Correcting for bias when estimating the cost of hospital-acquired infection : an analysis of lower respiratory tract infections in non-surgical patients

Hospital acquired infections (HAI) are costly but many are avoidable. Evaluating prevention programmes requires data on their costs and benefits. Estimating the actual costs of HAI (a measure of the cost savings due to prevention) is difficult as HAI changes cost by extending patient length of stay, yet, length of stay is a major risk factor for HAI. This endogeneity bias can confound attempts to measure accurately the cost of HAI. We propose a two-stage instrumental variables estimation strategy that explicitly controls for the endogeneity between risk of HAI and length of stay. We find that a 10% reduction in ex ante risk of HAI results in an expected savings of £693 ($US 984).

A review of non-traditional occupational therapy practice placement education : a focus on role-emerging and project placements

Practice placement education has been recognised as an integral and critical component of the training of occupational therapy students. Although there is an extensive body of literature on clinical education and traditional practice placement education models, there has been limited research on alternative placements.-------- This paper reviews the literature on various practice placement education models and presents a contemporary view on how it is currently delivered. The literature is examined with a particular focus on the increasing range of practice placement education opportunities, such as project and role-emerging placements. The drivers for non-traditional practice placement education include shortages of traditional placement options, health reform and changing work practices, potential for role development and influence on practice choice. The benefits and challenges of non-traditional practice placement education are discussed, including supervision issues, student evaluation, professional and personal development and the opportunity to practise clinical skills.--------- Further research is recommended to investigate occupational therapy graduates' perceptions of role-emerging and project placements in order to identify the benefits or otherwise of these placements and to contribute to the limited body of knowledge of emerging education opportunities.

Periodontal regeneration and mesenchymal stem cells

The ultimate goal of periodontal therapy is to regenerate periodontal supporting tissues, but this is hard to achieve as the results of periodontal techniques for regeneration are clinically unpredictable. Stem cells owing to their plasticity and proliferation potential provides a new paradigm for periodontal regeneration. Stem cells from mesenchyme can self renew and generate new dental tissues (including dentin and cementum), alveolar bone and periodontal ligament, and thus they have great potential in periodontal regeneration. This chapter presents an insight into mesenchymal stem cells and their potential use in periodontal regeneration. In this chapter the cellular and molecular biology in periodontal regeneration will be introduced, followed by a range of conventional surgical procedures for periodontal regeneration will be discussed. Mesenchymal stem cells applied in regenerated periodontal tissue and their biological characterizations in vitro will be also introduced. Lastly, the use of mesenchymal stem cell to repair periodontal tissues in large animal models will be also reviewed.

Silicate-based bioceramics for periodontal regeneration

Periodontal disease is characterized by the destruction of the tissues that attach the tooth to the alveolar bone. Various methods for regenerative periodontal therapy including the use of barrier membranes, bone replacement grafts, and growth factor delivery have been investigated; however, true regeneration of periodontal tissue is still a significant challenge to scientists and clinicians. The focus on periodontal tissue engineering has shifted from attempting to recreate tissue replacements/constructs to the development of biomaterials that incorporate and release regulatory signals to achieve in situ periodontal regeneration. The release of ions and molecular cues from biomaterials may help to unlock latent regenerative potential in the body by regulating cell proliferation and differentiation towards different lineages (e.g. osteoblasts and cementoblasts). Silicate-based bioactive materials, including bioactive silicate glasses and ceramics, have become the materials of choice for periodontal regeneration, due to their favourable osteoconductivity and bioactivity. This article will focus on the most recent advances in the in vitro and in vivo biological application of silicate-based ceramics, specifically as it relates to periodontal tissue engineering.

A comparative study of the proliferation and osteogenic differentiation of human periodontal ligament cells cultured on β-TCP ceramics and demineralized bone matrix with or without osteogenic inducers in vitro

The repair of bone defects that result from periodontal diseases remains a clinical challenge for periodontal therapy. β-tricalcium phosphate (β-TCP) ceramics are biodegradable inorganic bone substitutes with inorganic components that are similar to those of bone. Demineralized bone matrix (DBM) is an acid-extracted organic matrix derived from bone sources that consists of the collagen and matrix proteins of bone. A few studies have documented the effects of DBM on the proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The aim of the present study was to investigate the effects of inorganic and organic elements of bone on the proliferation and osteogenic differentiation of hPDLCs using three-dimensional porous β-TCP ceramics and DBM with or without osteogenic inducers. Primary hPDLCs were isolated from human periodontal ligaments. The proliferation of the hPDLCs on the scaffolds in the growth culture medium was examined using a Cell‑Counting kit‑8 (CCK-8) and scanning electron microscopy (SEM). Alkaline phosphatase (ALP) activity and the osteogenic differentiation of the hPDLCs cultured on the β-TCP ceramics and DBM were examined in both the growth culture medium and osteogenic culture medium. Specific osteogenic differentiation markers were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SEM images revealed that the cells on the β-TCP were spindle-shaped and much more spread out compared with the cells on the DBM surfaces. There were no significant differences observed in cell proliferation between the β-TCP ceramics and the DBM scaffolds. Compared with the cells that were cultured on β-TCP ceramics, the ALP activity, as well as the Runx2 and osteocalcin (OCN) mRNA levels in the hPDLCs cultured on DBM were significantly enhanced both in the growth culture medium and the osteogenic culture medium. The organic elements of bone may exhibit greater osteogenic differentiation effects on hPDLCs than the inorganic elements.

