Innovative blood transfusion strategies to address global blood deserts: a consensus statement from the Blood Delivery via Emerging Strategies for Emergency Remote Transfusion (Blood DESERT) Coalition.

In rural settings worldwide, many people live in effective blood deserts without access to any blood transfusion. The traditional system of blood banking is logistically complex and expensive for many resource-restricted settings and demands innovative and multidisciplinary solutions. 17 international experts in medicine, industry, and policy participated in an exploratory process with a 2-day hybrid seminar centred on three promising innovative strategies for blood transfusions in blood deserts: civilian walking blood banks, intraoperative autotransfusion, and drone-based blood delivery. Participant working groups conducted literature reviews and interviews to develop three white papers focused on the current state and knowledge gaps of each innovation. Seminar discussion focused on defining blood deserts and developing innovation-specific implementation agendas with key research and policy priorities for future work. Moving forward, advocates should prioritise the identification of blood deserts and address the context-specific challenges for these innovations to alleviate the ongoing crisis in blood deserts.

UDHAVI Community Support During India's Second COVID-19 Wave: A Descriptive Study on a Tertiary Care Center's Pandemic Response Helpline.

BACKGROUND: In April 2021, during the peak of the second wave of the COVID-19 pandemic in India, hospitals overflowed with COVID-19 patients, and people hesitated to seek necessary care due to fear of contracting the disease. The UDHAVI helpline was set up by a tertiary care hospital in Vellore with the help of district administration, nongovernmental organizations, and various supporting agencies to provide general information, medical advice, counseling, and logistics support to the community. METHODS: This is a retrospective study of all the phone calls made to the UDHAVI helpline between mid-May and mid-June 2021 during the second wave of the COVID-19 pandemic. The calls were electronically captured as part of the process, and the information was subsequently retrieved and analyzed. RESULTS: In all, 677 calls were received. The lines for general information, medical advice, counseling, and logistics support received 168 (25%), 377 (56%), 15 (2%), and 117 (17%) calls, respectively. Home care kits, oxygen concentrators, and food were delivered by volunteers from local nongovernmental organizations and hospitals. CONCLUSION: We believe the details of our experience would be useful in the preparedness and mobilization of resources in the event of any public health emergency. As a result of this initiative, we propose an integrated partnership model for emergency response to any pandemic situation.

Utility of Cryohemolysis Test in the Diagnosis of Hereditary Spherocytosis.

Diagnosis of Hereditary spherocytosis (HS) often requires time-consuming and/or expensive tests. Cryohemolysis test (CHT) is a simple and easy to perform test with high predictive value for HS diagnosis. In this prospective study, we evaluated the diagnostic utility of CHT for the diagnosis of HS. We included 60 suspected HS patients, 18 patients with Autoimmune hemolytic anemia (AIHA) and 120 healthy controls. Among the 60 suspected cases, there were 36 HS cases and 24 with other hemolytic anemias. The mean CHT (%) ± SD for controls, AIHA, other hemolytic anemias, and HS was 6.63 ± 2.79, 6.79 ± 4.36, 6.61 ± 2.76 and 26.7 ± 8.9, respectively. The CHT % was significantly higher in HS group when compared to controls (p = < 0.0001), AIHA (p = < 0.0001) and other hemolytic anemia groups (p = < 0.0001). At a CHT cut off of > 18.3%, the sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of HS in our study were 97.1%, 94.4%, 97.2% and 90.3%, respectively. CHT is a simple and sensitive test for the diagnosis of HS but remains underutilized. The addition of CHT in the diagnostic workup of HS will be very useful, especially in a resource limited setting.

Effectiveness of a monitored home isolation program for COVID-19 infection during the second wave of the pandemic.

