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Biomedical subjects

F Mulcahy

Publications and source records attributed to F Mulcahy.

At least 19 recordsLinked to original sources
PubMed2006

Role of individualization of hepatitis C virus (HCV) therapy duration in HIV/HCV-coinfected individuals.

OBJECTIVE: The aim of this study was to assess the efficacy, safety and tolerability of pegylated interferon and ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients, prescribed for the same duration and at the same dosage as that used in HCV monoinfection studies. DESIGN: It was an open-label, single-centre, prospective study. METHODS: Forty-five patients coinfected with HIV and HCV with CD4 counts >200 cells/microL were treated with pegylated interferon-alpha2b 1.5 microg/kg/week and ribavirin 1000-1200 mg/day for 24-48 weeks depending on HCV genotype. Safety and tolerability were assessed weekly for the first month and monthly thereafter. Virological response was assessed at weeks 4, 12 and 24 and at the end of treatment and 12 and 24 weeks post completion of treatment. The primary endpoint was defined as undetectable HCV RNA at 24 weeks post completion of treatment [sustained virological response (SVR)]. RESULTS: The majority of patients were male and had been injecting drug users. Sixty per cent were on antiretroviral therapy. In an intention-to-treat analysis, 53% had an SVR (genotype 1, 19% and genotype 2/3, 75%). All patients who had undetectable HCV RNA at week 4 of HCV treatment [very early virological response (VEVR)] had a SVR. On multivariate analysis only HCV genotype predicted SVR. Adverse events occurred frequently. CONCLUSIONS: These results indicate that 24 weeks of HCV treatment may be adequate for HIV-infected individuals coinfected with HCV genotype 2 or 3. VEVR can predict SVR in this group and may be used to guide the subgroup of genotype 2/3 individuals who will respond to 24 weeks of treatment.

Adult↗
PubMed2006

National guidelines for the management of HIV-1 in pregnancy.

Management of HIV-1 in pregnancy has reduced the mother-to-child-transmission (MTCT) rate from 25-30% to <2% in the developed world, including Ireland. In Ireland most HIV positive pregnant women are diagnosed through antenatal screening many of whom arrive here late in pregnancy. Geographic dispersal and subsequent involvement of obstetric units throughout the country has resulted in a need for clear, accessible management guidelines. The Irish Infection Society first published guidelines for the management of HIV-1 in pregnancy in 2001 (1). The updated guidelines became operational in January 2002 with some amendments in March 2003 and July 2004. These guidelines offer a broad management outline for HIV positive pregnant women. Ultimately, each woman is assessed individually by a multidisciplinary team and a careful plan is determined.

Anti-Retroviral Agents↗
PubMed2004

Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.

BACKGROUND: The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. METHODS: In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. FINDINGS: Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. INTERPRETATION: Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.

Adult↗
PubMed2004

Resurgence in infectious syphilis in Ireland: an epidemiological study.

INTRODUCTION: In 2000, a syphilis outbreak was identified in Ireland. MATERIALS AND METHODS: A prospective enhanced database was established in 2000. Crude incidence rates for the general population, men who have sex with men (MSM), and HIV-positive MSM were calculated. RESULTS: Three hundred fifty-six cases of infectious syphilis were diagnosed at 1 center. Eighty-five percent of cases were identified as MSM. Crude incidence rates in MSM, ranging in age between 20 and 44 years, peaked in 2001 at 719 cases per 100000 of the MSM population. A total of 17.4% of cases occurred in HIV-infected individuals. Crude incidence rates of syphilis in HIV-positive MSM in the center increased to 7280 per 100000. Similar percentages of MSM with and without HIV infection had unprotected anal intercourse (37% and 41%, respectively). CONCLUSION: High-risk sexual behavior continues among HIV-infected and -noninfected MSM. Crude incidence rates among MSM in Ireland are alarming when compared with other outbreaks.

Adult↗
PubMed2004

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study.

