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Changes in human lifestyles and environmental deterioration globally cause the emergence of new viruses, posing research challenges. The outburst of COVID-19 (nCoV19) is a recent example, wherein effective management of virus, using the conventional medication and effective diagnostic measures is a challenge. While many ongoing strategies from vaccine development to drug repurposing are currently being investigated, a targeted approach with nanotechnology can be helpful to meet the demand for preventive and diagnostic measures. The significant results of nanotechnology in providing better efficacy of pharmaceutical drugs is expected to combat nCoV19 by using nanotechnology- based solutions, preventive treatment, and diagnosis. This article addresses the dire need for nanotechnology-based solutions in the current pandemic, as well as analyzes the ongoing innovation and existing patents that can be used to provide better solutions. Multiple applications of nanotechnology are considered to be helpful in preventive and diagnostic measures, immune response modulation, and immunity boosters, along with projecting a pathway for industry and academic researchers for addressing such a pandemic.

Background: The treatment of wound-associated infections has always remained a challenge for clinicians, with the major deterring factor being microbial biofilms, majorly bacterial or fungal. Biofilm infections are becoming a global concern owing to resistance to antimicrobials. Various fungal pathogens form fungal biofilms, namely Candida sp., Aspergillus fumigates, Trichosporon sp., Saccharomyces cerevisiae, Cryptococcus neoformans, among others. The rising cases of fungal biofilm resistance add to the burden of wound care. Additionally, with an increase in the number of surgical procedures, transplantation, and the exponential use of medical devices, the fungal bioburden is rising. Objectives: The review discusses the methods of biofilm formation and the resistance mechanisms against conventional treatments. The potential of novel delivery strategies and the mechanisms involved therein are also highlighted. Further, the prospects of nanotechnology-based medical devices to combat fungal biofilm resistance have been explored. Some clinical trials and up-to-date patent technologies to eradicate biofilms are also mentioned. Conclusion: Due to the many challenges faced in preventing/eradicating biofilms, only a handful of approaches have made it to the market. Eradication of fungal biofilms are a fragmentary area that needs further exploration.

Background: Leukemia is a severe type of blood cancer that involves an abnormal proliferation of blood-forming cells. Its conventional treatment faces many challenges, including resistance, lack of specificity and high unwanted toxicity of drugs. Nano drug delivery systems help in overcoming these challenges by delivering the drug to the target site actively or passively. Solid lipid nanoparticles are gaining popularity because they reduce unwanted toxicity, are biocompatible, increase bioavailability and are versatile in terms of incorporated agents (hydrophilic as well as lipophilic drugs, genes, enzymes, etc.). Purpose: The aim of this review is to discuss recent advancements in anti-leukemic therapy utilizing solid lipid nanoparticles (SLNs) as successful carriers in enhancing the efficiency of the treatment and bioavailability of the incorporated drug along with overcoming multidrug resistance. Methods: This review represents the existing literature on the applications of SLNs in anti-leukemic therapy. A qualitative literature review has been performed for this purpose. We performed keyword research in popular databases such as Google Scholar, Wiley, Elsevier, Scopus, Google patent and PubMed. Only articles published in English and from reputed journals from specific fields were considered. Benchmark studies having major importance from 2000 to 2020 were selected to follow the progress in the field across the globe. Results: This article improves the understanding of the role of SLNs in the treatment of leukemia. Traditional anti-leukemic therapy involves many challenges, including resistance, lack of specificity and high unwanted toxicity of drugs. SLNs are emerging as a better alternative to conventional delivery systems as they can reduce unwanted toxicity, are biocompatible, and can provide active as well as passive molecular targeting. Conclusion: SLNs provide several advantages in drug delivery for leukemia, including enhancement of efficiency and bioavailability and reduction of toxicity by virtue of their small size, lipid core, non-dependency on organic solvents and versatility in terms of incorporated drugs.

