Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

The role of domestic reservoirs in domestically acquired Salmonella infections in Norway: epidemiology of salmonellosis, 2000-2015, and results of a national prospective case-control study, 2010-2012.

In Norway, incidence of sporadic domestically acquired salmonellosis is low, and most frequently due to Salmonalla Typhimurium. We investigated the risk factors for sporadic Salmonella infections in Norway to improve control and prevention measures. Surveillance data for all Salmonella infections from 2000 to 2015 were analysed for seasonality and proportion associated with domestic reservoirs, hedgehogs and wild birds. A prospective case-control study was conducted from 2010 to 2012 by recruiting cases from the Norwegian Surveillance System for Communicable Diseases and controls from the Norwegian Population Registry (389 cases and 1500 controls). Univariable analyses using logistic regression were conducted and a multivariable model was developed using regularised/penalised logistic regression. In univariable analysis, eating snow, dirt, sand or playing in a sandbox (aOR 4.14; CI 2.15-7.97) was associated with salmonellosis. This was also the only exposure significantly associated with illness in the multivariable model. Since 2004, 34.2% (n = 354) of S. Typhimuirum cases had an MLVA profile linked to a domestic reservoir. A seasonal trend with a peak in August for all Salmonella types and in February for S. Typhimurium was observed. Indirect exposure to domestic reservoirs remains a source of salmonellosis in Norway, particularly for children. Information to the public about avoiding environmental exposure should be strengthened and initiatives to combat salmonellosis in the food chain should be reinforced.

Necrotizing soft tissue infections - a multicentre, prospective observational study (INFECT): protocol and statistical analysis plan.

BACKGROUND: The INFECT project aims to advance our understanding of the pathophysiological mechanisms in necrotizing soft tissue infections (NSTIs). The INFECT observational study is part of the INFECT project with the aim of studying the clinical profile of patients with NSTIs and correlating these to patient-important outcomes. With this protocol and statistical analysis plan we describe the methods used to obtain data and the details of the planned analyses. METHODS: The INFECT study is a multicentre, prospective observational cohort study. Patients with NSTIs are enrolled in five Scandinavian hospitals, which are all referral centres for NSTIs. The primary outcomes are the descriptive variables of the patients. Secondary outcomes include identification of factors associated with 90-day mortality and amputation; associations between affected body part, maximum skin defect and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score and 90-day mortality; 90-day mortality in patients with and without acute kidney injury (AKI) and LRINEC score of six and above or below six; and association between affected body part at arrival and microbiological findings. Exploratory outcomes include univariate analyses of baseline characteristics associations with 90-day mortality. The statistical analyses will be conducted in accordance with the predefined statistical analysis plan. CONCLUSION: Necrotizing soft tissue infections result in severe morbidity and mortality. The INFECT study will be the largest prospective study in patients with NSTIs to date and will provide important data for clinicians, researchers and policy makers on the characteristics and outcomes of these patients.

Increased dietary protein for lactating sows affects body composition, blood metabolites and milk production.

Hyper-prolific sows nurse more piglets than less productive sows, putting a high demand on the nutrient supply for milk production. In addition, the high production level can increase mobilization from body tissues. The effect of increased dietary protein (104, 113, 121, 129, 139 and 150 g standardized ileal digestible (SID) CP/kg) on sow body composition, milk production and plasma metabolite concentrations was investigated from litter standardization (day 2) until weaning (day 24). Sow body composition was determined using the deuterium oxide dilution technique on days 3 and 24 postpartum. Blood samples were collected weekly, and milk samples were obtained on days 3, 10 and 17 of lactation. Litter average daily gain (ADG) peaked at 135 g SID CP/kg (P < 0.001). Sow BW and back fat loss reached a breakpoint at 143 and 127 g SID CP/kg (P < 0.001). Milk fat increased linearly with increasing dietary SID CP (P < 0.05), and milk lactose decreased until a breakpoint at 124 g SID CP/kg and 5.3% (P < 0.001) on day 17. The concentration of milk protein on day 17 increased until a breakpoint at 136 g SID CP/kg (5.0%; P < 0.001). The loss of body protein from day 3 until weaning decreased with increased dietary SID CP until it reached a breakpoint at 128 g SID CP/kg (P < 0.001). The body ash loss declined linearly with increasing dietary SID CP (P < 0.01), and the change in body fat was unaffected by dietary treatment (P=0.41). In early lactation (day 3 + day 10), plasma urea N (PUN) increased linearly after the breakpoint at 139 g SID CP/kg at a concentration of 3.8 mmol/l, and in late lactation (day 17 + day 24), PUN increased linearly after a breakpoint at 133 g SID CP/kg (P < 0.001) at a concentration of 4.5 mmol/l. In conclusion, the SID CP requirement for sows was estimated to 135 g/kg based on litter ADG, and this was supported by the breakpoints of other response variables within the interval 124 to 143 g/kg.

