SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study.

OBJECTIVE: To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. DESIGN: Nationwide cohort study. SETTING: Sweden. POPULATION: From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. MAIN OUTCOME MEASURES: Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. RESULTS: During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). CONCLUSIONS: Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. TWEETABLE ABSTRACT: Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.

Bone response to surface-modified titanium implants: studies on the early tissue response to implants with different surface characteristics.

In a series of experimental studies, the bone formation around systematically modified titanium implants is analyzed. In the present study, three different surface modifications were prepared and evaluated. Glow-discharge cleaning and oxidizing resulted in a highly stoichiometric TiO2 surface, while a glow-discharge treatment in nitrogen gas resulted in implants with essentially a surface of titanium nitride, covered with a very thin titanium oxide. Finally, hydrogen peroxide treatment of implants resulted in an almost stoichiometric TiO2, rich in hydroxyl groups on the surface. Machined commercially pure titanium implants served as controls. Scanning Auger Electron Spectroscopy, Scanning Electron Microscopy, and Atomic Force Microscopy revealed no significant differences in oxide thickness or surface roughness parameters, but differences in the surface chemical composition and apparent topography were observed. After surface preparation, the implants were inserted in cortical bone of rabbits and evaluated after 1, 3, and 6 weeks. Light microscopic evaluation of the tissue response showed that all implants were in contact with bone and had a large proportion of newly formed bone within the threads after 6 weeks. There were no morphological differences between the four groups. Our study shows that a high degree of bone contact and bone formation can be achieved with titanium implants of different surface composition and topography.

A summer school on vaccinology: Responding to identified gaps in pre-service immunisation training of future health care workers.

Immunisation is one of the corner stones of public health. Most health care consumers see the health care worker as their major source of information on immunisation and vaccine safety. Doctors, nurses and midwives should be appropriately and timely trained for that role. Within the Vaccine Safety, Attitudes, Training and Communication (VACSATC) EU-project a specific work package focused on the possible improvements of pre-service training of future health care workers. Surveys to assess current pre-service training about knowledge, skills and competences towards immunisation were distributed to students and curriculum managers of medical schools, universities and nursing training institutions in seven EU countries. In all responding institutions training on vaccines and immunisation is disseminated over a wide range of courses over several academic years. Topics as immunology and vaccine-preventable diseases are well covered during the pre-service training but major gaps in knowledge and competences were identified towards vaccine safety, communication with parents, addressing anti-vaccine arguments and practical skills. This assessment underlined the rationale for adequate pre-service training and identified opportunities for improvement of pre-service training. A prototype of an accurate pre-service immunisation curriculum was developed, implemented and evaluated in the summer of 2009 with a group of 36 students from 19 countries during a summer school on vaccinology at the Antwerp University, Belgium.

Asylum-seeking children with severe loss of activities of daily living: clinical signs and course during rehabilitation.

AIM: To investigate whether severe loss of activities of daily living (ADL) in asylum-seeking children is associated with physical disease or toxic influences and to describe the clinical course during the recovery process. METHODS: A total of 29 asylum-seeking children with severe loss of ADL were regularly assessed by physical examinations, laboratory tests and a structured evaluation of their ADL status during rehabilitation. RESULTS: A total of 12 children had previously recorded suicide attempts and 21 were recorded to have experienced traumatic events in their country of origin. The mean time from turning point to recovery was 6 months. Of the study participants, 22 needed enteral feeding and 18 gained weight during recovery. All children had a pulse rate and systolic blood pressure within the normal range. No sign of intoxication or physical disease was identified in laboratory tests or clinical examinations, with the exception of one case of epilepsy. CONCLUSION: Physical disease, pharmacological sedation or anorexia nervosa was not considered to be a probable cause of the loss of ADL in these children. The high rate of psychosocial risk factors and the stressful event of being in an asylum-seeking process call for further investigation of psychosomatic mechanisms.

Increase of circulating CD8+CD57+ lymphocytes after measles infection but not after measles vaccination.

