Assessment of chloroquine single dose treatment of malaria due to Plasmodium vivax in Brazilian Amazon

Malaria regions of the Amazon basin have been characterized by difficult access and non-compliance of the patients to treatment. In an attempt to assess the schizonticide efficacy of chloroquine in a single dose of 600 mg, the authors realized a double-blind, placebo-controlled trial in 132 outpatients with vivax malaria. Patients were distributed into two groups: group CPLA, given chloroquine 600 mg (single dose) on the first day of treatment, and two doses of placebo on second and third days. Group CHLO, given chloroquine 600 mg on first day and 450 mg on second and third day. Geometric means of the parasite density during the follow-up was similar in both groups. No differences were observed in the parasitological cure between the two groups (p = 0.442). There was clinical and parasitological efficacy in treatment of patients given a single-dose of chloroquine. This suggests that its restricted use could be indicated in remote areas of Brazilian Amazon Region, nevertheless the inadequate response of three patients indicates the need for further studies.

Physical therapy with drug treatment in bell palsy: a focused review

ABSTRACT: The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

Effects of self-administered exercises based on Tuina techniques on musculoskeletal disorders of professional orchestra musicians: a randomized controlled trial

Background Musicians are frequently affected by playing-related musculoskeletal disorders (PRMD). Common solutions used by Western medicine to treat musculoskeletal pain include rehabilitation programs and drugs, but their results are sometimes disappointing. Objective To study the effects of self-administered exercises based on Tuina techniques on the pain intensity caused by PRMD of professional orchestra musicians, using numeric visual scale (NVS). Design, setting, participants and interventions We performed a prospective, controlled, single-blinded, randomized study with musicians suffering from PRMD. Participating musicians were randomly distributed into the experimental (n = 39) and the control (n = 30) groups. After an individual diagnostic assessment, specific Tuina self-administered exercises were developed and taught to the participants. Musicians were instructed to repeat the exercises every day for 3 weeks. Main outcome measures Pain intensity was measured by NVS before the intervention and after 1, 3, 5, 10, 15 and 20 d of treatment. The procedure was the same for the control group, however the Tuina exercises were executed in points away from the commonly-used acupuncture points. Results In the treatment group, but not the control group, pain intensity was significantly reduced on days 1, 3, 5, 10, 15 and 20. Conclusion The results obtained are consistent with the hypothesis that self-administered exercises based on Tuina techniques could help professional musicians controlling the pain caused by PRMD. Although our results are very promising, further studies are needed employing a larger sample size and double blinding designs.

Ring enhancing intracranial lesion responding to antituberculous treatment in an HIV-infected patient

Cerebral tuberculomas constitute a major differential diagnosis of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected patients in developing countries. We report the case of a 34-year old woman co-infected with HIV and possible disseminated tuberculosis (hepatitis, lymphadenopathy, and pleural effusion) who presented a large and solitary intracranial mass lesion. Despite extensive diagnostic efforts, including brain, ganglionar, and liver biopsies, no definitive diagnosis was reached. However, a trial with first-line antituberculous drugs led to a significant clinical and radiological improvement. Atypical presentations of cerebral tuberculomas should always be considered in the differential diagnosis of intracranial mass lesions in HIV-infected patients and a trial with antituberculous drugs is a valuable strategy to infer the diagnosis in a subset of patients.

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

The Oncological and Functional Risks of the Organ Preservation Experimental Treatment Approach

