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Purpose: Upper gastrointestinal (GI) cancers contribute to 16.7% of UK cancer deaths. These patients make high use of acute hospital services, but detail about palliative care use is lacking. We aimed to determine the patterns of use of acute hospital and hospital specialist palliative care services in patients with advanced non-curative upper GI cancer. Methods: We conducted a service evaluation of hospital use and palliative care for all patients with non-curative upper GI cancer seen in one large hospital, using routinely collected data (2019–2022). We report and characterise hospital admissions and palliative care within the study time period, using descriptive statistics, and multivariable Poisson regression to estimate the unadjusted and adjusted incidence rate ratio of hospital admissions. Results: The total with non-curative upper GI cancer was 960. 86.7% had at least one hospital admission, with 1239 admissions in total. Patients had a higher risk of admission to hospital if: aged ≤ 65 (IRR for 66–75 years 0.71, IRR 76–85 years 0.68; IRR > 85 years 0.53; p < 0.05), or lived in an area of lower socioeconomic status (IMD Deciles 1–5) (IRR 0.90; p < 0.05). Over the 4-year period, the rate of re-admission was higher in patients not referred to palliative care (rate 0.52 readmissions/patient versus rate 1.47 readmissions/patient). Conclusion: People with advanced non-curative gastrointestinal cancer have frequent hospital admissions, especially if younger or from areas of lower socioeconomic status. There is clear association between specialist palliative care referral and reduced risk of hospitalisation. This evidence supports referral to specialist palliative care. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to evaluate the methodological quality of rigorous neuropathic pain assessment tools in applicable clinical studies, and determine the performance of screening tools for identifying neuropathic pain in patients with cancer.Methods: Systematic literature search identified studies reporting use of Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Douleur Neuropathique en 4 (DN4) or painDETECT (PDQ) in cancer patients with a clinical diagnosis of neuropathic or not neuropathic pain. Individual patient data were requested to examine descriptor item profiles.Results: Six studies recruited a total of 2301 cancer patients of which 1564 (68%) reported pain. Overall accuracy of screening tools ranged from 73 to 94%. There was variation in description and rigour of clinical assessment, particularly related to the rigour of clinical judgement of pain as the reference standard. Individual data from 1351 patients showed large variation in the selection of neuropathic pain descriptor items by cancer patients with neuropathic pain. LANSS and DN4 items characterized a significantly different neuropathic pain symptom profile from non-neuropathic pain in both tumour- and treatment-related cancer pain aetiologies.Conclusions: We identified concordance between the clinician diagnosis and screening tool outcomes for LANSS, DN4 and PDQ in patients with cancer pain. Shortcomings in relation to standardized clinician assessment are likely to account for variation in screening tool sensitivity, which should include the use of the neuropathic pain grading system. Further research is needed to standardize and improve clinical assessment in patients with cancer pain. Until the standardization of clinical diagnosis for neuropathic cancer pain has been validated, screening tools offer a practical approach to identify potential cases of neuropathic cancer pain. [ABSTRACT FROM AUTHOR]

Objective: Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA(1c) measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring.Research Design and Methods: A total of 56 children with type 1 diabetes (age 2-18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified.Results: Despite satisfactory HbA(1c) levels (7.7 +/- 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were >180 mg/dl (above target), and almost 50% were >300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose <60 mg/dl) in almost 70% of the children.Conclusions: Despite excellent HbA(1c) levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: It is recommended that patients with multiple myeloma should be assessed for unmet holistic needs at key times in their disease trajectory. The aim of this exploratory study was to characterise the holistic needs of advanced, intensively treated multiple myeloma using a structured assessment tool. Methods: Patients with multiple myeloma who had undergone a haematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease but were in stable plateau phase were included in the study. Patients' holistic needs were assessed using the self-reporting tool, Sheffield Profile for Assessment and Referral for Care (SPARC). Results: Thirty-two patients with a median age of 60 years at assessment and a median of 5.5 years from diagnosis were recruited. Using the SPARC, half of the patients reported tiredness as 'quite a bit/very much,' while one third complained that daytime somnolence and insomnia were 'quite a bit/very much.' Forty-four percent of patients reported pain. One third of patients were bothered and distressed by the side effects from their treatment and were worried about long-term effects of their treatment. Thirty-one percent of patients felt that the effect of their condition had an impact on their sexual life, and 40 % were worried about the effect that their illness was having on their family or other people. Conclusion: This is the first study to use a self-reported holistic needs assessment tool in multiple myeloma. A multidimensional structured questionnaire like the SPARC could provide a useful first step in the effective delivery of supportive and palliative care for patients with multiple myeloma. [ABSTRACT FROM AUTHOR]

Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duration of 6 years from diagnosis and three lines of intensive treatment, including at least one haematopoietic SCT procedure. All patients were off active treatment. There was a high prevalence of endocrine dysfunction: hypothyroidism (9%), hypogonadism (65% males) and elevated prolactin (19%). Adrenocortical function was preserved despite large cumulative corticosteroid pretreatment. Biochemical markers were consistent with postmenopausal status in all females and infertility in males. Nutritionally, 59% were vitamin D insufficient/deficient, reduced serum folate in 25% and vitamin B12 in 6%. Total body DEXA scanning confirmed 'sarcopenic-obesity' in 65%, but reduced bone density was seen in a minority. We conclude that potentially correctable endocrine, metabolic and nutritional abnormalities are prevalent in heavily-treated patients with stable multiple myeloma. Preservation of bone supports the efficacy of bisphosphonate treatment from diagnosis, but sarcopenic-obesity may contribute to frailty. Ultimately, multi-system screening and appropriate interventions may optimise quality of long-term survival and further studies are warranted. [ABSTRACT FROM AUTHOR]

Objective: To assess the concurrent validity of three screening tests for focal cognitive impairments after stroke.Design: Comparison of results from the screening tests with those from a more comprehensive neuropsychological battery.Setting: Stroke rehabilitation wards of a general hospital and a rehabilitation hospital.Subjects: Forty-nine stroke patients (25-91 years, 35% women).Measures: Screening tests were the Cognistat, the Screening Instrument for Neuropsychological Impairments in Stroke (SINS) and the Clock Drawing Test. Health professionals, blind to the results of the reference method, did the screening. Reference method was a neuropsychological assessment based on the Norwegian Basic Neuropsychological Assessment, classifying the patients as ;impaired' or ;not impaired' within the following cognitive domains: language, visuospatial function, attention and neglect, apraxia, speed in unaffected arm, and memory.Results: The best sensitivity (95% confidence interval) was achieved for language problems by Cognistat, naming (80%, 44-98); for visuospatial dysfunction, attention deficits and reduced speed, all by SINS visuocognitive (82%, 60-95, 72%, 39-94, and 78%, 56-93, respectively); and for memory problems by Cognistat memory (69%, 52-87). The data were insufficient to assess any subtest for apraxia. Sensitivity in detecting deficits in any domain was 82% (71-94) for the Cognistat composite score, 71% (57-85) for the SINS composite score, and 63% (49-78) for the most sensitive score of the Clock Drawing Test.Conclusion: The Cognistat and the SINS may be used as screening instruments for cognitive deficits after stroke, but cannot replace a neuropsychological assessment. The Clock Drawing Test added little to the detection of cognitive deficits. [ABSTRACT FROM AUTHOR]

