bluuebunny/crossref_metadata_2025 huggingface dataset:
Infections and cancer after ARV: a Portuguese cohort
Authors: Pereira N , Caldas C , Azevedo C , Andrade P , Serrão R , Sarmento A
Published: November 2012

Background and purpose of the study

The advent of antiretroviral therapy (ARV) resulted in a significant decrease in opportunistic infections; however these diseases still represent an important cause of morbidity and mortality. ARV also changed the spectrum of cancers presented by HIV patients as a result of immune recovery and increased life expectancy. We intend to describe the variety of infections and cancers, AIDS or non‐AIDS related, identified in our patients in the new era of ARV and also identify possible risk factors related to this conditions.

Methods

Assessment and registry of infectious and neoplastic conditions occurring after initiation of ARV in a cohort of HIV‐infected patients who started ARV between January 2007 and December 2011. We included records of these conditions until March 2012. Epidemiological, clinical and laboratory data were analyzed and compared with a control group of HIV‐infected patients that started ARV in the same period but did not experience those comorbidities. Patients lost to follow‐up were excluded. Statistical significance of the differences encountered was evaluated with T‐student test and chi‐square; differences were considered statistically significant when p<0.05.

Results

497 patients were included (71.0% were men) with a mean age of 43.4±12.5 years and average follow‐up of 30.9±16.8 months. In the analyzed period there were 112 events in 91 patients: 85 infections and 27 cancers. The most common infectious condition was tuberculosis (n=13) and the most common cancer was non‐Hodgkin's lymphoma (n=8). The interval between the introduction of ARV and the onset of these conditions was 15.1 months (min: 0.03, max: 57.40). We identified 22 deaths: 11 were result of infection and 11 from cancer. Statistically significant differences between the groups compared were identified in the following variables: risk factor for HIV infection, co‐infection with hepatitis B, clinical stage, viral load and CD4 T lymphocyte count before the beginning of ARV.

Conclusions

We identified a substantial number of infections and cancers in our cohort, with tuberculosis and lymphomas continuing to be particularly noteworthy. Patients who had these conditions initiated ART with more severe immunosuppression and higher viral load which reinforces the importance to establish a prompt diagnosis which enables an efficient treatment and low morbidity associated with infections and cancers, particularly those related to AIDS.
Optimisation of baseline genotypic testing for safe and efficient maraviroc administration
Authors: Sierra S , Dybowski J , Pironti A , Gueney L , Thielen A , Reuter S , Esser S , Fätkenheuer G , Lengauer T , Heider D , Hoffmann D , Pfister H , Jensen B , Kaiser R
Published: November 2012

Different diagnostic parameters may affect the tropism prediction reliability. The impact of usage of FPR cut‐offs<20%, use of viral RNA versus proviral DNA samples, single versus triple amplification, and presence of MVC resistance mutations on tropism prediction at baseline were analysed on 101 patients receiving maraviroc (MVC) and correlated with their clinical outcome. This was a non‐interventional, retrospective study. 82 RNA and 54 DNA samples from the 101 patients receiving MVC were obtained. The V3 region was sequenced and the tropism predicted using the geno2pheno[coreceptor] and T‐CUP tools with FPR cut‐offs of 5%, 7.5%, 10%, 15% and 20%. Additionally, 27/82 RNA and 28/54 DNA samples were analysed in triplicate and 34/82 samples with the ESTA assay. The influence of 16 MVC resistance mutations on clinical outcome was studied. The genotypic susceptibility score (GSS) of the concomitant drugs was mapped to numerical values: susceptible to 1 (or 0.5 for NRTIs), intermediate to 0.5 (0.25 for NRTIs) and resistant to 0. Detection of baseline R5 viruses in RNA (by geno2pheno[coreceptor] and T‐CUP) or DNA (by T‐CUP) samples correlated with MVC‐treatment success. Both tools performed very similarly, with PPVs close to 90%, even with FPR cut‐offs as low as 5%. The use of triple amplification did not improve the prediction value but reduced the number of patients elegible for MVC treatment. No influence of the GSS or MVC resistance mutations on the clinical outcome was detected. Genotypic tropism testing from viral RNA and proviral DNA using the geno2pheno[coreceptor] and T‐CUP systems is valid to select candidates for MVC treatment. Our data suggest that the use of FPR cut‐offs of 5–7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this potent antiretroviral drug.
A survey of patients’ willingness to switch from a single‐tablet regimen to 2 pills once a day as a cost‐saving strategy
Authors: Tan J , Sonecha S , Mandalia S , Nelson M
Published: November 2012

With the patent on efavirenz due to expire a potential cost‐saving strategy is to switch HIV‐infected patients who are stable on Atripla® (tenofovir, emtricitabine & efavirenz) to a regimen of 2 pills once a day of generic efavirenz and co‐formulated tenofovir & emtricitabine. We assessed patients’ willingness to switch and whether it would be perceived to affect their adherence to their antiretroviral (ARV) regimen and quality of life (QOL). Consecutive patients who had been prescribed Atripla® for at least 3 months were asked to anonymously complete a questionnaire detailing the number of pills they took and how many times a day they took them. They were asked about their willingness to switch for cost‐saving reasons and whether they perceived their adherence and QOL would change if they were to switch to 2 pills once a day. The questions were assessed using visual analogue scales with values from 0 to 10. Univariate and multivariable logistic regression models were employed to determine statistical difference. 143 patients completed questionnaires, mean age was 42.3 years and 121 (85%) were male. 57 (40%) were taking other regular medicines and 125 (88%) took their pills once a day. Patients’ willingness to switch scored a median of 2 (0=not willing at all, 5=neutral, 10=very willing). Perceived change in adherence and QOL both scored a median of 5 (0=considerably worse, 5=stay the same, 10=better). No significant associations were found between patients’ willingness to switch and age, gender, in those taking other regular medicines and in those taking their pills twice or more times a day. In those taking other regular medicines an increased willingness to switch was associated with increasing number of pills taken daily (p=0.037). Willingness to switch was significantly less likely in those who perceived poorer adherence (RR 0.20, p<0.001) and reduced QOL (RR 0.16, p<0.001). Adherence is key to viral load suppression and hence treatment success and what is essentially a lifelong treatment should maintain or even improve quality of life. These are critical factors to consider if switching strategies are to be implemented to reduce drug expenditure as strategies which could potentially lead to poorer adherence could result in treatment failure and counteractively increase drug costs by necessitating the use of more expensive 2nd‐ or 3rd‐line ARVs. It is therefore important to ensure patient involvement and address patient concerns in such strategies.
cART prescription trends in a prospective HIV cohort in rural Tanzania from 2007 to 2011
Authors: Franzeck F , Letang E , Mwaigomole G , Jullu B , Glass T , Nyogea D , Hatz C , Tanner M , Battegay M
Published: November 2012

