Successful multifaceted intervention aimed to reduce short peripheral venous catheter-related adverse events: a quasiexperimental cohort study.

BACKGROUND: Data concerning the effectiveness of strategies implemented to reduce short peripheral vein catheter (PVC)-related adverse events are scarce. METHODS: A quasiexperimental study (2004-2011) was conducted to evaluate an intervention to reduce peripheral vein phlebitis (PVP) and PVC-related bloodstream infections (BSIs). Bundle intervention consisted of health care worker education and training, withdrawal of unnecessary catheters, exchange catheter policy, withdrawal of catheters at early stages of PVP, use of scales as a measuring tool, and repeated period-prevalence surveillance of PVC adverse events on wards. A Poisson exponentially weighted moving average control chart was used to assess time series analysis. RESULTS: One thousand six hundred thirty-one patients with 2,325 short catheters inserted were prospectively followed. PVP decreased by 48% (12.1% [95% confidence interval (CI): 10.7-13.2] during the intervention period versus 23.3% [95% CI: 16.4-30.1] in preintervention period; P < .05), and no reduction of PVP measured as 1,000 catheter-days was noted (48.6 [95% CI: 46.1-51.2] vs 37.9 [95% CI: 24.5-51.4], P > .05). A significant incidence reduction in PVC-related BSIs and health care-acquired Staphylococcus aureus BSIs was also achieved. CONCLUSION: A comprehensive multifaceted hospital approach was successful in reducing PVC-related adverse effects. Poisson exponentially weighted moving average control chart fits well as time series using Poisson data when very few events are present.

"The 3/3 strategy": a successful multifaceted hospital wide hand hygiene intervention based on WHO and continuous quality improvement methodology.

BACKGROUND: Only multifaceted hospital wide interventions have been successful in achieving sustained improvements in hand hygiene (HH) compliance. METHODOLOGY/PRINCIPAL FINDINGS: Pre-post intervention study of HH performance at baseline (October 2007-December 2009) and during intervention, which included two phases. Phase 1 (2010) included multimodal WHO approach. Phase 2 (2011) added Continuous Quality Improvement (CQI) tools and was based on: a) Increase of alcohol hand rub (AHR) solution placement (from 0.57 dispensers/bed to 1.56); b) Increase in frequency of audits (three days every three weeks: "3/3 strategy"); c) Implementation of a standardized register form of HH corrective actions; d) Statistical Process Control (SPC) as time series analysis methodology through appropriate control charts. During the intervention period we performed 819 scheduled direct observation audits which provided data from 11,714 HH opportunities. The most remarkable findings were: a) significant improvements in HH compliance with respect to baseline (25% mean increase); b) sustained high level (82%) of HH compliance during intervention; c) significant increase in AHRs consumption over time; c) significant decrease in the rate of healthcare-acquired MRSA; d) small but significant improvements in HH compliance when comparing phase 2 to phase 1 [79.5% (95% CI: 78.2-80.7) vs 84.6% (95% CI:83.8-85.4), p<0.05]; e) successful use of control charts to identify significant negative and positive deviations (special causes) related to the HH compliance process over time ("positive": 90.1% as highest HH compliance coinciding with the "World hygiene day"; and "negative":73.7% as lowest HH compliance coinciding with a statutory lay-off proceeding). CONCLUSIONS/SIGNIFICANCE: CQI tools may be a key addition to WHO strategy to maintain a good HH performance over time. In addition, SPC has shown to be a powerful methodology to detect special causes in HH performance (positive and negative) and to help establishing adequate feedback to healthcare workers.

Short Communication: Natural killer cells and expression of KIR receptors in chronic HIV type 1-infected patients after different strategies of structured therapy interruption.

