Short-term and long-term effects of childhood cancer on income from employment and employment status: A national cohort study in Sweden.

BACKGROUND: There is insufficient knowledge regarding the economic impact of childhood cancer on parents. The objectives of the current study were to investigate the short-term and long-term effects of childhood cancer on mothers' and fathers' income from employment and employment status. METHODS: The study sample consisted of the parents of children diagnosed with cancer from 2004 to 2009 in Sweden (3626 parents of 1899 children). Annual register data concerning income from employment and employment status (employed/not employed) were retrieved from the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Using generalized linear models, the mean income from employment and employment status were compared with a matched control cohort of 34,874 parents sampled from the general population. RESULTS: Parents' income was found to decrease significantly after the child's cancer diagnosis. The effect was most pronounced for mothers, whose income was reduced for 6 years after diagnosis, whereas fathers' income was similar to that of control fathers 3 years after the diagnosis. Mothers were more likely to stop working after a child's cancer diagnosis compared with controls. No association was found for fathers' employment status. Younger age of parents; lower level of education; and, among mothers, being born outside of Sweden were found to be associated with more adverse effects on income. CONCLUSIONS: Parents' income from employment and employment status appear to be adversely affected by having a child with cancer. Socioeconomic consequences are not distributed equally: the income of fathers appears to catch up after a few years, whereas mothers tend to be disadvantaged in their professional life for several years after a child's cancer diagnosis. Cancer 2017;123:1238-1248. © 2016 American Cancer Society.

Maternal haemoglobin concentrations before and during pregnancy and stillbirth risk: a population-based case-control study.

BACKGROUND: Results of previous studies on the association between maternal haemoglobin concentration during pregnancy and stillbirth risk are inconclusive. It is not clear if haemoglobin concentration before pregnancy has a role. Using prospectively collected information from pre-pregnancy and antenatal visits, we investigated associations of maternal haemoglobin concentrations before and during pregnancy and haemoglobin dilution with stillbirth risk. METHODS: In a population-based case-control study from rural Golestan, a province in northern Iran, we identified 495 stillbirths (cases) and randomly selected 2,888 control live births among antenatal health-care visits between 2007 and 2009. Using logistic regression, we estimated associations of maternal haemoglobin concentrations, haemoglobin dilution at different stages of pregnancy, with stillbirth risk. RESULTS: Compared with normal maternal haemoglobin concentration (110-120 g/l) at the end of the second trimester, high maternal haemoglobin concentration (≥140 g/l) was associated with a more than two-fold increased stillbirth risk (OR = 2.31, 95 % CI [1.30-4.10]), while low maternal haemoglobin concentration (<110 g/l) was associated with a 37 % reduction in stillbirth risk. Haemoglobin concentration before pregnancy was not associated with stillbirth risk. Decreased haemoglobin concentration, as measured during pregnancy (OR = 0.61, 95 % CI [0.46, 0.80]), or only during the second trimester (OR = 0.75, 95 % CI [0.62, 0.90]), were associated with reduced stillbirth risk. The associations were essentially similar for preterm and term stillbirths. CONCLUSIONS: Haemoglobin concentration before pregnancy is not associated with stillbirth risk. High haemoglobin level and absence of haemoglobin dilution during pregnancy could be considered as indicators of a high-risk pregnancy.

Consanguineous marriage, prepregnancy maternal characteristics and stillbirth risk: a population-based case-control study.

INTRODUCTION: Consanguineous marriage is associated with increased risks for congenital anomalies, low birthweight, and other adverse perinatal outcomes. In this population-based, case-control study we investigated the association between consanguineous marriage (first-cousin marriage) and stillbirth risk, using prospectively collected information from prepregnancy visits. MATERIAL AND METHODS: From 2007 to 2009, we identified 283 stillbirths (cases) and 2088 randomly selected live control births through prepregnancy visits in rural Golestan, Iran. The associations between consanguinity and prepregnancy maternal characteristics and stillbirth risk were examined using multivariate logistic regression. RESULTS: The rate of consanguineous marriage was 19.4% among cases and 13.6% among controls. Consanguinity was associated with increased stillbirth risk [odds ratio (OR) 1.53; 95% CI 1.10-2.14]. The association was significantly increased for preterm stillbirth (< 37 gestational weeks) (OR 2.43; 95% CI 1.46-4.04) but not for term stillbirth (≥ 37 weeks) (OR 1.14; 95% CI 0.75-1.74). Low and high maternal age, underweight, obesity, nulliparity, a history of infertility or miscarriage, previous obstetric complications (preeclampsia, preterm delivery, and stillbirth in previous pregnancies) were also associated with increased stillbirth risks. CONCLUSIONS: Consanguineous marriage is associated with increased risk of stillbirth, particularly preterm stillbirth. Findings for other maternal risk factors for stillbirth in rural Iran are consistent with previously reported findings from high-income countries.

