Long-term follow-up of two patients with retained intraosseous sternal needles.

Sternal intraosseous devices are widely used in both civilian and military trauma when vascular access is difficult to establish. We discuss a rare complication of intraosseous needle insertion in two patients where the needle tip remained in the sternum after the device had been removed. Neither patient had evidence of any complication of the retained intraosseous needle tip after >6 years of follow-up.

Military trauma and orthopaedics experience of the UK COVID-19 pandemic: a lesson in versatility and how it can influence our deployed role.

The COVID-19 pandemic necessitated unprecedented change within the NHS. Some medical staff have been deployed into unfamiliar roles, while others have been exposed to innovative ways of working. The embedded military Trauma and Orthopaedic (T&O) cadre have been integral to this change. Many of these new skills and ways of working learnt will be transferable to deployed environments. Feedback from the T&O military cadre highlighted key areas of learning as changes in T&O services, use of technology, personal protective equipment, redeployment and training. This paper aims to discuss how these changes were implement and how they could be used within future military roles. The T&O cadre played important roles within their NHS trusts and the skills they learnt will broaden their skills and knowledge for future deployments.

Improving outcomes for amputees: The health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees.

AIM: Some amputees are unable to adequately ambulate using conventional socket prosthetics, osseointegrated prosthetics have been described as an alternative strategy in this patient group. This paper aims to assess the effect of osseointegrated prosthetics, commonly simply referred to as osseointegration, in transfemoral amputees on health-related quality of life and cost analysis. METHODS: Two centre analysis of patients receiving transcutaneous femoral osseointegration using The Osseointegration Group of Australia Osseointegration Prosthetic Limb (OGAP-OPL) implant. Retrospective health utility and cost analysis of prospectively collected patient reported health outcome data. Osseointegration cost was compared with the yearly cost of a poorly fitting conventional prosthetic determining cost/Quality Adjusted Life Year. RESULTS: Eighty amputees received osseointegration. Mean age was 39 years (range 20-57) and 66% were male (n = 53). The majority of subjects underwent unilateral (n = 62, 77.5%) rather than bilateral surgery (n = 18, 22.5%). Trauma was the most common indication (n = 59, 74%). Maximum follow up was 10.5-years. Mean preoperative EQ5D HUV in pooled data was 0.64 (SEM 0.025) increasing to 0.73 (0.036) at 5-years and 0.78 (0.051) at 6 years with continued improvement up to 10.5-years. In subgroup analysis those with a starting EQ5D HUV <0.60 reached a cost/QALY of <£30,000 at 5-years postoperatively and show statistically significant improvement in EQ5D HUV. The UK military experience was wholly positive with a mean starting EQ5D HUV of 0.48 (0.017) with significant (p < 0.05) improvement in EQ5D HUV at each time point and a resultant reducing cost/QALY at each time point being £28,616.89 at 5 years. CONCLUSION: There is both a quality of life and financial argument in favour of osseointegration in select patients with above transfemoral amputations. In those unable to mobilise satisfactorily with traditional prostheses and a pre-intervention score of <0.60, a consistent cost effectiveness and quality of life benefit can be seen. Such patients should be considered for osseointegration as these patients reap the maximum benefit and cost effectiveness of the device. This evidence lends strongly to the debate advocating the use of osseointegration through centrally funded resources, including the NHS.

ZD4190: an orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy.

There is evidence that vascular endothelial growth factor (VEGF) contributes to solid tumor growth through the promotion of both angiogenesis and tumor vascular permeability. To abrogate VEGF signaling, we developed a small molecular weight inhibitor of VEGF receptor tyrosine kinase (RTK) activity that was compatible with chronic oral administration. ZD4190, a substituted 4-anilinoquinazoline, is a potent inhibitor of KDR and Flt-1 RTK activity, and VEGF stimulated HUVEC proliferation in vitro. Chronic once-daily oral dosing of ZD4190 to young rats produced a dose-dependent increase in the femoral epiphyseal growth plate area, which may be attributed to the inhibition of VEGF signaling in vivo because vascular invasion of cartilage is a prerequisite to the process of ossification. Once-daily oral dosing of ZD4190 to mice bearing established (approximately 0.5 cm3) human tumor xenografts (breast, lung, prostate, and ovarian) elicited significant antitumor activity and at doses that would not be expected to have any direct antiproliferative effect on tumor cells. Prolonged tumor cytostasis was further demonstrated in a PC-3 xenograft model with 10 weeks of ZD4190 dosing, and upon withdrawal of therapy, tumor growth resumed after a short delay. These observations are entirely consistent with the proposed mode of action. ZD4190 is one of a series of VEGF RTK inhibitors that may have utility in the treatment of a range of histologically diverse solid tumor types.

Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors.

A series of substituted 4-anilinoquinazolines and related compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt and KDR) tyrosine kinase activity. Enzyme screening indicated that a narrow structure-activity relationship (SAR) existed for the bicyclic ring system, with quinazolines, quinolines, and cinnolines having activity and with quinazolines and quinolines generally being preferred. Substitution of the aniline was investigated and clearly indicated that small lipophilic substituents such as halogens or methyl were preferred at the C-4' position. Small substituents such as hydrogen and fluorine are preferred at the C-2' position. Introduction of a hydroxyl group at the meta position of the aniline produced the most potent inhibitors of Flt and KDR tyrosine kinases activity with IC(50) values in the nanomolar range (e.g. 10, 12, 13, 16, and 18). Investigation of the quinazoline C-6 and C-7 positions indicates that a large range of substituents are tolerated at C-7, whereas variation at the C-6 is more restricted. At C-7, neutral, basic, and heteroaromatic side chains led to very potent compounds, as illustrated by the methoxyethoxy derivative 13 (IC(50) < 2 nM). Our inhibitors proved to be very selective inhibitors of Flt and KDR tyrosine kinase activity when compared to that associated with the FGF receptor (50- to 3800-fold). Observed enzyme profiles translated well with respect to potency and selectivity for inhibition of growth factor stimulated proliferation of human umbilical vein endothelial cells (HUVECs). Oral administration of selected compounds to mice produced total plasma levels 6 h after dosing of between 3 and 49 microM. In vivo efficacy was demonstrated in a rat uterine oedema assay where significant activity was achieved at 60 mg/kg with the meta hydroxy anilinoquinazoline 10. Inhibition of growth of human tumors in athymic mice has also been demonstrated: compound 34 inhibited the growth of established Calu-6 lung carcinoma xenograft by 75% (P < 0.001, one tailed t-test) following daily oral administration of 100 mg/kg for 21 days.

Sleep quality in people with HIV disease.

This study examined sleep quality in HIV infected people. The research explored the incidence of the study variables (sleep quality, anxiety, well-being, and symptom severity) and found differences on the variables between subjects who reported HIV infection through male/male sex (n = 18) as compared to injecting drug use (n = 23). The instruments were the Pittsburgh Sleep Quality Index (PSQI), the HIV Assessment Tool (HAT), and the Spielberger State/Trait Anxiety Tool. The average subject (N = 56) was male, 48 years old, a person of color and reported HIV infection through injecting drug use. General well-being was significantly correlated (Pearson product moment correlations) with sleep quality (r = .46, p = .01). Significant differences on the global PSQI (t = 3.22, p = .003) and on the well-being factor of HAT (t = -2.05, p = .04) were found in that injecting drug users reported worse sleep quality and well-being. No significant differences were determined between the two groups on any of the other study variables.

Correlates of sleep quality in persons with HIV disease.

This study used the Symptom Experience dimension of the revised UCSF Symptom Management Conceptual model to examine correlates of sleep quality in HIV-infected persons. According to this model, person, health/illness, and environment categories influence perception of a symptom. The average person in the sample (N = 58) reported being HIV-infected for 8.5 years and was 46 years old, not working, and a person of color. Depending on the level of data, either chi square or Pearson correlations were computed between the person, health/illness, and environment categories and the dependent variable, sleep quality, as measured by the Pittsburgh Sleep Quality Index. Person variables significantly related to sleep quality were employment status, trait anxiety, and general well-being. Health/illness variables significantly related to sleep quality were length of time living with HIV disease and five health status measures (depressive symptoms, state anxiety, symptom severity, daytime sleepiness, and functional status). The environmental variables associated with sleep quality were sleeping alone, having a separate bedroom, and sleeping in a noisy room. Correlates of better sleep quality are positive general well-being, less anxious personality trait and emotional state, less daytime sleepiness, less depressive symptoms, and less symptom severity. Correlates of worse sleep quality are impaired functional status and longer duration of living with HIV disease.