We report fluorescence in situ hybridization (FISH) mapping of 152, mostly de novo, apparently balanced chromosomal rearrangement (ABCR) breakpoints in 76 individuals, 30 of whom had no obvious phenotypic abnormality (control group) and 46 of whom had an associated disease (case group). The aim of this study was to identify breakpoint characteristics that could discriminate between these groups and which might be of predictive value in de novo ABCR (DN-ABCR) cases detected antenatally. We found no difference in the proportion of breakpoints that interrupted a gene, although in three cases, direct interruption or deletion of known autosomal-dominant or X-linked recessive Mendelian disease genes was diagnostic. The only significant predictor of phenotypic abnormality in the group as a whole was the localization of one or both breakpoints to an R-positive (G-negative) band with estimated predictive values of 0.69 (95% CL 0.54-0.81) and 0.90 (95% CL 0.60-0.98), respectively. R-positive bands are known to contain more genes and have a higher guanine-cytosine (GC) content than do G-positive (R-negative) bands; however, whether a gene was interrupted by the breakpoint or the GC content in the 200kB around the breakpoint had no discriminant ability. Our results suggest that the large-scale genomic context of the breakpoint has prognostic utility and that the pathological mechanism of mapping to an R-band cannot be accounted for by direct gene inactivation. [ABSTRACT FROM AUTHOR]

A correction to the article "Endocrine, metabolic, nutritional and body composition abnormalities are common in advanced intensively-treated (transplanted) multiple myeloma" that was published in the 2014 issue is presented.

A correction to the article "FISH Mapping of De Novo Apparently Balanced Chromosome Rearrangements Identifies Characteristics Associated with Phenotypic Abnormality" that was published in April 2008 issue is presented.

Abstract: This study was conducted to examine pregnancy progression and fetal characteristics following transfer of vitrified bovine nuclear transfer versus in vivo-derived embryos. Nuclear transfer (NT) was conducted using cumulus cells collected from an elite Holstein–Friesian dairy cow. Expanding and hatching blastocysts on Day 7 were vitrified using liquid nitrogen surface vitrification. Day 7 in vivo embryos, produced using standard superovulation procedures applied to Holstein–Friesian heifers (n =6), were vitrified in the same way. Following warming, embryos were transferred to synchronized recipients (NT: n =65 recipients; Vivo: n =20 recipients). Pregnancies were monitored by ultrasound scanning on Days 25, 45 and 75 and a sample of animals were slaughtered at each time point to recover the fetus/placenta for further analyses. Significantly more animals remained pregnant after transfer of in vivo-derived embryos than NT embryos at all time points: Day 25 (95.0 versus 67.7%, P <0.05), Day 45 (92.8 versus 49.1%, P <0.01) and Day 75 (70.0 versus 20.8%, P <0.0). There was no significant difference (P =0.10) in the weight of the conceptus on Day 25 from NT transfers (1.14±0.23g, n =8) versus in vivo transfers (0.75±0.19g, n =8). On Day 45, there was no significant difference in the weight of either fetus (P =0.393) or membranes (P =0.167) between NT embryos (fetus: 2.76±0.40, n =12; membranes: 59.0±10.0, n =11) or in vivo-derived embryos (fetus: 2.60±0.15, n =6; membranes: 41.8±5.2, n =4). However, on Day 75 the weight of the fetus and several of the major organs were heavier from NT embryos. These data suggest that morphological abnormalities involving the fetus and the placenta of cloned pregnancies are manifested after Day 45. [Copyright &y& Elsevier]

AbstractWhile treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas. Diabet. Med. 18,... [ABSTRACT FROM AUTHOR]

