Tracking the prevalence and emergence of SARS CoV2 variants of concern using a regional genomic surveillance program.

SARS-CoV-2 molecular testing coupled with whole genome sequencing is instrumental for real-time genomic surveillance. Genomic surveillance is critical for monitoring the spread of variants of concern (VOC) as well as novel variant discovery. Since the beginning of the pandemic millions of SARS-CoV-2 genomes have been deposited into public sequence databases. This is the result of efforts of both national and regional diagnostic laboratories. Here we describe the results of SARS-CoV-2 genomic surveillance from February 2021 to June 2022 at a metropolitan hospital in the USA. We demonstrate that consistent daily sampling is sufficient to track the regional prevalence and emergence of VOC. Similar sampling efforts should be considered a viable option for local SARS-CoV-2 genomic surveillance at other regional laboratories.

Adult norms for the Corbett Targeted Coin Test.

STUDY DESIGN: Clinical measurement INTRODUCTION: Dexterity is important for daily activities. The Corbett Targeted Coin Test (CTCT) measures dexterity with palm-to-finger translation and proprioceptive target placement, but lacks established norms. PURPOSE OF THE STUDY: To establish norms for the CTCT with healthy adult subjects. METHODS: The inclusion criteria consisted of participants that were community dwelling, non-institutionalized, able to make a fist with both hands, perform finger-to-palm translation of twenty coins, and be at least 18 years of age. CTCT standardized testing procedures were followed. Quality of performance (QoP) scores were determined by speed in seconds and number of coin drops (each a 5-second penalty). QoP was summarized within each age, gender and hand dominance subgroup using the mean, median, minimum, and maximum. Correlation coefficients were computed for relationships between age and QoP, and between handspan and QoP. RESULTS: Of the 207 individuals who participated, 131 were females and 76 males with an age range of 18-86 and mean age of 37.16. Individual QoP scores ranged from 13.8 to 105.3 seconds, with median scores ranging from 28.7 to 53.3 seconds. The mean for males was 37.5 seconds for the dominant hand (range 15.7-105.3) and 42.3 seconds (range 17.9.-86.8) for the non-dominant hand. The mean for females was 34.7 seconds for the dominant hand (range 14.8-67.0) and 38.6 seconds (range 13.8.-82.7) for the non-dominant hand. Lower QoP scores indicate a faster and/or more accurate dexterity performance. Females showed better median QoP for most age groups. The best median QoP scores were seen in the 30-39 and 40-49 age ranges. DISCUSSION: Our study agrees to some extent with other research that reported dexterity decreases with age, and increases with smaller hand spans. CONCLUSION: Normative data for the CTCT can be a guide for clinicians evaluating and monitoring patient dexterity with palm-to-finger translation and proprioceptive target placement.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) serology in the vaccination era and post booster vaccination.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused over 6 million deaths world-wide. In the pre-vaccination era, we noted a 5·3% SARS-CoV-2 IgG antibody positivity rate in 81,624 subjects. Methods: Utilizing assays for serum SARS-CoV-2 spike (S) protein antibody (Roche) and neutralizing antibody (Diazyme), both >90% IgG, we measured antibodies in 13,189 subjects in the post-vaccination era, and in 69 subjects before and 60 days after booster vaccination. Results: In 2021, in 10,267 subjects, 25·0% had negative S protein levels (<0.80 U/L), 24·4% had low positive levels (0.80-250 U/L), and 50·7% had high positive levels (>250 U/L). Median neutralizing antibody levels were 1·16 and 2·06 AU/mL in the low and high positive groups, respectively. In 2022, we evaluated 2,016 subjects where samples were diluted 1:100 if S protein antibody levels were >250 U/L. Median S protein and neutralizing antibody levels were 2,065 U/L (86.3% positivity) and 2·68 AU/mL (68.0% positivity), respectively. Antibody levels were also measured in 69 subjects before and 60 days after receiving SARS-CoV-2 booster vaccinations. Treatment resulted in a 15-fold increase in S protein antibody levels from 1,010 to 17,236 U/L, and a 6-fold increase in neutralizing antibody from 1·51 to 12·51 AU/mL in neutralizing antibody levels, respectively (both P<0.00001), with a wide variability in response. Conclusions: Our data indicate that by early 2022 86% of subjects had positive SARS-CoV-2 S protein antibody levels, and that these levels and neutralizing antibody levels were increased 15-fold and 6-fold, respectively, 60 days after SARS-Cov-2 booster vaccination.

