A Clinical Study on the Efficacy and Tolerability of a New Topical Gel and Toothpaste in Patients with Xerostomia: A Randomized Controlled Trial

Objective: xerostomia is a very common problem in the general population. The objective of this study was to determine the efficacy of a new gel and toothpaste in patients with xerostomia, analyze the role of salivary cytokines as biomarkers of xerostomia and assess the possible changes in salivary cytokines following treatment. Materials and methods: A randomized, controlled double-blind clinical study was carried out in 73 patients with xerostomia divided into two groups: placebo and active treatment (cymenol; tocopheryl acetate; D-panthenol; Aloe barbadensis; citrate tribasic dihydrate; fluoride) with oral gel and toothpaste three times a day for four consecutive weeks. The Thomson Xerostomia Inventory was applied, with the assessment of oral quality of life (OHIP-14) at baseline and after four weeks of application of the product. Sialometry was also performed in both groups, with analysis of the IL-1b, IL-6, IL-8 and TNFa levels in saliva. Results: In the active treatment group, the xerostomia scores decreased significantly at the end of the study versus baseline, from 33.47 to 27.93 (p < 0.001). No significant decrease was recorded in the placebo group (34.5 to 32.75; p = 0.190). There were no adverse effects in either group. Regarding the saliva samples, the active treatment group showed significant differences in IL-6 concentration versus the control group (18.55 pg/mL (8–38.28) and 5.83 pg/mL (1.19–12.04), respectively; p = 0.002). No significant differences in salivary cytokines were observed in either the treatment group or the control group. Conclusions: The use of a new toothpaste and gel developed for patients with xerostomia proved effective, with greater symptom relief than in the placebo group. Further clinical studies involving longer time periods and larger samples are advisable in order to confirm the benefits of the described treatment.

USE OF NON-DRUG METHODS IN THE TREATMENT OF PATIENTS WITH ARTERIAL HYPERTENSION

The aim of the study is to optimize the comprehensive treatment of patients with severe arterial hypertension, through the use of multicomponent rational antihypertensive pharmacotherapy, followed by the use of unloading therapeutic exercises. 32 men with severe arterial hypertension were examined. Initially, a clinical, instrumental and laboratory examination, registration of blood pressure and its 24-hour monitoring were carried out. The average daily systolic (ADBPsyst.) and average daily diastolic (ADBPdiast.) blood pressure were determined. A multicomponent rational antihypertensive pharmacotherapy, according to the clinical recommendations for the treatment of arterial hypertension was selected for all the patients. In at least 3 months after the selection of pharmacotherapy, the patients were divided into two groups, comparable in gender, age, severity of the condition, features of the disease course and medicamentous therapy. Patients of the 1st group (active treatment group) against the background of pharmacotherapy were prescribed unloading therapeutic exercises according to a patented technique. The 2nd group of patients continued to take pharmacotherapy and it was used as a baseline group. The average age in the 1st and 2nd groups was 46,3±6,8 and 43,6±7,2 years, respectively. Patients of the 1st group were prescribed unloading therapeutic exercises and in 3 months in both groups the ADBPsyst. and ADBPdiast. were compared. Initially, there was a significant increase in ADBPsyst. and ADBPdiast. compared to the normal range in both groups. These indicators in both groups differed insignificantly. In 3 months after pharmacotherapy, there was a significant decrease in ADsyst. and ADdiast. in both groups, but these indicators remained elevated and did not reach the target level. Then, in the 1st group, unloading therapeutic exercises were included in the comprehensive treatment. Patients of the 2nd group continued to receive pharmacotherapy. In 3 months after including unloading therapeutic exercises in the 1st group, there was a significant decrease in ADBP (syst. and diast.) not only in comparison with the initial data, but also with the data in 3 months after pharmacotherapy. In the 2nd group, these indicators did not change significantly compared to the three-month data. In 6 months, ADBPsyst. and ADBPdiast. in the 1st group were significantly lower compared to similar indicators in the 2nd group, which proves significant clinical effectiveness of unloading therapeutic exercises in patients of the 1st group. The results obtained confirm that patients with severe arterial hypertension have such types of disorders at the cellular-tissue and microcirculatory level that are not eliminated only by drug therapy. For their high-grade correction, along with multicomponent pharmacotherapy, it is necessary to include unloading therapeutic exercises. To optimize the treatment of severe arterial hypertension against the background of receiving multicomponent antihypertensive pharmacotherapy, it is recommended to include unloading therapeutic exercises in the therapeutic complex.

