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Seven prospective real-world studies conducted in general practices in Belgium of antihypertensive treatment with valsartan-centric regimens were pooled to examine similarities and differences in determinants of blood pressure (BP) values (mmHg) and BP control rates between female and male patients.Pooled analysis of a total evaluable sample of 17,044 patients, including 8273 (48.5%) women and 8771 men (51.5%) treated over approximately 90 days with valsartan-centric regimens in second or later line. Hierarchical linear and logistic regressions were applied to identify patient- and physician-related determinants of BP outcomes and a potential physician class effect.Reductions in BP (mmHg) over 90 days were similar for women and men, and so were changes in BP control rates. Approximately a quarter of the variance in 90 day BP values was attributable to a physician class effect. Both gender groups shared some patient- and physician-related determinants of BP outcomes, though often varying in degree of influence. Analyses also revealed gender-specific determinants. Among others, modifiable/manageable patient-related determinants included BP at hypertension diagnosis (proxy for time of diagnosis), risk factors, antihypertensive treatment and adherence; while among the physician-related determinants clinical experience in hypertension treatment was modifiable/manageable.Valsartan-centric treatment regimens are associated with significant reductions in BP level and improvement in BP control in both women and men. The determinants revealed in modeling provide guidance to clinicians in the common and differential management of hypertension in female and male patients.

Aims Six prospective real-world studies of antihypertensive treatment with valsartan-centric regimens were pooled to: (1) examine the effectiveness of similar to 90 days of second- or later-line valsartan treatment in hypertensive patients with known comorbidities; and (2) identify physician- and patient-related determinants associated with systolic (SBP) and diastolic blood pressure (DBP) outcomes in these patients. Methods and materials A pooled analysis was performed of an evaluable sample of 11,999 hypertensive patients with known comorbidities treated similar to 90 days with valsartan-centric regimens. We applied hierarchical linear and logistic regression models to identify determinants of blood pressure (BP) outcomes and a potential physician class effect. Results Valsartan regimens resulted in mean (SD) SBP and DBP reductions of 18.0 (15.8) mmHg and 9.5 (10.1) mmHg, respectively, at similar to 90 days, yielding SBP, DBP and combined SBP/DBP control rates of 44.0%, 67.2% and 39.3%, respectively. About a quarter of the variance in 90 day BP values was attributable to a physician class effect. BP outcomes declined with physicians' increasing years in practice and being male. At the patient level, BP outcomes declined with SBP and DBP at diagnosis; diabetes; higher cholesterol and BMI; lower valsartan and hydrochlorothiazide (HCTZ) doses; and concomitant anti-hypertensives. Older age was associated with improved DBP. A proxy of physician vigilance, cardiovascular disease history, was associated with improved BP outcomes, as were patient adherence and higher doses of valsartan in combination with HCTZ. Conclusions Valsartan-centric regimens have significant BP lowering benefits in this pooled sample of patients with known comorbidities. Many observed determinants of BP outcomes are modifiable or manageable.

Background: In patients with a diagnosis of asthma, there is currently no consensus which allergy tests should be performed to confirm a diagnosis of allergy. Aims and Objectives: We aimed to gain insight in the decision making in allergy testing in patients with (severe) asthma in Belgium. Methods: Twenty-five respiratory physicians across Belgium were interviewed by means of a questionnaire. Results: Among respiratory physicians, an allergic component is suspected for the following reasons (in decreasing order of importance): seasonal allergen exposure, rhinosinusitis, family history of asthma, eczema, perennial allergen exposure, food allergy, animal exposure. If the patient has no obvious allergic complaints, allergic testing is nevertheless performed in 84% of the patients. As to the choice of allergy tests performed upon initial allergy work-up, 48% of respiratory physicians starts with skin prick tests alone, 12% with ImmunoCAP® tests alone and 16% performs both SPT and ImmunoCAP. The remaining physicians make a decision on an individual basis. Conclusions: There is a large heterogeneity among Belgian respiratory physicians regarding decision making in allergy testing in patients with asthma. Comorbidities and exposure play an important role in the suspicion of an allergic component in patients with asthma.

Background: In patients with asthma, there is currently no clear consensus which tests should be performed to confirm a diagnosis of allergy. Aims and Objectives: We aimed to gain insights in the decision making in allergy testing in patients with asthma in Belgium. Methods: Twenty-five Belgian respiratory physicians were interviewed by means of a questionnaire. Results: A majority (60%) of the respondents indicated to start, during initial allergic work-up, with skin prick testing (SPT), rather than testing for specific serum IgE (sIgE). Dermatophagoides pteronyssinus (Der p), birch, grass pollen mixture, cat epithelium, Aspergillus, Alternaria, dog epithelium, mugwort, plantago and Dermatophagoides farinae (Der f) were, in descending order, the most frequently performed SPT. When testing for sIgE, 64% of respondents indicated to start with a limited, fixed set of tests during initial allergy work-up, mainly due to reimbursement restrictions. Der p, grass pollen mixture, tree pollen mixture, mixture of fungi, birch, mixtures of herbs, mixture of pets, cat epithelium, Aspergillus fumigatus and Der f are, in descending order, the most frequently performed sIgE tests. When initial tests are negative, a majority (64%) of physicians considers performing additional testing, mainly guided by a history of specific exposures. Allergy testing is performed more frequently in patients with severe asthma compared to patients with asthma but in general, the choice of allergy tests does not differ between patients with asthma or severe asthma. Conclusions: There is a large heterogeneity among Belgian respiratory physicians regarding decision making in allergy testing in patients with asthma.

