Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes. METHODS: Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors. RESULTS: Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown. DISCUSSION: Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020216205.

Improving access to the treatment of hepatitis C in low- and middle-income countries: evaluation of a patient assistance programme.

Background Modern antiviral treatments have high cure rates against the hepatitis C virus however, the high cost associated with branded medicines and diagnostic tests, have resulted in poor access for many low-income patients residing in low-and-middle-income countries. Objective This study aimed to evaluate the role of a patient assistance programme and generic medicines in improving access to treatment of low-income hepatitis C patients in a low-and-middle-income country. Setting A major teaching public hospital in Islamabad, Pakistan. Methods Hepatitis C patients who presented and enrolled for the patient assistance programme during 12 months (1st July 2015 and 30th June 2016) were included. Demography, prescription characteristics, the total costs of Hepatitis C treatment, medicine cost supported by the programme, out-of-pocket cost borne by the patient and average cost effectiveness ratio per sustained virologic response were calculated and compared for different generic and branded regimens. Main outcome measure cost contribution of patient assistance programme. Results A total of 349 patients initiated the treatment through the programme and of those 334 (95.7%) completed the prescribed treatment. There were 294 (88.02%) patients who achieved sustained virologic response. Patient assistance programme contributed medicines cost averaging 60.28-86.26% of the total cost of treatment ($1634.6) per patient. The mean (SE) cost per patient for generic option (Sofosbuvir/Ribavirin) was the lowest [$658.36 (22.3) per patient, average cost effectiveness ratio = $720.1/SVR] than branded option (Sovaldi/Ribavirin) [$2218.66 (37.6) per patient, average cost effectiveness ratio = $2361.8/SVR] of the three available treatment regimens. From patients' perspectives, the mean (SE) out-of-pocket cost was $296.9 (6.7) which primarily included diagnostic cost (69.9%) of the total cost. Conclusions Patient assistance programme, combined with generic brands of newer hepatitis C treatment offered a significant reduction in cost and widens access to hepatitis C treatment in low-and middle-income countries. However, substantial out-of-pocket costs of the treatment presents an important barrier for service access. There is a scope to widen such financial assistance programme to offer other costs attributed to patients, specifically for diagnosis, to widen service use in low-and-middle-income countries.

Co-occurrence of autistic and psychotic traits: implications for depression, self-harm and suicidality.

BACKGROUND: There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality. METHODS: Cross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed. RESULTS: A positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits. CONCLUSIONS: This study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.

The management of depression following traumatic brain injury: A systematic review with meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is prevalent. Declining mortality has led to increasing survivors with chronic sequalae, including depression. With a lack of guidelines, this review aims to provide a comprehensive, evidence-based summary of the management of depression following TBI. METHODS: Systematic searches were conducted for quasi-experimental and randomized controlled trials (RCTs) assessing pharmacotherapy, psychological interventions, and transcranial magnetic stimulation (TMS). Databases searched CENTRAL, Medline, Embase, CINAHL, PsycINFO, Web of Science, and ProQuest dissertations. Data extraction and risk-of-bias tools were used. Where possible, outcomes were combined into meta-analyses. RESULTS: 2719 studies were identified. After abstract screening and full-text reading, 34 remained. Prophylactic sertraline significantly reduced the odds of depression (OR (odds ratio) = 0.31 [95%CI (confidence interval) = 0.12 to 0.82]). Meta-analysis of RCT's showed TMS to have the greatest reduction in depression severity (SMD (Standardized-Mean-Difference) = 2.43 [95%CI = 1.24 to 3.61]). Stimulants were the only treatment superior to control (SMD = -1.03 [95%CI = - 1.6 to -0.47]). CONCLUSION: Methylphenidate was the most effective pharmacotherapy. Sertraline appears effective for prevention. The efficacy of psychological interventions is unclear. TMS as a combination therapy appears promising. Heterogeneity of study populations and dearth of evidence means results should be interpreted cautiously.

A Randomized Controlled Trial to Assess the Impact of Clinical Pharmacy Interventions on Treatment Outcomes, Health Related Quality of Life and Medication Adherence Among Hepatitis C Patients.

