Effect of reduced two-dose (1+1) schedule of 10 and 13-valent pneumococcal conjugate vaccines (SynflorixTM and Prevenar13TM)) on nasopharyngeal carriage and serotype-specific immune response in the first two years of life: Results from an open-labelled randomized controlled trial in Indian children.

INTRODUCTION: This study aimed to assess the effect of a reduced dose regime (1 + 1) of PCV10 and PCV13 along with 3-dose regimes on pneumococcal vaccine-type (VT) carriage and immunogenicity in the first two years of life in PCV-naïve Indian children. METHODS: A total of 805 healthy infants aged 6-8 weeks were randomised to 7 groups (n = 115). Six groups received SynflorixTM(PCV10) or Prevenar13TM(PCV13) in the following schedules: 3 + 0 (three primary at 6, 10, and 14 weeks); 2 + 1 (two primary 6 and 14 weeks with booster at 9 months; 1 + 1 (one primary at 14 weeks with booster at 9 months). The 7th group was a PCV-naïve control group. Nasopharyngeal swabs were collected at 6, 18 weeks, 9, 10, 15, and 18 months of age. Venous blood samples were collected at 18 weeks, 9, 10, and 18 months of age for assessment of sero-specific IgG antibodies. Additionally, functional activity using a serotype specific opsonophagocytic assay (OPA) was assessed at 10 and 18 months of age in a subset (20%) of participants. RESULTS: All schedules of PCV13 showed significant 13VT carriage reduction in the second year of life as compared to control. At 15 months of age, PCV13 (1 + 1) showed 45 % reduction in 13VT-carriage compared to the control [OR = 0.55 (95% CI; 0.31-0.97), p= 0.038]. None of the PCV10 schedules showed significant reduction in 10VT carriage in the second year. Although not powered for these outcomes, at 18 months of age, 1 + 1 and 2 + 1 schedules of both vaccines demonstrated higher sero-responders for all serotypes, higher geometric mean concentrations (GMC) for all serotypes except 23F [with both vaccines], higher percent OPA responders and OPA geometric mean titres (GMT) compared to the 3 + 0 schedules for all serotypes. CONCLUSION: The reduced dose schedule (1 + 1) of PCV13 results in significant VT-carriage reduction in the second year of life. Immune protection provided by 1 + 1 schedules of PCV10 and PCV13 in the second year of life is comparable to WHO-recommended 3-dose schedules.

Fistulotomy versus Fistulectomy for Fistula-in-Ano: A Randomized Prospective Study.

Background Fistula-in-ano is common surgical ailment yet challenging to treat. Current management remains majorly dependent on two conventional surgical options (fistulotomy and fistulectomy), surgeon's preference, and their experience. Methods This prospective, randomized study was conducted to compare fistulotomy with fistulectomy in the management of patients with simple fistula-in-ano. Fifty patients were recruited and randomized into two groups each containing 25 patients: group I was managed by fistulotomy and group II was managed by fistulectomy. The outcomes of the study include operating time, postsurgery hospital stay, wound healing time, postoperative pain, and postoperative complications. Results Of the 50 patients, 11 (22%) were female and 39 (78%) were male with a mean age of 40.62 ± 12.86 years. The operating time in patients in the fistulotomy group was 21.96 ± 1.90 minutes and in the fistulectomy group was 31.32 ± 2.99 minutes ( p ≤ 0.001). The mean postsurgical hospital stay in the fistulotomy group was 1.32 ± 0.47 days and in the fistulectomy group was 2.32 ± 0.69 days ( p ≤ 0.001), respectively. Mean Visual Analog Scale score was higher in fistulectomy when compared with the fistulotomy at 6 hours and at discharge ( p ≤ 0.05). Postoperative complications were also found to be less in fistulotomy patients compared with patients who underwent fistulectomy. Conclusion In comparison to a fistulectomy, fistulotomy has a slight edge in terms of operating time, postsurgery hospital stay, wound healing time, postoperative pain, and postoperative complications. Fistulotomy yielded better results than fistulectomy and we recommend fistulotomy procedure as a treatment of choice in patients with simple low lying fistula-in-ano.

Efficacy and Safety of a Phytopharmaceutical Drug Derived from Cocculus hirsutus in Adults with Moderate COVID-19: a Phase 2, Open-label, Multicenter, Randomized Controlled Trial.

INTRODUCTION: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19. METHODS: In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18-75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints. RESULTS: A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference - 0.01 (95% CI - 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8-11) in the AQCH group versus 11 days (IQR 8-11) in the control group [HR 1.27 (95% CI 0.95-1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified. CONCLUSIONS: AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted. TRIAL REGISTRATION: Clinical Trials Registry - India (CTRI/2020/05/025397).

Robotic-assisted TKA leads to a better prosthesis alignment and a better joint line restoration as compared to conventional TKA: a prospective randomized controlled trial.

