bluuebunny/crossref_metadata_2025 huggingface dataset:
A cohort description and analysis of the effect of gabapentin on idiopathic cough
Authors: Van de Kerkhove Charlotte , Goeminne Pieter C , Van Bleyenbergh Pascal , Dupont Lieven J
Published: November 2012

Background

Chronic idiopathic cough (known as cough hypersensitivity syndrome) is defined by cough in the absence of an identifiable cause. Gabapentin has been suggested as a treatment but evidence is scarce. The aim of our study was to describe the clinical features of patients with unexplained chronic cough and to investigate the effect of gabapentin (600 mg twice a day for a minimal duration of 4 weeks) in reducing cough symptoms.

Methods

A patient cohort analysis was performed. Patients were retrieved using a query in our medical database for the words ‘cough’ and ‘gabapentin’ in 2011. Patients without a clear etiology of cough despite having performed a stepwise diagnostic approach, were included. Medical records of these patients were analyzed. A telephonic survey was performed and patients were asked to retrospectivally rate their cough when they attended the outpatient clinic. They were then asked to rate their cough after treatment with gabapentin. A scale from one to ten was used to score cough severity. They were also questioned about the triggers inducing cough. To evaluate the cough severity score, the results were correlated with questions of the Leicester Cough Questionnaire.

Results

We recruited 51 patients (87% female) with a mean age of onset of 47 years (± 14 y) and an average cough duration of 48 months. The most frequently reported cough triggers included change of temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge to cough was located in the throat area. Thirty-five patients effectively took the prescribed gabapentin. The average improvement in cough score was 2.8/10 (p<0.0001). Of the 35 patients, 20 achieved improvement of their cough symptoms. Responders had a higher pre-treatment cough severity score (p=0.02) and were more likely to have a history of pre-cough airway infection (p=0.04). Current cough severity score negatively correlated with the Leicester Cough Questionnaire scores (p=0.05).

Conclusion

Chronic idiopathic cough were predominantly middle-aged women, frequently reporting various cough triggers. We also demonstrated that gabapentin can significantly improve cough in these patients. Responders tend to have higher pre-treatment severity scores and have a history of an airway infection.
CooVar: Co-occurring variant analyzer
Authors: Vergara Ismael A , Frech Christian , Chen Nansheng
Published: November 2012

Background

Evaluating the impact of genomic variations (GV) on protein-coding transcripts is an important step in identifying variants of functional significance. Currently available programs for variant annotation depend on external databases or annotate multiple variants affecting the same transcript independently, which limits program use to organisms available in these databases or results in potentially incorrect or incomplete annotations.

Findings

We have developed CooVar (Co-occurring Variant Analyzer), a database-independent program for assessing the impact of GVs on protein-coding transcripts. CooVar takes GVs, reference genome sequence, and protein-coding exons as input and provides annotated GVs and transcripts as output. Other than similar programs, CooVar considers the combined impact of all GVs affecting the same transcript, generating biologically more accurate annotations. CooVar is operated from the command-line and supports standard file formats VCF, GFF/GTF, and GVF, which makes it easy to integrate into existing computational pipelines. We have extensively tested CooVar on worm and human data sets and demonstrate that it generates correct annotations in only a short amount of time.

Conclusions

CooVar is an easy-to-use and lightweight variant annotation tool that considers the combined impact of GVs on protein-coding transcripts. CooVar is freely available at http://genome.sfu.ca/projects/coovar/.
Toll-like receptor ligands induce the expression of interferon-gamma and interleukin-17 in chicken CD4+ T cells
Authors: St Paul Michael , Barjesteh Neda , Paolucci Sarah , Pei Yanlong , Sharif Shayan
Published: November 2012

Background

Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that mediate host responses to pathogens. To date, at least 10 different TLRs have been identified in chickens including TLR2, which binds lipopeptides and other similar ligands such as Pam3CSK4, TLR3, which binds double stranded RNA as well as synthetic molecules such as poly I:C, TLR4, which binds lipopolysaccharide (LPS), and TLR21, which binds CpG DNA motifs. In mammals, TLRs have been detected on CD4+ T cells where they mediate cellular survival, proliferation and the production of cytokines. However, the TLR-mediated responses in chicken CD4+ T cells remain to be determined. As such, the objective of the present study was to elucidate the kinetics of cytokine response to several different TLR ligands in chicken CD4+ T cells.