Integrating Care from Home to Hospital to Home: Using Participatory Design to Develop a Provincial Transitions in Care Guideline.

Introduction: Patients worldwide experience fragmented and uncoordinated care as they transition between primary and acute care. To improve system integration and outcomes for patients, in 2017/2018 Alberta Health Services (largest health services delivery organization in Canada) called for a coordinated approach to improve transitions in care (TiC). Healthcare leadership responded by initiating the development of a province-wide guideline outlining core components of effective transitions in care. This case study highlights the extensive design process used to develop this guideline, with a focus on the participatory design (PD) approach used throughout. Methods: An iterative, mixed methods PD approach was used to engage over 750 stakeholders through the following activities to establish Guideline content: i) learning collaborative; ii) design-team; iii) targeted online surveys; iv) primary care stakeholder consultation; v) modified Delphi panel; and vi) patient advisory committee. Results: The result was Alberta's first guideline for supporting patients through TiC: "Alberta's Home to Hospital to Home Transitions Guideline". Conclusion: The extensive design process used to create the Guideline was instrumental in establishing content, encouraging system integration, and creating conditions to support provincial implementation. While intended to improve and standardize patient care in Alberta, the methods used and lessons learned throughout the development of the Guideline are applicable internationally.

Discrimination in lending? Evidence from the Paycheck Protection Program.

Abstract: We assess the role of race in loans made through the Paycheck Protection Program (PPP). The PPP program, created by the U.S. government as a response to the Covid-19 pandemic, provides loans to small businesses so they can keep employees on their payroll. We argue that the historical record and PPP program design choices made it likely that many Black-owned businesses received smaller PPP loans than White-owned businesses. Using newly released data on the PPP program, we find that Black-owned businesses received loans that were approximately 50% lower than observationally similar White-owned businesses. The effect is marginally smaller in areas with more bank competition and disappeared over time as changes to the PPP program were implemented allowing for entry by fintechs and other non-traditional lenders. Plain English Summary: We find that Black-owned businesses received loans through the Paycheck Protection Program that were approximately 50 percent lower than White-owned businesses with similar characteristics. However, this difference in loan size shrank over time as more non-bank lenders such as fintechs were allowed to participate in the program and began approving PPP loans. Loan size differences were also slightly smaller in zip codes containing a larger number of bank branches. These results are consistent with prior research which shows lending discrimination by commercial banks against Black borrowers. It is also consistent with studies showing that greater access to and competition among banks and other lenders can reduce discrimination. In light of these results we recommend that policy makers account for existing racial inequalities within banking or other systems in their program design to produce more equitable outcomes.

Impact of Diabetes on Hospitalized Patients With Chronic Medical Conditions.

AIM: To measure cost and length of stay in patients with and without a diagnosis of diabetes admitted with cardiovascular, pulmonary, or cerebrovascular disease. METHODS: Retrospective study used International Classification of Diseases, 10th Revision, Clinical Modification codes to identify patients with diabetes, cardiovascular, pulmonary, or cerebrovascular disease. The All Patients Refined Diagnosis Related Groups, which classify patients according to admission diagnosis, severity of illness, and risk of mortality, was used to determine actual (discharge) diagnoses. Total admission cost and length of stay were compared using the Wilcoxon rank-sum test. RESULTS: Study reviewed 48,572 subjects who met inclusion criteria. When compared with patients without diabetes of similar age, sex, race, risk of mortality, and severity of illness and controlling for length of stay, individuals with diabetes had similar total admission costs. Lengths of stay were similar for individuals with and without diabetes admitted with a diagnosis of cerebrovascular disease or respiratory infection. However, patients with a primary diagnosis of congestive heart failure and a secondary diagnosis of diabetes incurred longer lengths of stay. CONCLUSION: Individuals with diabetes and congestive heart failure have longer lengths of stay than those without diabetes. To decrease the economic burden of diabetes and chronic conditions, primary care providers and hospitals need to implement guidelines regarding the management of care for individuals with two or more chronic conditions.

