An investigation of the effects of procalcitonin testing on antimicrobial prescribing in respiratory tract infections in an Irish university hospital setting: a feasibility study.

BACKGROUND: Diagnostic uncertainty and a high prevalence of viral infections present unique challenges for antimicrobial prescribing for respiratory tract infections (RTIs). Procalcitonin (PCT) has been shown to support prescribing decisions and reduce antimicrobial use safely in patients with RTIs, but recent study results have been variable. METHODS: We conducted a feasibility study of the introduction of PCT testing in patients admitted to hospital with a lower RTI to determine if PCT testing is an effective and worthwhile intervention to introduce to support the existing antimicrobial stewardship (AMS) programme and safely decrease antimicrobial prescribing in patients admitted with RTIs. RESULTS: A total of 79 patients were randomized to the intervention PCT-guided treatment group and 40 patients to the standard care respiratory control group. The addition of PCT testing led to a significant decrease in duration of antimicrobial prescriptions (mean 6.8 versus 8.9 days, P = 0.012) and decreased length of hospital stay (median 7 versus 8 days, P = 0.009) between the PCT and respiratory control group. PCT did not demonstrate a significant reduction in antimicrobial consumption when measured as DDDs and days of therapy. CONCLUSIONS: PCT testing had a positive effect on antimicrobial prescribing during this feasibility study. The successful implementation of PCT testing in a randomized controlled trial requires an ongoing comprehensive education programme, greater integration into the AMS programme and delivery of PCT results in a timely manner. This feasibility study has shown that a larger randomized controlled trial would be beneficial to further explore the positive aspects of these findings.

Cost-effectiveness of an Adjuvanted Recombinant Zoster Vaccine in older adults in the United States.

In the United States, herpes zoster (HZ) and related complications are estimated to result in approximately $1.3 billion in medical care costs and $1.7 billion in indirect costs annually. In this study, we compared the cost-effectiveness of a new Adjuvanted Recombinant Zoster Vaccine (RZV), containing recombinant varicella-zoster virus glycoprotein E and the AS01B Adjuvant System, versus No Vaccine, as well as versus the live attenuated HZ vaccine (Zoster Vaccine Live (ZVL)) in subjects aged 60+ years of age (YOA) and other age cohorts aged 50+ YOA. A multi-cohort Markov model was developed which follows 1 million individuals over their remaining lifetimes from the year of vaccination with annual cycle lengths. Second dose compliance for RZV was assumed to be 69%. Efficacy and waning parameters were derived from clinical trials for both vaccines. Epidemiological parameters, costs and utility model inputs were derived from US-specific population-based data. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analysis, along with scenario and threshold analysis were carried out to explore the overall uncertainty in the model. The model estimated that, compared to No Vaccine against HZ, RZV would prevent 103,603 HZ cases, 11,197 postherpetic neuralgia (PHN) cases, and 14,455 other complications, at an incremental cost of $11,863 per quality-adjusted life-year saved from a societal perspective. Compared to ZVL, the model estimated that, RZV would prevent 71,638 additional HZ cases, 6403 PHN cases, and over 10,582 other complications, resulting in net total societal cost savings of over $96 million. The results were robust to a wide range of sensitivity analyses. Vaccination against HZ with RZV is cost-effective compared to No Vaccine and cost-saving compared to ZVL, in the US population aged 60+ YOA. Clinicaltrial.gov. registered#: NA.

Increasing incidence of chronic subdural haematoma in the elderly.

BACKGROUND: Chronic subdural haematoma (CSDH) is a condition predominantly affecting the elderly. We reported an incidence of 8.2 per 100 000 per year in people above the age of 65 in 2002. AIM: Since recent studies have demonstrated a higher incidence, we repeated our study to estimate the current incidence of CSDH amongst people above the age of 65 in North Wales. DESIGN: We used radiological reports to identify patients with CSDH over a 1-year period. METHODS: We collected data on demographics, clinical presentations, indications for brain imaging, drug history and 30-day outcome from the case notes and electronic records. RESULTS: The population of North Wales was 687 937 of which 138 325 (20%) were above 65. There were 66 cases of CSDH giving an incidence of 48 per 100 000 per year. Mean age was 81 and there were 32 males and 34 females. Falls and confusion were the commonest indications to request a CT scan (90%). Other indications were drowsiness (9%) and focal neurological deficit (4%). 17 were on antiplatelets and 20 were on warfarin. Ten underwent surgical intervention. At 30 days 28 were discharged, 22 were still in hospital and 16 died. CONCLUSION: The incidence of CSDH is much higher than previously reported. Reasons include a low threshold for imaging patients with recurrent falls and confusion, increasing use of anti-thrombotics and ageing population. In many older patients CSDH is a marker of underlying co-morbidities rather than a primary event.

