Barbara Coughlan

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection

BACKGROUND/AIMS The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4–5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.

Underdiagnosis of hereditary haemochromatosis: lack of presentation or penetration?

Background: The majority of hereditary haemochromatosis (HH) patients are homozygous for the C282Y mutation in the HFE gene. We have demonstrated a homozygote frequency of 1 in 83 for the C282Y mutation in a retrospective analysis of Irish neonates. However, a fully developed phenotype is not observed at the same frequency clinically, suggesting that a large proportion of Irish HH patients may remain undiagnosed. Aims: To determine whether underdiagnosis of HH results from the non-specific nature of early symptoms or incomplete penetrance of the C282Y mutation. Methods: Seventy nine C282Y homozygous individuals identified from family screening for HH and 30 HH probands were investigated. Non-specific symptoms (fatigue, arthropathy, and impotence) and their association with iron indices (transferrin saturation and serum ferritin) and hepatic iron deposition were analysed. Results: We found that 78% of men (mean age 42 years) and 36% of women (mean age 39 years) who were identified as C282Y homozygotes following family screening had iron overload, as defined by a transferrin saturation ≥52% combined with a serum ferritin ≥300 μg/l for men and ≥200 μg/l for women. The frequency of reports of non-specific symptoms in those individuals with iron overload was not significantly different from those who did not have iron overload. Conclusions: Our findings indicate that underdiagnosis of HH may be due to the non-specific nature of early symptoms and less frequently to the incomplete penetrance of the C282Y mutation.

Complementary alternative medicine (CAM) use in Ireland: A secondary analysis of SLAN data

PURPOSE National prevalence studies on CAM use have been undertaken internationally, however, to date no such studies have been performed in Ireland. The aim of this study was to estimate the prevalence of CAM use among the general population in Ireland and to identify characteristics of typical Irish CAM users. METHODS A descriptive, quantitative design was used. A secondary data analysis of the SLAN (National Survey of Lifestyles, Attitudes and Nutrition) 1998 (N=6539) and 2002 (N=5992) surveys was undertaken, allowing access to data from a representative cross-section of the Irish adult population. Use of CAM was determined by whether or not respondents had ever attended a CAM practitioner. chi(2) test for independence of categorical variables and multivariate logistic regression analysis were used (stepwise function of SPSS software). RESULTS The prevalence rate for visits to CAM practitioners increased from 20% in 1998 to 27% in 2002. Similar to international findings, Irish CAM users are more likely to be well educated, affluent, middle-aged and employed. Self-employed persons in particular are more likely to visit CAM practitioners (a finding not commonly reported internationally). Irish persons suffering from pain, anxiety and depression are also more likely to use CAM. CONCLUSIONS Use of CAM is increasing among the Irish general population and predictors of CAM use in this study are broadly similar to those found internationally. The profile constructed from our study should assist health professionals to identify those persons who may wish to use CAM so that appropriate verbal/written guidance may be provided.

Investigating health‐related quality of life, mood and neuropsychological test performance in a homogeneous cohort of Irish female hepatitis C patients

Summary.  Neurocognitive dysfunction has been reported in individuals with chronic hepatitis C (CHC) infection, but HCV populations investigated have often included participants with numerous potential confounding comorbidities. This pilot study sought to investigate functional capacity and neurocognitive function in a homogeneous state‐infected HCV population with histologically defined mild liver disease, free from the comorbid factors typically associated with HCV populations. A further aim was to examine cognitive function in a treatment naive population with a similar history of iatrogenic HCV exposure and spontaneous viral clearance. A convenience sample of 29 women, all of whom were carefully screened to exclude relevant comorbidities, was recruited to the study. Twenty women with a history of iatrogenic HCV exposure were recruited from prospective specialist tertiary care liver clinics. A comparison group of healthy controls (n = 9) was also assessed. Study participants underwent mood, health‐related quality of life and neuropsychological assessment. CHC patients reported significantly higher levels of cognitive fatigue than healthy controls (F = 3.4, P = 0.04). On cognitive testing, CHC patients showed impairments compared with healthy controls on estimates of general memory [F(2,25) = 4.1, P = 0.03, partial eta squared = 0.25], delayed auditory recognition [F(2,25) = 4.2, P = 0.03, partial eta squared= 0.22] and sustained attention [F(2,25) = 3.6, P = 0.04, partial eta squared = 0.22]. Increased cognitive fatigue only correlated with delayed auditory memory recall ability (r = 0.724, P = 0.006). In conclusion, these findings appear to support the presence of neurocognitive abnormalities in an iatrogenically infected, homogeneous female HCV population who were carefully screened to eliminate other factors affecting neurocognitive test performance and may indicate underlying neurophysiological causative mechanisms.

Improving social functioning and reducing social isolation and loneliness among people with enduring mental illness: Report of a randomised controlled trial of supported socialisation

Background: This randomised controlled trial examined if for people with enduring mental illness, being supported to socialise leads to improved social functioning, increased self-esteem and extended social networks; a reduction in social isolation, social, emotional and family loneliness and a reduction in illness symptoms, namely depression. Methods: A prospective randomised controlled trial was undertaken from November 2007 to September 2011. Service users with a diagnosis of enduring mental illness (>18 years) were invited to participate. Participants were randomly allocated to intervention or control group conditions in a 1:1 ratio. Intervention group participants were matched with a volunteer partner, asked to engage in social/leisure activities for 2 hours weekly over a 9-month period, and received a €20 stipend monthly. Control group participants received a €20 monthly stipend and were asked to engage in a weekly social/leisure activity. Social functioning, the primary outcome, was measured using the Social Functioning Scale (SFS) at three time points (baseline, midpoint and endpoint). Findings: In all, 107 people completed this study. There were no significant differences between control and intervention groups at the commencement of the intervention on demographic characteristics or the main outcome measures of interest. Overall social functioning positively changed throughout the three time points from a mean of 99·7 (standard deviation (SD) = 15.1) at baseline, to a mean of 106.0 (SD = 27.0) at the endpoint for the control group, and from a mean of 100·4 (SD = 15.0) at Time 1 for the intervention group, to a mean of 104.1 (SD = 23.4) at the endpoint for the intervention group. Conclusions: The intervention showed no statistical differences between the control and intervention groups on primary or secondary outcome measures. The stipend and the stipend plus volunteer partner led to an increase in recreational social functioning; a decrease in levels of social loneliness, in depression and in the proportion living within a vulnerable social network.

