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Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: formulation development and in vitro characterization.

Phenytoin is a low solubility anticonvulsant drug. It has, nonetheless, other possible therapeutic indications, such as neuropathic pain, including trigeminal neuralgia, or wound healing. Its use has decreased due to side effects, but nasal/intranasal administration could significantly increase drug safety and efficacy. The aim of this work was to develop and study nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin, in combination, for intranasal administration, with immediate and sustained release profiles. Nanoemulsions were prepared by adding the aqueous phase, containing gelling polymers in the case of nanoemulgels, to emulsion preconcentrates, followed, in the optimized procedure, by premix membrane emulsification. Formulation design and optimization was guided by drug strength, rheological behavior, osmolality, mean droplet size and polydispersity. Fosphenytoin interfered significantly with Carbopol but not with Pluronic's gelation, and allowed to achieve drug strengths equivalent to 22 or 27 mg/g of phenytoin in lead nanoemulsions, and 16.7 mg/g of phenytoin in the lead nanoemulgel. The final selected low viscosity nanoemulsions had an immediate or prolonged fosphenytoin release profile, depending of anhydrous phase proportion (10% or 40%, respectively). The thermosensitive nanoemulgel, with 10% anhydrous phase, showed prolonged drug release. Future studies will establish whether they are more suited for topical effects or therapeutic brain delivery.

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Trigeminal Neuralgia: Basic and clinical aspects.

The trigeminal nerve is the largest of all cranial nerves. It has three branches that provide the main sensory innervation of the anterior two-thirds of the head and face. Trigeminal neuralgia (TN) is characterized by sudden, severe, brief and stabbing recurrent episodes of facial pain in one or more branches of the trigeminal nerve. Pain attacks can occur spontaneously or can be triggered by normally non-noxious stimuli, such as talking, eating, washing the face, brushing teeth, shaving, a light touch or even a cool breeze. In addition to pain attacks, a proportion of the patients also experience persistent background pain, which along with autonomic signs and prolonged disease duration represent predictors of worse treatment outcome. It is now widely accepted that the presence of a neurovascular compression at the trigeminal root entry zone is an anatomic abnormality with high correlation with classical TN. However, TN may be related to other etiologies, thus presenting, different and/or additional features. Since the 1960s, the anticonvulsant carbamazepine is the drug of choice for TN treatment. Although anti-epileptic drugs are commonly used to treat neuropathic pain in general, efficacy of carbamazepine has been largely limited to TN. Carbamazepine, however, is associated with dose-limiting side-effects. Thus, a better understanding and new treatment options are urgently warranted to this rare, but excruciating disease.

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Cytokine Levels in Neural Pain in Leprosy.

Pain is a frequent symptom in leprosy patients. It may be predominantly nociceptive, as in neuritis, or neuropathic, due to injury or nerve dysfunction. The differential diagnosis of these two forms of pain is a challenge in clinical practice, especially because it is quite common for a patient to suffer from both types of pain. A better understanding of cytokine profile may serve as a tool in assessing patients and also help to comprehend pathophysiology of leprosy pain. Patients with leprosy and neural pain ( = 22), neuropathic pain ( = 18), neuritis (nociceptive pain) ( = 4), or no pain ( = 17), further to those with diabetic neuropathy and neuropathic pain ( = 17) were recruited at Souza Araujo Out-Patient Unit (Fiocruz, Rio de Janeiro, RJ, Brazil). Serum levels of IL1β, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-γ, CXCL-10/IP-10, and TGF-β were evaluated in the different Groups. Impairment in thermal or pain sensitivity was the most frequent clinical finding (95.5%) in leprosy neuropathy patients with and without pain, but less frequent in Diabetic Group (88.2%). Previous reactional episodes have occurred in patients in the leprosy and Pain Group ( = 0.027) more often. Analysis of cytokine levels have demonstrated that the concentrations of IL-1β, TNF, TGF-β, and IL-17 in serum samples of patients having leprosy neuropathy in combination with neuropathic or nociceptive pain were higher when compared to the samples of leprosy neuropathy patients without pain. In addition, these cytokine levels were significantly augmented in leprosy patients with neuropathic pain in relation to those with neuropathic pain due to diabetes. IL-1β levels are an independent variable associated with both types of pain in patients with leprosy neuropathy. IL-6 concentration was increased in both groups with pain. Moreover, CCL-2/MCP-1 and CXCL-10/IP-10 levels were higher in patients with diabetic neuropathy over those with leprosy neuropathy. In brief, IL-1β is an independent variable related to neuropathic and nociceptive pain in patients with leprosy, and could be an important biomarker for patient follow-up. IL-6 was higher in both groups with pain (leprosy and diabetic patients), and could be a therapeutic target in pain control.

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Tazarotene 0.045% Lotion for the Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris in Adult Males

BACKGROUND: There has been an increasing interest in gender differences both in the pathogenesis and treatment of acne vulgaris (acne). However, while acne prevalence among adolescents is comparable across sexes, acne is much more common in adult women than in adult men which has been largely ignored. Acne is likely less common in adult men because of the declining rate of sebum secretion observed with increasing age, and yet it can be more severe than in adult women. In addition, adherence to topical medications is especially poor in adult men where tactile and sensory perceptions are low. The first lotion formulation of tazarotene was developed using polymeric emulsion technology to provide an important alternative option to treat these acne patients, especially those who may be sensitive to the irritant effects of other tazarotene formulations.

