Long Duration Of Action Research Articles

Extreme dilutions of mercuric chloride produce longer binding interaction with ?-amylase as compared to blank solvents

Background
 High and ultra low doses of HgCl2 modulate ?-amylase starch interaction through two different binding sites of the enzyme. Mercurius corrosivus at ultra high dilution (UHD) is reported to have a long duration of action for 30-60 days.
 Objectives
 (i) To see whether the mother tincture and UHDs of mercuric chloride could directly act on ?-amylase without intervention of its substrate starch. (ii) To see whether the MT and UHDs produce longer binding interaction with ?-amylase than the control.
 Methods
 Mercuric chloride MT (0.15 M) or Merc cor ? and its three UHDs, 30, 200, 1000 cH called potencies were in 90% ethanol. Blank 90% ethanol and deionised and distilled (DD) water were used as controls. All ethanol based ligands were diluted with DD water to reduce EtOH content to 0.09%. Using an ITC instrument each ligand was injected once at 10 µl into15µM ?-amylase at 25 0C and the reaction was observed for 2000 s. 
 Results
 While Merc cor ? produced endothermic reaction, all other ligands did exothermic reaction. Water control and blank ethanol maintained post injection heat change up to 1200 sec. All other ligands sustained heat change for the entire period of observation (2000 sec). 
 Conclusions
 Merc cor ? and potencies produced exactly the opposite reaction at the protein binding sites. The reaction was short-lived with water control and blank ethanol, but prolonged with Merc cor ? and potencies. Merc cor 200 cH and 1000 cH produced highest heat change (6 µl/sec) during interaction with ?-amylase.

Cisatracurium Versus Atracurium for Abdominal Surgeries Regarding Condition of Intubation and Hemodynamic Effect

Abstract Background: Neuromuscular-blocking drugs block neuromuscular transmission, causing paralysis of the affected skeletal muscles. In clinical use, neuromuscular block is used adjunctively to anesthesia to produce paralysis, first to paralyze the vocal cords, and permit intubation of the trachea, and second to optimize the surgical field by inhibiting spontaneous ventilation, and causing relaxation of skeletal muscles. Patients and Methods: This was a prospective, randomized study registered in Clinical Trials Registry of India (CTRI/2019/04/018580). We included 100 patients divided into two groups of 50 each. Group A received atracurium (0.5 mg/kg), whereas Group B received cisatracurium (0.15 mg/kg). Efficacy of both the drugs was compared in terms of onset of action, duration of action, duration of recovery, hemodynamic conditions during and after intubation, and signs of histamine release in both the drugs. Results: Mean duration of 25% recovery from the reversal in the atracurium group was 32.4 ± 1.90 min which was significantly less as compared to 49.46 ± 1.86 min of cisatracurium group (P < 0.001). The mean duration of recovery from the reversal in cisatracurium group was 2.18 ± 0.82 min which was significantly more as compared to 1.8 ± 0.75 min of atracurium group (P = 0.02). Conclusion: Cisatracurium in a dose of 0.15 mg/kg had a faster onset and duration of action than atracurium 0.5 mg/kg. At this dose, cisatracurium provides optimal intubating condition, rapid neuromuscular blocking with longer duration of action, stable hemodynamic status, no signs of histamine release clinically, and without any residual muscle paralysis compared to atracurium.

Comparative evaluation of analgesic efficacy of buprenorphine transdermal patch and fentanyl patch in management of postoperative pain after arthroscopic lower limb surgery: A randomized controlled trial.