An outbreak of Salmonella Typhimurium infections in Denmark, Norway and Sweden, 2008.

In November-December 2008, Norway and Denmark independently identified outbreaks of Salmonella Typhimurium infections characterised in the multiple-locus variable number of tandem repeats analysis (MLVA) by a distinct profile. Outbreak investigations were initiated independently in the two countries. In Denmark, a total of 37 cases were identified, and multiple findings of the outbreak strain in pork and pigs within the same supply chain led to the identification of pork in various forms as the source. In Norway, ten cases were identified, and the outbreak investigation quickly indicated meat bought in Sweden as the probable source and the Swedish authorities were alerted. Investigations in Sweden identified four human cases and two isolates from minced meat with the distinct profile. Subsequent trace-back of the meat showed that it most likely originated from Denmark. Through international alert from Norway on 19 December, it became clear that the Danish and Norwegian outbreak strains were identical and, later on, that the source of the outbreaks in all three countries could be traced back to Danish pork. MLVA was instrumental in linking the outbreaks in the different countries and tracing the source. This outbreak illustrates that good international communication channels, early alerting mechanisms, inter-sectoral collaboration between public health and food safety authorities and harmonised molecular typing tools are important for effective identification and management of cross-border outbreaks. Differences in legal requirements for food safety in neighbouring countries may be a challenge in terms of communication with consumers in areas where cross-border shopping is common.

Prevalence surveillance system of nosocomial infections in Norway.

In 1996, the Norwegian Ministry of Health issued regulations on the prevention of nosocomial infections (NIs). The regulations were revised in 2005. As part of the infection control programme, hospitals and long-term care facilities are obliged to have a surveillance system for NIs in place and to report the results to the Norwegian Institute of Public Health.

Sows with high milk production had both a high feed intake and high body mobilization.

Selection for increased litter size have generated hyper-prolific sows that nurses large litters, however limited knowledge is available regarding the connection between milk production, feed intake and body mobilization of these modern sows. The aim of the current study was to determine what characterized sows with high milk production and nursing large litters, differences between sows of different parities and effects of lactational performance on next reproductive cycle. In total 565 sows (parity 1 to 4) were studied from 7 days before farrowing until weaning. On day 2 postpartum litters were standardized to 14 piglets. Weight and back fat thickness of sows were measured at day 7 prepartum, day 2 postpartum and at weaning. Litters were weighed at day 2 and at weaning. Pearson correlation coefficients between variables were calculated and regression models were developed. The average daily feed intake (ADFI) of the sows was 6.1±1.1 kg/day, average daily gain (ADG) of the litter was 2.92±0.53 kg/day and sows weaned 13.0±1.1 piglets. First parity sows generally had a lower ADFI and milk production and a decrease in total born piglets in next litter compared with parity 2 to 4 sows, which could be explained by a relatively higher proportion of their body reserves being mobilized compared with multiparous sows. The ADG of the litter was positively related by ADFI of the sows, litter size and BW loss and increasing the ADFI with 1 kg/day throughout lactation likely increased the ADG of the litter with 220 to 440 g/day in parity 1 to 4, respectively. Increasing the ADFI by 1 kg/day reduced the BW loss with 6.6 to 13.9 kg of parity 1 to 4 sows, respectively, during lactation, whereas increasing the average milk yield with 1 kg/day raised the BW loss with 4.3 to 21.0 kg of the four parities during lactation. The number of total born piglets in the next litter was positively related to the number of piglets born in the previous litter. In conclusion, both a high feed intake and a high mobilization of body reserves was a prerequisite for a high milk production. The sows might be very close to the physical limit of what they can ingest and future research should therefore, focus on optimizing the dietary energy and nutrient concentrations of diets for lactating hyper-prolific sows and herein distinguish between primiparous and multiparous sows.

