Long-term patency of multiple lymphatic-venous anastomoses in cancer-related lymphedema: A single center observational study.

OBJECTIVES: Lymphedema is always initially treated by combined decongestive physiotherapy (CDP). Those cases, refractory to CDP, may be managed by surgical therapy. One of the most used microsurgical procedures is represented by the technique of lymphatic-venous anastomosis (LVA). But very few papers report long term results of LVA. The aim of this study is to assess the long-term patency of multiple lymphatic-venous anastomosis (MLVA) for the treatment of secondary lymphedemas. METHODS: From January 2014 to December 2014, 101 patients (mean age: 56.94 ± 8.98 years; female/male: 86/15) affected by secondary cancer-related lymphedema (38 lower and 63 upper limbs) were treated by MLVA. All lymphedemas had previously been treated by conservative therapy without sustained results. Many patients (78%) had 1-3 episodes of acute lymphangitis/year. Lymphoscintigraphy, venous duplex-ultrasonography, and abdominal or axillary ultrasound investigation were performed preoperatively. MLVA patency was assessed by the lymphatic transport index (LyTI) and lymphoscintigraphic pattern. RESULTS: At 1 year after surgery, excess volume reduction was 75%-90% in the early stage II secondary lymphedemas, and 60%-75% in the late stage II. The decrease in volume maintained stability in the 5-years follow-up period. Two more advanced lower and one upper limb lymphedemas had 45%-60% reduction. LyTI showed a significant decrease between the preoperative mean value (31.7 ± 9.43) and after 18 months from surgery (11.2 ± 1.91) (p < .001). MLVA patency was shown in 98 (97%) patients. No patients had evidence of postoperative lymphangitis. CONCLUSIONS: This study demonstrated the long-term patency of MLVA in the treatment of cancer-related lymphedemas.

In-111 octreotide SPECT/CT in the early diagnosis of pulmonary sarcoidosis: A case report.

Sarcoidosis is a granulomatous disease of unknown etiology. At present the best diagnostic imaging procedure to assess stage and activity of sarcoidosis is controversial. We report the case of a 50-year-old male admitted with a history of dyspnea and fatigue with past medical history negative for smoking, occupational and environmental risk factors. Physical examination, routine blood tests, and pulmonary function tests were normal except for hypercalciuria. A chest radiograph showed bilateral hilar lymphadenopathy. Single photon emission computed tomography and/or computed tomography (SPECT and/or CT) In-111 Octreotide (Octreoscan) scintigraphy confirmed morphologic involvement of bilateral hilar lymph nodes and a mediastinoscopy biopsy specimen provided diagnosis of pulmonary sarcoidosis (stage 0). This clinical case shows the effectiveness of In-111 Octreotide SPECT and/or CT in the early diagnosis of pulmonary sarcoidosis.

Lymphoscintigraphy for the evaluation of limb lymphatic flow disorders: Report of technical procedural standards from an Italian Nuclear Medicine expert panel. / Linfogammagrafía para la evaluación de trastornos del flujo linfático de las extremidades: informe de estándares de procedimientos técnicos de un panel de expertos de medicina nuclear italiano.

Lymphoscintigraphy represents the "gold standard" for diagnosis of lymphedema, but an important limitation is the lack of procedural standardization. The aim of this Italian expert panel was to provide a procedural standard for lymphoscintigraphy in the evaluation of lymphatic system disorders. Topic anaesthetic gels containing lidocaine should be avoided. Patients should remove compressive dressings. Total recommended activity for 99mTc-nanocolloid administration in adults is 74MBq, or 37MBq per limb and per investigated compartment, in single or multiple aliquots. 2-3 subcutaneous injections should be performed (II-III±I interdigital space of each hand/foot), avoiding intravascular injection. Deep lymphatic system of lower limbs should be evaluated in presence of dermal back-flow or lymphatic stasis (1-2 subfascial administrations in retro-malleolar or plantar region). Planar images should be acquired from injection site to liver with whole-body or serial static acquisitions 20' and 90' after subcutaneous administration. Additional information on lymphatic pathways is obtained after a quick and/or prolonged exercise protocol. SPECT/CT is recommended to study the thoracic, abdominal and pelvic territories. When required, deep lymphatic system of lower limbs should be evaluated with static acquisition 90' after subfascial administration. The report should describe administration and imaging procedure, exercise protocol, qualitative and semi-quantitative analysis (wash-out rate, transport index), potential sources of error. Due to the essential role fulfilled by lymphoscintigraphy in clinical management of primary and secondary lymphedema, an effort for the standardization of this technique should be made to provide the clinicians with a homogeneous and reliable technical methodology.

