Frequency Of Treatment Failure Research Articles

Efficacy and safety of a combined treatment of sodium stibogluconate at 20mg/kg/day with upper maximum daily dose limit of 850mg and Paromomycin 15mg/kg/day in HIV negative visceral leishmaniasis patients. A retrospective study, northwest Ethiopia.

BackgroundVisceral leishmaniasis (VL) is one of the most neglected tropical infectious diseases. It is fatal if left untreated. The objective of this study was to assess the efficacy and safety of 17-day injections of combined regimen of sodium stibogluconate and paromomycin (SSG/PM) in HIV-negative VL patients.MethodsA retrospective analysis of medical records of VL patients treated in the University of Gondar Hospital during period 2012–2019 was carried out.ResultsA total of 2836 patients were treated for VL from 2012 to 2019. Of these 1233 were treated with SSG-PM, and 1000 of them were included in the study. Initial cure was achieved in 922 (92.2%) patients. The frequency of treatment failure, treatment interruptions, default and deaths respectively were 30 (3%), 20 (2%), 13 (1.3%) and 15 (1.5%). Among 280 patients who completed 6-month follow up, the final cure was 93.9% (263/280), 4 (1.4%) relapsed and 13 (4.6%) developed post-kala-azar dermal leishmaniasis (PKDL). The most common adverse events (AEs) were raised liver transaminases (35.1%; 351 patients), injection site pain (29.1%, 291 patients) and raised serum alpha-amylase (29.1%, 291 patients). Factors associated with poor treatment outcomes were sepsis, pneumonia, and adverse events.ConclusionA combination of SSG at 20mg/kg with upper daily maximum dose of 850mg and PM was effective for achieving initial cure at end of treatment and safe for treatment of HIV negative VL patients in northwestern Ethiopia. Our data are consistent with previous reports and confirms effectiveness of SSG/PM treatment regimen in the Eastern African countries. Efficacy at 6-months (93.9%) was estimated on data derived from patients who completed follow up and needs to be interrogated by future studies.

Peritonsillar Abscess Size as a Predictor of Medical Therapy Success.

To evaluate the success of sole medical therapy (MT) versus surgical therapy (ST) in patients with both clinically and radiographically confirmed peritonsillar abscess (PTA). To also determine treatment safety based on abscess size, and identify predictors of treatment failure. This was a retrospective cohort of 3 hospitals in a single academic health system. A total of 214 immunocompetent patients diagnosed with uncomplicated PTA underwent a contrasted CT scan of the neck. About 87 patients were treated with sole MT (intravenous antibiotics and steroids), and 127 patients were treated with ST (MT plus drainage). Treatment failure occurred in 8.0% of the MT group and 7.9% of the ST group (P = 1.00). In PTAs <2 cm, treatment failure occurred in 5.3% of the MT group and 5.0% of the ST group (P = 1.00). In PTAs ≥2 cm, treatment failure occurred in 13.3% of the MT group and 9.0% treated with ST (P = .53). Size ≥2 cm (OR - 3.46, P = .08) and IV clindamycin as sole IV antibiotic (OR - 2.46, P = .15) trended toward predicting treatment failure. In addition to those considered failures, 7.0% of the ST group returned to the ED with pain versus 0% of the MT group (P = .01). Frequency of treatment failure was not significantly different among patients receiving MT and ST. Abscesses ≥2 cm in size were more likely to fail in both groups and ST was not statistically superior. Sole MT for uncomplicated PTA may help reduce unnecessary procedures and healthcare costs.

