V. López-Gómez

Prevalence of distal diabetic polyneuropathy using quantitative sensory methods in a population with diabetes of more than 10 years’ disease duration

OBJECTIVES Results of studies on the prevalence of distal diabetic polyneuropathy (DPN) are contradictory. Conventional methods used for the diagnosis of DPN in clinical practice have limited effectiveness. The present study aimed to assess the prevalence of DPN in a population with long-standing diabetes (more than 10 years disease duration) by measuring vibratory, thermal and tactile sensitivities with quantitative sensory devices, as well as their relationship with associated clinical risk factors. PATIENTS AND METHODS A total of 1011 diabetic patients were evaluated in a multicenter, cross-sectional, observational study. The three sensitivities were assessed by ultrabiothesiometer, aesthesiometer and thermoskin devices, respectively. The prevalence of neuropathic pain was validated by the DN4 questionnaire. RESULTS Of the 1011 cases included, 400 (39.6%) met the diagnostic criteria of DPN, while no DPN was found in the remaining 611 (60.4%). Of the 400 patients with DPN, 253 (63.2%) showed clinical manifestations, while 147 (36.8%) were diagnosed as subclinical DPN. The prevalence of DPN increased with disease duration. There was a progressive loss of the three sensitivities with increased disease duration, particularly thermal and vibratory sensitivities. This loss was statistically significant for the latter two sensitivities. Among patients with clinical DPN, 84.2% had painful neuropathic symptoms. The prevalence of DPN was positively related to micro- and macroangiopathic complications and with dyslipidemia. CONCLUSION This study reveals a high degree of underdiagnosis of DPN, most likely due to the asymptomatic nature of the disease in a considerable proportion of patients. Our observations provide evidence of the usefulness of specific equipment for quantitative and objective assessment of polyneuropathy.

Prevalence of Neuropathic Pain in Radiotherapy Oncology Units

PURPOSE Neuropathic pain (NP) in cancer patients severely impacts quality of life. Radiotherapy (RT) may cause NP, and at the same time, cancer patients visit RT units for pain relief. NP prevalence at these sites and current analgesic treatment should be assessed to improve management. METHODS AND MATERIALS This epidemiological, prospective, multicenter study was undertaken to assess NP prevalence, according to Douleur Neuropathique 4 questions questtionaire (DN4) test results, and analgesic management in cancer pain patients visiting RT oncologic units. Secondary analyses assessed NP etiology and pain intensity (using the Brief Pain Inventory-Short Form) and impact (using the Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study [MOS] for Sleep, and the Health Survey Short Form-12). RESULTS A total of 1,098 patients with any kind of pain were registered. NP prevalence was 31.1% (95% confidence interval, 28.4%--33.9%); 291 NP patients (mean age, 62.2 ±12.5 years and 57.7% men) were eligible for study; 49% of patients were overweight. The most frequent tumors were those of breast and lung, and stage IIIB was the most common cancer stage. The tumors caused 75% of NP cases. Anxiety, sleepiness, and depression were common. At 8 weeks, pain intensity and interference with daily activities decreased significantly for 50.8% of responders. Depression and anxiety (p < 0.0001) scores on the Physical Component Summary and Mental Component Summary measures (p < 0.0001) and all MOS-Sleep subscales, except for snoring, improved significantly. The percentage of satisfied patients increased from 13.8% to 87.4% (p < 0.0001) with the current analgesic treatment, which meant a 1.2- and 6-fold increase (p < 0.0001) in narcotic analgesics and anticonvulsants, respectively, compared to previous treatment. CONCLUSIONS NP is highly prevalent at RT oncology units, with sleepiness, anxiety, and depression as frequent comorbidities. There is a need to improve management of NP with increased use of more specific NP-targeting drugs.

The assessment of generalized anxiety disorder: psychometric validation of the Spanish version of the self-administered GAD-2 scale in daily medical practice.

