Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists

Patients attending for diagnostic oesophagogastroduodenoscopy (OGD) for dyspeptic symptoms are often receiving acid-suppression therapy that has not been discontinued prior to endoscopy, and this may reduce the diagnostic yield of endoscopy. The aim of this study was to compare the diagnostic yield of OGD in uncomplicated dyspepsia in patients receiving no medication, those receiving acid-suppression therapy, and those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of endoscopy.

"They come with multiple morbidities":a qualitative assessment of pharmacist prescribing

This paper presents qualitative findings from a larger sequential mixed methods study which sought to provide an in-depth understanding of pharmacist prescribing from the perspective of pharmacist prescribers, medical colleagues and key stakeholders in Northern Ireland. Transcriptions were analyzed using thematic analysis as the interviews progressed and emergent themes were identified and coded (along with supporting quotes) independently and by consensus of the research team. Three major themes emerged in relation to pharmacist prescribing: the effect on patient care; challenges facing pharmacist prescribers and the importance of the interprofessional team (where two or more different professions with varied, yet complementary experience work together with a common purpose). Pharmacist prescribing may have the potential to reduce the medication burden for patients (as reported by pharmacists) as pharmacists tend to provide a more comprehensive medication review than doctors; the additional time for consultations made this possible. Further research is required on how interprofessional team working can be maximized in the context of pharmacist prescribing, particularly in relation to the management of multi-morbidity.

Withholding, discontinuing and withdrawing medications in dementia patients at the end of life:a neglected problem in the disadvantaged dying?

Recent years have seen a growing recognition that dementia is a terminal illness and that patients with advanced dementia nearing the end of life do not currently receive adequate palliative care. However, research into palliative care for these patients has thus far been limited. Furthermore, there has been little discussion in the literature regarding medication use in patients with advanced dementia who are nearing the end of life, and discontinuation of medication has not been well studied despite its potential to reduce the burden on the patient and to improve quality of life. There is limited, and sometimes contradictory, evidence available in the literature to guide evidence-based discontinuation of drugs such as acetylcholinesterase inhibitors, antipsychotic agents, HMG-CoA reductase inhibitors (statins), antibacterials, antihypertensives, antihyperglycaemic drugs and anticoagulants. Furthermore, end-of-life care of patients with advanced dementia may be complicated by difficulties in accurately estimating life expectancy, ethical considerations regarding withholding or withdrawing treatment, and the wishes of the patient and/or their family. Significant research must be undertaken in the area of medication discontinuation in patients with advanced dementia nearing the end of life to determine how physicians currently decide whether medications should be discontinued, and also to develop the evidence base and provide guidance on systematic medication discontinuation.

A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease

This 12-week, multinational study compared the tolerability and cognitive effects of donepezil (up to 10 mg once daily) and rivastigmine (up to 6 mg twice daily) in 111 patients with mild to moderate Alzheimer's disease. Both medications were administered open label according to recommended dosing regimens from the respective product labelling available during the conduct of the study. More patients in the donepezil group (89.3%) completed the study compared with the rivastigmine group (69.1%; p=0.009), and 10.7% of the donepezil group and 21.8% of the rivastigmine group discontinued due to adverse events (AEs); 87.5% of donepezil-treated patients and 47.3% of rivastigmine-treated patients remained on the maximum approved dose of each drug at the last study visit. Both groups showed comparable improvements on the ADAS-cog administered by raters blind to study medication at weeks 4 and 12. Thus, using the recommended dosing schedules, donepezil was better tolerated with fewer discontinuations due to AEs, and both agents improved cognition to a similar extent.

