Applying blockchain technology to ensure compliance with sustainability standards in the PPE multi-tier supply chain

Because of the Covid-19 pandemic, urgent surging demand for healthcare products such as personal protective equipment (PPE) has caused significant challenges for multi-tier supply chain management. Although a given firm may predominantly focus on an arms-length solution by targeting the first-tier supplier, the firm can still struggle with extended multi-tier suppliers it cannot choose which use unsustainable practices. One key goal is compliance across various dimensions with production, environmental and labour standards across the multi-tier supply chain, a goal that blockchain technology can be applied to manage. Based on a comprehensive literature review, this research develops a system architecture of blockchain-based multi-tier sustainable supply chain management in the PPE industry designed to identify and coordinate standards in production and social and environmental sustainability in multi-tier PPE supply chains. The architecture was validated by theoretical basis, expert opinions and technical solutions. We conclude with managerial implications for implementing blockchain technology to advance sustainable multi-tier supply chain practices.

Correlating physicochemical and biological properties to define critical quality attributes of a recombinant AAV vaccine candidate

Recombinant adeno-associated viruses (rAAVs) are a preferred vector system in clinical gene transfer. A fundamental challenge to formulate and deliver rAAVs as stable and efficacious vaccines is to elucidate interrelationships between the vector's physicochemical properties and biological potency. To this end, we evaluated an rAAV-based COVID-19 vaccine candidate which encodes the Spike antigen (AC3) and is produced by a commercially viable process. First, state-of-the-art analytical techniques were employed to determine key structural attributes of AC3 including primary and higher-order structures, particle size, empty/full capsid ratios, aggregates and multi-step thermal degradation pathway analysis. Next, several quantitative potency measures for AC3 were implemented and data were correlated with the physicochemical analyses on thermal-stressed and control samples. Results demonstrate links between decreasing AC3 physical stability profiles, in vitro transduction efficiency in a cell-based assay, and importantly, in vivo immunogenicity in a mouse model. These findings are discussed in the general context of future development of rAAV-based vaccines candidates as well as specifically for the rAAV vaccine application under study.

The impact of COVID-19 restrictions on acute hospital presentations due to alcohol-related harm in Waitemata Auckland, New Zealand.

AIMS: New Zealand's public health response to the COVID-19 pandemic has largely been considered successful, although there have been concerns surrounding the potential harms of the lockdown restrictions enforced, including alteration of alcohol consumption. New Zealand utilised a four-tiered alert level system of lockdowns and restrictions, with Level 4 denoting strict lockdown. This study aimed to compare alcohol-related hospital presentations during these periods with corresponding calendar-matched dates from the preceding year. METHODS: We conducted a retrospective case-controlled analysis of all alcohol-related hospital presentations between 1 January 2019 to 2 December 2021 and compared COVID-19 restriction periods to corresponding calendar-matched pre-pandemic periods. RESULTS: A total of 3,722 and 3,479 alcohol-related acute hospital presentations occurred during the four COVID-19 restriction levels and corresponding control periods respectively. Alcohol-related presentations accounted for a greater proportion of all admissions during COVID-19 Alert Levels 3 and 1 than the respective control periods (both p⁢0.05), but not during Levels 4 and 2 (both p>0.30). Acute mental and behavioural disorders accounted for a greater proportion of alcohol-related presentations during Alert Levels 4 and 3 (both p≤0.02), although alcohol dependence was present in a lower proportion of presentations during Alert Levels 4, 3, and 2 (all p⁢0.01). There was no difference in acute medical conditions including hepatitis and pancreatitis during all alert levels (all p>0.05). CONCLUSION: Alcohol-related presentations were unchanged compared to matched control periods during the strictest level of lockdown, although acute mental and behavioural disorders accounted for a greater proportion of alcohol-related admissions during this period. New Zealand appears to have avoided the general trend of increased alcohol-related harms seen internationally during the COVID-19 pandemic and its lockdown restrictions.

The Legal and Socioeconomic Considerations in Spine Telemedicine.

