Number Of Treatment Failures Research Articles

The PATCH trial: 5% lidocaine-medicated plaster for trigeminal neuralgia-Results of a multicentric, enriched enrollment, randomized withdrawal, double-blind, vehicle-controlled, parallel-group study.

To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.

The Effectiveness of a Dietary Supplement with Honey, Propolis, Pelargonium sidoides Extract, and Zinc in Children Affected by Acute Tonsillopharyngitis: An Open, Randomized, and Controlled Trial.

Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study evaluated PediaFlù (Pediatrica S.r.l.), a dietary supplement already on the market composed of honey, propolis, Pelargonium sidoides extract, and zinc (DSHPP), in children affected by acute tonsillopharyngitis (ATR). The open-label, randomized, and controlled study compared DSHPP + standard of care (SoC) versus SoC alone for six days. Children between 3 and 10 years with an ATR ≤ 48 h, a negative rapid test for beta-hemolytic Streptococcus, or a culture identification of nasal and/or pharyngeal exudates were included. A tonsillitis severity score (TSS) and the number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) were the primary endpoints. DSHPP+ SoC showed better performance than SoC alone for TSS sub-scores: throat pain and erythema on day 6 (p < 0.001 and p < 0.05), swallowing (p < 0.01 on day 4), and TSS total score on days 4 and 6 (p < 0.05 and p < 0.001). Only one patient (SoC group) had treatment failure for ibuprofen administration. No adverse events were reported. DSHPP is an optimal adjuvant in the treatment of URTI and could potentially be useful in the daily clinical practice of paediatricians evaluating the correct antibiotic prescription.

Safety and effectiveness of vonoprazan-based rescue therapy for Helicobacter pylori infection

Vonoprazan (VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori (H. pylori) infection. However, their value as a rescue therapy needs to be explored.To assess a VPZ-based regimen as H. pylori rescue therapy.This prospective, single-center, clinical trial was conducted between January and August 2022. Patients with a history of H. pylori treatment failure were administered 20 mg VPZ twice daily, 750 mg amoxicillin 3 times daily, and 250 mg Saccharomyces boulardii (S. boulardii) twice daily for 14 d (14-d VAS regimen). VPZ and S. boulardii were taken before meals, while amoxicillin was taken after meals. Within 3 d after the end of eradication therapy, all patients were asked to fill in a questionnaire to assess any adverse events they may have experienced. At least 4-6 wk after the end of eradication therapy, eradication success was assessed using a 13C-urea breath test, and factors associated with eradication success were explored.Herein, 103 patients were assessed, and 68 patients were finally included. All included patients had 1-3 previous eradication failures. The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6% (63/68) and 92.3% (60/65), respectively. The eradication rate did not differ with the number of treatment failures (P = 0.433). The rates of clarithromycin, metronidazole, and levofloxacin resistance were 91.3% (21/23), 100.0% (23/23), and 60.9% (14/23), respectively. There were no cases of resistance to tetracycline, amoxicillin, or furazolidone. In 60.9% (14/23) patients, the H. pylori isolate was resistant to all 3 antibiotics (clarithromycin, metronidazole, and levofloxacin); however, eradication was achieved in 92.9% (13/14) patients. All patients showed metronidazole resistance, and had an eradication rate of 91.3% (21/23). The eradication rate was higher among patients without anxiety (96.8%) than among patients with anxiety (60.0%, P = 0.025). No severe adverse events occurred; most adverse events were mild and disappeared without intervention. Good compliance was seen in 95.6% (65/68) patients. Serological examination showed no significant changes in liver and kidney function.VAS is a safe and effective rescue therapy, with an acceptable eradication rate (> 90%), regardless of the number of prior treatment failures. Anxiety may be associated with eradication failure.

Remote Health Interventions: Effectiveness, Cost, and Cost-Effectiveness Considerations.

Remote Health Interventions: Effectiveness, Cost, and Cost-Effectiveness Considerations.

Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships.

Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of Pelophylax kl. esculentus and it displays a strong activity against Gram-positive bacteria, with an extreme cytotoxicity. Incorporating positively charged residues and introducing D-amino acids were the two main strategies adopted for the modifications. The transformation of the chirality of Ile could reduce haemolytic activity, and an analogue with appropriate D-isoforms could maintain antimicrobial activity and stability. The substitution of hydrophobic residues could bring about more potent and broad-spectrum antimicrobial activities. The analogues with Lys were less harmful to the normal cells and their stabilities remained at similarly high levels compared to temporin-PKE. The optimal number of charges was three, and the replacement on the polar face was a better choice. Temporin-PKE-3K exerted dually efficient functions includingstrong antimicrobial and anticancer activity. This analogue showed a reduced possibility for inducing resistance in MRSA and Klebsiella pneumoniae, a rather strong antimicrobial activity in vivo, and it exhibited the highest therapeutic index such that temporin-PKE-3K has the potential to be developed as a clinical drug.

Modelling of the transmission dynamics of carbapenem-resistant Klebsiella pneumoniae in hospitals and design of control strategies

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a major threat to global public health. Epidemiological and infection controls associated with CRKP are challenging because of several potential elements involved in a complicated cycle of transmission. Here, we proposed a comprehensive mathematical model to investigate the transmission dynamics of CRKP, determine factors affecting the prevalence, and evaluate the impact of interventions on transmission. The model includes the essential compartments, which are uncolonized, asymptomatic colonized, symptomatic colonized, and relapsed patients. Additionally, symptomatic colonized and relapsed patients were further classified into subpopulations according to their number of treatment failures or relapses. We found that the admission of colonized patients and use of antibiotics significantly impacted the endemic transmission in health care units. Thus, we introduced the treatment efficacy, defined by combining the treatment duration and probability of successful treatment, to characterize and describe the effects of antibiotic treatment on transmission. We showed that a high antibiotic treatment efficacy results in a significantly reduced likelihood of patient readmission in the health care unit. Additionally, our findings demonstrate that CRKP transmission with different epidemiological characteristics must be controlled using distinct interventions.

Clinical predictors of depressive symptom remission and response after racemic ketamine and esketamine infusion in treatment-resistant depression.

Major depressive disorder (MDD) is a leading cause of disability worldwide and most people do not achieve symptom remission. Treatment-resistant depression (TRD) is characterized by the failure of at least one adequate trial of a major class of antidepressant, with adequate time and dosage. We aimed to identify clinical predictors of depressive symptom remission and response 24h and 7days after racemic ketamine and esketamine infusions. A randomized, double-blind, active-controlled, non-inferiority trial using ketamine and esketamine in TRD. Individuals diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders version IV and fulfilling TRD criteria were recruited from March 2017 to June 2018. Participants received a single subanesthetic dose of ketamine (0.5mg/kg) or esketamine (0.25mg/kg) for 40min. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and symptom remission was defined as a MADRS score ≤7 and response defined as ≥50% reduction in depressive symptom severity, 24h and 7days after the infusion. Clinical variables were selected based on previous clinical trials. Stepwise backward logistic regression was used, considering a confidence level of 95%. 61 subjects were included: 39 (63.9%) were females with a mean age of 47.2±14.9. Higher number of therapeutic failures (Odds Ratio (OR)=0.677; 95% confidence interval (CI): 0.47-0.97) and higher severity of illness (OR=0.912; 95% CI: 0.83-0.99) were associated with fewer remissions of depressive symptoms 7days after intervention, and with fewer response in 24h (OR=0.583; 95% CI: 0,40; 0,84 and OR=0.909; 95% CI: 0,83; 0,99, respectively). Number of treatment failures and severity of illness were predictors of fewer remissions and responses of depressive symptoms in this TRD population. Study of predictors of remission may contribute to better selection patients that may benefit from receiving ketamine.

