Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: a three-way crossover study

BACKGROUND: Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. OBJECTIVE: The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. METHODS: Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. RESULTS: The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P<0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P<0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P<0.001) and DBP (-18.6 [4] mm Hg; P<0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P<0.001) and PSTP (36.6%; P<0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P<0.05) and PSTP (10.4%; P<0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. CONCLUSION: In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.     

A retrospective study on oral anticoagulant prophylaxis in 103 Italian patients with hereditary thrombophilia and thrombosis

Summary The clinical records of 103 Italian patients with inherited thrombophilia and thrombosis were reviewed to estimate the incidence of thrombotic recurrences and major bleeding complications according to the different duration of oral anticoagulant prophylaxis (OAP). The incidence of the first thrombotic recurrence was 2.9, 7.4 and 10.8×100 patients/year, respectively, in subjects receiving lifelong OAP, stopping OAP after a mean of 9 months (range 1–30 months) or not receiving OAP. The probability to remain free from thrombotic recurrences in patients undergoing lifelong OAP, as estimated by the Kaplan-Meier method, was significantly higher in comparison with untreated patients (p<0.001), but did not reach the statistical significance in comparison with patients who stopped prophylaxis. The incidence of further thrombotic recurrences was 1.2, 21.1 and 22.3×100 patients/year, respectively, in the three groups defined above. The difference between patients who prolonged indefinitely OAPvs those who stopped or did not receive OAP was statistically significant (p=0.003). Two intracranial bleedings, one of which fatal, were observed in patients undergoing lifelong OAP, whereas no major bleeding complications occurred in the other two groups. Our study supports the recommendations to continue indefinitely OAP in patients with inherited thrombophilia and recurrent thrombosis, but suggests caution in starting lifelong prophylaxis soon after the first thrombotic event in all patients. Members of the Study Group: F. Baudo (Milano); M. Berrettini (Perugia); G. Castaman (Vicenza); N. Ciavarella (Bari); S. Coccheri (Bologna); V. De Stefano (Roma); A. G. Dettori (Parma); N. Erba (Merate); G. Leone (Roma); P. M. Mannucci (Milano); C. Manotti (Parma); M. G. Mazzucconi (Roma); G. Palareti (Bologna); F. Panicucci (Pisa); E. Pogliani (Monza); F. Rodeghiero (Vicenza); A. Tripodi (Milano).     

Age Cohort Differences in the Nonmedical Use of Prescription Zolpidem: Findings from a Nationally Representative Sample

Background

Recent warnings from the FDA have highlighted the potential risks associated with zolpidem use. These risks may be especially acute in nonmedical users of zolpidem, but little work has examined the characteristics of such nonmedical users. This study aims to investigate the correlates of nonmedical use of zolpidem (NUPZ) across the lifespan and potential age cohort-based differences in NUPZ correlates.

Methods

Data from the 2009–2011 versions of the National Survey on Drug Use and Health were used (n = 174,667). Analyses used weighted design-based logistic regressions to examine a set of substance use and mental health correlates within five separate age cohorts and differences in correlate magnitude between these cohorts.

Results

Most examined substance use and mental health variables were significant correlates of NUPZ, though odds ratio (OR) magnitude tended to drop with increasing age. Age-based differences were most apparent for substance use correlates of both lifetime and past year NUPZ, with significantly higher ORs in adolescent nonmedical users. Mental health variables operated more consistently across age, with OR magnitudes that were generally in the same range, regardless of age cohort.

Conclusions

Age-based differences in NUPZ correlates suggest motives may change for NUPZ through the lifespan, though this cannot be established with the cross-sectional data used in this work. Clinicians screening for NUPZ should emphasize such screening in high-risk individuals with substance use and/or mental health problems.     

Healing of Post-Extraction Sockets Filled with Anorganic Bovine Bone and Covered with a Xenogeneic Collagen Matrix. Radiological 2D and 3D Results of a Pilot Study to Assess Dimensional Stability

Analysis of short-term results regarding dimensional stability of post-extraction sockets managed via a preservation protocol using deproteinized bovine bone matrix and a xenogeneic collagen matrix. Materials and methods Fifteen patients needing extraction of one single-rooted premolar tooth were treated in a pilot study. Five patients were treated in each centre. After tooth extraction, sockets were filled with anorganic bovine bone matrix and covered with a xenogeneic collagen matrix. Six months later, implants were placed. Dimensional changes in the treated sites were digitally evaluated using the best-fit superimposition of pre-and post-socket preservation models. Results After six months of healing, the vertical reduction of the grafted sites was 0.31 ± 0.24 mm (p < 0.001). Volumetric analysis of superimposed models showed an average palatal-lingual contraction of 0.33 ± 0.51 mm³ (p = 0.02). At the vestibular level, the average contraction was found to be 0.8 ± 0.3 mm³ (p < 0.001). Finally, the analysis of linear variations in the treated sites on a single sagittal section at the crystal level, and at 3 and 7 mm apically respect to the crest, both towards the vestibule and palate, generally showed more marked resorption at the crestal level compared to apical measurements. Conclusion: The clinical protocol herein employed for socket preservation showed a positive effect in preventing the physiological post-extraction remodeling.     

Cerebral vein thrombosis in patients with Philadelphia‐negative myeloproliferative neoplasms An European Leukemia Net study

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN‐CVT) to 87 with MPN and other venous thrombosis (group MPN‐VT) and 178 with MPN and no thrombosis (group MPN‐NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN‐CVT and MPN‐VT than in MPN‐NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN‐VT, MPN‐CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow‐up period (6.1 vs. 10.3 years, P = 0.019), a higher long‐term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN‐CVT than in MPN‐VT group (8.8% and 4.2% patient‐years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05–3.72 and 2.09, 1.09–4.00, respectively). Am. J. Hematol. 89:E200–E205, 2014. © 2014 Wiley Periodicals, Inc.     

Masked polycythemia Vera (mPV): Results of an international study

We examined the baseline features and clinical outcomes of 140 patients presenting with JAK2V617F positivity and a bone marrow morphology conforming with WHO criteria of polycythemia vera (PV), but a hemoglobin level of <18.5 g/dL in males (range 16.0–18.4) and <16.5 g/dL in females (range 15.0–16.4). This cohort operationally referred to as masked PV (mPV) was compared with 257 patients with overt PV and displayed male predominance, a more frequent history of arterial thrombosis and thrombocytosis. Incidence of thrombosis was similar between the two groups but mPV displayed significantly higher rates of progression to myelofibrosis and acute leukemia and inferior survival. In multivariable analysis mPV diagnosis was an independent predictor of poor survival along with age >65 years and leukocyte count >10 × 10⁹/L. Our data suggest that mPV is a heterogeneous myeloproliferative neoplasia and not necessarily an early/ pre‐polycythemic form of classical PV that at onset in a small fraction of patients clinically may mimic essential thrombocythemia. On the other hand, the majority mPV may have a longer prodrome of undiagnosed PV or a disease biology akin to primary myelofibrosis‐post PV myelofibrosis that could explain the worsening of outcome in comparison to overt/classical manifestations. Am. J. Hematol. 89:52–54, 2014. © 2013 Wiley Periodicals, Inc.