AimTo psychometrically validate the Spanish version of the self-administered 2-item GAD-2 scale for screening probable patients with generalised anxiety disorder (GAD).MethodsThe GAD-2 was self-administered by patients diagnosed with GAD according to DSM-IV criteria and by age- and sex-matched controls who were recruited at random in mental health and primary care centres. Criteria validity was explored using ROC curve analysis, and sensitivity, specificity and positive and negative predictive values were determined for different cut-off values. Concurrent validity was also established using the HAM-A, HADS, and WHODAS II scales.ResultsThe study sample consisted of 212 subjects (106 patients with GAD) with a mean age of 50.38 years (SD = 16.76). No items of the scale were left blank. Floor and ceiling effects were negligible. No patients with GAD had to be assisted to complete the questionnaire. Reliability (internal consistency) was high; Cronbach’s α = 0.875. A cut-off point of 3 showed adequate sensitivity (91.5%) and specificity (85.8%), with a statistically significant area under the curve (AUC = 0.937, p < 0.001), to distinguish GAD patients from controls. Concurrent validity was also high and significant with HAM-A (0.806, p < 0.001), HADS (anxiety domain, 0.825, p < 0.001) and WHO-DAS II (0.642, p < 0.001) scales.ConclusionThe Spanish version of the GAD-2 scale has been shown to have appropriate psychometric properties to rapidly detect probable cases of GAD in the Spanish cultural context under routine clinical practice conditions.

Effects of Pregabalin on Subjective Sleep Disturbance Symptoms during Withdrawal from Long-Term Benzodiazepine Use

Aim: To evaluate the effectiveness of pregabalin as a tapering therapy on the subjective sleep quality of patients who underwent a benzodiazepine withdrawal program in routine medical practice. Methods: Secondary analysis of a 12-week prospective, open noncontrolled study carried out in patients who met DSM-IV-TR criteria for benzodiazepine dependence. Sleep was evaluated with the Medical Outcomes Study Sleep Scale (MOS Sleep Scale). Results: 282 patients were included in the analysis. Mean (±SD) pregabalin dose was 315 ± 166 mg/day at the end of the trial. We observed a significant and clinically relevant improvement in sleep outcomes at the endpoint, with a total score reduction from 55.8 ± 18.9 to 25.1 ± 18.0 at week 12 (i.e. a 55% reduction). Similar findings were apparent using the six dimensions of the MOS Sleep Scale. Moderate correlations were observed between the MOS Sleep summary index and sleep domains, and there were improvements in anxiety symptoms and disease severity. Conclusions: These findings suggest that pregabalin may improve subjective sleep quality in patients who underwent a benzodiazepine withdrawal program. This effect appears to be partly independent of improvements in symptoms of anxiety or withdrawal. However, controlled studies are needed to establish the magnitude of the effect of pregabalin.

A cost-consequence analysis of pregabalin versus usual care in the symptomatic treatment of refractory low back pain: sub-analysis of observational trial data from orthopaedic surgery and rehabilitation clinics.

AbstractBackground: Low back pain is one of the most common reasons for outpatient consultation in both the primary-care and specialized-care settings. However, few studies have explored the effect of pregabalin in this context. Objective: To prospectively analyse the effect of adding pregabalin on costs and consequences in the treatment of refractory low back pain in routine medical practice. Methods: A secondary analysis was carried out in patients aged ≥18 years with a 6-month history of chronic refractory low back pain who had participated in a previous prospective, naturalistic, 12-week, two-visit study (RADIO study). The analysis compared patients receiving pregabalin with those receiving usual care. Severity of pain, healthcare resources utilization, lost workday equivalents due to pain, and related cost-adjusted reductions were assessed. The year of costing for all cost data reported in the study was 2007. Results: Data from a total of 683 patients (49.5% women, mean age 55.0 years), 82.6% of whom were receiving pregabalin, were analysed. Pregabalin was associated with a higher covariable-adjusted reduction in severity of pain, i.e. mean (SD) −3.4 (2.0) compared with −2.0 (2.1) points with usual care on a 10-point neuropathic pain questionnaire (p < 0.001), and a 61.6% response rate (defined as ≥50% reduction in pain from baseline) compared with 37.3% with usual care (p < 0.001). This resulted in fewer lost workday equivalents in the pregabalin group versus usual care (27.8 vs 34.6, p = 0.002), which produced more significant adjusted reductions in indirect costs, i.e. mean (SD) −€961.8 (€1242.9) compared with −€625.8 (€1169.2) with usual care (p = 0.004). The cost of pregabalin, i.e. mean (SD) €303.8 (€175.8) compared with €37.1 (€97.0) for usual care (p < 0.001), was offset by larger reductions in the other cost components. While the adjusted total costs were substantially reduced in both groups, pregabalin-treated patients showed more significant reductions, i.e. mean (SD) −€991.5 (€1702.3) compared with −€579.3 (€2410.3) with usual care (p = 0.023). Conclusion: Compared with usual care, addition of pregabalin to existing therapy for refractory low back pain was associated with a larger reduction in pain severity and lost workday equivalents. The acquisition cost of pregabalin was offset by a higher reduction in the indirect components of cost, resulting in a significant decrease in total costs.