Natural measles virus infection is recognised to induce immunosuppression, contributing to an increased susceptibility to other infections. A cell population that could be involved in this process is the CD8CD57 double-positive lymphocyte subset (CD8+CD57+), known to be significantly expanded in some viral infections, e.g. human immunodeficiency virus (HIV) infection. We therefore studied the level of CD8+CD57+ lymphocytes during measles infection and measles vaccination. Twenty-two measles patients were examined 5-57 days after the onset of fever and several months later. Healthy, age-matched controls were examined twice. Eleven children receiving measles-mumps-rubella (MMR) vaccination were examined before, 9-19 days and 5-9 months afterwards. Blood samples were analysed for the proportion of peripheral blood mononuclear cells carrying both CD8 and CD57, and for other cell surface markers (CD4, CD14, CD3, CD16(CD56) or CD20). Elevated proportions of CD8CD57 double-positive cells were found in the peripheral blood of children with natural measles early after infection (p < 0.05), whereas the proportion of other cell surface markers remained stable. No corresponding change in CD8+CD57+ lymphocytes was noted in MMR-vaccinated children or in healthy controls. Since CD8+CD57+ lymphocytes could be related to the immunosuppression seen in some viral infections, our finding of elevated CD8CD57 double-positive lymphocytes during acute measles infection would suggest that this population of lymphocytes is involved in measles-induced immunosuppression. The absence of an increase of CD8CD57 in children vaccinated with the conventional live attenuated measles vaccine, in contrast to children with natural measles infection, would thus indicate that the vaccine does not induce immunosuppression as measured in our in vitro system.

Haemocompatibility evaluation of DLC- and SiC-coated surfaces.

Diamond-like carbon (DLC) and silicon carbide (SiC) coatings are attractive because of low friction coefficient, high hardness, chemical inertness and smooth finish, which they provide to biomedical devices. Silicon wafers (Si(waf)) and silicone rubber (Si(rub)) plates were coated using plasma-enhanced chemical vapour deposition (PE-CVD) techniques. This article describes: 1- the characterization of modified surfaces using attenuated total reflection-Fourier transform infrared spectroscopy (ATR/FTIR) and contact angle measurements, 2- the results of three in-vitro haemocompatibility assays. Coated surfaces were compared to uncoated materials and various substrates such as polymethylmethacrylate (PMMA), polyethylene (LDPE), polydimethylsiloxane (PDMS) and medical steel (MS). Thrombin generation, blood platelet adhesion and complement convertase activity tests revealed the following classification, from the most to the least heamocompatible surface: Si(rub)/ DLC-Si(rub)/ DLC-Si(waf)/ LDPE/ PDMS/ SiC-Si(waf)/ Si(waf)/ PMMA/ MS. The DLC coating surfaces delayed the clotting time, tended to inhibit the platelet and complement convertase activation, whereas SiC-coated silicon wafer can be considered as thrombogenic. This study has taken into account three events of the blood activation: coagulation, platelet activation and inflammation. The response to those events is an indicator of the in vitro haemocompatibility of the different surfaces and it allows us to select biomaterials for further in vivo blood contacting investigations.

Adhesion of Pseudomonas aeruginosa strains to untreated and oxygen-plasma treated poly(vinyl chloride) (PVC) from endotracheal intubation devices.

Pseudomonas aeruginosa pneumonia is a life threatening complication in mechanically ventilated patients that requires the ability of the bacteria to adhere to, and colonize the endotracheal intubation device. New strategies to prevent or reduce these nosocomial infections are greatly needed. We report here the study of a set of P. aeruginosa clinical isolates, together with specific mutants, regarding their adhesion on native and chemically modified poly(vinyl chloride) (PVC) surfaces from endotracheal intubation devices. The adhesion of the different strains to untreated PVC varied widely, correlating with several physico-chemical characteristics known to influence the attachment of bacteria to inert surfaces. The adhesion patterns were compared to the calculations obtained with the DLVO theory of colloidal stability. These results illustrate the importance of testing different clinical isolates when investigating bacterial adhesion. Oxygen plasma treatment of the PVC pieces yielded a hydrophilic surface and reduced the number of adhering bacteria by as much as 70%. This reduction is however unlikely to be sufficient to prevent P. aeruginosa colonization of endotracheal intubation devices.