Results

The results suggest that these cells express TLRs 2, 3, 4 and 21 at the transcript level, and treatment with ligands for these TLRs significantly influenced the expression of the cytokines interferon (IFN)-γ and interleukin (IL)-17, but not IL-4, IL-10 and IL-13. Specifically, treatment with Pam3CSK4, poly I:C and LPS up-regulated IFN-γ transcripts, while CpG ODN significantly down-regulated them. In contrast, at least one dose of each of the TLR ligands, except for Pam3CSK4, significantly down-regulated IL-17 transcripts.

Conclusion

Chicken CD4+ T cells respond to ligands for TLRs 2, 3, 4 and 21 by up-regulating or down-regulating cytokine transcripts. Future studies may consider exploring how these TLR ligands may modulate other effector functions in chicken CD4+ T cells, as well as in other T cell subsets such as CD8+ T cells.
Brain region-specific altered expression and association of mitochondria-related genes in autism
Authors: Anitha Ayyappan , Nakamura Kazuhiko , Thanseem Ismail , Yamada Kazuo , Iwayama Yoshimi , Toyota Tomoko , Matsuzaki Hideo , Miyachi Taishi , Yamada Satoru , Tsujii Masatsugu , Tsuchiya Kenji J , Matsumoto Kaori , Iwata Yasuhide , Suzuki Katsuaki , Ichikawa Hironobu , Sugiyama Toshiro , Yoshikawa Takeo , Mori Norio
Published: November 2012

Background

Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.

Methods

For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (∆∆Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.

Results

Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients.NEFL(P= 0.038; Z-score 2.066) andSLC25A27(P= 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression ofDNAJC19,DNM1L,LRPPRC,SLC25A12,SLC25A14,SLC25A24andTOMM20were reduced in at least two of the brain regions of autism patients.

Conclusions

Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted.
Tubby is required for trafficking G protein-coupled receptors to neuronal cilia
Authors: Sun Xun , Haley James , Bulgakov Oleg V , Cai Xue , McGinnis James , Li Tiansen
Published: November 2012

Background

Tubby is the founding member of the tubby-like family of proteins. The naturally occurring tubby mutation in mice causes retinitis pigmentosa, hearing loss and obesity. Tubby has been proposed to function as an accessory factor in ciliary trafficking. We directly examined a role for tubby in ciliary trafficking in vivo.

Methods

We used immunofluoresence labeling to examine the subcellular localization of rhodopsin, somatostatin receptor 3 (SSTR3) and melanin concentrating hormone receptor 1 (MCHR1), all of which are G protein-coupled receptors (GPCR), in the retina and brain of wild type (WT) and tubby mutant mice.

Results

In tubby mouse retina, rhodopsin is not fully transported across the connecting cilia to the outer segments with ensuing photoreceptor degeneration. In the tubby mouse brain, SSTR3 and MCHR1 fail to localize at the neuronal primary cilia in regions where these receptors play critical roles in neural signaling. The tubby mutant does not manifest a generalized defect in ciliogenesis or protein trafficking.

Conclusions

Tubby plays a critical role in trafficking select GPCRs to the cilia. This role is reminiscent of tubby-like proteins 1 and 3, which have been proposed to facilitate trafficking of rhodopsin and select GPCRs in photoreceptors and the developing neural tube, respectively. Thus tubby-like proteins may be generally involved in transciliary trafficking of GPCRs.
Changes in body core and body surface temperatures during prolonged swimming in water of 10°C—a case report
Authors: Rüst Christoph Alexander , Knechtle Beat , Rosemann Thomas
Published: November 2012

Background

This case report describes an experienced open-water ultra-endurance athlete swimming in water of 9.9°C for 6 h and 2 min.

Methods

Before the swim, anthropometric characteristics such as body mass, body height, skinfold thicknesses, and body fat were determined. During and after the swim, body core (rectum) and body surface (forearm and calf) temperatures were continuously recorded.

Results

The swimmer (53 years old, 110.5 kg body mass, 1.76 m body height, 34.9% body fat, and a body mass index of 35.7 kg/m2) achieved a total distance of 15 km while swimming at a mean speed of 2.48 km/h, equal to 0.69 m/s, in water of 9.9°C. Body core temperature was at 37.8°C before the swim, increased to a maximum of 38.1°C after approximately 20 min of swimming, and then decreased continuously to 36.3°C upon finishing the swim. The lowest body core temperature was 36.0°C between 35 and 60 min after finishing the swim. Sixty minutes after the swim, the body core temperature continuously rose to 36.5°C where it remained. At the forearm, the temperature dropped to 19.6°C after approximately 36 min of swimming and decreased to 19.4°C by the end of the swim. The lowest temperature at the forearm was 17.6°C measured at approximately 47 min before the athlete stopped swimming. At the calf, the temperature dropped to 13.0°C after approximately 24 min of swimming and decreased to 11.9°C at the end of the swim. The lowest temperature measured at the calf was 11.1°C approximately 108 min after the start. In both the forearm and the calf, the skin temperature continuously increased after the swim.

