Testing metabolic scaling theory using intraspecific allometries in Antarctic microarthropods

Quantitative scaling relationships among body mass, temperature and metabolic rate of organisms are still controversial, while resolution may be further complicated through the use of different and possibly inappropriate approaches to statistical analysis. We propose the application of a modelling strategy based on the theoretical approach of Akaike's information criteria and non-linear model fitting (nlm). Accordingly, we collated and modelled available data at intraspecific level on the individual standard metabolic rate of Antarctic microarthropods as a function of body mass (M), temperature (T), species identity (S) and high rank taxa to which species belong (G) and tested predictions from metabolic scaling theory (mass-metabolism allometric exponent b = 0.75, activation energy range 0.2-1.2 eV). We also performed allometric analysis based on logarithmic transformations (lm). Conclusions from lm and nlm approaches were different. Best-supported models from lm incorporated T, M and S. The estimates of the allometric scaling exponent linking body mass and metabolic rate resulted in a value of 0.696 +/- 0.105 (mean +/- 95% CI). In contrast, the four best-supported nlm models suggested that both the scaling exponent and activation energy significantly vary across the high rank taxa (Collembola, Cryptostigmata, Mesostigmata and Prostigmata) to which species belong, with mean values of b ranging from about 0.6 to 0.8. We therefore reached two conclusions: 1, published analyses of arthropod metabolism based on logarithmic data may be biased by data transformation; 2, non-linear models applied to Antarctic microarthropod metabolic rate suggest that intraspecific scaling of standard metabolic rate in Antarctic microarthropods is highly variable and can be characterised by scaling exponents that greatly vary within taxa, which may have biased previous interspecific comparisons that neglected intraspecific variability.

Assessment of factors that influence physician decision making regarding medication use in patients with dementia at the end of life

Objective
This study aimed to evaluate the extent to which patient-related factors and physicians' country of practice (Northern Ireland [NI] and the Republic of Ireland [RoI]) influenced decision making regarding medication use in patients with end-stage dementia.

Methods
The study utilised a factorial survey design comprising four vignettes to evaluate initiating/withholding or continuing/discontinuing specific medications in patients with dementia nearing death. Questionnaires and vignettes were mailed to all hospital physicians in geriatric medicine and to all general practitioners (GPs) in NI (November 2010) and RoI (December 2010), with a second copy provided 3 weeks after the first mailing. Logistic regression models were constructed to examine the impact of patient-related factors and physicians' country of practice on decision making. Significance was set a priori at p ≤ 0.05. Free text responses to open questions were analysed qualitatively using content analysis.

Results
The response rate was 20.6% (N = 662) [21.1% (N = 245) for GPs and 52.1% (N = 38) for hospital physicians in NI, 18.3% (N = 348) for GPs and 36.0% (N = 31) for hospital physicians in RoI]. There was considerable variability in decision making about initiating/withholding antibiotics and continuing/discontinuing the acetylcholinesterase inhibitor and memantine hydrochloride, and less variability in decision making regarding statins and antipsychotics. Patient place of residence and physician's country of practice had the strongest and most consistent effects on decision making although effect sizes were small.

Conclusions
Further research is required into other factors that may impact upon physicians' prescribing decisions for these vulnerable patients and to clarify how the factors examined in this study influence prescribing decisions.

Use and views on social networking sites of pharmacy students in the United Kingdom

Objective. To investigate students' use and views on social networking sites and assess differences in attitudes between genders and years in the program.

Methods. All pharmacy undergraduate students were invited via e-mail to complete an electronic questionnaire consisting of 21 questions relating to social networking.

Results. Most (91.8%) of the 377 respondents reported using social networking Web sites, with 98.6% using Facebook and 33.7% using Twitter. Female students were more likely than male students to agree that they had been made sufficiently aware of the professional behavior expected of them when using social networking sites (76.6% vs 58.1% p=0.002) and to agree that students should have the same professional standards whether on placement or using social networking sites (76.3% vs 61.6%; p<0.001).

Conclusions. A high level of social networking use and potentially inappropriate attitudes towards professionalism were found among pharmacy students. Further training may be useful to ensure pharmacy students are aware of how to apply codes of conduct when using social networking sites.

Serine proteases in bone disease

Serine proteases are active in many physiological and pathological processes within bone tissue. Although essential to adequate maintenance of bone and cartilage, their inappropriate expression can lead to exacerbation of tissue destruction and inflammation. Their effects are exerted through multiple pathways, including interaction with signalling molecules such as transforming growth factor ß (TGFß), binding to protease-activated receptors (PARs), and direct proteolysis of extracellular matrix proteins, in some cases working synergistically with matrix metalloproteases in the remodelling of bone tissue. The overall effect of these interactions is not yet clear, but there are strong links between some serine proteases and arthropathies, in addition to metastatic bone invasion. Understanding the contribution of each of these enzymes to the molecular disease process is crucial to developing effective treatment based on inhibitors or agonists. Serine protease inhibitors have shown promise in reducing the severity of arthritis, but greater specificity is required to avoid undesired systemic effects. © 2009 Bentham Science Publishers Ltd.

