Heart rate and QRS duration as biomarkers predict the immediate outcome from pulseless electrical activity.

INTRODUCTION: Pulseless electrical activity (PEA) is commonly observed in in-hospital cardiac arrest (IHCA). Universally available ECG characteristics such as QRS duration (QRSd) and heart rate (HR) may develop differently in patients who obtain ROSC or not. The aim of this study was to assess prospectively how QRSd and HR as biomarkers predict the immediate outcome of patients with PEA. METHOD: We investigated 327 episodes of IHCA in 298 patients at two US and one Norwegian hospital. We assessed the ECG in 559 segments of PEA nested within episodes, measuring QRSd and HR during pauses of compressions, and noted the clinical state that immediately followed PEA. We investigated the development of HR, QRSd, and transitions to ROSC or no-ROSC (VF/VT, asystole or death) in a joint longitudinal and competing risks statistical model. RESULTS: Higher HR, and a rising HR, reflect a higher transition intensity ("hazard") to ROSC (p < 0.001), but HR was not associated with the transition intensity to no-ROSC. A lower QRSd and a shrinking QRSd reflect an increased transition intensity to ROSC (p = 0.023) and a reduced transition intensity to no-ROSC (p = 0.002). CONCLUSION: HR and QRSd convey information of the immediateoutcome during resuscitation from PEA. These universally available and promising biomarkers may guide the emergency team in tailoring individual treatment.

Pulseless electrical activity in in-hospital cardiac arrest - A crossroad for decisions.

BACKGROUND: PEA is often seen during resuscitation, either as the presenting clinical state in cardiac arrest or as a secondary rhythm following transient return of spontaneous circulation (ROSC), ventricular fibrillation/tachycardia (VF/VT), or asystole (ASY). The aim of this study was to explore and quantify the evolution from primary/secondary PEA to ROSC in adults during in-hospital cardiac arrest (IHCA). METHODS: We analyzed 700 IHCA episodes at one Norwegian hospital and three U.S. hospitals at different time periods between 2002 and 2021. During resuscitation ECG, chest compressions, and ventilations were recorded by defibrillators. Each event was manually annotated using a graphical application. We quantified the transition intensities, i.e., the propensity to change from PEA to another clinical state using time-to-event statistical methods. RESULTS: Most patients experienced PEA at least once before achieving ROSC or being declared dead. Time average transition intensities to ROSC from primary PEA (n = 230) and secondary PEA after ASY (n = 72) were 0.1 per min, peaking at 4 and 7 minutes, respectively; thus, a patient in these types of PEA showed a 10% chance of achieving ROSC in one minute. Much higher transition intensities to ROSC, average of 0.15 per min, were observed for secondary PEA after VF/VT (n = 83) or after ROSC (n = 134). DISCUSSION: PEA is a crossroad in which the subsequent course is determined. The four distinct presentations of PEA behave differently on important characteristics. A transition to PEA during resuscitation should encourage the resuscitation team to continue resuscitative efforts.

Anastomotic leak after surgery for colon cancer and effect on long-term survival.

AIM: An anastomotic leak after surgery for colon cancer is a recognized complication but how it may adversely affect long-term survival is less clear because data are scarce. The aim of the study was to investigate the long-term impact of Grade C anastomotic leak in a large, population-based cohort. METHOD: Data on patients undergoing resection for Stage I-III colon cancer between 2008 and 2012 were collected from the Swedish, Norwegian and Danish Colorectal Cancer Registries. Overall relative survival and conditional 5-year relative survival, under the condition of surviving 1 year, were calculated for all patients and stratified by stage of disease. RESULTS: A total of 22 985 patients were analysed. Anastomotic leak occurred in 849 patients (3.7%). Five-year relative survival in patients with anastomotic leak was 64.7% compared with 87.0% for patients with no leak (P < 0.001). Five-year relative survival among the patients who survived the first year was 88.6% vs 81.3% (P = 0.003). Stratification by cancer stage showed that anastomotic leak was significantly associated with decreased relative survival in patients with Stage III disease (P = 0.001), but not in patients with Stage I or II (P = 0.950 and 0.247, respectively). CONCLUSION: Anastomotic leak after surgery for Stage III colon cancer was associated with significantly decreased long-term relative survival.

