GENEDIA Multi Influenza Ag Rapid Test for detection and H1, H3, and H5 subtyping of influenza viruses

BackgroundRapid identification and subtype determination of influenza virus is important in managing infected patients. Rapid influenza diagnostic tests (RIDTs) are widely used in this manner, but most can only detect influenza A and B viruses without subtyping. A new RIDT, GENEDIA Multi Influenza Ag Rapid Test (GENEDIA), was developed for detection of influenza A and B viruses and also subtyping of influenza A to H1, H3, H5 which has not been possible with other RIDTs.ObjectivesAssess the performance of GENEDIA.Study designNasopharyngeal swabs were collected from 274 clinically suspected patients (influenza A/H1N1/2009 (n = 50), influenza A/H3 (n = 50), influenza B (n = 73) and influenza-negative (n = 101)) and analyzed with the real-time RT-PCR, GENEDIA, SD Bioline Influenza Ag, and Alere BinaxNow Influenza A&B Card. Also, 46 fecal specimens (H5N2 (n = 3), H5N3 (n = 3)) of spot-billed duck were analyzed with RT-PCR and GENEDIA.ResultsCompared to real-time RT-PCR, the sensitivities of GENEDIA, SD Bioline Influenza Ag, and Alere BinaxNow Influenza A&B Card were 73.0%, 57.0%, 58.0% for influenza A, respectively, and 68.5%, 65.8%, 57.5% for influenza B, respectively. Specifically, the sensitivity of GENEDIA was 70.0% for influenza A/H1N1/2009 and 76.0% for influenza A/H3. From the avian influenza samples, GENEDIA detected all six H5 subtype without any cross-reactions.ConclusionThe GENEDIA Multi Influenza Ag Rapid Test was sensitive in detecting influenza viruses compared with other commercial RIDTs and also useful for rapid subtype determination of influenza A.     

Rhino/enteroviruses in hospitalized children: A comparison to influenza viruses

BackgroundThe relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown.ObjectivesThis retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus.Study designRespiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review.ResultsOf the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p < 0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p < 0.01) with crackles (36.3% vs. 23.3%, p < 0.01) and wheezing (41.7% vs. 22.8%, p < 0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p < 0.01), duration of fever (1 days vs. 3 days, p < 0.01), and duration of hypoxemia (2 days vs. 3 days, p < 0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired.ConclusionsHRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.     

Use of rapid influenza diagnostic tests under field conditions as a screening tool during an outbreak of the 2009 novel influenza virus: Practical considerations

BackgroundRapid influenza diagnostic tests (RIDTs) are used in various settings as a first-line screen of patient specimens. During the initial outbreak of the 2009 novel influenza A/H1N1 virus, the Nebraska Public Health Laboratory (NPHL) adopted a testing algorithm, attempting to maximize the usefulness of RIDTs. However, it became apparent that a high percentage of the positive specimens received from off-site facilities were negative for influenza viruses by the confirmatory test, the Luminex xTAG Respiratory Viral Panel (RVP) molecular assay.ObjectivesTo explore the cause of discrepancies between RIDTs results obtained from on-site facility testing versus confirmatory testing performed at NPHL.Study designSpecimens (n = 336) tested with RIDTs at off-site facilities and screened for high-probability of containing H1N1 were sent to the NPHL for confirmatory testing by RVP.ResultsOf 336 specimens analyzed, 104 were negative for influenza A or B by both RIDT and RVP; 127 were positive by both tests; 102 were positive by RIDT only; and 3 were positive by RVP only. Using the RVP assay as the gold standard, overall RIDT characteristics in this screened population were: sensitivity = 97.7% (95%CI: 92.5, 99.3); specificity = 48.1% (95%CI: 40.4, 55.8); positive predictive value = 54.3% (95%CI: 47.0, 61.4); and negative predicative value = 97.1% (95%CI: 90.6, 99.1).ConclusionsThe results show that the confirmation of RIDT-positive results varied widely by testing site. Possible explanations for the discrepancies in performance characteristics include testing a narrowly defined sample population, test facility characteristics, facility work load, and seasonal timing.     

