The changing epidemiology of community-acquired pneumonia: nationwide register-based study in Sweden.

BACKGROUND: There is limited evidence on the impact of pneumococcal conjugate vaccine childhood immunization programmes (PCV-CIP) on community-acquired pneumonia (CAP) in individuals with underlying diseases. METHODS: A nationwide cohort study using Swedish health registers to assess the incidence of hospitalization with all-cause (AC-CAP) and pneumococcal or lobar (PL-CAP) CAP between 2005 and 2015, in relation to PCV-CIP introduction in 2007-09. RESULTS: In total, 303 691 episodes of AC-CAP occurred, of which 14 225 were PL-CAP. Comparing before (2005-06) with after (2014-15) PCV-CIP, relative incidence reductions were 36% (95% Confidence Interval 32-40), 20% (14-25) and 16% (11-22) of AC-CAP for age groups < 2, 2-4 and 5-17 years, respectively, with similar reductions in young children with and without comorbidities. The reductions were more pronounced for PL-CAP. In the age groups 40-64, 65-74, 75-84 and ≥85 years there were relative increases of 11% (8-14), 18% (15-22), 15% (12-17) and 30% (27-34) of AC-CAP, respectively, but these increases were attenuated after adjustment for admittance practices using four control conditions. In adults with comorbidities, there was an increase in incidence of AC-CAP, and PL-CAP, in contrast to adults without reported underlying diseases where the incidence was stable or diminished for some age groups. Over the study period, there was an increased proportion of pneumonia patients with underlying diseases in all ages. CONCLUSION: This emphasizes that direct preventive interventions should be targeted towards individuals with underlying diseases. Future studies should investigate reasons for the observed increased risk in adults with comorbidities, for example due to pneumococcal nonvaccine serotypes, or other pathogens, preferentially affecting subjects with underlying diseases.

Maternal and infant pregnancy outcomes in women with psoriatic arthritis: a Swedish nationwide cohort study.

OBJECTIVE: Studies on pregnancy outcomes in psoriatic arthritis (PsA) are scarce and typically of small size. Available studies have reported conflicting results. The aim of this study was to describe maternal and infant pregnancy outcomes among women with PsA compared with women without PsA. DESIGN: Nationwide cohort study. SETTING: Nationwide Swedish registers. POPULATION: A total of 41 485 singleton pregnancies in 1997-2014, of which 541 pregnancies were identified with PsA exposure and 40 944 pregnancies were unexposed. METHODS: By linkage of national health and population register data, we obtained information on individual pregnancies and compared outcomes among pregnancies with PsA and non-PsA pregnancies. Relative risks were estimated by odds ratios (ORs) with 95% CIs using a generalised linear regression model with generalised estimating equations. Adjustments were made for maternal factors and calendar year of birth. MAIN OUTCOME MEASURES: Maternal and infant pregnancy outcomes. RESULTS: Pregnancies to women with PsA had increased risks of preterm birth (adjusted OR 1.63; 95% CI 1.17-2.28), elective and emergency caesarean deliveries (adjusted OR 1.47; 95% CI 1.10-1.97 and adjusted OR 1.43; 95% CI 1.08-1.88, respectively) compared with non-PsA pregnancies. No increased risks were observed for pre-eclampsia, stillbirth or other infant outcomes apart from preterm birth. CONCLUSION: The majority of women with PsA have uneventful pregnancies with respect to adverse outcomes. In the present study, we found increased risks of preterm birth and caesarean delivery compared with non-PsA pregnancies. TWEETABLE ABSTRACT: Women with psoriatic arthritis have uneventful pregnancies but are at increased risk of preterm birth and caesarean delivery.

Complete mesocolic excision in right-sided colon cancer does not increase severe short-term postoperative adverse events.

