Incidence of persistent postpartum opioid use by mode of delivery: a 2016 cohort study of Danish women.

BACKGROUND: The use of oral opioids as standard treatment after cesarean delivery has been linked to persistent use in opioid-naïve women in the USA. In Denmark, the use of opioids after cesarean delivery is typically restricted to in-hospital use. The aim of this study was to estimate the incidence of persistent postpartum opioid use in Denmark and compare the incidence by mode of delivery. METHODS: This was a national cohort study of all women giving birth in Denmark in 2016, with one-year follow-up. Data from Danish registries were retrieved and combined using each woman's unique identification number. Persistent use of opioids was defined as ≥3 redeemed opioid prescriptions 31-365 days postpartum. RESULTS: A total of 62 520 births were included in the cohort: 49 859 vaginal deliveries, 5310 intrapartum cesarean deliveries, and 7351 pre-labor cesarean deliveries. For all births, persistent postpartum opioid use occurred in 85 (140 in 100 000) women of whom 36 (42%) had opioid use during pregnancy. The incidence of persistent opioid use was highest in the pre-labor cesarean delivery cohort (n=27; 360 in 100 000) and lowest in the intrapartum cesarean delivery cohort (n=3, 60 in 100 000; P<0.001). Women taking opioids during pregnancy were at increased risk of persistent opioid use (odds ratio 63.3; 95% CI 43.9 to 91.4). CONCLUSIONS: Women giving birth in Denmark, where use of post-discharge opioid treatment is generally restricted, have a low risk of developing persistent use of opioids, with very few women seeking additional analgesic treatment from their general practitioner.

Behçet's syndrome presenting with peripheral arterial aneurysms.

A case of Behçet's syndrome is described presenting with several peripheral arterial aneurysms. The diagnostic criteria are discussed and the need for increased vigilance of this disease is stressed due to an increasing number of immigrants.

Serum from NSAID-treated patients attenuates the capacity of rat leukocytes to synthesize leukotriene B4.

The synthesis of leukotriene B4 by A23187-stimulated rat peritoneal leukocytes was studied in the presence of 0.1% normal human serum, serum from patients treated with NSAIDs for either an inflammatory (rheumatoid arthritis, RA) or a non-inflammatory condition (lumbar disc protrusion, LDP), and serum from RA patients drawn one week after withdrawal from NSAID treatment. The capacity for LTB4 synthesis was significantly lower in the presence of serum from NSAID treated patients: thirty per cent less than observed in presence of normal serum in the RA group, and fifty per cent in the LDP group. When NSAIDs were withdrawn from RA patients, the LTB4 production in presence of serum increased, but was not completely normalized after one week. These results indicate that NSAID treatment may down-regulate the capacity for leukotriene synthesis by an indirect effect.

[Rapidly progressing glomerulonephritis. Microangiitis associated with antibodies against the glomerula membrane]. / Hurtigt progredierende glomerulonephritis. Mikroangiitis associeret med antistoffer mod den glomeruloere basalmembran.

A 53 year old man first presented with a mild anti-neutrophil cytoplasmic antibody (ANCA), type (MPO-ANCA) associated microscopic polyangiitis. Approximately one year later, he presented with fatigue, fever, cough, sore muscles and erythrocyturia. At admission he was uraemic. Kidney biopsy showed in LM extracapillary glomerulonephritis and in immunofluorescence microscopy linear deposition of IgG along the glomerular basement membrane (GBM). MPO-ANCA was still positive, but antibodies against GBM were now also present. Retrospective analysis revealed the presence of anti-GBM antibodies nine months before clinical illness. Pr3-ANCA (C-ANCA) was negative during the whole course. In spite of decreasing anti-GBM antibody levels during treatment, his condition aggravated, and he died from complications. Thus, coexisting anti-GBM antibodies may explain suddenly deteriorating renal function in patients with ANCA associated vasculitis.

Increased expression of complement receptor type 1 (CR1, CD35) on human peripheral blood T lymphocytes after polyclonal activation in vitro.

