Influenza A subtype H3N2 is associated with an increased risk of hospital dissemination - an observational study over six influenza seasons.

BACKGROUND: Previous studies on hospital-acquired influenza (HAI) have not systematically evaluated the possible impact of different influenza subtypes. HAI has historically been associated with high mortality, but clinical consequences may be less severe in a modern hospital setting. AIMS: To identify and quantify HAI for each season, investigate possible associations with varying influenza subtypes, and to determine HAI-associated mortality. METHODS: All influenza-PCR-positive adult patients (>18 years old) hospitalized in Skåne County during 2013-2019, were prospectively included in the study. Positive influenza samples were subtyped. Medical records of patients with suspected HAI were examined to confirm a nosocomial origin and to determine 30-day mortality. RESULTS: Of 4110 hospitalized patients with a positive influenza PCR, 430 (10.5%) were HAI. Influenza A(H3N2) infections were more often HAI (15.1%) than influenza A(H1N1)pdm09, and influenza B (6.3% and 6.8% respectively, P<0.001). The majority of HAI caused by H3N2 were clustered (73.3 %) and were the cause of all 20 hospital outbreaks consisting of ≥4 affected patients. In contrast, the majority of HAI caused by influenza A(H1N1)pdm09 and influenza B were solitary cases (60% and 63.2%, respectively, P<0.001). Mortality associated with HAI was 9.3% and similar between subtypes. CONCLUSIONS: HAI caused by influenza A(H3N2) was associated with an increased risk of hospital dissemination. Our study is relevant for future seasonal influenza infection control preparedness and shows that subtyping of influenza may help to define relevant infection control measures. Mortality in HAI remains substantial in a modern hospital setting.

Volume of ropivacaine 0.2% and common peroneal nerve block duration: a randomised, double-blind cohort trial in healthy volunteers.

The volume-duration relationship using low concentrations of ropivacaine for peripheral nerve blocks is unknown, even though low concentrations of ropivacaine are increasingly used clinically. We investigated the effect of ropivacaine 0.2% on common peroneal nerve block duration. With ethical committee approval, 60 consenting, healthy volunteers were randomly allocated to receive one of five volumes of ropivacaine 0.2% (2.5, 5.0, 10, 15 or 20 ml) administered by ultrasound-guided, catheter-based injection (at 10 ml.min-1 ) near the common peroneal nerve. Our primary outcome was duration of sensory block, defined by insensitivity to a cold stimulus. Our secondary outcome was duration of motor block. Outcomes were assessed every hour from onset of block to complete remission. Intergroup differences were tested using one-way ANOVA followed by regression analyses using the 20 ml intervention group as reference. Block durations varied significantly (p < 0.0001) between groups. Mean (SD) sensory block durations were 9.2 (3.3), 12.5 (3.0), 15.5 (4.4), 17.3 (3.5) and 17.3 (4.6) h. Mean (SD) motor block durations were 3.3 (2.1), 7.2 (2.5), 9.2 (2.2), 12.7 (2.5) and 12.5 (2.5) h. Regression analysis showed that the effect of volume on block duration was progressively smaller with increasing volume, reaching a threshold volume above which there was no effect on nerve block duration (10 ml for sensory block and 15 ml for motor block). We conclude that there is a ceiling effect of increasing volume of ropivacaine 0.2% on both sensory and motor block duration of the common peroneal nerve.

Initial placement and secondary displacement of a new suture-method catheter for sciatic nerve block in healthy volunteers: a randomised, double-blind pilot study.

We performed a randomised double-blind pilot study in 16 healthy volunteers to investigate the success rate for placing a new suture-method catheter for sciatic nerve block. A catheter was inserted into both legs of volunteers and each was randomly allocated to receive 15 ml lidocaine 2% through the catheter in one leg and 15 ml saline in the other leg. Successful placement of the catheter was defined as a 20% decrease in maximum voluntary isometric contraction for dorsiflexion of the ankle. Secondary outcomes were maximum voluntary isometric contraction for plantar flexion at the ankle, surface electromyography and cold sensation. After return of motor and sensory function, volunteers performed standardised physical exercises; injection of the same study medication was repeated in the same leg and followed by motor and sensory assessments. Fifteen of 16 (94%; 95%CI 72-99%) initial catheter placements were successful. The reduction in maximum voluntary isometric contraction and surface electromyography affected the peroneal nerve more often than the tibial nerve. Eleven of 15 (73%; 95%CI 54-96%) catheters remained functional with motor and sensory block after physical exercise, and the maximal displacement was 5 mm. Catheters with secondary block failure were displaced between 6 and 10 mm. One catheter was displaced 1.8 mm that resulted in a decrease in maximum voluntary isometric contraction of less than 20%. After repeat test injection, 14 of the 16 volunteers had loss of cold sensation. Neither motor nor sensory functions were affected in the legs injected with placebo. We conclude that the suture-method catheter can be placed with a high success rate, but that physical exercise may cause displacement.

