The cost-effectiveness of isavuconazole compared to voriconazole, the standard of care in the treatment of patients with invasive mould diseases, prior to differential pathogen diagnosis in Spain.

BACKGROUND: Invasive mould diseases are associated with high morbidity, mortality and economic impact. Its treatment is often started prior to differential pathogen diagnosis. Isavuconazole is approved for treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) when amphotericin-B is not indicated. OBJECTIVES: To estimate the cost-effectiveness of isavuconazole vs voriconazole for the treatment of adult patients with possible IA prior to differential pathogen diagnosis, in Spain. METHODS: A decision tree analysis was performed using the Spanish Healthcare System perspective. Among all patients with possible IA, it was considered that 7.81% actually had IM. Costs for laboratory analysis, management of adverse events, hospitalisation and drugs per patient, deaths and long-term effects in life years (LYs) and quality-adjusted LYs (QALYs) were considered. Efficacy data were obtained from clinical trials and utilities from the literature. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: In patients with possible IA and when compared to voricanozole, isavuconazole showed an incremental cost of 4758.53€, besides an incremental effectiveness of +0.49 LYs and +0.41 QALYs per patient. The Incremental Cost Effectiveness Ratio was 9622.52€ per LY gained and 11,734.79€ per QALY gained. The higher cost of isavuconazole was due to drug acquisition. Main parameters influencing results were mortality, treatment duration and hospitalisation days. The PSA results showed that isavuconazole has a probability of being cost-effective of 67.34%, being dominant in 24.00% of cases. CONCLUSIONS: Isavuconazole is a cost-effective treatment compared to voriconazole for patients with possible IA for a willingness to pay threshold of 25,000€ per additional QALY.

Clinical and economic outcomes of adjunctive therapy with pregabalin or usual care in generalized anxiety disorder patients with partial response to selective serotonin reuptake inhibitors.

BACKGROUND: This study is done to compare the effect of adjunctive therapy with pregabalin versus usual care (UC) on health-care costs and clinical and patients consequences in generalized anxiety disorder (GAD) subjects with partial response (PR) to a previous selective serotonin reuptake inhibitor (SSRI) course in medical practice in Spain. METHODS: Post hoc analysis of patients with PR to SSRI monotherapy enrolled in a prospective 6-month naturalistic study was done. PR was defined as a Clinical Global Impression (CGI) scale score ≥3 and insufficient response with persistence of anxiety symptoms ≥16 in the Hamilton Anxiety Rating Scale (HAM-A). Two groups were analyzed: 1) adjunctive therapy (AT) with pregabalin (150-600 mg/day) to existing therapy and 2) UC (switching to a different SSRI or adding another anxiolytic different than pregabalin). Costs included GAD-related health-care resources utilization. Consequences were a combination of psychiatrist-based measurements [HAM-A, CGI, and Montgomery-Asberg Depression Rating Scale (MADRS)] and patient-reported outcomes [Medical Outcomes Study Sleep (MOS-sleep) scale, disability (World Health Organization Disability Assessment Schedule II (WHO-DAS II) and quality-of-life (Euro Qol-5D (EQ-5D)]. Changes in both health-care costs and scale scores were compared separately at end-of-trial visit by a general linear model with covariates. RESULTS: Four hundred eighty-six newly prescribed pregabalin and 239 UC GAD patients [mean (SD) HAM-A 26.7 (6.9) and CGI 4.1 (0.5)] were analyzed. Adding pregabalin was associated with significantly higher mean (95% CI) score reductions vs. UC in HAM-A [-14.9 (-15.6; -14.2) vs. -11.2 (-12.2; -10.2), p < 0.001] and MADRS [-11.6 (-12.2; -10.9) vs. -7.8 (-8.7; -6.8), p < 0.001]. Changes in all patient-reported outcomes favored significantly patients receiving pregabalin, including quality-of-life gain; 26.4 (24.7; 28.1) vs. 19.4 (17.1; 21.6) in the EQ-VAS, p < 0.001. Health-care costs were significantly reduced in both cohorts yielding similar 6-month costs; €1,565 (1,426; 1,703) pregabalin and €1,406 (1,200; 1,611) UC, p = 0.777. The effect of sex on costs and consequences were negligible. CONCLUSION: In medical practice, GAD patients with PR to SSRI experienced greater consequence improvements with adjunctive therapy with pregabalin versus UC, without increasing health-care cost. The effect of pregabalin was independent of patient gender.

