Complex organisational factors influence multidisciplinary care for patients with hip fractures: a qualitative study of barriers and facilitators to service delivery.

BACKGROUND: Hip fractures are devastating injuries, with high health and social care costs. Despite national standards and guidelines, substantial variation persists in hospital delivery of hip fracture care and patient outcomes. This qualitative study aimed to identify organisational processes that can be targeted to reduce variation in service provision and improve patient care. METHODS: Interviews were conducted with 40 staff delivering hip fracture care in four UK hospitals. Twenty-three anonymised British Orthopaedic Association reports addressing under-performing hip fracture services were analysed. Following Thematic Analysis of both data sources, themes were transposed onto domains both along and across the hip fracture care pathway. RESULTS: Effective pre-operative care required early alert of patient admission and the availability of staff in emergency departments to undertake assessments, investigations and administer analgesia. Coordinated decision-making between medical and surgical teams regarding surgery was key, with strategies to ensure flexible but efficient trauma lists. Orthogeriatric services were central to effective service delivery, with collaborative working and supervision of junior doctors, specialist nurses and therapists. Information sharing via multidisciplinary meetings was facilitated by joined up information and technology systems. Service provision was improved by embedding hip fracture pathway documents in induction and training and ensuring their consistent use by the whole team. Hospital executive leadership was important in prioritising hip fracture care and advocating service improvement. Nominated specialty leads, who jointly owned the pathway and met regularly, actively steered services and regularly monitored performance, investigating lapses and consistently feeding back to the multidisciplinary team. CONCLUSION: Findings highlight the importance of representation from all teams and departments involved in the multidisciplinary care pathway, to deliver integrated hip fracture care. Complex, potentially modifiable, barriers and facilitators to care delivery were identified, informing recommendations to improve effective hip fracture care delivery, and assist hospital services when re-designing and implementing service improvements.

Dental Extractions under General Anesthesia: New Insights from Process Mining.

INTRODUCTION: Tooth extraction under general anesthetic (GA) is a global health problem. It is expensive, high risk, and resource intensive, and its prevalence and burden should be reduced where possible. Recent innovation in data analysis techniques now makes it possible to assess the impact of GA policy decisions on public health outcomes. This article describes results from one such technique called process mining, which was applied to dental electronic health record (EHR) data. Treatment pathways preceding extractions under general anesthetic were mined to yield useful insights into waiting times, number of dental visits, treatments, and prescribing behaviors associated with this undesirable outcome. METHOD: Anonymized data were extracted from a dental EHR covering a population of 231,760 patients aged 0 to 16 y, treated in the Irish public health care system between 2000 and 2014. The data were profiled, assessed for quality, and preprocessed in preparation for analysis. Existing process mining methods were adapted to execute process mining in the context of assessing dental EHR data. RESULTS: Process models of dental treatment preceding extractions under general anesthetic were generated from the EHR data using process mining tools. A total of 5,563 patients who had 26,115 GA were identified. Of these, 9% received a tooth dressing before extraction with an average lag time of 6 mo between dressing and extraction. In total, 11,867 emergency appointments were attended by the cohort with 2,668 X-rays, 4,370 prescriptions, and over 800 restorations and other treatments carried out prior to tooth extraction. DISCUSSION AND CONCLUSIONS: Process models generated useful insights, identifying metrics and issues around extractions under general anesthetic and revealing the complexity of dental treatment pathways. The pathways showed high levels of emergency appointments, prescriptions, and additional tooth restorations ultimately unsuccessful in preventing extractions. Supporting earlier publications, the study suggested earlier screening, preventive initiatives, guideline development, and alternative treatments deserve consideration. KNOWLEDGE TRANSFER STATEMENT: This study generates insights into tooth extractions under general anesthetic using process mining technologies and methods, revealing levels of extraction and associated high levels of prescriptions, emergency appointments, and restorative treatments. These insights can inform dental planners assessing policy decisions for tooth extractions under general anesthetic. The methods used can be combined with costs and patient outcomes to contribute to more effective decision-making.

'DrinkThink' alcohol screening and brief intervention for young people: a qualitative evaluation of training and implementation.

