Economic Evaluation of Nucleic Acid Testing for Screening of Blood Donations for Thalassemia Patients (ECONAT) in Western India.

Background: Transfusion Transmitted infections(TTI) are of significant concern for blood safety. The thalassemia patients who receive multiple transfusions are at an increased risk of TTIs and the Nucleic Acid Test (NAT ) has been advocated for safe blood. Though NAT can reduce the window period compared to serology, cost is a constraint. Methods: The thalassemia patient and NAT yield data from the centralized NAT lab in AIIMS Jodhpur was evaluated for cost-effectiveness using the Markov model. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between the cost for NAT and the cost of medical management of TTI-related complications by the product of the difference in utility value of a TTI health state with time and Gross National Income(GNI) per capita. Results: Out of the 48,762 samples tested by NAT, 43 samples were discriminated NAT yield all of which were reactive for Hepatitis B (NAT yield of 1:1134). There was no HCV and HIV NAT yield despite HCV being the most prevalent TTI in this population. The cost of this intervention was INR 5,85,14,400. The number of lifetime QALY saved was 1.38 years. The cost of medical management is INR 82,19,114. Therefore the ICER for intervention is INR 3,64,45,860 per QALY saved which is 274 times the GNI per capita of India. Conclusions: The provision of IDNAT-tested blood for thalassemia patients in Rajasthan state was not found to be cost-effective. Measures to bring down the cost or alternative options to increase blood safety should be explored.

Red cell alloimmunization in pregnancy: a study from a premier tertiary care centre of Western India.

OBJECTIVE: The study was conducted to determine the frequency of alloimmunization to various blood group antibodies in pregnant women, and the risk of hemolytic disease in the fetus and newborn. METHODS: All antenatal women, irrespective of the period of gestation or obstetric history, were included, whereas those taking anti-D immune-prophylaxis or with a history of blood transfusion were excluded. Antibody screening and identification were performed using a Bio-Rad ID microtyping system. RESULTS: Of 2,084 antenatal females, 1,765 were D-antigen positive and 319 D-antigen negative. Sixty-five (3.119%) women alloimmunized. Out of 54 (2.591%) who had sensitized to D-antigen, 11 (0.527%) also sensitized to other antibodies. These 11 alloantibodies identified included: anti-M (n=6; 9.23%), anti-C (n=1; 3.076%), anti-E (n=1; 1.538%), anti-e (n=1; 1.538%), anti-Lewis (a) (n=1; 1.538%), and unspecified antibodies (n=1; 1.538%). Multiple antibodies were seen in four patients that combined: anti-D and anti-C (n=2; 3.076%), anti-e and anti-c (n=1; 1.538%), and anti-D and anti-G (n=1; 1.538%). CONCLUSION: The rate of alloimmunization in D-antigen-negative women was high. Apart from this, the alloimmunization rate in women with bad obstetric history was very high, at 8.1%. In developing countries such as India, universal antenatal antibody screening, though desirable, may not be justified at present, as the cost and infrastructure required would be immense because of the lower alloimmunization rates in RhD antigen-positive women. However, it is necessary to impose properly formulated protocols to screen pregnant women with bad obstetric history.

Redefining the role of therapeutic plasma exchange in complications of Echis carinatus sochureki envenomation refractory to anti-snake venom: A case series.

INTRODUCTION: Saw-scaled viper (Echis carinatus) belongs to the Viperidae family. Its venom is hemotoxic and contains several small peptides and proteins affecting the coagulation system. Commonly used anti-snake venom (ASV) products in India are reported to be ineffective or less effective in cases with bites by Echis carinatus sochureki which are commonly found in desert areas in Rajasthan. Although therapeutic plasma exchange (TPE) has been successful in patients with snakebite envenomation in the past, American Society for Apheresis guidelines 2019 included this indication under category III with grade 2C recommendation. AIM AND OBJECTIVES: To report the safety and efficacy of therapeutic plasma exchange procedures in the setting of ASV refractory E. c. sochureki envenomation. MATERIALS AND METHODS: Four patients admitted to our institute in 2021 September with an alleged history of snake bites and who underwent at least one cycle of therapeutic plasma exchange were assessed for clinical outcome, laboratory parameters, and blood product consumption. RESULTS: Three adult patients and one pediatric patient are included in this case series, all of them males. Indication for TPE in one case was suspected diffuse alveolar hemorrhage (DAH), while in all the other cases was thrombotic microangiopathy (TMA). All received a variable number of sessions from 2 to 5 and 1.3-1.5 plasma volume was removed on an average per cycle. The endpoint of TPE was the resolution of DAH in one while a reduction in lactate dehydrogenase and an increase in platelet count was in TMA cases. Consumption of blood products was drastically reduced in all four patients after starting the procedure. All the adult patients fared well on follow-up while the child had developed acute cortical necrosis and was dialysis-dependent. It has been noted in the previous studies too that a subset of snakebite-induced TMA cases was getting converted to chronic kidney disease and becoming dialysis dependent in the long run. CONCLUSIONS: In regions where ASV treatment failure is very common, therapeutic plasma exchange is a safe and effective complementary treatment modality along with supportive care.