Economic aspects of pharmacotherapy for chronic constipation

Constipation is one of the most common digestive complaints. It is a symptom, not a disease. The subjectivity that this involves means that assessments of clinical epidemiology, socioeconomic costs and pharmacotherapy are difficult, since there is no definition of 'normal' bowel habit. Although constipation can affect all ages, the problem increases with age, and is of particular concern for those who are frail and in long term care. Cultural influences may affect the prevalence in older people. Drug therapy of constipation cannot be considered in isolation, since there are issues in the prevention of constipation and the principles of good management that also apply. Furthermore, some consideration of the pathophysiology and diagnosis is important. This is because a number of remediable causes can be identified, and the diagnostic process involves patient education, which in turn may be effective in reducing costs. It is the complaint of constipation which leads either to self-medication or to consultation with the medical profession. Both of these courses of action have a significant influence on utilisation of laxatives (cathartics), obtained both over-the-counter and by prescription. Although there are a large number of laxative preparations available, therapy has changed little in half a century. Costs may vary considerably, and with such a significant problem there is a need for comparative studies. However, study methodologies are difficult, and a significant placebo response may be found. Education and preventive measures have been shown to reduce laxative use and costs in institutions. Unfortunately, there are few comparative studies of individual laxatives and even fewer cost-effectiveness studies. Those that there are have been based in institutions, and so extrapolation to other situations may be difficult. In general, little attention is given to constipation. It is, however, an area with significant resource implications in which education and preventive measures have been shown to be beneficial. Even so, there is still a need for good comparative studies, particularly where cost effectiveness is concerned.

Clinical practice with anti-dementia drugs:a revised (second) consensus statement from the British Association for Psychopharmacology

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.

Obesity associated severe asthma represents a distinct clinical phenotype - Analysis of the British Thoracic Society Difficult Asthma Registry patient cohort according to body mass index

BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airways inflammation. However, the role of obesity in severe asthma remains unclear. OBJECTIVE: To explore the association between obesity (defined by BMI) and severe asthma. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics and healthcare utilisation between three body mass index (BMI) categories (normal weight: 18.5 -24.99, overweight: 25 -29.99, obese: =30) in a well characterised group of severe asthmatic adults. RESULTS: The study population consisted of 666 severe asthmatics with a median BMI of 29.8 (interquartile range 22.5 -34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% versus 40.4% and 34.5% in the overweight and normal weight groups, respectively), steroid burst therapy and short-acting ß2-agonist (SABA) use per day. Significant differences were seen with gastro-oesophageal reflux disease (GORD) (53.9% versus 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor (PPI) use. Bone density scores were higher in the obese group, whilst pulmonary function testing revealed a reduced FVC and raised Kco. Serum IgE levels decreased with increasing BMI and the obese group were more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Severe asthmatics display particular characteristics according to BMI that support the view that obesity associated severe asthma may represent a distinct clinical phenotype.1Royal Brompton Hospital, London, UK;2Department of Computing, Imperial College, UK3Airways Disease, National Heart & Lung Institute, Imperial College, UK;4Centre for infection and immunity, Queen's University of Belfast, UK;5University of Leicester, UK;6The University of Manchester and University Hospital of South Manchester, UK;7Birmingham Heartlands Hospital, University of Birmingham, UK;8Gartnavel General Hospital, University of Glasgow, UK;9Glasgow Royal Infirmary, Glasgow, UKCorrespondence: Dr Andrew N. Menzies-Gow, Royal Brompton Hospital, Fulham Road, London SW3 6HP.

The Utility of Fractional Exhaled Nitric Oxide Suppression in the Identification of Nonadherence in Difficult Asthma

Rationale: Nonadherence to inhaled corticosteroid therapy (ICS) is a major contributor to poor control in difficult asthma, yet it is challenging to ascertain. Objectives: Identify a test for nonadherence using fractional exhaled nitric oxide (FENO) suppression after directly observed inhaled corticosteroid (DOICS) treatment. Methods: Difficult asthma patients with an elevated FENO (>45 ppb) were recruited as adherent (ICS prescription filling >80%) or nonadherent (filling <50%). They received 7 days of DOICS (budesonide 1,600 µg) and a test for nonadherence based on changes in FENO was developed. Using this test, clinic patients were prospectively classified as adherent or nonadherent and this was then validated against prescription filling records, prednisolone assay, and concordance interview. Measurements and Main Results: After 7 days of DOICS nonadherent (n = 9) compared with adherent subjects (n = 13) had a greater reduction in FENO to 47 ± 21% versus 79 ± 26% of baseline measurement (P = 0.003), which was also evident after 5 days (P = 0.02) and a FENO test for nonadherence (area under the curve = 0.86; 95% confidence interval, 0.68-1.00) was defined. Prospective validation in 40 subjects found the test identified 13 as nonadherent; eight confirmed nonadherence during interview (three of whom had excellent prescription filling but did not take medication), five denied nonadherence, two had poor inhaler technique (unintentional nonadherence), and one also denied nonadherence to prednisolone despite nonadherent blood level. Twenty-seven participants were adherent on testing, which was confirmed in 21. Five admitted poor ICS adherence but of these, four were adherent with oral steroids and one with omalizumab. Conclusions: FENO suppression after DOICS provides an objective test to distinguish adherent from nonadherent patients with difficult asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 01219036). Copyright © 2012 by the American Thoracic Society.