Randomized Trial of Amoxicillin for Pneumonia in Pakistan

BackgroundThe World Health Organization (WHO) recommends oral amoxicillin for patients who have pneumonia with tachypnea, yet trial data indicate that not using amoxicillin to treat this condition may be noninferior to using amoxicillin.MethodsWe conducted a double-blind, randomized, placebo-controlled noninferiority trial involving children at primary health care centers in low-income communities in Karachi, Pakistan. Children who were 2 to 59 months of age and who met WHO criteria for nonsevere pneumonia with tachypnea were randomly assigned to a 3-day course of a suspension of amoxicillin (the active control) of 50 mg per milliliter or matched volume of placebo (the test regimen), according to WHO weight bands (500 mg every 12 hours for a weight of 4 to <10 kg, 1000 mg every 12 hours for a weight of 10 to <14 kg, or 1500 mg every 12 hours for a weight of 14 to <20 kg). The primary outcome was treatment failure during the 3-day course of amoxicillin or placebo. The prespecified noninferiority margin was 1.75 percentage points.ResultsFrom November 9, 2014, through November 30, 2017, a total of 4002 children underwent randomization (1999 in the placebo group and 2003 in the amoxicillin group). In the per-protocol analysis, the incidence of treatment failure was 4.9% among placebo recipients (95 of 1927 children) and 2.6% among amoxicillin recipients (51 of 1929 children) (between-group difference, 2.3 percentage points; 95% confidence interval [CI], 0.9 to 3.7). Results were similar in the intention-to-treat analysis. The presence of fever and wheeze predicted treatment failure. The number needed to treat to prevent one treatment failure was 44 (95% CI, 31 to 80). One patient (<0.1%) in each group died. Relapse occurred in 40 children (2.2%) in the placebo group and in 58 children (3.1%) in the amoxicillin group.ConclusionsAmong children younger than 5 years of age with nonsevere pneumonia, the frequency of treatment failure was higher in the placebo group than in the amoxicillin group, a difference that did not meet the noninferiority margin for placebo. (Funded by the Joint Global Health Trials Scheme [of the Department for International Development, Medical Research Council, and Wellcome] and others; RETAPP ClinicalTrials.gov number, NCT02372461.)

Efficacy of Home Phototherapy in Neonatal Jaundice

Background: Jaundice is one of the most common problems in the neonatal period. Phototherapy is one of the most commonly used treatments for jaundice that can be used as a simple, practical home-based treatment. Hospitalization during the first days of birth to conduct phototherapy may result in problems like nosocomial infections and mother separation from the baby. Objectives: The aim of this study was to evaluate the efficacy of home phototherapy in the duration of treatment, mean bilirubin level, and complications. Methods: This clinical trial was performed on newborns with jaundice in Isfahan health centers. The sample was randomly divided into two groups: Phototherapy at home (32 patients) and phototherapy at the hospital (32 patients). A demographic questionnaire and a researcher-made checklist were used to collect data on variables such as the duration of treatment, the frequency of treatment failure, mean bilirubin, and phototherapy complications. Results: The mean duration of phototherapy in both groups was two days, which showed no significant difference (P = 0.32). The most common complication in both groups was skin rashes and restlessness, which also showed no significant between two groups (P > 0.05). There was no significant difference in terms of treatment failure (P = 0.246). Statistical tests also revealed that bilirubin reduction was the same in both groups. Conclusions: Home phototherapy can be suggested as a safe treatment with no complication to the patients.

Analysis of reverse transcriptase and protease genes of HIV for antiretroviral drug resistance in treatment-exposed Jamaican pediatrics.

This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was amplified from 40 samples, sequenced, and analyzed for the identification of antiretroviral resistance-associated mutations (RAMs). All isolates belonged to subtype B and 39 possessed multiple RAMs in the reverse transcriptase genes that would compromise the efficacy of drugs being used to treat these patients. Four isolates possessed RAMs in the protease genes. The overall frequency of HIV drug resistance was 95%. The high frequency of drug resistance is supported by epidemiological data that revealed an equally high frequency of treatment failure (98%) among the study participants. The results of this study indicate the urgent need for greater access to drug resistance testing in Jamaica.