Telemedicine has become indispensable in today's health care because of the recent ongoing COVID-19 crisis. Although it has been beneficial in coping with the pandemic, there is still much uncertainty as to whether it will have a permanent role in treating spine patients. Some of the ongoing legal challenges include patient confidentiality, liability coverage for treating healthcare workers, and financial reimbursements by insurance companies. One of the impediments of telemedicine is its lack of a standard legal framework. Telehealth is currently regulated through a state-based system with each state having its own policy regarding this practice. In addition, each of the components of a virtual visit represent a potential area for legal concerns. Nonetheless, telemedicine has the ability to provide convenient and effective health care to patients. However, the spine surgeon, as well as other physicians, must consider the legal issues along with some socioeconomic factors identified herein. Moreover, without parity and uniformity, the incentive to offer telehealth services decreases. There may be a need for modifications in the law, insurance policies, and medical malpractice coverage to strengthen their support to telemedicine usage. As spine surgeons become more familiarized with the telemedicine framework, its role in patient care will likely expand.

Racial and sociodemographic predictors of COVID-19 compared with influenza, appendicitis, and all-cause hospitalization: retrospective cohort analysis.

OBJECTIVE: To determine whether inequities in COVID-19 infection and hospitalization differ from those for common medical conditions: influenza, appendicitis, and all-cause hospitalization. DESIGN: Retrospective study based on electronic health records of three healthcare systems in San Francisco (university, public, and community) examining (1) racial/ethnic distribution in cases and hospitalization among patients with diagnosed COVID-19 (March-August 2020) and patients with diagnosed influenza, diagnosed appendicitis, or all-cause hospitalization (August 2017-March 2020), and (2) sociodemographic predictors of hospitalization among those with diagnosed COVID-19 and influenza. RESULTS: Patients 18 years or older with diagnosed COVID-19 (N = 3934), diagnosed influenza (N = 5932), diagnosed appendicitis (N = 1235), or all-cause hospitalization (N = 62,707) were included in the study. The age-adjusted racial/ethnic distribution of patients with diagnosed COVID-19 differed from that of patients with diagnosed influenza or appendicitis for all healthcare systems, as did hospitalization from these conditions compared to any cause. For example, in the public healthcare system, 68% of patients with diagnosed COVID-19 were Latine, compared with 43% of patients with diagnosed influenza, and 48% of patients with diagnosed appendicitis (p < 0.05). In multivariable logistic regressions, COVID-19 hospitalizations were associated with male sex, Asian and Pacific Islander race/ethnicity, Spanish language, and public insurance in the university healthcare system, and Latine race/ethnicity and obesity in the community healthcare system. Influenza hospitalizations were associated with Asian and Pacific Islander and other race/ethnicity in the university healthcare system, obesity in the community healthcare system, and Chinese language and public insurance in both the university and community healthcare systems. CONCLUSIONS: Racial/ethnic and sociodemographic inequities in diagnosed COVID-19 and hospitalization differed from those for diagnosed influenza and other medical conditions, with consistently higher odds among Latine and Spanish-speaking patients. This work highlights the need for disease-specific public health efforts in at-risk communities in addition to structural upstream interventions.

COVID-19 Vaccination and The Eye.

PURPOSE: To summarize the current evidence on COVID-19 vaccine-associated ocular adverse events. DESIGN: Narrative literature review. METHODS: The literature search was conducted in August 2021 using 4 electronic databases: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic Reviews. Population-based pharmacovigilance surveillance data were retrieved from all governmental agencies participating in the World Health Organization (WHO) Programme for International Drug Monitoring with publicly available online adverse event databases in English. RESULTS: A small number of case reports have documented uveitis flares and acute corneal graft rejection occurring within the first 3 weeks following immunization, while isolated cases of optic neuropathies, retinal conditions, scleritis, and herpetic eye disease have also been highlighted. However, data from population-based pharmacovigilance surveillance systems suggest that the prevalence of vaccination-associated ocular adverse events are very rare. CONCLUSIONS: Vaccination-associated ocular adverse events are rare, and there is currently no substantive evidence to counterweigh the overwhelming benefits of COVID-19 immunization in patients with pre-existing ophthalmic conditions.

Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities.

