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.

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.

A microtiter plate enzyme-linked immunosorbent assay for measuring C3b receptors on human erythrocytes.

An enzyme-linked immunosorbent assay was developed for quantitation of complement C3b receptors (C3bR) on human erythrocytes fixed in monolayer to microtiter plates. The disadvantages of macro test tube systems (large consumption of sample material and reagents, tedious washing procedures, cell loss and hemolysis) were avoided, and the fixed cells could be stored. In return a modest reduction in antigenicity induced by glutaraldehyde was inevitable. The calibration curve expressed a detection limit of about 10% and discrimination between levels of C3bR in the interval of about 10-120% of a standard erythrocyte with a high uptake of anti-C3b-receptor antibodies. The determinations of C3bR in normals as well as in patients varied within these limits, and showed a preponderance of low levels in the patients. The between-day coefficient of variation was 10.3%; the within-assay interplate and intraplate determinations respectively gave coefficients of variation of 9.7% and 6.2%. The method is suitable for further development and use for investigation of erythrocyte-bound immune complexes.

In vitro binding of IgG from patients with primary and secondary Sjögren's syndrome to different components of keratinized stratified squamous epithelia.

The ability of serum IgG from patients with Sjögren's syndrome (SS) to bind to keratinized stratified squamous epithelium of human skin or rat oesophagus was examined, using an indirect immunofluorescence technique. No in vitro binding of serum IgG to the cell membranes of normal human epidermis was demonstrated in 7 patients with primary SS and two normal controls. Thus, the intraepidermal in vivo IgG deposits previously found in 5 of the 7 patients could not be imitated in vitro. Examination for in vitro binding to rat oesophageal epithelium of serum IgG from 21 consecutive patients with primary SS, 19 consecutive patients with rheumatoid arthritis and secondary SS and 22 normal controls showed that antikeratin antibodies occur more frequently (p less than 0.001) in the patients with secondary SS compared to patients with primary SS and to normal controls.

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.

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.

[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.

[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.

[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.

[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.

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.

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.

Inhibition of natural killer cell activity by antigen-antibody complexes.

The natural killer (NK) cell activity of human peripheral blood mononuclear cells was found to be inhibited by precipitated tetanus toxoid anti-tetanus toxoid complexes (Te/aTe) as well as soluble Te/aTe. Preincubation of the immune complexes with protein A decreased the inhibition of NK cell activity. When mononuclear cells were preincubated with interferon (IF) or interleukin 2 (Il-2) before incubation with Te/aTe, the immune complex-induced inhibition was decreased, while IF or Il-2 added after incubation with the immune complexes had no effect. Using NK cell-enriched suspensions in a single cell agarose assay, the immune complexes were shown to inhibit NK cell activity by inhibiting the formation of effector/target cell conjugates.

Erythrocyte complement C3b receptor (CR1) levels and immune complex-induced manifestations in patients with primary Sjögren's syndrome.

To assess the importance of low C3b receptor (CR1) numbers on erythrocytes for the development of clinical features in patients with primary Sjögren's syndrome (SS), two groups of patients were selected for investigation--one without (n = 13), and one with (n = 21) extraglandular, possibly immune complex-induced, clinical manifestations during the disease course. A preponderance (p less than 0.01) of low CR1 levels was found in patients with primary SS (mean 57%) as compared with normal controls (mean 70%), but the CR1 levels did not differ between the two groups of patients. The CR1 values did not correlate with the levels of circulating immune complexes and C3d. Although the preponderance of low CR1 levels is pathogenetically intriguing, it appears to be of little help in the clinical assessment of patients with primary SS.

Erythrocyte CR1 (C3b/C4b receptor) levels and disease activity in patients with SLE.

