A randomized controlled trial to evaluate the effectiveness of a novel mouth rinse in patients with gingivitis.

BACKGROUND: This single-center, randomized controlled trial aimed to determine the effectiveness of a novel, biofilm-disrupting, mouth rinse that combines Cetylpyridinium chloride (CPC) and essential oils in preventing re-accumulation of supragingival plaque and supragingival microbiome in patients with gingivitis after dental prophylaxis. METHODS: One hundred eighteen participants were randomly assigned in a 1:1 ratio to receive twice-daily test mouth rinse (59) or carrier rinse control (59) for 12 weeks after dental prophylaxis. RESULTS: In a per-protocol analysis that included patients who completed the intervention, the treatment group (39) had significantly lower supragingival plaque scores at 6 and 12 weeks compared to the control group (41; p = 0.022). Both groups showed similar improvement in gingivitis score, but neither group had improvement in bleeding score or probing depth. Thirty-eight (29%) patients did not complete the study due to loss of follow-up (17) or early discontinuation of the assigned intervention (21). Microbiome sequencing showed that the treatment rinse significantly depleted abundant and prevalent members of the supragingival plaque microbiome consortium. CONCLUSIONS: Among patients with gingivitis, the novel mouth rinse significantly reduced re-accumulation of supragingival plaque following dental prophylaxis by depleting supragingival plaque microbiome. However, long-term adherence to the rinse may be limited by adverse effects ( ClinicalTrials.gov number, NCT03154021).

Clinical efficacy of scaling and root planing with and without metronidazole on glycemic control: three-arm randomized controlled trial.

BACKGROUND: Treating periodontitis through non-surgical periodontal therapy (NSPT) may improve glycemic control in type-2 Diabetes Mellitus (T2DM) patients. However, the evidence to maintain this improvement beyond four months is insufficient. Hence, this trial was conducted to assess clinical efficacy of NSPT on glycemic control in T2DM patients. METHODS: This three-arm randomized controlled trial recruited 150 known T2DM participants (35-65 years), suffering from moderate to severe periodontitis, having HbA1c level ≥ 6.5% at baseline. Participants were followed up at 3 and 6 months. Intervention for test group-1 included scaling and root planing (SRP) with metronidazole (MET) and oral hygiene instructions (OHI). Test group-2 was intervened with SRP + OHI and control group with OHI only. Stata v. 14 was used to observe inter and intragroup mean changes in glycemic [glycated hemoglobin (HbA1c), fasting blood glucose (FBG)] and periodontal variables [bleeding on probing (BOP), periodontal pocket depth (PPD), clinical attachment loss (CAL)] using ANOVA and RMANOVA. Proportion of change in outcome variable (HbA1c) was assessed between treatment groups using chi-square test. Change was considered significant at p-value ≤ 0.05. RESULTS: A significant reduction was observed in BOP, PPD, CAL, HbA1c and FBG over time [p < 0.05]. Significant reductions were observed in same variables in both test groups in comparison to control arm [p < 0.05]. No change between the two test groups was observed [p > 0.05]. CONCLUSION: Scaling and root planing improves glycemic control of T2DM patients independently of the use of MET. Therefore, SRP after every 6 months may be suggested and included as a part of overall diabetes management for patients suffering from T2DM. Clinical trial registration NCT 03,343,366 [Date of Registration: 17/11/2017].

Effectiveness of adjunctive hyaluronic acid application in coronally advanced flap in Miller class I single gingival recession sites: a randomized controlled clinical trial.