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer’s Disease Patients

Pathological proteins contributing to Alzheimer’s disease (AD) are known to disrupt normal neuronal functions in the brain, leading to unbalanced neuronal excitatory-inhibitory tone, distorted neuronal synchrony, and network oscillations. However, it has been proposed that abnormalities in neuronal activity directly contribute to the pathogenesis of the disease, and in fact it has been demonstrated that induction of synchronized 40 Hz gamma oscillation of neuronal networks by sensory stimulation reverses AD-related pathological markers in transgenic mice carrying AD-related human pathological genes. Based on these findings, the current study evaluated whether non-invasive sensory stimulation inducing cortical 40 Hz gamma oscillation is clinically beneficial for AD patients. Patients with mild to moderate AD (n = 22) were randomized to active treatment group (n = 14; gamma sensory stimulation therapy) or to sham group (n = 8). Participants in the active treatment group received precisely timed, 40 Hz visual and auditory stimulations during eye-closed condition to induce cortical 40 Hz steady-state oscillations in 1-h daily sessions over a 6-month period. Participants in the sham group were exposed to similar sensory stimulation designed to not evoke cortical 40 Hz steady-state oscillations that are observed in the active treatment patients. During the trial, nighttime activities of the patients were monitored with continuous actigraphy recordings, and their functional abilities were measured by Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scale. Results of this study demonstrated that 1-h daily therapy was well tolerated throughout the 6-month treatment period by all subjects. Patients receiving gamma sensory stimulation showed significantly reduced nighttime active periods, in contrast, to deterioration in sleep quality in sham group patients. Patients in the sham group also showed the expected, significant decline in ADCS-ADL scores, whereas patients in the gamma sensory stimulation group fully maintained their functional abilities over the 6-month period. These findings confirm the safe application of 40 Hz sensory stimulation in AD patients and demonstrate a high adherence to daily treatment. Furthermore, this is the first time that beneficial clinical effects of the therapy are reported, justifying expanded and longer trials to explore additional clinical benefits and disease-modifying properties of gamma sensory stimulation therapy.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT03556280.

Possibilities of using platelet-rich autoplasm in the complex treatment of patients with intrauterine synechiae

Aim. To increase the effectiveness of complex treatment of women with intrauterine synechiae (IS) through intrauterine administration of platelet-rich plasma (PRP). Materials and methods. The authors studied the complex treatment results of 60 women with second and third degree intrauterine synechiae: 20 patients in the active treatment group, after hysteroscopic destruction of intrauterine synechiae, underwent intraoperative subendometrial administration of PRP followed by irrigating the uterine cavity with PRP on the 2nd and 3rd days after the operation, along with complex postoperative treatment (antibacteria and cyclic hormone therapy, physiotherapy); 40 patients in the comparison group underwent only complex postoperative treatment without PRP administration. The authors conducted comparative assessments of menstrual function, endometrial thickness and uterine cavity during check-up hysteroscopy procedure. Results. Two months after the treatment, a statistically more significant increase in the thickness of endometrial tissue was found with the use of PRP compared with patients treated without PRP (p=0.03 and 0.04). Statistically more significant changes in the state of the uterine cavity were revealed when using PRP in the group of patients with the second-degree process severity (p=0.00005), while in patients with the third-degree process severity there were no statistically significant differences identified depending on the method of treatment used. The authors confirm high safety and reliability of the method as well as no adverse reactions to parenteral and intracavitary administration of autologous PRP. Conclusion. The study confirmed applicability and prospects of using PRP as a stage in complex treatment of IS patients.

