (n = 268) were invited to call a phone advice centre. In both trials the control group received usual occupational health care. The primary outcome was sickness absence during a 12-month follow-up (register data). RESULTS: The high risk group, representing 31% of the cohort, accounted for 62% of sickness absence days. In the trial for the high risk group the mean sickness absence was 30 days in the usual care group and 19 days in the intervention group; the mean difference was 11 days (95% CI 1 to 20 days). In the trial for the intermediate risk group the mean sickness absence was 7 days in both arms (95% CI of the mean difference -2.3 to 2.4 days). CONCLUSIONS: The identification of high risk of work disability was successful. The occupational health intervention was effective in controlling work loss to a degree that is likely to be economically advantageous within the high risk group. The phone advice intervention for the intermediate risk group was not effective in controlling work loss primarily due to poor adherence.

Parental separation at birth and depression in adulthood: a long-term follow-up of the Finnish Christmas Seal Home Children.

BACKGROUND: Early separation of a child from the mother has been considered a risk factor for later depression. We investigated the association between very early separation and depression in adulthood in a unique dataset. METHOD: The index cohort consisted of 3020 subjects born in 1945-1965 in Finland, isolated from their family due to tuberculosis in the family and placed in special nurseries, immediately after birth, for an average time of 7 months. Those subjects alive at 1 January, 1971 were identified. For every index subject two reference subjects were chosen, the matching criteria being sex, year of birth and place of birth. Data on depression were obtained from the Finnish Hospital Discharge Register by the end of year 1998. RESULTS: In males, 4.2% of the index subjects and 2.6% (Adjusted Rate Ratio RR 1.7, 95% CI 1.3-2.3) of the reference subjects had been treated in hospital due to a depressive episode. In females the respective figures were 3.9% for index subjects and 3.6% (RR 1.1, 95% CI 0.8-1.5) for reference subjects. CONCLUSIONS: The index subjects had an elevated risk for hospital treated depression in adulthood. One explanation may be that the very early temporal separation from the mother at birth may have unfavourable effects on later psychological development. On the other hand, separation from the parents at birth was not found to be strongly associated with severe adulthood depression.

Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study.

BACKGROUND: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes in animals. Our aim was to ascertain whether or not vitamin D supplementation or deficiency in infancy could affect development of type 1 diabetes. METHODS: A birth-cohort study was done, in which all pregnant women (n=12055) in Oulu and Lapland, northern Finland, who were due to give birth in 1966 were enrolled. Data was collected in the first year of life about frequency and dose of vitamin D supplementation and presence of suspected rickets. Our primary outcome measure was diagnosis of type 1 diabetes by end of December, 1997. FINDINGS: 12058 of 12231 represented live births, and 10821 (91% of those alive) children were followed-up at age 1 year. Of the 10366 children included in analyses, 81 were diagnosed with diabetes during the study. Vitamin D supplementation was associated with a decreased frequency of type 1 diabetes when adjusted for neonatal, anthropometric, and social characteristics (rate ratio [RR] for regular vs no supplementation 0.12, 95% CI 0.03-0.51, and irregular vs no supplementation 0.16, 0.04-0.74. Children who regularly took the recommended dose of vitamin D (2000 IU daily) had a RR of 0.22 (0.05-0.89) compared with those who regularly received less than the recommended amount. Children suspected of having rickets during the first year of life had a RR of 3.0 (1.0-9.0) compared with those without such a suspicion. INTERPRETATION: Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes.

Dynamic pattern of disease-associated autoantibodies in siblings of children with type 1 diabetes: a population-based study.

To study the dynamics of disease-associated humoral immune responses, we analyzed autoantibodies to the IA-2 protein (IA-2A), glutamic acid decarboxylase (GADA), and insulin (IAA) and also islet cell antibodies (ICA) in a population-based, prospective, representative series of 710 siblings (<20 years of age) of children with type 1 diabetes. Positivity for single autoantibodies was observed in 8-13% of these siblings during an average follow-up of 4 years. The overall incidence rates per 1,000 years (number of cases/person-years in parentheses) for positive seroconversion of IA-2A were nine (19/2,123), followed by six (12/2,049) for GADA, 19 (40/2,111) for IAA, and 16 (31/1965) for ICA. Positive seroconversions seemed to be associated with a young age of the sibling, HLA DR3/DR4 heterozygosity, HLA identity, and a high initial number of detectable autoantibodies. The overall incidence rates per 1,000 years (number of cases/person-years in parentheses) for inverse seroconversion of IA-2A were 76 (12/157), followed by 42 (10/237) for GADA, 460 (32/70) for IAA, and 27 (9/331) for ICA. No consistent risk factor for inverse seroconversions was present, although seroconversions were most frequent in siblings with older age, male sex, HLA phenotypes other than DR3/DR4, a small family size, and no other autoantibodies detectable at seroconversion. Altogether, these observations indicate that beta-cell autoimmunity may be induced at any age in childhood and adolescence. HLA-conferred genetic disease susceptibility is a strong determinant of persistent beta-cell autoimmunity, but environmental factors may also contribute to such autoimmunity.