Severe arthritis predicts greater improvements in function following total knee arthroplasty.

PURPOSE: Although excellent outcomes are routinely reported following total knee replacement, up to 20 % of patients remain dissatisfied. The aim of this study was to determine whether pre-operative radiographic classification was associated with functional outcomes following surgery. METHODS: A retrospective review of a prospective arthroplasty database identified 256 patients that fulfilled the inclusion criteria over an 18-month period. Baseline demographic data on all patients were collected prospectively. All pre-operative radiographs were assessed using the Kellgren and Lawrence (K&L) classification system. Patients were prospectively assessed using the American Knee Society Score pre-operatively and at 1, 3 and 5 years post-surgery. RESULTS: An association was found between the pre-operative radiographic severity of arthritis and the pre-operative American Knee Society Knee (AKSK) scores, with worsening radiographic grade corresponding to worsening AKSK scores (p = 0.020). There was an association between K&L classification and improvement in AKSK scores from pre-operative to 1 year (p = 0.003) and 3 years (p = 0.04), with K&L grades 3 and 4 demonstrating the most significant improvements. On multivariate regression analysis, K&L classification was the only significant predictor of improvement in AKSK at 1 year (p = 0.009). No correlation was found between K&L grade and the American Knee Society Functional Scores at any stage. CONCLUSIONS: The results of this study may help to improve satisfaction rates in total knee replacement by targeting treatment. Patients can be counselled that although radiographic severity of arthritic changes can predict knee-specific functional improvement, the extent of their global functional improvement cannot. LEVEL OF EVIDENCE: IV.

Decompressive hemicraniectomy following malignant middle cerebral artery infarctions: a mixed methods exploration of carer experience and level of burden.

PURPOSE: This study explores the experiences and sense of burden of family carers of survivors of malignant middle cerebral artery infarctions who had undergone decompressive hemicraniectomy. To date, there have been no studies examining carer outcomes among this unique population. This study, taken alongside an already published study of survivor outcomes, provides a more holistic picture with regard to sequelae within the sample. METHOD: Six family carers completed the Sense of Competence Questionnaire and the Hospital Anxiety and Depression Scale. These results were compared with existing normative data. Carers also consented to a semi-structured interview. Interview data were examined using thematic content analysis. Consistent with the mixed methods design, quantitative and qualitative findings were integrated for further analysis. RESULTS: While carers experienced many losses, their overall sense of burden was not outside 'Average' limits, nor did they experience clinically significant symptoms of depression. All carers identified methods of coping with the demands of caregiving. These included intrapersonal, interpersonal and practical strategies. All carers apart from one were able to identify areas of post-traumatic growth. CONCLUSION: Carers will benefit from information, support and care. In addition, problem solving skills are essential in managing the myriad difficulties that arise in the aftermath of stroke.

COPD exacerbations -- a comparison of Irish data with European data from the ERS COPD Audit.

The European Respiratory Society COPD audit was a cross-sectional, multicentre study that analysed outcomes for COPD patients admitted to hospital with an exacerbation across Europe. We present the data on patients admitted to 11 Irish hospitals that participated in the audit. Among 237 patients (123 Male), the median age was 71 years and 79 (33%) patients were current smokers. 82 (35%) patients received high-flow oxygen before admission and 43 (18%) were cared for in a dedicated respiratory ward. 54 (23%) patients required ventilatory support. Median length of stay was 7 days, 98 (41%) patients were readmitted and 211 (89%) patients were alive at the 90 day follow up point. Irish patients were more likely to receive high-flow oxygen before admission, less likely to be managed in a dedicated respiratory ward and had a higher likelihood of readmission or death within 90 days than the European average.

The intensity of QuantiFERON TB-gold response does not differentiate active from latent tuberculosis.

