Hospitalisation and mortality among privately insured individuals with COVID-19 in the United States: The role of intellectual disabilities and Neurogenetic disorders.

BACKGROUND: Individuals with intellectual disabilities (IDs) and neurogenetic conditions (IDNDs) are at greater risk for comorbidities that may increase adverse outcomes for this population when they have coronavirus disease 2019 (COVID-19). The study aims are to examine the population-level odds of hospitalisation and mortality of privately insured individuals with COVID-19 with and without IDNDs IDs, controlling for sociodemographics and comorbid health conditions. METHODS: This is a retrospective, cross-sectional study of 1174 individuals with IDs and neurogenetic conditions within a population of 752 237 de-identified, privately insured, US patients diagnosed with COVID-19 between February 2020 and September 2020. Odds of hospitalisation and mortality among COVID-19 patients with IDNDs adjusted for demographic characteristics, Health Resources and Services Administration region, states with Affordable Care Act and number of comorbid health conditions were analysed. RESULTS: Patients with IDNDs overall had higher rates of COVID-19 hospitalisation than those without IDNDs (35.01% vs. 12.65%, P < .0001) and had higher rates of COVID-19 mortality than those without IDNDs (4.94% vs. .88%, P < .0001). Adjusting for sociodemographic factors only, the odds of being hospitalised for COVID-19 associated with IDNDs was 4.05 [95% confidence interval (CI) 3.56-4.61]. Adjusting for sociodemographic factors and comorbidity count, the odds of hospitalisation for COVID-19 associated with IDNDs was 1.42 (95% CI 1.25-1.61). The odds of mortality from COVID-19 for individuals with IDNDs adjusted for sociodemographic factors only was 4.65 (95% CI 3.47-6.24). The odds of mortality from COVID-19 for patients with IDNDs adjusted for sociodemographic factors and comorbidity count was 2.70 (95% CI 2.03-3.60). A major finding of the study was that even when considering the different demographic structure and generally higher disease burden of patients with IDNDs, having a IDND was an independent risk factor for increased hospitalisation and mortality compared with patients without IDNDs. CONCLUSIONS: Individuals with IDNDs had significantly higher odds of hospitalisation and mortality after adjusting for sociodemographics. Results remained significant with a slight attenuation after adjusting for sociodemographics and comorbidities. Adjustments for comorbidity count demonstrated a dose-response increase in odds of both hospitalisation and mortality, illustrating the cumulative effect of health concerns on COVID-19 outcomes. Together, findings highlight that individuals with IDNDs experience vulnerability for negative COVID-19 health outcomes with implications for access to comprehensive healthcare.

Modified Glasgow prognostic score (mGPS) is correlated with sarcopenia and dominates the prognostic role of baseline body composition parameters in advanced gastric and esophagogastric junction cancer patients undergoing first-line treatment from the phase III EXPAND trial.

BACKGROUND: Sarcopenia represents an established adverse prognostic factor in cancer patients. Consequently, different means to counteract sarcopenia have been proposed to improve cancer treatment. Computed tomography (CT)-based measurements, also labor intensive, are well validated for the analysis of sarcopenia. As inflammation plays a key role in the development of sarcopenia, we here studied the role of the modified Glasgow prognostic score (mGPS), consisting of inflammation parameters plasma C-reactive protein (CRP) and albumin, to predicting sarcopenia and adipose tissue-related body composition (BC) parameters at baseline and their changes during treatment and to analyze its prognostic role in conjunction with BC parameters. PATIENTS AND METHODS: CT measurements of BC parameters were carried out at baseline and week 12 in patients with advanced gastric or esophagogastric junction cancer from the phase III EXPAND trial, undergoing first-line platinum-fluoropyrimidine chemotherapy. mGPS was calculated from baseline CRP and albumin plasma levels. Pearson correlation and Cox regression analyses were carried out. RESULTS: mGPS is strongly prognostic for overall survival (OS). Baseline mGPS is significantly correlated with baseline mean muscle attenuation (MA; P < 0.0001). Baseline mGPS did not predict a decline in muscle or adipose tissue parameters during 12 weeks of treatment and a decline in muscle or adipose tissue parameters was not prognostic for OS. MA lost its prognostic role for OS when mGPS or CRP was entered into the Cox models. Eastern Cooperative Oncology Group performance status together with CRP or mGPS remained the sole baseline prognostic factors for OS. CONCLUSIONS: Our findings support a model where tumor-mediated inflammatory response represents a strong prognostic factor, which is causally related to sarcopenia, but with no direct causal path from sarcopenia to survival. Therefore, therapeutic targeting of systemic inflammation should be further explored as a promising strategy to improve both sarcopenia and the efficacy and tolerability of cancer treatment.

