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OR for being referred to an HPV center according to frequency of GP contacts 5 years prior to first vaccine registration divided into deciles, adjusted for household type and family socioeconomic group.
Source publication
Aim
No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicat...
Citations
... This might be due to the relatively long COVID-19 isolation period, which prevents infected children from immediately returning home to their family. Furthermore, some patients may complain about psychological and/or somatoform disturbances after vaccination (Lutzen et al., 2017;McMurtry, 2020;Poddighe et al., 2014). Intervention with psychological distress may also help to prevent adverse psychological events related to vaccination in both children and adolescents. ...
Background
Coronavirus disease 2019 (COVID-19) is profoundly affecting lives around the globe. Previous studies on COVID-19 mainly focused on epidemiological, clinical, and radiological features of patients with confirmed infection. Little attention has been paid to the follow-up of recovered patients. As a vulnerable population to adverse events, the health status of the COVID-19 recovered pediatric patients is of great concern. We aimed to investigate the prevalence of behavioral problems among pediatric patients recovered from the COVID-19 in Wuhan, China.
Methods
A total of 122 children who were suspected or confirmed COVID-19 cases and hospitalized for treatment were enrolled in the study between April 2020 and May 2020 in Wuhan, China. We collected related information about hospitalization and discharge of the children and emotional symptoms of their parents through electronic medical records and questionnaire. The behavioral problems of children were examined by applying the parent-reported the Strengths and Difficulties Questionnaire (SDQ).
Results
The participant children were discharged from hospital after about two months. Among them, 76 (62%) were boys, and the mean age was 6.71 years old. The highest prevalence of behavioral problems among pediatric children with COVID-19 was for prosocial behavior (15%), followed by total difficulties (13%), emotional symptoms (11%), hyperactivity (10%), conduct problems (9%), and peer problems (1%). With regarding to their parents, 26% reported having symptoms of anxiety and 23% as having symptoms of depression. The scores of SDQ were higher in those children whose parents have emotional problems compared to parents without.
Conclusion
Long-term follow up studies on the psychological and behavioral problems of COVID-19 recovered children and their parents are warranted.
... Although such cases do not prove that the vaccinations caused the injuries, they nevertheless raise the important question of why those patients, but not most others, experienced post-vaccination AEs. Intriguingly, some studies have shown increased healthcare utilization prior to HPV vaccination among those reporting AEs from the vaccine, e.g., [22,25], suggesting the presence of another, pre-existing factor which might increase the risk of developing post-vaccination AEs, yet such a factor has not yet been identified. One study showed universal inflammation of the epipharynx among HPV vaccine recipients despite minimal symptoms in this regard [26]. ...
For nearly a decade, case reports and series have emerged regarding dysautonomias—particularly postural orthostatic tachycardia syndrome (POTS)—presenting soon after vaccination against human papilloma virus (HPV). We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination. We detail 11 such cases here, posing a hypothesis that HPV vaccination (at least with the Gardasil product) may have triggered or exacerbated MCAS in teenagers previously not recognized to have it. Only recently recognized, MCAS is being increasingly appreciated as a prevalent and chronic multisystem disorder, often emerging early in life and presenting with inflammatory ± allergic phenomena following from known mast cell (MC) mediator effects. There is rising recognition, too, of associations of MCAS with central and peripheral neuropathic disorders, including autonomic disorders such as POTS. Given the recognized potential for many antigens to trigger a major and permanent escalation of baseline MC misbehavior in a given MCAS patient, we hypothesize that in our patients described herein, vaccination with Gardasil may have caused pre-existing (but not yet clinically recognized) MCAS to worsen to a clinically significantly degree, with the emergence of POTS and other issues. The recognition and management of MCAS prior to vaccinations in general may be a strategy worth investigating for reducing adverse events following HPV vaccinations and perhaps even other types of vaccinations.
... A possible explanation for this could be that having a test for infection at the GP is more likely influenced by healthcare attendance pattern than a hospitaltreated infection or receiving medication for an infection. This explanation is supported by Danish case-control studies reporting differences in healthcare attendance prior to HPV vaccination between females referred to an HPV centre and nonreferred females [37][38][39]. The associations detected for the treated infections using both study designs support the robustness of these findings. ...
Background
Public trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination.
Methods and findings
The study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results.
Conclusions
Treated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies.
... Previous research has focused on predictors for being referred to an HPV-centre and found that referred girls and women had significantly more GP contacts and were more likely to have had hospital contacts due to psychiatric disorders and to have redeemed psychiatric medication prior to vaccination compared with other HPV-vaccinated women. 12 Higher GP attendance prior to vaccination was also found in another study examining girls and women with reports of possible side effects registered in the Danish Medicine Agency. 13 These studies indicate that affected girls and women had increased morbidity or had a different healthcareseeking behavior, already prior to the time of vaccination. ...
