Swedish Patient Research Articles

Fecal incontinence in irritable bowel syndrome: Prevalence and associated factors in Swedish and American patients.

Fecal incontinence (FI) is a prevalent but poorly recognized problem in the general population with profound negative effects on daily life. The prevalence of FI in irritable bowel syndrome (IBS) and its association with clinical, demographic, and pathophysiological factors remain largely unknown. One US (n=304) and one Swedish (n=168) patient cohort fulfilling Rome III criteria for IBS completed Rome III diagnostic questions on FI and IBS symptoms, and questionnaires on IBS symptom severity, quality of life, anxiety and depression, and work productivity impairment. The patients also underwent assessments of colorectal sensitivity and motility. Fecal incontinence ≥ one day per month was reported by 19.7% (USA) and 13.7% (Sweden) of IBS patients. These proportions rose to 43.4% and 29.8% if patients with less frequent FI were included. Fecal incontinence prevalence was higher in older age groups, with a clear increase above age 40. Irritable bowel syndrome patients with FI reported greater overall IBS symptom severity, more frequent and loose stools, and greater urgency. Negative effects of FI on quality of life, psychological distress, and work productivity were demonstrated. No associations were found between colorectal physiology and FI. Fecal incontinence is common in IBS patients, and similar to previous general population reports, the major risk factors for FI in IBS are older age, rectal urgency, and loose, frequent stools. When IBS patients have comorbid FI, the impact on quality of life, psychological symptoms, and work impairment appears greater.

Injuries before and after diagnosis of cancer: nationwide register based study.

To examine the relative risks of iatrogenic and non-iatrogenic injuries during the period shortly before and after a diagnosis of cancer. Nationwide register based study. Swedish national population and health registers. 720 901 patients with diagnosis of cancer, 1991-2009, in Sweden. All hospital admissions in patients with cancer with a main discharge diagnosis of iatrogenic (from medical complications) or non-iatrogenic injuries in 1990-2010 identified from the Swedish patient register. Conditional Poisson regression was used to compare the incidence rate of injuries during the "diagnostic period" (16 weeks before to 16 weeks after diagnosis) with the incidence rate during a "pre-diagnostic period" (the same 32 weeks one year before diagnosis) among the same patients. During the diagnostic period, there were 7306 iatrogenic (incidence rate 0.60 per 1000 person months) and 8331 non-iatrogenic injuries (incidence rate 0.69 per 1000 person months). For iatrogenic injuries, the incidence rate ratio was 7.0 (95% confidence interval 6.6 to 7.4) during the diagnostic period compared with the pre-diagnostic period. The increase in risk started two weeks before cancer diagnosis and peaked during the two weeks after diagnosis (48.6, 37.3 to 63.5). For non-iatrogenic injuries, the incidence rate ratio was 1.9 (1.8 to 2.0) during the diagnostic period compared with the pre-diagnostic period. The increase in risk began four weeks before diagnosis and peaked during the two weeks before diagnosis (5.3, 4.6 to 6.1). There were increased risks of both types of injury during the diagnostic period for all common cancers, with the smallest risk increase noted for non-melanoma skin cancer. Patients with cancer have highly increased risks of both iatrogenic and non-iatrogenic injuries requiring inpatient care : shortly before and after their diagnosis. These findings shed further light on the total burden of medical complications and call for prevention of intentional and unintentional injuries during the diagnostic process of cancer.

Detecting hospital-acquired infections: A document classification approach using support vector machines and gradient tree boosting.

Hospital-acquired infections pose a significant risk to patient health, while their surveillance is an additional workload for hospital staff. Our overall aim is to build a surveillance system that reliably detects all patient records that potentially include hospital-acquired infections. This is to reduce the burden of having the hospital staff manually check patient records. This study focuses on the application of text classification using support vector machines and gradient tree boosting to the problem. Support vector machines and gradient tree boosting have never been applied to the problem of detecting hospital-acquired infections in Swedish patient records, and according to our experiments, they lead to encouraging results. The best result is yielded by gradient tree boosting, at 93.7 percent recall, 79.7 percent precision and 85.7 percent F1 score when using stemming. We can show that simple preprocessing techniques and parameter tuning can lead to high recall (which we aim for in screening patient records) with appropriate precision for this task.