Patient adherence is often not monitored because existing methods of evaluating adherence are either burdensome or do not accurately predict treatment outcomes.To examine whether two simple, single-item physician-administered measures of patient adherence to antihypertensive medication are predictive of blood pressure outcomes.Retrospective database analysis of patients with hypertension treated in Belgian primary care.Using pooled data from five observational studies, a sample was identified of 9725 patients who were assessed using two single-item physician-administered measures of adherence to antihypertensive medication: the first item of the Basel Assessment of Adherence Scale (BAAS) and the Visual Analogue Scale (VAS). These two assessment tools were administered by GPs during regular appointments with patients. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and combined SBP/DBP were measured at baseline and at 90 days.BAAS-identified adherent patients achieved lower mean SBP and DBP compared with non-adherent patients at 90 days (P0.001), and had odds ratios of achieving blood pressure control of 0.66 (95% confidence intervals (CI) = 0.61 to 0.73, P0.001) for SBP, 0.69 (95% CI = 0.62 to 0.76, P0.001) for DBP, and 0.65 (95% CI = 0.59 to 0.72, P0.001) for combined SBP/DBP. For VAS-identified adherent patients, the odds ratios of achieving blood pressure control were 0.93 (95% CI = 0.86 to 1.00, P0.001) for SBP, 0.79 (95% CI = 0.73 to 0.85, P0.001) for DBP, and 0.91 (95% CI = 0.84 to 0.99, P0.001) for combined SBP/DBP.The first item of the BAAS and the VAS are independent predictors of blood pressure control. These methods can be integrated seamlessly into routine clinical practice by allowing GPs to quickly evaluate a patient's adherence and tailor treatment recommendations accordingly.

Using data from the Belgian Paget's Disease Registry of 142 patients treated with a 5 mg intravenous infusion of zoledronic acid, we examined disease remission over 3 years in 98 patients with Paget disease of bone (PDB) seen in routine practice. Median age was 76 years, most patients (60.2 %) were male, and all were Caucasian. Median time since PDB diagnosis was 11.5 years, few patients (5.1 %) had a family history of PDB, and 32.6 % had received prior bisphosphonate and/or other treatments. The most common pagetic locations were pelvis, spine, femur, tibia, and skull. The most common symptoms included pain, impaired mobility, bone deformities, and joint disease: 36.7 % of patients had comorbid osteoarthritis and 16.3 % comorbid osteoporosis. Response rates were 93.3 % at 1 year, 89.5 % at 2 years, and 91.6 % at 3 years, statistically similar to an extension study of the original zoledronic acid trials. Twenty-one patients experienced a relapse over the 3-year period at a median of 20.7 months posttreatment; of these, 13 regained remission by the end of the observation period. Relapse was not associated with osteoarthritis, osteoporosis, or other comorbidities. Safety data were similar to those reported elsewhere. In summary, in this somewhat frailer sample of patients with PDB, effectiveness and safety data were similar to those observed in the original trial populations. These findings, which are the first on the use of zoledronic acid for PDB in routine clinical practice, underscore the therapeutic benefits and relative safety of zoledronic acid in the management of PDB in "real-world'' clinical settings.

AIM: To evaluate the outcomes of ≥6y ranibizumab therapy in neovascular age-related macular degeneration (AMD). METHODS: HELIX was a retrospective, observational effectiveness study using medical records of patients treated in three clinics in Belgium. Patients had neovascular AMD and were initially treated with intravitreal ranibizumab (0.5 mg) between November 1, 2007 and October 31, 2008, had ≥6y of data available, and were treated on an ongoing, as-needed basis. Outcomes included best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: The sample consisted of 88 eyes from 69 patients. Mean age was 76.4±6.5y, most patients were female (62.3%). Most eyes (62.5%) were treatment-naive, 33 previously treated eyes had received predominantly other anti-vascular endothelial growth factor agents and verteporfin. Mean baseline BCVA was 57.4±12.7 ETDRS letters and CRT was 291.5±86.1 μm. On average, patients received 20.6±11.9 ranibizumab injections over the ≥6y. Intervals between injections were on average 12.7±16.1wk. Mean change in BCVA from baseline to last observation for the sample was less than one letter (-0.9±17.3 letters), with an average loss of -3.2±15.6 letters in previously treated eyes versus a gain of 0.6±18.4 letters in treatment-naïve eyes. When considering a loss of

We pooled data from 6 valsartan-related studies including 3,658 diabetic and 11,624 nondiabetic patients to evaluate blood pressure (BP) outcomes after approximately 90 days of second- or later-line valsartan treatment. Hierarchical linear and logistic regressions were applied to identify determinants of BP outcomes. Similar reductions in BP values and similar BP control rates were achieved in both groups after approximately 90 days of therapy. The modeling analyses identified several common and different patient- and physician-related determinants of BP outcomes for both groups, many of which are modifiable or clinically manageable. Through varying in terms of association and influence between the diabetic and nondiabetic groups, patient-related determinants included age, BP at diagnosis of hypertension, risk factors, valsartan regimen, concomitant antihypertensive treatment, and adherence; and physician-related determinants included gender, years in practice, and hypertension management. In summary, in both diabetic and nondiabetic patients, the use of valsartan-centric treatment regimens in second- or later-line antihypertensive treatment is associated with significant reductions in BP level and improvement in BP control. The determinants identified in modeling provide guidance to clinicians in the common and differential management of hypertension in diabetic and nondiabetic patients.

