Geometrical frustration and cluster spin glass with random graphs.

We develop a based on a sparse random graph to account for the interplay between geometric frustration and disorder in cluster magnetism. Our theory allows introduction of the cluster network connectivity as a controllable parameter. Two types of inner cluster geometry are considered: triangular and tetrahedral. The theory was developed for general, nonuniform intracluster interactions, but in the present paper the results presented correspond to uniform, antiferromagnetic (AF) intraclusters interaction J_{0}/J. The clusters are represented by nodes on a finite connectivity random graph, and the intercluster interactions are randomly Gaussian distributed. The graph realizations are treated in replica theory using the formalism of order parameter functions, which allows one to calculate the distribution of local fields and, as a consequence, the relevant observable. In the case of triangular cluster geometry, there is the onset of a classical spin liquid state at a temperature T^{*}/J and then, a cluster spin glass (CSG) phase at a temperature T_{/}J. The CSG ground state is robust even for very weak disorder or large negative J_{0}/J. These results does not depend on the network connectivity. Nevertheless, variations in the connectivity strongly affect the level of frustration f_{p}=-Θ_{CW}/T_{f} for large J_{0}/J. In contrast, for the nonfrustrated tetrahedral cluster geometry, the CSG ground state is suppressed for weak disorder or large negative J_{0}/J. The CSG boundary phase presents a reentrance which is dependent on the network connectivity.

Ising spin glass in a random network with a Gaussian random field.

We investigate thermodynamic phase transitions of the joint presence of spin glass (SG) and random field (RF) using a random graph model that allows us to deal with the quenched disorder. Therefore, the connectivity becomes a controllable parameter in our theory, allowing us to answer what the differences are between this description and the mean-field theory i.e., the fully connected theory. We have considered the random network random field Ising model where the spin exchange interaction as well as the RF are random variables following a Gaussian distribution. The results were found within the replica symmetric (RS) approximation, whose stability is obtained using the two-replica method. This also puts our work in the context of a broader discussion, which is the RS stability as a function of the connectivity. In particular, our results show that for small connectivity there is a region at zero temperature where the RS solution remains stable above a given value of the magnetic field no matter the strength of RF. Consequently, our results show important differences with the crossover between the RF and SG regimes predicted by the fully connected theory.

Stoma reversal after intended restorative rectal cancer resection in Denmark: nationwide population-based study.

BACKGROUND: Data on stoma reversal following restorative rectal resection (RRR) with a diverting stoma are conflicting. This study investigated a Danish population-based cohort of patients undergoing RRR to evaluate factors predictive of stoma reversal during 3 years of follow-up. METHODS: Patients from national registries with rectal cancer undergoing RRR or Hartmann's procedure with curative intent between May 2001 and April 2012 were included. Patients with a diverting stoma were followed from the time of primary rectal cancer resection to date of stoma reversal, death, emigration, or end of 3-year follow-up. The cumulative incidence proportion (CIP) of stoma reversal at 1 and 3 years was calculated, treating death as a competing risk. Factors predictive of stoma reversal were explored using Cox regression analysis. RESULTS: Of 6859 patients included, 35·7, 41·9 and 22·4 per cent respectively had a RRR with a diverting stoma, RRR without a stoma, and Hartmann's procedure with an end-colostomy. In patients with a diverting stoma, the CIP of stoma reversal was 70·3 (95 per cent c.i. 68·4 to 72·1) per cent after 1 year, and 74·3 (72·5 to 76·0) per cent after 3 years. Neoadjuvant treatment (hazard ratio (HR) 0·75, 95 per cent c.i. 0·66 to 0·85), blood loss greater than 300 ml (HR 0·86, 0·76 to 0·97), anastomotic leak (HR 0·41, 0·33 to 0·50), T3 category (HR 0·63, 0·47 to 0·83), T4 category (HR 0·62, 0·42 to 0·90) and UICC stage IV (HR 0·57, 0·41 to 0·80) were possible predictors of delayed stoma reversal. CONCLUSION: In one-quarter of the patients the diverting stoma had not been reversed 3 years after the intended RRR procedure.