Hydrogen desorption from sand-blasted and acid-etched titanium surfaces after glow-discharge treatment.

Hydrogen desorption from argon plasma-treated titanium implants with a high surface roughness was studied. Implants with a high surface roughness have shown an increase in mechanical stability in bone tissue and a different behavior of osteoblasts in vitro. High surface roughness was produced by grit blasting and acid etching, resulting in an increase of the sub-surface hydrogen concentration and the formation of a titanium hydride. After an argon plasma treatment the surface oxide, which always covers titanum surfaces exposed to an oxygen-containing environment, and some of the hydrogen were sputtered away, decreasing the hydrogen concentration in the sub-surface region. Nuclear reaction analysis was used to determine the hydrogen concentration as a function of depth. The total amount of sub-surface (down to a depth of < or = 2 microm) hydrogen remaining after plasma treatment decreased with increasing plasma intensity to below the levels observed in non-acid-etched samples (approximately 1-2%). Thermal desorption spectroscopy was used for desorption studies and investigation of H(2) desorption activation energies. With a surface oxide present, the onset of hydrogen desorption is at ca 400 degrees C, which is the oxide decomposition temperature in vacuum, with an activation energy of ca 2 eV/molecule of H(2). After plasma treatment, that is, without surface oxide present, the onset of desorption was observed at ca 300 degrees C and with an activation energy of ca 0.8 eV/molecule of H(2), indicating a bulk diffusion-limited desorption.

Glow discharge plasma treatment for surface cleaning and modification of metallic biomaterials.

Glow discharge plasma treatment is a frequently used method for cleaning, preparation, and modification of biomaterial and implant surfaces. The merits of such treatments are, however, strongly dependent on the process parameters. In the present work the possibilities, limitations, and risks of plasma treatment for surface preparation of metallic materials are investigated experimentally using titanium as a model system, and also discussed in more general terms. Samples were treated by different low-pressure direct current plasmas and analyzed using Auger electron spectroscopy (AES), x-ray photoelectron spectroscopy (XPS), atomic force microscopy, scanning electron microscopy, and light microscopy. The plasma system is a home-built, ultra-high vacuum-compatible system that allows sample introduction via a load-lock, and precise control of pressure, gas composition and flow rate, etc. This system allows uniform treatment of cylindrical and screw-shaped samples. With appropriate plasma parameters, argon plasma remove all chemical traces from former treatments (adsorbed contaminants and other impurities, and native oxide layers), in effect producing cleaner and more well-controlled surfaces than with conventional preparation methods. Removal (sputtering) rates up to 30 nm/min are possible. However, when inappropriate plasma parameters are used, the result may be increased contamination and formation of unintentional or undesired surface layers (e.g., carbides and nitrides). Plasma-cleaned surfaces provide a clean and reproducible starting condition for further plasma treatments to form well-controlled surface layers. Oxidation in pure O2 (thermally or in oxygen plasmas) results in uniform and stoichiometric TiO2 surface oxide layers of reproducible composition and thicknesses in the range 0.5-150 nm, as revealed by AES and XPS analyses. Titanium nitride layers were prepared by using N2 plasmas. While mild plasma treatments leave the surface microstructure unaffected, heavy plasma treatment can give rise to dramatic morphologic changes. Comparison of these results with corresponding analyses of commercial implants and electropolished and/or anodically oxidized samples shows that the plasma treatment offers superior control of the surface status. However, it is also shown that improper control of the plasma process can produce unwanted and irreproducible results.

Bone response to surface modified titanium implants - studies on the tissue response after 1 year to machined and electropolished implants with different oxide thicknesses.

