Twice-daily Use Research Articles

Patient-reported barriers for adherence to prophylactic enoxaparin after orthopedic trauma surgery

IntroductionVenous thromboembolism following orthopedic trauma surgery remains prevalent despite prophylaxis being a standard of care. Enoxaparin injection is a commonly utilized prophylaxis regimen among high-risk patients. Patient-reported rates of nonadherence and barriers to enoxaparin use are not described in the literature. A better understanding of these barriers and their impact on adherence to post-discharge prophylaxis regimens may shed light on persistent outcomes gaps. Materials and methodsSemi-structured interviews were administered to adult patients prescribed prophylactic enoxaparin and presenting to orthopedic surgery outpatient clinic at an urban level 1 trauma center for a post-operative appointment following traumatic injury from April to July 2023. Patients self-reported their age, gender, race, and mobility. Inductive thematic analysis with three-reviewer consensus identified common barriers among responses. Adherence rates were calculated by dividing patients’ estimated number of missed doses over total prescribed doses at the point of inquiry. ResultsWe identified 154 eligible patients through chart review, and 50 enrolled and interviewed. Participants had a mean age of 37 years. Of 50 participants, 20 identified as female; 25 identified as Black or African American, 16 as White, 5 as Hispanic, 2 as Asian, and 2 as multiracial. Twenty-one participants were non-ambulatory at time of interview. Mean and median patient-reported adherence were 64.5 % (SD 35.5) and 70.5 % (IQR 33–100) respectively. Five patients reported complete nonadherence, while 17 patients reported perfect adherence. Every participant reporting complete nonadherence identified as Black or African American, as compared to 8 out of 17 reporting perfect adherence. Despite acknowledging a twice-daily prescription, 17 patients reported once-daily rather than twice-daily use. Inductive thematic analysis revealed the following six barriers to prophylaxis adherence (number of participants reporting): Inconvenience (18 patients), Pain (16), Fear (12), Acquisition (7), Bruising (7), and Mechanism (7). Altogether, 40 patients endorsed at least one barrier to adherence. Discussion & conclusionsMost patients face barriers to adherence with post-discharge prophylactic enoxaparin, and the resultant rates of adherence are low. This may contribute to persistent outcomes gaps in the orthopedic trauma population despite prophylaxis standards. Changes in prescribing patterns and patient engagement techniques may improve post-operative thromboembolic outcomes.

Quantitative analysis of the effects of essential oil mouthrinses on clinical plaque microbiome: a parallel-group, randomized trial.

The rich diversity of microorganisms in the oral cavity plays an important role in the maintenance of oral health and development of detrimental oral health conditions. Beyond commonly used qualitative microbiome metrics, such as relative proportions or diversity, both the species-level identification and quantification of bacteria are key to understanding clinical disease associations. This study reports the first-time application of an absolute quantitative microbiome analysis using spiked DNA standards and shotgun metagenome sequencing to assess the efficacy and safety of product intervention on dental plaque microbiome. In this parallel-group, randomized clinical trial, essential oil mouthrinses, including LISTERINE® Cool Mint Antiseptic (LCM), an alcohol-containing prototype mouthrinse (ACPM), and an alcohol-free prototype mouthrinse (AFPM), were compared against a hydroalcohol control rinse on clinical parameters and the oral microbiome of subjects with moderate gingivitis. To enable a sensitive and clinically meaningful measure of bacterial abundances, species were categorized according to their associations with oral conditions based on published literature and quantified using known amounts of spiked DNA standards. Multivariate analysis showed that both LCM and ACPM shifted the dysbiotic microbiome composition of subjects with gingivitis to a healthier state after 4 weeks of twice-daily use, resembling the composition of subjects with clinically healthy oral conditions recruited for observational reference comparison at baseline. The essential oil-containing mouthrinses evaluated in this study showed statistically significant reductions in clinical gingivitis and plaque measurements when compared to the hydroalcohol control rinse after 6 weeks of use. By establishing a novel quantitative method for microbiome analysis, this study sheds light on the mechanisms of LCM mouthrinse efficacy on oral microbial ecology, demonstrating that repeated usage non-selectively resets a gingivitis-like oral microbiome toward that of a healthy oral cavity. The trial was registered on ClinicalTrials.gov on 10/06/2021. The registration number is NCT04921371.

Comparative evaluation of the efficacy of probiotic, Aloe vera, povidine-iodine, and chlorhexidine mouthwashes in the treatment of gingival inflammation: A randomized controlled trial.

