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.

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.

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.

Tau factor from Escherichia coli mediates accurate and efficient termination of transcription at the bacteriophage T3 early termination site in vitro.

The termination signal that limits transcription through the early region of bacteriophage T3 (T3Te) has been cloned and sequenced. The nucleotide sequence of T3Te is identical with that of T7Te, with the exception of a single G to U substitution in the 3' tail of the terminated transcript, and addition of an AC to the loop in the terminator stem-loop, enlarging the loop to six residues. Previous studies of the properties of T3Te have shown that this site is rho independent and is highly efficient for termination in vivo, but is used poorly in vitro during transcription with purified Escherichia coli RNA polymerase. In contrast, the equivalent site in bacteriophage T7 (T7Te) is an efficient termination signal both in vivo and in vitro. However, T3Te becomes an efficient termination site in vitro in the presence of preparations of tau factor. This factor also alters the sites of RNA chain termination found in vitro at T3Te. Transcripts formed in the presence of tau are several nucleotides shorter than those produced with RNA polymerase alone, and have 3' termini that are almost identical with transcripts found in vivo. These latter results are similar to our earlier findings with T7Te, and suggest that other rho independent terminators may act with transcription termination factors in vivo.

Sequence of a conditionally essential region of bacteriophage T3, including the primary origin of DNA replication.

The 3526 base-pair nucleotide sequence from near the end of bacteriophage T3 gene 1 to within the coding sequence of gene 2.5 is given. It includes the complete coding sequences for nine known or presumptive proteins, most of which are only conditionally essential for phage growth. The sequence includes five promoters for the phage RNA polymerase, the terminator for early (host enzyme-catalyzed) transcription, and two recognition sites for RNAase III. The primary origin of T3 DNA replication that is utilized by the phage in vivo has been localized to a 142 base-pair region. It has several features in common with the phage T7 origin of DNA replication, and exhibits considerable homology to recognition sites for the mRNA processing enzyme RNAase III. It is proposed that the primary origin of T3 DNA replication may have evolved directly from an RNAase III recognition site. The deletions present in a number of T3 mutant strains and the location of the nucleotide changes in several T3 strains that are defective in their ability to grow on F+-containing strains or on optA mutant hosts have been determined. We discuss how T3 may have become genetically isolated from its relatives in the T7-T3 group and simultaneously acquired novel biological and biochemical properties.

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.

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.

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.

Broad resistance to tobamoviruses is mediated by a modified tobacco mosaic virus replicase transgene.

Tobacco plants made transgenic to express the wild type tobacco mosaic virus (TMV) 183-kDa replicase gene were not resistant to TMV. However, transgenic plants containing essentially the same sequences, but with an additional insertion that would terminate translation in the middle of the 183-kDa gene, were highly resistant to systemic infection by TMV and other tobamoviruses. The 1.4-kbp insertion in the replicase open reading frame (ORF) of the resistant plants was shown by DNA sequencing to be an IS10-like transposable element, which apparently inserted itself into the TMV sequence at nucleotide 2875 sometime during the propagation of this replicase ORF plasmid (pREP21). Because of four stop codons, in frame with the TMV replicase ORF on the immediate 5' border of the IS insertion, REP21 effectively represents domain 1 (putative methylase domain) and a portion of domain 2 (putative helicase domain) of the TMV replicase ORF. REP21 Xanthi tobacco plants had a level of resistance to TMV similar to other reported transgenic replicase plants. No TMV was detected in upper leaves of these plants at 1-mo postinoculation. In addition, REP21 plants were resistant to an unusually broad range of tobamoviruses including tomato mosaic virus, tobacco mild green mosaic virus, TMV-U5, green tomato atypical mosaic virus, and ribgrass mosaic virus. These plants were not resistant to cucumber mosaic cucumovirus. The lack of systemic infection by TMV was due to reduced multiplication in inoculated leaves rather than complete prevention of replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Preference, choice, and persons with disabilities: a synopsis of assessments, interventions, and future directions.