... Extensive research on the safety of the vaccines concludes no link to their reported symptoms, and with a relatively low proportion of affected girls and women, it is possible that other factors such as morbidity prior to vaccination may affect their susceptibility. 12,13,15 The increased morbidity and GP attendance in referred girls already prior to vaccination, may indicate that the extensive media coverage may have caused them to link the onset of pre-existing symptoms to the time of vaccination. It is therefore important to examine whether there is a temporal link between vaccination and symptom experience, considering changes in GP attendance frequency in close proximity to vaccination, as a proxy for illness. ...
... 18 Previous results have also shown that cases more often had psychiatric comorbidity prior to vaccination compared DovePress to controls, and psychiatric morbidity diagnosed up to five years prior to the first vaccine registration was therefore also included as a covariate in order to adjust for GP contacts related to this. 12 Psychiatric comorbidity was defined according to redeemed prescriptions or hospital contacts due to psychiatric morbidity in the five years prior to the first vaccine registration. Redeemed prescriptions were identified through ATC codes in the Danish Register of Medicinal Product Statistics, and the following codes were included: N06A* (antidepressants), N05A* (antipsychotics), N06BA* (attention deficit hyperactivity disorder [ADHD]), N05BA* (anxiolytics), N05BB* (anxiolytics), N03AX16 (anxiolytics) and N05BE01 (anxiolytics). ...
Aim
This study aimed to describe and compare general practitioner (GP) attendance patterns in the years surrounding HPV-vaccination among cases suspected to experience adverse events and their matched controls in order to determine if a potential larger change in GP attendance among cases was observed in temporal relation to vaccination.
Methods
Register-based, matched case–control study. Cases were defined as women referred to specialized hospital settings (HPV-centers) for suspected adverse event between June 1st 2015 and December 31st 2015 (n=1458). Information on referral was obtained from the HPV-centers directly. Each case was matched with five controls on age at vaccination, region, time of first vaccine registration and total number of doses, resulting in a total study population of 8670 girls and women. Negative binomial regression analyses were used (i) to estimate mean yearly GP contacts among cases and controls, and (ii) to further investigate the relative difference in change in GP attendance following vaccination between cases and controls.
Results
Overall, cases displayed higher GP attendance than controls from five years before vaccination up until five years after. Compared to controls, cases increased their GP attendance more in the years following HPV vaccination, corresponding to a 40% increase in the incidence rate ratios (IRR) from before to after vaccination (ratio-IRR = 1.40 [1.36; 1.44]). The change occurred in close proximity to vaccination, and the pattern was the same independently of the year of vaccination. However, for the later vaccination years cases displayed an additional increase in their GP attendance around time of extensive media attention.
Conclusion
Girls and women being referred for suspected adverse events after HPV-vaccination changed their GP attendance pattern in close proximity to their first HPV-vaccination and not solely in temporal linkage to the onset of public debate.
... It is important to explore the shortterm and long term health status of these people since the previous study reported that 90% of the women were terminated without a somatic diagnosis [14]. Furthermore, some of Jeannett Kjaer 1 , Tina S. Jensen 1 , Nanna Rolving 1 , Vibeke N. Sørensen 1 , Jan Blaakaer 2 & Anne Hammer 3,4 these women report feeling stigmatised and dismissed by the health authorities [15]. Here, we aim to describe the characteristics and symptomatology of the women previously terminated from the HPV clinic in Silkeborg and to explore whether a lack of symptom improvement may be associated with a belief in the vaccine as a causal agent of symptoms. ...
Introduction:
Due to increased reporting of presumed side effects following human papilloma virus (HPV) vaccination, the Danish Health Authority established five HPV clinics aiming to improve the diagnostics and treatment of affected women. Here, we aimed to describe characteristics of affected women 1-2 years after they attended an HPV clinic and to explore whether women who believed their symptoms were caused by the HPV vaccine were less likely to report symptom improvement than those who did not.
Methods:
A hospital-based, cross-sectional study was conducted at the HPV clinic in Silkeborg, 2017-2018. Information on symptoms, HPV vaccination, basic characteristics, etc. was retrieved using a validated questionnaire. Data were analysed descriptively and by logistic regression.
Results:
A total of 120 women were included. The median age at the first vaccine dose and the first visit to the clinic was 15 years (interquartile range (IQR): 13-23) and 23 years (IQR: 20-27), respectively. The median time from the first visit to the time the questionnaire was completed was 1.3 years (IQR: 1-1.6). At the time of the questionnaire, most women reported a wide range of symptoms, with physical symptoms being more common than psychological symptoms, and 70% of the reported symptoms had not improved over time. Of note, 90% believed that their symptoms were caused by the HPV vaccine. No difference in symptom improvement was found between women who believed that their symptoms occurred because of the HPV vaccine and those who did not.