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

INTRODUCTION: The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. METHODS: Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. RESULTS: Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. CONCLUSION: The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti-NR2 or anti-P antibodies.

BACKGROUND AND PURPOSE: Migraine is frequent in patients with systemic lupus erythematosus (SLE), but the pathogenesis and pathophysiology are poorly understood. Migraine is assumed to be a consequence of abnormal neuronal excitability. Based on the hypothesis that the threshold for migraine is lower in SLE patients due to cerebral disturbances, whether structural abnormalities of the brain or relevant biomarkers are associated with headaches in SLE was investigated. METHODS: Sixty-seven SLE patients and age- and gender-matched healthy subjects participated. Volumes of grey matter (GM) and white matter (WM) were estimated from cerebral magnetic resonance images with SPM8 software. Anti-NR2 and anti-P antibodies and protein S100B were measured in cerebrospinal fluid. RESULTS: In regression analyses, larger GM volumes in SLE patients reduced the odds for headache in general [odds ratio (OR) 0.98, P = 0.048] and for migraine in particular (OR 0.95, P = 0.004). No localized loss of GM was observed. Larger WM volumes in patients increased the odds for migraine (OR 1.04, P = 0.007). These findings could not be confirmed in healthy subjects. Neither anti-NR2 and anti-P antibodies nor S100B were associated with headaches in SLE patients. CONCLUSIONS: Systemic lupus erythematosus patients with migraine have a diffuse reduction in GM compared to patients without migraine. This finding was not observed in healthy subjects with migraine, and selected biomarkers did not indicate specific pathophysiological processes in the brain. These findings indicate that unknown pathogenic processes are responsible for the increased frequency of migraine in SLE patients.

Epidemiology and classification of gastroenteropancreatic neuroendocrine neoplasms using current coding criteria.

BACKGROUND: The lack of uniform criteria for coding of gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) has hampered previous epidemiological studies. The epidemiology of GEP-NEN was investigated in this study using currently available criteria. METHODS: All patients diagnosed with GEP-NEN between January 2003 and December 2013 in a well defined Norwegian population of approximately 350 000 people were included. Age- and sex-adjusted incidence rates were calculated. The current 2010 World Health Organization criteria, European Neuroendocrine Tumour Society classification and International Union Against Cancer (UICC) classification were used. RESULTS: A total of 204 patients (114 male, 55.9 per cent) were identified. The median age at diagnosis was 61 (range 10-94) years. The annual overall crude incidence was 5.83 per 100,000 inhabitants, with an increasing trend (P = 0.033). The most frequent location was small intestine (60 patients, 29.4 per cent) followed by appendix (48 patients, 23.5 per cent) and pancreas (33 patients, 16.2 per cent). Grade 1 tumours were more common in gastrointestinal (100 patients, 58.5 per cent) than in pancreatic (9 patients, 27 per cent) NEN. According to the UICC classification, 77 patients (37.7 per cent) had stage I, 17 patients (8.3 per cent) stage II, 37 patients (18.1 per cent) stage III and 70 patients (34.3 per cent) had stage IV disease. No patient with stage I disease had grade 3 tumours; advanced tumour grade increased with stage. CONCLUSION: A high crude incidence of GEP-NEN, at 5.83 per 100,000 inhabitants, was noted together with a significant increasing trend over time.

High headache-related disability in patients with systemic lupus erythematosus and primary Sjögren's syndrome.