Chemical plaque control with mouthwashes as an adjunct to mechanical plaque control with a toothbrush and dental floss has been considered an effective method for controlling gingivitis. The anti-inflammatory effects of chemical plaque control benefit the oral tissues by reducing inflammation and bleeding. The aim of the present study was to evaluate and compare the clinical efficacy of probiotic, Aloe vera, povidine-iodine, and chlorhexidine (CHX) mouthwashes in treating gingivitis patients by assessing changes in their clinical parameters. This prospective study was conducted on 40 patients from our outpatient department, divided into 4 groups of 10 patients each: probiotic mouthwash group (group 1); herbal (Aloe vera) mouthwash group (group 2); povidone-iodine mouthwash group (group 3); and CHX mouthwash group (group 4). All participants were provided with the same type of manual toothbrush, the Pepsodent® toothpaste and a respective mouthwash for twice-daily use until the end of a 28-day observation period. Clinical parameters, such as the marginal plaque index (MPI) and bleeding on interdental brushing (BOIB), were recorded at baseline, and on the 14th and 28th day of the study period. All groups showed a significant decrease in the MPI and BOIB scores. The results were similar in patients who used a probiotic mouthwash and those who used a CHX mouthwash. A comparable change in the mean scores was observed among the herbal and povidone-iodine groups from baseline to day 28. In the treatment of chronic gingivitis patients,a probiotic mouthwash was nearly as effective as CHX in reducing the plaque and bleeding scores. It showed better results in all clinical parameters than herbal and povidone-iodine mouthwashes. Using a mouthwash along with routine tooth brushing can help in treating gingivitis and slow the progression of the periodontal disease.

Efficacy of an experimental toothpaste containing sodium bicarbonate, sodium hyaluronate and sodium fluoride on gingivitis

BackgroundGingivitis is driven by plaque accumulation and, if left untreated, can progress to irreversible periodontitis. For many, the mechanical action of toothbrushing does not achieve adequate plaque control. The aim of this study was to investigate whether twice-daily use of a toothpaste containing 0.2% high molecular weight (HMW) sodium hyaluronate with 67% sodium bicarbonate and 0.221% sodium fluoride (experimental toothpaste) could improve gingival health compared with a regular fluoride toothpaste (negative control). The study also assessed whether the experimental toothpaste could provide additive gingival health benefit over a toothpaste containing only 67% sodium bicarbonate and 0.221% sodium fluoride (positive control).MethodsThis was a single-center, examiner-blinded, randomized, clinical study in healthy adults with mild-to-moderate gingivitis. At baseline, after abstaining from toothbrushing for 12 h, prospective participants underwent oral soft tissue (OST) and oral hard tissue examination followed by assessments for gingival inflammation (Modified Gingival Index [MGI]), gingival bleeding (Bleeding Index [BI]), and supra-gingival plaque (Turesky Plaque Index [TPI]). Eligible participants were stratified by gender and baseline number of bleeding sites (low: <45; high: ≥45 bleeding sites). Following randomization, participants underwent prophylactic dental treatment. Participants received a full OST examination, MGI, BI and TPI assessments after 3 days, 1, 2 and 6 weeks of product use.ResultsIn total, 110 participants were screened for study entry and all were randomized to receive one of three toothpastes (experimental: sodium hyaluronate, sodium bicarbonate, sodium fluoride; positive control: sodium bicarbonate, sodium fluoride; negative control: regular fluoride toothpaste). For all measures, significant improvements were observed in participants receiving either sodium bicarbonate-containing toothpaste (experimental or positive control) compared with the regular fluoride toothpaste (negative control) at week 6. No significant difference was observed in any assessment or visit comparing the experimental toothpaste with the positive control.ConclusionsBoth the experimental and the positive control toothpastes demonstrated clinically relevant improvements in gingival health compared with a regular fluoride toothpaste (negative control). However, no additional gingival health improvement was observed for the experimental toothpaste compared with the positive control, therefore, no additional gingival health benefit can be attributed to the inclusion of sodium hyaluronate in this formulation.Trial registrationClinicalTrials.gov Identifier: NCT04737538 (04/02/2021).

Aesthetic Efficacy of a Novel Topical Combination Brightening Regimen to Treat Facial Hyperpigmentation

