Daratumumab in Indian patients with relapsed and refractory multiple myeloma: a prospective, multicenter, phase IV study.

Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients. Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.

Cost of implementing the QualityRights programme in public hospitals in Gujarat providing mental healthcare.

Background & objectives: Investment in mental health is quite meagre worldwide, including in India. The costs of new interventions must be clarified to ensure the appropriate utilization of available resources. The government of Gujarat implemented QualityRights intervention at six public mental health hospitals. This study was aimed to project the costs of scaling up of the Gujarat QualityRights intervention to understand the additional resources needed for a broader implementation. Methods: Economic costs of the QualityRights intervention were calculated using an ingredients-based approach from the health systems' perspective. Major activities within the QualityRights intervention included assessment visits, meetings, training of trainers, provision of peer support and onsite training. Results: Total costs of implementing the QualityRights intervention varied from Indian Rupees (₹) 0.59 million to ₹ 2.59 million [1United States Dollars (US $) = ₹ 74.132] across six intervention sites at 2020 prices with 69-79 per cent of the cost being time cost. Scaling up the intervention to the entire State of Gujarat would require about two per cent increase in financial investment, or about 7.5 per cent increase in total cost including time costs over and above the costs of usual care for people with mental health conditions in public health facilities across the State. Interpretation & conclusions: The findings of this study suggest that human resources were the major cost contributor of the programme. Given the shortage of trained human resources in the mental health sector, appropriate planning during the scale-up phase of the QualityRights intervention is required to ensure all staff members receive the required training, and the treatment is not compromised during this training phase. As only about two per cent increase in financial cost can improve the quality of mental healthcare significantly, the State government can plan for its scale-up across the State.

Relationship between Hemispheric Preference Score and Academic Performance among Preclinical Medical Students Studying Medicine and Dentistry.

Background: Understanding the style of learning and thinking (SOLAT) of the students is necessary to keep students actively involved in learning, which could influence the academic performance of the students. Aim: The objective of this study was to compare the right and left hemisphere preferences for processing information with academic performance of medical students in both theory and practical exams. Materials and Methods: The hemispheric preference score for learning and thinking style among first year MBBS (95) and BDS (42) students was determined by SOLAT tool prepared by Dr. V. Venkataraman (1994). A comparison of the hemispheric score between high achievers and low achievers in theory and practical exams was performed by using the unpaired Student's t-test and Mann-Whitney U-test. Results: The mean hemispheric scores for the right hemisphere, left hemisphere, and whole brain were 26.51, 14.5, and 6.76, respectively. High achievers in theory exam and practical exam received a higher left-hemispheric score and whole-brain score than low achievers; the difference in the mean value of hemispheric score was statistically not significant. Conclusion: There was no statistically significant relationship between academic achievement and hemispheric preference scores.

Correction to: Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

[This corrects the article DOI: 10.1007/s12288-022-01602-5.].

Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18-65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP. Trial registration number and date of registration: CTRI/2019/04/018614.

Safety and Efficacy of Thalidomide and Hydroxyurea Combination in Beta Thalassemia Patients.

Beta thalassemia results from imbalance in alpha and beta globin chains causing severe anemia, transfusion dependency, and iron overload. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Patients without the option of HSCT may benefit from Hemoglobin F (HbF) inducing agents like thalidomide and hydroxyurea (HU). We conducted a retrospective analysis on 87 beta thalassemia patients who received a combination of low dose thalidomide and HU from January 2017 to December 2020. Patients received combination of HU 500 mg everyday (> 30 kg) or every alternate day (< 30 kg) and thalidomide 100 mg (> 30 kg) or 50 mg (< 30 kg) once daily. Parameters such as transfusion requirement, anthropometry, Hb levels, ferritin, drug side effects etc. were monitored and evaluated at the end of one year of therapy. Sixty-three patients (72%) achieved transfusion independence and were eligible for the study. Median time to transfusion independence was 6 months (range 3-11 months). At the end of 1 year, overall response rate was 72%. There was significant improvement in the Hb levels, ferritin values and height at the end of 1 year of follow up. No grade 3 or 4 toxicities were noted. We document improvement of Hb levels, transfusion independence, reduction in iron overload, and improvement in growth parameters with minimal side effects at the end of 1 year of follow up.

Rapid Diagnostic Testing for Response to the Monkeypox Outbreak - Laboratory Response Network, United States, May 17-June 30, 2022.

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

Experience of Nivolumab Prior to Autologous Stem Cell Transplant for Relapsed Refractory Hodgkin Lymphoma.

