COVID-19 Pandemic Lockdown: A Cloud with a Silver Lining for the Road Traffic Accidents Pandemic.

Context: Effects of coronavirus disease 2019 (COVID-19) pandemic lockdown on road traffic accidents (RTAs) in Chhattisgarh, India. Background: Most neurosurgical emergencies are from brain and spine trauma. RTA is the leading cause of such injuries. While the nationwide lockdown was an extreme measure to control the COVID pandemic, it influenced the overall road traffic dynamics and neurotrauma. Objective: This study aims to assess the impact of the lockdown on neurotrauma. Methods and Materials: This retrospective study included all patients with brain and spine injuries who were admitted between January 17th and May 31st, 2020. The study population was divided into prelockdown (PL) and lockdown (L) groups. Results: Of the 668 patients, 436 were placed in the PL and 232 in the L group. The mean ages were 36.34 (SD = 17.96) and 35.98 (SD = 16.93), respectively. Male to female ratios were 82.3:17.7 in the PL group and 79.7:20.3 for the L group. RTA-related injuries were significantly lower during the lockdown period (n = 335 PL vs. 162 L [P = 0.048]). During the lockdown, there were more mild injuries (25.91% PL vs. 36.63% L) and less severe injuries (33.25% PL vs. 18.96% L [P = 0.0002]). Mortality was significantly less (P = 0.029) during the lockdown (n = 48 L vs. 124 PL). The proportion of RTA-related neurotrauma cases increased (33.33% L1, 57.14% L2, 73.13% L3, and 80.39% L4) with each phase of lockdown (L1-L4). Conclusions: During the lockdown period, the number of trauma cases had decreased, with a significant decrease in RTA-related admissions, along with their severity and mortality. The number of trauma cases and their severity increased gradually with each phase of lockdown.

An insight on topically applied formulations for management of various skin disorders.

Various types of skin disorders across each age group and in each part of geographical world are very dreadful. Despite not being fatal each time they are always of social and mental concern for suffering individuals, causing complications in millions of patients every day and require comparatively longer duration of treatment. Off late, various topical/transdermal formulations have been widely explored for the treatment of various skin ailments. The efficiency of topical therapy depends on various physiochemical properties of drugs like particle size, particle size distribution, partition coefficient, viscosity of dosage form, skin permeability, skin condition and the site of application. Therefore, in plenty of examples, long-acting topical formulations have shown to be markedly excellent in comparison to conventional dosage forms. The major advantages of topical formulations accrue from their demonstrated ability: (i) Reduced serious side effects that may occur due to undesirably higher systemic absorption of drug. (ii) Enhancement of drug accumulation at the desired site. (iii) Easy incorporation of enormous range of hydrophilic and hydrophobic drugs and (iv) Reduced risk of dose dumping and comparatively easy termination of drug release. The prospective applications of topically applied formulations and the deposition of pharmaceuticals into the skin are examined.

Mucormycosis: A deadly black fungus infection among COVID-19 patients in India.

After first phase of Covid-19, the second wave affects a lot to the Indians with mysterious fungal infection known as Mucormycosis. Here, we reviewed clinical pathogenesis, signs, symptoms and treatment against black fungus. The conclusion revealed that use of immunosuppressant to combat Covid-19 also increases the risk to get infected with mucormycosis. Patients with hyperglycemia, ketoacidosis, solid organ or bone marrow transplantion, liver cirrhosis, neutropenia are more susceptible to get attacked by Mucormycosis moulds. Early diagnosis, removal of predisposing factors, timely antifungal therapy with surgical removal of all infected tissues and adjunctive therapies are four major factors to eradicate Mucormycosis.

Rapid Spontaneous Resolution of the Acute Subdural Hematoma: Case Series and Review of Literature.

BACKGROUND: Traumatic acute subdural hematoma (ASDH) is an oft encountered entity in neurosurgery. While resolution of such thick SDHs usually takes time, certain cases of rapid spontaneous resolution have also been reported. This article attempts to review the pathophysiology, clinical and radiological features of such cases, as well as provide an insight into decision making for their management. METHODS: Electronic literature search was done to look for similar cases of spontaneous rapid resolution of ASDH. Five of authors cases have been described. Their clinical and radiological features along with those of cases from literature search were tabulated and analyzed. RESULTS: A total of 44 relevant cases were included for analyses. Of these, 39 cases were from 33 articles found in existing literature and 5 cases were from author's collection. The M:F ratio was 25:19 with a mean age was 41.84(SD-4.094) years. Twenty -six patients showed "Rapid" neurological improvement (24 hours) occurred in 10 patients. The mean hematoma resolution time on CT scan was 13.78 hours (SD 16.46) ranging from 1- 72 hours. Twenty-nine patients showed redistribution of hematoma, most commonly to tentorium and falx cerebelli. CT scan findings were classified into 5 types as per the nature of hypodensity around hematoma. The geometric mean time to resolution of hematoma was least for type 2 (7.27 hours) and type 1(7.52 hours) patients. CONCLUSION: Selected patients of ASDH with rapid neurological improvement and specific CT findings may show spontaneous resolution of ASDH. Multicentric studies with larger study population may provide better insight into the nature and outcomes of such entities.