ANTECEDENTES: Los datos sobre el cierre del estoma (stoma reversal, SR) tras la exéresis el recto con intención reconstructiva (restorative rectal resection, RRR) y estoma derivativo (diverting stoma, DS) son contradictorios. Este estudio analizó los factores predictivos del SR en una cohorte danesa de base poblacional de pacientes sometidos a RRR con un seguimiento de 3 años. MÉTODOS: Los pacientes con cáncer de recto a los que se realizó una RRR o una operación de Hartmann (Hartmann's operation, HO) con intención curativa desde mayo de 2001 hasta abril de 2012, se seleccionaron a partir de registros nacionales. Los pacientes con SD fueron seguidos desde la resección primaria del cáncer rectal hasta la fecha del SR, del fallecimiento, de su cambio de residencia o hasta el final del seguimiento (3 años). Se calculó la tasa de incidencia acumulada (cumulative incidence proportion, CIP) de RS a 1 y 3 años utilizando la muerte como factor de riesgo competitivo. Se identificaron los factores predictivos de SR mediante regresión múltiple de Cox. RESULTADOS: De los 6.859 pacientes incluidos, el 35,7%, 41,9% y 22,4% tenían una RRR con DS, una RRR sin estoma y una HO con colostomía terminal, respectivamente. En pacientes con SD, el CIP de SR fue del 70,3% (i.c. del 95%: 68,4-72,1) al año y del 74,3% (i.c. del 95%: 72,5-76,0) a los 3 años. Se identificaron como posibles factores predictivos relacionados con el retraso del SR, el tratamiento neoadyuvante (cociente de riesgos instantáneos, hazard ratio, HR 0,75; i.c. del 95% 0,66-0,85), una pérdida de sangre > 300 mL (HR 0,86; i.c. del 95% 0,76-0,97), la fuga anastomótica (HR 0,41; i.c. del 95% 0,33-0,50), las categorías T3 (HR 0,63; i.c. del 95% 0,47-0,83) y T4 (HR 0,62; i.c. del 95% 0,42-0,90) y el estadio IV UICC (HR 0,57; i.c. del 95%: 0,41-0,80). CONCLUSIÓN: En una cuarta parte de los pacientes no se había cerrado el estoma derivativo tres años después de la resección de cáncer rectal con intención reconstructiva.

Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis.

AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure. METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis. RESULTS: Over a median 11.4 years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy. CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.

Multicritical points and topology-induced inverse transition in the random-field Blume-Capel model in a random network.

The interplay between quenched disorder provided by a random field (RF) and network connectivity in the Blume-Capel (BC) model is the subject of this paper. The replica method is used to average over the network randomness. It offers an alternative analytic route to both numerical simulations and standard mean field approaches. The results reveal a rich thermodynamic scenario with multicritical points that are strongly dependent on network connectivity. In addition, we also demonstrate that the RF has a deep effect on the inverse melting transition. This highly nontrivial type of phase transition has been proposed to exist in the BC model as a function of network topology. Our results confirm that the topological mechanism can lead to an inverse melting transition. Nevertheless, our results also show that as the RF becomes stronger, the paramagnetic phase is affected in such way that the topological mechanism for inverse melting is disabled.

Corticosteroid use and mortality risk in patients with perforated colonic diverticular disease: a population-based cohort study.

BACKGROUND: Corticosteroids are a potential risk factor for mortality in patients with perforated diverticular disease, due to blinding of disease severity, hampered wound healing or adrenal insufficiency. We examined mortality in corticosteroid users and non-users among patients with perforated diverticular disease. METHODS: A cohort study based on medical databases including all patients ≥18 years in Denmark (source population 5 289 261 inhabitants) admitted to a hospital with incident perforated diverticular disease between 2005 and 2013. 7-day, 1-month, 3-month and 1-year mortality risks in corticosteroid users and non-users were calculated using the Kaplan-Meier method, and compared with Cox proportional hazard regression adjusted for age, sex and comorbidities. RESULTS: The study included 4640 patients with perforated diverticular disease. Of these, 3743 (80.7%) had not used corticosteroids in the year before admission and 725 (15.6%) had been exposed to systemic corticosteroid treatment. The remaining 172 patients had been exposed to either inhaled or intestinal acting corticosteroid therapy. Mortality risk in non-users was 4.4% after 7 days and 15.6% after 1 year. This risk was doubled for corticosteroid users who filled their last prescription during the 90 days before admission, with mortality risks ranging from 14.2% after 7 days to 47.6% after 1 year. 1-year mortality risk was even higher for corticosteroid users with a first filled prescription ≤90 days before admission: 52.5%. CONCLUSIONS: Corticosteroid use was associated with clearly increased mortality risk after perforated diverticular disease. Thus, use of corticosteroids should be regarded as an important clinical prognostic factor for mortality in patients with this condition.