Few data evaluating the NK cell profile during structured therapy interruption (STI) in chronic HIV-1 infection are available. Changes in NK cell percentages and KIR and NKG2A receptors were analyzed at baseline and after 2 years of follow-up in 121 patients on ART with CD4(+) >450 cells/ml and VL <200 copies/ml randomized in three arms according to the criteria employed to resume ART during STI: virological arm (VA n = 47, VL >30,000 copies/ml or CD4 <350 cells/ml), immunological arm (IA n = 37, CD4< 350 cells/ml), and a control arm (n = 37) in which ART was maintained. After 2 years of follow-up, a decrease in CD3(-)CD56(+) CD16(+) cell percentages in VA and IA patients, but not in CA patients, was observed. Those patients with higher decrease in CD3(-)CD56(+)CD16(+) cells had a higher decrease in CD4(+) cells (r = 0.35, p = 0.001) and higher increase in PVL (r = -0.26, p = 0.02). KIR and NKG2A receptor expression tended to increase in CA and decreased in the other two arms (more in IA than in VA). Patients who displayed a greater decrease in CD4(+) T cells and a greater rise in PVL after 2 years of follow-up had a significantly higher decrease in KIR and NKG2A receptors expressed in CD3(-)CD56(+) cells. Patients who presented the lowest levels of total NK cells and KIR and NKG2A receptor expression after STI showed the poorest virology or immunology outcomes. This finding suggests that STI could decrease the number of NK subsets, which is related to the worst clinical development in these patients.

Relevance of HIV-1-specific CD4+ helper T-cell responses during structured treatment interruptions in patients with CD4+ T-cell nadir above 400/mm3.

OBJECTIVES: To analyze the dynamics of both HIV-1-specific CD4 and CD8 T-cell responses during structured treatment interruptions (STIs) in chronically HIV-1-infected (CHI) patients and to correlate them with the viral set point achieved. METHODS: Forty-five early-stage CHI patients who were on highly active antiretroviral therapy (HAART) for at least 1 year and underwent STI were included. Plasma viral load (VL), peripheral blood mononuclear cell (PBMC) lymphoproliferative (LPR) response to HIV p24 protein, and HIV-1 epitope-specific interferon-gammarelease from CD8 T cells were measured over a minimum study period of 2 years. RESULTS: VL set point during final STI was both significantly lower than, and positively correlated to, baseline VL (P < 0.0001: mean VL reduction 0.77 log10, and r = 0.42, P = 0.004, respectively). CD4 LPRs to p24 increased significantly (P = 0.001) between day 0 of the first STI cycle and 4th STI but decreased thereafter. VL set point during final STI was significantly and negatively correlated with LPRs to p24 at both 2nd STI and 4th STI. Nevertheless, at week 52, 12 weeks after the end of the last STI, LPRs were weak and transient in all patients and were not correlated with VL set point. Moreover, the magnitude and breadth of HIV-1-specific CD8 T-cell responses increased significantly (P < 0.0001) between day 0 and week 52. The largest increases occurred during the final STI. Even though VL reached set point by week 12 of the final STI, HIV-1-specific CD8 T-cell responses did not stabilize but rather increased until the end of the follow-up and did not correlate with plasma VL (r = 0.01, P = 0.88). CONCLUSIONS: STIs do not lead to control of viral replication in CHI patients, probably due to the fact that boosted CTL responses lack strong and durable helper T-cell responses. To reset the VL set point, new approaches that effectively augment and preserve helper T-cell responses should be investigated.

Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count.

Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.

A prospective trial of structured treatment interruptions in human immunodeficiency virus infection.

BACKGROUND: According to the "autovaccination hypothesis," reexposure to human immunodeficiency virus (HIV) during treatment interruptions may stimulate the HIV-specific immune response and lead to low viremia after withdrawal of highly active antiretroviral treatment (HAART). Many patients who started HAART earlier in their disease course than is currently recommended would like to discontinue, but it is unknown whether it is safe to do so. OBJECTIVES: To determine whether repeated treatment interruptions of HAART (1) stimulated the cytotoxic HIV-specific immune response and whether such stimulation correlated with low viremia off treatment, and (2) were safe with respect to clinical complications, development of viral resistance, and decline in CD4 cell counts. DESIGN: Interventional study with before-after comparison. SETTING: Outpatient clinics of university hospitals in Switzerland and Spain. PATIENTS: A total of 133 patients receiving HAART, with a median CD4 cell count of 740/ microL, and whose viral load had been undetectable for a median of 21 months. INTERVENTIONS: HAART was interrupted for 2 weeks, restarted, and continued for 8 weeks. After 4 such cycles, treatment was indefinitely suspended 40 weeks after study entry. MAIN OUTCOME MEASURES: HIV-specific cytotoxic T-cell responses were evaluated by interferon gamma enzyme-linked immunospot analysis. The proportion of "responders" (viral load <5000 copies/mL) was measured at weeks 52 and 96. HIV-related diseases and CD4 cell counts were recorded. RESULTS: Seventeen percent of patients (95% confidence interval, 11%-25%) were responders at week 52, and 8% at week 96. Low pre-HAART viral load and lack of rebound during weeks 0 to 40 predicted response. HIV-specific CD8+ T cells increased between week 0 (median, 343 spot-forming cells per million peripheral blood lymphocytes [SFC/106 PBL]) and week 52 (median, 1930 SFC/106 PBL), but there was an inverse correlation between response and the number of spot-forming cells. Eighty-five (64%) of 133 patients stopped therapy for at least 12 weeks, and 55 (41%) for at least 56 weeks. The median CD4 cell count decreased from 792/ microL to 615/ microL during the first 12 weeks without treatment, but stabilized thereafter. One patient (0.75%) developed drug resistance necessitating salvage treatment. There were no AIDS-related clinical complications. CONCLUSIONS: Results of this study do not favor the autovaccination hypothesis. Treatment interruptions did not provoke clinical complications, and there was little drug resistance. Comparative trials will have to show what benefit, if any, is associated with intermittent, as opposed to continuous treatment.