PURPOSE: The role of specialized pharmacy services remains unexplored in clinical practice for hepatitis C patients in Pakistan. This study aimed to evaluate the impact of clinical pharmacy interventions on treatment outcomes, health-related quality of life (HRQoL), and medication adherence among hepatitis C patients. METHODS: A randomized control trial was conducted at two tertiary-care teaching hospitals in Pakistan. Hepatitis C patients who attended the outpatient clinics between October 2015 and September 2018 were randomized to two groups [usual care (UC) and pharmaceutical care (PC)] in a 1:1 ratio, applying simple envelope method. The PC group received pharmaceutical care led by a clinical pharmacist. The care that patients received included education and counseling on medication compliance, labeling of medication packs, and monitoring of adverse drug events, led by a qualified clinical pharmacist during the 15- to 20-minute monthly sessions, while the UC group received standard care at hospital, which did not involve clinical pharmacist input. Outcome measures, such as sustained virological response, HRQoL, and adherence rate (pharmacy data) were assessed at enrolment and distinct time intervals: 4 weeks, 8 weeks, and end of treatment. RESULTS: A total of 931 patients were included in the study (UC 466 and PC 465), with mean age 42.35±1.9 years. Sustained virological response at 12 weeks was achieved in 86.0% patients in the PC group, significantly (p<0.001) higher than the UC (69.3%) group. Fewer patients (9.9%) in the PC group reported mobility problems, significantly fewer (p<0.001) than the UC group (11.8%). Self-care, usual activity, pain, and depression were relieved significantly in the PC group compared to the UC group. The EuroQol visual analogue scale (baseline 56.1 of UC group versus 55.2 for PC group) was raised to 71.8 and 71.9 in the UC and PC groups, respectively. Medication adherence was significantly improved (p<0.001) in the PC group (88.6%) when compared to the UC group (77.9%, 95% CI 88.9%-91.9%). CONCLUSION: Pharmacist-led clinical pharmacy interventions as part of multidisciplinary care had a significant impact on improving cure rates, HRQoL, and medication adherence for hepatitis C patients. This study suggests that clinical pharmacists should be incorporated into the multidisciplinary health-care team for care of hepatitis C patients.

Do patients actually do what we ask: patient fidelity and persistence to the Targets and Self-Management for the Control of Blood Pressure in Stroke and at Risk Groups blood pressure self-management intervention.

OBJECTIVE: Self-management of hypertension can reduce and control blood pressure (BP) compared with clinic monitoring. However, self-management relies on patients following an algorithm, which may be variably adhered to. This study reports fidelity of high-risk patients to the self-management algorithm set by the TASMIN-SR trial. METHODS: Patients with hypertension, above target clinic BP and one or more of stroke, diabetes, coronary heart disease or chronic kidney disease, were invited to self-monitor following an individualized self-titration algorithm. Home BP readings and medication change details were submitted monthly for 12 months. Readings downloaded from patients' electronic monitors were compared with written submissions, and protocol fidelity was assessed. RESULTS: Two hundred and seventy-six patients were randomized to self-management and 225 (82%) completed the required training sessions. Of these, 166 (74%) completed self-management. A total of 11385 (89.6%) submitted readings were accurate compared with corresponding downloaded monitor readings. Mean error rate was 5.2% per patient, which increased with age but not comorbidities. Patients made 475 of 683 (69.5%) algorithm-recommended medication changes, equating to nearly three medication changes per patient. Mean SBP for patients who completed training and made all recommended changes dropped from 141 mmHg (95% CI 138.26-144.46) to 121 mmHg (95% CI 118.30-124.17 mmHg) compared with 129 mmHg (95% CI 125.27-136.73 mmHg) for patients who made none. CONCLUSION: Most patients randomized to self-management completed training; however, 36% of these had dropped out by 12 months. Self-monitoring was largely undertaken properly and accurately recorded. Fidelity with self-management was associated with lower achieved SBP. Successful implementation of self-management into daily practice requires careful training and should be accompanied by monitoring of fidelity.

Interarm Difference in Systolic Blood Pressure in Different Ethnic Groups and Relationship to the "White Coat Effect": A Cross-Sectional Study.

BACKGROUND: Interarm differences (IADs) ≥10 mm Hg in systolic blood pressure (BP) are associated with greater incidence of cardiovascular disease. The effect of ethnicity and the white coat effect (WCE) on significant systolic IADs (ssIADs) are not well understood. METHODS: Differences in BP by ethnicity for different methods of BP measurement were examined in 770 people (300 White British, 241 South Asian, 229 African-Caribbean). Repeated clinic measurements were obtained simultaneously in the right and left arm using 2 BPTru monitors and comparisons made between the first reading, mean of second and third and mean of second to sixth readings for patients with, and without known hypertension. All patients had ambulatory BP monitoring (ABPM). WCE was defined as systolic clinic BP ≥10 mm Hg higher than daytime ABPM. RESULTS: No significant differences were seen in the prevalence of ssIAD between ethnicities whichever combinations of BP measurement were used and regardless of hypertensive status. ssIADs fell between the 1st measurement (161, 22%), 2nd/3rd (113, 16%), and 2nd-6th (78, 11%) (1st vs. 2nd/3rd and 2nd-6th, P < 0.001). Hypertensives with a WCE were more likely to have ssIADs on 1st, (odds ratio [OR] 1.73 (95% confidence interval 1.04-2.86); 2nd/3rd, (OR 3.05 (1.68-5.53); and 2nd-6th measurements, (OR 2.58 (1.22-5.44). Nonhypertensive participants with a WCE were more likely to have a ssIAD on their first measurement (OR 3.82 (1.77 to -8.25) only. CONCLUSIONS: ssIAD prevalence does not vary with ethnicity regardless of hypertensive status but is affected by the number of readings, suggesting the influence of WCE. Multiple readings should be used to confirm ssIADs.