Background and Aims:Transdermal opioids are newer modality in use for the control of postoperative pain, because of its noninvasiveness, longer duration of action, sustained blood levels, and with minimal side effects. The study was aimed to evaluate the efficacy of analgesia of buprenorphine patch 10, 20 μg·h-1 and fentanyl patch 25 μg·h-1 for relief of pain in the postoperative period in patients undergoing arthroscopic lower limb surgeries.Materials and Methods:It was a randomized, double-blinded, prospective study in which adult patients undergoing lower limb arthroscopic surgery were randomly segregated into three groups. In Group 1 (fentanyl patch 25 μg·h-1), Group 2 (buprenorphine patch 10 μg·h-1), and Group 3 (buprenorphine patch 20 μg·h-1), transdermal patches were applied 12 h prior to surgery. Mean NRS score, total rescue analgesic requirement, drug-related adverse effects, and hemodynamic status were evaluated till 72 h in the postoperative period.Results:Out of 175 screened patients, 150 patients were finally analyzed. Baseline characteristics were the same among all the three groups. Median NRS score was lowest in Group 3 [P value < 0.05 at 2, 4, 8, 12, and 24 h after surgery (Kruskal Wallis test). The total consumption of postoperative rescue analgesic diclofenac was the lowest in Group 3 as compared to other groups without any significant increase in adverse events.Conclusions:In arthroscopic lower limb surgery, buprenorphine patch (20 μg·h-1) applied 12 h prior to surgery is an effective postoperative analgesic and it is not associated with any significant adverse effects.

COVID-­19 pandemic and chronic urticaria

Objective — to improve the management of patients with COVID-19 and chronic urticaria (CU).Materials and methods. A review of the literature is presented and the mutual influence and principles of management of patients with COVID-19 and CU were analyzed.Results and discussion. To date, more than 106 million patients have been diagnosed with COVID-19 worldwide, and more than 2.3 million patients died in 900 countries. The prevalence of CU, defined as episodic or daily episodes of urticarial rash lasting 6 weeks or more, is approximately 1.8 % of the adult and 0.1—0.3 % of the children population. Patients with CU and their physicians are affected by social distancing, blocking, travel restrictions, and changes in treatment regimens due to the risk of SARS-CoV-2 infection.The pandemic has significantly worsened the level of medical care for all categories of patients with chronic diseases, and CU is not an exception. The essence of the algorithm for the treatment of CU is the prescription of modern non-sedative antihistamines as first-line drugs with the possibility of increasing their dosage by up to 4 times in the second-line therapy. Studies show that the COVID-19 pandemic does not significantly affect the use of first-, second-, and third-line CU therapies in expert centers.The ideal antihistamines should be effective in relieving symptoms, have a rapid effect and long duration of action, preferably administered once a day and not cause side effects such as drowsiness. Bilastin meets this profile for the treatment of patients with CU.Conclusions. COVID-19 significantly reduces the availability of medical care to patients with CU and negatively affects the treatment of the disease. Remote forms of counseling and control of symptoms and treatment of CU are becoming more commonly used, and the prescription of immunosuppressive therapy - more rare. Treatment of CU in patients with COVID-19 should begin with the use of modern non-sedative antihistamines, with the increase of their dose by up to 4 times if necessary.

Cefovecin pharmacokinetics after single-dose intramuscular administration in cheetahs (Acinonyx jubatus).

Cefovecin is a third-generation cephalosporin with potential value for use in exotic felids due to its long duration of action. A sparse sampling protocol was implemented with 18 zoo-housed cheetahs (Acinonyx jubatus) to evaluate the pharmacokinetics of cefovecin (Convenia® ) after a single 8mg/kg intramuscular injection. Blood was collected serially for 15days following administration, and plasma cefovecin concentrations were determined using high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were estimated using population pharmacokinetic methods and non-linear mixed effects modeling (NLME). Cefovecin was well tolerated by all cats, with no adverse effects observed. Peak plasma cefovecin concentration was 84.75µg/ml, with a mean residence time of 207.9h and an elimination half-life of 144.1h (6.00days). Plasma concentrations of cefovecin were maintained >7µg/ml in all individuals for the entire study duration (15days). These concentrations are lower, and the half-life slightly shorter, than the values reported for domestic cats. Cefovecin was highly protein-bound (approximately 99.9%) in cheetah plasma, which is nearly identical to domestic cats. These results indicate that cefovecin is potentially useful as a long-acting antibiotic in cheetahs.

