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Predicting incident radiographic knee osteoarthritis in middle-aged women within 4 years
Objective Develop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis (RKOA) in middle-aged women. Methods We analysed 649 women in the Chingford 1000 Women study. The outcome was incident RKOA, defined as Kellgren/Lawrence grade 0-1 at baseline and ≥2 at year 5. We estimated predictors’ effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and ilium’s vertical cortex (hip α-angle)). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve, AUC). Results The clinical model contained age, quadriceps circumference, and a cartilage degradation marker (CTX-II) as predictors (AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence 1 (versus 0), greater hip α-angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors (AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA. A clinical risk score tool was developed from the clinical model. Conclusion Two models predicting incident RKOA within 4 years were developed; including radiographic variables improved model performance. First-time predictor hip α-angle and contralateral RKOA suggest osteoarthritis origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but should be externally validated.
Predicting incident radiographic knee osteoarthritis in middle-aged women within 4 years: the importance of knee-level prognostic factors.
OBJECTIVE: Develop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis (RKOA) in middle-aged women. METHODS: We analysed 649 women in the Chingford 1000 Women study. The outcome was incident RKOA, defined as Kellgren/Lawrence grade 0-1 at baseline and ≥2 at year 5. We estimated predictors' effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and ilium's vertical cortex (hip α-angle)). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve, AUC). RESULTS: The clinical model contained age, quadriceps circumference, and a cartilage degradation marker (CTX-II) as predictors (AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence grade 1 (versus 0), greater hip α-angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors (AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA. A clinical risk score tool was developed from the clinical model. CONCLUSION: Two models predicting incident RKOA within 4 years were developed; including radiographic variables improved model performance. First-time predictor hip α-angle and contralateral RKOA suggest osteoarthritis origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but should be externally validated. This article is protected by copyright. All rights reserved.
SUPERVIVENCIA EN PERSONAS INFECTADAS POR EL VIH. BARCELONA, 2001-2013
788. SUPERVIVENCIA EN PERSONAS INFECTADAS POR EL VIH. BARCELONA, 2001-2013 C. Garriga, P. García de Olalla, J.A. Caylà Agencia de Salud Pública de Barcelona (ASPB); Programa de Epidemiología Aplicada de Campo (PEAC), CNE; Centros de Investigación Biomédica en Red (CIBER). Antecedentes/Objetivos: El tratamiento antirretroviral ha supuesto la disminución de la mortalidad por el VIH. El objetivo de este trabajo es analizar los factores asociados con la supervivencia y describir la causa de muerte en pacientes diagnosticados de infección por el VIH. Métodos: De los nuevos diagnósticos incluidos en el registro de VIH de Barcelona ciudad entre 2001-12 se buscaron los fallecidos en el censo de población hasta el 30.06.2013. La causa específica de muerte se obtuvo del registro de mortalidad. Las causas se clasificaron: causa externa (CIE-10: X), VIH (B20-B24, B44.9, C83.7 y C85.9) y no-VIH (resto de códigos). La tasa de mortalidad se calculó en personas año en seguimiento por 1.000 y su intervalo de confianza al 95% (M; IC95%). Se realizó un análisis descriptivo y multivariado de regresión de Cox para evaluar factores sociodemográficos, epidemiológicos y clínicos asociados con supervivencia. La medida de asociación usada fue la hazard ratio (HR) y su IC95%. Resultados: De los 3.533 nuevos diagnósticos de VIH, 168 individuos (5%) fallecieron (M: 8,2; IC95%: 6,9-9,4). Se obtuvo la causa de muerte de 93 (55%). En estos, 43% fallecieron por causas no relacionadas con el VIH (M: 1,9; IC95%: 1,3-2,5); 42% por causas relacionadas (M: 1,9; IC95%: 1,3-2,5) y 15% por causas externas (M: 0,7; IC95%: 0,3-1,0). La peor supervivencia se observó en usuarios de drogas inyectadas (UDI) (HR: 