OBJECTIVES: To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan-European, observational cohort study. METHODS: Generalized estimating equations were used to determine changes over time in the proportion of patients admitted and the median duration of admission. Logistic regression was used to determine factors related to admission in March 1995, March 1998 and March 2001. RESULTS: The proportion of patients admitted during March declined from 7.4% in 1995 to 2.6% in 2003. After adjustment, the estimated reduction in the proportion of patients admitted was 5.5% per year [95% confidence interval (CI) 2.5-8.5%; P=0.0004], a 26% reduction. The median duration of hospital admission declined by 58% from 12 days in 1995 [interquartile range (IQR) 5-19 days] to 5 days in 2003 (IQR 3-12 days), a significant decline of 0.7 days per year after adjustment (95% CI 0.5-0.9 days; P=0.031). Patients with a lower CD4 lymphocyte count, and with an AIDS diagnosis made within the 3 months prior to March, all had increased odds of admission during March 1995, 1998 or 2001. In March 2001, patients whose treatment regimen was changed as a consequence of toxicities had increased odds of admission [odds ratio (OR) 2.34; 95% CI 1.26-4.37; P=0.0074]. In addition, patients who were hepatitis C virus-positive during March 2001 (OR 1.66; 95% CI 1.02-2.68; P=0.041) had increased odds of admission. CONCLUSIONS: There has been a considerable decline in both the proportion of patients admitted to hospital and the median duration of the stay. Patients with hepatitis C had increased odds of admission, but there was little evidence of an increase in admissions among patients taking highly active antiretroviral therapy (HAART) associated with serious adverse events, although longer follow up is required.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Assessing limiting factors to the acceptance of antiretroviral therapy in a large cohort of injecting drug users.

OBJECTIVE: A comprehensive questionnaire was designed to assess the knowledge and understanding of injecting drug users (IDUs) regarding their HIV disease, and to determine any factors that may increase the acceptance of antiretroviral therapy (ART) by this group. RESULTS: Twenty percent of the total IDU cohort attending the GUIDE (GenitoUrinary Medicine and Infectious Diseases) clinic participated in the study. Fifty-two percent had been homeless in the past 5 years and 84% are unemployed. Seventy-two percent of patients did not complete second level education and 10% were illiterate. Fifty-one percent had siblings or parents with a history of injection drug misuse, and 25% had at least one sibling also HIV positive. Forty-seven percent started using drugs before the age of 13 years, and the most common initial drug was heroin (44%). Ninety-five percent had attended for methadone maintenance therapy (MMT), with 39% currently attending for daily therapy. The majority of patients were unable to simply explain or interpret CD4 cell counts (54%) and 'viral loads' (65%). Fifty-seven percent of patients were receiving highly active antiretroviral therapy (HAART). There was a statistically significant association between patients receiving HAART and both attendance at a primary care physician for methadone maintenance therapy (P = 0.005), and weekly take-outs of methadone (P = 0.005). There was also an association between adherence to HAART and attendance at a methadone maintenance clinic (P = 0.04). CONCLUSIONS: This study highlights the chaotic lifestyle and complex social background of the IDU. Such factors were not, however, associated with acceptance of HAART. The primary factor associated with both the acceptance of and adherence to HAART was regular and stable attendance for methadone therapy.

Adolescent↗
PubMed2003

p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep smears.

AIM: To examine the potential of p16(INK4A) as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep smears. METHODS: Immunocytochemical analysis of p16(INK4A) expression was performed on 22 normal cervical tissue samples, five cervical glandular intraepithelial neoplasia (cGIN), 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, and 10 invasive cancer cases (eight squamous and two adenocarcinomas). All samples were formalin fixed and paraffin wax embedded, and immunohistochemical analysis was carried out using a mouse monoclonal anti-p16(INK4A) antibody after antigen unmasking. The staining intensity was assessed using a 0 to 3 scoring system. In addition, the expression status of p16(INK4A) was examined in 12 normal ThinPrep smears, one smear exhibiting cGIN, and a total of 20 smears exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) detection was carried out using a modified SYBR green assay system. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: p16(INK4A) immunoreactivity was absent in all normal cervical tissues examined. Dysplastic squamous and glandular cells were positive for p16(INK4A) expression in all cases included in this study, except for one CIN3 case. p16(INK4A) expression was mainly nuclear in CIN1 cases, and both nuclear and cytoplasmic in CIN2, CIN3, cGIN, and invasive cases. All cases positive for HPV expressed the p16(INK4A) protein, although not all cases found positive for p16(INK4A) were HPV positive. In general, the p16(INK4A) staining intensity was lower in cases negative for HPV or those containing a low risk HPV type. CONCLUSION: This pattern of overexpression demonstrates the potential use of p16(INK4A) as a diagnostic marker for cervical squamous and also glandular neoplastic lesions. In addition, the technique can be used to identify individual dyskaryotic cells in ThinPrep smears. Thus, p16(INK4A) is a useful marker of cervical dyskaryosis.