OBJECTIVES: The aim of this randomized controlled clinical trial was to evaluate the possible advantages of adjunctive hyaluronic acid (HA) application in the coronally advanced flap (CAF) procedure in single Miller class I/recession type 1 (RT1) gingival recession treatment. MATERIAL AND METHODS: Thirty patients with one recession were enrolled; 15 were randomly assigned CAF + HA and 15 to CAF alone. The recession reduction (RecRed), clinical attachment level gain (CAL-gain), changes in probing pocket depth (PPD) and in the width of keratinized tissue (KT), complete root coverage (CRC), and mean root coverage (MRC) were calculated after 18 months. Post-operative morbidity (pain intensity, discomfort, and swelling) was recorded 7 days after treatment using visual analogue scale (VAS). RESULTS: After 18 months, RecRed was statistically significantly higher in the test group (2.7 mm [1.0]) than in the control group (1.9 mm [1.0]; p = 0.007). PPD were found to be slightly but statistically significantly increased in both groups. No statistically significant difference was found for KT gain between treatments. CRC was 80% for test and 33.3% for control sites (p < 0.05). A MRC of 93.8 ± 13.0% for test and 73.1 ± 20.8% for control sites was calculated (p < 0.05). The test group reported lower swelling and discomfort values 7-days post-surgery (p < 0.05). Statistically significant difference was not found for pain intensity. CONCLUSIONS: The adjunctive use of HA was effective in obtaining CRC for single Miller class I/RT1 gingival recession sites. CLINICAL RELEVANCE: Adjunctive application of HA in the coronally advanced flap procedure may improve the reduction of the recessions and increase the probability of CRC in Miller class I recessions.

Utility of Coproporphyrin-I Determination in First-in-Human Study for Early Evaluation of OATP1B Inhibitory Potential Based on Investigation of Ensitrelvir, an Oral SARS-CoV-2 3C-Like Protease Inhibitor.

Coproporphyrin-I (CP-I) has been investigated as an endogenous biomarker of organic anion transporting polypeptide (OATP) 1B. Here, we determined the CP-I concentrations in a cocktail drug-drug interaction (DDI) study of ensitrelvir to evaluate the OATP1B inhibitory potential because ensitrelvir had increased plasma concentrations of rosuvastatin in this study, raising concerns about breast cancer resistance protein and OATP1B inhibition. Furthermore, CP-I concentrations were compared between active and placebo groups in a first-in-human (FIH) study of ensitrelvir to verify whether the OATP1B inhibitory potential could be estimated at an early drug development stage. In the cocktail DDI study, CP-I did not differ between with/without administration of ensitrelvir, indicating that ensitrelvir has no OATP1B inhibitory effect. Although there were some individual variabilities in CP-I concentrations among the treatment groups in the FIH study, the normalization of CP-I concentrations with pre-dose values minimized these variabilities, suggesting that this normalized method would be helpful for comparing the CP-I from different participants. Finally, we concluded that CP-I concentrations were not affected by ensitrelvir in the FIH study. These results suggested that the CP-I determination in an FIH study and its normalized method can be useful for an early evaluation of the OATP1B-mediated DDI potential in humans.

A Quantitative Clinical Pharmacology-Based Framework For Model-Informed Vaccine Development.

Historically, vaccine development and dose optimization have followed mostly empirical approaches without clinical pharmacology and model-informed approaches playing a major role, in contrast to conventional drug development. This is attributed to the complex cascade of immunobiological mechanisms associated with vaccines and a lack of quantitative frameworks for extracting dose-exposure-efficacy-toxicity relationships. However, the Covid-19 pandemic highlighted the lack of sufficient immunogenicity due to suboptimal vaccine dosing regimens and the need for well-designed, model-informed clinical trials which enhance the probability of selection of optimal vaccine dosing regimens. In this perspective, we attempt to develop a quantitative clinical pharmacology-based approach that integrates vaccine dose-efficacy-toxicity across various stages of vaccine development into a unified framework that we term as model-informed vaccine dose-optimization and development (MIVD). We highlight scenarios where the adoption of MIVD approaches may have a strategic advantage compared to conventional practices for vaccines.

Modified free gingival graft technique for treatment of gingival recession defects at mandibular incisors: A randomized clinical trial.