We analyzed positive QuantiFERON (QFT) assays, performed between July 2009 and April 2011 in the Mercy University Hospital, Cork, Ireland, which included, 94 patients with latent tuberculosis (LTBI) and 35 patients with active tuberculosis. There was no difference in the intensity of response between patients with LTBI and active tuberculosis (p = 0.1589). In patients with LTBI, there were no correlations between age (p = 0.353), sex (p = 0.476), smoking (p = 0.323), contact (p = 0.612), Mantoux response (p = 0.055), Irish nationality (p=0.768), previous BCG vaccination (p = 0.504), WCC (p = 0.187), lymphocyte count (p = 0.786), neutrophil count (p = 0.157) and the intensity of QFT response. Similarly in patients with active TB, there were no correlations between these variables and QFT response. The intensity of QFT response does not help to differentiate active from LTBI. The intensity of QFT response is not influenced by age, sex, smoking, remoteness of contact history, Mantoux response, nationality, CXR abnormalities, BCG vaccination and peripheral lymphocyte count.

An unusual cause of a pain in the neck: pseudoaneurysm from tuberculous lymphadenitis.

A pseudoaneurysm is a haematoma which is surrounded by connective tissue and communicates with the lumen of a ruptured blood vessel. It has no true defined capsule. We describe a case of tuberculous pseudoaneurysm. This is a rare complication of tuberculosis. The clinical presentation of these lesions is highly variable. Definitive diagnosis should consist of contrast-enhanced CT and arteriography. Treatment should include repair of the arterial wall by surgery, endovascular stent-graft insertion, or embolization followed by a full course of antituberculous chemotherapy. Our case is highly unusual in that the pseudoaneurysm arose from the subclavian vasculature in a patient with extrapulmonary tuberculosis only.

Emerging anticoagulants.

Warfarin, heparin and their derivatives have been the traditional anticoagulants used for prophylaxis and treatment of venous thromboembolism. While the modern clinician is familiar with the efficacy and pharmacokinetics of these agents, their adverse effects have provided the impetus for the development of newer anticoagulants with improved safety, ease of administration, more predictable pharmacodynamics and comparable efficacy. Research into haemostasis and the coagulation cascade has made the development of these newer anticoagulants possible. These drugs include the factor Xa inhibitors and IIa (thrombin) inhibitors. Direct and indirect factor Xa inhibitors are being developed with a relative rapid onset of action and stable pharmacokinetic profiles negating the need for close monitoring; this potentially makes them a more attractive option than heparin or warfarin. Examples of direct factor Xa inhibitors include apixaban, rivaroxaban, otamixaban, betrixaban and edoxaban. Examples of indirect factor Xa inhibitors include fondaparinux, idraparinux and idrabiotaparinux. Direct thrombin inhibitors (factor IIa inhibitors) were developed with the limitations of standard heparin and warfarin in mind. Examples include recombinant hirudin (lepirudin), bivalirudin, ximelagatran, argatroban, and dabigatran etexilate. This review will discuss emerging novel anticoagulants and their use for the prophylaxis and management of venous thromboembolism, for stroke prevention in nonvalvular atrial fibrillation and for coronary artery disease.

Long-term neuropsychological and psychosocial outcomes of decompressive hemicraniectomy following malignant middle cerebral artery infarctions.

PURPOSE: This study examines long-term neuropsychological and psychosocial outcomes of survivors of malignant middle cerebral artery infarction treated via decompressive hemicraniectomy. METHOD: A case series design facilitated a detailed analysis of the outcomes among five participants. Neuropsychological domains assessed included premorbid and current IQ, sustained, selective and divided attention, visual and auditory memory, executive functioning and visuo-spatial ability. Psychosocial domains assessed included self-rated depression, anxiety and quality of life. Participants and their main carer were asked about their retrospective view of surgery. RESULTS: All participants showed neuropsychological impairments in multiple cognitive domains, with preserved ability in others. Effects of laterality of brain function were evident in some domains. Clinically significant depression was evident in two participants. Overall quality of life was within average limits in three of four assessed participants. Four participants retrospectively considered surgery as having been a favourable course of action. CONCLUSION: While neuropsychological impairments are highly likely post-surgery, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life. Results do not support the suggestion that decompressive hemicraniectomy following malignant middle cerebral artery infarction necessarily leads to unacceptable neuropsychological or psychosocial outcomes. [ IMPLICATIONS FOR REHABILITATION: • Malignant middle cerebral artery infarction is a life threatening condition.• The neurosurgical procedure, "decompressive hemicraniectomy" has been shown to be life-saving among patients with this condition.• There is little known about the long-term neuropsychological and psychosocial outcomes following decompressive hemicraniectomy for malignant middle cerebral artery infarction.• This study concludes that neuropsychological impairments are highly probable post-surgery. However, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life.]