Natural and synthetic polymeric antimicrobials with quaternary ammonium moieties: a review

The excessive use of antibiotics has led to the development of antimicrobial resistance and, in turn, to the inefficiency of actual drugs. Therefore, scientists have recently focused on conceiving new antimicrobials with a longer duration of action and a minimum environmental toxicity, such as polymers modified with quaternary ammonium moieties. Indeed, these quaternary ammonium moieties have a net positive charge that interacts better with and inhibit negatively charged microorganisms. This article reviews natural and synthetic polymers modified with quaternary ammonium moieties with focus on biocompatible polymers. Polymers include cashew gum, cellulose, chitosan, dextran, polylactide, pullulan, starch, polyamidoamine, polyurethane, polysiloxane, polymethacrylate and polyethylene. The interaction of new antimicrobials with a wide range of bacteria and fungi is controlled by microenvironmental factors and polymer properties. The use of other functional groups or chemical compounds in synergy with quaternary ammonium moieties is actually emerging to improve the efficiency.

Discovery of Potent Carbonic Anhydrase Inhibitors as Effective Anticonvulsant Agents: Drug Design, Synthesis, and In Vitro and In Vivo Investigations.

Two sets of benzenesulfonamide-based effective human carbonic anhydrase (hCA) inhibitors have been developed using the tail approach. The inhibitory action of these novel molecules was examined against four isoforms: hCA I, hCA II, hCA VII, and hCA XII. Most of the molecules disclosed low to medium nanomolar range inhibition against all tested isoforms. Some of the synthesized derivatives selectively inhibited the epilepsy-involved isoforms hCA II and hCA VII, showing low nanomolar affinity. The anticonvulsant activity of selected sulfonamides was assessed using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) in vivo models of epilepsy. These potent CA inhibitors effectively inhibited seizures in both epilepsy models. The most effective compounds showed long duration of action and abolished MES-induced seizures up to 6 h after drug administration. These sulfonamides were found to be orally active anticonvulsants, being nontoxic in neuronal cell lines and in animal models.

Acceptability of immediate postpartum and post-abortion long-acting reversible contraception provision to adolescents: A systematic review.

Long-acting reversible contraception (LARC) methods are safe for adolescents and provide the greatest assurance against rapid repeated pregnancy when inserted during the immediate postpartum (IPP) and immediate post-abortion (IPA) period. Despite increasing enthusiasm for IPP/IPA LARC insertion, adolescents' preferences and experiences have seldom been examined. The objective of this review was to examine the attitudes of adolescents (aged 10-19years) towards IPP/IPA LARC, their experiences and perceptions around having an LARC device fitted IPP/IPA and the factors involved in decision-making to use, not use or discontinue IPP/IPA LARC. In January 2021, we searched seven bibliographic databases for original research articles published in English, from the year 2000. Studies of any design focused on IPP/IPA LARC were eligible for inclusion. Three of the authors assessed articles for eligibility and extracted data relevant to the outcomes of the review. Joanna Briggs Institute Critical Appraisal Tools were used to assess methodological quality. Key themes emerging from the data were synthesized and reported narratively. We identified 10 relevant articles, four of which were entirely adolescent-focused. Only three addressed IPA LARC. IPP availability was important for ensuring access to LARC postpartum. Attitudes towards LARC IPP were associated with adolescents' sociodemographic characteristics and positive perceptions related to the long duration of action. Determinants of discontinuation and nonuse included poor-quality contraceptive counseling, intolerable side effects and subsequent distress, misconceptions about LARC safety IPP and the influence of partners and community on autonomy. No factors involved in IPA LARC decision-making were available. Limited evidence demonstrated that adolescents may favor contraceptive implants over intrauterine devices, and in certain contexts may face greater barriers to IPA LARC access than adult women do. Immediate insertion of LARC postpartum appears acceptable to adolescents who do not experience side effects and those with the opportunity to make autonomous contraception decisions. This important topic has been addressed in few studies involving an entirely adolescent population. Very limited evidence is available on IPA LARC. Further research on adolescents' lived experiences of IPP/IPA LARC access and use is necessary to inform the provision of person-centered care when assisting adolescents' contraceptive choice following pregnancy.

