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author:("bernfield, S")
1.  The administration of intermittent parathyroid hormone affects functional recovery from pertrochanteric fractured neck of femur: a protocol for a prospective mixed method pilot study with randomisation of treatment allocation and blinded assessment (FRACTT) 
BMJ Open  2014;4(1):e004389.
Pertrochanteric hip fractures occur in an elderly population and cause considerable morbidity and loss of functional ability as the fracture heals. Recently, parathyroid hormone (PTH), which is licensed for the treatment of osteoporosis, has been shown to potentially accelerate bone healing in animal and human studies. If its administration could allow a faster functional recovery after pertrochanteric hip fracture, then a patient's hospital stay may be reduced and rehabilitation could be potentially accelerated. PTH can currently only be administered by subcutaneous injection. The acceptability of this intervention is unknown in this elderly population. The aim of this pilot study is to inform the design of a future powered study comparing the functional recovery after pertrochanteric hip fracture in patients undergoing standard care versus those who undergo administration of subcutaneous injection of PTH.
Methods and analysis
The study is an open label, prospective, randomised, comparative pilot study with blinded outcomes assessment to establish feasibility of the trial design. Patients will be randomised to receive a 6-week course of PTH or usual treatment. Functional outcomes will be assessed at 6 weeks and 12 weeks. Blinded assessment will be used to minimise the effect of bias of an open label study design. A nested qualitative study will investigate the patient experience of, and expectations following, hip fracture and the patient important aspects of recovery compared with the outcome measures proposed.
Results will be analysed to establish the potential recruitment, compliance and retention rates using 95% CIs, and trial outcomes quoted with SDs and 95% CIs for the effect size.
Ethics and dissemination
The study has been approved by the South West 2 Research Ethics committee (reference 10/H0206/34). The findings of this study will be disseminated to the medical community via presentations to orthopaedic, orthogeriatric and osteoporosis societies, and their relevant specialist journals.
Trial Registration
ISRCTN Register reference number: ISRCTN03362357.
Eudract Number: 2010-020081-22
PMCID: PMC3913027  PMID: 24477319
Geriatric Medicine; Rehabilitation Medicine; Qualitative Research
2.  The Effects of Gender on Adolescent Suicide in Ontario, Canada 
Identify patterns of suicide amongst male and female adolescents aged 11–18 years in Ontario.
All 370 adolescent suicides in Ontario between January 2000 and November 2006 were analyzed. Previous attempts, history of psychiatric treatment, location committed and method of suicide were assessed. Data was analyzed using 2-tailed t-tests and chi-square without Yates’ correction.
Male adolescent suicide was twice as common as female suicide. Males were more likely to use violent methods (p=0.0352) and females were more likely to have a history of a previous suicide attempt (p=0.0001).
While most of the data agree with previous studies in adult populations, the ratio of male to female suicides was much lower in our adolescent population.
PMCID: PMC3413467  PMID: 22876263
suicide; adolescents; gender; Ontario; suicide; adolescents; sexe; Ontario
3.  Hip precautions after hemiarthroplasty: what is happening in the UK and at what cost? 
The aim of this study was to observe current practice of the use of hip precautions following hemiarthroplasty for hip fractures in England and to audit the cost of hip precautions in this patient group.
A telephone review was undertaken of all units identified by the National Hip Fracture Database as receiving centres for hip fractures across England to ascertain current practice in the use of hip precautions. A prospective audit of occupational therapy (OT) practice including the cost of equipment provision and OT time was carried out locally.
All 174 units in England were successfully contacted. Practice varied between centres but hip precautions were in use at 78% of centres. Prior to stopping hip precautions at the local hospital, we audited the costs associated with their use. Mean equipment costs per patient decreased by £12 (from £49 to £37, range: £0–£83) and mean OT time per patient decreased by 1.5 hours (from 8 hours to 6.5 hours, range: 1–22 hours) following removal of hip precaution guidelines. A mean of 0.25 days' discharge delay (range: 0–4 days) due to equipment provision was identified prior to removing hip precautions with no discharge delay following.
This study has highlighted the variation in practice across the country and inconsistency with the advice published by the British Orthopaedic Association and British Geriatrics Society in the ‘Blue Book’ (The Care of Patients with Fragility Fracture). Hip precautions are unnecessary after hemiarthroplasty, cost money both in therapist time and equipment provision and increase the length of hospital stay. Nevertheless, they continue to be used by three-quarters of trauma hospitals in England.
PMCID: PMC3365459
Femoral neck fractures; Hip fractures; Dislocations; Occupational therapy; Physical therapy; Rehabilitation
4.  How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review 
BMC Medical Education  2010;10:64.
Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review.
We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers.
Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool.
There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect.
PMCID: PMC2958160  PMID: 20920240
5.  Teaching trainers to incorporate evidence-based medicine (EBM) teaching in clinical practice: the EU-EBM project 
Evidence based medicine (EBM) is considered an integral part of medical training, but integration of teaching various EBM steps in everyday clinical practice is uncommon. Currently EBM is predominantly taught through theoretical courses, workshops and e-learning. However, clinical teachers lack confidence in teaching EBM in workplace and are often unsure of the existing opportunities for teaching EBM in the clinical setting. There is a need for continuing professional development (CPD) courses that train clinical trainers to teach EBM through on-the-job training by demonstration of applied EBM real time in clinical practice. We developed such a course to encourage clinically relevant teaching of EBM in post-graduate education in various clinical environments.
