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Biomedical subjects

C Sabin

Publications and source records attributed to C Sabin.

At least 19 recordsLinked to original sources
PubMed2006

Nutritional status and prognosis in cirrhotic patients.

BACKGROUND AND AIM: The potential prognostic value for survival of nutritional status in cirrhotics after adjusting Child-Pugh classification and Model for End-Stage Liver Disease has not been evaluated. METHODS: We used Kaplan-Meier and Cox proportional hazards regression models to identify factors associated with mortality in a cohort of 222 cirrhotics [M/F:145/77 median age 52 (18-68) years] with prospectively collected nutritional parameters as well as modified subjective global nutritional assessment, Royal Free Hospital-Subjective Global Assessment index. Follow-up was censored at the time of transplantation. Other variables were ones in Child-Pugh and Model for End-Stage Liver Disease scores, age, aetiology of cirrhosis and renal function. RESULTS: Pretransplant mortality (Kaplan-Meier) was 21% by 2 years (135 patients were transplanted). Among the nutritional parameters, only Royal Free Hospital-Subjective Global Assessment remained significantly associated with mortality in multivariable models (P = 0.0006). The final model included the following variables: urea (P = 0.0001), Royal Free Hospital-Subjective Global Assessment (P = 0.003), age (P = 0.0001), Child-Pugh grade (P = 0.009) and prothrombin time (P = 0.003). The results were similar when the Child-Pugh grade was replaced by the Model for End-Stage Liver Disease score in the model, and whether a competing risks model was used. CONCLUSIONS: Nutritional indices add significantly to both Child-Pugh grade and Model for End-Stage Liver Disease scores when assessing the patient prognosis.

Adolescent↗
PubMed2006

Cervical screening in HIV-positive women: characteristics of those who default and attitudes towards screening.

OBJECTIVES: To determine the characteristics of HIV-positive women who undergo cervical screening and to identify negative attitudes and experiences of these women to screening and the factors associated with these. METHODS: We compared the Royal Free Cohort data from 59 newly diagnosed HIV-infected women, 31 of whom did and 28 of whom did not attend for cervical screening in 2001, and from 227 women under active cervical screening follow-up (at least one cervical screen since June 2001) and 88 HIV-infected women lost to follow-up (not screened since January 2001). Attitudes to screening were investigated with the aid of a questionnaire given to all women attending clinic who had had a previous colposcopy. RESULTS: Of the 59 newly HIV diagnosed women, 31 (53%) underwent cervical screening. These 31 women were more likely to be heterosexual (100 vs 89%, P=0.05), to have lower median viral loads (< 50 vs 3210 HIV-1 RNA copies/mL) and to be receiving antiretrovirals (ARVs) (74 vs 54%, P=0.1) than those not screened. Of the 315 women who had at least one screen, 72% returned for further follow-up. There were no differences in age or ethnicity between these groups. Those under active follow-up had a higher CD4 count (P=0.04) and lower viral load (P=0.0001) at their last visit. They were also more likely to be on highly active antiretroviral therapy (HAART) (68 vs 52%, P=0.006). A total of 78 of 104 questionnaires (75%) were returned. Women participating in the questionnaire study were mainly of back ethnicity (68%), did not speak English as their first language (59%) and were taking ARVs (76%). Most agreed that regular smears and colposcopy were valuable. Women of white ethnicity, and those speaking English as a first language, were more likely to dislike colposcopy compared with those of nonwhite ethnicity (87 vs 25%, respectively, P=0.0007) and not speaking English as a first language (74 vs 26%, respectively, P=0.002). Those of white ethnicity were more likely to find smears and colposcopy painful (60 and 73%) compared with those of black ethnicity (46 and 51%, P=0.47 and 0.28, respectively). CONCLUSIONS: Our results suggest that women on HAART with better disease control, older women, and those of black African ethnicity are more likely to take up cervical screening. Cervical screening experience varies by ethnicity and language.

Adult↗
PubMed2006

Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion.

OBJECTIVE: To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion. DESIGN: Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout. RESULTS: In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log(10) HIV-1 RNA copies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/microL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/microL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/microL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log(10) copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion. CONCLUSION: Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses.

Adult↗
PubMed2006

Providing written information on HIV testing improves patient knowledge but does not affect test uptake.

The objective of this study is to determine the effect of providing written information about HIV testing on patient knowledge and test uptake. Patients attending our genitourinary medicine clinic in July 2003 were offered written information about HIV and the test. They were asked to complete a questionnaire which elicited knowledge provided on the leaflet. A control group of individuals were offered verbal discussion only.A total of 382 questionnaires were completed. Individuals given written information were more likely to believe that HIV could not be transmitted by insect bites (P = 0.01), more aware of current treatments and that a negative test would not affect a future mortgage application (P = 0.001). There was no difference in test uptake or reasons for declining a test in both groups. Providing written information on HIV testing increases patient knowledge, but does not affect test uptake.

