Assessing the risk factors for myocardial infarction in diet-induced prediabetes: myocardial tissue changes.

BACKGROUND: Hyperglycaemia is known to result in oxidative stress tissue injury and dysfunction. Interestingly, studies have reported hepatic and renal oxidative stress injury during prediabetes; however, any injury to the myocardium during prediabetes has not been investigated. Hence this study aims to assess changes in the myocardial tissue in an HFHC diet-induced model of prediabetes. METHODS: Male Sprague Dawley rats were randomly grouped into non-prediabetes and prediabetes (n = 6 in each group) and consumed a standard rat chow or fed a high-fat-high-carbohydrate diet respectively for a 20-week prediabetes induction period. Post induction, prediabetes was confirmed using the ADA criteria. Aldose reductase, NADH oxidase 1, superoxide dismutase, glutathione peroxide, cardiac troponins were analysed in cardiac tissue homogenate using specific ELISA kits. Lipid peroxidation was estimated by determining the concentration of malondialdehyde in the heart tissue homogenate according to the previously described protocol. Myocardial tissue sections were stained with H&E stain and analysed using Leica microsystem. All data were expressed as means ± SEM. Statistical comparisons were performed with Graph Pad instat Software using the Student's two-sided t-test. Pearson correlation coefficient was calculated to assess the association. Value of p < 0.05 was considered statistically significant. RESULTS: The prediabetes group showed a markedly high oxidative stress as indicated by significantly increased NADH oxidase 1 and malondialdehyde while superoxide dismutase and glutathione peroxide were decreased compared to non-prediabetes group. There was no statistical difference between cardiac troponin I and T in the non-prediabetes and prediabetes groups. Cardiac troponins had a weak positive association with glycated haemoglobin. CONCLUSION: The findings of this study demonstrate that prediabetes is associated with myocardial injury through oxidative stress. Future studies are to investigate cardiac contractile function and include more cardiac biomarkers.

Clinical Testing of Walking Bleach, In-Office, and Combined Bleaching of Endodontically Treated Teeth.

Objective. The causes of internal posteruptive discoloration of teeth are bleeding, necroses, infections, and endodontic filling materials. The aim of this study was to establish the results of bleaching endodontically treated teeth using walking bleach, in-office, and combined techniques, using 30% carbamide peroxide and 35% hydrogen peroxide, as well as the effect of etiological factors, and the time elapsed after endodontic treatment on the success of bleaching. Materials and Methods. The research involved 30 endodontically treated teeth in healthy patients. Retroalveolar X-rays were taken to check the quality of root canal obturation. Endodontic treatment and obturation were carried out on the discolored non-vital teeth without any previous endodontic treatment. Before bleaching, two millimeters of the filling were removed from the root canal and the very entry into the canal was protected with glass ionomer cement. The teeth were divided into three groups, depending on the bleaching technique: walking bleach technique (10 patients), in-office technique (10 patients), and combined technique (10 patients). The teeth were bleached with 30% carbamide peroxide and 35% hydrogen peroxide. The bleaching procedure was repeated in all the patients three times. The color of all teeth was determined based on the Vita Classic guide before and after bleaching. The Χ2 square and Kruskal−Wallis tests were used to identify differences in teeth bleaching results. Results. A statistically significant difference (p < 0.05) was established between bleaching success and the time elapsed after endodontic treatment. There were no statistically significant differences observed between the bleaching success and etiological factors, bleaching techniques, or bleaching agents. Conclusions. The effectiveness of non-vital tooth bleaching is affected by the time elapsed after endodontic treatment.

Effectiveness and adverse effects of at-home dental bleaching with 37% versus 10% carbamide peroxide: A randomized, blind clinical trial.