Modern aspects of complex therapy for recurrent genital herpes

Incidence of reported cases of genital herpes in different countries has increased dramatically during the last years, which is essentially caused by spread of asymptomatic or atypical types of herpes. Frequent relapses of herpes infection are characterized by changes in the immunological status. The authors of presented article analysed the findings of foreign and domestic studies on the treatment of the disease, systematized information about the features of antiviral chemotherapy drugs used in the treat-ment of genital herpes, identified criteria for the efficacy and duration of suppressive therapy, and the feasibility of its combination with courses of immunomodulatory drugs. The article summarizes the authors’ own experience in the treatment of genital herpes in 50 patients, who were randomly divided into 2 groups: (active treatment) group 1 consisted of 25 women who received antiviral (acyclovir and its analogues) and immunomodulatory therapy (aminodihydrophthalasindione sodium, suppositories), (comparison) group 2 consisted of 25 patients who received antiviral therapy only. The following were criteria for the inclusion of patients: genital herpes history, clinical presentation of genital herpes during the prodromal period or exacerbation, and no more than 48 hours after the rash occurred.The results of evaluation of the treatment effectiveness showed that the vesicles disappeared and the crusts formed during aminodihydrophthalasindione sodium therapy in the active treatment group of patients as early as Day 2-5 after starting treatment, while the acute phase of local inflammation in the comparison group was reversed only by Day 4-5. Complete reepitheli-alization occurred in the active treatment and comparison groups by Day 6-7 of the treatment. At the same time, the PCR test did not detect HSV-2 in smears in 24 (96.0%) women in the active treatment group and in 25 (88.0%) women in the comparison group. No one had any fresh rashes in the course of treatment with the drug. In addition, the authors reported prolongation of clinical remission in the active treatment group up to 5 months (up to 55 days on average).As can be seen from the above, the inclusion of immunomodulatory drugs in the combination specific antiviral therapy leads to faster achievement of the clinical effect, allows to reduce frequency of relapses and improves the patients’ quality of life.

Reduction of Pressure Pain Sensitivity as Novel Non-pharmacological Therapeutic Approach to Type 2 Diabetes: A Randomized Trial

BackgroundAutonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism in the mammalian body. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects this convention.ObjectivesThe present study tested the role of cerebral regulation of ANSD as consequence of novel understanding of glucose metabolism and treatment target in type 2 diabetes (T2D), suggested by the claim that the pressure pain sensitivity (PPS) of the chest bone periosteum may be a measure of cerebral ANSD.DesignIn a randomized controlled trial of 144 patients with T2D, we tested the claim that 6 months of this treatment would reduce PPS and improve peripheral glucose metabolism.ResultsIn the active treatment group, mean glycated hemoglobin A1c (HbA1c) declined from 53.8 to 50.5 mmol/mol (intragroup p = 0.001), compared with the change from 53.8 to 53.4 mmol/mol in the control group, with the same level of diabetes treatment but not receiving the active treatment (between group p = 0.036). Mean PPS declined from 76.6 to 56.1 units (p &lt; 0.001) in the active treatment group and from 77.5 to 72.8 units (p = 0.02; between group p &lt; 0.001) in the control group. Changes of PPS and HbA1c were correlated (r = 0.37; p &lt; 0.001).ConclusionWe conclude that the proposed approach to treatment of T2D is a potential supplement to conventional therapy.Clinical Trial Registration:www.clinicaltrials.gov (NCT 03576430).

Effectiveness of chiropractic manipulation versus sham manipulation for recurrent headaches in children aged 7–14 years - a randomised clinical trial