Background: Controlled oral dosage forms have always been preferred for drugs with variable absorption, and short biological half life and frequent dosing. The prime goal with sustained release systems is to maintain uniform therapeutic blood levels for more extended periods of time. Interpenetrating networks (IPNs) have been evidenced as uniform sustained release systems. In the current study, polyvinyl alcohol (PVA) and locust bean gum (LBG) based IPNs were developed for the oral sustained release drug delivery of gliclazide (shows variable absorption). Methods: The IPNs were synthesized by emulsion cross-linking method using glutaraldehyde (GA) as a cross linking agent. Gliclazide is a potential second generation, and short-acting sulfonylurea oral hypoglycemic agent having a short biological half-life (2-4 h), variable absorption and poor oral bioavailability. Various batches of IPNs were formulated by varying LBG: PVA ratio and evaluated for percentage yield, drug entrapment efficiency (DEE), swelling properties and in vitro drug release studies. Further characterizations were done by Fourier Transform Infrared Spectroscopy (FTIR), C13 Solid state NMR, X-Ray diffraction study (XRD), Scanning electron microscopy (SEM), and Differential scanning microscopy (DSC) studies. Results: The percentage yield, drug entrapment and equilibrium swelling were observed to be dependent on PVA-LBG ratio and GA amount. Sustained release of drug was observed in all IPN formulations (approx 59 - 86% in 8 h in various batches) with variable release kinetics. SEM studies revealed the regular structures of IPNs. FTIR, XRD, C13 Solid state NMR and DSC studies proposed that drug was successfully incorporated into the formed IPNs. Conclusion: IPNs of LBG and PVA can be used as a promising carrier with uniform sustained release characteristics.

Background: Protecting intellectual property rights are important and particularly pertinent for inventions that are an outcome of rigorous research and development. While the grant of patents is subject to establishing novelty and inventive step, it further indicates the technological development and is helpful for researchers working in the same technical domain. The aim of the present research work is to map the existing work through an analysis of patent literature in the field of Coronaviruses (CoV), particularly COVID-19 (2019-nCoV). CoV is a large family of viruses known to cause illness in humans and animals, particularly known for causing respiratory infections, as evidenced in earlier times, such as in MERS i.e., Middle East Respiratory Syndrome; and SRS i.e., Severe Acute Respiratory Syndrome. A recently identified novel-coronavirus, known as COVID-19, has caused pandemic situations across the globe. Objective: To expand the analysis of patents related to CoV and 2019-nCoV, an evaluation has been conducted by patenting trends of particular strains of identified CoV diseases by present legal status, main concerned countries via the earliest priority years and its assignee types and inventors of identified relevant patents. The global patent documents were analyzed to check the scope of claims along with focuses and trends of the published patent documents for the entire CoV family, including 2019-nCoV through the present landscape. Methods: To extract the results, the Derwent Innovation database was used by a combination of different keystrings. Approximately 3800 patents were obtained and further scrutinized and analyzed. The present write-up also discusses the recent progress of patent applications in a period of the year 2010 to 2020 (present) along with the recent developments in India for the treatment options for CoV and 2019-nCoV. Results: Present analysis showed that key areas of the inventions were the vaccines and diagnostic kits apart from the composition for the treatment of CoV. It was also observed that no specific vaccine treatments are available for the treatment of 2019-nCov; however, developing novel chemical or biological drugs and kits for early diagnosis, prevention, and disease management is the primary governing topic among the patented inventions. The present study also indicates potential research opportunities for the future, particularly to combat 2019-nCoV. Conclusion: The present paper analyzes the existing patents in the field of Coronaviruses and 2019-nCoV and suggests a way forward for the effective contribution in this upcoming research area. From the trend analysis, an increase in the filing of the overall trend of patent families was observed for a period of 2010 to the current year. This multifaceted analysis of identified patent literature provides an understanding of the focuses on present ongoing research and a grey area in terms of the trends of technological innovations in disease management in patients with CoV and 2019-nCoV. Furthermore, the findings and outcome of the present study offer insights for the proposed research and innovation opportunities and provide actionable information in order to facilitate policymakers, academia, research-driven institutes and also investors to make better decisions regarding programmed steps for research and development for the diagnosis, treatment and taking preventive measures for CoV and 2019-nCoV. The present article also emphasizes the need for future development and the role of academia and collaboration with industry for speedy research with a rationale.