PURPOSE: The aim of this trial was to evaluate bleaching effectiveness, tooth sensitivity and gingival irritation of whitening patients with 10% versus 37% carbamide peroxide (CP). METHODS: Eighty patients were selected by inclusion and exclusion criteria and randomly allocated into two groups (n = 40): 37% CP and 10% CP. In both groups, patients performed whitening for 3 weeks, 4 h/day for 10% group and 30 min/day for 37% group. Color was evaluated with Vita Classical, Vita Bleachedguide 3D Master and Spectrophotometer Easyshade, at baseline, weekly and 30 days after treatment. Absolute risk and intensity of tooth sensitivity (TS) and gingival irritation (GI) were assessed with numeric rating scale (NRS) and a visual analog scale (VAS). Color changes were compared with t-test for independent samples. TS and GI were evaluated with Fisher's exact tests. Mann-Whitney test was used for NRS, and t-tests for VAS (α = 0.05). RESULTS: The 37% CP group showed faster whitening than 10% group at 1-3 weeks. However, 1 month after conclusion, both groups showed equivalent bleaching (p = 0.06). Regarding sensitivity and gingival irritation, 10% and 37% groups met no significant differences (p > 0.05). CONCLUSION: The use of 37% CP 30 min/day showed equivalent results to 10% 4 h/day. CLINICAL SIGNIFICANCE: The use of 37% carbamide peroxide 30 min/day may decrease the time of tray use in at-home protocol for whitening because it presents equivalent results to 10% carbamide peroxide 4 h/day.

Is it time to reconsider the use of vital teeth bleaching in children and adolescents in Europe?

PURPOSE: The aim of this study was to determine whether carbamide peroxide is effective in bleaching vital permanent teeth in children. METHODS: A literature search was conducted using all keywords relevant to the research subject. The outcome measures were identified as colour change, tooth sensitivity, oral irritation and patient satisfaction. The certainty of evidence for each outcome was assessed using the current GRADE guidelines. RESULTS: Of 115 potentially relevant articles, 112 were excluded, as they did not exclusively involve children, intervention involved additional treatment such as microabrasion or restorative work, or case studies. Patient satisfaction was not assessed in the three articles so no analysis could be made with regards to this outcome. The GRADE assessment showed that all of the three articles demonstrated very low certainty of evidence for the other assessed outcomes. The overall findings from the studies suggest that a 10% carbamide peroxide overnight tray system is effective at bleaching vital permanent teeth in children and associated tooth sensitivity and oral irritation are found to be in a similar range compared to those reported in adult studies. However, due to the very low certainty of the evidence, it is not possible to draw these conclusions. CONCLUSION: Better quality randomised controlled trials are needed to investigate the indication, short and long term effectiveness and side effects of carbamide teeth in vital permanent teeth in children.

A review on dental whitening.

OBJECTIVES: To provide a narrative review on vital dental whitening chemistry, toxicity and safety, vital dental whitening techniques, whitening systems, potential side effects of whitening and cyclic whitening using products with a range of concentrations and pH values. In addition, new developments and recommendations in the field of vital dental whitening will be presented to help clinicians understand the whitening process, its advantages, limitations, and the impact of whitening concentration and pH on enamel providing guidance in tailoring whitening treatments. DATA: Data were gathered using the following keywords: dental whitening, roughness, hardness, sensitivity, hydrogen peroxide, whitening pH, whitening concentration, whitening chemistry, colour, and toxicity. SOURCES: An electronic search was performed using PubMed and Scopus databases. Bibliographic material from papers reviewed was then used to find other relevant publications. CONCLUSIONS: The effectiveness of vital dental whitening depends on many factors, such as the concentration/pH of the whitening agent, application duration, chemical additives, and re-mineralising agents used. Developing new whitening products and technologies such as nano-additives and alternative carrier systems is showing promising results, and might prove efficient in maximising whitening benefits by accelerating the whitening reaction and/or minimising expected reversible/irreversible enamel structural damage.

Liver Enzyme Elevations in Plasmodium falciparum Volunteer Infection Studies: Findings and Recommendations.

Malaria volunteer infection studies (VISs) accelerate new drug and vaccine development. In the induced blood-stage malaria (IBSM) model, volunteers are inoculated with erythrocytes infected with Plasmodium falciparum. Observations of elevated liver enzymes in the IBSM model with new chemical entities (NCEs) promoted an analysis of available data. Data were reviewed from eight IBSM studies of seven different NCEs, plus two studies with the registered antimalarial piperaquine conducted between June 2013 and January 2017 at QIMR Berghofer, Brisbane, Australia. Alanine aminotransferase (ALT) was elevated (> 2.5 times the upper limit of normal [×ULN]) in 20/114 (17.5%) participants. Of these, 8.9% (10/114) had moderate increases (> 2.5-5 × ULN), noted in seven studies of six different NCEs ± piperaquine or piperaquine alone, and 8.9% (10/114) had severe elevations (> 5 × ULN), occurring in six studies of six different NCEs ± piperaquine. Aspartate aminotransferase (AST) was elevated (> 2.5 × ULN) in 11.4% (13/114) of participants, across six of the 10 studies. Bilirubin was > 2 × ULN in one participant. Published data from other VIS models, using sporozoite inoculation by systemic administration or mosquito feeding, also showed moderate/severe liver enzyme elevations. In conclusion, liver enzyme elevations in IBSM studies are most likely multifactorial and could be caused by the model conditions, that is, malaria infection/parasite density and/or effective parasite clearance, or by participant-specific risk factors, acetaminophen administration, or direct hepatotoxicity of the test drug. We make recommendations that may mitigate the risk of liver enzyme elevations in future VISs and propose measures to assist their interpretation, should they occur.