4,7; IC95%: 2,9-7,7) y hombres heterosexuales (HTS) (HR: 2,4; IC95%: 1,4-3,9), en españoles (HR: 2,5; IC95%: 1,6-4,0), en residentes del distrito de Gràcia (HR: 2,0; IC95%: 1,1-3,7), en personas sin estudios/primarios (HR: 1,5; IC95%: 1,1-2,2) y en individuos con < 200 CD4 (HR: 1,8; IC95%: 1,2-3,0). Las causas de muerte relacionadas con el VIH fueron infecciones (48%), más frecuentes en hombres que tienen sexo con hombres (HSH) (63%), seguidas de mujeres HTS (60%) y neoplasias malignas (23%) en hombres HTS (50%). Las no relacionadas fueron cáncer (29%), que afectó más a hombres (32%), personas con estudios secundarios/universitarios (39%) y hombres HTS (50%); enfermedades cardiovasculares (22%) en mujeres HTS (57%) y personas sin estudios/primarios (35%) y; enfermedades hepáticas (19%) en UDI (37%). Conclusiones: La mayor probabilidad de morir se asoció con ser UDI, hombre HTS, español con bajo nivel de estudios y un sistema inmune muy deteriorado. Las infecciones representan la mitad de las muertes relacionadas con el VIH y afectan más a HSH y mujeres. El cáncer fue la principal causa de muerte entre las no relacionas con la infección siendo más frecuente en españoles con mayor nivel de estudios. La frecuencia según la causa de muerte (relacionadas clásicamente con el VIH y las no relacionadas) fue similar.
Geographical Variation in Outcomes of Primary Hip and Knee Replacement
Importance: Little is known about variation in outcomes of surgery, nor about factors that can explain why such variation exists. Objectives: To describe variation in patient outcomes and costs for primary hip and knee replacement across health areas and to identify whether patient, surgical and hospital factors can explain such variation. Design: Retrospective observational cohort study Setting: National Joint Registry, linked to English Hospital Episode Statistics and Patient Reported Outcome Measures datasets Participants: Patients undergoing primary total hip/knee replacement aged ≥18 from 2014 to 2016 Exposures: Patient (age, gender, body mass index, deprivation); surgical (surgeon volume, surgeon grade); hospital organisation (operating theatres, specialist consultants, hospital volume) Main outcome measures: Multilevel regression models were generated for the outcomes: length of stay, bed-day costs, change in Oxford hip/knee scores 6-months after surgery, complications by 6 months. Geographical Information Systems were used to display maps describing adjusted estimates of variation in outcomes across health areas. Results: 173,107 primary total hip replacements and 210,275 total knee replacements were available, nested in 207 health areas. We identified a number of factors that predicted poorer outcomes of surgery: Public hospitals, low volume of surgeries per surgeon and hospital and workforce with a high number of less experienced doctors were associated with poorer outcomes of surgery. Although these factors did not attenuate the magnitude of variation across health areas, they had ecological correlations with the observed geographical variations in outcomes of surgery by health area. Across health areas, predicted mean length of stay ranged from 3 to 7 days and associated bed-day costs from £4727 to £8800, for both total hip and knee replacement. The absolute predicted mean change in Oxford hip score varied from 18.7 to 24.6 points (13.1 to 18.8 for Oxford knee score). Predicted 6-month complications ranged from 3% to 6%, for both total hip and knee replacement. Conclusions and Relevance: Our models indicate that a minimum surgical volume by surgeon and by hospital; and private hospitals are associated with better outcomes of surgery, while a higher proportion of less experienced doctors by hospital might compromise achieving those outcomes. This variation is observed geographically.
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy
Background: Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g. R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex.Results: The cross-sectional study carried out with >200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations.Conclusions: Our study shows the association of R284K and TAM1 mutations in individuals failing therapy with tenofovir/emtricitabine, and unveils a novel mechanism by which secondary mutations are selected in the context of drug-resistance mutations. © 2012 Betancor et al.; licensee BioMed Central Ltd.
