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1.  Risk of cardiovascular disease in HIV, Hepatitis C, or HIV/Hepatitis C patients compared to the general population 
Background
Due to effective antiretroviral therapy HIV patients are living longer, and their risk of cardiovascular disease (CVD) is a growing concern. It is unknown whether co-infection with hepatitis C (HCV) changes an HIV person’s CVD risk, and how the risks compare to the general population. The objective of this study was to compare the Framingham Risk Score (FRS) and vascular age differences in persons with HIV, HCV or HIV/HCV disease to the general population.
Methods
HIV, HCV and HIV/HCV patients with clinic visits between 2004–2009 were sampled from medical clinics in Rochester, NY. Uninfected persons were randomly selected from the National Health and Nutrition Examination Survey (NHANES) and individually matched on sex, race, and age. We stratified by infection group and conducted separate multivariable linear regression between each infection group and the sex, race, and age matched participants from NHANES.
Results
Rochester patients (HIV=239, HCV=167, HIV/HCV=182) were compared 3:1 to the NHANES participants. After controlling for weight, marital status, current pharmacotherapies, and the matching variables of sex, race and age, HIV/HCV patients had a 2% higher general FRS compared to the general population (p=0.03) and vascular age differences that were 4.1 years greater (p=.01). HCV patients had a 2.4% higher general FRS than the general population (p<.001), and vascular age differences that were 4.4 years greater (p<.001). CVD risk was elevated, but not significantly different between HIV patients and the general population.
Conclusion
CVD risk is elevated among HIV/HCV and HCV infected persons compared to the general population.
doi:10.1111/j.1742-1241.2012.02953.x
PMCID: PMC3533243  PMID: 23241046
HIV; Hepatitis C; HIV/HCV co-infection; cardiovascular disease risk; Framingham Risk Score
2.  Power and Control: Contracts and the Patient-Physician Relationship 
Contracts with patients have become increasingly common in clinical practice and the medical literature. These include behavioral contracts for managing “difficult patients” 1, opioid contracts2–5, suicide prevention contracts6,7, and healthy living contracts8. Some physician practices have even asked patients to sign contracts promising not to litigate or post defamatory comments on the Internet9. Despite widespread adoption, few have stopped to consider the potential risks and ethical concerns with using these documents. This perspective will describe how patient contracts are ultimately about power and control, and if not used carefully could damage the patient-physician relationship.
doi:10.1111/j.1742-1241.2011.02762.x
PMCID: PMC3227003  PMID: 22093528
3.  Comorbid anxiety and substance use disorders associated with a lower use of mood stabilisers in patients with rapid cycling bipolar disorder: a descriptive analysis of the cross-sectional data of 566 patients 
SUMMARY
Objective
To study mood stabiliser treatment in patients with bipolar disorder with or without anxiety disorders (ADs) and/or substance use disorders (SUDs).
Methods
Extensive clinical interview and Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV diagnoses of rapid cycling bipolar I (RCBDI) or II (RCBDII), SUDs and ADs. Previous treatment statuses with a mood stabiliser after the first onset of mania/hypomania (unmedicated, mismedicated and correctly medicated) were retrospectively determined in patients enrolled into four similar clinical trials. T-test and chi-square/Fisher’s exact were used wherever appropriate.
Results
Of 566 patients (RCBDI n = 320, RCBDII n = 246), 46% had any lifetime AD, 67% had any lifetime SUD and 40% had any recent SUD. Overall, 12% of patients were unmedicated, 37% were mismedicated at the onset of first mania/hypomania and 51% were correctly medicated. Presence of lifetime ADs and recent SUDs was associated with fewer mood stabiliser treatments. Patients with RCBDI were more likely correctly medicated than those with RCBDII (OR = 3.64) regardless of the presence (OR = 2.6) or absence (OR = 4.2) of ADs, or the presence (OR = 2.8) or absence (OR = 3.13) of recent SUDs. Presence of lifetime ADs and recent SUDs increased the risk for mismedicated in RCBDI with odds ratios of 1.8 and 1.9, respectively, but not in RCBDII.