Background: Several health problems, especially musculoskeletal disorders, are causedby differences in work cultures and human lifestyles around the world. While the conventional approachto treating such conditions emphasizes a balanced work-life and daily exercise, nutraceuticalshave proven to be successful. Nutraceuticals are dietary compounds that help sustain cartilagemetabolism homeostasis, reducing articular pain. Dietary intake of a variety of nutraceuticals isthought to be essential for controlling and, more specifically, preventing osteoarthritis and osteoporosis. Objective: The current article offers a succinct overview in which data was gathered and searchedusing specific key terms related to nutraceuticals, osteoarthritis, and osteoporosis that were availablein public domains for analysis and evaluation. Methods: The current write-up offers a concise summary of disease and its relevance as to hownutraceuticals are helpful, based on the defined findings and their interpretation. The present reviewalso discusses the existing literature, patents, and current studies in the era of nutraceuticalsfor osteoarthritis and osteoporosis treatment, offering a rational basis for further investigation andresearch. Result: This article discusses a wide variety of nutraceuticals with possible uses for osteoarthritisand osteoporosis patients. An analysis revealed that nutraceuticals' efficacy has been established.However, further study and investigation are needed to determine their protection. Conclusion: As a result of this analysis, it was concluded that more innovation and technologytransfer were required. It was also concluded that greater industry-academic collaboration was requiredto begin more effective research in the treatment of osteoarthritis and osteoporosis withnutraceuticals.

Background: Piperine is a key bioactive alkaloid found in plants of piperaceae family. The compound possesses various medicinal and pharmacological activities (cholesterol-lowering, anti-cancer, Alzheimer’s disease etc.). Owing to its various target receptors (TRPV1, P-gp, CYP3A4 etc.) and several mechanisms, piperine has been studied as bio-enhancer for other drugs and its role has been evidenced in the literature. When administered with other drugs, it increases the absorption of other drugs, thereby reducing the dose and dose-related toxic potential. There are various mechanisms of piperine as a bio-enhancer and the common ones are i) prevention of efflux of drug molecules out of the cells; ii) decreased metabolism of drugs, thereby prolonging the halflife of drugs resulting in reduced urinary excretion. The detailed mechanism indicating the bio-enhancing role of piperine along with various target receptors has not been comprehensively summarised to date. Methods: Literature related to the molecular, enzymatic and receptor targets of piperine were studied, and database was collected using various search engines such as j-gate, google scholar, scihub, pubmed, sciencedirect, etc. The literature related to therapeutic activities of piperine and its bio-enhancer role for other drugs has been thoroughly studied and compiled in brief. Results: A detailed summary of piperine targets, along with related mechanisms, has been stated. A brief therapeutic profile of piperine alone has been produced with supporting literature. Piperine role as a potential bio-enhancer for other drugs has been summarized. Conclusion: Piperine is a fascinating molecule of natural origin with several modes of its action, not only possesses its own therapeutic activity but also enhances the therapeutic efficacy of other synthetic and natural drug molecules. Combination dosage forms of various API incorporating piperine as a bio-enhancer can be a potential area of thrust for upcoming drug design and development.

Background: Lovastatin is a statin drug used for lowering cholesterol in those with hypercholesterolemia to reduce the risk of cardiovascular disease. It is a BCS class II drug i.e. it has low aqueous solubility and high permeability. Objectives: Improvement of solubility and in vivo efficacy was investigated by formulating binary solid dispersions. Methods: Binary solid dispersions of lovastatin were formulated in the current study using two polymers i.e. Soluplus and PEG 4000. Seven batches of solid dispersions were prepared (S1, P1, SP1, SP2, SP3, SP4, and SP5) via the solvent evaporation method. The prepared dispersions were evaluated for equilibrium solubility, FTIR, XRD, DSC, SEM studies, and further in vitro drug release were evaluated. The results revealed significant enhancement in the solubility of drug-using polymer hybrids as compared to that of individual polymer dispersion batches. Results: A significant solubility enhancement was observed with SP5 (approx 40 times) having a higher concentration of Soluplus. FTIR studies indicated no drug to polymer interaction. DSC studies revealed complete amorphization of polymer and also X-RD data is also in compliance with DSC results. In vitro drug release studies showed almost 100% release in 2h in polymer hybrid batches in comparison to individual polymer batch (S1 and P1). The best dissolution characteristics were observed in SP3 and SP5 which is also in compliance with solubility data. Further in vivo efficacy studies revealed a significant reduction in LDL, HDL, TG, AST, and ALT levels in comparison to pure drug lovastatin group and hypercholesterolemia control group. Conclusion: Hybrid polymer may be a prospective carrier system for the enhancement of solubility of BCS class II drugs.

