https://orcid.org/0000-0002-5926-0478
ABSTRACT
Background
Objectives were to 1) assess COVID-19-associated medical and psychological challenges facing persons with inherited bleeding disorders (PIBD) and their parents/guardians (PG) in Germany, the US, and the UK; 2) describe similarities and differences among these countries; 3) identify needs and opportunities for intervention by patient advocacy organizations (PAGs).
Research Design & Methods
A cross-sectional, international survey was conducted in three countries using validated psychometric instruments and investigator-developed items.
Results
Five hundred and four surveys were included. Significant differences between countries were found including experiences with medical care, specific thoughts, and concerns about COVID-19, anxiety, and other mental health measures, as well as resources used to cope with stress. Age, education, income, race, IBD diagnosis, PIBD vs. BD group, and gender had moderating effects on resources used. Communication with friends/relatives and use of PAG and HTCs as resources for information/coping decreased in all countries during the pandemic.
Conclusions
There were similarities and differences between respondents across the country in the perceived impact of the pandemic, mental health scores, and strategies used to cope with stress. Recommendations: strategies to increase PAG access for PIBD and their PG during pandemics and natural disasters, ongoing assessment and adaptation to provide supportive resources to specific patient subgroups.
Plain Language Summary
Persons with inherited bleeding disorders (PIBD) and their parents faced many challenges during the COVID-19 pandemic. An online survey was conducted within three countries: Germany, the United States, and the United Kingdom to explore these challenges and address how patient advocacy organizations can better meet their needs. Areas explored included experiences with medical care, concerns, and thoughts expressed during the pandemic, and coping resources used before and during the pandemic. In addition, mental health issues were explored addressing anxiety, COVID-related fears, depression, and resilience. Differences were found regarding experiences with medical care, specific thoughts, and concerns about COVID-19, anxiety, and other mental health measures, as well as resources used to cope with stress. These results provide an opportunity for advocacy organizations for PIBD to develop appropriate assessment, adaptation, and education resources to help patients during pandemics and/or natural disasters in the future.
1. Introduction
In late 2019, an infectious respiratory disease caused by the SARS-CoV-2 virus (COVID-19) was identified in China. By March 2020, the World Health Organization (WHO) declared Corona Virus Disease of 2019 (COVID-19) a pandemic. As of 4 October 2023, 771,151,224 cases were reported worldwide with 6,960,782 global deaths [Citation1]. At the time of writing, the United States (US) leads the number of COVID-19 cases and deaths worldwide; Germany is 5th; and the United Kingdom (UK) in 10th place [Citation1].
Management of this new health threat, together with the exponential increase in patient hospitalizations and deaths, resulted in an enormous burden to global health care systems and challenges accessing routine medical care with immediate and long-term effects on the world’s health, economy, and societal organization [Citation2].
The pandemic disrupted day-to-day living in many ways. Those with chronic conditions had the added burden of managing their health while dealing with unprecedented lockdowns and social distancing practices causing increased anxiety [Citation3–6]. The general population expressed significant anxiety related to potential exposure to this virus and health risks affecting their ability to access health care. In Ireland, COVID-19 resulted in a 63% decrease in hemophilia medical/nursing clinic consultations compared to the same period in 2019 [Citation7]. In a German survey conducted during the first lockdown in 2020 among 355 patients with inherited bleeding disorders (PIBD), half reported postponed or canceled medical appointments, interrupted physiotherapy, and a few reported less reachability of their hemophilia treatment center (HTC) [Citation8]. As part of the same study, significant differences in medical experiences were found between non-hospital clinics, where more delayed medication supply was experienced, and hospital-based clinics where doctor’s appointments and routine screening appointments were more frequently postponed or canceled [Citation9]. In a French cross-sectional, multicenter study evaluating COVID-19 lockdown, 1,274 adults with chronic diseases (including 183 with hemophilia) were evaluated. Subjects reported at least one missed scheduled visit with a physician, although medication adherence remained high [Citation5]. A phone survey conducted by a French HTC [Citation10] explored the impact of the first COVID-19 lockdown on 239 hemophilia patients (adults and children). Medication adherence (hemostatic and other medicines) remained high (adults 82.0%, children 98.2%) and patients on prophylaxis self-adjusted treatment (17%) by spacing out intervals between injections due to reduced physical or professional activities and/or fear of drug shortage [Citation10].
Inadequate knowledge regarding the route of transmission and incubation period of the virus, treatment, and safety measures caused fear and anxiety in the general public [Citation6,Citation11].
Few studies addressed mental health (MH) of PIBD during the pandemic. The von Mackensen et al. [Citation8] study reported feelings of being at the mercy of the pandemic, anger, and helplessness. Significant differences between caregivers and patients were found related to thoughts and worries. Although 40.1% felt their feelings were unchanged, many respondents expressed anxiety and worries about; i) getting COVID-19; ii) what will happen if they contracted COVID-19; iii) if they were part of a high-risk group; iv) and delivery difficulties of their treatment product. Caregivers were more concerned if: i) their child contracted COVID-19; ii) adequate care would continue, and iii) could they could go to the emergency room for care. An Italian single-center study [Citation12] evaluated the impact of the pandemic and isolation measures on 23 hemophilia patients receiving regular prophylaxis who also reported anxiety and worry citing concerns about factor supply and production. Most felt supported by their HTC, judging the support and availability of the HTC personnel as sufficiently important.
Boulin et al. [Citation5] reported that during the pandemic respondents experienced worse MH, psychological distress, deterioration in sleep time, physical activity, weight gain, and increase in screen-time. Unhealthy behaviors such as alcohol and/or drug use, and decreased activity were associated with urban living, worse self-reported MH, and psychological distress. Volot et al. [Citation10] also reported poor lifestyle behavior changes including increased screen time, decreased physical activity, weight gain, and increased smoking/vaping among adults.
Although not associated with high risk for severe illness related to COVID-19 [Citation13], PIBD are a vulnerable population who require adjustment to maintain adherence to their prescribed treatment regimens while dealing with unforeseen changes and events [Citation14]. The negative consequences of pandemic-related restrictions could also be greater, given the usual close collaboration between PIBD and HTC staff on health care and lifestyle modifications needed for effective treatment, especially, during acute bleeding events [Citation15].
Due to the paucity of data on the perceived impact of the pandemic on the lives of PIBD and their parents/caregivers (PG), a cross-cultural international study was designed to:
Assess the COVID-19-associated impact and psychological challenges facing the inherited bleeding disorder community in Germany, the US, and the UK.
Describe the similarities and differences among these countries.
Identify areas of need and potential intervention by patient advocacy groups (PAGs).
2. Patients and Methods
The cross-sectional, international study was conducted in Germany, the US, and the UK. Each country’s IRB determined the study to have exempt status. An interdisciplinary team of experienced researchers created an electronic survey which included validated psychometric instruments and investigator-developed items. Survey versions for PIBD and PG were made available in English (American and British versions), German, and Spanish. Potential subjects received recruitment materials sent via their respective PAGs: i) Germany: Deutsche Hämophiliegesellschaft (DHG), Interessengemeinschaft Hämophiler (IGH) and Deutsche Bluthilfe (DBH); ii) US: National Hemophilia Foundation (NHF), Hemophilia Federation of America (HFA) and chapter organizations; iii) UK: The Haemophilia Society. Recruitment strategies also included social media avenues in all countries and: i) Germany: postcards with a QR code linking to the survey and PAG websites; ii) US: PAG websites, iii) UK: PAG social media. All recruitment materials were uniform in design ensuring that participants recognized the study and did not take the survey more than once. The 20-minute online electronic survey was open from March 15 to 31 May 2021 utilizing an electronic click-to-consent. Data were collected anonymously excluding the 18 HIPPA identifiers [Citation16]. Sequential survey questions could not be skipped. Respondents could revise their responses and stop and/or exit the survey at any time. No payment was offered for participating.
