Indian Biosimilars and Vaccines at Crossroads-Replicating the Success of Pharmagenerics.

BACKGROUND: The global pharma sector is fast shifting from generics to biologics and biosimilars with the first approval in Europe in 2006 followed by US approval in 2015. In the form of Hepatitis B vaccine, India saw its first recombinant biologics approval in 2000. Around 20% of generic medications and 62% of vaccines are now supplied by the Indian pharmaceutical industry. It is this good position in biologics and biosimilars production that could potentially improve healthcare via decreased treatment cost. India has witnessed large investments in biosimilars over the years. Numerous India-bred new players, e.g., Enzene Biosciences Ltd., are keen on biosimilars and have joined the race alongside the emerging giants, e.g., Biocon and Dr. Reddy's. A very positive sign was the remarkable disposition during the COVID-19 pandemic by Bharat Biotech and the Serum Institute of India. India's biopharmaceutical industry has been instrumental in producing and supplying preventives and therapeutics to fight COVID-19. Despite a weak supply chain and workforce pressure, the production was augmented to provide reasonably priced high-quality medications to more than 133 nations. Biosimilars could cost-effectively treat chronic diseases involving expensive conventional therapies, including diabetes, respiratory ailments, cancer, and connective tissue diseases. Biologics and biosimilars have been and are being tested to treat and manage COVID-19 symptoms characterized by inflammation and respiratory distress. PURPOSE OF REVIEW: Although India boasts many universities, research centers, and a relatively skilled workforce, its global University-Industry collaboration ranking is 24, IPR ranking remains 47 and innovation ranking 39. This reveals a wide industry-academia gap to bridge. There are gaps in effective translational research in India that must be promptly and appropriately addressed. Innovation demands strong and effective collaborations among universities, techno-incubators, and industries. METHODOLOGY: Many successful research findings in academia do not get translation opportunities supposedly due to low industrial collaboration, low IP knowledge, and publication pressure with stringent timelines. In light of this, a detailed review of literature, including policy papers, government initiatives, and corporate reviews, was carried out, and the compilation and synthesis of the secondary data were meticulously summarized for the easy comprehension of the facts and roadmap ahead. For easy comprehension, charts, figures, and compiled tables are presented. RESULTS: This review assesses India's situation in the biosimilar space, the gaps and areas to improve for Indian investment strategies, development, and innovation, addressing need for a more skilled workforce, industrial collaboration, and business models. CONCLUSIONS: This review also proposes forward an approach to empowering technopreneurs to develop MSMEs for large-scale operations to support India in taking innovative thoughts to the global level to ultimately realize a self-reliant India. The limitations of the compilation are also highlighted towards the end.

Analgesic efficacy of ketamine and magnesium after laparoscopic sleeve gastrectomy: A randomized, double-blind, placebo-controlled trial.

Background Ketamine and magnesium are antagonists of the N-methyl-d-aspartate receptor, and are valuable adjuvants for multimodal analgesia and opioid sparing. Data are limited regarding the opioid sparing efficacy of the combined intraoperative application of these agents in laparoscopic bariatric surgery. The objective of this study was to compare the postoperative opioid sparing properties of a single intraoperative dose of ketamine versus a combination of single doses of ketamine and magnesium after laparoscopic gastric sleeve resection in bariatric patients. Methods One hundred and twenty- six patients were randomly assigned to receive single boluses of ketamine alone 0.5 mg kg-1 IV (ketamine group); combined ketamine bolus of 0.5 mg kg-1 IV and magnesium 2 g IV (ketamine and magnesium group); or placebo. Opioid consumption at 24 h (in morphine equivalents); pain at rest; postoperative nausea and vomiting impact score; sedation scores; and trends of transcutaneous carbon-di-oxide values were analysed. Results The median (inter-quartile range [range]) morphine consumption at 24 h were 32 (24-47 [4.8-91]) mg in the ketamine group, 37 (18-53 [1-144]) mg in the ketamine and magnesium group, and 26 (21-36 [5-89]) mg in the control group and were not significantly different between the groups. There were no differences for all other outcomes examined. Conclusion Combined single intraoperative bolus doses of ketamine and magnesium did not result in postoperative opioid sparing after laparoscopic gastric sleeve resection.

Current understanding of the fascial plane blocks for analgesia of the chest wall: techniques and indications update for 2020.

PURPOSE OF REVIEW: Thoracic myofascial plane blocks have gained popularity because of their ease of performance and relative safety. This review highlights current research demonstrating the efficacy of these blocks for specific surgical procedures and provides a brief description of how these techniques are performed. RECENT FINDINGS: Fascial plane blocks of the thorax and chest wall have been shown to be beneficial in providing perioperative analgesia for a variety of surgical procedures. Studies discussed in this review compare thoracic fascial plane blocks to systemic analgesia alone, contrast these novel methods of pain control to more traditional techniques, such as paravertebral nerve blocks and epidural anesthesia, and attempt to determine, which fascial plane blocks provide optimal postsurgical analgesia. SUMMARY: Thoracic fascial plane blocks provide the anesthesiologist a number of techniques to address postsurgical pain. The relative ease of performance and safety profile of these blocks make them an appealing option for pain control for many patients undergoing thoracic or chest wall surgery. Further research is needed to not only define additional indications for each of these blocks, but also explore optimal dosing including the use of continuous catheter techniques.