Conclusions

This case report shows that (1) it is possible to swim for 6 h in water of 9.9°C and that (2) the athlete did not suffer from hypothermia under these circumstances. The high body mass index, high body fat, previous experience, and specific preparation of the swimmer are the most probable explanations for these findings.
Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia
Authors: Shang Yu , Gurley Katelyn , Symons Brock , Long Douglas , Srikuea Ratchakrit , Crofford Leslie J , Peterson Charlotte A , Yu Guoqiang
Published: November 2012

Introduction

Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.

Methods

Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value.

Results

Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion.

Conclusions

Our results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle.
Community forensic psychiatry and the forensic mental health liaison model
Authors: Natarajan Muthusamy , Srinivas Jayanth , Briscoe Gill , Forsyth Steven
Published: November 2012

Care and follow-up of patients discharged from medium secure units in England and Wales is uncoordinated and inconsistent, although the perceived risk of violence by people with mental disorders is a primary political issue. This article outlines models of community support for these individuals, and describes a forensic mental health liaison service in operation in England.
Controlling the confusion: using barrier analysis in the care home sector
Authors: Colgate Robert , Davies Karyn , Lambert Helen , Turner Alison
Published: November 2012

The provision of mental health teaching and training to staff in the care home sector by a dedicated educational team was established in Bridgend in 2003. A multiprofessional old age liaison psychiatry team was created in 2009 specifically to link closely with the teaching staff, further building on previous work on referral coordination and a single point of access. This article describes the application of barrier analysis to deliver both this new service and mental health education to the care home sector. Imaginative uses of information technology and multimedia to support the efforts of all staff are described, as are some pitfalls and hazards to avoid. The most effective elements of these developments are discussed, using barrier analysis as the explanatory model, with an emphasis on aspects that could be adopted more widely.
Home assessment in old age psychiatry: a practical guide
Authors: Ng Bradley , Atkins Martin
Published: November 2012

An initial psychiatric assessment of elderly people at home is an important component of many old age psychiatry services. This article explores the clinical aspects of conducting such assessments and the skills required in addition to those brought to a standard psychiatric interview. Safety considerations and risk management when conducting home assessments are also discussed.
Your patient and weight-loss surgery
Authors: Stevens Tom , Spavin Samantha , Scholtz Samantha , McClelland Lisa
Published: November 2012

Obesity is common in patients with mental illness. Weight-loss surgery, known as bariatric surgery, is becoming a familiar intervention for treating people who are morbidly obese and for whom other weight-reduction methods have failed. This article offers guidance for mental health professionals on the assessment and management of patients with mental illness undergoing such treatment. Assessment is of the patient's suitability for surgery, taking into account their mental health diagnosis, expectations, knowledge and insight into the psychological impact of surgery, and ability to address and cope with lifestyle changes before and after surgery. The patient's capacity and ability to cooperate and engage with services are also assessed. Potential risks and complications of bariatric surgery and how the weight-loss procedures may affect patients' mental health and management of their medication are addressed.
Improving quality of life for people with dementia in care homes: making psychosocial interventions work
Authors: Lawrence Vanessa , Fossey Jane , Ballard Clive , Moniz-Cook Esme , Murray Joanna
Published: November 2012

Background

Psychosocial interventions can improve behaviour and mood in people with dementia, but it is unclear how to maximise their effectiveness or acceptability in residential settings.

Aims

To understand what underlies the successful implementation of psychosocial interventions in care homes.

Method

Systematic review and meta-synthesis of qualitative research.

Results

The synthesis of 39 qualitative papers revealed that beneficial psychosocial interventions met the needs of people with dementia to connect with others, make a meaningful contribution and reminisce. Successful implementation rested on the active engagement of staff and family and the continuing provision of tailored interventions and support. This necessitated staff time, and raised issues around priorities and risk, but ultimately helped redefine staff attitudes towards residents and the caregiving role.