BACKGROUND AND PURPOSE: It is often argued that patients with systemic lupus erythematosus (SLE) have more headaches than healthy subjects, but this association remains controversial. Thus the magnitude and severity of headaches in SLE were evaluated in comparison with another autoimmune disease, namely primary Sjögren's syndrome (pSS). METHODS: Sixty-seven patients with SLE, 71 pSS patients and 108 healthy subjects were included. The International Classification of Headache Disorders, Headache Impact Test-6 (HIT-6), and the Migraine Disability Assessment (MIDAS) questionnaire were used to classify and assess headache-related disability. RESULTS: Primary headaches were more prevalent in SLE patients than in healthy subjects (82% vs. 69%, P = 0.01). Amongst the headache sufferers, SLE patients (N = 55) and pSS patients (N = 51) had higher HIT-6 scores (median 51, range 36-67, and median 54, range 36-72, respectively) than healthy subjects (N = 69) (median 46, range 36-72; P = 0.02 and P = 0.0009, respectively). Also, MIDAS scores were higher in SLE (median 0, range 0-110) and pSS patients (median 1, range 0-40) than in healthy subjects (median 0, range 0-10; P = 0.04 and P = 0.003, respectively). CONCLUSION: Patients with SLE and pSS have a higher burden from headaches and more severe headaches than headache sufferers without these diseases. However, evidence of a specific bothersome SLE headache was not possible to identify as the headaches had the same characteristics and similar impact and severity in pSS patients. Depressive mood significantly influenced headache severity.

Factors predicting the use of therapeutic hypothermia and survival in unconscious out-of-hospital cardiac arrest patients admitted to the ICU.

INTRODUCTION: Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival. METHOD: We conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals. RESULTS: A total of 715 unconscious patients older than 18 years of age, who suffered OHCA of both cardiac and non-cardiac causes, were included. With an overall TH use of 70%, the survival to discharge was 42%, with 90% of the survivors having a favourable cerebral outcome. Known positive prognostic factors such as witnessed arrest, bystander cardio pulmonary resuscitation (CPR), shockable rhythm and cardiac origin were all positive predictors of TH use and survival. On the other side, increasing age predicted a lower utilisation of TH: Odds Ratio (OR), 0.96 (95% CI, 0.94 to 0.97); as well as a lower survival: OR 0.96 (95% CI, 0.94 to 0.97). Female gender was also associated with a lower use of TH: OR 0.65 (95% CI, 0.43 to 0.97); and a poorer survival: OR 0.57 (95% CI, 0.36 to 0.92). After correcting for other prognostic factors, use of TH remained an independent predictor of improved survival with OR 1.91 (95% CI 1.18-3.06; P <0.001). Analysing subgroups divided after initial rhythm, these effects remained unchanged for patients with shockable rhythm, but not for patients with non-shockable rhythm where use of TH and female gender lost their predictive value. CONCLUSIONS: Although TH was used in the majority of unconscious OHCA patients admitted to the ICU, actual use varied significantly between subgroups. Increasing age predicted both a decreased utilisation of TH as well as lower survival. Further, in patients with a shockable rhythm female gender predicted both a lower use of TH and poorer survival. Our results indicate an underutilisation of TH in some subgroups. Hence, more research on factors affecting TH use and the associated outcomes in subgroups of post-resuscitation patients is needed.

Headache in primary Sjøgren's syndrome: a population-based retrospective cohort study.

BACKGROUND: We investigated whether the prevalence of primary headaches was higher in patients with primary Sjøgren's syndrome (PSS) than in healthy individuals. METHODS: This retrospective cohort study included 71 patients with PSS (patients) based on the American European Consensus Classification criteria, and 71 age- and gender-matched healthy subjects (controls). Headaches were classified according to the International Classification of Headache Disorders. We measured depression with the Beck Depression Inventory, and fatigue with the Fatigue Severity Scale. RESULTS: Fifty-one patients and 42 controls had headaches in the previous 12 months (71.8% vs. 59.2%, P = 0.10). Thirty-eight patients and 28 controls had tension type headaches (TTHs) (53.5% vs. 39.4%, P = 0.12). Eight patients (11.3%) and one control had chronic TTHs (P = 0.05). Migraines and migraines with aura were equally prevalent in patients (26.8% and 11.3%, respectively) and controls (28.2% and 15.5%, respectively; P = 0.61). CONCLUSIONS: In general, patients did not have more migraines or headaches than controls. However, patients had more chronic TTHs than controls. Chronic TTHs were not associated with PSS-related autoantibodies, fatigue, depression, abnormalities on magnetic resonance imaging or abnormalities in the cerebrospinal fluid. Patients with PSS did, however, have higher depression and fatigue scores than controls.

