Olof Akre

Increased risk for cardiovascular mortality in psoriasis inpatients but not in outpatients

We have conducted a historical cohort study to assess cardiovascular mortality among psoriasis patients. Using the Swedish Inpatient Registry, we selected 8991 patients hospitalized for psoriasis at dermatological wards. To represent an outpatient cohort, 19,757 members of the Swedish Psoriasis Association were selected. Mortality from cardiovascular diseases was compared with the general population. We found no increased cardiovascular mortality among outpatients with psoriasis (standardized mortality ratio, SMR 0.94; 95% confidence interval, CI: 0.89–0.99). The overall risk among inpatients admitted at least once was increased by 50%(SMR 1.52; 95% CI: 1.44–1.60). The excess risk increased with increasing number of hospital admissions (p for trend <0.001). Cardiovascular mortality was higher among those admitted at younger ages (p for trend <0.001; SMR 2.62, 95% CI: 1.91–3.49, for patients aged 20 to 39 years at first admission). Young age at first admission appeared to further increase the risk among those who were repeatedly admitted. We conclude that a diagnosis of psoriasis per se does not appear to increase the risk for cardiovascular mortality. Severe psoriasis, however, here measured as repeated admissions, and early age at first admission, is associated with increased risk for cardiovascular death.

Risk Factor Patterns for Cryptorchidism and Hypospadias

To evaluate the hypothesis of a common etiology for cryptorchidism and hypospadias, we conducted two case-control studies nested in a nationwide cohort in Sweden, using record linkage between the Inpatient and Birth Registries. Cases were 2,782 and 1,220 boys operated for cryptorchidism or hypospadias, respectively. Five matched controls per case were randomly selected. Pregnancy and perinatal data were prospectively recorded in the Birth Registry. Data were modeled through conditional logistic regression. Both cryptorchidism (odds ratio (OR) = 2.22) and hypospadias (OR = 2.75) were positively associated with other congenital malformations and inversely with maternal parity (OR = 0.77 and 0.52, respectively, for parity 4+ compared with primiparae). There is evidence that being born small-for-gestational-age and before the 33rd gestational week have a greater-than-additive effect with respect to both cryptorchidism (OR = 6.19 vs 1.72 expected) and hypospadias (OR = 4.39 vs 2.60 expected) compared with non-small-for-gestational-age boys born at term. Hypospadias was positively associated with severe preeclampsia (OR = 2.11). We conclude that the etiologies of the two conditions are partly shared.

Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes

Objective To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer. Design Observational study. Setting Sweden, 1996-2010. Participants 34 515 men primarily treated for prostate cancer with surgery (n=21 533) or radiotherapy (n=12 982). Patients were categorised by risk group (low, intermediate, high, and metastatic), age, and Charlson comorbidity score. Main outcome measures Cumulative incidence of mortality from prostate cancer and other causes. Competing risks regression hazard ratios for radiotherapy versus surgery were computed without adjustment and after propensity score and traditional (multivariable) adjustments, as well as after propensity score matching. Several sensitivity analyses were performed. Results Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy v prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings. Conclusions This large observational study with follow-up to 15 years suggests that for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localised prostate cancer might have a greater benefit from surgery.

Perinatal Risk Factors for Ischemic Heart Disease Disentangling the Roles of Birth Weight and Preterm Birth

Background— Several studies have reported an association between low birth weight and ischemic heart disease, but it remains unclear whether the association is mediated through poor fetal growth or short gestational duration. Methods and Results— In a cohort study, we have identified all subjects born preterm or with a low birth weight at 4 major delivery units in Sweden from 1925 through 1949. For comparison, an equal number of subjects with none of these criteria were identified within the same source population. The study population consists of 6425 subjects, of whom 2931 were born before 37 weeks of gestation and 2176 had a birth weight <2500 g. Fetal growth was estimated through birth weight for gestational age. The cohort was followed up for occurrence of ischemic heart disease through the nationwide Hospital Discharge and Cause of Death Registries during the period of 1987 through 2002. In the cohort, 617 cases of ischemic heart disease occurred. Compared with subjects with a normal fetal growth, those born small for gestational age (birth weight ≤−2 SD below the mean) were at increased risk of ischemic heart disease (adjusted hazard ratio, 1.64; 95% confidence interval, 1.23 to 2.18). The negative association between fetal growth and risk of ischemic heart disease was independent of gestational duration. Conclusions— The association between low birth weight and adult risk of ischemic heart disease appears to be mediated entirely by poor fetal growth.

