Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.

Assessment of the LOVO device for final harvest of novel cell therapies: a Production Assistance for Cellular Therapies multi-center study.

BACKGROUND AIMS: The final harvest or wash of a cell therapy product is an important step in manufacturing, as viable cell recovery is critical to the overall success of a cell therapy. Most harvest/wash approaches in the clinical lab involve centrifugation, which can lead to loss of cells and decreased viability of the final product. Here the authors report on a multi-center assessment of the LOVO Cell Processing System (Fresenius Kabi, Bad Homburg, Germany), a cell processing device that uses a spinning filtration membrane instead of centrifugation. METHODS: Four National Institutes of Health Production Assistance for Cellular Therapies cell processing facilities (CPFs) assessed the LOVO Cell Processing System for final harvest and/or wash of the following three different cell products: activated T cells (ATCs), tumor-infiltrating lymphocytes (TILs) and bone marrow-derived mesenchymal stromal cells (MSCs). Each site compared their current in-house, routinely used method of final cell harvest and/or wash with that of the LOVO device. RESULTS: Final harvest and/or wash of ATCs, TILs and MSCs using the LOVO system resulted in satisfactory cell viability and recovery with some substantial improvement over the in-house methods of CPFs. Processing time was variable among cell types/facilities. CONCLUSIONS: The LOVO Cell Processing System provides an alternative to centrifuge-based technologies. The system employs a spinning membrane filter, exposing cells to minimal g-forces compared with centrifugation, and is automated and closed. This small multi-center study demonstrated the ability of the LOVO device to yield satisfactory cell viability and recovery of T cells and MSCs.

The National Heart, Lung, and Blood Institute-funded Production Assistance for Cellular Therapies (PACT) program: Eighteen years of cell therapy.

The Production Assistance for Cellular Therapies (PACT) Program, is funded and supported by the US Department of Health and Human Services' National Institutes of Health (NIH) National Heart Lung and Blood Institute (NHLBI) to advance development of somatic cell and genetically modified cell therapeutics in the areas of heart, lung, and blood diseases. The program began in 2003, continued under two competitive renewals, and ended June 2021. PACT has supported cell therapy product manufacturing, investigational new drug enabling preclinical studies, and translational services, and has provided regulatory assistance for candidate cell therapy products that may aid in the repair and regeneration of damaged/diseased cells, tissues, and organs. PACT currently supports the development of novel cell therapies through five cell processing facilities. These facilities offer manufacturing processes, analytical development, technology transfer, process scale-up, and preclinical development expertise necessary to produce cell therapy products that are compliant with Good Laboratory Practices, current Good Manufacturing Practices, and current Good Tissue Practices regulations. The Emmes Company, LLC, serves as the Coordinating Center and assists with the management and coordination of PACT and its application submission and review process. This paper discusses the impact and accomplishments of the PACT program on the cell therapy field and its evolution over the duration of the program. It highlights the work that has been accomplished and provides a foundation to build future programs with similar goals to advance cellular therapeutics in a coordinated and centralized programmatic manner to support unmet medical needs within NHLBI purview.

Community Based Assessment of Behavior and Awareness of Risk Factors of Cystic Echinococcosis in Major Cities of Pakistan: A One Health Perspective.

Background: The parasitic disease, cystic echinococcosis (CE), is a serious health problem in Pakistan. Risk of disease transmission is increased by economic and political instability, poor living conditions, and limited awareness of hygienic practices. The current study aimed to investigate the community perception and awareness regarding the risk factors of CE in Pakistan, from a One Health perspective. Methods: We conducted a community-based survey involving 454 participants in the major cities of Pakistan. Quantitative data based on knowledge, attitude, and practices (KAP), the One Health concept, risk factors, and community perception of CE among the general population of the major cities of Pakistan were collected. The questions included those related to knowledge, attitude, practices, One Health concept, risk factors, and community perception. The Chi-squared test was applied to determine the associations regarding KAPs across socio-demographic parameters. Results: KAPs had no significant associations with sociodemographic aspects such as age, sex, religion, ethnicity, education, marital status, occupation, or financial status of the participants. The findings indicated a lack of awareness about CE among the participants. Respondents were unaware of the risk factors and the One Health concept of CE. However, the community attitude and perception were positive toward the control of CE. Conclusion: Illiteracy, deficient sanitation systems and lack of awareness are the contributing factors to CE in Pakistan. It is necessary to make the community aware regarding CE and its importance. Increasing this awareness represents an important step toward the eradication and control of CE.

