Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2.

Adenosine deaminases acting on RNA (ADAR) are RNA-editing enzymes that may restrict viral infection. We have utilized deep sequencing to determine adenosine to guanine (A→G) mutations, signifying ADAR activity, in clinical samples retrieved from 93 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in the early phase of the COVID-19 pandemic. A→G mutations were detected in 0.035% (median) of RNA residues and were predominantly nonsynonymous. These mutations were rarely detected in the major viral population but were abundant in minor viral populations in which A→G was more prevalent than any other mutation (P < 0.001). The A→G substitutions accumulated in the spike protein gene at positions corresponding to amino acids 505 to 510 in the receptor binding motif and at amino acids 650 to 655. The frequency of A→G mutations in minor viral populations was significantly associated with low viral load (P < 0.001). We additionally analyzed A→G mutations in 288,247 SARS-CoV-2 major (consensus) sequences representing the dominant viral population. The A→G mutations observed in minor viral populations in the initial patient cohort were increasingly detected in European consensus sequences between March and June 2020 (P < 0.001) followed by a decline of these mutations in autumn and early winter (P < 0.001). We propose that ADAR-induced deamination of RNA is a significant source of mutated SARS-CoV-2 and hypothesize that the degree of RNA deamination may determine or reflect viral fitness and infectivity.

Enrichment reveals extensive integration of hepatitis B virus DNA in hepatitis delta-infected patients.

INTRODUCTION: Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited. METHODS: We investigated 50 pieces of liver explant tissue from five patients with hepatitis D-induced cirrhosis, using a deep sequencing strategy targeting HBV RNA. RESULTS: We found that integrations were abundant and highly expressed, however with large variation in number of integration derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of both HBsAg. Still, most of the HBV reads represented a few predominant integrations. CONCLUSIONS: The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small part of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV co-infected patients with liver cirrhosis.

Hepatitis B virus particles in serum contain minus strand DNA and degraded pregenomic RNA of variable and inverse lengths.

This study utilized digital PCR to quantify HBV RNA and HBV DNA within three regions of the HBV genome. Analysis of 75 serum samples from patients with chronic infection showed that HBV RNA levels were higher in core than in S and X regions (median 7.20 vs. 6.80 and 6.58 log copies/mL; p < .0001), whereas HBV DNA levels showed an inverse gradient (7.71 vs. 7.73 and 7.77 log copies/mL, p < .001). On average 80% of the nucleic acid was DNA by quantification in core. The core DNA/RNA ratio was associated with viral load and genotype. In individual patients, the relations between RNA levels in core, S and X were stable over time (n = 29; p = .006). The results suggest that pregenomic RNA is completely reverse transcribed to minus DNA in ≈75% of the virus particles, whereas the remaining 25% contain both RNA and DNA of lengths that reflect variable progress of the polymerase.

Occult hepatitis B infection in children born to HBeAg-positive women confers a low long-term risk for HBsAg-positive infection.

PURPOSE: Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI. METHODS: One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018. RESULTS: Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections. CONCLUSION: The results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.

Iodine intake in the Swiss population 100 years after the introduction of iodised salt: a cross-sectional national study in children and pregnant women.

PURPOSE: The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100 years, but dietary habits are changing and today only one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in children and pregnant women. METHODS: We conducted a nationwide cross-sectional study in children (6-12 years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. RESULTS: The median UIC was 127 µg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97 µg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65 µg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150 µg/day). Compared to non-users, users had higher median UIC (129 vs. 81 µg/L, P < 0.001), lower prevalence of inadequacy (< 160 µg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29 µg/L, P < 0.001). All women were euthyroid. CONCLUSIONS: The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013.

Parents' perceptions of care quality at child health centres: A cross-sectional study from Sweden.

AIM: To examine parents' perceptions of care quality at child health centres. Specific objectives were to examine parents' perceptions of the care received and the subjective importance of such care. Furthermore, to examine the relationship between parents' sociodemographic characteristics and the perceptions of care quality. DESIGN: A cross-sectional study. METHODS: A random sample of parents of children born in Sweden in 2021 participated. Data were collected by the QPP-CHC questionnaire and analysed using descriptive and analytical statistics. RESULTS: The response rate was 19.4%. The targeted sample size of 210 participants was reached as 584 parents responded to the questionnaire. Parents' overall ratings of care quality at child health centres indicated optimal quality with mean values >3. However, various potential improvements areas were identified as needing additional information. These included dental care (m = 2.82), allergy prevention (m = 2.25), breastfeeding (m = 2.97), sleep (m = 2.83), the child's behaviour (m = 2.47) and the child's crying (m = 2.47). Also, parents rated suboptimal quality regarding that the care was based on healthcare routines rather than parental preferences and needs (m = 2.86). Parents born outside of the Nordic countries rated higher care quality than those born in the Nordic countries, as well as parents with a non-academic education. CONCLUSION: Parents want information based on their preferences and needs. Parent's perceptions of areas for improvement are new and important knowledge for registered nurses at child health centres. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The findings indicate that parents feel that insufficient attention is given to areas of care that they perceive as important. Parents' perspectives on the care quality at child health centres is an important component of quality work and might lead to improvements in the care quality at child health centres. REPORTING METHOD: The Strengthening the Reporting of Observational Studies (STROBE) checklist for cross-sectional studies was used to guide reporting. IMPLICATIONS FOR POLICY AND PRACTICE: The findings of this study suggests that parents feel that insufficient attention is given to areas of care that they perceive as important. Parents' perspectives on the care quality at child health centres provides important knowledge which can guide further development of care quality at child health centres. The findings indicate that a family-centred approach that integrates relational and routine-oriented nursing can be a way to ensure that the care is based on parents' preferences and needs. No patient or public contribution.

