Integrating behaviour change counselling into chronic disease management: a square peg in a round hole? A system-level exploration in primary health care.

OBJECTIVES: The objective of this study is to evaluate the uptake of competency-based behaviour change counselling training within a primary healthcare setting. Specific questions concerning provider readiness for training, perceived importance of training in the context of service demands and perceptions of competence after training were addressed. STUDY DESIGN: A process-focused study which adopted a complex systems approach to implementation. Each step was evaluated before the next step was developed. The design was guided by the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. METHODS: Four specific primary care services were identified and behaviour change counselling training tailored to each service was provided, based on a model of training built around competencies in establishing change-based relationships, assessing and promoting readiness to change, using evidence-based behaviour modification skills when ready and addressing psychosocial determinants of behaviour within scope of practice. Before training, a manager's readiness to facilitate training and identification of peer leaders to support ongoing practice of skills were completed. RESULTS: Two programs negotiated 8 h of formal training, one program received 10 h and one program received 12 h. All programs engaged in peer support activities. Despite willingness to support training, 90% of managers were ambivalent about training activities, relative to one half of healthcare providers (HCPs). Few HCPs and no managers self-identified as ready without ambivalence. Furthermore, HCPs were reluctant to be evaluated by an expert and preferred self-evaluation methods. In contrast, HCPs uniformly endorsed the relevance, value and professional commitment to all component skills of the behaviour change counselling model. At the end of the training, over 75% of staff reported receiving formal training (reach). Almost 80% of staff reported using change-based relationship skills daily, with less frequent use of skills associated with addressing psychosocial issues. The degree of corrective feedback was generally low, however. An index of competency based on formal training, frequent use and receiving corrective feedback indicated that most HCPs did not meet these criteria. CONCLUSION: Training in behaviour change counselling competencies was successfully implemented in this project. The vast majority of HCPs received training, despite ambivalence. Furthermore, HCPs strongly valued these skills and used them frequently. However, they were reluctant to accept corrective feedback. Future research is needed to evaluate innovative strategies to overcome obstacles to receiving corrective feedback in the use of behaviour change counselling skills.

Utility of HbA1c assessment in people with diabetes awaiting liver transplantation.

AIMS: To investigate the relationship between HbA1c and glucose in people with co-existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease. METHODS: HbA1c and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non-alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non-cirrhotic portal hypertension and α-1-antitrypsin-related disease. RESULTS: The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49-63) years compared to 60 (50-71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro-Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA1c was 41 (32-56) mmol/mol [5.9 (5.1-7.3)%] vs 61 (52-70) mmol/mol [7.7 (6.9-8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0-11.2) mmol/l vs 7.3 (5.2-11.5) mmol/l (P=0.17). HbA1c was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α-1-antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA1c (r=-0.28 and r=-0.26, respectively) in the diabetes group with cirrhosis. CONCLUSION: HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation.

Predicting inpatient hypoglycaemia in hospitalized patients with diabetes: a retrospective analysis of 9584 admissions with diabetes.

AIMS: To explore whether a quantitative approach to identifying hospitalized patients with diabetes at risk of hypoglycaemia would be feasible through incorporation of routine biochemical, haematological and prescription data. METHODS: A retrospective cross-sectional analysis of all diabetic admissions (n=9584) from 1 January 2014 to 31 December 2014 was performed. Hypoglycaemia was defined as a blood glucose level of <4 mmol/l. The prediction model was constructed using multivariable logistic regression, populated by clinically important variables and routine laboratory data. RESULTS: Using a prespecified variable selection strategy, it was shown that the occurrence of inpatient hypoglycaemia could be predicted by a combined model taking into account background medication (type of insulin, use of sulfonylureas), ethnicity (black and Asian), age (≥75 years), type of admission (emergency) and laboratory measurements (estimated GFR, C-reactive protein, sodium and albumin). Receiver-operating curve analysis showed that the area under the curve was 0.733 (95% CI 0.719 to 0.747). The threshold chosen to maximize both sensitivity and specificity was 0.15. The area under the curve obtained from internal validation did not differ from the primary model [0.731 (95% CI 0.717 to 0.746)]. CONCLUSIONS: The inclusion of routine biochemical data, available at the time of admission, can add prognostic value to demographic and medication history. The predictive performance of the constructed model indicates potential clinical utility for the identification of patients at risk of hypoglycaemia during their inpatient stay.