Proportion and Characteristics of Patients in Sweden Remaining at High Risk of Fracture Despite Prior Treatment

PurposeFragility fractures are a clinical consequence of osteoporosis (OP). Evidence suggests however, current OP treatments may be inadequate in reducing fracture risk. The purpose of this study was to estimate the proportion and characteristics of Swedish patients who remain at high risk of fracture after 2 years of treatment, as evidenced by osteoporotic bone mineral density (BMD), a decrease in BMD, or the occurrence of new fractures. MethodsThis was a retrospective, descriptive analysis of a subset of participants obtained from a Swedish osteoporosis patient registry from 1991 to 2009. Patients were required to be osteoporotic, to be treatment naive at baseline, to have returned for at least 1 follow-up visit, and to have reported osteoporosis treatment use for ≥2 years after the baseline visit with a BMD T score. Two overlapping cohorts remaining at high risk of fracture were defined using the BMD T score measured after 2 years of treatment from baseline. The osteoporosis cohort comprised patients who remained osteoporotic, whereas the BMD decrease cohort included patients whose total hip or lumbar spine T score decreased by ≥3%. FindingsA total of 3292 osteoporotic patients were identified in the registry, of whom 392 met the study inclusion criteria. The mean (SD) patient age was 68.3 (8.5) years, with most patients being female (92.3%). Among all patients, 297 (75.8%) remained osteoporotic after at least 2 years of treatment, 90 (23.0%) experienced a BMD decrease of ≥3%, and 23 (5.9%) reported an incident fracture between the baseline and first follow-up visit. More than three-quarters (76.8%) of all patients reported taking bisphosphonates, whereas only 72.4% and 47.8% reported this in the osteoporosis and BMD decrease cohorts, respectively. Raloxifene was the only nonbisphosphonate used, with 24.2% of all patients reportedly taking it. ImplicationsThis study highlighted that despite 2 years of osteoporosis treatment, a high percentage of patients remain at high risk of fracture. There is a need for improved treatment strategies that reduce fracture risk and improve patient outcomes in the real-world setting.

The Incidence of Senile Cataract and Glaucoma is Increased in Patients with Plasma Cell Dyscrasias: Etiologic Implications.

Plasma cell dyscrasias, including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), Waldenström macroglobulinemia (WM) and light chain AL amyloidosis, are characterized by clonal expansion of plasma cells which produce a vast amount of an immunoglobulin-derived M-protein. We noted that MGUS diagnosis often coincided with diagnoses of senile cataract and glaucoma and tested the associations of MGUS, MM, WM and AL amyloidosis with subsequent eye diseases identified from the Swedish patient registers between 1997 and 2012. Standardized incidence ratios (SIRs) for senile cataract was significantly increased to 1.80 after MGUS, 1.70 after MM, 1.85 after WM and 2.31 after AL amyloidosis. The SIR for glaucoma was 1.60 after MGUS, 1.76 after WM and 2.18 after AL amyloidosis. All SIRs decreased systematically from age below 60 years to over 79 years, but most risks were also significant in age group over 79 years. The M-protein and the related increase in blood viscosity could be a novel etiologic discovery for these common eye diseases. As MGUS prevalence is around 3% at 60 years and close to 10% at age over 80 years, its contribution to the eye disease burden is expected to be remarkably high.

Treatment-seeking patients with binge-eating disorder in the Swedish national registers: clinical course and psychiatric comorbidity.

BackgroundWe linked extensive longitudinal data from the Swedish national eating disorders quality registers and patient registers to explore clinical characteristics at diagnosis, diagnostic flux, psychiatric comorbidity, and suicide attempts in 850 individuals diagnosed with binge-eating disorder (BED).MethodCases were all individuals who met criteria for BED in the quality registers (N = 850). We identified 10 controls for each identified case from the Multi-Generation Register matched on sex, and year, month, and county of birth. We evaluated characteristics of individuals with BED at evaluation and explored diagnostic flux across eating disorders presentations between evaluation and one-year follow-up. We applied conditional logistic regression models to assess the association of BED with each comorbid psychiatric disorder and with suicide attempts and explored whether risk for depression and suicide were differentially elevated in individuals with BED with or without comorbid obesity.ResultsBED shows considerable diagnostic flux with other eating disorders over time, carries high psychiatric comorbidity burden with other eating disorders (OR 85.8; 95 % CI: 61.6, 119.4), major depressive disorder (OR 7.6; 95 % CI: 6.2, 9.3), bipolar disorder (OR 7.5; 95 % CI: 4.8, 11.9), anxiety disorders (OR 5.2; 95 % CI: 4.2, 6.4), and post-traumatic stress disorder (OR 4.3; 95 % CI: 3.2, 5.7) and is associated with elevated risk for suicide attempts (OR 1.8; 95 % CI: 1.2, 2.7). Depression and suicide attempt risk were elevated in individuals with BED with and without comorbid obesity.ConclusionsConsiderable flux occurs across BED and other eating disorder diagnoses. The high psychiatric comorbidity and suicide risk underscore the severity and clinical complexity of BED.

Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a previous Sjögren’s syndrome diagnosis

Background: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren’s syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4-RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma.Methods: Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964–2007 and the Cancer Register 1990–2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD.Results: Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B-cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies.Conclusion: Histopathological findings of IgG4-RD may co-exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD.

567. CRISPR-Cas9 Mediated Gene Editing in a Monogenic Form of Alzheimer's Disease

BackgroundIndividuals heterozygous for the Swedish mutation of the amyloid precursor protein (APPswe) display an increased β-secretase cleavage leading to higher Aβ levels - both in brain and peripheral tissues, such as fibroblasts and plasma. The mutation is a double base change adjacent to each other and has a dominant effect. We hypothesize that the CRISPR system would selectively disrupt the mutated allele without affecting the wild-type allele. Therefore we set out to use the CRISPR system to disrupt expression of mutant APP to counteract Aβ overproduction in Swedish patient fibroblasts.MethodsHuman APPswe fibroblasts and non-mutated control fibroblasts from subjects of the same family (n=3 for both mutated and control cell lines) were cultured in DMEM medium with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Approximately one million cells were used for transfection with the SpCas9 plasmid together with different guide RNAs (gRNAs) designed to bind either the mutated or non-mutated site with the mutation in the gRNA recognition sequence. Four days after transfection, the GFP positive cells were sorted by FACS, enabling separation of Cas9-transfected from non-transfected cells. DNA was extracted from one fraction of the sorted cells, followed by Sanger sequencing and targeted deep sequencing. Another fraction of the cells was further cultured until they were confluent, after which they were kept for 48 h in FBS free media. ELISAs specific for Aβ40 and Aβ42 were used to measure peptide levels in conditioned media from the various cell populations.ResultsSanger sequencing was performed on cells that had been successfully transfected with CRISPR plasmids. On such cells, both the APPswe mutant and wt alleles could be disrupted with gRNAs designed against the mutated and non-mutated sites, respectively. Moreover, these effects appeared to be highly specific as assayed by deep sequencing as we did not find any random mutations on the wt allele with the gRNA targeting the mutated site or vice versa. Most of the genomic changes were deletions, but there were some insertions as well. ELISA measurements indicated robustly decreased levels of both Aβ40 and Aβ42 in conditioned media from both mutated and wt cells treated with the respective gRNAs. Shortening the gRNA led to decreased on-target effectivity.ConclusionsWith the CRISPR/Cas 9 system we could selectively disrupt both the mutated and wt site in fibroblasts from subjects with and without the APPswe mutation. The adjacent double base change created a unique opportunity to selectively disrupt the mutant allele with one of our gRNAs. Furthermore, we could demonstrate a decreased generation of Aβ40 and Aβ42 in the conditioned media from cells treated with the specific gRNAs. This study provides the first experimental evidence that the CRISPR/Cas9 method could be used to develop a novel treatment strategy against familial forms of Alzheimer's disease caused by dominant mutations.

A Case-Control Study of Risk Markers and Mortality in Takotsubo Stress Cardiomyopathy

BackgroundTakotsubo stress cardiomyopathy (TSC) is a syndrome characterized by transient myocardial dysfunction with unknown etiology. Although recent studies have suggested that the syndrome is associated with comorbidity and has a dismal prognosis, there is a lack of comprehensive data describing the epidemiology and prognosis of TSC. ObjectivesThis study compared risk markers and mortality in patients with TSC with that of individuals with or without coronary artery disease (CAD). MethodsPatients with TSC and control subjects were identified from the Swedish Coronary Angiography and Angioplasty Register between 2009 and 2013 and linked with the Swedish national patient registry, cause of death registry, prescription drug registry, and education and income registries. ResultsPatients with TSC were characterized by a low cardiovascular risk factor profile but with increased chronic obstructive pulmonary disease, migraine, and affective disorders. The use of beta-blockers was less common but use of β2-adrenergic agonist agents was more common in patients with TSC compared with either of the control groups. Being a patient with TSC was associated with a hazard ratio of 2.1 for death compared with the control subjects without CAD (95% confidence interval: 1.4 to 3.2). This was similar to the excess mortality risk seen among the CAD control subjects compared with control subjects without CAD (hazard ratio: 2.5; 95% confidence interval: 1.8 to 3.3). These associations remained significant after adjusting for CAD risk factors and risk markers for TSC. ConclusionsThe findings of increased risk associated with β2-adrenergic agonist agents together with stress related to affective disorders emphasize the pathogenic role of sympathetic stimulation. The prognosis regarding mortality is worse than in control subjects without CAD and similar to patients with CAD emphasizing the urgent need for studies on optimal treatment of TSC.

