[Study Protocol] Palliative long-term abdominal drains versus repeated drainage in individuals with untreatable ascites due to advanced cirrhosis: study protocol for a feasibility randomised controlled trial

Background: UK deaths due to chronic liver diseases such as cirrhosis have quadrupled over the last 40 years, making this condition now the third most common cause of premature death. Most patients with advanced cirrhosis (end–stage liver disease, [ESLD]) develop ascites. This is often managed with diuretics, but if refractory then the fluid is drained from the peritoneal cavity every 10-14 days by large volume paracentesis (LVP), a procedure requiring hospital admissions. As the life expectancy of patients with ESLD and refractory ascites (if ineligible for liver transplantation) is on average ≤ 6 months, frequent hospital visits are inappropriate from a palliative perspective. One alternative is long-term abdominal drains (LTAD), used successfully in patients whose ascites is due to malignancy. Although inserted in hospital, these drains allow ascites management outside of a hospital setting. LTAD have not been formally evaluated in patients with refractory ascites due to ESLD. Methods: Due to uncertainty about appropriate outcome measures and whether patients with ESLD would wish or be able to participate in a study, a feasibility randomised controlled trial (RCT) was designed. Patients were consulted on trial design. We plan to recruit 48 patients with refractory ascites and randomise them (1:1) to either a) LTAD or b) current standard of care (LVP) for 12 weeks. Outcomes of interest include acceptability of LTAD to patients, carers and healthcare professionals as well as recruitment and retention rates. Palliative care Outcome Scale (IPOS), the Short Form Liver Disease Quality of Life (SF-LDQOL), the EuroQol (EQ-5D) and carer (Zarit Burden Interview [ZBI-12]) reported outcomes will also be assessed. Preliminary data on cost effectiveness will be collected and patients and healthcare professionals will be interviewed about their experience of the trial with a view to identifying barriers to recruitment. Discussion: LTAD could potentially improve end-of-life care in patients with refractory ascites due to ESLD by improving symptom control, reducing hospital visits and enabling some self-management. Our trial is designed to see if such patients can be recruited, as well as informing the design of a subsequent definitive trial. Trial registration: ISRCTN30697116, date assigned: 07/10/201

Effectiveness of psychoeducational interventions for family carers of people

Psychoeducational interventions for family carers of people with psychosis are effective for improving compliance and preventing relapse. Whether carers benefit from these interventions has been little explored. This systematic review investigated the effectiveness of psychoeducation for improving carers' outcomes, and potential treatment moderators. We searched for randomised controlled trials (RCTs) published in English or Chinese in eight databases. Carers' outcomes included wellbeing, quality of life, global morbidities, burden, and expressed emotion. Thirty-two RCTs were included, examining 2858 carers. Intervention duration ranged from 4 to 52 weeks, and contact times ranged from 6 to 42 hours. At post intervention, findings were equivocal for carers' wellbeing (SMD 0.103, 95% CI − 0.186 to 0.392). Conversely, psychoeducation was superior in reducing carers' global morbidities (SMD − 0.230, 95% CI − 0.386 to − 0.075), perceived burden (SMD − 0.434, 95% CI − 0.567 to − 0.31), negative caregiving experiences (SMD − 0.210, 95% CI − 0.396 to − 0.025) and expressed emotion (SMD − 0.161, 95% CI − 0.367 to − 0.045). The lack of available data precluded meta-analysis of outcomes beyond short-term follow-up. Meta-regression revealed no significant associations between intervention modality, duration, or contact time and outcomes. Further research should focus on improving carers' outcomes in the longer-term and identifying factors to optimise intervention design

Effectiveness of psychoeducational interventions for family carers of people with psychosis: A systematic review and meta-analysis.