Purpose Nivolumab is an anti-programmed cell death protein 1 (PD1) monoclonal antibody that is indicated in relapsed/refractory Hodgkin lymphoma (R/R HL) after autologous stem cell transplant (autoSCT). Purpose of our retrospective study was to assess safety and efficacy of Nivolumab in R/R HL as a bridge to autoSCT in patients who are refractory to ≥ 2 lines of chemotherapy. Methods Demographic data, number of chemotherapy regimens given previously, number of Nivolumab doses taken, and disease status on PET/CT were noted. Nivolumab was administered as a 3 mg/kg IV infusion every 2 weeks. The immunotherapy related adverse events (irAEs) were noted if any and documented. Results A total of 16 patients were included in the study. Ten patients were male and 6 were female. Median age was 22 years (range 3-32 years). The median number of treatment lines prior to Nivolumab was 3 (range 2-7). Nine patients had Complete Response (CR), 3 had Partial response (PR), 2 had Stable Disease (SD), 1 patient had pseudo-progression; classified as IR (3) and 1 expired before end of treatment evaluation. The drug was well tolerated, with mild irAEs noted. Twelve patients (75%) successfully underwent autoSCT. At a median follow up of 17.5 months (range 0.5-35 months), the progression- free survival (PFS) was 75% and overall survival (OS) was 87.5%. Conclusion Nivolumab is effective and safe in patients with R/R HL and is a good bridging therapy to autoSCT.

Genomic sequence of the HLA-B*15:01:02 and HLA-C*08:72:01 alleles identified in Gujarati individuals.

The full length sequence of HLA-B*15:01:02 and HLA-C*08:72:01 are reported.

Genomic sequence of the HLA-A*11:01:54 allele identified by next-generation sequencing in a transplant donor.

The full-length sequence of the HLA-A*11:01:54 allele was identified.

The novel HLA-A*24:49:02 and HLA-DQB1*06:428 alleles identified in Indian bone marrow donors.

Identification of two novel HLA alleles in Indian bone marrow donors.

Lived Experiences of Bereaved Family Members During COVID-19 Pandemic in a Tertiary Care Hospital With Special Reference to Imposed Restrictive COVID Guidelines-a Qualitative Study.

This study aimed to understand the experiences of bereaved family members in view of restrictive COVID guidelines using qualitative approach. 10 Hindu, Gujarati bereaved family members who lost their loved ones during the first wave were interviewed telephonically after a month of their loss. Findings were difficulty in proper communication during hospitalization, disrupted end-of-life and funeral rituals and accepting harsh realities related to the changes imposed by using content analysis. Most of the family members felt that there was a need of staying with the patients. Telephonic mode of communication was not sufficient for them and created doubts related to death. Most of them felt remorseful as they were not able to see or bring their loved one home during their last moments and felt deprived of the traditional rituals. Also, they had to deal with their grief by themselves.

Analysis of change in knowledge, attitude, and practices about COVID-19 following and awareness session in rural population of Western India.

BACKGROUND: Beginning of the pandemic showed our limitations in our understanding of the spread of the dreaded coronavirus-19 that had sprung from China and spread through thick and thin across the world. The measures to contain the spread of virus in the absence of specific treatment protocol had everyone grope for the solutions in a very short time frame. One such is the knowledge, attitude, and practice in the rural setup. AIM: The aim of the study is to measure the change in knowledge, attitude, and practices (KAP) regarding COVID-19 following an awareness session in rural population. MATERIALS AND METHODS: A cross-section interventional study was carried out in January 2021. An interactive awareness session was conducted with the help of audiovisual aids following MOHFW guidelines for COVID-19, and the change in KAP about COVID-19 was measured by pre- and posttest standardized questionnaire. RESULTS: Of all the participants, statistically significant change in knowledge was seen from 43% to 52%. The villagers were educated about preventive steps and a positive change was measured in the practice of changing masks regularly (84%-100%), maintaining social distancing (44%-64%), frequent handwashing (52%-64%). No change was seen in wearing of masks (92%) and negative change was seen in avoiding handshakes (32%-28%). The preventive practices regarding COVID-19 pandemic changed significantly from 50% to 58%. Our study measured positive attitude change toward getting vaccinated from 64% to 72%. CONCLUSION: A single, short awareness session led to significant change in KAP about COVID-19 in rural population.

Unmanipulated Stem Cell Boost for Mixed Chimerism in Transfusion Dependent Thalassemia.