Conclusion
In this multi-morbid cohort of patients with RCBD, 51% of patients (64% of RCBDI and 33% with RCDBII) were correctly medicated with a mood stabiliser after the onset of first mania/hypomania. The presence of ADs and SUDs was associated with an increased risk of mismedicated in patients with RCBDI, but not with RCBDII.
doi:10.1111/j.1742-1241.2009.02284.x
PMCID: PMC3457056  PMID: 20456174
4.  Methods for Evaluating Novel Biomarkers – a New Paradigm 
doi:10.1111/j.1742-1241.2010.02469.x
PMCID: PMC3057673  PMID: 21070520
5.  The Association of Nocturia with Incident Falls in an Elderly Community-Dwelling Cohort 
Summary
Objective
To examine the association of nocturia with incident falls in a population-based sample of community-dwelling elderly persons.
Methods
The University of Alabama at Birmingham Study of Aging is a prospective cohort study of 1000 community-dwelling older adults in the USA designed to examine factors associated with impaired mobility. Subjects were recruited from a stratified, random sample of Medicare beneficiaries to include equal numbers of black women, black men, white women and white men. Nocturia was assessed at baseline and falls were assessed at baseline and every six months for a total of 36 months of follow-up.
Results
692 individuals (mean age 74.5±6.2, 48% female, 52% black) did not fall in the 12 months prior to baseline. Of these 692, 214 (30.9%) reported falling at least once during the subsequent three years. In unadjusted analysis, three or more nightly episodes of nocturia was associated with an incident fall (RR=1.27, 95% CI (1.01-1.60)). After multivariable logistic regression, three or more episodes of nocturia was associated with an increased risk of falling (RR=1.28, (1.02-1.59)).
Discussion
In a racially diverse, community-based sample of older men and women who had not fallen in the previous year, nocturia three or more times a night was associated in multivariable analysis with a 28% increased risk of an incident fall within three years. While this study has several advantages over previous reports (longitudinal follow-up, performance-based measures of function, population-based sampling), causality cannot be ascertained. Further research is needed to ascertain the impact of treatments to reduce nocturia as part of a multi-component program to reduce fall risk.
doi:10.1111/j.1742-1241.2009.02326.x
PMCID: PMC3222329  PMID: 20456212
Nocturia; Falls; Aged
6.  Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis 
Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin.
doi:10.1111/j.1742-1241.2010.02382.x
PMCID: PMC2904489  PMID: 20412332
7.  Expectations about and experiences with insulin therapy contribute to diabetes treatment satisfaction in insulin-naïve patients with type 2 diabetes 
Aim:
The aim of this study was to investigate how patients’ expectations about and experiences with insulin therapy contribute to diabetes treatment satisfaction.
Methods:
The Expectations about Insulin Therapy (EAITQ) and the Experience with Insulin Therapy Questionnaires (EWITQ) were administered at baseline and end-point, respectively to insulin-naïve patients with type 2 diabetes in a randomised trial comparing treatment algorithms for inhaled insulin. Pearson correlation coefficients were calculated between EAITQ and EWITQ scores, patient characteristics and patient-reported outcomes measures. Wilcoxon Signed Rank test compared EAITQ and EWITQ item score distributions. Differences between EAITQ and EWITQ scores were calculated to categorise patients according to the extent to which their expectations were met by experiences (i.e. unmet, met, exceeded).
Results:
EAITQ and EWITQ data were available for 240 patients (61% male, mean age 58 years, mean diabetes duration 10 years, mean baseline HbA1c 8.4%). Increasingly positive expectations were significantly associated with greater self-efficacy; greater levels of positive experiences were significantly associated with greater positive expectations, shorter diabetes duration, less symptom distress, greater well-being, self-efficacy and diabetes treatment satisfaction. Overall, patients’ experiences with inhaled insulin therapy were significantly more positive than their expectations: 58% patients’ experiences exceeded expectations, 29% patients’ experiences met expectations and 13% patients’ experiences did not meet expectations. Post hoc tests indicated that treatment satisfaction scores differed among these groups (all p < 0.01).
Conclusion:
Expectations may not independently impact treatment satisfaction, but the relationship with experiences significantly contributes to it. The EAITQ and EWITQ may be useful tools for clinicians to better understand patients’ expectations about and experiences with insulin therapy.
doi:10.1111/j.1742-1241.2010.02363.x
PMCID: PMC2904491  PMID: 20370840
8.  Diagnosis of Insulin Resistance in Hypertensive Patients by the Metabolic Syndrome: AHA vs. IDF Definitions 
SUMMARY
Background
Subjects with the metabolic syndrome are accompanied by insulin resistance (IR). However, it is not clear how well the newly-defined metabolic syndrome identifying IR specifically in hypertensive subjects.