Comprehensive information on combined antiretroviral therapy (cART) regimens in rural Sub‐Saharan Africa over time is scarce, particularly on the use of stavudine (d4T) and second‐line regimens. Since 2010, World Health Organization (WHO) guidelines discourage using stavudine in first‐line regimens due to frequent and severe side‐effects. This study examined the practical adaption of this phasing‐out and described trends in use of various cART combinations in a rural Tanzanian setting. We analyzed longitudinal, prospectively collected data of HIV‐1‐infected adults initiating cART within the Kilombero Ulanga Antiretroviral Cohort (KIULARCO) in Ifakara, Tanzania from 2007–2011. This analysis included data of 3068 patients over a 5‐year period. Of these subjects, 1997 (66.9%) were female, median age was 37 (interquartile range [IQR] 31–44) years and median CD4 cell count at enrollment was 178 cells/µl (IQR 88‐291). The percentage of prescriptions containing stavudine in initial regimens (Table 1) fell from a peak of 75% in 2008 to 12.2% in 2011 (p for trend<0.001). TDF/FTC/EFV became available in 2009 and was used in 117 (41.6%) patients initiating cART in 2011. An overall on‐treatment analysis (Figure 1) revealed that d4T/3TC/NVP and AZT/3TC/EFV were the most prescribed combinations in each year, including 2011 (684 [32.5%] and 642 [30.5%] patients respectively). Of those on d4T/3TC/NVP in 2011, 632 (92.4%) were initiated in earlier years. The ratio of second‐line to total regimens remained stable over time (p for trend=0.19) with a maximum of 34 (1.2%) patients in 2011, whereof 32 (94.1%) received a combination of ABC/ddI/LPVr.

Overall on‐treatment count of patients on cART combinations by year.

image

Initial cART combinations prescribed by year.

2007
2008
2009
2010
2011

d4T/3TC/NVP
426 (66.6%) 536
536 (71.2%)
362 (46.8%)
93 (19.4%)
52 (12.2%)

d4T/3TC/EFV
25 (3.9%)
29 (3.8%)
25 (3.2%)
6 (1.2%)
0 (0%)

AZT/3TC/EFV
177 (27.7%)
174 (23.1%)
324 (41.9%)
160 (33.4%)
138 (32.4%)

AZT/3TC/NVP
7 (1.1%)
10 (1.3%)
5 (0.6%)
21 (4.4%)
54 (12.7%)

TDF/FTC/EFV
2 (0.3%)
2 (0.2%)
57 (7.3%)
199 (41.5%)
177 (41.6%)

Total
639
752
773
479
425

 Initial cART with stavudine declined to low levels according to recommendations but the overall use of stavudine remains substantial. The usage of second‐line treatment is unusually low in view of expected therapeutic failure rates, indicating potential difficulties in management of suspected treatment failure cases. Monitoring of prescription trends is a simple and feasible approach to identify deficits in the implementation of treatment guidelines for optimal outcomes.
Clinical manifestations and survival of HIV/AIDS‐infected patients, southern region of Thailand
Authors: Chaimay B , Woradet S , Chantutanon S , Phuntara S , Suwanna K
Published: November 2012

Objective

The purpose of this study was to determine magnitude of clinical manifestations on survival of HIV/AIDS patients.

Methods

The HIV/AIDS information system, a database containing demographic factors and clinical manifestations was used. A prospective, hospital‐based cohort study was conducted in HIV/AIDS patients registered in both provincial and community hospitals from 14 provinces in southern region of Thailand, between January 1993 and April 2010. Totally, 52,459 of HIV/AIDS patients were routinely observed and followed up. One‐fifth of the HIV/AIDS patients died (n=11,767, 22.43%) during the follow‐up period. The outcome was timed from diagnosis of HIV/AIDS infection to death. Cox's proportional hazard model was used to analyze the magnitude of clinical manifestations on survival of HIV/AIDS patients.

Results

A statistically significant corresponding risk of clinical manifestation on death was found. HIV/AIDS patients who had clinical manifestations including: invasive cervical cancer (HR=0.14, 95% CI: 0.44 to 0.43), herpes simplex (0.81, 0.66 to 0.98), histoplasmosis (0.67, 0.46 to 0.97), Mycobacterium other species (0.78, 0.64 to 0.97) were more likely to have a longer life. However, patients expressed clinical manifestations including; candidiasis (1.45, 1.34 to 1.56), cryptococcosis (1.77, 1.64 to 1.91), cytomegalovirus retinitis (1.58, 1.26 to 1.98), HIV encephalopathy (2.17, 1.92 to 2.47), Mycobacterium avium complex (1.76, 1.32 to 2.33) Mycobacterium tuberculosis (1.25, 1.21 to 1.30), pneumonia recurrent (1.78, 1.61 to 1.96), Pneumocystis carinii (1.71, 1.63 to 1.78), salmonella septicemia (1.85, 1.43 to 2.39) toxoplasmosis (1.47, 1.30 to 1.66) and wasting syndrome (2.13, 2.04 to 2.21) were more likely to die faster.