The bone formation around titanium implants with varied surface properties was investigated after 1 year in rabbits. Machined and electropolished samples with and without thick, anodically formed surface oxides were prepared, surface characterized and inserted in the cortical bone of rabbits. Scanning electron microscopy, scanning Auger electron spectroscopy and atomic force microscopy revealed marked differences in oxide thickness, surface topography and roughness, but no significant differences in surface chemical composition between the different groups of implants. Light microscopic morphology and morphometry showed that all implants were in contact with bone and had a large proportion of bone within the threads. There were no significant differences between the differently prepared implant groups. Our study shows that a high degree of bone contact and bone formation is achieved after 1 year with titanium implants which are modified with respect to oxide thickness and surface topography. There is no indication that a reduction of surface roughness, which in the initial phase decreases the rate of bone formation, had any influence on the amount of bone after 1 year in rabbit cortical bone.

Bone response to surface-modified titanium implants: studies on the early tissue response to machined and electropolished implants with different oxide thicknesses.

The bone formation around titanium implants with varied surface properties is investigated. Machined and electropolished samples with and without thick, anodically formed surface oxides were prepared, surface characterized and inserted in the cortical bone of rabbits (1, 3 and 6 weeks). Scanning electron microscopy, scanning Auger electron spectroscopy and atomic force microscopy revealed marked differences in oxide thickness, surface topography and roughness, but no significant differences in surface chemical composition, between the different groups of implants. Light microscopic morphology and morphometry showed that all implants were in contact with bone and had a large proportion of bone within the threads at 6 weeks. The smooth, electropolished implants, irrespective of anodic oxidation, were surrounded by less bone than the machined implants after 1 week. After 6 weeks the bone volume as well as the bone-implant contact were lower for the merely electropolished implants than for the other three groups. Our study shows that a high degree of bone contact and bone formation are achieved with titanium implants which are modified with respect to oxide thickness and surface topography. However, the result with the smooth (electropolished) implants indicates that a reduction of surface roughness, in the initial phase, decreases the rate of bone formation in rabbit cortical bone.

Response to a booster dose 18 months after a low anti-HBs response (10-99 IU/l) to three doses of intradermally or intramuscularly administered recombinant hepatitis B vaccine.

The response to a booster dose, given by the same route 18 months after the completion of the primary vaccination scheme, was studied in hospital staff members who responded with anti-HBs levels in the range of 10-99 IU/l after three intradermal (i.d., n = 51) or intramuscular (i.m., n = 11) doses of recombinant hepatitis B virus (HBV) vaccine administered at 0, 1 and 6 months. At the time of boostering the anti-HBs levels had declined to < 10 IU/l in 44/51 (86%) of the i.d. and 10/11 of the i.m. vaccines. All i.m. and 90% of i.d. vaccinees responded to the booster dose with anti-HBs level > or = 10 IU/l, and with geonmetric mean titres 1,074 IU/l and 121 IU/l, respectively. It was concluded that all i.m. and 90% of i.d. vaccinees with an initial anti-HBs response of 10-99 IU/l after three doses of HBV vaccine (among whom the anti-HBs levels in the majority had declined < 10 IU/l) mounted an anti-HBs level > or = 10 IU/l after a booster dose. The anti-HBs concentrations were generally higher after i.m. than i.d. booster doses in accordance with the response to primary vaccination.

Titanium with different oxides: in vitro studies of protein adsorption and contact activation.

Adsorption of albumin (HSA) and fibrinogen (Fib) from human blood plasma onto titanium surfaces with varying oxide properties was studied with an enzyme-linked immunosorbent assay. The intrinsic activation of blood coagulation (contact activation) was studied in vitro using a kallikrein-sensitive substrate. The sample surfaces were characterized with Fourier transform Raman spectroscopy. Auger electron spectroscopy and atomic force microscopy. Low Fib and high HSA adsorption was observed for all titanium samples except for the radio frequency plasma-treated and water-incubated samples, which adsorbed significantly lower amounts of both. Oxide thickness and carbon contamination showed no influence on protein adsorption or contact activation. Smooth samples with a surface roughness (Rrms) < 1 nm showed some correlation between surface wettability and adsorption of Fib and HSA, whereas rough surfaces (Rrms > 5 nm) did not. To varying degrees, all titanium surfaces indicated activation of the intrinsic pathway of coagulation as determined by their kallikrein formation in plasma.