Conclusions

The findings from the meta-synthesis can help to inform the development and evaluation of psychosocial interventions in care homes and support their widespread implementation in clinical settings.
The new generation of psychosocial interventions for dementia
care
Authors: Orrell Martin
Published: November 2012

The new generation of psychosocial interventions for dementia has been
characterised by great improvements in methodology and high-quality
randomised controlled trials, including cost-effectiveness analyses. There
are a growing number of interventions with established effectiveness but
despite this there can be difficulties with implementation in practice.
Mathematical models as an aid for improving the validity of
descriptive psychiatry
Authors: Goodyer Ian M.
Published: November 2012

Despite available therapies, mental disorders are the predominant chronic
diseases of young people. Increasing the validity of descriptive psychiatry
is now essential. Mathematical approaches can help characterise clinical
phenotypes and aid both causal research and therapeutics in the community
and the clinic.
Depression and cardiovascular disease: the end of simple models
Authors: de Jonge Peter , Roest Annelieke M.
Published: November 2012

In this editorial, we propose that the association between depression and cardiovascular disease may be conceptualised as a continuous, bidirectional process that originates in youth. The paper by Åberg and colleagues in this issue adds to this literature showing that low cardiovascular fitness at adolescence increases the risk of future depression.
Advice on driving while under the care of a crisis resolution team: findings from two audits
Authors: Curwen Joanna , Jebreel Amy
Published: November 2012

Aims and method

To examine the documentation regarding patients driving while under the care of a crisis resolution team and whether advice is being given by all members of the team. An audit was carried out looking at the case records of patients and information was collated about whether they had been asked if they were driving and whether any advice had been given. Following the audit there was a team presentation and guidelines distributed. The audit was repeated 6 months later.

Results

The first cycle of the audit included 58 patients. There was documentation about driving for two patients and appropriate advice given for one. The second cycle included 53 patients. There was documentation about two patients and advice given for one.

Clinical implications

Patients are not being asked whether they drive and advice is not routinely being given despite clear guidelines. Further research is needed to look at interventions at a local level that could improve this.
Trainees' views of portfolios in psychiatry
Authors: Halder Neel , Subramanian Ganesh , Longson Damien
Published: November 2012

Aims and method

Portfolios are now used extensively within the field of psychiatry and our aim was to obtain trainees' feedback on their value. We used a questionnaire to evaluated trainees' priorities, what educational tools they found most helpful, how much time trainees spent on preparing their portfolios and the best and worst aspects of the portfolios.

Results

The survey was completed by 207 out of 228 trainees (90.8%). The majority (58.4%) rated ‘Passing the ARCP [Annual Review of Competence Progression]’ as their top priority. More trainees found benefit from the feedback of workplace-based assessments (33.3%) than the ratings given (24.1%). Time spent on portfolios on a weekly basis ranged from 5 min to 12 h (the most common answer was 1–2 h). A total of 50.7% felt they did not have enough time to spend on their portfolios. Many found it encouraged reflective practice, but wanted more training for both trainees and trainers on how to use them properly.

Clinical implications

The expansion of portfolios within the changing National Health Service requires careful planning and training, and perhaps some allocated time to complete them, so that trainees can derive the maximum benefits from the portfolio's intended purpose.
Enhancing the effectiveness of community drug and alcohol teams working with opioid-dependent pregnant women: results of an audit
Authors: Sairam Mani , Magon Rakesh , Kouimtsidis Christos
Published: November 2012

Aims and method

To evaluate the quality of services offered by community drug and alcohol teams (CDATs) to pregnant women in substitution treatment. A full audit of the practice across all local CDATs against national standards was undertaken in 2008 and 2010.

Results

Quality of services improved and met three standards in 100% and the fourth standard in 96% of cases. There was good implementation of the recommendations arising out of the action plan of the first cycle, which resulted in significant improvements in interagency liaison and risk-benefit analysis documentation within the CDATs.

Clinical implications

Management of pregnant women in substitution treatment can be improved by adhering to a multipronged approach as identified by this audit.
Genetic testing of adults with intellectual disability
Authors: de Villiers Jana , Porteous Mary
Published: November 2012

Method

Patients known to learning disability services in two health boards in southeast Scotland were cross-matched with the patients tested at the Western General Hospital in Edinburgh. Those with a positive genetic diagnosis were identified. Semi-structured interviews were conducted with senior learning disability psychiatrists and clinical genetics consultants.