Rationale for Study of the Deep Subfascial Lymphatic Vessels During Lymphoscintigraphy for the Diagnosis of Peripheral Lymphedema.

PURPOSE: The current study aimed to determine the utility of including the study of deep subfascial lymphatic vessels in a 2-compartment lymphoscintigraphy for the diagnosis of lymphedema in patients with limb swelling. Lymphoscintigraphy is a valuable imaging tool for the timely diagnosis of peripheral lymphedema. However, there is a lack of standardization in its application, especially regarding which type of lymphatic vessels to examine (superficial, deep, or both). METHODS: Two hundred fifty-eight patients with lymphedema underwent segmental lymphoscintigraphy. The transport index (TI) was calculated to categorize the flow of the superficial and deep vessels as normal (<10) or pathological (≥10). The scores from 248 patients (48 unilateral arm, 86 unilateral leg, 114 bilateral leg) were tested with a 3-way analysis of variance to examine the relationship between affected limb, deep or superficial pathways, and primary or secondary lymphedema. The relationship between clinical presentation and TI was also investigated. RESULTS: In general, primary and secondary lymphedema patients had similar patterns of lymphoscintigraphic lymphatic abnormalities. Patients with unilateral clinical presentation can have bilateral TI abnormalities. The vast majority of patients (88%-98%) had either the deep subfascial vessels alone, or both the superficial and deep vessels, with a pathological TI. CONCLUSIONS: A 2-compartment lymphoscintigraphy is able to accurately detect lymphatic flow abnormalities in patients with limb swelling. Given that the vast majority of patients had deep lymphatic vessels abnormalities, inclusion of these vessels in the lymphoscintigraphic diagnostic protocol is recommended.

Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring.

RATIONALE: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. METHODS: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99mTc. The baseline SB counting rate (CR) was assessed using a γ-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99mTc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. RESULTS: RLF averaged 2.3 ± 1.5%, while the systemic/circuit TNF-α ratio was 0.05 ± 0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88 ± 0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6 ± 3.5 ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02 ± 0.005 ng/ml (p < 0.01). CONCLUSIONS: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema.

BACKGROUND: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema. METHODS: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein. RESULTS: The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer. CONCLUSIONS: The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs.

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses.

DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.

Safety and immunogenicity of a recombinant hepatitis B vaccine manufactured by a modified process in renal pre-dialysis and dialysis patients.

