Local Side Effects Research Articles

The Effectiveness of the Bacteria Derived Extremolyte Ectoine for the Treatment of Allergic Rhinitis.

Nonpharmacological therapies with a good tolerability and safety profile are of interest to many patients with allergic rhinitis, as a relevant proportion of them have reservations about guideline-concordant pharmacological therapies due to their local irritations and side effects. Ectoine is a bacterial-derived extremolyte with an ability to protect proteins and biological membranes against damage caused by extreme conditions of salinity, drought, irradiation, pH, and temperature. Evidence from preclinical and clinical studies attests its effectiveness in the treatment of several inflammatory diseases, including allergic rhinitis. In this review, we analyzed 14 recent clinical trials investigating ectoine nasal spray in patients with allergic rhinitis and/or conjunctivitis, including sensitive patient groups like children or pregnant women. Some studies investigated monotherapy with ectoine; others investigated combination therapy of ectoine and an antihistamine or a corticosteroid. Analysis of the study results demonstrated that patients with mild-to-moderate symptoms of allergic rhinitis can be successfully treated with ectoine-containing nasal spray. When applied as monotherapy, ectoine exerted noninferior effects compared to first-line therapies such as antihistamines and cromoglicic acid. Using ectoine as an add-on therapy to antihistamines or intranasal glucocorticosteroids accelerated symptom relief by days and improved the level of symptom relief. Importantly, concomitant treatment with ectoine was proven beneficial in a group of difficult-to-treat patients suffering from moderate-to-severe rhinitis symptoms. Taken together, the natural substance ectoine represents a viable alternative for allergic rhinitis and conjunctivitis patients who wish to avoid local reactions and side effects associated with pharmacological therapies.

Ketoconazole-p aminobenzoic cocrystal, an improved antimycotic drug formulation, does not induce skin sensitization on the skin of BALBc mice.

Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole and para-amino benzoic acid, named KET-PABA. The aim was to increase bioavailability, biocompatibility, and efficiency of the parent drug-ketoconazole. Based on our previous results showing the cocrystal improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency compared to ketoconazole, the current study investigated the local possible side effects induced on the skin of BALBc mice by the application of KET-PABA cocrystal, in view of a further use as a topically applied antimycotic drug. A specific test (mouse ear-swelling test) was used, combined with the histopathological examination and the measurement of pro and anti-inflammatory cytokines and inflammation mediators. KET-PABA application was safe, without signs of skin sensitization shown by the mouse ear sensitization test, or histopathology. KET-PABA strongly inhibited proinflammatory cytokines such as IL1 α, IL1 β, IL6 and TNF α, and other proinflammatory inducers such as NRF2, compared to vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NF-κB pathway. Overall, KET-PABA application induced no sensitization, moreover, it decreased the skin levels of proinflammatory molecules. The lack of skin sensitization effects on BALBc mice skin along with the inhibition of the proinflammatory markers show a good safety profile for topical applications of KET-PABA and show promise for a further clinical use in the treatment of cutaneous mycosis.

Side Effects Reported by Jordanian Healthcare Workers Who Received COVID-19 Vaccines.

Background Distribution of COVID-19 vaccines has been surrounded by suspicions and rumors making it necessary to provide the public with accurate reports from trustworthy experts such as healthcare professionals. Methods We distributed a questionnaire in Jordan among physicians, dentists and nurses who received a COVID-19 vaccine to explore the side effects (SE) they encountered after the first or the second dose of one of three vaccines namely: AstraZeneca Vaxzevria (AZ), Pfizer-BioNTeck (PB), and SinoPharm (SP) vaccines. Results A total of 409 professionals participated. Approximately 18% and 31% of participants reported no SE after the first dose and second dose, respectively. The remainder had mostly local side effects related to injection site (74%). Systemic side effects in the form of fatigue (52%), myalgia (44%), headache (42%), and fever (35%) prevailed mainly after the first dose. These were significantly associated with AZ vaccine, and age ≤ 45 years (p = 0.000 and 0.01, respectively). No serious SE were reported. Conclusions We can conclude that SE of COVID-19 vaccines distributed in Jordan are within the common range known so far for these vaccines. Further studies are needed to include larger sample size and longer follow-up period to monitor possible serious and long-term SE of the vaccines.