GIP(3-30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release.

Alternative processing of the precursor protein pro-GIP results in endogenously produced GIP(1-30)NH2, that by DPP-4 cleavage in vivo results in the metabolite GIP(3-30)NH2. We showed previously that GIP(3-30)NH2 is a high affinity antagonist of the human GIPR in vitro. Here we determine whether it is suitable for studies of GIP physiology in rats since effects of GIP agonists and antagonists are strictly species-dependent. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation or assayed in competition binding using human 125I-GIP(1-42) as radioligand. In isolated perfused rat pancreata, insulin, glucagon, and somatostatin-releasing properties were evaluated. Competition binding demonstrated that on the rat GIP receptor (GIPR), rat GIP(3-30)NH2 bound with high affinity (Ki of 17nM), in contrast to human GIP(3-30)NH2 (Ki of 250nM). In cAMP studies, rat GIP(3-30)NH2 inhibited GIP(1-42)-induced rat GIPR activation and schild-plot analysis showed competitive antagonism with a pA2 of 13nM and a slope of 0.9±0.09. Alone, rat GIP(3-30)NH2 displayed weak, low-potent partial agonistic properties (EC50>1µM) with an efficacy of 9.4% at 0.32µM compared to GIP(1-42). In perfused rat pancreata, rat GIP(3-30)NH2 efficiently antagonized rat GIP(1-42)-induced insulin, somatostatin, and glucagon secretion. In summary, rat GIP(3-30)NH2 is a high affinity competitive GIPR antagonist and effectively antagonizes GIP-mediated G protein-signaling as well as pancreatic hormone release, while human GIP(3-30)NH2, despite a difference of only one amino acid between the two (arginine in position 18 in rat GIP(3-30)NH2; histidine in human), is unsuitable in the rat system. This underlines the importance of species differences in the GIP system, and the limitations of testing human peptides in rodent systems.

Emergence of enterovirus D68 in Denmark, June 2014 to February 2015.

From June 2014 through February 2015, respiratory samples from 130 Danish patients were screened for enterovirus D68 (EV-D68). Fourteen EV-D68 cases were detected, of which 12 presented with respiratory symptoms, and eight had known underlying disease. The median age of EV-D68 cases was three years (interquartile range: 0­30 years). Acute flaccid paralysis (AFP) was not detected although Danish EV-D68 strains showed > 98% nt identity with EV-D68-strains from AFP cases from the United States and France.

The VGF-Derived Neuropeptide TLQP-21 Shows No Impact on Hormone Secretion in the Isolated Perfused Rat Pancreas.

TLQP-21 is a VGF-derived neuropeptide proposed to be involved in regulation of metabolism. More specifically it has been suggested that TLQP-21 has the ability to enhance glucose stimulated insulin secretion, making it a candidate for treatment of patients with type 2 diabetes.In this study, we investigated the impact of TLQP-21 on insulin, glucagon, and somatostatin secretion in the perfused rat pancreas. We found that administration of 5 and 50 nM TLQP-21 had no impact on pancreatic hormone secretion at 3.5 or 8 mM glucose levels. Increasing TLQP-21 (200 nM) and glucose concentration (3.5 and 16 mM) led to a nonsignificant decrease in glucagon secretion, though insulin and somatostatin secretory patterns remained unaffected. In a final set of experiments, perfusions were performed with infusion of 50 and 1 000 nM TLQP-21 to ensure sufficient stimulation. However, administration of TLQP-21 under this setup showed no impact on the pancreatic hormone secretion either. In conclusion, the outcome of this study does not concur with previous findings, suggesting that the effect of TLQP-21 does not directly involve silent hormone secretion.

