Douglas Steinke

Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

ABSTRACT Bacteria belonging to the normal colonic microbiota are associated with the etiology of ulcerative colitis (UC). Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown. The aim of this investigation was to characterize mucosal biofilm communities over time and to determine the relationship of these bacteria to patient age and disease severity and duration. Multiple rectal biopsy specimens were taken from 33 patients with active UC over a period of 1 year. Real-time PCR was used to quantify mucosal bacteria in UC patients compared to 18 noninflammatory bowel disease controls, and the relationship between indicators of disease severity and bacterial colonization was evaluated by linear regression analysis. Significant differences were detected in bacterial populations on the UC mucosa and in the control group, which varied over the study period. High clinical activity indices (CAI) and sigmoidoscopy scores (SS) were associated with enterobacteria, desulfovibrios, type E Clostridium perfringens, and Enterococcus faecalis, whereas the reverse was true for Clostridium butyricum, Ruminococcus albus, and Eubacterium rectale. Lactobacillus and bifidobacterium numbers were linked with low CAI. Only E. rectale and Clostridium clostridioforme had a high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in UC and that bacterial community structure is related to disease severity.

Examining Trends in Type 2 Diabetes Incidence, Prevalence and Mortality in the UK between 2004 and 2014

Contemporary data describing type 2 diabetes prevalence, incidence and mortality are limited. We aimed to (1) estimate annual incidence and prevalence rates of type 2 diabetes in the UK between 2004 and 2014, (2) examine relationships between observed rates with age, gender, socio‐economic status and geographic region, and (3) assess how temporal changes in incidence and all‐cause mortality rates influence changes in prevalence.

A comparison of medication adherence/persistence for asthma and chronic obstructive pulmonary disease in the United Kingdom.

To describe and compare adherence and persistence with maintenance therapies in patients with asthma or chronic obstructive pulmonary disease (COPD) in the United Kingdom (UK).

Clinical inertia in type 2 diabetes: a retrospective analysis of pharmacist-managed diabetes care vs. usual medical care

Background Evidence suggests that patients with type 2 diabetes (T2DM) suffer from a high rate of “clinical inertia” or “recognition of the problem but failure to act.” Objective The aim of this study is to quantify the rate of clinical inertia between two models of care: Pharmacist-Managed Diabetes Clinic (PMDC) vs. Usual Medical Care (UMC). Methods Patients in a university based medical clinic with type 2 diabetes (T2DM) were analyzed in this retrospective cohort study. Patients were exposed to either PMDC or UMC. The difference in days to intervention in response to suboptimal laboratory values and time to achieve goal hemoglobin A1c (A1c), systolic blood pressure (SBP) and low-density lipoprotein (LDL) was compared in the two models of care. Results A total of 113 patients were included in the analysis of this study, 54 patients were in the PMDC and 59 patients were in the UMC group. Median time (days) to intervention for A1c values >7% was 8 days and 9 days in the PMDC and UMC groups, respectively (p>0.05). In patients with baseline A1c values >8%, median time to achieving A1c<7% was 259 days vs. 403 days in the PMDC and UMC groups, respectively (p<0.05). Median time to goal SBP was 124 days in the PMDC group and 532 days in the UMC group (p<0.05). Median time to goal LDL was 412 days in the PMDC group vs. 506 days in the UMC group (p<0.05). Conclusions Rates of clinical inertia, defined as time to intervention of suboptimal clinical values, did not differ significantly between patients enrolled in a PMDC compared to patients with UMC with respect to A1c, SBP and LDL. Participation in PMDC, however, was associated with achieving goal A1c, SBP, and LDL levels sooner compared to UMC.

Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records

To examine the risk of major cardiovascular events associated with second‐line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors.

Performance of a Divided-Load Intravenous Vancomycin Dosing Strategy for Critically Ill Patients:

Background: Current guidelines recommend vancomycin trough concentrations 15 to 20 µg/mL in complicated infections and all trough concentrations above 10 µg/mL. Objective: We assessed the performance of a novel divided-load protocol designed to attain target trough concentrations within 24 hours of initiation and prevent doses given at concentrations above the target range, in critically ill patients. Methods: The protocol was evaluated in 79 critically ill patients through retrospective medical record review. Vancomycin serum concentrations were drawn before the third dose after initiation and after any dosing change. Steady-state concentrations were drawn before the fifth or sixth doses. Vancomycin concentrations before the second dose were predicted using a nonparametric expectation maximization algorithm. Results: Sixty-nine of 79 patients received scheduled doses, and 62 (90%) of the scheduled-dose patients attained therapeutic target concentrations 12 to 24 hours after therapy initiation. Eight scheduled-dose patients weighed > 150% of ideal body weight (IBW) and were significantly more likely to exhibit supratherapeutic trough concentrations before the fifth or sixth doses (P = .0004) compared with patients weighing ≤150% of IBW. Ten of 79 patients (8 dialysis dependent and 2 experiencing acute kidney injury) were dosed in response to measured serum drug concentrations drawn according to the divided-load protocol. All the 8 dialysis-dependent patients (100%) attained therapeutic concentrations 12 hours after therapy initiation. Conclusion: The divided-load vancomycin dosing strategy achieved measured trough concentrations 15 to 20 µg/mL for most critically ill patients within 24 hours of initial dosing, without allowing doses given during supratherapeutic concentrations.