Impact of fat source and dietary fibers on feed intake, plasma metabolites, litter gain and the yield and composition of milk in sows.

Sow lactation diets often include fat sources without considering the impact on digestion, metabolism and performance. Fiber ingredients may reduce feed intake and are often completely excluded from lactation diets, although locally available ingredients may be cost-efficient alternatives to partly replace cereals in lactation diets. Thus, a standard lactation diet low in dietary fiber, and two high-fiber diets based on sugar beet pulp (SBP) or alfalfa meal (ALF) were formulated. The SBP diet was high in soluble non-starch polysaccharides (NSP), whereas ALF being high in insoluble NSP. Each diet was divided in three portions and combined with 3% soybean oil (SOYO), palm fatty acid distillate (PFAD), or glycerol trioctanoate (C8TG) as the dietary fat source. Equal amounts of metabolizable energy were fed to 36 second parity sows from day 105 of gestation and throughout lactation to study the impact on feed intake, plasma metabolites, milk production and litter performance. Backfat thickness and BW of sows were recorded on days 3, 17 and 28 of lactation; blood was sampled on days 3 and 17; milk samples were obtained on days 3, 10, 17 and 24 of lactation; and piglets were weighed on days 2, 7, 14, 21 and 28 of lactation. Litter gain and milk yield during late lactation were greater in sows fed C8TG or SOYO than in sows fed PFAD (P=0.05), whereas loss of BW (P=0.60) and backfat (P=0.70) was unaffected by fat source. Milk protein on days 3 and 10 of lactation were lower in C8TG and SOYO sows, than in PFAD sows (P<0.05). The lowest concentration of plasma lactate on day 3 (P<0.05) and plasma acetate on day 17 (P<0.05) was observed in C8TG sows. Milk yield was unaffected by fiber treatment (P=0.43), whereas milk protein concentration was lowest in ALF sows (P<0.05). Feed intake tended to be lower (P=0.09), and litter gain during the 3rd week of lactation was decreased (P<0.05) in SBP sows. In conclusion, performance was enhanced in SOYO and C8TG compared with PFAD sows, possibly associated with reduced energy intake in PFAD-fed sows. Furthermore, the SBP diet seemed to impair feed intake and litter gain at peak lactation, suggesting that effects of the dietary fiber fraction on energy intake determines the potential inclusion level of fiber-rich ingredients.

Dietary supplement rich in fiber fed to late gestating sows during transition reduces rate of stillborn piglets.

The beneficial effects of dietary fiber (DF) from a behavioral and welfare perspective have been thoroughly studied. However, data on the effects of DF on reproductive performance are scarce. Therefore, the aim of this study was to investigate the impact of increased DF supply during the last 2 wk of gestation on stillbirth rate, preweaning mortality, and total piglet mortality. A total of 644 sows were selected for the experiment from a commercial farm, and the sows were inseminated in weekly batches. Sows in the control group ( = 310) were fed according to the normal feeding strategy of the farm with a gestation diet until 1 wk before expected farrowing, then a transition diet until d 5 of lactation, and then a lactation diet until weaning. Sows in the treatment group ( = 334) were fed as the control group except that 280 g/d of the gestation diet (from d 102 to 108 of gestation) and 570 g/d of the transition diet (from d 109 of gestation until farrowing) was daily replaced with 350 and 700 g/d, respectively, of a DF-rich supplement. Both groups received isocaloric diets on a NE basis. The numbers of live-born and stillborn piglets as well as mortality of live-born piglets with presumed causes of death were recorded. The supplemented DF reduced the proportion of stillborn piglets from 8.8 to 6.6% ( < 0.001) and mortality of total born piglets from 22.3 to 19.9% ( = 0.004) but had no impact on preweaning mortality of the piglets ( = 0.21). Moreover, supplemented DF reduced the proportion of death due to poor viability ( < 0.001; 2.8 vs. 1.5% in the control and treatment groups, respectively) and prevalence of piglet diarrhea ( = 0.004; 0.7 vs. 0.3% in the control and treatment groups, respectively). Crushing, low birth weight, and poor viability were the top 3 contributors to preweaning mortality of live-born piglets, in descending order. In conclusion, the supplemented DF reduced the proportion of stillborn piglets and total piglet mortality as well as mortality due to poor viability and piglet diarrhea in lactation.