BACKGROUND: Patients with renal insufficiency are hyporesponsive to vaccination, including to hepatitis B vaccines. A manufacturing process modification for a hepatitis B vaccine (mpHBV) was studied in renal pre-dialysis and dialysis patients. METHODS: This randomized, open-label, multicenter, estimation study enrolled previously unvaccinated, HBV-seronegative adult dialysis and pre-dialysis patients (N=276, median age 72.0 years). At 0, 1, 6, and 8 months, group 1 received a 1 mL intramuscular dose of mpHBV (containing 40 µg HBsAg) as a single injection, while group 2 received a 1 mL intramuscular dose of a licensed hepatitis B vaccine as two injections (each containing 20 µg HBsAg; 40 µg HBsAg total). Serum antibody to HBsAg (anti-HBs) was measured predose 1, and 1 month postdose 3 and 4. Anti-HBs geometric mean concentration (GMC) and seroprotection rate (SPR, % of subjects with anti-HBs titer ≥10 mIU/mL) were estimated at months 7 and 9. RESULTS: For group 1, month 7 SPR was 48.5% (49/101, 95% CI: 38.4%, 58.7%); with an additional dose, month 9 SPR increased to 66.7% (66/99, 95% CI: 56.5%, 75.8%). For group 2, month 7 SPR was 57.7% (64/111, 95% CI: 47.9%, 67.0%); with an additional dose, month 9 SPR increased to 69.2% (72/104, 95% CI: 59.4%, 77.9%). group 1 GMCs at months 7 and 9 were 27.5 mIU/mL (95% CI: 15.7, 48.0) and 61.7 mIU/mL (95% CI: 34.2, 111.5), respectively. group 2 GMCs at months 7 and 9 were 48.7 mIU/mL (95% CI: 28.7, 82.7) and 115.8 mIU/mL (95% CI: 65.2, 205.5), respectively. There were 22 serious adverse events; none were considered related to study vaccine. CONCLUSIONS: Both formulations were immunogenic in this population but required more vaccinations to reach seroprotective levels than comparable regimens in healthy individuals, as expected. The relatively reduced SPRs seen in this population support the need for routine screening and re-dosing in this population.

Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results.

OBJECTIVES: DISTINCT (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) aimed to determine the dose-response and tolerability of nifedipine GITS and/or candesartan cilexetil therapy in participants with hypertension. METHODS: In this 8-week, multinational, multicentre, randomized, double-blind, placebo-controlled study, adults with mean seated DBP of at least 95 to less than 110 mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60 mg and candesartan cilexetil (C) 4, 8, 16 or 32 mg, or placebo. The primary endpoint, change in DBP from baseline to Week 8, was analysed using the response surface model (RSM); this analysis was repeated for mean seated SBP. RESULTS: Overall, 1381 participants (mean baseline SBP/DBP: 156.5/99.6 mmHg) were randomized. Both N and C contributed independently to SBP/DBP reductions [P < 0.0001 (RSM)]. A positive dose-response was observed, with all combinations providing statistically better blood pressure (BP) reductions from baseline versus respective monotherapies (P < 0.05) and N60C32 achieving the greatest reduction [-23.8/-16.5 mmHg; P < 0.01 versus placebo (-5.3/-6.7 mmHg) and component monotherapies]. Even very low-dose (N20 and C4) therapy provided significant BP-lowering, and combination therapy was similarly effective in different racial groups. N/C combination demonstrated a lower incidence of vasodilatory adverse events than N monotherapy (18.3 versus 23.6%), including headache (5.5 versus 11.0%; P = 0.003, chi-square test) and peripheral oedema over time (3.6 versus 5.8%; n.s.). CONCLUSION: N/C combination was effective in participants with hypertension and showed an improved side effect profile compared with N monotherapy.

The role of sentinel lymph node biopsy in patients with local recurrence or in-transit metastasis of melanoma.