Trastorno psicológico en mujeres y hombres con VIH en España: estudio transversal telefónico
Resumen Antecedentes/Objetivos Los objetivos de este estudio fueron determinar la prevalencia de trastorno psicológico en mujeres y hombres con VIH e identificar factores de riesgo asociados. Methods 99 mujeres y 464 hombres fueron entrevistados por teléfono entre 2010 y 2014 sobre características socio-demográficas, consumo de fármacos y sustancias, salud autopercibida y mental y adherencia a la terapia antirretroviral (TAR). Los entrevistados provenían de una cohorte prospectiva de pacientes VIH (CoRIS). Este estudio transversal definió como paciente a riesgo de trastorno psicológico aquel puntuando ≥3 en el cuestionario de salud general 12-item. Se usó imputación múltiple para evitar el impacto de los valores perdidos. Se realizó un análisis de regresión logística hacia atrás para identificar factores de riesgo asociados con trastorno psicológico. Results Hubo mayor proporción de trastorno psicológico entre mujeres que entre hombres, 51 (51.5%) y 179 (38.6%). Factores de riesgo comunes a mujeres y hombres fueron el consumo de substancias psicoactivas, [odds ratio: 8.1 y 2.1, intervalos de confianza 95%: (2.0‒32.3) y (1.1‒4.1), respectivamente]; pobre salud autopercibida [4.1 y 2.7, (1.3‒12.7) y (1.6‒4.7)]; pobre adherencia al TAR [4.5 y 2.5, (1.3‒15.0) y (1.3‒4.6)]; y no ser usuario de TAR [8.4 y 2.0, (2.2‒32.3) y (1.2‒3.3)]. Pobre actividad física fue un factor de riesgo solo para mujeres [3.1, (1.1‒9.0)]. Importantes factores de riesgo para los hombres fueron vivir sólo [2.1, (1.3‒3.3)]; y estar desempleado. [2.2, (1.4‒3.6)]. El atazanavir también se relacionó con trastorno psicológico en hombres [2.9, (1.0‒8.3)]. El estudio estuvo limitado por el bajo número de mujeres y la falta de información clínica en el 15% de los pacientes. Conclusiones La mayor proporción de mujeres con trastorno psicológico debería ser tenida en cuenta por los profesionales sanitarios. El enfoque de género es necesario para conducir los diferentes factores de riesgo encontrados en mujeres y hombres. La adherencia al TAR no se asoció con trastorno psicológico pero el atazanavir precisa de posterior farmacovigilancia para establecer su relación con trastorno psicológico.
DR_SEQAN: A PC/windows-based software to evaluate drug resistance using human immunodeficiency virus type I genotypes
Background: Genotypic assays based on DNA sequencing of part or the whole reverse transcriptase (RT)- and protease (PR)-coding regions of the human immunodeficiency virus type 1 (HIV-1) genome have become part of the routine clinical management of HIV-infected individuals. However, the results are difficult to interpret due to complex interactions between mutations found in viral genes. Results: DR_SEQAN is a tool to analyze RT and PR sequences. The program output includes a list containing all of the amino acid changes found in the query sequence in comparison with the sequence of a wild-type HIV-1 strain. Translation of codons containing nucleotide mixtures can result in potential ambiguities or heterogeneities in the amino acid sequence. The program identifies all possible combinations of 2 or 3 amino acids that derive from translation of triplets containing nucleotide mixtures. In addition, when ambiguities affect codons relevant for drug resistance, DR_SEQAN allows the user to select the appropriate mutation to be considered by the program's drug resistance interpretation algorithm. Resistance is predicted using a rule-based algorithm, whose efficiency and accuracy has been tested with a large set of drug susceptibility data. Drug resistance predictions given by DR_SEQAN were consistent with phenotypic data and coherent with predictions provided by other publicly available algorithms. In addition, the program output provides two tables showing published drug susceptibility data and references for mutations and combinations of mutations found in the analyzed sequence. These data are retrieved from an integrated relational database, implemented in Microsoft Access, which includes two sets of non-redundant core tables (one for combinations of mutations in the PR and the other for combinations in the RT). Conclusion: DR_SEQAN is an easy to use off-line application that provides expert advice on HIV genotypic resistance interpretation. It is coded in Visual Basic for use in PC/Windows-based platforms. The program is freely available under the General Public License. The program (including the integrated database), documentation and a sample sequence can be downloaded from http://www2.cbm.uam.es:8080/lmenendez/ DR_SEQAN.zip. © 2006 Garriga and Menéndez-Arias; licensee BioMed Central Ltd.