Intradermal tranexamic acid microinjections: a novel treatment option for erythematotelangiectatic rosacea

Treatment options for erythematotelangiectatic rosacea (ETR) are still scarce. Tranexamic acid (TXA) is an antifibrinolytic drug that was recently used for the treatment of ETR. To evaluate the efficacy and safety of intradermal microinjections of TXA for ETR. This was a retrospective study enrolling patients, treated with TXA intradermal microinjections for ETR, from January 2019 to February 2020. Response to treatment was assessed based on subjective symptoms, clinical photographs, and the Investigator Global Assessment of Rosacea Severity Score (IGA-RSS). Six patients were included. The mean number of monthly intradermal TXA microinjections was 5.1±1.3. The mean decrease of IGA-RSS was 2.4±0.5. Local side effects, mainly transient erythema and swelling, were noticed in three cases. No systemic effects were noted. Clinical improvement, in respondent patients, lasted after 3months of follow-up. Intradermal TXA microinjections are a safe and effective treatment option for ETR. The optimal number of monthly sessions has yet to be determined.

Results of the use of low-intensity laser radiation in the treatment of occupational polyneuropathies of the upper extremities

Introduction. Effective therapy of occupational polyneuropathy of the upper extremities is a difficult task, because the characteristic clinical and neurophysiological manifestations of this disease persist for many years even after the termination of contact with the etiological harmful production factor - physical overload. Taking into account the low efficiency of existing treatment methods, as well as the peculiarities of the effect of low-intensity laser therapy (LILT), the task of developing a technique for using LILT for the treatment of patients with professional polyneuropathy and assessing its effectiveness during follow-up is very urgent. The aim of the study was to evaluate the effectiveness of LILT for the treatment of occupational polyneuropathy of the upper extremities. Materials and methods. The results of treatment of 236 patients with an established diagnosis of occupational polyneuropathy of the upper extremities are presented. All patients received usual drug therapy, the treatment of patients of the main group differed from the comparison group in that they were additionally treated with LILT according to the developed method. Results. The effectiveness of the therapy was assessed by studying the dynamics of pain in the hands using a visual pain rating scale, pulse velocity along the sensory fibers of the median and ulnar nerves. Changes in each of these parameters in subgroups were assessed at different stages of follow-up (before and immediately after treatment, after 3 and after 6 months). The division of patients into subgroups was carried out by determining type of the nerve fibers' damage. Conclusion: The developed method of LILT of professional polyneuropathy is simple and convenient for use in clinical practice: it is applicable both in a hospital and on an outpatient basis. After treatment, in patients from the main group, in contrast to the comparison group, there was a statistically significant increase in the parameters of pulse velocity along the sensory fibers of the median and ulnar nerves with a simultaneous decrease in the severity of pain. The effect of LILT in patients from the main group decreased after 6 months, which allows us to recommend such courses of LILT 2 times a year. LILT has a limited list of contraindications and is generally well tolerated by patients with minimal local side effects.

Emulgel for improved topical delivery of Tretinoin: Formulation design and characterization