Molecular Determinants of the Kinetic Binding Properties of Antihistamines at the Histamine H1 Receptors.

The binding affinity of ligands for their receptors is determined by their kinetic and thermodynamic binding properties. Kinetic analyses of the rate constants of association and dissociation (kon and koff, respectively) of antihistamines have suggested that second-generation antihistamines have a long duration of action owing to the long residence time (1/koff) at the H1 receptors. In this study, we examined the relationship between the kinetic and thermodynamic binding properties of antihistamines, followed by an evaluation of the structural determinants responsible for their kinetic binding properties using quantitative structure–activity relationship (QSAR) analyses. We found that whereas the binding enthalpy and entropy might contribute to the increase and decrease, respectively, in the koff values, there was no significant relationship with the kon values. QSAR analyses indicated that kon and koff values could be determined by the descriptors FASA_H (water-accessible surface area of all hydrophobic atoms divided by total water-accessible surface area) and vsurf_CW2 (a 3D molecular field descriptor weighted by capacity factor 2, the ratio of the hydrophilic surface to the total molecular surface), respectively. These findings provide further insight into the mechanisms by which the kinetic binding properties of antihistamines are regulated by their thermodynamic binding forces and physicochemical properties.

COMPARATIVE EVALUATION OF ONSET, DURATION AND SAFETY BETWEEN MIDAZOLAM, DEXMEDETOMIDINE SEDATION AND THEIR COMBINATION IN PRESCHOOLERS: A RANDOMIZED CLINICAL TRIAL

Introduction: Dental anxiety is a global problem in pediatric dentistry. Moderate sedation is an acceptable option for uncooperative preschoolers dental patients. Objective: To compare midazolam (MDZ), dexmedetomidine (DEX) and their combination (DEX/MDZ) as sedative drugs for preschoolers undergoing dental treatment regarding onset, duration and safety of sedation. Materials and methods: The study was a three-arm randomized clinical trial with a parallel design. Seventy-two healthy uncooperative preschoolers were selected from the Faculty of Dentistry, Alexandria University, Egypt. The participants were randomly allocated into, control group received 0.5mg/kg MDZ, study group I received 5µg/kg DEX, and study group II received 0.3mg/kg MDZ followed by 3µg/kg DEX. Each child received quadrant treatment. Time until optimum sedation and recovery were recorded. Vital signs were recorded throughout the treatment session. Results: All children were comparable regarding demography, physical status and baseline vital signs (blood pressure, heart rate, and oxygen saturation). There was a statistically significant difference regarding onset and duration of the effect of sedative drugs (P=<0.001). Dexmedetomidine had the most delayed onset of action (17.08 ± 5.88 min), while DEX/ MDZ had the longest duration of action (68.13 ± 17.12). There was a significant decrease in blood pressure throughout the sedation session for all children. Children who were sedated with DEX and DEX/MDZ had a significant decrease in heart rate than children sedated with MDZ. No statistically significant effect of drugs on oxygen saturation levels was recorded. Conclusion: Midazolam, Dexmedetomidine and their combination are safe drugs during moderate sedation for children undergoing dental treatment.

Ropivacaine: A NovelLocal Anaesthetic Drug to Use in OtorhinolaryngologyPractice.

Ropivacaine is a long-acting amide local anaesthetic agent which has a significant vasoconstrictive property, long duration of action, least central nervous system and cardiac complications due to the pure (S)-enantiomer property by reversible inhibition of sodium ion influx in nerve fibres. By using additives the duration of analgesia may be prolonged. Ropivacaine has been used routinely in our otorhinolaryngology procedures since 2010 (10years). The present article details the clinical applications of ropivacaine and its current place as a local anaesthetic in otorhinolaryngology practice.