Glucose tolerance and cognitive impairment in an elderly population.

We investigated the associations between abnormal glucose tolerance and cognitive impairment in elderly subjects, taking into account some other known determinants of cognitive function. The study population consisted of community-living northern Finnish subjects aged 70 y or over (n=379, of whom were 141 men). Thirty-one percent of the men and women (n=43 for the men and n=75 for the women) scored 23 or less in the Mini Mental State Examination. A low level of basic education and high age were the most powerful predictors of impaired cognition. When adjusted for age, gender, educational level, presence of cardiovascular disease (or hypertension), use of alcohol, number of depressive symptoms and poor vision, abnormal glucose tolerance (including IGT) was also weakly associated with impaired cognitive function among these elderly subjects.

Decreasing incidence and improved survival of laryngeal cancer in Finland.

The decreasing incidence rate and improvement in survival of laryngeal cancer patients in Finland are exceptions among western countries. A descriptive study of these trends was conducted including both nationwide population-based cancer registry data with 5 766 patients diagnosed in 1956-1995 and regional hospital-based data from Northern Finland, allowing classification into supraglottic and glottic cancers, with 353 patients diagnosed in 1976-1995. In Finland, the age-adjusted incidence rate among males decreased from 6.5 per 100 000 in 1956-1965 to 3.5 in 1986-1995, while in females the rate remained around 0.3 per 100 000. The rates in Northern Finland were slightly higher and the supraglottic to glottic incidence ratio diminished from 1.4:1 in 1976-1985 to 0.5:1 in 1986-1995. The 5-year relative survival rate improved in both Northern Finland and the whole country, most noticeably among males and the elderly. In the data from Northern Finland, the survival rate was more favourable in glottic (80%) than in supraglottic cancer (64%). Considering the marked decrease in the incidence of the less favourable supraglottic disease, the observed improvement in survival was small.

Comparison of ultrasound, radiography, and clinical examination in the diagnosis of acute maxillary sinusitis: a systematic review.

The objective of this study was to assess the discriminative properties of the methods for diagnosing acute maxillary sinusitis (AMS) in unselected patients. The study design was a systematic review of evaluation studies identified by using Medline, by searching reference lists, by hand searches, and by contacting investigators. Evaluation studies were conducted anywhere in the world. Subjects were adults with suspected AMS. Main outcome measures were: sensitivity, specificity, positive and negative likelihood ratios of the primary studies, weighted means of these parameters in each comparison (clinical examination, radiography, and ultrasound compared to a reference standard in diagnosing AMS), and summary ROC curves and their Q* points where sensitivity equals specificity. For the years from 1962 to present, 49 study reports were found; 11 articles on studies that included a total of 1144 patients were eligible. Compared to sinus puncture, radiography was the most accurate method for diagnosing AMS: the Q* point on the summary ROC curve was 0.82 (95% confidence interval, CI, 0.78-0.85). Ultrasound was slightly less accurate than radiography compared to sinus puncture (Q* 0.80, 95% CI 0.76-0.83). Only two articles reported clinical examination compared to sinus puncture and the Q* for them was 0.75 (95% 0.58-0.86). Clinical examination is a rather unreliable method for diagnosing AMS, even in the hands of experienced specialists. Using radiography or ultrasound improves the accuracy of diagnosis. The diagnosis of AMS is rarely studied in primary care settings. Future comparative trials should preferably combine diagnosis and treatment, evaluating the two aspects of clinical management as unit.

Search for an optimal combination of structural and functional parameters for the diagnosis of glaucoma. Multivariate analysis of confocal scanning laser tomograph, blue-on-yellow visual field and retinal nerve fiber layer data.

BACKGROUND: The purpose of this study was to evaluate which of the structural and functional parameters--the Heidelberg Retina Tomograph (HRT), white-on-white (W/W) and blue-on-yellow (B/Y) visual fields and semiquantitative retinal nerve fiber layer (RNFL) scoring parameters--can give the best separation between non-glaucomatous and glaucomatous eyes. METHODS: Fifty-five subjects were included in this study: 32 nonglaucomatous subjects with mean age of 54 years, and 23 patients with ocular hypertension or glaucoma and mean age of 59 years. The HRT with software 1.11, the Humphrey 30-2 W/W and lens coloration-corrected B/Y visual fields, and semiquantitative RNFL scores were utilized. Stepwise logistic regression analysis was used in finding, from a given set of parameters, a best discriminating parsimonious subset to a logistic model, the discriminatory performance of which was evaluated by the area under the ROC curve. RESULTS: When all the structural and functional variables were considered, the RNFL total overall score gave the best separation between glaucomatous and non-glaucomatous eyes (ROC area 0.98). Without the RNFL scores and optic disc size-dependent HRT parameters in the model, the cup shape measure was selected first (ROC area 0.88). In the second step the RNFL thickness was selected (ROC area 0.91), and in the third step the corrected B/Y mean deviation (MD) was selected (ROC area 0.91). With only the HRT parameters in the model, the cup/disc ratio was selected first (ROC area 0.88). However, when the groups were matched for optic disc size, all disc size-dependent HRT variables lost their discriminant power. CONCLUSION: Cup shape measure and RNFL thickness, together with age- and lens coloration-corrected MD of the B/Y perimetry provided good discrimination between healthy individuals and patients with glaucoma.