Development of a model predicting non-satisfaction 1 year after primary total knee replacement in the UK and transportation to Switzerland
© 2018 The Author(s). We aimed to develop a predictive model for non-satisfaction following primary total knee replacement (TKR) and to assess its transportability to another health care system. Data for model development were obtained from two UK tertiary hospitals. Model transportation data were collected from Geneva University Hospitals in Switzerland. Participants were individuals undergoing primary TKR with non-satisfaction with surgery after one year the outcome of interest. Multiple imputation and logistic regression modelling with bootstrap backward selection were used to identify predictors of outcome. Model performance was assessed by discrimination and calibration. 64 (14.2%) patients in the UK and 157 (19.9%) in Geneva were non-satisfied with their TKR. Predictors in the UK cohort were worse pre-operative pain and function, current smoking, treatment for anxiety and not having been treated with injected corticosteroids (corrected AUC = 0.65). Transportation to the Geneva cohort showed an AUC of 0.55. Importantly, two UK predictors (treated for anxiety, injected corticosteroids) were not predictive in Geneva. A better model fit was obtained when coefficients were re-estimated in the Geneva sample (AUC = 0.64). The model did not perform well when transported to a different country, but improved when it was re-estimated. This emphasises the need to re-validate the model for each setting/country.
Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery article
© 2018 The Author(s). To develop and validate a clinical prediction model of patient-reported pain and function after undergoing total knee replacement (TKR). We used data of 1,649 patients from the Knee Arthroplasty Trial who received primary TKR across 34 centres in the UK. The external validation included 595 patients from Southampton University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors including patient characteristics and clinical factors were considered. Bootstrap backward linear regression analysis was used. Low pre-operative OKS, living in poor areas, high body mass index, and patient-reported anxiety or depression were associated with worse outcome. The clinical factors associated with worse outcome were worse pre-operative physical status, presence of other conditions affecting mobility and previous knee arthroscopy. Presence of fixed flexion deformity and an absent or damaged pre-operative anterior cruciate ligament (compared with intact) were associated with better outcome. Discrimination and calibration statistics were satisfactory. External validation predicted 21.1% of the variance of outcome. This is the first clinical prediction model for predicting self-reported pain and function 12 months after TKR to be externally validated. It will help to inform to patients regarding expectations of the outcome after knee replacement surgery.
Mortality, causes of death and associated factors relate to a large HIV population-based cohort
© 2015 Garriga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013. Materials and Methods: We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models. Mortality Results: 182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0-16.1/1000 py], 81.3%of them had a known cause of death. Mortality rate by HIVrelated causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7-6.1/1000 py), external was lower [1.7/1000 py; (1.0-2.4/1000 py)]. Survival Results: Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5-7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3-5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4-1.7) and heterosexual female (sHR:2.8; CI:1.1-7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7-123.2) and heterosexual male (sHR:11.8; CI:2.5-56.4) versusMSM. Conclusion and Recommendation: There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.
Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients
© 2017 The Authors Introduction Rheumatoid arthritis is a systemic inflammatory disease, and classical disease-modifying antirheumatic drugs (cDMARDs) have proven efficacy. It is unknown what impact cDMARDs might have on dementia as an outcome. Methods Incident diagnoses of rheumatoid arthritis in persons over 18 years from 1995 to 2011 were identified from the UK Clinical Practice Research Datalink. There were 3876 cDMARD users and were propensity score matched to 1938 nonusers, on a wide range of confounders. Impact on dementia was assessed using survival models. Results cDMARD users were at reduced risk of dementia (hazard ratio: 0.60; 95% confidence interval: 0.42–0.85). The effect was strongest in methotrexate users (hazard ratio: 0.52; 95% confidence interval; 0.34–0.82). Discussion The strong effect of cDMARD use on halving of dementia risk requires replication in a trial and may provide an important therapeutic pharmacological treatment.