Triclabendazole for the treatment of human fascioliasis and the threat of treatment failures

ABSTRACT Introduction The only drug effective against the infection caused by Fasciola hepatica or F. gigantica is triclabendazole (TCBZ), recommended by the WHO and recently approved by the FDA. Here, we describe the evolution of TCBZ regimens and the emergence of TCBZ failure to Fasciola infection. Areas covered The present review focuses on the evidence of TCBZ for the treatment of fascioliasis. For acute fascioliasis, there is a lack of studies to measure the presence of eggs of Fasciola in stool samples on the follow-up after initial TCBZ treatment. For chronic fascioliasis, WHO recommends a single oral dose of TCBZ 10 mg/kg whereas CDC recommends two doses of TCBZ 10 mg/kg 12 h apart. Incremental number of treatment failures have been documented worldwide. There are currently no therapeutic alternatives for the treatment of fascioliasis in humans. Expert opinion Most cases of human fascioliasis are successfully treated with TCBZ, but some continue excreting eggs in the stools despite 1–2 standard of care regimens of TCBZ. A precise regimen is unclear for those patients who fail the initial treatment with TCBZ. Further clinical trials are needed to address the possible TCBZ emerging resistance.

Effects of Teriparatide on Treatment Outcomes in Osteoporotic Hip and Pelvic Bone Fractures: Meta-analysis and Systematic Review of Randomized Controlled Trials.

The primary objective of this study was to evaluate randomized controlled trials (RCTs) that have reported the effects of teriparatide on bone-healing in osteoporotic hip and pelvic bone fractures to determine the efficacy of teriparatide in lowering the rate of treatment failure. A total of 2,809 studies were identified using a comprehensive literature search (MEDLINE [n=1,061], Embase [n=1,395], and Cochrane Library n=353]). Five RCTs were included in the final analysis. Treatment failure rates at the last follow-up of osteoporotic hip and pelvic bone fractures between the teriparatide and control groups was the primary outcome. Treatment failure was defined as non-union, varus collapse of the proximal fragment, perforation of the lag screw, and any revision in cases due to mechanical failure of the implant during the follow-up period. The number of treatment failures in the teriparatide and placebo groups were 11.0% (n=20 out of 181) and 17.6% (n=36 out of 205), respectively. Although the rate of treatment failure in the teriparatide group was lower than that in the control group, this difference was not significant (odds ratio, 0.81 [95% confidence interval, 0.42–1.53]; P=0.16; I2=42%). This meta-analysis did not identify any significant differences in the rate of treatment failure between the teriparatide and control groups at final follow-up. Based on these results, we believe that there is a lack of evidence to confirm efficacy of teriparatide in reducing treatment failures in osteoporotic hip and pelvic bone fractures.

Economic Burden Increased with Number of Treatment Failures in Migraine Patients - A Retrospective Claims Database Analysis in the United States (1485)

Economic Burden Increased with Number of Treatment Failures in Migraine Patients - A Retrospective Claims Database Analysis in the United States (1485)

Prospective, Randomized, Phase II, Non-Inferiority Study to Evaluate the Safety and Efficacy of Topical Thrombin (Human) Grifols as Adjunct to Hemostasis During Vascular, Hepatic, Soft Tissue, and Spinal Open Surgery

