Primary care usage at the end of life: a retrospective cohort study of cancer patients using linked primary and hospital care data.

PURPOSE: Health service use is most intensive in the final year of a person's life, with 80% of this expenditure occurring in hospital. Close involvement of primary care services has been promoted to enhance quality end-of-life care that is appropriate to the needs of patients. However, the relationship between primary care involvement and patients' use of hospital care is not well described. This study aims to examine primary care use in the last year of life for cancer patients and its relationship to hospital usage. METHODS: Retrospective cohort study in Victoria, Australia, using linked routine care data from primary care, hospital and death certificates. Patients were included who died related to cancer between 2008 and 2017. RESULTS: A total of 758 patients were included, of whom 88% (n = 667) visited primary care during the last 6 months (median 9.1 consultations). In the last month of life, 45% of patients were prescribed opioids, and 3% had imaging requested. Patients who received home visits (13%) or anticipatory medications (15%) had less than half the median bed days in the last 3 months (4 vs 9 days, p < 0.001, 5 vs 10 days, p = 0.001) and 1 month of life (0 vs 2 days, p = 0.002, 0 vs 3 days, p < 0.001), and reduced emergency department presentations (32% vs 46%, p = 0.006, 31% vs 47% p < 0.001) in the final month. CONCLUSION: This study identifies two important primary care processes-home visits and anticipatory medication-associated with reduced hospital usage and intervention at the end of life.

Student veterans' construction and enactment of resilience: A constructivist grounded theory study.

WHAT IS KNOWN ON THE SUBJECT?: Resilience is an ability and a process that allows an individual to develop positive adaptation despite challenges and adversities. Many military veterans returning to college after their military service have difficulty transitioning to civilian life. Although some research exists that explores factors related to the resilience of college student veterans, limited theoretical descriptions exist that explain how student veterans construct resilience, and how resilience is enacted and enhanced in their academic and personal (non-academic) lives. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The resilience of student veterans involves a complex process of transitioning from military to civilian life and an iterative journey between positive adaptation and transient perturbations. Student veterans' resilience is a result of integrating and resolving various aspects of their academic and personal challenges. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses can apply this grounded theory as a practical framework for equipping student veterans with effective strategies to develop and enhance resilience. Nurses can employ a holistic approach of care in their interactions with military veterans and student veterans that includes fostering psychological resilience, helping to manage their multiple non-academic responsibilities and supporting their academic success. ABSTRACT: Introduction Adjusting to college life is one of the most difficult experiences in a military veteran's transition to civilian life. Many military veterans returning to college not only encounter academic challenges, but also deal with physical and psychiatric disabilities, loss of military camaraderie and social disconnect. These often negatively affect their personal and academic lives. Hence, it is important to explore resilience to best support student veterans as they transition from military to civilian life. Aim The aim of this study was to explore how student veterans construct and enact resilience within their personal and academic lives. Method Using constructivist grounded theory methodology, in-depth individual interviews were conducted with 20 military veterans enrolled as undergraduate students at a U.S. university. Results The process of "integrating," which represents student veterans' construction and enactment of resilience, was the core category. This category has three subcategories: (1) the aspects; (2) the expressions; and (3) the enactments of resilience. Implications for practice Nurses can use this grounded theory as the practical framework for their interactions with military veterans, and more particularly with supporting student veterans in their academic lives, in their personal lives and in the transition from military to civilian life.

Six-year follow-up of the SPHERE RCT: secondary prevention of heart disease in general practice.