Inclusion criteria included: i) self-report of an inherited bleeding disorder (IBD) or the parent/guardian of a IBD, ii) able to read, write, and understand English, German, or Spanish, iii) able to access electronic survey via the internet, iv) age of consent/assent in each country. PIBD who lived outside of Germany, US, or UK were excluded from this study. Responses were collected and stored in the password protected, HIPAA compliant Qualtrics-XM® server.
provides data collection domains and data elements. Self-reported basic demographic information was collected. In order to compare different categories of education and occupation across countries, the International Standard Classification of Education [Citation17] and the International Classification of Occupations [Citation18] were used, respectively. Current net household income (monthly in Germany and UK, and yearly in the US) was transformed into monthly US dollars (USD) for comparison, utilizing the foreign exchange rate at the time of the questionnaire. Monthly income was ranked on a 7-point scale (low to high), ranging from < $1,600 to > $9,200 (see ).
Table 1. Data collection domains.
Table 2. Demographic data*.
Clinical data included medical information related to the respondents’ bleeding disorder (see ). COVID-19 experiences were explored via general questions such as COVID-19 status, known someone who died from COVID, quarantine/vaccination practices, and the Post COVID-19 Functional Scale (PCFS) [Citation19,Citation20], with five grades of functional status related to limitations in usual activities ranging from 0 (no limitation) to 4 (severe limitation). Satisfaction with the health care from HTCs and general practitioners/pediatricians during the Coronavirus pandemic was asked on a 5-point Likert scale ranging from 1 (not at all satisfied) to 5 (very satisfied). Satisfaction with the health care from HTC and general practitioner/pediatrician during the Coronavirus pandemic was asked on a 5-point Likert scale ranging from 1 (not at all satisfied) to 5 (very satisfied).
Mental health was measured with COVID-specific and generic validated instruments. The Coronavirus Anxiety Scale (CAS) [Citation21] has five items on a 1–5 scale (range 0–20) with scores ≥ 9 indicating dysfunctional COVID anxiety. The Fears Questionnaire for Chronic Medical Conditions (FQCMC) [Citation22] was adapted for use in the context of the Coronavirus with 10 items on a 1–5 scale (range 10–50); with higher scores indicating greater fear. The PROMIS Short Form-Anxiety 8a (PROMIS-Anxiety) [Citation23] is a widely used screening tool with eight items on a 1–5 scale (range 8–40) with higher scores suggesting greater anxiety. The Intolerance of Uncertainty Scale (IUS) [Citation24] has 12 items on a 1–5 scale (range 12–60) with higher scores indicating more anxiety in the context of uncertainty. The Brief Resilient Coping Scale (BRCS) [Citation25] evaluates ability to cope with stress adaptively and has four items on a 1–5 scale (range 4–20) with higher scores indicating better ability to cope with stress. Low resilience is defined as a score of 4–13, medium resilience as 14–16, and high resilience as 17–20. The Patient Health Questionnaire-2 (PHQ-2) [Citation26] is widely used screening tool for depression, with two items on a 0–4 scale (range 0–8) with higher scores indicating greater likelihood of depression.
Investigator-initiated questions were developed to address experiences with medical care and thoughts/fears during the pandemic. Resources and strategies used to cope with stress before and during the pandemic were queried utilizing an ad-hoc list of 13 coping strategies.
2.1. Statistical analysis
Demographics, medical data, MH data, information on medical experiences and resource utilization were described for the PIBD and PG groups and for the overall study population as frequencies and percentages for categorical data. Means and standard deviations (SD) were used for interval/ratio level data, and median and interquartile range (IQR) were used for rank ordered data. Comparisons between groups were analyzed with Pearson Chi-square tests (or Fisher exact tests if n in any cell was < 10) for frequency count data, the Kruskal–Wallis test for rank-ordered data (with Bonferroni correction for multiple post-hoc Dunn’s pairwise tests), ANOVA with Benjamini-Yekutiell procedure for three group comparisons of normally or near-normally distributed data, and t-tests (with correction for unequal variances) for bivariate comparisons and post-hoc pairwise comparisons. For correlational analyses, Spearman’s rho was used for rank-ordered data, and Pearson’s r was used for normally or near-normally distributed data. Sub-group analyses were also completed among the different domains.
One-hundred twenty-four surveys (120 PIBD English and Spanish, 4 PG Spanish) erroneously did not include one item on the COVID-19 Fears Questionnaire for Chronic Medical Conditions (FQCMC). Results for this question were then imputed using a stochastic regression model. Otherwise, missing data were pairwise deleted to allow for inclusion of as many partially completed surveys as possible. All statistical analyses were performed using Stata 15.1 [Citation27].
3. Results
3.1. Demographics
Six-hundred and twenty-eight surveys were initiated. Data from 124 were eliminated (see ) resulting in 504 surveys for analysis. Excluded respondents who completed basic demographic data only (n = 54) differed from those who continued with the survey in that they were less likely to have a IBD (vs. being a PG respondent) (p = 0.022), were younger (p = 0.005), had fewer children with an IBD (p = 0.003), had a lower level of education (p = 0.011), and lower income level (p = 0.037). They did not differ by country, ethnicity, total number of children, child age, gender, marital status, living situation/location, income, or employment change during the pandemic.
Figure 1. Flow chart of respondent enrollment.
summarizes and compares demographic data by country. There were significant differences between countries for age (respondent, PG, and child) with the UK having the youngest adult respondents and Germany having the youngest child age. Of those who identified their ethnicity (456/90, 4%), 94.1% were white/Caucasian with highest percentage of Caucasians in Germany. Gender of PG or child was not significantly different between countries. The majority of PIBD respondents were male, and the US had the highest percentage of females in PIBD and combined groups.
For the combined group, education rank was lower in Germany compared to the US and UK. Income rank was significantly different between countries (highest in the US, followed by the UK, then Germany). The majority of respondents did not have a change in income during the pandemic; however, when it changed it was most likely to decrease, with Germany having the lowest percentage of respondents with a decrease. German respondents were least likely to have a change in employment status compared to the US and UK. When employment status changed during the pandemic, the specific nature of the employment change did not differ significantly between countries. Loss of employment was the most frequent type of change and increased work hours were the least frequent. Germany had the highest percentage of those who transitioned to working from home. Occupation also differed between countries, with German respondents more likely to be in clerical and professions, while US and UK respondents were more likely to be in professional and manager occupations.
3.2. Clinical Data
Clinical data results are depicted in . Most PIBD had hemophilia A and were severely affected, although specific diagnosis, severity, inhibitor status, and treatment regimen differed significantly between countries. Germany had the highest percentage of hemophilia, the UK had the highest percentage of platelet disorder, and the US had the highest percentage of von Willebrand Disease (vWD). Germany had the highest percentage of mild hemophilia, those diagnosed with an inhibitor (either past or current) and PIBD on a prophylaxis regimen. US had the highest percentage of PIBD on no treatment. Type of product used did not differ significantly between countries. Recombinant products were dominant in all countries, followed by plasma products and non-factor replacement therapies. Other therapies comprised less than 14% usage. The presence of any comorbidity did not differ significantly between countries; however, the presence of viral infection (hepatitis-C or human immunodeficiency virus (HIV) was significantly different between countries and highest in Germany. Among those tested for COVID-19, US respondents had the highest percentage of positive tests and were more likely to have been quarantined. Supplement Table S1a describes COVID-19 test results and quarantine status by diagnosis, hemophilia severity, and treatment regimen within each country. The majority of US respondents knew someone who had died from COVID-19. Among the 36 PIBD with a positive COVID status, 16 were adults who reported in average moderate-to-severe limitations in their everyday life.