Clinico-etiological profile of hyponatremia among elderly age group patients in a tertiary care hospital in Sikkim.

BACKGROUND: Hyponatremia is a common condition observed in hospitalized patients. The incidence is much more in the elderly patients owing to impaired ability to maintain water and electrolyte homeostasis. It is important to evaluate and understand the causes and patient characteristics in order to deliver precise management. MATERIALS AND METHODS: Study was conducted at a teaching referral hospital in Sikkim and total of 100 elderly patients, diagnosed with hyponatremia, were enrolled in the study. Detailed medical history, clinical and laboratory examination were performed and data including treatment details were collected. Descriptive analysis was performed and results were correlated with patient characteristics. RESULTS: Mean age of the patients was 73.87 ± 6.54 years with a male to female ratio of 1:0.96. About 81% of patients were symptomatic among which lethargy (50%), drowsiness (40%), and abnormal behavior (39%) were common symptoms. Most patients (51%) had profound hyponatremia and Syndrome of inappropriate antidiuretic hormone secretion (SIADH) (36%) and drugs (26%) were the most common cause of hyponatremia in this study. The common treatment given in this study was 0.9% NaCl (71%). Mortality of patients in this study was 20%. CONCLUSION: Clinicians need to be aware of the common occurrence of hyponatremia in the elderly, especially acutely sick elderly. A systematic approach to its diagnosis with the application of simple standardized diagnostic algorithms can significantly improve the assessment and management of hyponatremia as the outcome in profound hyponatremia is governed by etiology, and not by the serum sodium level.

Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception.

Coated microneedles have emerged as a promising drug delivery system for inflammatory pain treatment. We have previously shown that tramadol injection into the rat temporomandibular joint (TMJ) induces an antinociceptive and anti-inflammatory effect. In this study, microneedles coated with tramadol were investigated as a platform to treat TMJ pain. Male Wistar rats were administered tramadol using an intra-TMJ injection or with microneedles coated with tramadol, followed by 1.5% formalin nociceptive challenge administered 15 minutes later. The nociceptive behavior of rats was evaluated, and their periarticular tissues were removed after euthanasia for analysis. The duration of antinociceptive effect was determined by performing the formalin challenge at different time points extending up to 6 days post tramadol administration. Microneedles coated with tramadol produced an antinociceptive effect similar to injection of tramadol into the rat TMJ. Surprisingly, tramadol delivery using coated microneedles produced a more durable antinociceptive effect lasting as much as 2 days post tramadol delivery as compared with an antinociceptive effect lasting under 2 hours from intra-TMJ injection of tramadol. The proinflammatory cytokines tumor necrosis factor-α and interleukin-1ß (IL-1ß) were found to be reduced, whereas the anti-inflammatory cytokine IL-10 was found to be elevated in tramadol-treated groups. In conclusion, microneedles coated with tramadol can offer a therapeutic option for pain control of inflammatory disorders in the TMJ.

Carbon nanomaterials in oncology: an expanding horizon.

Carbon nanomaterials have been attracting attention in oncology for the development of safe and effective cancer nanomedicines in increasing improved patient compliance for generally recognized as safe (GRAS) prominence. Toxicity, safety and efficacy of carbon nanomaterials are the major concerns in cancer theranostics. Various parameters such as particle size and shape or surface morphology, surface charge, composition, oxidation and nonoxidative-stress-related mechanisms are prone to toxicity of the carbon nanomaterials. Currently, few cancer-related products have been available on the market, although some are underway in preclinical and clinical phases. Thus, our main aim is to provide comprehensive details on the carbon nanomaterials in oncology from the past two decades for patient compliance and safety.

Microneedles enhance topical delivery of 15-deoxy-Δ12,14-prostaglandin J2 and reduce nociception in temporomandibular joint of rats.