Prospective Cohort Study Comparing Varying Doses of Cisatracurium and Atracurium on Intubating Conditions in Patients Undergoing Laparoscopic Cholecystectomy

Introduction: Cisatracurium and atracurium are non-depolarising muscle relaxants belonging to benzylisoquinolinium group. Intubating dose of cisatracurium is found to be safer than atracurium owing to the histamine release and resultant respiratory and cardiac side-effects associated with the latter. However, intubating conditions of twice the ED95 dose (2xED95) of cisatracurium are not as satisfactory as equipotent dose of atracurium because of its higher potency. Aim: To compare the time of onset, intubating conditions and mean duration of action of three and four times ED95 doses (3 and 4xED95) of cisatracurium with 2xED95 dose of atracurium so as to find out an ideal intubating dose of cisatracurium that is comparable with 2xED95 of atracurium. Materials and Methods: The present study was a prospective cohort study that included 102 patients who underwent elective laparoscopic cholecystectomy. They were divided into three groups of 34 each to receive atracurium 0.5 mg/kg (group A), cisatracurium 0.15 mg/kg (group B) or cisatracurium 0.2 mg/kg (group C) for intubation. Onset and duration of neuromuscular block were assessed using Train Of Four (TOF) stimuli. Total time for intubation and mean intubation scores were also noted. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software version 18.0. Qualitative data were compared using Chi-square test and quantitative data compared using Analysis of Variance (ANOVA). Results: Onset of neuromuscular blockade in groups A, B and C were 292.06±61.486, 204.71±39.407 and 120.88±37.284 seconds (p-value &lt;0.001), respectively. Mean intubation score was highest in group C along with least intubating time (p-value &lt;0.001). The mean duration of action in groups A, B and C were 40.44±5.275, 48.24±5.888 and 63.38±7.659 minutes, respectively (p-value &lt;0.001). Conclusion: The 3 and 4xED95 doses of cisatracurium are superior to 2xED95 dose of atracurium in providing faster onset of action, better intubating conditions, shorter intubation time and longer duration of action. The 4xED95 dose of cisatracurium may be considered for rapid intubation in two minutes.

Современная стратегия в лечении артериальной гипертонии: комбинированная терапия и фиксированные комбинации

The introduction of fixed combinations for the treatment of arterial hypertension (AH) is an effective strategy to address the public health burden of cardiovascular disease. This strategy is reflected in modern international guidelines for the treatment of AH and is supported by World Health Organization. The use of fixed combinations allows solving key practical problems to achieve better results and improve the prognosis of AH: ensuring the greatest decrease in blood pressure (BP) and a lower target BP level, shortening the time period for obtaining target BP, increasing adherence to treatment. Fixed combinations include classes of antihypertensive drugs, which, when combined, have an additive or synergistic effect in lowering BP, help to reduce/mitigate side effects, reduce the number of pills and increase patient adherence, solving the problem of polypharmacy. Single dosing per day of fixed combinations is another important benefit, providing adherence, longer duration of action, and reduced diurnal fluctuations in BP. The clinical benefits of fixed combinations have been confirmed in a number of large studies and meta-analyzes. The modern tactics of using fixed combinations provides for their use at different stages/degrees of BP increase. In this regard, fixed combinations with subtherapeutic, therapeutic and maximum therapeutic doses of components have been developed. For the use of fixed combinations as an initial therapy for AH, drugs with subtherapeutic doses of components that are not used in monotherapy are proposed. In such cases, thanks to the complementary selection of combined drugs, it is possible to achieve a more significant and timely BP reduction, with fewer side effects. Modern fixed combinations are based on three main classes of antihypertensive drugs – RAAS blockers (ACE inhibitors and ARBs), calcium antagonists and diuretics. There are 2 principal approaches to combinations: a combination of RAAS blockers with diuretics (diurethic-use) or a combination of RAAS blockers with calcium antagonists (diuretic-free). This preference is due to evidence-based medicine data, including questions of efficacy, tolerability, side effects, and confirmation in clinical trials. In the clinical guidelines for the treatment of hypertension, these combinations are considered preferred (evidence level A). Over time, more and more fixed combinations become generic and reliable generic combination drugs for the treatment of hypertension appear, which reduces the cost factor and makes the therapy economically acceptable.