AIM: The aim was to assess whether complete mesocolic excision (CME) in patients with right-sided colon cancer is related to short-term mortality or postoperative adverse events requiring reoperation. The complete mobilization of an integral mesocolon and central ligation of blood vessels are essential steps in CME surgery. The resultant specimen, with an intact mesocolic fascia and a high number of harvested lymph nodes, is believed to be oncologically favourable. However, it has been suggested that CME surgery may increase the risk of intra-operative severe adverse events, due to exposure of vital retroperitoneal organs and large blood vessels. METHOD: In a population-based, nested case-control study, all residents in the Stockholm County operated for right-sided colon cancer from 2004 until 2012 were identified from the Swedish Colorectal Cancer Registry. Patients who died within 90 days after surgery or were reoperated within 30 days after surgery, or during the index hospital stay, were defined as cases. Two controls per case were randomly sampled and individually matched for age, sex, TNM stage and emergency vs elective surgery. Exposure status (CME surgery) was assessed from original surgical reports. RESULTS: The estimated proportion of CME surgery was 14.8% (35 of 236) for cases and 19.5% (92 of 473) for controls. The unadjusted OR for short-term mortality or reoperation after CME surgery was 0.72 (95% CI: 0.47-1.10; P = 0.15). The ORs were lower in the late part of the study (0.51; 95% CI: 0.26-1.01) and in high volume hospitals (0.61, 95% CI: 0.35-1.06). CONCLUSIONS: The present study does not indicate that CME surgery is associated with an increased risk of severe adverse events such as 90-day mortality or reoperation.

Risk of second primary cancer in patients treated with radiotherapy for rectal cancer.

BACKGROUND: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR). METHODS: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not. RESULTS: A total of 13 457 patients were included in this study; 7024 (52·2 per cent) received RT and 6433 (47·8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1·03; 95 per cent c.i. 0·92 to 1·15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1·33, 1·01 to 1·74) but not within (HR 1·11, 0·73 to 1·67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 0·68, 0·51 to 0·91). CONCLUSION: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.

Editor's Choice - Dual Antiplatelet Therapy Improves Outcome in Diabetic Patients Undergoing Endovascular Femoropopliteal Stenting for Critical Limb Ischaemia.

OBJECTIVE: The purpose of this study was to analyse the effect of dual antiplatelet therapy (DAPT) compared to aspirin on outcome after endovascular interventions in patients with CLI. METHODS: This was a population based retrospective nationwide cohort analysis. Several linked national databases in Sweden: Swedish National Vascular Registry, Prescribed Drug Registry and National Discharge Registry. A total of 1941 patients (median age 79; range 43-103 years; women 58%) were identified with CLI who had undergone primary femoropopliteal endovascular intervention between 2006 and 2012. Of these, 599 (31%) patients were treated after the intervention with DAPT (aspirin and clopidogrel) and 1342 (69%) patients were treated with aspirin only. Percutaneous transluminal angioplasty (PTA) was performed in 1131 patients (58%), stenting in 633 patients (33%), and subintimal angioplasty (SAP) in 177 patients (9%). RESULTS: DAPT was given after PTA, stenting, and SAP to 17% (n = 188), 53% (n = 334), and 44% (n = 77) of the patients, respectively. During the study period, 77 patients (13%) with DAPT and 228 patients (17%) with aspirin underwent a major amputation. Patients receiving DAPT after stenting had a lower rate of amputation (HR 0.56; 95% CI 0.36-0.86) than patients receiving aspirin alone. In the subgroup analysis, the protective effect of DAPT on amputation seemed to be confined to patients with diabetes mellitus receiving a stent (HR 0.26; 95% CI 0.13-0.52; p < .001). DAPT after PTA or SAP did not influence limb salvage, and there was no overall difference in mortality. There was no significant difference in bleeding complications between DAPT and aspirin. CONCLUSION: DAPT with aspirin and clopidogrel compared to aspirin alone was associated with a lower amputation rate but not a higher bleeding rate in patients with diabetes and CLI after endovascular femoropopliteal stenting.

A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up.