Evolution of acute hepatitis C virus infection in a large European city: Trends and new patterns
© 2017 Garriga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The aims of this study were to describe the evolution of acute hepatitis C virus (HCV) infections since 2004 and to determine its associated factors. Acute HCV infections diagnosed in Barcelona from 2004 to 2015 were included. Incidence ratios (IR) were then estimated for sex and age groups. Cases were grouped between 2004–2005, 2006–2011 and 2012–2015, and their incidence rate ratios (IRR) were calculated. In addition, risk factors for acute HCV infection were identified using multinomial logistic regression for complete, available and multiple imputed data. 204 new HCV cases were identified. Two peaks of higher IR of acute HCV infection in 2005 and 2013 were observed. Men and those aged 35–54 had higher IR. IRR for men was 2.9 times greater than in women (95% confidence intervals (CI): 1.8 - 4.7). Factors related to the period 2012–2015 (versus 2006–2011) were: a) sexual risk factor for transmission versus nosocomial (relative-risk ratio (RRR): 13.0; 95% CI: 2.3 - 72.1), b) higher educated versus lower (RRR: 5.4; 95% CI: 1.6 - 18.7), and c) HIV coinfected versus not HIV-infected (RRR: 53.1; 95% CI: 5.7 - 492.6). This is one of the few studies showing IR and RRRs of acute HCV infections and the first focused on a large city in Spain. Sexual risk for transmission between men, higher educational level and HIV co-infection are important factors for understanding current HCV epidemic. There has been a partial shift in the pattern of the risk factor for transmission from nosocomial to sexual.
Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure
Previous studies showed an increased prevalence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) thumb subdomain polymorphisms Pro272, Arg277, and Thr286 in patients failing therapy with nucleoside analogue combinations. Interestingly, wild-type HIV-1BH10 RT contains Pro272, Arg277, and Thr286. Here, we demonstrate that in the presence of zidovudine, HIV-1BH10 RT mutations P272A/R277K/T286A produce a significant reduction of the viral replication capacity in peripheral blood mononuclear cells in both the absence and presence of M41L/T215Y. In studies carried out with recombinant enzymes, we show that RT thumb subdomain mutations decrease primer-unblocking activity on RNA/DNA complexes, but not on DNA/DNA template-primers. These effects were observed with primers terminated with thymidine analogues (i.e., zidovudine and stavudine) and carbovir (the relevant derivative of abacavir) and were more pronounced when mutations were introduced in the wild-type HIV-1BH10 RT sequence context. RT thumb subdomain mutations increased by 2-fold the apparent dissociation equilibrium constant (Kd) for RNA/DNA without affecting the Kd for DNA/DNA substrates. RNase H assays carried out with RNA/DNA complexes did not reveal an increase in the reaction rate or in secondary cleavage events that could account for the decreased excision activity. The interaction of Arg277 with the phosphate backbone of the RNA template in HIV-1 RT bound to RNA/DNA and the location of Thr286 close to the RNA strand are consistent with thumb polymorphisms playing a role in decreasing nucleoside RT inhibitor excision activity on RNA/DNA template-primers by affecting interactions with the template-primer duplex without involvement of the RNase H activity of the enzyme. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments
Human immunodeficiency virus type 1 (HIV-1) antiviral drug resistance is a major consequence of therapy failure and compromises future therapeutic options. Nelfinavir and lopinavir/ritonavir-based therapies have been widely used in the treatment of HIV-infected patients, in combination with reverse transcriptase inhibitors. The aim of this observational study was the identification and characterization of mutations or combinations of mutations associated with resistance to nelfinavir and lopinavir/ritonavir in treated patients. Nucleotide sequences of 1,515 subtype B HIV-1 isolates from 1,313 persons with different treatment histories (including naïve and treated patients) were collected in 31 Spanish hospitals over the years 2002-2005. Chi-square contingency tests were performed to detect mutations associated with failure to protease inhibitor-based therapies, and correlated mutations were identified using statistical methods. Virological failure to nelfinavir was associated with two different mutational pathways. D30N and N88D appeared mostly in patients without previous exposure to protease inhibitors, while K20T was identified as a secondary resistance mutation in those patients. On the other hand, L90M together with L10I, I54V, A71V, G73S, and V82A were selected in protease inhibitor-experienced patients. A series of correlated mutations including L10I, M46I, I54V, A71V, G73S, and L90M appeared as a common cluster of amino acid substitutions, associated with failure to lopinavir/ritonavir-based treatments. Despite the relatively high genetic barrier of some protease inhibitors, a relatively small cluster of mutations, previously selected under drug pressure, can seriously compromise the efficiency of nelfinavir-and lopinavir/ritonavir- based therapies. © 2007 Wiley-Liss, Inc.