The Role of CAM (Complementary and Alternative Medicine): The Different Perspectives of Patients, Oncology Professionals and CAM Practitioners

Semi-structured interviews were undertaken with 31 women with breast cancer, 20 oncology professionals (13 oncology nurses and 7 oncologists) and 20 CAM practitioners2. Interviews were analysed using a thematic networks technique (Attride-Stirling, 2001). Thematic analysis is the recognition of themes through a thorough reading and rereading of the transcripts (Ezzy, 2002, Liamputtong & Ezzy, 2005). For this study, thematic analysis was supported by and presented as thematic networks: “web-like illustrations (networks) that summarize the main themes constituting a piece of text” (Attride-Stirling 2001, p. 386).

Research Priorities for Children's Nursing in Ireland: A Delphi Study

This paper is a report of a study which identified research priorities for childrens nursing in an acute care setting in Ireland. A limited number of studies have examined research priorities for childrens nursing. This study was undertaken against the backdrop of significant proposed changes to the delivery of childrens healthcare. A three round Delphi survey design was used to identify and rate the importance of research priorities for childrens nursing. In round I participants were asked to identify five of the most important research priorities for childrens nursing. Participants in round II were asked to rate the importance of each research priority on a 7-point Likert scale. In round III participants were presented with the mean score of each research priority from the second questionnaire, and again asked to consider the importance of each topic on a 7-point Likert scale. The aim was to reach consensus on the priorities. The top three priorities identified were recognition and care of the deteriorating child, safe transfer of the critically ill child between acute health care facilities, and the child and familys perceptions of care at end-of life. The wide variation of priorities reflects the scope of care delivery of childrens nurses and mirrors many global care concerns in caring for children.

Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term

OBJECTIVE We sought to assess amniotic fluid lactate (AFL) at diagnosis of spontaneous labor at term (≥37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD). STUDY DESIGN This was a single-institution, prospective cohort study of 905 singleton, cephalic, term (≥37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds. RESULTS AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n = 118), 5.0-9.9 mmol/L (n = 707), and ≥10.0 mmol/L (n = 80). Increasing AFL was associated with higher total oxytocin dose (P = .001), labor disorders (P = .005), and CD (P ≤ .001). Multivariable regression analysis demonstrated that women with AFL ≥5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06-2.39) and AFL ≥10.0 mmol/L (OR, 1.72; 95% CI, 1.01-2.93) were independent predictors of a labor disorder. AFL ≥5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL ≥10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73-6.46). AFL ≥5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL ≥10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method. CONCLUSION AFL at diagnosis of labor in spontaneously laboring single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol.

Friendship and money: A qualitative study of service users’ experiences of participating in a supported socialisation programme:

Background: Social opportunities can be limited in the lives of people with enduring mental illness (EMI) due to psychiatric stigma, restricted home environments and employment barriers. Supported socialisation programmes have the potential to redress the impact of social isolation. Aim: To explore the experiences of service users with EMI taking part in a supported socialisation programme, using written diary entries. Methods: This article reports on the qualitative component of a randomised controlled trial of supported socialisation for people with EMI (published previously in this journal). Trial participation involved (1) being matched with a volunteer partner and engaging in social/leisure activities while receiving a stipend of €20 or (2) receiving this stipend only and engaging in self-driven socialisation. Participants completed written diaries documenting their perspectives on their experiences of supported socialisation. Data were analysed using Thematic Analysis. Results: Experiences of participation were characterised by involvement ‘normalising’ life, fostering a sense of connectedness, improving physical health, and facilitating engagement with culture. Taking part helped participants integrate socialising into their identity, enhanced their perceived capacity to be social, and cemented/expanded social networks. Participants also experienced significant obstacles to socialisation. Conclusion: Supported socialisation can increase confidence, social competence and self-agency; buffer against psychiatric stigma; build social capital; and afford opportunities to enhance social integration, inclusion and belonging.

Correlates of hepcidin and NTBI according to HFE status in patients referred to a liver centre.

Background/Aims: Innately low hepcidin levels lead to iron overload in HFE-associated hereditary haemochromatosis. Methods: This study compared hepcidin and non-transferrin bound iron (NTBI) levels in untreated iron-loaded and non-iron-loaded C282Y homozygotes to levels in C282Y/H63D compound heterozygotes and individuals with other HFE genotypes associated with less risk of iron overload. Results: As the genotypic risk for iron overload increased, transferrin saturation and serum NTBI levels increased while serum hepcidin levels decreased. Overweight and obese male C282Y homozygotes had significantly higher hepcidin levels than male C282Y homozygotes with a normal BMI. Pearson product-moment analysis showed that serum hepcidin levels significantly correlated with HFE status, serum ferritin, age, NTBI, transferrin saturation, gender and BMI. Subsequent multiple regression analysis showed that HFE status and serum ferritin were significant independent correlates of serum hepcidin levels. Conclusions: In summary, this study has shown that while serum ferritin and HFE status are the most important determinants of hepcidin levels, factors such age, gender, BMI, transferrin saturation and NTBI all interact closely in the matrix of homeostatic iron balance.