Serious adverse events within 30days of groin hernia surgery.

To analyze severe complications after groin hernia repair with respect to age, ASA score, hernia anatomy, method of repair and method of anesthesia, using nationwide registers. The annual rate of 20 million groin hernia operations throughout the world renders severe complications, although rare, important both for the patient, the clinician, and the health economist. Two nationwide registers, the Swedish Hernia Register and the National Swedish Patient Register were linked to find intraoperative complications, severe cardiovascular events and severe surgical adverse events within 30days of groin hernia surgery. 143,042 patients, 8% women and 92% men, were registered between 2002 and 2011. Intraoperative complications occurred in 801 repair, 592 patients suffered from cardiovascular events and 284 patients from a severe surgical event within 30days of groin hernia surgery. Emergency operation was a risk factor for both cardiovascular and severe surgical adverse events with odds ratios for cardiovascular events of 3.1 (2.5-4.0) for men and 2.8 (1.4-5.5) for women. Regional anesthesia was associated with an increase in cardiovascular morbidity compared with local anesthesia, odds ratio 1.4 (1.1-1.9). In men, bilateral hernia and sliding hernia approximately doubled the risk for severe surgical events; odds ratio 1.9 (1.1-3.5) and 2.2 (1.6-3.0), respectively. Methods other than open anterior mesh repair increased the risk for surgical complications. Awareness of the increased risk for cardiovascular or surgical complications associated with emergency surgery, bilateral hernia, sliding hernia, and regional anesthesia may enable the surgeon to further reduce their incidence.

Validation of the Swedish translation of eating assessment tool (S-EAT-10)

ABSTRACTConclusion The Swedish Eating Assessment Tool (S-EAT-10) is a reliable and valid self-administered tool in assessment of dysphagia in adult Swedish patients with high internal consistency, reliability, and discriminative validity. The normative data show that a score of 3 or more is abnormal. S-EAT-10 is recommended to be used in preliminary diagnostics of dysphagia. Objective To translate and adapt the EAT-10 for use in the Swedish patient population, and to present norms and measures of discriminative validity and reliability of a Swedish version of the Eating Assessment Tool-10 (S-EAT-10). Methods Prospective consecutive clinical study. In total, 134 community-dwelling adult respondents/controls without dysphagia completed the S-EAT-10, as did 119 patients referred for fiberendoscopic evaluation of swallowing at Karolinska University Hospital, Stockholm, Sweden. Patient vs control status was used as the criterion for discriminative validity assessment by logistic regression analysis. Results The mean S-EAT-10 score was 0.2 (range = 0–3) for controls and 18 (range = 0–38) for patients. Based on a cut-off score of ≥ 3 which was considered to be reflective of abnormalities, sensitivity was 98.5% and specificity 94.1%. Internal consistency reliability was high (Cronbach’s alpha = 0.88), as was test–re-test reliability (ICC = 0.90).

Ischemic Stroke in Children and Young Adults With Congenital Heart Disease.