Conclusion

In conclusion, HIV/AIDS patients expressed clinical manifestations which were a risk of death must be monitored closely and intensively care to extend their life and increase their quality of life.
Dynamics of Epstein‐Barr Virus DNA concentrations in whole blood of HIV‐1‐infected patients during primary HIV‐1 infection
Authors: Steingrover R , Bekker V , Beld M , Lange J , Wolthers K , Kuijpers T , Prins J
Published: November 2012

Introduction

Epstein‐Barr virus (EBV) viraemia is associated with nasopharyngeal carcinoma and lymphoproliferative diseases. In HIV‐1 infection, persistent EBV viraemia is a common phenomenon. The underlying mechanism of these high EBV DNA loads has not been clarified. We studied EBV viraemia during primary HIV‐1 infection (PHI) to explore the mechanism of EBV viraemia in HIV‐1 infection.

Methods

Patients with PHI, participating in Primo‐SHM study, a clinical trial with three study arms: no treatment, 24 weeks of combination antiretroviral therapy (cART) and 60 weeks of cART, were sampled longitudinally during PHI and 24 and 48 weeks thereafter. EBV DNA was assayed by PCR on stored samples of lysed whole blood.

Results

39 patients were tested, in 22 of whom EBV DNA was detected at one or more time points. All patients tested positive for anti‐VCA and anti‐EBNA antibodies, most patients that had EBV viraemia did not receive cART or interrupted cART. The prevalence of EBV viraemia at baseline was 29%, 18% and 33% for the untreated, 24 weeks cART and continuous cART groups. At week 48, these percentages were 38, 64 and 17 respectively (p < 0.05). Individual concentrations of EBV DNA for the three groups are shown in Figure 1.

The Black lines show the individual log10 transformed EBV DNA concentrations in whole blood in patients that remained untreated (panel a), patients that were treated for 24 weeks with cART (panel b) and patients that were treated continuously with cART (Panel c).

image

Conclusion

Intermittent EBV viraemia is highly prevalent in patients with PHI. Assuming that patients with very early HIV‐1 infection are still immunocompetent, this indicates that EBV viraemia is not caused by immunodeficiency. Antiretroviral therapy started during PHI but not later during chronic HIV infection might reduce the prevalence of EBV viraemia in HIV‐1 infection.
Particularities of tuberculosis in HIV‐infected patients: 10‐year experience of a Portuguese hospital
Authors: Nunes S , Coutinho D , Maio A , Velez J , Freitas F , Oliveira C
Published: November 2012

The incidence of tuberculosis (TB) has dramatically increased since the advent of the human immunodeficiency virus (HIV) pandemic. In Portugal, tuberculosis is still common in HIV‐negative patients, despite earlier diagnosis and countrywide directly observed therapy strategies. With the purpose of comparing some demographic and clinical aspects of TB in HIV‐infected and uninfected patients, the authors reviewed the files of patients admitted with a diagnosis of tuberculosis between January 2002 and December 2011. During this time period, there were 234 cases of tuberculosis, 43 (18%) of which occurred in HIV‐infected patients. In this group, 74% of patients were male, with a mean age of 38±11 years and the majority (51%) acquired HIV from heterosexual risk behavior. The most common site of infection was the lung, in both groups, but cases of extrapulmonary TB were significantly higher in the HIV‐infected group (67% versus 39%, p<0.01). Disseminated TB was the most common extrapulmonary diagnosis in the former group (28%) and lymph node TB (8%) in the latter. The duration of hospitalization was not statistically different between the two groups (mean of 26±16 days in HIV‐infected patients and 21±15 days in the HIV‐negative group, p=0.21). The mean CD4 count at TB diagnosis was 180±177/mm3. In 11 (26%) of the patients, HIV was diagnosed during the TB episode and in 5 cases, the diagnosis of tuberculosis occurred with immune reconstitution syndrome. In the majority of patients (60%), TB was the first AIDS‐defining condition. In 26 (60%) of patients there was microbiologic confirmation of TB, mainly by direct observation (69%), positive culture (46%) and molecular diagnostic technics (27%). While most patients were treated with the 4‐drug standard regimen, 16 (37%) of cases received alternative treatment. The mean duration of treatment was 8.5±4.8 months and the majority of patients (58%) were considered cured. About one‐third of patients were lost to follow‐up (32%). Tuberculosis is a heterogeneous disease, varying accordingly with the immunologic status of the host. The risk of extrapulmonary and disseminated TB increases with immunosuppression but, in this cohort, it did not seem to influence the length of hospitalization. The authors alert to the need of HIV screening whenever TB occurs, allowing for earlier diagnosis and prompt start of antiretroviral therapy.
Re‐infection of hepatitis C virus infection in HIV/HCV co‐infected inmates of correctional institutions, Canada
Authors: Farley J , Truong A , Horvath G , Nguyen T , Shum W
Published: November 2012