Aims
The purpose of the study is to evaluate the performance of the metabolic syndrome, defined by the American Heart Association (AHA) and the International Diabetes Federation (IDF) definitions, in identifying IR in hypertension.
Methods
The analysis is a cross-sectional study. Totally, 228 hypertensive patients and 92 non-diabetic normotensive controls who received insulin suppressive tests to directly evaluate their insulin sensitivity were included from the Stanford Asia and Pacific Program for Hypertension and IR. McNemar’s tests were used to compare sensitivity and specificity of the AHA-defined with the IDF-defined metabolic syndrome in diagnosis of IR.
Results
The sensitivity of the metabolic syndrome for IR in hypertension was 89.7 % and the specificity 45.9 % by the AHA definition. Using the IDF definition, the sensitivity was 77.6 %, and the specificity increased to 63.5 %. The diagnostic power of individual components of the syndrome was also modest. The predictive discrimination of wider waist circumference was similar to that of the AHA-defined metabolic syndrome.
Conclusions
Use of the metabolic syndrome by the AHA definition provided good sensitivity but low specificity to diagnose IR in hypertension. The IDF definition improved in false positive rate, but it was still not specific enough to identify IR in hypertension.
doi:10.1111/j.1742-1241.2008.01818.x
PMCID: PMC2569973  PMID: 18564200
hypertension; insulin resistance; metabolic syndrome; steady-state plasma glucose
10.  Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptan 
Aims:
To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen.
Methods:
Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire.
Results:
More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication.
Conclusion:
Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure.
doi:10.1111/j.1742-1241.2008.01935.x
PMCID: PMC2704938  PMID: 19166436
11.  Analysis of health-related quality of life and costs based on a randomised clinical trial of escitalopram for relapse prevention in patients with generalised social anxiety disorder 
Background:
Social anxiety disorder (SAD) is associated with substantial reduction in health-related quality of life (HRQoL). Escitalopram has proven efficacy in the short-term treatment of SAD and prevention of relapse.
Objectives:
To determine whether the clinical effects of treatment translated into HRQoL benefits and to investigate costs of SAD treatment.
Methods:
Data on HRQoL and resource utilisation were collected in a previously published clinical trial of escitalopram in relapse prevention. Among 517 patients, 371 responded to 12 weeks of open-label treatment with escitalopram and were randomised to escitalopram or placebo for 24 weeks. HRQoL was assessed using the short form (SF)-36 instrument and SF-6D utilities (preference-based index scores for overall HRQoL) were calculated. Costs were calculated for responders over the acute phase and for non-relapsed patients over the continuation phase, applying UK unit costs.
Results:
Health-related quality of life was significantly improved after the acute phase when compared with baseline. The SF-6D utility increased by 0.047 in responders (p < 0.0001) and 0.021 in non-responders (p = 0.0005). Healthcare costs were non-significantly lower in acute phase than during prestudy phase (p = 0.0587 from NHS perspective), as were productivity costs (p = 0.1440). HRQoL at last visit was lower in relapsed than non-relapsed patients. The difference in utility was −0.026 (p = 0.0007). Healthcare and productivity costs were non-significantly lower in the escitalopram group than in the placebo group.
Conclusions:
Both effective acute treatment of SAD and prevention of relapse with escitalopram are associated with significant HRQoL benefits. Despite some limitations, the cost analysis suggests that savings in physician-visits and inpatient care may offset drug acquisition costs.
doi:10.1111/j.1742-1241.2008.01879.x
PMCID: PMC2704928  PMID: 18759783
12.  Insulin for type 2 diabetes: choosing a second-line insulin regimen 
Guidance has been published on the choice of initial insulin regimen for patients with type 2 diabetes [NPH (isophane) insulin or a long-acting insulin analogue] but not on how to choose a second regimen when glycaemic control becomes unsatisfactory.
Aims:
To develop pragmatic clinical guidance for choosing a second-line insulin regimen tailored to the individual needs of patients with type 2 diabetes after failure of first-line insulin therapy.
