Enhancing the experience of carers in the chemotherapy outpatient setting: an exploratory randomised controlled trial to test impact, acceptability and feasibility of a complex intervention co-designed by carers and staff.

PURPOSE: Supporting someone through chemotherapy can be emotionally and physically demanding. However, research has yet to establish the type of support carers require or the best way to provide this. This study tested the feasibility and acceptability of a complex intervention for carers that was co-designed by staff and carers of patients starting chemotherapy. METHODS: Forty-seven carers were recruited, randomised between the intervention (n = 24) and control (n = 23) groups. A questionnaire was completed pre- and post-intervention measuring knowledge of chemotherapy and its side effects, experience of care, satisfaction with outpatient services, coping and emotional wellbeing. The intervention process was evaluated by carers and healthcare professionals (HCPs) in focus groups. RESULTS: Recruitment to the study was unproblematic and attrition from it was low, suggesting the intervention and study processes were acceptable to patients and carers. Carers in receipt of the 'Take Care' intervention reported statistically significantly better understanding of symptoms and side effects and their information needs being more frequently met than carers in the control. Confidence in coping improved between baseline and follow-up for the intervention group and declined for the control although differences were insufficient to achieve statistical significance. There was no significant difference between the two groups' emotional wellbeing. HCP and carer focus groups confirmed the feasibility and acceptability of the intervention. CONCLUSIONS: The 'Take Care' intervention proved acceptable to carers and HCPs and demonstrates considerable promise and utility in practice. Study findings support the conduct of a fully powered RCT to determine the intervention's effectiveness and cost-effectiveness.

Informal carers' experiences and needs when supporting patients through chemotherapy: a mixed method study.

Informal carers provide important emotional support to patients having chemotherapy and assistance in monitoring and managing side-effects. If they are inadequately supported in this, patient and carer morbidity may result. This study explored needs of informal carers supporting patients with cancer having chemotherapy. The study used a mixed methods approach. Carers of colorectal or lymphoma cancer patients at one comprehensive cancer centre participated. Questionnaire data informed semi-structured interviews conducted with a subsample of respondents. Interviews were analysed using Framework analysis. Questionnaire data were analysed descriptively. Fifty-nine informal carers were invited to participate; 48 returned the questionnaire (response rate 81%) and 13 were interviewed. Informal carers' needs for information about chemotherapy and its side-effects were largely met although a third felt completely or somewhat unprepared to deal with particular symptoms experienced by patients at home. Many carers had unmet needs regarding financial support and their own needs as carers. Assertiveness was important to many caring roles, but it appeared difficult for informal carers to adopt when they were unsupported in this and their role was unrecognised by health professionals. Future research should develop interventions to systematically prepare carers for their carer role, improve carer involvement and ultimately improve patient outcomes.

Using the 4-hour Post-ERCP amylase level to predict post-ERCP pancreatitis.

CONTEXT: Post-ERCP pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). A simple method of predicting patients who are at risk of developing post-ERCP pancreatitis is needed to allow those at low risk to be discharged on the same day of their procedure. The aim of this study was to confirm that 4-hour post-ERCP serum amylase level is predictive of post-ERCP pancreatitis. PATIENTS: A study of 886 ERCPs performed at a single centre was conducted. MAIN OUTCOME MEASURE: Four-hour amylase level was recorded, along with patient demographics, procedural details, presence of pancreatogram, and morbidity and mortality. RESULTS: Pancreatitis occurred in 4.4% of ERCPs. Hyperamylasaemia was found to be predictive of post-ERCP pancreatitis, with other risk factors being a younger age and pancreatogram. Hyperamylasaemia was also predictive of post-ERCP pancreatitis in the subgroup of patients who had undergone pancreatogram. CONCLUSIONS: The 4-hour amylase level is a useful measure in the prediction of post-ERCP pancreatitis. Patients who have undergone pancreatogram should be admitted if 4-hour amylase level is greater than 2.5 times the upper limit of reference. Patients who have not undergone pancreatogram should be admitted if 4-hour amylase level is greater than 5 times the upper limit of reference.

The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis.

G-protein-coupled receptors (GPCRs) represent diverse, multifamily groups of cell signaling receptors involved in many cellular processes. We identified Xenopus laevis GPR84 as a member of the A18 subfamily of GPCRs. During development, GPR84 is detected in the embryonic lens placode, differentiating lens fiber cells, retina, and cornea. Anti-sense morpholino oligonucleotide-mediated knockdown and RNA rescue experiments demonstrate GPR84's importance in lens, cornea, and retinal development. Examination of cell proliferation using an antibody against histone H3 S10P reveals significant increases in the lens and retina following GPR84 knockdown. Additionally, there was also an increase in apoptosis in the retina and lens, as revealed by TUNEL assay. Reciprocal transplantation of the presumptive lens ectoderm between uninjected controls and morpholino-injected embryos demonstrates that GPR84 is necessary in the retina for proper development of the retina, as well as other eye tissues including the lens and cornea.

Gene expression profiles of lens regeneration and development in Xenopus laevis.