Parenteral nutrition and oxidant stress in the newborn: A narrative review.

There is strong evidence that oxidant molecules from various sources contaminate solutions of parenteral nutrition following interactions between the mixture of nutrients and some of the environmental conditions encountered in clinical practice. The continuous infusion of these organic and nonorganic peroxides provided us with a unique opportunity to study in cells, in vascular and animal models, the mechanisms involved in the deleterious reactions of oxidation in premature infants. Potential clinical impacts of peroxides infused with TPN include: a redox imbalance, vasoactive responses, thrombosis of intravenous catheters, TPN-related hepatobiliary complications, bronchopulmonary dysplasia and mortality. This is a narrative review of published data.

Contact sensitization to hydroperoxides of limonene and linalool: Results of consecutive patch testing and clinical relevance.

BACKGROUND: Hydroperoxides of limonene and linalool are potent sensitizers. OBJECTIVES: To investigate the prevalence of contact allergy to both hydroperoxides of limonene and hydroperoxides of linalool, to report clinical relevance, and to investigate patient demographics. METHODS: A total of 821 patients (35.6% male, mean age 42.4 years ± 17.8 years) were consecutively patch tested with our departmental baseline series and our fragrance series, including hydroperoxides of limonene 0.3% pet. and hydroperoxides of linalool 1.0% pet. The clinical relevance was assessed for all positive reactions. RESULTS: Positive patch test reactions to hydroperoxides of limonene and to hydroperoxides of linalool were observed in 77 patients (9.4%, 95% confidence interval [CI]: 7.4%-11.4%) and in 96 patients (11.7%, 95%CI: 9.5%-13.9%), respectively; 38 of these patients (4.6%, 95%CI: 3.2%-6.0%) reacted to both. Most reactions were considered to be possibly or probably clinically relevant (66.3% and 68.8%, respectively), and a small proportion were deemed to be of certain clinical relevance (18.2% and 19.8%, respectively). CONCLUSION: As compared with previous studies, high numbers of positive reactions to both hydroperoxides of limonene and hydroperoxides of linalool were observed, the majority of which were clinically relevant, supporting their inclusion in the European baseline series.

The Evidence Behind Peroxide in Orthopedic Surgery.

Peroxide is a strong oxidizing agent and disinfectant frequently used in orthopedic surgery. The authors conducted a systematic literature review of peroxide in orthopedic surgery, evaluating use, complications, efficacy, and appropriate concentrations. One hundred seventy-five reports were identified, with 24 being eligible for analysis. Orthopedic surgeons used peroxide for irrigation and bacterial reduction in various procedures. Complications included cytotoxicity, allergic reactions, suture damage, and inflammation. Use of the standard concentration of 3% peroxide and standard time in situ are without evidence. Laboratory studies suggest that diluted concentrations retain the benefit of bacterial decolonization without increasing the risk for complications. [Orthopedics. 2018; 41(6):e756-e764.].

High-concentration carbamide peroxide can reduce the sensitivity caused by in-office tooth bleaching: a single-blinded randomized controlled trial.