ADHD in the United Kingdom Regional and Socioeconomic Variations in Incidence Rates Amongst Children and Adolescents (2004-2013)

Objective: To describe the incidence and distribution of ADHD within the United Kingdom, and to examine whether there was any association between ADHD incidence and socioeconomic deprivation. Method: The study used data from the Clinical Practice Research Datalink (CPRD). Patients diagnosed with ADHD before the age of 19 between January 1, 2004 and December 31, 2013 were stratified according to the region in which their general practice was based. Practice Index of Multiple Deprivation (IMD) score was used as a surrogate measure of patients’ deprivation status. Results: ADHD incidence was relatively stable between 2004 and 2013, but peaked in the last 2 years studied. Statistically significant (p ≤ .05) differences in incidence were observed between U.K. regions. In almost every year studied, incidence rates were highest among the most deprived patients and lowest among the least deprived patients. Conclusion: In the United Kingdom, ADHD may be associated with socioeconomic deprivation.

Performance of a Divided-Load Intravenous Vancomycin Dosing Strategy for Obese Patients

Background: Current guidelines recommend vancomycin trough concentrations of 15 to 20 µg/mL in complicated infections and all trough concentrations >10 µg/mL to avoid developing microbial resistance. To date, no published protocol reliably meets these recommendations for obese patients. Objective: We assessed the performance of a novel, obese-specific, divided-load vancomycin protocol for attaining target trough concentrations within 12 to 24 hours of dosing initiation, and during maintenance dosing, in obese patients. Methods: The protocol was evaluated through prospective medical record review in 54 consecutive obese patients. Vancomycin serum concentrations were drawn before the third and fifth dose after initiation. Steady-state concentrations were drawn after the third dose once maintenance dosing was achieved and periodically thereafter. Results: Within 12 hours after dosing initiation, 48 (89%) study patients exhibited trough concentrations of 10 to 20 µg/mL averaging 14.5 ± 3.2 µg/mL; 51 (94%) study patients exhibited trough concentrations >10 µg/mL within 12 hours after dosing initiation, and 3 (6%) had trough concentrations >20 µg/mL. Thirty-one participants had second trough concentrations drawn within 24 hours of dosing initiation, averaging 15.0 ± 3.1 µg/mL; 24 patients had a total of 32 trough concentrations drawn during maintenance dosing, averaging 15.1 ± 2.5 µg/mL. Conclusion: Obese-specific, divided-load dosing achieved trough concentrations of 10 to 20 µg/mL for 89% of obese patients within 12 hours of initial dosing and 97% of obese patients within 24 hours of initial dosing while preventing doses given during supratherapeutic trough levels; 97% of troughs measured during steady state were within target range.

Identifying, highlighting and reducing polypharmacy in a UK hospice inpatient unit using improvement Science methods

Polypharmacy, the concurrent use of multiple medications by one individual is a growing global issue driven by an ageing population and increasing prevalence of multi-morbidity[1]. Polypharmacy can be problematic: interactions between medications, reduced adherence to medication, burden of medication to patients, administration time, increased risk of errors and increased cost. Quality improvement methods were applied to identify and highlight polypharmacy patients with the aim of reducing their average number of regular tablets/capsules per day by 25%. The project was delivered within a UK based 27 bedded hospice inpatient unit. A series of PDSA cycles studied interventions focusing on the identification of patients with polypharmacy, the highlighting of these patients to prescribers for review and the views of patients about their medication. For the purposes of the study, polypharmacy was defined as greater than ten regular medicines and/or greater than twenty regular tablets/capsules each day. The interventions tested included patients on regular paracetamol and strong opioids being offered a trial without regular paracetamol, a constipation guide promoting the use of combination laxatives, education of prescribers around dose strengths, checklist of recommendations was placed in case notes and a sticker was used on the medicine chart to highlight patients in need of polypharmacy review. The introduction of a trial without paracetamol and a laxative guide led to reductions in polypharmacy. The sticker and checklist were successful interventions for highlighting patients with polypharmacy. Quality improvement methods were used to plan, try, test and implement simple interventions for patients on the hospice inpatient unit. This has led to a 25% reduction in the average regular tablet/capsules burden , a 16% reduction in the average number of regular medications and a 30% reduction in the average volume of liquid medication per patient without an increase in the use of ‘as required’ medication or length of stay.

Pharmacists' attitudes towards a pharmaceutical assessment screening tool to help prioritise pharmaceutical care in a UK hospital

Objective To establish the thoughts of pharmacists using the pharmaceutical assessment screening tool (PAST) when assigning a patient acuity level (PAL) and establish other decision factors. A PAL is a pharmaceutical assessment of a patient (lowest=1 to highest=3), higher PALs highlight the requirement for a more intensive pharmaceutical input to reduce potential harm. Method A questionnaire designed to elicit attitudes about the PAST was circulated to 32 pharmacists working in a 900 bed UK university teaching hospital. Respondents were asked to document what PAL they would assign for six theoretical patient cases with an explanation. The data collected was analysed using Microsoft Excel and further analysis was undertaken about the strength of agreement to PAST using the κ statistic using Stata V.12 (StataCorp, Texas, USA). Results The questionnaire was completed by 28/32 pharmacists (87.5% response rate). The mean confidence (SD) for assigning a PAL was 81% (±20%). 26/28 pharmacists (93%) agreed or strongly agreed that professional judgement guided them most when allocating a PAL. The PAL assigned to the case studies presented both overestimations and underestimations compared with the guidance but overall the strength of agreement was considered to be ‘fair’ (κ=0.202). Conclusions Pharmacists feel confident about using PAST to help them assign a PAL. However, the use of professional judgement to assign an acuity level overrides any predicted level from PAST.