OBJECTIVES: To investigate the association between vaccination with Pandemrix and risk of selected neurological and immune-related diseases including narcolepsy. DESIGN: Population-based prospective cohort study using data from regional vaccination registries and national health registries. SETTING: Seven healthcare regions in Sweden comprising 61% of the Swedish population. SUBJECTS: Study population of 3,347,467 vaccinated and 2,497,572 nonvaccinated individuals (vaccination coverage ≈ 60%) followed between 2009 and 2011 for 6.9 million person-years after exposure and 6.0 million person-years without exposure. MAIN OUTCOME MEASURE AND ANALYSIS: First recorded diagnosis of neurological and immune-related diseases. Relative risks [hazard ratios (HRs) with 95% confidence intervals (CIs)] assessed using Cox regression, adjusted for covariates. RESULTS: For all selected neurological and immune-related outcomes under study, other than allergic vaccine reactions (for which we verified an expected increase in risk) and narcolepsy, HRs were close to 1.0 and always below 1.3. We observed a three-fold increased risk of a diagnosis of narcolepsy (HR: 2.92, 95% CI: 1.78-4.79; that is, four additional cases per 100,000 person-years) in individuals ≤ 20 years of age at vaccination and a two-fold increase (HR: 2.18, 95% CI: 1.00-4.75) amongst young adults between 21 and 30 years of age. The excess risk declined successively with increasing age at vaccination; no increase in risk was seen after 40 years of age. CONCLUSIONS: For a large number of selected neurological and immune-related diseases, we could neither confirm any causal association with Pandemrix nor refute entirely a small excess risk. We confirmed an increased risk for a diagnosis of narcolepsy in individuals ≤ 20 years of age and observed a trend towards an increased risk also amongst young adults between 21 and 30 years.

Local recurrence after prone vs supine abdominoperineal excision for low rectal cancer.

AIM: Tumour-involved circumferential resection margins (CRMs) and intra-operative perforation (IOP) are well known risk factors for local recurrence after surgery for low rectal cancer. In conventional abdominoperineal excision (APE) the patient remains in the supine position for the perineal part of the procedure. However, turning the patient to the prone position may improve visualization which potentially might reduce the risk of involved CRMs and IOP and thus improve local control. The study was carried out to assess local recurrence rates after APE in relation to the positioning of the patient during the perineal part of the procedure. METHOD: This cohort study includes 466 patients having APE for low rectal cancer between 2001 and December 2010. Data were retrieved from the regional rectal cancer registry in Stockholm and from a retrospective review of patient files. RESULTS: An incomplete resection was reported in 12.4% after APE in the supine position and in 6.8% after APE in the prone position (P = 0.038). Corresponding figures for IOP were 12.4% and 4.0% (P < 0.001). Prone APE was associated with a 39% relative reduction in local recurrence events compared with APE in the supine position, although the difference was not statistically significant (hazard ratio 0.61, 95% CI 0.27-1.37). CONCLUSION: APE in the prone position reduced the incidence of incomplete resection and IOP, but the study did not find a statistically significant difference in local failure rates related to the position of the patient.

Evaluation of prevalent and incident ovarian cancer co-morbidity.

BACKGROUND: The peak in incidence of ovarian cancer occurs around 65 years and concurrent increasing risk by age for a number of diseases strongly influence treatment and prognosis. The aim was to explore prevalence and incidence of co-morbidity in ovarian cancer patients compared with the general population. METHODS: The study population was patients with ovarian cancer in Sweden 1993-2006 (n=11 139) and five controls per case (n=55 687). Co-morbidity from 1987 to 2006 was obtained from the Swedish Patient Register. Prevalent data were analysed with logistic regression and incident data with Cox proportional hazards models. RESULTS: Women developing ovarian cancer did not have higher overall morbidity than other women earlier than 3 months preceding cancer diagnosis. However, at time of diagnosis 11 of 13 prevalent diagnosis groups were more common among ovarian cancer patients compared with controls. The incidence of many common diagnoses was increased several years following the ovarian cancer and the most common diagnoses during the follow-up period were thromboembolism, haematologic and gastrointestinal complications. CONCLUSION: Women developing ovarian cancer do not have higher overall morbidity the years preceding cancer diagnosis. The incidence of many common diagnoses was increased several years following the ovarian cancer. It is crucial to consider time between co-morbidity and cancer diagnosis to understand and interpret associations.

High birth weight and obesity--a vicious circle across generations.