We devised an e-learning course targeting trainers with EBM knowledge to impart educational methods needed to teach application of EBM teaching in commonly used clinical settings. The curriculum development group comprised experienced EBM teachers, clinical epidemiologists, clinicians and educationalists from institutions in seven European countries. The e-learning sessions were designed to allow participants (teachers) to undertake the course in the workplace during short breaks within clinical activities. An independent European steering committee provided input into the process.
The curriculum defined specific learning objectives for teaching EBM by exploiting educational opportunities in six different clinical settings. The e-modules incorporated video clips that demonstrate practical and effective methods of EBM teaching in everyday clinical practice. The course encouraged focussed teaching activities embedded within a trainer's personal learning plan and documentation in a CPD portfolio for reflection.
This curriculum will help senior clinicians to identify and make the best use of available opportunities in everyday practice in clinical situations to teach various steps of EBM and demonstrate their applicability to clinical practice. Once fully implemented, the ultimate outcome of this pilot project will be a European qualification in teaching EBM, which will be used by doctors, hospitals, professional bodies responsible for postgraduate qualifications and continuing medical education.
PMCID: PMC2753626  PMID: 19744327
6.  Relation between viral fitness and immune escape within the hepatitis C virus protease 
Gut  2006;55(2):266-274.
The hepatitis C virus (HCV) mutates within human leucocyte antigen (HLA) class I restricted immunodominant epitopes of the non‐structural (NS) 3/4A protease to escape cytotoxic T lymphocyte (CTL) recognition and promote viral persistence. However, variability is not unlimited, and sometimes almost absent, and factors that restrict viral variability have not been defined experimentally.
We wished to explore whether the variability of the immunodominant CTL epitope at residues 1073–1081 of the NS3 protease was limited by viral fitness.
Venous blood was obtained from six patients (four HLA‐A2+) with chronic HCV infection and from one HLA‐A2+ patient with acute HCV infection.
NS3/4A genes were amplified from serum, cloned in a eukaryotic expression plasmid, sequenced, and expressed. CTL recognition of naturally occurring and artificially introduced escape mutations in HLA‐A2‐restricted NS3 epitopes were determined using CTLs from human blood and genetically immunised HLA‐A2‐transgenic mice. HCV replicons were used to test the effect of escape mutations on HCV protease activity and RNA replication.
Sequence analysis of NS3/4A confirmed low genetic variability. The major viral species had functional proteases with 1073–1081 epitopes that were generally recognised by cross reactive human and murine HLA‐A2 restricted CTLs. Introduction of mutations at five positions of the 1073–1081 epitope prevented CTL recognition but three of these reduced protease activity and RNA replication.
Viral fitness can indeed limit the variability of HCV within immunological epitopes. This helps to explain why certain immunological escape variants never appear as a major viral species in infected humans.
PMCID: PMC1856491  PMID: 16105887
hepatitis C virus; NS3; immune escape; cytotoxic T lymphocyte; viral fitness; replicon
7.  Mice with a Targeted Mutation of Patched2 Are Viable but Develop Alopecia and Epidermal Hyperplasia†  
Molecular and Cellular Biology  2006;26(17):6609-6622.
Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in Drosophila melanogaster and vertebrates. The Patched1 (Ptc1) gene, encoding the Hh receptor, is mutated in nevoid basal cell carcinoma syndrome, a human genetic disorder associated with developmental abnormalities and increased incidences of basal cell carcinoma (BCC) and medulloblastoma (MB). Ptc1 mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1 is a tumor suppressor. We previously identified a second mammalian Patched gene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping pattern with Shh in the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis. Here, we describe the generation and phenotypic analysis of Ptc2tm1/tm1 mice. Our molecular analysis suggests that Ptc2tm1 likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2tm1/tm1 mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2tm1/tm1 male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis.
PMCID: PMC1592833  PMID: 16914743
8.  MyD88 Expression Is Required for Efficient Cross-Presentation of Viral Antigens from Infected Cells 
Journal of Virology  2005;79(5):2964-2972.
While virus-infected dendritic cells (DCs) in certain instances have the capacity to activate naïve T cells by direct priming, cross-priming by DCs via the uptake of antigens from infected cells has lately been recognized as another important pathway for the induction of antiviral immunity. During cross-priming, danger and stranger signals play important roles in modulating immune responses. Analogous to what has been shown for other microbial infections, virally infected cells may contain several pathogen-associated molecular patterns that are recognized by Toll-like receptors (TLRs). We analyzed whether the efficient presentation of antigens derived from infected cells requires the usage of MyD88, which is a common adaptor molecule used by all TLRs. For this study, we used murine DCs that were wild type or deficient in MyD88 expression and fibroblasts that were infected with an alphavirus replicon to answer this question. Our results show that when DCs are directly infected, they are able to activate antigen-specific CD8+ T cells in a MyD88-independent manner. In contrast, a strict requirement of MyD88 for cross-priming was observed when virally infected cells were used as a source of antigen in vitro and in vivo. This indicates that the effects of innate immunity stimulation via the MyD88 pathway control the efficiency of cross-presentation, but not direct presentation or DC maturation, and have important implications in the development of cytotoxic T lymphocyte responses against alphaviral replicon infections.
PMCID: PMC548467  PMID: 15709016
9.  Salt and hypertension. 
PMCID: PMC1418243  PMID: 3929887

Results 1-10 (10)