BACKGROUND: The aim of this study was to evaluate clinical and patient-reported outcomes following surgical root coverage at RT1 gingival recession defects at mandibular incisors, using either a conventional free gingival graft (FGG) or a modified FGG (ModFGG). METHODS: Total of 30 patients with RT1 gingival recessions at mandibular incisors were enrolled and randomly allocated to either a control (FGG) or test group (ModFGG). Evaluations of clinical changes (recession depth, height of keratinized tissue) and patient satisfaction were performed over a follow-up period of 12 months. Post-surgical changes of keratinized tissue height (shrinkage) were assessed from 1 month and onward. RESULTS: ModFGG resulted in more pronounced root coverage at 1 year compared to FGG (91.8% vs. 60.7%, p < 0.001). Height of keratinized tissue was improved by 4.2 and 2.2 mm (p < 0.001), respectively, with significantly less shrinkage in ModFGG. Post-surgical morbidity was significantly lower for ModFGG at 2 weeks and patient satisfaction was significantly higher 12 months after treatment (9.1 vs. 5.4; p < 0.001). CONCLUSIONS: ModFGG represents a valid approach for the management of RT1 recession defects at mandibular incisors. The technique is superior to traditional FGG in terms of root coverage, the gain of keratinized tissue height, and patient satisfaction.

Volumetric assessment of changes in the alveolar ridge dimension following guided bone regeneration using a combination freeze-dried bone allograft with collagen membrane or novel resorbable scaffold: A prospective two-center clinical trial.

BACKGROUND: The aim of this study was to examine osseous changes following lateral bone augmentation using a novel scaffold (OV) alone and compare it to combination therapy using freeze-dried bone allograft (FDBA) and resorbable collagen membrane (FDBA/CM). METHODS: Thirty patients completed this 9-months prospective two-center cohort clinical trial. Before surgery and 9-months re-entry, linear measurements were performed, and impressions taken. Cone-beam computed tomography (CBCT) were done at baseline and 9 months. DICOM slice data were converted into volumetric images using 3D Slicer. Following 3D volumetric image construction, pre- and post-op Standard Triangle Language files were superimposed and volumetric data were extracted for a 10-mm region of interest. Linear measurements were compared similarly. RESULTS: Baseline clinical parameters were similar in both groups (4.22 and 4.53 mm for OV and FDBA/CM at -2 mm, respectively). Following treatment, vertical distance from the stent had changed minimally (-0.36 and -0.12 mm, respectively). Similarly, lateral bone gain ranged from 0 to 0.4 mm, for both groups. To the contrary, the CBCT measurements showed a significantly greater increase in horizontal width in the control at -2 mm (0.95 ± 0.2 mm) compared with -0.62 mm for the OV (P = 0.000). Similar changes were observed at -5 mm (0.63 and -0.41 mm, respectively, P = 0.01). Sites volume had increased from 266 ± 149 mm3 to 360 ± 138 mm3 (P = 0.001) for FDBA/CM with negligible changes for OV (from 334 to 335 mm3 , P = 0.952). these between-group changes being statistically significant (P = 0.023). CONCLUSION: FDBA/CM yielded better albeit moderate increase in the volume of the edentulous ridge, while OV scaffolds failed to produce similar results.

Repeated delivery of chlorhexidine chips for the treatment of peri-implantitis: A multicenter, randomized, comparative clinical trial.

BACKGROUND: Peri-implantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of peri-implantitis. This study compared the safety and efficacy of chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive treatment to subgingival debridement in patients afflicted with peri-implantitis. METHODS: A multicenter, randomized, single-blind, two-arm, parallel Phase-3 study was conducted. Peri-implantitis patients with implant pocket depths (IPD) of 5-8 mm underwent subgingival implant surface debridement followed by repeated bi-weekly supragingival plaque removal and chlorhexidine chips application (ChxC group) for 12 weeks, or similar therapy but without application of ChxC (control group). All patients were followed for 24 weeks. Plaque and gingival indices were measured at every visit whereas IPD, recession, and bleeding on probing were assessed at 8, 12, 16, 24 week. RESULTS: A total of 290 patients were included: 146 in the ChxC group and 144 in the control. At 24 weeks, a significant reduction in IPD (P = 0.01) was measured in the ChxC group (1.76 ± 1.13 mm) compared with the control group (1.54 ± 1.13 mm). IPD reduction of ≥2 mm was found in 59% and 47.2% of the implants in the ChxC and control groups, respectively (P = 0.03). Changes in gingival recession (0.29 ± 0.68 mm versus 0.15 ± 0.55 mm, P = 0.015) and relative attachment gain (1.47 ± 1.32 mm and 1.39 ± 1.27 mm, P = 0.0017) were significantly larger in the ChxC group. Patients in the ChxC group that were < 65 years exhibited significantly better responses (P < 0.02); likewise, non-smokers had similarly better response (P < 0.02). Both protocols were well tolerated, and no severe treatment-related adverse events were recorded throughout the study. CONCLUSIONS: Patients with peri-implantitis that were treated with an intensive treatment protocol of bi-weekly supragingival plaque removal and local application of chlorhexidine chips had greater mean IPD reduction and greater percentile of sites with IPD reduction of ≥2 mm as compared with bi-weekly supra-gingival plaque removal.