Biomarkers↗
PubMed2002

St Johns wort increases expression of P-glycoprotein: implications for drug interactions.

AIMS: St John's Wort (SJW) is widely used in the treatment of depression but concerns have been raised about its potential to interact with other drugs. Co-administration with SJW has resulted in significant reductions in trough plasma concentrations of indinavir and cyclosporin [1, 2]. Induction of cytochrome P450 3A4 (CYP3A4) has been implicated as the most likely interaction mechanism. However, the magnitude of the interaction seen in clinical practice is greater than that predicted by in vitro studies suggesting additional interaction mechanisms may exist. As indinavir and cyclosporin are substrates for both CYP3A4 and the multi drug transporter P-glycoprotein we hypothesized that modulation of P-glycoprotein expression and function by SJW may contribute to the development of potentially harmful drug-drug interactions. METHODS: Healthy volunteers were randomized to either SJW (0.15%) 600 mg three times daily for 16 days (n = 15) or placebo (n = 7). Blood samples were obtained for P-glycoprotein expression and function at baseline, 16 and 32 days post treatment. Peripheral blood lymphocytes (PBMCs) were isolated by Ficoll density gradient centrifugation, fixed and permeabilized. Cells were stained with a P-glycoprotein specific antibody, quantified by flow cytometry and median fluorescence intensity (MFI) values obtained. Vimentin and IE (nonsense antibody) were used as controls. The presence of the MDR 1 gene product was confirmed by RT-PCR. P-glycoprotein mediated drug efflux was determined as a function of rhodamine efflux in the absence and presence of ritonavir. Data are expressed as mean +/- s.d. and were subjected to nonparametric analysis. RESULTS: P-glycoprotein expression increased 4.2 fold from baseline in subjects treated with SJW (7.0 +/- 1.9 vs 29.5 +/- 14.3 (MFI); P < 0.05). There was no effect with placebo (5.1 +/- 1.3 vs 6.0 +/- 1.9 MFI). SJW increased P-glycoprotein mediated rhodamine efflux (reduced ratio) compared with baseline (0.12 +/- 0.04 vs 0.24 +/- 0.18 P < 0.05). There was no change with placebo. Ritonavir (5 microm) inhibited P-glycoprotein mediated efflux in both groups producing greater intracellular accumulation of rhodamine. However, this effect was attenuated following treatment with SJW (23.9 +/- 15.3% vs 75.4 +/- 16.4% P < 0.05). CONCLUSIONS: SJW increased expression and enhanced the drug efflux function of the multi drug transporter P-glycoprotein in PBMCs of healthy volunteers. This may represent a second mechanism for the drug-herb interactions seen in clinical practice and account for the discrepancies between in vitro and in vivo data. Since P-glycoprotein and CYP3A4 have distinct though overlapping substrates, patients receiving drugs, which are P-glycoprotein substrates should be warned against self-medication with SJW as clinically significant drug interactions may occur.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Evaluation of liquid-based cytology in cervical screening of high-risk populations: a split study of colposcopy and genito-urinary medicine populations.

A split study evaluated the ThinPrep(R) PapTesttrade mark (TP; Cytyc Corp., Boxborough, MA) compared with current methodologies of cervical cytology in two high-risk cohorts. One thousand, three hundred cases from a colposcopy clinic and a genito-urinary medicine outpatient clinic were examined. The TP reported increased detection of all grades of dyskaryosis (mild, moderate and severe; + 4.5%) and a decrease in borderline and unsuitable cases (- 4.9%). Four cases of high-grade dyskaryosis (moderate or severe) were detected only using the TP, while an additional four cases classified as high-grade dyskaryosis with the TP were reported as borderline by our conventional methods. The split-study finding of increased sensitivity with the TP provides for improved clinical management of patients in our high-risk cohorts.

Cell Nucleus↗
PubMed2002

Candida dubliniensis candidaemia in an HIV-positive patient in Ireland.