Background: Psoriasis is an autoimmune disease that ingeminates itself with the repeated proliferation of keratinocytes. It globally strikes a 2-5 % population on an average. Management of psoriasis remains a daunting task with various challenges influencing treatment, such as patient conformity and adherence to therapy, delicate patient profiles, psychological aspects, and skin as a barrier to topical delivery. The first part reviewed pathophysiology, triggering factors, and clinical classification. The second part reviewed all the therapies, such as topical, oral, biological, parenteral therapy, phototherapy, and the phyto-pharmaceuticals. Methods: The research data related to the existing and upcoming therapies for psoriasis treatment, several nanocarriers, existing marketed formulations, and detailed description of phytopharmaceuticals with their mechanism. Results: Topical therapy is the mainstay treatment option with limited adverse effects. Biological therapy has reformed conventional psoriasis treatment by being more efficacious and has increased patient acceptance due to decreased adverse events. Nanoformulations present an edge over conventional therapy due to improved anti-psoriatic effect and decreased side effects. Phyto-pharmaceuticals act as a complementary and alternative therapy for diminishing psoriasis symptoms. Conclusion: A rationalized cost-effective patient compliant therapy is required for effective management and complete cure of psoriasis.

Any kind of injury may lead to wound formation. As per World Health Organization Report, “more than 5 million people die each year due to injuries. This accounts for 9% of the world’s population death, nearly 1.7 times the number of fatalities that result from HIV/AIDS, tuberculosis and malaria combined. In addition, ten million people suffer from non-fatal injuries which require treatment”. This scenario leads to increased health and economic burden worldwide. Rapid wound healing is exigent subject-field in the health care system. It is imperative to be updated on wound care strategies as impaired wound healing may lead to chronic, non-healing wounds and thus further contributes to the national burden. This article is a comprehensive review of wound care strategies. The first and second part of this review article focuses on the understanding of wound, its types and human body’s healing mechanism. Wound healing is natural, highly coordinated process that starts on its own, immediately after the injury. However, individual health condition influences the healing process. Discussion of factors affecting wound healing has also been included. Next part includes the detailed review of diverse wound healing strategies that have already been developed for different types of wound. A detailed description of various polymers that may be used has been discussed. Amongst drug delivery systems, oligomers, dendrimers, films, gels, different nano-formulations, like nanocomposites, nanofibers, nanoemulsions and nanoparticles are discussed. Emphasis on bandages has been made in this article.

Background: Periodontal disease is an immuno-inflammatory condition of tissues that surround and hold the teeth. It is the disease which succeeds in all races, groups and both genders. Almost 10 to15% of the global population gets suffered from severe periodontitis as per WHO reports. Periodontal disease may likely cause other systemic diseases such as cardiovascular disease and pre-term low birth weight infants. Mechanical removal of plaques and calculus deposits from supra and subgingival environment is the backbone of periodontal treatment till date whereas complete elimination of these deleterious agents is quite unrealistic as the pocket depth increases. Recent Approaches: Recently controlled local drug delivery application is more encouraging in comparison to systemic approach as it mainly targets to enhance the therapeutic efficacy by maintaining site-specificity, avoiding first pass metabolism, reduction in gastrointestinal (GI) side effects and decreasing the dose. Several drugs such as antiseptics and antibiotics alongwith various carriers are being formulated as local drug delivery systems for effective management of the disease. Various local delivery systems reported are fibers, films, strips, compacts, injectables, microparticles, vesicular carriers, gels and nanoparticles. These local carriers provide effective prolonged treatment at the site of infection at reduced doses. This review enlightens detailed pathophysiology and various phases of periodontitis, challenges in treatment of disease and various antimicrobial agents (along with their marketed formulations) used. The main emphasis of the review is to cover all carrier systems developed so far for local delivery application in the effective management of periodontitis, as a patient compliant drug therapy.