The Effectiveness of Conservative Management for Acute Whiplash Associated Disorder (WAD) II: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: To evaluate the effectiveness of conservative management (except drug therapy) for acute Whiplash Associated Disorder (WAD) II. DESIGN: Systematic review and meta-analysis of Randomised Controlled Trials (RCTs) using a pre-defined protocol. Two independent reviewers searched information sources, decided eligibility of studies, and assessed risk of bias (RoB) of included trials. Data were extracted by one reviewer and checked by the other. A third reviewer mediated any disagreements throughout. Qualitative trial and RoB data were summarised descriptively. Quantitative syntheses were conducted across trials for comparable interventions, outcome measures and assessment points. Meta-analyses compared effect sizes with random effects, using STATA version 12. DATA SOURCES: PEDro, Medline, Embase, AMED, CINAHL, PsycINFO, and Cochrane Library with manual searching in key journals, reference lists, British National Bibliography for Report Literature, Center for International Rehabilitation Research Information & Exchange, and National Technical Information Service were searched from inception to 15th April 2015. Active researchers in the field were contacted to determine relevant studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCTs evaluating acute (<4 weeks) WADII, any conservative intervention, with outcome measures important to the International Classification of Function, Disability and Health. RESULTS: Fifteen RCTs all assessed as high RoB (n=1676 participants) across 9 countries were included. Meta-analyses enabled 4 intervention comparisons: conservative versus standard/control, active versus passive, behavioural versus standard/control, and early versus late. Conservative intervention was more effective for pain reduction at 6 months (95%CI: -20.14 to -3.38) and 1-3 years (-25.44 to -3.19), and improvement in cervical mobility in the horizontal plane at <3 months (0.43 to 5.60) compared with standard/control intervention. Active intervention was effective for pain alleviation at 6 months (-17.19 to -3.23) and 1-3 years (-26.39 to -10.08) compared with passive intervention. Behavioural intervention was more effective than standard/control intervention for pain reduction at 6 months (-15.37 to -1.55), and improvement in cervical movement in the coronal (0.93 to 4.38) and horizontal planes at 3-6 months (0.43 to 5.46). For early (<4 days) versus late (>10 days) interventions, there were no statistically significant differences in all outcome measures between interventions at any time. CONCLUSIONS: Conservative and active interventions may be useful for pain reduction in patients with acute WADII. Additionally, cervical horizontal mobility could be improved by conservative intervention. The employment of a behavioural intervention (e.g. act-as-usual, education and self-care including regularly exercise) could have benefits for pain reduction and improvement in cervical movement in the coronal and horizontal planes. The evidence was evaluated as low/very low level according to the Grading of Recommendations Assessment, Development and Evaluation system.

Social network support for individuals receiving opiate substitution treatment and its association with treatment progress.

BACKGROUND/AIMS: Social networks have been hypothesized to protect people from the harmful effects of stress, but may also provide dysfunctional role models and provide cues associated with drug use. This study describes the range, type and level of social support available to patients engaged in UK opiate substitution treatment (OST) programmes, and explores the association between network factors and continued use of illicit heroin. METHODS: A cross-sectional survey of a randomly selected sample of OST patients (n = 118) utilised measures of current substance use and social network structure and support. RESULTS: More than half of the participants had used heroin in the previous month, and most described networks that were both supportive and positive about treatment. Multivariate analysis showed that the substance use involvement of network members was higher in those patients still using heroin, even when other treatment factors were controlled for. CONCLUSION: There was a strong association between ongoing contact with other drug users and continued use of illicit heroin in this treatment sample. Whilst there is potential for the involvement of social networks in treatment, future research needs to ascertain the exact nature of the relationship between social support and drug use.

The relationship between serum TSH and free T4 in older people.