Long-term variability of serum total IgE (sIgE tot ) has been reported in asthmatics. This study evaluates the dynamics and the factors predictive of this variability. sIgE tot levels were prospectively measured over 1 year in 41 moderate-to-severe asthmatics treated with high-dose of inhaled corticosteroids and long-acting β 2 agonists (and untreated with omalizumab). Patients were divided into 3 groups according to their baseline sIgE tot level: low (≤75 IU/mL; n=10), intermediate (76-700 IU/mL; n=20) or high (>700 IU/mL; n=11). The sIgE tot variability and factors predictive of IgE tot variability were studied. The mean sIgE tot (whole group) fluctuated over 1 year and showed an overall non-significant decrease from baseline ( p =0.21). Four to 29% of the sIgE tot variability depended on within-patient variability. No factor predictive of the within-patient variability was identified in the intermediate sIgE tot group. In the low sIgE tot group, however, the level of sIgE tot increased over 1 year in patients exposed to allergens ( p p =0.011), and the odds of having an exacerbation since the previous visit increased by 30% if sIgE tot increased by 100 IU/mL ( p tot group, the odds of having an exacerbation since the previous visit decreased by 5% if sIgE tot increased by 100 IU/mL ( p =0.005). These trends should be confirmed in a bigger cohort. In this small cohort of moderate-to-severe asthmatics, a limited within-patient variability of sIgE tot levels was observed over 1 year. This variability depended on allergen exposure, OCS use (probably related to exacerbation management) and exacerbations in patients with low and high baseline sIgE tot .

Onbrace is a Belgian non-interventional study evaluating the use of indacaterol (IND), a long-acting β 2 agonist indicated for COPD maintenance treatment. Known COPD patients requiring the initiation of maintenance inhaled treatment i) with IND used in monotherapy or in combination with other COPD treatment (IND group; n=1756); or ii) without IND (comparator group; n=221) were enrolled. The physician initiated the maintenance treatment per his/her current daily practice and the choice of the drugs was made at his/her own discretion. Subjective and objective measures of treatment effectiveness were collected during 6 months. Most of the enrolled patients (93%) were followed by general physicians. Per daily practice, the participating physicians included inhaled corticosteroids (ICS) as part of the first-line maintenance treatment for 50% of their patients. According to the physicians, ICS were most frequently used to improve COPD symptoms and prevent exacerbations. Prior to the study, COPD was diagnosed on the basis of clinical history (63%) and/or spirometry (45%), and was treated with short-acting bronchodilators (73%). Upon maintenance treatment initiation, an improvement in perceived treatment effectiveness, a decrease in COPD symptoms and a trend towards decrease in the number of exacerbations were observed in both groups. Few adverse events were reported ( In this study, spirometry is underused for COPD diagnosis and ICS are overused for COPD treatment (both being partly correlated) according to the GOLD document. The efficacy and the safety of IND-containing treatment are confirmed in real-life conditions.

Omalizumab (OMA) (Xolair ® ) is an anti-IgE monoclonal antibody indicated for the maintenance treatment of persistent severe allergic asthma (PSAA). OMA treatment requires (once/twice) monthly injections causing concerns for persistence and adherence to treatment; hereto, the long-term use of OMA was studied in a real-life setting. A prospective observational study was conducted over 120 weeks in 50 PSAA patients treated with OMA. As from week 16 (evaluation time point for clinical response to OMA), the persistence to treatment, the appointment adherence and the OMA effectiveness were evaluated. OMA effectiveness was defined as a change ≥0.5 point from week 0 in asthma quality of life questionnaire (AQLQ) total score (or sub-score); and/or an absence of severe exacerbation; and/or a reduction in oral corticosteroid use. At least 92% of the patients (46/50) were responders to OMA at week 16. From these 46 responders, 39 (85%), 33 (72%), 31 (67%) and 30 (65%) were persistent to treatment at week 52, 68, 104 and 120, respectively (all p from visit-to-visit p >0.05 from week 16 to week 52, then all p from visit-to-visit p from visit-to-visit >0.05). In this limited cohort of PSAA patients, initial persistence and adherence to OMA treatment were high in real-life. Subsequently, physicians and patients must optimize long-term persistence and adherence, as OMA proved effectiveness over 120 weeks in most patients.

Background European guidelines recommend that antihypertensive management should be graded as a function of total cardiovascular risk. Aims To examine the multilevel (patient- and physician-level) determinants of blood pressure and residual total cardiovascular risk outcomes associated with second-line valsartan therapy. Methods The BSCORE study was a prospective, multi-centre, pharmacoepidemiological study of the real-world effectiveness of second-line valsartan with or without hydrochlorothiazide. Results A total of 3497 patients were recruited by 354 physicians. Mean age was 63.8 ± 12.0 years; 52.3% were male; 20.9% were smokers; 47.7% were dyslipidaemic; and 23.6% had diabetes. On average, reductions in blood pressure and increases in the proportions of patients with controlled blood pressure after 90 days were statistically significant (all P < 0.001). Twenty-one percent of systolic blood pressure and 25.6% of diastolic blood pressure variability at follow-up was attributable to physician-level characteristics. Significant reductions in total cardiovascular risk were observed (P < 0.001); with 12.5% of the variability in total cardiovascular risk change attributable to physician-level characteristics. Several independent determinants of blood pressure outcomes were identified, many of which are modifiable. Conclusions Second-line valsartan therapy improves blood pressure outcomes under variable real-world conditions, and is associated with a decrease in total cardiovascular risk. Optimizing antihypertensive effectiveness, including the reduction of residual cardiovascular risk, involves managing concomitant conditions and risk factors, improving adherence, and identifying physician-level factors amenable to intervention.

Gender-specific determinants of blood pressure (BP) values and control have not been the focus of clinical hypertension research. The purpose of this analysis was to identify gender-specific and multi-level (physician and patient) determinants of BP values and predictors of uncontrolled BP. We completed a subgroup analysis comparing men and women who participated in the Belgian PREVIEW study of second-line treatment effectiveness of valsartan, applying two-level hierarchical modelling of 90-day BP values and guideline-defined BP control. In total, 1665 women and 1525 men were treated by 504 general practitioners. Fewer women than men reached systolic BP (SBP) (P=0.015) and combined BP targets at 90 days (P=0.007). More than 26% of the variance in 90-day SBP (intra-class correlation coefficient (ICC)=0.270) and diastolic BP (DBP) (ICC=0.262) was attributable to physician-level factors for men; the physician-level ICCs for SBP and DBP were 0.259 and 0.268, respectively, for women. Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by gender. Many of the multi-level determinants of BP by gender are amenable to intervention, and the remainder can serve as warning signs to clinicians that patients may remain vulnerable to poor outcomes associated with sub-optimal BP control.