Results

Of the 3323 patients with intellectual disability across both health boards, 41% have had genetic tests and 6% have an identified genetic abnormality as the cause for their intellectual disability. Of the 1349 patients who have been tested, a genetic abnormality was found in 14%. Psychiatrists named several benefits to genetic testing, but they also highlighted a number of non-medical reasons for not testing adults with intellectual disability.

Clinical implications

Identifying genetic aetiology in intellectual disability has a number of benefits. Our study would indicate that genetic diagnoses are being missed due to a lack of genetic testing in this patient group. Adult learning disability services need to consider increasing genetic testing.
Catatonia in a woman who is profoundly deaf-mute: case report
Authors: Akintomide Gbolagade Sunmaila , Porter Stuart Williams , Pierce Anita
Published: November 2012

Catatonia is a common but underrecognised complication of bipolar disorder, with a quarter of in-patients with bipolar disorder developing catatonia. Almost 9 million people in the UK are deaf or have a significant hearing problem and British Sign Language is the preferred language of 50 000–70 000 people within the UK. Between 1 and 2% of these individuals (i.e. the same as in the rest of the population) will experience bipolar disorder in their lifetime and therefore the accurate diagnosis of catatonia is important. We report a case of catatonia presenting with dysphagia in a woman who is profoundly deaf–mute and who has bipolar disorder. This report highlights some modifications of presentation and difficulties of accurate diagnosis and management of catatonia in this patient. To the best of our knowledge, this is the first case report of catatonia in someone who is profoundly deaf–mute.
Older patients and falls in hospital
Authors: Healey Frances , Darowski Adam
Published: November 2012

Over a quarter of a million falls are reported by the UK hospitals each year, predominantly harming older patients whose vulnerability to falling arises from a complex interaction of risk factors, including impaired mobility, dementia, delirium, medication and the effects of long term and acute illness. Systematic review of research trials indicates that multifactorial assessment and intervention to treat, modify or better manage these underlying risk factors can reduce falls by 20–30%. However, the evidence base is not always reflected in hospitals’ falls prevention policies, and is not consistently delivered to patients. The organizational culture and processes that can increase the effective delivery of evidence-based falls prevention are discussed, alongside learning from quality improvement projects. Systematic learning from reported falls and essential care after an inpatient fall are also explored.
Treatment of older people
Authors: Rai Gurcharan S , Abdulla Aza
Published: November 2012

Decisions to treat older people rely on accurate assessment of the patient, on clinical needs of the individual, based on risks and benefits of specific treatment and ethical principles, including the right of individuals to accept or refuse treatment. In those who lack capacity to make decisions, the physician tries to ensure that his decision is based on “best interests” principles set out in the Mental Capacity Act 2005. While no physician will admit to age discrimination, in reality there is evidence of inequalities in care and treatment in hospitals, and it is this fact that has led the Government to outlaw discrimination in healthcare under the new provision of the Equality Act 2010. This of course will not mean that all individuals with the same condition will have the right to receive the same treatment—decisions in each case will be based on an individual's clinical need—this fact alone may lead to difficult discussions with relatives and carers, particularly in relation to end-of-life care. This article provides an overview of the basis of management of older patients, and illustrates the importance of taking a holistic approach in the decision-making process.
Elder abuse and death claims
Authors: Bennett Daniel
Published: November 2012

The number of avoidable deaths of people in care homes is in the thousands per year. The numbers of those abused by carers is in the hundreds of thousands. Despite the extent of the scandal, the issue goes largely unlitigated. However, the issues are relatively straightforward and cases that are brought are generally successful.
Current management of prostate cancer: dilemmas and trials
Authors: O'Hanlon Brown C , Waxman J
Published: November 2012

The past decade has witnessed significant advances in our understanding of the biology of prostate cancer. Androgen ablation/androgen receptor inhibition remains as the mainstay of treatment for advanced prostate cancer. Our understanding of the biology of prostate cancer has increased exponentially owing to advances in molecular biology. With this knowledge many intriguing issues have come to light, which clinicians and scientists alike strive to answer. These include why prostate cancer is so common, what drives the development of prostate cancer at a molecular level, why prostate cancer appears refractory to many families of cytotoxic chemotherapeutics, and why prostate cancer preferentially metastasizes to bone. Two clinical forms of prostate cancer have been identified: indolent organ confined disease, which elderly men often die of, and aggressive metastatic disease. A method of distinguishing between these two forms of the disease at an organ-confined stage remains elusive. Understanding the mechanisms of castrate resistance is a further issue of clinical importance. New trials of treatments, including molecular agents that target prostate cancer from a range of angles, have been instituted over the past 10–15 years. We can look at these trials not only as a chance to investigate the effectiveness of new treatments but also as an opportunity to further understand the complex biology of this disease.
High dose rate prostate brachytherapy: an overview of the rationale, experience and emerging applications in the treatment of prostate cancer
Authors: Challapalli A , Jones E , Harvey C , Hellawell G O , Mangar S A
Published: November 2012