Conclusions:
Most women did not experience any improvement in their symptoms over time, and no association was found between lack of symptom improvement and believing that the HPV vaccine was causing the symptoms.
Funding:
funded by the Danish Cancer Society.
Trial registration:
not relevant.
... In Denmark, this instigated behaviour change in the public with national immunization rates falling from over 90% in 2000 to under 20% in 2005 [75]. In turn, this led to further research that showed many 'vaccine victims' exhibited symptoms prior to vaccination and no association existed between HPV vaccination and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis [76][77][78]. In healthcare providers, the behaviour change was a shift in clinician opinion and a determined response by public health officials in Denmark [75] and globally [79]. ...
Behaviour change can refer to any transformation or modification of human behaviour. Within healthcare it refers to a broad range of activities and approaches that focus on the individual, community, or environmental influences on health-related behaviour. For e-Health (or digital health) it refers to behavioural impacts mediated through a specific e-Health intervention. However, there are also other health-related behaviour changes being quietly imposed upon both the populace and the healthcare professions broadly, by use of information and communications technologies for health. To better understand these deliberate or incidental impacts on the behaviour of healthcare consumers and providers alike, a scoping narrative review was performed using peer-reviewed and grey literature resources. Qualitative information was charted from the selected literature. This created an objective analysis of both contemporary and less commonly appreciated aspects of behaviour change in our 'digital' age. Many contemporary examples exist. The Internet and www brought alternate approaches moving from face-to-face or paper-based to websites, electronic diaries, and now mobile phones (particularly smartphones) to personalize health-related behaviour change in a myriad of diseases and conditions. Segments of the population have also exhibited health-related behaviour change through their growing www-based health-information seeking. More recent examples include 'spontaneous telemedicine' where physicians have changed the behaviour of themselves and colleagues through use of Instant Messaging, e.g., WhatsApp. Patients are also changing their behaviour spontaneously through taking and providing 'medical selfies'. However, the recent and rapid growth in accessibility and popularity of social media has markedly impacted behaviour change through the speed with which information can be spread, by both legitimate users and socialbots. Insidious examples include spread of health-related 'misinformation' (e.g., vaginal cleansing,), and now 'disinformation' (e.g., the 'anti-vaccination' movement, now resulting in recurrence of once eradicated diseases). These, and other examples, represent the broader, sometimes incidental, impact of some current e-health approaches on health-related behaviour change and should be identified and acknowledged as such. Doing so may fundamentally change opinion and efforts to redirect elements of behaviour change and aspects of behaviour change theory in unexpected ways.
... A previously published registerbased case-control study found that females reporting severe adverse effects to the Danish Medicines Agency were more likely to have had previous contacts to both the primary and secondary health care system in the two years prior to receiving the HPV vaccination compared to a matched population with no reports of adverse effects [21]. These results are in concordance with a study by Lützen et al. reporting that young females referred to an HPV center had more contacts with their general practitioner and were more likely to have used psychiatric medication prior to the vaccination compared to the source population of those who had received the HPV vaccination [22]. These studies thus indicate that health status prior to HPV vaccination plays a role in the symptoms reported after the vaccination. ...
... The study was designed as a nationwide register-based matched case-control study. The study population has been described in detail previously [22]. Shortly, every citizen in Denmark is registered with a unique 10-digit civil personal registration (CPR) number [23]. ...
... Our findings are in line with findings by Lützen et al. [22], showing that referred females had an increased frequency of contacts to general practitioners five years before the HPV vaccination. Furthermore, they reported an association between having had psychiatric disorders and usage of psychiatric medications five years before the HPV vaccination and referral to an HPV center. ...
Background:
High health care utilization before Human Papilloma Virus (HPV) vaccination might be associated with increased risk of suspected adverse effects (AE's) after vaccination. We investigated the association between hospital contacts and diagnoses before HPV vaccination and risk of later referral to a specialized hospital setting (HPV center) for suspected AE's.
Methods:
The study was a Danish register-based matched case-control study. Cases were females referred to an HPV center. Five controls per case were randomly selected in the source population of HPV vaccinated females. Information on hospital contacts and diagnoses was obtained from the Danish National Patient Registry. Conditional logistic regression analyses were used to investigate the association between having one or more diagnoses in each specific International Classification of Diseases 10th version (ICD-10) chapter five years before the HPV vaccination and subsequent referral to an HPV center.
Results:
We identified 1496 cases and 7480 controls. In total, 80% of the cases versus 65% of the controls had at least one hospital contact prior to HPV vaccination (Prevalence Proportion Ratio - PPR: 1.24 (95% Confidence Interval - CI: 1.21-1.27)), with 24% vs 12% (PPR: 1.97 (95% CI: 1.76-2.19)) having six or more contacts. Cases were more likely to have had a diagnosis in 15 out of 19 ICD-10 chapters before the vaccination, with ORs larger than 1.8 for infectious diseases, psychiatric diseases, diseases of the nervous, circulatory, digestive and musculoskeletal system, unspecific symptoms and unspecific contacts.