Purpose: Hyperpigmentation is a multifaceted condition that is often challenging to treat. Due to this complexity, a combination therapy providing a holistic approach of removal and prevention of pigmentation has shown greater efficacy than a monotherapy treatment. A clinical usage study was conducted to assess the cosmetic changes of a combination take-home skincare topical regimen of a novel brightening platform in subjects with mild to severe facial hyperpigmentation.&#x0D; Procedure: Participants received a take-home multimodal brightening skincare regimen (EC Regimen) that consisted of twice-daily use of EC brightening Pads and EC serum, and once-daily evening use of EC spot cream. Clinical Efficacy and tolerability assessments, and participant self-assessments of facial skin appearance were conducted.&#x0D; Results: Nineteen participants aged 31-69 years, with Fitzpatrick Skin Types I-IV, who self-identified their ethnicity as Asian, White, American Indian, and Hispanic, were included in the study. The EC Regimen provided statistically significant improvements as early as week 1 in Dark Spot Severity and Dark Spot Contrast grades with continued significant improvements through week 12 versus baseline (p&lt;0.01). There were significant improvements in Overall Hyperpigmentation and the validated Modified Melasma Area and Severity Index scores as early as week 2 with continued significant improvements through week 12 versus baseline (p&lt;0.03). Additionally, improvements in a variety of photoaging concerns such as Overall Photodamage, Tactile Roughness, Skin Tone Evenness, Fine and Coarse Lines/Wrinkles and Radiance were observed at all time points.&#x0D; The EC Regimen was highly rated by participants with an overall satisfaction of 94% by week 12. At week 12, participants stated that EC Regimen “faded the dark spots that I have had for more than 5 years” (89%), “helped prevent new dark spots” (94%), and “improved my most stubborn spots that bother me the most” (89%). At week 12, EC Regimen improved quality-of-life parameters and participants stated that EC Regimen “makes me feel happier with how I look” (83%) and “makes me more confident” (83%). EC Regimen was well-tolerated as tolerability assessments remained mild for the duration of the study.&#x0D; Conclusions: Combination therapy of EC Regimen provides a well-tolerated, effective treatment for multiple hyperpigmentation and photoaging parameters with high patient satisfaction.

Relationship between 1-, 3-, and 6-Month Gingival Bleeding Outcomes.

Results from systematic reviews and meta-analyses show generally consistent antigingivitis effects between 3- and 6-mo observation time points with twice-daily use of stannous fluoride (SnF2) dentifrice. However, the relationship between 1-, 3-, and 6-mo gingivitis responses has not been investigated. This pooled analysis was conducted to understand the relationship of 1-, 3-, and 6-mo gingival bleeding outcomes. Number of bleeding sites, derived from Löe-Silness Gingival Index (LSGI) or Gingival Bleeding Index, was identified as the primary end point of the analysis for the biological and clinical relevance. Randomized, double-blinded, controlled clinical studies meeting the following predefined selection criteria were identified: 1) published and unpublished gingivitis clinical trials conducted from 1995 to 2022 comparing efficacy of 0.454% SnF2 dentifrices to negative controls (sodium fluoride or sodium monofluorophosphate dentifrice) and 2) studies with a 3-mo assessment and at least a 1- or 6-mo assessment. The search resulted in ten 6-mo and fourteen 3-mo studies meeting selection criteria. A mixed-effects model was performed on the pooled data to assess gingival bleeding outcomes across time. The bleeding efficacy significantly increased between months 1 and 3 (P < 0.0001) and plateaued between months 3 and 6 (P = 0.007), supporting the fact that bleeding reduction relative to control established by 1 mo will increase and be maintained through 3 and 6 mo (R2 = 0.857). In addition, gingival bleeding and gingivitis efficacy, as measured by LSGI, were found to be highly correlated (R2 = 0.874). A clear relationship has been demonstrated between 1-, 3-, and 6-mo gingival bleeding outcomes in gingivitis clinical studies comparing SnF2 dentifrice to negative control dentifrice. These findings have important implications to the dental practice and scientific research as antigingivitis efficacy evaluations can be observed as early as 1 mo and are consistent with those seen at 3 or 6 mo. Outcomes from this investigation indicate that the clinical evaluation of antigingivitis efficacy at 1 mo is predictive of that at 3 and 6 mo, supporting studies of 1-mo duration as a viable method of knowledge acquisition. This more efficient, expedited research design has positive implications for patient care, clinical practice guidelines, protocols, and policies.

The anti-SARS-CoV-2 effect and mechanism of Chiehyuan herbal oral protection solution