Nonadherence in difficult asthma - facts, myths, and a time to act

Nonadherence to prescribed treatment is an important cause of difficult asthma. Rates of nonadherence amongst asthmatic patients have been shown to range between 30% and 70%. This is associated with poor health care outcomes and increased health care costs. There is no such thing as a "typical" nonadherent patient. The reasons driving nonadherence are multifactorial. Furthermore, adherence is a variable behavior and not a trait characteristic. Adherence rates can vary between the same individual across treatments for different conditions. There is no consistent link between socioeconomic status and nonadherence, and although some studies have shown that nonadherence is more common amongst females, this is not a universal finding. The commonly held perception that better adherence is driven by greater disease severity has been demonstrated to not be the case, in both pediatric and adult patients. Identification of nonadherence is the first step. If adherence is not checked, it is likely that poor adherence will be labeled as refractory disease. Failure to identify poor adherence may lead to inappropriate escalation of therapy, including the potential introduction of complex biological therapies. Surrogate measures, such as prescription counting, are not infallible. Nonadherence can be difficult to identify in clinical practice, and a systematic approach using a variety of tools is required. Nonadherence can be successfully addressed. Therefore, assessment of adherence is of paramount importance in difficult asthma management, in order to reduce exacerbations and steroid-related side effects as well as hospital and intensive care admissions, health care cost, and inappropriate treatment escalation. In this paper, we present an overview of the literature surrounding nonadherence in difficult asthma. We explore the facts and myths surrounding the factors driving nonadherence as well as how it can be identified and addressed.

Antibiotic resistance in Prevotella species isolated from patients with cystic fibrosis

To compare the antimicrobial susceptibility of Prevotella spp. isolated from cystic fibrosis (CF) and non-CF patients and analyse the impact of antibiotic prescribing in the preceding year on resistance amongst CF isolates.

Evaluation of a Final Year Work-shadowing Attachment

The transition from medical student to junior doctor is well recognised to be a difficult and stressful period. To ease this transition, most UK universities have a work-shadowing period (WSP), during which students can learn practical skills needed for forthcoming employment. The aim of this study was to evaluate the WSP at Queen's University Belfast, and gain the views of both students and Foundation Programme Supervisors and Directors (FPSDs). The study utilised both qualitative (focus groups) and quantitative (questionnaires) approaches. The FPSDs completed a specific questionnaire designed for this study, while the students completed the university's internal quality assurance questionnaire. Twenty-eight of the 37 (76%) FPSDs and 106 / 196 (54%) students completed the questionnaires. Focus groups were conducted with up to 10 students in each group in both a regional centre and a district general hospital at the start and the end of the WSP as well as 8 weeks into working life. The transcripts of the focus groups were analysed and themes identified. A number of deficiencies with the current WSP were identified, including concerns about the use of log books, the timing of the attachment and relatively low levels of supervision provided by senior hospital staff members. As a result, students felt unprepared for commencing work, with particular mention given to medical emergencies, prescribing, and the emotional aspects of the job. A number of recommendations are made, including the need for more senior input to ensure better student attendance, participation and clinical interaction. Furthermore, students should be offered additional supervised responsibility for delivery of patient care and more experiential learning with respect to drug prescribing and administration. The study also suggests that more needs to be done to help ease the emotional and psychological stresses of the early FY1 period. These issues have been resolved to a large extent with the introduction of the new final year Student Assistantship module in the academic year 2010-2011. © The Ulster Medical Society, 2012.

Impact of different health systems on the burden of type 2 diabetes in two populations

Objectives: Health policy directs the management of patients with chronic disease in a country, but evaluating nationwide policies is difficult, not least because of the absence of suitable comparators. This paper examines the management of patients with type 2 diabetes in two demographically comparable populations with different health care systems to see if this represents a viable approach to evaluation.

Methods: A secondary analysis of centralized prescribing databases for 2010 was undertaken to compare the levels and costs of care of patients with type 2 diabetes in Northern Ireland’s National Health Service (NHS) (NI, n = 1.8 million) which has structured care, financial incentives related to diabetes care and an emphasis on generic prescribing, with that of the Republic of Ireland (ROI, n = 4.3 million) where management of diabetes care is guided solely by clinical and other guidelines.

Results: The prevalence of treated type 2 diabetes was 3.59% in NI and 3.09% in ROI, but there were similar and high levels of prescribing of secondary cardiovascular medications. Medication costs per person for anti-diabetic, anti-obesity and cardiovascular medication were 46% higher in ROI than NI, due to differences in levels of generic prescribing.