From January 2003 to March 2010, a prospective study was undertaken at the National Cancer Research Institute of Genoa in 15 patients with melanoma who had local recurrence (LR) or a few (≤ 3) in-transit metastases and clinically-negative regional lymph nodes with the aim of defining: i) the feasibility of sentinel node re-staging (r-sN) of the regional nodal basin; ii) the prognostic value of sentinel node status, and iii) the potential benefit in terms of disease-free survival and overall survival in patients with an histologically-positive sentinel node undergoing therapeutic regional lymph node dissection. Preoperative lymphoscintigraphy was performed to identify the r-sN: the radiotracer was intra-dermally injected around the LR or in-transit metastasis. Moreover, 10 min prior to the operative procedure, 0.5 ml intradermal injection of Patent-Blue-V dye was given around each LR or in-transit metastasis site, so that r-sN identification was achieved by both visualization of the nodal blue dye staining and the information supplied by gamma-detection probe. At least one sentinel node was intra-operatively identified in each patient, and a tumor-positive r-sN was required in four out of fifteen patients. The interval between the diagnosis of primary melanoma and the onset of recurrence was longer, although not significantly, in patients with tumor-negative r-sN, a compared to tumor-positive r-sN (49 ± 47 months vs. 25 ± 19 months, p=0.342). There was a trend toward an improved 1-, 3-, and 5-year disease-free survival and overall survival in patients with tumor-negative r-sN a compared to tumor-positive r-sN. Hence, the r-sN proved to be a feasible and accurate staging procedure even in patients with a few localizations of LR or in-transit metastases (≤ 3). r-sN identified those with a more favorable prognosis, supporting an aggressive therapeutic approach in the natural history of their disease; moreover, an unnecessary regional lymph node dissection was safely avoided in 11 out of 15 73.3% patients because they had a tumor-negative r-sN.

Phosphate levels in patients treated with low-flux haemodialysis, pre-dilution haemofiltration and haemodiafiltration: post hoc analysis of a multicentre, randomized and controlled trial.

BACKGROUND: Whether convective therapies allow better control of serum phosphate (P) is still undefined, and no data are available concerning on-line haemofiltration (HF). The objectives of the study are to evaluate the effect of convective treatments (CTs) on P levels in comparison with low-flux haemodialysis (HD) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial. METHODS: This analysis was performed in the database of a multicentre, open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: on-line pre-dilution HF (36 patients) or on-line pre-dilution haemodiafiltration (40 patients). RESULTS: CTs did not affect P (P = 0.526), calcium (Ca) (P = 0.849) and parathyroid hormone levels (P = 0.622). P levels were associated with the use of phosphate binders including aluminium-based phosphate binders (P < 0.001) and sevelamer (P < 0.001), pre-dialysis bicarbonate levels (P < 0.001) and pre-dialysis blood K levels (P < 0.001). On multivariate analysis (generalized linear model), serum P was again largely unassociated with CTs (P = 0.631). Notably, participating centres were by far the strongest independent correlate of serum P, explaining 45.3% of the variance of serum P over the trial and this association was confirmed at multivariate analysis. Bicarbonate (P < 0.001) and, to a weaker extent, serum K (P = 0.032) were independently related to serum P. CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly affect serum P levels. Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders, serum bicarbonate and, to a weak extent, serum potassium levels (ClinicalTrials.gov Identifier: NCT011583309).

Efficacy and safety of once-monthly continuous erythropoietin receptor activator in patients with chronic renal anemia.

BACKGROUND: In the management of anemia in patients with chronic kidney disease stage 5 undergoing dialysis (CKD-5D), maintaining hemoglobin (Hb) within the range recommended by the guidelines is challenging. METHODS: The CARISMA study aim was to evaluate the efficacy, safety and tolerability of a once-monthly continuous erythropoietin receptor activator (CERA) for the treatment of anemia in CKD-5D patients. In this single-arm, multicenter, open-label, phase IIIb study, we screened adult patients from 66 centers in Italy receiving intravenous epoetin alfa or beta or darbepoetin alfa. Eligible patients entered the CERA dose titration phase (DTP), followed by an efficacy evaluation period (EEP) and a long-term safety period (LTSP). Patients were analyzed by intention-to-treat (ITT), per protocol (PP) and safety populations. RESULTS: The rate of patients maintaining Hb within the range 10.0-12.0 g/dL throughout the EEP was 63.22% (220/348), and concentration from baseline to any postbaseline time point. CERA may thus offer a convenient and effective treatment 73.94% (122/165) in the ITT and PP population, respectively, periods in both populations. The rate of patients requiring a dose change was higher during the DTP (69.2%) and the LTSP (73.0%) than during the EEP (54.5%), as expected. CERA treatment was generally well tolerated. CONCLUSIONS: Once-monthly CERA administered to CKD-5D patients was associated with negligible changes in mean Hb option for these patients.

Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.

Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of ß2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits ß2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.

Lymphatic microsurgery to treat lymphedema: techniques and indications for better results.

This study aimed to report new clinical approaches to the treatment of lymphatic disorders by microsurgical techniques based on histological and immunohistochemical findings. The authors' wide clinical experience in the treatment of patients with peripheral lymphedema by microsurgical techniques is reported. Microsurgical methods included derivative lymphatic-venous anastomoses and lymphatic reconstruction by interpositioned vein grafted shunts. In all patients, lymphatic and lymph nodal tissues were sent for histological assessment, together with specimen of the interstitial matrix. Diagnostic investigations consisted in venous duplex scan and lymphoscintigraphy. Results were assessed clinically by volumetry performed preoperatively and postoperatively at 3 to 6 months and at 1, 3, and 5 years. The outcome obtained in treating lymphedemas at different stages was analyzed for volume reduction, stability of results with time, reduction of dermatolymphangioadenitis attacks, necessity of wearing elastic supports, and use of conservative measures postoperatively. Microsurgical lymphatic derivative and reconstructive techniques allow bringing about positive results in the treatment of peripheral lymphedema, above all in early stages when tissular changes are slight and allow almost a complete restore of lymphatic drainage.

Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer.

OBJECTIVE: Lower limb lymphedema (LLL) is the most disabling adverse effect of surgical treatment of vulvar cancer. This study describes the use of microsurgical lymphatic venous anastomosis (LVA) to prevent LLL in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND). METHODS: The study included 8 patients with invasive carcinoma of the vulva who underwent unilateral or bilateral ILND. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). An historical control group of 7 patients, which underwent ILND without LVA, was used as comparison. After 1 month from the surgery, all patients underwent a lymphoscintigraphy. RESULTS: In the study group, 4 patients underwent bilateral ILND, and 4 patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean (SD) time required to perform a monolateral LVA was 23.1 (3.6) minutes (range, 17-32 minutes). The mean (SD) follow-up was 16.7 (6.2) months; there was only 1 case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed a total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (P = 0.092). CONCLUSIONS: This study shows for the first time the feasibility of LVA in patients with vulvar cancer undergoing ILND. Future studies including larger series of patients should clarify whether this microsurgical technique reduces the incidence of LLL after ILND.

Time savings associated with C.E.R.A. once monthly: a time-and-motion study in hemodialysis centers in five European countries.

OBJECTIVE: This time-and-motion study aimed to quantify healthcare personnel time associated with routine anemia-management tasks for maintenance therapy with C.E.R.A. (continuous erythropoietin receptor activator) that treats anemia with once-monthly injections versus other erythropoiesis-stimulating agents ('Other ESAs'), including shorter-acting ESAs (epoetin alfa, epeotin beta) and darbepoetin alfa. METHODS AND DESIGN: This was a non-interventional, observational study where patients were treated for anemia according to individual center practices. Time taken to complete frequent anemia-management tasks for both groups (C.E.R.A. vs. 'Other ESAs') was recorded and potential annual time savings per patient and per center following assumed 100% uptake of C.E.R.A. once monthly were estimated. RESULTS: For 'Other ESAs', the average total time spent per patient per year on frequent anemia management-related tasks ranged from 48 minutes in Spain to 265 minutes in Poland. For C.E.R.A. once monthly, the average total time spent per patient per year ranged from 12 minutes in Spain to 39 minutes in Poland, a reduction in actual time spent of 76-89% versus 'Other ESAs'. 100% adoption of C.E.R.A. once monthly may result in average annual time savings of 26-553 hours, a reduction of 67-95% depending on center size and frequency distribution of 'Other ESAs'. LIMITATIONS: Due to variability in treatment practices between centers (differences in task, description and frequency distribution of 'Other ESAs') and the small numbers of centers participating in each country, it is difficult to generalize annual per patient time results to reflect each country. Per center results should be interpreted with caution as they were derived based on specific center sizes that may not reflect typical center sizes in the country. CONCLUSIONS: Adoption of C.E.R.A. once monthly could offer substantial time savings on frequent anemia management-related tasks versus 'Other ESAs'; allowing re-allocation of scarce resources to other aspects of patient care.