A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes.

Genetic testing has the potential to guide the prevention and treatment of disease in a variety of settings, and recent technical advances have greatly increased our ability to acquire large amounts of genetic data. The interpretation of this data remains challenging, as the clinical significance of genetic variation detected in the laboratory is not always clear. Although regulatory agencies and professional societies provide some guidance regarding the classification, reporting, and long-term follow-up of variants, few protocols for the implementation of these guidelines have been described. Because the primary aim of clinical testing is to provide results to inform medical management, a variant classification program that offers timely, accurate, confident and cost-effective interpretation of variants should be an integral component of the laboratory process. Here we describe the components of our laboratory's current variant classification program (VCP), based on 20 years of experience and over one million samples tested, using the BRCA1/2 genes as a model. Our VCP has lowered the percentage of tests in which one or more BRCA1/2 variants of uncertain significance (VUSs) are detected to 2.1% in the absence of a pathogenic mutation, demonstrating how the coordinated application of resources toward classification and reclassification significantly impacts the clinical utility of testing.

Validation of an algorithm combining haemoglobin A(1c) and fasting plasma glucose for diagnosis of diabetes mellitus in UK and Australian populations.

AIM: To determine whether glycated haemoglobin (HbA(1c)) can be used in combination with fasting plasma glucose (FPG) for the diagnosis of diabetes in patients with impaired fasting glucose (IFG) and in a broader spectrum of patients. METHODS: An algorithm was derived from oral glucose tolerance test (OGTT) capillary samples in 500 consecutive UK patients with IFG by World Health Organization criteria. It was validated in a further 500 UK patients and, with venous specimens, in 1175 unselected Australian patients. RESULTS: The derivation cohort was aged 61 years (50-69 years) (median IQ range) with 52% male and 12% South Asian. Diabetes Control and Complications Trial-aligned HbA(1c) was 6.2% (5.8-6.6%) (reference interval < 6.0%) and FPG 6.7 mmol/l (6.3-7.2 mmol/l). FPG was in the diabetes range in 36% of patients, with an OGTT identifying a further 12% with diabetes. The derived algorithm, (HbA(1c) >or= 6.0% with FPG < 7.0 mmol/l) identified those patients requiring an OGTT to diagnose diabetes. When applied to the UK validation cohort, sensitivity was 97% and specificity 100%. The algorithm was equally effective in the unselected group, aged 59 years (49-68 years) and 54% male, with sensitivity 93% and specificity 100%. HbA(1c) was 6.0% (5.6-6.6%) and FPG 6.0 mmol/l (5.3-6.8 mmol/l), with 26% having IFG. Use of the algorithm would reduce the number of OGTTs performed in the UK validation cohort by 33% and by 66% in the Australian patients studied. CONCLUSIONS: Use of this algorithm would simplify procedures for diagnosis of diabetes and could also be used for monitoring pre-diabetes. Validation is now required in other populations and patient groups.

Spinodal decomposition in a model colloid-polymer mixture in microgravity.

We study phase separation in a deeply quenched colloid-polymer mixture in microgravity on the International Space Station using small-angle light scattering and direct imaging. We observe a clear crossover from early-stage spinodal decomposition to late-stage, interfacial-tension-driven coarsening. Data acquired over 5 orders of magnitude in time show more than 3 orders of magnitude increase in domain size, following nearly the same evolution as that in binary liquid mixtures. The late-stage growth approaches the expected linear growth rate quite slowly.

Calibration of HbA1c and its measurement in the presence of variant haemoglobins: report on questionnaire to manufacturers.