RNA interference (RNAi) using small interfering RNA (siRNA) has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes. However, siRNA delivery faces several challenges, including stability, targeting, off-target effects, endosomal escape, immune response activation, intravascular degradation, and renal clearance. A variety of nanotherapeutics like lipidic nanoparticles, liposomes, polymeric nanoparticles, and solid lipid nanoparticles have been developed to improve siRNA cellular uptake, protect it from degradation, and enhance its therapeutic efficacy. Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity. This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases, including rheumatoid arthritis, osteoarthritis, etc. siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology, nanotechnology, and formulation sciences.

Background: Management of the health of oral tissues is a prime requirement in dentistry. The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges. The limitations in dental materials, medications, instruments, procedures put off the accomplishment of this goal. Rationalization of science and technology has made possible to work out these limitations. Nanotechnology which is the outcome of this rationalization has become one of the most favored technologies in medical and dental application. The substantial contribution of nano dental materials is the identification of oral health related problems by better diagnosis and management of dental disorders by bionanomaterials. Conclusion: Application of nanodentistry holds promise for comprehensive dental care by utilizing nanomaterials and ultimately by nanorobots. This review discusses the rationale of nanodentistry, nanocarriers researched in treatment of different dental diseases, the latest innovations in nanomaterials in various disciplines of dentistry; patent literature and related marketed products. Advances in nanotechnology have placed plenty of hopes in terms of improving the oral health care of dental patients.

Objective: The main aim of this study was to improve bioavailability of aceclofenac using neem gum as water soluble carrier for the development of solid dispersion based dosage form of the drug. Methods: Solid dispersions (SD) of aceclofenac were prepared by solvent evaporation technique and in the form of co-grinding mixture (CGM). Four batches of neem gum based solid dispersions of aceclofenac were prepared by varying the drug polymer ratio (1:1, 1:2, 1:3 and 1:5). Prepared solid dispersions were evaluated for solubility, FTIR, DSC, X-RD, SEM and in vitro release and the optimized batch was utilized to develop solid dosage form in the form of tablet. The final dosage form (tablet of neem gum based solid dispersion) was evaluated for physicochemical characterization, in vitro release and in vivo pharmacodynamic studies. Results: Solubility studies indicated 1:3 drug to neem gum ratio for the formulation of solid dispersion of drug. CGM also indicated improved solubility of drug. FTIR studies indicated no interaction of drug to polymer (presence of characteristic peaks of drug). DSC and X-RD studies indicated transition from crystalline to amorphous state of drug. SEM images of dispersion showed change in surface characteristics of drug particles in solid dispersions as compared to pure drug (crystallinity of pure drug). In vitro release studies revealed enhanced dissolution rate in solid dispersion (SD1 to SD3) and solid dispersion based tablet (T1) as compared to 47% in case of pure drug. Results of in vivo pharmacodynamic studies indicated faster analgesic potential and efficacy of optimized solid dispersion based tablet formulation than that of pure drug and marketed formulation. Conclusion: The solubility, drug release and in vivo results suggested applicability of neem gum as a prospective carrier of poorly soluble drugs.

Objective: Self-microemulsifying drug delivery system (SMEDDS) of aceclofenac was developed to alleviate poor solubility and bioavailability issues. Methods: The selection of components (oil, surfactant and co-surfactant) was based on saturated solubility studies and self emulsification ability. Pseudoternary phase diagrams were constructed to identify the self-emulsifying region. Isopropyl Myristate (IPM) was selected as oil phase; Cremophore as surfactant and Transcutol as co-surfactant (S/CoS mix) (in ratio of 1:1) respectively as optimized components for the SMEDDS formulation. The formulated liquid SMEDDS was evaluated for its self-emulsification time, phase separation, viscosity, cloud point and droplet size analysis. The liquid SMEDDS were converted to Solid SMEDDS by adsorption on solid carrier (Neusilin US2). Solid SMEDDS were further characterized for SEM, XRD, FTIR studies and evaluated for drug content, micrometric properties. Further Solid SMEDDS were compressed into tablet dosage form. Results: In vitro drug release of liquid and Solid SMEDDS, optimized tablet batch was carried out in buffer (pH 7.4) at 37oC. The optimized formulation showed almost 100% drug release in 30 min and it was significantly higher than that of pure drug. Conclusion: The study indicated the significance of aceclofenac SMEDDS as prospective carrier with enhanced dissolution characteristics for oral administration.