Amino acid digestibility by weanling pigs of processed ingredients originating from soybeans, 00-rapeseeds, or a fermented mixture of plant ingredients.

An experiment was conducted to determine the apparent ileal digestibility (AID) and the standardized ileal digestibility (SID) of CP and AA in 4 sources of processed soybean products, in conventional dehulled soybean meal (SBM-CV), in conventional 00-rapeseed expellers (RSE), and in a fermented coproduct mixture (FCM) that contained rapeseed meal, wheat, soy molasses, and potato peel fed to weanling pigs. The 4 processed soybean products included 2 sources of enzyme-treated soybean meal (ESBM-1 and ESBM-2), extruded soybean meal, and soy protein concentrate (SPC). Twenty-seven weanling barrows (9.29 ± 0.58 kg initial BW) were surgically equipped with a T-cannula in the distal ileum. Pigs were randomly allotted to three 9 × 5 Youden squares with 9 pigs and five 7-d periods in each square. Seven cornstarch-based diets were prepared using each of the protein sources as the sole source of CP and AA. A N-free diet was prepared to calculate basal endogenous losses of CP and AA, and this diet was fed to 2 groups of pigs, which resulted in a total of 9 dietary treatments. Results indicate that the SID of CP was greater ( < 0.05) in ESBM-1 than in SPC, RSE, or FCM. The SID of Arg, His, Ile, Leu, Met, and Phe were greater ( < 0.05) in ESBM-1 than in SPC, and the SID of Lys was greater ( < 0.05) in SBM-CV than in ESBM-2. The SID of Thr, Trp, Val, and total indispensable AA were not different among the soybean products, but the SID of total dispensable AA in ESBM-1 was greater ( < 0.05) than in SPC. Therefore, the SID of total AA was greater ( < 0.05) in ESBM-1 than in SPC, but no other differences were observed among soybean meal (SBM) products. The SID of most AA in RSE and the SID of all AA in FCM were less ( < 0.05) than in all the SBM products, but the SID of all AA in RSE were greater ( < 0.05) than in FCM. Results of this research indicate that although processing of SBM results in increased concentration of CP, processing may also reduce the digestibility of AA, which is likely due to heat damage during processing. There are, however, differences among processed soy products, with some products having greater SID of AA than others. Results also indicate that fermentation of a mixture of rapeseed meal, wheat, and relatively low quality coproducts does not result in SID values that are similar to those of unfermented 00-rapeseed expellers or soybean products.

The effect of increasing the dietary valine-to-lysine ratio on sow metabolism, milk production, and litter growth.

A study was conducted to investigate the effect of increasing the dietary valine-to-lysine ratio (Val:Lys) for lactating sows weaning more than 12 piglets. Five hundred fifty-eight sows (parity 1 to 4) were allotted to 6 dietary treatments from 2 d postpartum, when litters were standardized to 14 piglets. Diets were analyzed to have a total dietary Val:Lys of 0.84, 0.86, 0.88, 0.90, 0.95, or 0.99:1. On all 558 sows, BW, back fat thickness (BF), and litter weight were registered at d 108 of gestation and d 2 and 25 (weaning) postpartum. On a subsample of 72 sows, additional measurements were made: sow BW and BF were measured on d 17 and litter weight was measured on d 10 and 17, and blood and urine samples were collected weekly. The litter size at weaning was not affected by the dietary Val:Lys ( = 0.23) and, on average, the sows weaned 13.0 ± 1.1 piglets. Average daily gain of the litter (2.93 ± 0.53 kg/d; = 0.84), litter weight at weaning ( = 0.67), the average milk yield (11.3 ± 1.4 kg/d; = 0.49), and milk contents of fat ( = 0.57), protein ( = 0.18), and lactose ( = 0.20) were not affected by the dietary Val:Lys. Increasing the dietary Val:Lys increased the milk concentration of Val ( < 0.05) and Ile ( < 0.01). The change in sow BW and BF were similar for all sows from d 2 to 17, d 17 to 25, and d 2 to 25 ( > 0.05). During lactation, sows, on average, had a BW and back fat loss of 22.1 ± 12.7 kg and 2.9 ± 1.7 mm, respectively. Plasma concentrations of glucose ( = 0.26), lactate ( = 0.95), urea N ( = 0.84), NEFA ( = 0.24), and creatinine ( = 0.42); urine concentration of creatinine ( = 0.57); and concentrations of AA in whole blood ( > 0.05) were not affected by the dietary Val:Lys. In conclusion, there was no effect of increasing the total dietary Val:Lys above 0.84:1 on sow metabolism and litter performance during lactation.