Novel agents in the management of lung cancer.

Lung cancer is the leading cause of cancer death worldwide. Survival remains poor as approximately 80% of cases present with advanced stage disease. However, new treatments are emerging which offer hope to patients with advanced disease. Insights into cell biology have identified numerous intracellular and extracellular peptides that are pivotal in cancer cell signalling. Disrupting the function of these peptides inhibits intracellular signal transduction and diminishes uncontrolled proliferation, resistance to apoptosis and tumour angiogenesis. The most widely studied signalling pathway is the Epidermal Growth Factor (EGF) pathway. EGF signalling can be disrupted at numerous points. Blockade of the cell surface receptor is achieved by the monoclonal antibody cetuximab; intracellular tyrosine kinase activity is inhibited by erlotinib. Vascular Endothelial Growth Factor (VEGF) regulates another pathway important for tumour growth. Inhibition of VEGF impairs angiogenesis and disrupts metastatic spread. Bevacizumab is a monoclonal antibody that binds to VEGF and blocks interaction with its cell surface receptor. Clinical trials have demonstrated that disruption of these signalling pathways can improve survival in advanced lung cancer. New compounds including folate antimetabolites such as pemetrexed, proteasome inhibitors such as bortezomib, modified glutathione analogues such as TLK286, and other agents such as epothilones and other small molecules are currently being evaluated in patients with lung cancer. As more and more signalling peptides are targeted for manipulation, it is hoped that a new era is dawning in the treatment of advanced stage lung cancer. This review will focus on emerging new therapies in the management of lung cancer.

Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: A phase III trial demonstrated that cetuximab is the first agent in 30 years to improve survival when added to platinum-based chemotherapy (platinum-fluorouracil) first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). This analysis of the trial assessed the impact of treatment on quality of life (QoL). PATIENTS AND METHODS: The European Organisation for Research and Treatment of Cancer QoL Questionnaire-Core 30 (QLQ-C30) and QLQ-Head and Neck 35 (QLQ-H&N35) module were used to assess QoL. RESULTS: Of 442 patients randomly assigned, 291 (QLQ-C30) and 289 (QLQ-H&N35) patients completed at least one evaluable questionnaire. For QLQ-C30, cycle 3 and month 6 mean scores for platinum-fluorouracil plus cetuximab were not significantly worse than those for platinum-fluorouracil. Pattern-mixture analysis demonstrated a significant improvement in the global health status/QoL score in the cetuximab arm (P = 0.0415) but no treatment differences in the social functioning scale. For QLQ-H&N35, the mean score for the cetuximab arm was not significantly worse than that for the chemotherapy arm for all symptom scales at all post-baseline visits. At cycle 3, some symptom scores significantly favored the cetuximab arm (pain, swallowing, speech problems, and social eating). CONCLUSION: Adding cetuximab to platinum-fluorouracil does not adversely affect the QoL of patients with recurrent and/or metastatic SCCHN.

Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

IMPORTANCE OF THE FIELD: The macrolides are a class of antibiotics widely prescribed in infectious disease. More recently, there has been considerable interest in potential indications for these agents, in addition to their simple antibacterial indications, in a number of lung pathophysiologies. AREAS COVERED IN THIS REVIEW: Demonstrated clinical efficacy of macrolides in diseases such as diffuse panbronchiolitis was difficult to ascribe to a direct antimicrobial action. More recently, positive experiences in dealing with post-transplant bronchiolitis obliterans syndrome suggests that other chronic lung diseases may benefit from macrolide therapy. This is important, as the treatment options for such diseases are often very limited. In this review, potential antibiotic and non-antibiotic beneficial actions of macrolide therapy are discussed and conclusions drawn from a limited but growing literature. WHAT THE READER WILL GAIN: The reader will gain an overview of lung diseases that may benefit from macrolides, and a consideration of the possible mechanisms underlying such benefit. TAKE HOME MESSAGE: The key message from our review is that this class of agents may prove to be a useful therapeutic option for a range of respiratory diseases, but that further trials and mechanistic studies are required to clarify their role.