Objectives A single-blinded, randomized, parallel clinical trial evaluated the use of 37% carbamide peroxide (CP) on bleaching effectiveness and tooth sensitivity reported by patients undergoing in-office tooth bleaching, in comparison with the results of using 35% hydrogen peroxide. Material and Methods Forty patients were allocated to receive two sessions of in-office tooth bleaching using either 35% hydrogen peroxide (HP) or 37% CP. Each patient's sensitivity level was evaluated during and up to 24 h after bleaching. The effectiveness of the bleaching procedures was evaluated with a spectrophotometer one week after each session and 30 days after the last session. The impact of tooth bleaching on the patients' perceptions regarding smile changes, in addition to the bleaching procedures and their results, were also recorded. Absolute and relative sensitivity risks were calculated. Data on sensitivity level were analyzed using the Mann-Whitney or T-test, and data from the color evaluation were subjected to 2-way repeated measures ANOVA. Results The use of CP reduced the risk and level of tooth sensitivity to values close to zero, whereas the difference between the bleaching agents disappeared after 24 h. An increased bleaching effect was observed for HP, mainly due to an improved reduction of redness and yellowness. Participants perceived improved tooth bleaching for HP and reduced sensitivity for CP, but no differences regarding the comfort of the techniques were noted. Conclusions In our study, 37% CP resulted in reduced tooth sensitivity but decreased the tooth bleaching effectiveness. However, both bleaching agents resulted in high levels of patient satisfaction.

Neurosensory analysis of tooth sensitivity during at-home dental bleaching: a randomized clinical trial.

Objective The objective of this study was to evaluate dental sensitivity using visual analogue scale, a Computerized Visual Analogue Scale (CoVAS) and a neurosensory analyzer (TSA II) during at-home bleaching with 10% carbamide peroxide, with and without potassium oxalate. Materials and Methods Power Bleaching 10% containing potassium oxalate was used on one maxillary hemi-arch of the 25 volunteers, and Opalescence 10% was used on the opposite hemi-arch. Bleaching agents were used daily for 3 weeks. Analysis was performed before treatment, 24 hours later, 7, 14, and 21 days after the start of the treatment, and 7 days after its conclusion. The spontaneous tooth sensitivity was evaluated using the visual analogue scale and the sensitivity caused by a continuous 0°C stimulus was analyzed using CoVAS. The cold sensation threshold was also analyzed using the TSA II. The temperatures obtained were statistically analyzed using ANOVA and Tukey's test (α=5%). Results The data obtained with the other methods were also analyzed. 24 hours, 7 and 14 days before the beginning of the treatment, over 20% of the teeth presented spontaneous sensitivity, the normal condition was restored after the end of the treatment. Regarding the cold sensation temperatures, both products sensitized the teeth (p<0.05) and no differences were detected between the products in each period (p>0.05). In addition, when they were compared using CoVAS, Power Bleaching caused the highest levels of sensitivity in all study periods, with the exception of the 14th day of treatment. Conclusion We concluded that the bleaching treatment sensitized the teeth and the product with potassium oxalate was not able to modulate tooth sensitivity.

Aged coconut oil with a high peroxide value induces oxidative stress and tissue damage in mercury-treated rats.

Background Exposure to mercury (Hg) and the ingestion of peroxidized edible oil represent a health risk. This study evaluated the effects of peroxidized coconut oil (CO) on the liver and kidney of rats treated with Hg. Methods Male albino Wistar rats were administered HgCl2 and CO separately or as a combination for 21 days. The concentrations of glutathione (GSH) and malondialdehyde (MDA), as well as the activities of superoxide dismutase (SOD) and catalase (CAT), which were used as markers of oxidative stress were measured in the liver and kidney homogenates. The activities of gamma glutamyl transferase (γ-GT), lactate dehydrogenase (LDH) as well as the levels of bilirubin and creatinine (CREA) as markers of liver and kidney functions were analyzed in the serum. Results The level of MDA in the kidney and liver homogenates was significantly increased in the HgCl2, CO, and CO+HgCl2 groups when compared to control values (p<0.05). Liver SOD activity and GSH level were increased and CAT activity was decreased, whereas kidney GSH level and SOD activity were decreased and CAT activity was increased in the CO and CO+HgCl2 groups when compared to control values (p<0.05). The increase in CREA and bilirubin levels as well as γ-GT and LDH activities observed in the CO+HgCl2 group when compared to the control values (p<0.05) were associated with pathological changes in both tissues, and were considered to be due to oxidative stress. Conclusions In summary, peroxidized CO and Hg alone or in combination induces oxidative damage in the liver and kidney of rats.

Does the Use of a "Walking Bleaching" Technique Increase Bone Resorption Markers?