Quaternary Lidocaine Derivatives: Past, Present, and Future.

Local anesthetics have the advantage of complete analgesia with fewer side effects compared to systemic analgesics. However, their clinical use is limited due to their short duration of action. Thus, local anesthetics with fast onset, long duration of action, selective nociceptive block, and low local and systemic toxicity are highly desirable. In the past electrophysiological studies, quaternary lidocaine derivatives (QLDs) showed these characteristics. Here, we review electrophysiological properties of QLDs and their pharmacodynamic characteristics to shed light on potential problems.

Актуальность ситуационного использования назальных деконгестантов в современной клинической практике

Nasal decongestants (ND) are representatives of the pharmacological group of α-adrenomimetics and are widely used in clinical practice. These drugs are successfully used as symptomatic therapy of acute rhinosinusitis (AR), as well as as part of the complex therapy of acute otitis during unloading therapy for the auditory tube. The use of ND is necessary before conducting an endoscopic examination of the nasal cavity, for a better assessment of the state of the ostiomeatal complex, the olfactory cleft, as well as differential diagnosis of various forms of rhinitis and dysosmia. ND are indispensable in the prevention of complications of AR, such as acute eustachiitis, exudative otitis media and acute otitis media. Also, these drugs are used in the prevention of the development of aerotitis and ear barotrauma. The most commonly used nasal medications of medium and long duration of action, such as xylometazoline and oxymetazoline. This article presents clinical studies demonstrating the high efficacy and safety of these drugs as part of the treatment of AR. It is shown that oxymetazoline and xylometazoline are well tolerated by patients with a minimum number of adverse events. Modern representatives of ND are such drugs as Otrivin express 0.05% with the aroma of menthol, the main active ingredient of which is oxymetazoline, Otrivin 0.1% Moisturizing formula and Otrivin 0.1% with menthol and eucalyptus, which includes xylometazoline as the main active ingredient. These drugs have confirmed their effectiveness and safety in a large number of clinical studies and can be recommended as local vasoconstrictors.

Prediction of Half-Life Extension of Peptides via Serum Albumin Binding: Current Challenges.

The development of peptide therapeutics has increased enormously in recent decades. Many of the peptide drugs and antibody fragments that lack Fc backbone have a short half-life in circulation. In general, the half-life supports the design of the dosing regimen and frequency of administration, which are key aspects in the discovery of peptide drugs intended for long duration of action. Less frequent administration such as weekly or monthly can improve compliance and adherence to therapy. Serum albumin binding is a key approach to extend the half-life of peptide drugs. Despite the evidence of half-life prolongation of a variety of peptide drugs via albumin, quantitative prediction for humans is still a key question. Challenges in the measurement ofalbumin binding and in understanding the clearance mechanisms can limit quantitative prediction. We integrated pharmacokinetic concepts and albumin binding across species in a quantitative model to be used as a tool for prediction of half-life. Preliminary validation on a limited dataset indicated a good correlation between predicted and observed values. Further development of more quantitative models is warranted.