Exploring the complexity of sleep disturbances in persons with HIV/AIDS.

Sleep disturbances are influenced by physiological, psychological, and environmental factors. Many persons living with HIV/AIDS manifest a variety of sleep disorders. Although completion of a brief sleep assessment can be helpful to determine the presence of a sleep problem, more in-depth investigation is necessary when sleep problems are reported. This pilot work used an open-ended interview guide developed from elements of Hauri's comprehensive sleep history. A convenience sample of six HIV-positive clients was interviewed during January 1997. In addition to answering open-ended questions about sleep-wake patterns, participants completed the Pittsburgh Sleep Quality Index and a personal characteristics form. HIV-severity information was obtained from the medical record. A complete sleep evaluation includes a thorough history and physical assessment, with a special focus on underlying pathology and medication use such as over-the-counter drugs, vitamins and herbal products, and mood-altering substance use. Treatment plans can include instruction about a variety of cognitive behavioral strategies. The nurse plays a major role in assessing, evaluating, teaching, and referring, which can contribute to identification of strategies that can improve quality of life.

Alternative/complementary therapies used by persons with HIV disease.

The authors examined the kind of alternative and complementary therapies used by persons with HIV disease. A convenience sample of 145 persons with HIV disease who were receiving health care in either New York City (n = 72) or Boston (n = 73) completed the Alternative Therapies Check List. This instrument consists of 55 alternative or complementary therapies; respondents were asked to identify whether they knew the therapy and how often they used it. Frequencies were computed, demonstrating that all of the identified alternative or complementary therapies were used by at least one person with HIV disease. The different therapies were ranked according to their mean or average use. Findings showed that vitamins were the most commonly used and trigger was the least commonly used alternative/complementary therapy.

Development of an HIV educational needs assessment tool.

The learning needs of persons with HIV/AIDS continue to grow more complex as new treatments are developed and HIV disease shifts from being a terminal to a chronic illness. Clinicians could use a simple tool to help them to focus on what clients think is important to know about living with HIV/AIDS. This article describes the development of the HIV Educational Needs Assessment Tool (HENAT). HIV+ persons (N = 363) who were receiving health care in a variety of ambulatory and institutional settings participated in this research during 1990 and 1993-1994. Factor analysis was used to shorten the instrument into a form that could be used in any nurse/client interaction. Principal axis factor extraction and varimax rotation deleted 16 items. The remaining 34 items were grouped into six factors: Treatments, Entitlements, Relationships, Preventing Infections, Social Support, and Working. Cronbach's alphas were computed and results ranged from .70 to .88. Two month test-retest correlations for a subset of participants (n = 195) ranged from .54 to .67. HENAT can be used (a) to examine differences in perception of learning needs between clients with HIV disease and their health care providers, (b) to measure shifts in learning needs over time, (c) to relate HIV-specific learning needs to length of time living with HIV disease, (d) to give clients an opportunity to assess their learning needs, and (e) as part of a larger intervention study that evaluates the effectiveness of patient education.

Severe open tibial fractures in combat trauma: management and preliminary outcomes.

The aim of this study was to report the pattern of severe open diaphyseal tibial fractures sustained by military personnel, and their orthopaedic-plastic surgical management.The United Kingdom Military Trauma Registry was searched for all such fractures sustained between 2006 and 2010. Data were gathered on demographics, injury, management and preliminary outcome, with 49 patients with 57 severe open tibial fractures identified for in-depth study. The median total number of orthopaedic and plastic surgical procedures per limb was three (2 to 8). Follow-up for 12 months was complete in 52 tibiae (91%), and half the fractures (n = 26) either had united or in the opinion of the treating surgeon were progressing towards union. The relationship between healing without further intervention was examined for multiple variables. Neither the New Injury Severity Score, the method of internal fixation, the requirement for vascularised soft-tissue cover nor the degree of bone loss was associated with poor bony healing. Infection occurred in 12 of 52 tibiae (23%) and was associated with poor bony healing (p = 0.008). This series characterises the complex orthopaedic-plastic surgical management of severe open tibial fractures sustained in combat and defines the importance of aggressive prevention of infection.