We increasingly face conservative surgery for rectal cancer and even the so called ‘wait and see’ approach, as far as 10–20% patients can reach a complete pathological response at the time of surgery. But what can we say to our patients about risks? Standard surgery with mesorectal excision gives a <2% local recurrence with a post operative death rate of 2–8% (may reach 30% at 6 months in those over 85), but low AR has some deterioration in bowel function and in low cancer a permanent stoma may be required. Also a long-term impact on urinary and sexual function is possible. Distant metastasis rate seem to be identical in the standard and conservative approach. It is difficult to evaluate conservative approach because a not clear standardization of surgery for low rectal cancer. Rullier et al tried to clarify, and they found identical results for recurrence (5–9%), disease free survival (70%) at 5y for coloanal anastomosis and intersphinteric resection. Other series have found local recurrence higher than with standard approach and functional results may be worse and, in some situations, salvage therapy is compromised or has more complications. In this context, functional outcomes are very important but most studies are incomplete in measuring bowel function in the context of conservative approach. In 2005 Temple et al made a survey of 122/184 patient after sphinter preserving surgery and found a 96.9% of incomplete evacuation, 94.4% clustering, 93.2% food affecting frequency, 91.8% gas incontinence and proposed a systematic evaluation with a specific questionnaire. In which concerns ‘Wait and see’ approach for complete clinical responders, it was first advocated by Habr Gama for tumors up to 7cm, with a low locoregional failure of 4.6%, 5y overall survival 96%, 72% for disease free survival; one fifth of patients failed in the first year; a Dutch trial had identical results but others had worse recurrence rates; in other series 25% of patients could not be salvaged even with APR; 30% have subsequent metastatic disease what seems equal for ‘wait and see’ and operated patients. In a recent review Glynne Jones considers that all the evaluated ‘wait and see’ studies are heterogeneous in staging, inclusion criteria, design and follow up after chemoradiation and that there is the suggestion that patients who progress while under observation fare worse than those resected. He proposes long-term observational studies with more uniform inclusion criteria. We are now facing a moment where we may be more aggressive in early cancer and neoadjuvant treatment to be more conservative in the subsequent treatment but we need a better stratification of patients, better evaluation of results and more clear prognostic markers.

The Role of Prostaglandins in the Lower Urinary Tract Dynamics of Prostatectomized Patients: a Trial with Indomethacin and Aspirin

Using 49 prostatectomized patients as experimental subjects, we studied the effects of Inclometnacin and acetylsalicylic acid — accredited prostaglandin synthetase inhibitors — from a urodynamic and clinical standpoint. Relevant urodynamic data was gathered 1 hr 30 mi after the patients had taken the drugs and placebo. Clinical results were further scrutinized after 8 days of treatment, at which time a new urodynamic workup was again performed on some patients. Results were again studied shortly after the end of treatment. The effect of the drugs on bladder and urethral structures was borne out by clear-ct!t clinical and urodynamic changes. After statistically analyzing such changes, we concluded that prostaglandin synthesis inhibition resulting in the inhibition of prostaglandin action had, at least in part, led to the changes noted. In the present report we shall discuss the role played by the highly complex mechanisms at work.

Long-Term Lamivudine Treatment of Children with Chronic Hepatitis B: Durability of Therapeutic Responses and Safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.

Therapeutic trial in experimental tegumentary leishmaniasis caused by Leishmania (Leishmania) amazonensis. A comparative study between mefloquine and aminosidine

One hundred and eighty-two male inbred C57/BL/6 mice were infected with 3 x 106 Leishmania (Leishmania) amazonensis promastigotes of the MHOM/BR/PH8 strain by means of a subcutaneous injection in the right ear. The animals were separated in three groups: 1) oral mefloquine hydrochloride treatment (16mg/kg/day/10 days), 2) intramuscular aminosidine (Paromomycin®) treatment (20mg/kg/20 days) and 3) control. Twenty six mice of each treated group were sacrificed, one at the end of treatment (nine weeks after inoculation), and one six weeks later (fifteen weeks after inoculation). Control Group animals were sacrificed at weeks six, nine and fifteen after inoculation. There was no significant difference between Group 1 (mefloquine) and Group 3 (control) subjects. Group 2 animals (aminosidine) presented the smallest differences of all, both at the end of the treatment and six weeks later. The histopato-logical parameters have shown the following findings: a) there was no significant difference between the mefloquine treated group and the control group; the group treated with aminosidine showed fewer of vacuolated macrophages than the control group, at week 9 (end of treatment). b) both at the end of treatment and six weeks later, evaluation of tissue necrosis and tissue fibrosis revealed no differences between the treated groups. It was found that six weeks after the end of treatment, mice in the control group presented significantly more severe degrees of fibrosis than mice in the other groups. It can be concluded that mefloquine showed limited therapeutic effect in this experimental model, whereas aminosidine had a significant effect. Nevertheless, neither of them resulted in cure of the lesions.

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.