Reproductive performance of "nurse sows" in Danish piggeries.

The use of nurse sows in Danish piggeries is common practice because of large litter sizes; however, the effect of being selected as a nurse sow on subsequent reproductive performance is unknown. Therefore, the aim of this study was to quantify a nurse sow's reproductive performance in the subsequent litter. Nurse sows were defined as sows weaning their own litter at least 18 days postpartum and thereafter nursing another litter (nurse litter) before service. Data (2012-2013) from 20 piggeries with more than 14.5 live born piglets per litter and a stable distribution of sows among parities over time were selected. Records from 79,864 litters were obtained and analyzed using mixed linear and logistic regression models. The average lactation lengths were 40.3 days for nurse sows and 27.8 days for non-nurse (normal) sows. Nurse sows weaned on average 12.4 piglets and subsequently 11.5 nurse piglets, whereas non-nurse weaned 11.7 piglets in their single weaning. There was no difference in re-service rate between nurse and non-nurse sows in the subsequent reproductive cycle. Subsequent litter size in the next reproductive cycle was higher for nurse sows than that for non-nurse sows (18.69 vs. 18.11 total born piglets; P < 0.001). Nurse sows were of a slightly lower parity than non-nurse sows (3.12 vs. 3.27, P < 0.001), and nurse sows had an increased weaning to estrus interval compared to non-nurse sows (4.23 vs. 4.19 days, P < 0.001). The results indicate that nurse sows were selected among sows nursing large litters and could therefore suggest that these sows represent the best percentile of sows in a given piggery. In conclusion, this survey indicated no negative effects of being selected as a nurse sow on the subsequent reproductive performance. On the contrary, nurse sows gave birth to more piglets compared to non-nurse sows in their subsequent litter.

Herpes simplex virus type 1 inhibits in vitro differentiation and selected functions of human blood-derived monocytes.

We have studied the effect of herpes simplex virus type 1 (HSV1) infection on in vitro differentiation of blood-derived human monocytes into macrophages using morphological, functional and biochemical parameters that alter during macrophage differentiation. Purified preparations of HSV modified the monocyte-macrophage differentiation, in spite of the fact that the virus did not replicate in monocytes. Disappearance of expression of a monocyte-specific surface antigen and the typical development of morphological appearance were delayed in HSV- infected cells. Production of the lysosomal enzyme acid phosphatase, which normally increases during differentiation, was also reduced in infected cells. Transcription of the oncogenes c-myc and c-fos, and the Hsp70 gene was modified in cells from some donors but not in other cell preparations. Possible mechanisms of these effects are discussed.

Interaction of herpes simplex virus with mononuclear phagocytes is dependent on the differentiation stage of the cells.