Methods:
Formulation of a consensus by expert panel based on published evidence and best clinical practice, taking into account patient preferences, lifestyle and functional capacity.
Results:
Six patient-dependent factors relevant to the choice of second-line insulin regimen and three alternative insulin regimens (twice-daily premixed, basal-plus and basal-bolus) were identified. The panel recommended one or more insulin regimens compatible with each factor, emphasising the fundamental importance of a healthy lifestyle that includes exercise and weight reduction. These recommendations were incorporated into an algorithm to provide pragmatic guidance for clinicians.
Conclusion:
The three alternative insulin regimens offer different benefits and drawbacks and it is important to make the right choice to optimise outcomes for patients.
doi:10.1111/j.1742-1241.2008.01909.x
PMCID: PMC2680733  PMID: 19143853
13.  Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study 
Purpose:
We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.
Materials and methods:
The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of ≥ 8 voids per 24 h and episodes of urgency or urgency incontinence ≥ 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King’s Health Questionnaire.
Results:
A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).
Conclusions:
Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.
doi:10.1111/j.1742-1241.2008.01898.x
PMCID: PMC2680337  PMID: 19143854
14.  Understanding gastro-oesophageal reflux disease: a patient-cluster analysis 
Objective:
To determine whether patients with gastro-oesophageal reflux disease (GERD) can be grouped according to the physical and psychological impact of their disease.
Methods:
In this multinational study, 7713 primary care physicians (PCPs) and gastrointestinal (GI) specialists took part in a structured online survey to determine how they perceive the clinical and psychological needs of their GERD patients, based on their three most recent consultations. Patients were grouped according to one of the five clusters that were subjectively developed based on preceding qualitative research.
Results:
Findings are reported for 1157 respondents (875 PCPs, 282 GI specialists), who reviewed 3471 patient records. Two of the five original clusters were collapsed because of overlapping characteristics, giving rise to three patient clusters. Patients with ‘long-term, disrupting GERD’ (39%) had symptoms considered to have not only high physical but also psychological impact. Patients with ‘recurrent, distressing GERD’ (14%) experienced both physical and psychological impact and were worried about the recurrent, restrictive nature of their disease or the possibility of having a more serious underlying condition. Patients with ‘inconveniencing GERD’ (48%) had less frequent symptoms with overall lower impact. Overall, there was a trend for GI specialists to more likely see patients at higher clinical need than PCPs.
Conclusions:
Patients with GERD can generally be classified according to the physical and psychological impact of their disease. Recognition that such patients have different needs may facilitate improved management of GERD by allowing treatment to be tailored according to the patient's need.
doi:10.1111/j.1742-1241.2008.01929.x
PMCID: PMC2680331  PMID: 19166432
15.  A retrospective database study comparing treatment outcomes and cost associated with choice of fixed-dose inhaled corticosteroid/long-acting β2-agonists for asthma maintenance treatment in Germany 
Aims:
This retrospective, observational cohort study aimed to compare treatment outcomes and healthcare costs in the year after initiation of maintenance treatment with budesonide/formoterol or salmeterol/fluticasone in a German healthcare setting.
Methods:
Data on German asthma patients initiating treatment with budesonide/formoterol or salmeterol/fluticasone between June 2001 and June 2005 were obtained from the IMS Disease Analyzer database. The primary outcome was the probability of treatment success, defined according to short-acting β2-agonist prescriptions and switches or addition of controller medications, during the postindex year. A secondary definition of treatment success included hospitalisations and oral corticosteroid (OCS) prescriptions. Secondary outcomes included severe asthma exacerbations, defined as ≥1 OCS prescription, asthma-related hospitalisation and/or referral. The effect of treatment on costs was estimated using generalised linear models, adjusting for patient and physician characteristics.
Results:
There were no significant differences between the budesonide/formoterol (n=1456) and salmeterol/fluticasone (n=982) groups in disease severity markers in the pre-index year. Patients on budesonide/formoterol had a 44% greater probability of treatment success [odds ratio (OR): 1.44; p = 0.0003] according to the primary definition and a 26% greater probability (OR: 1.26; p = 0.0119) according to the secondary definition, fewer severe exacerbations (−33.4%; p = 0.0123) and fewer OCS prescriptions (−31.5%; p = 0.0082) compared with salmeterol/fluticasone, after controlling for baseline characteristics. Adjusting for covariates, budesonide/formoterol had a significant inverse relationship on asthma-related costs compared with salmeterol/fluticasone (−13.4%; p < 0.001). Total cost (asthma- and non-asthma-related costs) was 12.6% lower for budesonide/formoterol (p < 0.0001).