Combined haploidentical and cord blood transplantation for refractory severe aplastic anaemia and hypoplastic myelodysplastic syndrome.

Umbilical cord blood (UCB) transplantation is a potentially curative treatment for patients with refractory severe aplastic anaemia (SAA), but has historically been associated with delayed engraftment and high graft failure and mortality rates. We conducted a prospective phase 2 trial to assess outcome of an allogeneic transplant regimen that co-infused a single UCB unit with CD34+ -selected cells from a haploidentical relative. Among 29 SAA patients [including 10 evolved to myelodysplastic syndrome (MDS)] who underwent the haplo cord transplantation (median age 20 years), 97% had neutrophil recovery (median 10 days), and 93% had platelet recovery (median 32 days). Early myeloid engraftment was from the haplo donor and was gradually replaced by durable engraftment from UCB in most patients. The cumulative incidences of grade II-IV acute and chronic graft-versus-host disease (GVHD) were 21% and 41%, respectively. With a median follow-up of 7·5 years, overall survival was 83% and GVHD/relapse-free survival was 69%. Patient- and transplant-related factors had no impact on engraftment and survival although transplants with haplo-versus-cord killer-cell immunoglobulin-like receptor (KIR) ligand incompatibility had delayed cord engraftment. Our study shows haplo cord transplantation is associated with excellent engraftment and long-term outcome, providing an alternative option for patients with refractory SAA and hypoplastic MDS who lack human leucocyte antigen (HLA)-matched donors.

Can addressing inequality unleash economic growth?

Barriers to entering the field of invention have led to negative outcomes for individuals and for the economy. We built a vibrant middle class in the post-war era because we started to tear down many of the barriers that had kept women of all races and men of color from contributing their full talents. A quarter of the growth in aggregate output from 1960 to 2010 can be explained by improved allocation of talent. We didn't finish the work. We allowed barriers to opportunity to return, or new ones to grow up. This turned out to be a tragedy, not only for those people who lost their livelihoods, but also for the economy. Policy can make a difference. The Civil Rights Act really did make a huge difference in the opportunities and gains for Black Americans and for women. Subsequent advancements in automation and trade, which left a lot of workers behind, were not accompanied by changes in policy to help those workers adapt. One thing that we know is that, especially in laboratories or patent teams where people are working together, equality of opportunity is much more than just getting things like as many job interviews. Women and underrepresented minorities are not pulled in and kept in the same way as others. We may, in fact, as a society be underinvesting in the people who could be creating the companies that would be creating the jobs that put those people to better use. A key concern now is that this could be a recession that would harm pathways to the middle class for a long time.

Economists tackle the challenges of a pandemic.

The COVID-19 pandemic radically and rapidly changed the world, including the world of business economists. Eight NABE members employed in a wide variety of fields discuss how their lives and work were transformed.

Association between continuity and access in primary care: a retrospective cohort study.