Background: Alcohol Screening and Brief Intervention (ASBI) helps reduce risky drinking in adults, but less is known about its effectiveness with young people. This article explores implementation of DrinkThink, an ASBI co-produced with young people, by health, youth and social care professionals trained in its delivery. Methods: A qualitative evaluation was conducted using focus groups with 33 staff trained to deliver DrinkThink, and eight interviews with trained participants and service managers. These were recorded, transcribed and a thematic analysis undertaken. Results: DrinkThink was not delivered fully by health, youth or social care agencies. The reasons for this varied by setting but included: the training staff received, a working culture that was ill-suited to the intervention, staff attitudes towards alcohol which prioritized other health problems presented by young people, over alcohol use. Conclusions: Implementation was limited because staff had not been involved in the design and planning of DrinkThink. Staffs' perceptions of alcohol problems in young people and the diverse cultures in which they work were subsequently not accounted for in the design. Co-producing youth focused ASBIs with the professionals expected to deliver them, and the young people whom they target, may ensure greater success in integrating them into working practice.

Phase I study of every 2- or 3-week dosing of ramucirumab, a human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2 in patients with advanced solid tumors.

BACKGROUND: Ramucirumab is a fully human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2). An initial phase I study evaluated ramucirumab administered weekly in advanced cancer patients. This phase I study of ramucirumab [administered every 2 or 3 weeks (Q2W or Q3W)] examined safety, maximum tolerated dose, pharmacokinetics, immunogenicity, antitumor activity, and pharmacodynamics. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of ramucirumab i.v. over 1 h. Blood was sampled for pharmacokinetics studies throughout treatment; levels of circulating vascular endothelial growth factor-A (VEGF-A) and soluble VEGF receptors (R)-1 and -2 were assessed. RESULTS: Twenty-five patients were treated with ramucirumab: 13 with 6, 8, or 10 mg/kg Q2W, and 12 with 15 or 20 mg/kg Q3W. The median treatment duration was 12 weeks (range 2-81). No dose-limiting toxicities were observed. The most frequently reported adverse events (AEs) included proteinuria and hypertension (n = 6 each), and diarrhea, fatigue and headache (n = 4 each). Treatment-related grade 3/4 AEs were: two grade 3 hypertension (10 and 20 mg/kg), one each grade 3 vomiting, fatigue (20 mg/kg), atrial flutter (15 mg/kg), and one each grade 4 duodenal ulcer hemorrhage (6 mg/kg) and grade 4 pneumothorax (20 mg/kg). Pharmacokinetic analysis revealed low clearance and half-life of ∼110-160 h. Analysis of serum biomarkers indicated considerable patient-to-patient variability, but trends toward elevated VEGF-A and a transient decline in soluble VEGFR-2. Fifteen patients (60%) had best response of stable disease, with a median duration of 13 months (range 2-18 months) in tumor types including colorectal, renal, liver, and neuroendocrine cancers. CONCLUSION: Ramucirumab was well tolerated. Study results led to recommended phase II doses of 8 mg/kg Q2W and 10 mg/kg Q3W. Prolonged stable disease was observed, suggesting ramucirumab efficacy in various solid tumors. CLINICALTRIALSGOV: NCT00786383.

Exploring experiences of physical activity among people with Alzheimer's disease and their spouse carers: a qualitative study.

OBJECTIVES: To improve understanding about the barriers and facilitators to physical activity for people with Alzheimer's disease and their spouse carers, and to consider the development of activity interventions that would be acceptable, sustainable and feasible for both groups. DESIGN: A qualitative approach, using semi-structured interviews, facilitated exploration of physical activity in a small group of people with Alzheimer's disease and their spouse carers. SETTING: Participants were recruited from one memory clinic in South West England. PARTICIPANTS: Potential participants were identified by clinical psychologists at the memory clinic and were given information about participating in the research. Five people with Alzheimer's disease and their spouse carers were subsequently recruited for semi-structured interviews, which took place at the memory clinic. Interviews were audio-recorded and transcribed verbatim. MAIN OUTCOME MEASURES: Qualitative data were analysed using thematic analysis. Three major themes have been presented. RESULTS: The findings illustrate the complex interplay between the overarching themes 'self', 'others' and 'couple' that affect physical activity for both people with Alzheimer's disease and their spouse carers, and which are linked to the progression of dementia. CONCLUSIONS: An individually tailored approach for couples, which values the role of the carer and accounts for the progressive and changing nature of dementia, should be a guiding principle for intervention design.

"It's crucial they're treated as patients": ethical guidance and empirical evidence regarding treating doctor-patients.