Background: The rapidity of spread of COVID-19 infection during the second wave of the pandemic placed tremendous stress on healthcare resources. This study evaluated the effectiveness of a monitored home isolation (HI) program. Methods: In this descriptive longitudinal study, symptomatic patients were screened in the HI clinic and eligible patients were followed up at home using tele-consultation, until recovery or hospitalization. HI failure was defined as need for hospitalization. Factors associated with HI failure were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Results: During April and May 2021, 1957 RT-PCR confirmed patients (984 male) with mean (SD) age 40 (13.5) years were enrolled; 93.3% (n = 1825) were successfully managed at home. Of the 132 patients (6.7%) who failed HI, 57 (43.2%) required oxygen therapy and 23 needed intensive care admissions. Overall mortality was 0.4% (7/1957). On adjusted analysis, factors associated with HI failure were age ≥60 years (OR 2.24; 95%CI 1.26-3.99), male gender (OR 2.26; 95%CI 1.44-3.57), subjective reporting of breathing difficulty (OR 3.64; 95%CI 2.08-6.37), history of cough (OR 2.08; 95%CI 1.37-3.17), and higher heart rate (OR 1.04; 95%CI 1.02-1.05). Although patient status (non-healthcare workers), no prior vaccination and ≥2 comorbidities were associated with HI failure on unadjusted analysis, these were non-significant on adjusted analysis. Conclusion: Monitored HI program can be used successfully during a pandemic wave to judicially use scare hospital resources. Older male patients presenting with breathlessness or cough may warrant closer monitoring.

Protective effect conferred by prior infection and vaccination on COVID-19 in a healthcare worker cohort in South India.

BACKGROUND: The emergence of newer variants with the immune escape potential raises concerns about breakthroughs and re-infections resulting in future waves of infection. We examined the protective effect of prior COVID-19 disease and vaccination on infection rates among a cohort of healthcare workers (HCW) in South India during the second wave driven mainly by the delta variant. METHODS AND FINDINGS: Symptomatic HCWs were routinely tested by RT-PCR as per institutional policy. Vaccination was offered to all HCWs in late January, and the details were documented. We set up a non-concurrent cohort to document infection rates and estimated protective efficacy of prior infection and vaccination between 16th Apr to 31st May 2021, using a Cox proportional hazards model with time-varying covariates adjusting for daily incidence. Between June 2020 and May 2021, 2735 (23.9%) of 11,405 HCWs were infected, with 1412, including 32 re-infections, reported during the second wave. 6863 HCWs received two doses of vaccine and 1905 one dose. The protective efficacy of prior infection against symptomatic infection was 86.0% (95% CI 76.7%-91.6%). Vaccination combined with prior infection provided 91.1% (95% CI 84.1%-94.9%) efficacy. In the absence of prior infection, vaccine efficacy against symptomatic infection during the second wave was 31.8% (95% CI 23.5%- 39.1%). CONCLUSIONS: Prior infection provided substantial protection against symptomatic re-infection and severe disease during a delta variant driven second wave in a cohort of health care workers.

The clinical demand and supply of blood in India: A National level estimation study.

BACKGROUND: Estimating the clinical demand for blood and components arising in a health facility is crucial to ensure timely availability of blood. This study aims to estimate disease-specific clinical demand, supply and utilization of whole blood and components in India. METHODS: We conducted a national level cross-sectional study in five randomly selected states from five regions of the country. We included 251 public and private facilities representing primary, secondary and tertiary care facilities. We collected annual disease-specific demand, supply and utilization of blood and components using a structured tool. We estimated the national demand by extrapolating the study data (demand and beds) to the total number of estimated beds in the country. FINDINGS: According to the study, the total clinical demand of 251 health facilities with 51,562 beds was 474,627 whole blood units. Based on this, the clinical demand for India was estimated at 14·6 million whole blood units (95 CI: 14·59-14·62), an equivalent of 36·3 donations per 1,000 eligible populations, which will address whole blood and component requirement. The medicine specialty accounted for 6·0 million units (41·2%), followed by surgery 4·1 million (27·9%), obstetrics and gynecology 3·3 million (22·4%) and pediatrics 1·2 million (8·5%) units. The supply was 93% which is equivalent to 33·8 donations against the demand. CONCLUSION: The study indicated a demand and supply gap of 2.5 donations per 1,000 eligible persons which is around one million units. The gap emphasises the need for sustained and concerted efforts from all stakeholders and for increasing the awareness about repeat voluntary non-remunerated blood donation (VNRBD); optimizing the availability of blood components through efficient blood component separation units; promoting modern principles of patient blood management and strengthening capacities of human resources in the blood transfusion system in India.

Stability and utility of flow cytometric platelet activation tests: A modality to bridge the gap between diagnostic demand and supply.