Table 3. Clinical data of persons with inherited bleeding disorders*.
At the time of this survey, COVID-19 vaccinations were available to all countries under study [Citation28,Citation29–33]. The WHO issued a follow-up statement in August 2021 regarding COVID-19 boosters for vulnerable populations [Citation34]. Although the majority of respondents were not vaccinated at the time of the survey, the percentage of vaccinated respondents was highest in the UK and lowest in Germany. When compared to the general population of their respective countries, respondents in Germany were more likely to be vaccinated (12.9% vs. 0.4%, p < 0.001). Respondents in the US and UK had response rates similar to their respective populations (US: 43.5% vs 50.4%, p = 0.06; UK: 48.4% vs. 47.2, p = 0.89 [Citation35–40].
Further analyses showed (data not shown) in all countries, those who typically received their usual vaccines prior to the pandemic were most likely to plan to get the vaccine or already completed vaccination (69.0%, p = 0.02). Of those who did not receive all of the normally scheduled vaccinations prior to the pandemic, 50% planned to be vaccinated against COVID-19 or had already been vaccinated. There were no differences between occupation types with respect to COVID-19 testing status for the combined groups or individual countries (p>0.15). Those with higher levels of education or income were more likely to have been or plan to be vaccinated (p < 0.005). Vaccination acceptance increased with age demonstrating a weak but statistically significant association with vaccine acceptance (rho=.225, p < 0.001). Those with higher scores on the PHQ-2, PROMIS-Anxiety, CAS, or FQCMC, were more likely to be unsure or hesitant (p < 0.03) than either accepting/not accepting vaccination. Scores on the BCRS and IUS were not significantly associated with vaccination acceptance. In all countries, male respondents were more likely to accept vaccinations than females (76.8% vs. 56.0%, p < 0.001). Vaccine acceptance was similar between countries within each occupation group with the exception of trades, which had higher vaccine acceptance in Germany compared to US (p < 0.001). In the US, vaccine acceptance was highest for clerical workers and lowest in trades and technicians (p = 0.001).
3.3. Experiences with medical care during COVID pandemic
Experiences with medical care differed between countries in all categories (see ) including cancellation or postponement of appointments, delays in or change in process to receiving medications, postponed surgical procedures, interrupted physiotherapy, canceled preventative medical care, and limited visits or access to the HTC; although it was noted that telemedicine was offered in all countries. Cancellation or postponement of appointments/surgical procedures/physiotherapy as well as limited visits or access to the HTC was highest in UK and lowest in Germany. By contrast, the UK ranked highest in HTC telemedicine availability and adjustment to medication home delivery.
Figure 2. Experiences with medical care during the coronavirus pandemic.
The majority of respondents (88.6% in all countries) did not experience delays in drug supply although delays differed between countries with Germany reporting the least delays.
When comparing PIBD and PG experiences with medical care during the pandemic, the PG group described more drug delays (16.4% vs. 9.0%, p = 0.050) but better access to telemedicine for appointments (64.8% vs. 48.8%, p = 0.007). Despite changes in the methods of care delivery during the pandemic, overall average ranking of HTC care was 4.5 (1–5 scale; 1= not at all satisfied; 5=very satisfied), and 4.2 for their primary care provider. Satisfaction with HTC and primary care differed between countries (p < 0.001) with Germany scoring highest followed by the US, then UK.
3.4. Concerns and thoughts expressed during the coronavirus pandemic
Participants expressed a variety of COVID-19-related concerns and thoughts during the pandemic summarized in . Statistically significant differences were identified between countries regarding concerns about if: i) they/their child belonged to the high-risk group due to their IBD; ii) they would receive adequate care in the event of bleeding; iii) the treatment for the bleeding disorder should be adjusted, iv) COVID-19 could be transmitted via plasma products/blood plasma, v) if they became COVID-19 positive, what would happen, and vi) they would have sufficient financial resources. UK respondents expressed the highest rates of concern about adequate care provided in the event of bleeding, need for possible adjustment in treatment, and potential COVID-19 transmission within blood products. Respondents in the US and UK were more concerned about lacking sufficient financial resources than those in Germany. German respondents reported the most concerns regarding testing positive for COVID-19 and being in a high-risk group.
Figure 3. Concerns/Thoughts expressed during the coronavirus pandemic.
PIBD and PG groups had comparable concerns and thoughts during the COVID-19 pandemic. Although in some aspects the PG group expressed more concerns for their child compared to PIBD self-concerns. The PG group were more concerned about being able to go to hospital in an emergency (55.2% vs. 44.1%, p = 0.026), if adequate care would be provided during a bleeding event (54.6% vs. 42.6%, p < 0.017), whether treatment adjustments were needed (35.7% vs. 20.2%, p < 0.001), and whether sufficient financial resources were available (51.8% vs. 40.8%, p = 0.028).
Sub-group analyses revealed that respondents in the combined group (PIBD + PG describing their child’s condition) who had a previous history of a viral infection (e.g. HIV, hepatitis C; 25.4%) were significantly less concerned that COVID-19 could be transmitted through plasma or blood products compared to those without history of viral infection (16.5% vs. 83.5%, p = 0.03). Among those who used plasma-derived products (27.6%), only 10.4% were concerned about the possibility of COVID-19 exposure in plasma-derived products but this did not differ between those who utilized or did not use a blood/plasma product (p = 0.055), with a trend toward more concern in those who were not currently using a blood/plasma product.
3.5. Mental health
Scores on MH measures were similar between countries (combined PIBD and PG groups) except for the PROMIS-Anxiety score which was highest in the US (p = 0.007) (see ). Average score for all respondents on the BRCS was in the ‘medium resilience’ range. There was a trend for the BRCS suggesting lower resilience for UK respondents (p = 0.051), but scores were still in the medium resilience range. CAS scores were well below the cutoff for dysfunctional COVID anxiety (average score = 1.5; cutoff for dysfunctional COVID anxiety is ≥ 9). The other standardized assessment tools (IUS, PHQ-2, PROMIS-Anxiety, and FQCMC) do not have suggested cutoff values for interpretation other than higher scores indicate greater severity of symptoms. Average score for the combined group of respondents was near or below the midpoint of total possible scores for each of these measures. All of the MH measures significantly correlated with each other in the expected direction. While statistically significant, the absolute values for these correlations ranged from r = .20 (weak) to r = .73 (moderately strong).
Table 4. Mental health (MH) scores.
Resilience was inversely correlated with IUS, PROMIS-Anxiety, CAS, FQCMC, and PHQ-2, while all other measures were positively correlated with each other (p < 0.05 for all relationships).
The highest ranking FQCMC scores (mean score, 1–5 Likert scale) reflecting COVID-19 associated fears were; i) to be infected and healthcare professionals will not be familiar with the needs of a person with their condition (2.6), ii) close people (e.g. family, close friends) will be infected and become ill (2.6), and iii) to be infected with the virus (2.5).
Subgroup analyses of MH measures for various socio-demographic and clinical aspects were completed. Those with vWD had higher CAS scores (p = 0.001) and higher FQCMC scores (p = 0.011) (see Supplement Table S1b). Female respondents were found to have greater anxiety (PROMIS-Anxiety and CAS) (p < 0.001) and more fears related to COVID-19 (FQCMC) (p = 0.003) when compared to males (not shown in the table).