Blood pressure control and treatment adherence in hypertensive patients with metabolic syndrome: protocol of a randomized controlled study based on home blood pressure telemonitoring vs. conventional management and assessment of psychological determinants of adherence (TELEBPMET Study).

BACKGROUND: Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient's therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. METHODS/DESIGN: The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension--both in the office and in ambulatory conditions over 24 h--and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n = 84) or HBPT (n = 168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets (< 135/85 mmHg) 24 weeks and 48 weeks after randomization. In addition, the study will assess the psychological determinants of adherence and persistence to drug therapy, through specific psychological tests administered during the course of the study. Other secondary study endpoints will be related to the impact of HBPT on additional clinical and economic outcomes (number of additional medical visits, direct costs of patient management, number of antihypertensive drugs prescribed, level of cardiovascular risk, degree of target organ damage and rate of cardiovascular events, regression of the metabolic syndrome). DISCUSSION: The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT01541566.

An observational, prospective, open-label, multicentre evaluation of aliskiren in treated, uncontrolled patients: a real-life, long-term, follow-up, clinical practice in Italy.

INTRODUCTION: The addition of the direct renin inhibitor aliskiren is demonstrated to improve blood pressure (BP) control rate and reduce progression of organ damage in treated hypertensive patients in clinical trials with a relatively short follow-up period. AIM: The objective of this study was to assess the effectiveness, safety and tolerability of aliskiren as an add-on antihypertensive therapy in high-risk, treated, hypertensive patients, who were not controlled with concomitant treatment with at least two antihypertensive drugs under 'real-life' conditions, during a planned observation and treatment period of at least 12 months in Italy. METHODS: Clinical data were derived from medical databases of treated, uncontrolled, hypertensive patients followed by specialized physicians operating in different clinical settings (hospital divisions or outpatient clinics) in Italy. Aliskiren was added to stable antihypertensive treatment, including at least two drug classes (independently of class or dosage) and unable to achieve BP control. Follow-up visits for measuring clinic BP levels and collecting data on drug safety and tolerability were planned at time intervals of 1, 6 and 12 months. At each predefined follow-up visit, aliskiren could be up-titrated from 150 to 300 mg daily if BP control was not achieved. RESULTS: From May 2009 to June 2011, a total of 1186 treated, uncontrolled, hypertensive patients (46.3% female, aged 65.2 ± 11.7 years, mean duration of hypertension 13.2 ± 9.3 years, mean clinic BP levels 156.5 ± 15.9/90.3 ± 9.5 mmHg) were enrolled. Systolic and diastolic BP levels were 141.1/82.4, 134.9/79.8 and 133.6/78.9 mmHg at 1-, 6- and 12-month follow-up visits, respectively (p < 0.0001 vs baseline for all comparisons). These effects were consistent in all predefined subgroups, including those with left ventricular hypertrophy, renal disease, diabetes mellitus, coronary artery disease or cerebrovascular disease. Reduced levels of microalbuminuria were also reported, without affecting other renal and electrolyte parameters. Overall, compliance to study medication was high (93.0%), with a very low proportion of patients experiencing adverse events leading to drug discontinuation (3.6%). CONCLUSIONS: In this observational, prospective, open-label, multicentre study, we reported the 12-month clinical effectiveness, safety and tolerability of adding aliskiren to treated, uncontrolled, hypertensive patients in a 'real-life' setting in Italy. This strategy leads to a significantly improved BP control rate and low incidence of drug-related side effects or discontinuations.

Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial.

BACKGROUND: Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes. METHODS: Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients). RESULTS: CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta(2) 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta(2) 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170). CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.