OBJECTIVES: Rates of high birth weight infants, overweight and obese children and adults are increasing. The associations between birth weight and adult weight may have consequences for the obesity epidemic across generations. We examined the association between mothers' birth weight for gestational age and adult body mass index (BMI) and these factors' joint effect on risk of having a large-for-gestational-age (LGA) offspring (>+2 s.d. above the mean). DESIGN: A cohort of 162 676 mothers and their first-born offspring with birth information recorded on mothers and offspring in the nation-wide Swedish Medical Birth Register 1973-2006. RESULTS: Compared with mothers with appropriate birth weight for gestational age (AGA; -1 to +1 s.d.), mothers born LGA had increased risks of overweight (BMI 25.0-29.9; odds ratio (OR), 1.50; 95% CI 1.39-1.61), obesity class I (BMI 30.0-34.9; OR 1.77; 95% CI 1.59-1.98), obesity class II (BMI 35.0-39.9; OR 2.77; 95% CI 2.37-3.24) and obesity class III (BMI ≥40.0; OR 2.04; 95% CI 1.49-2.80). In each stratum of mother's birth weight for gestational age, risk of having an LGA offspring increased with mother's BMI. The risk of an LGA offspring was highest among women with a high (≥30) BMI who also had a high birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI (≤24.9). However, the strongest increase in risk by BMI was seen among mothers born SGA: the OR of having an LGA offspring was 13 times as high among SGA mothers with BMI ≥35.0 compared with the OR among SGA mothers with normal BMI (ORs=4.61 and 0.35, respectively). CONCLUSIONS: Prenatal conditions are important for the obesity epidemic. Prevention of LGA births may contribute to curtail the intergenerational vicious cycle of obesity.

Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer.

BACKGROUND: This was a population-based cohort study to determine the incidence, prevalence and risk factors for peritoneal carcinomatosis (PC) from colorectal cancer. METHODS: Prospectively collected data were obtained from the Regional Quality Registry. The Cox proportional hazards regression model was used for multivariable analysis of clinicopathological factors to determine independent predictors of PC. RESULTS: All 11 124 patients with colorectal cancer in Stockholm County during 1995-2007 were included and followed until 2010. In total, 924 patients (8.3 per cent) had synchronous or metachronous PC. PC was the first and only localization of metastases in 535 patients (4.8 per cent). The prevalence of synchronous PC was 4.3 per cent (477 of 11 124). The cumulative incidence of metachronous PC was 4.2 per cent (447 of 10 646). Independent predictors for metachronous PC were colonic cancer (hazard ratio (HR) 1.77, 95 per cent confidence interval 1.31 to 2.39; P = 0.002 for right-sided colonic cancer), advanced tumour (T) status (HR 9.98, 3.10 to 32.11; P < 0.001 for T4), advanced node (N) status (HR 7.41, 4.78 to 11.51; P < 0.001 for N2 with fewer than 12 lymph nodes examined), emergency surgery (HR 2.11, 1.66 to 2.69; P < 0.001) and non-radical resection of the primary tumour (HR 2.75, 2.10 to 3.61; P < 0.001 for R2 resection). Patients aged > 70 years had a decreased risk of metachronous PC (HR 0.69, 0.55 to 0.87; P = 0.003). CONCLUSION: PC is common in patients with colorectal cancer and is associated with identifiable risk factors.

Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus: a Swedish nationwide cohort study.

BACKGROUND: Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available. OBJECTIVES: To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE. METHODS: A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers. RESULTS: A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1·8 (95% CI 1·5-2·2) for cancer overall. Median follow-up was 4·1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer. CONCLUSIONS: Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.

Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden.

BACKGROUND: Numerous case reports about drug-induced (DI) subacute cutaneous lupus erythematosus (SCLE) have been published. Various drug types with different latencies has been proposed as triggers for this autoimmune skin disease. OBJECTIVES: To evaluate the association between exposure to certain suspected drugs (previously implicated to induce SCLE) and a subsequent diagnosis of SCLE. METHODS: We performed a population-based matched case-control study in which all incident cases of SCLE (n=34) from 2006 to 2009 were derived from the National Patient Register. The control group was selected from the general population, matched (1:10) for gender, age and county of residence. The data were linked to the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between exposures to certain suspected drugs and the development of SCLE. RESULTS: During the 6 months preceding SCLE diagnosis, 166 (71%) of the patients with SCLE had at least one filled prescription of the suspected drugs. The most increased ORs were found for terbinafine (OR 52.9, 95% CI 6.6-∞), tumour necrosis factor-α inhibitors (OR 8.0, 95% CI 1.6-37.2), antiepileptics (OR 3.4, 95% CI 1.9-5.8) and proton pump inhibitors (OR 2.9, 95% CI 2.0-4.0). CONCLUSIONS: We found an association between drug exposure and SCLE. More than one third of the SCLE cases could be attributed to drug exposure. No significant OR was found for thiazides, which might be due to longer latency and therefore missed with this study design. DI-SCLE is reversible once the drug is discontinued, indicating the importance of screening patients with SCLE for potentially triggering drugs. A causal relationship cannot be established from this study and the underlying pathogenesis remains unclear.