Candida dubliniensis was first identified in Dublin in 1995 in oral isolates recovered from human immunodeficiency virus (HIV)-infected individuals. Although C. dubliniensis has been primarily recovered from the oral cavities of HIV-infected individuals, the number of reports describing its isolation from HIV-negative individuals, including cases of candidaemia, is growing. To date there has only been one report of C. dubliniensis candidaemia in an HIV-infected patient, in this case from the USA. In the present study, 2 Candida isolates recovered from blood samples were presumptively identified as C. dubliniensis on the basis of their dark green coloration on CHROMagar Candida medium and lack of growth at 45 degrees C. This identification was confirmed by carbohydrate assimilation profile analysis and by polymerase chain reaction (PCR) analysis with C. dubliniensis-specific PCR primers. Both isolates were susceptible to fluconazole. The isolates were found retrospectively to be from a single HIV-infected patient who was receiving broad-spectrum antibacterials at the time of isolation of C. dubliniensis from blood. This study represents the first documented case of C. dubliniensis bloodstream infection in Ireland and is only the second case of C. dubliniensis bloodstream infection identified in an HIV-infected individual anywhere in the world.

Adult↗
PubMed2001

The changing epidemiology of HIV infection in injecting drug users in Dublin, Ireland.

INTRODUCTION: Injecting drug users (IDUs) represent 41.6% of the total cohort of HIV-infected patients in Ireland. Between January 1999 and December 2000, referrals to the largest tertiary centre for HIV infection in Dublin have increased dramatically. This has occurred on a background of a reduction in the overall incidence of HIV infection in Ireland between 1990 and 1998. Here we describe the changing epidemiology of HIV disease in IDUs and explore potential aetiological factors. METHODS: This is a retrospective study, collecting all data relating to new HIV diagnoses occurring in IDUs, referred to the GenitoUrinary Medicine and Infectious Diseases (GUIDE) clinic between 1987 and 2000. We calculated 6-month incidence rates of new HIV diagnoses in IDUs referred to the GUIDE clinic and performed a more detailed analysis of those patients diagnosed between January 1999 and December 2000, documenting age, sex, time and place of diagnosis, drug use history and primary drug of misuse, needle sharing history, attendance at a drug treatment clinic, prior HIV testing history, hepatitis B and hepatitis C status, and CD4 cell counts and HIV RNA levels at diagnosis. RESULTS: The number of new HIV diagnoses in IDUs increased fivefold between 1995 and 2000. Moreover, 40% of patients diagnosed since then have been under 22 years old. There has also been a significant reversal of the initial male to female ratio seen in the initial epidemic of the 1980s. CONCLUSION: There has been a significant increase in the incidence of HIV infection in IDUs between 1995 and 2000. Similar trends have been described recently in other risk groups. The aetiology of these trends is multifactorial, and a multidisciplinary, rejuvenated approach is required to focus on improving health education to reduce both sexual and needle sharing practices.

Adolescent↗
PubMed2001

The great pretender returns to Dublin, Ireland.

BACKGROUND: An outbreak of syphilis has been identified primarily in Dublin, Ireland. On a background of a stable low incidence of syphilis, a significant increase in the number of cases of syphilis has been observed over the past 18 months. RESULTS: 181 cases of syphilis were seen in this period. 121 were defined as early syphilis. These cases were mainly among men who have sex with men (92%). A high rate of HIV co-infection was present; 16 patients who regularly attended HIV clinics were diagnosed with early syphilis. Nine patients were co-diagnosed with HIV and early syphilis. High risk behaviour and concurrent diagnoses with other sexually transmitted infections were prevalent in this cohort. Sexual networks were also investigated. CONCLUSION: An education campaign, widespread advertisements, and on-site testing in commercial venues have revealed further cases. Safer sex messages need to be emphasised particularly among the HIV population. Further innovative strategies continue to be explored.

Adult↗
PubMed2001

Cervical smears: comparison of knowledge and practice of a general practice sample with a high-risk group.

Successful cervical screening programmes depend on the participation of an informed target population. A national cervical screening programme is shortly to be introduced in the Republic of Ireland. We compare the knowledge, attitudes and practice of 395 Irish urban women with 323 high-risk women, genitourinary medicine (GUM) clinic attenders. There was little difference in knowledge between the 2 groups. Fifty-five per cent of the general practice (GP) sample and 45% of the GUM sample correctly identified the purpose of a smear. Eighty-three per cent of both groups had had at least one smear but only 59% of the high-risk group had had a smear before attending the GUM clinic. Both groups expressed a preference for a female provider. Socio-economic grouping is the strongest predictor of knowledge and uptake of cervical smears and high-risk women were less likely to have opportunistic cervical smears. Information programmes to encourage participation in screening programmes must build on pre-existing knowledge and focus on the relevance and acceptability of the test.