The pain arising from temporomandibular disorders is often treated with opioids and agents that inhibit the immune response and are associated with substantial adverse effects and long-term risks. Thus, the development of new therapies that are safer and more effective is of great interest to patients and clinicians. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is naturally produced in the human body and has anti-inflammatory properties. We have previously shown in a rat temporomandibular joint (TMJ) model that injection of 15d-PGJ2 into the rat TMJ can provide antinociceptive relief against a subsequent noxious challenge from formalin injection into the same TMJ. However, intra-TMJ injections are painful. Thus, to make the treatment patient friendly, this study aimed to evaluate whether the antinociceptive property of 15d-PGJ2 cream can be enhanced with microneedles (MNs). We found that topical application of 15d-PGJ2 cream for 15min directly on the rat TMJ skin did not induce any significant antinociceptive effect. However, if MNs were inserted in the skin for 5min, removed, and then 15d-PGJ2 cream was applied, a significant reduction in formalin-induced nociceptive behavior was observed. This reduction in nociception was comparable to an intra-TMJ injection of 15d-PGJ2. A concentration-dependent effect of 15d-PGJ2 was observed, with higher concentrations of 15d-PGJ2 in the cream showing a more durable effect up to 8h. 15d-PGJ2 cream associated with MNs also significantly reduced the release of tumor necrosis factor-α and interleukin-1 beta, which are pro-inflammatory cytokines. Our findings suggest that 15d-PGJ2 cream associated with MNs provides antinociceptive and anti-inflammatory effect, and can offer a potential patient-friendly therapeutic option for pain control related to inflammatory disorders of the TMJ.

5-Aminolevulinic acid coated microneedles for photodynamic therapy of skin tumors.

This study evaluated the potential of coated microneedles for improved dermal delivery of 5-aminolevulinic acid (5-ALA), which naturally gets converted by cells of the tissue in to a photosensitizer called protoporphyrin IX (PPIX). Microneedle patches containing 57 microneedles were coated with 5-ALA using an in-house developed micro-precision dip coater. The coating process was optimized to achieve higher 5-ALA loading on microneedles and a high delivery efficiency into porcine cadaver skin. Using 5 dips with 25% w/v 5-ALA solution, a mass of about 350µg of 5-ALA was coated per patch, which gave a delivery efficiency of about 90% in porcine cadaver skin. Bright-field and scanning electron microscopy established that coatings of 5-ALA on microneedles of the patch were uniform. In vivo dermal pharmacokinetics showed that delivery of just 350µg of 5-ALA using coated microneedles led to about 3.2-fold higher PPIX formation after 4h, as compared to topical application of 20% w/w 5-ALA in a conventional cream formulation (25mg cream). Furthermore, with use of coated microneedles, PPIX was observed in deeper regions of the skin (~480µm) as compared to topical 5-ALA cream formulation (~150µm). The potential of PPIX for photodynamic therapy was tested in vivo. After light exposure (633nm; 118J/cm(2)), PPIX got photosensitized, and due to higher initial amount of PPIX in the coated microneedle group, about twice the amount of PPIX was photobleached compared to topical cream application. Finally, even with a lower dose of just 1.75mg 5-ALA, coated microneedles suppressed the growth of subcutaneous tumors by ~57%, while a topical cream containing 5mg of 5-ALA did not suppress the tumor volume and led to tumor growth comparable to the untreated control group. Overall, the strategy of delivering 5-ALA using coated microneedles could be a promising approach for photodynamic therapy of skin tumors.

Advances in oral delivery of anti-cancer prodrugs.

INTRODUCTION: Most anticancer drugs have poor aqueous solubility and low permeability across the gastrointestinal tract. Furthermore, extensive efflux by P-glycoproteins (P-gp) in the small intestine also limits the efficient delivery of anticancer drugs via oral route. Area covered: This review explores the prodrug strategy for oral delivery of anticancer drugs. Different categories of oral anticancer prodrugs along with recent clinical studies have been comprehensively reviewed here. Furthermore, novel anticancer prodrugs such as polymer-prodrugs and lipid-prodrugs have been discussed in detail. Finally, various nanocarrier-based approaches employed for oral delivery of anticancer prodrugs have also been discussed. Expert opinion: Premature degradation of anticancer prodrugs in the gastrointestinal tract could lead to variable pharmacokinetics and undesired toxicity. Despite their increased aqueous solubility, the oral bioavailability of several anticancer prodrugs are limited by their poor permeability across the gastrointestinal tract. These limitations can be overcome by the use of functional excipients (polymers, lipids, amino acids/dipeptides), which are specifically absorbed via transporters and receptor-mediated endocytosis. Oral delivery of anticancer prodrugs using nanocarrier-based drug delivery system is a recent development; however it should be justified based on the comparative advantages of encapsulating prodrug in a nanocarrier versus the use of anticancer prodrug molecule itself.