Psychoeducational interventions for family carers of people with psychosis are effective for improving compliance and preventing relapse. Whether carers benefit from these interventions has been little explored. This systematic review investigated the effectiveness of psychoeducation for improving carers' outcomes, and potential treatment moderators. We searched for randomised controlled trials (RCTs) published in English or Chinese in eight databases. Carers' outcomes included wellbeing, quality of life, global morbidities, burden, and expressed emotion. Thirty-two RCTs were included, examining 2858 carers. Intervention duration ranged from 4 to 52weeks, and contact times ranged from 6 to 42hours. At post intervention, findings were equivocal for carers' wellbeing (SMD 0.103, 95% CI -0.186 to 0.392). Conversely, psychoeducation was superior in reducing carers' global morbidities (SMD -0.230, 95% CI -0.386 to -0.075), perceived burden (SMD -0.434, 95% CI -0.567 to -0.31), negative caregiving experiences (SMD -0.210, 95% CI -0.396 to -0.025) and expressed emotion (SMD -0.161, 95% CI -0.367 to -0.045). The lack of available data precluded meta-analysis of outcomes beyond short-term follow-up. Meta-regression revealed no significant associations between intervention modality, duration, or contact time and outcomes. Further research should focus on improving carers' outcomes in the longer-term and identifying factors to optimise intervention design

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Caves and karst of the Chalk in East Sussex, UK: implications for groundwater management

The Upper Cretaceous Chalk of East Sussex is well exposed on the coastal cliff sections between Brighton and Eastbourne. Previous work by Terry Reeve and members of the Chelsea Spelaeological Society identified several caves along the Sussex coast, highlighting the presence of karst. Other evidence of karst comes from active conduits intersected in boreholes and in adits dug for groundwater abstraction, dissolution pipes and cavities encountered in construction projects, and dolines observed on remote sensing data. To understand the extent of cave and conduit development in the Chalk, and how they are related to Chalk lithostratigraphy, a review of the evidence for karst in the area was undertaken, coupled with a detailed survey of the coastal section between Seaford and Eastbourne. Over 50 cave and karst features were identified along the coast, the vast majority being associated with key inception horizons in the Chalk, particularly marl seams and sheet flints. Some are developed on vertical fractures. The data are used to develop a conceptual understanding of Chalk karst and examine the implications for groundwater management

Pharmacoeconomic Analysis of 3 Treatment Strategies for Cytomegalovirus Retinitis in Patients with AIDS

A decision-analytical simulation model was constructed to perform a pharmacoeconomic analysis of the following 3 treatment strategies for previously untreated cytomegalovirus (CMV) retinitis in patients with AIDS: (i) intravenous foscarnet (IVF) for induction and maintenance therapy; (ii) intravenous ganciclovir (IVG) for induction and maintenance therapy; and (iii) intravenous ganciclovir for induction therapy, followed by oral ganciclovir for maintenance therapy (IVG-ORG). Patients who experienced significant adverse effects during, or who failed, initial therapy were switched once to one of the other 2 treatments. The model was used to estimate the direct medical cost (from the perspective of a public payer), survival, and survival adjusted for disutility because of lost vision, for each strategy in the first year following treatment initiation. The expected first-year costs of treatment initiated with IVF, IVG and IVG-ORG were $US47 918,$US38 817 and $US32 036 (1994 values), respectively, while expected first-year survival was 41 weeks, 35 weeks and 35 weeks, respectively. The incremental cost per incremental year of survival using IVF was$US78 000 versus IVG and $US138 000 versus IVG-ORG before adjustment for lost vision, and$US93 000 versus IVG and $US166 000 versus IVG-ORG after adjustment for lost vision. About 23% of the cost of the IVG treatment strategy was attributable to treatment-related adverse events, compared with 14% of the cost of IVF and 16% of the cost of IVG-ORG. Because of the high failure rate with IVG-ORG, initial treatment with IVG-ORG frequently led to switching to another treatment. Only 27% of the costs associated with the IVG-ORG treatment strategy were in fact attributable to the cost of induction and maintenance therapy prior to a switch to alternative treatment. In this analysis, initial treatment with IVG-ORG was the least costly approach for treating CMV retinitis in patients with AIDS. Initial treatment with IVF resulted in slightly longer survival adjusted for vision-related quality of life. New treatments for AIDS may reduce the survival benefit of initial treatment with IVF.Pharmacoeconomics, Cytomegalovirus-infections, Foscarnet, Ganciclovir, Drug-delivery-systems, Intravenous-preparations, Cost-effectiveness, Cost-utility, Quality-adjusted-life-years, Acquired-immunodeficiency-syndrome, Retinitis, Antivirals