Broadening of Generalized Anxiety Disorders Definition Does not Affect the Response to Psychiatric Care: Findings from the Observational ADAN Study.

Objective: To elucidate the consequences of broadening DSM-IV criteria for generalized anxiety disorder (GAD), we examined prospectively the evolution of GAD symptoms in two groups of patients; one group diagnosed according to DSM-IV criteria and the other, according to broader criteria. Method: Multicentre, prospective and observational study conducted on outpatient psychiatric clinics. Patients were selected from October 2007 to January 2009 and diagnosed with GAD according to DSM-IV criteria (DSM-IV group) or broader criteria. Broader criteria were considered 1-month of excessive or non-excessive worry and only 2 of the associated symptoms listed on DSM-IV for GAD diagnosis. Socio-demographic data, medical history and functional outcome measures were collected three times during a 6-month period. Results: 3,549 patients were systematically recruited; 1,815 patients in DSM-IV group (DG) and 1,264 in broad group (BG); 453 patients did not fulfil inclusion criteria and were excluded. Most patients (87.9% in DG, 82.0% in BG) were currently following pharmacological therapies (mainly benzodiazepines) to manage their anxiety symptoms. The changes observed during the study were: 49.0% and 58.0%, respectively of patients without anxiety symptoms as per HAM-A scale at the 6 month visit (p=0.261) and 59.7% and 67.7%, respectively (p=0.103) of responder rates (> 50% reduction of baseline scoring). Conclusion: Broadening of GAD criteria does not seem to affect psychiatric care results in subjects with GAD, is able to identify the core symptoms of the disease according to the DSM-IV criteria and could lead to an earlier diagnosis.

P01-150 Cultural adaptation into Spanish of the generalized anxiety disorder scale - 7 (GAD-7) scale

Purpose To carry out cultural adaptation and validation into Spanish of the 7-items self-administered GAD-7 scale; a tool to identify probable patients with Generalized Anxiety Disorder (GAD). Material and methods The adaptation, conducted by an eight-expert panel, was performed by means of a conceptual equivalence process, including forward and backward translations in duplicate to the original language. The content validity was assessed by inter-ratter-agreement (item-goal congruence index of Rovinelli-Hambleton). The adapted version was administered to patients with GAD according to DSM IV criteria and their respective controls, matched by age and sex, who were recruited at random in Mental Health and Primary Care centres to verify scale feasibility and potential understanding problems. Results The inter-ratter reliability confirmed the correct inclusion of items in the corresponding dimension of GAD. The study sample consisted of 8 patients with GAD and 8 controls (62.5% male), mean age 50.38 years (SD=16.76). The average time to completion was 2’30”. No items of the scale were left blank. Floor and ceiling effects were negligible. No patients with GAD had to be assisted to fill in the questionnaire. All the items, except item 5 (p=0,105), showed statistically significant differences among groups (p Conclusion After the adaptation process, a Spanish version of the GAD-7 scale was obtained, confirming its content validity, pertinence and adequacy of items in the Spanish cultural context. The brief time to completion precluded a fast and easy self-administration in the routine medical practice to promptly detect probable cases of GAD.