Size of gastroesophageal varices: its behavior after the surgical treatment of portal hypertension

The size of gastroesophageal varices is one of the most important factors leading to hemorrhage related to portal hypertension. An endoscopic evaluation of the size of gastroesophageal varices before and after different operations for portal hypertension was performed in 73 patients with schistosomiasis, as part of a randomized trial: proximal splenorenal shunt (PSS n=24), distal splenorenal shunt (DSS n=24), and esophagogastric devascularization with splenectomy (EGDS n=25). The endoscopic evaluation was performed before and up to 10 years after the operations. Variceal size was graded according to Palmer's classification: grade 1 -- up to 3 mm, grade 2 -- from 3 to 6 mm, grade 3 -- greater than 6 mm, and were analyzed in four anatomical locations: inferior, middle or superior third of the esophagus, and proximal stomach. The total number of points in the pre-operative grading minus the number of points in the post-operative grading gave a differential grading, allowing statistical comparison among the surgical groups. Good results, in terms of disappearance or decrease of variceal size, were observed more frequently after PSS than after DSS or EGDS - 95.8%, 83.3%, and 72%, respectively. When differential grading was analyzed, a statistically significant difference was observed between PSS and EGDS, but not between proximal and distal splenorenal shunts. In conclusion, shunt surgeries were more efficient than devascularization in diminishing variceal size.

Predictors of dropout in a controlled clinical trial of psychotherapy for moderate depression

A significant number of psychotherapy clients remain untreated, and dropping out is one of the main reasons. Still, the literature around this subject is incoherent. The present study explores potential pre-treatment predictors of dropout in a sample of clients who took part in a clinical trial designed to test the efficacy of narrative therapy for major depressive disorder compared to cognitive-behavioral therapy. Logistic regression analysis showed that: (1) treatment assignment did not predict dropout, (2) clients taking psychiatric medication at intake were 80% less likely to drop out from therapy, compared to clients who were not taking medication, and (3) clients presenting anxious comorbidity at intake were 82% less likely to dropout compared to those clients not presenting anxious comorbidity. Results suggest that clinicians should pay attention to depressed clients who are not taking psychiatric medication or have no comorbid anxiety. More research is needed in order to understand this relationship.

Myopia control with a novel peripheral gradient soft lens and orthokeratology: a 2-year clinical trial

Objective. To evaluate the degree of axial elongation with soft radial refractive gradient (SRRG) contact lenses, orthokeratology (OK), and single vision (SV) spectacle lenses (control) during a period of 1 year before treatment and 2 years after treatment. Methods. This was a prospective, longitudinal, nonrandomized study. The study groups consisted of 30, 29, and 41 children, respectively. The axial length (AL) was measured during 2 years after recruitment and lens fitting. Results. The baseline refractive sphere was correlated significantly (r 2 = 0.542; P < 0.0001) with the amount of myopia progression before baseline. After 2 years, the mean myopia progression values for the SRRG, OK, and SV groups were −0.56 ± 0.51, −0.32 ± 0.53, and −0.98 ± 0.58 diopter, respectively. The results represent reductions in myopic progression of 43% and 67% for the SRRG and OK groups, respectively, compared to the SV group. The AL increased more in the SV group compared to the SRRG and OK groups, with 27% and 38% lower axial elongation, respectively, compared to the SV group at the 2-year visit (P < 0.05). SRRG and OK showed no differences (P = 0.430). Conclusion. The SRRG lens significantly decreased AL elongation compared to the SV control group. The SRRG lens was similarly effective to OK in preventing myopia progression in myopic children and adolescent.

Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil

Intracoronary brachytherapy using beta or gamma radiation is currently the most efficient type of therapy for preventing the recurrence of coronary in-stent restenosis. Its implementation depends on the interaction among interventionists, radiotherapists, and physicists to assure the safety and quality of the method. The authors report the pioneering experience in Brazil of the treatment of 2 patients with coronary in-stent restenosis, in whom beta radiation was used as part of the international multicenter randomized PREVENT study (Proliferation REduction with Vascular ENergy Trial). The procedures were performed rapidly and did not require significant modifications in the traditional techniques used for conventional angioplasty. Alteration in the radiological protection devices of the hemodynamic laboratory were also not required, showing that intracoronary brachytherapy using beta radiation can be incorporated into the interventional tools of cardiology in our environment.

Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: dummy run and individual case review.

INTRODUCTION: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.