The technological advances in real-time ultrasound image guidance for high dose rate (HDR) prostate brachytherapy places this treatment modality at the forefront of innovation in radiotherapy. This review article will explore the rationale for HDR brachytherapy as a highly conformal method of dose delivery and safe dose escalation to the prostate, in addition to the particular radiobiological advantages it has over low dose rate and external beam radiotherapy. The encouraging outcome data and favourable toxicity profile will be discussed before looking at emerging applications for the future and how this procedure will feature alongside stereotactic radiosurgery.
If hip implant retrievals could speak, what would they tell us?
Authors: Cuckler J. M.
Published: November 2012

Hip implant retrieval analysis is the most important source of insight into the performance of new materials and designs of hip arthroplasties. Even the most rigorous in vitro testing will not accurately simulate the behavior of implant materials and new designs of prosthetic arthroplasties. Retrieval analysis has revealed such factors as the effects of gamma-in-air sterilisation of polyethylene, fatigue failure mechanisms of polymethylmethacrylate bone cement, fretting corrosion of Morse taper junctions, third body wear effects of both hard-on-hard and hard-on-soft bearing couples, and the effects of impingement of components on the full spectrum of bearing surfaces, none of which was predicted by pre-implantation in vitro testing of these materials and combinations. The temporal sequence of the retrieval process is approximately six years from first implantation through retrieval analysis, laboratory investigation, and publication of results, and thus, in addition to rigorous clinical evaluation, represents the true development and insight cycle for new designs and materials.
Functional results and complications following conversion of hip fusion to total hip replacement
Authors: Aderinto J. , Lulu O. B. , Backstein D. J. , Safir O. , Gross A. E.
Published: November 2012

Eighteen hip fusions were converted to total hip replacements. A constrained acetabular liner was used in three hips. Mean follow up was five years (two to 15). Two (11%) hips failed, requiring revision surgery and two patients (11%) had injury to the peroneal nerve. Heterotopic ossification developed in seven (39%) hips, in one case resulting in joint ankylosis. No hips dislocated.

Conversion of hip fusion to hip replacement carries an increased risk of heterotopic ossification and neurological injury. We advise prophylaxis against heterotropic ossification. When there is concern about hip stability we suggest that the use of a constrained acetabular liner is considered. Despite the potential for complications, this procedure had a high success rate and was effective in restoring hip function.
Osteolysis in the well-fixed socket
Authors: Haidukewych G. J.
Published: November 2012

Osteolysis remains a common reason for revision after total hip arthroplasty (THA). For osteolysis associated with loose cups, revision is indicated. For osteolysis around a well-fixed cup, the decision is more controversial. The data available data support retention of the cupwith lesional treatment, working through screw holes and access channels for debridement and grafting. The choice of graft material to fill defects, if any, remains controversial. Several studies demonstrate good survivorship with cup retention strategies. Complete revision allows more complete debridement of the lesion and better graft fill, and allows implantation of a modern cup, typically with a full line of liners and bearing surfaces available. Additionally, revision allows fine tuning of the orientation of the cup, which may be advantageous for optimising hip stability. The author prefers to retain a well-fixed cup if it meets the following criteria: it is well-fixed to intra-operative testing, it is well-positioned, it is of sufficient size to allow insertion of a new liner with a reasonable head size, new liners are available, and the hip is stable to intra-operative trialing after liner insertion.
Alternatives to revision total knee arthroplasty
Authors: Jones R. E. , Russell R. D. , Huo M. H.
Published: November 2012

Most problems encountered in complex revision total knee arthroplasty can be managed with the wide range of implant systems currently available. Modular metaphyseal sleeves, metallic augments and cones provide stability even with significant bone loss. Hinged designs substitute for significant ligamentous deficiencies. Catastrophic failure that precludes successful reconstruction can be encountered. The alternatives to arthroplasty in such drastic situations include knee arthrodesis, resection arthroplasty and amputation. The relative indications for the selection of these alternatives are recurrent deep infection, immunocompromised host, and extensive non-reconstructible bone or soft-tissue defects.
Use of smart trials for soft-tissue balancing in total knee replacement surgery
Authors: Gustke K.
Published: November 2012