Ethical guidance from the British Medical Association (BMA) about treating doctor-patients is compared and contrasted with evidence from a qualitative study of general practitioners (GPs) who have been patients. Semistructured interviews were conducted with 17 GPs who had experienced a significant illness. Their experiences were discussed and issues about both being and treating doctor-patients were revealed. Interpretative phenomenological analysis was used to evaluate the data. In this article data extracts are used to illustrate and discuss three key points that summarise the BMA ethical guidance, in order to develop a picture of how far experiences map onto guidance. The data illustrate and extend the complexities of the issues outlined by the BMA document. In particular, differences between experienced GPs and those who have recently completed their training are identified. This analysis will be useful for medical professionals both when they themselves are unwell and when they treat doctor-patients. It will also inform recommendations for professionals who educate medical students or trainees.

A reassessment of comparative pregnancy and implantation rates following embryo transfer in recipients vs their infertile donors also trying to conceive in the background of performing salpingectomy for hydrosalpinx.

PURPOSE: To compare pregnancy and implantation rates in egg donors trying to conceive vs their recipients in the background of salpingectomy for hydrosalpinx prior to IVF-ET. METHODS: A retrospective six-year review of all donor egg cycles where the eggs are supplied by an infertile donor trying to conceive herself was carried out. Salpingectomy for hydrosalpinx was performed prior to IVF-ET. RESULTS: Clinical and delivered pregnancy rates (PRs) following fresh ET were not significantly different in donors vs recipients (60.0%, 45.8% vs 56.8%, 50.8%). Implantation rates were 27.3% vs 32.6%. The respective implantation rates following frozen ET were 13.8% and 14.4%. CONCLUSIONS: In the background of salpingectomy for hydrosalpinges the much higher PRs in recipients vs donors is no longer seen. The trend for higher implantation rates in recipients (about 20%) following fresh but not frozen transfer could still reflect some adverse effect of the controlled ovarian hyperstimulation regimen in a minority of women.

Efficacy of sharing oocytes from compensated donors between two recipients.

PURPOSE: To see if sharing of donated oocytes from a compensated donor lowers outcome following embryo transfer compared to recipients keeping all oocytes. METHOD: Retrospective review. Recipients have the option of keeping all oocytes or sharing to reduce costs. RESULTS: There were equal clinical, and ongoing/delivered pregnancy rates and implantation rates in the two groups. There were almost twice as many frozen embryos available to recipients who did not share for potential future use. CONCLUSIONS: Sharing of oocytes between two recipients reduces the financial burden for the recipient without affecting efficacy. Such a policy would make more oocytes available to recipients and thus shorten the long waiting times.

An evaluation of the efficacy of using oocyte donors aged 36-39.

PURPOSE: To determine if oocyte donors aged 36-39 can provide adequate pregnancy rates for recipients. METHODS: Retrospective analysis of clinical, ongoing/delivered pregnancy and implantation rates for a group of recipients receiving oocytes from a pilot group of older donors. RESULTS: Comparable pregnancy and implantation rates were found in recipients transferring embryos derived from donors aged 36-39 as recipients using oocytes from donors < or = 35. CONCLUSIONS: The demonstration of adequate outcome following embryo transfer from embryos derived from fertilization of oocytes from donors aged 36-39 should expand the pool of donor oocytes and reduce the long waiting times for recipients.

Fresh embryo transfer is more effective than frozen for donor oocyte recipients but not for donors.

BACKGROUND: Recipients of donor oocytes need to be synchronized to the donor's cycle if fresh embryos are to be transferred on the cycle of oocyte retrieval. It would be much easier to merely retrieve the oocytes from the donor, fertilize the oocytes with the recipient's male partner's spermatozoa, cryopreserve the embryos, then transfer on an oestrogen/progesterone treatment programme. METHODS: The IVF outcomes of all patients enrolled in a shared oocyte programme from January 1997 to June 1999 were reviewed. Pregnancy and implantation rates were computed and statistically analysed. RESULTS: There was a significantly higher clinical pregnancy rate for recipients who had a fresh embryo transfer compared with recipients whose first embryo transfer consisted of frozen/thawed embryos (63.4 versus 43.6%). CONCLUSIONS: Conception is more likely after fresh than frozen embryo transfer with recipients but is similar to donor conception rates. If a uterine defect, per se, even without the use of the controlled ovarian stimulation regimen, could explain the difference between fresh pregnancy and implantation rates in donors versus recipients, then these same differences would have been seen when comparing frozen transfers, but they were, in fact, similar.

Time course of osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen peptide during callus distraction.