Cardiovascular risk in patients with sleep apnoea with or without continuous positive airway pressure therapy: follow-up of 4.5 million Danish adults.

BACKGROUND: The prognostic significance of age and continuous positive airway pressure (CPAP) therapy on cardiovascular disease in patients with sleep apnoea has not been assessed previously. METHODS: Using nationwide databases, the entire Danish population was followed from 2000 until 2011. First-time sleep apnoea diagnoses and use of CPAP therapy were determined. Incidence rate ratios (IRRs) of ischaemic stroke and myocardial infarction (MI) were analysed using Poisson regression models. RESULTS: Amongst 4.5 million individuals included in the study, 33 274 developed sleep apnoea (mean age 53, 79% men) of whom 44% received persistent CPAP therapy. Median time to initiation of CPAP therapy was 88 days (interquartile range 34-346). Patients with sleep apnoea had more comorbidities compared to the general population. Crude rates of MI and ischaemic stroke were increased for sleep apnoea patients (5.4 and 3.6 events per 1000 person-years compared to 4.0 and 3.0 in the general population, respectively). Relative to the general population, risk of MI [IRR 1.71, 95% confidence interval (CI) 1.57-1.86] and ischaemic stroke (IRR 1.50, 95% CI 1.35-1.66) was significantly increased in patients with sleep apnoea, in particular in patients younger than 50 years (IRR 2.12, 95% CI 1.64-2.74 and IRR 2.34, 95% CI 1.77-3.10, respectively). Subsequent CPAP therapy was not associated with altered prognosis. CONCLUSIONS: Sleep apnoea is associated with increased risk of ischaemic stroke and MI, particularly in patients younger than 50 years of age. CPAP therapy was not associated with a reduced rate of stroke or MI.

Retinal vein and artery occlusions: a risk factor for stroke in atrial fibrillation.

BACKGROUND: Retinal vascular occlusions may constitute an independent risk factor for stroke in patients with atrial fibrillation. METHODS: We performed a retrospective study on a nationwide cohort with atrial fibrillation from 1997 to 2008. The rate of stroke/systemic thromboembolism (TE)/transitory ischemic attack (TIA) was determined for atrial fibrillation patients with and without a history of retinal vascular occlusion. A Cox regression analysis, adjusted for risk factors and medications, was performed to determine the independent predictive value of retinal arterial or venous occlusion for the risk of ischemic stroke, TE or TIA in atrial fibrillation patients. RESULTS: We included 87 202 patients with non-valvular atrial fibrillation. At baseline, a history of retinal arterial occlusion was diagnosed in 224 patients (0.26%) and a history of retinal venous occlusion in 361 (0.41%). Patients without retinal occlusion had a rate of stroke/TE/TIA of 4.52 (95% confidence interval [CI] 4.44-4.60). For patients with retinal arterial occlusion, the rate of stroke/TE/TIA was 8.16 (95% CI 6.35-10.49) per 100 person-years, and for patients with retinal venous occlusion it was 7.28 (95% CI 5.93-8.94) per 100 person-years. In multivariate analysis, both retinal arterial occlusions (hazard ratio [HR] 1.39, 95% CI 1.08-1.79) and retinal venous occlusions (HR 1.26, 95% CI 1.02-1.54) were associated with an increased risk of future stroke/TE/TIA. CONCLUSIONS: A history of retinal arterial or retinal venous occlusion is associated with an increased risk of stroke/TE/TIA in patients with atrial fibrillation. Thus, prior retinal vascular occlusion may be considered as a previous thromboembolic event when evaluating stroke risk in patients with atrial fibrillation.

Prevalence of sexually transmitted infections among women attending antenatal clinics in Tanga, north eastern Tanzania.