Overview of Humira® Biosimilars: Current European Landscape and Future Implications.

Humira® (adalimumab) by AbbVie has been the top-selling biologic drug product for the last few years - reaching nearly $20 billion in annual sales in 2018. Upon the October 2018 release of four adalimumab biosimilars into the European market, those sales began to shrink. By the end of 2019, the annual sales of Humira®, albeit still high, dipped closer to $19 billion as nearly 35% of European patients had been switched from Humira® to a biosimilar. Diminishing sales are expected to continue as the adoption of adalimumab biosimilars increases in Europe and Humira®'s patent protection is lost in the United States come 2023. In this review we discuss how impactful the availability of biosimilars has been to the European adalimumab market approximately two years after their release. We further analyze the marketed biosimilars with regards to differences in their formulation, delivery devices, biological activity, physicochemical properties, clinical trials data, and current financial foothold. More importantly, though, we highlight how "similar" these biosimilars are to Humira®. In doing so, we seek to educate the public on what they may be able to expect once adalimumab biosimilars enter the United States market in 2023.

Blinding Approaches for Large Clinical Trials Involving Sub-Cutaneous Administration of Biologicals - A CMC Perspective.

A well-controlled clinical trial is one of the critical steps to evaluate the efficacy and safety of novel medicaments. The use of a placebo is employed in several types of clinical trials in order to set a baseline against which the efficacy of the investigational drug is evaluated. An ideal placebo should match the final formulation as close as possible such that the patient/health care providers are unable to identify any difference. This is difficult for high concentration biologic intended for subcutaneous administration, mainly because of their color and viscosity. Currently, the challenge is overcome by using opaque labels or by unblinded pharmacists, both solutions are expensive. The present study provides an efficient alternative where a protein excipient (recombinant albumin) is used to prepare a placebo for biologicals. We have demonstrated that the use of recombinant albumin can match the color of the active when used in the right quantity. The evaluated solution is highly flexible and has the potential to match the color of different biopharmaceuticals at different concentrations/formulations.

Topical Pilocarpine Formulation for Diagnosis of Cystic Fibrosis.

Cystic fibrosis is diagnosed in infants by estimating the levels of chloride ions present in the sweat induced by iontophoresis of pilocarpine solution. Elevated levels of chloride (≥60 mMol/L) in sweat are indicative of cystic fibrosis. However, the iontophoretic method of delivering pilocarpine is cumbersome and usually is associated with several side effects such as skin burn, skin rashes, erythema, and so forth. The objective of this study was therefore to develop a topical formulation that delivers adequate amount of pilocarpine. The drug delivery of formulation was compared with iontophoresis of aqueous solution of pilocarpine nitrate in vitro using porcine skin model. The pilocarpine levels in the skin exposed to topical pilocarpine solution under mild hyperthermia was 152.04 ± 52.23 µg/cm2 after 10 min of application, whereas it was 97.05 ± 27.93 µg/cm2 in the skin after 10 min of iontophoresis. The topical formulation was subjected to clinical evaluation to assess the efficacy of the product to induce sweat production. The average amount of the sweat secreted on application of topical formulation was found to be 77.28 ± 18.97 mg. Based on these results, it was found that the topical formulation was successful in delivering pilocarpine and to stimulate sweat secretion.

