Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL.

Efficacy of paraspinal anesthetic block in patients with chronic pelvic pain refractory to drug therapy: a randomized clinical trial

PURPOSE: To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy.METHODS: Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI).RESULTS: Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03.CONCLUSIONS:Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.

Effectiveness of an illustrated home exercise guide on promoting urinary continence during pregnancy: a pragmatic randomized clinical trial

OBJETIVO: Avaliar a efetividade de um manual de orientação de exercícios domiciliares (MOED) para o assoalho pélvico (AP) na promoção da continência urinária em gestantes primigestas.MÉTODOS: Ensaio clínico com 87 participantes, avaliadas 6 vezes durante a gestação e divididas aleatoriamente em 3 grupos: Grupo supervisionado (Gsup), que praticou exercícios com supervisão; Grupo observado (Gobs), que praticou exercícios sem supervisão, e Grupo referência (Gref), que não praticou exercícios. Incontinência urinária (IU) (desfecho primário) e força muscular perineal (FMP) (desfecho secundário) foram avaliadas por intermédio de diário de perdas urinárias e perineometria, respectivamente. Foram utilizados o teste de Kruskal-Wallis, seguido do teste post hoc de Dunn, para variáveis contínuas, e o teste do χ2 e testes Z, com correções de Bonferroni, para proporções, com nível de significância de 5%.RESULTADOS: O Gsup e o Gobs apresentaram 6,9% de gestantes incontinentes, enquanto o Gref apresentou 96,6% de incontinentes. Quanto à FMP, o Gsup e o Gobs apresentaram valores médios de contração de 10 e 8,9 cmH2O, respectivamente, enquanto o Gref apresentou valor de 4,7 cmH2O. Ambos os resultados significantes.CONCLUSÃO: A utilização de um MOED é eficaz na promoção da continência urinária e no aumento da FMP em gestantes primigestas, independentemente de supervisão permanente.

Conservative Treatment of Stress Urinary Incontinence: A Systematic Review with Meta-analysis of Randomized Controlled Trials

We performed a systematic review and meta-analysis of randomized controlled trials that studied the conservative management of stress urinary incontinence (SUI). There were 1058 results after the initial searches, from which 37 studies were eligible according to previously determined inclusion criteria. For the primary outcomes, pelvic floor muscle training (PFMT) was more efficacious than no treatment in improving incontinence-specific quality of life (QoL) scales (SMD = [1]1.24SDs; CI 95% = [1]1.77 to [1]0.71SDs). However, its effect on pad tests was imprecise. Combining biofeedback with PFMT had an uncertain effect on QoL (MD = [1]4.4 points; CI 95% = [1]16.69 to 7.89 points), but better results on the pad test, although with elevated heterogeneity (MD = 0.9g; 95%CI = 0.71 to 1,10g); group PFMT was not less efficacious than individual treatment, and home PFMT was not consistently worse than supervised PFMT. Both intravaginal and superficial electrical stimulation (IES and SES) were better than no treatment for QoL and pad test. Vaginal cones had mixed results. The association of IES with PFMT may improve the efficacy of the latter for QoL and pad test, but the results of individual studies were not consistent. Thus, there is evidence of the use of PFMT on the treatment of SUI, with and without biofeedback.

Randomized clinical trial comparing the efficacy of the vaginal use of metronidazole with a Brazilian pepper tree (Schinus) extract for the treatment of bacterial vaginosis

A 7.4% vaginal extract of the Brazilian pepper tree (Schinus terebinthifolius Raddi) was compared with 0.75% vaginal metronidazole, both manufactured by the Hebron Laboratory, for the treatment of bacterial vaginosis, used at bedtime for 7 nights. The condition was diagnosed using the combined criteria of Amsel and Nugent in two groups of 140 and 137 women, aged between 18 and 40 years. Intention-to-treat analysis was performed. Women were excluded from the study if they presented delayed menstruation, were pregnant, were using or had used any topical or systemic medication, presented any other vaginal infections, presented hymen integrity, or if they reported any history suggestive of acute pelvic inflammatory disease. According to Amsel’s criteria separately, 29 patients (21.2%) treated with the extract and 87 (62.1%) treated with metronidazole were considered to be cured (P < 0.001). According to Nugent’s score separately, 19 women (13.9%) treated with the extract and 79 (56.4%) treated with metronidazole were considered to be cured (P < 0.001). Using the two criteria together, the so-called total cure was observed in 17 women (12.4%) treated with the extract and in 79 women (56.4%) treated with metronidazole (P < 0.001). In conclusion, the cure rate for bacterial vaginosis using a vaginal gel from a pepper tree extract was lower than the rate obtained with metronidazole gel, while side effects were infrequent and non-severe in both groups.

Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial

This study evaluated whether the use of continuous positive airway pressure (CPAP) in the delivery room alters the need for mechanical ventilation and surfactant during the first 5 days of life and modifies the incidence of respiratory morbidity and mortality during the hospital stay. The study was a multicenter randomized clinical trial conducted in five public university hospitals in Brazil, from June 2008 to December 2009. Participants were 197 infants with birth weight of 1000-1500 g and without major birth defects. They were treated according to the guidelines of the American Academy of Pediatrics (APP). Infants not intubated or extubated less than 15 min after birth were randomized for two treatments, routine or CPAP, and were followed until hospital discharge. The routine (n=99) and CPAP (n=98) infants studied presented no statistically significant differences regarding birth characteristics, complications during the prenatal period, the need for mechanical ventilation during the first 5 days of life (19.2 vs 23.4%, P=0.50), use of surfactant (18.2 vs 17.3% P=0.92), or respiratory morbidity and mortality until discharge. The CPAP group required a greater number of doses of surfactant (1.5 vs 1.0, P=0.02). When CPAP was applied to the routine group, it was installed within a median time of 30 min. We found that CPAP applied less than 15 min after birth was not able to reduce the need for ventilator support and was associated with a higher number of doses of surfactant when compared to CPAP applied as clinically indicated within a median time of 30 min.

Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials

There has been concern regarding the use of controversial paradigms for repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase, CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to identify relevant studies, and randomized controlled trials (RCTs) on bilateral rTMS for TRD patients were included. The response was defined as the primary outcome, and remission was the secondary outcome. Ten RCTs that included 634 patients met the eligibility criteria. The risk ratio (RRs) of both the primary and secondary outcomes of bilateral rTMS showed non-significant increases compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22). Notably, the RR of the primary bilateral rTMS outcome was significantly increased compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis demonstrated that bilateral rTMS was significantly more effective than sham rTMS but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a useful paradigm for patients with TRD.

Contact force-guided catheter ablation for the treatment of atrial fibrillation: a meta-analysis of randomized, controlled trials

Contact force (CF) sensing technology allows real-time monitoring during catheter ablation for atrial fibrillation (AF). However, the effect of CF sensing technology on procedural parameters and clinical outcomes still needs clarification. Because of the inconsistent results thus far in this area, we performed a meta-analysis to determine whether CF sensing technology can improve procedural parameters and clinical outcomes for the treatment of AF. Studies examining the benefits of CF sensing technology were identified in English-language articles by searching the MEDLINE, Web of Science, and Cochrane Library databases (inception to May 2015). Ten randomized, controlled trials involving 1834 patients (1263 males, 571 females) were included in the meta-analysis (681 in the CF group, 1153 in the control group). Overall, the ablation time was significantly decreased by 7.34 min (95%CI=-12.21 to -2.46; P=0.003, Z test) in the CF group compared with the control group. CF sensing technology was associated with significantly improved freedom from AF after 12 months (OR=1.55, 95%CI=1.20 to 1.99; P=0.0007) and complications were significantly lower in the CF group than in the control group (OR=0.50, 95%CI=0.29 to 0.87; P=0.01). However, fluoroscopy time analysis showed no significantly decreased trend associated with CF-guided catheter ablation (weighted mean difference: -2.59; 95%CI=-9.06 to 3.88; P=0.43). The present meta-analysis shows improvement in ablation time and freedom from AF after 12 months in AF patients treated with CF-guided catheter ablation. However, CF-guided catheter ablation does not decrease fluoroscopy time.

Comparison of totally tubeless percutaneous nephrolithotomy and standard percutaneous nephrolithotomy for kidney stones: a randomized, clinical trial

This study aimed to compare the totally tubeless percutaneous nephrolithotomy and standard percutaneous nephrolithotomy techniques regarding their rates of success and complications in patients with kidney stones. Patients were randomly assigned to two groups. Forty-four patients (24 men; mean age: 50.40±2.02 years) received totally tubeless percutaneous nephrolithotomy (PCNL; no nephrostomy catheter or ureteral catheter after PCNL) and 40 patients (18 men; mean age: 49.95±13.38 years) underwent standard PCNL (a nephrostomy catheter and ureteral catheter were used after PCNL). All surgeries were performed by one surgeon. Postoperative changes in hemoglobin, the blood transfusion rate, changes in creatinine levels, operation time, analgesic need, hospitalization time, and complication rate were compared between the groups. No significant differences were observed in age, gender, stone size, and surgery side between the groups (P<0.05). The operation time was significantly lower in the totally tubeless PCNL group than in the standard PCNL group (P=0.005). Pethidine requirements were significantly higher in the standard PCNL group than the totally tubeless PCNL group (P=0.007). Hospitalization time was significantly higher in the standard PCNL group than in the totally tubeless PCNL group (P<0.0001). The complication rate was 15% in the standard PCNL group and 9.1% in the totally tubeless PCNL group (P=0.73). The totally tubeless PCNL technique is safe and effective, even for patients with staghorn stones. This technique is associated with decreased pain, analgesic needs, and operative and hospitalization time. We believe that a normal peristaltic ureter is the best drainage tube.