This study involved 15 patients who were undergoing extremity lengthening by callus distraction. Blood samples and radiographs of the callus distraction segment were obtained before surgery, every 2 weeks during the distraction phase, and every 4 weeks between the end of distraction and removal of the fixator. A digital radiograph analysis system was used to determine the radiographic density of the callus distraction segments. In addition, the serum parameters osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen peptide (PICP) were evaluated. The radiographic density was constant during the distraction phase, but increased logarithmically during the consolidation period. Similar kinetics were observed for osteocalcin, with an average coefficient of correlation between these two parameters of 0.66+/-0.15. PICP levels rose rapidly after surgery and increased further during the consolidation period. Serum levels of bone-specific alkaline phosphatase were not uniform between patients, and there was no correlation to the kinetics of radiographic density or the other serum parameters. The similarity between radiographic density and osteocalcin kinetics, as well as the rapid postoperative increase in PICP, imply that further information may be obtained about osteoneogenesis from the study of these two serum parameters.

New humanitarianism: does it provide a moral banner for the 21st century?

There is a 'new humanitarianism' for the new millennium. It is 'principled', 'human-rights based' and politically sensitive. Above all it is new. It marks a break from the past and a rejection of the traditional principles that guided humanitarianism through the last century. New humanitarians reject the political naivety of the past, assess the long-term political impact of relief and are prepared to see humanitarian aid used as a tool to achieve human rights and political goals. New Humanitarianism is compelling, in tune with our times and offers a new moral banner for humanitarians to cling to as we enter the new millennium. Or does it? After outlining the key elements of new humanitarianism, including the human rights approach and developmental relief, the paper spells out some of the dangers. The author claims that new humanitarianism results in an overt politicisation of aid in which agencies themselves use relief as a tool to achieve wider political goals. The paper shows how this approach has spawned a new conditionality which allowsfor aid to be withheld and has produced a moral hierarchy of victims in which some are more deserving than others. The paper concludes with a plea for a revival of the principle of universalism as the first step to a new set of principles.

The presence of small uterine fibroids not distorting the endometrial cavity does not adversely affect conception outcome following embryo transfer in older recipients.

PURPOSE: To determine if uterine fibroids have a negative impact in older patients having embryo transfer (ET). METHODS: Comparison of clinical and viable pregnancy rates, implantation rates, and spontaneous abortion rates in older (>35) oocyte or embryo recipients with uterine leiomyomata compared to comparable patients without fibroids. RESULTS: The clinical pregnancy rate per transfer was 56% in the fibroid group vs 64% for the controls. Implantation rates were also very similar (33 vs 32%7). There were no spontaneous abortion or preterm deliveries <32 weeks in the fibroid group and the average term of pregnancies was also similar. CONCLUSION: Small fibroids not distorting the uterine cavity do not seem to negatively affect conception outcome even in older women.

Depressed IL-12-mediated signal transduction in T cells from patients with Sézary syndrome is associated with the absence of IL-12 receptor beta 2 mRNA and highly reduced levels of STAT4.

Sézary syndrome (SS) is the leukemic phase of cutaneous T cell lymphoma characterized by the proliferation of clonally derived CD4+ T cells that release cytokines of the Th2 T cell phenotype (IL-4, IL-5, IL-10), whereas Th1 T cell cytokines (IL-2, IFN-gamma) are markedly depressed as is expression of IL-12, a pivotal cytokine for Th1 cell differentiation. Normal Th1 cells express both the beta 1 and beta 2 chains of the IL-12 receptor (IL-12R) and tyrosine phosphorylate STAT4 in response to IL-12. Th2 T cells express only the IL-12R beta 1 and thus do not tyrosine phosphorylate STAT4 in response to IL-12. To determine whether SS cells are Th2-like at the level of IL-12 signal transduction, we analyzed RNA from seven patients for the presence of message for the IL-12R beta 1 and beta 2 genes using RNase protection assays and assessed whether IL-12 induced tyrosine-phosphorylation of STAT4 by immunoblotting. In PBL from six of seven SS patients tested, beta 2 message was expressed at low to undetectable levels and its expression could not be stimulated by either IFN-alpha or IFN- gamma, which stimulated beta 2 expression in control PBL. The absence of beta 2 expression is further supportive evidence for the Th2 lineage of SS cells. However, unlike normal Th2 cells, SS cells also showed severely reduced levels of STAT4, suggesting that they have a depressed response to any inducer of the STAT4 signal transduction pathway, including IFN-alpha. This is the first observation linking STAT4 gene expression with a human disease and suggests that dysregulation of STAT4 expression may be significant to the development and/or progression of SS.

Retinoids synergize with interleukin-2 to augment IFN-gamma and interleukin-12 production by human peripheral blood mononuclear cells.