Thrombin-based formulations have been used for topical hemostasis in surgery for decades. However, the number of randomized clinical trials comparing bovine vs human thrombin is limited. A randomized, double-blind, non-inferiority phase II study evaluated the hemostatic efficacy and safety of plasma-derived topical thrombin (human) Grifols (TTH-Grifols; Instituto Grifols SA) vs bovine THROMBIN JMI (BT-JMI; GenTrac Inc) (2:1 ratio) in vascular, hepatic, soft tissue, and spinal operations. The primary efficacy end point was the percentage of patients achieving hemostasis at target bleeding sites with mild to moderate bleeding (response) within 5 minutes (T5) of treatment application. Non-inferiority was met if the lower limit of the 95% CI of the response ratio of TTH-Grifols relative to BT-JMI by T5 exceeded 0.8. Secondary efficacy variables were the cumulative response by 3 and 4 minutes (T3 and T4), and the number of treatment failures. Safety parameters were assessed. Randomized patients in TTH-Grifols and BT-JMI groups were n= 137 and n= 68, respectively. In modified intention-to-treat population, rates of hemostasis by T5 were 78.3% (94 of 120) in TTH-Grifols and 80.3% (49 of 61) in BT-JMI (response ratio: 0.973; 95% CI 0.833 to 1.135). Rates of hemostasis in vascular, hepatic, soft tissue, and spinal operations ranged from 75.0% to 82.5% for TTH-Grifols and from 54.5% to 91.7% for BT-JMI. No significant differences in adverse events were observed between treatment groups. Antibodies to bovine factor V antigen were detected in 2 patients exposed to BT-JMI and in none exposed to TTH-Grifols. The TTH-Grifols was safe and well tolerated as a local hemostatic agent and was non-inferior to BT-JMI. No antibodies to thrombin developed in TTH-Grifols-treated patients.

Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.

Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure. Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early orstandard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality. We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies. In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Personalized medicine for connective tissue disease: Historical and future perspectives

Abstract Connective tissue disease (CTD), previously termed collagen disease, is a group of disorders, characterized by rheumatic symptoms, autoimmunity, and degeneration of the pathohistology of the extracellular matrix. Better classification and disease subsetting, as well as introduction of immunosuppressants and molecular-targeting drugs, have much improved patients' quality of life and prognosis. The treat-to-target strategy in combination with emphasis on early diagnosis and intervention is now advocated for many CTDs. However, there remains a need to determine the appropriate management for individual patients, as clinical presentation and treatment response are highly variable among patients. A personalized medicine approach based on comprehensive patient profiles can improve patient care and long-term outcomes by decreasing the number of treatment failures, improving drug safety, and reducing the complications and organ damage associated with the disease and its treatment. Tremendous efforts have been made to identify patients who require early aggressive treatment, but the current knowledge on predicting the treatment response to individual drugs is limited. Better coordination between basic and clinical science is the key to providing a basis for tailored approaches for individual patients with CTD.

Intranasal versus intravenous midazolam in control of generalized tonic–clonic seizures in children

Background: Seizures are very common in pediatric patients. As the duration of seizures impacts morbidity and mortality to child’s life, control of seizures should be achieved as early as possible, preferably at home. Intranasal (IN) midazolam is a simple method for control of seizures and can be administered by the parents. Objectives: To study the effectiveness of IN versus intravenous (IV) midazolam in control of generalized tonic–clonic seizures in children between 2 months and 12 years. Materials and Methods: We assessed the efficacy of IN midazolam in comparison with the same drug given by IV route. Neonates, children having partial seizures, and children who got prior medication for the present seizure and seizures that settled spontaneously were excluded from the study. 100 children were enrolled with 50 in each group. The two groups were analyzed for the time taken to control seizures from the time of drug administration. The number of treatment failures, recurrences, and treatment failure of recurrence were noted and compared. Results: The mean time for seizure control, treatment failures, number of recurrences, and treatment failure of recurrences were similar in both groups statistically. Conclusion: IN midazolam and IV midazolam are comparable in efficacy, however, IN midazolam is an easy route of drug delivery to control seizures.

Combined treatment of miltefosine and paromomycin delays the onset of experimental drug resistance in Leishmania infantum.