Presence of a comorbidity in addition to an IBD was associated with higher PROMIS-Anxiety, PHQ-2, CAS, and FQCMC scores in the combined group, PIBD group, and PG group (all with p < 0.05). PG of someone with an IBD plus another chronic medical condition had higher scores on the IUS (p = 0.011). BRCS scores were not significantly different between those with and without co-morbidity in either the PIBD or PG group.
BCRS (resiliency) scores did not differ significantly by ethnicity, type of bleeding disorder, gender, age, or PIBD vs. PG groups; however, higher education (rho = 0.162, p < 0.001) and income (rho = 0.119, p = 0.012) had weak positive correlations with resilience.
Those who had been quarantined had higher CAS scores (PG, p = 0.044; PIBD, p = 0.035), while PIBD (but not PG) had higher PROMIS-Anxiety scores (p = 0.05). Knowing someone who died from COVID-19 was associated with higher FQCMC scores in the PG (p < 0.02) and combined group (p < 0.04), but was not associated with higher scores on any of the other MH measures.
Higher education (rho = 0.162, p < 0.001) and current net monthly household income (rho = 0.119, p = 0.012) had weak positive correlations with BCRS (resilience) scores.
Respondents with a current net monthly household income level 1 (<$1,600/month) and level 5 ($4,301–$6,150/month) who experienced a decrease in income associated with COVID-19 had significantly higher PROMIS-Anxiety scores when compared to other income groups (p < 0.02). This was not seen in countries individually but was consistent across the combined PIBD+PG group (p < 0.001), PIBD group (p = 0.004) and PG group (p < 0.001). A decrease in income was associated with greater CAS scores only in the PG group (p = 0.044) and not significant in the PIBD or combined group. Income decrease was associated with higher scores on the PHQ-2 in all groups (combined PIBD and PG: p < 0.001, PIBD; p = 0.008, PG; p = 0.037).
In the combined group there was a main effect of occupation on anxiety, with those in service and sales having the highest PROMIS-Anxiety (p = 0.04) and CAS scores (p = 0.002), while trade workers had the highest FQCMC scores (p < 0.0001). When comparing occupations within individual countries, the only main effect on any of the MH measures was in Germany, where trade workers had the highest FQCMC scores (p = 0.014) and those in service/sales had the highest CAS scores (p = 0.003). There were no significant differences in PROMIS-Anxiety, CAS, and FQCMC scores between occupations in the UK and US.
3.6. Coping resources utilized before and during COVID pandemic
Respondents were asked to select from a list of 13 coping strategies defined. Examples included seeking support from PAG or HTC, ignoring the situation, using digital apps, and use of alcohol/drugs (see ). The US had the highest percentage of respondents using the HTC, advocacy groups, information-seeking, mindfulness/meditation, meeting with friends/relatives, digital apps, social media, being creative, and physical activity. Use of medication, drugs/alcohol, therapy, and ‘other’ was highest in the UK. Analyses evaluating significant differences between countries included number and specific resources used, moderating effects of socio-demographic variables, and relationship between resilience and resources used.
Figure 4. Resources used to cope with stress before/during the coronavirus pandemic.
3.6.1. Coping resources utilized in relationship to country, moderating variables, and resilience
Supplement Table S2 shows the overall differences between countries in use of resources before or during the COVID-19 pandemic. Changes in use of resources before vs. during the pandemic were also evaluated between countries, within countries, and within individuals.
Age, education, income, ethnicity, gender, hemophilia vs. other IBD, and PIBD vs. BD group, had significant (all with p < 0.05) moderating effects on resources used within each country. In Germany, the mean age was significantly younger for respondents who used ignoring (43.6 vs. 49.5), interacting with friends/relatives (47.1 vs. 54.4), use of digital applications (apps) (45.2 vs. 51.5), social media (44.1 vs. 52.3), being creative (46.4 vs. 51.4), physical activity (47.1 vs. 52.5), and drugs/alcohol (43.4 vs.49.5).
Age did not have a moderating effect on any of these variables in the UK, while in the US respondent mean age was significantly younger for mindfulness/meditation (46.9 vs. 51.5), ignoring (43.5 vs. 50.9), or therapy (45.5 vs. 50.7).
In Germany, median education levels were significantly higher in those seeking information (5 vs. 4), ignoring (6 vs. 4), interacting with friends/relatives (5 vs. 3), and physical activity (5 vs. 4). In the UK, median education level was only significantly higher in those who sought support from the HTC (6 vs. 3). In the US, median education level was significantly higher in those who either sought therapy (6.5 vs. 6) or used drugs/alcohol (6 vs. 5.5) as a resource to cope with stress.
German median income rank was significantly higher among those who met with friends/relatives (income level 4.5 vs.3) or engaged in physical activity (4 vs. 3.5). In the UK, median income rank was significantly lower in those who used medication (4 vs. 7). The US median income rank was significantly higher in those who used mindfulness/mediation (6 vs. 5), meeting with friends/relatives (6 vs. 5), and physical activity (6 vs.4).
Ethnicity was not associated with use of any specific individual coping resources within the US or UK. Valid relationships between ethnicity and coping resources in Germany could not be determined due to low number of non-Caucasians (n = 3; 1.4%).
Overall, there were more moderating effects of gender on choice of coping resources in Germany compared to other countries (7 resources with significant differences between genders in Germany, none in the UK, and 4 in the US). When significant differences were present, they were all in the direction of females being more likely to use a resource compared to males. In Germany, females were more likely than males to seek support from the HTC (41.3% vs. 23.1%), advocacy groups (23.8% vs. 11.0%), information (73.8% vs. 49.7%), mindfulness/meditation (45.0% vs. 27.8%), friends/relatives (87.5% vs. 78.0%), being creative (68.8% vs. 54.4%), physical activity (91.3% vs. 67.6%), or professional therapy (22.5% vs. 10.4%). In the UK, choice of coping resource did not differ by gender. In the US, females were more likely to use mindfulness/meditation (59.6% vs. 35.9%), friends/relatives (89.0% vs. 69.8%), being creative (81.7% vs. 52.8%), or professional therapy (33.9% vs. 18.9%).
Those with hemophilia vs. other IBDs in Germany were less likely to use information-seeking (54.5% vs. 71.4%), physical activity (72.5% vs. 88.1%) or professional therapy (11.9% 26.2%). There were no differences in use of coping resources between those with hemophilia vs. another IBD in the UK. In the US, those with another IBD were more likely to use social media (73.6% vs. 54.5%) or professional therapy (41.5% vs. 23.2%) compared to those with hemophilia.
When compared to PIBD respondents, PG respondents in Germany were more likely to seek support from the HTC (59.3% vs. 25.6%), advocacy groups (31.5% vs. 10.6%), friends/relatives (90.7% vs. 78.4%), and physical activity (87.0% vs. 71.9%). In the UK, PGs were more likely to utilize advocacy groups (66.7% vs. 20.8%). PGs in the US were more likely to use the HTC (62.3% vs. 43.2%), being creative (83.1% vs. 62.5%), and physical activity (89.6% vs. 72.7%).
When exploring resilience, the BRCS did not correlate significantly with the number of resources used, either for total score (r = .004, p = 0.930) or rank (rho=.021, p = 0.662) within any of the three countries (all correlations were <|.01|, p > 0.47). No significant correlations were observed between resilience and number of resources used by the PIBD or PG group (all correlations were <|.1|, all p > 0.44).
Significant relationships were found with use of specific resources. In the combined group of all respondents (all countries), those with higher BRCS scores were more likely to utilize physical activity (p = 0.003) and less likely to use therapy (p = 0.01). In Germany, BRCS scores were higher in those who used digital apps (p = 0.035) or physical activity (p = 0.004). In the UK, BRCS scores were higher only in those who utilized the HTC as a resource (p = 0.046), and in the US it was significantly higher only in those who used digital apps (p < 0.001).