Conclusion:
This study suggests that for patients with chronic asthma in Germany, budesonide/formoterol rather than salmeterol/fluticasone had a higher likelihood of treatment success, and that budesonide/formoterol is the less costly option. Although the cohorts appeared to be well matched at baseline, the results should be interpreted with caution given the observational nature of the study.
doi:10.1111/j.1742-1241.2008.01895.x
PMCID: PMC2680329  PMID: 18803555
16.  The Information Technology Aided Relapse Prevention Programme in Schizophrenia: an extension of a mirror-design follow-up 
Aims:
Decreasing a number of hospital admissions is important for improving outcomes for people with schizophrenia. The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) programme enables early pharmacological intervention in psychosis by identification of prodromal symptoms of relapse using home telemonitoring via a phone-to-PC SMS platform.
Methods:
This study was a 1-year extension of a previously published mirror-design follow-up evaluation of programme clinical effectiveness. In total, 73 patients with psychotic illness (45 patients from original sample and 28 newly added subjects) collaborating with 56 family members participated in the clinical evaluation.
Results:
There was a statistically significant 77% decrease in the number of hospitalisations during the mean 396.8 ± 249.4 days of participation in ITAREPS, compared with the same time period before participation in ITAREPS (Wilcoxon-signed ranks test, p < 0.00001), as well as significantly reduced number of hospitalisation days when in the ITAREPS (2365 hospitalisation days before and 991 days after ITAREPS enrolment respectively, Wilcoxon-signed ranks test, p < 0.003).
Conclusion:
The ITAREPS programme represents an effective tool in the long-term treatment of patients with psychotic disorders.
doi:10.1111/j.1742-1241.2008.01903.x
PMCID: PMC2680266  PMID: 18795967
17.  Darifenacin treatment for overactive bladder in patients who expressed dissatisfaction with prior extended-release antimuscarinic therapy 
Introduction and objective:
Patient perception of overactive bladder (OAB) treatment outcomes can be a useful indicator of benefit and may help drive persistence on treatment, which is known to be poor in OAB. It remains unclear whether OAB patients dissatisfied with one antimuscarinic can achieve satisfaction with another and supporting data are limited. This study investigated patient-reported outcomes and clinical parameters during darifenacin treatment in OAB patients who expressed dissatisfaction with prior extended-release (ER) oxybutynin or tolterodine therapy (administered for ≥ 1 week within the past year).
Methods:
This open-label study was conducted in darifenacin-naïve OAB patients. Patients received 7.5 mg darifenacin once daily with the possibility of up-titrating to 15 mg after 2 weeks, for up to 12 weeks. Efficacy parameters included the Patient’s Perception of Bladder Condition (PPBC), patient satisfaction with treatment, micturition frequency and number of urgency and urge urinary incontinence (UUI) episodes. Adverse events (AEs) were also recorded.
Results:
In total, 497 patients were treated (84.1% women). Darifenacin treatment resulted in statistically significant improvements in PPBC scores, micturition frequency, urgency and UUI episodes from baseline at 12 weeks. The improvements were similar for patients previously treated with oxybutynin ER or tolterodine ER. More than 85% of patients expressed satisfaction with darifenacin. As noted in other studies, the most common AEs were dry mouth and constipation, but these infrequently resulted in treatment discontinuation, which was low overall.
Conclusions:
In this study, PPBC score and OAB symptoms were significantly improved, and satisfaction was high during treatment with darifenacin (7.5/15 mg) in patients who were dissatisfied with the previous antimuscarinic treatment.
doi:10.1111/j.1742-1241.2008.01893.x
PMCID: PMC2680263  PMID: 18811599
18.  The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of gastro-oesophageal reflux disease following treatment with a full dose proton pump inhibitor 
Background:
Some patients with gastro-oesophageal reflux disease (GORD) remain symptomatic despite proton pump inhibitor (PPI) treatment. There is a need to determine the most appropriate management of these patients.