OBJECTIVE: This randomized clinical trial evaluated the effect of 35% hydrogen peroxide in comparison with 37% carbamide peroxide in a nonvital bleaching technique of "walking bleaching" (four sessions of treatment) on periodontal markers: nuclear factor kappa B-ligand (RANK-L-process of root resorption marker) and interleukin 1ß (IL-1ß-inflammatory response marker). METHODS AND MATERIALS: Fifty volunteers presenting with discoloration of nonvital teeth and endodontic treatment in good condition participated. Fifty teeth were randomly divided into two study groups according to bleaching gel: HP = 35% hydrogen peroxide (n=25) and 37% carbamide peroxide (n=25). Nonvital bleaching was performed with a walking bleaching technique consisting of four sessions of bleach application. Gingival crevicular fluid samples were taken in order to quantify the RANK-L and IL-1ß levels by enzyme-linked immunosorbent assay. Samples were obtained from six periodontal sites for each bleached tooth: three vestibular and three palatine (mesial, middle, and distal) at seven time periods: baseline, after each of the four sessions of nonvital bleaching, at one week, and at one month after nonvital bleaching. Tooth color variations were analyzed in each session by VITA Bleachedguide 3D-MASTER (ΔSGU). RESULTS: Significant increments in the RANK-L and IL-1ß levels were detected in each evaluated time compared with baseline ( p<0.05); however, no differences were detected between hydrogen peroxide and carbamide peroxide on increments of the biomarkers studied. The change of color was effective for both nonvital bleaching therapies ( p<0.05). CONCLUSIONS: Nonvital bleaching induced a significant increment in the RANK-L and IL-1ß levels in periodontal tissues around bleached, nonvital teeth.

Impact of SMOFLipid on Pulmonary Alveolar Development in Newborn Guinea Pigs.

BACKGROUND: Parenteral nutrition (PN) is associated with bronchopulmonary dysplasia in premature infants. In animals, PN leads to alveolar loss following stimulation of apoptosis by oxidative stress (oxidized redox potential). Peroxides and aldehydes generated in PN can induce hypo-alveolarization. The implication of peroxides, which is reduced by light protection, is demonstrated. The implication of aldehydes from omega-6 fatty acids oxidation is expected. The hypothesis is that composition and light exposure of PN influences bronchopulmonary dysplasia development. Since SMOFLipid (SMOF) contains a lower amount of omega-6 fatty acids than Intralipid (IL), the aim was to compare, the impacts of PN compounded with SMOF or IL, photo-protected or not, on alveolar development. MATERIALS AND METHODS: Three-day-old Guinea pigs received PN, photo-protected or not, made with SMOF or IL through a jugular vein catheter. After 4 days, lungs were sampled for determinations of redox potential of glutathione, apoptosis (caspase-3, caspase-8, and caspase-9) and alveolarization index (histology: number of intercepts/mm). RESULTS: Compared with IL, SMOF induces a greater oxidation of redox potential (-200 ± 1 versus [vs] -205 ± 1 mV), apoptosis (caspase-3: 0.27 ± 0.04 vs 0.16 ± 0.02; caspase-9: 0.47 ± 0.03 vs 0.30 ± 0.03), and a lower alveolarization index (27.2 ± 0.8 vs 30.0 ± 0.9). Photo-protection prevented activation of caspase-9 and was statistically without effect on redox potential, caspase-3, and alveolarization index. CONCLUSION: In our model, SMOF is pro-oxidant and induces hypo-alveolarization following exaggerated apoptosis. These results highlight the need for further studies before introducing SMOFLipid in standard neonatal care.

In vivo tissue distribution and safety of polyacrylic acid-modified titanium peroxide nanoparticles as novel radiosensitizers.

Polyacrylic acid (PAA)-modified titanium peroxide nanoparticles (PAA-TiOx NPs) are promising radiosensitizers. PAA-TiOx NPs were synthesized from commercial TiO2 nanoparticles that were modified with PAA and functionalized by H2O2 treatment. To realize practical clinical uses for PAA-TiOx NPs, their tissue distribution and acute toxicity were evaluated using healthy mice and mice bearing tumors derived from xenografted MIAPaCa-2 human pancreatic cancer cells. Healthy mice were injected with PAA-TiOx NPs at 25 mg/kg body weight via the tail vein, and tumor-bearing mice were injected either into the tumor locally or via the tail vein. The concentration of PAA-TiOx NPs in major organs was determined over time using inductively coupled-plasma atomic emission spectrometry. After 1 h, 12% of the PAA-TiOx NP dose had accumulated in the tumor, and 2.8% of the dose remained after 1 week. Such high accumulation could be associated with enhanced permeability and retention effects of the tumor, as PAA-TiOx NPs are composed of inorganic particles and polymers, without tumor-targeting molecules. The liver accumulated the largest proportion of the injected nanoparticles, up to 42% in tumor-bearing mice. Blood biochemical parameters were also investigated after intravenous injection of PAA-TiOx NPs in healthy mice. PAA-TiOx NPs invoked a slight change in various liver-related biochemical parameters, but no liver injury was observed over the practical dose range. In the future, PAA-TiOx NPs should be modified to prevent accumulation in the liver and minimize risk to patients.