Adolescent↗
PubMed2001

National guidelines for the active management of HIV in pregnancy.

The number of HIV positive women becoming pregnant in Ireland is increasing, with many pregnancies occurring in women from countries of high HIV prevalence. The management of such patients offers the challenge of reducing the risk of maternal-fetal transmission of HIV infection, avoiding fetal-infant toxicities, and maintaining future maternal antiretroviral options. Guidelines for the optimal management of HIV disease in pregnancy have been produced by a subgroup of the Irish Infection Society consisting of GenitoUrinary Medicine and Infectious Diseases Consultants. They are based on currently available international data and guidelines. The national guidelines offer a broad management outline for HIV positive pregnant patients. Ultimately, each patient is assessed individually by a multidisciplinary team, and a careful plan for antenatal, intrapartum, and postpartum care is determined.

Anti-HIV Agents↗
PubMed2000

AIDS across Europe, 1994-98: the EuroSIDA study.

BACKGROUND: The clinical presentation of HIV-1 related diseases could have changed after the introduction of highly active antiretroviral treatment (HAART). We aimed to assess changes over time in the incidence of ADIs overall and within CD4 lymphocyte count strata, the relationship with treatment and degree of immunodeficiency at diagnosis of ADIs. METHODS: We did a prospective observational multicentre study of over 7300 patients in 52 European HIV-1 outpatient clinics. Incidence rates per 100 patient-years of observation were calculated. FINDINGS: In total, we recorded 1667 new ADIs; the incidence of ADIs declined from 30.7 per 100 patient-years of observation during 1994 (95% CI 28.0-33.4) to 2.5 per 100 patient-years of observation during 1998 (95% CI 2.0-3.0, p<0.0001, test for trend). Median CD4 lymphocyte count at diagnosis of a new ADI increased from 28 cells/microL to 125 cells/microL between 1994 and 1998 (p<0.0001), yet a steep decline in the rate of ADIs was seen after stratification by latest CD4 lymphocyte count within each year (< or = 50, 51-200, and > 200 cells/microL). Patients on HAART had a lower rate of ADIs than patients not on this treatment within each CD4 lymphocyte count strata. The proportion of ADIs attributable to cytomegalovirus retinitis and Mycobacterium avium complex declined over time (p=0.0058 and 0.0022, respectively), whereas the proportion of diagnoses attributable to non-Hodgkin lymphoma has increased (p<0.0001). In 1994, less than 4% of ADIs were non-Hodgkin lymphoma, in 1998 the proportion was almost 16%. This condition has become one of the most common ADIs in patients on HAART. INTERPRETATION: Our findings lend support to the idea that treatment regimens can lower the incidence of ADIs. The immediate risk of an ADI for a given CD4 lymphocyte count has declined over time and is lower among patients on HAART. Long-term follow-up of patients on combination treatment is essential to monitor the incidence of new and emerging diagnoses.

AIDS-Related Opportunistic Infections↗
PubMed2000

Regional differences in presentation of AIDS in Europe.

Data were collected on 6578 patients diagnosed with AIDS at 52 clinical centres in 17 European countries during an 1-year period from 1979 to 1989. The centres were divided into four regions, North, Central, Southeast, and Southwest. Differences in the incidence of most AIDS-defining opportunistic infections and malignancies were found. After adjusting for known possible confounders, statistically significant differences between regions remained. Pneumocystis carinii pneumonia (PCP) was more common in Northern Europe, Kaposi's sarcoma and toxoplasmosis in Central Europe, cytomegalovirus retinitis in South-eastern Europe, and extrapulmonary tuberculosis in South-western Europe. These differences we attribute primarily to different degrees of exposure to the respective underlying pathogens. The prevalence of these and other micro-organisms will determine the clinical course of HIV infections in parts of Eastern Europe and elsewhere where the virus now is spreading.

AIDS-Related Opportunistic Infections↗
PubMed2000

The tolerability of efavirenz after nevirapine-related adverse events.

Eight patients who were infected with human immunodeficiency virus, and who had each sustained an adverse drug reaction while following a regimen including nevirapine, were switched to a regimen including efavirenz. None of the patients experienced adverse events identical to that which necessitated discontinuation of nevirapine. This study demonstrates that adverse events related to nevirapine are not a class-specific effect.

Adult↗