Risk of renal disease in patients with both type 1 diabetes and coeliac disease.

AIMS/HYPOTHESIS: Our aim was to study the risk of renal disease in patients with type 1 diabetes (T1D) and coexisting coeliac disease (CD). METHODS: Individuals with T1D were defined as having a diagnosis of diabetes recorded at ≤30 years of age in the Swedish Patient Register between 1964 and 2009. Individuals with CD were identified through biopsy reports with villous atrophy (Marsh stage 3) from 28 pathology departments in Sweden between 1969 and 2008. We identified 954 patients with both T1D and CD. For each patient with T1D + CD, we selected five age- and sex-matched reference individuals with T1D only (n = 4,579). Cox regression was used to estimate the following risks: (1) chronic renal disease and (2) end-stage renal disease in patients with CD + T1D compared with T1D patients only. RESULTS: Forty-one (4.3%) patients with CD + T1D and 143 (3.1%) patients with T1D only developed chronic renal disease. This corresponded to an HR of 1.43 for chronic renal disease (95% CI 0.94, 2.17) in patients with CD + T1D compared with T1D only. In addition, for end-stage renal disease there was a positive (albeit statistically non-significant) HR of 2.54 (95% CI 0.45, 14.2). For chronic renal disease, the excess risk was more pronounced after >10 years of CD (HR 2.03, 95% CI 1.08, 3.79). Risk estimates were similar when we restricted our cohort to the following T1D patients: (1) those who had an inpatient diagnosis of T1D; (2) those who had never received oral glucose-lowering medication; and (3) those who had not received their first diabetes diagnosis during pregnancy. CONCLUSIONS/INTERPRETATION: Overall this study found no excess risk of chronic renal disease in patients with T1D and CD. However, in a subanalysis we noted a positive association between longstanding CD and chronic renal disease in T1D.

Risk of diabetes and cardiovascular disease in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is associated with increased mortality. Cardiovascular disease is a leading cause of death in the Western world. We examined the risk of cardiovascular disease and diabetes (type 1 and type 2) in patients with PSC and their first-degree relatives. METHODS: This prospective multicentre cohort study included 678 individuals with PSC diagnosed between 1970 and 2004, and 6347 non-PSC reference individuals matched for age, and sex. Through linkage of the Swedish Multigeneration Register we identified 3139 first-degree relatives to PSC patients and 30,953 first-degree relatives to the matched comparison cohort. We retrieved data on cardiovascular disease and type 1 and type 2 diabetes (T1D and T2D) from the National Patient Register, and then examined the association with PSC or having a family history of PSC using Poisson regression. RESULTS: During 125,127 person-years of follow-up, 203 individuals with PSC had a diagnosis of cardiovascular disease. This corresponded to a 3.34-fold increased relative risk (RR) of cardiovascular disease in individuals with PSC (95% CI=2.86-3.91). The highest risk estimates were seen for diseases of the arteries, veins, and lymphatic vessels while the RR was neutral for ischemic heart disease (0.90) or only slightly elevated for cerebrovascular disease (1.74). Meanwhile, PSC first-degree relatives were at no increased risk of cardiovascular disease (RR=0.87; 95% CI=0.80-0.95). Individuals with PSC (RR=7.95; 95% CI=4.82-13.12), and to some extent also their first-degree relatives (RR=1.73; 95% CI=1.19-2.52) were at increased risk of T1D. Also for T2D were the RR is higher in individuals with PSC (RR=2.54; 95% CI=1.56-4.13) than in PSC first-degree relatives (RR=0.81; 95% CI=0.65-1.02). CONCLUSIONS: PSC was associated with T1D, T2D, and non-ischemic cardiovascular disease. In contrast, first-degree relatives to PSC patients were only at a moderately increased risk of T1D, and at no increased risk of either cardiovascular disease or T2D.

Infectious disease at gluten introduction and risk of childhood diabetes mellitus.

