Sociodemographic disparities in non-diabetic hyperglycaemia and the transition to type 2 diabetes: evidence from the English Longitudinal Study of Ageing.

AIM: To explore whether there are social inequalities in non-diabetic hyperglycaemia (NDH) and in transitions to type 2 diabetes mellitus and NDH low-risk status in England. METHODS: Some 9143 men and women aged over 50 years were analysed from waves 2, 4, 6 and 8 (2004-2016) of the English Longitudinal Study of Ageing (ELSA). Participants were categorized as: NDH 'low-risk' [HbA1c < 42 mmol/mol (< 6.0%)], NDH [HbA1c 42-47 mmol/mol (6.0-6.4%)] and type 2 diabetes [HbA1c > 47 mmol/mol (> 6.4%)]. Logistic regression models estimated the association between sociodemographic characteristics and NDH, and the transitions from NDH to diagnosed or undiagnosed type 2 diabetes and low-risk status in future waves. RESULTS: NDH was more prevalent in older participants, those reporting a disability, those living in deprived areas and in more disadvantaged social classes. Older participants with NDH were less likely to progress to undiagnosed type 2 diabetes [odds ratio (OR) 0.27, 95% confidence interval (CI) 0.08, 0.96]. NDH individuals with limiting long-standing illness (OR 1.72, 95% CI 1.16, 2.53), who were economically inactive (OR 1.60, 95% CI 1.02, 2.51) or from disadvantaged social classes (OR 1.63, 95% CI 1.02, 2.61) were more likely to progress to type 2 diabetes. Socially disadvantaged individuals were less likely (OR 0.64, 95% CI 0.41, 0.98) to progress to NDH low-risk status. CONCLUSIONS: There were socio-economic differences in NDH prevalence, transition to type 2 diabetes and transition to NDH low-risk status. Disparities in transitions included the greater likelihood of disadvantaged social groups with NDH developing type 2 diabetes and greater likelihood of advantaged social groups with NDH becoming low-risk. These socio-economic differences should be taken into account when targeting prevention initiatives.

Understanding economic evidence for the prevention and treatment of atopic eczema.

BACKGROUND: Atopic eczema is an inflammatory skin condition, with a similar impact on health-related quality of life as other chronic diseases. Increasing pressures on resources within the National Health Service increase the importance of having good economic evidence to inform their allocation. OBJECTIVES: To educate dermatologists about economic methods with reference to currently available economic evidence on eczema. METHODS: The role of different types of economic evidence is illustrated by evidence found in a systematic literature search conducted across 12 online databases up to 22 May 2017. Primary empirical studies either reporting the results of a cost-of-illness study or evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema were included. Two reviewers independently assessed studies for eligibility and performed data abstraction, with disagreements resolved by a third reviewer. Evidence tables of results were produced for narrative discussion. The reporting quality of economic evaluations was assessed. RESULTS: Seventy-eight studies (described in 80 papers) were deemed eligible. Thirty-three (42%) were judged to be economic evaluations, 12 (15%) cost analyses, six (8%) utility analyses, 26 (33%) cost-of-illness studies and one a feasibility study (1%). The calcineurin inhibitors tacrolimus and pimecrolimus, as well as barrier creams, had the most economic evidence available. Partially hydrolysed infant formula was the most commonly evaluated prevention. CONCLUSIONS: The current level of economic evidence for interventions aimed at preventing and treating eczema is limited compared with that available for clinical outcomes, suggesting that greater collaboration between clinicians and economists might be beneficial.

An introduction to the methods of decision-analytic modelling used in economic evaluations for Dermatologists.

Economic evaluations are used to identify which health treatments or preventions offer the most effective use of resources, or value for money. This is achieved by identifying, measuring and valuing the inputs and outcomes of alternative interventions. These evaluations are often conducted alongside clinical trials; however, these trials may end before the outcomes of economic interest have been observed and measured. An alternative to within trial economic evaluation is to use decision modelling, which can model the cost-effectiveness of interventions over an extended time period. This paper aims to provide an overview for clinicians of the different modelling techniques used within health economic evaluations and to introduce methods for critical appraisal. The most common modelling approaches, and their associated strengths and weaknesses, were discussed. Alongside this, practical examples specific to dermatology were given. These examples include studies where the model chosen or the methods used may not have been the most appropriate. Methods for critical appraisal were also highlighted. Common modelling approaches include Decision Trees, Markov Cohort, extensions to the Markov model (Monte Carlo Simulation) and Discrete Event Simulation models. Items of the Philips Checklist were discussed in the context of performing critical appraisal. Health economic decision models are multi-faceted and can often be complex. Full critical appraisal requires clinicians' unique knowledge, which is complementary to the knowledge of health economists.

Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series.