Aims:
To assess the effectiveness of esomeprazole 40 mg in GORD symptoms persisting in patients receiving a full daily dose PPI.
Methods:
In this multi-centre open label study patients who had received full daily dose PPI for 8 weeks, but were still experiencing persistent GORD symptoms, were treated with esomeprazole 40 mg for 8 weeks (n = 99). The primary outcome variable was the change in the frequency of heartburn. Patient-reported outcomes were also assessed using the Reflux Disease Questionnaire (RDQ) and the GORD Impact Scale (GIS).
Results:
The mean frequency of heartburn was reduced by 78% from 4.4 days a week to 1 day a week at the end of the 8-week treatment period (p < 0.0001). Other GORD symptoms were also significantly reduced following of treatment with esomeprazole (all p < 0.0001). All RDQ dimensions and the level of symptom control as measured by the GIS also showed significant improvement at 8 weeks.
Conclusions:
In patients with persistent GORD symptoms despite full dose daily PPI therapy, esomeprazole 40 mg significantly improved the frequency and severity of all GORD symptoms.
doi:10.1111/j.1742-1241.2008.01923.x
PMCID: PMC2680259  PMID: 19166433
19.  A novel programme to evaluate and communicate 10-year risk of CHD reduces predicted risk and improves patients' modifiable risk factor profile 
Aims
We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease (CHD) risk could lower patients' predicted Framingham CHD risk vs. usual care.
Methods
The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospective, controlled, cluster-randomised trial in nine European countries, among patients at moderate cardiovascular risk. Following baseline assessments, physicians in the intervention group calculated patients' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme. Usual care physicians did not calculate patients' risk and provided usual care only. The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care.
Results
Of 1103 patients across 100 sites, 524 patients receiving intervention, and 461 receiving usual care, were analysed for efficacy. After 6 months, mean predicted risks were 12.5% with intervention, and 13.7% with usual care [odds ratio = 0.896; p = 0.001, adjusted for risk at baseline (17.2% intervention; 16.9% usual care) and other covariates]. The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention (25.4%) than usual care (14.1%; p < 0.001), and 29.3% of smokers in the intervention group quit smoking vs. 21.4% of those receiving usual care (p = 0.04).
Conclusions
A physician-implemented CHD risk evaluation/communication programme improved patients' modifiable risk factor profile, and lowered predicted CHD risk compared with usual care. By combining this strategy with more intensive treatment to reduce residual modifiable risk, we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice.
doi:10.1111/j.1742-1241.2008.01872.x
PMCID: PMC2658032  PMID: 18691228
20.  The impact of analytic method on interpretation of outcomes in longitudinal clinical trials 
Aims
Various analytical strategies for addressing missing data in clinical trials are utilised in reporting study results. The most commonly used analytical methods include the last observation carried forward (LOCF), observed case (OC) and the mixed model for repeated measures (MMRM). Each method requires certain assumptions regarding the characteristics of the missing data. If the assumptions for any particular method are not valid, results from that method can be biased. Results based on these different analytical methods can, therefore, be inconsistent, thereby making interpretation of clinical study results confusing. In this investigation, we compare results from MMRM, LOCF and OC in order to illustrate the potential biases and problems in interpretation.
Methods
Data from an 8-month, double-blind, randomised, placebo-controlled (placebo; n= 137), outpatient depression clinical trial comparing a serotonin-noradrenalin reuptake inhibitor (SNRI; n= 273) with a selective serotonin reuptake inhibitor (SSRI; n= 274) were used. The study visit schedule included efficacy and safety assessments weekly to week 4, bi-weekly to week 8, and then monthly. Visitwise mean changes for the 17-item Hamilton Depression Rating Scale (HAMD17) Maier subscale (primary efficacy outcome), blood pressure, and body weight were analysed using LOCF, MMRM and OC.
Results
Last observation carried forward consistently underestimated within-group mean changes in efficacy (benefit) and safety (risk) for both drugs compared with MMRM, whereas OC tended to overestimate within-group changes.