Ivo Abraham1,2, Christopher Lee1,2, MinKyoung Song1,3, Stefaan Vancayzeele4, Heidi Brié4, Christine Hermans4, Patricia Van der Niepen5, Karen MacDonald21University of Arizona, Tucson, AZ, USA; 2Matrix45, Earlysville, VA, USA; 3School of Nursing, University of Pennsylvania, Philadelphia, PA, USA; 4Department of Nephrology and Hypertension, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 5Novartis Pharma, Vilvoorde, BelgiumObjective: Vulnerability profiling, an alternative to deterministic risk assessment, offers clinicians a more intuitive but empirically-grounded assessment of patient risk. This study aimed to determine whether a heuristic profile of high vulnerability is an independent predictor of uncontrolled hypertension.Methods: Secondary analysis of prospective observational study data on 2999 hypertensive patients treated with valsartan. Predictive validity of vulnerability profiling for first-line, secondline, and first-or-second-line antihypertensive treatment was inferred from 1) logistic regression models with adequate statistical fit, 2) statistically significant odds ratios for uncontrolled BP for the high-vulnerability cluster exceeding 1.00, and 3) correct classification rates for patients’ BP control status.Results: All models of uncontrolled BP were significant (P < 0.001); all odds ratios for the high-vulnerability cluster were greater than 1.00 and significant (P < 0.001). Correct classification rates for the highly-vulnerability cluster on uncontrolled BP after first-line, second-line, or either treatment were 91.1%, 61.2%, and 93.5% for systolic BP; 74.5%, 65.8%, and 76.7% for diastolic BP; and 92.8%, 65.3%, and 94.6% for combined systolic and diastolic BP.Conclusion: The heuristic profile of “later, lazier, and unluckier” is an intuitive and valid tool to help identify patients at greater risk for poor BP control seen in general practice.Keywords: hypertension, heuristics, vulnerability, profiling, risk

If well-designed, longitudinal observational studies (LOSs) can provide insights to the linkages between real-world outcomes and their multilevel determinants. In this article, some of the scientific and methodologic issues related to LOSs in pharmacotherapeutic evaluations are discussed. A case of such a study in the treatment of mild to moderate dementia is provided-a case in which a pharmaceutic sponsor addressing a medical question (long-term effectiveness) realized that caring for patients who have Alzheimer's disease involves the clinical community of caregivers, physicians, families, nurses, psychologists, and pharmacists, among others, and partnered with nurse researchers to design their inquiry. The authors conclude by presenting an argument for nurses to take the lead in effectiveness research.

Summary Background Hypertensive patients with established cardiovascular or renal disease (ECVRD) have an added 10-year risk of cardiovascular events, classified by the European Society of Hypertension/European Society of Cardiology as ‘very high’. Aims To identify determinants of blood pressure (BP) outcomes in hypertensive patients with and without ECVRD treated in second-line with valsartan. Methods This was a subgroup analysis comparing patients with and without ECVRD who participated in the PREVIEW study, a 90-day observational prospective effectiveness study of valsartan, conducted in Belgium. Two-level (patients ‘nested’ under physicians) hierarchical linear and logistic modelling of BP values and BP control (140/90 mmHg; 130/80 mmHg for diabetics) at 90 days was applied to data from 1107 patients with and 2087 patients without ECVRD treated with valsartan by 504 general practitioners. Results Absolute reductions in BP were similar across subgroups, with minor variations in actual BP levels in general and by subgroup. Fewer patients with versus without ECVRD achieved targets for systolic BP, diastolic BP and combined systolic/diastolic BP control. Variability in BP values and control at 90 days attributable to a physician-level class effect ranged from 24.6% to 28.1% and 15.0% to 22.4%, respectively. Physician- and patient-related determinants of 90-day BP outcomes varied considerably between the two subgroups. Conclusion Several determinants of BP outcomes were identified comparing patients with and without ECVRD, including amenable physician-level and patient-level factors and warning signs for continued risk of uncontrolled BP. ECVRD patients present with differential characteristics, conditions and determinants that mandate individualized attention to complement general evidence-based antihypertensive treatment.

BACKGROUND: Both patient- and physician-related factors have been shown to explain variability in the outcomes of antihypertensive treatment. Total cardiovascular risk (TCVR) is increasingly used as a determinant of treatment effectiveness but has also been proposed as a treatment outcome. To our knowledge, no studies have reported how antihypertensive treatment impacts blood pressure and TCVR outcomes. OBJECTIVE: To examine in patients treated with a regimen including single-pill combinations (SPCs) of amlodipine/valsartan (1) blood pressure (BP) reduction and control, total cardiovascular risk (TCVR) change, and TCVR reduction of 1 class or more; (2) hierarchical patient- and physician-level determinants of these outcomes; and (3) predictors of uncontrolled BP and improved TCVR classification. METHODS: A prospective (90 days), multicenter, multilevel pharmacoepidemiologic study was conducted in 3546 patients with hypertension treated with SPC amlodipine/valsartan by 698 general practitioners. Statistical analysis included hierarchical linear and logistic modeling of BP and TCVR outcomes. RESULTS: Mean (SD) systolic BP (SBP) reductions were 20.1 (15.5) mm Hg and diastolic BP (DBP) reductions were 9.8 (10.3) mm Hg, with higher reductions among high-risk patients. SBP, DBP, and SBP/DBP control rates were 33.3%, 45.3%, and 25.5%, respectively, with lower rates among high-risk patients. Mean TCVR improvement was a reduction of 0.73 (0.96) classes (-4 [best] to +4 [worst]), with higher reductions for high-risk patients; 58.2% of patients achieved a TCVR reduction of 1 or more classes, with lower percentages for high-risk patients. Twenty-two percent of systolic variability and 26% of diastolic variability in 90-day BP values were attributable to a physician class effect, as was 16% of TCVR change. CONCLUSIONS: Regimens that include SPC amlodipine/valsartan formulations are effective in reducing BP and TCVR in a real-world observational setting. Hierarchical modeling identified patient- and physician-related determinants of BP values and TCVR change, as well as independent predictors of uncontrolled BP and reduced TCVR. TCVR is a scientifically feasible and clinically relevant effectiveness outcome of antihypertensive treatment.