This study aimed to determine the prevalence of sexually transmitted infections (STIs) among HIV-infected and uninfected pregnant women in Tanga, Tanzania. Retrospective data on syphilis and HIV status during 2008-2010 were collected from antenatal clinic (ANC) records. Prospective data were collected from HIV-infected (n = 105) and HIV-uninfected pregnant women (n = 100) attending ANCs between April 2009 and August 2010. Syphilis prevalence showed a declining trend (3.1%, 1.4% and 1.3%), while HIV prevalence was stable (6.1%, 6.4% and 5.4%) during 2008-2010. HIV-infected women had significantly higher prevalence of trichomoniasis (18.8% versus 5.0%; P < 0.003) and candidiasis (16.5% versus 2.0%; P < 0.001) while the higher rate of gonorrhoea (3.5% versus 0%; P = 0.095) was not statistically significant when compared with HIV-uninfected women. There were no statistically significant differences in prevalence of chlamydial infection (0% versus 3.0%; P = 0.156) or syphilis (2.4% versus 3.0%; P = 1) between HIV-infected and uninfected women. Other STIs were common in both HIV-infected and uninfected pregnant women.

[Population screening for HIV in Sisimiut, Greenland]. / Befolkningsscreening for hiv i Sisimiut, Grønland.

INTRODUCTION: In the years 1985-1998, 91 HIV-positive persons were diagnosed in Greenland, resulting in an incidence of HIV infection three times higher in Greenland than in Denmark. Of these cases 25% were diagnosed in Sisimiut, which, however, only comprises 10% of the total population of Greenland. In spite of an active HIV case-tracing programme at the Health Centre, there was a fear of unknown HIV-positives in the town. Therefore, the Health Centre initiated an HIV screening campaign among all adults and school children in the town of Sisimiut and two adjacent settlements. MATERIAL AND METHODS: The screening campaign was carried out in the weeks 46 and 47 in November 1998 by the staff at the Health Centre. All participants filled out a questionnaire concerning demographic variables, and had blood samples drawn. For adults the campaign mainly took place in the community centre and the large work places, and for the children at the schools. Blood samples were tested for antibodies against HIV 1 and 2 at Statens Serum Institut using ELISA tests and confirmatory Western Blot. RESULTS: Of the total population of 4807, 2858 persons took part in the screening campaign (participation rate 59%). Among adults the participation rate was 50%, and for children aged 6-17 years the rate was 86%. Four HIV-positive persons were tested positive. Of these three were already known HIV-positives, and the last person was highly suspect of HIV infection. DISCUSSION: There is no evidence of widespread HIV infection in Sisimiut. No unknown groups of HIV-positive persons were identified. Thus, the intensive case-tracing programme as carried out by the Health Centre seems effective.

Markers of sexually transmitted diseases in seminal fluid of male clients of female sex workers.

OBJECTIVES: To screen for certain STD markers in a group of male clients of female sex workers. METHOD: Condoms with seminal fluid were collected at 10 "massage parlours" in Copenhagen. The seminal fluid samples were examined for HIV antibodies, markers of hepatitis B virus (HBV), Chlamydia trachomatis, and Mycoplasma genitalium. RESULTS: All samples (n = 332) were negative for HIV antibodies. Out of 327 samples examined for HBV markers 32 (9.8%) were positive for HBV core antibodies, one of which was also positive for HBV antigen. C trachomatis could be demonstrated in six out of 122 (4.9%) samples and M genitalium in one out of 122 samples. CONCLUSIONS: The finding of a C trachomatis prevalence of 4.9% is considerable higher than expected in men with a presumed age of 35-55 years. The demonstration of a prevalence of HBV markers of 9.8% indicates that these clients have an increased risk of HBV infection, a finding that further consolidates the recommendation of HBV vaccination of sex workers. As shown in this study, STD transmission in commercial sex may also have the client as the source.

9-year HIV-2-associated mortality in an urban community in Bissau, west Africa.

BACKGROUND: Community studies with 1-3 years of follow-up have reported four to five times higher mortality in HIV-2-infected than in uninfected adults. In a cohort study of HIV-1, an increasing difference in mortality rates of HIV-1-infected and uninfected individuals is expected over time, because of rising mortality with advancing HIV-1 infection. We therefore investigated long-term survival of HIV-2-infected adults. METHODS: Adults enrolled in 1987 in a community study of HIV-2 infection in Guinea-Bissau were followed up with serological surveys in 1989 and 1992. Survival was assessed in 1995, 9 years after enrollment. FINDINGS: The annual incidence of HIV-2 was 0.7% for adults and tended to be higher for older individuals than for participants aged 15-44 years (relative risk 3.21 [95% CI 0.91-11.37]). With control for age, HIV-2-infected adults had twice as high mortality as uninfected individuals (mortality ratio 2.32 [1.18-4.57]); the mortality ratio was highest in the first year of the study (4.50 [1.31-15.43]). The difference between infected and uninfected individuals was stronger for adults under 45 years of age (mortality ratio 4.72 [1.86-11.97]) than for older people (1.35 [0.51-3.56]). HIV-2-infected individuals living with an infected spouse had significantly higher mortality than HIV-2-infected individuals living with an uninfected spouse (p = 0.027). INTERPRETATION: HIV-2-associated mortality is not increasing with length of follow-up. Mortality in HIV-2-infected adults is only twice as high as that in uninfected individuals. In the majority of adults, HIV-2 has no effect on survival.