HIV Infections↗
PubMed2006

Medical student attitudes towards HIV.

The aim of the study was to determine medical student attitudes towards HIV-related issues, to examine if the following student factors can affect attitudes: gender, perception of HIV infectivity, exposure to an HIV+ individual, career intent and attending a clinical attachment. A self-administered questionnaire was given to students at the beginning and end of a clinical attachment. Of the 240 questionnaires handed out at the beginning of the attachment, 183 (76%) were completed. Students generally expressed positive attitudes towards people with HIV. Female students and individuals who had considered working in a related specialty or had met an HIV+ person expressed more patient-centred attitudes in some of their responses. Following the course, 72 questionnaires were returned. Responses to several of the attitudinal statements had changed significantly. Medical students generally have enlightened attitudes towards HIV-related issues, which may be affected by student factors and attending a clinical attachment.

Adult↗
PubMed2005

The epidemiology of genital infection with herpes simplex virus types 1 and 2 in genitourinary medicine attendees in inner London.

OBJECTIVE: To characterise the epidemiological and clinical features of genital herpes and the diagnostic role of HSV-2 specific serology in an ethnically diverse cohort of genitourinary medicine (GUM) attendees in inner London. METHODS: Genital swabs (n = 186) were tested by real time polymerase chain reaction (PCR) and serum samples (n = 70) by HSV-2 specific enzyme linked immunoassay (ELISA). RESULTS: Among 186 patients (median age 29 years), 104/186 (56%) were male and 176/186 (95%) heterosexual; ethnicity was predominantly black Caribbean (76/186, 41%), white (65/186, 35%), or black-African (41/186, 22%). The most common lesion sites were penis (85/104 men, 82%) and vulva (63/82 women, 77%); 114/186 (61%) patients were diagnosed clinically with first episode disease. Women were more likely to present <5 days of onset (p = 0.008). Black Caribbean patients were more likely to present > or = 5 days (p = 0.04) and decline HIV testing (p = 0.03). By PCR, 108/186 (58%) swabs tested positive for HSV-1 (7/108, 6.5%) or HSV-2 (101/108, 93.5%). Independent predictors of a positive PCR were heterosexual group, <5 days of onset, and visible genital ulceration on examination. HSV-2 was associated with black Caribbean and black African ethnicity; HSV-1 with white ethnicity (p = 0.006). By HSV-2 specific serology, 16/42 (38%) first episodes caused by HSV-2 were recurrent infections, and 7/19 (37%) patients with recurrent genital disease but negative PCR had genital herpes. CONCLUSIONS: Epidemiological trends in genital HSV-1 and HSV-2 infection appear to vary between ethnic groups in the United Kingdom. HSV-2 specific serology improves diagnostic accuracy in GUM populations where most genital infections are caused by HSV-2.

Adolescent↗
PubMed2005

The attitude of patients towards medical students in a sexual health clinic.

OBJECTIVES: To determine patient attitudes toward medical students in the sexual health clinic, and to describe factors associated with patient refusal of medical student involvement. METHOD: A self administered questionnaire was given to 259 consecutive patients attending the general genitourinary medicine clinic. Participants were asked to indicate their attitude to questioning and/or examination by medical students. Information was also collected on sex, age, ethnicity, and previous visits to sexual health clinics and previous exposure to medical students. The proportion of patients reporting comfort with student involvement, and association with age, sex, country of birth, language spoken, and previous experience of student and/or genitourinary medicine clinics are reported. RESULTS: 82.6% of patients agreed to participate. The proportion reporting feeling comfortable with students ranged from 64% for female students questioning them with a doctor present to 35% for a male student questioning them alone. Comfort levels were associated with the sex of the student and previous exposure to medical students, but not age, country of birth, language spoken, or previous attendance at a sexual health clinic. The most common reasons for feeling uncomfortable with students were privacy concerns and poorer quality of care. CONCLUSION: Many patients feel uncomfortable with medical student involvement in a sexual health clinic consultation; particularly patients with no previous contact with medical students. Privacy and standard of care were the most common concerns, which are potentially amenable to change through better explanation of the students' role in the clinic.

Adolescent↗
PubMed2002

Chlamydial co-infection among patients with gonorrhoea.

