Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

RCT of real versus placebo acupuncture in IVF

The efficacy of acupuncture in in vitro fertilization treatment is a very controversial issue. Four metaanalysis have been published over the last months (El-Toukhy et al., 2008; Manheimer et al., 2008; Ng et al., 2008; El-Toukhy and Khalaf, 2009) leading to opposite conclusions. Three metaanalysis conclude that there is no evidence of acupuncture efficacy (El-Toukhy et al., 2008; Manheimer et al., 2008; El-Toukhy and Khalaf, 2009), whereas another one concludes that acupuncture improves rates of pregnancy and live birth (Manheimer et al., 2008)

Meconium-stained amniotic fluid: a risk factor for postpartum hemorrhage

Carlo Bouchè,1 Uri Wiesenfeld,1 Luca Ronfani,1 Roberto Simeone,2 Paolo Bogatti,1 Kristina Skerk,1 Giuseppe Ricci1,2 1Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy Background/aim: Clinical data with respect to the impact of meconium on the risk of maternal hemorrhage are scarce. Therefore, in this study, we aimed to determine whether meconium-stained amniotic fluid (MSAF) represents a risk factor for postpartum hemorrhage (PPH) after vaginal delivery in a large unselected population. Patients and methods: A retrospective cohort study evaluated 78,542 consecutive women who had a vaginal delivery between 24th and 44th weeks of gestation. The women who had undergone cesarean section were excluded to avoid possible bias. Postpartum blood loss was measured with graduated blood sack. Postpartum blood loss between 1,000 and 2,000 mL and >2,000 mL were classified as moderate and severe PPH, respectively. Results: A total of 74,144 patients were available for analysis. According to the color of amniotic fluid (AF), two groups of patients were identified: MSAF (n=10,997) and clear AF (n=63,147). The rates of severe and massive PPH were found to be significantly higher in the MSAF group than that of clear AF group (OR=1.3, 95% CI: 1.2–1.5, p<0.001 and OR=2.5, 95% CI: 1.5–4.2, p<0.001). Operative vaginal delivery rate was found to be higher in the MSAF group than that of clear AF group, but the difference was only borderline significant (OR=1.5, 95% CI: 1.0–2.2, p=0.05). There were no significant differences between the MSAF and the clear AF groups with respect to episiotomies, second- or third-degree perineal tears, vaginal–perineal thrombus, cervical lacerations, vaginal births after cesarean section, twin deliveries, and placental retention rates. Conclusion: To the best of our knowledge, this is the first clinical study that has investigated the role of MSAF as a risk factor for PPH after vaginal delivery in an unselected population. Our results suggest that MSAF is significantly associated with higher risk of moderate and severe PPH than clear AF. Keywords: amniotic fluid, delivery complications, meconium, postpartum hemorrhag

Finasteride and Fertility: Case Report and Review of the Literature

Although millions of men have taken or are taking finasteride, there are no documented cases of successful pregnancy in the literature after discontinuation of the drug. Early studies did not show significant influence of finasteride on semen parameters, whereas some recent observations have suggested that in subfertile patients, the effects of the drug might be amplified. Therefore, counseling is particularly difficult for men taking finasteride and planning pregnancy. We report the case of a couple whose male partner had used finasteride for approximately 10 years and who presented for primary infertility. The first semen analysis, carried out 3 months after finasteride cessation, revealed severe oligospermia. One month later, sperm concentration increased, and the following month, the couple spontaneously conceived. A healthy baby was delivered at full term. To the best of our knowledge, this is the first case of successful full-term pregnancy and live birth after long-term use of finasteride, which suggests that treatment with finasteride, even after several years, does not prevent normal conception. However, caution should be advised with the use of finasteride in male partners of couples who are attempting to become pregnant