Background: Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM. Methods: We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5-7-day fast every 1-2 months combined with a modified ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse effects were assessed. Results: Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. The mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). The most common adverse effects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. The metabolic strategy did not interfere with standard oncological treatments. Conclusion: This is the first study to observe the feasibility and safety of repeated, prolonged fasting combined with a modified ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5-6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse effects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: This study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. The study was registered on 4 December 2020.

The effect of arprinocid on the reproductive potential of a field isolate of Eimeria tenella.

Oocyst production by an isolate of Eimeria tenella propagated from birds medicated with 50 ppm arprinocid was compared with that of the same isolate propagated from unmedicated birds. Statistically significant (P less than 0.05) reductions in oocyst production were found for the drug-exposed isolate for inocula levels of 64 and 250 sporulated oocysts per bird. Numerical reductions were observed for inocula levels of 1,000 oocysts per bird, but with higher levels of inocula, no differences were seen. Inhibitory drug effects for the inocula levels of 64 and 250 oocysts per bird appear to be meaningful because they coincide with the maximum reproductive potential (oocysts produced per oocyst inoculated). The results indicated that significant information can be masked by excessive inoculum with consequent crowding and reduction in reproductive potential.

Effects of arprinocid on developmental stages of Eimeria tenella.

Restricted medication experiments were done to correlate time of arprinocid medication with developmental stages of the life cycle of Eimeria tenella. By the criterion of histopathology and using a massive inoculum (10(6) sporulated oocysts), 50 ppm was partially active and 70 ppm was fully active against the first asexual generation when medication was delayed until day 1. When medication was delayed until day 2, full activity was demonstrated against the late, first asexual generation. When medication was delayed until day 3, definite but less complete activity was shown against the late, second asexual generation. Using the conventional efficacy parameters and with an inoculum of 5 X 10(4), full activity occurred with 50 ppm when medication was started up to day 2. Essentially full activity was observed with 60 ppm started at day 3. The combined results of the two tests are interpreted to indicate high activity against both the first and second asexual generations. Medication with 70 ppm changed the wall-forming bodies of the macrogamete. They were indistinct and less intensely eosinophilic than controls.

Histopathologic features of canine heartworm microfilarial infection after treatment with ivermectin.

Tissues of dogs treated with ivermectin were examined microscopically to learn the fate of microfilariae of canine heartworm that disappear from the peripheral circulation within a few days of treatment. Medicated dogs were killed 18 hours, 3 days, and 6 days after treatment with 0.5 mg of ivermectin/kg of body weight subcutaneously. Ivermectin was dissolved in 60% propylene glycol and 40% glycerol formal. In dogs killed at posttreatment hour 18, the peripheral microfilaremia had decreased by an average of 89%. At this time, a dense mass of RBC, WBC, and macrophages plus many microfilariae was found in pulmonary alveolar septae. Similar reactions were seen in liver, kidney, and spleen. Phagocytosis of microfilarial fragments was evident. In dogs killed at posttreatment day 3, many microfilariae were fragmented and phagocytosis of the fragments was common. In dogs killed at posttreatment day 6, microgranulomas were common, particularly in such vascular organs as lungs, kidney, and liver. Microgranulomas containing microfilariae were also seen in spleen, skeletal and cardiac muscles, diaphragm, lymph nodes, gastrointestinal tract, and pancreas. Small glial nodules were seen in the CNS. Denudation of the atrial epicardium was associated with fragments of microfilariae and granulomatous inflammatory cells. Renal epithelial crescents were observed in treated and nontreated dogs. Plasma cells were conspicuous in treated and nontreated dogs, especially in some livers and kidneys. Before treatment, all dogs were severely microfilaremic. At the end of the experiment, the peripheral microfilaremia was reduced by 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Battery efficacy studies with arprinocid against field strains of Coccidia.

Graded levels of 9-[2-chloro-6-fluorophenyl)methyl]-9H-purin-6-amine (arprinocid) ranging from 30 ppm to 90 ppm in the diet have been tested for anticoccidial efficacy in controlled battery experiments against 20 field isolates of coccidia. These isolates, representing five major species of Eimeria, were collected from various geographic locations and all but one were found to be resistant to one or more of the currently marketed products. Arprinocid prevented mortality, increased weight gains, and reduced or eliminated intestinal lesions and oocyst production. A level of 60 ppm arprinocid provided adequate control of all isolates and no evidence of cross resistance was observed between arprinocid and the marketed products tested. On the basis of these studies, it is concluded that arprinocid at levels of 60 ppm to 70 ppm is effective in controlling coccidiosis in broilers, even that caused by isolates refractory to many of the marketed products.

Anticoccidial and tolerance studies in the chicken with two 6-amino-9-(substituted benzyl)purines.