The receptor for C3b and C4b--complement receptor type 1 (CR1, CD35)--is present on a variety of cell types including erythrocytes, phagocytic cells, B lymphocytes and a small subpopulation of T lymphocytes. The function of the receptor varies according to the different cell types, but on T lymphocytes the function is as yet not known. The present study concerns the influence of polyclonal stimulation on CR1-expressing T lymphocytes. Incubation with PHA resulted in a dose-dependent increase in the number of CR1-positive T lymphocytes. The CR1-expression T lymphocytes were found in both the CD4- and the CD8-positive subpopulation, but a significant stimulatory increase was only found in the CD4-positive population. A significant increase in the number of CR1-expressing T lymphocytes was found when monocytes were present during stimulation, indicating an importance of monocytes and/or monocyte products. However, the increase was not regulated by arachidonic acid metabolites of the cyclo-oxygenase pathway as indomethacin failed to inhibit the increase. Neither did rIL-1 alpha, rIL-1 beta, rTNF alpha nor rIL-6 alter the number of CR1-expressing T lymphocytes. The results of this study indicate a role for CR1 on T lymphocytes in the regulation of the immune system.

[Fish oils and rheumatoid arthritis. A randomized and double-blind study]. / Fiskeolie og reumatoid artrit. En randomiseret og dobbeltblind undersøgelse.

The effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with active rheumatoid arthritis was evaluated in a multicentre, randomized and double blind study. Fifty-one patients with active rheumatoid arthritis were included from three Danish hospital Departments of Rheumatology. The patients were allocated to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with a fat composition averaging the Danish diet. Small but significant improvements in morning stiffness, joint tenderness and C-reactive protein were observed. There were no serious side-effects. Dietary supplementation with n-3 PUFA in patients with active rheumatoid arthritis has a modest effect on three out of eight disease variables, without effect on other traditional parameters for monitoring disease activity.

[Pelvic insufficiency during pregnancy. Is pelvic girdle relaxation an unambiguous concept?]. / Insufficientia pelvis in graviditate. Er boekkenløsning et entydigt begreb?

Pelvic insufficiency during pregnancy, pelvic girdle relaxation, is defined as a condition with pain at the pubic symphysis and/or the sacroiliac joint developing in connection with pregnancy or delivery. No unambiguous criteria for the diagnosis of pelvic girdle relaxation exist but the following findings occur: Direct tenderness at the pubic symphysis and/or sacroiliac joint, waddling gait, pain on change of position, positive Trendelenburg's sign, iliac compression test, iliac gapping test and sacral pressure test. The frequency is 7.6-18.5 per 1000 deliveries. The incidence is increased in multiparae and women with occupations which strain the back. Recurrence occurs in 41-77%. The condition appears for the first time usually in the 5th-8th months of pregnancy. The majority of patients recover shortly after delivery but in some a condition of prolonged pain persists. The cause of pelvic girdle relaxation is unknown. Hormonal and biomechanical factors are considered to be of significance. No increased mobility in the pelvic joints nor general hypermobility have been demonstrated. Treatment is symptomatic and consists of information, instruction in relief and psychosocial support. Exercises and a trochanter belt may be useful. No controlled investigations of the value of treatment are available.

The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial.

STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.

Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids.

The effects of dietary supplementation with n-3 fatty acids on the level of cytokines and complement activation in plasma from patients with rheumatoid arthritis were examined. Thirty-two patients with active rheumatoid arthritis were included in a 12-week double-blind, randomized study of dietary supplementation with n-3 fatty acids (3.6 g per day) or placebo. The cytokines were measured in plasma before and after treatment with fish oil or placebo. In general, cytokine values at the upper limits of the calculated normal areas were found. The Interleukin-1 beta concentration in plasma was reduced significantly after 12 weeks of dietary supplementation with fish oil (p < 0.03). No significant difference was observed in the placebo group. The tumour necrosis factor alpha activity in plasma did not change significantly (p = 0.167). No significant changes were observed in the degree of complement activation. The clinical status of the patients was improved in the fish oil group, but not in the placebo group, judged by Ritchie's articular index (p < 0.02). We conclude that dietary supplementation with n-3 fatty acids results in significantly reduced plasma IL-1 beta levels in patients with rheumatoid arthritis. Even though the cytokine levels were low, the anti-inflammatory effect of n-3 fatty acids could in part be explained by their ability to decrease cytokine production.

Levels of complement receptor type one (CR1, CD35) on erythrocytes, circulating immune complexes and complement C3 split products C3d and C3c are not changed by short-term physical exercise or training.