OBJECTIVE: To determine the long-term effectiveness of a complex intervention in primary care aimed at improving outcomes for patients with coronary heart disease. DESIGN: A 6-year follow-up of a cluster randomised controlled trial, which found after 18 months that both total and cardiovascular hospital admissions were significantly reduced in intervention practices (8% absolute reduction). SETTING: 48 general practices in the Republic of Ireland and Northern Ireland. PARTICIPANTS: 903 patients with established coronary heart disease at baseline in the original trial. INTERVENTION: The original intervention consisted of tailored practice and patient plans; training sessions for practitioners in medication prescribing and behavioural change; and regular patient recall system. Control practices provided usual care. Following the intervention period, all supports from the research team to intervention practices ceased. PRIMARY OUTCOME: hospital admissions, all cause and cardiovascular; secondary outcomes: mortality; blood pressure and cholesterol control. RESULTS: At 6-year follow-up, data were collected from practice records of 696 patients (77%). For those who had died, we censored their data at the point of death and cause of death was established. There were no significant differences between the intervention and control practices in either total (OR 0.83 (95% CI 0.54 to 1.28)) or cardiovascular hospital admissions (OR 0.91 (95% CI 0.49 to 1.65)). We confirmed mortality status of 886 of the original 903 patients (98%). There were no significant differences in mortality (15% in intervention and 16% in control) or in the proportions of patients above target control for systolic blood pressure or total cholesterol. CONCLUSIONS: Initial significant differences in the numbers of total and cardiovascular hospital admissions were not maintained at 6 years and no differences were found in mortality or blood pressure and cholesterol control. Policymakers need to continue to assess the effectiveness of previously efficacious programmes. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN24081411.

Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production.

TNF promotes a regulated form of necrosis, called necroptosis, upon inhibition of caspase activity in cells expressing RIPK3. Because necrosis is generally more pro-inflammatory than apoptosis, it is widely presumed that TNF-induced necroptosis may be detrimental in vivo due to excessive inflammation. However, because TNF is intrinsically highly pro-inflammatory, due to its ability to trigger the production of multiple cytokines and chemokines, rapid cell death via necroptosis may blunt rather than enhance TNF-induced inflammation. Here we show that TNF-induced necroptosis potently suppressed the production of multiple TNF-induced pro-inflammatory factors due to RIPK3-dependent cell death. Similarly, necroptosis also suppressed LPS-induced pro-inflammatory cytokine production. Consistent with these observations, supernatants from TNF-stimulated cells were more pro-inflammatory than those from TNF-induced necroptotic cells in vivo. Thus necroptosis attenuates TNF- and LPS-driven inflammation, which may benefit intracellular pathogens that evoke this mode of cell death by suppressing host immune responses.

Elasticity and breaking strength of synthetic suture materials incubated in various equine physiological and pathological solutions.

REASONS FOR PERFORMING STUDY: Selection of suture material in equine surgery is often based on costs or subjective factors, such as the surgeon's personal experience, rather than objective facts. The amount of objective data available on durability of suture materials with regard to specific equine physiological conditions is limited. OBJECTIVES: To evaluate the effect of various equine physiological and pathological fluids on the rate of degradation of a number of commonly used suture materials. STUDY DESIGN: In vitro material testing. METHODS: Suture materials were exposed in vitro to physiological fluid, followed by biomechanical analysis. Three absorbable suture materials, glycolide/lactide copolymer, polyglactin 910 and polydioxanone were incubated at 37°C for 7, 14 or 28 days in phosphate-buffered saline, equine serum, equine urine and equine peritoneal fluid from an animal with peritonitis. Five strands of each suture material type were tested to failure in a materials testing machine for each time point and each incubation medium. Yield strength, strain and Young's modulus were calculated, analysed and reported. RESULTS: For all suture types, the incubation time had a significant effect on yield strength, percentage elongation and Young's modulus in all culture media (P<0.0001). Suture type was also shown significantly to influence changes in each of yield strength, percentage elongation and Young's modulus in all culture media (P<0.0001). While the glycolide/lactide copolymer demonstrated the highest Day 0 yield strength, it showed the most rapid degradation in all culture media. For each of the 3 material characteristics tested, polydioxanone showed the least variation across the incubation period in each culture medium. CONCLUSIONS: The duration of incubation and the type of fluid have significant effects on the biomechanical properties of various suture materials. These findings are important for evidence-based selection of suture material in clinical cases.

Which anatomical region determines a positive flexion test of the distal aspect of a forelimb in a nonlame horse?