Conclusions
Inferences are based on between-group comparisons. Therefore, whether or not underestimating (overestimating) within-group changes was conservative or anticonservative depended on the relative magnitude of the bias in each treatment and on whether within-group changes represented improvement or worsening. Preference should be given in analytic plans to methods whose assumptions are more likely to be valid rather than relying on a method based on the hope that its results, if biased, will be conservative.
doi:10.1111/j.1742-1241.2008.01808.x
PMCID: PMC2658028  PMID: 18564199
21.  Postprandial blood glucose response to a standard test meal in insulin-requiring patients with diabetes treated with insulin lispro mix 50 or human insulin mix 50 
Gao, Y | Li, G | Li, Y | Guo, X | Yuan, G | Gong, Q | Yan, L | Zheng, Y | Zhang, J
Aim
To compare the 2-h postprandial blood glucose (PPBG) excursion following a standard test meal in insulin-requiring patients with diabetes treated twice daily with human insulin mix 50 vs. insulin lispro mix 50 (LM50).
Methods
This was a multicentre, randomised, open-label, crossover comparison of two insulin treatments for two 12-week treatment periods in 120 Chinese patients. One- and 2-h PPBG and excursion values were obtained following a standardised test meal. Fasting blood glucose (FBG), haemoglobin A1c (HbA1c), insulin dose, rate of hypoglycaemia and safety data were obtained. A crossover analysis using SAS Proc MIXED was employed.
Results
Mean 2-h PPBG excursion decreased from 6.32 ± 3.07 mmol/l at baseline to 3.47 ± 2.97 mmol/l at end-point in the LM50 group, and from 6.31 ± 2.88 at baseline to 5.02 ± 3.32 mmol/l at end-point in the human insulin mix 50 group (p < 0.001). Two-hour PPBG (p = 0.004) and 1-h PPBG excursion (p < 0.001) were significantly lower with LM50 as compared with human insulin mix 50. Both treatment groups were equivalent for HbA1c control, 1-h PPBG and insulin dose requirements. Mean FBG was higher with LM50 than with human insulin mix 50 (p = 0.023). The overall incidence of treatment-emergent adverse events and hypoglycaemia rate per 30 days were similar between treatment groups.
Conclusions
Insulin lispro mix 50 provided better postprandial glycaemic control compared with human insulin mix 50 while providing the convenience of injecting immediately before meals. Both treatments were generally well tolerated by all randomly assigned patients.
doi:10.1111/j.1742-1241.2008.01850.x
PMCID: PMC2658027  PMID: 18657196
22.  How strong is the association between abdominal obesity and the incidence of type 2 diabetes? 
Background:
Quantitative evidence on the strength of the association between abdominal obesity and the incidence of type 2 diabetes was assessed.
Methods:
Systematic review of longitudinal studies assessing the relationship between measures reflecting abdominal obesity and the incidence of type 2 diabetes.
Results:
There was a strong association between measures reflecting abdominal obesity and the incidence of type 2 diabetes, the pooled odds ratio was 2.14 (95% CI: 1.70–2.71; p < 0.0001). Waist circumference (WC) was at least as good as other measures in predicting outcome.
Conclusions:
There is a strong association between measures reflecting abdominal obesity and the development of type 2 diabetes. Reducing WC may reduce the risk of developing type 2 diabetes.
doi:10.1111/j.1742-1241.2008.01805.x
PMCID: PMC2658023  PMID: 18557792
23.  Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain 
Background and objectives:
Opioid-induced constipation can have a major negative impact on patients’ quality of life. This randomised clinical trial evaluated patient assessment of the efficacy and tolerability of oral prolonged-release (PR) oxycodone when co-administered with oral naloxone PR.
Methods:
Two hundred and two patients with chronic cancer- or non-cancer-related pain undergoing stable oxycodone PR therapy (40, 60 or 80 mg/day) were randomised to one of four intervention groups: 10, 20 or 40 mg/day naloxone PR or placebo. Following a 4-week maintenance phase, patients were followed-up for 2 weeks in which time they received oxycodone PR only. At the end of the maintenance phase, patients and investigators were asked to assess treatment efficacy and tolerability, as well as preference for the titration or maintenance phase.
