COVID-19 Cliff Notes: A COVID-19 Multidisciplinary Care Compendium.

As we pass the nearly 9 month mark of the coronavirus virus disease 2019 (COVID-19) pandemic in the United States, we sought to compile a brief multi-disciplinary compendium of COVID-19 information learned to date. COVID-19 is an active viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confers high morbidity and mortality. COVID-19 has been associated with: pulmonary compromise and acute respiratory distress syndrome, thrombotic events, inflammation and cytokine, and post-infectious syndromes. Mitigation of these complications and expeditious therapy are a global urgency; this is brief summary of current data and management approaches synthesized from publications, experience, cross-disciplinary expertise (Figure 1).

A cross-sectional study of non-attendance among patients at a US hemophilia treatment center 2010-2014.

INTRODUCTION: Among patients with chronic disease, non-attendance at scheduled healthcare visits is associated with poor outcomes. The impact of non-attendance among patients with bleeding disorders is unknown. METHODS: Scheduling and medical record data over a 5-year period for all individuals with at least one scheduled appointment during 2010-2014 at a US Hemophilia Treatment Center (HTC) were analysed. Non-attendance rates were calculated as the number of non-attended visits divided by the number of years as a patient during the time period. Consistent non-attenders were patients who did not attend more than one scheduled appointment per person-year on average. Logistic regression determined characteristics associated with consistent non-attendance and Poisson regression estimated adjusted incidence rate ratios (aIRRs) describing associations between non-attendance and emergency department (ED) visits and hospitalizations. RESULTS: There were 8028 appointments scheduled for 950 individuals; 12% were not attended. Consistent non-attenders (n = 62; 7% of the HTC patient population) accounted for over one-third of non-attended appointments and over one-quarter of hospitalizations. Characteristics associated with consistent non-attendance included public health insurance and black race. Higher non-attendance rates were associated with more ED visits (aIRR 1.78; 95% CI: 1.37-2.30) and hospitalizations (aIRR 2.73; 95% CI: 2.18-3.42). Consistent non-attenders had more ED visits (aIRR 2.49; 95% CI: 1.56-3.96) and hospitalizations (aIRR 4.73; 95% CI: 2.96-7.57) compared with patients who never missed appointments. CONCLUSIONS: Frequent non-attendance identified a small but at-risk population. Interventions to improve disease management that target them may have an impact on health outcomes and healthcare utilization.

The spectrum of bleeding in women and girls with haemophilia B.

Although hemophilia B affects 1 in 25,000 males there may be 3 female hemophilia B carriers per affected male. This clinical review highlights the unique challenges faced by hemophilia B carriers including the under-recognition of bleeding symptoms associated with and without FIX deficiency, discrepancies in correlation between genotype and bleeding phenotype and therapeutic considerations utilizing clinical vignettes of common scenarios.

Impact of diagnosis of von Willebrand disease on patient outcomes: Analysis of medical insurance claims data.

The inherited bleeding disorder von Willebrand disease (VWD) is challenging to diagnose owing to disease heterogeneity, lack of a definitive laboratory test and variations in diagnostic criteria. We evaluated the impact of diagnosis and diagnostic delay on patient outcomes. The PharMetrics Plus Database was interrogated for medical claims for VWD (ICD-9 286.4) and bleeding events between 1 January 2006 and 30 June 2015. Longitudinal analysis was performed of patients newly diagnosed with VWD (≥9 months' continuous enrolment before first VWD claim) through 24 months following diagnosis. In total, 32 028 diagnosed, including 18 182 newly diagnosed, patients were identified. Most patients (72%) were female. Prediagnosis, bleeding symptoms were most commonly managed by a hospitalist/emergency room physician. Misrecognition of VWD was common, with 25% of patients visiting the same specialist type at least twice for an episodic bleed before diagnosis. Thirty-seven percentage of patients had no diagnostic laboratory test within 24 months of their initial diagnostic claim. Bleed claims reduced following diagnosis: 41% and 26% of female and male patients, respectively, had claims in the year prediagnosis, falling to 21% and 9% of patients at 1-2 years postdiagnosis. The proportion of patients with multiple bleed claims also decreased, from 17% to 6% (females) and 7% to 3% (males). Serially misrecognized patients continued to have more bleeding episodes than other patients, although bleed frequency was lower than before diagnosis. There is a need for improved patient management from bleeding presentation onward to reduce the time to VWD diagnosis and to enhance patient outcomes.

Haemophilia A carriers experience reduced health-related quality of life.

INTRODUCTION: Haemophilia A is an X-linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite factor VIII activity within the normal range. AIM: Data regarding the effect of increased bleeding on health-related quality of life (HR-QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR-QOL related to bleeding symptoms. METHODS: We conducted a cross-sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18-60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology-oncology clinic. Trained interviewers administered the Rand 36-Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR-QOL, to each study participant. Mann-Whitney U-tests were used to compare median scores for the eight health domains between the case and control groups. RESULT: Forty-two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of 'Pain' (73.75 vs. 90; P = 0.02) and 'General health' (75 vs. 85; P = 0.01) compared to control subjects. CONCLUSION: Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36-item Health Survey 1.0 in the domains of 'Pain' and 'General Health' compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR-QOL in this population.

Proteinase expression during differentiation of human osteoclasts in vitro.

Osteoclasts are macrophage-derived polykaryons that degrade bone in an acidic extracellular space. This differentiation includes expression of proteinases and acid transport proteins, cell fusion, and bone attachment, but the sequence of events is unclear. We studied two proteins expressed at high levels only in the osteoclast, cathepsin K, a thiol proteinase, and tartrate-resistant acid phosphatase (TRAP), and compared this expression with acid transport and bone degradation. Osteoclastic differentiation was studied using human apheresis macrophages cocultured with MG63 osteosarcoma cells, which produce cytokines including RANKL and CSF-1 that mediate efficient osteoclast formation. Immunoreactive cathepsin K appeared at 3-5 days. Cathepsin K activity was seen on bone substrate but not within cells, and cathepsin K increased severalfold during further differentiation and multinucleation from 7 to 14 days. TRAP also appeared at 3-5 d, independently of cell fusion or bone attachment, and TRAP activity reached much higher levels in osteoclasts attached to bone fragments. Two proteinases that occur in the precursor macrophages, cathepsin B, a thiol proteinase related to cathepsin K, and an unrelated lysosomal aspartate proteinase, cathepsin D, were also studied to determine the specificity of the differentiation events. Cathepsin B occurred at all times, but increased two- to threefold in parallel with cathepsin K. Cathepsin D activity did not change with differentiation, and secreted activity was not significant. In situ acid transport measurements showed increased acid accumulation after 7 days either in cells on osteosarcoma matrix or attached to bone, but bone pit activity and maximal acid uptake required 10-14 days. We conclude that TRAP and thiol proteinase expression begin at essentially the same time, and precede cell fusion and bone attachment. However, major increases in acid secretion and proteinases expression continue during cell fusion and bone attachment from 7 to 14 days.