Mark Belger

The GERAS Study: A Prospective Observational Study of Costs and Resource Use in Community Dwellers with Alzheimer's Disease in Three European Countries – Study Design and Baseline Findings

To address socioeconomic challenges associated with its increasing prevalence, data are needed on country-level resource use and costs associated with Alzheimers disease (AD). GERAS is an 18-month observational study being conducted in France, Germany, and the U.K. (with an 18-month extension in France and Germany), aimed at determining resource use and total costs associated with AD, stratified by AD severity at baseline. Resource use information and time spent on informal care by non-professional caregivers was obtained using the Resource Utilization in Dementia instrument. Total baseline societal costs were based on four cost components: patient health care costs, patient social care costs, caregiver health care costs, and caregiver informal care costs. Overall, 1,497 community-dwelling patients with AD were analyzed at baseline. Estimated mean monthly total societal costs per patient at baseline differed significantly between groups with mild, moderate, and moderately severe/severe AD (p < 0.001 in each country): euro

Caregiver Burden in Alzheimer's Disease: Differential Associations in Adult-Child and Spousal Caregivers in the GERAS Observational Study

1,418, euro 1,737, and euro 2,453 in France; euro 1,312, euro

Determinants of societal costs in Alzheimer's disease: GERAS study baseline results

2,412, and euro 3,722 in Germany; and euro 1,621, euro 1,836, andeuro 2,784 in the U.K., respectively. All cost components except caregiver health care costs increased with AD severity. Informal caregiver costs were the largest cost component accounting for about half to just over 60% of total societal costs, depending on country and AD severity group. In conclusion, GERAS study baseline results showed that country-specific costs increase with AD severity. Informal care costs formed the greatest proportion of total societal costs, increasing with AD severity independent of costing method. Longitudinal data will provide information on cost trends with disease progression.

Analysis of burden in caregivers of people with Alzheimer’s disease using self-report and supervision hours

Background/Aims: To examine factors influencing the caregiver burden in adult-child and spousal caregivers of community-dwelling patients with Alzheimers disease (AD). Methods: Baseline data from the 18-month, prospective, observational GERAS study of 1,497 patients with AD in France, Germany, and the UK were used. Analyses were performed on two groups of caregivers: spouses (n = 985) and adult children (n = 405). General linear models estimated patient and caregiver factors associated with subjective caregiver burden assessed using the Zarit Burden Interview. Results: The caregiver burden increased with AD severity. Adult-child caregivers experienced a higher burden than spousal caregivers despite spending less time caring. Worse patient functional ability and more caregiver distress were independently associated with a greater burden in both adult-child and spousal caregivers. Additional factors were differentially associated with a greater caregiver burden in both groups. In adult-child caregivers these were: living with the patient, patient living in an urban location, and patient with a fall in the past 3 months; in spouses the factors were: caregiver gender (female) and age (younger), and more years of patient education. Conclusion: The perceived burden differed between adult-child and spousal caregivers, and specific patient and caregiver factors were differentially associated with this burden.

Sexual Satisfaction in Men with Erectile Dysfunction: Correlates and Potential Predictors

To identify the main factors associated with societal costs of Alzheimers disease (AD) in community‐dwelling patients across three European countries.

Evaluation of Patient Expectations and Treatment Satisfaction after 1-Year Tadalafil Therapy for Erectile Dysfunction: The DETECT Study