Estimation of the monetary burden of treated human cystic echinococcosis in Pakistan.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato tapeworms, continues to be a public health problem in many endemic countries, including Pakistan. Patient level data, including age, sex, and cyst(s) location for surgically managed CE patients for the years 2013-2016 from hospitals located in Punjab and Khyber Pakhtunkhwa provinces were obtained from medical charts. Direct and indirect costs associated with surgically managed CE patients treated in private and public hospitals were then estimated and applied to country-level case numbers estimated through the Global Burden of Disease Study. A total cost of US$4,068,666 (95% CI: US$3,097,684 - US$5,295,702) was estimated for the year 2017, with US$3,951,853 (95% CI: US$2,981,400 - US$5,177,610) attributable to direct diagnosis and treatment-related costs and US$117,137 (95% CI: US$91,841 - US$146, 979) attributable to wage losses during the treatment period. Mean direct cost per patient (US$1,056) was approximately 72% of the country's per capita gross domestic product (GDP). Surgical management continues to be the treatment of choice for CE patients in Pakistan. If physicians were to adhere to World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) cyst stage-specific treatment guidelines, it is likely that the number of surgical interventions would decrease as would treatment costs.

Demographic representation in clinical trials for cell-based therapy.

Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.

Community-Based Assessment of Knowledge, Attitude, Practices and Risk Factors Regarding COVID-19 Among Pakistanis Residents During a Recent Outbreak: A Cross-Sectional Survey.

Exceptional precautionary measures have been adopted to stop the transmission and control of COVID-19 through the world and Pakistan is facing lockdown in this scenario. Public loyalty to precautionary measures is affected by their knowledge, attitude, risk factors and practices (KAP) towards COVID-19. The present study was conducted among the Pakistani residents to observe the knowledge, attitude, practices and risk factors towards COVID-19 outbreak in Pakistan. A questionnaire was designed, and a cross-sectional survey was conducted among participants of the study area. Participants were asked the questions regarding knowledge, attitude, practices and risk factors towards COVID-19. Data were analyzed by SPSS and t/F test and correlation was applied among the knowledge, attitude, risk factors and practices. A total of 1060 questionnaires were received. 1004 were included while 56 were excluded. The highest representation was from Punjab province (65.6%), female (63%) and age group of 21-30 years (62.1%). Most participants were single (85%), Muslim (99.4%), Urdu speaking (45.6%) and were graduates (51.5%). Most of the participants were students (52.9%) and were from economically middle-class families (40.8%). The knowledge was positively correlated with attitude and practices whereas negatively correlated with risk factors (P < 0.05). The attitude was negatively correlated with risk factor and positively correlated with practices. The risk factors and practices were positively correlated with each other. Health education program to improve the COVID-19 knowledge, attitude, practices and risk factors should be initiated to combat current health challenge.

The impact of patient sex on the response to intramyocardial mesenchymal stem cell administration in patients with non-ischaemic dilated cardiomyopathy.

AIMS: Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown. We hypothesize that males and females with NIDCM respond similarly to MSC therapy. METHODS AND RESULTS: Male (n = 24) and female (n = 10) patients from the POSEIDON-DCM trial who received MSCs via transendocardial injections were evaluated over 12 months. Endothelial function was measured at baseline and 3 months post-transendocardial stem cell injection (TESI). At baseline, ejection fraction (EF) was lower (P = 0.004) and end-diastolic volume (EDV; P = 0.0002) and end-systolic volume (ESV; P = 0.0002) were higher in males vs. females. In contrast, baseline demographic characteristics, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-min walk test (6MWT) were similar between groups. EF improved in males by 6.2 units (P = 0.04) and in females by 8.6 units (P = 0.04; males vs. females, P = 0.57). EDV and ESV were unchanged over time. The MLHFQ score, New York Heart Association (NYHA) class, endothelial progenitor cell-colony forming units, and serum tumour necrosis factor alpha improved similarly in both groups. CONCLUSION: Despite major differences in phenotypic presentation of NIDCM in males and females, this study is the first of its kind to demonstrate that MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex. These findings have important clinical and pathophysiologic implications regarding the impact of sex on responses to cell-based therapy for NIDCM.

Reduce Disease Burden of Human Schistosomiasis in Asia Through Biological Control.

Schistosomiasis is a chronic parasitic disease caused by a trematode blood fluke of the genus Schistosoma that belongs to the Schistosomatidae family. It is a neglected disease in different regions of Asia. In this review, 218 articles (between 2000 and 2017) related to the topic were collected from PubMed and Google scholar and reviewed. After thoroughly reading collected articles, due to irrelevant topic requirements, 94 articles were excluded. Articles that have data associated with Asian regions are considered. In Asia, the disease is prevalent in China, Philippines, Indonesia, Yemen, Nepal and Laos, etc. While in Pakistan, India and Bangladesh, the disease is not endemic and very few cases were reported. The disease was eliminated from Japan and Iran. The current review highlights the geographical distribution among Asian countries, transmission patterns, diagnosis, control strategies based on the use of anthelmintic plants and management practices implemented in Asia for the control of schistosomiasis. However, new implementations to treat schistosomiasis in humans should be proved to eliminate the disease finally in the future. This review emphasizes the biological control of schistosomiasis for the eradication of the disease from Asia in the near future.