BACKGROUND: The successful development of multiple COVID-19 vaccines has led to a global vaccination effort to reduce severe COVID-19 infection and mortality. However, the effectiveness of the COVID-19 vaccines wane over time leading to breakthrough infections where vaccinated individuals experience a COVID-19 infection. Here we estimate the risks of breakthrough infection and subsequent hospitalization in individuals with common comorbidities who had completed an initial vaccination series. METHODS: Our study population included vaccinated patients between January 1, 2021 to March 31, 2022 who are present in the Truveta patient population. Models were developed to describe 1) time from completing primary vaccination series till breakthrough infection; and 2) if a patient was hospitalized within 14 days of breakthrough infection. We adjusted for age, race, ethnicity, sex, and year-month of vaccination. RESULTS: Of 1,218,630 patients in the Truveta Platform who had completed an initial vaccination sequence between January 1, 2021 and March 31, 2022, 2.85, 3.42, 2.75, and 2.88 percent of patients with CKD, chronic lung disease, diabetes, or are in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.46 percent of the population without any of these four comorbidities. We found an increased risk of breakthrough infection and subsequent hospitalization in individuals with any of the four comorbidities when compared to individuals without these four comorbidities. CONCLUSIONS: Vaccinated individuals with any of the studied comorbidities experienced an increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the people without any of the studied comorbidities. Individuals with immunocompromising conditions and chronic lung disease were most at risk of breakthrough infection, while people with CKD were most at risk of hospitalization following breakthrough infection. Patients with multiple comorbidities have an even greater risk of breakthrough infection or hospitalization compared to patients with none of the studied comorbidities. Individuals with common comorbidities should remain vigilant against infection even if vaccinated.

Racial inequality in COVID-treatment and in-hospital length of stay in the US over time.

Introduction: Demonstrated health inequalities persist in the United States. SARS-CoV-2 (COVID) has been no exception, with access to treatment and hospitalization differing across race or ethnic groups. Here, we aim to assess differences in treatment with remdesivir and hospital length of stay across the four waves of the pandemic. Materials and methods: Using a subset of the Truveta data, we examine the odds ratio (OR) of in-hospital remdesivir treatment and risk ratio (RR) of in-hospital length of stay between Black or African American (Black) to White patients. We adjusted for confounding factors, such as age, sex, and comorbidity status. Results: There were statistically significant lower rates of remdesivir treatment and longer in-hospital length of stay comparing Black patients to White patients early in the pandemic (OR for treatment: 0.88, 95% confidence interval [CI]: 0.80, 0.96; RR for length of stay: 1.17, CI: 1.06, 1.21). Rates became close to parity between groups as the pandemic progressed. Conclusion: While inpatient remdesivir treatment rates increased and length of stay decreased over the beginning course of the pandemic, there are still inequalities in patient care.

Lessons from the COVID-19 pandemic and recent developments on the communication of clinical trials, publishing practices, and research integrity: in conversation with Dr. David Moher.

BACKGROUND: The torrent of research during the coronavirus (COVID-19) pandemic has exposed the persistent challenges with reporting trials, open science practices, and scholarship in academia. These real-world examples provide unique learning opportunities for research methodologists and clinical epidemiologists-in-training. Dr. David Moher, a recognized expert on the science of research reporting and one of the founders of the Consolidated Standards of Reporting Trials (CONSORT) statement, was a guest speaker for the 2021 Hooker Distinguished Visiting Professor Lecture series at McMaster University and shared his insights about these issues. MAIN TEXT: This paper covers a discussion on the influence of reporting guidelines on trials and issues with the use of CONSORT as a measure of quality. Dr. Moher also addresses how the overwhelming body of COVID-19 research reflects the "publish or perish" paradigm in academia and why improvement in the reporting of trials requires policy initiatives from research institutions and funding agencies. We also discuss the rise of publication bias and other questionable reporting practices. To combat this, Dr. Moher believes open science and training initiatives led by institutions can foster research integrity, including the trustworthiness of researchers, institutions, and journals, as well as counter threats posed by predatory journals. He highlights how metrics like journal impact factor and quantity of publications also harm research integrity. Dr. Moher also discussed the importance of meta-science, the study of how research is carried out, which can help to evaluate audit and feedback systems and their effect on open science practices. CONCLUSION: Dr. Moher advocates for policy to further improve the reporting of trials and health research. The COVID-19 pandemic has exposed how a lack of open science practices and flawed systems incentivizing researchers to publish can harm research integrity. There is a need for a culture shift in assessing careers and "productivity" in academia, and this requires collaborative top-down and bottom-up approaches.