3.6.2. Coping resources utilized before vs. during the COVID-19 pandemic
While there was no significant change in average number of resources used before vs. during the pandemic (4.7, p = 0.739 for all respondents; p > 0.3 for all countries), there were significant changes in use of specific resources, both within and between countries (Table 5). Significant differences in how the use of these resources changed (i.e. increase, decrease, or no change) before vs. during the pandemic were found for total respondents (PIBD + PG in all countries), within countries, and between countries.
Meeting with friends and relatives as a resource to cope with stress during COVID-19 decreased significantly for the entire group, within each country, and between countries. Use of physical activity decreased significantly in the entire group, in Germany and US, but not in the UK. While change in information-seeking was significantly different between countries, a within-country difference (increase) was significant only in Germany. Being creative significantly increased for the entire group, Germany, and the US, with no significant difference between countries. Use of digital apps and social media increased significantly for the total and in Germany, with significant between-country differences for both. Change in use of the following resources was significantly different between (but not within) countries: use of the HTC, advocacy groups, mindfulness/meditation, drugs or alcohol, and therapy. No significant changes within or between countries were observed for ignoring the situation or for use of resources classified by the respondent as ‘other.’
demonstrates the percentages of those using/not using each resource before vs. during the pandemic, those who did not change, and direction of change (using → not using, not using → using). The number of individuals who changed in use of a specific resource ranged from 6% who changed in drug/alcohol use to 44.6% who changed in meeting with friends/relatives. The distribution of these changes differed significantly between countries for use of the HTC and advocacy groups, mindfulness/meditation, meeting with friends/relatives, being creative, medication, and therapy (p < .05), with the lowest percentages of within-person changes in Germany. The highest percentages of within-person changes occurred in the US for use of advocacy groups and mindfulness/meditation, and in the UK for use of the HTC, friends/relatives, being creative, medication, drugs/alcohol, therapy, and other. Within-person changes did not differ significantly between countries for seeking information, ignoring the situation, use of digital apps, social media, and physical activity (p > 0.17).
Figure 5. Changes in resources used before vs. during the coronavirus pandemic by country.
4. Discussion
4.1. Demographics findings
The survey was based on a convenience sample, with many potential explanations for interactions between demographics and survey responses. It is noted that in our study, populations within countries were similar with respect to age, hemophilia versus other bleeding disorders, severity of hemophilia, factor product, and male gender and were mainly Caucasian. Differences were noted between countries related to age of parent/caregiver, age of child or dependent, percentage of Caucasians, gender in both groups, rank in education and income and change in income and employment status.
Overall, the US reported more females, higher income and education, and change in income whereas Germany reported lower income, education, and change in income.
More income support was noted in the UK versus the US during COVID-19. Decrease in income exceeded an increase in income across all countries, where Germany had the least change and the US had the most decrease in the income, but the highest income overall. These demographic differences between countries could influence access to care and other resources.
4.2. Clinical data findings
Type of bleeding disorder, severity, inhibitor status, and treatment regimen varied between countries although hemophilia A was the predominant diagnosis. Despite the recognition of prophylaxis therapy for hemophilia as the ‘gold standard’ for care, there remained differences within countries which are unclear. Types of treatment therapies varied between countries.
The world statistics regarding COVID-19 is congruent with our results where the US represented the highest COVID-19-positive results. Compared to Germany and the UK, US respondents in our study had a higher percentage of those who were quarantined or knew a person who died as a result of COVID-19. The UK had the highest percentage of those who were already vaccinated. Germany had more respondents who preferred to ‘wait and see’ before vaccination. It was noted that those with higher anxiety tended to wait and see or were unsure about vaccinations, suggesting the need for available, medically appropriate information that addresses concerns expressed by PIBD and PGs. This is an opportunity for PAGs to collaborate with HTCs to promote optimal consistent messaging that includes access to high-quality evidence-based research. The scientific understanding of COVID-19 is evolving. Currently, recommendations have been made regarding the mechanism for vaccination for PIBD to reduce bleeding risk [Citation41]. Communicating the risks, prevention measures, and treatment options before, during, and after a pandemic are essential to slowing the contagion and improving health outcomes in this population. Ongoing research is needed with respect to vaccinations in PIBD so that all information is current thus allowing PAGs to disseminate accurate consistent messaging. This study did not explore the reasons for vaccination hesitancy demonstrating an area of future research.
4.3. Experiences with medical care during COVID pandemic
Access to care was a challenge for many respondents with PGs more concerned than PIBD about access to medications and care during emergencies, drug delays, and access to care with telemedicine. One would expect a caregiver to express greater concerns for a vulnerable dependent/child as compared to an independent PIBD. Our findings are similar to other studies who also reported access issues and concerns [Citation5,Citation8–10,Citation12,Citation42].
During the pandemic, the need to pivot to other strategies for access to care was critical to limit delays. The UK experienced the highest cancellation of appointments/surgical procedures, yet demonstrated efficiency in converting to telemedicine to maintain access to their patient population, similar to other disease states [Citation6]. These results identify major concerns expressed by PIBD and PGs, offering HTCs and PAGS insights to ensure appropriate access and care during times of emergencies and the need for alternative methods of connecting and maintaining care with PIBD.
Seamless transition during times of crisis can minimize delays. Emergency contingency plans that can be readily implemented are essential to limit potential future interruptions in care. There are limited data on emergency planning for people with disabilities including PIBD, yet the need for tailored approaches to support these populations during emergencies is not new [Citation5,Citation43].
All countries transitioned to a variation of telemedicine to maintain access. Patient acceptance of, and satisfaction with, telemedicine has generally been favorable; with expressed comfort in the use of technology and belief that the quality of care was comparable to in-person visits [Citation44]. Telemedicine has the potential to increase convenience, access, and patient safety as well as financial management. At the same time, telemedicine limits exposures to patients and healthcare providers while reducing the burden on healthcare facilities [Citation7,Citation45]. Previous insurance reimbursement barriers for telemedicine were quickly overcome during this time, further supporting its use during the pandemic.
Challenges remain for telemedicine including those who do not have internet access such as i) ethnic populations (African American [Citation46]), ii) rural locations [Citation47], iii) low financial status, or iv) age where they may lack skills for digital access. Healthcare systems need to have available technological resources to transition to telemedicine providing a fluid relationship between the HTC and patient by allowing remote visits to dispense medication and thus avoid patient visits to the center minimizing contagion exposure [Citation15].
4.4. Concerns and thoughts expressed during the coronavirus pandemic
This cross-sectional study was completed early in the pandemic and provides a reflection of thoughts and concerns of respondents at that time. Feelings about COVID-19 May have changed as people became accustomed to its presence in their lives. Our results are similar to other studies regarding concerns voiced about sufficient resources for care, emergency care, and potential staff shortages all affecting access [Citation8,Citation9]. Additionally, concerns of unknown potential of COVID-19 transmission via blood products were expressed similar to other studies [Citation9]. It was surprising that those respondents previously exposed to hepatitis C and/or HIV and those who are currently using blood-based products did not demonstrate greater concern. It is possible that these populations have grown accustomed to or are more educated regarding blood-borne pathogen exposure or have a higher tolerance now. It may also be that those who are more fearful already shield themselves by avoiding plasma-derived products. This is unclear based on this survey and a potential area of future research.