Evaluation of a new rapid influenza A diagnostic test for detection of pandemic (H1N1) 2009 and seasonal influenza A virus

BackgroundRapid influenza A diagnostic tests (RIDTs) play an important role in the clinical setting, especially in the influenza post-pandemic era with three influenza A viruses in circulation.ObjectivesDetermine the sensitivity and specificity of a new RIDT (FluA Dot) by comparison with BD Directigen EZ FluA+B and CDC rRT-PCR.Study designTwo sets of experiments were conducted to determine the performance of the new test. (1) Serial dilutions of eight pandemic (H1N1) 2009 (pH1N1) isolates, five seasonal H3N2 isolates, five seasonal H1N1 isolates and three recombinant nucleoproteins were tested by FluA Dot assay, Directigen EZ FluA+B test and CDC real-time RT-PCR. (2) Using CDC rRT-PCR as the gold standard, the clinical sensitivity and specificity of the FluA Dot and Directigen EZ FluA+B were evaluated in nasopharyngeal swab (NPS) specimens of 807 patients presenting with influenza-like illness.ResultsThe average analytical sensitivity of FluA Dot (0.06 ng/mL for recombinant nucleoproteins and 2.16 ± 0.85 log 10 TCID₅₀ for viruses) was approximately 10-fold higher than Directigen EZ FluA+B (1–2 ng/mL for recombinant nucleoproteins and 3.54 ± 0.81 log 10 TCID₅₀ for viruses), and was approximately 10-fold lower than the CDC rRT-PCR (1.09 ± 0.69 log 10 TCID₅₀ for viruses). Among 807 NPS specimens tested, the sensitivities and specificities of FluA Dot were 91.1% (95%CI: 86.7–94.4%)/99.7% (95%CI: 98.7–99.9%), and the Directigen EZ FluA+B were 71.9% (95%CI: 65.7–77.6%)/99.8%(95%CI: 99.0–99.9%).ConclusionThe new test (FluA Dot) exhibit higher sensitivity than Directigen EZ FluA+B both in pH1N1 and seasonal influenza A detection. The promising RIDT can play important roles in influenza diagnosis and therapy.     

Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course

BackgroundEarly antibody responses to influenza infection are important in both clearance of virus and fighting the disease. Acute influenza antibody titers directed toward H1-antigens and their relation to infection type and patient outcomes have not been well investigated.ObjectiveUsing hemagglutination inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers in patients with influenza infection or another respiratory infection before and after the H1N1-pandemic influenza outbreak. Among patients with acute influenza infection we related duration of illness, severity of symptoms, and need for hospitalization to antibody titers.MethodsThere were 134 adult patients (average age 34.7) who presented to an urban academic emergency department (ED) from October through March during the 2008–2011 influenza seasons with symptoms of fever and a cough. Nasal aspirates were tested by viral culture, and peripheral blood serum was run in seven H1-subtype HI assays.ResultsAcutely infected influenza patients had markedly lower antibody titers for six of the seven pseudotype viruses. For the average over the seven titers (log units, base 2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92) among patients who had a non-influenza respiratory illness, p < 0.0001. Among patients with seasonal influenza infection, titers of some antibodies correlated with severity of symptoms and with total duration of illness (p < 0.02).ConclusionIn patients with acute respiratory infections, lower concentrations of H1-influenza-specific antibodies were associated with influenza infection. Among influenza-infected patients, higher antibody titers were present in patients with a longer duration of illness and with higher severity-of-symptom scores.     

Severe enterovirus 68 respiratory illness in children requiring intensive care management

BackgroundEnterovirus 68 (EV-D68) causes acute respiratory tract illness in epidemic cycles, most recently in Fall 2014, but clinical characteristics of severe disease are not well reported.ObjectivesChildren with EV-D68 severe respiratory disease requiring pediatric intensive care unit (PICU) management were compared with children with severe respiratory disease from other enteroviruses/rhinoviruses.Study designA retrospective review was performed of all children admitted to Children’s Mercy Hospital PICU from August 1-September 15, 2014 with positive PCR testing for enterovirus/rhinovirus. Specimens were subsequently tested for the presence of EV-D68. We evaluated baseline characteristics, symptomatology, lab values, therapeutics, and outcomes of children with EV-D68 viral infection compared with enterovirus/rhinovirus-positive, EV-D68-negative children.ResultsA total of 86 children with positive enterovirus/rhinovirus testing associated with respiratory symptoms were admitted to the PICU. Children with EV-D68 were older than their EV-D68-negative counterparts (7.1 vs. 3.5 years, P = 0.01). They were more likely to have a history of asthma or recurrent wheeze (68% vs. 42%, P = 0.03) and to present with cough (90% vs. 63%, P = 0.009). EV-D68 children were significantly more likely to receive albuterol (95% vs. 79%, P = 0.04), magnesium (75% vs. 42%, P = 0.004), and aminophylline (25% vs. 4%, P = 0.03). Other adjunctive medications used in EV-D68 children included corticosteroids, epinephrine, and heliox; 44% of EV-D68-positive children required non-invasive ventilatory support.ConclusionsEV-D68 causes severe disease in the pediatric population, particularly in children with asthma and recurrent wheeze; children may require multiple adjunctive respiratory therapies.     