The Chiehyuan herbal oral protection solution (GB-2) is a herbal mixture commonly utilized in Taiwan for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per traditional Chinese medicine practices. This study assessed the clinical impact of GB-2 through prospective clinical trials. With twice-daily use for a week, GB-2 was shown to diminish the expression of angiotensin-converting enzyme 2 (ACE2) in oral mucosal cells. Moreover, after two weeks of use, it could reduce transmembrane protease, serine 2 (TMRPSS2) expression in these cells. Additionally, in vitro experiments demonstrated that GB-2 lessened the entry efficiency of the Omicron, L452R–D614G, T478K–D614G, and L452R–T478K–D614G variants of the SARS-CoV-2 pseudotyped lentivirus. It also impeded the interaction between ACE2 and the receptor-binding domain (RBD) presenting N501Y–K417N–E484A–G339D–Q493R–G496S–Q498R and L452R–T478K mutations. Glycyrrhizic acid, a major compound in GB-2, also hindered the entry of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus by obstructing the binding between ACE2 and the RBD presenting the N501Y–K417N–E484A–G339D–Q493R–G496S–Q498R mutation. To sum up, these findings suggest that GB-2 can decrease ACE2 and TMPRSS2 expression in oral mucosal cells. Both glycyrrhizic acid and GB-2 were found to reduce the entry efficiency of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus and block the binding between ACE2 and the RBD with the N501Y–K417N–E484A–G339D–Q493R–G496S–Q498R mutation. This evidence implies that GB-2 might be a potential candidate for further study as a preventative measure against SARS-CoV-2 infection.

PA14 Aquagenic palmar wrinkling in a 15-year-old swimmer

Abstract A 15-year-old girl presented with a 1-year history of recurrent palmar wrinkling on contact with water. This was associated with a burning sensation within minutes of water exposure and progressive persistent thickening of the palmar skin. She was otherwise well, with no family history of note, including cystic fibrosis (CF). She had no regular medication or newly introduced medications before the onset of wrinkling. Moderate improvement in hyperkeratosis was seen with twice-daily use of urea 10% and salicylic acid 10% creams; however, the discomfort experienced in water was negatively affecting her ability to continue competitive swimming. On examination, there was palmar hyperlinearity with focal hyperkeratosis over the thenar and hypothenar eminences. Immersion of the hands in lukewarm water resulted in wrinkling within 2 min and peaking at 3 min, at which point the patient reported a burning sensation. Wrinkling resolved within 30 min of drying her hands. Baseline laboratory investigations were normal. Biopsy of the palm in the wrinkled state showed subtle prominence and dilation of sweat gland ducts. A diagnosis of aquagenic syringeal keratoderma (ASK) was made. At the 3- and 6-month reviews, the patient reported spontaneous resolution of wrinkling on contact with water, which was confirmed clinically. Residual hyperkeratosis had similarly resolved, although subtle palmar hyperlinearity persisted. She was able to resume competitive swimming activities without symptoms. The ASK is a rare condition, classically affecting the palms of young women, in which palmar wrinkling occurs within minutes of immersion in water. It may be asymptomatic or associated with stinging, burning or paraesthesia. Palmar wrinkling typically resolves after drying of the hands without persisting signs. The mechanism for this phenomenon is unclear, with theories including acquired abnormalities in eccrine glands, an underlying primary keratoderma, or potential induction by cyclooxygenase. Aquagenic palmar wrinkling is also recognized in association with CF, both in individuals with the disease and carriers, with more rapid onset of wrinkling in the former. In this case, there was no suggestion of personal or family histories of CF, and hyperkeratosis persisted for months at a time until liberal regular use of keratolytic topical agents was introduced. Hereditary papulotranslucent acrokeratoderma, a differential diagnosis in this case, was considered; however, in this condition once papules and wrinkling appear, they typically remain and are further exacerbated by water exposure. For this patient, a diagnosis of atypical ASK was favoured due to the persisting sequelae, with probable mild atopic dermatitis reflected by palmar hyperlinearity. This case serves to highlight this rare dermatological phenomenon and its impact on a teenage swimmer.

Real-World, Open-Label Study of the Efficacy and Safety of a Novel Serum in Androgenetic Alopecia.

Pattern-type hair loss is a highly prevalent condition affecting the majority of men and women at some point in their lifetime. Although genetics and androgens are instrumental in the pathogenesis of this type of hair loss, it is increasingly recognized that inflammation, stress, and environmental factors play a central role. The few and widely used monotherapies approved by the US Food and Drug Administration, such as minoxidil or finasteride, are not efficacious in all people and cause adverse events that prevent patient compliance. Therefore, new treatments that are easy to use and that holistically address the multi-factorial pathophysiology of pattern-type hair loss are needed. Clinical studies have already demonstrated the safety and efficacy of a plethora of bioactive natural products, such as epigallocatechin gallate (EGCG), Vitis vinifera seed extract, Glycyrrhiza root extract, apigenin, and saw palmetto extract to name a few, in improving hair follicle homeostasis via anti-inflammatory, anti-androgen, anti-microbial, and anti-oxidant action. Here, we present a novel topical serum, REVIVV&reg;, that contains a proprietary blend of phytochemicals designed to stimulate hair growth, reduce shedding, and restore homeostasis to the hair follicle. The serum&rsquo;s safety and efficacy were assessed in 150 participants in a real-world clinical setting. Findings demonstrate that twice-daily use of the serum significantly improves hair growth, and reduces shedding after 8 weeks of use. All participants rated the serum as easy to use and stated plans for continued use. Overall, the topical serum REVIVV&reg; showed evidence of good efficacy related to hair growth and had positive cosmetic properties warranting further evaluation in clinical studies. Rapaport J, Sadgrove NJ, Arruda S, et al. Real-world, open-label study of the efficacy and safety of a novel serum in androgenetic alopecia. J Drugs Dermatol. 2023;22(6):559-564. doi:10.36849/JDD.7403.