Addition of Somatostatin After Successful Endoscopic Variceal Ligation Does not Prevent Early Rebleeding in Comparison to Placebo: A Double Blind Randomized Controlled Trial

Efficacy of endoscopic sclerotherapy in controlling acute variceal bleeding is significantly improved when vasoactive drug is added. Endoscopic variceal ligation (EVL) is superior to sclerotherapy. Whether efficacy of EVL will also improve with addition of somatostatin is not known. We compared EVL plus somatostatin versus EVL plus placebo in control of acute variceal bleeding. Consecutive cirrhotic patients with acute esophageal variceal bleeding were enrolled. After emergency EVL, patients were randomized to receive either somatostatin (250mcg/hr) or placebo infusion. Primary endpoint was treatment failure within 5 days. Treatment failure was defined as fresh hematemesis ≥2h after start of therapy, or a 3gm drop in Hb, or death. 61 patients were enrolled (EVL plus somatostatin group, n=31 and EVL plus placebo group, n=30). The baseline characteristics were similar. Within the initial 5-day period, the frequency of treatment failure was similar in both the groups (EVL plus somatostatin group 8/31 [26%] versus EVL plus placebo group 7/30 [23%]; P=1.000). The mortality was also similar in the two groups (3/31 [10%] vs. 3/30 [10%]; P=1.000). Baseline HVPG ≥19mm Hg and active bleeding at index endoscopy were independent predictors of treatment failure. Addition of somatostatin infusion to EVL therapy does not offer any advantage in control of acute variceal bleeding or reducing mortality. The reason for this may be its failure to maintain sustained reduction in portal pressure for five days. Active bleeding at index endoscopy and high baseline HVPG should help choose early alternative treatment options. Trial registered with ClincalTrials.gov vide NCT01267669.

Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes

OBJECTIVEThis study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.RESEARCH DESIGN AND METHODSIn this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups.RESULTSGlycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86).CONCLUSIONSResults of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

Differences in inpatient glycemic control and response to subcutaneous insulin therapy between medicine and surgery patients with type 2 diabetes

ObjectiveTo determine differences in inpatient glycemic control and response to two different glargine-based insulin regimens in general medicine and surgery patients with type 2 diabetes (T2D). MethodsThis is a post-hoc analysis of a prospective, multicenter, randomized trial of 298 non-ICU medicine and surgery patients with T2D treated with Basal Bolus regimen with glargine once daily and glulisine before meals and with Basal Plus regimen with glargine once daily and supplemental doses of glulisine before meals for blood glucose (BG)>140mg/dl. Major study outcomes included differences in mean daily BG, frequency of treatment failures (defined as >2 consecutive BG>240mg/dl or a mean daily BG>240mg/dl), and hypoglycemia between the medicine and surgery cohorts. ResultsPatients treated with Basal Bolus or with Basal Plus experienced similar improvement in mean daily BG after 1st day of therapy (p=0.16), number of treatment failures (p=0.11) and hypoglycemic events (p=0.50). Compared to surgery patients (n=130), medicine patients (n=168) had higher admission BG (p=0.01) and HbA1c levels (p<0.01); however, they had similar response to either treatment regimen without differences in mean daily BG after 1st day of therapy (p=0.18), number of treatment failures (p=0.58), daily insulin requirements (p=0.36), or in the frequency of hypoglycemia (p=0.79). ConclusionThe Basal Plus regimen with glargine once daily and correction doses with glulisine before meals resulted in similar glycemic control to basal bolus regimen. We observed no differences in response to either basal insulin regimen between medicine and surgery patients with type 2 diabetes.

Comparison of Alternative Primary Outcome Measures for Use in Lupus Nephritis Clinical Trials

Clinical trials of therapies for lupus nephritis have used many different primary outcome measures, ranging from complete response to time to end-stage renal disease. The objective of this study was to compare several possible outcome measures, using data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which outcome measure, if any, was best able to discern differences among treatment groups. Study patients received either abatacept or placebo, on a background of mycophenolate mofetil and glucocorticoids. Using data from this trial, the following primary outcome measures at 24 and 52 weeks were compared: complete response rate, major clinical response rate, total response rate (complete plus partial response), improvement in proteinuria, improvement in estimated glomerular filtration rate, and frequency of treatment failure. Time to complete response was also evaluated. Complete response rate, major clinical response rate, and time to complete response were the measures that best discriminated between the abatacept groups and placebo, and the sensitivities of these 3 measures were comparable. For these measures, sample sizes of 50 patients would have been sufficient to demonstrate a statistically significant difference between treatment and control at 52 weeks. Each of the other measures also discriminated between treatment and control, but much larger group sizes would have been required to determine statistical significance. The choice of primary outcome measure can substantially influence the ability to detect therapeutic benefit in lupus nephritis trials. This study suggests that complete response rate, major clinical response rate at 52 weeks, and time to complete response may be the most sensitive outcome measures for detecting differences among therapeutic regimens.