The interaction of herpes simplex virus (HSV) with mononuclear phagocytes (MP), i.e. monocytes and macrophages, is of importance for the pathogenesis of HSV infections. MP are known to play a significant role in the cellular defence against infections with HSV, but it has also been shown that HSV-1 affects MP. The infection of these cells at different stages of differentiation has different outcomes, and may result in the alteration of important cellular functions. HSV-1 inhibits the morphological differentiation of human monocytes, and this inhibition occurs in spite of the fact that human monocytes are non-permissive to HSV-1. We have studied the effect of HSV infection of monocytes and macrophages on production of essential cytokines and related this effect to the reproduction of the virus. Blood-derived MP were cultured in vitro and inoculated with HSV at different stages of differentiation. Replication of the virus was measured by infectivity titration, detection of HSV antigens by immunofluorescence and detection of HSV-specific mRNA. In monocytes, no viral replication and no production of late protein was seen. HSV IE gene was transcribed in monocytes from some donors, but not from others. In macrophages, virus replicated, but less efficiently than in fully permissive fibroblast cells. The production of IL-1 beta, IL-6 and TNF-alpha in both non-permissive monocytes and permissive macrophages was assayed both at the transcriptional level, as mRNA, and as protein released from the cells. Production of cytokines by MP was affected by HSV-1. The level of cytokine mRNA and cytokine protein did not correspond for all cytokines, which may suggest that translational regulation and/or cytokine inhibitors are important in the regulation of the cytokine response. The cytokine modulation, both at the transcriptional level and measured as biological activity, was different in monocytes and macrophages, and varied between different donors. Our results indicate a relation between permissiveness and cytokine response in mononuclear phagocytes infected with HSV-1. Such a relation may be of importance to both intrinsic and extrinsic defence mechanisms of MP against HSV-1. Our study also demonstrates that even the functions of non-permissive cells such as blood-derived monocytes may be affected by viral infections.

Scinderin-derived actin-binding peptides inhibit Ca(2+)- and GTPgammaS-dependent exocytosis in mouse pancreatic beta-cells.

Using capacitance measurements, we have explored the effects of three different scinderin actin-binding peptides (Sc(77-89); Sc(138-146); Sc(511-523)) on Ca(2+)- and GTPgammaS-induced exocytosis in single mouse pancreatic beta-cells. Sc(77-89) (10 microM) reduced exocytosis by 43% in whole-cell experiments in which secretion was triggered by intracellular dialysis with a Ca(2+)-EGTA buffer with a free Ca(2+) concentration of 2 microM. A more pronounced reduction of the rate of exocytosis was observed with Sc(138-146) (72%) but not with Sc(511-523) (39%). Sc(138-146) also reduced depolarisation-induced exocytosis by 61% without affecting the whole-cell Ca(2+) current. When exocytosis was triggered by infusion of GTPgammaS, all scinderin-binding peptides reduced exocytosis by 59-75%. These data suggest that scinderin might be important for controlling cortical actin network dynamics in mouse pancreatic beta-cells and that scinderin-induced cortical filamentous actin disassembly is required for insulin secretion.

[Abuse potential during use and withdrawal psychosis after treatment with the hypnotic zolpidem (Stilnoct)]. / Misbrugspotentiale under brug og abstinenspsykose efter behandling med sovemidlet zolpidem (Stilnoct).

Three cases are presented. Withdrawal symptoms and ultimately psychosis developed in two cases following cessation of the hypno-sedative zolpidem. Two cases involve dependence upon and abuse of the drug; in one, a well-known alcoholic, it was abused in combination with alcohol, the other had prior well-known dependence on sedative hypnotics. One patient had chronic dysphoria and one encephalopatia toxica. Adverse effects such as withdrawal symptoms, dependence and abuse have not previously been reported in relation to zolpidem. Chemically unrelated to benzodiazepines, zolpidem is thought to have fewer adverse effects, but shares a pharmacokinetic profile with the benzodiazepine triazolam. It is advised that normal criteria for the prescription of benzodiazepines also be used when prescribing non-benzodiazepine sedatives and hypnotics, as they act upon the same receptor, namely the benzodiazepine-GABA-chloride complex.

Necrotizing soft tissue infections caused by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis of groups C and G in western Norway.