Characterisation and mechanical testing of hydrothermally treated HA/ZrO2 composites.

Hydrothermal treatment is traditionally employed to improve the sinterability of powder compacts by reducing porosity and increasing apparent density. The effect of hydrothermal treatment on green powder compacts has been assessed in order to better understand how treatment may affect the sinterability of the bodies. Laboratory synthesised nano sized hydroxyapatite (HA) and a commercial zirconia (ZrO(2)) powder have been ball milled together to create composite mixtures containing 0-5 wt% ZrO(2) loadings. Disc shaped bodies have been formed using uniaxial and subsequent isostatic pressure. The resultant coherent samples were subjected to hydrothermal treatment at either 120 or 250 degrees C for 10 h in order to assess the effect of this processing technique on the physical, mechanical and microstructural properties of the green composites. ZrO(2) loadings up to 3 wt% increased apparent density from 90 to 92%, whereas increased loading to 5 wt% increased flexural strength, from 6 to 9 MPa. Increasing the hydrothermal treatment temperature increased open porosity, from ~44 to ~48% and reduced biaxial flexural strengths of the treated bodies compared to those of their room temperature isostatically pressed counterparts (~10 to ~6 MPa).

A secure web-based approach for accessing transitional health information for people with traumatic brain injury.

A web-based transitional health record was created to provide regional healthcare professionals with ubiquitous access to information on people with brain injuries as they move through the healthcare system. Participants included public, private, and community healthcare organizations/providers in Eastern Ontario (Canada). One hundred and nineteen service providers and 39 brain injury survivors registered over 6 months. Fifty-eight percent received English and 42% received bilingual services (English-French). Public health providers contacted the regional service coordinator more than private providers (52% urban centres, 26% rural service providers, and 22% both areas). Thirty-five percent of contacts were for technical difficulties, 32% registration inquiries, 21% forms and processes, 6% resources, and 6% education. Seventeen technical enquiries required action by technical support personnel: 41% digital certificates, 29% web forms, and 12% log-in. This web-based approach to clinical information sharing provided access to relevant data as clients moved through or re-entered the health system. Improvements include automated digital certificate management, institutional health records system integration, and more referral tracking tools. More sensitive test data could be accessed on-line with increasing consumer/clinician confidence. In addition to a strong technical infrastructure, human resource issues are a major information security component and require continuing attention to ensure a viable on-line information environment.

Effect of 4-aminopyridine on gait in ambulatory spinal cord injuries: a double-blind, placebo-controlled, crossover trial.

UNLABELLED: Animal and human research have shown that the drug 4-aminopyridine (4-AP) may improve gait in spinal cord lesions by enhancing nerve transmission to affected muscles. STUDY DESIGN: Prospective, randomized, double-blind, placebo-controlled, crossover trial. OBJECTIVES: To determine the efficacy of 4-AP in improving lower limb muscle strength and biomechanical gait patterns of chronic spinal cord injuries (SCI). SETTING: The Rehabilitation Centre (Ottawa, Canada). METHODS: In all, 15 chronic, ambulatory SCI persons were randomized to an initial 2 weeks of 40 mg/day, oral medication of either placebo or immediate-release, 4-AP and subsequently crossed over to the alternate medication for the following 2 weeks. Evaluations were conducted at baseline (before starting 4-AP or placebo medication), 2 weeks, and 4 weeks. Measures included dynamometer lower limb isometric muscle force and biomechanical gait measures including temporal-spatial parameters, electromyographic activation patterns, joint kinematics and kinetics. Subjective impressions of the drug by the participants were obtained from an exit survey. RESULTS: Despite some positive comments from subjects, statistical and clinical analyses showed no within-subject differences between placebo and 4-AP measures of lower limb muscle force and objective gait analyses (ANOVA statistic P>0.05). CONCLUSION: Results demonstrated the importance of placebo-controlled trials and quantitative outcome measures for the evaluation of 4-AP aimed to enhance gait for chronic, ambulatory SCI persons. Energy expenditure measures and mood may relate more to subjective comments and is suggested for future investigations.