PIP: While HIV-2 infection can lead to AIDS, it takes longer than HIV-1 to induce immunosuppression and AIDS, it is less transmissible, and it is associated with lower mortality than HIV-1 infection. 1329 people from among 100 houses in Guinea-Bissau participated in a 1987 study of HIV seroprevalence in their community. 8.9% of the family members older than age 14 years were infected with HIV-2, as well as 0.6% of the 677 children, but no one was infected with HIV-1. All subjects enrolled in the 1987 study over age 14 were followed up with serological surveys in 1989 and 1992, with their survival assessed in 1995. HIV-2 associated mortality did not increase over time and mortality in HIV-2-infected adults was only twice as high as that among uninfected individuals. In the majority of adults, HIV-2 has no effect upon survival. The difference in mortality between the infected and the uninfected was greater for adults under age 45 years than for older people. Furthermore, HIV-2-infected individuals living with an infected spouse had significantly higher mortality than those living with an uninfected spouse.

EBV-positive primary central nervous system lymphomas in monozygote twins with common variable immunodeficiency and suspected multiple sclerosis.

Common variable immunodeficiency represents the most frequently occurring primary immunodeficiency disorder and is usually detected sporadically in patients with no family history of immunodeficiency. We present the case stories of two monozygote twins, who following a period of decreasing serum immunoglobulins developed primary central nervous system lymphomas. One twin had clinical and paraclinical features mimicking multiple sclerosis. Immunohistochemical investigations on biopsy tissue showed expression of the bcl-2 and p53 gene products, and Epstein-Barr virus (EBV) encoded small RNA's (EBER) indicating latent infection were detected in lymphoma cells using in situ hybridisation techniques. The pathogenetic role of EBV in oncogenesis is discussed.

[Infection with human immunodeficiency virus type 2--HIV-2]. / Infektion med human immundefektvirus type 2--HIV-2.

The majority of patients with HIV-2 infection come from West Africa or have had sexual contact with a person from there, as HIV-2 is prevalent in this area. HIV-2 is phylogenetically closer related to SIVsm and SIVmac than to HIV-1. HIV-2 is mainly transmitted by heterosexual contact, whereas the risk of mother-to-child infection is very low. Nine cases of HIV-2 infection have been diagnosed in Denmark. Out of these, seven are from West Africa and two have been infected in Denmark by individuals from West Africa.

False negative anti-HIV-1/HIV-2 ELISAs in acute HIV-2 infection.

Since HIV-2 was isolated in 1986, only 1 case of acute HIV-2 infection has been reported. We have identified another patient with primary HIV-2 infection. Follow-up samples were requested from the patient due to discrepant results. The HIV-2 infection was confirmed with HIV-2-specific proviral DNA amplification by PCR. The HIV-2 seroconversion panel obtained was used to evaluate the sensitivity of both combined and specific ELISAs currently in use in Europe, and to investigate the Western-blot patterns on both HIV-1-and HIV-2-specific Western blots. The window period was determined to be less than 37 days with the most sensitive assays. A remarkable difference in sensitivity to HIV-2 antibodies in acute HIV-2 infection was found in combined HIV-1/HIV-2 ELISAs. Three out of the 4 combined sandwich ELISAs appeared to be less sensitive than the indirect ELISAs in HIV-2 seroconversion, leading to a prolonged window period. One HIV-2-specific ELISA was also negative on the first sample, but positive on the second sample. In the HIV-2 Western blot, early reaction with HIV-2-specific env and gag proteins was seen, whereas the HIV-1 Western blot on the first sample revealed gag (p24, p55) reactivity only.