Successful outcome after timely management of severe fetal anemia with intrauterine transfusion in female with bad obstetric history.

Development of severe fetal anemia due to red cell destruction in intrauterine life, most commonly implicated with hemolytic disease of fetus or newborn. Untreated cases lead to hydrops and even death of newborn. We are reporting a case of severe fetal anaemia successfully delivered after intrauterine transfusion. A 28-year-old female having bad obstetric history G10 P3600, came to our fetal unit at 23 + 4 weeks gestation. Middle cerebral artery peak systolic velocity (MCA PSV) value was 2.2 mom before 1st intrauterine procedure. Subsequent intrauterine session was planned at 1-2 week interval. After completion of 3rd intrauterine transfusion, MCA PSV value was 0.8 mom and baby was delivered at 32 + 1 week via lower segment cesarean section. Intervention at appropriate time, appropriate volume of selected unit and appropriate rate of transfusion definitely improves perinatal outcome.

Efficacy and Safety of Concentrated Growth Factors and Platelet- Rich Fibrin on Stability and Bone Regeneration in Patients with Immediate Dental Implants: A Randomized Controlled Trial.

PURPOSE: Immediate dental implants revolutionized the field of implant dentistry with significant advantages over conventional implants. The lack of adequate bone in the extraction socket raises the question of the appropriate timing of implant loading. Platelet concentrates have been used widely to accelerate bone regeneration in the maxillofacial region. This study evaluates the effect of platelet concentrates on bone healing and implant stability in the maxillary and mandibular molar regions. Bone regeneration is regulated by several growth factors, particularly vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1); therefore, quantification of these factors in platelet concentrates and its correlation with bone healing has been assessed in this study. MATERIALS AND METHODS: The primary aim of this randomized clinical trial was to compare the stability of immediate dental implants in the maxillary and mandibular molar regions treated with platelet-rich fibrin (PRF) versus concentrated growth factors (CGF) using resonance frequency analysis (RFA). The secondary objectives were to evaluate the bone regenerate around implants with the use of PRF and CGF and to quantify growth factors VEGF and TGF-ß1 in the prepared CGF and PRF and their correlation with bone healing, if any. A total of 36 patients were randomized into three groups (12 each): control, PRF, and CGF. In all patients, immediate implants were placed either with or without platelet concentrate (PRF or CGF). Implant stability was measured using RFA immediately postoperatively and at 4, 8, and 12 or 16 weeks (12 weeks for mandible and 16 weeks for maxilla) postoperatively. Radiodensity and the bone gap (horizontal/vertical) were measured on intraoral periapical radiographs immediately postoperatively and at 8 weeks and 12 or 16 weeks postoperatively. RESULTS: On comparing the implant stability quotient (ISQ), radiodensity/grayscale (GS), and horizontal and vertical bone gap (HG and VG), there was no significant difference noted between the three groups at any point in time. On ISQ analysis at 8 weeks, the control group showed a significant improvement (P = .04), whereas at 12 or 16 weeks, significant improvement was seen in PRF (P = .03) and CGF groups (P = .02). In GS assessment, only the control group showed significant improvement at 12 or 16 weeks (P = .009). In horizontal and vertical bone gap analysis all three groups showed significant improvement at 8 weeks (control [P < .001], PRF [P = .001], CGF [P = .01]) as well as 12 or 16 weeks (control [P < .001], PRF [P < .001], CGF [P = .006]). The enzyme-linked immunosorbent assay (ELISA) quantification of VEGF and TGF-ß1 showed significant concentration of VEGF in PRF as compared to the plasma, while concentration of TGF-ß1 was found to be comparable in both groups. CONCLUSION: The application of platelet concentrates seems to enhance stability of implants, but intergroup results were nonsignificant at all time points. There was no statistically significant difference between the three groups when comparing quality (radiodensity/grayscale) and quantity (horizontal and vertical gap reduction) of bone regenerate. Studies with larger sample sizes are required to make conclusive assertions regarding efficacy of platelet concentrates in dental implants.

Case Report: Delayed Diffuse Alveolar Hemorrhage in Echis sochureki Envenoming, Jodhpur, India.

Snakebite envenoming is a common occupational hazard in the tropics. Venom-induced consumption coagulopathy and acute kidney injury are the most frequently encountered complications of viper bites. Diffuse alveolar hemorrhage (DAH) is an unusual presentation reported rarely in the literature. Our case report highlights the uncommon presentation of delayed pulmonary hemorrhage after snakebite envenoming. A 40-year-old healthy man presented to our emergency department after 6 hours of Echis sochureki (a saw-scaled viper subspecies) bite. He had abnormal coagulation parameters and thrombocytopenia with no signs of acute kidney injury. Transfusion protocols were initiated because of active bleeding and a rapid decrease in hemoglobin levels over next few days. Around day 10, his coagulation profile and hemoglobin were corrected, but he developed hemoptysis with rapidly progressive respiratory distress. Computed tomography of the chest was suggestive of DAH and the patient was started on plasma exchange with pulse methylprednisolone. After the initial worsening, he had rapid symptomatic improvement and radiological resolution. The patient had persistent hypofibrinogenemia, which resolved, and was discharged and remained healthy at the 60-day follow-up. This case highlights a presentation with an initial phase of venom-induced consumption coagulopathy followed by delayed DAH in saw-scaled viper envenoming that was treated successfully with immunosuppressants and plasma exchange.