Performance of a rapid antigen test (Binax NOW® RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population

BackgroundInfants from Alaska's Yukon–Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity.ObjectiveWe compared Binax NOW^® RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance.Study designBetween October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR.Results79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p = 0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p < 0.001), and children with a shorter duration of symptoms before testing (0–1 (92%) vs. 2–4 (78%) vs. 5+ (65%) days; p = 0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01 × 10⁹ copies/mL vs. a median of 5.25 × 10⁷ copies/mL for NPW positive by RT-qPCR only (p < 0.001).ConclusionRT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing.     

Comparison of commercial influenza A virus assays in detecting avian influenza H7N9 among poultry cloacal swabs,China

BackgroundAvian H7N9 virus emerged in China in February 2013 and has since spread widely among China's poultry, causing numerous human infections.ObjectivesTo compare World Health Organization (WHO) and US commercial influenza assays in detecting avian H7N9 virus in poultry cloacal specimens.Study designBetween April 6 and July 15, 2013, 261 cloacal swabs were collected from commercial poultry in Nanjing and Wuxi City, Jiangsu Province, China. Swabs were screened with the WHO's influenza A and H7N9 real-time RT-PCR (qRT-PCR) assays. A blinded panel of 97 specimens (27 H7N9-positive and 70 influenza A-negative) was then used to compare 3 antigen based commercial assays (Remel Xpect Flu A&B, Quidel Quickvue influenza, and Quidel Sofia Influenza A + B), and 2 molecular commercial assays (Quidel Molecular Influenza A + B assay and Life Technologies VetMAX™-Gold SIV Detection Kit). None of these commercial assays were approved for use with poultry specimens.ResultsConsidering the WHO H7N9 qRT-PCR assay as the gold standard, all assays except the Quidel Quickvue influenza assay had high specificity (ranging from 96 to 99%). Regarding sensitivity, the Life Technologies VetMAX™-Gold SIV Detection Kit (100%; 95% CI 87–100%) and the Quidel Molecular Influenza A + B assay (85%; 95% CI 66–96%) performed the best. The sensitivities of the non-molecular antigen detection assays were either unable to detect small amounts of H7N9 viral RNA or were inhibited by specimen type.ConclusionsThe Life Technologies VetMAX™-Gold SIV Detection Kit and the Quidel Molecular Influenza A + B assay are comparable in performance to the WHO H7N9 qRT-PCR assay in detecting H7N9 from poultry cloacal specimens.     

Clinical presentation and response to treatment of novel influenza A H1N1 in a university-based summer camp population

BackgroundLittle is known about the clinical presentation and course of novel H1N1 influenza in summer camps.ObjectivesTo describe the clinical course and evaluate the effect of influenza treatment in a summer camp population.Study designTwo large influenza outbreaks occurred in university-based residential camps between May 21 and August 2, 2009. Through active daily surveillance, medical evaluation at symptom onset, and data collection during isolation, we describe the clinical course of a large outbreak of novel H1N1 influenza.ResultsInfluenza-like illness (ILI) was documented in 119 individuals. Influenza A was confirmed in 66 (79%) of 84 samples tested. Three early samples were identified as novel H1N1. ILI cases had an average age of 15.7 years and 52% were male. Sixty-three were treated with oseltamivir or zanamivir, which was initiated within 24 h of diagnosis. Cough, myalgia and sore throat occurred in 69, 64 and 63% of cases, respectively. The highest temperature over the course of illness (T_max) occurred within 48 h after symptom onset in 87.5% of individuals. Average T_max was 38.4 °C (range 36.1–40.2 °C). Among confirmed influenza cases, 69% defervesced by 72 h and 95% defervesced by 96 h. Defervescence at 72 h was not different in the treated and untreated groups (p = 0.12).ConclusionsNovel H1N1 generally has a mild, self-limited course in healthy adolescent campers. Defervescence occurred within 72 h and was unaffected by treatment.     