BackgroundPatients with congenital heart disease (CHD) may be at increased risk of ischemic stroke due to residual shunts, arrhythmias, and other cardiovascular abnormalities. We studied the relative risk and potential factors for developing ischemic stroke in children and young adults with CHD in Sweden.Methods and ResultsAll patients in the Swedish Patient Register with a diagnosis of CHD, born between 1970 and 1993, were identified and compared with 10 controls for each patient, matched for age, sex, and county and randomly selected from the general population. Follow‐up data through 2011 were collected for both groups. Of 25 985 children and young adults with CHD (51.5% male, 48.5% female), 140 (0.5%) developed ischemic stroke. The hazard ratio for CHD patients developing ischemic stroke was 10.8 (95% CI, 8.5–13.6) versus controls. All major Marelli groups had significantly increased risk, but because of small CHD‐group sizes, only atrial septal defect/patent foramen ovale, double‐inlet ventricle, and aortic coarctation displayed significantly increased risk. In multivariate analysis of CHD patients, congestive heart failure carried the highest risk for developing ischemic stroke (hazard ratio 6.9 [95% CI, 4.7–10.3]), followed by hypertension and atrial fibrillation, which were also significantly associated with increased risk of ischemic stroke.ConclusionsThe risk of developing ischemic stroke was almost 11 times higher in young patients with CHD than in the general population, although absolute risk is low. Cardiovascular comorbidities were strongly associated with the development of ischemic stroke in young CHD patients.

Soluble urokinase plasminogen activator receptor and incidence of venous thromboembolism.

Raised plasma levels of the soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased incidence of cardiovascular diseases. Whether suPAR is associated with venous thromboembolism (VTE) is largely unknown. The purpose of the present study was to investigate the relationship between suPAR and incidence of VTE in a cohort study. suPAR was measured in 5,203 subjects (aged 46-68 years, 58 % women) from the general population, who participated in the Malmö Diet and Cancer (MDC) study between 1991 and 1994. Incident cases of VTE were identified from the Swedish patient register during a mean follow-up of 15.7 years. Of 5,203 subjects with measurements of suPAR, 239 had VTE during follow-up (127 venous thrombosis, 86 lung embolism, 26 both). Incidence of VTE was significantly higher in subjects with suPAR levels in the top quartile. Adjusted for age and sex, the HR (4th vs 1st quartile) was 1.74 (95 %CI: 1.2-2.6, p for trend=0.003). After adjustments for risk factors, the HR was 1.66 (95 %CI: 1.1-2.5, p for trend=0.016). High level of suPAR was a risk indicator for incidence of VTE in this population-based cohort study. The causal relationships between suPAR and VTE remain to be explored.

Early death among head and neck cancer patients.

Management of advanced head and neck cancer (HNC) is characterized by high mortality. Furthermore, the treatment involves significant burden to patients and high costs to healthcare systems. Recognizing the risks of early death in patients with a high probability of noncurable disease is important for each individual treatment decision-making. It is thus critical to consider the benefits and side-effects of the planned treatment in relation to the expected survival and to discuss these factors with the patient. However, only few studies have documented early death in HNC patients, that is, during the first posttreatment 6 months. We performed a systematic literature review to find the incidence of this phenomenon and to outline the probable cause. Early mortality in patients with HNC can be explained either by direct effect of malignant disease, may be related to comorbidities, or secondary to the treatment. These factors act together resulting in expected or unexpected early death. The present review provides information on the mechanisms leading to early phase mortality (<6 months) after management of HNC. It also reports the incidence of this phenomenon among Finnish and Swedish patient populations.

Surgical Stabilization Improves Survival of Spinal Fractures Related to Ankylosing Spondylitis.

Study Design.National registry cohort study.Objective.The aim of this study was to investigate the effect of surgical stabilization on survival of spinal fractures related to ankylosing spondylitis (AS).Summary of Background Data.Spinal fractures related to AS are associated with considerable morbidity and mortality. Multiple studies suggest a beneficial effect of surgical stabilization in these patients.Methods.In the Swedish patient registry, all patients treated in an inpatient facility are registered with diagnosis and treatment codes. The Swedish mortality registry collects date and cause of death for all fatalities. Registry extracts of all patients with AS and spinal fractures including date of death and treatment were prepared and analyzed for epidemiological purposes.Results.Seventeen thousand two hundred ninety-seven individual patients with AS were admitted to treatment facilities in Sweden between 1987 and 2011. Nine hundred ninety patients with AS (age 66 ± 14 years) had 1131 spinal fractures, of which 534 affected cervical, 352 thoracic, and 245 lumbar vertebrae. Thirteen percent had multiple levels of injuries during the observed period. Surgically treated patients had a greater survival than those treated nonsurgically [hazard ratio (HR) 0.79, P = 0.029]. Spinal cord injury was the major factor contributing to mortality in this cohort (HR 1.55, P < 0.001). The proportion of surgically treated spinal fractures increased linearly during the last decades (r = 0.92, P < 0.001) and was 64% throughout the observed years.Conclusions.Spinal cord injury threatened the survival of patients with spinal fractures related to AS. Even though surgical treatment is associated with a considerable complication rate, it improved the survival of spinal fractures related to AS.Level of Evidence: 3

Cost-effectiveness of tiotropium versus usual care and glycopyrronium in the treatment of chronic obstructive pulmonary disease in Sweden.