BackgroundSince miltefosine monotherapy against visceral leishmaniasis (VL) caused by Leishmania donovani has been discontinued in the Indian subcontinent due to an increase in the number of treatment failures, single dose liposomal amphotericin B is now advocated as a treatment option of choice. Paromomycin-miltefosine combination therapy can be used as substitute first-line treatment in regions without cold-chain potential. Previous laboratory studies in the closely related species Leishmania infantum have demonstrated that paromomycin monotherapy fairly rapidly selects for resistance producing a phenotype with increased fitness. Given the possible clinical implications of these findings for the current field situation, the present study aimed to identify the potential hazards of paromomycin-miltefosine combination therapy.Principal findingsDrug interaction studies using the fixed-ratio isobologram method revealed an indifferent interaction between paromomycin and miltefosine. In hamsters infected with L. infantum, the combination resulted in cumulative efficacy in reducing parasite burdens in the liver, spleen and bone marrow. Selected resistant lines against the single drugs did not display cross-resistance. When the intracellular amastigote stage was repeatedly exposed to the paromomycin-miltefosine combination, either in vitro or in vivo, no significant susceptibility decrease towards either drug was noted.ConclusionsThese results suggest that implementation of paromomycin-miltefosine combination therapy indeed could represent a safe and affordable treatment option for L. donovani VL as miltefosine appears to overrule the anticipated rapid development of PMM resistance.

Pharmacogenomic Information In The Treatment Of Major Depression: Results From A Randomized Clinical Trial

Mental disorders are one of the leading causes of disability globally. Inherited genetic variation in pharmacokinetic (PK) and pharmacodynamic (PD) genes may contribute to the observed interindividual differences in clinical efficacy and tolerability of psychopharmaceuticals. Therefore, strategies for improving effectiveness of pharmacological treatments translating pharmacogenomic information from bench to clinic have been recently attempted. However, effectiveness of available psychiatric pharmacogenomic tools in ameliorating clinical symptoms has not been analyzed in populations of suitable size by means of adequately powered multicentric randomized clinical trials.The Neuropharmagen personalized medicine platform integrates pharmacogenomic data from the analysis of PK and PD genes to provide actionable recommendations for psychoactive drugs, including genotype-specific dose adjustments and the risk of specific adverse effects based on FDA-approved drug labelling, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, and meta-analyses of clinical studies. Moreover, within the Neuropharmagen platform, pharmacogenomic recommendations can be complemented combined with alerts on drug-drug, drug-clinical condition and drug-environmental factor interactions. Notably, the later can be updated by the doctor whenever there are changes in the condition of the patient or the pharmacological treatment.Clinical efficacy of the Neuropharmagen test has been evaluated in two multicentric clinical studies totaling 462 patients analyzed for the primary outcome at study endpoint. A retrospective study evaluating patients with different psychiatric diagnoses and at least 1 treatment failure found that patients whose treatment followed the pharmacogenetic (PGx) test recommendations had odds of improvement about 4 times higher than patients whose treatment did not (adjusted OR = 3.86, 95%CI 1.36–10.95; p = 0.011). Recently, we have completed a prospective randomized clinical trial conducted in 316 patients with major depressive disorder with a wide range of depression severities and number of treatment failures. In this talk, I will describe the main results of both studies, with a major focus in those obtained in the multicentric randomized clinical trial. Overall, the combined results of studies conducted with Neuropharmagen show that PGx-guided treatment constitutes a significant tool to improve clinical response and medication tolerability, especially in subjects with moderate to severe depression and in those with previous failed drug trials.

Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial

Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild. Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks. Ixodes AG.