Molecular classification of cutaneous malignant melanoma by gene expression profiling

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

Applications of medical image processing in the diagnosis and treatment of spinal deformity

In Chapter 10, Adam and Dougherty describe the application of medical image processing to the assessment and treatment of spinal deformity, with a focus on the surgical treatment of idiopathic scoliosis. The natural history of spinal deformity and current approaches to surgical and non-surgical treatment are briefly described, followed by an overview of current clinically used imaging modalities. The key metrics currently used to assess the severity and progression of spinal deformities from medical images are presented, followed by a discussion of the errors and uncertainties involved in manual measurements. This provides the context for an analysis of automated and semi-automated image processing approaches to measure spinal curve shape and severity in two and three dimensions.

Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations : pilot study

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.

Physical activity amongst people with chronic back pain : an investigation of perceived barriers and facilitators to inform intervention development

Previous research has indicated people with non-specific low back pain who are physically inactive face a poorer prognosis than people with back pain who participate in low or moderate intensity physical activity. They also face a greater risk of other lifestyle related health conditions, such as diabetes and heart disease. For these reasons, contemporary non-surgical interventions for low back pain aim to incorporate a return to physical activity. However, there is a lack of empirical evidence supporting physical activity interventions for this purpose. It is likely that people with low back pain face additional challenges when trying to commence (or return to) regular physical activity. This exploratory qualitative research aimed to map out perceived barriers and facilitators to undertaking physical activity among people with non-specific low back pain to inform future intervention development.

Interventions for increasing ankle joint dorsiflexion : a systematic review and meta-analysis

BACKGROUND: Ankle joint equinus, or restricted dorsiflexion range of motion (ROM), has been linked to a range of pathologies of relevance to clinical practitioners. This systematic review and meta-analysis investigated the effects of conservative interventions on ankle joint ROM in healthy individuals and athletic populations. METHODS: Keyword searches of Embase Medline Cochrane and CINAHL databases were performed with the final search being run in August 2013. Studies were eligible for inclusion if they assessed the effect of a non-surgical intervention on ankle joint dorsiflexion in healthy populations. Studies were quality rated using a standard quality assessment scale. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and results were pooled where study methods were homogenous. RESULTS: Twenty-three studies met eligibility criteria, with a total of 734 study participants. Results suggest that there is some evidence to support the efficacy of static stretching alone (SMDs: range 0.70 to 1.69) and static stretching in combination with ultrasound (SMDs: range 0.91 to 0.95), diathermy (SMD 1.12), diathermy and ice (SMD 1.16), heel raise exercises (SMDs: range 0.70 to 0.77), superficial moist heat (SMDs: range 0.65 to 0.84) and warm up (SMD 0.87) in improving ankle joint dorsiflexion ROM. CONCLUSIONS: Some evidence exists to support the efficacy of stretching alone and stretching in combination with other therapies in increasing ankle joint ROM in healthy individuals. There is a paucity of quality evidence to support the efficacy of other non-surgical interventions, thus further research in this area is warranted.

Obesity and comorbid risk factors for cardiovascular disease among physically inactive patients with musculoskeletal disorders : a targeted intervention for this priority patient group is warranted

Introduction The benefits of physical activity are established and numerous; not the least of which is reduced risk of negative cardiovascular events. While sedentary lifestyles are having negative impacts across populations, people with musculoskeletal disorders may face additional challenges to becoming physically active. Unfortunately, interventions in ambulatory hospital clinics for people with musculoskeletal disorders primarily focus on their presenting musculoskeletal complaint with cursory attention given to lifestyle risk factors; including physical inactivity. This missed opportunity is likely to have both personal costs for patients and economic costs for downstream healthcare funders. Objectives The objective of this study was to investigate the presence of obesity, diabetes, diagnosed cardiac conditions, and previous stroke (CVA) among insufficiently physically active patients accessing (non-surgical) ambulatory hospital clinics for musculoskeletal disorders to indicate whether a targeted risk-reducing intervention is warranted. Methods A sub-group analysis of patients (n=110) who self-reported undertaking insufficient physical activity level to meet national (Australian) minimum recommended guidelines was conducted. Responses to the Active Australia Survey were used to identify insufficiently active patients from a larger cohort study being undertaken across three (non-surgical) ambulatory hospital clinics for musculoskeletal disorders. Outcomes of interest included body mass index, Type-II diabetes, diagnosed cardiac conditions, previous CVA and patients’ current health-related quality of life (Euroqol-5D). Results The mean (standard deviation) age of inactive patients was 56 (14) years. Body mass index values indicated that n=80 (73%) were overweight n=26 (24%), or obese n=45 (49%). In addition to their presenting condition, a substantial number of patients reported comorbid diabetes n=23 (21%), hypertension n=25 (23%) or an existing heart condition n=14 (13%); 4 (3%) had previously experienced a CVA as well as other comorbid conditions. Health-related quality of life was also substantially impacted, with a mean (standard deviation) multi-attribute utility score of 0.51 (0.32). Conclusion A range of health conditions and risk factors for further negative health events, including cardiovascular complications, consistent with physically inactive lifestyles were evident. A targeted risk-reducing intervention is warranted for this high risk clinical group.