Patterns and predictive factors of complications after endoscopic retrograde cholangiopancreatography.

BACKGROUND: With an increased use of magnetic resonance imaging, the indications for endoscopic retrograde cholangiopancreatography (ERCP) have changed. Consequently, the patterns and factors predictive of complications after ERCP performed during current routine clinical practice are not well known. METHODS: A prospective multicentre cohort study was undertaken in 11 Norwegian hospitals. Complications and mortality within 30 days after ERCP were analysed by univariable and multivariable regression analysis. RESULTS: There were 2808 ERCP procedures, of which 2573 (91·6 per cent) were therapeutic. More than half of the patients were aged 70 years or more. Common bile duct cannulation was achieved in 2557 procedures (91·1 per cent). Complications occurred in 327 (11·6 per cent) of the procedures, including cholangitis in 100 (3·6 per cent), pancreatitis in 88 (3·1 per cent), bleeding in 66 (2·4 per cent), perforation in 25 (0·9 per cent) and cardiovascular-respiratory events in 32 (1·1 per cent). In the multivariable regression analysis, older age, increasing American Society of Anesthesiologists fitness score, centre ERCP volumes of more than 150 procedures annually and precut sphincterotomy were predictive factors for severe complications. The overall 30-day mortality rate was 2·2 per cent (63 patients), with a procedure-related mortality rate of 1·4 per cent (39 patients). Malignancy was diagnosed in 46 (73 per cent) of the patients who died. CONCLUSION: ERCP is a procedure with considerable risk for complications. Morbidity and mortality are related to patient age and co-morbidity, as well as hospital volume of ERCP procedures and the type of intervention.

Survival effect of implementing national treatment strategies for curatively resected colonic and rectal cancer.

BACKGROUND: The surgical management of rectal cancer has changed substantially over the past decade. There are limited data on the long-term outcome of implementing systematic management strategies. METHODS: Survival of a national cohort of patients treated surgically for colonic and rectal cancer over a 10-year interval was analysed. All 31 158 patients in Norway diagnosed with adenocarcinoma of the colon and rectum between 1994 and 2003 were identified from the Cancer Registry of Norway and the Norwegian Rectal Cancer Registry. Changes in 5-year relative survival were compared by age, stage and tumour location during the early and late years. RESULTS: The study population included 19 053 patients who had a curative resection. The relative 5-year survival rate significantly improved for both colonic cancer (73·8 versus 78·0 per cent; P < 0·001) and rectal cancer (72·1 versus 79·6 per cent; P < 0·001). The 5-year relative survival was significantly better for rectal than colonic cancer during the late period (P = 0·030). Improved 5-year relative survival was related to better outcomes in patients with positive lymph nodes (67·2 and 62·1 per cent for rectal and colonic cancer respectively; each P < 0·001 versus early period), but not for the subgroup aged over 75 years with lymph node-positive colonic cancer. CONCLUSION: In this national cohort, survival after curative surgery for colorectal cancer increased significantly after implementation of national management strategies. Improvements were most evident for rectal cancer and in lymph node-positive disease; they were less substantial for colonic cancer and elderly patients (over 75 years). Strategic treatment changes may be warranted for the latter group.

Cerebral white matter hyperintensities are not increased in patients with primary Sjögren's syndrome.

BACKGROUND AND PURPOSE: It is frequently thought that cerebral white matter hyperintensities (WMHs) on T-2 weighted MRI scans are increased in patients with autoimmune diseases. An increased frequency of WHMs has been described in primary Sjögren's syndrome (PSS), but no controlled studies exist. The aim of this study was therefore to compare WMHs in PSS patients and healthy subjects applying the new European-American criteria for PSS. METHODS: Cross-sectional controlled study of 68 unselected PSS patients and 68 healthy subjects was carried out. WMHs were rated using Scheltens method. RESULTS: There were no differences in total or any regional WMH scores between PSS patients and healthy subjects. CONCLUSIONS: Patients with PSS do not have increased WMH load or distribution when compared with healthy subjects.

Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: a comparative population-based study.

OBJECTIVES: To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. METHODS: A population-based study was conducted including 68 patients with SLE (mean (SD) age 43.8 (13.6) years) and 72 with PSS (age 57.8 (13.0) years). Specialists in internal medicine, neurology and neuropsychology performed standardised examinations. Cerebral MRI scans and neurophysiological studies were performed in all patients. RESULTS: Similar prevalences in SLE and PSS were observed for headaches (87% vs 78%, p = 0.165), cognitive dysfunction (46% vs 50%, p = 0.273), mood disorders (26% vs 33%, p = 0.376), anxiety disorders (12% vs 4%, p = 0.095), cranial neuropathy (1% vs 4%, p = 0.339) and seizure disorders (7% vs 3%, p = 0.208). Cerebrovascular disease was more common in SLE than PSS (12% vs 3%, p = 0.049); but mononeuropathy (0% vs 8%, p = 0.015) and polyneuropathy (18% vs 56%, p<0.001) were less common in SLE than PSS. Other syndromes were rare or absent in both patient groups. CONCLUSIONS: Headache, cognitive dysfunction and mood disorders are common in both diseases, but otherwise there are distinct differences in NP involvement, with cerebrovascular diseases more prevalent in SLE and neuropathies more common in PSS. This indicates that some NP disease mechanisms are shared while others differ between the two diseases.

The prevalence of dementia in an urban Turkish population.

A cross-sectional, population-based, 2-stage prevalence study was conducted in a sample of 1019 community-dwelling persons over the age of 70 years living in Istanbul. In the first phase, participants were screened with the Mini-Mental State Examination for evidence of cognitive impairment. In the second phase, 79% of those who screened positive (n = 322) and 9% of screen-negatives (n = 63) underwent a standardized diagnostic workup. Diagnosis of dementia and Alzheimer's disease (AD) was made according to established criteria. Ninety-three cases of dementia were identified, 58 of whom were diagnosed with probable AD. Based on these numbers, the prevalence rates of probable AD and dementia were calculated to be 11.0% (95% CI, 7.0% to 15.0%) and 20.0% (95% CI, 14.0% to 26.0%), respectively, in this population. Prevalence rates of dementia and AD in Istanbul, Turkey, are comparable with those seen in the Western world.

The effect of age of onset of PD on risk of dementia.

BACKGROUND: Dementia occurs in the majority of patients with Parkinson's disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. METHODS: Two community-based studies of PD in New York (n=281) and Rogaland county, Norway (n=227) and two population-based groups of healthy elderly from New York (n=180) and Odense, Denmark (n=2414) were followed prospectively for 3-4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. FINDINGS: In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. INTERPRETATION: This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD.

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure.

BACKGROUND: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. METHODS: Sixteen men and four women aged 63.0+/-10.4 (mean+/-S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. RESULTS: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables CONCLUSION: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

Variability in methotrexate serum and cerebrospinal fluid pharmacokinetics in children with acute lymphocytic leukemia: relation to assay methodology and physiological variables.

Methotrexate (MTX) steady state concentrations were evaluated in 42 children who had received high-dose infusions (6-8 g/m2) for acute lymphocytic leukemia. Concentrations in serum and cerebrospinal fluid (CSF) measured by immunoassay were found to be highly variable. Reanalysis by a reference high-pressure liquid chromatography method ruled out analytical factors as a source of this variability. The correlation coefficient between the analytical methods was 0.77 for the serum data and 0.88 for the CSF data. The variability of serum and CSF concentrations was higher in younger patients (serum; P = 0.05 and CSF; P = 0.18), and the CSF concentration decreased with decreasing age and in later courses. Body surface area, body mass index, weight, and gender were not significantly related to MTX variability. We conclude that the pronounced pharmacokinetic variability seen during MTX infusions remains largely unexplained.