Summary Aims: The ‘DRIVER’ study was designed to investigate the ‘real-world’ effectiveness of aliskiren-based treatment of hypertension. This article reports the 180-day blood pressure (BP) outcomes, and the multilevel (physician- and patient-level) determinants thereof. Methods and results: DRIVER was a prospective, observational, open-label, multi-centre, pharmaco-epidemiologic study of hypertensive patients treated with aliskiren in whom prior treatment failed or was not tolerated. 2070 patients (enrolled by 426 physicians) were enrolled; 1695 patients (81.9%) completed the 180-day aliskiren treatment period. Mean patient age was 64.2 ± 12.1 years; 53.7% were men, 25.3% diabetic and 40.7% had a high or very high cardiovascular (CV) risk. At 180 days, the mean ± SD reductions in systolic and diastolic BP were −22.9 ± 16.7 mmHg and −10.5 ± 10.9 mmHg respectively (both p

Achieving guideline-recommended blood pressure targets is difficult in older adults with hypertension. We completed a subgroup analysis of patients 65 years of age or older enrolled in PREVIEW, a prospective, multicenter, pharmacoepidemiological study of the determinants and outcomes of second-line antihypertensive treatment with valsartan in Belgium. Multilevel modeling was used to identify physician-and patient-level determinants of blood pressure values and practice guideline-derived definitions of blood pressure control. Data on 1560 patients and 504 physicians were used in this analysis. Blood pressure control rates for patients age 65 and over were lower for systolic (34.2% vs. 38.6%) and combined systolic/diastolic blood pressure (31.2% vs. 34.4%) compared to the entire PREVIEW sample. Twenty-seven percent of the variability in systolic, and 32% in diastolic pressure after 90 days of treatment were attributable to such variables as physicians' knowledge and adherence to evidence-based guidelines, practice patterns, and experience; with the remaining variance attributable to various demographic, behavioral, and clinical patient-related factors. Several independent predictors of uncontrolled blood pressure after 90 days of treatment were identified, largely confirming factors identified as determinants of blood pressure values. Recommendations for managing hypertension in the elderly are made in view of these findings. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Background Patient- and clinician-related factors may explain variability in blood pressure (BP) outcomes and the differences between real-world effectiveness and efficacy seen in randomized trials of antihypertensive agents. Objective To examine the effectiveness of 90 days of second-line valsartan treatment and identify patient- and physician-level determinants that impact BP outcomes. Methods A prospective, multicenter, multilevel pharmacoepidemiologic study was conducted in 3194 hypertensive patients (systolic BP [SBP] ≥140 mm Hg, diastolic BP [DBP] ≥90 mm Hg; for diabetic patients, ≥130 and ≥80 mm Hg, respectively) treated by 504 general practitioners (GPs). Statistical analysis included heuristic data mining, and hierarchical linear and logistic modeling. Results With valsartan treatment, mean ± SD SBP decreased from 154.4 ± 15.5 mm Hg to 139.0 ± 12.0 mm Hg and mean DBP decreased from 91.3 ± 9.2 mm Hg to 82.6 ± 7.4 mm Hg. SBP control rates increased from 9.0% to 38.6%, DBP from 25.5% to 65.5%, and combined SBP/DBP from 7.3% to 34.4%. A highly vulnerable cohort (n = 1063;35.4%) of patients was identified. Twenty-four percent of variability in SBP and 25% of variability in DBP at 90 days were attributable to physician-related variables: guideline-compliant BP management, hypertension, practice patterns, hypertensive patient volume, and years in practice. The remaining 76% and 75% of variability in SBP and DBP, respectively, were due to patient factors, notably diabetes and related complications, vulnerability to uncontrolled BP, nonadherence, cardiovascular risk, and age. Simitar factors increased the odds of treatment nonresponse, with diabetes being the single largest determinant of uncontrolled SBP (OR 8.99), DBP (OR 20.35), and combined SBP/DBP (OR = 18.64). Conclusions Valsartan is effective and well tolerated in a broad range of patients in whom first-line antihypertensive treatment failed or was not tolerated. Mitigating the impact of BP-elevating variables and optimizing the effect of BP-lowering factors provides therapeutic benefits incremental to valsartan's pharmacologic effect. Improving outcomes in hypertensive patients involves 3 steps: (1) identifying, intuitively rather than formally, patients less likely to achieve BP control; (2) targeting modifiable or manageable patient- and physician-level determinants with BP-elevating or BP-lowering effects; and (3) managing variables that increase the odds and optimizing those that lower the odds of uncontrolled BP.