Efficacy and safety of topical cyclosporine 0.1% in moderate-to-severe dry eye disease refractory to topical cyclosporine 0.05% regimen.

To evaluate the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) following prior treatment with 0.05% cyclosporine A anionic emulsion (CsA AE) in moderate to severe dry eye disease (DED). We retrospectively identified patients with moderate-to-severe DED who had shown an inadequate response to twice-daily use of topical 0.05% CsA AE but showed a significant improvement after switching to 0.1% CsA CE daily. Dry eye parameters before and after CsA CE were evaluated by tear break-up time (TBUT), corneal fluorescein staining (CFS), cornea sensitivity, Schirmer's test without anesthetics, and Ocular Surface Disease Index questionnaire. Twenty-three patients, including ten patients with Sjogren syndrome and five patients with rheumatoid arthritis, were reviewed. After a 2-month course of treatment with topical 0.1% CsA CE, significant improvements were noted for CFS (P < 0.001), corneal sensitivity (P = 0.008), and TBUT (P = 0.01). Efficacy was similar in the autoimmune versus nonautoimmune group. 39.1% of patients reported treatment-related adverse events, while the majority was transient instillation pain. Visual acuity and intraocular pressure had no significant changes during the study. In patients with moderate to severe DED refractory to 0.05% cyclosporine, shifting to 0.1% cyclosporine showed improvement in objective signs but with lower treatment tolerability in the short term.

Anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time in patients treated with factor Xa inhibitors.

The regimens for factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) vary with venous thromboembolism (VTE) or non-valvular atrial fibrillation (NVAF). The dosage and duration of FXa inhibitor therapy also differ. However, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each FXa inhibitor has not fully been assessed. Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage. Each FXa inhibitor showed various ranges of AXA values, and twice-daily use resulted in higher absolute AXA values than once-daily use. AXA values and PT for 20mg apixaban at both trough and peak times were significantly higher than those for 5mg or 10mg. AXA values for 60mg edoxaban at peak time were significantly higher than those for 15mg or 30mg. AXA values for 30mg of rivaroxaban at both trough and peak times were significantly higher than those for 10mg or 15mg. In a nonlinear regression model of the relationship between AXA and PT or APTT, PT was positively correlated with AXA values for each FXa inhibitor. This study obtained trough and peak levels of AXA, PT, and APTT in patients with VTE or NVAF who were administered apixaban, edoxaban, and rivaroxaban.

A case study investigating the short-term efficacy and tolerability of a daily serum composed from a unique sunflower sprout extract.

Fatigued skin, defined as dehydrated skin with lack of visual facial firmness and dull appearance, can be attributed to intrinsic and extrinsic factors of aging. An anti-aging daily serum (AADS) containing a unique sunflower sprout extract (SSE) was formulated to target fatigued and photodamaged skin. Utilizing both preclinical and clinical testing models, the efficacy of the AADS was investigated to improve fatigued and photodamaged skin. Preclinical studies included in vitro analysis of adenosine triphosphate (ATP) production in fatigued dermal fibroblasts, inhibition of ultraviolet radiation A (UVA) induced advanced glycation end products (AGEs) in keratinocytes, and ex vivo gene expression after incubation with the SSE. An institutional review board (IRB)-approved short-term, 7-day, clinical case study was conducted on 28 female subjects, Fitzpatrick skin type I-IV, aged 30-60 years with moderate overall photodamage and skin fatigue. This was a double-blinded, randomized, controlled, single-center case study testing the AADS alone and in combination with an anti-aging facial moisturizer (AAFM). The SSE boosted intracellular ATP production in fatigued fibroblasts and reduced the formation of AGEs in keratinocytes. The SSE increased expression of genes related to epidermal keratinization and downregulated genes related to inflammation. Statistically significant improvement was found after 7 days of twice-daily use of the AADS alone and in combination with the AAFM. Products were well tolerated and perceived by subjects. Preclinical results combined with the clinical results strongly suggest that the AADS containing the SSE was tolerable and effective in targeting fatigued and photodamaged skin.