Comparison of two kinds of noninvasive ventilation mode in premature infants with respiratory failure

Objective To investigate the difference of two models of respiratory failure in preterm infants with nasal continuous positive airway pressure(nCPAP) and nasal biphasic positive airway pressure(nBiPAP). Methods Comparative analysis of 81 cases of premature infants with respiratory failure requiring respiratory support was needed.They were applied nCPAP and nBiPAP ventilation mode treatment.The use of breathing machine and total oxygen inhalation time, the number of treatment failures, the PEEP parameters of the ventilator, the total number of recent complications and secondary infections were compared. Results In the nBiPAP treatment group, the average time of noninvasive ventilation was(96.34 ± 31.5)h, the total time of oxygen inhalation was(10.11 ± 9.39)d, 3 cases of treatment failure, the incidence of severe complications was 5.56%(2/36), PEEP(4.08±0.73)cmH2O(1 cmH2O=0.098 kPa). In the nCPAP group, the average time of noninvasive ventilation was(114.14±41.69)h, the total time of oxygen inhalation was(17.53±15.96)d, 15 cases were failed, the incidence of severe complications was 15.56%(7/45), PEEP(5.11±1.01)cmH2O.There were significant differences between the two groups(P 0.05). Conclusion nBiPAP as one of the first choice treatment for premature infants with respiratory failure significantly better than nCPAP, as soon as the proper use can avoid invasive ventilation. Key words: Positive airway pressure; Mechanical ventilation; Preterm infants; Newborn; Respiratory failure

Outcome of second- and third-line Helicobacter pylori eradication therapies based on antimicrobial susceptibility testing.

The objective of this study was to assess the outcome of antimicrobial susceptibility-guided therapies in Helicobacter pylori-infected individuals who had undergone unsuccessful prior eradication treatments. From October 2004 to December 2013, 481 H. pylori-positive patients with prior unsuccessful eradication treatments were administered susceptibility-guided salvage eradication treatments. Six months on, treatment outcome was assessed by urea breath test, stool antigen ELISA, Helicobacter urease test or microbiology and/or histopathology. Resistance to metronidazole and clarithromycin was high in patients with prior unsuccessful eradication treatments and was dependent on the number of treatment failures. Susceptibility-guided salvage eradication treatments achieved eradication rates of nearly 70% in these patients. No particular regimen was significantly better than another. Antimicrobial susceptibility testing prevents prescription of inefficient antimicrobials and enables individualized and promising salvage treatments in patients with prior unsuccessful eradication treatments.

The efficacy of prophylactic antibiotics in the management of children with kerosene-associated pneumonitis: a double-blind randomised controlled trial

Context. Hydrocarbons, especially kerosene (paraffin), are the most common agents causing childhood poisoning in low and middle income countries (LMICs). Aspiration of kerosene causes an inflammatory sterile chemical pneumonitis, which may increase susceptibility to secondary lower respiratory tract bacterial infection. This study aimed to assess the efficacy of prophylactic antibiotics in the management of kerosene-associated pneumonitis in children and to identify risk factors associated with severity or outcome. Methods. A double-blind placebo-controlled trial of prophylactic antibiotics in the management of kerosene-associated pneumonitis of children presenting to a referral hospital was performed from July 2010 to September 2011. Sequential children with a history of kerosene ingestion and mild respiratory illness were randomised to receive placebo or amoxicillin. Each child was followed-up at Day 3 and Day 5 post-ingestion. The primary outcome measure was the number of treatment failures in each group, defined as any child who deteriorated within this time, necessitating a change in treatment regimen. Secondary outcome measures were length of hospital stay and symptoms and signs at follow-up. Results. Seventy-four patients were enrolled. Thirty-five (47%) received placebo and 39 (53%) active treatment. There was no significant difference in treatment failures between placebo (3/35, 9%; 95% CI, 3–22) and active (2/39, 5%; 95% CI, 1–17) groups (relative risk, 0.60; 95% CI, 0.11–3.37). The median length of hospital stay was identical (placebo 0.5 days; IQR, 0–1.0 and active 0.5 days; IQR, 0.5–1.0). Symptoms and signs at Days 3 and 5 post-ingestion were similar. The only significant risk factor for treatment failure was residence in formal housing. Clinical severity at presentation was similar for treatment successes and failures. Conclusion. Prophylactic antibiotics do not improve the outcome in children with mild respiratory illness after kerosene ingestion.