A recent revolution in service delivery for persons with developmental disabilities encompasses increased client independence and improved quality of life. Specifically, care providers have focused on client expressions of preference, choice-making, and choice availability as key elements of study in this new revolution. We review and critique the primary methods of assessing preference and choice for persons with disabilities, including interviews and questionnaires, pictorial presentations, technological apparati, and direct observation. We also provide an overview of the burgeoning literature on intervention programs designed to enhance choice for this population, such as giving more choice to clients, teaching choice-making skills, and improving staff member skills regarding choice availability. Finally, we provide a synopsis of the future directions in this area that should receive the most attention from researchers and caregivers.

Tarsal navicular stress fracture in athletes.

Stress fracture of the tarsal navicular bone is now frequently recognised. The majority of navicular stress fractures are partial fractures in the sagittal plane. They occur mainly in track and field athletes. A number of theories regarding the aetiology of this fracture have been proposed. Athletes with a history of vague, activity-related midfoot pain, with associated tenderness over the dorsal proximal navicular ('N' spot) should be suspected of having a navicular stress fracture. Plain radiography frequently fails to demonstrate the fracture, thus radionuclide scanning is the investigation of choice to detect navicular stress injury. A computed tomography (CT) scan should be performed to confirm the presence of the fracture. Various methods of treatment have been employed. A minimum of 6 weeks of strict non-weightbearing cast immobilisation is the treatment of choice. After removal of the cast, a further 6 week programme of rehabilitation with a graduated return to activity, joint mobilisation and soft tissue massage is required. Surgery for nonunion or delayed union is rarely required if initial treatment is appropriate.

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.

Outcome of conservative and surgical management of navicular stress fracture in athletes. Eighty-six cases proven with computerized tomography.

Eighty-two athletes with 86 clinical navicular stress fractures, all imaged with computerized tomography, were followed for an average of 33 months (range, 6 to 108) after diagnosis. Initial treatment consisted of at least 6 weeks of nonweightbearing cast immobilization for 22 fractures, at least 6 weeks of limitation of activity with continued weightbearing for 34 fractures, and a period of less than 6 weeks of conservative treatment for another 19 fractures. Five patients attempted to continue playing sports. Six patients had immediate surgery. Nineteen of 22 patients (86%) who had initial non-weightbearing cast immobilization treatment returned to sports, compared with only 9 of 34 patients (26%) who initially continued weightbearing with limited activity (P < 0.001). After failure of the latter treatment, successful outcomes were seen for 6 of 7 patients (86%) treated with nonweightbearing cast immobilization, while 11 of 15 patients (73%) who had one surgical procedure were able to return to sports. These results indicate that nonweightbearing cast immobilization is the treatment of choice for navicular stress fractures. Also, this treatment compares favorably with surgical treatment for patients who present after failed weightbearing treatments. Computerized tomographic appearances of healing fractures do not necessarily mirror clinical union, and postimmobilization management should be monitored clinically.

A critical review of pharmacotherapy for youth with anxiety disorders: things are not as they seem.

Given the increasing trend in clinical child psychology and psychiatry toward cost-effective and pharmacological treatment, a review of key factors that influence treatment outcomes in this area seems warranted. This is especially important for the rapidly changing area of childhood anxiety disorders. In this article, we look at different change producing procedures to illustrate the claim that pharmacological studies are not necessarily what they seem. Specifically, pharmacological outcome studies are classified and reviewed on the basis of varying "secondary" treatments described in method sections. Three groups and efficacy rates were determined: (a) pharmacotherapy only (42.83%), (b) pharmacotherapy plus general/supportive psychotherapy (27.74%), and (c) pharmacotherapy plus a behavior therapy component (65.28%). We also discuss the implications of these findings for research as well as other methodological and theoretical concerns regarding the reviewed articles. These concerns include (a) methods used to diagnose participants, (b) methods used to assess improvement, (c) emphasis on diagnostic categories, (d) exclusionary criteria and comorbidity, (e) participant attrition and follow-up, and (f) key developmental and social contextual variables.

The phenomenology of panic disorder in youngsters: an empirical study of a clinical sample.