Treatment failure among Kenyan children with severe pneumonia--a cohort study.

Pneumonia is the leading cause of childhood mortality worldwide. The World Health Organization recommends presumptive treatment based on clinical syndromes. Recent studies raise concerns over the frequency of treatment failure in Africa. We applied a definition of treatment failure to data prospectively collected from children who were 2-59 months of age with severe, or very severe, pneumonia admitted to Kilifi District Hospital, Kenya, from May 2007 through May 2008 and treated using World Health Organization guidelines. The primary outcome was treatment failure at 48 hours. Of 568 children, median age 11 months, 165 (29%) had very severe pneumonia, 30 (5.3%) a positive HIV test and 62 (11%) severe malnutrition. One hundred eleven (20%; 95% confidence interval: 17-23%) children failed treatment at 48 hours and 34 (6.0%) died; 22 (65%) deaths occurred before 48 hours. Of 353 children with severe pneumonia, without HIV or severe malnutrition, 42 (12%) failed to respond at 48 hours, 15 (4.3%) failed at 5 days and 1 child (0.3%) died. Among 215 children with either severe pneumonia complicated by HIV or severe malnutrition, or very severe pneumonia, 69 (32%) failed to treatment at 48 hours, 47 (22%) failed at 5 days and 33 (16%) died. Treatment failure at 48 hours was associated with shock, bacteremia, very severe pneumonia, oxygen saturation in hemoglobin <95%, severe malnutrition, HIV and age <1 year in multivariable models. In this setting, few children with uncomplicated severe pneumonia fail treatment or die under current guidelines. Deaths mainly occurred early and may be reduced by improving prevention, prehospital care and treatment of sepsis.

1160 Adding Ciprofloxacin to Adalimumab Results in a Higher Fistula Closure Rate in Perianal Fistulizing Crohn's Disease

Background: There is clear benefit of combination therapy for infliximab (IFX) with immunosuppressive drugs (IS), whether commenced together, or later, but no data are available for ADA. The aim was to assess whether IS combotherapy (CoT) was more effective than monotherapy for Crohn’s disease (CD) patients treated with ADA, using the semester approach. Methods: Retrospective study of patients with CD (n = 181) treated for at least one year with ADA in Oxford, UK or Liege, Belgium. Treatment periods were divided into 6 month semesters and the treatment failure compared between semesters with or without CoT (thiopurines or methotrexate). ADA failure was defined as dose modification during therapy, drug modification, perineal complications, or surgery for active CD. Results: 569 semesters were studied in 181 patients (Oxford n = 98, Liege 83), including 147 semesters in 45 patients having received CoT during the first semester. More patients in Oxford received CoT than Liege (OR: 4.82, p < 0.0001) and fewer females (OR 0.50, p = 0.01). When considering only patients on CoT during the first semester, treatment failures were less frequent in semesters with IS (20%) compared to semesters without IS (80%; OR 0.30, p = 0.02). This protective effect of the CoT was maintained over time (p = 0.01). When considering all the patients, CoT in the first semester was associated with a lower frequency of treatment failures (34% vs 66%, OR 0.69, p = 0.046) in univariate analysis but not in multivariate analysis. CoT later after induction of ADA was not associated with treatment failures. Female gender (OR 1.68, p = 0.01), previous surgery (OR 1.89, p = 0.001) and active perianal disease (OR 1.57, p = 0.02) were risk factors of failure on multivariate analysis. Although failures were less common in Oxford (OR 0.52, p = 0.001), more failures in Oxford had surgery (OR 8.85, p = 0.001) or perianal complications (OR 3.33, p = 0.01) and fewer had ADA weekly (OR 0.24, p = 0.0003) on multivariate analysis. The overall number of operations and perianal complications did not differ between CoT and ADA monotherapy. Thiopurines appeared more effective than methotrexate for preventing failure (OR 0.35, p = 0.03). The probablility of failure did not increase over the semesters (p = 0.86). Conclusions: When it was given during the first semester, CoT with ADA in CD was associated with fewer semesters with treatment failures (essentially the need for dose escalation or treatment modification, but not the rate of surgery or perianal complications). OP16 Adding ciprofloxacin to adalimumab results in a higher fistula closure rate in perianal fistulizing Crohn’s disease P. Dewint1 *, B. Hansen1, E. Verhey1, B. Oldenburg2, D.W. Hommes3, M. Pierik4, C. Ponsioen5, H. van Dullemen6, M.G. Russel7, A. van Bodegraven8, C.J. van der Woude1, on behalf of ICC (Initative on Crohn’s and Colitis). 1Erasmus Medical Center, Department of Gastroenterology & Hepatology, Rotterdam, Netherlands, 2University Medical Centre Utrecht, Department of Gastroenterology, Utrecht, Netherlands, 3UCLA, Division of Digestive Diseases, Los Angeles, United States, 4Maastricht University Medical Center, Dept of Gastroenterology, Maastricht, Netherlands, 5Academic Medical Center, Gastroenterology and Hepatology, Amsterdam, Netherlands, 6UMC Groningen, Gastroenterology, Groningen, Netherlands, 7Medisch Spectrum Twente, Gastroenterology, Enschede, Netherlands, 8VU University Medical Center, Gastroenterology, Amsterdam, Netherlands