Increased lymph node harvest in patients operated on for right-sided colon cancer: a population-based study.

AIM: In recent decades, the focus has been on the treatment of rectal cancer with improved surgical techniques. This has resulted in improved results for patients with rectal cancer. Recently, the focus has shifted to colon cancer surgery with the introduction of preoperative staging, new surgical techniques, quality control and enhanced recovery programmes. The change in operative techniques has been most pronounced for patients with tumours on the right side of the colon, with more extensive resections and proximal ligations of the vessels. The aim of this study was to assess the number of analysed lymph nodes and the metastatic index (MI) in patients operated on for right-sided colon cancer in the Stockholm area between 1996 and 2009. METHOD: All patients operated on for cancer of the right colon between January 1996 and December 2009 were divided into three groups based on the year in which they were operated (period 1, 1996-1999; period 2, 2000-2004; and period 3, 2005-2009). The number of lymph nodes and lymph node status were analysed. RESULTS: In total, 3536 patients were operated on for right-sided colon cancer during the study period. There was a significantly lower proportion of emergency operations in the third time period. The mean number of lymph nodes examined increased significantly during the overall study period (seven in period 1, 11 in period 2 and 18 in period 3; P < 0.001). A significant drop in MI was seen during the third time period (0.25, compared with 0.40 in period 1 and 0.40 in period 2; P < 0.001). CONCLUSION: During the study period there was an increase in the number of analysed lymph nodes and a decrease in MI after right-sided hemicolectomies. Further investigations are needed to evaluate the potential impact on short-term and long-term outcome.

Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden.

BACKGROUND: Studies reporting the incidence of isolated cutaneous lupus erythematosus (CLE) are rare. OBJECTIVES: To examine in a population-based cohort study the incidence of CLE and its subsets in Sweden. The short-term probability of receiving an additional diagnosis of systemic lupus erythematosus (SLE) is also assessed. METHODS: A population-based open cohort study including all patients with CLE [International Classification of Diseases (ICD) code, ICD-10: L93] in Sweden, 2005-2007. Patients (n=1088) were identified in the Swedish National Patient Register. RESULTS: The incidence of CLE was 4·0/100,000; the female/male ratio was 3:1. Mean age at disease onset was 54 years. The most common subset was discoid lupus erythematosus (DLE) (80%, n = 868). A quarter of the patients (24%, n=260) were already diagnosed with SLE at the time they were diagnosed with CLE. During the whole observation period (2005-2007), an additional 18% (n = 107) were diagnosed with SLE, the probability of receiving an additional SLE diagnosis being highest for the subacute CLE (SCLE) subset. CONCLUSIONS: This is the first nationwide epidemiological study on CLE. We found the incidence of CLE to be about equal to that of SLE, and found a higher short-term probability for receiving an additional diagnosis with SLE than previously described for CLE. Subsets other than DLE and SCLE were rarely reported in our system; an update of the ICD codes for this diagnostic group could increase reporting of these more unusual cases. Our study clarifies that monitoring and follow-up are called for in this patient group due to the risk for SLE, and underscores the need for clear criteria for risk assessment in the large group of patients with CLE who also fulfil criteria for SLE.

Rheumatoid arthritis and birth outcomes: a Danish and Swedish nationwide prevalence study.