A Randomised Clinical Study to Evaluate Efficacy on Gingival Health of 62% and 67% Sodium Bicarbonate Toothpastes.

This randomised, examiner-blind, parallel study compared gingival bleeding and plaque control following 12 weeks' twice-daily use of 67%, 62% or 0% sodium bicarbonate (NaHCO3)-containing toothpastes. Adults with mild-to-moderate gingivitis, ≥ 20 gingival bleeding sites and bleeding after brushing were randomised to toothpastes containing 923 ppm sodium fluoride and either 67% NaHCO3, 62% NaHCO3 + 5% w/w silica, or 0% NaHCO3. Gingival bleeding was assessed with the Saxton and van der Ouderaa Bleeding Index (BI), plaque was assessed with the Turesky modification of the Quigley-Hein Plaque Index (TPI). There were significantly fewer bleeding sites at Week 12 (primary endpoint) for 67% NaHCO3 (n = 110) and 62% NaHCO3 (n = 110) groups compared with the 0% NaHCO3 group (n = 110) (treatment differences: -3.1 [97.5% confidence interval (CI) -5.5, -0.7] P = 0.0068 and -2.4 [-4.8, 0.0] P = 0.0448, respectively). Statistically significant differences were also seen at Week 6 (P = 0.0361 for 67% NaHCO3, P = 0.0044 for 62% NaHCO3 compared to 0% NaHCO3). Compared with the 0% NaHCO3 group, BI was significantly lower in the 67% NaHCO3 group at Weeks 6 and 12 (P = 0.0477 and P = 0.0066, respectively). TPI was significantly lower in the 67% NaHCO3 and 62% NaHCO3 groups at Week 6 (P = 0.0336 and 0.0009, respectively) but not at Week 12. No statistically significant differences were found between the 67% NaHCO3 and 62% NaHCO3 toothpastes for any variable. No treatment-related adverse events were reported. Twice-daily brushing over 12 weeks with toothpastes containing 67% NaHCO3 or 62% NaHCO3 significantly improved plaque control and reduced indices of bleeding in participants with mild-to-moderate gingivitis.

The effect of a toothpaste containing oleanolic acid in reducing plaque and gingivitis: a proof-of-concept randomized trial.

To assess the safety and efficacy of an oleanolic acid (OA)-containing toothpaste in reducing gingival inflammation and plaque in patients with gingivitis. This proof-of-concept parallel, double-blind, randomized controlled clinical trial included 99 patients. Following a 1-week washout, patients were randomized into three groups: OA group (fluoride toothpaste containing 0.1% OA and placebo mouthwash); negative control (fluoride toothpaste and placebo mouthwash); and CHX group (fluoride toothpaste and 0.12% chlorhexidine mouthwash). Patients were clinically assessed at inclusion, pre-washout visit, baseline and after 4days, 1week and 2weeks of twice-daily use of the products. Patients received a diary for documentation of bleeding on brushing and provided unstimulated saliva samples. After two weeks, all groups showed significant reductions in all clinical parameters. The CHX group exhibited significantly greater reductions in gingival index and interproximal gingival index scores at week 2, as compared to patients in the negative control (p=0.04). In contrast, reductions in gingival index scores did not differ between CHX and OA groups and between OA and negative control groups at week 2. The CHX group had significantly greater reductions in plaque index scores at day-4, 1-week and 2-week evaluations, as compared to the negative control and OA groups. The frequency of adverse events was similar among the groups. None of the groups reduced salivary transferrin levels. Finally, the OA group had the lowest percentage of self-reported bleeding events. OA toothpaste failed to provide antiplaque and antigingivitis effects superior to those of a fluoride toothpaste after 2weeks of use.

Protocol for a family-centered behavioral intervention to reduce early childhood caries: the MySmileBuddy program efficacy trial