The frequency distribution of serum thyroid stimulating hormone (TSH) shows a skewed pattern that may change with age. The set point of the hypothalamic-pituitary-thyroid axis for an individual is thought to be genetically determined and has been described as a log-linear relationship of serum TSH to free thyroxine (T4); however, the validity of this hypothesis has yet to be established in older people. The aim of the study was to describe the relationship between serum TSH and free T4 in older people and define factors influencing this relationship. We conducted a cross-sectional, observational study of thyroid function in a community population of older subjects over 65 years of age. The relationship between serum TSH and free T4 was not linear as previously described, but is best described as a fourth-order polynomial. Both gender and smoking status affected the relationship. This suggests that more complex modelling is required when investigating the hypothalamic-pituitary-thyroid axis.

The relationship between serum TSH and free T4 in older people.

The frequency distribution of serum thyroid stimulating hormone (TSH) shows a skewed pattern that may change with age. The set point of the hypothalamic-pituitary-thyroid axis for an individual is thought to be genetically determined and has been described as a log-linear relationship of serum TSH to free thyroxine (T4); however, the validity of this hypothesis has yet to be established in older people. The aim of the study was to describe the relationship between serum TSH and free T4 in older people and define factors influencing this relationship. We conducted a cross-sectional, observational study of thyroid function in a community population of older subjects over 65 years of age. The relationship between serum TSH and free T4 was not linear as previously described, but is best described as a fourth-order polynomial. Both gender and smoking status affected the relationship. This suggests that more complex modelling is required when investigating the hypothalamic-pituitary-thyroid axis.

Rural Kenyan men's awareness of danger signs of obstetric complications.

BACKGROUND: For many women in Kenya, their husbands act as gate-keepers to access of healthcare services. Awareness of the danger signs of obstetric complications is the essential first step in accepting appropriate and timely referral to obstetric care. The objectives of this study were to assess men's awareness of the danger signs of obstetric complications, and to identify any associated demographic factors. METHODS: A cross-sectional study using a non-validated questionnaire was completed by 167 men with a wife or partner that had been pregnant in the last 36 months. The study took place in Muhoroni, in the Nyanza province of Kenya. Statistical comparisons were done using Kruskal-Wallis, Mann-Whitney and the Spearman's correlation coefficient. RESULTS: Men displayed good knowledge of the danger signs of obstetric complications (median, 9/10; range 0-10; IQR, 7-10), with 92.2% (n=154) of participants recognizing severe abdominal pain, 91.6% (n=153) recognizing absence of foetal movement, and 90.4% (n=151) recognizing long labour as obstetric danger signs. More educated participants were significantly more knowledgeable than less educated participants (Kruskal-Wallis H=14.47; df=3; p=0.002). CONCLUSION: Participants were very proficient in identifying the danger signs of obstetric complications, with better knowledge in more educated men. Maternal mortality across Kenya remains high, however, so assessing knowledge nationally, and researching whether men are translating this knowledge into action would be recommended.

No association between neuregulin 1 and psychotic symptoms in Alzheimer's disease patients.

Alzheimer's disease (AD) patients commonly suffer from behavioral and psychological symptoms of dementia (BPSD). Variants within the neuregulin-1 (NRG1) gene have been investigated both in early onset psychiatric disorders, such as schizophrenia and recently in AD patients with psychosis. In this study, we analyzed NRG1 variants in AD patients with and without psychosis. Our large cohort of 399 probable AD patients had longitudinal information on the BPSD, which was used to dichotomize patients into whether they had ever suffered from psychotic symptoms within the study period. The NRG1 single nucleotide polymorphisms rs3924999, rs35753505 (SNP8NRG221533) and the microsatellites 478B14-848 and 420M9-1395 were investigated for association with psychosis using genotype, allele, and haplotype analyses. No associations were found between any of these variants or haplotypic combinations with delusions, hallucinations, psychosis, or elation/mania in our cohort. Positive associations with polymorphisms and haplotype combinations of NRG1 have been reported in psychiatric disorders. One previous study found an association with psychosis in AD, with a SNP outside the haplotype block first reported for association with schizophrenia. We found no association with any of these variants in our cohort. Further investigations of this region on chromosome 8 are clearly required, with replication in different large longitudinal cohorts.

A longitudinal study of hypomania and depression symptoms in pregnancy and the postpartum period.