A Landscape Analysis of Human Milk Banks in India.

OBJECTIVES: To evaluate the existing status of human milk banks in India with reference to infrastructure, human resources, funding mechanisms, operating procedures and quality assurance. METHODS: A pretested questionnaire was administered to 16 out of 22 human milk banks across India, operational for more than one year prior to commencing the study. RESULTS: 11 (69%) milk banks were in government or charitable hospitals; only 2 (12.5%) were established with government funding. 8 (50%) had a dedicated technician and only 1(6%) had more than five lactation counsellors. Milk was collected predominantly from mothers of sick babies and in postnatal care wards followed by pediatric outpatient departments, camps, satellite centers, and homes. 10 (63%) reported gaps between donor milk demand and supply. 12 (75%) used shaker water bath pasteurizer and cooled the milk manually without monitoring temperature, and 4 (25%) pooled milk under the laminar airflow. 10 (63%) tracked donor to recipient and almost all did not collect data on early initiation, exclusive breastfeeding or human milk feeding. CONCLUSIONS: Our study reports the gaps of milk banking practices in India, which need to be addressed for strengthening them. Gaps include suboptimal financial support from the government, shortage of key human resources, processes and data gaps, and demand supply gap of donor human milk.

Understanding Barriers and Facilitators for Human Milk Banking Among Service Providers, Mothers, and Influencers of Preterm and Sick Neonates Admitted at Two Health Facilities in a Metropolitan City in India.

BACKGROUND: Scaling-up human milk banks (HMBs) is a promising solution for saving vulnerable newborns. Exploring perceptions and practices on donor human milk (DHM) and HMBs is essential to strengthen and scale-up an integrated HMB system resting on a model called the "Mother Baby Friendly Initiative Plus" (MBFI+), which includes promoting breastfeeding, encouraging kangaroo mother care, and providing safe DHM to vulnerable babies without access to mother's own milk. MATERIALS AND METHODS: A qualitative research was conducted among 56 service recipients including mothers and key influencers and 9 service providers to understand their perceptions and practices on DHM and HMBs. RESULTS: Service providers opined that DHM is safe and lifesaving for vulnerable babies. Challenges shared were limited supply of DHM because of low awareness on milk donation, shortage of trained staff, and risk of milk contamination. They stated that although most mothers were comfortable in donating milk, few were reluctant to donate milk as they feared shortage of milk for their own babies, or milk expression may cause weakness. Recipient mothers accepted use of DHM as per facility norms but had concerns about donor mothers' health and hygiene and measures for ensuring milk safety. Most grandmothers were resistant toward donating or receiving DHM for their grandchildren. Many fathers were comfortable with donating once they knew it is lifesaving and did not compromise supply for their babies. Service providers shared opportunities for scale-up, like improving awareness and infrastructure, lactation counseling by skilled personnel, supportive hospital environment, and establishing HMBs in every city and district. CONCLUSIONS: Human milk banking should be strengthened as part of the MBFI+ model. For this, behavior change communication targeted at mothers and influencers about breastfeeding and HMB from the antenatal period, capacity-building among service providers, and government ownership is necessary.

National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities.

Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.

Quantitative assessment of islet cell products: estimating the accuracy of the existing protocol and accounting for islet size distribution.

The ability to consistently and reliably assess the total number and the size distribution of isolated pancreatic islet cells from a small sample is of crucial relevance for the adequate characterization of islet cell preparations used for research or transplantation purposes. Here, data from a large number of isolations were used to establish a continuous probability density function describing the size distribution of human pancreatic islets. This function was then used to generate a polymeric microsphere mixture with a composition resembling those of isolated islets, which, in turn, was used to quantitatively assess the accuracy, reliability, and operator-dependent variability of the currently utilized manual standard procedure of quantification of islet cell preparation. Furthermore, on the basis of the best fit probability density function, which corresponds to a Weibull distribution, a slightly modified scale of islet equivalent number (IEQ) conversion factors is proposed that incorporates the size distribution of islets and accounts for the decreasing probability of finding larger islets within each size group. Compared to the current calculation method, these factors introduce a 4-8% downward correction of the total IEQ estimate, but they reflect a statistically more accurate contribution of differently sized islets.