A strategy to prioritize emerging drugs of abuse for analysis: Abuse liability testing using intracranial self-stimulation (ICSS) in rats and validation with α-pyrrolidinohexanophenone (α-PHP)

Novel psychoactive substances (NPS) threaten public health and safety while also straining the limited resources of forensic laboratories. To efficiently allocate the finite resources available, we propose a new strategy for prioritizing NPS with abuse liability testing using a preclinical behavioral procedure in rats known as intracranial self-stimulation (ICSS). To validate this assay, the recently-scheduled synthetic cathinone α-PHP was compared to cocaine, a mechanistically similar drug of abuse, as a positive control and saline as a negative control. Male Sprague-Dawley rats (n=6) were implanted with electrodes targeting the medial forebrain bundle and trained to respond by lever-press for electrical brain stimulation. The rats were tested with doses of 0.32, 1.0, and 3.2 mg/kg α-PHP as well as 10 mg/kg of cocaine and saline administered by intraperitoneal injection. Neither saline nor 0.32 mg/kg α-PHP altered ICSS response rates compared to baseline levels of responding; however, doses of 1.0 and 3.2 mg/kg α-PHP and 10 mg/kg cocaine facilitated ICSS responding. This ICSS profile suggests that α-PHP has high abuse potential, with a rapid onset of effects and a long duration of action, and supports the decision to schedule this compound. This study demonstrates the ability of ICSS to distinguish between compounds of low and high potential for abuse. A strategy is proposed here to screen NPS using ICSS and classify emerging drugs into four priority categories for further analysis.

Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel.

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.

A brief review on newer Glucagon like Peptide-1 analogues

GLP-1 (Glucagon like Peptide-1) receptor agonists have been shown to be effective in the treatment of type 2 diabetes mellitus (T2DM). Although the first GLP-1 receptor agonist, Exenatide, was approved in the year 2000, other agents with a longer duration of action that do not require twice-daily dosing are now being developed. Indeed, Liraglutide, a once-daily GLP-1 receptor agonist, was approved in 2010, a once-weekly extended-release formulation of Exenatide (Exenatide ER) was approved in 2011 and now more recently Semaglutide, an oral GLP 1 receptor agonist was approved for medical use in the United States in September 2019 and in the European Union in April 2020. The importance of GLP-1 itself and the use of GLP-1 receptor agonists in T2DM are discussed. An overview of the clinical development of the GLP-1 receptor agonists (Exenatide ER, Liraglutide, Lixisenatide, Albiglutide, Taspoglutide and Semaglutide) is provided and their mechanism of action, efficacy in terms of glycaemic control, weight loss and tolerability are reviewed. Keywords: GLP1 receptor agonist; Liraglutide; Exenatide ER; Lixisenatide; Semaglutide

Different injection patterns of incobotulinumtoxinA for crow's feet: a split-face comparative study.

IncobotulinumtoxinA has been previously used for the treatment of lateral periorbital lines (crow's feet). However, a standardized injection technique has not been established. To compare the efficacy and effect duration of two injection techniques of incobotulinumtoxinA for crow's feet treatment. Forty-eight patients with crow's feet were recruited and randomly assigned to receive bilateral treatments using either a 3-point intramuscular or a 6-point intradermal injection technique (8-12 units of incobotulinumtoxinA on each side). Improvement was assessed at 1, 2, 4, 8, 12, 16, 20 and 24weeks postinjection. An objective evaluation was assessed by the indentation index using a 3D camera and a subjective evaluation was assessed by a blinded dermatologist using the Flynn validated assessment scale (FVAS) for the upper face. The patients assessed the results using the Global Aesthetic Improvement Scale (GAIS). Side-effects were evaluated at each visit. After treatment, a significantly greater reduction in the indentation index of periorbital wrinkles on the 3-point intramuscular injection side compared with the 6-point intradermal injection side was observed at 8, 12, and 16weeks. The results from the FVAS and GAIS scores showed significantly longer median times to relapse of the periorbital wrinkle for the 3-point intramuscular injection compared with the 6-point intradermal injection. Pain and bruising were slightly greater with the 6-point intradermal technique. This study reaffirmed the efficacy of incobotulinumtoxinA for the treatment of crow's feet. The 3-point intramuscular injection technique yielded greater efficacy and longer duration of action than the 6-point intradermal injection technique.