Prevalence of antibodies against hepatitis C virus infection among health care workers in Stockholm.

The prevalence of hepatitis C virus (HCV) markers was investigated among health care staff with a high rate of exposure to blood or needle-stick injuries. After screening sera in pools of 10 at a time and individual testing of all reactive pools, totally 6 of 880 (0.7%; 95% confidence interval, 0.25-14.8%) were positive for anti-HCV, a figure of the same order as that found among Swedish first-time blood donors. Among the seropositives, all of five evaluable had been exposed to blood and four of five to needle-stick injuries. Our data suggest that HCV, in addition to hepatitis B virus, may constitute an occupational hazard for health care workers in Stockholm, even though the risk appears to be low, and personal risk factors such as intravenous drug abuse or blood transfusion could not be ruled out as sources of the infection.

Immunosuppression after measles vaccination.

The influence of conventional live attenuated measles vaccine on cellular immune responsiveness was investigated in Sweden and Guinea-Bissau. Sixteen children in a residential area in Bissau and 16 living in southern Stockholm were examined before and 8-10 days after vaccination. Lymphoproliferation was measured to concanavalin A (con-A), PPD and tetanus toxoid (TT) using a whole-blood 3H-thymidine incorporation assay. Stimulation indices were significantly lower after vaccination than before, in the case of con-A (p = 0.03) and TT (p = 0.01) in the Guinean children and in the case of PPD (p = 0.009) and TT (p = 0.03) in the Swedish children. Stimulation of lymphocytes from measles-immune children with measles antigens resulted in weak lymphoproliferative responses. These observations may be relevant to the increased mortality found in children immunized with high-titre measles vaccines, as compared to controls, in recent studies. The study confirms the applicability and usefulness under field conditions of the whole blood version of the thymidine incorporation assay.

Seroconversion after additional vaccine doses to non-responders to three doses of intradermally or intramuscularly administered recombinant hepatitis B vaccine.

Hospital staff members who failed to respond (anti-HBs < 10 IU/l) after 3 doses of a recombinant hepatitis B (HBV) vaccine (given either as 20 micrograms intramuscularly (n = 8) or 2 micrograms intradermally (n = 15)) received 1 or 2 additional doses by the same route as the initial vaccination. After the first additional dose, 12/23 responded with anti-HBs levels > or = 10 IU/l and after the second, another 2/5 responded, corresponding to a total response rate of 61%. No significant difference was seen in the response rate according to vaccination route, gender, age, or whether the vaccinee was a smoker or not. In this limited study some 50% of non-responders to 3 intradermal or intramuscular doses of recombinant HBV vaccine seroconverted after an additional 1-2 doses given by the same route as the initial vaccination, suggesting that additional doses can be administered by the same route as the initial one.

Comparative evaluation of a new molecular method for typing Staphylococcus epidermidis.

The discriminatory powers of several techniques for typing Staphylococcus epidermidis were evaluated in an epidemiological study of bacteria isolated from intensive care patients and from neonates. Genomic DNA fingerprinting using BclI restriction endonuclease was an effective epidemiological marker. The distinct restriction fragment profiles produced with this enzyme were highlighted with specific probes in a Southern blot technique. Cloned Escherichia coli rRNA gene probes proved to have lower discriminatory power and be less suitable for intraspecies typing. However, a panel of random genomic Staphylococcus epidermidis DNA clones provided almost the same level of discrimination as the DNA fingerprinting technique and also provided a clearer profile. DNA and gene fingerprinting techniques were reproducible and highly discriminatory compared to typing based on antigen and plasmid profiles, antibiotic susceptibility patterns and biotypes.