ObjectivesThis study aimed to describe the baseline characteristics of informal carers of community-living Alzheimer’s disease (AD) patients by AD severity group and to identify factors associated with two measures of caregiver burden.Design and settingGERAS is a prospective observational study in France, Germany, and the UK, designed to assess costs and resource use associated with AD, for patients and their caregivers, stratified by disease severity.Participants1497 community-dwelling AD patients and their primary caregivers.MeasurementsSubjective caregiver burden assessed using the Zarit Burden Interview [ZBI] and time spent supervising patients (an objective measure of burden recorded using the Resource Utilization in Dementia instrument) during the month before the baseline visit were recorded. Separate multiple linear regression analyses using ZBI total score and caregiver supervision time as dependent variables were performed to identify patient and caregiver factors independently associated with caregiver burden.ResultsIncreasing AD severity was associated with both subjective caregiver burden (ZBI total score) and overall caregiver time, which includes supervision time (both p<0.001, ANOVA). Better patient functioning (on instrumental activities of daily living) was independently associated with both a lower ZBI total score and less supervision time, whereas higher levels of caregiver distress due to patient behavior were associated with greater caregiver burden. Other factors independently associated with an increased ZBI total score included younger caregiver age, caregiver self-reported depression, caring for a male patient, and longer time since AD diagnosis. Caregivers living with the patient, being a male caregiver, patient living in a rural location, higher patient behavioral problem subdomain scores for apathy and psychosis, more patient emergency room visits, not receiving food delivery and receiving financial support for caregiving were all associated with greater caregiver supervision time.ConclusionOur results show that subjective caregiver burden and caregiver time are influenced by different factors, reinforcing the need to consider both aspects of caregiving when trying to minimize the burden of AD. However, interventions that minimize caregiver distress and improve patient functioning may impact on both subjective and objective burden.

The effect of tadalafil on psychosocial outcomes in Swedish men with erectile distress: a multicentre, non‐randomised, open‐label clinical study

INTRODUCTION Sexual satisfaction is an important treatment objective for men with erectile dysfunction (ED). AIMS To evaluate potential associations between International Index of Erectile Function (IIEF) satisfaction at study endpoint and a range of baseline, on-treatment, and endpoint variables. METHODS An exploratory analysis was conducted involving 3,935 subjects with ED randomized to on-demand tadalafil (N = 2,824) or placebo (N = 1,111) in randomized, controlled trials across 28 countries. Patients achieving scores > or =16 on IIEF questions 7, 8, 13, and 14 at study endpoint were operationally defined as satisfied (vs. <16, not satisfied). Multivariate logistic regression and other analyses were conducted to ascertain correlates and potential predictors of improvements in the IIEF-erectile function domain (IIEF-EF). MAIN OUTCOME MEASURES Satisfaction on the IIEF at study endpoint, on-treatment improvements in IIEF-EF, and endpoint sexual frequency. RESULTS Patients who were satisfied with sexual function were on average younger and had less severe ED, a shorter history of the condition, and no history of vascular disorders, hypertension, or diabetes mellitus/insulin use at baseline (P < 0.01 vs. not satisfied for each). Satisfied patients were also more likely to experience a > or =4-point increase on the IIEF-EF domain on treatment (adjusted odds ratio [OR] = 22.4; 95% CI = 17.6-28.5; P < 0.0001) or IIEF-EF > or =26 at endpoint (adjusted OR = 41.0; 95% CI = 33.6-50.2; P < 0.0001). Satisfaction emerged as a strong correlate of a > or =4-point increase in the IIEF-EF on treatment; however, as a correlate of endpoint sexual frequency, baseline sexual frequency was stronger than endpoint satisfaction. CONCLUSIONS Satisfaction is associated with certain baseline, on-treatment, and endpoint variables in ED patients. Further studies are needed to confirm these preliminary findings and explore their meaning for female partners.

Systematic literature review and meta-analysis of diagnostic test accuracy in Alzheimer's disease and other dementia using autopsy as standard of truth.

INTRODUCTION Erectile dysfunction (ED) is a self-reported condition and satisfaction with sexual performance is individual, subjective, and multi-factorial. Treatment success depends on several outcomes. Tadalafil is a long-acting, selective inhibitor of phosphodiesterase 5 that has been shown to be effective at treating men with ED. AIM To investigate patients ED treatment expectations at baseline; patient satisfaction with tadalafil treatment after 12 months; factors associated with satisfaction; and effect of early tadalafil treatment satisfaction on tadalafil continuation at 12 months. METHODS The Determinants of Continued Use of Tadalafil study is a 12-month, prospective, pan-European, noninterventional, observational study, which enrolled 1,900 patients with ED wishing to initiate or change their treatment to tadalafil. Assessments were made on predefined treatment outcomes in a routine clinical setting. MAIN OUTCOME MEASURES International Index of Erectile Function-erectile function domain scores (at baseline, 1, 6, and 12 month visit), ED Inventory of Treatment Satisfaction (EDITS) scores (after 1, 6, and 12 months), and patient expectation questionnaire (at baseline visit) were analyzed for these patients. RESULTS Data were available from 1,567 patients (82%) after 12 months, with similar baseline characteristics as the initial cohort. Treatment expectations identified as important included: erection hardness and ability to maintain erection through intercourse completion (>92% of patients); confidence, partner satisfaction, and naturalness (>84% of patients); rapid effect and long duration of treatment (>75% of patients). Continued tadalafil use from 1,319 (84%) patients at 12 months were reported. Total EDITS scores for those continuing treatment was 85.9 (95% CI: 85.1-86.7). Increased satisfaction was associated with higher effectiveness, number of sexual attempts, partner support, good relationships, and good drug tolerance. Treatment satisfaction at 1 month was best predictive of treatment continuation at 12 months. CONCLUSIONS Eighty-four percent of patients reported continued use of tadalafil after 12 months. High satisfaction after first month of treatment was the best predictor of treatment continuation.