The effect of heavy short-term physical exercise on the levels of complement receptor type one (CR1, CD35) on erythrocytes, the concentrations of circulating immune complexes (IC), and the complement C3 split products C3c and C3d were examined in young healthy males. Fourteen untrained volunteers underwent a 60-min bicycle exercise test at 75% of maximal oxygen uptake (VO2max). Six of the volunteers were exercised twice with an interval of at least one month. Before the second bicycle test they received oral indomethacin. With an interval of at least 1 week, 6 also went through a 60-min back-muscle exercise at up to 30% of VO2max. Blood samples were collected before and during the last few minutes of exercise as well as 2 h and 24 h afterwards. The same parameters were examined once in 29 highly trained racing cyclists. There were no consistent or significant exercise-induced changes in the levels of erythrocyte CR1, circulating IC, C3c nor C3d as measured by an enzyme-linked immunosorbent assay, polyethylene glycol precipitation complement consumption method, and by intermediate gel rocket immunoelectrophoresis, respectively. Neither did these parameters differ from controls in the highly trained group. The results indicate that CR1 on erythrocytes, circulating immune complexes and complement cleavage products C3c and C3d in healthy subjects remain unaffected by short-term heavy physical activity and training.

Loss of erythrocyte complement receptors (CR1; CD35) in patients with acute episodes of septicaemia or bacterial meningitis.

14 patients with septicaemia or bacterial meningitis were examined for serum levels of erythrocyte complement receptors CR1 (C3b/C4b; CD35) by an enzyme-linked immunosorbent assay and levels of circulating immune complexes (IC) by a polyethylene glycol precipitation complement consumption method, and concentrations of complement C3d split products in plasma by intermediate gel rocket immunoelectrophoresis. The CR1 receptor levels were significantly lower on day 7-8 after admission than on day 1-2 (p = 0.01), and than the levels 3-4 months later (p = 0.002). Both the levels of IC in serum and the C3d concentrations were significantly higher on day 7-8 than 3-4 months later (p = 0.02 and p = 0.004). The mechanism behind a temporary decreased expression of CR1 in patients with acute episodes of septicaemia or purulent meningitis is not fully known, and further investigations are needed to clarify whether this reduction in erythrocyte CR1 causes an impaired disposal of IC in patients with infections.

Elastolytic activity of human monocytes from synovial fluid and blood of patients with arthritis. Relations to levels of interleukin 6 and soluble interleukin 2 receptor.

Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (MøE) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood MøE was lower in OA than in IH, both measured as basal MøE activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF MøE was higher than MøE in blood (p less than 0.01). This increase in SF MøE could be mimicked in vitro by prestimulation of blood Mø with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF MøE, IL-6 and sIL-2R in patients with IH, points to a stimulation of Mø and lymphocytes in the joint.

[Humero-scapular periarthrosis]. / Periarthrosis humeroscapularis.

Humero-scapular periarthrosis (PH) is defined as an idiopathic painful condition in the shoulder with simultaneous limitation of active and passive movements in all directions. The condition is characterized by three phases: a painful period, a period dominated by stiffness and a period of recovery. PH is commonest between the ages of 40 and 60 years and the cumulated risk is estimated to be 2%. The incidence is higher in diabetics. The cause of PH is unknown and knowledge of the pathogenesis is very limited. Histological examination shows inflammation and fibrosis. Association with other pathological conditions of the upper limb or medical conditions, except diabetes mellitus, has not been documented with certainty. The average duration is 30 months but recovery without functional defects is common. Treatment is symptomatic and consists primarily of analgesics and rest during the painful phase. Local injections of steroids may be of effect. Exercises may be employed once the pain is under control and these have the object of improving mobility and increasing muscular strength.

Complement receptor type 1 (CR1, CD35) expression on peripheral T lymphocytes: both CD4- and CD8-positive cells express CR1.

T lymphocytes from 42 healthy blood donors were examined for expression of CR1 on the cell surface using a fluorescence-activated cell sorter. The fraction of CR1-positive T lymphocytes varied in the range from 1 to 8% (median 2.4%). The CR1-positive T lymphocytes constituted a homogeneous group of cells regarding both size and granulation; they seemed to be larger and more granulated than the average T lymphocytes. The CR1-expressing T lymphocytes were found both in the CD4- and in the CD8-positive subpopulations of T lymphocytes, and although the CD4-positive cells expressed CR1 with a slightly higher percentage than did the CD8-positive cells, this difference was not significant. The number of CR1-positive T lymphocytes did not correlate with the level of CR1 on erythrocytes. The presence of CR1 on a small T lymphocyte population suggests that CR1 on T lymphocytes might play a role in the immune regulation.