PURPOSE: Correct positioning and alignment of the prosthesis is a very important factor for durability of prosthesis and implant survival which is improved with the use of technology in total knee arthroplasty. However, the long-term functional outcomes and survivorship are unclear. For this study, it was hypothesized that mechanical axis alignment of lower limb, post-operative joint line restoration, femoral and tibial component alignment is more accurate with the new handheld semi-active robotic-assisted TKA. METHOD: From April-2019 to March-2020, 60 patients with unilateral knee osteoarthritis who underwent total knee arthroplasties were included in this prospective randomised controlled study. Computer generated randomization was used. Study included 48 female patients and 12 male patients. Pre-operative and post-operative radiographic measurements were done and compared between the two groups. RESULTS: There was a significant difference between two groups with respect to mechanical axis deviation, joint line deviation and coronal alignment of femoral and tibial prosthesis. Mechanical axis deviation > 3° was seen in eight cases (28.5%) in C-TKA group compared to one case (3.1%) in RA-TKA (p 0.019). Joint line deviation of 3.5 mm was noted in C-TKA group as compared to 0.9 mm in RA-TKA group (p < 0.001) which was statistically significant. However, whether this difference of 2.6 mm of joint line elevation between C-TKA and RA-TKA leads to any difference in clinical outcome in terms of knee kinematics and knee flexion needs to be investigated with further studies. Clinically restoring normal joint line is important for improved knee function after primary TKA. No significant difference was noted in femoral component rotation on post-operative computed tomography (CT) scan. CONCLUSION: The novel imageless, handheld semi-autonomous robotic system for TKA is highly accurate with respect to component positioning in coronal plane and mechanical alignment as compared to conventional TKA. Joint line is elevated in conventional TKA but is accurately restored using the robotic-assisted TKA which may lead to better patellofemoral kinematics. LEVEL OF EVIDENCE: I.

Assessment of accuracy of an imageless hand-held robotic-assisted system in component positioning in total knee replacement: a prospective study.

In recent years, robotic technology is becoming more pervasive in joint arthroplasty. The role of robotics in joint replacement surgery is to bring precision and accuracy in bone preparation, implant positioning and soft tissue balancing. However, there is yet to be a study conducted to determine the accuracy of bone preparation done by a new robotic system. The purpose of this study is to evaluate and report on the accuracy of bone cuts using imageless semiautonomous freehand robotic sculpting system, Navio (Smith & Nephew) based on the data provided by the robotic system. Between August 2018 and May 2019, a total of 62 patients were prospectively enrolled in this study. All surgeries were done by the senior author using a medial para-patellar approach and using a posterior stabilised implant (Anthem, Smith & Nephew Inc.). The study included 37 female patients and 25 male patients. The parameters assessed in this study were: (1) mechanical axis, (2) femoral coronal alignment, (3) femoral rotation, (4) femoral sagittal alignment, (5) tibial slope and (6) tibial coronal alignment using paired t test and root mean squared error (RMSE). The robotic system was accurate in achieving the bone cuts as planned in mechanical axis alignment (p = 0.89, RMSE = 0.56), femoral coronal alignment (p = 0.36, RMSE = 0.36), femoral sagittal alignment (p = 0.10, RMSE = 0.44), femoral rotation (p = 0.91, RMSE = 0.11), tibial coronal alignment (p = 0.81, RMSE = 0.24) and tibial slope (p = 0.30, RMSE = 0.37) with the maximum RMSE being 0.56. This study demonstrated that semi-autonomous hand-held robotic system, Navio (Smith & Nephew) for total knee arthroplasty produced accurate component positioning as per plan in all planes. The maximum RMSE was 0.56°.

Bioink: a 3D-bioprinting tool for anticancer drug discovery and cancer management.

'Bioinks' are important tools for the fabrication of artificial living-tissue constructs that are able to mimic all properties of native tissues via 3D bioprinting technologies. Bioinks are most commonly made by incorporating live cells of interest within a natural or synthetic biocompatible polymeric matrix. In oncology research, the ability to recreate a tumor microenvironment (TME) using by 3D bioprinting constitutes a promising approach for drug development, screening, and in vitro cancer modeling. Here, we review the different types of bioink used for 3D bioprinting, with a focus on its application in cancer management. In addition, we consider the fabrication of bioink using customized materials/cells and their properties in the field of cancer drug discovery.

Comprehensive approach of hybrid nanoplatforms in drug delivery and theranostics to combat cancer.

To date, various chemically synthesized and biosynthesized nanoparticles, or hybrid nanosystems and/or nanoplatforms, have been developed under the umbrella of nanomedicine. These can be introduced into the body orally, nasally, intratumorally or intravenously. Successfully translating hybrid nanoplatforms from preclinical proof-of-concept to therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. This review aims to identify gaps in our understanding of the current strengths of nanomedicine platforms in drug delivery and cancer theranostics. We report on the current approaches of nanomedicine at preclinical and clinical stages.

Immunogenicity and lot-to-lot consistency of a ready to use liquid bovine-human reassortant pentavalent rotavirus vaccine (ROTASIIL - Liquid) in Indian infants.

BACKGROUND: A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency. METHODS: This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards. RESULTS: Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related. CONCLUSION: The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®. TRIAL REGISTRATION NUMBER: Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].

Comprehensive cytotoxicity studies of superparamagnetic iron oxide nanoparticles.