OP15 Immunosuppressive co-treatment with adalimumab (ADA) may be more effective than ADA monotherapy for maintaining remission in Crohn's disease (CD)

Background: There is clear benefit of combination therapy for infliximab (IFX) with immunosuppressive drugs (IS), whether commenced together, or later, but no data are available for ADA. The aim was to assess whether IS combotherapy (CoT) was more effective than monotherapy for Crohn’s disease (CD) patients treated with ADA, using the semester approach. Methods: Retrospective study of patients with CD (n = 181) treated for at least one year with ADA in Oxford, UK or Liege, Belgium. Treatment periods were divided into 6 month semesters and the treatment failure compared between semesters with or without CoT (thiopurines or methotrexate). ADA failure was defined as dose modification during therapy, drug modification, perineal complications, or surgery for active CD. Results: 569 semesters were studied in 181 patients (Oxford n = 98, Liege 83), including 147 semesters in 45 patients having received CoT during the first semester. More patients in Oxford received CoT than Liege (OR: 4.82, p < 0.0001) and fewer females (OR 0.50, p = 0.01). When considering only patients on CoT during the first semester, treatment failures were less frequent in semesters with IS (20%) compared to semesters without IS (80%; OR 0.30, p = 0.02). This protective effect of the CoT was maintained over time (p = 0.01). When considering all the patients, CoT in the first semester was associated with a lower frequency of treatment failures (34% vs 66%, OR 0.69, p = 0.046) in univariate analysis but not in multivariate analysis. CoT later after induction of ADA was not associated with treatment failures. Female gender (OR 1.68, p = 0.01), previous surgery (OR 1.89, p = 0.001) and active perianal disease (OR 1.57, p = 0.02) were risk factors of failure on multivariate analysis. Although failures were less common in Oxford (OR 0.52, p = 0.001), more failures in Oxford had surgery (OR 8.85, p = 0.001) or perianal complications (OR 3.33, p = 0.01) and fewer had ADA weekly (OR 0.24, p = 0.0003) on multivariate analysis. The overall number of operations and perianal complications did not differ between CoT and ADA monotherapy. Thiopurines appeared more effective than methotrexate for preventing failure (OR 0.35, p = 0.03). The probablility of failure did not increase over the semesters (p = 0.86). Conclusions: When it was given during the first semester, CoT with ADA in CD was associated with fewer semesters with treatment failures (essentially the need for dose escalation or treatment modification, but not the rate of surgery or perianal complications). OP16 Adding ciprofloxacin to adalimumab results in a higher fistula closure rate in perianal fistulizing Crohn’s disease P. Dewint1 *, B. Hansen1, E. Verhey1, B. Oldenburg2, D.W. Hommes3, M. Pierik4, C. Ponsioen5, H. van Dullemen6, M.G. Russel7, A. van Bodegraven8, C.J. van der Woude1, on behalf of ICC (Initative on Crohn’s and Colitis). 1Erasmus Medical Center, Department of Gastroenterology & Hepatology, Rotterdam, Netherlands, 2University Medical Centre Utrecht, Department of Gastroenterology, Utrecht, Netherlands, 3UCLA, Division of Digestive Diseases, Los Angeles, United States, 4Maastricht University Medical Center, Dept of Gastroenterology, Maastricht, Netherlands, 5Academic Medical Center, Gastroenterology and Hepatology, Amsterdam, Netherlands, 6UMC Groningen, Gastroenterology, Groningen, Netherlands, 7Medisch Spectrum Twente, Gastroenterology, Enschede, Netherlands, 8VU University Medical Center, Gastroenterology, Amsterdam, Netherlands