Smart trials are total knee tibial trial liners with load bearing and alignment sensors that will graphically show quantitative compartment load-bearing forces and component track patterns. These values will demonstrate asymmetrical ligament balancing and misalignments with the medial retinaculum temporarily closed. Currently surgeons use feel and visual estimation of imbalance to assess soft-tissue balancing and tracking with the medial retinaculum open, which results in lower medial compartment loads and a wider anteroposterior tibial tracking pattern. The sensor trial will aid the total knee replacement surgeon in performing soft-tissue balancing by providing quantitative visual feedback of changes in forces while performing the releases incrementally. Initial experience using a smart tibial trial is presented.
Femoroacetabular impingement
Authors: Brooks P. , Bershadsky B.
Published: November 2012

Femoroacetabular impingement (FAI) is commonly associated with early hip arthritis. We reviewed our series of 1300 hip resurfacing procedures. More than 90% of our male patients, with an average age of 53 years, had cam impingement lesions. In this condition, there are anterior femoral neck osteophytes, and a retroverted femoral head on a normally anteverted neck. It is postulated that FAI results in collision of the anterior neck of the femur against the rim of the acetabulum, causing damage to the acetabular labrum and articular cartilage, resulting in osteoarthritis. Early treatment of FAI involves arthroscopic or open removal of bone from the anterior femoral neck, as well as repair or removal of labral tears. However, once osteoarthritis has developed, hip replacement or hip resurfacing is indicated. Hip resurfacing can re-orient the head and re-shape the neck. This helps to restore normal biomechanics to the hip, eliminate FAI, and improve range of motion. Since many younger men with hip arthritis have FAI, and are also considered the best candidates for hip resurfacing, it is evident that resurfacing has a role in these patients.
A primer in cartilage repair
Authors: Minas T.
Published: November 2012

Hyaline articular cartilage has been known to be a troublesome tissue to repair once damaged. Since the introduction of autologous chondrocyte implantation (ACI) in 1994, a renewed interest in the field of cartilage repair with new repair techniques and the hope for products that are regenerative have blossomed. This article reviews the basic science structure and function of articular cartilage, and techniques that are presently available to effect repair and their expected outcomes.
The Hip Society
Authors: Lombardi, Jr A. V. , Barrack R. L. , Berend K. R. , Cuckler J. M. , Jacobs J. J. , Mont M. A. , Schmalzried T. P.
Published: November 2012

Since 1996 more than one million metal-on-metal articulations have been implanted worldwide. Adverse reactions to metal debris are escalating. Here we present an algorithmic approach to patient management. The general approach to all arthroplasty patients returning for follow-up begins with a detailed history, querying for pain, discomfort or compromise of function. Symptomatic patients should be evaluated for intra-articular and extra-articular causes of pain. In large head MoM arthroplasty, aseptic loosening may be the source of pain and is frequently difficult to diagnose. Sepsis should be ruled out as a source of pain. Plain radiographs are evaluated to rule out loosening and osteolysis, and assess component position. Laboratory evaluation commences with erythrocyte sedimentation rate and C-reactive protein, which may be elevated. Serum metal ions should be assessed by an approved facility. Aspiration, with manual cell count and culture/sensitivity should be performed, with cloudy to creamy fluid with predominance of monocytes often indicative of failure. Imaging should include ultrasound or metal artifact reduction sequence MRI, specifically evaluating for fluid collections and/or masses about the hip. If adverse reaction to metal debris is suspected then revision to metal or ceramic-on-polyethylene is indicated and can be successful. Delay may be associated with extensive soft-tissue damage and hence poor clinical outcome.
Metal-on-metal hip arthroplasty
Authors: Berend K. R. , Morris M. J. , Adams J. B. , Lombardi Jr A. V.
Published: November 2012

Metal-on-metal hip arthroplasty gained significant favor in the first decade of the millennium. However, the past several years have seen increasing reports of failure, pseudotumor and other adverse reactions. This study presents the results of a single center’s 15-year experience with metal-on-metal total hip arthroplasty as strong evidence that metal-on-metal is going, going, gone.
Single stage revision
Authors: Gulhane S. , Vanhegan I. S. , Haddad F. S.
Published: November 2012