OBJECTIVES: To investigate the risk of future diabetes mellitus type 1 (T1D) in children who suffered from infection at time of gluten introduction. STUDY DESIGN: Population-based prospective study. Parents filled out a diary at home. We hereby obtained data on date of gluten introduction, breastfeeding duration, and infections in 9414 children born in the southeast of Sweden from October 1, 1997, through October 1, 1999 (the All Babies in Southeast Sweden cohort). The Cox proportional hazards model was used to investigate the risk of future T1D until February 1, 2012, among children with infection at time of gluten introduction. RESULTS: Forty-six children (0.5%) developed T1D and were compared with 9368 reference children from the general population. Some 10 of 46 children with later T1D had an infection at time of gluten introduction (22%) compared with 2520 reference children (27%, P=.43). Later T1D was not associated with age at end of breastfeeding, age at any infection, or age at gluten introduction. Breastfeeding at time of gluten introduction was not protective against future T1D (hazard ratio 1.2; 95% CI, 0.5-2.7). In our final model, when we adjusted for age at gluten introduction, age at infection, and breastfeeding duration, infection at time of gluten introduction did not influence the risk of future T1D (hazard ratio 0.8; 95% CI, 0.3-1.6). CONCLUSION: Infection at time of gluten introduction is not a major risk factor for future T1D in nonselected children.

Co-morbidity, body mass index and quality of life in COPD using the Clinical COPD Questionnaire.

INTRODUCTION: Quality of life is an important patient-oriented measure in COPD. The Clinical COPD Questionnaire (CCQ) is a validated instrument for estimating quality of life. The impact of different factors on the CCQ-score remains an understudied area. The aim of this study was to investigate the association of co-morbidity and body mass index with quality of life measured by CCQ. METHODS: A patient questionnaire including the CCQ and a review of records were used. A total of 1548 COPD patients in central Sweden were randomly selected. Complete data were collected for 919 patients, 639 from primary health care and 280 from hospital clinics. Multiple linear regression with adjustment for sex, age, level of education, smoking habits and level of care was performed. Subanalyses included additional adjustment for lung function in the subgroup (n = 475) where spirometry data were available. RESULTS: Higher mean CCQ score indicating lower quality of life was statistically significant and independently associated with heart disease (adjusted regression coefficient (95%CI) 0.26; 0.06 to 0.47), depression (0.50; 0.23 to 0.76) and underweight (0.58; 0.29 to 0.87). Depression and underweight were associated with higher scores in all CCQ subdomains. Further adjustment for lung function in the subgroup with this measure resulted in statistically significant and independent associations with CCQ for heart disease, depression, obesity and underweight. CONCLUSION: The CCQ identified that heart disease, depression and underweight are independently associated with lower health-related quality of life in COPD.

Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis.

AIM: To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age. METHODS: Among 401 newborn infants < 28 days of age with suspected sepsis, nine signs of sepsis and C-reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex. RESULTS: Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures. CONCLUSION: In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants.

Self-perceived oral health and obesity among 65 years old in two Swedish counties.

The aim of this study was to explore the association between oral health and obesity. The study was conducted in the spring of 2007 as a postal survey of all inhabitants born in 1942 and living in the two Swedish counties of Orebro and Ostergötland.This questionnaire survey has been conducted everyfiveyears since 1992 but has been updated continually with additional questions and for the sweep used here, height and weight data were collected. A total of 8,313 individuals received the questionnaire and 6,078 of those responded (73.1%). The outcome variable oral health was measured using one global question and four detailed questions representing different aspects of oral health. The independent variable Body Mass Index (BMI) was calculated using self-reported height and weight. A difference in oral health between various BMI groups was found. The difference was both statistically significant and of clinical importance, particularly among the group with severe obesity who reported poorer self-perceived chewing capacity, lower satisfaction with dental appearance, increased mouth dryness and fewer teeth and lower overall satisfaction with oral health. In view of the increased risk of poor oral health demonstrated in this study for those with severe obesity, it may be of value to increase cooperation between dental care and primary health care for these patients.

Cancer risk among patients with cystic fibrosis and their first-degree relatives.

Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population-based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first-degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1-4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow-up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk.

Maternal country of birth and previous pregnancies are associated with breast milk characteristics.

Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

Coeliac disease and body mass index: a study of two Swedish general population-based registers.