The chief objective of the present research was to reduce local side effects by reducing the dose, controlling the release, and improving the stability by developing and optimizing tretinoin (TRT)-loaded topical emulgel formulation. TRT emulgel (TE) was prepared and optimized at varying ratios of excipients and using 32 optimal response surface design (ORSD). The TRT emulgel was optimized based on TRT content and in vitro release profile of TRT from formulated emulgel batches. The optimized TRT was characterized for physical properties, pH, viscosity, spreadability, extrudability, photomicroscopy, in vitro anti-acne, in vivo skin irritation, in vivo anti-inflammatory activity, and stability study. The FTIR and DSC analysis revealed the compatibility between TRT and formulation excipients of emulgel. The batch F5 of emulgel formulation displayed maximum drug content (98.69±1.26%), and controlled TRT release (78.27±0.69%). Thus, batch F5 was selected as an optimized batch for further characterization. The photomicroscopic analysis of optimized TE exhibited the presence of spherical globules. The pH and viscosity of optimized TE were found to be 6.20±0.12 and 3240cP respectively. Besides, the optimized TE showed good spreadability and extrudability. The in vitro anti-acne activity against Propionibacterium acne (P. acne) of optimized TE (diameter of zone of inhibition 34.54±0.26mm) was found to be the comparatively same as that of marketed Sotret® gel (diameter of zone of inhibition 36.13±0.43mm). Moreover, no sign of irritation was observed in rats treated with optimized TE indicating the safety of TE. Furthermore, the optimized TE displayed significant (p<0.01) in vivo anti-inflammatory activity when compared to marketed gel. Besides, optimized TE was found to be stable when stored in cool conditions for three months. Thus, the emulgel could be a promising approach for the topical delivery of TRT with improved performance and reduced side effects.

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936–0.954) and 80.2% (95% CI 0.56–0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939–0.997) and second (98.2%; 95% CI 0.980–0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines’ adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma.

To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive.

Spinal Modulation by Dexamethasone Sodium Phosphate, Cyclophosphamide and Miconazole Iontophoresis in Asymptomatic SARS-CoV-2 Patient with Extensive Myelitis

A very rare neurological complication of SARS-CoV-2 infection includes transverse myelitis. I assume a post-infectious etiology in terms of secondary immunogenic overreaction. Iontophoresis is the process of the permeation of ionic (charged) drugs into the body under the influence of electrical current. Besides increasing therapeutic efficiency by, by passing first pass metabolism there are less risks of systemic absorption and undesirable side effects. The study was conducted in a SARS-CoV-2 patient with transverse myelitis, by transdermal application of dexamethasone sodium phosphate, cyclophosphamide and miconazole by iontophoresis at corresponding vertebral levels to look for the neurological outcome who had been unresponsive to intravenous methylprednisolone. With Dexamethasone sodium phosphate and cyclophosphamide iontophoresis there was modulation of the activity of posterior grey column, fasiculus gracilis and corticospinal tracts, and with miconazole iontophoresis I was able to ameliorate the dyesthesias, fasiculations and muscle atrophy probably due to neuromodulation at substantia gelatinosa and lamina IX and remyelination effect. There were no systemic or localized side effects and no adverse effects occurred during the treatment period.

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study

SummaryBackgroundThe Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting.MethodsIn this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m2vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities).FindingsBetween Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days.InterpretationSystemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.FundingZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.

A Quest for a Universal Plasma-Derived Antivenom Against All Elapid Neurotoxic Snake Venoms.

This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the 1980s were of low potency, especially against the elapid venoms. This was thought to be due to the low immunogenicity of the α-neurotoxins, which are the most lethal toxins in these venoms. Comparisons of various α-neurotoxin conjugates and polymers, and also different immunological adjuvants, showed that the adjuvant used is the major determinant in the antibody response in horses. The potent Freund’s adjuvant was not used due to its severe local side-effect in horses. Therefore, a novel immunization protocol termed ‘low dose, low volume multi-site’ was developed for use in horses. This immunization protocol has led to the production of highly potent monospecific antivenoms against several elapid and viperid venoms, and two potent polyspecific antivenoms, one against 4 neurotoxic and another against 3 hematotoxic venoms. The immunization protocol has also led to other improvements in antivenom production including: several fold increases in antiserum potency, a reduction in the time required to reach therapeutically useful antibody titers, a 90% reduction in the amount of venom used, and 100% of the horses responding to the immunization program. This development is partly responsible for significant decrease in the Thailand’s annual snakebite death toll from a few dozens to mostly nil in recent years. Finally, a simple and novel immunization strategy, using a ‘diverse toxin repertoire’ composed of numerous elapid toxin fractions as immunogen, was proposed and tested. This immunization procedure has resulted in the successful production of a widely paraspecific antiserum against at least 36 neurotoxic venoms of 28 species encompassing 10 genera and from 20 countries on four continents, and possibly against all elapid venoms with α-neurotoxins as the lethal toxins. These results indicate that, with optimizations of the composition of the ‘diverse toxin repertoire’, the immunization scheme and antibody fractionation to increase the antivenom neutralizing potency, an effective universal antivenom against the neurotoxic elapid snakes of the world can be produced.

