Gergana Zlateva

Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

BackgroundAge-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours.MethodsA systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated.ResultsIncreasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels.ConclusionsSmoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.

Minimal Clinically Important Difference in the Fibromyalgia Impact Questionnaire

Objective. The Fibromyalgia Impact Questionnaire (FIQ) is a disease-specific composite instrument that measures the effect of problems experienced by patients with fibromyalgia (FM). Utilization of the FIQ in measuring changes due to interventions in FM requires derivation of a clinically meaningful change for that instrument. Analyses were conducted to estimate the minimal clinically important difference (MCID), and to propose FIQ severity categories. Methods. Data from 3 similarly designed, 3-month placebo-controlled, clinical treatment trials of pregabalin 300, 450, and 600 mg/day in patients with FM were modeled to estimate the change in the mean FIQ total and stiffness items corresponding to each category on the Patient Global Impression of Change. FIQ severity categories were modeled and determined using established pain severity cutpoints as an anchor. Results. A total of 2228 patients, mean age 49 years, 93% women, with a mean baseline FIQ total score of 62 were treated in the 3 studies. Estimated MCID on a given measure were similar across the studies. In a pooled analysis the estimated MCID (95% confidence interval) was 14% (13; 15) and for FIQ stiffness it was 13% (12; 14). In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. Conclusion. The analysis indicates that a 14% change in the FIQ total score is clinically relevant, and results of these analyses should enhance the clinical utility of the FIQ in research and practice.

Economic Burden of Bilateral Neovascular Age-Related Macular Degeneration : Multi-Country Observational Study

BackgroundThere is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD.ObjectiveTo document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective.Study design, setting and participants: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians’ records and subjects’ standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMDrelated socioeconomic costs were calculated in €, year 2005 values. Main outcome measures: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures.ResultsThe demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12–22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21–59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54–81%) were living with a spouse or family member and 19–41% reported receiving assistance for activities of daily living.The average annual societal cost per bilateral NV-AMD patient treated was estimated to be €7879 in Canada, €7349 in France, €12 445 in Germany, €5732 in Spain and €5300 in the UK, and direct vision-related medical costs accounted for 23–63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with an average length of 5 months; there were no statistically significant differences in total annual costs per patient between these patients and those who were diagnosed with bilateral disease for ≥1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from €268 to €1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from €671 to €3278 million.ConclusionsBilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.

Photodynamic therapy with verteporfin in age-related macular degeneration: a systematic review of efficacy, safety, treatment modifications and pharmacoeconomic properties

Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age‐related macular degeneration (AMD), and specifically of choroidal neovascularization (CNV), since the advent of antiangiogenic therapies. Recently, there has been a renewed interest in PDT as an adjunct to these and other agents in the treatment of neovascular AMD. In light of this new development and the European Medicines Evaluation Agency’s (EMEA) recent labelling decision to rescind approval for the use of PDT in occult CNV lesions, the present systematic review was undertaken to revisit the evidence supporting its clinical application. Photodynamic therapy provided the first pharmacological treatment for patients suffering from subfoveal CNV, the major cause of severe vision loss in AMD. Key clinical trials evaluating efficacy and safety have examined patients with all lesion subtypes, with the primary labelled indication (i.e. lesions containing a classic component of ≥ 50% ) deriving from the results of the Treatment of Age‐related Macular Degeneration with Photodynamic Therapy (TAP) Study. The subsequent TAP Study Group post hoc categorization of lesions as predominantly classic is open to question, however, as it appears that the overall efficacy in this group only may have reflected the especially strong response in 100% classic lesions. Based on a subgroup analysis of the Verteporfin in Photodynamic Therapy Study, the indication for PDT subsequently was expanded in some jurisdictions, including that of the EMEA, to include occult lesions with no classic component. However, the subsequent Visudyne in Occult Study found no benefit in 100% occult lesions, resulting in the EMEA rescinding its approval for this indication.