Pharmacokinetic Evaluation by Modeling and Simulation Analysis of a Donepezil Patch Formulation in Healthy Male Volunteers.

INTRODUCTION: This study characterized the pharmacokinetics (PKs) of a donepezil patch formulation currently under development, using mixed effect modeling analysis, and explored optimal patch dosing regimens in comparison with the donepezil oral formulation. METHODS: PK data used in this analysis were from 60 healthy Korean male subjects participating in two Phase I studies, where subjects received single or multiple doses of donepezil of 43.75, 87.5, and 175 mg via patches, and 12 of them received a single oral dose of 10 mg of donepezil, followed by a single dose of donepezil via a patch. Donepezil PKs were analyzed by nonlinear mixed effect modeling using NONMEM software. RESULTS: A well-stirred model with two-compartment distribution and delayed absorption was chosen as the best model for the oral formulation. The PKs of donepezil after the patch applications were best described by a two-compartment linear model with zero-order absorption (D2) and absorption delay. The relative bioavailability (BA) of donepezil after the patch application compared with oral dosing was described to be affected by the duration of patch application. CONCLUSION: PK simulations based on the chosen PK models suggested that, overall, donepezil exposure in plasma is similar whether with 10 mg of oral donepezil every 24 h or a 175 mg patch every 72 h, and likewise with 5 mg of oral donepezil every 24 h or an 87.5 mg patch every 72 h.

Immunogenicity of Cas9 Protein.

Clustered regularly interspaced short palindromic repeats (CRISPR) form the adaptive immune system in archaea and bacteria and have been modified for genome engineering in eukaryotic cells. CRISPR systems contain 2 components, a single-guide RNA, which is a short RNA composed of a 20 nucleotide sequence that targets specific sites in the genomic DNA and a scaffold necessary for its binding to the CRISPR-associated endonuclease (Cas9). Because of its high efficiency and accuracy, the CRISPR-Cas9 genome editing based therapies are poised to treat a multitude of human diseases with a promise to target previously "undruggable" proteins. As the first in-body clinical trial with CRISPR-Cas9 is embarked on, the risks associated with administering the genome editing machinery to patients become increasingly relevant. Recent studies have demonstrated an innate and adaptive cellular immune response to Cas9 in mouse models and the presence of anti-Cas9 antibodies and T-cells in human plasma. Pre-existing immunity against therapeutic Cas9 delivery could decrease its efficacy in vivo and may pose significant safety issues. This review focuses on the immunogenicity of the Cas9 protein and summarizes potential approaches to circumvent the problem of immune recognition.

Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial.

INTRODUCTION: The present study aimed to evaluate the effects of flash glucose monitoring (FGM) and conventional self-monitoring of blood glucose (SMBG) on glycemic control in patients with non-insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: In this 24-week, multicenter, open-label, randomized (1:1), parallel-group study, patients with non-insulin-treated type 2 diabetes at five hospitals in Japan were randomly assigned to the FGM (n=49) or SMBG (n=51) groups and were provided each device for 12 weeks. The primary outcome was change in glycated hemoglobin (HbA1c) level, and was compared using analysis of covariance model that included baseline values and group as covariates. RESULTS: Forty-eight participants in the FGM group and 45 in the SMBG group completed the study. The mean HbA1c levels were 7.83% (62.1 mmol/mol) in the FGM group and 7.84% (62.2 mmol/mol) in the SMBG group at baseline, and the values were reduced in both FGM (-0.43% (-4.7 mmol/mol), p<0.001) and SMBG groups (-0.30% (-3.3 mmol/mol), p=0.001) at 12 weeks. On the other hand, HbA1c was significantly decreased from baseline values in the FGM group, but not in the SMBG group at 24 weeks (FGM: -0.46% (-5.0 mmol/mol), p<0.001; SMBG: -0.17% (-1.8 mmol/mol), p=0.124); a significant between-group difference was also observed (difference -0.29% (-3.2 mmol/mol), p=0.022). Diabetes Treatment Satisfaction Questionnaire score was significantly improved, and the mean glucose levels, SD of glucose, mean amplitude of glycemic excursions and time in hyperglycemia were significantly decreased in the FGM group compared with the SMBG group. CONCLUSIONS: Glycemic control was better with FGM than with SMBG after cessation of glucose monitoring in patients with non-insulin-treated type 2 diabetes. TRIAL REGISTRATION NUMBER: UMIN000026452, jRCTs041180082.