Airway Management in the Operating Room and Interventional Suites in Known or Suspected COVID-19 Adult Patients: A Practical Review.

Current evidence suggests that coronavirus disease 2019 (COVID-19) spread occurs via respiratory droplets (particles >5 µm) and possibly through aerosol. The rate of transmission remains high during airway management. This was evident during the 2003 severe acute respiratory syndrome epidemic where those who were involved in tracheal intubation had a higher risk of infection than those who were not involved (odds ratio 6.6). We describe specific airway management principles for patients with known or suspected COVID-19 disease for an array of critical care and procedural settings. We conducted a thorough search of the available literature of airway management of COVID-19 across a variety of international settings. In addition, we have analyzed various medical professional body recommendations for common procedural practices such as interventional cardiology, gastroenterology, and pulmonology. A systematic process that aims to protect the operators involved via appropriate personal protective equipment, avoidance of unnecessary patient contact and minimalization of periprocedural aerosol generation are key components to successful airway management. For operating room cases requiring general anesthesia or complex interventional procedures, tracheal intubation should be the preferred option. For interventional procedures, when tracheal intubation is not indicated, cautious conscious sedation appears to be a reasonable approach. Awake intubation should be avoided unless it is absolutely necessary. Extubation is a high-risk procedure for aerosol and droplet spread and needs thorough planning and preparation. As updates and modifications in the management of COVID-19 are still evolving, local guidelines, appraised at regular intervals, are vital in optimizing clinical management.

Low-Cost Haptic Simulation Using Material Fracture.

Medical simulation training is widely used to effectively train for invasive medical procedures such as peripheral nerve blocks. Traditionally, accurate haptic training relies on expensive cadavers, manikins, or advanced haptic robots. Proposed herein is a novel concept for haptic training called the low-cost haptic force needle insertion simulator (LCNIS), which uses material fracture inside disposable cartridges to accurately replicate the force of inserting a needle into tissue. Cadaver and material fracture experiments were performed to develop and determine the accuracy of the LCNIS. The material testing showed that polycarbonate had the highest maximum needle puncture force of the materials tested, 9.85 N, and that fluorinated ethylene propylene had the lowest maximum puncture force, 0.84 N. The cadaver results showed that the error between the three peak forces in a cadaver and a cadaver mimicking cartridge was 1.00 N, 0.01 N, and 1.54 N. The standard deviation of these peaks was 0.60 N, 0.55 N, and 0.41 N. This novel method of haptic simulation can easily be adapted to recreate any type of force and, therefore, could be utilized to train for a wide variety of medical procedures.

An update on regional analgesia for rib fractures.

PURPOSE OF REVIEW: To provide an update on new strategies for pain management after rib fractures utilizing regional analgesia. RECENT FINDINGS: Pain management for patients with rib fractures can be very challenging. Traditionally, intravenous patient-controlled analgesia (IVPCA) with opioids, epidural, and paravertebral blocks have been used. These techniques, however, may be contraindicated or have limited application in certain patient populations. Recently, ultrasound-guided myofascial plane blocks such as the erector spinae plane (ESP) block and the serratus anterior plane (SAP) block have emerged as alternatives; providing excellent analgesia with minimal side effects. These blocks have the flexibility to be employed in a wide variety of circumstances where epidural and paravertebral approaches may not be feasible such as in anticoagulated patients and in patients with vertebral fractures where positioning options are limited. Myofascial blocks are less invasive and allow for broader and earlier application (e.g. in the emergency department). Further research on myofascial plane blocks is a priority. SUMMARY: Until recently, epidural, paravertebral, and intercostal blocks have been advocated as primary management techniques for pain associated with rib fractures. Newer myofascial plane blocks may play a key role in the future as part of alternative pain management strategies.

Erector Spinae Plane Block Versus Retrolaminar Block: A Magnetic Resonance Imaging and Anatomical Study.

BACKGROUND AND OBJECTIVES: The erector spinae plane (ESP) and retrolaminar blocks are ultrasound-guided techniques for thoracoabdominal wall analgesia involving injection into the musculofascial plane between the paraspinal back muscles and underlying thoracic vertebrae. The ESP block targets the tips of the transverse processes, whereas the retrolaminar block targets the laminae. We investigated if there were differences in injectate spread between the 2 techniques that would have implications for their clinical effect. METHODS: The blocks were performed in 3 fresh cadavers. The ESP and retrolaminar blocks were performed on opposite sides of each cadaver at the T5 vertebral level. Twenty milliliters of a radiocontrast dye mixture was injected in each block, and injectate spread was assessed by magnetic resonance imaging and anatomical dissection. RESULTS: Both blocks exhibited spread to the epidural and neural foraminal spaces over 2 to 5 levels. The ESP block produced additional spread to intercostal spaces over 5 to 9 levels and was associated with a greater extent of craniocaudal spread along the paraspinal muscles. CONCLUSIONS: The clinical effect of ESP and retrolaminar blocks can be explained by epidural and neural foraminal spread of local anesthetic. The ESP block produces additional intercostal spread, which may contribute to more extensive analgesia. The implications of these cadaveric observations require confirmation in clinical studies.