REASONS FOR PERFORMING STUDY: The flexion test is used routinely as part of lameness and prepurchase examinations. However, little is known about the mechanisms that cause a positive response to a flexion test. OBJECTIVE: To determine which anatomical regions play a role in a positive outcome of a flexion test of the distal aspect of a forelimb in a nonlame horse. METHODS: Eight clinically sound Dutch Warmblood horses were subjected to a standardised flexion test (force 250 N, time 60 s) inducing a consistent lameness. To discriminate between different areas of the distal aspect of a forelimb, effects of various nerve blocks on the outcome of the flexion test were investigated. Low palmar digital, palmar at the abaxial aspects of the base of the proximal sesamoids, high palmar, ulnar and low 4-point nerve blocks were performed. Flexion test induced lameness was scored before and after each nerve block in separate sessions. RESULTS: The low palmar digital nerve blocks and nerve blocks of the palmar nerves at the abaxial aspect of the base of the proximal sesamoid bones had no significant effect on the flexion test induced lameness score. The ulnar, high palmar and, most dramatically, the low 4-point nerve blocks all caused a significant (P<0.05) reduction in the flexion test induced lameness score. CONCLUSIONS: Anatomical structures (soft tissue nor synovial structures) located distal to the metacarpophalangeal joint appear to contribute only minimally to the outcome of a positive flexion test of the distal aspect of a forelimb in a clinically nonlame horse. The structures in the region of, and including, the metacarpophalangeal joint appear to contribute most to a positive flexion test of the distal aspect of a forelimb in a nonlame horse. POTENTIAL RELEVANCE: The flexion test of the distal aspect of a forelimb may be sensitive for investigating the metacarpophalangeal joint region in horses free from lameness, but may be less relevant for structures distal to this region.

Nanoscale anisotropic plastic deformation in single crystal aragonite.

The nanoscale anisotropic elastic-plastic behavior of single-crystal aragonite is studied using nanoindentation and tapping mode atomic force microscopy imaging. Force-depth curves coaxial to the axis exhibited load plateaus indicative of dislocation nucleation events. Plasticity on distinct slip systems was evident in residual topographic impressions where four pileup lobes were present after indentation with a conospherical probe and distinct, protruding slip bands were present after indentation with a Berkovich pyramidal probe. A finite element crystal plasticity model revealed the governing roles of the {110}<001>slip system family, as well as the (100)[010], (100)[001], (010)[100], (010)[001], (001)[100] and (001)[010] systems.

Combretastatin A-4 resistance in H460 human lung carcinoma demonstrates distinctive alterations in beta-tubulin isotype expression.

Tubulin isotype distribution may play a role in the development of anti-cancer anti-tubulin drug resistance as well as in drug efficacy and specificity. Stepwise selection was used to establish non-small cell lung carcinoma (NSCLC) H460 cells resistant to combretastatin A-4 (CA4), paclitaxel or vinblastine. The results demonstrated that the rate of CA4 drug resistance development was slower than that for paclitaxel. Western analysis demonstrated alterations in total beta-tubulin and classes I, III and IV tubulin isotypes among the resistant H460 cell lines. Class III beta-tubulin was significantly altered in all resistant cell lines. Cells resistant to paclitaxel, a structural stabilizer of microtubules, exhibited an increased expression while cells resistant to CA-4 and vinblastine, structural destabilizers of tubulin, demonstrated a reduction of the same isotype. To our knowledge, this is the first demonstration of resistance development and of the corresponding tubulin isotype response for the combretastatins.

Long-term patient satisfaction with cosmetic outcome of minor cutaneous surgery.

We evaluated our patients' own assessment of the cosmetic outcome of minor dermatological surgery procedures. A postal questionnaire was sent to patients who had undergone surgery between 12 and 18 months previously. Patient satisfaction was correlated with variables, including age, sex, lesion size and site, indication for excision, histological diagnosis and operator. Two hundred and seven excisional procedures were identified in 193 patients. Seventy-nine per cent of the questionnaires (163/207) were returned. Seventy per cent of patients reported that the scar was invisible or better than expected and 9% rated it to be worse than expected. Ninety per cent of patients said they would undergo the procedure again. Patient dissatisfaction was associated significantly and independently with excisions from the back, younger age and benign histology.

Allergic contact dermatitis to cinchocaine.

A case of allergic contact dermatitis to cinchocaine is presented to highlight the confusion regarding the classification of, and cross-reactivity between, topical anaesthetic agents and the inadequacy of the use of benzocaine as a single screening agent for topical anaesthetic contact allergy. Our patient presented with a 10-day history of acute perianal dermatitis. Allergic contact dermatitis to Proctosedyl ointment, which was applied for 3 weeks prior, was suspected. On patch testing, he reacted to cinchocaine, a constituent of Proctosedyl ointment, and to the actual product, but had no reaction to benzocaine or lignocaine.