The effect of risk communication on periodontal treatment outcomes: A randomized controlled trial.

BACKGROUND: This study determines the effects of a routine assessment (Treatment as Usual, TAU) versus a risk communication intervention (Risk) versus a Goal-Setting, Planning and Self-Monitoring (GPS) intervention on periodontal disease patients' clinical and psychological outcomes. METHODS: In a three-arm randomized controlled trial (RCT; registration: ISRCTN59696243) adults (N = 97) judged to have moderate oral hygiene attended a primary dental care setting for a standard consultation. Intervention participants received an individualized calculation of their periodontal disease risk using only the Previser Risk Calculator (Risk group) or supplemented with a GPS-behavioral intervention (GPS group). Clinical, behavioral and psychological measures were obtained at baseline, 4 and 12 weeks later. RESULTS: Percent plaque reduced significantly (P < 0.05) in intervention groups but not in TAU group. Percent of sites bleeding-on-probing reduced in all groups, but the effect was more pronounced in the intervention groups. Interdental cleaning frequency improved only in the intervention groups (P < 0.05). Brushing frequency and probing depths showed little variation across time/groups. Disease risk and most thoughts about periodontal disease changed across time (P < 0.05). CONCLUSIONS: A simple behavioral intervention using individualized periodontal disease risk communication, with or without GPS, reduced plaque and bleeding and increased interdental cleaning over 12 weeks. This is the first study in the field to show that risk communication and behavioral techniques such as Goal-Setting, Planning and Self-Monitoring can improve periodontal outcomes.

Effect of Overencapsulation on the Disintegration and Dissolution of Licensed Formulations for Blinding in Randomized Controlled Trials.

Overencapsulation is a technique used to conceal tablet products for blinding in randomized controlled trials. A tablet is inserted in an opaque capsule shell with backfill excipient to prevent rattling. Regulatory authorities require evidence that such modification does not materially alter drug release to approve their use in trials. The objective of this study was to assess impact of overencapsulation on disintegration and dissolution of 4 immediate-release drug products (penicillin V, gemfibrozil, ciprofloxacin, and furosemide). Each unmodified tablet was compared to 3 overencapsulated tablets with differing backfill excipient (colloidal silica, lactose monohydrate, or microcrystalline cellulose). All 12 overencapsulated tablets met disintegration and dissolution acceptance criteria. Dissolution acceptance was dependent on apparatus as only 4/12 formulations met specifications using the rotating basket compared to 12/12 using the rotating paddle. Significant differences in release were observed at early time points (T5-T15). No correlation was observed between aqueous solubility and release, although dissolution of the lipophilic drug gemfibrozil was least impacted by overencapsulation. There was evidence that type/quantity of backfill delays release at early time points. These findings indicate that under the specified conditions, overencapsulated formulations of 4 drugs, 1 from each class of the Biopharmaceutics Classification System, met compendial requirements for release testing.

Efficacy and safety of linagliptin in Hispanic/Latino patients with type 2 diabetes mellitus: a pooled analysis from six randomized placebo-controlled phase 3 trials.