Interleukin 1, but not interleukin 1 inhibitor, is released from human monocytes by immune complexes.

Immune complexes (IC) are believed to play a role in the pathogenesis of some autoimmune diseases in which interleukin 1 (IL-1) and probably other cytokines also take part. This investigation shows that tetanus toxoid-human anti-tetanus toxoid IC induce human monocytes to release IL-1. The activity was identified as being mainly IL-1 beta by molecular size chromatography, isoelectric focusing, and anti-IL-1 beta affinity chromatography. Endotoxins were eliminated by repetitive washing of the IC suspension and by preincubation of IC with polymyxin B. The IL-1-inducing effect of IC was destroyed by heating at 80 degrees C, and it was not blocked by the cytoskeleton inhibitor cytochalasin B. IL-1 inhibitors were not detected in the supernatants.

Frozen shoulder: current concepts.

The literature on frozen shoulder (FS) is reviewed. The etiology of FS is still not known and our understanding of the pathogenesis is limited. Studies on treatment programs under controlled conditions are few and incomplete. Further research is urgently needed.

Epidermal cell surface-associated IgG in patients with primary Sjögren's syndrome: in vitro evidence for immune complex binding.

In vivo deposits of IgG have previously been demonstrated in the epidermal intercellular area of clinically unaffected skin from 68% of patients with primary Sjögren's syndrome (primary SS). This study compared circulating IgG from patients with primary SS with that from secondary SS in their ability to bind normal human epidermal cells in vitro. We observed a granular pattern of IgG binding to the normal epidermal cell surfaces with 9 of 18 sera from patients with primary SS (50%), 3 of 19 sera from patients with SS secondary to rheumatoid arthritis (16%) (p = 0.025), and none of 24 normal control sera (p less than 0.001). In a subsequent analysis of polyethylene glycol separated sera from two normal controls and two primary SS patients, the epidermal IgG binding capacity was found only in the precipitates of the patients. These findings support our previous hypothesis that the in vivo intraepithelial IgG deposits in primary SS patients are due, at least in part, to cell surface-bound immune complexes.

Hereditary, complete deficiency of complement factor H associated with recurrent meningococcal disease.

Complement factor H (beta-1H globulin) is an important regulatory protein which inhibits the spontaneous complement activation via the alternative pathway. We describe a 15-year-old girl without any detectable factor H in plasma. She has had two episodes of meningococcal disease, but is otherwise completely healthy. Secondary to the factor-H deficiency, the levels of factor B, properdin, C3, and C5-C9 were strongly reduced due to spontaneous in vivo activation of the alternative complement pathway. Plasma C3dg was strongly elevated in spite of the factor-H deficiency; apparently erythrocyte CR1 substitutes for factor H in C3 degradation. Neither C3 nor complement lesions were demonstrable on her erythrocytes which did, however, show increased, spontaneous haemolysis in vitro in citrate plasma, but not in serum. The patient is a single child and her parents, who are unrelated and healthy, had half-normal levels of factor H. This reduction of factor H is sufficient to cause increased, spontaneous activation of the alternative pathway.

Effect of methylprednisolone on endotoxemia and complement activation during cardiac surgery.

The influence of high doses of methylprednisolone on complement activation and endotoxin concentration was investigated in two groups of eight patients undergoing coronary artery bypass grafting. Group 1 received methylprednisolone, 30 mg/kg, at the induction of anesthesia; group 2 served as the control group. The endotoxin concentrations increased significantly in both groups at the start of cardiopulmonary bypass. During cardiopulmonary bypass, the endotoxin concentrations were significantly higher in the steroid group compared with the control group (p less than 0.01). After completion of surgery, the endotoxin concentrations declined to almost zero within seven days in both groups. Complement activation was significantly reduced in the steroid-treated group during cardiopulmonary bypass compared with the control group (P less than 0.01). The clinical outcome after the first postoperative week was the same in the two groups. It appears that high-dose steroids can reduce complement activation during cardiopulmonary bypass, although the clearance of endotoxins may also be reduced.