BackgroundAlthough largely preventable through diet management and topical fluoride use, early childhood caries (ECC) often progresses to severity that necessitates surgical repair. Yet repair often fails to mitigate caries progression. Needed is an effective behavioral intervention to address underlying behavioral causes.MethodsThis randomized controlled trial will evaluate the efficacy of a behaviorally focused, family-centered intervention, the MySmileBuddy Program (MSB Program), to reduce ECC progression in high-risk preschoolers in New York City. Recruitment will target 858 children ages 24–71 months with ECC and their parents from primary care medical and dental clinics. The study aims to assess the MSB Program’s efficacy to: (1) decrease ECC progression measured 12-months post-randomization; and (2) enhance adoption of a low cariogenic diet and twice-daily fluoridated toothpaste use compared to control group. Potential causal pathways (mediators and moderators) will be explored. The MSB Program equips community health workers (CHWs) with an app that facilitates multilevel risk assessment and provides motivational interviewing-based counseling to inform parents about the caries process, develop personalized goals, and create family-level action plans to achieve targeted behaviors. Social support from CHWs (4 interactions during the 6-month intervention, supplemented by up to 4 in-person/remote contacts throughout the 12-month study period, based on need) is bolstered by automated text messages. Participants will be randomized to a Control Group (paper-based educational handout plus toothbrushes and fluoridated toothpaste for the child) or Intervention Group (MSB Program, two tooth-brushing observations with feedback and instruction, and toothbrushes and toothpaste for the entire family). All children will receive visual ICDAS dental examinations and parents will complete study measures at baseline and 12-months. An incentive up to $150 plus round-trip transit cards ($5.50 value) will be provided.DiscussionThis study hypothesizes that the MSB Program can reduce ECC progression in a high-risk population. Sufficient incentives and a focus on establishing rapport between participants and CHWs are anticipated to mitigate recruitment and retention challenges. If successful, this study will advance the long-term goal of reducing pediatric oral health disparities by demonstrating the efficacy of an acceptable and feasible intervention that shifts attention from dental repair to behavioral risk mitigation.Trial registration: Trial registration was completed on 4/13/2021 through the U.S. National Library of Medicine ClinicalTrials.gov website (Identifier: NCT04845594).

A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers

The management of Parkinson's disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complications of therapy in PD. This study evaluated the safety, tolerability, and pharmacokinetics of escalating single and multiple doses of mesdopetam. We conducted a prospective, single‐center, randomized, double‐blind, placebo‐controlled phase I, and first‐in‐human (FIH) study with mesdopetam administered to healthy male subjects. Overall, mesdopetam was well‐tolerated up to a 120 mg single dose and up to 80 mg upon multiple dosing. Adverse events (AEs) were mainly related to the nervous system and were dose‐dependent. No serious adverse events occurred and no AEs led to withdrawal. The results of the single‐ascending‐dose and multiple‐ascending‐dose parts indicated dose‐ and time‐independent pharmacokinetics with rapid absorption and maximum plasma levels that were generally reached within 2 h after dosing. No accumulation was observed upon multiple dosing. It is concluded that mesdopetam was safe and well‐tolerated in healthy male volunteers. Pharmacokinetic analysis indicated rapid absorption and dose‐linear pharmacokinetics of mesdopetam, with a plasma half‐life of around 7 h, upon single and repeated dosing. The pharmacokinetics of mesdopetam supports twice‐daily use in patients.

Clinical outcomes of once-daily darunavir in treatment-experienced patients with darunavir resistance-associated mutations through 48 weeks of treatment.

Darunavir (DRV) is approved for once-daily use in patients with no DRV resistance-associated mutations (RAMs) and twice-daily use in those with DRV RAMs. Several studies suggest that once-daily DRV retains efficacy in the setting of 1-2 DRV RAMs whereas three or more DRV RAMs are needed for DRV resistance. There are few data to support the long-term use of once-daily DRV in patients with DRV RAMs. This observational study evaluated 48-week clinical outcomes of 22 treatment-experienced patients with ≥1 DRV RAMs switched to once-daily DRV between 2014 and 2017. The primary endpoint was HIV-1 RNA <50 copies/ml at week 48. Safety parameters were analyzed throughout the study. The median age of the sample was 53 years, 18 (82%) had baseline HIV-1 RNA <50copies/ml, and the median number of historical DRV RAMs was 2. At week 48, 20 (91%) had HIV-1 RNA < 50copies/ml, and 2 (9%) had HIV-1 RNA of 82 and 59,637copies/ml and reported non-adherence. No adverse drug reactions were observed through week 48. Once-daily DRV maintained virologic control in patients with ≥1 historical DRV RAMs and was safe and well-tolerated. Further data are needed to validate this as a viable treatment option in this population.

Efficacy of an anhydrous stannous fluoride toothpaste for relief of dentine hypersensitivity: A randomized clinical study.