High-concentration carbamide peroxide can reduce the sensitivity caused by in-office tooth bleaching: a single-blinded randomized controlled trial

Abstract Objectives A single-blinded, randomized, parallel clinical trial evaluated the use of 37% carbamide peroxide (CP) on bleaching effectiveness and tooth sensitivity reported by patients undergoing in-office tooth bleaching, in comparison with the results of using 35% hydrogen peroxide. Material and Methods Forty patients were allocated to receive two sessions of in-office tooth bleaching using either 35% hydrogen peroxide (HP) or 37% CP. Each patient's sensitivity level was evaluated during and up to 24 h after bleaching. The effectiveness of the bleaching procedures was evaluated with a spectrophotometer one week after each session and 30 days after the last session. The impact of tooth bleaching on the patients' perceptions regarding smile changes, in addition to the bleaching procedures and their results, were also recorded. Absolute and relative sensitivity risks were calculated. Data on sensitivity level were analyzed using the Mann-Whitney or T-test, and data from the color evaluation were subjected to 2-way repeated measures ANOVA. Results The use of CP reduced the risk and level of tooth sensitivity to values close to zero, whereas the difference between the bleaching agents disappeared after 24 h. An increased bleaching effect was observed for HP, mainly due to an improved reduction of redness and yellowness. Participants perceived improved tooth bleaching for HP and reduced sensitivity for CP, but no differences regarding the comfort of the techniques were noted. Conclusions In our study, 37% CP resulted in reduced tooth sensitivity but decreased the tooth bleaching effectiveness. However, both bleaching agents resulted in high levels of patient satisfaction.

Neurosensory analysis of tooth sensitivity during at-home dental bleaching: a randomized clinical trial

Abstract Objective The objective of this study was to evaluate dental sensitivity using visual analogue scale, a Computerized Visual Analogue Scale (CoVAS) and a neurosensory analyzer (TSA II) during at-home bleaching with 10% carbamide peroxide, with and without potassium oxalate. Materials and Methods Power Bleaching 10% containing potassium oxalate was used on one maxillary hemi-arch of the 25 volunteers, and Opalescence 10% was used on the opposite hemi-arch. Bleaching agents were used daily for 3 weeks. Analysis was performed before treatment, 24 hours later, 7, 14, and 21 days after the start of the treatment, and 7 days after its conclusion. The spontaneous tooth sensitivity was evaluated using the visual analogue scale and the sensitivity caused by a continuous 0°C stimulus was analyzed using CoVAS. The cold sensation threshold was also analyzed using the TSA II. The temperatures obtained were statistically analyzed using ANOVA and Tukey's test (α=5%). Results The data obtained with the other methods were also analyzed. 24 hours, 7 and 14 days before the beginning of the treatment, over 20% of the teeth presented spontaneous sensitivity, the normal condition was restored after the end of the treatment. Regarding the cold sensation temperatures, both products sensitized the teeth (p<0.05) and no differences were detected between the products in each period (p>0.05). In addition, when they were compared using CoVAS, Power Bleaching caused the highest levels of sensitivity in all study periods, with the exception of the 14th day of treatment. Conclusion We concluded that the bleaching treatment sensitized the teeth and the product with potassium oxalate was not able to modulate tooth sensitivity.

Assessment of Efficacy and Safety of Arterolane Maleate-Piperaquine Phosphate Dispersible Tablets in Comparison With Artemether-Lumefantrine Dispersible Tablets in Pediatric Patients With Acute Uncomplicated Plasmodium falciparum Malaria: A Phase 3, Randomized, Multicenter Trial in India and Africa.

BACKGROUND: Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children. METHODS: This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days. RESULTS: The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar. CONCLUSIONS: The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients. CLINICAL TRIALS REGISTRATION: CTRI/2014/07/004764.