Efficiency of topical rifampin on infection in open neural tube defects: a randomized controlled trial

Objectives Neural tube defects are the second most common congenital malformation in humans. Despite significant decreases in neural tube defects and related mortality and morbidity with recent developments, infections remain an important problem. Research on the role of topical therapy for managing neural tube defects and associated infections in the neonatal period has been limited. This randomized controlled trial aimed to investigate the efficiency of topical Rifampin on infection control in paraplegic newborns with open neural tube defects. Methods Thirty-seven patients who underwent an operation for neural tube defects were included. Topical Rifampin and cefotaxime were administered to 19 patients constituting the case group and local saline and cefotaxime were administered to a control group. Patients were examined for ventriculoperitoneal shunt infection/dysfunction, surgical site infection, urinary tract infection, and sepsis. Results None of the patients using topical rifampin had ventriculoperitoneal shunt infection/dysfunction, surgical site infection, urinary tract infection, or sepsis. In the control group, ventriculoperitoneal shunt infection/dysfunction was found in 4 (22.2%) cases, surgical site infection in 3 (27.7%), urinary tract infection in 3 (27.7%), and sepsis in 5 (27.7%), with statistically significant differences between the groups (p = 0.01, p = 0.032, p = 0.032, and p = 0.002, respectively). No local or systemic side effect was observed regarding rifampin use. Conclusion Topical Rifampin is effective in minimizing complications like sepsis, surgical site infection, urinary tract infection, and ventriculoperitoneal shunt infection due to neural tube defect operations. Further research with larger numbers of cases is needed to implement this practice routinely.

Prevalence of COVID-19 Vaccine Side Effects among Healthcare Workers in the Czech Republic.

Background: COVID-19 vaccine side effects have a fundamental role in public confidence in the vaccine and its uptake process. Thus far, the evidence on vaccine safety has exclusively been obtained from the manufacturer-sponsored studies; therefore, this study was designed to provide independent evidence on Pfizer–BioNTech COVID-19 vaccine side effects. Methods: A cross-sectional survey-based study was carried out between January and February 2021 to collect data on the side effects following the COVID-19 vaccine among healthcare workers in the Czech Republic. The study used a validated questionnaire with twenty-eight multiple-choice items covering the participants’ demographic data, medical anamneses, COVID-19-related anamneses, general, oral, and skin-related side effects. Results: Injection site pain (89.8%), fatigue (62.2%), headache (45.6%), muscle pain (37.1%), and chills (33.9%) were the most commonly reported side effects. All the general side effects were more prevalent among the ≤43-year-old group, and their duration was mainly one day (45.1%) or three days (35.8%) following the vaccine. Antihistamines were the most common drugs associated with side effects, thus requiring further investigation. The people with two doses were generally associated with a higher frequency of side effects. Conclusions: The distribution of side effects among Czech healthcare workers was highly consistent with the manufacturer’s data, especially in terms of their association with the younger age group and the second dose. The overall prevalence of some local and systemic side effects was higher than the manufacturer’s report. Further independent studies on vaccine safety are strongly required to strengthen public confidence in the vaccine.

Comparative Evaluation of Analgesic Efficacy of Adductor Canal Block Versus Intravenous Diclofenac in Patients Undergoing Knee Arthroscopic Surgery.