In this paper we make the case for the use of single-stage revision for infected knee arthroplasty.
Massive bone loss
Authors: Mayle Jr R. E. , Paprosky W. G.
Published: November 2012

Revision total hip arthroplasty (THA) is projected to increase by 137% from the years 2005 to 2030. Reconstruction of the femur with massive bone loss can be a formidable undertaking. The goals of revision surgery are to create a stable construct, preserve bone and soft tissues, augment deficient host bone, improve function, provide a foundation for future surgery, and create a biomechanically restored hip. Options for treatment of the compromised femur include: resection arthroplasty, allograft prosthetic composite (APC), proximal femoral replacement, cementless fixation with a modular tapered fluted stem, and impaction grafting. The purpose of this article is to review the treatment options along with their associated outcomes in the more severe femoral defects (Paprosky types IIIb and IV) in revision THA.
The stiff total knee arthroplasty
Authors: Vince K. G.
Published: November 2012

Seven stiff total knee arthroplasties are presented to illustrate the roles of: 1) manipulation under general anesthesia; 2) multiple concurrent diagnoses in addition to stiffness; 3) extra-articular pathology; 4) pain as part of the stiffness triad (pain and limits to flexion or extension); 5) component internal rotation; 6) multifactorial etiology; and 7) surgical exposure in this challenging clinical problem.
Management of extensor mechanism rupture after TKA
Authors: Rosenberg A. G.
Published: November 2012

Disruption of the extensor mechanism in total knee arthroplasty may occur by tubercle avulsion, patellar or quadriceps tendon rupture, or patella fracture, and whether occurring intra-operatively or post-operatively can be difficult to manage and is associated with a significant rate of failure and associated complications. This surgery is frequently performed in compromised tissues, and repairs must frequently be protected with cerclage wiring and/or augmentation with local tendon (semi-tendinosis, gracilis) which may also be used to treat soft-tissue loss in the face of chronic disruption. Quadriceps rupture may be treated with conservative therapy if the patient retains active extension. Component loosening or loss of active extension of 20° or greater are clear indications for surgical treatment of patellar fracture. Acute patellar tendon disruption may be treated by primary repair. Chronic extensor failure is often complicated by tissue loss and retraction can be treated with medial gastrocnemius flaps, achilles tendon allografts, and complete extensor mechanism allografts. Attention to fixing the graft in full extension is mandatory to prevent severe extensor lag as the graft stretches out over time.
Current guidelines for total joint VTE prophylaxis
Authors: Barrack R. L.
Published: November 2012

Venous thromboembolism (VTE) remains an immediate threat to patients following total hip and knee replacement. While there is a strong consensus that steps should be taken to minimise the risk to patients by utilising some forms of prophylaxis for the vast majority of patients, the methods utilised have been extremely variable. Clinical practice guidelines (CPGs) have been published by various professional organisations for over 25 years to provide recommendations to standardise VTE prophylaxis. Historically, these recommendations have varied widely depending in underlying assumptions, goals, and methodology of the various groups. This effort has previously been exemplified by the American College of Chest Physicians (ACCP) and the American Academy of Orthopaedic Surgeons (AAOS). The former group of medical specialists targeted minimising venographically proven deep vein thrombosis (DVT) (the vast majority of which are asymptomatic) as their primary goal prior to 2012. The latter group of surgeons targeted minimising symptomatic VTE. As a result prior to 2012, the recommendations of the two groups were widely divergent. In the past year, both groups have reassessed the current literature with the principal goals of minimising symptomatic VTE events and bleeding complications. As a result, for the first time the CPGs of these two major subspecialty organisations are in close agreement.
Cementless fixation in total knee arthroplasty
Authors: Ranawat C. S. , Meftah M. , Windsor E. N. , Ranawat A. S.
Published: November 2012

There has been a recent increase in interest for non-cemented fixation in total knee arthroplasty (TKA), however the superiority of cement fixation is an ongoing debate.

Whereas the results based on Level III and IV evidence show similar survivorship rates between the two types of fixation, Level I and II evidence strongly support cemented fixation. United Kingdom, Australia, Sweden, and New Zealand registry data show lower failure rates and greater usage of cemented than non-cemented fixation. Case series studies have also indicated greater functional outcomes and lower revision rates among cemented TKAs. Non-cemented fixation involves more patellofemoral complications, including increased susceptibility to wear due to a thinner polyethylene bearing on the cementless metal-backed component. The combination of results from registry data, prospective randomised studies, and meta-analyses support the current superiority of cemented fixation in TKAs.