High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4+CD25high cells in children with type 1 diabetes

PurposeDespite the rapidly rising incidence of diabetes in children, with the highest rise in children < 5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.Material/methodsThe study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children < 5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.ResultsThe frequency of CD4⁺CD25^highOX40⁺ was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p = 0.003). Moreover, T1D children had higher frequency of CD4⁺CD25^high4-1BB⁺ cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p = 0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r = 0.54, 95% CI [0.19–0.77], p = 0.004). In comparison with age-matched controls, children < 5 years had higher frequency of CD4⁺CD25^highOX40⁺ (p = 0.004) and CD4⁺CD25^high4-1BB⁺ cells (p = 0.079).ConclusionsOur study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children < 5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.     

Clinical characteristics and outcomes of severe rhinovirus-associated pneumonia identified by bronchoscopic bronchoalveolar lavage in adults: Comparison with severe influenza virus-associated pneumonia

BackgroundRhinoviruses (RVs) may cause pneumonia, but the characteristics of RV-associated pneumonia have not been adequately evaluated.ObjectiveWe aimed to compare characteristics, complications, and outcomes between severe RV- and influenza virus (IFV)-associated pneumonia in adults.Study designWe used prospective cohort data of adult patients with severe pneumonia who had been admitted to the medical intensive care unit of a tertiary care hospital over a 4-year period. The clinical features and outcomes of 27 patients with RV-positive bronchoscopic bronchoalveolar lavage (BAL) fluid were compared to those of 51 pneumonia patients with IFV-positive BAL fluid or IFV-positive nasopharyngeal specimens.ResultsOf 356 patients who underwent bronchoscopic BAL and respiratory virus polymerase chain reaction (PCR), RV was the most commonly identified virus (8.1%) from BAL fluid. Patients with RV-associated pneumonia were more likely to be immunocompromised than patients with IFV-associated pneumonia (81.5% vs. 33.3%, p < 0.001). Bacterial coinfection tended to be less common in the RV group (18.5% vs. 37.3%, p = 0.09). Although septic shock was less common in the RV group (29.6% vs. 54.9%, p = 0.03), other clinical manifestations, laboratory findings, and radiologic patterns were similar between the groups. The 28-day mortality of patients with severe RV- and IFV-associated pneumonia was similarly high (29.6% vs. 35.3% respectively, p = 0.61).ConclusionsSevere RV-associated pneumonia patients were more likely to be immunocompromised and less likely to present septic shock. Overall clinical features were similar and mortalities of both groups were comparably high. Studies of larger cohorts encompassing mild to moderate pneumonia patients are needed.     

The prognosis of highly active antiretroviral therapy (HAART) treated HIV infected patients in Serbia,related to the time of treatment initiation

BackgroundWith the introduction of highly active antiretroviral treatment (HAART) an impressive improvement in patient survival and quality of life has bee observed. However, the optimal timing of initial HAART is still under consideration.ObjectiveTo investigate the prognosis of HAART treated patients in Serbia, related to the timing of HAART initiation.Study designA series of 563 patients on HAART was retrospectively analyzed to investigate treatment response and survival.ResultsAfter a mean of 6 years (range 1–14) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 72.4%, treatment failure occurred in 7.9%, while 19.7% had a dissociative immunological/virological response. If treatment was initiated during primary HIV infection it took a shorter time to achieve a favorable response than in patients who began HAART in chronic HIV infection (2.7 ± 2.2 years vs. 6.9 ± 2.7 years, P < 0.01). A higher proportion of patients with primary HIV infection then those treated in the chronic phase achieved a favorable response to HAART (88.4% vs. 71.9%, P = 0.045). Patients who initiated HAART when their CD4 cell counts were below 200 cells/μL needed longer treatment for favorable response (8 years vs. 6 years, log rank P < 0.01). Forty-seven (8.3%) patients died. The overall estimated survival was 13 years. Patients older then 40 and IVDU were more likely to die during HAART (OR 2.6, 95% CI 1.1–5.9, P = 0.016, and OR 2.0, 95% CI 1.0–3.7, P = 0.02, respectively). However, reaching and maintaining undetectable viremia was an independent predictor of longer survival (OR 11.3, 95% CI 4.6–27.7, P < 0.01).ConclusionReaching and maintaining undetectable viremia during HAART predicted longer survival, even if sub-clinical immunodeficiency remained.     

Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children

BackgroundHuman non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children.ObjectivesTo compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes.Study designThis study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011.ResultsOf 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV-B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p = 0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p = 0.030), and significantly more in HPeV-1 than HPeV-3 infected children (p < 0.001).ConclusionsEV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection.     

Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013–14

BackgroundInfluenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection.ObjectivesTo describe the spectrum and clinical impact of co-infections.Study designRetrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis.ResultsOf 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p = 0.003), leukocytosis (>11 K/μl, OR 3.7 [2.2–6.2], p < 0.001; reference: normal WBC 3.5–11 K/μl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0–1.2], p = 0.001). Bacterial co-infections (OR 2.2 [1.4–3.6], p = 0.001) and viral co-infections (OR 3.1 [1.3–7.4], p = 0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p < 0.05) in bivariable analysis.ConclusionsBacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.     

Comparing usability testing outcomes and functions of six electronic nursing record systems

ObjectivesThis study examined the usability of six differing electronic nursing record (ENR) systems on the efficiency, proficiency and available functions for documenting nursing care and subsequently compared the results to nurses' perceived satisfaction from a previous study.MethodsThe six hospitals had different ENR systems, all with narrative nursing notes in use for more than three years. Stratified by type of nursing unit, 54 staff nurses were digitally recorded during on-site usability testing by employing validated patient care scenarios and think-aloud protocols. The time to complete specific tasks was also measured. Qualitative performance data were converted into scores on efficiency (relevancy), proficiency (accuracy), and a competency index using scoring schemes described by McGuire and Babbott. Six nurse managers and the researchers completed assessments of available ENR functions and examined computerized nursing process components including the linkages among them.ResultsFor the usability test, participants' mean efficiency score was 94.2% (95% CI, 91.4–96.9%). The mean proficiency was 60.6% (95% CI, 54.3–66.8%), and the mean competency index was 59.5% (95% CI, 52.9–66.0). Efficiency scores were significantly different across ENRs as was the time to complete tasks, ranging from 226.3 to 457.2 s (χ² = 12.3, P = 0.031; χ² = 11.2, P = 0.048). No significant differences were seen for proficiency scores. The coverage of the various ENRs' nursing process ranged from 67% to 100%, but only two systems had complete integration of nursing components. Two systems with high efficiency and proficiency scores had much lower usability test scores and perceived user satisfaction along with more complex navigation patterns.ConclusionsIn terms of system usability and functions, different levels of sophistication of and interaction performance with ENR systems exist in practice. This suggests that ENRs may have variable impacts on clinical outcomes and care quality. Future studies are needed to explore ENR impact on nursing care quality, efficiency, and safety.     

Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: A randomized controlled trial

ObjectiveTo evaluate the effects of escitalopram 10–20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes.Study designA double-blind, placebo-controlled randomized trial of escitalopram 10–20 mg/day vs. identical placebo was conducted among 205 women ages 40–62 years with an average of ≥4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010.Main outcome measuresThe primary trial outcomes, reported previously, were the frequency and severity of vasomotor symptoms at 8 weeks. Here, we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and the pain intensity and interference scale (PEG).ResultsOutcome data were collected on 97% of randomized women and 87% of women took at least 70% of their study medication. Treatment with escitalopram resulted in significantly greater improvement in total MENQOL scores (mean difference at 8 weeks of −0.41; 95% confidence interval (CI) −0.71 to −0.11; p < 0.001), as well as Vasomotor, Psychosocial, and Physical domain scores with the largest difference seen in the Vasomotor domain (mean difference −0.75; 95% CI −1.28 to −0.22; p = 0.02). There was no significant treatment group difference for the Sexual Function domain. Escitalopram treatment resulted in statistically significant improvements in PEG scores compared to placebo (mean treatment group difference at 8 weeks of −0.33; 95% CI −0.81 to 0.15; p = 0.045).ConclusionsTreatment with escitalopram 10–20 mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain.     