4.5. Mental health
MH measures were similar and not significantly different between countries with exception of the PROMIS-Anxiety which was higher in the US. It is noted that the US reported more females overall in both groups (PIBD and PG). Previous studies have confirmed more anxiety in females with PIBD prior to a pandemic situation [Citation48–54]. In addition, Cikili-Uytun et al. [Citation55] confirmed higher anxiety and depression scores in mothers caring for children of IBD when compared to the general population. Other studies confirmed higher anxiety in females during the pandemic as well [Citation6,Citation56]. The finding that women experience more anxiety suggests that PAGs should also target support services to improve mental health toward women as well.
The MH results demonstrated average scores in the middle range of possible scores for the majority of measures, with the exception of the CAS (which was particularly low), suggesting there was effective coping during the pandemic similar to the Zhang study [Citation57]. Although the survey was early in the pandemic, vaccinations were becoming readily available and hope regarding vaccination effectiveness may have influenced scores on MH measures.
Fears identified by the respondents were dissimilar to other studies [Citation20,Citation58]. The Bunevicience et al. [Citation58] study examined 371 patients with different preexisting conditions and although their study identified more fears related to infection of close people similar to our study; they also feared the inability to receive treatment for their pre-existing condition. Wu et al. [Citation20] identified 787 scleroderma patients who feared the need for prolonged isolation and becoming infected and as a result, experience more severe complications related to their pre-existing condition. It is possible the differences could be related to the timing of study during the pandemic as the Wu et al. study was done at the height of the pandemic when many issues surrounding COVID-19 were unknown.
Higher anxiety scores related to change in income were particularly noted for respondents at the lowest net monthly level of income (<$1,600) and at income level $4,301–$6,150). A decrease in income would increase respondents’ concerns about providing for their families during this time. US respondents at level 5 ($4,301-$6,150) income were just above the point at which they were likely to receive government assistance, thus potentially increasing financial and overall anxiety. During the pandemic, governmental support for lost income due to COVID-19 varied across countries. The US provided variable support programs; UK government paid 90% of the salary those employees who worked less or not at all, with remaining 10% covered by employers; and in Germany, a short-term allowance (60% of their net income, 67% if they had at least one child) was paid by employers and reimbursed by the government. Differences in income and occupation related to anxiety have been confirmed in other studies [Citation56]. While this study confirms similar levels of anxiety and coping by respondent’s type of occupation, they were not always similar within each country. Respondents in sales and service occupations had higher PROMIS-Anxiety and CAS scores with the main effect accounted for primarily by the larger German cohort. Multiple similarities were noted between this study and the Hossain study [Citation56] including anxiety related to quarantine and/or the presence of a medical comorbidity, concerns about changes in their health, access to care, and the care of others. Also identified were concerns about face-to-face exposure although our study did not distinguish between occupations who might be working face-to-face and those who might be working remotely.
These results demonstrate the importance of optimizing MH support for this population (PIBD and PGs) on an ongoing basis particularly for at-risk sub-populations, especially for female with the need to increase access to optimal resources during times of crisis.
It was also noted that resilience was greater for those respondents with a higher income and education. The reasons for this remain unclear and an area worthy of future study.
4.6. Coping resources used before and during COVID pandemic
It is important to know how people access information for self-education and how they cope during times of crisis such as the pandemic. Respondents reported multiple strategies in seeking information and managing their MH needs during the pandemic where some strategies were less than optimal. This variability of coping strategies during the pandemic has been confirmed in other studies [Citation59]. Changes in support resource utilization during the pandemic overall were noted, where use of digital apps increased in all countries while meeting with friends and relatives decreased in all countries, possibly related to quarantine measures and fear of transmitting the virus. Maladaptive coping such as use of drugs and alcohol increased or were unchanged in all countries similar to other studies [Citation5,Citation10].
Interacting with PAGs and HTCs decreased during the pandemic. While the survey demonstrated a reduction in PAG access as a resource by respondents during the pandemic, anecdotally PAGs leadership described a high level of information sharing and engagements occurring with PIBD. The PAGs felt they were providing information and connecting with respondents, whereas the results of this study indicate that respondents did not utilize this resource as much as expected. It is unclear if the method of message delivery (virtual vs. in-person, content, timing, or the individuals’ anxiety and overwhelming aspect of the pandemic) was the issue. This disconnect requires a deeper review, thus providing a future research opportunity to increase bidirectional positive engagement between PAGs, PIBDs, and their families. Objective introspective evaluation would help PAGs overcome an internal sense of achievement in the face of nonparticipation by the community. Strategies could include outreach to unique demographic groups with initiatives to promote appropriate positive coping strategies, implementation of accessible resources, and recognition of how and when to access those resources. PAG targeted education and ongoing messaging via a variety of social media avenues in appropriate areas could also be helpful. Additional strategies reaching subset populations with limited internet access can be explored. Joining forces with local government entities and public programs may be helpful to ensure broadband coverage.
4.7. Limitations
As this is a convenience sample of PIBD, the sample may not be representative of the countries studied. Recruitment methods varied between countries which may have affected the sample population characteristics. The UK represented only a small number of respondents which may have been related to a previous survey completed prior to this study. Respondents were predominantly white/Caucasian, with a very small percentage of other ethnic groups identified; thus, extrapolation to other ethnic groups is unlikely and thus an area for future research. A number of survey drop-outs occurred during the section involving MH questions, suggesting either discomfort with the type of questions or survey fatigue despite the estimated 20 min time frame for completion. Complete data including the MH questions may have improved the validity and generalizability of results.
5. Conclusions
The Coronavirus pandemic has demonstrated that HTCs and PAGs need to address short- and long-term remedies for future preparedness efforts to mitigate risks and overcome obstacles to access to care [Citation60]. This includes methods to quickly adjust strategies to maintain access to care and treatment. The PAGs of the respective countries provision of up-to-date, evidence-based information on their websites are essential.
The pandemic has brought attention to MH and remains a priority for PAGs, PIBD, and PGs focusing on de-stigmatization, education, and access to appropriate educational resources supporting positive strategies addressing MH during time of stress. Critical evaluation of optimal outcome measures by PAGs that define and measure appropriate access to their resources and education to better address the dissonance between perception and actual utilization of PAGs identified in our findings are needed.
It is essential that research continues in PIBD with updates regarding potential ongoing risks for PIBD with COVID-19. PAGs can be instrumental in increasing messaging to PIBD and PG groups, providing the most recent research findings as well as a venue to link PIBD and PG groups to participate in ongoing research. By doing so, results will increase information and future preparedness in future national crises.
Averting or mitigating the likely adverse economic impacts from pandemics should be of concern to governments and other stakeholders. Finally, we agree with Okoloba et al [Citation61] that governments and other stakeholders learn from this recent experience and better prepare for the likelihood of similar future events, including natural disasters, requiring swift action to facilitate access to healthcare services, especially for persons with chronic medical conditions.
Declaration of interest
M Santaella is employed with NBDF. C Nichols is contracted by NBDF as a statistician. A Lambing was part of the NBDF speaker’s bureau at the time of this manuscript. M Wiktop was employed with NHF at the time of this manuscript. The remaining authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.
Ethics approval and consent to participate
This survey has been performed in accordance with the principles stated in the Declaration of Helsinki. Each country’s Internal Review Board determined the study to have exempt status. Although this survey was anonymous, PIBD and caregivers were asked to give their informed consent to participate in the research by ticking a box in the online survey after reading the study information.
Author contributions
S von Mackensen, K Khair, M Santaella, and M Witkop designed the study and developed the survey questionnaire. S von Mackensen, K Kair, M Santaella, and M Witkop recruited PIBD in the respective countries through the patient advocacy group (PAGs). C Nichols performed statistical analysis. All authors contributed to data analysis and interpretation. A Lambing drafted the initial manuscript. All authors agreed on the journal to which the article will be submitted, critically revised the manuscript, and all authors approved the final version of the manuscript for publication and any significant changes introduced in the proofing stage, and agree to take responsibility and accountability for the contents of the article and share responsibility to resolve any questions raised about the accuracy of integrity of the published work.