Predictors of tonsillar tissue HIV-1 viral burden at baseline and after 1 year of antiretroviral therapy.

In 81 antiretroviral-navie HIV-1 chronic-infected patients, we found a correlation among tonsillar tissue viral load, and virological and immunological measures in blood at baseline. No correlation was observed after 1 year of antiretroviral therapy. A protease inhibitor-containing regimen was the best predictor of good tonsillar tissue virological response.

Metabolic and immunological effects of antiretroviral agents in healthy individuals receiving post-exposure prophylaxis.

We have assessed metabolic and immunological effects of a nelfinavir-containing regimen in healthy HIV-1-uninfected individuals receiving post-exposure prophylaxis. Our data suggest that this regimen is well tolerated and did not modify the lipid or hepatic profiles. This antiretroviral regimen seems to have no effect on lymphocyte T cell subsets, however, it could have an immune-modulator role, inducing an increase in the proliferative responses to mitogens.

Immunological and virological factors at baseline may predict response to structured therapy interruption in early stage chronic HIV-1 infection.

BACKGROUND: The objective was to analyse which baseline factors could predict a favourable outcome after structured therapy interruption (STI). METHODS: Data of three Spanish pilot studies of STI in early stage chronic HIV-1-infected patients were analysed. A set of 37 variables at baseline was used. Plasma and tonsillar tissue viral load (VL), lymphocyte immunophenotyping and proliferative responses (LPR) to mitogens and specific antigens, and HIV-1 specific cytotoxic T lymphocyte responses were assessed at baseline. Response was defined as a VL set-point after 6 months off antiretroviral therapy after the last interruption of < 5000 copies/ml and 0.5 log(10) below baseline PVL before any antiretroviral therapy. RESULTS: After STI, the 44 patients were classified as follows: 18 (41%) as responders, 26 (59%) as non-responders. In the univariate analysis patients who responded had a significantly lower baseline level of CD4CD38 (P = 0.0068) and naive CD4 T cells (P = 0.03), and a higher level of memory CD4 T cells (P = 0.03) and proliferative response to tetanus toxoid (TT) (P = 0.01) and HIV-1 p24 (P = 0.03) than non-responders. A model incorporating five qualitative variables transformed according to the median value (CD4CD38, CD4 naive and memory T cells and stimulation index to TT and HIV-1 p24) at baseline could classify 97% of patients correctly (P = 0.0001). CONCLUSIONS: A level of memory CD4 T cells and proliferative response to recall antigens above the median may predict a good response to STI, suggesting that preserved memory response in CD4 T cells is important factor.

Genotypic and phenotypic resistance patterns in early-stage HIV-1-infected patients failing initial therapy with stavudine, didanosine and nevirapine.