Conclusions: These different health care systems appear to be producing similar levels of care for patients with type 2 diabetes, although at different levels of cost. The findings question the need for financial incentives in NI and highlight the large cost savings potentially accruing from a greater shift to generic prescribing in ROI. Cross-country comparison, though not without difficulties, may prove a useful adjunct to within-country analysis of policy impact.

Non-steroidal anti-inflammatory drug use and brain tumour risk:a case-control study within the Clinical Practice Research Datalink

Purpose: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed. Methods: The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively.

Results: In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology.

Conclusions: This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma. © 2013 Springer Science+Business Media Dordrecht.

Outcome Measures in Glaucoma:A Systematic Review of Cochrane Reviews and Protocols

In clinical trials, the selection of appropriate outcomes is crucial for the assessment of whether one intervention is better than another. Selection of inappropriate outcomes can compromise the utility of a trial. However, the process of selecting the most suitable outcomes to include can be complex. Ideally, glaucoma trials aim to evaluate important outcomes for clinicians and patients. A high variability in the selection of outcomes suggests that there is no consensus on how best to evaluate the effect of glaucoma interventions. Further, it makes evidence synthesis difficult. The purpose of this review is to determine the extent of clinical outcome measures used in published glaucoma Cochrane Reviews and Protocols.

Management of hyperkalaemia

Hyperkalaemia, an elevated extracellular fluid potassium concentration, is a common electrolyte disorder and is present in 1-10% of hospitalised patients. Elevated serum potassium concentrations are usually asymptomatic but may be associated with electrocardiogram (ECG) changes. Hyperkalaemia occasionally leads to life-threatening cardiac arrhythmias. Prompt recognition of this disorder, patient risk management and administration of appropriate treatment can prevent serious cardiac complications of hyperkalaemia. Further assessment of the underlying basis for hyperkalaemia usually reveals a problem with renal potassium excretion (rather than transcellular shift of potassium or excess potassium intake). Reduced potassium excretion is typically associated with decreased potassium secretion in the aldosterone-sensitive distal nephron of the kidney. Common causes for hyperkalaemia include kidney failure, limited delivery of sodium and water to the distal nephron and drugs that inhibit the renin-angiotensin-aldosterone system. Treatment of life-threatening hyperkalaemia (particularly those patients with ECG changes) involves administration of intravenous calcium salts to stabilise the resting cardiac membrane potential. The potassium concentration can be lowered by administration of intravenous insulin combined with an infusion of glucose to stimulate intracellular uptake of potassium. Nebulised β-2 adrenoceptor agonists can augment the effects of intravenous insulin and glucose pending more definitive management of the recurrent hyperkalaemia risk. Additional management steps include stopping further potassium intake and careful review of prescribed drugs that may be adversely affecting potassium homeostasis. Changes to prescribing systems and an agreed institutional protocol for management of hyperkalaemia can improve patient safety for this frequently encountered electrolyte disorder.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study

Background: Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers.

Objectives: To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma.

Methods: Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case–control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing.

Results: Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68–1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56–1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality.

Conclusions: Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

Learning fluid prescription skills: why is it so challenging?

IIt is well recognised that medical students and junior doctors find fluid prescription a challenging topic. This study was designed to gain a greater understanding of the experiences that medical students face related to learning about fluid prescribing. Methods: A qualitative approach, using focus groups, was employed in this research. Final-year medical students in academic year 2011-12 at Queen's University Belfast were invited to participate during their 'Assistantship' placement in March 2012. Discussions in focus groups, consisting of between six and eight students, were recorded and transcribed verbatim. The research team, consisting of three separate investigators, conducted thematic analysis independently. A final consensus regarding emerging themes was reached by discussion within the whole research team. Medical students and junior doctors find fluid prescription a challenging topic Results: Five prominent themes emerged: 'Teaching experience: a disruptive variation'; 'Curricular disconnections'; 'The driving test: Theory-practice transformation'; 'Role modelling: which standard to aspire to?'; and finally 'Reconciling the perceived risk'. Discussion: This re search provided insights into medical students' opinions of the teaching practices and learning experiences related to fluid prescribing. The learning of prescribing skills is complex andcontextual. In the development of such skills, medical students are often exposed to conflicting educational experiences that challenge the novicelearner in making judgements on best prescribing practice. This study adds to the body of evidence that fluid prescription is a difficult topic, and has generated a number of multifaceted and strategic recommendations to potentially improve fluid prescription teaching.