Hepatitis C (HCV) and HIV are commonly acquired through intravenous drug use (IDU). Treatment of HCV is beneficial in reducing hepatic complications and likely decelerating the rate of progression of HIV. HCV therapy in HCV/HIV co‐infected individuals is increasingly being reported to be feasible. However, re‐infection is emerging as an important concern, especially in the prison population where likely related to surreptitious IDU. In this study, we report the re‐infection rate of inmates in the Pacific region of Canada who have HCV/HIV and were successfully treated for HCV. Retrospective medical chart reviews of 57 co‐infected inmates with a history of IDU who received HCV therapy between April 2003 and June 2012. All received standard doses of pegylated interferon alpha 2a or 2b and weight‐base ribavirin for durations of 24–48 weeks depending on genotypes. After successfully attaining SVR, inmates are routinely monitored for re‐infection every 6–12 months with HCV RNA qualitative analysis. Of the 57 inmates with HCV/HIV, 48 (82.8%) were Caucasians and 10 (17.2%) were First Nations. 94.7% (54) of the study population were males. The mean age at the start of treatment was 39.6±7.5 years. 100% (inclusion criteria) admitted to IDU before treatment and 7 (12.1%) admitted IDU after treatment. Genotype 1 made up 56.1% (32), followed by genotype 3 at 35.1% (20) and genotype 2 at 8.8% (5). Treatment was discontinued due to adverse side effects in 4 (6.9%) and discontinued due to no response in 9 (15.5%) inmates. 2 (3.7%) were lost to follow up due to discharge to community. SVR was attained in 33 (56.9%) inmates and of those 30.3% (10) were re‐infected. These re‐infected cases were noted mainly in genotype 3 (60%) and genotype 1 (40%). Six had viral relapsed. SVR results are pending for three. Achieving a SVR is encouraging in HCV/HIV co‐infected. Our study revealed that 30.3 % of the inmate population became re‐infected after treatment. Of note, these numbers are relatively small. However, it is important that counseling regarding harm reduction and strategies should be provided before, during and after treatment to help reduce the rate of re‐infection.
Evaluation of the HIV‐HCV co‐infection status in a cohort of southeastern of Spain
Authors: Moreno Hernández A , Smilg Nicolás C , Vera Méndez F , Martínez Madrid O , Jimeno Almazán A , Alcalde Encinas M , Alcaraz Vidal B , Trujillo Santos J , Tornel Sánchez G , Vega Cervantes J , Mozo Cuadrado M , Belmonte Martínez L
Published: November 2012

Purpose of the study

To know the main epidemiological, virological and therapeutic characteristics of HCV infection and the degree of hepatic fibrosis in a cohort of HIV‐HCV co‐infected patients in a health area of southeastern of Spain.

Methods

Prospective cohort of co‐infected HIV‐HCV patients followed in the University Hospital of Saint Lucia (Spain), which describes the main epidemiological characteristics, degree of liver fibrosis assessed by transient elastography and the level of response to treatment for HCV during the period November 30, 2011–February 28, 2012.

Summary of results

The cohort included 109 patients, of whom 27 were females (25%) and 82 males (75%), with a mean age of 45.8 (SD: 6.2) years and a mean time of infection of 18.8 (SD: 5.7) years. The main route of transmission was in this order: IDUs in 90 patients (83%), 13 (12%) by heterosexual intercourse and 3 (2.8%) in MSM. There were no statistically significant differences between the years of evolution of HCV based on the route of transmission (p=0.36). In the genotypic analysis, 55 patients were genotype 1a (51%), 13 genotype 1b (13%), 19 genotype 3 (17%) and 9 genotype 4 (8.3%). The median HCV viral load was 868,000 IU/ml (6.15 log10). In this cohort 31 patients (28%) received antiviral therapy for HCV: 2 (1.8%) Interferon (INF) non‐pegylated, 3 (2.8%) INF non‐pegylated with Ribavirin (RBV) and 25 (23%) INF pegylated with RBV. In 6 cases (19%) were achieved sustained viral response (SVR). In the 25 cases without SVR (81%), 9 (36%) were partial responders, 7 (28%) null responders, 6 (24%) relapsers and 3 (12%) discontinued treatment due to problems of tolerability. In 108 patients were determined the degree of liver fibrosis by transient elastography: 48 patients (44%) had significant fibrosis (F3–F4;>9.5 kpascal) and 30 (28%) liver cirrhosis (F4;>14.5 kpascal). In patients with F4, 5 (17%) had values between 14.5–20 kpascal, 14 (47%) values between 21–40 kpascal and 11 (37%) values over 40 kpascal.

Conclusions

In our cohort, the gender predominant was male and the abuse of intravenous drugs was the main cause of HCV transmission. Most patients had genotype 1a, high viral load (>800,000 UI/mL) and a poor rate of SVR (19.3%), predominating the partial response rate among non‐responders. A high proportion of patients (28%) had liver cirrhosis (F4), of which, a significant proportion of subjects (37%) were at high risk of hepatic decompensation (>40 kpascal).
Hepatotoxicity of antiretrovirals in patients with human immunodeficiency virus and viral hepatitis coinfections
Authors: Parenti P , Marconi L , Lupo S
Published: November 2012

Background

Antiretroviral drugs used to treat HIV may cause hepatotoxicity. The high prevalence of persons with chronic hepatitis B or C coinfected, raised aminotransferases have many causes and neither specific markers is a indicator of liver injury, difficulties in interpreting the hepatotoxicity.

Objective

We evaluated hepatotoxicity in HIV/HCV‐ and/or HBV‐coinfected patients, risk factors and severity.

Methods

Prospective study of HIV‐1 patients with start HAART in Hospital Provincial del Centenario from Rosario, Argentina. Patients were classified into two groups, HCV and/or HBV coinfected vs. no coinfected. The major endpoint was hepatotoxicity defined as Benichou's Score within the first 6 months. This score is among the few validated, but little used in clinical practice. Secondary endpoints were risk factors and severity of hepatotoxicity.