OBJECTIVE: To examine the relationship between body mass index (BMI) and an inpatient diagnosis of coeliac disease (CD) in two independent Swedish national registers. MATERIAL AND METHODS: Study 1: Cohort study of women. The relationship between (pre-pregnancy) BMI and CD in pregnant women was evaluated (174 undiagnosed CD (at time of pregnancy), 550 diagnosed CD, 787,986 without a diagnosis of CD). The association between BMI and undiagnosed CD was estimated by Cox regression. Study 2: Case-control study of men. The relationship between BMI and CD in male conscripts was evaluated (70 undiagnosed CD, 1,047 diagnosed CD and 6,887 without a diagnosis of CD). The association between BMI and undiagnosed CD was estimated by logistic regression. Prevalence of underweight, normal weight and overweight was compared between diagnosed CD, undiagnosed CD and no diagnosis of CD. RESULTS: The prevalence of underweight (BMI <18.5) in women was: reference individual: 5.2%; undiagnosed CD: 16.7% and prior diagnosis of CD: 6.4%. In men, the corresponding figures were 6.5%; 14.3% and 9.8%, respectively. Underweight was associated with undiagnosed CD (future diagnosis of CD) in both women (hazard ration (HR) = 2.5; 95% CI = 1.6-3.7) and men (odds ratio (OR) = 2.4; 95% CI = 1.2-4.9). In women, overweight was negatively associated with undiagnosed CD (HR = 0.6; 95% CI = 0.4-0.9), but not in men (OR = 1.1; 95% CI = 0.6-2.2). 9.2% of women with undiagnosed CD and 14.3% of men with undiagnosed CD were overweight. CONCLUSIONS: Underweight individuals are at increased risk of having undiagnosed CD. However, overweight does not rule out CD.

Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa.

BACKGROUND: Antibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD. METHODS: The records of ten Swedish pathology departments were used to identify individuals with biopsies indicating normal duodenal/jejunal mucosa. Using the national personal identification number, these data were linked with CD serology data (antigliadin, antiendomysial and tissue transglutaminase antibodies); and we thereby identified 3,736 individuals with normal mucosa but positive CD serology. Two independent reviewers then manually reviewed their biopsy reports to estimate comorbidity. We also randomly selected 112 individuals for validation through patient chart review. RESULTS: The majority of the 3,736 individuals were females (62%). Children (0-15 years) made up 21.4%. The median number of biopsy specimen was 3. Our review of biopsy reports found that other gastrointestinal comorbidity was rare (inflammatory bowel disease: 0.4%; helicobacter pylori infection: 0.2%). Some 22% individuals selected for patient chart review had a relative with CD. The most common symptoms among these individuals were diarrhea (46%) and abdominal pain (45%), while 26% had anemia. Although 27% of the individuals selected for validation had been informed about gluten-free diet, only 13% were adhering to a gluten-free diet at the end of follow-up. CONCLUSION: Individuals with positive CD serology but normal mucosa often have CD-like symptoms and a family history of CD.

Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers.

BACKGROUND: Small intestinal biopsy with villous atrophy (VA) is the gold standard for the diagnosis of celiac disease (CD). We validated VA (Marsh 3) and small intestinal inflammation without VA (Marsh 1+2) in Swedish regional biopsy registers. METHODS: All pathology departments in Sweden (n = 28) were searched to identify individuals with VA or duodenal/jejunal inflammation. The validation consisted of blinded examination of biopsy samples, manual review of biopsy reports, web surveys, and patient chart reviews of 121 individuals with VA and 39 with inflammation. RESULTS: We identified 29,148 individuals with VA and 13,446 individuals with inflammation. In a blinded examination, Swedish pathologists correctly classified 90% of biopsies with VA. Manual screening of 1,534 biopsy reports (performed by co-author JFL and a research assistant) found that comorbidity other than CD was rare. IBD was the most common comorbidity and occurred in 0.3% of biopsies with VA (1.6% in inflammation). Among 114 patients with VA and available data, 108 (95%) had a clinical diagnosis of CD. 79% of the validated individuals with VA and 64% of those with inflammation had documented gastrointestinal symptoms prior to biopsy. 88% of the validated individuals with VA had positive CD serology before their first biopsy. 172/180 (96%) of Swedish gastroenterologists and 68/68 (100%) of pediatricians perform a small intestinal biopsy in at least 9 out of 10 individuals prior to diagnosis of CD. CONCLUSION: Regional biopsy data are feasible to identify individuals with CD and small-intestinal inflammation. The specificity of CD is high in villous atrophy.

Small-intestinal histopathology and mortality risk in celiac disease.

CONTEXT: Studies of mortality in celiac disease have not taken small-intestinal pathology into account. OBJECTIVE: To examine mortality in celiac disease according to small-intestinal histopathology. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage 1-2; n = 13,306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age- and sex-matched controls from the general population. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: There were 3049 deaths among patients with celiac disease, 2967 with inflammation, and 183 with latent celiac disease. We found an increased hazard ratio (HR) for death in celiac disease (HR, 1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years), inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years). The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7-7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk increase was also seen in children. Excluding the first year of follow-up, HRs decreased somewhat. CONCLUSION: Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.

Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients.

OBJECTIVES: Curing of hepatitis C virus (HCV) infection primarily aims to prevent severe liver complications. Our objectives were to investigate the long-term presence and impact of occult HCV infection (OCI) and to study the outcomes in terms of liver disease after virological cure. PATIENTS AND METHODS: A total of 97 patients with achieved sustained virological response (SVR) during 1990-2005 were followed either by a clinical follow-up (FU) visit with blood sampling and liver elastography (n=54) or through national registries for outcomes (n=43). To diagnose OCI among patients with SVR, a highly sensitive method was used to detect HCV-RNA traces in whole blood. The FU duration was a median of 10.5 years, with samples up to 21.5 years after the end of treatment (EOT). RESULTS: The majority of patients [52 (96%)] were HCV-RNA negative at FU, and regression of fibrosis was statistically significant. OCI was found in two (4%) of them at 8 and 9 years after EOT. These patients had F1 and F2 fibrosis before treatment and F2 at FU, but no other abnormal findings. Three previously noncirrhotic men were diagnosed with hepatocellular carcinoma 8-11 years after EOT. CONCLUSION: Occult infection could be detected many years after the achievement of SVR but was not associated with serious liver disease. The majority had persistent viral eradication and regression of fibrosis after SVR. However, an increased risk of hepatocellular carcinoma may persist in the long term after SVR even in noncirrhotic patients. Further studies with FU after direct-acting antiviral therapy and on the long-term impact after cure are needed.

Risk of thyroid disease in individuals with celiac disease.

BACKGROUND: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort. METHODS: A total of 14,021 individuals with celiac disease (1964-2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up of more than 1 yr and with no thyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease. RESULTS: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR) = 4.4; 95% confidence interval (CI) = 3.4-5.6; P < 0.001], thyroiditis (HR = 3.6; 95% CI =1.9-6.7; P < 0.001) and hyperthyroidism (HR = 2.9; 95% CI = 2.0-4.2; P < 0.001). The highest risk estimates were found in children (hypothyroidism, HR = 6.0 and 95% CI = 3.4-10.6; thyroiditis, HR = 4.7 and 95% CI = 2.1-10.5; hyperthyroidism, HR = 4.8 and 95% CI = 2.5-9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI = 2.7-4.4; P < 0.001), 3.3 for thyroiditis (95% CI = 1.5-7.7; P < 0.001), and 3.1 for hyperthyroidism (95% CI = 2.0-4.8; P < 0.001). CONCLUSION: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.

Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. METHODS: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. RESULTS: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). CONCLUSIONS: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania.

BACKGROUND: The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored. METHODS: Structured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors. RESULTS: Among 265 mothers and household heads, 244 (92%, CI = 88%-95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%-61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2-3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug. CONCLUSION: WTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem fully at governmental health care facilities and at a consumer price of TSh 300-500 (US$ 0.28-0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.

Increased risk of immune thrombocytopenic purpura among inpatients with coeliac disease.

OBJECTIVE: Case reports have indicated a link between coeliac disease (CD) and immune thrombocytopenic purpura (ITP). Two national, register-based studies were carried out to investigate a possible association between CD and ITP and vice versa. MATERIAL AND METHODS: In a cohort study of 14,347 individuals with inpatient diagnoses of CD and 69,967 reference individuals matched for age, gender, calendar year and county, the Cox regression was used to estimate the risk of subsequent inpatient diagnoses of ITP (of any type or chronic). In a case control design, conditional logistic regression was used to assess the risk of exposure (diagnosis of ITP prior to CD) in 15,382 cases (individuals with diagnoses of CD) and 76,824 matched controls. Diagnoses of CD and ITP were identified through the Swedish National Inpatient Register. RESULTS: Individuals with CD were at increased risk of both subsequent ITP of any type (hazard ratio (HR)=1.91; 95% CI=1.19-3.11; p=0.008) and subsequent chronic ITP (HR 2.77; 95% CI=1.09-7.04; p=0.033). Risk estimates were similar when reference individuals were restricted to inpatients. There was also a positive association between CD and prior ITP of any type (odds ratio (OR)=2.96; 95% CI=1.60-5.50; p=0.001) or with prior chronic ITP (OR=6.00; 95% CI=1.83-19.66; p=0.003). CONCLUSIONS: We found a positive association between CD and both ITP of any type and chronic ITP, irrespective of which disease came first, and suggest there should be increased awareness of CD in patients with ITP.