BACKGROUND: Continuity of care is a tenet of primary care. Our objective was to explore the relation between a change in access to a primary care physician and continuity of care. METHODS: We conducted a retrospective cohort study among physicians in a primary care network in southwest Alberta who measured access consistently between 2009 and 2016. We used time to the third next available appointment as a measure of access to physicians. We calculated the provider and clinic continuity, discontinuity and emergency department use based on the physicians' own panels. Physicians who improved, worsened or maintained their level of access within a given year were assessed in multilevel models to determine the association with continuity of care at the physician and clinic levels and the emergency department. RESULTS: We analyzed data from 190 primary care physicians. Physicians with improved access increased provider continuity by 6.8% per year, reduced discontinuity by 2.1% per year, and decreased emergency department encounters by 78 visits per 1000 patients per year compared to physicians with stable access. Physicians with worsening access had a 6.2% decrease in provider continuity and an increased number of emergency department encounters (64 visits per 1000 panelled patients per year) compared to physicians with stable access. INTERPRETATION: Changes in access to primary care can affect whether patients seek care from their own physician, from another clinic or at the emergency department. Improving access by reducing the delay in obtaining an appointment with one's primary care physician may be one mechanism to improve continuity of care.

SARS-CoV-2 serology and virology trends in donors and recipients of convalescent plasma.

SARS-CoV-2 has infected millions worldwide. The virus is novel, and currently there is no approved treatment. Convalescent plasma may offer a treatment option. We evaluated trends of IgM/IgG antibodies/plasma viral load in donors and recipients of convalescent plasma. 114/139 (82 %) donors had positive IgG antibodies. 46/114 donors tested positive a second time by NP swab. Among those retested, the median IgG declined (p < 0.01) between tests. 25/139 donors with confirmed SARS-CoV-2 were negative for IgG antibodies. This suggests that having had the infection does not necessarily convey immunity, or there is a short duration of immunity associated with a decline in antibodies. Plasma viral load obtained on 35/39 plasma recipients showed 22 (62.9 %) had non-detectable levels on average 14.5 days from positive test versus 6.2 days in those with detectable levels (p < 0.01). There was a relationship between IgG and viral load. IgG was higher in those with non-detectable viral loads. There was no relationship between viral load and blood type (p = 0.87) or death (0.80). Recipients with detectable viral load had lower IgG levels; there was no relationship between viral load, blood type or death.

Factors Associated with Good Patient Outcomes Following Convalescent Plasma in COVID-19: A Prospective Phase II Clinical Trial.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a viral respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel virus was discovered in Wuhan City, Hubei Province, China, in December 2019. As of September 6, 2020, confirmed cases have risen to more than 27,000,000 worldwide and more than 885,000 people have died. Currently, no cure or standard treatment for COVID-19 exists. We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19. METHODS: Convalescent plasma with sufficient total anti-SARS-CoV-2 IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge. RESULTS: Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in the disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p < 0.02) and shorter mean hospital length of stay 15.4 vs 33 days (p < 0.01). One patient experienced a transient transfusion reaction. No other adverse effects of convalescent plasma infusion were observed. CONCLUSIONS: Our results suggest that convalescent plasma with adequate anti-SARS-CoV-2 antibody titer is safe and has the potential for positive impact on clinical outcomes including recovery and survival if given to patients early in the course of COVID-19 disease. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier, NCT04343261, IND #19805.

A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.

Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10-60 min and 18-24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).

Implementation of a Physician-Patient Attachment Initiative in Alberta.

Attachment to a primary care physician (PCP) is a foundational component of the Patient's Medical Home. Yet how can attachment exist in a system that does not limit where patients seek care? This article describes a top-down approach with the ideologies of a bottom-up collaborative to address attachment within an Alberta primary care network. The steps taken to reduce the number of patients listed on multiple PCP panels from 27% to 4% will be described. Learnings from this initiative suggest that direct involvement with providers, coupled with engaged physician leadership, can create a local system of information delivery that supports the attachment of patients to their most responsible PCP.

Author Correction: The prognostic effects of somatic mutations in ER-positive breast cancer.

The original version of this Article contained errors in the depiction of confidence intervals in the NF1 BCSS data illustrated in Figure 3b. These have now been corrected in both the PDF and HTML versions of the Article. The incorrect version of Figure 3b is presented in the associated Author Correction.

The prognostic effects of somatic mutations in ER-positive breast cancer.

Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.