AIMS: To review 'Diabetes Control and Complications Trial (DCCT)-aligned' HbA(1c) reporting in UK, use of individual/network equations relating IFCC calibration to 'DCCT alignment', and whether HbA(1c) in the presence of variant haemoglobins is, according to manufacturers, suitable for current, clinical guidelines. METHODS: Questionnaire sent to nine manufacturers and responses analysed. RESULTS: All methods were certified as 'DCCT-aligned' by National Glycohemoglobin Standardization Program (NGSP); UK EQA schemes reported 95% of results 'DCCT-aligned' in December 2004. The master equation relating networks was used by six manufacturers and specific equations for individual methods by three. HbA(1c) results from laboratory/point of care testing analysers can be affected by variant haemoglobins including elevated HbF; only IE HPLC (and LPLC) detect their presence. If chromatographic separation is ideal in heterozygous patients, laboratories either choose not to report HbA(1c) and propose another strategy for monitoring glycaemia, or report HbA(1c) and issue a caution that it may not be appropriate for guidelines. HbA(1c) reported from immunochemistry or affinity chromatography in presence of variant haemoglobins, may not be reliable for use with clinical guidelines. CONCLUSIONS: For clinical care, HbA(1c) must reflect its relationship to glycaemia in clinical trials underpinning national guidelines. A flowchart to establish if HbA(1c) measurement is appropriate has been produced for use in a clinical setting.

Glasslike arrest in spinodal decomposition as a route to colloidal gelation.

Colloid-polymer mixtures can undergo spinodal decomposition into colloid-rich and colloid-poor regions. Gelation results when interconnected colloid-rich regions solidify. We show that this occurs when these regions undergo a glass transition, leading to dynamic arrest of the spinodal decomposition. The characteristic length scale of the gel decreases with increasing quench depth, and the nonergodicity parameter exhibits a pronounced dependence on scattering vector. Mode coupling theory gives a good description of the dynamics, provided we use the full static structure as input.

Gravitational collapse of colloidal gels.

We present a unified framework for understanding the compaction of colloidal gels under their own weight. The dynamics of the collapse are determined by the value of the gravitational stress sigma(g), as compared to the yield stress sigma(Y) of the network. For sigma(g)sigma(Y), the network eventually yields, leading to rapid settling. In both cases, the rate of collapse is backflow limited, while its overall magnitude is determined by a balance between gravitational stress and network elastic stress.

Time-dependent strength of colloidal gels.

Colloidal silica gels are shown to stiffen with time, as demonstrated by both dynamic light scattering and bulk rheological measurements. Their elastic moduli increase as a power law with time, independent of particle volume fraction; however, static light scattering indicates that there are no large-scale structural changes. We propose that increases in local elasticity arising from bonding between neighboring colloidal particles can account for the strengthening of the network, while preserving network structure.

The BeWo choriocarcinoma cell line as a model of iodide transport by placenta.

Cultured human choriocarcinoma cells of the BeWo line exhibited saturable accumulation of radioiodide. Inhibition by competing anions followed the affinity series perchlorate >> iodide > or = thiocyanate, consistent with uptake through the thyroid iodide transporter, NIS, whose messenger RNA was found in BeWo cells, and whose protein was distributed towards the apical pole of the cells. Efflux obeyed first order kinetics and was inhibited by DIDS, an antagonist of anion exchangers including pendrin, whose messenger RNA was also present. In cultures where iodide uptake through NIS was blocked with excess perchlorate, radioiodide accumulation was stimulated by exposure to medium in which physiological anions were replaced by 2-morpholinoethanesulfonic acid (MES), consistent with the operation of an anion exchange mechanism taking up iodide. Chloride in the medium was more effective than sulfate at inhibiting this uptake, matching the ionic specificity of pendrin. These studies provide evidence that the trophoblast accumulates iodide through NIS and releases it to the fetal compartment through pendrin.

Limits to gelation in colloidal aggregation.

We show that the dynamics of large fractal colloid aggregates are well described by a combination of translational and rotational diffusion and internal elastic fluctuations, allowing both the aggregate size and internal elasticity to be determined by dynamic light scattering. The comparison of results obtained in microgravity and on Earth demonstrates that cluster growth is limited by gravity-induced restructuring. In the absence of gravity, thermal fluctuations ultimately inhibit fractal growth and set the fundamental limitation to the lowest volume fraction which will gel.

Introduction of IFCC reference method for calibration of HbA: implications for clinical care.