Light transmission aggregometry (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs). The requirement of customized aggregometer, large blood volume, normal platelet count and processing within 4 hours of venipuncture for LTA makes platelet function testing inaccessible to wider population. Flow cytometric platelet activation test (PACT) may overcome these limitations. This study compares the performance of PACT with LTA, characterizes diagnostic patterns of PFDs on PACT and assesses the stability of PACT beyond 4 hours of venipuncture in controls (n = 5) at different temperature conditions. LTA and PACT were performed in 121 healthy controls and 66 patients with suspected PFD. PACT had excellent agreement (kappa = 0.93) with LTA and 94.1% sensitivity, 98.5% specificity. PACT had distinct patterns in Bernard Soulier Syndrome (n = 10), Glanzmann Thrombasthenia (n = 24), δ-granule disorder (n = 7), and other PFDs (n = 12). PACT could assess platelet function in patients (14%) with thrombocytopenia/lipemia wherein LTA was inconclusive. PACT was stable up to 24 hours in samples stored/transported at 2-8◦C. The results of utility and stability are only valid for the specific markers, agonist concentrations, and conditions investigated in this paper. PACT is a useful modality for the diagnosis of PFD, especially in children, thrombocytopenia cases or in the setup where an aggregometer is not readily available.

Laboratory characterization of obligate carriers of type 3 von Willebrand disease with a potential role for Platelet Function Analyzer (PFA-200).

INTRODUCTION: Type 3 von Willebrand disease (VWD) is a rare autosomal recessive disorder characterized by undetectable von Willebrand Antigen (VWF:Ag). Carriers of type 3 VWD carry one null allele and have von Willebrand factor (VWF) at about 50% of normal. The aim of this study was to characterize type 3 VWD carriers and to study the role of Platelet Function Analyzer (PFA-200) in this cohort. METHODS: This was a cross-sectional study where data were collected from carriers (parents/offspring) of type 3 VWD patients and evaluated with activated partial thromboplastin time, factor VIII, blood group, ristocetin cofactor assay (VWF:RCo), VWF:Ag, and closure time on PFA-200 with collagen/epinephrine (COL/EPI), and collagen/ADP (COL/ADP). RESULTS: One hundred carriers were included in the study of which 85 were included for PFA-200 analysis. The mean (SD) of VWF:Ag (IU/ml) and VWF:RCo (IU/ml) was 0.63 (0.24) and 0.61 (0.26), respectively. Among the 100 carriers, based on VWF levels (VWF:Ag and/or VWF:RCo) and bleeding history, there were 7 type 1 VWD, 10 type 2 VWD, 25 borderline VWF (0.30-0.50 IU/ml and no bleeding), and 58 normal VWF (>0.50 IU/ml). PFA-200 was prolonged in 71% of the carriers, all carriers with type 1 and type 2 VWD phenotype, 80% carriers with borderline VWF, and 59% with normal VWF. COL/EPI was more sensitive than COL/ADP and showed better correlation with VWF parameters than COL/ADP. CONCLUSION: Carriers of type 3 VWD can have a variable laboratory phenotype. PFA-200 showed good sensitivity among the carriers at VWF levels <0.50 IU/ml.

A review of legal, regulatory, and policy aspects of blood transfusion services in India: Issues, challenges, and opportunities.

BACKGROUND: Blood transfusion services (BTS) in India have progressed significantly during the last three decades. However, there is still inequity in the availability and access to blood due to various demand and supply-side issues. Appropriate laws, regulations, policies, and guidelines are critical to ensure universal access to blood. AIMS AND OBJECTIVES: This article aims to review the evolution and current status of legal, regulatory, and policy framework and analyses the issues, challenges, and opportunities for improvement of BTS in India. METHODS: This article is based on an extensive review of currently available literature and government documents. RESULTS: The review highlights the gaps and challenges in terms of licensing, safety and quality, voluntary blood donations, the organization of BTS, access to services, and regulatory bodies. The findings emphasize the need for a coordinated response by either the National Blood Transfusion Council or a newly established autonomous "National Blood Authority" consisting of technical, administrative, and legal experts which must be exclusively responsible for regulating the BTS. As adherence to quality management systems in blood banks is not a mandatory requirement, it recommends a legal measure to ensure mandatory quality assurance in blood banks and storage centers. Towards ensuring efficiency and universal access to blood, this article recommends evidence-based criteria for establishing new blood banks to avoid skewed distribution of blood banks, component separation facilities, and blood storage centers. CONCLUSION: The review emphasizes the need for periodic reviews and updates of the legal, regulatory and policy framework, considering the rapid developments and technical advancements with increasingly complex systems and processes in transfusion medicine.

Assessment of Performance of Blood Banks in India: A National Level Cross Sectional Study.