Background:Adductor canal block is a new and promising approach for providing postoperative pain relief in arthroscopic knee surgery.Aim:The aim is to compare the postoperative analgesic efficacy of adductor canal block and intravenous (i.v.) diclofenac in patients undergoing knee arthroscopic surgeries.Set and Design:This was a prospective, randomized double-blinded comparative study comprising 60 American Society of Anesthesiologists Physical status Classes I and II patients posted for unilateral knee arthroscopic surgery.Materials and Methods:Patients were randomized into two groups of 30 patients each. Patients were given general anaesthesia with fentanyl, propofol, and vecuronium. Ultrasound (USG) guided adductor canal block with 30 ml of 0.5% ropivacaine was given in Group A patients and patients in Group B received i.v. diclofenac before extubation. After adequate recovery, patients were shifted to postanesthetic care unit. Visual Analogue Scale score was assessed at rest, on standing and on walking 3 m.Statistical Analysis:Student's independent t-test was employed for comparing continuous variables. Chi-square test or Fisher's exact test, whichever is appropriate, was applied for comparing categorical variables.Results:The mean duration of analgesia was longer in Group A as compared to Group B and mean consumption of rescue analgesic was lower in Group A. Both were statistically significant. No significant postoperative complications or local side effects related to the block were noted.Conclusions:Adductor canal block provides a longer duration of postoperative analgesia promotes early mobilization and has a good safety profile in unilateral knee arthroscopic surgeries.

Role of Intravesical Granulocyte-Macrophage Colony-Stimulating Factor in Controlling Hemorrhagic Cystitis in Patients Undergoing Stem Cell Transplantation - A Retrospective Cohort Study

Introduction: Hemorrhagic cystitis (HC) is a well-known complication in patients undergoing hematopoeitic stem cell transplantation (HSCT), contributing considerably to morbidity and prolonged hospital stay. Granulocyte-macrophage colony-stimulating factor (GM-CSF) affects the proliferation and differentiation of hematopoietic stem/progenitor cells and the functioning of monocytes, granulocytes, lymphocytes, and endothelial cells. The objective of this study was to evaluate the efficacy and safety of GM-CSF bladder irrigation for HC post-HSCT. Materials and Methods: We conducted a retrospective cohort study to assess the clinical effects of GM-CSF (GM-CSF group) in controlling HC in patients who had undergone HSCT at our institute. We also compared these patients with those who did not receive GM-CSF. Results: There were 12 patients in the GM-CSF group and seven patients in the non-GM-CSF (control) group. The median ages were 16 years (range: 4–33 years) and 19 years (range; 6–41 years), respectively. Median time-to-resolution of HC from day of onset was 9.5 days in the GM-CSF group versus 59 days in the non GM-CSF group (P = 0.001). Mortality was 85% in the control group as compared to 16% in GM-CSF group (P = 0.008). Among the GM-CSF responders, complete response was seen in eight patients (67%). None of the patients developed any systemic or local side effects to GM-CSF. Overall survival in the two groups was 75% and 14%, respectively (P = 0.043). Conclusion: GM-CSF was shown to be effective in controlling HC in post-HSCT patients, without any major side effects, along with decreased mortality and improved overall survival.

Эффективность и безопасность лечения препаратом Фастум® гель у лиц с болью в нижней части спины