The Evaluation of an Interdisciplinary Pain Protocol in Long Term Care

Objectives: To evaluate the effectiveness of (1) dissemination strategies to improve clinical practice behaviors (eg, frequency and documentation of pain assessments, use of pain medication) among health care team members, and (2) the implementation of the pain protocol in reducing pain in long term care (LTC) residents. Design: A controlled before-after design was used to evaluate the effectiveness of the pain protocol, whereas qualitative interviews and focus groups were used to obtain additional context-driven data. Setting: Four LTC facilities in southern Ontario, Canada; 2 for the intervention group and 2 for the control group. Participants: Data were collected from 200 LTC residents; 99 for the intervention and 101 for the control group. Intervention: Implementation of a pain protocol using a multifaceted approach, including a site working group or Pain Team, pain education and skills training, and other quality improvement activities. Measurements: Resident pain was measured using 3 assessment tools: the Pain Assessment Checklist for Seniors with Limited Ability to Communicate, the Pain Assessment in the Communicatively Impaired Elderly, and the Present Pain Intensity Scale. Clinical practice behaviors were measured using a number of process indicators; for example, use of pain assessment tools, documentation about pain management, and use of pain medications. A semistructured interview guide was used to collect qualitative data via focus groups and interviews. Results: Pain increased significantly more for the control group than the intervention group over the 1-year intervention period. There were significantly more positive changes over the intervention period in the intervention group compared with the control group for the following indicators: the use of a standardized pain assessment tool and completed admission/initial pain assessment. Qualitative findings highlight the importance of reminding staff to think about pain as a priority in caring for residents and to be mindful of it during daily activities. Using onsite champions, in this case advanced practice nurses and a Pain Team, were key to successfully implementing the pain protocol. Conclusions: These study findings indicate that the implementation of a pain protocol intervention improved the way pain was managed and provided pain relief for LTC residents.

The influence of evidence-based medicine training on decision-making in relation to over-the-counter medicines: a qualitative study

Objectives
To explore the role of evidence of effectiveness when making decisions about over-the-counter (OTC) medication and to ascertain whether evidence-based medicine training raised awareness in decision-making. Additionally, this work aimed to complement the findings of a previous study because all participants in this current study had received training in evidence-based medicine (unlike the previous participants).

Methods
Following ethical approval and an e-mailed invitation, face-to-face, semi-structured interviews were conducted with newly registered pharmacists (who had received training in evidence-based medicine as part of their MPharm degree) to discuss the role of evidence of effectiveness with OTC medicines. Interviews were recorded and transcribed verbatim. Following transcription, all data were entered into the NVivo software package (version 8). Data were coded and analysed using a constant comparison approach.

Key findings
Twenty-five pharmacists (7 males and 18 females; registered for less than 4 months) were recruited and all participated in the study. Their primary focus with OTC medicines was safety; sales of products (including those that lack evidence of effectiveness) were justified provided they did no harm. Meeting patient expectation was also an important consideration and often superseded evidence. Despite knowledge of the concept, and an awareness of ethical requirements, an evidence-based approach was not routinely implemented by these pharmacists. Pharmacists did not routinely utilize evidence-based resources when making decisions about OTC medicines and some felt uncomfortable discussing the evidence-base for OTC products with patients.

