Effectiveness of intravenous propafenone for conversion of recent-onset atrial fibrillation: A placebo-controlled study

To evaluate the efficacy of propafenone in converting recent-onset atrial fibrillation (AF) lasting <7 days, 182 patients were treated intravenously with propafenone (Group 1, n = 98) and with placebo 0.9% saline solution (Group 2, n = 84) in a double blind study. The treatment was continued until sinus rhythm (SR) was restored, but for no more than 24 h. Eighty-nine patients treated with propafenone (90.8%) and 27 patients treated with placebo (32.1%) responded to the treatment and SR was restored (p < 0.0005). The mean time for SR restoration was 2.51± 2.77 h in Group 1, and 17.15± 7.8 h in Group 2 (p < 0.0005). In both groups the patients in whom SR was not restored (nonresponders) had larger left atrial size and longer duration of AF than responders at the onset of the arrhythmia. Nonresponders in Group 1 showed a decrease in mean ventricular rate (MVR) from 143± 16 to 101± 18 (p < 0.0005), while in the nonresponders in Group 2 no reduction of MVR was observed. Two patients whose SR was restored with propafenone had sinus standstill lasting 3.4 and 3.8 s, respectively. Propafenone used intravenously is an effective, quick, and safe drug for treating AF. Moreover, it significantly reduces MVR in nonresponders.     

Is there a difference in phenotype between males and females with non-transfusion-dependent thalassemia? A cross-sectional evaluation

Objectives: Non-transfusion-dependent thalassemia includes a variety of phenotypes and genotypes that rarely require regular transfusions. However, these patients can experience a wide range of complications. The objective of this retrospective study was to verify whether there is a significant difference in non-transfusion-dependent thalassemia-related complications and treatment among males and females.

Methods: We performed a re-analysis of samples evaluated in a previously published cross-sectional study, regarding 96 non-transfusion-dependent thalassemia patients followed at the ‘UOSD Malattie Rare del Globulo Rosso’ Centre of the Cardarelli Hospital in Naples, Italy.

Results: We found that females were more anemic than males, but there was no significant difference in prevalence of common complications among genders, except for hypogonadism. Furthermore, the transitory regular transfusions regimen in women who had been pregnant does not seem to have a significant impact on overall prognosis.

Discussion: In non-transfusion-dependent thalassemia patients, the lower levels of hemoglobin found in females do not seem to indicate a higher prevalence of complications.

Conclusion: This data should be considered in studies with experimental treatments aiming to correct anemia in patients with non-transfusion-dependent thalassemia. It should probably also be taken into account in order to set up different transfusion regimens among genders in transfusion-dependent patients.     

Glycation of human high density lipoprotein by methylglyoxal: Effect on HDL-paraoxonase activity

Objective

Methylglyoxal (MG), a reactive carbonyl compound formed primarily from triose phosphates, appears to be involved in the molecular mechanisms of diabetes, end-stage renal disease and neurodegenerative diseases. Methylglyoxal exerts several biological activities. Among these it promotes advanced glycation end products (AGEs), which are crucial in pathogenesis of human disease. Previous studies have demonstrated that MG reacts with proteins and compositional modifications reflect loss of biological activity. The aim of the study was to investigate the effect of in vitro MG-induced glycation on human high density lipoprotein (HDL) and on the activity of the enzyme paraoxonase-1 (PON1).

Methods

HDL was incubated in the absence or in the presence of MG (0.2 mmol/L and 1.0 mmol/L) (MG-HDL) for different times (3, 6, 24 h) at 37 ° C. We evaluated apoprotein compositional changes, in both control and MG treated HDL, using intrinsic fluorescence of tryptophan and monitoring the decrease of free amino groups. Furthermore we evaluated fluorescent advanced glycation end products (Ex = 370 nm, Em = 440 nm) and the activity of HDL-paraoxonase.

Results

We demonstrated that human HDL is susceptible to glycation by MG (0.2 mmol/L and 1 mmol/L). The decrease of free amino groups and of intrinsic fluorescence of tryptophan demonstrates HDL apoprotein modifications in HDL incubated with MG. The compositional changes are associated with a significant increase in fluorescent advanced glycation end products and with a significant decrease of paraoxonase-1 enzyme activity associated with the HDL surface.

Conclusions

HDL-associated paraoxonase is responsible for the anti-inflammatory and anti-oxidative properties of HDL and detoxification against homocysteine-thiolactone. Therefore, modifications of apoprotein composition and the decrease of paraoxonase-1 activity in MG-treated HDL could affect the protective effect exerted by HDL against oxidative damage and could contribute to complications in patients affected by diseases associated with aging and oxidative stress.     

A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.     

Do mobile family planning clinics facilitate vasectomy use in Nepal?

Background

Nepal has a distinct topography that makes reproductive health and family planning services difficult to access, particularly in remote mountain and hill regions where over a quarter of modern contraceptive users rely exclusively on vasectomy.

Study design

A three-level random intercept logistic regression analysis was applied on data from the 2011 Nepal Demographic and Health Survey to investigate the extent of influence of mobile family planning clinics on the odds of a male or a female sterilization, adjusting for relevant characteristics including ecological differences and random effects. The analyses included a sample of 2014 sterilization users, considering responses from currently married women of reproductive ages.

Results

The odds of a male sterilization were significantly higher in a mobile clinic than those in a government hospital (odds ratio, 1.65; 95% confidence interval, 1.21–2.25). The effects remained unaltered and statistically significant after adjusting for sociodemographic and clustering effects. Random effects were highly significant, which suggest the extent of heterogeneity in vasectomy use at the community and district levels. The odds of vasectomy use in mobile clinics were significantly higher among couples residing in hill and mountain regions and among those with three or more sons or those with only daughters.

Conclusion

Mobile clinics significantly increase the uptake of vasectomy in hard-to-reach areas of Nepal. Reproductive health interventions should consider mobile clinics as an effective strategy to improve access to male-based modern methods and enhance gender equity in family planning.

Implications

Family planning interventions in hard-to-reach communities could consider mobile clinic as an effective strategy to promote male-based modern methods. Improving access to vasectomy could substantially reduce unmet need for family planning in countries experiencing rapid fertility transition.