Целью исследования было изучение эффективности и безопасности терапии препаратом Фастум® гель у лиц с болью в нижней части спины (БНЧС) на фоне дегенеративно-дистрофических изменений позвоночника. Материалы и методы. Обследованы 24 человека мужского и женского пола в возрасте 50–69 лет с БНЧС продолжительностью более 14 дней с последующим делением на две группы. Группа I — 12 пациентов, получавших кетопрофен в виде аппликаций тонким слоем на поясничную область 2 раза в сутки в течение 10 дней. Группа II — 12 пациентов, которым проводили аппликации вазелина тонким слоем на тот же участок 2 раза в сутки в течение 10 дней. Пациенты применяли исследуемые препараты в качестве монотерапии. Обследование проводили перед началом терапии и на 10-й и 20-й день лечения. Результаты. У пациентов, получавших аппликации кетопрофеном, достоверно снижалась интенсивность боли по четырем составляющим визуально-аналоговой шкалы и опроснику Роланда — Морриса. Вместе с этим достоверно улучшались функциональные возможности согласно результатам теста Шобера (t = 3,54, р = 0,005) и Томайера (t=3,08, р = 0,01). По результатам шкалы EuroQul-5D показатели качества жизни у пациентов, применявших локальную форму кетопрофена, достоверно улучшились на 45 % (t = 4,19, р=0,002), на 39,3 % согласно анкете Освестри через 10 суток лечения (t = 3,9, р = 0,002). 75 % пациентов основной группы и 33,3 % группы сравнения оценили эффективность лечения как высокую согласно индексу Ликерта. В обеих группах не было зарегистрировано ни одного локального и системного побочного эффекта. Выводы. Кетопрофен гель в виде монотерапии достоверно снижал интенсивность болевого синдрома и улучшал функциональные возможности больных с БНЧС. Отсутствие побочных эффектов при лечении препаратом свидетельствует о его высоком профиле безопасности для пациентов.

Optimizing overnight oral appliance for sustained-release varnish delivery system of sirolimus

<h3>Objectives</h3> Intraoral trays can be used to deliver treatment materials and medications for dental or mucosal conditions. Maintaining appropriate salivary levels of the active ingredient is challenging when using local application. We have previously analyzed salivary levels and local effects of slow-release varnishes (with clotrimazole or sirolimus as the active ingredient) during the daytime. The aims of the present study were as follows: (1) to optimize overnight appliances for slow-release medications by measuring saliva and blood levels and (2) to evaluate the safety of overnight use. <h3>Methods</h3> An acrylic tray containing 0.5 mg of sirolimus in a sustained-release varnish was applied to 6 anterior teeth for 12 hours in 10 healthy volunteers. Whole unstimulated saliva was collected 1, 2, 10, and 12 hours after application, and a blood sample was taken after 12 hours. Drug levels were analyzed. Results from slow- and fast-release formulations, varnish application position on the tray (buccal, palatal, or lingual), and tray placement (mandibular vs maxillary) were compared. The volunteers evaluated the varnish and tray. The study was approved the hospital ethics committee. <h3>Results</h3> Salivary sirolimus was undetected with use of the slow formulation. The faster formulation produced salivary concentrations of 0.3-45 ng/mL. The highest salivary levels were observed with a mandibular tray with lingual varnish application (up to 178 ng/mL). The sialometry of all participants was within normal range (0.2-2 mL/min), and the highest drug levels were found when salivary flow was lowest. The medication was undetected in the blood. No local reactions or side effects were reported. <h3>Conclusions</h3> Salivary concentrations of medications delivered using an oral tray can be affected by the release rate of formulation and, more important, by the position of the tray and the varnish within it and salivary flow rate. Overnight oral trays can be used to deliver medications especially when 24-hour drug exposure is desired. Further studies regarding local factors affecting drug release and salivary levels are required.

Medical management of pediculosis palpebrarum

: To know the efficacy of only conservative management without manual removal of adult parasite in treatment of pediculosis palpebrarum.: Seventeen patients with pediculosis palpebrarum underwent health education on personal hygiene, avoid overcrowding, counseling and psychotherapy. Deparasitisation of associated axillary and pubic area with Permethrin 1% cream application two courses at weeks gap. Washing clothes and linen in hot water. Face wash with shampoo lotion and simultaneously rubbing of the eye for 1-2 minutes thrice daily. Topically Antibiotic - steroid drops and ointment thrice daily for 6 weeks. No manual removal of adult parasite, epilation or trimming of the eye lashes was done.: The mean age of patient is 19.5 +/- 13.4 years. Male: Female ratio was 10:7. Mean duration of symptom is 13.+/-6.6 weeks. Commonest presentation was itching in all patients. 82.3% (14/17) patients had bilateral involvement of both upper and lower lids with associated pubic and axillary area infestation. By 1 week all had resolution of symptoms and on 3 week 82.3% (14/17) free from infestation. (3 dropout) only discomfort was transient blurring of vision due to eye ointment.: Conservative management without manual removal of adult parasite is equally effective in treating pediculosis palpebrarum. Acceptable to children, anxious and non cooperative patients. It wiil avoid the discomfort to patients, complications of sedation and local side effects of topical parasiticidal agents. Only side effect was transient blurring of vision due to eye ointment.