P01-153 - Effect of Pregabalin on patients with refractory-severe generalized anxiety disorder and concomitant severe symptoms of depression in daily medical practice

Purpose To analyse the effect of Pregabalin (PGB) on anxiety and depression symptoms in patients with refractory-severe Generalized Anxiety Disorder (GAD) and severe concomitant depressive disorder. Methods Post-hoc analysis of a multicentre, prospective and observational study conducted in outpatient psychiatric clinics to ascertain the impact of broadening GAD criteria. Men and women above 18 years, with GAD (DSM-IV criteria), PGB naive and refractory to a previous course of benzodiazepines and/or anti-depressive drugs (minimum 3 months) and severe symptoms of anxiety (HAM-A ≥ 24) and depression (MADRS ≥ 35) were included. Changes in HAM-A and MADRS were assessed after 6 months of receiving PGB as per psychiatrists judgement. Results 159 patients [69.2% women, 45.9 (12.6) years] fulfilled criteria for analysis. Respectively, 92% and 90% of subjects were previously exposed to benzodiazepines and anti-depressives before adding PGB [mean dose: 223.1 (126.3) mg/day]. PGB therapy reduced both anxiety and depressive baseline symptoms by a mean of, respectively in HAM-A and MADRS scales, 57.9% (from 35.5±5.8 to 14.8±9.4; p Conclusion Despite limitations, Pregabalin therapy had a meaningful and significant effect of symptoms of anxiety and depression in patients with severe refractory GAD and concomitant severe depressive disorder.

PW01-51 - The effect of broadening generalized anxiety disorders definition on healthcare resources utilization and costs: a corollary from the adan study

Purpose To analyse the consequences of broadening DSM-IV criteria for generalized anxiety disorder (GAD) on the utilization of health care resources and corresponding costs. Methods Multicentre, prospective and observational study conducted in outpatient psychiatric clinics selected at random and weighted by geographical density of population. Patients with GAD according to DSM-IV criteria and subjects with anxiety symptoms fulfilling broader criteria were compared. Broadening criteria was considered 1-month of excessive or non-excessive worry and only 2 associated symptoms listed on DSM-IV for GAD. Socio-demographic data, medical history and health care resources and corresponding costs were recorded during a 6-month period. Results A total of 3,549 patients were systematically recruited; 12.8% excluded because not fulfilling inclusion criteria, 1,815 patients in DSM-IV criteria group (DG) and 1,264 in broad criteria group (BG). Both groups were similar on their sociodemographic characteristics at baseline. Type of treatments prescribed at psychiatric clinics during the study were similar in frequency; anti-depressives (77.0% in DG vs. 75.3% in BG, ns), benzodiazepines (71.5% vs. 67.2% respectively, ns), and anti-convulsants (72.1% vs. 67.0% respectively, ns). Health care resources utilization were statistically reduced to a similar extent in both groups as a consequences of treatments yielding to a cost-of-illness in the 6-month period of €1,196 (1,158) and €1,112 (874), respectively; p=0.304. Conclusion In a large sample of subjects, broadening of GAD criteria could lead to earlier diagnosis that would not be associated necessarily to an increase in health care resources utilization or costs to the National Health System.

PW01-241 - The effect of pregabalin on subjective sleep problems during withdrawal from long-term benzodiazepine use

Objective To evaluate the effect of pregabalin as a tapering therapy over the subjective sleep quality of patients who underwent a benzodiazepine withdrawal program. Method This was a secondary analysis of a 12-week, prospective, and observational study carried out in patients aged 18 years or over, who met DSM-IV-TR criteria for benzodiazepine dependence without other major psychiatry disorder. Evaluations included the Benzodiazepine Withdrawal Symptom Questionnaire, the Hamilton Anxiety Rating Scale, the Clinical Global Impression scale, and the MOS-Sleep Scale. Changes from baseline to the endpoint in the different scales’ scores as well as correlations of these changes with those of the MOS-Sleep scores were calculated. Results 282 patients met the criteria for analysis. Mean pregabalin dose was 315 (166) mg/day at end-of-trial. We observed a significant and clinically relevant improvement in sleep outcomes at the study endpoint as measured with the MOS-Sleep Summary Index, that was reduced from 55.8 (18.9) pts at baseline to 25.1 (18.0) pts at week 12 (55% reduction), as well as with the six dimensions of the MOS-Sleep Scale. Moderate correlations were observed between Summary Index and sleep domains with improvements in the anxiety symptoms and in the disease severity as well. Also, sleep ameliorations were observed in the 52% successfully benzodiazepines withdrawals but, although to a lesser extent, in the remaining failures as well. Conclusion Pregabalin treatment improves subjective sleep quality in patients who underwent a benzodiazepine withdrawal program and this effect appears partly independent of the improvement of anxiety or withdrawal symptoms.