Results

140 patients were included, 39% coinfected and 61% no coinfected. Females were similar in both groups; 21% and 27% respectively. The hepatotoxicity within the first 6 month was 44.3%, 75% in coinfected patients and 25% in no‐coinfected. RR 3.97 (95% confidence interval 2.34–6.75, p<0.0001). The hepatotoxicity was associated with the use of illicit drugs and alcohol, symptoms, high level aminotransferases previous to HAART and NNRTI+PI. 3% of hepatotoxicity was severe.

Conclusions

44% of HIV patients experienced hepatotoxicity, 75% in coinfected vs 25% in no coinfected. The relative risk of hepatoxocity was almost 4 times higher among in chronic hepatitis‐coinfected patients, compared with those with HIV non‐coinfected. In multivariate analysis, the risk factors were illicit drugs, alcohol, symptoms, high level aminotransferases and NRTI+PI. Only 3% of hepatotoxicity was severe. The Benichou's Score is better than level of aminotransferase for evaluated hepatotoxicity, so it would be recommended for use in clinical practice.
HBV and neurological impairment in HIV‐infected patients
Authors: Manolescu L , Marinescu P
Published: November 2012

Objective

HIV can affect CNS in early stages of disease and determine neurological impairment. HBV DNA was found in CSF of HIV co‐infected patients, but little is known about the neurotropic character of this virus. Here we assessed the degree of association between HBV infection and neurological impairment in a large cohort of long‐term survivors, HIV‐infected patients that experienced multiple therapeutic schemes over time.

Methods

A total of 462 HIV‐1‐infected patients were retrospectively followed up for 10 years for HBV infection and neurological impairment. The patients were tested for immune (flow cytometry) and virological parameters of HIV infection (Roche Amplicor, version 1.5/ COBAS AmpliPrep/COBAS TaqMan HIV‐1 test) and for HBV infection markers (HBsAg, anti HBc: Murex Biotech ELISA tests). Many of these patients have experienced between one and six regimens such as: 2 NRTIs, 3 NRTIs, 2 NRTIs+1 NNRTI, 1 NRTI+1 NNRTI+1 PI, 2 NRTIs+2 PIs.

Results

After 10 years 29.87% of the patients presented neurological impairment. Out of them 56.52% were HBV‐infected. The prevalence of HIV encephalopathy (HE) in our studied cohort was 22.7% and 50.4% of these patients were HBV‐infected. The median HIV diagnosis age was 7 and the median age of HE diagnosis was 10. In order to establish a possible correlation between HBV infection and HE we first reviewed and excluded the main risk factors associated with HE at the moment of diagnosis: low weight, anemia, constitutional symptoms, low CD4+count, high plasma HIV‐RNA load. No patient was infected with HCV. The groups of patients that presented HE and HBsAg and HE without HBsAg were balanced regarding sex, number of deceased patients, number of class C3 patients, but the patients in first group presented lower CD4 values at HE diagnosis vs patients from second group 2: 44.5 vs 95 cells/µL, p=0.3; lower nadir CD4 count: 38 vs 51 cell/µL, p=0.1; and slightly higher HIV viral load: 5.2 vs 5 log10 copies/mL, p = 0.2. There were only 53 patients that presented at the same time HE and HBV infection and the majority, 78.69%, were first infected with HBV.

Conclusions

In our studied cohort HBV infection was associated with HE but further studies are needed to prove HBV neurotropic potential. Absolute CD4 nadir count and class C3 are proved to be strong predictors of HE in HIV‐infected patients even after several changes in antiretroviral therapy schemes.
Persistence and clearance of HPV infection at anal site in a cohort of HIV‐positive males
Authors: Comi L , Pandolfo A , Rovati M , Cicconi P , Bini T , Cassani B , Romagnoli S , Marchetti G , d'Arminio Monforte A
Published: November 2012

We aimed to assess the persistence and clearance of HPV‐DNA at anal site in a cohort of HIV‐positive patients (pts) asymptomatic for sexually transmitted diseases (STD). Consecutive HIV‐pos males underwent anoscopy, and each anal sample was analyzed for HPV‐PCR detection/genotyping (high‐risk genotypes: HR‐HPV) and for cytologic abnormalities (Bethesda System 2001: low and high grade SIL, LSIL‐HSIL). Immune activation in peripheral blood (CD8/CD38+) was assessed by flow cytometry. Pts were re‐examined at a 12–18 months follow‐up visit. Comparisons were assessed by Mann‐Whitney and chi‐square test. Factors related to HPV persistence were identified by logistic regression. 105 HIV‐pos males were studied: 89 (84%) were MSM, 76 (72%) were on HAART, median age was 42 (IQR:34–47), median CD4 count of 500 cell/mmc (IQR:366–680). HPV‐DNA was detected in anal swabs from 96 (91.4%) pts, 77 of them (80%) harbored HR‐HPV; 46 were coinfected with>1 HR‐HPV. Most frequent genotypes were HPV‐16 (30%), HPV‐58 (25%). In a median follow up of 18 months (IQR 12–24), 83/96 (86.4%) pts showed persistent HPV infection, while 13 (13.5%) became negative; conversely, 6 (5%) pts, HPV‐negative at baseline, acquired HPV infection. Younger pts and those with a shorter duration of HIV infection showed a higher prevalence of HPV persistence (Table).

 Conversely being on HAART and a longer duration of therapy were associated to viral clearance. Interestingly, pts with persistent HPV infection showed an activated immune profile at baseline, with significantly higher CD8+CD38+%. In the multivariate analysis only SIL at baseline (AOR 4.11, 95% CI 0.89–18.9, p=.06), being MSM (AOR 5.11, 95% CI 0.87–29.8, p=.06) and higher CD8+CD38+% (AOR 1.93, 95% CI 0.88–4.24, p=.09) were borderline associated with persistent anal HPV infection. Our results confirm a higher prevalence and persistence of anal HPV infection in HIV‐positive males; HIV‐pos pts with anal HPV infection should be thus strictly followed‐up for the early detection of pre‐cancerous lesions.