How Prepared are UK Medical Graduates for Practice? Final report from a programme of research commissioned by the General Medical Council

This programme of research aimed to understand the extent to which current UK medical graduates are prepared for practice. Commissioned by the General Medical Council, we conducted: (1) A Rapid Review of the literature between 2009 and 2013; (2) narrative interviews with a range of stakeholders; and (3) longitudinal audio-diaries with Foundation Year 1 doctors. The Rapid Review (RR) resulted in data from 81 manuscripts being extracted and mapped against a coding framework (including outcomes from Tomorrow's Doctors (2009) (TD09)). A narrative synthesis of the data was undertaken. Narrative interviews were conducted with 185 participants from 8 stakeholder groups: F1 trainees, newly registered trainee doctors, clinical educators, undergraduate and postgraduate deans and foundation programme directors, other healthcare professionals, employers, policy and government and patient and public representatives. Longitudinal audio-diaries were recorded by 26 F1 trainees over 4 months. The data were analysed thematically and mapped against TD09. Together these data shed light onto how preparedness for practice is conceptualised, measured, how prepared UK medical graduates are for practice, the effectiveness of transition interventions and the currently debated issue of bringing full registration forward to align with medical students’ graduation. Preparedness for practice was conceptualised as both a long- and short-term venture that included personal readiness as well as knowledge, skills and attitudes. It has mainly been researched using self-report measures of generalised incidents that have been shown to be problematic. In terms of transition interventions: assistantships were found to be valuable and efficacious for proactive students as team members, shadowing is effective when undertaken close to employment/setting of F1 post and induction is generally effective but of inconsistent quality. The August transition was highlighted in our interview and audio-diary data where F1s felt unprepared, particularly for the step-change in responsibility, workload, degree of multitasking and understanding where to go for help. Evidence of preparedness for specific tasks, skills and knowledge was contradictory: trainees are well prepared for some practical procedures but not others, reasonably well prepared for history taking and full physical examinations, but mostly unprepared for adopting an holistic understanding of the patient, involving patients in their care, safe and legal prescribing, diagnosing and managing complex clinical conditions and providing immediate care in medical emergencies. Evidence for preparedness for interactional and interpersonal aspects of practice was inconsistent with some studies in the RR suggesting graduates were prepared for team working and communicating with colleagues and patients, but other studies contradicting this. Interview and audio-diary data highlights concerns around F1s preparedness for communicating with angry or upset patients and relatives, breaking bad news, communicating with the wider team (including interprofessionally) and handover communication. There was some evidence in the RR to suggest that graduates were unprepared for dealing with error and safety incidents and lack an understanding of how the clinical environment works. Interview and audio-diary data backs this up, adding that F1s are also unprepared for understanding financial aspects of healthcare. In terms of being personally prepared, RR, interview and audio diary evidence is mixed around graduates’ preparedness for identifying their own limitations, but all data points to graduates’ difficulties in the domain of time management. In terms of personal and situational demographic factors, the RR found that gender did not typically predict perceptions of preparedness, but graduates from more recent cohorts, graduate entry students, graduates from problem based learning courses, UK educated graduates and graduates with an integrated degree reported feeling better prepared. The longitudinal audio-diaries provided insights into the preparedness journey for F1s. There seems to be a general development in the direction of trainees feeling more confident and competent as they gain more experience. However, these developments were not necessarily linear as challenging circumstances (e.g. new specialty, new colleagues, lack of staffing) sometimes made them feel unprepared for situations where they had previously indicated preparedness.

The relationship between BMI and the prescription of anti-obesity medication according to social factors: a population cross sectional study

Background: Obesity is a global public health problem. There are a range of treatments available with varying short and long term success rates. One option is the use of anti-obesity medication the prescription of which has increased dramatically in recent years. Despite this, little is known about the individual and GP practice factors that influence the prescription of anti-obesity medication. Methods: Multi-level logistic regression analysis was used to investigate factors associated with the prescription of anti-obesity medication in Northern Ireland using a population primary care prescribing database (~1.5 million people aged 16+ years) during 2009/10. Results: While 25.0% of people are obese, only 1.3% (2.1% of females, 0.6% of males) received anti-obesity medication. The relationship between medication rates and age differed by gender (P < 0.001) with prescriptions higher in younger females and older males. Prescribing of anti-obesity medication reflected obesity prevalence across urban/rural areas and deprivation. There was an unexplained two-fold difference, between the 25th and 75th percentile, in the GP practice prescription of anti-obesity medication. Conclusions: There is evidence of relative under-prescribing in males compared to females despite a similar prevalence of obesity. While the prevalence (and presumably the health consequences) of obesity worsens with age, younger females are more likely to be prescribed anti-obesity medication. This suggests an element of patient demand. Educational material to improve the understanding of the role of anti-obesity medication, for patients and practitioners, is recommended. But further study is needed to understand the factors responsible for the variation in prescribing between GP practices.