Abstract: Cloned animals often suffer from loss of development to term and abnormalities, typically classified under the umbrella term of Large Offspring Syndrome (LOS). Cattle are an interesting species to study because of the relatively greater success rate of nuclear transfer in this species compared with all species cloned to date. The imprinted insulin-like growth factor receptor (IGF2R; mannose-6-phosphate) gene was chosen to investigate aspects of fetal growth and development in cloned cattle in the present study. IGF2R gene expression patterns in identical genetic clones of several age groups were assessed in day 25, day 45, and day 75 fetuses as well as spontaneously aborted fetuses, calves that died shortly after birth and healthy cloned calves using single stranded conformational polymorphism gel electrophoresis. A variable pattern of IGF2R allelic expression in major organs such as the brain, cotyledon, heart, liver, lung, spleen, kidney and intercotyledon was observed using a G/A transition in the 3’UTR of IGF2R. IGF2R gene expression was also assessed by real time RT-PCR and found to be highly variable among the clone groups. Proper IGF2R gene expression is necessary for survival to term, but is most likely not a cause of early fetal lethality or an indicator of postnatal fitness. Contrary to previous reports of the transmission of imprinting patterns from somatic donor cells to cloned animals within organs in the same cloned animal the paternal allele of IGF2R can be imprinted in one tissue while the maternal allele is imprinted in another tissue. This observation has never been reported in any species in which imprinting has been studied. [Copyright &y& Elsevier]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). Hypothesis: The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. Animals: Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. Methods: The study was randomized, blinded, and placebo controlled with parallel groups (days 21–42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3–5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. Results: For CSOM activity, there was a significant time by treatment effect ( P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 ( P=.030), with the amantadine group being more active. Conclusions and Clinical Importance: In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain. [ABSTRACT FROM AUTHOR]

The current method of choice for astronauts to treat space motion sickness is an intra-muscular injection of promethazine hydrochloride (PMZ HCl) which is invasive and causes considerable local irritation and discomfort at the site of injection. Intra-nasal delivery is considered a feasible alternative route for administration of medications to treat space motion sickness. The purpose of this research is to develop a PMZ HCl formulation that can be administered intra-nasally without irritation (i.e. leukocyte infiltration) in the nasal epithelium when dosed at PMZ HCl concentrations greater than the cytotoxic limit. The biocompatibility of PMZ HCl was tested in vitro and was shown to be cytotoxic at concentrations greater than 10-5 molar regardless of pH. A controlled-release microencapsulated dosage formulation was developed using spinning disk atomization and release rates for the PMZ HCl microcapsules were determined in phosphate buffered saline. An animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated and non-encapsulated PMZ HCl. [ABSTRACT FROM AUTHOR]

Use of microencapsulation technology in combination with absorption enhancers eliminated epithelium irritation and necrosis commonly associated with nasal delivery of cytotoxic therapeutic agents. Phenothiazines, such as ethopropazine (ETZ), promethazine, trimeprazine and propiomazine have been used for the treatment of allergenic conditions, motion sickness, nausea, Parkinson's disease, Prion disease and as a sedative for psychiatric disorders. The enantiomers of commercially available racemic phenothiazines were isolated and purified using classical diastereomeric salt techniques. The racemate and the enantiomers of ETZ were tested in vitro for their cellular toxicity using lung fibroblast cells. Each enantiomer was shown to be cytotoxic at concentrations greater than 10 -5 molar. The ETZ enantiomers were encapsulated using spinning disk atomization to prepare a nasal delivery dosage form that does not produce an irritation response. Release rates for the ETZ microcapsules were determined in vitro and an animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated vs. non-encapsulated ETZ. [ABSTRACT FROM AUTHOR]

Introduction Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Some have questioned whether these medications are equally effective in older adults. Objectives To compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, venlafaxine, vilazodone, and vortioxetine for the treatment of MDD in older adults and to assess whether efficacy differed in older adults compared with the adults of all ages. Methods To identify relevant studies, we searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and CINAHL through December, 2014. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. We conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants and we conducted meta-regression by assessing whether efficacy differed in trials that enrolled older adults compared with trials that enrolled adults of any age. The outcome was treatment response as measured by ≥50% improvement from baseline on the HAM-D. Results Evidence on older adults compared with adults of any age is sparse. In older adults, evidence indicates that efficacy does not differ substantially among second-generation antidepressants; however, there may be some differences in adverse events. Our meta-regression found a trend toward lesser efficacy of SGAs in older adults than adults of any age. Conclusions Our findings suggests that SGAs may be less effective in older populations. There is a great need for research focusing directly on the efficacy and safety of SGAs in older adults. [ABSTRACT FROM AUTHOR]