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Pathogenesis of Fallopian tube damage caused by Chlamydia trachomatis infections

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide resulting in 4–5 million new cases of Chlamydia annually and an estimated 100 million cases per annum. Infections of the lower female genital tract (FGT) frequently are asymptomatic so they often remain undiagnosed or untreated. If infections are either not resolved, or are left untreated, chlamydia can ascend to the upper FGT and infect the fallopian tubes (FTs) causing salpingitis that may lead to functional damage of the FTs and tubal factor infertility (TFI). Clinical observations and experimental data have indicated a role for antibodies against C. trachomatis proteins such as the 60 kDa heat-shock protein 60 (cHSP60) in the immunopathogenesis of TFI. When released from infected cells cHSP60 can induce pro-inflammatory immune responses that may functionally impair the FTs leading to fibrosis and luminal occlusion. Chlamydial pathogenesis of irreversible and permanent tubal damage is a consequence of innate and adaptive host immune responses to ongoing or repeated infections. The extracellular matrix (ECM) that is regulated by metalloproteinases (MMPs) may also be modified by chlamydial infections of the FGT. This review will highlight protective and pathogenic immune responses to ongoing and repeated chlamydial infections of the FGT. It will also present two recent hypotheses to explain mechanisms that may contribute to FT damage during a C. trachomatis infection. If Chlamydia immunopathology can be controlled it might yield a method of inducing fibrosis and thus provide a means of non-surgical permanent contraception for women.

Tarsal tunnel syndrome: A narrative literature review

Background Tarsal tunnel syndrome is classified as a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches individually or collectively. The tunnel courses deep to fascia, the flexor retinaculum and within the abductor hallucis muscle of the foot/ankle. The condition is rare and regularly under-diagnosed leading to a range of symptoms affecting the plantar margins of the foot. There are many intervention strategies for treating tarsal tunnel syndrome with limited robust evidence to guide the clinical management of this condition. The role of conservative versus surgical interventions at various stages of the disease process remains unclear, and there is a need for a structured, step-wise approach in treating patients with this syndrome based on derived empirical evidence. This narrative review attempts to scrutinize the literature to date by clarifying initial presentation, investigations and definitive treatment for the purpose of assisting future informed clinical decision and prospective research endeavours. Process The literature searches that have been incorporated in compiling a rigorous review of this condition have included: the Cochrane Neuromuscular Group's Specialized Register (Cochrane Library 2013), the databases of EMBASE, AMED, MEDLINE, CINAHL, Physiotherapy evidence database (PEDRO), Biomed Central, Science Direct and Trip Database (1972 to the present). Reference listings of located articles were also searched and scrutinized. Authors and experts within the field of lower-limb orthopaedics were contacted to discuss applicable data. Subject-specific criteria searches utilizing the following key terms were performed across all databases: tarsal tunnel syndrome, tibial neuralgia, compression neuropathy syndromes, tibial nerve impingement, tarsal tunnel neuropathy, entrapment tibial nerve, posterior tibial neuropathy. These search strategies were modified with differing databases, adopting specific sensitivity-searching tools and functions unique to each. This search strategy identified 88 journal articles of relevance for this narrative literature review. Findings This literature review has appraised the clinical significance of tarsal tunnel syndrome, whilst assessing varied management interventions (non-surgical and surgical) for the treatment of this condition in both adults and children. According to our review, there is limited high-level robust evidence to guide and refine the clinical management of tarsal tunnel syndrome. Requirements for small-scaled randomized controlled trials in groups with homogenous aetiology are needed to analyse the effectiveness of specific treatment modalities. Conclusions It is necessary that further research endeavours be pursued for the clinical understanding, assessment and treatment of tarsal tunnel syndrome. Accordingly, a structured approach to managing patients who have been correctly diagnosed with this condition should be formulated on the basis of empirical evidence where possible.