Cow's milk consumption, HLA-DQB1 genotype, and type 1 diabetes: a nested case-control study of siblings of children with diabetes. Childhood diabetes in Finland study group.

The evidence for the putative role of cow's milk in the development of type 1 diabetes is controversial. We studied infant feeding patterns and childhood diet by structured questionnaire (n = 725) and HLA-DQB1 genotype by a polymerase chain reaction-based method (n = 556) in siblings of affected children and followed them for clinical type 1 diabetes. In a nested case-control design in a population who had both dietary and genetic data available, we selected as cases those siblings who progressed to clinical diabetes during the follow-up period (n = 33). For each case, we chose as matched control subjects siblings who fulfilled the following criteria: same sex, age within 1 year, not from the same family, the start of the follow-up within 6 months of that of the respective case, and being at risk for type 1 diabetes at the time the case presented with that disease (n = 254). The median follow-up time was 9.7 years (range 0.2-11.3). Early age at introduction of cow's milk supplements was not significantly associated with progression to clinical type 1 diabetes (relative risk adjusted for matching factors, maternal education, maternal and child's ages, childhood milk consumption, and genetic susceptibility markers was 1.60 [95% CI 0.5-5.1]). The estimated relative risk of childhood milk consumption for progression to type 1 diabetes was 5.37 (1.6-18.4) when adjusted for the matching and aforementioned sociodemographic factors, age at introduction of supplementary milk feeding, as well as for genetic susceptibility markers. In conclusion, our results provide support for the hypothesis that high consumption of cow's milk during childhood can be diabetogenic in siblings of children with type 1 diabetes. However, further studies are needed to assess the possible interaction between genetic disease susceptibility and dietary exposures in the development of this disease.

Psoriasis, its treatment, and cancer in a cohort of Finnish patients.

This study was designed to estimate the relative cancer risk of patients with moderate to severe psoriasis, with reference to different treatments. A cohort of 5687 hospitalized patients with psoriasis obtained from the Finnish Hospital Discharge Register in 1973-84 was linked with the records of the Finnish Cancer Registry. Standardized incidence ratios for cancer were calculated by dividing the observed number of cases by the expected cases, which were based on the national sex-specific and age-specific cancer incidence rates. By the end of 1995, 533 cancer cases were observed in the cohort. The overall cancer incidence was increased (standardized incidence ratio 1.3, 95% confidence interval 1.2-1.4). The estimated relative risks were highest for Hodgkin's disease (standardized incidence ratio 3.3, 95% confidence interval 1.4-6.4), squamous cell skin carcinoma (standardized incidence ratio 3.2, 95% confidence interval 2.3-4.4), non-Hodgkin's lymphoma (standardized incidence ratio 2.2, 95% confidence interval 1.4-3.4), and laryngeal cancer (standardized incidence ratio 2.9, 95% confidence interval 1.5-5.0). The role of prior oral antipsoriatic medications or phototherapy on the development of these cancers was assessed in a nested case-control study, for which 67 cases and 199 sex and age matched controls were selected from the psoriasis cohort. The relative risks were estimated using conditional logistic regression analysis. Oral 8-methoxy-psoralen plus ultraviolet-A radiation therapy and the use of retinoids were associated with an increased risk of squamous cell skin carcinoma (relative risk adjusted for the other treatment variables 6.5, 95% confidence interval 1.4-31, and 7.4, 95% confidence interval 1.4-40, respectively), whereas none of the treatments could be linked with the occurrence of non-Hodgkin's lymphoma.

Changes in glucose tolerance during three years' follow-up in an elderly population.

The aim of this study was to describe changes in glucose tolerance over 3 y and to establish the prevalence of diabetes and impaired glucose tolerance in an unselected non-institutionalised elderly population aged 70 y or over at the beginning of the study. Diabetes was assessed on the basis of self-reports and 2 h oral glucose tolerance tests which were classified according to the 1985 WHO criteria. At the end of the follow-up period, 15% (n=14) of the men were diagnosed as having previously diagnosed diabetes, 8% (n=7) as having previously undiagnosed diabetes, 36% (n=33) as having IGT and the remaining 41% (n=38) as having normal glucose tolerance. The corresponding figures for the women were: 22% (n=37), 8% (n=13), 37% (n=61) and 34% (n=56), respectively. More than one third of the people with baseline normal glucose tolerance (NGT) had progressed to impaired glucose tolerance (IGT) or diabetes mellitus (DM) (n=44). Almost one third of those with baseline IGT had reverted to NGT (n=24), half had persisting IGT (n=41) and one fifth had progressed to DM (n=14). Almost one fifth of the subjects with baseline DM had reverted to IGT (n=12), and only one had reverted to NGT. In conclusion, a comparatively high proportion of both previously diagnosed diabetes, previously undiagnosed diabetes and IGT were found in the follow-up examinations of this elderly study population. The rate of deterioration of glucose tolerance during 3 y follow-up was also moderately high among these elderly subjects.