Abstract HbA(1c) is recommended for monitoring glycaemic control and quantifying the risk of complications in patients with diabetes. National guidelines for treatment of patients with diabetes in UK specify that HbA(1c) measurements should be Diabetes Control and Complications Trial (DCCT)-aligned i.e. comparable to the DCCT and UK Prospective Diabetes Study (UKPDS). The IFCC reference method for HbA(1c) will be introduced in Europe in December 2003 for calibration of all laboratory and POCT (point of care testing) methods for HbA(1c) following the recent EC "In Vitro Diagnostic" (IVD) directive. This reference method involves measurement of HbA(1c) and HbA(0) by electron-spray ionisation-mass spectrometry or capillary electrophoresis with the reference range approximately 2% HbA(1c) lower than the corresponding range from the DCCT. However, this EC IVD directive will not change reporting of DCCT-aligned HbA(1c) in the UK. Professionals involved in the care of patients with diabetes in the UK met with Dr Sue Roberts in London in July 2003. It was decided that in the UK DCCT-aligned HbA(1c) will continue to be reported from December 2003 for patient care and that laboratories currently reporting non-aligned DCCT HbA(1c) should change to reporting DCCT-aligned results as soon as possible. It was considered important for diabetes care in the UK that the reporting of HbA(1c) should not fragment. The UK HbA(1c) Standardization Committee was set up to hold "a watching brief " on HbA(1c) especially with relation to reporting of HbA(1c) in other countries.

Facilitation of renal autoregulation by angiotensin II is mediated through modulation of nitric oxide.

AIMS: This study was designed to investigate the influence of angiotensin II (Ang II) and nitric oxide (NO) on autoregulation of renal perfusion. METHODS: Autoregulation was investigated in isolated perfused kidneys (IPRK) from Sprague-Dawley rats during stepped increases in perfusion pressure. RESULTS: Ang II (75-200 pM) produced dose-dependent enhancement of autoregulation whereas phenylephrine produced no enhancement and impaired autoregulation of GFR. Enhancement by Ang II was inhibited by the AT1 antagonist, Losartan, and the superoxide scavenger, Tempol. Under control conditions nitric oxide synthase (NOS) inhibition by 10 microm N-omega-nitro-L-arginine methyl ester (L-NAME) facilitated autoregulation in the presence of non-specific cyclooxygenase (COX) inhibition by 10 microm indomethacin. Both COX and combined NOS/COX inhibition reduced the autoregulatory threshold concentration of Ang II. Facilitation by 100 pm Ang II was inhibited by 100 microm frusemide. Methacholine (50 nm) antagonised Ang II-facilitated autoregulation in the presence and absence of NOS/COX inhibition. Infusion of the NO donor, 1 microm sodium nitroprusside, inhibited L-NAME enhancement of autoregulation under control conditions and during Ang II infusion. CONCLUSIONS: The results suggest than an excess of NO impairs autoregulation under control conditions in the IPRK and that endogenous and exogenous NO, vasodilatory prostaglandins and endothelium-derived hyperpolarizing factor (EDHF) activity antagonise Ang II-facilitated autoregulation. Ang II also produced a counterregulatory vasodilatory response that included prostaglandin and NO release. We suggest that Ang II facilitates autoregulation by a tubuloglomerular feedback-dependent mechanism through AT1 receptor-mediated depletion of nitric oxide, probably by stimulating generation of superoxide.

Universal non-diffusive slow dynamics in aging soft matter.

We use conventional and multispeckle dynamic light scattering to investigate the dynamics of a wide variety of jammed soft materials, including colloidal gels, concentrated emulsions, and concentrated surfactant phases. For all systems, the dynamic structure factor f(q,t) exhibits a two-step decay. The initial decay is due to the thermally activated diffusive motion of the scatterers, as indicated by the q(-2) dependence of the characteristic relaxation time, where q is the scattering vector. However, due to the constrained motion of the scatterers in jammed systems. the dynamics are arrested and the initial decay terminates in a plateau. Surprisingly, we find that a final, ultraslow decay leads to the complete relaxation of f(q,t), indicative of rearrangements on length scales as large as several microns or tens of microns. Remarkably, for all systems the same very peculiar form is found for the final relaxation of the dynamic structure factor: f(q,t) approximately exp[-(t/tau s)p], with p approximately equal to 1.5 and tau s approximately q(-1), thus suggesting the generality of this behavior. Additionally, for all samples the final relaxation slows down with age. although the aging behavior is found to be sample dependent. We propose that the unusual ultraslow dynamics are due to the relaxation of internal stresses, built into the sample at the jamming transition, and present simple scaling arguments that support this hypothesis.

Nonuniversal velocity fluctuations of sedimenting particles.