The objective was to determine how often gonococcal (GC) infection is accompanied by chlamydial co-infection and to determine risk factors for dual infection. All GC-positive cultures were identified between 24 April and 9 September 1998, among patients seen at the three genitourinary medicine (GUM) clinics across the Chelsea and Westminster Directorate. Chlamydia trachomatis was diagnosed using an enzyme-linked immunosorbent assay (ELISA) (Dade-Behring). One hundred and fifty-three episodes of gonorrhoea were identified. Information on chlamydial infection was available for 149 cases of GC of whom 16 (10.7%) were found to be co-infected with C. trachomatis. In univariate analysis, chlamydial co-infection was exclusively diagnosed in heterosexuals, and was more likely to be diagnosed among females, in younger individuals and in individuals of black Caribbean ethnic group. In multivariable analyses, however, only the sex and age of the individual were independently associated with chlamydial co-infection. The rate of co-infection was 10.7%. Independent risk factors were being less than 20 years old and being female.

Adolescent↗
PubMed2001

Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals.

BACKGROUND: Relatively little is known about the long-term durability of viral suppression in individuals initially achieving a viral load of less than 50 copies/ml within 24 weeks of starting antiretroviral therapy, nor the extent to which therapy interruption accounts for the loss of suppression. METHODS: We intensely followed all 336 antiretroviral-naive patients attending the Goethe Universitat Clinic who began multi-drug combination regimens and in whom a viral load of less than 50 copies/ml was achieved within 24 weeks, in order to assess the risk of viral load rebound. Inspection of case notes allowed the distinction of viral rebound according to whether there was an associated complete interruption of therapy. RESULTS: A total of 61 patients experienced viral rebound during 543.1 person-years of follow-up, giving a 25.3% risk of rebound by 3.3 years from first achieving viral suppression. However, for 47 of the patients with viral rebound there was an associated documented complete interruption of antiretroviral therapy, mostly as a result of co-morbidities, leaving 14 who appear to represent a failure of the virological efficacy of therapy (viral breakthrough; 5.2% risk by 3.3 years). The risk of viral breakthrough declined with the increased duration of suppression (P = 0.01). CONCLUSION: The intrinsic virological effectiveness of multi-drug antiretroviral therapy in previously drug-naive individuals appears to be such that viral suppression, once achieved, can be maintained for several years in patients not interrupting therapy. The major challenge is to develop regimens that can be taken consistently and safely for such long periods of time.

Adult↗
PubMed2000

Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure.

OBJECTIVE: To analyse the immunological and virological effects of treatment interruptions in HIV-1-infected patients with treatment failure and multidrug-resistant virus. METHODS: Drug susceptibility was assessed using Antivirogram and genotypic analysis was based on population and clonal sequencing for 48 patients who had interrupted treatment (> or = 2 months). RESULTS: Treatment interruption resulted in viral load increases (mean 0.7 log 10 copies/ ml; P = 0.0001) and CD4 cell count decreases (mean 89 x 10(6) cells/l; P = 0.0001). A complete shift to wild-type virus at the phenotypic, genotypic and clonal level was observed in 28/45 patients. These patients differed from those that did not show a shift to wild type in baseline CD4 cell counts (192 versus 59 x 10(6) cells/l; P= 0.007) and in the relationship between baseline viral load and CD4 cell count (no correlation versus a significant negative correlation; P= 0.008). Response to re-initiation of treatment fell with increasing viral load [relative hazard (RH) 0.33; P= 0.001] and with increasing total number of drugs with reduced susceptibility (RH 0.51; P = 0.0003); it improved with the number of new drugs received (RH 2.12; P = 0.0002) and a shift to wild type (RH 5.22, P = 0.006). CONCLUSIONS: Changes in surrogate markers suggest that treatment provided benefit in spite of virological failure and resistant virus. Although patients with a shift to wildtype virus responded better in the short term to treatment re-initiation, the long-term effects are not known and the risk of immune deterioration needs to be carefully considered.

Adult↗
PubMed2000

The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema.

Atopic eczema (AE) is characterized by the persistence of infiltrating T lymphocytes in the dermis. To test the hypothesis that dysregulation of normal T cell apoptosis may contribute to the pathogenesis and chronicity of AE we compared patients with a normal resolving immune response (Mantoux reaction (MR)) induced in healthy volunteers by cutaneous PPD injection. Significantly less T cell apoptosis was observed in lesional skin of AE patients compared with either the peak or the resolution phase of the MR (P < 0.0001). The low incidence of T cell apoptosis in AE was associated with significantly increased levels of Bcl-2 relative to Bax (P < 0.0001) and significantly decreased CD95-L expression (P < 0.002) compared with the resolving MR. The cytokines IL-15 and interferon-beta (IFN-beta), which prevent activated T cell apoptosis, were expressed maximally on day 7 and day 14 of the MR, respectively. In contrast, AE patients expressed high levels of both IL-15 and IFN-beta in cutaneous lesions at the same time. This suggests that the co-expression of two anti-apoptotic cytokines, which are not found together during resolving cutaneous responses, may contribute to excessive T cell survival which leads to the persistence of inflammation in patients with AE.