We have demonstrated previously that cells from both the skin and peripheral blood from patients with cutaneous T cell lymphoma (CTCL) have elevated levels of protein and mRNA for Th2 cytokines, interleukin-4 (IL-4) and IL-5, and depressed levels of Thl cytokines, IL-2 and interferon-gamma (IFN-gamma). Furthermore, IL-12 in vitro can restore IFN-gamma production by these patients' cells to near normal levels. Because retinoids exert therapeutic activity in CTCL and are potent modulators of growth and differentiation of hematopoietic cells, we investigated the role of retinoids in modulating Thl cytokine production. Peripheral blood mononuclear cells (PBMC) from normal donors and patients with CTCL were cultured with medium, IL-2, 13-cis-retinoic acid, all-trans-retinoic acid, acetretin or etretinate alone, or IL-2 plus the retinoids for 24 h, and levels of IFN-gamma were determined using ELISA. IL-2 or retinoids alone could induce low but significant levels of IFN-gamma. However, when IL-2 was cultured with each retinoid, a synergistic augmentation of IFN-gamma levels (4-fold to 90-fold) was observed except in the case of etretinate. All-trans-retinoic acid (ATRA) was the most potent IFN-y inducer. Similar studies performed using PBMC from CTCL patients indicated the IFN-gamma augmentation occurred but in a blunted manner. The IFN-y-inducing effect of ATRA and 13-cis-retinoic acid could be abrogated by addition of anti-IL-12 antibodies, suggesting that IL-12 plays a role in the synergistic upregulation of IFN-gamma. Using an IL-12 p40-specific radioimmunoassay (RIA), we confirmed the presence of IL-12 in IL-2 plus retinoid-treated culture supernatants. Purified monocytes cultured with IL-2 plus ATRA did not secrete IL-12. Only when monocytes were cocultured with lymphocytes was there an increase in IL-12 production, suggesting the involvement of a paracrine feedback loop requiring both monocytes and lymphocytes. These data suggest that retinoids can induce Th1 cytokines from normal and CTCL PBMC and that this induction may be mediated through IL-12 production.

Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed, and malignant T lymphocytes: implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders.

Hypericin is a photodynamic compound activated by either visible (400-700 nm) or UVA (320-400 nm) light, and has been shown to inhibit the growth of a variety of neoplastic cell types. In this study, hypericin was found to inhibit proliferative responses of malignant T cells derived from the blood of patients with cutaneous T cell lymphoma. Control cells included peripheral blood mononuclear cells (PBMC) from normal volunteers or Epstein-Barr virus-transformed lymphocytes. Cells from each of these populations were incubated with serial dilutions of hypericin or 8-methoxypsoralen and then stimulated with the mitogen ConA (10 microg per ml). Cultures were prepared in the dark to minimize photoactivation of the hypericin. Proliferation was measured by [3H]thymidine labeling after 72 h. Hypericin, photoactivated with 1.1-3.3 J white light per cm2, inhibited cellular proliferation of malignant T cells with IC50 values from 0.34 to 0.53 microM, normal PBMC with IC50 values of 0.11-0.76 microM, and Epstein-Barr virus-transformed cells with IC50 values of 0.75-3.2 microM. UVA-photoactivated hypericin (0.5-2.0 J per cm2) could also inhibit proliferation with IC50 values of 0.57-1.8 microM, 0.7-4.6 microM, and 2.0-3.7 microM for malignant, normal, or Epstein-Barr virus-transformed cells, respectively. Hypericin, photoactivated with either UVA or white light, could induce near complete apoptosis (94%) in malignant cutaneous T cell lymphoma T cells, whereas lower levels of apoptosis (37-88%) were induced in normal PBMC. These data indicate that hypericin inhibits mitogen-induced proliferation of malignant T cells from patients with cutaneous T cell lymphoma, PBMC from normal individuals, as well as Epstein-Barr virus-transformed lymphocytes, and that inhibition of cell proliferation is dependent on the concentration of hypericin used and the dose of light required to photoactivate the compound. Induction of apoptosis is, in part, one mechanism by which photoactivated hypericin inhibits malignant T cell proliferation.

Use of biological response modifiers in the treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is typically a skin-infiltrating, clonal proliferative disorder of CD4+ T cells that exhibit a T-helper type 2 cytokine phenotype. Therapeutic decisions are based on the extent of disease and the observations that host-antitumor responses occur and that these responses may be blunted by the immunosuppressive cytokines produced by the malignant T cells. Biologic response modifiers, which may enhance cell-mediated immunity and antitumor responses, are active agents in the treatment of CTCL. The rationale and use of biologic response modifiers to treat CTCL are reviewed in this article.