Therapeutic Response after First Month of Tadalafil Treatment Predicts 12 Months Treatment Continuation in Patients with Erectile Dysfunction: Results from the DETECT Study

A multicentre, non‐randomised, open‐label study assessed whether personal distress caused by erectile dysfunction (ED) affected psychosocial outcomes of tadalafil treatment. Eligible Swedish men at least 18 years old reporting ≥3‐month history of ED were stratified into two groups (manifest or mild/no distress) based upon a distress question administered at enrolment. Tadalafil 20 mg was taken as needed for 8 weeks. The primary outcome was the difference between the two distress groups in change from baseline in the Psychological and Interpersonal Relationship Scales (PAIRS) spontaneity domain. Secondary outcome measures were PAIRS sexual self‐confidence and time concerns domains, Life Satisfaction (LiSat‐11) checklist and a Global Assessment of Treatment Response. The study also assessed tolerability. Of 662 men enrolled, 88% had manifest distress and 12% had mild/no distress. Baseline‐to‐endpoint changes for PAIRS domains were not significantly different between groups. Baseline‐to‐endpoint changes in LiSat‐11 items were not significantly different between groups except for satisfaction with sexual life. Compared with men without ED, below normal baseline satisfaction with partner relationship and family life were normalised at endpoint. Over 90% of men reported improved erection and ability to engage in sexual activity. The most common treatment‐emergent adverse events were headache, myalgia, dyspepsia, flushing and back pain. One man discontinued because of myalgia; 630 (95%) completed the study. In conclusion, erectile distress levels vary among patients with ED and distress can affect intra‐familiar aspects of life, which may have implications for clinical practise. However, distress does not appear to hinder improvement in both mechanical and psychosocial outcomes of tadalafil treatment.

Combining randomized and non-randomized evidence in network meta-analysis

BACKGROUND Early diagnosis of Alzheimers disease (AD) is crucial to implement the latest treatment strategies and management of AD symptoms. Diagnostic procedures play a major role in this detection process but evidence on their respective accuracy is still limited. OBJECTIVE To conduct a systematic literature on the sensitivity and specificity of different test modalities to identify AD patients and perform meta-analyses on the test accuracy values of studies focusing on autopsy-confirmation as the standard of truth. METHODS The systematic review identified all English papers published between 1984 and 2011 on diagnostic imaging tests and cerebrospinal fluid biomarkers including results on the newest technologies currently investigated in this area. Meta-analyses using bivariate fixed and random-effect models and hierarchical summary receiver operating curve (HSROC) random-effect model were applied. RESULTS Out of the 1,189 records, 20 publications were identified to report the accuracy of diagnostic tests in distinguishing autopsy-confirmed AD patients from other dementia types and healthy controls. Looking at all tests and comparator populations together, sensitivity was calculated at 85.4% (95% confidence interval [CI]: 80.9%-90.0%) and specificity at 77.7% (95% CI: 70.2%-85.1%). The area under the HSROC curve was 0.88. Sensitivity and specificity values were higher for imaging procedures, and slightly lower for CSF biomarkers. Test-specific random-effect models could not be calculated due to the small number of studies. CONCLUSION The review and meta-analysis point to a slight advantage of imaging procedures in correctly detecting AD patients but also highlight the limited evidence on autopsy-confirmations and heterogeneity in study designs.