Supplemental Material
Download MS Word (38.7 KB)Acknowledgements
We thank Mabel Crescioni who had worked at Hemophilia Federation of America at the time of the design of the study for her contribution to develop the survey. We would also like to thank Yves Douma, who assisted us in the search and selection of the appropriate validated Mental Health Questionnaires which are included in this survey. We are grateful to all PAQs in Germany (Deutsche Hämophiliegesellschaft (DHG), Interessengemeinschaft Hämophiler (IGH) and Deutsche Bluthilfe (DBH)); the US (National Bleeding Disorders Foundation (NBDF), Hemophilia Federation of America (HFA) and chapter organizations) and the UK (The Haemophilia Society) who helped to recruit PIBD for this survey. Finally, we would like to thank all patients and caregivers of children with inherited bleeding disorders for their participation in this survey.
Data availability statement
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474086.2023.2277323
Additional information
Funding
References
- World health Organization (WHO) COVID virus dashboard. Available from: https://covid19.who.int/
- Lillicrap D, Morrissey JH. COVID-19: 2020 A year in turmoil. J Thromb Haemost. 2020;18(5):993. doi: 10.1111/jth.14816
- Souza JC, Pettengill EC, Pettengill CA. Psychosocial aspects of quarantine, social isolation and social distance. Psychology. 2020;11(8):1200–1214. doi: 10.4236/psych.2020.118080
- McLoone J, Wakefield CE, Marshall GM, et al. It’s made a really hard situation even more difficult: the impact of COVID-19 on families of children with chronic illness. PLoS One. 2022;17(9):e0273622. doi: 10.1371/journal.pone.0273622
- Boulin M, Cransac-Miet A, Maynadié M, et al. COVID-19 lockdown in patients with chronic diseases: a cross-sectional study. Int j environ res public health. 2022;19(7):3957. doi: 10.3390/ijerph19073957
- Gurvich C, Thomas N, Thomas EHX, et al. Coping styles and mental health in response to societal changes during the COVID-19 pandemic. Int J Social Psychiatry. 2021;67(5):540–549. doi: 10.1177/0020764020961790
- O’Donovan M, Buckley C, Benson J, et al. Telehealth for delivery of haemophilia comprehensive care during the COVID-19 pandemic. Haemophilia. 2020;26(6):984–990. doi: 10.1111/hae.14156
- von Mackensen S, Halimeh S, Siebert M, et al. Impact of COVID-19 pandemic on mental health of patients with inherited bleeding disorders in Germany. Haemophilia. 2020;26(6):e272–e281. doi: 10.1111/hae.14130
- Olivieri M, Halimeh S, Wermes C, et al. Auswirkungen der COVID-19 Pandemie auf die medizinische Versorgung von Patienten mit angeborenen Blutungsneigungen [Impact of COVID-19 pandemic on medical care of patients with inherited bleeding disorders]. Gesundheitswesen. 2021;83(4):282–290. German. doi: 10.1055/a-1399-9166
- Volot F, Soudry-Faure A, Callegarin A, et al. Impact of first COVID-19 lockdown on paediatric and adult haemophilia patients treated in a French Haemophilia comprehensive care Centre. Haemophilia. 2022;28(3):462–471. doi: 10.1111/hae.14526
- Kar SK, Yasir Arafat SM, Kabir R, et al. Coping with mental health challenges during COVID-19. Coronavirus Disease 2019 (COVID-19). 2020 Apr 30;199–213. doi: 10.1007/978-981-15-4814-7_16
- Napolitano M, Mansueto MF, Sirocchi D, et al. Emotions and opinions of adult patients with haemophilia during the COVID-19 (coronavirus Disease 2019) pandemic caused by SARS-CoV-2: a monocentric survey. Patient Preference Adherence. 2020;14:1145–114. doi: 10.2147/PPA.S257225
- Centers for Disease Control and Prevention. COVID-19: underlying medical conditions associated with higher risk for severe COVID-19: information for healthcare professionals. Atlanta (GA); [ Updated 2022 Dec 5; cited 2022 Dec 21]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
- Hermans C, Weill A, Pierce GF. The COVID-19 pandemic: new global challenges for the haemophilia community. Haemophilia. 2020;26(3):371–372. doi: 10.1111/hae.14001
- la Cortez-Rodriguez H D, Alverez-Roman M, Rodriquez-Merchan EC, et al. What COVID-19 can mean for people with hemophilia beyond the infection risk. Exp Rev Hematol. 2020;13(10):1073–1079. doi: 10.1080/17474086.2020.1818066
- The 18 HIPPA identifiers. Loyola University Chicago. Available from: https://www.luc.edu/hipaa/policiesandguidelines/the18hipaaidentifiers/
- United Nations Educational, Scientific, and Cultural Organization. International standard classification of education 2011. [Internet]. Montreal (Canada). 2012 [Cited 2022 Dec 21]. Available from: https://uis.unesco.org/sites/default/files/documents/international-standard-classification-of-education-isced-2011-en.pdf
- International classification of occupations (ISCO-08). Available from: https://ilostat.ilo.org/resources/concepts-and-definitions/classification-occupation/
- Klok A, Boon GJAM, Barco S, et al. The post-COVID-19 functional status scale: a tool to measure functional status over time after COVID-19. Eur Respir J. 2020;56(1):2001494. doi: 10.1183/13993003.01494-2020
- Machado FVC, Meys R, Delbressine JM, et al. Construct validity of the Post-COVID-19 functional status scale in adult subjects with COVID-19. Health Qual Life Outcomes. 2021;19(1):40. doi: 10.1186/s12955-021-01691-2
- Lee SA. Coronavirus anxiety scale: a brief mental health screener for COVID-19 related anxiety. Death Stud. 2020;44(7):393–401. doi: 10.1080/07481187.2020.1748481
- Wu Y, Kwakkenbos L, Henry RS, et al. Validation of the COVID-19 fears questionnaires for chronic medical conditions: a scleroderma patient-centered intervention network COVID-19 cohort study. J Psychosom Res. 2020;139:110271. doi: 10.1016/j.jpsychores.2020.110271
- Schalet BD, Pilkonis PA, Yu L, et al. Clinical validity of PROMIS depression, anxiety, and anger across diverse clinical samples. J Clinical Epidemiol. 2016;73:119–127. doi: 10.1016/j.jclinepi.2015.08.036
- Khawaja NG, Yu LNH. A comparison of the 27-item and 12-item intolerance of uncertainty scales. Clinical Psychologist. 2010;14(3):97–106. doi: 10.1080/13284207.2010.502542
- Sinclair VG, Wallston KA. The development and psychometric evaluation of the Brief Resilient coping scale. Assessment. 2004;11(1):94–101. doi: 10.1177/1073191103258144
- Löwe B, Wahl I, Rose M, et al. A 4-item measure of depression and anxiety: validation and standardization of the patient health Questionnaire-4 (PHQ-4) in the general population. J Affective Disorders. 2010;122(1–2):86–95. doi: 10.1016/j.jad.2009.06.019
- StataCorp. Stata statistical Software: release 15. College Station (TX): StataCorp LLC; 2017.