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

AIM: To psychometrically validate the Spanish version of the self-administered 2-item GAD-2 scale for screening probable patients with generalised anxiety disorder (GAD). METHODS: The 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. RESULTS: The 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. CONCLUSION: The 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.

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.

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.

Changes in seizure severity and quality of life in patients with refractory partial epilepsy.

This 6-month observational, prospective, multicenter study assessed the influence of changes in seizure severity on quality of life in patients with refractory partial epilepsy. Patients (N = 262) diagnosed with partial epilepsy and receiving two antiepileptic drugs as determined by usual clinical practice were enrolled in this study. The primary endpoint was the mean seizure severity score obtained from the Seizure Severity Questionnaire. Reductions in seizure severity were detected from baseline to months 3 and 6 (P<0.0001). Improvements compared with baseline were found for several secondary measures: Hamilton Anxiety and Depression scales (P<0.0001), most Medical Outcomes Study-Sleep subscales (P<0.05), and seven subscales of the Quality of Life in Epilepsy Inventory-31 (QOLIE-31; P<0.0005). Seizure severity correlated directly with anxiety (P<0.0001) and inversely with QOLIE-31 measures (P<0.0001). In conclusion, reducing seizure severity with appropriate medication may lead to improvement in the overall quality of life of patients with refractory partial epilepsy.

Cultural adaptation into Spanish of the generalized anxiety disorder-7 (GAD-7) scale as a screening tool.

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent mental health condition which is underestimated worldwide. This study carried out the cultural adaptation into Spanish of the 7-item self-administered GAD-7 scale, which is used to identify probable patients with GAD. METHODS: The adaptation was performed by an expert panel using a conceptual equivalence process, including forward and backward translations in duplicate. Content validity was assessed by interrater agreement. Criteria validity was explored using ROC curve analysis, and sensitivity, specificity, predictive positive value and negative value for different cut-off values were determined. Concurrent validity was also explored using the HAM-A, HADS, and WHO-DAS-II scales. RESULTS: The study sample consisted of 212 subjects (106 patients with GAD) with a mean age of 50.38 years (SD = 16.76). Average completion time 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. The scale was shown to be one-dimensional through factor analysis (explained variance = 72%). A cut-off point of 10 showed adequate values of sensitivity (86.8%) and specificity (93.4%), with AUC being statistically significant [AUC = 0.957-0.985); p < 0.001]. The scale significantly correlated with HAM-A (0.852, p < 0.001), HADS (anxiety domain, 0.903, p < 0.001), and WHO-DAS II (0.696, p > 0.001). LIMITATIONS: Elderly people, particularly those very old, may need some help to complete the scale. CONCLUSION: After the cultural adaptation process, a Spanish version of the GAD-7 scale was obtained. The validity of its content and the relevance and adequacy of items in the Spanish cultural context were confirmed.

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.

BACKGROUND: 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 >or=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) -euro961.8 (euro1242.9) compared with -euro625.8 (euro1169.2) with usual care (p = 0.004). The cost of pregabalin, i.e. mean (SD) euro303.8 (euro175.8) compared with euro37.1 (euro97.0) 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) -euro991.5 (euro1702.3) compared with -euro579.3 (euro2410.3) 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.

Pregabalin for the treatment of patients with generalized anxiety disorder with inadequate treatment response to antidepressants and severe depressive symptoms.

To evaluate the effectiveness of pregabalin in patients with resistant generalized anxiety disorder (GAD) and severe depressive symptoms, we carried out a post-hoc analysis of a multicenter, prospective, and observational 6-month study. We included patients who were at least 18 years old, fulfilled the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for GAD, showed inadequate responses to previous courses of antidepressant treatment, had Montgomery-Asberg Rating Scale scores of at least 35, had not received pregabalin previously, and were prescribed pregabalin upon entry into this study. We included 1815 patients fulfilling the DSM-IV criteria for GAD, and 133 (7.3%) fulfilled the selection criteria for these analyses. Ninety-seven percent of the patients received pregabalin (mean dose: 222 mg/day) in combination with other psychotropics. The Hamilton Anxiety Scale total score was reduced by a mean of 20.3 points (95% confidence interval, 22.1-18.4) (57.2% reduction) at month 6. Pregabalin also ameliorated comorbid depressive symptoms, with a reduction in the mean score of the Montgomery-Asberg Rating Scale of 22.3 points (95% confidence interval, 24.2-20.4) (56.6% reduction). Our results suggest that pregabalin, as part of a combination regimen with antidepressants and/or benzodiazepines, might be effective for the treatment of patients with GAD who have shown inadequate response to previous antidepressants and have severe depressive symptoms.