Efficacy and safety of paliperidone extended-release in schizophrenia patients with prominent affective symptoms

BackgroundThis post-hoc analysis evaluated the effects of paliperidone extended-release (ER) in patients with schizophrenia and prominent affective symptoms.MethodsPooled data from three 6-week, randomized, double-blind, placebo-controlled studies were analyzed. Subjects received fixed doses of paliperidone ER 3–12 mg/day or placebo. Prominent affective symptoms were defined as depressive (Positive and Negative Syndrome Scale [PANSS] depression item score of ≥ 5 [moderately severe]) and/or manic (PANSS grandiosity score of ≥ 4 [moderate], plus a score of ≥ 4 [moderate] on at least 1 PANSS item for excitement, hostility, uncooperativeness, or poor impulse control). Assessments included PANSS, Clinical Global Impressions-Severity (CGI-S), Personal and Social Performance (PSP) scale, and adverse events (AEs).ResultsAmong 193 patients with prominent affective symptoms, 140 received paliperidone ER and 53 received placebo. Paliperidone ER showed significant mean (SD) improvements vs. placebo in PANSS total (? 20.5 [23.8] vs. ? 6.3 [27.2]; p < 0.001, respectively) and all factor scores (p < 0.01). Significant mean (SD) improvements were observed in PSP (7.2 [15.8] vs. 0.4 [14.6]; p = 0.004) and CGI-S (? 0.9 [1.2] vs. ? 0.3 [1.2]; p < 0.001) scores. Most common AEs with paliperidone ER vs. placebo: headache (16.4% vs. 13.2%), insomnia (7.9% vs. 9.4%), akathisia (7.1% vs. 1.9%), sedation (7.1% vs. 3.8%).LimitationsThese studies were not designed to examine patients with prominent affective symptoms. Authors' clinical judgment was used to define prominent affective symptoms, using relevant PANSS items.ConclusionsPaliperidone ER was well tolerated and associated with significantly greater improvements in symptomatology, functioning, and overall clinical status vs. placebo in patients with schizophrenia and prominent affective symptoms.     

Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment

BackgroundAnaemia is a common side-effect of ribavirin (RBV) use that overwhelms management of hepatitis C when protease inhibitors are added.AimTo assess the pharmacogenomic impact of candidate genes SLC28A2, SLC28A3 and ITPA on anaemia in patients receiving triple therapy.MethodsPatients (n = 161) with chronic hepatitis C genotype 1 treated with telaprevir (n = 95) or boceprevir (n = 66) were included. Using RT-PCR we genotyped ITPA (rs1127354, rs7270101) and SLC28A3 (rs56350726, rs10868138) and SLC28A2 (rs11854484). Clinically significant anaemia (CSA) was diagnosed when at least one of the following criteria was observed: (a) haemoglobin <8.5 g/dL during treatment; (b) blood transfusion required; (c) erythropoietin administered.ResultsCSA occurred in 44% (69/157) of patients and was associated with SLC28A2 rs11854484 [CC/CT genotypes: 33% (26/78) vs. TT genotype: 56% (36/64); p = 0.006]. Further, the needed for blood transfusion was related to genotype [CC: 0% (0/18) vs. CT: 13% (8/61) vs. TT: 27% (17/64); p = 0.016]. Similarly, ITPA rs1127354 genotypes [AA/AC: 19% (3/16) vs. CC: 45% (61/135; p = 0.060] were linked to CSA. In multivariate analysis, SLC28A2 rs11854484 TT genotype (OR:2.33;95%CI:1.10–4.95; p = 0.027), female sex (OR:2.54;95% CI:1.13–5.71;p = 0.024) and Hb drop at week 4) OR: 1.36; 95CI%: 1.11–1.67; p = 0.003) were independently associated with CSA. Similarly, ITPA rs1127354 genotypes [AA/AC: 16% (3/19) vs. CC: 63% (85/134); p = 0.0001] and ITPA rs6051702 genotypes [CC/CA: 46% (26/57) vs. CC: 65% (60/93); p = 0.023] were related to Hb drop of >3g/dL at week 4.ConclusionsIn patients receiving first generation protease inhibitors, genotype SLC28A2 rs11854484 predicts CSA, and helps to identify a subgroup of patients with better tolerance of triple therapy.