\u201cPregressa miomectomia: modalit\ue0 e management del parto\u201d

In considerazione della tendenza, indotta dai mutamenti sociali, a posporre l'et\ue0 della prima gravidanza e del fatto che il riscontro dei fibromi aumenta nella quarta decade di vita, \ue8 probabile che la prevalenza dei miomi associati ad infertilit\ue0 sia in aumento e quindi il clinico sia sempre pi\uf9 di frequente obbligato a scegliere condotta ed eventuali terapie in caso di donna gravida con pregressa miomectomia. In concreto, se \ue8 disponibile una buona documentazione dell\u2019intervento (eventualmente videoregistrazione), che attesti una sua corretta esecuzione, e/o eventualmente il parere scritto di chi ha eseguito l\u2019intervento, la paziente pu\uf2 essere assimilata a una paziente con pregresso taglio cesareo. Ogni sforzo deve esser fatto per reperire la documentazione. Il management dovr\ue0 essere ispirato alle linee guida disponibili in merito. In caso contrario, appare prudente, discussi con la donna i pro e i contro, programmare un taglio cesareo elettivo. Questo atteggiamento non \ue8 suffragato da alcuno studio clinico, ma solo dall\u2019analisi dei case reports, che dimostra come il fattore determinante nelle donne con tale complicanza non sia la sede o il numero o le dimensioni del mioma, n\ue9 l\u2019intervallo fra l\u2019intervento e la gravidanza, ma un difetto della tecnica chirurgica

Fecondazione assistita per tutte? Quando bisogna dire no!

Di fatto, l\u2019unico criterio riportato in documenti ufficiali (disposizioni di legge, linee-guida, raccomandazioni di organismi sanitari e scientifici, ecc.), che regoli l\u2019accesso alla fecondazione in vitro \ue8 rappresentato dall\u2019et\ue0, anche se come visto, la normativa italiana rimanda al singolo medico la decisione \u201cdi non procedere alla procreazione medicalmente assistita, esclusivamente per motivi di ordine medico-sanitario.\u201d (art. 6, c. 4 L. 40/2004). Tuttavia, procedere o non procedere al trattamento rappresenta una difficile decisione in cui sono in gioco interessi che confliggono. Da una parte la coppia che ha l\u2019interesse di provare tutto il possibile per avere un bambino. Dall\u2019altra il medico che ha l\u2019interesse di evitare danni ai pazienti e ai nascituri, e di evitare la frustrazione di fornire trattamenti virtualmente certi di fallimento, oltre l\u2019interesse comune, nel caso di procedure in centri del sistema sanitario pubblico, di evitare speco di risorse (spese per personale, spazi, apparecchiature, farmaci, ecc.), che potrebbero essere pi\uf9 opportunamente allocate

Fluoroquinolone-macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction.

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500\ua0mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500\ua0mg week(-1)) with ciprofloxacin at the rate of 750\ua0mg day(-1) for 4 weeks rather than at 500\ua0mg day(-1) for 6 weeks increased the eradication rates from 62.35\% to 77.32\% and the total bacteriological success from 71.76\% to 85.57\%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation

Macrolides for the treatment of chronic bacterial prostatitis: an effective application of their unique pharmacokinetic and pharmacodynamic profile (Review).

Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate characterized by poor quality of life mainly due to frequent relapse episodes caused by incomplete eradication of causative pathogens. Aggressive antibacterial therapy is required to attenuate the severe symptoms of CBP and to achieve a permanent cure. Although fluoroquinolones are currently recommended as first-choice agents, macrolide antibiotics are emerging as a noteworthy option for the treatment of CBP. Macrolide antibiotics are characterized by an impressive array of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These properties include high intracellular accumulation in phagocytes and at sites of infection, including the prostate; broad antibiotic but also biofilm-inhibiting properties; immunomodulating and inflammation-resolving activities. These features offer particular advantages for the treatment of chronic infections of the prostate gland, which are not easily amenable to drug therapy. Macrolides may be exploited to counteract the unsatisfactory rates of clinical symptom improvement and pathogen eradication. The results of a number of clinical trials support this proposal