India lacks comprehensive information about blood transfusion systems, which could help ensure universal access to safe blood through evidence-based strategies and programs. We conducted the first national assessment of blood bank systems, services, practices, and performance in India. We conducted a cross-sectional survey of all 2626 blood banks and assessed the administrative, technical, and quality aspects in 2016. In addition to descriptive analysis, we compared the means of different variables using independent t-test or ANOVA and a generalized linear model. We performed linear regression analysis between the collection of blood per 100 people and the number of blood banks per million people. The disaggregated mean score of quality management system and overall performance are presented by different groups. Besides, we graded the performance based on tertile classification, as low, medium and high-performance blood banks. Of the 2493 blood banks that participated in the study, most were public (38%) or not-for-profit(38%), and 51% had component separation facilities. Of the 11.65 million units of blood collected annually, 72% was through voluntary blood donation. There were 2.2 blood banks per one million people, collecting around one unit per 100 persons annually with wide variation between states. The mean overall performance score was 62(95% confidence interval [CI]:61.6-62.5), and the mean quality management system score was 57.4(95% CI:56.8-58.0), with significant variation across different categories of blood banks. This assessment provides critical information for developing evidence-based policies, programs, and monitoring systems to improve the performance of blood transfusion services in India.

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.

A national level estimation of population need for blood in India.

BACKGROUND: The population need for blood is the total volume required to transfuse all the individuals who need transfusion in a defined population over a defined period. The clinical demand will arise when people with a disease or condition who require transfusion, access healthcare services, and subsequently the clinicians request blood. Essentially, the conversion of need to demand must be maximum to avoid preventable mortality and morbidity. The study estimated the population need for blood in India. METHODS: The methodology included a comprehensive literature review to determine the diseases and conditions requiring transfusion, the population at risk, and prevalence or incidence; and Delphi method to estimate the percentage of people requiring transfusion, and the quantum. RESULTS: The estimated annual population need was 26.2 million units (95% CI; 17.9-38.0) of whole blood to address the need for red cells and other components after the separation process. The need for medical conditions was 11.0 million units (95% CI:8.7-14.7), followed by surgery 6.6 million (95% CI:3.8-10.0), pediatrics 5.0 million (95% CI:3.5-7.0), and obstetrics and gynecology 3.6 million units (95% CI:1.9-6.2). The gap between need and demand which depends upon the access and efficiency of healthcare service provision was estimated at 13 million units. CONCLUSION: The study brings evidence to highlight the gap between need and demand and the importance of addressing it. It cannot be just the responsibility of blood transfusion or health systems, it requires a multi-sectoral approach to address the barriers affecting the conversion of need to clinical demand for blood.

Slow parasite clearance, absent K13-propeller gene polymorphisms and adequate artesunate levels among patients with malaria: A pilot study from southern India.

Background: Artemisinin-based combination therapy (ACT) is widely used in India and many generic preparations are available. Delayed response has been reported, suggesting inadequate response to artesunate (AS) or genotypic resistance. We designed a prospective observational study to assess the therapeutic response, elaborate pharmacokinetics of AS and identify Plasmodium falciparum kelch 13 (pfk13) propeller gene polymorphisms among hospitalized Indian patients with severe malaria. Methods: We collected blood samples from adult patients with severe P. falciparum or mixed (P. falciparum and P. vivax) malaria on ACT. We calculated the parasite clearance (CL) half-life using the Worldwide Antimalarial Resistance Network (WWARN) online parasite clearance estimator (PCE). We used the liquid chromatography tandem mass spectrophoto-metry method for simultaneous quantification of AS and dihydroartemisinin. We genotyped longitudinally archived DNA samples obtained pre-treatment (day 0) to study the point mutations in the pfk13 propeller domain. Results: A total of 54 patients with malaria were included, with a majority fulfilling the definitions of severe malaria. The median parasite CL slope half-life was estimated to be 6.44 hours (interquartile range 4.79-10.24). AS pharmacokinetics, assessed in 17 patients, were found to be similar in the groups with rapid (<48 hours) and slow CL (>48 hours) of parasites. No known mutations associated with artemisinin resistance in Southeast Asia were observed in our study participants. Conclusions: Slow parasite CL was seen with a high parasite burden without genotypic evidence of AS resistance. There is a need to standardize definitions of therapeutic efficacy of AS in cases of severe malaria.

Automated Segmentation of Nuclei in Breast Cancer Histopathology Images.

The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E) stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP) algorithm on a Markov Random Field (MRF). The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods-Wienert et al. (2012) and Veta et al. (2013), which were tested using their own datasets.