Streptococcus pyogenes (group A streptococcus, GAS) is a major cause of necrotizing soft tissue infection (NSTI). On rare occasions, other ß-haemolytic streptococci may also cause NSTI, but the significance and nature of these infections has not been thoroughly investigated. In this study, clinical and molecular characteristics of NSTI caused by GAS and ß-haemolytic Streptococcus dysgalactiae subsp. equisimilis of groups C and G (GCS/GGS) in western Norway during 2000-09 are presented. Clinical data were included retrospectively. The bacterial isolates were subsequently emm typed and screened for the presence of genes encoding streptococcal superantigens. Seventy cases were identified, corresponding to a mean annual incidence rate of 1.4 per 100 000. Sixty-one of the cases were associated with GAS, whereas GCS/GGS accounted for the remaining nine cases. The in-hospital case fatality rates of GAS and GCS/GGS disease were 11% and 33%, respectively. The GCS/GGS patients were older, had comorbidities more often and had anatomically more superficial disease than the GAS patients. High age and toxic shock syndrome were associated with mortality. The Laboratory Risk Indicator for Necrotizing Fasciitis laboratory score showed high values (≥6) in only 31 of 67 cases. Among the available 42 GAS isolates, the most predominant emm types were emm1, emm3 and emm4. The virulence gene profiles were strongly correlated to emm type. The number of superantigen genes was low in the four available GCS/GGS isolates. Our findings indicate a high frequency of streptococcal necrotizing fasciitis in our community. GCS/GGS infections contribute to the disease burden, but differ from GAS cases in frequency and predisposing factors.

Meticillin-resistant Staphylococcus aureus in Norway, a low-incidence country, 2006-2010.

BACKGROUND: Antibiotic resistance is a global public health threat. Norway has managed to keep the incidence of resistant bacteria at a low level in both the healthcare system and the community. Reporting of both individual cases and meticillin-resistant Staphylococcus aureus (MRSA) outbreaks is mandatory. All isolates are genotyped. AIM: To describe the epidemiology of MRSA in Norway and to analyse how MRSA is spreading in a low-incidence country. METHODS: All cases of laboratory-confirmed MRSA colonisation and infection reported in Norway from 2006 to 2010 were subject to epidemiological analysis. FINDINGS: A total of 3620 cases of MRSA were found. Around one-third of the cases were imported, one-third acquired in the Norwegian healthcare system and one-third acquired in the community. Twelve percent of the cases were linked to known outbreaks. The total incidence of infected and colonized patients is slowly increasing. The numbers of severe infections remain stable at around 20 cases annually and the proportion of MRSA cases associated with healthcare has decreased. CONCLUSION: MRSA is still rare in the Norwegian population and the strategic objective of preventing MRSA from becoming a permanent part of the bacterial flora in hospitals and nursing homes has so far been met.

Invasive group A, C and G streptococcal disease in western Norway: virulence gene profiles, clinical features and outcomes.

Invasive group A streptococcal (iGAS) disease is endemic in Norway, but data on invasive group C and group G streptococcal (iGCS/GGS) disease are lacking. We investigated the characteristics of iGAS and iGCS/GGS infections in western Norway from March 2006 to February 2009. Clinical information was retrospectively obtained from medical records. GAS and GCS/GGS isolates were emm typed and screened for the presence of 11 superantigen (SAg) genes and the gene encoding streptococcal phospholipase A2 (SlaA). GCS/GGS isolates were also subjected to PCR with primers targeting speG(dys) . Sixty iGAS and 50 iGCS/GGS cases were identified, corresponding to mean annual incidence rates of 5.0 per 100,000 and 4.1 per 100,000 inhabitants, respectively. Skin and soft tissue infections were the most frequent clinical manifestations of both iGAS and iGCS/GGS disease, and 14 iGAS patients (23%) developed necrotizing fasciitis. The 30-day case fatality rates of iGAS and iGCS/GGS disease were 10% and 2%, respectively. emm1, emm3 and emm28 accounted for 53% of the GAS isolates, and these types were associated with severe clinical outcome. SAg gene and SlaA profiles were conserved within most of the GAS emm types, although five profiles were obtained within isolates of emm28. stG643 was the most prevalent GCS/GGS emm type, and speG(dys) was identified in 73% of the GCS/GGS isolates. Neither GAS SAg genes nor SlaA were detected in GCS/GGS. Our findings indicate a considerable burden of both iGAS and iGCS/GGS disease and a high frequency of necrotizing fasciitis caused by GAS in our community.