OBJECTIVE: The number of individuals diagnosed with type 2 diabetes mellitus is expected to rise disproportionately in Hispanic/Latino populations. We therefore aimed to assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin specifically in Hispanic/Latino patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Data from 745 patients who self-identified their ethnicity as Hispanic or Latino were pooled from six randomized, placebo-controlled phase 3 trials. Participants received linagliptin (5 mg/day) or placebo as monotherapy, or in combination with other oral antidiabetes drugs for 18 or 24 weeks. RESULTS: The placebo-adjusted mean change (95% CI) in glycated hemoglobin from baseline (mean 8.2%) was -0.63% (-0.77 to -0.48; p<0.0001) at week 18, and -0.58% (-0.74 to -0.42; p<0.0001) at week 24. The placebo-adjusted mean change (95% CI) in fasting plasma glucose from baseline was -11.7 mg/dL (-19.3 to -4.0; p=0.0028) at week 18 and -14.1 mg/dL (-22.0 to -6.3; p=0.0004) at week 24. Hypoglycemia incidence was 17.4% with linagliptin and 21% with placebo. In patients not receiving concomitant sulfonylurea, the hypoglycemia incidence was 10.1% with linagliptin and 19.4% with placebo. The overall incidence of adverse events (AEs), drug-related AEs, and serious AEs with linagliptin was similar to placebo (AEs 67.6% vs 68.9%; drug-related AEs 15.1% vs 18.7%; serious AEs 3.6% vs 3.0%). The mean body weight remained unchanged in both groups. CONCLUSIONS: In Hispanic/Latino patients with inadequately controlled type 2 diabetes mellitus, linagliptin provided clinically meaningful improvements in glycemic control without weight gain or increased risk of hypoglycemia.

A equoterapia na reabilitação de indivíduos com paralisia cerebral: uma revisão sistemática de ensaios clínicos / The hippotherapy in the rehabilitation of individuals with cerebral palsy: a systematic review of clinical trials

[{"text": "Introdução: Um dos principais acometimentos crônicos que ocorrem na infância é a Paralisia Cerebral\r\n(PC), que tem como proposta terapêutica de atendimento, entre outras, a terapia assistida com cavalo, que no Brasil\r\nrecebe o nome de Equoterapia. Objetivo: Este estudo se propôs a verificar o papel da Equoterapia na reabilitação\r\nda função motora em indivíduos com paralisia cerebral por meio de uma revisão sistemática de ensaios clínicos.\r\nMétodo: Foram utilizadas as bases PUBMed (MEDLINE), Cochrane, Web of Science, Scielo, EBsco, Scopus,\r\nLilacs e PEDro, incluindo os descritores propostos no MeSH e DeCS associados a uma lista de termos para busca\r\nde ensaios clínicos, disponíveis em língua portuguesa, espanhola e inglesa e sem restrição de ano. Resultados: Foram\r\nincluídos 12 estudos considerados relevantes e que preenchiam os critérios de inclusão. Conclusão: Em relação à\r\nfunção motora de crianças com paralisia cerebral, foram identificados efeitos positivos agudos após uma sessão de\r\nEquoterapia de 8 a 30 minutos e efeitos crônicos após 5 a 12 semanas, com frequência de 1 a 3 vezes semanais e\r\ncom o tempo de 30 a 60 minutos sobre o cavalo. Embora existam mais estudos produzidos recentemente, ainda se\r\nidentifica a necessidade de realização de futuras pesquisas com um maior número de sujeitos e com grupo controle\r\ndivididos de forma randomizada.", "_i": "pt"}, {"text": "Introduction: Cerebral Palsy (PC) is one of the main pediatric chronic affections. Assisted therapy\r\nwith horses is among the therapeutic care proposals, which in Brazil is called Equoterapia. Objective: This study\r\naimed to verify the role of equine therapy in the motor function rehabilitation of individuals with cerebral palsy\r\nthrough a systematic review of clinical trials. Method: PubMed (MEDLINE), Cohrane, Web of Science, Scielo,\r\nEBsco, Scopus, Lilacs and PEDro databases were used, including the descriptors proposed in the MeSH and DeCS\r\nassociated with a list of search terms for clinical trials, available in Portuguese, Spanish and English and without\r\nrestriction of year. Results: We included twelve studies that were considered relevant and fulfilled the inclusion\r\ncriteria. Conclusion: Data show acute positive effects to the motor function of children with cerebral palsy after one\r\n8 to 30 minutes therapy session, and chronic effects after 5 to 12 weeks of 30-60 minutes therapy, 1 to 3 times a\r\nweek. Although there are several recent studies in this field, the subject stills requires more research with a greater\r\nnumber of subjects and a randomized control group.", "_i": "en"}]