Adolescent↗
PubMed2000

Detection of antibodies to human herpesvirus 8 in Italian children: evidence for horizontal transmission.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), has been shown to be the causative agent for Kaposi's sarcoma (KS) and to be more prevalent in populations or risk groups at increased risk for KS. HHV-8 infection is rare in children from the US and the UK, but has been reported in African children. In this study we examine HHV-8 infection in children from Italy, a country with an elevated prevalence of HHV-8 in adults and high socio-economic conditions.

Adolescent↗
PubMed1999

Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy.

OBJECTIVE: HIV-induced CD4 lymphocyte depletion is partially reversed by antiretroviral therapy but it is unclear if the degree to which the CD4 count rises depends on viral suppression (if so, the extent of viral suppression required to achieve a maximal CD4 count rise), whether the rise is sustainable and whether it occurs in patients with CD4 count <10 x 10(6) cells/l. We aimed to address these issues. METHODS: We studied CD4 count and plasma HIV RNA values every 4 weeks for 72 weeks in 154 patients starting indinavir-containing regimens. RESULTS: Mean baseline HIV RNA and CD4 count were 4.8 log10 copies/ml and 180 x 10(6) cells/l, respectively. Overall, there was a mean increase in CD4 count of 143 x 10(6) cells/l by 72 weeks. The adjusted mean increase (adjusted for initial viral load, CD4 count and age) was strongly related to the mean viral suppression over the follow-up period (P < 0.0001). Importantly, there was a highly significant difference (P = 0.0004) in the rise in CD4 count between those with 2-3 log suppression (161 x 10(6) cells/l) and those with > 3 log suppression (314 x 10(6) cells/l; mean 3.6 log suppression in this group), suggesting that with even greater suppression the rise in CD4 lymphocytes may be still larger. We also studied whether CD4 counts were still rising after 72 weeks in patients with sustained suppression of at least 3 log in viral load. There was a significant (P = 0.004; paired t-test) rise in count of 43 x 10(6) cells/l between weeks 64 and 72 in these patients, suggesting that regeneration continues at least up to 72 weeks after therapy, provided virus replication continues to be suppressed. Patients with initial CD4 counts < 10 x 10(6) cells/l experienced no smaller rises than those at higher levels, even after adjustment for other factors. CONCLUSION: These results strongly support a direct causal relationship between HIV replication and CD4 lymphocyte count depletion. The rise in those with > 3 log suppression provides the best available indicator of the potential for natural CD4 regeneration in HIV-infected patients. However, since still greater CD4 count rises may be seen with more suppressive regimens, it may not be possible to study the intrinsic CD4 regenerative capacity until such regimens are available.

Adult↗
PubMed1999

Virological response to protease inhibitor therapy in an HIV clinic cohort.

OBJECTIVE: New antiretroviral strategies aim to reduce plasma HIV RNA (viral load) to below the limits of detectability of assays with the objective of reducing viral replication in order to stop or reverse the pathogenic process and prevent development of drug resistance. First use of a protease inhibitor might offer the most realistic chance of achieving this aim. Our objective was to study the virological response to protease inhibitors in patients taking them for the first time. METHODS: A total of 901 patients from a large outpatient clinic were followed a mean of 15 months from the time of starting a protease inhibitor until 1 May 1998. Viral load and CD4 cell count measurements were made on average every 34 days. RESULTS: Overall there was a 79% [95% confidence interval (CI), 76-82] probability of the patients achieving a viral load < 500 copies/ml by 24 weeks after starting the protease inhibitor. In a multiple Cox regression model, those with lower initial viral load [relative hazard (RH), 0.72; P < 0.0001], higher CD4 cell count (RH, 1.07; P = 0.002), those starting other new drugs at same time as the protease inhibitor (RH, 1.46 for two versus none; P = 0.003), those who were antiretroviral-naive, and those using indinavir or nelfinavir were more likely to achieve such levels. In those 651 patients achieving viral load < 500 copies/ml within 24 weeks, there was an estimated 53% (95% CI, 51-55) probability of rebound of viral load to > 500 copies/ml by 52 weeks from the first undetectable value. Again, those who had started other new drugs at the same time as the protease inhibitor (RH, 0.57; P = 0.003 for starting two versus none) tended to experience a lower probability of viral load rebound, as did those with higher initial CD4 cell count (RH, 0.87 per 100 x 10(6)/l higher; P = 0.0007). Those who took saquinavir achieved less durable virological responses than those who took other protease inhibitors. CONCLUSIONS: Starting protease inhibitor therapy with two other new antiretroviral drugs simultaneously with protease inhibitor therapy offers a better best chance of achieving sustained viral load < 500 copies/ml than starting fewer new drugs.

Adult↗