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. There were 70 transplants done for 69 TDT patients at our center between September 2005 and January 2020. Mixed chimerism was defined by > 5% recipient cells and the severity was assigned according to the proportion of recipient cells as level 1 = < 10%, level 2 = 10-25%, level 3 = > 25%. For patients developing MC level 2 and 3, we administered unmanipulated SCB and analyzed its safety and efficacy. Out of 70 transplants 7 (10%) had MC level 2 (3/7) and 3 (4/7). These patients received unmanipulated SCB at a median CD34 cell dose of 4.5 × 106/kg (range-3.5 × 106/kg-5.5 × 106/kg). Overall Response (stable MC and/or transfusion independency) to unmanipulated SCB was seen in 5 patients (71.4%). Five patients (71.4%) developed acute graft versus host disease (GVHD) of which 1 patient expired due to severe GVHD. SCB infusion was well tolerated by majority of our patients. The 3 year overall survival and thalassemia free survival was 85.7% (6/7) and 57.1% (4/7) respectively. Timely monitoring of chimerism is important for detecting early MC. Development of acute GVHD is common after administration of unmanipulated SCB and requires vigilance and prompt management. Unmanipulated SCB is a feasible modality for treating progressive MC and salvaging the graft especially in resource-constrained settings.

Spontaneous Renal Artery Dissection in COVID-19 Pneumonia: Potential Danger of Cytokine Storm.

The coronavirus disease (COVID-19) pandemic has rapidly spread across the globe since its first detection in March 2020. Its widespread manifestations and vascular complications are increasingly being reported even in young and middle-aged patients. Hyperinflammation is a continuum of host's exaggerated inflammatory response representing cytokine dysregulation/storm which produces coagulopathy and vascular endothelial dysfunction, apart from a prothrombotic state. Cytokine storm or direct viral invasion of the vascular endothelial cells through surface angiotensin-converting enzyme 2 receptors may result in endothelial dysfunction which can potentially result in dissection. Only a few case reports have been published in the literature describing vascular dissection without any inciting factors in COVID-19 patients. Herein, we present the first case report of bilateral renal artery dissection in a 41-year-old male patient who recently recovered from COVID-19 and was managed successfully in stages after many medical hurdles.

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.

OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.

Post-transplant Hemophagocytic Lymphohistiocytosis in Benign Hematological Disorders: Experience of 4 Cases with Review of Literature.

Post transplant Hemophagocytic lymphohistiocytosis (HLH) is a form of secondary HLH, which can be either early onset or late onset and is associated with significant morbidity and mortality. With the increasing popularity of post transplant cyclophosphamide based haploidentical stem cell transplantation (SCT), post transplant HLH is becoming a significant complication especially in benign hematological disorders. Methods: We present 4 cases of post transplant HLH occurring in 2 cases of severe aplastic anemia (post haploidentical SCT) and 2 cases of thalassemia major (post matched sibling SCT). All 4 cases had early onset variety with dismal prognosis. Conclusion: Post-transplant HLH is an important entity in benign hematological disorders, which needs to be identified early and treated promptly with steroids, monoclonal agents or immunosuppressive therapy. Serum ferritin levels are an important biomarker and help in monitoring response.

Impact of a community-based mental health awareness program on changing attitudes of the general population toward mental health in Gujarat, India - A study of 711 respondents.

CONTEXT: In India, there is a large mental illness treatment gap, especially in rural areas. Contributors to this problem include stigma and a general lack of mental health knowledge. The State Health Department of Gujarat, India, released a video tool, in 2003, with the goal being to educate the community on topics related to mental health. AIMS: The aim of this study was to evaluate the ability of the government-developed video tool to improve attitudes toward mental health in rural Gujarat. SETTINGS AND DESIGN: Eight hundred and sixty-five individuals, in 17 villages in Gujarat, agreed to attend a mental health awareness workshop that used the government-developed video tool. One workshop was held in each village. A structured questionnaire evaluating attitudes was administered to the participants before and after the workshop. SUBJECTS AND METHODS: government-developed video tool, standardized questionnaire for attitude evaluation. STATISTICAL ANALYSIS USED: A McNemar's test was used to evaluate the difference between pre- and post-scores. RESULTS: A total of 711 participants completed the pre- and post-questionnaire. Attitudes related to psychosis, suicidal ideation, postpartum depression, learning disability, general mental illness, and perceptions of dangerousness showed significantly favorable improvement (P <.005). Attitudes related to substance abuse worsened (P < 0.005). CONCLUSIONS: Results suggest that a government-developed video tool can successfully improve short-term attitudes. Attitudes toward substance abuse may require a different approach than attitudes toward other types of mental illness.