Jean-Marie Rakic,1 Anita Leys,2 Heidi Brié,3 Kris Denhaerynck,4 Christy Pacheco,4 Stefaan Vancayzeele,3 Christine Hermans,3 Karen MacDonald,4 Ivo Abraham4,5 1Department of Ophthalmology, Centre Hospitalier Universitaire de Liège, Site du Sart Tilman, Liège, Belgium; 2Leuven University Eye Hospital, Leuven, Belgium; 3Novartis Pharma, Vilvoorde, Belgium; 4Matrix45, Tucson, AZ, USA; 5Center for Health Outcomes and Pharmacoeconomic Research, University of Arizona, Tucson, AZ, USA Introduction: The aim of this study was to examine ranibizumab treatment patterns in "real-world" practice and clinical settings, as well as to assess quality of life outcomes over a 24-month period. Materials and methods: This was a prospective, observational, multicenter, open-label study of 0.5 mg of ranibizumab administered intravitreally. Patients were followed over 24 ± 3 months with intermediate data points at 6 ± 2 months and 12 ± 2 months, and a limited data point at 2.5 ± 1 month that coincided with the end of the loading phase. Outcomes included visual acuity (Early Treatment Diabetic Retinopathy Study), visual function (National Eye Institute Visual Function Questionnaire-25 [NEI VFQ-25]), quality of life (Health Utilities Index Mark III [HUI3]), and safety. Results: A total of 267 patients with wet age-related macular degeneration (mean ± standard deviation [SD] age = 78.5 ± 7.3 years; 62.4% were female; 34.5% with dual eye involvement; 74.9% were treatment-naïve) were treated (309 eyes were treated). The mean ± SD Early Treatment Diabetic Retinopathy Study score at baseline was 56.3 ± 14.3 letters. The mean ± SD number of injections over 24 months was 7.6 ± 4.1, including 2.5 ± 0.7 and 5.9 ± 3.6 during the loading and maintenance phases, respectively, with corresponding treatment intervals of 4.8 ± 1.4 weeks and 11.5 ± 9.5 weeks, respectively. Improvements in visual acuity over baseline were reached at 2.5 months and maintained at 6 months (both P < 0.0001). The mean visual acuity increase over baseline at 12 months was not significant (P = 0.08); the decline over baseline at 24 months statistically significant (P = 0.02). Overall, 94.3% of patients showed stable or improved disease at 6 months and 81.5% of patients showed stable or improved disease at 24 months. At 6 months, improvements over baseline were significant for VFQ-25 (P = 0.03) and HUI3 (P = 0.02), but not at 12 months and 24 months. Improvements in VFQ-25 and HUI3 were maintained at 24 months in 38% and 34% of patients, respectively. In total 78 serious adverse events were reported in 40 patients and 77 nonserious adverse events in 34 patients. Nine serious adverse events and nine nonserious adverse events in 14 patients were suspected to be related to ranibizumab treatment. Conclusion: The "real-world" clinical effectiveness of ranibizumab was evidenced by the initial improvements over baseline in visual acuity and quality of life, as well as the maintenance of these outcomes at baseline levels at 24 months, and this was observed under variable treatment conditions. The findings underscore the need for individualized treatment with regular monitoring to achieve optimal vision and quality of life outcomes. Keywords: ranibizumab, age-related macular degeneration, neovascular macular degeneration, visual acuity, visual function, quality of life

Background Apart from clinical outcomes, the "real-world" outcomes of intermittent short-course cyclosporine treatment remain poorly documented. Objective To evaluate various outcomes of short-course cyclosporine treatment for severe psoriasis; and to describe dermatologists' use of the Rule of Tens. Methods A 12-week pharmacoepidemiological study; 112 evaluable patients recruited by 43 dermatologists. Results The mean initial cyclosporine dose was 2.88±0.74 mg/kg/day. At 12 weeks, 64.3% of patients were continued beyond the study period at mean dose of 2.51±0.91 mg/kg/day. Percent body surface affected, Psoriasis Area Severity Index score, and patient and physician rating of psoriasis severity decreased significantly, while quality of life (QoL) improved significantly. Median patient satisfaction at 12 weeks was 85 (0~100 scale). Patient-reported non-adherence was 43.9% and 56.1%, respectively at both the time points (p=0.18). In modeling on logarithmized outcomes variables, living along was consistently the single most important (negative) determinant of therapeutic and patient outcomes. Safety and tolerance parameters were similar to the ones reported in the literature. Only 7.3% of physicians correctly identified the measures included in the Rule of Tens and the Rule's criterion for inferring severe psoriasis. Conclusion With adequate monitoring and patient adherence, cyclosporine treatment reduces the severity of severe psoriasis, improves QoL, and is appropriately tolerated; leading to high patient satisfaction. Social support is a key determinant of therapeutic and patient outcomes and patients living along may require clinical attention. The relevance of the Rule of Tens was not evident.

The pharmacological efficacy of various monotherapy, single pill, and combination therapies of the angiotensin II receptor blocker valsartan have been established, mainly through randomized controlled trials that used similar methodological and statistical platforms and thus enabled synthesis of evidence. The real world effectiveness of valsartan has been studied extensively, but the relative lack of scientific and technical congruence of these studies render synthesis virtually impossible. To date, all have focused on blood pressure outcomes, despite evidence-based calls to grade antihypertensive treatment to patients' total cardiovascular risk. We review a T3 translational research program of seven studies involving valsartan monotherapy as well as single and separate pill combinations, and the determinants and effect on blood pressure and total cardiovascular risk outcomes. All seven studies examined not only the impact of valsartan-based regimens on blood pressure values and control, but also, within a statistical hierarchical approach, the physician- and patient-related determinants of these blood pressure outcomes. Two studies also investigated the determinants and outcomes of valsartan-based treatment on total cardiovascular risk - among the first studies to use this risk coefficient as an outcome rather than only a determinant. These seven studies included a total of 19,533 patients, contributed by 3434 physician-investigators in Belgium - a country particularly well-suited for observational effectiveness studies because of demographics and epidemiology. Each study used the same methodological and statistical platform. We summarize the impact of various valsartan regimens on such outcomes as blood pressure values and control, change in total cardiovascular risk, and reduction in risk by at least one category. We also review the results of statistical multilevel and logistic modeling of physician- and patient-related determinants on these outcomes, including the proportion of variance attributable to a physician class effect before patients enter the equation. In its different formulations, valsartan has major real-world benefits in lowering blood pressure and total cardiovascular risk within a 90-day period. It is essential to understand the physician- and patient-related determinants of blood pressure and total cardiovascular risk outcomes associated with valsartan treatment. Antihypertensive research should expand its historical focus on lowering blood pressure with an emphasis on lowering total cardiovascular research.