New regimen of inhaled corticosteroid in preschool children with asthma

aily low-dose inhaled corticosteroid in preschool children with asthma is recommended to prevent the development of asthma symptom and sign based on many asthma manage- ment guidelines. But the retarded growth after long-term steroid inhalation has been concerned. Recently the method of intermittent high-dose (suspension, 1,000 μg, 2 times a day for 7 days) budesonide inhalation when the initial phase to develop the asthma exacerbation was studied to compare the efficacy and safety with daily low-dose budesonide (500 μg) inhalation regimen in preschool children positive with modified asthma predictive index in recurrent wheezer during the study period with 52 weeks. There were no significant difference between two regimen with respect to the frequency of exacerbations, the time to the first exacerbation and to the second exacerbation, and the frequency of treatment failure. The total exposure to budesonide over the period was less in the intermittent high-dose regimen than in the daily low-dose regimen. There were no significant difference in change in height. But the change in height from baseline in intermittent high-dose regimen group was 8.01 cm and in daily low-dose was 7.76 cm. We need the more clinical studies in preschool children with persistent moderate and severe asthma and in various country and nations. It is suggested the intermittent high-dose budesonide inhalation regimen in preschool children with freqeunt wheezing may be a very good alternative to control the allergic inflammation and symptoms of asthma without concerning the adverse effect of steroid.

Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial

Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment. In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5-18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 μg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 μg) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329. 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)-555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37-61), the frequency of exacerbations was lower in the daily (28%, 18-40, p=0·03), combined (31%, 21-43, p=0·07), and rescue (35%, 24-47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14-43) in the placebo group, compared with 5·6% (1·6-14) in the combined (p=0·012), 2·8% (0-10) in the daily (p=0·009), and 8·5% (2-15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis. Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided. National Heart, Lung and Blood Institute.

Effectiveness and safety of the schedules of short and long term treatment for tuberculous meningoencephalitis at two hospitals of Lima - Peru

Introduction To compare the effectiveness and safety of short-term 6 month-treatment and long term 12 month-treatment schedules for meningoencephalitis due to tuberculosis in two hospitals from Lima-Peru. Methods Comparative, retrospective and observational study. The patients were divided in two groups: Group 1: long term 12 month-treatment with isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months; then isoniazid and rifampin for 10 months. Group 2: short-term 6 month-treatment with isoniazid and rifampin, pyrazinamide and ethambutol for the first 2 months; then isoniazid and rifampin for 4 months. Clinical records, effectiveness, treatment failure, treatment side effects, mortality and late consequences after treatment were reviewed. Results Twenty-six patients with meningoencephalitis level I were included, 10 received the long term schedule and 16 the short-term schedule treatment. From 51 patients with meningoencephalitis level II, 27 received the long term schedule and 24 the short-term schedule treatment and of 31 patients with meningoencephalitis level III, 18 received the long term schedule treatment and 13 the short-term schedule treatment. There was no statistically significant differences among levels I, II and III when effectiveness of short and long term schedule was evaluated. Moreover, there was no statistically significant difference in the frequency of treatment failure, treatment side effects, mortality and late consequences among groups. Conclusions Long term 12 month-treatment and short-term 6 month-treatment had similar effectiveness and safety in the treatment of meningoenchephalitis due to tuberculosis in HIV negative patients.bility in work protocols and rationalises the use of the available health care resources.