OBJECTIVES: Childbirth is a potent precipitant of severe episodes of bipolar disorder. We investigate mood longitudinally through pregnancy and the postpartum period, using the Highs Scale and the Edinburgh Postnatal Depression Scale (EPDS), to examine if the postpartum period is a time of increased risk for hypomanic symptoms in the general population. METHODS: A total of 446 women were recruited at 12 weeks of pregnancy from the Birmingham Women's Hospital and four midwife-led community clinics. Women completed the Highs Scale and the Edinburgh Postnatal Depression Scale at 12 weeks of pregnancy, one week postpartum, and eight weeks postpartum. RESULTS: Cases of probable depression, as defined by an EPDS score of 13 or greater, did not significantly increase from pregnancy to the postpartum period. The prevalence of 'the highs' was eightfold higher in the postpartum week than during pregnancy. CONCLUSIONS: Consistent with the increased rates of severe manic illness following childbirth, we find that more minor hypomanic states are also increased. We consider the clinical relevance of postpartum hypomanic symptoms and the implications of these findings for research into postpartum-onset mood symptoms.

Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts.

The impact of disease recurrence on graft survival following liver transplantation: a single centre experience.

Many diseases that cause liver failure may recur after transplantation. A retrospective analysis of the rate and cause of graft loss of 1840 consecutive adults receiving a primary liver transplant between 1982 and 2004 was performed to evaluate the rate of graft loss from disease recurrence. The risk of graft loss from recurrent disease was greatest, when compared to primary biliary cirrhosis (PBC), in those transplanted for hepatitis C virus (HCV) [hazard ratio (HR) 11.6; 95% confidence interval (CI) 5.1-26.6], primary sclerosing cholangitis (PSC) (HR 6.0; 95% CI 2.5-14.2) and autoimmune hepatitis (AIH) (HR 4.1; 95% CI 1.3-12.6). The overall risk of graft loss was also significantly greater in HCV (HR 2.1 vs. PBC; 95% CI 1.5-3.0), PSC (HR 1.6 vs. PBC; 95% CI 1.2-2.3) and AIH (HR 1.6; 95% CI 1.0-2.4) than in PBC. There was no statistically significant difference in the risk of graft loss because of recurrent disease, when compared with PBC, for patients transplanted for alcohol related liver disease, nonalcoholic steatohepatitis and fulminant hepatic failure. Disease recurrence is a significant cause of graft loss particularly in HCV, PSC and AIH. Recurrent disease, in part, explains the increased overall risk of graft loss in these groups.

Role of 5HT 2A and 5HT 2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) patients suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. Polymorphisms within serotonin receptors 5HT(2A) and 5HT(2C) have been previously investigated in a few interesting studies reviewed here, however, their role remains unclear. METHODS: Our large cohort of 394 patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period and give each patient a severity score. These measures were related to the 5HT(2A) T102C and 5HT(2C) cys23ser genotype and allele frequencies. RESULTS: Our data supports previous reports of an increased frequency of the C allele and CC genotype of the T102C variant of 5HT(2A) with hallucinations, delusions, psychosis and aberrant motor behaviour, however, we dispute previous associations with depression and aggression. We describe for the first time an increase in the C allele and CC genotype frequencies of the cys23ser variant of 5HT(2C) with anxiety and support previous associations with appetite disturbances in females. CONCLUSION: This review and extension of previous data presents support for the role of 5HT(2A) and 5HT(2C) in the development of certain symptoms, although the effect size may be small.

Clinical presentation of postnatal and non-postnatal depressive episodes.

BACKGROUND: The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. METHOD: In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. RESULTS: The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. CONCLUSIONS: The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.

A comparative cross-sectional questionnaire survey of the work of UK and US mental health nurses.

BACKGROUND: Comparative inter-country research which identifies similarities and differences in the work of mental health nurses in different social and political contexts is an important means of determining how changes in health care systems could lead to better outcomes for patients. OBJECTIVE: This study sought to compare aspects of the work of nurses in US and UK mental health care settings. Nurses were invited to reflect on aspects of their role including identifying the most and least satisfying elements of their work and suggesting ways in which it could be improved. METHODS AND PARTICIPANTS: A 12-item questionnaire, comprising closed and open-ended questions, based on the literature and the authors' own experiences of mental health nursing practice, was piloted and subsequently distributed to respondents in both countries. RESULTS: The US nurses tended to be more willing to accept a wider range of clients than their UK counterparts, although they had lower expectations of their clients' likelihood of recovery. Both groups of nurses felt that being part of a team and having direct contact with clients were the most satisfying aspects of their work, while administration was the least. Although both US and UK nurses utilised a variety of intervention models, it would appear that Cognitive Behavioural Therapy was the favoured model for the majority of nurses. CONCLUSIONS: The implications of these findings for the work of nurses and mental health care services in the UK and US, and the purpose, nature and need for future international comparative research are discussed.