Velocity fluctuations in sedimentation are studied to investigate the origin of a hypothesized universal scale [P. N. Segre, E. Herbolzheimer, and P. M. Chaikin, Phys. Rev. Lett. 79, 2574 (1997)]. Our experiments show that fluctuations decay continuously in time for sufficiently thick cells, never reaching steady state. Simulations and scaling arguments suggest that the decay arises from increasing vertical stratification of particle concentration due to spreading of the sediment front. The results suggest that the velocity fluctuations in sedimentation depend sensitively on cell geometry.

Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption.

Previous work demonstrated that the locomotor stimulant actions of amphetamine, cocaine and nicotine were increased when these drugs were given during the abstinence phase after chronic ethanol consumption. These changes were seen at 6 days and at 2 months after cessation of alcohol. The present study examined neuronal alterations which might be related to these changes in behaviour. Markedly reduced spontaneous firing rates of dopaminergic cells in the ventral tegmental area (VTA) in midbrain slices were seen 6 days into the abstinence period after cessation of chronic ethanol consumption, but by 2 months the firing rates had returned to control values. Increased affinity of striatal receptors for the D1-like receptor ligand 3H-SCH23390, but no change in the receptor density, was found both at the 6 day and the 2 month intervals. The binding properties of striatal D2-like receptors, of D1-like and D2-like receptors in the frontal cerebral cortex, and the release of tritiated dopamine from slices of striatum or frontal cerebral cortex, were unchanged at 6 days and 2 months. It is suggested that the decreased neuronal firing leads to a persistent increase in sensitivity of D1-like receptors and that these changes could explain the increased effects of the other drugs of abuse.

Lack of association of prostate carcinoma nuclear grading with prostate specific antigen recurrence after radical prostatectomy.

PURPOSE: Grading prostate cancer using the Gleason system relies only on architectural tumor growth, in contrast to other systems, such as the WHO system, which grade prostate carcinoma based on nuclear features as well as architectural patterns. The prognostic significance of nuclear grading remains controversial since most studies were performed before prostate specific antigen (PSA) screening became widely available. We evaluated the significance of nuclear grade for predicting PSA recurrence in a contemporary cohort of patients treated with radical prostatectomy for clinically localized prostate carcinoma. MATERIALS AND METHODS: Nuclear grades 1 to 3 were determined in 141 consecutive radical prostatectomies in 1995. Predominant and worst nuclear grade was determined by a consensus of 3 pathologists. Statistical analysis compared nuclear grade with Gleason score using the chi-square test. The Cox proportional hazards analysis was performed to calculate the ability of nuclear grade, Gleason score and other variables to predict PSA recurrence. RESULTS: We identified a significant association of Gleason score with worst nuclear grade (p = 0.007). All 6 cases with a Gleason score of 8 or greater had a worst nuclear grade of 3, in contrast to 36 of 60 (60%) with a score 6 or less, in which the worst nuclear grade was 3. Of the 141 patients 31 (21.9%) had PSA recurrence at a median followup of 3.7 years. The univariate Cox model revealed significant associations of PSA recurrence with Gleason score 8 or greater (hazards ratio 5.5, p = 0.005), extraprostatic extension (hazards ratio 3.4, p = 0.001), positive surgical margin (hazards ratio 2.6, p = 0.009), seminal vesicle involvement (hazards ratio 7.3, p <0.001), preoperative serum PSA (hazards ratio 1.03, p = 0.007), tumor stage (hazards ratio 3.6, p = 0.001) and maximal tumor dimension (hazards ratio 2.4, p <0.001). However, overall and worst nuclear grade did not predict PSA recurrence (p = 0.89 and 0.13, respectively). Nuclear grade did not fit any multivariate model tested, which otherwise included Gleason score, log(PSA), surgical margin status, extraprostatic extension, seminal vesicle status, tumor size and pathological stage. By varying sample fixation time we also showed that benign prostate tissue in the same section as prostate carcinoma had grade 2 or 3 nuclear changes, that is moderate to marked anaplasia. CONCLUSIONS: High nuclear grade is associated with high Gleason score. However, prostate carcinoma with a Gleason score of 6 or less shows extreme variability. Nuclear grade determined by light microscopy failed to predict PSA recurrence in a contemporary series of men with clinically localized prostate cancer treated with radical prostatectomy. Nuclear morphology is subject to tissue fixation and processing artifact. Any nuclear morphometric study must consider this artifact.