Perinatal Risk Factors for Diabetes in Later Life

OBJECTIVE—Low birth weight is consistently associated with an increased risk of type 2 diabetes in adulthood, but the individual contributions from poor fetal growth and preterm birth are not known. We therefore investigated the significance of these two factors separately. RESEARCH DESIGN AND METHODS—We identified a cohort of subjects born preterm or with low birth weight at term at four major delivery units in Sweden from 1925 through 1949. A comparison cohort of subjects was identified from the same source population. Of 6,425 subjects in all, 2,931 were born at <37 weeks of gestation and 2,176 had a birth weight <2,500 g. Disease occurrence among participants was assessed through nationwide hospital registers from 1987 through 2006. RESULTS—During follow-up, there were 508 cases of diabetes. Low birth weight was strongly negatively associated with risk of diabetes (P for trend <0.0001). Both short gestational duration and poor fetal growth were associated with later diabetes (P for trend <0.0001 and <0.0004, respectively). Very preterm birth (≤32 weeks of gestation at birth) was associated with a hazard ratio (HR) of 1.67 (95% CI 1.33–2.11) compared with term birth. Birth weights below 2 SDs of mean birth weight for gestational age were associated with an HR of 1.76 (1.30–2.38) compared with birth weights between the mean weight and the weight at 1 SD above the mean. CONCLUSIONS—Our results suggest that the association between low birth weight and diabetes is due to factors associated with both poor fetal growth and short gestational age.

Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients

PURPOSE There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. METHODS We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer-specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. CONCLUSION The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.

A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer—experiences of the son

BACKGROUND We undertook a systematic review and meta-analysis of perinatal variables in relation to testicular cancer risk, with a specific focus upon characteristics of the son. METHODS Literature databases Scopus, EMBASE, PubMed and Web of Science were searched using highly sensitive search strategies. Of 5865 references retrieved, 67 articles met the inclusion criteria, each of which was included in at least one perinatal analysis. RESULTS Random effects meta-analysis produced the following results for association with testicular cancer risk: birth weight [per kilogram, odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.88-1.01, I(2)= 12%], low birth weight (OR = 1.34, 95% CI 1.08-1.67, I(2)= 51%), high birth weight (OR = 1.05, 95% CI 0.96-1.14, I(2)= 0%), gestational age (per week, OR = 0.95, 95% CI 0.92-0.98, I(2)= 38%; low vs not, OR = 1.31, 95% CI 1.07-1.59, I(2)= 49%), cryptorchidism (OR = 4.30, 95% CI 3.62-5.11, I(2)= 44%), inguinal hernia (OR = 1.63, 95% CI 1.37-1.94, I(2)= 38%) and twinning (OR = 1.22, 95% CI 1.03-1.44, I(2)= 22%). Meta-analyses of the variables birth length, breastfeeding and neonatal jaundice did not provide evidence for an association with testicular cancer risk. When low birth weight was stratified by data ascertainment (record/registry vs self-report), only the category of self-report was indicative of an association. Meta-regression of data ascertainment (record/registry vs self-report) inferred that record-/registry-based studies were less supportive of an association with gestational age (per week = 0.97, 95% CI 0.94-1.00, I(2)( )= 29%; low vs not = 1.08, 95% CI 0.91-1.28, I(2)= 32%). CONCLUSION In conclusion, this systematic review and meta-analysis finds evidence that cryptorchidism, inguinal hernia and twinning, and tentative evidence that birth weight and gestational age, are associated with risk of testicular cancer.

Human fertility does not decline: evidence from Sweden

OBJECTIVE To assess changes in human fertility over time. DESIGN Time-trend analyses and age-period-cohort modeling. SETTING Sweden, 1983-1993. PATIENT(S) All primiparous women aged > or =20 years during the study period. There were 401,653 women who were identified through the nationwide Medical Birth Register. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Risk of subfertility, defined as > or =1 year of involuntary childlessness. RESULT(S) Subfertility problems decreased dramatically over successive maternal birth cohorts. Further, the risk of subfertility increased with age and decreased with increasing formal education. CONCLUSION(S) A decrease in male fertility cannot be ruled out on the basis of these results, but if present, it is minor and totally outweighed by other favorable developments. As the main explanation for our findings, we propose a decrease in the prevalence of secondary subfertility as a result of the eradication of gonorrhea.

Maternal and Gestational Risk Factors for Hypospadias

Background An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. Objectives Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. Methods We conducted a case–control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. Results A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) = 4.6; 95% confidence interval (CI), 1.6–13.3]. Boys born to obese [body mass index (BMI) ≥ 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6; 95% CI, 1.2–5.7) compared with boys born to mothers with a normal weight (BMI = 20–24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy’s risk of hypospadias 2.0-fold (95% CI, 1.1–3.7) and 1.8-fold (95% CI, 1.2–2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6; 95% CI, 1.1–53). Conclusions A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.

Sickness in pregnancy and sex of child

We report a female predominance among the offspring of mothers with hyperemesis gravidarum.