Recently lots of efforts have been taken to develop superparamagnetic iron oxide nanoparticles (SPIONs) for biomedical applications. So it is utmost necessary to have in depth knowledge of the toxicity occurred by this material. This article is designed in such way that it covers all the associated toxicity issues of SPIONs. It mainly emphasis on toxicity occurred at different levels including cellular alterations in the form of damage to nucleic acids due to oxidative stress and altered cellular response. In addition focus is been devoted for in vitro and in vivo toxicity of SPIONs, so that a better therapeutics can be designed. At the end the time dependent nature of toxicity and its ultimate faith inside the body is being discussed.

Attitudes and Perceptions of Medical Undergraduates Towards Mobile Learning (M-learning).

INTRODUCTION: Mobile technology is one of the latest extensions of technological innovations that can be integrated into medical education. With the aid of these devices, students learn faster outside the classroom by having quick access to the internet and easy retrieval of required health related learning resources to keep alongside of recent trend and development. In medicine practice one has to continuously update his/her medical knowledge and mobile learning will serve as a tool for self-directed learning. AIM: To explore the attitudes and perceptions of undergraduate students towards M-learning. MATERIALS AND METHODS: This educational research included 90 third year MBBS students having clinical posting under the Department of Community Medicine from tertiary healthcare institute in Nashik. Students learning approach was studied with the help of pre-validated questionnaire to know whether they have deep or surface approach to learning. M-learning group was formed on mobile social app to supplement conventional teaching-learning. One subject topic (Tuberculosis, Dengue fever/DHF, Hypertension and Diabetes Mellitus etc.) per week was allotted and after conventional teaching on first day of week the learning materials for the topic chosen for that week were uploaded on the group and students could download as well as share their ideas, learning resources, ask doubts and answer questions at least twice weekly through this mobile platform anytime, anywhere. At the end of three months students attitudes and perceptions towards M-learning were studied by pre-validated structured questionnaires. A five point Likert scale was used (5= strongly agree to 1= strongly disagree) for answering each item of all three questionnaires. The score of 60% (90 out of 150) and the score of 75% (30 out of 40) for each item was considered as the measure that indicates whether or not the student had a positive attitude and perceived the importance of M-learning respectively. Utilisation of M-learning was also studied. RESULTS: It was found that 47 (52.2%) students had deep learning approach, 10 (11.1%) students had surface learning approach. An 80% of students had positive attitude towards M-learning and 76.7% students had perceived the importance of M-learning. A 52.2% of students were actively involved in M-learning group for learning purpose. But 57.8% students did not download (at least twice weekly) the shared reference material, 38.9% students never read and/or replied to the questions asked and 60.0% students never asked any doubts/questions related to the discussion. CONCLUSION: Students had positive attitude and perceived the importance of M-learning. But when they were provided with the opportunity, they did not show appreciable M-learning utilization. This could be because, M-learning was not implemented by all departments; also it was not the part of student's regular assessment and probably a lesser study duration.

A Cross-sectional Study of Common Psychiatric Morbidity in Children Aged 5 to 14 Years in an Urban Slum.

AIM: Study of the prevalence of common psychiatric disorders in children aged 5 to 14 years in a health post area of an urban slum. OBJECTIVES: (1) To study frequency of specific psychiatric disorders in the study population, (2) To study the relationship between sociodemographic variables and psychiatric morbidity. SETTINGS AND DESIGN: The present study was conducted in one of the five health posts of an urban slum, which is a field practice area of the teaching medical institute. It was a cross-sectional study. MATERIALS AND METHODS: Sample size was estimated by using 20% as a prevalence of psychiatric morbidity which was obtained from previous studies done in developing countries. Household was used as a sampling unit and systematic random sampling method was used for selecting household. Total 257 children aged 5 to 14 years were included in the study. A pre-designed, semi-structured diagnostic interview schedule based on DSM-IV criteria was used for data collection. STATISTICAL ANALYSIS USED: The tests of significance used were Chi-square and Logistic regression analysis. RESULTS: The prevalence of psychiatric morbidity in this study was 14.8%. Non-organic enuresis, Attention deficit hyperactivity disorder, Conduct disorder, and Mental retardation were identified as the common mental health problems. CONCLUSIONS: Factors like nuclear family, parents not living together, large family size, and positive family history of psychiatric disorder were associated with psychiatric morbidity in children.

Chemical characterization, mineral analysis, and antioxidant potential of two underutilized berries (Carissa carandus and Eleagnus conferta) from the Western Ghats of India.

Diversity needs to be "conserved through use." Owing to the global need, the present study includes two underutilized berries, Carissa carandus and Eleagnus conferta, to explore their potential as supplementary food by evaluating their antioxidant activity and approximate chemical composition. Berries of E. conferta are a richer source of carotene, ascorbic acid, protein, and magnesium, whereas berries of C. carandus are rich in sugars, lipids, iron, and magnesium. The antioxidant properties of the berries and a comparative account on their performance using DPPH and FRAP assay was studied. Both assays revealed high activity in the peel extract of berries of C. carandus. The LC-MS/MS profile of C. carandus reveals the presence of eleven different polyphenolic compounds while E. conferta had only four of these compounds.