Mortality and cardiovascular diseases risk in patients with Barrett's oesophagus: a population-based nationwide cohort study.

BACKGROUND: Patients with Barrett's oesophagus may be at increased risk of mortality overall, and cardiovascular disease has been suggested as the main underlying cause of death. AIM: To examine cause-specific mortality and risk of cardiovascular events among patients with Barrett's oesophagus. METHODS: Utilising existing Danish data sources (1997-2011), we identified all patients with histologically verified Barrett's oesophagus (n = 13 435) and 123 526 members of the general population matched by age, sex and individual comorbidities. We calculated cause-specific mortality rates and incidence rates of cardiovascular diseases. We then compared rates between patients with Barrett's oesophagus and the general population comparison cohort, using stratified Cox proportional hazard regression. RESULTS: Patients with Barrett's oesophagus had a 71% increased risk of overall mortality. The cause-specific mortality rate per 1000 person-years for patients with Barrett's oesophagus was 8.5 for cardiovascular diseases, 14.7 for non-oesophageal cancers, and 5.4 for oesophageal cancer. Compared to the general population cohort, corresponding hazard ratios were 1.26 (95% confidence interval (CI): 1.15-1.38), 1.77 (95% CI: 1.65-1.90), and 19.4 (95% CI: 16.1-23.4), respectively. The incidence rates of cardiovascular diseases per 1000 person-years for Barrett's oesophagus patients and for persons from the general population cohort, respectively, varied from 0.4 and 0.2 for subarachnoid bleeding (hazard ratio 1.10, 95% CI: 0.87-1.39) to 8.1 and 5.9 for congestive heart failure (hazard ratio 1.33, 95% CI: 1.21-1.46). CONCLUSION: Prophylactic measures targeted at cardiovascular diseases and non-oesophageal cancers potentially could be more important than measures against oesophageal cancer, for improving prognosis among patients with Barrett's oesophagus.

Inflammatory bowel disease and venous thromboembolism during pregnancy and the postpartum period.

Essentials Risk of pregnancy-related venous thromboembolism may be increased in inflammatory bowel disease. We performed a study on inflammatory bowel disease and pregnancy-related venous thromboembolism. Inflammatory bowel disease is a risk factor for pregnancy-related venous thromboembolism. Proper disease control before conception is pivotal to avoid venous thromboembolism. SUMMARY: Background The incidence of inflammatory bowel disease (IBD) increases, and thus is more common, in pregnant women. IBD is a risk factor for venous thromboembolism (VTE) but it is not clear whether IBD predisposes women to an excess risk of VTE during pregnancy and the postpartum period. Methods This was a nationwide population-based cohort study of all deliveries during 1980-2013 in Denmark, using data from two nationwide health registries: the Danish National Patient Registry and the Medical Birth Registry. We computed incidence rates (IRs) per 1000 person-years, and crude and adjusted relative risks (RRs) with 95% confidence intervals (CIs) for VTE during pregnancy and the first 12 postpartum weeks in women with and without IBD. Results We included 1 046 754 women with 1 978 701 deliveries. We identified 3465 VTE events during pregnancy and 1302 VTE events postpartum. The IR for VTE during pregnancy was 4.20 (95% CI, 2.83-5.58) in IBD patients and 2.41 (95% CI, 2.33-2.50) in women without IBD, corresponding to an RR of 1.72 (95% CI, 1.22-2.43). Adjustment for maternal age and smoking (pregnancies during 1991-2013) yielded an adjusted RR of 1.67 (95% CI, 1.15-2.41). IBD flare was associated with an RR of 2.64 (95% CI, 1.69-4.14) for VTE during pregnancy. The IR for postpartum VTE was 7.03 (95% CI, 3.87-10.20) among IBD patients and 2.88 (95% CI, 2.72-3.04) in women without IBD, corresponding to an adjusted RR of 2.10 (95% CI, 1.33-3.30). Conclusions IBD is a risk factor for VTE during pregnancy and postpartum.

Nationwide population-based cohort study to assess risk of surgery for adhesive small bowel obstruction following open or laparoscopic rectal cancer resection.

