Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa.

The post-viral fatigue syndromes long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have multiple, potentially overlapping, pathological processes. These include persisting reservoirs of virus, e.g., SARS-CoV-2 in long COVID patient's tissues, immune dysregulation with or without reactivation of underlying pathogens, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV6), as we recently described in ME/CFS, and possibly yet unidentified viruses. In the present study we tested saliva samples from two cohorts for IgG against human adenovirus (HAdV): patients with ME/CFS (n = 84) and healthy controls (n = 94), with either mild/asymptomatic SARS-CoV-2 infection or no infection. A significantly elevated anti-HAdV IgG response after SARS-CoV-2 infection was detected exclusively in the patient cohort. Longitudinal/time analysis, before and after COVID-19, in the very same individuals confirmed HAdV IgG elevation after. In plasma there was no HAdV IgG elevation. We conclude that COVID-19 triggered reactivation of dormant HAdV in the oral mucosa of chronic fatigue patients indicating an exhausted dysfunctional antiviral immune response in ME/CFS, allowing reactivation of adenovirus upon stress encounter such as COVID-19. These novel findings should be considered in clinical practice for identification of patients that may benefit from therapy that targets HAdV as well.

Physical-mental multimorbidity in a large primary health care population in Stockholm County, Sweden.

BACKGROUND: Multimorbidity of mental and physical disorders may be common. Our objectives were to estimate the prevalence of mental disorders and determine physical-mental multimorbidity relationships adjusted for sex and age within a primary care population in Region Stockholm, Sweden. METHODS: From 2.4 million Region Stockholm inhabitants, we included adult patients with ≥ 1 primary care consultation from 2013 through 2017. We clustered 40 physical diagnoses into 9 categories and grouped mental disorders into mild-moderate (i.e., depression, anxiety, stress disorder, sleep disturbance) or severe (i.e., bipolar disorder, schizophrenia). RESULTS: Of 1 105 065 patients, mean age was 49 years, 56% were females, and nearly one-third had a mental disorder (97% mild-moderate). Adjusted odds ratios (AOR) for mild-moderate and severe mental disorders were highest in patients with alcohol abuse (AOR=3.7, 95% CI 3.6-3.8; AOR=7.2, 95% CI 6.7-7.6, respectively) vs. those with no abuse. Higher odds for either level of mental comorbidity occurred in patients with chronic heart failure (CHF), cerebrovascular disease, Transient ischemic attack (TIA), Chronic obstructive pulmonary disease (COPD), Gastroesophageal reflux disease- irritable bowel syndrome (GERD-IBS), chronic pain, dementia, nicotine dependence, and Parkinson's disease. For mild-moderate mental disorders, AOR in males was highest (1.45) at age 28 and was below 1.0 after age 46; AOR in females was highest (1.30) at age 38 and was below 1.0 after age 38. For severe mental disorders, AOR was below 1.0 after age 58 in males and after age 62 in females. CONCLUSION: Physical-mental multimorbidity was common in primary care patients in Sweden, with the highest odds occurring in those who were female, younger, and/or had an alcohol abuse disorder.

Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts. Methods: Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva. Results: At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs. Conclusion: Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.

"As If Neck Injuries Did Not Exist": An Interview Study of Patients' and Relatives' Perceptions of Web Information on and Management of Whiplash Injuries in Sweden.

BACKGROUND: If purposefully designed, patient information can help individuals make well-founded health care decisions. This study was initiated to improve the information on whiplash injuries found in the national health care portal Healthcare Guide 1177, operated by the Swedish government. OBJECTIVE: The objective of this study was to describe the thoughts of patients and relatives on (1) information about whiplash injuries presented in the portal and (2) the Swedish health care system's management of whiplash injuries. METHODS: A total of 5 interviews were conducted with patients (n=10) who had experienced a whiplash injury and with relatives (n=3) of such patients. The interviews were taped, transcribed verbatim, and analyzed by means of conventional content analysis. RESULTS: The following two themes emerged from the latent content analysis: (1) confidence and trust in the public health care system and (2) a disappointment with health care encounters. CONCLUSIONS: We found that most of the study participants felt distress due to insufficient information; respondents perceived a discrepancy between the public health care system's authority and the information provided. The Web information on whiplash injuries may greatly impact patients' care decisions as well as their physical, mental, and social well-being. We would recommend detailed patient information on whiplash injuries, with less emphasis on psychology and more data on pathophysiology, prognosis, and treatment.

General practitioners' reasoning on risk screening and primary prevention of stroke - a focus group study.