Erector spinae plane block as an alternative to epidural analgesia for post-operative analgesia following video-assisted thoracoscopic surgery: A case study and a literature review on the spread of local anaesthetic in the erector spinae plane.

Post-operative pain after minimally invasive video-assisted thoracoscopic surgery (VATS) in adults is commonly managed with oral and parenteral opioids and invasive regional techniques such as thoracic epidural blockade. Emerging research has shown that the novel erector spinae plane (ESP) block, can be employed as a simple and safe alternative analgesic technique for acute post-surgical, post-traumatic and chronic neuropathic thoracic pain in adults. We illustrate this by presenting a paediatric case of VATS, in which an ESP block provided better analgesia, due to greater dermatomal coverage, as well as reduced side-effects when compared with a thoracic epidural that had previously been employed on the same patient for a similar procedure on the opposite side.

Erector spinae plane block for the management of chronic shoulder pain: a case report.

PURPOSE: The erector spinae plane (ESP) block has been described in the successful management of both thoracic and abdominal pain. Since the erector spinae muscle extends to the cervical spine, the ESP block may be potentially useful in painful conditions of the shoulder girdle. CLINICAL FEATURES: We performed a series of ESP blocks at the T2/T3 level in an elderly male patient with chronic shoulder pain. Immediate and profound analgesia with improved range of motion was consistently observed following the block. There was detectable sensory block in the congruent cervico-thoracic dermatomes with no motor block. Computed tomography imaging showed the spread of radiocontrast up to the C3 level in the vicinity of the neural foramina. Clinical analgesia generally outlasted the expected duration of conduction blockade and significantly contributed to overall improvement in the patient's symptoms. CONCLUSIONS: The ESP block may be a promising alternative to other interventional procedures in the management of chronic shoulder pain and deserves further study.

Coagulation testing in the perioperative period.

Perioperative coagulation management is a complex task that has a significant impact on the perioperative journey of patients. Anaesthesia providers play a critical role in the decision-making on transfusion and/or haemostatic therapy in the surgical setting. Various tests are available in identifying coagulation abnormalities in the perioperative period. While the rapidly available bedside haemoglobin measurements can guide the transfusion of red blood cells, blood product administration is guided by many in vivo and in vitro tests. The introduction of newer anticoagulant medications and the implementation of the modified in vivo coagulation cascade have given a new dimension to the field of perioperative transfusion medicine. A proper understanding of the application and interpretation of the coagulation tests is vital for a good perioperative outcome.

Transversus abdominis plane block as the primary anesthetic for laparotomy.

Elderly patients undergoing emergency intra-abdominal surgery are at high risk for morbidity and mortality. The risks and side-effects associated with intubation and mechanical ventilation or neuraxial anesthesia must be balanced against the need to maintain hemodynamic stability while maximizing pain control. Providing anesthesia and analgesia without either of these techniques can be a difficult prospect. We present three cases of ultrasound guided transversus abdominis plane (TAP) block as the primary anesthetic for laparotomy in elderly patients with multiple comorbidities. We have demonstrated the efficacy of and recommend the use of TAP blocks as the primary surgical anesthetic in a selected group of patients undergoing laparotomy.

Oxidative stress-associated hypertension in surgically induced brain injury patients: effects of ß-blocker and angiotensin-converting enzyme inhibitor.

BACKGROUND: Postoperative hypertension is a common problem in patients undergoing surgical procedures, and the modification of this response could result in improved surgical outcome. Although it is recognized that the incidence of postoperative hypertension is higher in neurosurgical procedures, mechanisms behind this are not well understood. Oxidative stress is an important component of brain injury, and free radicals can influence blood pressure by a number of mechanisms. This study examined the effect of pretreatment with antihypertensive agents on postoperative hypertension in patients undergoing neurosurgery for supratentorial brain tumors and the role of oxidative stress in the process. METHODS: Forty-nine consecutive patients who underwent surgery for supratentorial brain tumors were divided in to three groups (control, Tab. Glucose; atenolol; and lisinopril groups). Blood was drawn at three time points (1 d before the surgery, at the time of dura opening, and at the time of extubation). Hemodynamic parameters in all three groups and levels of malondialdehyde, protein carbonyl content, nitrate, and α-tocopherol in serum at various time points were analyzed. RESULTS: The results showed that perioperative hemodynamic changes were highly associated with oxidative stress parameters in all the three groups. It was seen that atenolol and lisinopril significantly decreased levels of malondialdehyde, protein carbonyl content, and nitrate in the intraoperative period (P < 0.05), an effect which continued postoperatively. CONCLUSIONS: The results demonstrate that pretreatment with ß-receptor blocker (atenolol) or angiotensin-converting enzyme inhibitor (lisinopril) reduces postoperative hypertension in patients undergoing neurosurgery, and inhibition of oxidative stress may be a potential mechanism for this effect.