- AJMC. A timeline of COVID-19 vaccine developments in 2021. [Internet]. Cranbury (NJ); 2021. Jun 3 [cited 2022 Dec 12]. Available from: https://www.ajmc.com/view/a-timeline-of-covid-19-vaccine-developments-in-2021
- Reuters. Germany to start first COVID-19 vaccination in elderly homes on December 27. [Internet]. 2020. Dec 21 [Cited 2022 Dec 21]. Available from: https://www.reuters.com/article/us-health-coronavirus-eu-vaccine-germany-idUSKBN28V1UM
- Food and Drug Administration. FDA news Release: FDA approves first COVID-19 vaccine. 2021 [Cited 2022 Dec 21]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine#:~:text=Today%2C%20the%20U.S.%20Food%20and,years%20of%20age%20and%20older
- World Health Organization. WHO issues its first emergency use validation for a COVID-19 vaccine and emphasizes need for equitable global access. [Internet]. Geneva (Switzerland); 2020 Dec 31 [cited 2022 Dec 21]. Available from: https://www.who.int/news/item/31-12-2020-who-issues-its-first-emergency-use-validation-for-a-covid-19-vaccine-and-emphasizes-need-for-equitable-global-access
- Ledford H, Cyranoski D, Van Noorden R. The UK has approved a COVID vaccine — Here’s what scientists now want to know. Nature. 2020;588(7837):205–206. doi: 10.1038/d41586-020-03441-8
- DW Made for Minds. 101-year-old among first to get vaccinated in Germany. [Internet]. 2020 Dec 26 [Cited 2022 Dec 22]. Available from: https://www.dw.com/en/coronavirus-101-year-old-woman-among-first-in-germany-to-receive-biontech-pfizer-covid-vaccine/a-56065181
- World Health Organization. Interim statement on COVID-19 vaccine booster doses. [Internet]. Geneva (Switzerland). 2021 Aug 10 [Cited 2022 Dec 21]. Available from: https://www.who.int/news/item/10-08-2021-interim-statement-on-covid-19-vaccine-booster-doses
- Development of population numbers in Germany from 1990 to 2021. Statista.com. Available from: https://www.statista.com/statistics/672608/development-population-numbers-germany/
- Vaccination status; Germany. Impfdashboard.de. Available from: https://impfdashboard.de/en/
- US and World Population Clock. United States Census Bureau. Available from: https://www.census.gov/popclock/
- US Coronavirus Vaccine Tracker. Available from: https://usafacts.org/visualizations/covid-vaccine-tracker-states/
- Population estimates for the UK, England, Wales, Scotland and Northern Ireland: 2021. Office of National Statistics. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/bulletins/annualmidyearpopulationestimates/mid2021
- UK vaccination status GOV.UK coronovirus (COVID-19) in the UK. Available from: https://coronavirus.data.gov.uk/details/vaccinations?areaType=nation&areaName=England
- Pfrepper C, Holstein K, Königs C, et al. Consensus recommendations for intramuscular COVID-19 vaccination in patients with hemophilia. Hamostaseologie. 2021;41(3):190–196. doi: 10.1055/a-1401-2691
- Chang C, Zhang L, Dong F, et al. Asthma control, self-management, and healthcare access during the COVID-19 epidemic in Beijing. Allergy. 2021;76(2):586–588. doi: 10.1111/all.14591
- Chen CL, Brozen M, Rollman JE, et al. Transportation access to health care during the COVID-19: trends and implications for significant patient populations and health care needs. UC Office of the Presidents, ITS reports. 2020. Available from: https://escholarship.org/uc/item/22b3b1rc
- Valentino L, Skinner MW, Pipe W. The role of telemedicine in the delivery of health care in the COVID-19 pandemic. Haemophilia. 2020;26(5):e230–e231. doi: 10.1111/hae.14044
- Santaella M, Nichols C, Ryan S, et al. Telegenetic counseling for females: My Life, Our future participants. Res Pract Thromb Haemost. 2021;5(S1):HTRS.P1.15.e12554.32.
- Chunara R, Zhao Y, Chen J, et al. Telemedicine and healthcare disparities: a cohort study in a large healthcare system in New York City during COVID-19. J Am Med Inf Assoc. 2021;28(1):33–41. doi: 10.1093/jamia/ocaa217
- Hirko KA, Kerver JM, Ford S, et al. Telehealth in response to the COVID-19 pandemic: implications for rural health disparities. J Am Med Inf Assoc. 2020;27(11):1816–1818. doi: 10.1093/jamia/ocaa156
- Rambod M, Sharif F, Molazem Z, et al. Health-related quality of life & psychological aspects of adults with hemophilia in Iran. Clin App Thromb & Hem. 2018;24(7):1073–1081. doi: 10.1177/1076029618758954
- Ianone M, Pennick L, Tom A, et al. Prevalence of depression in adults with haemophilia. Haemophilia. 2012;18(6):868–872. doi: 10.1111/j.1365-2516.2012.02863.x
- Fakhari A, Dolatkhah R Psychiatric disorders in hemophilia patients. Priory.Com. Available from: https://www.priory.com/fam/hemophil.htm
- Iyoriobhe J, O’Hara J, Camp C, et al. Physician & patient reported anxiety & depression in hemophilia. Int J Technol Assess Health Care. 2017;33(S1):138–139. doi: 10.1017/S0266462317002902
- Buckner TW, Witkop M, Guelcher C, et al. Management of US men, women, & children with hemophilia & methods & demographics of the bridging hemophilia B experiences, results & opportunities into solutions (B‐HERO‐S) study. Eur J Haematol. 2017;98(S86):5–17. doi: 10.1111/ejh.12854
- Carlsson KS, Winding B, Asermark J, et al. Pain, depression and anxiety in people with haemophilia from three Nordic countries: cross-sectional survey data from the MIND study. Haemophilia. 2022;28(4):557–567. doi: 10.1111/hae.14571
- Roberts JC, Kulkarni R, Kouides PA. Depression and anxiety in persons with Von Willebrand disease. Haemophilia. 2023;29(2):545–554. doi: 10.1111/hae.14725
- Cikili-Uytun M, Cetin FH, Yilmaz R, et al. Psychiatric problems & its contributing factors in children & adolescents with hemophilia: a single centre study in a Turkish sample. Gaz Egypt Paediatr Assoc Gaz. 2020;68(1). doi: 10.1186/s43054-020-00032-0
- Hossain M, Tasnim S, Sjultana A, et al. Epidemiology of mental health problems in COVID-19: a review. F1000Res. 2020;9:636. doi: 10.12688/f1000research.24457.1
- Zhang Y, Ma ZF. Impact of the COVID-19 pandemic on mental health and quality of life among local residents in Liaoning Province, China: a cross-sectional study. Int J Environ Res Public Health. 2020;17(7):2381. doi: 10.3390/ijerph17072381
- Buneviciene I, Bunevicius R, Bagdonas S, et al. Psychometric properties of the COVID-19 fears Questionnaire for chronic medical conditions in patients with pre-existing medical conditions. Health Soc Care Community. 2022;30(5):e2866–e2873. doi: 10.1111/hsc.13730
- Ogueji IF, Okoloba MM, Ceccaldi MMD. Coping strategies of individuals in the United Kingdom during the COVID-19 pandemic. Curr Psychol. 2022;41(11):7493–7499. doi: 10.1007/s12144-020-01318-7
- Sabatello M, Burke TB, McDonald KE, et al. Disability, ethics, and health care in the COVID-19 pandemic. Am J Public Health. 2020;110(10):1523–1527. doi: 10.2105/AJPH.2020.305837
- Okoloba MM, Ogueli IA, Darroch SJ, et al. A multinational pilot study on the lived experiences and mental health impacts from the COVID-19 pandemic. Gob Psychiatry Arch. 2020;3(2):211–226. doi: 10.52095/gpa.2020.1378