Impact of fibromyalgia severity on health economic costs

BackgroundFibromyalgia (FM) is a chronic disorder characterized by persistent and widespread pain, often accompanied with fatigue, sleep disturbance and other symptoms. FM affects a population mostly of a productive age and is thus associated with significant lost productivity and disability, in addition to healthcare costs for medications and physician office visits. While other studies have examined FM costs in Europe, few, if any, have examined cost by FM severity level.ObjectiveThe objective of this study was to examine health resource utilization (HRU) and costs associated with FM in routine clinical practice in France and Germany across disease severity levels.MethodsA total of 299 patients with FM, previously diagnosed by a rheumatologist, were recruited from physician offices in France and Germany during routine visits. Subjects completed questions about their pain, health-related quality of life, treatment satisfaction, productivity and FM-related out-of-pocket expenses; site staff recorded clinical, treatment and HRU information for the previous 3 months based on a review of medical records. FM severity was defined using subjects’ Fibromyalgia Impact Questionnaire (FIQ) total scores. Annual costs from a societal perspective were calculated in h, year 2008 values, and included direct costs (e.g. physician office visits, medications, out-of-pocket expenses) and indirect costs (e.g. missed days of work and lost productivity). The mean annual costs were calculated based on 3-month data.ResultsSubjects were reported to have a mean (SD) of 2.9 (1.9) physician office visits in France and 4.9 (3.2) visits in Germany over the past 3 months, corresponding to an average of 11.6 and 19.6 visits a year, respectively. A total of 91% of subjects were receiving prescription medication for their FM. French subjects reported a lower use of anti-inflammatories (39% of subjects) and a higher use of other analgesics (59% of subjects) than German subjects (67% and 34%, respectively). Subjects in full- or part-time employment reported missing a mean (SD) of 2.7 (6.0) days of work due to FM in France and 2.1 (3.8) days in Germany over the last 4 weeks (corresponding to 32.4 and 25.2 days of work missed due to FM per year in France and Germany, respectively). In France, total costs were €7900 (direct €910, indirect €6990). In Germany, total costs were €7256 (direct €1765, indirect €5491). A trend of higher total costs was seen as FM severity increased; however, the results were significant (p = 0.003) only for Germany.ConclusionsFM imposes a significant economic burden on society. Consistent with other studies, FM subjects were found to have substantial costs, over 75% of which were driven by indirect costs from lost productivity. These costs increased as FM severity increased, resulting in a more than 200% difference in cost between mild and severe FM. Overall FM costs were similar between France and Germany; although lost productivity accounted for a higher proportion of costs in France.

Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies

BackgroundOlder patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) was conducted to evaluate the efficacy and safety of pregabalin in older patients.MethodsData from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs). Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction.Results2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595) were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236), 65 to 74 years (n = 766), and ≥75 years (n = 514). Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009), except for the lowest dosage (150 mg/day) in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain.ConclusionsPregabalin (150-600 mg/day) significantly reduced pain in older patients (age ≥65 years) with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the lowest effective dose should allow for effective pain relief while minimizing AEs in older patients with neuropathic pain. Given the common use of polypharmacy in older patients, the absence of known drug-drug interactions makes pregabalin an important treatment option for older patients with pain of neuropathic origin.

Toward development of a fibromyalgia responder index and disease activity score: OMERACT module update.

Following development of the core domain set for fibromyalgia (FM) in Outcome Measures in Rheumatology Clinical Trials (OMERACT) meetings 7 to 9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials in FM. Possible clinical domains that could be included in a responder index and disease activity score include pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed. The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represents heuristic models for our work, but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions, nor are there objective markers that define thresholds of severity or response to treatment. The process of developing candidate dichotomous responder definitions and continuous quantitative disease activity measures is described, along with participant discussions from OMERACT 10. Final results of this work will be published in a separate report pending completion of analyses.

Health-resource use and costs associated with fibromyalgia in France, Germany, and the United States

Background Fibromyalgia (FM) is a chronic disorder characterized by widespread, persistent pain. Prospective and retrospective studies have demonstrated substantial health-care costs associated with FM in a number of countries. This study evaluated and compared health-resource use (HRU) and associated costs related to FM in routine clinical practice across the US, France, and Germany. Methods Two separate, cross-sectional, observational studies of subjects with FM were conducted: one in the US and one in France and Germany. HRU related to prescription medication, physician office visits, diagnostic tests, and hospitalizations was abstracted from chart review; patient out-of-pocket costs and lost productivity were collected via subject self-report. Costs were assigned to HRU based on standard algorithms. Direct and indirect costs were evaluated and compared by simple linear regression. Results A total of 442 subjects (203 US, 70 France, 169 Germany) with FM were analyzed. The mean (standard deviation) age in the US, France, and Germany was 47.9 (10.9), 51.2 (9.5), and 49.2 (9.8), respectively (P = 0.085). Most subjects were female (95% US, 83% France, 80% Germany) (P < 0.001). Adjusted annual direct costs per subject for FM were significantly higher in the US (

Identifying Fibromyalgia‐Associated Symptoms and Conditions from a Clinical Perspective: A Step Toward Evaluating Healthcare Resource Utilization in Fibromyalgia

7087) than in France (

The Comparative Burden of Chronic Widespread Pain and Fibromyalgia in the United States.

481, P < 0.001) or Germany (