Background: More than 60% of the new drug molecules are lipophilic in nature. Low aqueous solubility and thus poor bioavailability is the main issue for these drugs for successful formulations into oral dosage form. Self-microemulsifying drug delivery systems (SMEDDS) have gained much attention. These are isotropic mixtures of different components (oil, surfactant and cosurfactant) that quickly disperse in gastrointestinal fluid yielding micro/nano-emulsions. These systems contain solubilized drug that is absorbed by lymphatic pathway along with other pathways like diffusion, collisional transfer, intracellular junctions, biliary acid pathway (BA), biliary acid mixed micelles pathway (BAMM) etc. and thus hepatic first pass metabolism is reduced. Stability of conventional SEDDS is considered very high with reference to other drug delivery systems as liposome, nanoparticles, nanoemulsion and micro emulsion. In fact SEDDS does not contain water in their composition which enhances their chemical and physical stability. Very few works have studied the stability of conventional SEDDS as it was confirmed. The major drawback for conventional SEDDS could be- i) high manufacturing cost (as they have to be filled in soft gelatin capsules); ii) interaction of capsule shell components with SEDDS. Therefore, attention has been given to transform liquid into solid SMEDDS by several techniques such as spray drying, spray cooling, super critical fluid technology and using adsorption carriers. Adsorption using solid carriers (Neusilin, Fujicalin, and dextran) is the successful inexpensive technique at initial research level whereas other requires expensive instrumentation. Conclusion: Current review focuses on biopharmaceutical aspects, characterization of SMEDDS and excipients used in the formulation, techniques used for conversion of liquid SMEDDS to solid SMEDDS (including examples of various research reports where these techniques are used). Various adsorbent carriers (alongwith their different features) which have been reported in research papers have been detailed. It thoroughly covers patent literature on SMEDDS and research carried on solid SMEDDS as well which is the most imperative part of the review.

Ensemble methods have been known to improve the quality of clusters/biclusters. We present in this paper an ensemble method for the biclustering problem using optimisation techniques. Extensive experiments performed on synthetic datasets and gene expression data have shown that the proposed method provides superior biclusters than the existing biclustering solutions most of the times.

In the last few decades, the development of biocompatible polymeric materials for biomedical applications has advanced significantly, which is of utmost necessity for skin regeneration and wound management. Nowadays, natural and synthetic based polymers are more favorable in the management of wound care and possess encouraging properties compared to conventional treatment which include grafting (autografts, allografts and xenografts), but due to its limitations such as lack of skin donor sites, immune rejection and immunological response, thus not act as an appropriate skin substitute in dermal regeneration. The current review highlights the recent advancement in the field of biopolymeric materials (single or in combination) and the various types of dressings used in dermal regeneration and wound management. Moreover, we also summarise the various biopolymer materials accompanying its commercially available wound dressings, their uniqueness, advantages, and disadvantages, and suggest how to overcome the problems associated with individual biopolymers and produce a perfect wound dressing with superior mechanical and cellular characteristics. This review will provide current knowledge in the research of biomaterials used for dermal regeneration and in wound management, including their limitations. We also believed that understanding the correctness of biomaterials for skin regeneration would enable us to provide the best wound dressings based on their specific applications.

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients. Results: In total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome. Conclusions: Based on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.

We present the case of a 26-year-old man who was brought into our emergency department in cardiorespiratory arrest, having taken Kratom 24 h previously. Despite multi-organ support, he deteriorated and died from cardiorespiratory failure and hypoxic brain damage 12 h later. Lipid emulsion was given, with significant temporary improvement in the cardiorespiratory failure. Kratom is derived from Mitragyna speciosa, a tropical deciduous and evergreen tree in the coffee family, and is native to Southeast Asia, and its leaves are used as a legal high in some parts of the world. Here, we review the pharmacochemistry of the drug, and wish to highlight that the effects of Kratom may not be as benign as are commonly reported, and the possible role of intralipid in managing the Kratom toxicity in this case.

Published ahead of print June 16, 2017.