Results:
Patient and investigator global assessment of efficacy and tolerability improved with increasing naloxone dose. Efficacy was ranked as ‘good’ or ‘very good’ by 50.0%, 67.4% and 72.5% of patients in the 10, 20 and 40 mg naloxone PR dose groups, respectively, compared with 43.5% of patients in the placebo group. Patient assessment of tolerability was similar between treatment groups and placebo, being ranked as ‘good’ or ‘very good’ by 83.3%, 79.1% and 82.5% of patients in the 10, 20 and 40 mg/day naloxone PR dose groups, respectively, compared with 71.7% of patients in the placebo group. The maintenance treatment phase was preferred by patients in the naloxone groups. A 2 : 1 dose ratio of oxycodone to naloxone was also assessed. Efficacy was ranked as ‘good’ or ‘very good’ by 70.4% of patients treated with the 2 : 1 dose ratio compared with 43.5% of patients receiving placebo. Tolerability of the 2 : 1 dose ratio was ranked as being ‘good’ or ‘very good’ by 81.5% of patients compared with 71.1% for the placebo group and patients preferred the maintenance phase.
Conclusions:
The co-administration of oral naloxone PR with oxycodone PR improves patient assessment of analgesic opioid therapy for severe chronic pain, in terms of both efficacy and tolerability.
doi:10.1111/j.1742-1241.2008.01820.x
PMCID: PMC2658020  PMID: 18705820
24.  The design of an observational study of hypertension management, adherence and pressure control in Blood Pressure Success Zone Program participants 
Aims
The Blood Pressure Success Zone (BPSZ) Program, a nationwide initiative, provides education in addition to a complimentary trial of one of three antihypertensive medications. The BPSZ Longitudinal Observational Study of Success (BPSZ-BLISS) aims to evaluate blood pressure (BP) control, adherence, persistence and patient satisfaction in a representative subset of BPSZ Program participants. The BPSZ-BLISS study design is described here.
Methods
A total of 20,000 physicians were invited to participate in the study. Using a call centre supported Interactive Voice Response System (IVRS), physicians report BP and other data at enrolment and every usual care visit up to 12 ± 2 months; subjects self-report BPs, persistence, adherence and treatment satisfaction at 3, 6 and 12 months post-BPSZ Program enrolment. In addition to BPSZ Program enrolment medications, physicians prescribe antihypertensive medications and schedule visits as per usual care. The General Electric Healthcare database will be used as an external reference.
Results
After 18 months, over 700 IRB approved physicians consented and enrolled 10,067 eligible subjects (48% male; mean age 56 years; 27% newly diagnosed); 97% of physicians and 78% of subjects successfully entered IVRS enrolment data. Automated IVRS validations have maintained data quality (< 5% error on key variables). Enrolment was closed 30 April 2007; study completion is scheduled for June 2008.
Conclusions
The evaluation of large-scale health education programmes requires innovative methodologies and data management and quality control processes. The BPSZ-BLISS design can provide insights into the conceptualisation and planning of similar studies.
doi:10.1111/j.1742-1241.2008.01840.x
PMCID: PMC2658016  PMID: 18647193
25.  Clinical characteristics of patients with diabetic polyneuropathy: the role of clinical and electromyographic evaluation and the effect of the various types on the quality of life 
Objective
This study was performed to identify the relationship between the quality of life and polyneuropathy which is one of the complications of diabetes.
Methods
Total 111 patients with diabetes mellitus were taken into the study as type 1 and type 2. Patients were accepted having polyneuropathy according to their electroneuromyography (ENMG) results. To evaluate the quality of life in the patients Short Form 36 (SF-36) and World Health Organization Quality of Life Questionnaire abbreviated version (WHOQOL-BREF) were used.
Results
Clinical polyneuropathy was found in 46% of the patients, while polineuropathy was found in 63% of the patients with evaluation ENMG. The patients with polyneuropathy had poor quality of life according to SF-36 and WHOQOL-BREF (p < 0.001). The mean quality of life scores of patients who had sensoriomotor and mix polyneuropathy, were lower than sensory type and axonal polyneuropathy.
Conclusion
Diabetic polyneuropathy influences the quality of life in a negative way. The quality of life scores of patients who had polyneuropathy continuing with mixed pathogenesis and sensoriomotor type, become worse for this reason, even if the patients do not have any clinical polyneuropathy, this being evaluated with ENMG.
doi:10.1111/j.1742-1241.2008.01730.x
PMCID: PMC2658015  PMID: 18410351

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