Table Demographic characteristics of study population at baseline according to persistence of HPV infection

Characteristics at baseline
HPV+ pts that become negative at follow‐up (n=13)
HPV+ pts that remain positive at follow‐up (n=83)
p

Age*
48 (42–60)
41 (33–46)
0.008

MSM°
9 (69%)
74 (89%)
0.071

HAART°
13 (100%)
57 (68%)
0.017

HAART duration (mths)*
121 (41.5–180)
46 (21.25–119.3)
0.030

HIV duration (mths)*
125 (56–202)
43 (22–130)
0.007

CD4+T cells/mmc*
525 (407–656)
500 (362–680)
0.59

Nadir CD4+T cells/mmc*
285 (173–403.5)
300 (163–396)
0.99

CD8+T cells/mmc*
846 (638–1008)
884 (748–1060)
0.26

HIV‐RNA cp/mL*
59 (39–59)
59 (39–16967)
0.15

CD8+CD37+%
1 (1–1)
2 (1–4)
0.003

Dysplasia
3 (23%)
52 (62.6%)
0.011

HR‐HPV°
8 (61.5%)
69 (83%)
0.12

Follow‐up duration (mths)*
18 (12.5–30)
18 (12–24)
0.58

Data are presented as the median (IQ R); °Data are presented as the number (percentage).
Significance of sex in achieving sustained remission in the consortium of rheumatology researchers of north america cohort of rheumatoid arthritis patients
Authors: Jawaheer Damini , Messing Susan , Reed George , Ranganath Veena K. , Kremer Joel M. , Louie James S. , Khanna Dinesh , Greenberg Jeffrey D. , Furst Daniel E.
Published: November 2012

Objective

To determine whether men with rheumatoid arthritis (RA) are more likely to achieve remission compared to women.

Methods

RA patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) cohort between October 2001 and January 2010 were selected for the present analyses. Detailed clinical, demographic, and drug utilization data were available at enrollment (baseline) and at subsequent followup visits. We examined the influence of sex on the Clinical Disease Activity Index remission score (≤2.8) using sustained remission or point remission as the primary outcome measure in multivariate stepwise logistic regression models. We stratified the data by RA duration at baseline (≤2 years or >2 years) to investigate whether RA duration had differential effects on remission in men and women.

Results

A total of 10,299 RA patients (2,406 men and 7,893 women) were available for this study. In both early and established RA, women had more severe disease at baseline with worse disease activity measures, modified Health Assessment Questionnaire disability index score, pain on a visual analog scale, and depression. Women were also more likely to have been treated with disease‐modifying antirheumatic drugs and anti–tumor necrosis factor therapy compared to men. In the regression models, male sex was associated with sustained remission in early RA (odds ratio [OR] 1.38, 95% confidence interval [95% CI] 1.07–1.78, P = 0.01), but not in established RA. However, for point remission, an inverse association was observed with male sex in established RA (OR 0.65, 95% CI 0.48–0.87, P = 0.005) and not in early RA.

Conclusion

Within the large real‐life CORRONA cohort of RA patients, men were more likely to achieve sustained remission compared to women in early RA, although not in established RA.
Do patients with juvenile idiopathic arthritis in clinical remission have evidence of persistent inflammation on 3T magnetic resonance imaging?
Authors: Brown Amanda , Hirsch Raphael , Laor Tal , Hannon Michael J. , Levesque Marc C. , Starz Terence , Francis Kimberly , Kwoh C. Kent
Published: November 2012

Objective

Up to 90% of adults with rheumatoid arthritis (RA) in clinical remission have persistent synovitis and/or bone marrow lesions (BMLs) on magnetic resonance imaging (MRI). MRI findings in patients with juvenile idiopathic arthritis (JIA) in clinical remission have not been described. We utilized 3T MRI with contrast enhancement to examine JIA patients with hand and/or wrist involvement who were in clinical remission and compared them with a cohort of adult RA patients.

Methods

In total, 11 JIA patients and 10 RA patients with arthritis involving the hands and/or wrists were identified by their primary rheumatologist as being in physician‐defined clinical remission, having no signs or symptoms of active arthritis and no medication changes for at least 6 months. A study rheumatologist performed a joint evaluation for tenderness, swelling, and limitation of motion, and study participants self‐reported tender joint counts. The participants underwent MRI with intravenous contrast enhancement of 1 hand and wrist with a history of prior symptoms. A pediatric musculoskeletal radiologist blinded to the clinical data scored the MRIs for synovitis, tenosynovitis, and/or BMLs.

Results

Sixty‐three percent of the JIA cohort and 70% of the RA cohort had MRI findings of synovitis, BMLs, and/or tenosynovitis. All pediatric patients with MRI abnormalities had normal physician tender and swollen joint counts. The patients' self‐report of painful joint counts did not predict MRI abnormalities.

Conclusion

Over one‐half of the patients in clinical remission had MRI evidence of persistent inflammation, defined as the presence of synovitis, tenosynovitis, or BMLs. A substantial portion of patients with JIA may have subclinical disease despite clinical remission.
Association of systemic lupus erythematosus with angiographically defined coronary artery disease: A retrospective cohort study
Authors: Kaul Mala S. , Rao Sunil V. , Shaw Linda K. , Honeycutt Emily , Ardoin Stacy P. , St.Clair E. William
Published: November 2012

Objective

To determine if systemic lupus erythematosus (SLE) is associated with a higher prevalence of coronary artery disease (CAD) in select patients undergoing coronary angiography. We compared the extent of angiographic abnormalities, CAD risk factors, and all‐cause mortality in SLE patients with non‐SLE controls.