Efectividad y seguridad de los esquemas de tratamiento corto y largo para meningoencefalitis tuberculosa en dos hospitales de Lima-Perú

Introduction To compare the effectiveness and safety of short term 6 month-treatment and long term 12 month-treatment schedules for meningoencephalitis due to tuberculosis in two hospitals from Lima-Peru. Methods Comparative, retrospective and observational study. The patients were divided in two groups: Group 1: long term 12 month-treatment with isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months; then isoniazid and rifampin for 10 months. Group 2: short term 6 month-treatment with isoniazid and rifampin, pyrazinamide and ethambutol for the first 2 months; then isoniazid and rifampin for 4 months. Clinical records, effectiveness, treatment failure, treatment side effects, mortality and late consequences after treatment were reviewed. Results Twenty-six patients with meningoencephalitis level I were included, 10 received the long term schedule and 16 the short term schedule treatment. From 51 patients with meningoencephalitis level II, 27 received the long term schedule and 24 the short term schedule treatment and of 31 patients with meningoencephalitis level III, 18 received the long term schedule treatment and 13 the short term schedule treatment. There was no statistically significant differences among levels I, II and III when effectiveness of short and long term schedule was evaluated. Moreover, there was no statistically significant difference in the frequency of treatment failure, treatment side effects, mortality and late consequences among groups. Conclusions Long term 12 month-treatment and short term 6 month-treatment had similar effectiveness and safety in the treatment of meningoenchephalitis due to tuberculosis in HIV negative patients.

Oral combination therapy: repaglinide plus metformin for treatment of type 2 diabetes

Type 2 diabetes is characterized by decreases in insulin secretion and insulin sensitivity. Several classes of oral antidiabetic medications are currently approved for the treatment of type 2 diabetes. A stepwise treatment approach from monotherapy to combination therapy is traditionally used; however, the frequency of treatment failure with monotherapy has resulted in a move towards earlier treatment with combination therapies that target the two principal defects in glycaemic control. One such combination regimen is repaglinide (a prandial glucose regulator that increases insulin release) plus metformin (an insulin sensitizer that inhibits hepatic glucose output, increases peripheral glucose uptake and utilization and minimizes weight gain). Findings from several clinical trials have shown that combination therapy with repaglinide plus metformin is well tolerated and results in greater reductions of haemoglobin A(1c) and fasting plasma glucose values compared with either monotherapy. Repaglinide may also provide a more suitable alternative to combination therapy with sulphonylureas and metformin because of its reduced propensity for hypoglycaemia. The combination regimen of repaglinide plus metformin should therefore be considered as a valuable option in the management of patients with type 2 diabetes when monotherapy is no longer adequate.

Heterogeneous response to HAART across a diverse population of people living with HIV: results from the ANRS-EN12-VESPA Study

Benefits from HAART may be heterogeneous across people living with HIV. We measured the differences in the rate of HAART failure across the various subgroups represented at the level of a country. We used data from a national representative sample of people living with HIV and followed at hospital in France (ANRS-EN12-VESPA Study). Analyses were restricted to 896 participants on HAART for 6 months or more, who were antiretroviral naive at HAART initiation. Different indicators of treatment failure were defined: immunological failure (absence of an increase of 100 CD4 cells/microl or more); immunovirological failure (CD4 cell count of 200 cells/microl or less and detectable HIV-RNA); clinical failure (occurrence of an AIDS-defining illness more than 3 months after HAART initiation). Differences in the frequency of treatment failure were measured using logistic regression models adjusted for major established determinants of response to HAART. Overall, 19.6% of the study participants experienced immunological failure, 3.4% immunovirological failure, and 3.0% clinical failure, with substantial variations across the various subgroups. Compared with homo/bisexual men, migrants had higher rates of immunological failure (adjusted odds ratio 2.27, 95% confidence interval 1.14-4.56 for migrant men and 2.19, 1.17-4.08 for migrant women), immunovirological failure (8.23, 1.77-38.33 and 6.91, 1.03-46.32), and clinical failure (4.60, 1.01-20.86 and 4.22, 0.84-21.17). In France, migrants consistently appear to be at increased risk of treatment failure compared with other people with HIV. Understanding the reasons underlying such heterogeneity in terms of living conditions and educational/cultural background will be important.

