Compensation in Neonatal Clinical Trials: A Perspective.

Well conducted clinical trials are the mainstay for generating evidence on preferred treatments. In order to adequately protect the interests of the trial participants, the Central Licensing Authority of India has formulated guidelines to determine the quantum of compensation in cases of regulatory clinical trial related injury or death. However, these guidelines do not address the nuances of trials recruiting children aged under 16 years, within which, neonates are the most vulnerable population. Thus, there is a need for addressing this lacuna in the current guidelines. This article examines the challenges in determining the quantum of compensation in neonatal clinical trials using the current formula, which is a corollary to the challenges faced by the authors in procuring clinical trial insurance for the Probiotic supplementation for Prevention of Neonatal Sepsis (ProSPoNS) trial. Further, it suggests a template for a differential formula using birthweight of infants, which is one of the many important factors impacting neonatal mortality.

Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial.

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

Current trends and advancements in spine surgery.

In recent years, spine surgery has undergone remarkable advancements, revolutionized the field, and transformed patient care. This special issue of the Journal of Orthopedics provides the best possible knowledge for its readers about the current trends and recent innovations in the field of spine surgery and supports clinicians and surgeons in their daily practice and decision-making process. It covers various topics like artificial intelligence in spine surgery, 3D printing, minimally invasive spine surgery. It also provides needed information on modic changes, management of eary onset scoliosis and recent trends in spinal cord injury management.

Ultrasonic bone scalpel in spine surgery.

Background: Spine surgery has always been considered technically demanding even in the hands of the most experienced surgeon on account of close proximity of vital soft tissue structures. Technical advancements over the last few decades have been crucial for the progress of this complex speciality which not only increased the surgical accuracy, but patient safety as well. Ultrasonic devices are one such innovation based on piezoelectric vibrations, patented by Fernando Bianchetti, Domenico Vercellotti, and Tomaso Vercellotti in 1988. Methods: We did an extensive literature search on ultrasonic devices and their applications in the field of spine surgery. Results: We present the various ultrasonic bone devices available including their physical, technologic and clinical aspects in spine surgery. We also attempt to cover the limitations and future advances of Ultrasonic bone scalpel (UBS) in particular, which would be interesting and informative for any spine surgeon who is novice in this field. Conclusion: UBS has been found to be safe and effective in all forms of spine surgeries offering distinct advantages over conventional instruments, although limited by an inherent learning curve.

Study protocol for economic evaluation of probiotic intervention for prevention of neonatal sepsis in 0-2-month old low-birth weight infants in India: the ProSPoNS trial.

INTRODUCTION: The ProSPoNS trial is a multicentre, double-blind, placebo-controlled trial to evaluate the role of probiotics in prevention of neonatal sepsis. The present protocol describes the data and methodology for the cost utility of the probiotic intervention alongside the controlled trial. METHODS AND ANALYSIS: A societal perspective will be adopted in the economic evaluation. Direct medical and non-medical costs associated with neonatal sepsis and its treatment would be ascertained in both the intervention and the control arm. Intervention costs will be facilitated through primary data collection and programme budgetary records. Treatment cost for neonatal sepsis and associated conditions will be accessed from Indian national costing database estimating healthcare system costs. A cost-utility design will be employed with outcome as incremental cost per disability-adjusted life year averted. Considering a time-horizon of 6 months, trial estimates will be extrapolated to model the cost and consequences among high-risk neonatal population in India. A discount rate of 3% will be used. Impact of uncertainties present in analysis will be addressed through both deterministic and probabilistic sensitivity analysis. ETHICS AND DISSEMINATION: Has been obtained from EC of the six participating sites (MGIMS Wardha, KEM Pune, JIPMER Puducherry, AIPH, Bhubaneswar, LHMC New Delhi, SMC Meerut) as well as from the ERC of LSTM, UK. A peer-reviewed article will be published after completion of the study. Findings will be disseminated to the community of the study sites, with academic bodies and policymakers. REGISTRATION: The protocol has been approved by the regulatory authority (Central Drugs Standards Control Organisation; CDSCO) in India (CT-NOC No. CT/NOC/17/2019 dated 1 March 2019). The ProSPoNS trial is registered at the Clinical Trial Registry of India (CTRI). Registered on 16 May 2019. TRIAL REGISTRATION NUMBER: CTRI/2019/05/019197; Clinical Trial Registry.

Rare Presentation of Meningitis Due to Lumbar Facetal Septic Abscess: A Case Report.

CASE: An elderly obese woman with comorbidities presented with acute-onset altered sensorium. She was diagnosed with meningitis and started on empirical antibiotics. She became oriented after 48 hours and mentioned that she had severe low backache in the previous week. Examination revealed bilateral lower limb weakness. Magnetic resonance imaging showed L3-L4 lumbar facetal abscess (LFA) with epidural extension. Posterior instrumented decompression was performed. Tissue culture grew Enterococcus, and the patient was administered vancomycin and linezolid. At 3 months, there was complete neurological recovery, and she was normal at the 1-year follow-up. CONCLUSION: This report highlights the rare presentation of LFA complicating meningitis and its treatment.

Thoracolumbar Fracture Dislocations Without Spinal Cord Injury: Classification and Principles of Management.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Thoracic and lumbar fracture dislocations (TLFD) are high-velocity injuries and frequently result in gross neurological deficit. Very rarely, such patients present with intact neurology. Pathomechanics of injury, radiological assessment, surgical techniques, and principles of fixation in such challenging situations have not been described previously. METHODS: Retrospective review of 36 patients of TLFD without cord injury was performed for demographics, clinical and radiological data, and management. The injuries were classified based on the direction of translation into 4 types: coronal translation (type 1), sagittal translation (type 2), combined translation-antero (type 3a), and combined translation-retro (type 3b). The injuries were managed by meticulous unilateral exposure and temporary fixation, decompression, gradual reduction of dislocation, and long segment fixation. RESULTS: In 36 patients, the injuries were classified as type 1 (n = 9), type 2 (n = 10), type 3a (n = 14), and type 3b (n = 3). Imaging/intraoperative observation showed varying degrees of disintegrity of disc, facet joints, and posterior ligamentous complex in the 4 different injury types. Patients with the different injury types also needed individualistic surgical approaches to aid safe reduction of dislocation. Neurological assessment was performed using American Spinal Injury Association score (ASIA), and 16 patients had minimal neurological deficits (ASIA-D) and all were type 3 injury. The mean anteroposterior and lateral translation were corrected from 8.3 ± 3.4 to 1.7 ± 1.3 mm, and 4.7 ± 4.8 to 0.7 ± 0.8 mm respectively. CONCLUSION: This is the largest case series of TLFD without cord injury. Knowledge of the different injury types and principles of safe surgical reduction of the dislocation are important for the treating surgeon to ensure successful outcomes.