A human monoclonal antibody 264RAD targeting αvß6 integrin reduces tumour growth and metastasis, and modulates key biomarkers in vivo.

αvß6 integrin expression is upregulated on a wide range of epithelial tumours, and is thought to play a role in modulating tumour growth. Here we describe a human therapeutic antibody 264RAD, which binds and inhibits αvß6 integrin function. 264RAD cross-reacts with human, mouse and cynomolgus monkey αvß6, and inhibits binding to all ligands including the latency-associated peptide of TGF-ß. Screening across a range of integrins revealed that 264RAD also binds and inhibits the related integrin αvß8, but not the integrins α5ß1, αvß3, αvß5 and α4ß1. In vitro 264RAD inhibited invasion of VB6 and Detroit 562 cells in a Matrigel invasion assay and αvß6 mediated production of matrix metalloproteinase-9 in Calu-3 cells. It inhibited TGF-ß-mediated activation of dermal skin fibroblasts by preventing local activation of TGF-ß by NCI-H358 tumour cells in a tumour cell-fibroblast co-culture assay. In vivo 264RAD showed dose-dependent inhibition of Detroit 562 tumour growth, regressing established tumours when dosed at 20 mg/kg once weekly. The reduction in growth associated with 264RAD was related to a dose-dependent inhibition of Ki67 and phospho-ERK and a reduction of αvß6 expression in the tumour cells, coupled to a reduction in fibronectin and alpha smooth muscle actin expression in stromal fibroblasts. 264RAD also reduced the growth and metastasis of orthotopic 4T1 tumours. At 20 mg/kg growth of both the primary tumour and the number of metastatic deposits in lung were reduced. The data support the conclusion that 264RAD is a potent inhibitor of αvß6 integrin, with some activity against αvß8 integrin, that reduces both tumour growth and metastasis.

The open blast pelvis: the significant burden of management.

The open blast fracture of the pelvis is considered to be the most severe injury within the spectrum of battlefield trauma. We report our experience of 29 consecutive patients who had sustained this injury in Afghanistan between 2008 and 2010. Their median new injury severity score (NISS) was 41 (8 to 75), and mean blood requirement in the first 24 hours was 60.3 units (0 to 224). In addition to their orthopaedic injury, six had an associated vascular injury, seven had a bowel injury, 11 had a genital injury and seven had a bladder injury. In all, eight fractures were managed definitively with external fixation and seven required internal fixation. Of those patients who underwent internal fixation, four required removal of metalwork for infection. Faecal diversion was performed in nine cases. The median length of hospital stay following emergency repatriation to the United Kingdom was 70.5 days (5 to 357) and the mean total operating time was 29.6 hours (5 to 187). At a mean follow-up of 20.3 months (13.2 to 29.9), 24 patients (82.8%) were able to walk and 26 (89.7%) had clinical and radiological evidence of stability of the pelvic ring. As a result of the increase in terrorism, injuries that were previously confined exclusively to warfare can now occur anywhere, with civilian surgeons who are involved in trauma care potentially required to manage similar injuries. Our study demonstrates that the management of this injury pattern demands huge resources and significant multidisciplinary input. Given the nature of the soft-tissue injury, we would advocate external fixation as the preferred management of these fractures. With the advent of emerging wound and faecal management techniques, we do not believe that faecal diversion is necessary in all cases.

Modern military surgery: lessons from Iraq and Afghanistan.

The types of explosive devices used in warfare and the pattern of war wounds have changed in recent years. There has, for instance, been a considerable increase in high amputation of the lower limb and unsalvageable leg injuries combined with pelvic trauma. The conflicts in Iraq and Afghanistan prompted the Department of Military Surgery and Trauma in the United Kingdom to establish working groups to promote the development of best practice and act as a focus for research. In this review, we present lessons learnt in the initial care of military personnel sustaining major orthopaedic trauma in the Middle East.