Maternal and Child Health Pipeline Training Programs: A Description of Training Across 6 Funded Programs.

PURPOSE: The HRSA-funded maternal and child health pipeline training programs (MCHPTPs) are a response to the critical need to diversify the MCH workforce, as a strategy to reduce health disparities in MCH populations. These MCHPTPs support students from undergraduate to graduate education and ultimately into the MCH workforce. DESCRIPTION: The models and components of training across the six MCHPTPs funded in 2016-2021 are summarized, to examine the design and delivery of undergraduate pipeline training and the insights gained across programs. ASSESSMENT: Strategies that emerged across training programs were organized into three themes: recruitment, support for student persistence (in education), and pipeline-to-workforce intentionality. Support for student persistence included financial support, mentoring, creating opportunity for students to develop a sense of belonging, and the use of research as a tool to promote learning and competitiveness for graduate education. Finally, the link to Maternal and Child Health Bureau (MCHB) long-term training and other MCHB opportunities for professional development contributed significant nuance to the pipeline-to-workforce objectives of these programs. CONCLUSIONS: The MCHPTPs not only increase the diversity of the MCH workforce, they also actively prepare the next generation of MCH leaders. The intentional connection of undergraduates to the infrastructure and continuum of MCH training, underscores the comprehensive impact of this funding.

Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8+ T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer.

Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study.

The effect of gestational age on neonatal outcome in low-risk singleton term deliveries.

OBJECTIVE: To assess the association between gestational age at delivery and adverse neonatal outcome among term low-risk singleton neonates. METHODS: A retrospective cohort study design was used. The study group included all low-risk singleton term (37 + 0 to 41 + 6 weeks) newborns delivered in a single tertiary university-affiliated medical center over a 5-year period. Outcome of neonates delivered at 37 + 0 to 37 + 6 weeks of gestation (early term) and 41 + 0 to 41 + 6 weeks of gestation (late term) was compared to that of neonates delivered at 39 + 0-39 + 6 weeks of gestation (control). RESULTS: Overall, the outcome of 30 229 neonates was analyzed. The incidence of neonatal mortality was 1.0 per 1000 live-born neonates, with no significant difference between the various gestational age groups. Early term newborns were at higher risk for respiratory morbidity, hypoglycemia, hypocalcemia, thrombocytopenia and unexplained jaundice, and had higher rates of prolonged hospital stay, NICU admission, sepsis workup and antibiotic treatment. On multivariate analysis, early term delivery was an independent predictor for composite respiratory morbidity (OR=2.4, 95% CI 1.6-3.8, p < 0.001), unexplained jaundice (OR=2.1, 95% CI 1.7-2.5, p < 0.001), hypoglycemia (OR=2.5, 95% CI 1.5-4.3, p < 0.001) and NICU admission (OR=1.9, 95% CI 1.5-2.5, p < 0.001). Late term neonates had a significantly higher rate of large for gestational date, but did not differ from controls with respect to the rate of composite neurologic or respiratory complications, NICU admission, birth trauma or infectious morbidity. CONCLUSION: Even in low-risk singleton deliveries, early term is associated with an increased risk of neonatal morbidity.

Macrosomic newborns of non-diabetic mothers: anthropometric measurements and neonatal complications.

OBJECTIVE: To assess the association of anthropometric measurements with neonatal complications in macrosomic newborns of non-diabetic mothers. DESIGN: Retrospective cohort study. PATIENTS: All liveborn, singleton, full term newborns with birth weight ≥4000 g born to non-diabetic mothers at a tertiary medical centre in 1995-2005 (n=2766, study group) were matched to the next born, healthy, full term infant with a birth weight of 3000-4000 g (control group). Exclusion criteria were multiple birth, congenital infection, major malformations and pregnancy complications. INTERVENTION: Data collection by file review. OUTCOME MEASURES: Complication rates were compared between study and control groups and between symmetric and asymmetric macrosomic newborns, defined by weight/length ratio (WLR), Body Mass Index and Ponderal Index. RESULTS: The 2766 non-diabetic macrosomic infants identified were matched to 2766 control infants. The macrosomic group had higher rates of hypoglycaemia (1.2% vs 0.5%, p=0.008), transient tachypnoea of the newborn (1.5% vs 0.5%, p<0.001), hyperthermia (0.6% vs 0.1%, p=0.012), and birth trauma (2% vs 0.7%, p<0.001), with no cases of symptomatic polycythaemia, and only one case of hypoglycaemia. Hypoglycaemia was positively associated with birth weight. It was significantly higher in the asymmetric than the symmetric macrosomic newborns, defined by WLR (1.7% vs 0.3%, p<0.001). CONCLUSIONS: Macrosomic infants of non-diabetic mothers are at increased risk of neonatal complications. However, routine measurements of haematocrit and calcium may not be necessary. Symmetric macrosomic infants (by WLR) have a similar rate of hypoglycaemia as normal-weight infants. Thus, repeat glucose measurements in symmetric macrosomic infants are not justified.