Conclusion:
Pre-vaccination morbidity and health care utilization seem to play a role in the path leading to suspected AE's after HPV vaccination. Since many of the diagnoses that were particularly increased before vaccination in referred females are overlapping with the most frequent symptoms reported, we cannot exclude that for some of the females, the suspected AE's might have been existing already before the vaccination.
... Studies have shown that women reporting symptoms to the Danish Medicines Agency and women referred to the diagnostic centres had a different health care seeking behaviour and use of psychiatric medicines prior to vaccination compared with other HPV-vaccinated women. 10,11 Hence, factors prior to vaccination may be important for suspecting the HPV vaccines of causing the reported symptoms. So far, little attention has been paid to the sociodemographic background of the referred girls and young women and whether this background is associated with the risk of being referred. ...
... During the study period, we identified 527 939 records of a first HPV vaccination in females aged [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. After individuals with missing information on sociodemographic variables were excluded, the study cohort consisted of the remaining 453 216 individuals (figure 1). ...
... Danish females referred to a diagnostic centre or reporting severe adverse events following HPV vaccination are shown to have had a higher pre-vaccination use of psychiatric medicine and more contact to health care compared with other HPV vaccination females. 10,11 Combined, the results of these studies suggest that factors prior to vaccination are associated with the risk of reporting suspected adverse events. ...
Background:
In Denmark, the human papillomavirus (HPV) vaccines have been suspected of adverse events since 2014. However, as no causal associations between the HPV vaccines and numerous diseases have been demonstrated, factors prior to vaccination may influence the risk of suspecting the HPV vaccines of causing symptoms. We studied the associations between individual and parental socioeconomic characteristics and the risk of referral to a diagnostic centre in a female population aged 11-29 years with a first HPV vaccination in January 2008 to June 2015.
Methods:
Individual and parental data from national registries were linked using the unique personal identification number. Logistic regression analyses were used to estimate crude and adjusted odds ratio's according to each individual and parental socioeconomic factor with two-sided 95% 95% CI.
Results:
The cohort consisted of 453 216 individuals of which 1316 (0.29%) were referred to a diagnostic centre in 2015. Having a mother outside the workforce or an unemployed mother was associated with an increased risk of referral, while girls and women who had fathers with a higher educational level were less likely to be referred. In addition, women aged 20-29 years who were unemployed or outside the workforce prior to vaccination had increased odds of being referred to a diagnostic centre.
Conclusion:
We found social inequality in the referral to a diagnostic centre following HPV vaccination. This might be explained by an increased morbidity in girls and women of lower socioeconomic status.
... In 2015 the European Medicines Agency (EMA) reviewed the literature and found no evidence for a causal association between HPV-vaccination and POTS and related syndromes [11]. Later studies in Denmark found girls reporting possible adverse effects to have been more frequent users of the health-care system than other girls even before the HPVvaccination [12,13], indicating that factors other than the vaccination might have caused the syndromes. ...
Background:
In the Danish childhood vaccination program, the human papillomavirus (HPV) vaccination coverage is lower than for other vaccines. To tailor a targeted HPV vaccination effort, we aimed to identify girls in Denmark with lower first dose HPV vaccination coverage than girls in general.
Methods:
A population-based retrospective cohort study was performed of girls born in 2001-2004, residing in Denmark in September 2019 (N = 128,351). Data from the Danish Vaccination Register was linked to sociodemographic data from the Danish Civil Registration System and Statistics Denmark. Cox's proportional hazard regression models were used to compare vaccination uptake rates between subgroups of girls.
Results:
HPV vaccination coverage at 14 years of age varied widely by municipality (53.4-80.6%). Girls living with neither of their parents had a lower chance of being vaccinated compared to girls living with both their parents (HR 0.43; 95% CI 0.41-0.46), likewise for girls attending special need education compared with girls attending public schools (HR 0.50; 95% CI 0.42-0.59). The vaccination uptake among immigrants was lower compared to Danish-born girls (HR 0.51; 95% CI 0.49-0.54), especially among immigrant girls whose parents had not passed any Danish exams. Finally, girls who were DTaP-IPV revaccinated had a 50% greater chance of being HPV vaccinated compared to girls who were not (HR 1.61; 95% CI 1.58-1.64).
Conclusion:
To increase the HPV vaccination uptake, we recommend vaccination efforts targeting girls living without any of their parents, girls attending special need education, immigrants, and girls who are not DTaP-IPV revaccinated. When targeting immigrants, the effort should focus on disseminating sufficient and understandable information about the Danish childhood vaccination program to the parents.