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm2/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

Tuberculosis (TB) is a life-threatening infectious disease caused by the bacteria Mycobacterium tuberculosis (MTB), which mostly affects the lungs. According to the World Health Organization (WHO) report 2020, there were over 10 million cases of tuberculosis worldwide, with around 1.4 million people dying, wherein India accounts for over 26% of the global burden. Prolonged treatment, high pill burden, low compliance, development of multiple drug resistance and subsequent intolerable toxicity lead to the emergence of new nanotechnology-based drug delivery approaches involving micro-metric and nano-metric carriers. Nanotechnology is superior to conventional therapies as it offers site specific drug delivery of antimicrobial drugs that increases therapeutic efficacy and reduces systemic toxicity associated with higher doses and also prevents the drug from early degradation, increased solubility and blood retention time. This review focuses on the different nanotechnological carriers via pulmonary route, including liposomes, niosomes, solid lipid nanocarriers, dendrimers, nanoparticles, microspheres and microparticles for tackling the problems related to the treatment of TB. The current review gives a summary of the possible utilization of nanotechnologybased carrier systems to overcome the disadvantages of TB therapy. It also provides a summary of the importance and advancements of directing nanocarriers at bacterial reservoir. Eventually, the article presents an overview of the success in clinical application of such systems.

Emergency laparotomy is a high-risk surgical procedure with mortality and morbidity up to 10 times higher than for a similar procedure performed electively. An enhanced recovery approach has been shown to improve outcomes. A focus on rapid correction of underlying deranged acute physiology and proactive management of conditions associated with aging such as frailty and delirium are key. Patients are at high risk of complications and prevention and avoidance of failure to rescue are essential to improve outcomes. Other enhanced recovery components such as opioid-sparing analgesia and early postoperative mobilization are beneficial.

IMPORTANCE: Patients undergoing emergency laparotomy have high mortality, but few studies exist to improve outcomes for these patients. OBJECTIVE: To assess whether a collaborative approach to implement a 6-point care bundle is associated with reduction in mortality and length of stay and improvement in the delivery of standards of care across a group of hospitals. DESIGN, SETTING, AND PARTICIPANTS: The Emergency Laparotomy Collaborative (ELC) was a UK-based prospective quality improvement study of the implementation of a care bundle provided to patients requiring emergency laparotomy between October 1, 2015, and September 30, 2017. Participants were 28 National Health Service hospitals and emergency surgical patients who were treated at these hospitals and whose data were entered into the National Emergency Laparotomy Audit (NELA) database. Post-ELC implementation outcomes were compared with baseline data from July 1, 2014, to September 30, 2015. Data entry and collection were performed through the NELA. INTERVENTIONS: A 6-point, evidence-based care bundle was used. The bundle included prompt measurement of blood lactate levels, early review and treatment for sepsis, transfer to the operating room within defined time goals after the decision to operate, use of goal-directed fluid therapy, postoperative admission to an intensive care unit, and multidisciplinary involvement of senior clinicians in the decision and delivery of perioperative care. Change management and leadership coaching were provided to ELC leadership teams. MAIN OUTCOME AND MEASURES: Primary outcomes were in-hospital mortality, both crude and Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM) risk-adjusted, and length of stay. Secondary outcomes were the changes after implementation of the separate metrics in the care bundle. RESULTS: A total of 28 hospitals participated in the ELC and completed the project. The baseline group included 5562 patients (2937 female [52.8%] and a mean [range] age of 65.3 [18.0-114.0] years), whereas the post-ELC group had 9247 patients (4911 female [53.1%] and a mean [range] age of 65.0 [18.0-99.0] years). Unadjusted mortality rate decreased from 9.8% at baseline to 8.3% in year 2 of the project, and so did risk-adjusted mortality from a baseline of 5.3% to 4.5% post-ELC. Mean length of stay decreased from 20.1 days during year 1 to 18.9 days during year 2. Significant changes in 5 of the 6 metrics in the care bundle were achieved. CONCLUSIONS AND RELEVANCE: A collaborative approach using a quality improvement methodology and a care bundle appeared to be effective in reducing mortality and length of stay in emergency laparotomy, suggesting that hospitals should adopt such an approach to see better patient outcomes and care delivery performance.