BACKGROUND. Patterns, prevalence, and associated pt variables of CML pts’ nonadherence (PNA) with ImRx are being better understood. Reducing ImRx PNA may impact on treatment outcomes. Various AESs have been proposed but their perceived value and clinical applicability to treating MDs are unknown. OBJECTIVES. 1. Describe the perceptions of ImRx prescribing MDs of the utility (in terms of FX, FB, CO) of 13 AESs. 2. Describe MD rankings of the applicability in daily practice of each AES. DESIGN AND SUBJECTS. MD data subset from prospective, 90d observational, open-label, multicenter study [1]. 51 evaluable MDs: age 45.6±11.2 years (ys); ys of practice 17.7±8.1; 74% hematologists, 26% oncologists; 65.3% practicing in university(-affiliated) hospital, 34.7% in other hospitals. MEASUREMENTS. Utility rated 0=none to 3=high. For applicability to daily practice, MDs were asked to give top 5 AESs (5=most applicable); nonranked AESs were given zero value. RESULTS. See Table 1. CONCLUSIONS. MDs tended to rate the utility and applicability of AESs higher if an AES involved active MD participation or decision-making. AESs requiring significant patient involvement, behaviorally or through assistive devices, were perceived as less helpful and applicable in clinical practice. Importantly, the critical role of patient education was recognized, thus challenging clinicians to accept greater responsibility for this AES. Nurses in particular may prove pivotal in patient education. These findings provide significant direction for interdisciplinary healthcare education, especially in terms of chronic illness management. Further research is needed to elucidate the physician-centric approach to adherence enhancement in CML pts on ImRx. Table 1 - Physician Utility Ratings and Applicability Rankings of Adherence-Enhancing Strategies Utility (0–3) Applicability FX FB CO in Practice (0–5) M±SD M±SD M±SD M±SD Rx selection per pt characteristics 1.9±1.1 1.6±1.1 1.3±1.0 1.0±1.5 Pt education 2.6±0.6 2.1±0.8 1.4±0.8 3.1±1.9 Improved pt-MD communication 2.7±0.5 2.3±0.8 1.3±0.8 2.8±1.7 Simplifying Rx regimen 2.5±0.7 2.3±0.7 1.6±0.9 2.3±1.9 Pt self-monitoring 1.7±0.8 1.5±0.8 1.1±0.9 0.4±1.1 Pt health status diary 1.7±0.8 1.5±0.8 1.0±0.8 0.5±1.3 Memory aids 1.7±0.8 1.9±0.8 1.0±0.8 0.6±1.3 Spouse/family involved 2.2±0.9 2.0±0.9 0.6±0.8 1.3±1.4 Regular MD contact 2.4±0.5 2.2±0.7 1.7±0.8 2.2±1.8 MD monitoring of PA 2.2±0.7 1.8±0.9 1.4±0.8 0.7±1.1 Electronic reminders 1.5±0.9 1.2±0.8 2.3±0.9 0.3±1.1 Electronic Rx monitoring 1.6±0.9 1.3±0.7 2.3±0.9 0.3±1.1 Rewards for good PA 1.4±1.0 1.3±0.8 1.8±0.9 0.5±1.4

BACKGROUND. ImRx for CML is a long-term treatment. Patterns and prevalence of NA to ImRx remain largely unknown. Short-term NA trends may be indicative of long-term NA. Methods for clinical NA assessment vary in reliability. A multimethod approach is indicated. OBJECTIVE. Multimethod estimation of patterns and prevalence of ImRx NA in CML pts at baseline (BL) and follow-up (FU) at 90 days (90d), incl. BL to 90d changes. DESIGN AND PATIENTS. Data subset from prospective, 90d observational, open-label, multicenter study. 169 evaluable pts on ImRx for minimum 30d at enrollment [[1][1]]. METHODS OF NA ASSESSMENT. At BL (NA with prior ImRx) and 90d (NA during study): visual analog scale (VAS) for physicians (phs; mVAS), pts (pVAS), cos (cVAS); Basel Assessment of Adherence Scale for pts (pBAAS; structured interview re NA in past 4 weeks [4wks]); pts reported persistence (pPST); % clinic appointments (%CAPPTS) kept (if any scheduled). At 90d also: % of ImRx taken per pill count (%pts@ImRx). RESULTS. See Table 1. CONCLUSIONS. Intuitive adherence ratings (VAS) by phs, pts, and cos are very high and differ from those from structured interview, where about one-third of patients exhibited NA behavior in 4wks prior to BL and FU - despite high persistence. Pill count suggests patterns of under- and overtaking, with only 1 out 7 patients being perfectly adherent. Rate of clinic appointments may be affected by physician scheduling practices and collateral input is a function of availability of collateral person. Consenting to participate in the ADAGIO study did not reduce NA. Though patient self-reports in structured interview (pBAAS) and pill counts have inherent biases, both indices suggest that NA with ImRx may be similar to NA rates in other disease categories. Especially pBAAS and pill count may be useful rapid clinical assessment tools, with pBAAS having the benefit of validated categorical assessment (vs. continuous in other methods). Determinants of NA and the impact of NA on treatment outcomes must be examined. | Method | | BL | 90d | | |:--------- | --- | --------------- | --------------------- | ----- | | | n | M±SD/Min-Max | M±SD/Min-Max | P | | mVAS | 164 | 95.0±7.6/60–100 | 94.9±9.9/0–100 | ns | | pVAS | 169 | 95.3±8.5/25–100 | 95.7±6.1/75–100 | ns | | cVAS | 56 | 97.1±5.1/80–100 | 97.4±5.1/75–100 | ns | | %pts@ImRx | 162 | - | 91.0±21.1/29.5–2002.2 | | | | | | 71.0% @ < 100% ImRx | | | | | | 14.2% @ 100% ImRx | | | | n | % NA | % NA | P | | pBAAS | 163 | 36.2% | 32.5% | ns | | %CAPPTS | 51 | 94.1% | 88.2% | 0.001 | | pPST | 163 | 98.8% | 100.0% | ns | Table 1 - Multimethod Assessment of Non-Adherence with Imatinib [1]: #ref-1