AimTo compare efficacy of an anhydrous 0.454% w/w stannous fluoride/sodium fluoride toothpaste (Test) versus a sodium monofluorophosphate toothpaste (Negative control) and a stannous chloride/sodium fluoride toothpaste (Positive control) for dentine hypersensitivity relief after 8 weeks’ twice‐daily use.Materials and MethodsIn this randomized, examiner‐blind, stratified, parallel study, primary and secondary efficacy variables were mean changes in Schiff score (evaporative [air] sensitivity) and tactile threshold (Yeaple probe), respectively, from baseline to Week 8 between Test (n = 62) and Negative control (n = 62). Test and Positive control (n = 61) comparisons were exploratory objectives.ResultsAll groups significantly improved from baseline on both dentine hypersensitivity measures (p < .0001). Difference between adjusted mean changes from baseline in Schiff sensitivity scores at Week 8 for Test versus Negative control groups was 0.19 (95% CI 0.002, 0.374), in favour of the Negative control (p = .0476; 12.57% difference). Difference in tactile threshold was −7.20 g (95% CI −16.376, 1.975), and this was not statistically significant (p = .3715; −21.83% difference). Test group showed no significant difference versus Positive control for either measure. Toothpastes were generally well tolerated.ConclusionWhile twice‐daily use of Test toothpaste significantly reduced dentine hypersensitivity from baseline, there was no significant advantage over negative or positive controls. Study registration: Clinicaltrials.gov; NCT03310268.

Efficacy of a Hybrid Toothbrush versus Comparative Manual Toothbrush for Plaque Removal - Randomized In-Use Study.

PurposeAn innovative hybrid toothbrush was designed to function either in manual sonic mode or combined mode (manual and sonic). The primary objective was to assess the efficacy of a new hybrid powered toothbrush (PTB) used in combined mode versus a comparative manual toothbrush (MTB) for plaque removal, after 14 days of twice-daily use under normal conditions. The secondary objectives were to evaluate the gingival state, to evaluate the tolerance of the hybrid PTB and to evaluate its acceptability.Materials and MethodsThis study was a monocentric, block-randomized, dual treatment, parallel group, and examiner-blinded trial with before and after evaluation. It was conducted on two groups of 55 subjects presenting a visible plaque accumulation (score ≥2 as measured by the Turesky Modification of the Quigley-Hein Plaque Index (TMQHPI)). On Day 1/Day 8/Day 15, the same investigator conducted blind clinical examinations on each subject and evaluated TMQHPI and Papillary Bleeding Score (PBS). On Day 1, the subjects received either the hybrid PTB or the comparative MTB and used it twice daily under normal conditions of use.ResultsThe hybrid PTB used in its combined mode eliminates dental plaque more efficiently than the comparative MTB, especially in difficult-to-access areas such as posterior and interproximal dental surfaces, while remaining gentle on the gingivae. The PBS was significantly lower with the hybrid toothbrush compared with the reference manual one.ConclusionThe new device confirmed previous findings and should improve oral hygiene following the manufacturer’s instructions. Moreover, the specific design of the toothbrush means that it can be used according to the oral environment conditions and personal feeling.

Effects of a chlorhexidine mouthwash on clinical parameters of gingivitis, dental plaque and oral polymorphonuclear leukocytes [PMN

ObjectiveHistological features of oral inflammation include infiltration of polymorphonuclear leukocytes [PMN], however studies have not examined the effects of interventions mitigating inflammation on oral PMN. Methods: This double-blind clinical study examined the effects of rinsing with mouthwashes formulated with chlorhexidine [CHX], an ingredient widely utilized in the dental clinic in comparison to a control on oral PMN representing a novel measure of inflammation. A concurrent evaluation of dental plaque and gingival inflammation using widely accepted clinical indices was included in the study. The study enrolled adult subjects providing informed consent, met study criteria and registered gingival index scores of 1.0 or more at the screening visit. Subjects [n = 90; age range 19–58 years] completed a washout phase prior to baseline evaluations for PMN and clinical assessments for dental plaque and gingivitis. Treatments [CHX or a control mouthwash] were randomly assigned to subjects for twice-daily use for the next two weeks. Post-treatment evaluations similar to baseline were conducted after one and two week use of assigned treatment. Results: At baseline, no statistically significant differences between treatment groups for PMN or clinical indices for dental plaque or gingivitis were noted. Rinsing with CHX demonstrated significant reductions for PMN and dental plaque, gingivitis in comparison to the control group. After one and two week use of CHX, PMN demonstrated a 35.9% and 54.9% reduction respectively in comparison to the control group representing significant differences [p < 0.05]. At the one and two week post-treatment evaluations, rinsing with CHX demonstrated 15% and 25% reductions in gingivitis respectively and were significantly different from the control [p < 0.05]. Rinsing with CHX also demonstrated significant reductions in dental plaque of 15% and 19% at the one and two-week post-treatment evaluations respectively in comparison to the control [p < 0.05]. The CHX group also demonstrated reductions in interproximal scores and registered the lowest frequency of gingival index or dental plaque scores on all oral surfaces. Conclusions: Results outline an objective approach to evaluate oral inflammation demonstrating a large and sustained reduction in oral PMN by CHX with these outcomes numerically higher than a clinical index evaluating gingivitis.