Methods

We identified SLE patients (n = 86) and controls matched by sex and year of cardiac catheterization (n = 258) undergoing cardiac catheterization for the evaluation of CAD (median followup duration of 4.3 years). Multivariable logistic regression was used to determine if SLE was associated with obstructive CAD, defined as ≥70% stenosis in a major epicardial coronary artery. Risk‐adjusted survival differences between the 2 groups were assessed using Cox proportional hazards modeling.

Results

The SLE patients (85% women) were younger than the non‐SLE patients (median age 49 years versus 70 years; P < 0.001) and were less likely to have diabetes mellitus and hyperlipidemia, but had similar rates of hypertension (70% versus 71%; P = 0.892). In unadjusted analyses, SLE and non‐SLE patients had similar rates of obstructive CAD by angiography (52% versus 62%; overall P = 0.11). After adjustment for known CAD risk factors, SLE was associated with a significantly increased likelihood of CAD (odds ratio 2.24 [95% confidence interval (95% CI) 1.08–4.67]). SLE was also associated with a nonsignificant increase in all‐cause mortality (hazard ratio 1.683 [95% CI 0.98–2.89], P = 0.060).

Conclusion

In this selected population, SLE was significantly associated with the presence of CAD as defined by coronary angiography, the gold standard for assessing flow‐limiting lesions in this disease. The patients with SLE showed a similar severity of CAD as the controls despite having less than half the rate of diabetes mellitus and being 20 years younger.
Predictors of pain and functioning over time in fibromyalgia syndrome: An autoregressive path analysis
Authors: Van Liew Charles , Brown Kimberly C. , Cronan Terry A. , Bigatti Silvia M. , Kothari Dhwani J.
Published: November 2012

Objective

Fibromyalgia is a disabling, chronic pain condition of unknown etiology. Although many factors have been recognized as important contributors to the pain experiences and functional abilities of fibromyalgia patients, the factors that are most impactful (and therefore represent optimal targets for intervention) are still unclear. The aim of the present study was to examine the pathways among depression, self‐efficacy, pain, and physical functioning in a large sample of fibromyalgia patients over a 1‐year timeframe.

Methods

Data from 462 participants (441 women) were analyzed using an autoregressive path analytical model with first‐ and second‐order cross‐lagged effects.

Results

Self‐efficacy was the only significant predictor of depression, physical functioning, and pain intensity ratings across time. Physical functioning at 6 months predicted self‐efficacy at 1 year; no other factors related significantly to self‐efficacy in the model.

Conclusion

Our model suggests that self‐efficacy is a salient factor in fibromyalgia symptomatology. Our findings support designing interventions that use a multimodal approach, with an explicit focus on combining exercise (or other means) to improve physical functioning and psychotherapy (e.g., cognitive–behavioral therapy) with the intention of reprocessing the functional improvements and the implications of these improvements for the patients' ability to manage their fibromyalgia symptoms. By doing so, self‐efficacy should be enhanced, and this would produce the greatest and broadest benefits for fibromyalgia patients.
Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis
Authors: Kollert Florian , Christoph Sophie , Probst Corina , Budweiser Stephan , Bannert Bettina , Binder Moritz , Sehnert Bettina , Voll Reinhard E. , Warnatz Klaus , Zissel Gernot , Walker Ulrich A. , Prasse Antje , Saalbach Anja
Published: November 2012

Objective

Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH).

Methods

sCD90 serum concentrations were assessed in 76 patients with SSc and related to clinical data, lung function, 6‐minute walk distance, echocardiography, bronchoalveolar lavage fluid, and laboratory parameters. Thirty‐one healthy volunteers and 29 patients with idiopathic retroperitoneal fibrosis (IRF) served as controls.

Results

sCD90 serum concentrations were elevated in patients with SSc compared to healthy volunteers (P = 0.001) and patients with IRF (P = 0.01). SSc patients with pulmonary fibrosis (P = 0.006) and patients with PAH (P < 0.001) had increased sCD90 serum concentrations compared to patients without the respective pulmonary manifestation of SSc. sCD90 levels correlated with diffusing capacity for carbon monoxide (n = 65; r = −0.348, P = 0.005) and systolic pulmonary artery pressure (n = 53; r = 0.469, P < 0.001). Receiver operating characteristic curve testing determined an optimal cutoff value of ≥626 ng/ml with a sensitivity of 68% and a specificity of 83% for PAH (area under the curve 0.773, 95% confidence interval 0.648–0.898; P < 0.001).

Conclusion

sCD90 concentrations were increased in the sera of SSc patients, particularly in patients with vascular involvement of the lungs. These data suggest that sCD90 should be further evaluated as a marker for diagnosis of PAH in SSc.
Is symptomatic knee osteoarthritis a risk factor for a trajectory of fast decline in gait speed? Results from a longitudinal cohort study
Authors: White Daniel K. , Niu Jingbo , Zhang Yuqing
Published: November 2012

Objective

Gait speed is an important marker of health in adults and slows with aging. While knee osteoarthritis (OA) can result in difficulty walking, it is not known if radiographic knee OA (ROA) and/or knee pain are associated with a fast decline trajectory of gait speed over time.

Methods

Gait speed trajectories were constructed using a multinomial modeling strategy from repeated 20‐meter walk tests measured annually over 4 years among participants from the Osteoarthritis Initiative, a prospective cohort study of adults ages 45–79 years at baseline with or at high risk of knee OA. We grouped participants into 4 knee OA categories (having neither ROA nor knee pain, ROA only, knee pain only, or symptomatic knee OA [ROA and pain]) and examined their association with trajectories of gait speed using a multivariable polytomous regression model adjusting for age and other potential confounders.