Expression and prognostic value of transcription factor PROX1 in colorectal cancer.

BACKGROUND: PROX1 is a specific target of the ß-catenin/TCF pathway in the intestinal epithelium. It acts as a regulator of progression from a benign to a highly dysplastic phenotype in colorectal tumours. However, the clinical significance of PROX1 expression is not known. METHODS: We studied the prognostic value of immunohistochemical expression of PROX1 in a series of 517 patients with colorectal cancer (CRC). RESULTS: The majority of the tumour samples expressed PROX1 (91%, 471 out of 517). High PROX1 expression was associated with a poor grade of tumour differentiation (P<0.0001). In the subgroup of patients with colon cancer, high PROX1 expression was associated with unfavourable colorectal cancer-specific survival (CCSS) as compared with low PROX1 expression (CCSS 47% vs 62%; P=0.045; RR 1.47). The association between high PROX1 and poor outcome was further strengthened in female colon cancer patients (CCSS 38% vs 63%; P=0.007; RR 2.02). Nonetheless, in multivariate survival analysis PROX1 expression was not retained as an independent prognostic factor. CONCLUSION: High PROX1 expression is associated with a poor grade of tumour differentiation, and, in colon cancer patients, also with less favourable patient outcome. Our results strengthen the previous preclinical observations that PROX1 has a role in tumour progression in CRC.

Long-term outcome following selective serotonin reuptake inhibitor induced neonatal abstinence syndrome.

OBJECTIVE: To assess the long-term neurodevelopment of children exposed in utero to selective serotonin reuptake inhibitors (SSRIs) that developed a neonatal abstinence syndrome (NAS). STUDY DESIGN: Neurodevelopmental evaluation was performed at the age of 2 to 6 years. Children who developed NAS were compared with those who did not using univariate and logistic regression analyses. RESULT: Thirty children with NAS and 52 without NAS participated in the study. Both groups were similar in mean cognitive ability (106.9±14.0 vs 100.5±14.6, P=0.12) and developmental scores (98.9±11.4 vs 95.7±9.9, P=0.21). However, there was a trend towards small head circumference in the NAS group (20 vs 6%, P=0.068). NAS was associated with an increased risk of social-behavior abnormalities (odds ratio (OR) 3.03, 95% confidence interval (CI) 1.07 to 8.60, P=0.04) and advanced maternal age (OR 1.12, 95% CI 1.00 to 1.25, P=0.04). CONCLUSION: Infants who developed NAS had normal cognitive ability, but were at an increased risk for social-behavioral abnormalities. Follow-up evaluation of symptomatic neonates should be considered.

Continuous-flux MOVPE growth of position-controlled N-face GaN nanorods and embedded InGaN quantum wells.

We demonstrate the fabrication of N-face GaN nanorods by metal organic vapour phase epitaxy (MOVPE), using continuous-flux conditions. This is in contrast to other approaches reported so far, which have been based on growth modes far off the conventional growth regimes. For position control of nanorods an SiO(2) masking layer with a dense hole pattern on a c-plane sapphire substrate was used. Nanorods with InGaN/GaN heterostructures have been grown catalyst-free. High growth rates up to 25 microm h(-1) were observed and a well-adjusted carrier gas mixture between hydrogen and nitrogen enabled homogeneous nanorod diameters down to 220 nm with aspect ratios of approximately 8:1. The structural quality and defect progression within nanorods were determined by transmission electron microscopy (TEM). Different emission energies for InGaN quantum wells (QWs) could be assigned to different side facets by room temperature cathodoluminescence (CL) measurements.

Organic labeling influences food valuation and choice.