Seven hundred and thirty-four unique genes were recovered from a cDNA library enriched for genes up-regulated during the process of lens regeneration in the frog Xenopus laevis. The sequences represent transcription factors, proteins involved in RNA synthesis/processing, components of prominent cell signaling pathways, genes involved in protein processing, transport, and degradation (e.g., the ubiquitin/proteasome pathway), matrix metalloproteases (MMPs), as well as many other proteins. The findings implicate specific signal transduction pathways in the process of lens regeneration, including the FGF, TGF-beta, MAPK, Retinoic acid, Wnt, and hedgehog signaling pathways, which are known to play important roles in eye/lens development and regeneration in various systems. In situ hybridization revealed that the majority of genes recovered are expressed during embryogenesis, including in eye tissues. Several novel genes specifically expressed in lenses were identified. The suite of genes was compared to those up-regulated in other regenerating tissues/organisms, and a small degree of overlap was detected.

Role of the serotonergic system in alcohol dependence: from animal models to clinics.

Alcohol dependence remains among the most common substance abuse problems worldwide, and compulsive alcohol consumption is a significant public health concern. Alcohol is an addictive drug that alters brain function through interactions with multiple neurotransmitter systems. These neurotransmitter systems mediate the reinforcing effects of alcohol. Specifically, the serotonergic system is important in mediating alcohol reward, preference, dependence, and craving. In this review chapter, we first discuss the serotonin system as it relates to alcoholism, and then outline interactions between this system and other neurotransmitter systems. We emphasize the serotonin transporter and its possible role in alcoholism, then present several serotonergic receptors and discuss their contribution to alcoholism, and finally assess the serotonin system as a target for pharmacotherapy, with an emphasis on current and potential treatments.

Herpes simplex virus ICP27 induces cytoplasmic accumulation of unspliced polyadenylated alpha-globin pre-mRNA in infected HeLa cells.

Transcripts of most intron-bearing cellular genes must be processed by the splicing machinery in order to efficiently accumulate and gain access to the cytoplasm. However, we found that herpes simplex virus induces cytoplasmic accumulation of both spliced and unspliced polyadenylated alpha-globin RNAs in infected HeLa cells. Accumulation of the unspliced RNA required the immediate-early protein ICP27, and ICP27 was sufficient (in combination with ICP4) to produce this effect in a transient-transfection assay. However, expression of ICP27 did not markedly alter the levels of fully spliced alpha-globin transcripts in infected cells. These data demonstrate that the previously documented effects of ICP27 on the cellular splicing apparatus do not greatly inhibit splicing of alpha-globin RNA and argue that ICP27 induces a splicing-independent pathway for alpha-globin RNA accumulation and nuclear export.

Processing of alpha-globin and ICP0 mRNA in cells infected with herpes simplex virus type 1 ICP27 mutants.

Herpes simplex virus (HSV) ICP27 is an essential and multifunctional regulator of viral gene expression that modulates RNA splicing, polyadenylation, and nuclear export. We have previously reported that ICP27 causes the cytoplasmic accumulation of unspliced alpha-globin pre-mRNA. Here we examined the effects of a series of ICP27 mutations that alter important functional regions of the protein on the processing and nuclear transport of alpha-globin and HSV ICP0 RNA. The results demonstrate that ICP27 mutants that are impaired for growth in noncomplementing cells, including mutants in the N- and C-terminal regions, are defective in the accumulation of alpha-globin pre-mRNA. Unexpectedly, several mutants that are competent to repress the expression of reporter genes in transient transfection assays failed to accumulate unspliced RNA, implying that different mechanisms are responsible for transrepression and pre-mRNA accumulation. Several mutants caused a marked increase in the length and heterogeneity of the alpha-globin mRNA poly(A) tail, suggesting that ICP27 may directly or indirectly affect the regulation of poly(A) polymerase. ICP27 was also required for the accumulation of multiple ICP0 intron-bearing transcripts, but this effect displayed a mutational sensitivity profile different from that of accumulation of unspliced alpha-globin RNA. Moreover, unlike spliced and unspliced alpha-globin RNAs, which were efficiently exported to the cytoplasm, spliced and intron-containing ICP0 transcripts were predominantly nuclear in localization, and ICP27 was not required for nuclear retention of the spliced message. We propose that these transcript- and ICP27 allele-specific differences may be explained by the presence of a strong cis-acting ICP27 response element in the alpha-globin transcript.

Hantavirus pulmonary syndrome in northern Alberta, Canada: clinical and laboratory findings for 19 cases.

We reviewed the clinical and laboratory findings for 19 cases of hantavirus pulmonary syndrome (HPS) identified either serologically or by immunohistochemical testing of archival tissue at our tertiary care center. Fever (95%), cough (89%), and dyspnea (89%) were the most common presenting symptoms. The most prevalent presenting signs were respiratory abnormalities (95%) and tachycardia (84%). Common laboratory findings included thrombocytopenia (95%) and leukocytosis (79%). Elevated aspartate aminotransferase and lactate dehydrogenase levels were found in all patients tested. Intubation was required in 58% of the patients, and inotropic support was required in 53%. Our study confirms that serological responses appear early during clinical illness, making the enzyme immunoassay a useful tool for the diagnosis of acute HPS. The mortality (26%) and severity of disease that we observed among patients with HPS appear to be less than those reported elsewhere.