OBJECTIVE: To evaluate the efficacy and safety of a new tazarotene 0.045% lotion formulation based on polymeric emulsion technology in treating adult male subjects with moderate or severe acne, in comparison with adolescent males treated with the same tazarotene 0.045% lotion.

METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-or-severe acne. Subjects (aged 10 and older, N=1614) were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear or almost clear). Quality of Life was assessed using the validated Acne-QoL scale. Safety, adverse events (AEs) were evaluated throughout; cutaneous tolerability (using a 4-point scale where 0=none and 3=severe) at each study visit.

RESULTS: A total of 268 male subjects (85≥18 years old and 183<18 years old) were treated with tazarotene 0.045% lotion once-daily for 12 weeks. At week 12, percent reductions in inflammatory and noninflammatory lesions with tazarotene 0.045% lotion were 62.3% and 59.5% in the adult male population, compared with 49.4% (P=0.001) and 49.5% (P=0.016) in the adolescent male population. Treatment success was achieved by 33.0% of adult male subjects treated with tazarotene 0.045% lotion, compared with 21.6% in the adolescent male population (P=0.059). Quality of life (as assessed by Acne-QoL domain scores) was better in adolescent males at baseline. Improvements in QoL domain scores were similar to those seen in the overall study population, with greater absolute change in domain scores in the adult males. Improvement in acne symptom scores was significantly greater in adult males (P=0.029). Tazarotene 0.045% lotion was well-tolerated. The number of subjects reporting any AE in the adult male population was 11 (13.6%) compared with 39 (21.4%) in the adolescent male population. There was only one (1.2%) treatment-related AE (application site pain) reported in the adult males compared with 11 (6.0%) in the adolescent males, where the most common treatment-related AEs were application site pain (3.3%), dryness (1.1%), and erythema (1.1%). Mean scores for hyper- and hypopigmentation were very low at baseline in both groups with no appreciable change with treatment.

CONCLUSIONS: Tazarotene 0.045% lotion provides greater efficacy and better tolerability in adult males (above 18 years old) than the adolescent male population with moderate-to-severe acne patients.

J Drugs Dermatol. 2020;19(1):78-85. doi:10.36849/JDD.2020.3979

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Comparison of ultrasound-guided intermediate vs subcutaneous cervical plexus block for postoperative analgesia in patients undergoing total thyroidectomy: A randomised double-blind trial.

Intermediate cervical plexus block (CPB) is a new procedure whose analgesic efficacy compared to superficial cervical plexus block is yet to be established. We compared the analgesic efficacy of superficial vs intermediate CPB for post-operative analgesia after thyroid surgery.

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Hypertension prevalence in patients attending tertiary pain management services, a registry-based Australian cohort study.

Persistent pain and hypertension often co-occur, and share several biological and lifestyle risk factors. The present study aimed to provide insight into the prevalence of, and factors associated with, hypertension in the largest cohort of patients seeking treatment in 43 tertiary pain clinics in Australia. Adults aged > = 18 years registered to the electronic Persistent Pain Outcomes Collaboration registry between 2013 and 2018 were included if they had persistent non-cancer pain (N = 43,789). Risk Ratios (RRs) compared prevalence of self-reported hypertension with the general and primary care Australian populations, and logistic regression examined factors associated with hypertension. One in four (23.9%) patients had hypertension, which was higher than the Australian adult population (2014-15: RR = 5.86, 95%CI: 5.66, 6.06; 2017-18: RR = 9.40, 95%CI: 9.01, 9.80), and in primary care patients (2011-13: RR = 1.17, 95%CI: 1.15, 1.20). Adjusting for covariates, patients with higher odds of hypertension were older, lived in regions with higher socioeconomic disadvantage, had higher levels of BMI, were born outside the Oceania/Australasia region, and had comorbid arthritis, diabetes, or severe-extremely severe anxiety symptoms. Female patients and those with depression symptoms had lower adjusted odds. Unadjusted analyses showed an association between widespread pain, pain duration, pain severity and interference, and lower pain self-efficacy with hypertension; however, only pain severity remained significant in adjusted analyses. Hypertension was more prevalent in people with persistent pain than in the general community, was associated with more severe pain, and commonly co-occurred with pain-related impairments. Routine hypertension screening and treatment targeting shared mechanisms of hypertension and pain may improve treatment outcomes in the pain clinic setting.

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A case of acute unilateral maxillary atelectasis following endoscopic pituitary surgery.

Chronic maxillary atelectasis (CMA) is traditionally described as a rare, acquired condition of persistent and progressive antral wall collapse causing a reduction in maxillary sinus volume. In a handful of cases, CMA has been identified in patients with previously normal computed tomography (CT) imaging. However, maxillary atelectasis occurring rapidly after pituitary surgery, despite a normal pre-operative CT scan, has not previously been described in the literature.

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Efficacy of spinal chiropractic manipulative therapy for adjusting the relationship between cervical facet joints to treat headache caused by acute mountain sickness.

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Adrenocortical carcinoma in a young adult male with chronic urticaria: A case report and literature review.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Radical adrenalectomy is the gold standard of treatment of localized disease.

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Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain: Erratum.

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