Background To investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in children aged 7–14 with recurrent headaches. Methods Design: A two-arm, single-blind, superiority randomised controlled trial. Setting: One chiropractic clinic and one paediatric specialty practice in Denmark, November 2015 to August 2020. Participants: 199 children aged 7 to 14 years, with at least one episode of headache per week for the previous 6 months and at least one musculoskeletal dysfunction identified. Interventions: All participants received standard oral and written advice to reduce headaches. In addition, children in the active treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a period of 4 months. Number and frequency of treatments were based on the chiropractor’s individual evaluation in the active treatment group; the children in the control group received approximately eight visits during the treatment period. Primary outcome measures: ‘Number of days with headache’, ‘pain intensity’ and ‘medication’ were reported weekly by text messages, and global perceived effect by text message after 4 months. A planned fixed sequence strategy based on an initial outcome data analysis was used to prioritize outcomes. ‘Number of days with headache’ and ‘pain intensity’ were chosen as equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for the first two outcomes was fixed to 0.025 to take multiplicity into account. Results Chiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p = 0.019, NNT = 7 for 20% improvement) and better global perceived effect (dichotomized into improved/not improved, OR = 2.8 (95% CI: 1.5–5.3), NNT = 5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use. Conclusions Chiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor side effects. It did not lower the intensity of the headaches. Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered as a valuable treatment option for children with recurrent headaches. Trial registration ClinicalTrials.gov, identifier NCT02684916, registered 02/18/2016 – retrospectively registered.

Effectiveness of chiropractic manipulation versus sham manipulation for recurrent headaches in children aged 7-14 years. A randomised clinical trial

Background: To investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in children aged 7-14 with recurrent headaches. Methods: Design: A two-arm , single - blind, superiority randomised superiority single-blinded clinical controlled trial. Setting: One chiropractic clinic and one paediatric specialty practice in Denmark Participants : 199 children aged 7 to 14 years, who experienced at least one episode of headache per week for the previous 6 months and with at least one musculoskeletal dysfunction identified. Interventions: All participants and parents received standard oral and written advice to reduce headaches. In addition, children in the active treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a period of 4 months. The n N umber and frequency of treatments were based on the chiropractor’s individual evaluation in the active treatment group, and the children in the control group received approximately eight visits during the treatment period. Primary outcome measures: ‘Number of days with headache’, ‘pain intensity’ and ‘medication’ were reported weekly by text messages, and global perceived effect by text message after 4 months. A planned fixed sequence strategy based on an initial outcome data analysis was used to prioritize outcomes. ‘Number of days with headache’ and ‘pain intensity’ were chosen as equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for the first two outcomes was fixed to 0.025 to take multiplicity into account. Results: Chiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p=0.019, NNT=7 for 20% improvement ) and better global perceived effect ( dichotomized into improved/not improved, OR= 2.8 (95% CI: 1.5-5.3) 2.63 vs. 3.24 , p<0.001 , NNT=5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use. Conclusions: Chiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor side effects. It did not lower the intensity of the headaches. Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered as a valuable treatment option for children with recurrent headaches.

A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered.

Effectiveness of chiropractic manipulation versus sham manipulation for recurrent headaches in children aged 7-14 years. A randomised clinical trial

Background To investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in children aged 7-14 with recurrent headaches.Methods Design: A two-arm, single-blind, superiority randomised controlled trial.Setting: One chiropractic clinic and one paediatric specialty practice in Denmark Participants: 199 children aged 7 to 14 years, who experienced at least one episode of headache per week for the previous 6 months and with at least one musculoskeletal dysfunction identified. Interventions: All participants and parents received standard oral and written advice to reduce headaches. In addition, children in the active treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a period of 4 months. Number and frequency of treatments were based on the chiropractor’s individual evaluation in the active treatment group, and the children in the control group received approximately eight visits during the treatment period.Primary outcome measures: ‘Number of days with headache’, ‘pain intensity’ and ‘medication’ were reported weekly by text messages, and global perceived effect by text message after 4 months. A planned fixed sequence strategy based on an initial outcome data analysis was used to prioritize outcomes. ‘Number of days with headache’ and ‘pain intensity’ were chosen as equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for the first two outcomes was fixed to 0.025 to take multiplicity into account.Results Chiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p=0.019, NNT=7 for 20% improvement) and better global perceived effect (dichotomized into improved/not improved, OR=2.8 (95% CI: 1.5-5.3), NNT=5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use.Conclusions Chiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor side effects. It did not lower the intensity of the headaches.Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered as a valuable treatment option for children with recurrent headaches.Trial registration ClinicalTrials.gov, identifier NCT02684916, registered 02/18/2016 – retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02684916