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.

BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS: We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS: Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS: Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).

Molecular Mechanisms of Cerebrovascular Diseases.

Cerebrovascular disease involves a range of conditions including ischemic and hemorrhagic stroke, vascular malformations, and vascular cognitive impairment and dementia (VCID) [...].

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

Immediate impacts of COVID-19 on female and male farmers in central Myanmar: Phone-based household survey evidence.

This article provides evidence of the immediate impacts of the first months of the COVID-19 crisis on farming communities in central Myanmar using baseline data from January 2020 and follow-up phone survey data from June 2020 with 1,072 women and men. Heterogeneous effects among households are observed. Fifty-one percent of the sample households experienced income loss from various livelihood activities, and landless households were more severely affected by the crisis, mainly because of lost farm and nonfarm employment and negative impacts on rural enterprises. Women and men in these landless households were equally engaged and affected by lower wages or more difficulties in finding farm work; fewer women were engaged in nonfarm work, but almost all of them lost such nonfarm wage employment. Women in landless households are also particularly vulnerable in terms of worsened workload and increased tension in the household during COVID-19. Landed households were also affected through lower prices, lower demand for crops, and difficulties in input access. Women and men differ in levels of stress, fear, and pessimism regarding the effects of COVID-19. In most households, there were no signs that household task-sharing and work balance improved, and no clear shift in intrahousehold relations was observed.

Early Outcomes of a National Cancer Center's Strategy Against COVID-19 Executed Through a Disease Outbreak Response Taskforce.

PURPOSE: We present the strategy of a comprehensive cancer center organized to make operations pandemic proof and achieve continuity of cancer care during the COVID-19 pandemic. METHODS: Disease Outbreak Response (DORS) measures implemented at our center and its satellite clinics included strict infection prevention, manpower preservation, prudent resource allocation, and adaptation of standard-of-care treatments. Critical day-to-day clinical operations, number of persons screened before entry, staff temperature monitoring, and personal protection equipment stockpile were reviewed as a dashboard at daily DORS taskforce huddles. Polymerase chain reaction swab tests performed for patients and staff who met defined criteria for testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tracked. Descriptive statistics of outpatient attendances and treatment caseloads from February 3 to May 23, 2020, were compared with the corresponding period in 2019. RESULTS: We performed COVID-19 swabs for 80 patients and 93 staff, detecting three cancer patients with community-acquired COVID-19 infections with no nosocomial transmission. Patients who required chemotherapy, radiotherapy, or surgery and patients who are on maintenance treatment continued to receive timely treatment without disruption. The number of intravenous chemotherapy treatments was maintained at 97.8% compared with 2019, whereas that of weekly radiotherapy treatments remained stable since December 2019. All cancer-related surgeries proceeded without delay, with a 0.3% increase in workload. Surveillance follow-ups were conducted via teleconsultation, accounting for a 30.7% decrease in total face-to-face clinic consultations. CONCLUSION: Through the coordinated efforts of a DORS taskforce, it is possible to avoid nosocomial SARS-CoV-2 transmissions among patients and staff without compromising on care delivery at a national cancer center.

The Focused Neurosurgical Examination During Telehealth Visits: Guidelines During the COVID-19 Pandemic and Beyond.