The objectives of this study were to determine the genotypic and phenotypic patterns of resistance in a group of early-stage antiretroviral-naive patients failing initial therapy with didanosine, stavudine and nevirapine. These patterns of resistance were determined at baseline and at time of virological failure in 89 antiretroviral-naive patients with CD4 cells >500 cells/ml and viral load >5000 copies/ml who received initial antiretroviral therapy with didanosine plus stavudine and nevirapine as part of the SCAN study, and who failed after having reached undetectable plasma levels (<200 copies/ml). Of the 89 patients recruited in the SCAN study, 14 (16%) developed a virological failure after reaching a viral load below 200 copies/ml after a median of 20 months of follow-up. At baseline, none of these 14 patients had genotypic resistance. At time of failure, six out of 14 (43%) failing patients had wild-type genotype and no phenotypic resistance. Suboptimal compliance could be documented in four of these six patients. Seven patients (50%) had nevirapine resistance mutations (mainly K103N [4/7], Y181C/I [2/7], G190A/S [2/7] and V108I [1/7]) associated with phenotypic high-level resistance to nevirapine, delavirdine and efavirenz (nevirapine >47.4- to 58.1-fold, delavirdine >74.4- to 168.9-fold and efavirenz >56.0- to 347.2-fold). Four of these seven patients also had thymidine analogue-associated mutations (TAM) (T215Y/F [2/4], M41L [1/4], D67N [2/4] and K70R [1/4]). Finally, one patient (7%) had exclusively TAM mutations (M41L). None of the patients developed mutations associated with didanosine resistance or phenotypic resistance to didanosine or stavudine. Suboptimal compliance or selection of nevirapine resistance often with TAM mutations was frequently associated with virological failure in a cohort of early-stage chronic HIV-1-infected patients treated with a protease inhibitor-sparing regimen.

Evaluación del impacto en la calidad asistencial y análisis coste-efectividad de la reforma de un servicio de urgencias de medicina / Reform of an emergency department and its impact on health care quality and cost-effectiveness

FUNDAMENTO: Determinar el efecto sobre la eficacia, calidad y eficiencia asistencial de una reforma de una unidad de urgencias de medicina (UUM). MATERIAL Y MÉTODO: Las reformas consistieron en la ampliación del 50 por ciento de los recursos estructurales y del 34 por ciento de los recursos humanos. Así mismo, se rediseñaron los roles de cada miembro de la guardia, se implantaron nuevos circuitos y se redefinió la relación entre la UUM y el resto de los servicios del hospital. Como indicadores de eficacia se utilizaron el número de pacientes que esperaban empezar a ser atendidos (Pesp), el tiempo de espera del paciente para ser atendido (Tesp) y el tiempo total de estancia en urgencias (Ttotal). Los indicadores de calidad fueron el índice de pacientes no visitados (IPNV), revisitados (IPR) y fallecidos (IPF). Todos estos parámetros, además del número de visitas, se determinaron a diario durante tres semanas antes (febrero de 1999) y después (febrero de 2000) de las reformas. Para estimar la efectividad se utilizaron los cocientes Ptotal/Tesp (E1) y Ptotal/Pesp (E2). El cálculo de costes se efectuó a partir del control presupuestario y se realizó un análisis coste-efectividad (C/E) para conocer la eficiencia. RESULTADOS: Durante el año 2000, las visitas se incrementaron un 12 por ciento (intervalo de confianza [IC] del 95 por ciento, 2 a 22 por ciento). A pesar de ello, se observó una mejoría significativa de casi todos los indicadores estudiados tras la implantación de la reforma: Pesp -57 por ciento (IC del 95 por ciento, -37 a -77 por ciento); Tesp -72 por ciento (IC del 95 por ciento, -51 a -93 por ciento); Ttotal -29 por ciento (IC del 95 por ciento, -13 a -45 por ciento); IPNV -2 por ciento (IC del 95 por ciento, +42 a -46 por ciento); IPR -75 por ciento (IC del 95 por ciento: -45 por ciento a -105 por ciento) y IPF -51 por ciento (IC 95 por ciento: +12 por ciento a -114 por ciento). La E1 mejoró un 996 por ciento (IC del 95 por ciento, 335 a 1.658 por ciento) y la E2 un 186 por ciento (IC del 95 por ciento, -23 a 395 por ciento). El análisis de C/E indica una mejora del 70 por ciento (IC del 95 por ciento, 33 a 107 por ciento) y del 56 por ciento (IC del 95 por ciento, 18 a 94 por ciento) en relación con E1 y E2 respectivamente tras la reforma. CONCLUSIÓN: La dotación de un servicio de urgencias con los recursos necesarios permite mejorar de forma sustancial su eficacia y calidad, y en última instancia el servicio prestado y la calidad percibida por el usuario. Además, a pesar del incremento del coste por la reforma, se consigue una mayor eficiencia (AU)