Everyday we choose between a variety of different food items trying to reach a decision that fits best our needs. These decisions are highly dependent on the context in which the alternatives are presented (e.g. labeling). We investigate the influence of cognition on food evaluation, using an fMRI experiment in which subjects saw and bid on different foods labeled with (or without) a widely known German emblem for organically produced food. Increased activity in the ventral striatum was found for foods labeled "organic" in comparison to conventionally labeled food. Between-subject differences in activity were related to actual everyday consumption behavior of organic food.

Anthropometric indices at age 17 years of full-term neonates born short.

BACKGROUND: Measurements at the end of puberty of neonates short for gestational age (SGA-L) are scant. OBJECTIVE: To determine the correlation between birth length and weight in neonates, with height and weight at age 17 years. SUBJECTS AND METHODS: 385 full-term neonates, measuring less than 48 cm (SGA-L) and 585 full-term neonates, measuring 48 cm or greater (adequate birth length for gestational age; AGA-L) were included. 234 SGA-L and 359 AGA-L were identified at age 17 years. RESULTS: Comparison of the two groups revealed that both sexes born SGA-L were also shorter at age 17 years than those born AGA-L (girls 158.9 cm (SD 7.6) vs 164.2 cm (SD 64) (p<0.001) and boys 167.3 cm (SD 8.7) vs 173.8 cm (SD 7.1) (p<0.001)). The subjects born SGA-L also weighed significantly less than those born AGA-L (p<0.001) both at birth and at age 17 years. CONCLUSIONS: Children born SGA-L become short adults and weigh less at age 17 years than children with a normal birth length.

Mortality of full-term infants during the first month of life in a tertiary care hospital.

OBJECTIVE: The neonatal mortality rate is disproportionately influenced by preterm infants and does not reflect the rate in full-term infants. Our objectives were to estimate the full-term neonatal mortality rate and to identify causes of death in full-term infants during the first month of life. STUDY DESIGN: A retrospective study of full-term infant deaths during a 6-year period from 2000 to 2005, in a tertiary medical center. RESULT: During the study period there were 44,703 full-term births and 31 deaths, representing a mortality rate of 0.69 per 1,000 live births. The main cause of death was congenital anomalies (64.5%), specifically cardiac anomalies. Other causes were chromosomal anomalies or syndromes (12.9%), labor complications (12.9%), infections (3.2%), congenital diseases (3.2%) and metabolic disorders (3.2%). CONCLUSION: The mortality rate of full-term infants may be lower than previous estimates. Efforts aimed at decreasing mortality among full-term infants should focus on prenatal diagnosis.

Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer.

BACKGROUND: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. AIM: To assess the clinical relevance of XOR expression in gastric cancer. METHODS: XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease-specific survival, was assessed. RESULTS: XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non-curative disease, cellular aneuploidy, high S-phase fraction and high cyclooxygenase-2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5-year gastric cancer-specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I-II (p = 0.01) and lymph node-negative (p = 0.02) disease, as well as in patients with smaller (< or =5 cm) tumours (p = 0.02). CONCLUSION: XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer.

High-repetition-rate white-light pump-probe spectroscopy with a tapered fiber.

We have realized a 76 MHz white-light differential transmission spectroscopy system. The technique employs a Ti:sapphire laser oscillator and a tapered fiber to generate a white-light continuum spanning almost the full visible to near-infrared spectral range. Using acousto-optical modulation and subsequent lock-in detection, transient relative transmission changes as small as 10(-5) are detected. The method is applied to study the ultrafast gain dynamics of the active layer of a vertical-external-cavity surface-emitting laser based on a multiple-quantum-well structure.

Risk factors associated with candidaemia in the neonatal intensive care unit: a case-control study.

The incidence of candidaemia is steadily increasing in neonatal intensive care units (NICUs). Several neonatal risk factors for candidaemia have been identified, however, the number of cases in controlled studies is small and knowledge concerning maternal and perinatal risk factors is limited. The present study attempted to identify modifiable, independent maternal, perinatal and neonatal risk factors for candidaemia using a retrospective case-control study in the NICU of a tertiary-care paediatric medical centre. The study group consisted of 56 neonates admitted to the NICU between 1996 and 2000 who acquired candidaemia. The control group comprised the first infant admitted immediately after each study infant matched for gestational age (+/-10 days) and birthweight (+/-200 g). Potential maternal, perinatal and neonatal risk factors were compared between the groups using statistical methods and analysed by univariate and multivariate stepwise logistic regression models. The independent risk factors found to be significantly associated with increased risk of candidaemia were duration of ventilation and presence of bacteraemia before candidaemia. Maternal steroids had a significant protective effect. The positive predictive value using these three parameters was 78.38%. Maximizing in-utero steroid treatment in high-risk pregnancies, minimizing the days of mechanical ventilation and investment of efforts in prevention of bacteraemia may help to reduce the incidence of candidaemia in the NICU.