OBJECTIVE:  To provide guidelines to healthcare workers for performing a focused neurological examination via telemedicine during the coronavirus disease-2019 (COVID-2019) pandemic. METHODS:  We reviewed our department's outpatient clinic visits after the implementation of a telemedicine protocol in response to the COVID-19 crisis. Crossover rates from telehealth to in-person visits were evaluated and guidelines for performing a telemedicine neurological exam were created based on the consensus of 16 neurosurgical attending providers over a four-month period. RESULTS:  From March 23, 2020 to July 20, 2020, some 2157 telehealth visits were performed in our department. Some 26 were converted to in-person visits by the provider request with the most cited reason for conversion being the need for a more detailed patient evaluation. Based on these experiences, we created a graphical tutorial to address the key components of the neurological exam with adaptations specific to the telehealth visit. CONCLUSIONS:  In response to the global coronavirus pandemic, telemedicine has become an integral part of neurosurgeons' daily practice. Telemedicine failures remain low but primarily occur due to a need for more comprehensive evaluations. We provide guidelines for the neurosurgical exam during telehealth visits in an effort to assuage some of these issues.

Evidence and magnitude of the effects of meteorological changes on SARS-CoV-2 transmission.

IMPORTANCE: Intensity and duration of the COVID-19 pandemic, and planning required to balance concerns of saving lives and avoiding economic collapse, could depend significantly on whether SARS-CoV-2 transmission is sensitive to seasonal changes. OBJECTIVE: Hypothesis is that increasing temperature results in reduced SARS CoV-2 transmission and may help slow the increase of cases over time. SETTING: Fifty representative Northern Hemisphere countries meeting specific criteria had sufficient COVID-19 case and meteorological data for analysis. METHODS: Regression was used to find the relationship between the log of number of COVID-19 cases and temperature over time in 50 representative countries. To summarize the day-day variability, and reduce dimensionality, we selected a robust measure, Coefficient of Time (CT), for each location. The resulting regression coefficients were then used in a multivariable regression against meteorological, country-level and demographic covariates. RESULTS: Median minimum daily temperature showed the strongest correlation with the reciprocal of CT (which can be considered as a rate associated with doubling time) for confirmed cases (adjusted R2 = 0.610, p = 1.45E-06). A similar correlation was found using median daily dewpoint, which was highly colinear with temperature, and therefore was not used in the analysis. The correlation between minimum median temperature and the rate of increase of the log of confirmed cases was 47% and 45% greater than for cases of death and recovered cases of COVID-19, respectively. This suggests the primary influence of temperature is on SARS-CoV-2 transmission more than COVID-19 morbidity. Based on the correlation between temperature and the rate of increase in COVID-19, it can be estimated that, between the range of 30 to 100 degrees Fahrenheit, a one degree increase is associated with a 1% decrease-and a one degree decrease could be associated with a 3.7% increase-in the rate of increase of the log of daily confirmed cases. This model of the effect of decreasing temperatures can only be verified over time as the pandemic proceeds through colder months. CONCLUSIONS: The results suggest that boreal summer months are associated with slower rates of COVID-19 transmission, consistent with the behavior of a seasonal respiratory virus. Knowledge of COVID-19 seasonality could prove useful in local planning for phased reductions social interventions and help to prepare for the timing of possible pandemic resurgence during cooler months.

Ångström- and Nano-scale Pore-Based Nucleic Acid Sequencing of Current and Emergent Pathogens.

State-of-the-art nanopore sequencing enables rapid and real-time identification of novel pathogens, which has wide application in various research areas and is an emerging diagnostic tool for infectious diseases including COVID-19. Nanopore translocation enables de novo sequencing with long reads (> 10 kb) of novel genomes, which has advantages over existing short-read sequencing technologies. Biological nanopore sequencing has already achieved success as a technology platform but it is sensitive to empirical factors such as pH and temperature. Alternatively, ångström- and nano-scale solid-state nanopores, especially those based on two-dimensional (2D) membranes, are promising next-generation technologies as they can surpass biological nanopores in the variety of membrane materials, ease of defining pore morphology, higher nucleotide detection sensitivity, and facilitation of novel and hybrid sequencing modalities. Since the discovery of graphene, atomically-thin 2D materials have shown immense potential for the fabrication of nanopores with well-defined geometry, rendering them viable candidates for nanopore sequencing membranes. Here, we review recent progress and future development trends of 2D materials and their ångström- and nano-scale pore-based nucleic acid (NA) sequencing including fabrication techniques and current and emerging sequencing modalities. In addition, we discuss the current challenges of translocation-based nanopore sequencing and provide an outlook on promising future research directions.