BACKGROUND: Laparoscopic surgery has been reported to reduce the formation of adhesions following colorectal surgery. The aim of this nationwide cohort study was to investigate the risk of surgery for adhesive small bowel obstruction (SBO) following open and laparoscopic rectal cancer resection. METHODS: Patients undergoing rectal cancer resection between 2005 and 2013 were identified in the Danish Colorectal Cancer Group database. The primary outcome of surgery for adhesive SBO was identified in the Danish National Patient Registry. The risk of surgery for adhesive SBO was estimated as the cumulative incidence proportion, treating death as a competing risk. Cox proportional hazards regression analysis with multivariable adjustment was used to compute hazard ratios (HRs). The secondary outcome was 30-day mortality after surgery for adhesive SBO. RESULTS: Of 7657 patients, 340 (4·4 per cent) underwent surgery for adhesive SBO. The 5-year risk of surgery for adhesive SBO was 4·5 per cent among 4472 patients undergoing open resection and 3·0 per cent among 3185 patients having a laparoscopic resection. Laparoscopic rectal resection was associated with a lower risk of subsequent operation for adhesive SBO (adjusted HR 0·65, 95 per cent c.i. 0·50 to 0·86; P = 0·002). The adjusted HR of mortality after adhesive SBO was 0·84 (0·37 to 1·91; P = 0·671) comparing patients with previous laparoscopic and open resection. CONCLUSION: Laparoscopic rectal cancer resection was associated with a decreased risk of surgery for adhesive SBO. There was a substantial difference in 30-day mortality after surgery for adhesive SBO based on the surgical approach used at the time of rectal resection.

The increasing incidence and prevalence of eosinophilic oesophagitis outpaces changes in endoscopic and biopsy practice: national population-based estimates from Denmark.

BACKGROUND: National population-based medical registries in Denmark offer a unique opportunity to study eosinophilic oesophagitis (EoE) epidemiology. AIM: To determine the incidence and prevalence of EoE in Denmark, and evaluate whether an increase in endoscopy with biopsy activity explains changes in these trends. METHODS: The Danish National Pathology Registry, Danish National Patient Registry and Danish Registry of Medicinal Product Statistics were queried from 1997 to 2012. Using an EoE case-finding algorithm validated for Danish patients, EoE cases were identified during each year of the study period; we also identified all patients with oesophageal eosinophilia. Using the known population of Demark, the annual incidence and prevalence of EoE were determined. We also determined the number of oesophageal biopsies performed each year in Denmark, and compared the change in the incidence rate to the change in biopsy rate. RESULTS: Between 1997 and 2012, 1708 patients had oesophageal eosinophilia, of whom 844 met the case definition of EoE. There were seven new cases of EoE in 1997 and 145 new cases in 2012, corresponding to a 19.5-fold increase in incidence (0.13/100 000 to 2.6/100 000). There were 769 total cases in 2012 (prevalence of 13.8/100 000). Over the same time frame, the oesophageal biopsy rate increased only 1.9 fold, from 91.1/100 000 to 175.3/100 000. CONCLUSIONS: The incidence and prevalence of EoE markedly increased in Denmark over the past 15 years. This increase far outpaced the increase in oesophageal biopsy utilisation, indicating that changes in the frequency of EoE are not due to changes in biopsy rates alone.

Pre-admission use of glucocorticoids and 30-day mortality following colorectal cancer surgery: a population-based Danish cohort study.

BACKGROUND: Previous studies indicate that pre-admission glucocorticoids increase the risk of perioperative complications. AIM: To examine whether pre-admission use of glucocorticoids affects 30-day mortality after colorectal cancer (CRC) surgery. METHODS: We conducted a nationwide population-based cohort study by linking Danish medical registries. All residents in Denmark who underwent CRC surgery from 2001 to 2011 were included. We characterised subjects who filled their most recent glucocorticoid prescription ≤90, 91-365 and >365 days before their surgery date as prevalent, recent and former users, respectively. Prevalent users were subgrouped into new (first-ever prescription ≤90 days before surgery date) and continuing users. We estimated 30-day cumulative mortality by the Kaplan-Meier method and corresponding mortality rate ratios (MRRs) using Cox proportional hazard regression, adjusting for potential confounders. RESULTS: Of the 34 641 CRC patients included, 3966 (11.5%) had filled one or more prescriptions of glucocorticoids within the year before the surgery date. Thirty-day mortality among prevalent users of oral glucocorticoids was 15.0% vs. 7.3% among non-users [MRR = 1.28; 95% confidence interval (CI): 1.03, 1.58]. Among new users, the 30-day mortality was 17.8% (MRR = 1.92; 95% CI: 1.30, 2.83) while it was 14.2% among continuing users (MRR = 1.13; 95% CI: 0.88, 1.44). No associations were found for recent or former use of oral glucocorticoids nor for use of inhaled, intestinal-acting, and mixed glucocorticoids. CONCLUSIONS: Prevalent use, particulary new use, of oral glucocorticoids was associated with markedly increased 30-day mortality after colorectal cancer surgery compared to patients not exposed to any glucocorticoids.

Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study.

BACKGROUND: It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions. METHODS: We conducted a cohort study (1995-2010) of all Danish CRC patients (n=56963), and five times as many persons from the general population (n=271670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities. RESULTS: Among CRC patients with a CCI score=1, the 0-1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis. CONCLUSION: Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.

Inverse melting and inverse freezing in a three-state spin-glass model with finite connectivity.

The phase diagrams of the three-state Ghatak-Sherrington spin-glass (or random Blume-Capel) model are obtained in mean-field theory with replica symmetry in order to study the effects of a ferromagnetic bias and finite random connectivity in which each spin is connected to a finite number of other spins. It is shown that inverse melting from a ferromagnetic to a low-temperature paramagnetic phase may appear for small but finite disorder and that inverse freezing appears for large disorder. There can also be a continuous inverse ferromagnetic to spin-glass transition.

Use of systemic glucocorticoids and the risk of colorectal cancer.

BACKGROUND: Systemic glucocorticoids are potent immunosuppressants, potentially facilitating carcinogenesis. Studies examining glucocorticoids and colorectal cancer risk are few. AIM: To investigate the association between use of systemic glucocorticoids and colorectal cancer risk, both overall and by cancer stage (localised versus metastatic). METHODS: We conducted a nested population-based case-control study in Northern Denmark (1.8 million people) using medical registries. The study included 14,158 patients with a first-time diagnosis of colorectal cancer from 1991 through 2010. Using risk set sampling, we identified 141,580 population controls, matched on age and gender. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for covariates. RESULTS: Frequent use of systemic glucocorticoids (defined as >2 prescriptions) was not associated with overall colorectal cancer risk [adjusted OR (aOR) = 0.93 (95% CI: 0.85-1.00)], compared with never/rare use (≤2 prescriptions). Associations according to duration of use and doses (quartiles of cumulative prednisolone equivalents) were also near the null. Examining colorectal cancer by stage, no substantial associations were found between long-term use (>5 years) of high-dose (>5500 mg) systemic glucocorticoids and localised [aOR = 1.12 (95% CI: 0.81-1.55)] or metastatic [aOR = 0.82 (95% CI: 0.59-1.14)] cancer. CONCLUSION: Despite immunological and metabolic effects of frequent use of systemic glucocorticoids, which would be expected to increase colorectal cancer risk, we found no substantial association between the two.

Quality of ICD-10 colorectal cancer diagnosis codes in the Danish National Registry of Patients.

This study examined the quality of International Classification of Diseases-10 colorectal cancer (CRC) diagnosis coding in the Danish National Registry of Patients (DNRP), using the Danish Cancer Registry (DCR) as a reference. We included all patients in Denmark with a CRC diagnosis in the DNRP and/or in the DCR from 2001 through 2006. Data quality was evaluated by estimating completeness and positive predictive value (PPV) of data in different subcategories of patients. We estimated mortality and date of diagnosis, to evaluate the effect of potential differences in data quality. Overall completeness of data in the DNRP for CRC was 93.4% [95% confidence interval (CI): 93.1-93.7] and the PPV was 88.9% (95% CI: 88.5-89.2). Completeness and PPV improved during the study period. However, the completeness of data for patients >75 years in the 2001-2003 period [88.8% (95% CI: 87.8-89.6)] was lower than average, and cancers in more unspecific locations and cancers in the colorectal junction also had lower estimates (below 90%). There were no differences in survival estimates in the DNRP compared to the DCR. In conclusion, this study shows high CRC data quality in the DNRP measured by completeness and PPV, except in a few subgroups.