BackgroundTiotropium (TIO) is a well-established bronchodilator, LAMA (long-acting anticholinergic), for the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). Clinical evidence suggests that tiotropium is superior to usual non-LAMA care (UC) but may also have benefits compared to other LAMAs in preventing and limiting the effects of severe exacerbations. The primary objective of this study was to undertake a cost-effectiveness analysis of adding tiotropium to usual care versus usual care alone. A secondary objective was to assess the cost-effectiveness of tiotropium compared to glycopyrronium (GLY), another LAMA. The study was conducted with a Swedish setting in mind.MethodsA Markov cohort model, incorporating the effects of exacerbations, was populated with efficacy data from the UPLIFT and SPARK trials and epidemiological data relevant for a Swedish patient population. Treatment efficacy of tiotropium was modelled as a lowering of the risk of exacerbations and as a slow-down of overall disease progression. The model followed patients over their remaining life-time.ResultsThe base case analysis showed that patients treated with tiotropium gained 0.07 quality-adjusted life years (QALYs) compared to usual care alone at an incremental cost of SEK 15,041, resulting in a cost per QALY gained of SEK 224,850. Compared to glycopyrronium the QALY gained was estimated to 0.23 QALYs in favour of tiotropium at an incremental cost of SEK 2423, yielding a cost per QALY gained of SEK 10,456. The results were mainly driven by differences in the risk of severe exacerbations.ConclusionAt the current implicit willingness-to-pay (WTP) per QALY threshold in Sweden, the results from this study indicate that tiotropium is a highly cost-effective intervention when added to usual non-LAMA care in the treatment of moderate to very severe COPD in Sweden. In addition, tiotropium is a highly cost-effective intervention when compared to glycopyrronium monotherapy.

Lower CYP2C9 activity in Turkish patients with Behçet's disease compared to healthy subjects: a down-regulation due to inflammation?

We previously reported on a Swedish patient with Behçet's disease (BD) who was an ultra-rapid metaboliser of drugs catalysed by CYP2C9. Was this extreme metabolism caused by the disease? This study aims to compare the genotype/phenotype of CYP2C9 in patients with BD and healthy subjects. As the occurrence of BD is high in Turkey, all subjects were recruited from this country. Genotyping of CYP2C9 was performed using standard PCR-RFLP and allele-specific PCR methods. Phenotyping of CYP2C9 was performed by administration of a 50-mg single oral dose of losartan and by calculating the urinary metabolic ratio (MR) of probe drug to its metabolite E-3174. Quantitation was performed by HPLC. The frequency of CYP2C9*2 and *3 was not significantly different between the Behçet's disease patients (12.5 and 8.7%) and the healthy subjects (8.9 and 8.2%). The geometric mean losartan MR was higher in the 52 patients (1.75) than in the 96 healthy subjects (1.02) (p = 0.002; t-test). Within the genotypes *1/*1, there was a significant difference of MR between patients and healthy subjects (P = 0.006). All but three of the Behçet's disease patients were treated with colchicine. In nine subsequent patients, we found no significant effect of 2 weeks of treatment with colchicine on the CYP2C9 MR. Contrary to expectation, the CYP2C9 activity was lower in Turkish BD patients compared to healthy subjects. As this seems not to be due to colchicine treatment, our hypothesis is that inflammation related to BD might have caused the down-regulation of the CYP2C9 activity due to immune cytokine reactions. The ultra-rapid metabolism of CYP2C9 substrate drugs in the Swedish patient was not due to her BD.

Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients: A Swedish National Population-Based Cohort Study.

Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, or nonselective NSAIDs or totally unexposed to NSAIDs. We performed a national register-based cohort study on patients with AS or SpA (n = 21,872) identified in the Swedish national patient register from 1987-2009. Treatment exposure was assessed time dependently based on the prescription drug register from 2006-2009, adjusting for sociodemographics and comorbidities derived from national population-based registers. Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively. No major risk differences for serious cardiovascular, gastrointestinal, or renal adverse events were seen among the 3 exposure groups. Patients unexposed to NSAIDs had more baseline comorbidities and an increased relative risk for congestive heart failure events during the study period (2.0, 95% confidence interval [95% CI] 1.3-3.2). The relative risk for atherosclerotic events was nonsignificant when compared to the nonselective NSAID group (1.0, 95% CI 0.7-1.5), while the relative risk for gastrointestinal events was lower for unexposed patients (0.5, 95% CI 0.4-0.7). Overall, serious adverse events related to nonselective NSAIDs, etoricoxib, and celecoxib were similar and in the range of what would be expected in a group of SpA patients. Patients unexposed to NSAIDs had considerably more baseline comorbidities and increased risk for congestive heart failure, reflecting a selection of patients being prescribed NSAIDs in clinical practice.

Psychiatric disorders and suicide attempts in Swedish survivors of the 2004 southeast Asia tsunami: a 5 year matched cohort study

Survivors of natural disasters are thought to be at an increased risk of psychiatric disorders, however the extent of this risk, and whether it is linked to pre-existing psychopathology, is not known. We aimed to establish whether Swedish survivors of tsunamis from the 2004 Sumatra-Andaman earthquake had increased risks of psychiatric disorders and suicide attempts 5 years after repatriation. We identified Swedish survivors repatriated from southeast Asia (8762 adults and 3742 children) and 864 088 unexposed adults and 320 828 unexposed children matched for sex, age, and socioeconomic status. We retrieved psychiatric diagnoses and suicide attempts from the Swedish patient register for the 5 years after the tsunami (from Dec 26, 2004, to Jan 31, 2010) and estimated hazard ratios (HRs), then adjusted for pre-tsunami psychiatric disorders, and, for children, for parental pre-tsunami disorders. Exposed adults were more likely than unexposed adults to receive any psychiatric diagnosis (547 [6·2%] vs 47 734 [5·5%]; adjusted HR 1·21, 95% CI 1·11-1·32), particularly stress-related disorders (187 [2·1%] vs 8831 [1·0%]; 2·27, 1·96-2·62) and suicide attempts (38 [0·43%] vs 2752 [0·32%]; 1·54, 1·11-2·13), but not mood or anxiety disorders. Risk of psychiatric diagnoses did not differ between exposed and unexposed children and adolescents (248 [6·6] vs 22 081 [6·9%]; 0·98, 0·86-1·11), although exposed children and adolescents had a higher risk for suicide attempts with uncertain intent (1·43; 1·01-2·02) and stress-related disorders (1·79; 1·30-2·46), mainly during the first 3 months after the tsunami. The 2004 tsunami was, independently of previous psychiatric morbidity, associated with an increased risk of severe psychopathology, mainly stress-related disorders and suicide attempts, in children and adults. Survivors of natural disasters should be targeted with early interventions and active long-term follow-up to prevent, detect, and alleviate psychiatric disorders that might follow. The Swedish Council for Working Life and Social Research, Swedish Board of Health and Welfare, Polish Ministry of Science and Higher Education, Swedish Society for Medical Research.

Wound Healing Following Open Groin Hernia Surgery: The Impact of Comorbidity.

The aim of this study was to explore the impact of chronic concomitant disease on the risk for postoperative complications following open groin hernia surgery. During the study period (2002-2011), 133,074 open repairs were registered in the Swedish Hernia Register. History of peripheral vascular disorders, connective tissue disease, chronic renal failure, obesity, and liver cirrhosis as well as data on hemorrhage or hematoma, wound dehiscence, postoperative infection, and reoperation for superficial infection or bleeding within 30 days after surgery were obtained by matching with the Swedish Patient Register. In the multivariate logistic regression analysis, a significantly increased risk for hemorrhage or hematoma within 30 days after surgery was seen for older patients, males, liver cirrhosis, peripheral vascular disease, and connective tissue disease (p < 0.05). High age (>80 years), previous history of peripheral vascular disease, connective tissue disease, and male gender were risk factors for wound dehiscence (p < 0.05). Liver cirrhosis, chronic kidney disease, BMI > 25, and male gender were associated with increased risk for postoperative wound infection (p < 0.05). A significantly increased risk for reoperation for superficial infection or bleeding was seen in patients with peripheral vascular disease and elderly patients (p < 0.05). Risk for postoperative complications in open groin hernia surgery is increased in elderly patients, patients with liver cirrhosis, and those with peripheral vascular disease. The indications for surgery should be weighed against the risk for wound-healing complications in these patient groups. Watchful waiting may be an alternative, although this carries the risk of emergency surgery.