[Characteristics of cases of infectious syphilis diagnosed in prisons, 2007-2008].
To describe the characteristics of cases of syphilis amongst prison inmates. Descriptive study. Confirmed cases of primary, secondary and early latent syphilis were identified in prisons in Spain during 2007-2008. Socio-demographic and clinical information, as well as variables related to transmission, was collected by the attending physicians in a standard form. Frequency distributions of each variable were performed. Annual incidence rates were calculated. To evaluate the association between qualitative variables, the χ2and Fisher's exact tests were used; the Mann-Whitney test was utilized to compare quantitative variables. During the study period, 94 syphilis cases were identified (35.1% primary, 20.2% secondary and 44.7% early latent). The incidence rates were 0.9 cases/1000 prisoners in 2007 and 0.7 cases/1000 prisoners in 2008. Most cases were male (90.4%), between 31-40 years old (30.9%) and foreigners (52.1%). The majority of patients were diagnosed through screening (80.9%). Heterosexual contact was the most frequent transmission route (83.0%). Overall HIV prevalence was 5.3%, and 16.0% of the patients had a history of previous sexually transmitted infections (STI). Almost 40% of the cases reported being a client of a sex worker. Incidence of syphilis in prison is high. Many syphilis patients were detected through screening, highlighting the role of the Spanish prison health service in STI control.
Impact of a national enhanced recovery after surgery programme on patient outcomes of primary total knee replacement: an interrupted time series analysis from “The National Joint Registry of England, Wales, Northern Ireland and the Isle of Man”
© 2019 The Authors Objective: We aimed to test whether a national Enhanced Recovery After Surgery (ERAS) Programme in total knee replacement (TKR) had an impact on patient outcomes. Design: Natural-experiment (April 2008–December 2016). Interrupted time-series regression assessed impact on trends before-during-after ERAS implementation. Setting: Primary operations from the UK National Joint Registry (NJR) were linked with Hospital Episode Statistics (HES) data which contains inpatient episodes undertaken in National Health Service (NHS) trusts in England, and Patient Reported Outcome Measures (PROMs). Participants: Patients undergoing primary planned TKR aged ≥18 years. Intervention: ERAS implementation (April 2009–March 2011). Outcomes: Regression coefficients of monthly means of Length of stay (LOS), bed day costs, change in Oxford knee scores (OKS) 6-months after surgery, complications (at 6 months), and rates of revision surgeries (at 5 years). Results: 486,579 primary TKRs were identified. Overall LOS and bed-day costs decreased from 5.8 days to 3.7 and from £7607 to £5276, from April 2008 to December 2016. Oxford knee score (OKS) change improved from 15.1 points in April 2008 to 17.1 points in December 2016. Complications decreased from 4.1 % in April 2008 to 1.7 % in March 2016. 5-year revision rates remained stable at 4.8 per 1000 implants years in April 2008 and December 2011. After ERAS, declining trends in LOS and bed costs slowed down; OKS improved, complications remained stable, and revisions slightly increased. Conclusions: Different secular trends in outcomes for patients having TKR have been observed over the last decade. Although patient outcomes are better than a decade ago ERAS did not improve them at national level.