Prenatal exposure to acid-suppressive drugs and the risk of childhood asthma: a population-based Danish cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) may activate the immune system and cause asthma. AIM: To investigate the association of prenatal exposure to PPIs and histamine 2-receptor antagonists (H2RAs) with risk of asthma. METHODS: In this cohort study, 197,060 singletons born between 1996 and 2008 in northern Denmark were followed until the end of 2009. Data were obtained through Danish medical registries. Asthma in offspring was defined as at least two prescriptions of both a ß-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during the follow-up. Cox proportional-hazard regression was used to compute incidence rate ratios, adjusting for covariates. RESULTS: A total of 2238 (1.1%) children were prenatally exposed to PPIs and 24,506 (12.4%) children developed asthma during follow-up (median follow-up = 6.8 years). The adjusted IRR (aIRR) of asthma associated with prenatal exposure to PPIs was 1.41 (95% confidence interval (CI): 1.27-1.56), compared with those unexposed. The association did not vary by trimester of exposure, and prenatal exposure to H2RAs was associated with similar increase in risk. The aIRR for maternal PPI and H2RA use in the year after, but not during pregnancy was 1.32 (95% CI: 1.20-1.46) and 1.13 (0.93-1.36), respectively, compared with non-use during and in the year after pregnancy. CONCLUSIONS: Prenatal exposure to both PPIs and H2RAs was associated with an increased risk of asthma in our study. Because the observed association is not drug specific and also observed for maternal postnatal use it may be explained by a 'class effect' or maternal underlying condition.

Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer patients: a nationwide cohort study.

BACKGROUND: There is conflicting evidence regarding bisphosphonates and atrial fibrillation (AF) risk in osteoporosis patients. However, bisphosphonates are used in much higher doses in treatment of bone metastasis and hypercalcemia, but little is known about the AF risk in cancer patients. METHODS: We conducted a nationwide population-based cohort study using Danish databases. All cancer patients exposed to intravenous bisphosphonates during 2000-2008 were matched with two non-exposed cancer patients by cancer type, distant metastasis presence at diagnosis, age, and gender. We used Cox proportional hazard regression to estimate hazards ratios (HRs) of AF/flutter adjusting for important confounding factors. RESULTS: Of the 3981 cancer patients exposed to intravenous bisphosponates, 128 (3.2%) developed AF/flutter. This condition occurred in 192 (2.4%) of the 7906 non-exposed cancer patients, corresponding to an adjusted HR of 1.7 (95% CI: 1.2-2.4). CONCLUSION: Intravenous bisphosphonates may increase AF/flutter risk in cancer patients.

Survival of invasive bladder cancer patients, 1998-2009; a central and northern Denmark population-based cohort study.

OBJECTIVE: Invasive bladder cancer (IBC) is a common urological malignancy accounting for 4%-5% of all cancers in Denmark. Our aim was to examine possible changes in short- and long-term survival of patients with IBC during 1998-2009. STUDY DESIGN AND SETTING: Data on all patients (N = 4032) with an incident diagnosis of IBC within a population of 1.8 million were retrieved from the Danish National Registry of Patients from 1998 to 2009. We computed survival after 1, 3, and 5 years, stratified by age and gender, and estimated mortality rate ratios (MRR) using Cox proportional hazard regression to compare mortality over time, controlling for age and gender. Data on tumor stage or histology were not included. RESULTS: During the study period, the annual numbers of incident IBC patients remained stable. The median age was 74 years in each of the four 3-year periods in the study. The survival was relatively stable during the first three periods, whilst data from the last period showed modest improvement. The overall 1-year survival increased from 68% in 1998-2000 to 70% in 2007-2009, corresponding to an age and gender adjusted MRR of 0.89 (95% confidence interval [CI] 0.76-1.03). The 3- and 5-year survival was predicted to increase from 44% to 49% and from 35% to 40% respectively. This corresponded to a 3-year age and gender adjusted MRR of 0.87 (95% CI 0.77-0.98) and a 5-year MRR of 0.88 (95% CI 0.79-0.99). The 1-, 3-, and 5-year survival increased for men in all age groups (<70 years, 70-79 years, ≥80 years) and in women only in the 70-79-year age group. CONCLUSION: The survival of IBC patients increased slightly in northern and central Denmark in the 1998-2009 period.

Phase transitions in the three-state Ising spin-glass model with finite connectivity.

The statistical mechanics of a two-state Ising spin-glass model with finite random connectivity, in which each site is connected to a finite number of other sites, is extended in this work within the replica technique to study the phase transitions in the three-state Ghatak-Sherrington (or random Blume-Capel) model of a spin glass with a crystal-field term. The replica symmetry ansatz for the order function is expressed in terms of a two-dimensional effective-field distribution, which is determined numerically by means of a population dynamics procedure. Phase diagrams are obtained exhibiting phase boundaries that have a reentrance with both a continuous and a genuine first-order transition with a discontinuity in the entropy. This may be seen as "inverse freezing," which has been studied extensively lately, as a process either with or without exchange of latent heat.