BACKGROUND. ImRx for CML is a long-term treatment potentially compromised by NA. Identifying APVs may assist in reducing NA and optimizing treatment outcomes. OBJECTIVE. To model the relationships between two NA measures and selected APVs using CCA, a multivariate analog of multiple regression to accommodate multiple criterion variables. DESIGN AND PATIENTS. Data subset from prospective, 90d observational, open-label, multicenter study. 169 evaluable pts on ImRx for minimum 30d at enrollment [1]. MEASUREMENTS. NA at 90d vector: Basel Assessment of Adherence Scale for pts (pBAAS; 0/1 with 1=NA); and % of ImRx taken per pill count (%ImRx, subtracted from 100 to reflect NA). APVs at BL vector: age; months since CML diagnosis (mCML); months since ImRx initiation (mImRx); knowledge of CML disease, treatment, and ImRx (KCMLRx); and general health (SF-8). RESULTS. The criterion (dependent) vector of NA indicators included pBAAS and %ImRX. The predictor (independent) vector of APVs included: age, mCML, mImRx, KCMLRx, and SF-8. Two canonical correlations were generated: 0.389 (Bartlett Chi-squared=23.564, P=0.009) and 0.170 (Bartlett Chi-squared= 3.590, P=0.464); the second correlation was deleted due to nonsignificance from zero. The canonical loadings (or structure coefficients) for the retained model were: age 0.951, mCML 0.205, mImRx 0.145, SF-8 0.016, and KCMLRx -0.367. Redundancy analysis showed that 22.1% of variance in the predictor set was explained by variables within that set. CONCLUSIONS. The patient NA vector (composed of a binary assessment of NA per pBAAS 0/1 with 1=NA) and continuous quantification of % of ImRx not taken was related to the APV vector as follows: NA increased as patients were older, had been diagnosed with CML for a longer period of time, had been on imatinib treatment for a longer period time, and were in slightly better health at enrollment. These may be considered warning signs for NA for clinicians to consider in practice, given the long-term nature of ImRx. Importantly, better patient knowledge of disease and treatment, a clinically modifiable APV, was associated with a decrease in NA. The initial insights in patient NA with ImRX provided by these findings, though some are counterintuitive to the NA literature at large, must be studied further to better understand the dynamics of NA in the CML population.

SummaryObjectiveTo evaluate the 16- and 52-week effectiveness of add-on omalizumab treatment under real-life heterogeneity in patients, settings, and physicians in an open-label, multicenter, pharmaco-epidemiologic study of patients with severe persistent allergic asthma in Belgium.MethodsEffectiveness outcomes included improvement in 2005 global initiative for asthma (GINA) classification, physician-rated global evaluation of treatment effectiveness (GETE), quality of life (Juniper asthma-related quality of life (AQLQ) and European quality of life questionnaire 5 dimensions (EQ-5D)), and severe asthma exacerbations. Patients studied included both intent-to-treat and per-protocol populations.ResultsThe sample (n=158) had a mean age of 48.17±17.18 years, and a slight majority were female (53.8%). Despite being treated with high-dose inhaled corticosteroids and long-acting β2-agonists, all patients experienced frequent symptoms and had exacerbations in the past year. At 16 weeks, >82% had good/excellent GETE (P values 82% had an improvement in total AQLQ scores of ≥0.5 points (P91% were severe exacerbation-free (P72% had a good/excellent GETE rating (P84% had improvements in total AQLQ score of ≥0.5 points (P56% had minimally important improvements in EQ-5D utility scores (P=0.012), and >65% were severe exacerbation-free (P

Background and aims Obesity combined with hypertension places patients at greater risk for target-organ damage and cardiovascular disease. The purpose of this secondary analysis was to identify physician- and patient-levels determinants of blood pressure (BP) values and predictors of uncontrolled BP through subgroup analysis by body mass index (BMI). Methods and results We conducted a subgroup analysis of 3006 patients with High-BMI (BMI >25 kg/m 2 ; n = 2124) and Normal-BMI (BMI 2 ; n = 882) treated by 504 physicians and enrolled in PREVIEW, a Belgian prospective, multi-center, pharmaco-epidemiological study of 90-day second-line treatment with valsartan. Physician- and patient-level determinants of BP values and BP control were identified by means of hierarchical linear and logistic regression. Blood pressure values and control after 90 days of treatment were consistently lower for the High-BMI group. The 25.5% of variance in 90-day systolic and 28.3% of the variance in 90-day diastolic BP were attributable to physician-level determinants for the High-BMI group; versus 27.3% and 29.8% for the Normal-BMI group (ICC = 0.273 and 0.298, respectively). Determinants of 90-day BP values and predictors of uncontrolled BP varied considerably by BMI status. Conclusion Several common and unique patient- and physician-level determinants of BP values and control were identified for the High-BMI and Normal-BMI groups. These findings highlight the need for differentiating healthcare interventions to account for patient and physician variables, particularly with respect to effective BP management in vulnerable populations.