BACKGROUND: By screening and modifying risk factors, stroke incidence can be reduced. Clinical guidelines states that primary prevention of stroke is a responsibility and task of primary health care, but research shows that this not always the case. The aim of the study was to explore and describe what characterizes GPs' reasoning around risk screening and primary prevention among persons at risk for stroke in primary health care. METHODS: A qualitative design based in a grounded theory approach was chosen in order to investigate this unexplored research area. Data collection was done using focus group interviews and data was analysed using a constant comparative method. Twenty-two GPs were interviewed in four focus groups. RESULTS: Findings showed that GPs perceived difficulties in prioritizing patients with an unhealthy lifestyle and described a lack of systematicity in their procedures, which complicated their clinical decisions concerning patients with stroke risk factors. The results showed a lack of systematic risk screening methods. Time constraints and the reimbursement system were described as hindering the preventive work. CONCLUSION: There is a need for a more proactive, transparent and systematic approach in the distribution of GPs' time and reimbursement of prevention in primary health care. The findings suggest, by developing new methods and approaches such as digital clinical decision-making tools and by implementing inter-professional team-work, the quality of the primary prevention of stroke could be improved.

Swedish adaptation of the General Medical Council's multisource feedback questionnaires: a qualitative study.

OBJECTIVES: to explore potential users' opinions of a translated and culturally adapted Swedish version of the General Medical Council's MultiSource Feedback Questionnaires. METHODS: In this qualitative study, we used content analysis on semi-structured interviews from 44 resident doctors, 29 medical colleagues and 28 patients to analyse their opinions of the Swedish adapted version, created through translation and expert review. Transcribed interview data concerning the informants' general thoughts about the tool were coded manually by three independent coders into categories, compiled as themes, and exemplified by citations. Data regarding specific question wording and relevance were used as a basis for final questionnaire revision. RESULTS: The informants valued the tool's potential to provide essential feedback to support the development of residents' medical competences and communication skills. Resident doctors welcomed support in their self-reflection. Colleagues saw it as a valuable tool for assessment that needs to be used sensitively. Patients appreciated opportunities to communicate feedback.  Ambiguous or irrelevant questions and response options were identified. Some colleague-related questions about specific skills and knowledge appeared ambiguous to residents. The final questionnaire revision - based on the expert review and the interview analysis - resulted in a number of changes: four questions were deleted, twelve were reformulated, and six were added. CONCLUSIONS: Potential users perceived the Swedish adapted version as a beneficial tool for residents in their professional development. Further research is needed to explore how this tool can influence doctors' development when used in real-life settings.

Psychometric analysis of the Swedish version of the General Medical Council's multi source feedback questionnaires.

OBJECTIVES: To determine the internal consistency and the underlying components of our translated and adapted Swedish version of the General Medical Council's multisource feedback questionnaires (GMC questionnaires) for physicians and to confirm which aspects of good medical practice the latent variable structure reflected. METHODS: From October 2015 to March 2016, residents in family medicine in Sweden were invited to participate in the study and to use the Swedish version to perform self-evaluations and acquire feedback from both their patients and colleagues. The validation focused on internal consistency and construct validity. Main outcome measures were Cronbach's alpha coefficients, Principal Component Analysis, and Confirmatory Factor Analysis indices. RESULTS: A total of 752 completed questionnaires from patients, colleagues, and residents were analysed. Of these, 213 comprised resident self-evaluations, 336 were feedback from residents' patients, and 203 were feedback from residents' colleagues. Cronbach's alpha coefficients of the scores were 0.88 from patients, 0.93 from colleagues, and 0.84 in the self-evaluations. The Confirmatory Factor Analysis validated two models that fit the data reasonably well and reflected important aspects of good medical practice. The first model had two latent factors for patient-related items concerning empathy and consultation management, and the second model had five latent factors for colleague-related items, including knowledge and skills, attitude and approach, reflection and development, teaching, and trust. CONCLUSIONS: The current Swedish version seems to be a reliable and valid tool for formative assessment for resident physicians and their supervisors. This needs to be verified in larger samples.

The pain drawing as an instrument for identifying cervical spine nerve involvement in chronic whiplash-associated disorders.

OBJECTIVE: The aim of the study was to investigate the psychometric properties of a standardized assessment of pain drawing with regard to clinical signs of cervical spine nerve root involvement. DESIGN: This cross-sectional study included data collected in a randomized controlled study. PATIENTS: Two hundred and sixteen patients with chronic (≥6 months) whiplash-associated disorders, grade 2 or 3, were included in this study. METHODS: The validity, sensitivity, and specificity of a standardized pain drawing assessment for determining nerve root involvement were analyzed, compared to the clinical assessment. In addition, we analyzed the interrater reliability with 50 pain drawings. RESULTS: Agreement was poor between the standardized pain drawing assessment and the clinical assessment (kappa =0.11, 95% CI: -0.03 to 0.20). Sensitivity was high (93%), but specificity was low (19%). Interrater reliability was good (kappa =0.64, 95% CI: 0.53 to 0.76). CONCLUSION: The standardized pain drawing assessment of nerve root involvement in chronic whiplash-associated disorders was not in agreement with the clinical assessment. Further research is warranted to optimize the utilization of a pain/discomfort drawing as a supportive instrument for identifying nerve involvement in cervical spinal injuries.