Questions about the existence of panic disorder in youngsters are now evolving into questions about the phenomenology of panic disorder in children and adolescents. The current study thus examined the primary clinical features of panic disorder in an outpatient sample of older children and adolescents with panic disorder. Youngsters with panic disorder were compared to a matched-gender group of youngsters with non-panic anxiety disorders. Dependent variables included diagnoses and self-ratings of fear, depression, general anxiety, and anxiety sensitivity. The panic group was found to display more frequent diagnoses of depression and greater levels of self-reported anxiety sensitivity than the non-panic group. These results are discussed in the context of one potential cognitive developmental pathway of panic disorder, and preliminary assessment and treatment recommendations are offered.

Treatment of an adolescent with obsessive-compulsive disorder by alternating response prevention and cognitive therapy: an empirical analysis.

This paper reports on the treatment of a 14-year-old boy with severe obsessive-compulsive disorder. Baseline measures indicated that two checking behaviors were of extreme frequency. Personal discomfort was severe and parental ratings of anxiety and depression were high. Treatment employed an alternating design of response prevention and cognitive therapy. Parent and client ratings of levels of anxiety and depression were taken daily in addition to frequency levels of the compulsive behaviors. The treatment procedures over 24 sessions eliminated the compulsive behaviors and reduced self-reported anxiety. The study is unique in demonstrating that the cognitive therapy had a significant influence in diminishing the obsessive-compulsive behaviors.

Listening to our clinical partners: informing researchers about children's fears and phobias.

We surveyed a national sample of clinical psychologists to expand on Graziano and De Giovanni's (Behaviour Research and Therapy, 1979, 17, 161-162) findings that 6.8% of clinically referred children present with problems with fears and/or phobias. The survey was also conducted to assess how clinicians could inform researchers about current needs for investigations in this area. Questions involved epidemiological, demographical, and treatment characteristics of cases recently seen by therapists. The percentage of referred cases for fears/phobias in children was determined to be similar over time. In addition, types of fears, length of history of fear, intensity of fear, length of treatment, types of treatments used, and degree of parental involvement were measured and reported. The results were found to suggest a substantial degree of heterogeneity among types of fears and treatment methods for this population, as well as important lines of future research. They also suggest the need for controlled studies to assess the efficacy of a number of widely used treatments that lack an empirical base.

A preliminary analysis of a functional model of assessment and treatment for school refusal behavior.

We assessed whether treatment of children and adolescents with school refusal behavior is effective when based upon an individualized, functional analysis. Seven children and adolescents, who were currently experiencing difficulties attending school, were evaluated with the School Refusal Assessment Scale (SRAS), an instrument designed to identify maintaining variables surrounding school refusal behavior. These included specific fearfulness/general overanxiousness, escape from aversive social situations, attention-getting or separation anxious behavior, and tangible reinforcement. Prescriptive treatment was given in accordance with the assessed motivating condition and included systematic desensitization/relaxation training, modeling and cognitive restructuring, shaping and differential reinforcement of other behavior, and contingency contracting for each condition, respectively. Daily measures of anxiety, depression, distress, and school attendance were taken, as well as pretreatment, posttreatment, and 6-month follow-up child and/or parent questionnaires. Results indicated that 6 of the subjects maintained full-time school attendance by posttreatment and at the 6-month follow-up. All reported moderate improvements in daily levels of anxiety, depression, and/or distress. The implications of a prescriptive treatment approach for school refusal behavior are discussed.

New Jersey Caucasian, African American, and Hispanic population data on the PCR-based loci HLA-DQA1, LDLR, GYPA, HBGG, D7S8, and Gc.

New Jersey Caucasian, African American, and Hispanic genotype and allele frequencies were determined for the six PCR-based loci, HLA-DQA1, LDLR, GYPA, HBGG, D7S8, and Gc. All but one locus (HLA-DQA1 for African Americans) meet Hardy-Weinberg expectations. However, observing one departure in 18 loci over the three New Jersey sample populations is not unexpected. There is little evidence for departures from independence between pairs of loci in the three populations studied. Thus, multiple locus profile frequencies can be determined using the product rule.