Fifty-four patients with systemic lupus erythematosus (SLE) were examined for (1) CR1 (C3b/C4b receptor) levels on erythrocytes by an enzyme-linked immunosorbent assay, (2) levels of circulating immune complexes (IC) by a polyethylene glycol precipitation complement consumption method, and (3) concentrations of C3d split products in plasma by intermediate gel rocket immunoelectrophoresis. A preponderance of low CR1 levels was found among patients with SLE (mean 40%, range 13-106) as compared with normal controls (mean 70%, range 24-130) (p less than 0.001). The concentrations of circulating IC were elevated in 38% of 58 samples. The concentrations of C3d were elevated in 72%, and were positively correlated with the levels of IC (tau = 0.28; p less than 0.005) and with disease activity as assessed by a modification of the UCH/Middlesex criteria. Negative correlations were seen between the CR1 numbers and disease activity (p = 0.01), concentrations of circulating IC (tau = -0.14; p less than 0.005), and C3d (tau = -0.21; p less than 0.005). The changes found in CR1 levels on repeated study were, however, relatively small (less than or equal to 27%; median 5), even during periods of changing disease activity.

Complement C3b receptors on erythrocytes, circulating immune complexes, and complement C3 split products in patients with primary Sjögren's syndrome.

Twenty-one patients with primary Sjögren's syndrome (SS) and 22 age- and sex-matched healthy controls were examined for levels of C3b receptors (CR1) on erythrocytes (by an enzyme-linked immunosorbent assay), levels of circulating immune complexes (IC) (by a polyethylene glycol precipitation complement consumption method), and C3 split products, C3d and C3c (by intermediate gel rocket immunoelectrophoresis). CR1 varied within a wide range (20-124%), and a preponderance of low numbers was found among patients with primary SS (P less than 0.05). The levels of circulating IC and C3d were elevated in primary SS patients (P less than 0.01) and were mutually correlated (P less than 0.01; tau = 0.5), but levels of circulating IC and C3d did not correlate with CR1 values. C3c concentrations were the same in patients and controls. It is possible that the CR1 level serves as a predictor for the development of IC-induced manifestations, and the C3d concentration serves as an objective parameter for disease activity in primary SS.

Release of immune complexes bound to CR1 on erythrocytes; suramin inhibits factor I in the presence of EDTA.

An experimental model was established in order to study the release of immune complexes (IC) bound by complement C3b receptors (CR1) on human erythrocytes (RBC). Soluble tetanus toxoid anti-tetanus toxoid complexes were incubated with RBC in the presence of autologous serum at optimal conditions for binding. The RBC carrying complement-opsonized complexes were incubated with appropriate serum reagents, and it was shown that factor I was required for release of the complexes, which occurred without loss of CR1. Suramin was, irrespective of factor I, found to induce release of CR1-bound IC in the absence of EDTA, whereas factor I-mediated release was inhibited by suramin in the presence of EDTA. EDTA probably interfered through a charge-dependent interaction. These observations are decisive for the interpretation of in vitro experiments involving these reagents. The combination of EDTA and suramin was found inappropriate for use in quantitative determination of in vivo CR1-bound IC.

Erythrocyte CR1 determination using monoclonal antibody in a microtiter plate ELISA; receptors are not masked by immune complexes.

The microtiter plate ELISA using monoclonal antibody is a specific, sensitive and quantitative technique for measuring CR1 on human erythrocytes. The present investigations established that receptor occupancy by immune complexes did not affect the measurements. The monoclonal anti-CR1 antibody To5 bound unimpeded to receptors that had reacted with an excess of complement-opsonized tetanus toxoid anti-tetanus toxoid complexes prepared at antigen:antibody ratios between 32:1 and 1:8. The CR1 levels on erythrocytes from 11 patients with systemic lupus erythematosus (SLE) were not increased (P greater than 0.30) after release of CR1-bound immune complexes by incubation with factor I. Neither did the serum from these patients contain blocking anti-CR1 activity (P greater than 0.10). Additionally, the number of antigenic CR1 sites in 10 normals and in the 11 patients with SLE was well correlated with the number of functional receptor sites as assessed by binding of soluble complexes (P less than 0.001). These data establish that the true CR1 levels are determined using the microtiter plate ELISA for quantitation of CR1 in patients with diseases involving immune complexes and/or autoantibodies.

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.

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.