Results

Of the 4,179 participants (mean ± SD age 61.1 ± 9.1 years, 57.6% women, mean ± SD body mass index 28.5 ± 4.8 kg/m2), 5% (n = 205) were in a fast decline trajectory, slowing at a rate of 2.75%/year. People with symptomatic knee OA had an almost 9‐fold risk (odds ratio 8.9; 95% confidence interval [95% CI] 3.1, 25.5) of being in a fast decline trajectory compared with those with neither pain nor ROA. Participants with knee pain had 4.5 times the odds of a fast decline (95% CI 1.4, 14.6), and those with ROA only had a slight but non–statistically significant increased risk.

Conclusion

People with symptomatic knee OA have the highest risk of a fast decline trajectory of gait speed compared with people with ROA or pain alone.
Neuromuscular fatigue and exercise capacity in fibromyalgia syndrome
Authors: Bachasson Damien , Guinot Michel , Wuyam Bernard , Favre‐Juvin Anne , Millet Guillaume Y. , Levy Patrick , Verges Samuel
Published: November 2012

Objective

To assess quadriceps strength and fatigability by using femoral nerve magnetic stimulation (FNMS) and their relationship to exercise capacity in patients with fibromyalgia syndrome (FMS) and healthy controls.

Methods

Twenty‐two women (11 with FMS, 11 controls) performed a maximal incremental cycling test and a quadriceps fatigue test on 2 separate visits. For quadriceps assessment, we used FNMS during and after maximum voluntary contraction (MVC) to evaluate central and peripheral factors of neuromuscular fatigue. Subjects performed sets of 10 intermittent (5 seconds on/5 seconds off) isometric contractions starting at 10% MVC, in 10% MVC increments from one set to another until exhaustion. Neuromuscular fatigue was assessed with FNMS after each set.

Results

FMS patients had reduced initial MVC compared to controls (mean ± SD 102 ± 18 versus 120 ± 24 Nm; P < 0.05) without significant impairment of voluntary activation (mean ± SD 93.5% ± 3.0% versus 93.1% ± 3.4%; P = 0.74). During the fatigue task, FMS patients exhibited a greater fall in evoked muscular responses (mean ± SD −26% ± 6% versus −16% ± 8% at set 50% MVC; P < 0.05), but not in MVC (mean ± SD −24% ± 7% versus −19% ± 4% at set 50% MVC; P = 0.12). During the cycling test, FMS patients had lowered maximal exercise capacity and an enhanced rate of perceived exertion (RPE) compared to controls. The percent reduction in evoked muscular responses during the quadriceps fatigue test correlated with maximum oxygen consumption (r = 0.56, P < 0.05) and RPE at submaximal intensity (r = 0.84, P < 0.05) during cycling.

Conclusion

Greater impairment in muscle contractility is associated with enhanced perception of exertion and reduced maximal exercise capacity in FMS patients. Neuromuscular impairments should be considered as an important factor underlying functional limitations in FMS patients.
Reactive Aramid Nanostructures as High‐Performance Polymeric Building Blocks for Advanced Composites
Authors: Cao Keqin , Siepermann Carlos Pons , Yang Ming , Waas Anthony M. , Kotov Nicholas A. , Thouless M. D. , Arruda Ellen M.
Published: November 2012

Traditionally, the field of advanced nanocomposites has relied on a fairly limited set of building blocks; many with low reactivity and of limited variability. These limitations have been addressed by the creation of functionalized nanometer‐scale aramid structures, in the form of nanofibers and nanosheets. These were obtained by deprotonating macroscale, commercial Kevlar yarns using potassium hydroxide in dimethyl sulfoxide to yield stable dispersions of nanometer‐scale aramid fibers that were then hydrolyzed using phosphoric acid (PA). To illustrate the use of these functionally‐active nanostructures as building blocks for nanocomposites, they were crosslinked by glutaraldehyde (GA), and formed into macroscopic thin films by vacuum‐assisted filtration. It was shown that the mechanical properties of these PA/GA treated films can be tuned by varying the amounts of PA and GA used during synthesis, adjusting the relative amounts of hydrolysis and polymerization. These results are the first demonstration that aramid nanometer‐scale fibers can be used to form versatile nanometer‐sized building blocks that can then be crosslinked to fabricate a wide variety of nanostructured aramid materials with tailorable properties.
Phelan–McDermid syndrome: Clinical report of a 70‐year‐old woman
Authors: Verhoeven Willem M.A. , Egger Jos I.M. , Cohen‐Snuijf Ruthy , Kant Sarina G. , de Leeuw Nicole
Published: November 2012

Phelan–McDermid or 22q13.3 deletion syndrome is characterized by global intellectual disability, childhood hypotonia, severely delayed or absent speech, features of autism spectrum disorder, without any major dysmorphisms or somatic anomalies. It is typically diagnosed before adolescence and data about adult patients are virtually absent. The expression of its phenotypical characteristics appears to be linearly related to the deletion size. Here, an intellectually disabled geriatric female patient is described with a long history of challenging behaviors in whom Phelan–McDermid syndrome was demonstrated. Detailed analysis of the patient's history and functioning resulted in a psychiatric diagnosis of atypical bipolar disorder and her behavior significantly improved upon maintenance treatment with a mood stabilizing agent. The present article confirms recent findings that atypical bipolar disorder may be part of the psychopathological phenotype of Phelan–McDermid syndrome, reason why careful etiological search is warranted, also in the geriatric population. © 2012 Wiley Periodicals, Inc.