Conclusions
The evidence-based medicine training that these pharmacists received appeared to have limited influence on OTC decision-making. More work could be conducted to ensure that an evidence-based approach is routinely implemented in practice

A comparison of the application of STOPP/START to patients' drug lists with and without clinical information

Background A European screening tool (STOPP/START) has been formulated to identify the prescribing of potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs). Pharmacists working in community pharmacies could use STOPP/START as a guide to conducting medication use reviews; however, community pharmacists do not routinely have access to patients' clinical records. Objective To compare the PIM and PPO detection rates from application of the STOPP/START criteria to patients' medication details alone with the detection rates from application of STOPP/START to information on patients' medications combined with clinical information. Setting Community Pharmacy. Method Three pharmacists applied STOPP/START to 250 patient medication lists, containing information regarding dose, frequency and duration of treatment. The PIMs and PPOs identified by each pharmacist were compared with those identified by consensus agreement of two other pharmacists, who applied STOPP/START criteria using patients' full clinical records. Main outcome measure The main outcome measures were: (1) PIM and PPO detection rates among pharmacists with access to patients' clinical information compared to PIM and PPO detection rates among pharmacists using patients' medication information only, and (2) the levels of agreement (calculated using Cohen's kappa statistic (k)) for the three most commonly identified PIMs and PPOs. Results Pharmacists with access to patients' clinical records identified significantly fewer PIMs than pharmacists without (p = 0.002). The three most commonly identified PIMs were benzodiazepines, proton pump inhibitors and duplicate drug classes, with kappa (k) statistic agreement ranges of 0.87-0.97, 0.60-0.68 and 0.39-0.85 respectively. PPOs were identified more often (p 

The meaning of medications:another look at compliance

Most research on compliance with medical regimens takes a doctor-centered perspective and proceeds from certain assumptions. This paper presents an alternative, patient-centered approach to managing medications, using data from 80 in-depth interviews of people with epilepsy. This approach focuses on the meanings of medication in people's everyday lives and looks at why people take their medications as well as why they do not. I argue that from a patient's perspective the issue is more one of self-regulation than compliance. When we examine 'noncompliance' beyond difficulties with 'side effects' an drug efficacy, the meanings of self-regulation include testing, controlling dependence destigmatization and creating a practical practice. What appears to be noncompliance from a medical perspective may actually be a form of asserting control over one's disorder.

Trends in the use of psychotropic medications among adolescents, 1994 to 2001

Objectives: Few psychotropic medications are approved for use among children younger than 18 years. Yet previous studies have shown an increase in the use of psychotropic medications among school-age children and adolescents. Most previous studies examined data only up to 1997; therefore, the results predate any impact of changing federal policies and newly marketed medications. This study examined trends in the prescription of psychotropic medications to adolescents aged 14 to 18 years in office-based care in the United States from 1994 to 2001. Methods: Data from the National Ambulatory Medical Care Survey (NAMCS) were used to determine visit rates and prescribing patterns from 1994 to 2001 for psychotropics that were prescribed in office-based treatment settings to adolescents aged 14 to 18 years. Rates of visits that resulted in a prescription for psychotropic medication were calculated for two-year periods. Analyses were conducted by type of medication, gender, and the prescribing physician's specialty. Results: Rates of visits that resulted in a psychotropic prescription increased from 3.4 percent in 1994-1995 to 8.3 percent in 2000-2001. These trends were evident for males and females. The average annual growth rates for psychotropic prescriptions were much higher after 1999. Trends were also significant across drug classes. By 2001, one out of ten office visits by adolescent males resulted in a prescription for a psychotropic medication. Conclusions: Average annual growth rates for the prescription of psychotropics to adolescents increased from 1994 to 2001, with especially rapid acceleration after 1999. This increase may be associated with changing thresholds of diagnosis and treatment, availability of new medications, and changes in federal regulatory policies concerning promotion of medications by the pharmaceutical industry.

Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data

Background: Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods: On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data.

Results: Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with ‘low cancer-risk’ characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring ‘high cancer-risk” characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest ‘high cancer- risk’ cluster were different than those contributing to the classifiers for the ‘low cancer-risk’ clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different.

Conclusions: The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs. © 2013 Emmert-Streib et al; licensee BioMed Central Ltd.

Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications

Internalizing behaviors in children between 4 and 5 years of age who had been prenatally exposed to psychotropic medications were investigated. The authors had previously reported the effects of prenatal medication exposure in this same cohort when they were newborns and infants at 3 and 8 months of age.