SARS-CoV-2 IgG Antibody and its Clinical Correlates in Convalescent Plasma Donors: An Indian Experience.

SARS-CoV-2, a novel coronavirus, emerged a year ago in Wuhan, China causing a new pandemic. Convalescent plasma therapy has been applied previously to many infectious diseases and has shown a successful result. This study was planned to assess the Anti-SARS-CoV-2 IgG antibody levels in convalescent COVID-19 patients. In this study, serum samples from 210 persons infected by SARS-CoV-2, treated and discharged from the hospital were collected. Anti-SARS-CoV-2 IgG antibody levels were detected using a chemiluminescence assay. A directory of convalescent plasma donors was created. Anti-SARS-CoV-2 IgG antibody levels vary substantially in the study population with a mean of 51.2 AU/ml. On comparing the serum anti-SARS-CoV-2 IgG antibody levels, a significant difference was observed between the subjects who had cough and those who did not (p = 0.0004). Similar significant findings were found with total protein and globulin levels on comparing the individuals with different antibody status (positive, negative and equivocal). The middle-aged and old age people had high Ab titres compared to younger individuals and the duration of the hospital stay was found to be positively correlated with the anti-SARS-CoV-2 IgG antibody. Cough, age and duration of the hospital stay was found to play a significant role in the development of Anti-SARS-CoV-2 IgG levels. Further, the data suggests that blood groups have a lesser impact on the severity of disease and the development of antibodies. Patients who present with the cough are more likely to develop antibodies.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

Regenerative efficacy of therapeutic quality platelet-rich plasma injections versus phonophoresis with kinesiotaping for the treatment of chronic plantar fasciitis: A prospective randomized pilot study.

BACKGROUND: Plantar fasciitis (PF) a common chronic musculoskeletal pain routinely diagnosed and treated in rehabilitation practices. When conservative management fails in this degenerative disease, local injections of corticosteroids, platelet rich plasma (PRP), botulinum toxin, extracorporeal shockwave therapy, surgical release are used. In our prospective randomized pilot study we compared the regenerative efficacy of Platelet Rich Plasma vs Kinesiotaping with phonophoresis who were resistant to conservative management of PF. MATERIALS AND METHODS: Sixty-four chronic plantar fasciitis patients nonresponding to conservative management were evaluated for two interventions.36 patients received ultrasound guided 2.5 ml autologous platelet rich plasma (PRP) injection and 28 participant received phonophoresis and total10 Kinesiotaping on alternate days. 54 participants 33 in PRP intervention group and 21 in KT group were analyzed, by Numerical Rating Scale (NRS), plantar fascia thickness (ultrasound guided) and disability and activity limitation measured by foot function index in every two weeks up to 6 months. RESULTS: Post intervention assessment at 2 weeks revealed improvement in pain relief was better in Kinesiotaping group (NRS-4.619) as compared to PRP group (NRS- 6.061). But evaluation at 12 and 24 weeks showed statistically significant improvement in NRS and Foot function index in PRP group than in Kinesiotaping. Similarly, at the end of 24-week improvement in foot function index (FFI) was more in PRP group (P<0.0001). At end of 12 and 24 weeks there was significant reduction in plantar fascia thickness in PRP group (p<0.0001) as compared to KT group (p<0.05). CONCLUSION: Our study concluded that therapeutic quality autologous PRP injection (1x106 platelets/µl) has regenerative effect with long and better efficacy in pain management of chronic recalcitrant plantar fasciitis than Phonophoresis and Kinesiotaping.

Daily plasma exchange in severe Guillain-Barré syndrome helps in early weaning from ventilator: A lesson from a case.

Intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE) are well-known therapeutic modalities in Guillain-Barré syndrome (GBS). In developing countries like India, where plasma-derived products (IVIG) are not easily available, and affordable TPE is preferred. Here, we reported a case of severe GBS, who was treated with daily plasma exchange (PLEX) rather than recommended alternate day schedule. A 16-year-old male adolescent of severe GBS, i.e., on mechanical ventilator was treated with the plasmapheresis regimen consisted of removal of 1.3 plasma volumes in each cycle for total of five cycles, on daily basis. The patient's condition started improving after three cycles of TPE with power in the upper limbs 4/5 and lower limbs 3/5 and completely weaned off from ventilator after the 4th TPE, i.e. the 4th day of admission. This case emphasizes the need of daily PLEX regimen particularly in severe GBS patients because early weaning from ventilator reduces the ventilator-associated complications, hospital stay as wells as less morbidity, and mortality in severe GBS.