Disinfection with 10% povidone-iodine versus 0.5% chlorhexidine gluconate in 70% isopropanol in the neonatal intensive care unit.

AIM: The finding that 10% povidone-iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. METHODS: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992-1993 when only 10% povidone-iodine was used as a skin disinfectant, and 2) in 1995-1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. RESULTS: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of < 1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination. CONCLUSION: The use of 0.5% chlorhexidine gluconate solution in 70% isopropanol as a skin disinfectant is justified in neonatal intensive care units because it is not associated with an increased incidence of infections as opposed to 10% povidone-iodine and is devoid of detrimental effects.

Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols.

BACKGROUND: We conducted a 3-year follow-up study of long-term antibody persistence following vaccination of low-risk preterm infants with recombinant hepatitis B vaccine (HBV). Two three-dose protocols were compared: vaccination beginning within 24 h of birth to initial vaccination delayed until a weight of 2,000 g was reached. SUBJECTS AND METHODS: The study population included 136 children, divided into three groups: children born prematurely (< or = 35 weeks, n = 57), children born at term (> or = 37 weeks, n = 39), both groups receiving the first dose of HBV within 24 h of birth, and children born prematurely (< or = 35 weeks, n = 40), who received the first dose of HBV when a weight of 2,000 g was reached. All infants received the second hepatitis vaccination 1 month after the first, and the third dose 6 months after the first. Hepatitis B surface antibody (AntiHBs) was measured at an age of 3-3.5 years (at least 2.5 years after completion of the three-dose HBV series). An AntiHBs level of > or = 10 IU/l was considered positive. RESULTS: At 3-3.5 years of age, a higher percentage of the premature-delayed vaccination group had a positive AntiHBs level (92.5%) compared to both the premature (54.4%, p < 0.001) and full-term groups (71.8%, p < 0.05) vaccinated soon after birth. The premature-delayed vaccination group also had a significantly higher geometric mean concentration (GMC) (119 vs 14.2 IU/l, p < 0.001 and 119 vs 32.7 IU/l, p < 0.005, respectively). CONCLUSION: Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3-3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

Deposition of whole blood platelets on extracellular matrix under flow conditions in preterm infants.

BACKGROUND: A previous study showed greater adhesion by platelets of healthy full term infants to subendothelial extracellular matrix (ECM) under flow conditions compared with healthy adult platelets. AIM: To investigate the adhesion and aggregation of platelets from preterm infants on ECM under defined shear conditions. METHODS: In vitro platelet function was investigated in 106 preterm infants, 74 full term infants, and 26 healthy adults. Blood samples were obtained from all infants within 24 hours of birth, and weekly until discharge from preterm infants only. Citrated whole blood was placed in ECM precoated tissue culture plates and subjected to shear stress (1300 s-1) for two minutes using a rotating Teflon cone. Platelet adhesion (surface coverage) and aggregation (average size) to ECM were assayed using an image analyser. Assays for von Willebrand factor (vWF) antigen, ristocetin cofactor, and vWF collagen-binding activity were performed on samples from an additional 70 preterm infants, 23 healthy full term infants, and 24 healthy adults. Preterm infants with hyaline membrane disease (HMD) were analysed separately in both cohorts. RESULTS: Platelets from preterm infants displayed significantly less platelet adhesion than those from full term infants but similar aggregation and levels of vWF antigen, ristocetin cofactor, and collagen binding activity. Mean surface coverage was 22.0 (8.4)% for preterm infants with HMD, 28.7 (8.0)% for healthy preterm infants, and 35.7 (7.9)% for full term infants. Surface coverage in the preterm infants correlated with gestational age during the first 24 hours only, and did not reach full term levels during 10 weeks of follow up. CONCLUSION: Platelet adhesion to ECM is significantly poorer in preterm than in full term infants, and poorer in preterm infants with HMD than in healthy preterm infants. Intrinsic platelet properties rather than the concentration or activity of vWF may be responsible for this difference.