Effectiveness and Safety of Abacavir, Lamivudine, and Zidovudine in Antiretroviral Therapy-Naive HIV-Infected Patients

To analyze the safety and effectiveness of abacavir, lamivudine, and zidovudine (ABC/3TC/ZDV) in antiretroviral therapy (ART)-naive HIV-infected patients. Retrospective observational cohort study. We analyzed all consecutive ART-naive HIV-infected patients who initiated ABC/3TC/ZDV in 71 centers throughout Spain and had a clinical visit and laboratory data at least 16 weeks after initiating this regimen. We assessed safety, mortality, new AIDS-defining conditions (ADCs) and treatment failure, the latter defined by any of the following: (1) reduction in plasma HIV-1 viral load (pVL) <1 log during the first 12 weeks of ART, unless it was less than the lower limit of quantification (LOQ); (2) failure to achieve a pVL <LOQ after 24 weeks of ART; and (3) rebound to 2 consecutive pVLs > or = LOQ after achieving a pVL <LOQ. A total of 730 patients were included, median patient age was 37 years, prior ADCs occurred in 20%, median pVL was 4.76 log, and median CD4 count was 255 cells/mm; 109 (14.9%) patients had <100 CD4 cells/mm. After a median follow-up of 50.5 weeks (interquartile ratio: 28-78), 104 (14.25%) patients discontinued therapy because of adverse events and 36 (4.93%) had a suspected hypersensitivity reaction to ABC. The frequency of treatment failure according to an intention-to-treat (ITT) analysis of observed data was 14.4%. In a more rigorous approach considering losses to follow-up and interruptions or switches of therapy as failures, however, the frequency of treatment failure was 22.92%. Factors independently associated with treatment failure by observed data ITT analysis were adherence <90% (hazard ratio [HR] = 4.248, 95% confidence interval [CI]: 2.640 to 6.833), methadone use (HR = 2.116, 95% CI: 1.180 to 3.797), baseline pVL (HR = 1.651, 95% CI: 1.190 to 2.292 per log), and prior ADC (HR = 1.639, 95% CI: 1.009 to 2.662). The triple-nucleoside regimen of ABC/3TC/ZDV is a reasonable option for ART-naive patients with a pVL <100,000 copies/mL in whom, for any reason, preferred regimens are not advisable, even in patients with a baseline CD4 cell count <100 cells/mm.

Monitoring of the therapeutic efficacy of chloroquine for the treatment of uncomplicated,Plasmodium falciparummalaria in Iran

Between 2002 and 2004, the standardized 28-day protocol recently developed by the World Health Organization was used to explore the efficacy of chloroquine, in the treatment of uncomplicated, Plasmodium falciparum malaria, in five sentinel sites in southern Iran. All but 14 of the 158 patients enrolled (128, 28 and two from the provinces of Sistan-Baluchestan, Hormozgan and Kerman, respectively) were successfully followed-up. The overall frequency of treatment failure by day 28 was 78.5%, with 17.4% of the patients being classed as early treatment failures, 34.7% as late clinical failures, and 26.4% as late parasitological failures. There appeared to be no significant change in the frequency of treatment failure between the 2002-2003 and 2003-2004 transmission seasons, nor any significant between-site variation in the efficacy of chloroquine. Given these observations, the replacement of chloroquine, as the first-line drug for the treatment of uncomplicated, P. falciparum malaria in Iran, was inevitable. Artesunate-sulfadoxine-pyrimethamine is now the recommended first-line treatment, with artemether-lumefantrine used for second-line treatment. The efficacies of these combination therapies are currently being evaluated and monitored.