Recombination between a 3-kilobase tobacco mosaic virus transgene and a homologous viral construct in the restoration of viral and nonviral genes.

Transgenic plants harboring various plant virus sequences have shown resistance to viral infections. An environmental risk associated with the use of these plants is the possibility of forming a novel virus by recombination between challenging viruses and transgenic viral mRNA. Two experiments were designed using tobacco mosaic virus (TMV) vectors and transgenic Nicotiana benthamiana to determine if recombinant viral RNA would be detectable. N. benthamiana was transformed with a nontranslatable portion of a TMV viral vector including part of the replicase gene, the movement protein gene, a gene for green fluorescent protein (GFP), and the coat protein gene. When transformed plants were inoculated with a TMV vector coat protein mutant which could not move efficiently through the host, recombinant RNA was detected in 32% of the infected plants, although virions were not detected. When transformed plants were infected with a TMV vector with a normal coat sequence but three base changes in the GFP sequence, no recombinant RNA or virions were detected. Thus, recombinant RNA between TMV RNA and host mRNA did not accumulate to detectable levels under nonselective conditions, and though recombinant RNA did accumulate in the presence of selective pressure, an encapsidated recombinant viral population did not develop.

Deoxyribonuclease for cystic fibrosis.

BACKGROUND: Recombinant human deoxyribonuclease is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. OBJECTIVES: To determine whether the use of recombinant human deoxyribonuclease in cystic fibrosis is associated with improved mortality and morbidity as compared to placebo and to identify any adverse events associated with its use. To compare the efficacy of recombinant human deoxyribonuclease with other mucolytics. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and abstracts from conferences. The company producing recombinant human deoxyribonuclease was also contacted. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised and quasi-randomised trials where recombinant human deoxyribonuclease was compared to either placebo, standard therapy or another mucolytic for any duration, dose regimen and age of patient with cystic fibrosis of any disease severity. DATA COLLECTION AND ANALYSIS: Trials were independently assessed for inclusion criteria, methodological quality and data extraction by the two reviewers. Comparisons were between recombinant human deoxyribonuclease and placebo and recombinant human deoxyribonuclease and other mucolytics. The following outcomes were recorded: Mean % change from baseline in forced vital capacity (FVC), forced expiratory voloume at one second (FEV1) and weight, mean number of respiratory tract exacerbations, days intravenous and oral antibiotics used, mean number of days as inpatient, number of deaths, adverse events and the cost of therapy. MAIN RESULTS: Seven primary clinical trials were identified, totalling 1710 patients. Two further studies examined the health care cost of patients from one of the clinical trials. No eligible studies compared recombinant human deoxyribonuclease to another mucolytic. Five trials presented outcomes at up to one month, one at three months and one at six months. No reduction in mortality for treated patients was identified (Relative Risk (RR) at six month 1.01, 95%Confidence Interval (CI) 0.09, 11.11). Lung function improved to a greater extent in the treated groups (at six months Weighted Mean Difference (WMD) FEV1 5.7, 95%CI 4.18, 7.23, at three months 7.3, 95%CI 4.04, 10.65). Pooled data from the five trials of up to one month gave WMD 9.2 95%CI 0.93, 17. 6 although there was significant heterogeneity). Recombinant human deoxyribonuclease was well tolerated with no excess of serious adverse events (RR haemoptysis 0.89, 95%CI 0.54, 1.45, pneumothorax 0.97 95%CI 0.19, 4.96). Voice alteration was, however, reported more frequently in the treated groups (RR 2.33 95%CI 1.38, 3.93). No study analysed our pre-defined outcome measure for respiratory exacerbations and insufficient data was available to analyse differences in antibiotic treatment, inpatient stay and quality of life. REVIEWER'S CONCLUSIONS: Studies are of insufficient duration to identify a reduction in mortality or number of respiratory exacerbations. Further trials are required to answer these important questions. Recombinant human deoxyribonuclease therapy is associated with an improvement in lung function after six months treatment, but it is not possible to assess whether this effect on lung function is sustained in the long-term. No studies were identified that compared recombinant human deoxyribonuclease to another mucolytic.