OBJECTIVES: To examine the prevalence of preterm birth, infants with low Apgar score, small for gestational age (SGA) birth, stillbirth and congenital abnormalities in women with rheumatoid arthritis (RA) compared with women without RA. DESIGN: Prevalence study. SETTING: Combined Sweden and Denmark nationwide from 1994 to 2006. SUBJECTS: We included 871,579 women with a first-time singleton birth identified through population-based healthcare databases. MAIN OUTCOME MEASURES: We compared the prevalence of preterm birth, low Apgar score (<7 at 5 min), SGA birth, stillbirth and congenital abnormalities amongst women with RA compared with women without RA using prevalence odds ratio (OR) with 95% confidence interval (95% CI), whilst controlling for maternal age, smoking, parental cohabitation and year. We stratified analyses by period of birth (1994-1997, 1998-2001 and 2002-2006). RESULTS: Amongst 1199 women with RA, 7.8% gave birth between 32 and 36 gestational weeks (adjusted OR, 1.44; 95% CI, 1.14-1.82), 1.4% gave birth before gestational week 32 (adjusted OR, 1.55; 95% CI, 0.97-2.47), 1.6% had an infant with a low Apgar score (OR, 0.99; 95% CI, 0.95-1.65), 5.9% had an SGA birth (adjusted OR, 1.56; 95% CI, 1.2-2.01), 0.9% experienced stillbirth (adjusted OR, 2.07; 95% CI, 0.98-4.35) and 4.3% gave birth to an infant with congenital abnormalities (adjusted OR,1.32; 95% CI, 0.98-1.79). The OR for congenital abnormalities decreased from 2.57 (95% CI, 1.59-4.16) in 1994-1997 to 1.00 (95% CI, 0.64-1.56) in 2002-2006. CONCLUSIONS: Women with RA had a high prevalence of most adverse birth outcomes. This could be due to inflammatory activity, medical treatment or other factors not controlled for.

Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit.

BACKGROUND: We investigated the incidence and severity of post-injury morbidity and mortality in intensive care unit (ICU)-treated trauma patients. We also identified risk factors in the early phase after injury that predicted the later development of complications. METHODS: A prospective observational cohort study design was used. One hundred and sixty-four adult patients admitted to the ICU for more than 24 h were included during a 21-month period. The incidence and severity of morbidity such as multiple organ failure (MOF), acute lung injury (ALI), severe sepsis and 30-day post-injury mortality were calculated and risk factors were analyzed with uni- and multivariable logistic regression analysis. RESULTS: The median age was 40 years, the injury severity score was 24, the new injury severity score was 29, the acute physiology and chronic health evaluation II score was 15, sequential organ failure assessment maximum was 7 and ICU length of stay was 3.1 days. The incidences of post-injury MOF were 40.2%, ALI 25.6%, severe sepsis 31.1% and 30-day mortality 10.4%. The independent risk factors differed to some extent between the outcome parameters. Age, severity of injury, significant head injury and massive transfusion were independent risk factors for several outcome parameters. Positive blood alcohol was only a predictor of MOF, whereas prolonged rescue time only predicted death. Unexpectedly, injury severity was not an independent risk factor for mortality. CONCLUSIONS: Although the incidence of morbidity was considerable, mortality was relatively low. Early post-injury risk factors that predicted later development of complications differed between morbidity and mortality.

Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register.

BACKGROUND: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern. METHODS: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67,743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471,024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals. RESULTS: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26,981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365,026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3,355,849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent. CONCLUSION: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.

Allergy and autoimmune disease: a registry-based study.

BACKGROUND: Allergy and autoimmunity are two potential outcomes of a dysregulated immune system, but the relationship between them is unclear. It has been hypothesized that they could be inversely associated because of different T helper cell reactivity patterns. However, both positive and negative associations have been reported. Therefore, our aim was to perform a large epidemiological study with a defined allergic disease cohort. METHODS: During the years 1990-2002, 68 770 subjects were tested for total serum IgE (Total-IgE) and 72 228 were tested with Phadiatop for diagnosing allergic disease at Karolinska University Hospital, Stockholm, Sweden. This cohort was then linked with the Swedish Inpatient Registry 1968-2004 for a follow-up with regard to recorded discharges for 28 autoimmune diseases. We then used Cox regression and logistic regression to estimate the risk of autoimmune diseases in general in the allergy-tested subjects. RESULTS: Subjects with positive Phadiatop test were at a statistically decreased risk of subsequent autoimmune disease in comparison with subjects with negative test; hazard ratio (HR): 0.80 [95% (Confidence interval) CI: 0.68-0.94). Prior autoimmune disease was associated with a decreased risk of positive Phadiatop test [odds ratio: 0.83 (95% CI: 0.72-0.96)] in comparison with negative test. Subjects with highly elevated Total-IgE were at a statistically increased risk of a subsequent autoimmune disease in comparison with subjects with normal levels [HR: 1.36 (95% CI: 1.09-1.70)], but no association was found between prior autoimmune disease and different Total-IgE levels. CONCLUSION: The study supports the hypothesis that allergy, defined as positive Phadiatop test, could be inversely related to autoimmune disease but this association is weak.