In Vitro Cytotoxic Protective Effect of Alginate-Encapsulated Capsaicin Might Improve Skin Side Effects Associated with the Topical Application of Capsaicin.

Chronic neuropathic pain, particularly peripheral pain, is a cause of great concern for diabetic patients. Current treatments include numerous agents such as capsaicinoids, a known deterrent of neuropathic pain despite the inconvenience associated with local side effects. In this context, the current work aims to elucidate the potential mechanisms involved in cytotoxicity by capsaicin and proposes an efficient formulation of capsaicin in alginate microcapsules, which significantly reduces side effects from capsaicin topical administration. For this, human dermal fibroblast cells were treated with alginate-microencapsulated capsaicin extracts and screened for potential cytotoxic effects produced by the treatment. Cell viability and morphology were examined, as well as oxidative stress status and anti-inflammatory potential. Our results show that the alginate encapsulated formulation of capsaicin exerted lower cytotoxic effects on human dermal fibroblasts as measured by cell viability and reactive oxygen species (ROS) production. Furthermore, the expression profiles of inflammatory cytokines were significantly altered by the treatment as compared with the control culture.

The Effectiveness and Safety of Commonly Used Injectates for Ultrasound-Guided Hydrodissection Treatment of Peripheral Nerve Entrapment Syndromes: A Systematic Review.

Background: Peripheral nerve entrapment syndromes commonly result in pain, discomfort, and ensuing sensory and motor impairment. Many conservative measures have been proposed as treatment, local injection being one of those measures. Now with high-resolution ultrasound, anatomical details can be visualized allowing diagnosis and more accurate injection treatment. Ultrasound-guided injection technique using a range of injectates to mechanically release and decompress the entrapped nerves has therefore developed called hydrodissection or perineural injection therapy. Several different injectates from normal saline, local anesthetics, corticosteroids, 5% dextrose in water (D5W), and platelet-rich plasma (PRP) are available and present clinical challenges when selecting agents regarding effectiveness and safety. Aims: To systematically search and summarize the clinical evidence and mechanism of different commonly used injectates for ultrasound-guided hydrodissection entrapment neuropathy treatment. Methods: Four databases, including PubMed, EMBASE, Scopus, and Cochrane were systematically searched from the inception of the database up to August 22, 2020. Studies evaluating the effectiveness and safety of different commonly used injectates for ultrasound-guided hydrodissection entrapment neuropathy treatment were included. Injectate efficacy presents clinical effects on pain intensity, clinical symptoms/function, and physical performance, electrodiagnostic findings, and nerve cross-sectional areas. Safety outcomes and mechanism of action of each injectate were also described. Results: From ten ultrasound-guided hydrodissection studies, nine studies were conducted in carpal tunnel syndrome and one study was performed in ulnar neuropathy at the elbow. All studies compared different interventions with different comparisons. Injectates included normal saline, D5W, corticosteroids, local anesthetics, hyaluronidase, and PRP. Five studies investigated PRP or PRP plus splinting comparisons. Both D5W and PRP showed a consistently favorable outcome than those in the control group or corticosteroids. The improved outcomes were also observed in comparison groups using injections with normal saline, local anesthetics, or corticosteroids, or splinting. No serious adverse events were reported. Local steroid injection side effects were reported in only one study. Conclusion: Ultrasound-guided hydrodissection is a safe and effective treatment for peripheral nerve entrapment. Injectate selection should be considered based on the injectate mechanism, effectiveness, and safety profile.