Genome evolution of tobacco mosaic virus populations during long-term passaging in a diverse range of hosts.

The effects of host changes on plant virus genome evolution was studied by nucleotide sequencing. A single tobacco (Nicotiana tabacum cv. Xanthi) plant was inoculated with in vitro transcripts from a plasmid clone of tobacco mosaic tobamovirus (TMV). This initial viral population was then transferred 11-12 times in parallel populations in 7 plant host species (1-4 replicates each) over a period of 413-515 days. Virion RNA was then isolated, reverse transcribed, amplified, cloned in bacteria, and sequenced. Portions of the coat protein, movement protein, and replicase genes were sequenced. Fourteen unique mutations were detected from a total of 188 clones (35,607 bases) sequenced, indicating a relatively small overall mutation rate of 3.1 x 10(-4) nucleotide substitutions/base-year. A small Ka/Ks value of 0.09 was also found, indicating selection against amino acid changes. Eighty-five percent of the substitutions were transitions. A G'(ST) value of 0.7 for the coat protein gene suggested that host type affected sequence changes in this region of the genome, but chi(2) analysis did not support this conclusion. This is the first study using sequencing to compare representative sample sections of a plant viral genome following a major selective disturbance such as extended passaging in an alternate host.

Prevention of postmenopausal bone loss at lumbar spine and upper femur with tibolone: a two-year randomised controlled trial.

OBJECTIVE: To examine the effects of tibolone on bone mineral density and its concurrent safety and subject acceptability. DESIGN: Prospective randomised controlled study. SETTING: Centre for Metabolic Bone Disease, Hull. POPULATION: Forty-seven healthy post-menopausal women aged 50-57 years with normal bone mineral density at lumbar spine. METHODS: Bone mineral density was assessed every 24 weeks at lumbar spine and proximal femur using dual energy X-ray absorptiometry. RESULTS: The bone mineral density of the tibolone treated subjects tended to increase while those of the controls tended to fall. The higher densities in the tibolone group were significant at lumbar spine from week 24 (P = 0.002) and at the trochanter from week 72 (P = 0.014). The lower bone densities in the controls were significant at Ward's Triangle and femoral neck at week 96 (P < 0.0001), and at lumbar spine from week 24 onwards (P < 0.05). Between-treatment analysis indicated that, by the 96th week, the bone densities at all sites in the tibolone group were significantly different from those in the control group. At the lumbar spine the differences were highly significant throughout the study (P < 0.0004). Four women receiving tibolone withdrew from the study due to unacceptable adverse events. Two women withdrew from the control group. There was no significant difference between the groups in the number of subjects suffering adverse experiences. Vaginal bleeding occurred in seven women, all from the tibolone treated group, resulting in one withdrawal from the study. CONCLUSION: Tibolone is thus an effective and well-tolerated alternative to oestrogen in the prevention of osteoporosis with its beneficial effects being most apparent at the lumbar spine.

Clinical interpretation of ultrasound biometry for dating and for assessment of fetal growth using a wheel and chart: is it sufficiently accurate?

OBJECTIVES: To investigate how accurately practicing obstetricians (experts) can apply dating rules and compare the interpretation of gestation-sensitive ultrasound data with those of a computer system. SUBJECTS: Seventeen practicing obstetricians. Members of the Royal College of Obstetricians and Gynaecologists, from 14 different units throughout the UK. DESIGN: Six cases with menstrual and ultrasound data together with identical ultrasound charts and obstetric wheels. MAIN OUTCOME MEASURES: Concordance between the calculated estimated date of delivery (EDD) and growth assessment provided by the experts and the computer system. RESULTS: The calculation of the EDD by the experts was imprecise (59% within 3 days overall). Concordance with the computer calculation was poorest when the ultrasound measurements lay close to the upper or lower centile lines (average 7% within 3 days of the computer). Interpretation of growth showed good concordance with the computer when gestation was not critical to the interpretation (94%), but very poor when gestation was critical (7%). CONCLUSIONS: Calculation of EDD by means of an obstetric wheel and charts is not precise. Compared with the computer system, these errors have a significant effect on the subsequent interpretation of growth scans when the data are borderline. A computer system provides the more accurate method for interpreting gestation-sensitive ultrasound biometry.