Effectiveness of pregabalin as monotherapy or combination therapy for neuropathic pain in patients unresponsive to previous treatments in a Spanish primary care setting.

BACKGROUND AND OBJECTIVE: Patients from a previous study of neuropathic pain (NP) in the Spanish primary care setting still had symptoms despite treatment. Subsequently, patients were treated as prescribed by their physician and followed up for 3 months. Since pregabalin has been shown to be effective in NP, including refractory cases, the objective of this study was to assess the effectiveness of pregabalin therapy in patients with NP refractory to previous treatments. METHODS: This was a post hoc analysis of pregabalin-naïve NP patients treated with pregabalin in a 3-month follow-up observational multicenter study to assess symptoms and satisfaction with treatment. Patients were evaluated with the Douleur Neuropathique en 4 questions (DN4), the Brief Pain Inventory (BPI) and the Treatment Satisfaction for Medication Questionnaire (SATMED-Q) overall satisfaction domain. RESULTS: 1,670 patients (mean age 58 years, 59 % women), previously untreated or treated with ≥1 drug other than pregabalin, were treated with pregabalin (37 % on monotherapy). At 3 months, pain intensity and its interference with activities decreased by half (p < 0.0001), while the number of days with no or mild pain increased by a mean of 4.5 days (p < 0.0001). Treatment satisfaction increased twofold (p < 0.0001). Patients with a shorter history of pain and those with neuralgia and peripheral nerve compression syndrome (PCS) as etiologies had the highest proportion on monotherapy and showed the greatest improvements in pain-related parameters in their respective group categories. CONCLUSION: Treatment with pregabalin (as monotherapy or combination therapy) provides benefits in pain and treatment satisfaction in patients with NP, including refractory cases. Shorter disease progression and neuralgia and PCS etiologies are favorable factors for pregabalin treatment response.

Cultural adaptation and validation of the painDETECT scale into Spanish.

OBJECTIVE: The aim of this study was to culturally adapt into Spanish and validate the painDETECT questionnaire, a brief self-administered instrument designed to screen the presence of a neuropathic pain component in usual clinical practice. METHODS: The original English painDETECT questionnaire was culturally adapted into Spanish (Spain) by 2 independent translators under supervision of an expert panel. The LANNS, and a pain visual analog scale were administered along with the painDETECT questionnaire to a sample of 252 patients with neuropathic, nociceptive, or mixed pain for at least 3 months. Patients were classified by experienced specialists under normal conditions of clinical practice. A retest measure after 24 to 48 hours was also carried out. Reliability, construct validity, convergent validity, criterion, and discriminant validity were assessed. RESULTS: An effective sample of 221 patients with chronic pain was recruited, 32% diagnosed of neuropathic origin, 32% of nociceptive, and remaining 36% presented mixed pain. The average age was 57.8 years (SD=14.2) and 59% were women. Cronbach alpha attained a value of 0.86, and the intraclass correlation coefficient with the retest was 0.93. The factor structure was coherent with the one informed for the original instrument. Pearson correlation with the LANSS scale was 0.88. Area under the receiver operating characteristic curve was 0.88 when comparing neuropathic and nociceptive groups. Using the suggested cutoff value for pain presence of 19 points or higher, the following discriminant values are obtained: sensitivity=75%, specificity=84%, Youden Index=0.595, positive predictive value=92%, and negative predictive value=60%. The absence cutoff value of 12 points or bellow raised the following values: sensitivity=93%, specificity=68%, Youden Index=0.61, positive predictive value=87%, and negative predictive value=80%. When mixed pain patients are included in the group with a neuropathic component, discriminant values are slightly reduced, as expected. CONCLUSIONS: The culturally adapted version of the painDETECT presents good psychometric properties and shows to be a valid patient-reported outcome for measuring the presence of a neuropathic component in patients with chronic pain.

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.

Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health.

BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.

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.