Initial assays of 6-amino-9-(2-chloro-6-fluorobenzyl) purine (MK-302) and 6-amino-9-(2,6-dichlorobenzyl)purine (coded L-628,914) showed potential as anticoccidial agents on the basis of broad-spectrum activity and safety. In battery efficacy studies, dietary levels of 60 to 70 p.p.m. and above MK-302 and 45 to 60 p.p.m. L-628,914 proved to have excellent broad-spectrum anticoccidial activity in chickens given heavy exposure to virulent field isolates of coccidia. Eight-week floor-pen tolerance trials showed that the maximum tolerated diet concentration (MTC) of MK-302 was approximately 95 p.p.m. while the MTC of L-628,914 was approximately 60 p.p.m. Dietary relationships (p.p.m. MK-302:p.p.m. L-628,914 for equivalent effects) derived from the efficacy and tolerance results were 1.2:1 and 1.6:1 respectively and clearly demonstrated a higher therapeutic ratio for MK-302.

Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery.

OBJECTIVES: To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome. DESIGN: Randomised controlled trial with double blinding between inotrope groups. SETTING: York District Hospital, England. SUBJECTS: 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. INTERVENTIONS: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care. MAIN OUTCOME MEASURES: Hospital mortality and morbidity. RESULTS: Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital. CONCLUSION: Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.

Freedom to enjoy learning in the 21st century: developing an active learning culture in nursing.

In 1994, the Wolfson School of Health Sciences was created in Thames Valley University, UK. This paper discusses an active learning approach being implemented throughout the university, and gives an outline of its application within nursing education. Practising as a confident, competent, reflective practitioner in the profession of nursing cannot automatically commence on the day of registration. Rather, the philosophical underpinnings necessary should be fostered throughout the initial nursing education curricula. In a political climate where there is a strong emphasis on efficiency, nurse teachers need to reconsider how the acquisition of nursing knowledge is facilitated. A description of how an active learning approach is being further developed in the nursing skills laboratory and the physiology laboratory is given. An outline identifies how these facilities may help students of nursing to gain knowledge and skills in relation to respiration. The authors recognize that while laboratories have been used widely in general education, their use has been limited in nursing education, particularly in the UK. Informal feedback from students implies that not only do they enjoy learning in these facilities, but also motivation towards learning is raised, an important element in the learning process. It is suggested that this will result ultimately in increased nursing competence. The authors acknowledge that these are preliminary informal findings and that formal investigation is required.

Decision making and work loads as predictors of student nurses' health status.

This study was conceived as a means of exploring the factors that could contribute to student nurses' burnout with their educational programs. Current literature mainly addresses this process in terms of the experience of registered nurses. This descriptive study sought to determine the relationships between nursing students' latitude in academic decision making and school work load demands and their effects on the students' health status. Thirty-four female, second-quarter senior nursing students completed a written tool, adapted from one developed by Karasek. Data analysis revealed that for this study, alterations in the nursing students' health status could be predicted from the independent variables, latitude in academic decision making, and school work load demand.

Health promotion and social support for community-based clients with chronic mental illness.

The purpose of this study was to determine the health promotion practices and life styles of 35 chronically mentally ill clients who resided in four group homes in a medium-sized southern community. Supervision in these homes ranged from full supervision to none. The Pender Health Promotion and Lifestyle Instrument (HPLP), the Duke-University of North Carolina Functional Support Questionnaire, and the Hollingshead Four Factor Index of Social Status were used. The Pender instrument had internal consistency scores that ranged from .92 for health promotion and lifestyle scale to .70 for the stress management subscale. Several findings emerged. The total scores were low for this sample on the HPLP and the six subscales: nutrition, exercise, health responsibility, stress management, internal support, and self-actualization. There were strong positive correlations between social interaction and age, father's education, and HPLP.

The use of ketoconazole in the treatment of blastomycosis.

We retrospectively reviewed our experience using ketoconazole in the therapy of blastomycosis. Over the course of 30 months, blastomycosis was diagnosed in 11 patients. Their clinical presentations ranged from the asymptomatic pulmonary nodule to the adult respiratory distress syndrome. Six of 8 patients treated with ketoconazole completed a 6-month course of 400 mg daily. Seventeen to 40 months after completion of therapy, the patients who had completed 6 months of therapy were well. Ketoconazole should play a major role in the therapy of blastomycosis because of its efficacy and because its administrative costs are lower than those of amphotericin B. It can be recommended for patients who have been symptomatic for longer than 3 wk and are not improving and for those who undergo resection of an asymptomatic pulmonary nodule. Amphotericin B remains the drug of choice in patients with life-threatening illness who require ventilatory assistance, have developed renal failure, or have central nervous system involvement. Severely immunocompromised patients with disseminated disease should also be treated with amphotericin B. Patients treated with ketoconazole should have close medical follow-up.