Complex norovirus transmission dynamics at hospital wards revealed by deep sequencing.

Detailed knowledge regarding norovirus transmission within hospitals is limited. We investigated a norovirus hospital outbreak affecting 65 patients at five different wards. PCR showed that 61 (94%) of the patients were infected with genotype II.4 strains. Successful Ion Torrent deep sequencing of GII.4 positive samples from 59 patients followed by phylogenetic analysis revealed that all sequences but two clustered into four distinct clades. Two of the clades belonged to GII.4 Sydney 2012, while the other two belonged to GII.4 New Orleans 2009. One of the clades was predominant at two wards, while two clades were predominant at one ward each. The fourth clade was found in sporadic cases at several wards. Thus, at four out of five wards, variants from one clade were predominant. At one ward, a single clade accounted for all cases, while at three wards the predominant clade accounted for 60%-71% of cases. Analysis of quasispecies variation identified positions that could further discriminate between variants from separate wards. The results illustrate a complex transmission of healthcare-associated norovirus infections and show that sequencing can be used to discriminate between related and unrelated cases.

Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib-A retrospective analysis on consecutive patients from a well-defined region.

OBJECTIVE: Ibrutinib treatment is associated with cardiovascular side effects, in particular atrial fibrillation (AF) and hypertension, as well as increased risk of bleeding. Here, we aimed at describing the incidence of these events during long-term follow-up in patients with chronic lymphocytic leukemia treated outside clinical trials as well as identifying clinical factors predictive of developing AF. Additionally, other reasons for treatment withdrawal were analyzed. METHODS: The study was retrospective, data were collected from medical records. RESULTS: A total of 134 patients were identified. Median follow-up was 32 months (range 3-103) and median duration of ibrutinib treatment was 26 months (range 1-103). Of 110 patients with no prior history of AF, 24.5% were diagnosed during treatment. Newly diagnosed or worsening of pre-existing hypertension occurred in 15.7%. Sixty-six % of the patients experienced bleeding events, of which 7.5% grade 3-4. Treatment discontinuation and dose reduction occurred in 68% and 47% of the patients, respectively, mostly due to toxicity. CONCLUSIONS: The incidence of AF was high and at a median follow-up of 2.5 years, two-thirds of the patients discontinued treatment mostly due to bleeding and infections. Treatment-related toxicity of any grade should be regarded as a concern of prolonged ibrutinib therapy.

Thyroid function and urinary concentrations of iodine, selenium, and arsenic in vegans, lacto-ovo vegetarians and pescatarians.

PURPOSE: Populations following a plant-based diet may be at particular risk of thyroid dysfunction due to low iodine and selenium intakes. The main purpose was to assess thyroid function and urinary concentration of iodine, selenium, and arsenic, in subjects following a vegan, lacto-ovo vegetarian, or pescatarian diet. METHODS: In Norway, a country without mandatory dietary iodine fortification, 205 adults, following vegan (n = 115), lacto-ovo vegetarian (n = 55) and pescatarian diet (n = 35) were included. Thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and serum anti-TPO (S-anti-TPO) were measured in a venous blood sample and concentrations of iodine (UIC), creatinine (UCC), selenium, and arsenic were measured from single spot urine samples. RESULTS: Subclinical hypothyroidism (TSH > 4.0 mU/L) was observed in 3% of subjects. The overall median (p25, p75) Tg was 17 (9, 30) µg/L and vegans had higher Tg compared to pescatarians. Vegans not consuming iodine-containing supplements (n = 43) had higher Tg, than supplement users (n = 72), 27 (11, 44) vs. 16 (8, 25) µg/L and higher fT4, 16 (15, 17) vs. 15 (14, 17) pmol/L, respectively. The overall median UIC was 57 (28, 130) µg/L, all dietary groups had median UIC below WHO thresholds. Median urinary selenium and arsenic concentration was 13 (6, 22) and 3 (2, 8) µg/L, respectively. CONCLUSION: The prevalence of subclinical hypothyroidism was low and fT4 and fT3 were within the normal range for all dietary groups. Vegans had significantly increased Tg compared to pescatarians.

Health literacy in individuals with knee pain-a mixed methods study.

BACKGROUND: Low health literacy is associated with worse pain and poorer self-management. This study (1) examined the level of health literacy and associations with lifestyle habits, health status, chronic pain, and radiographic knee osteoarthritis; and (2) explored experiences illuminating health literacy among individuals with knee pain. METHODS: A convergent parallel mixed-methods design was used, including 221 individuals. Health literacy was assessed by HLS-EU-Q16 and eHEALS. The questionnaire included questions on lifestyle habits, health status, and pain distribution. Radiographic knee osteoarthritis was assessed with x-rays. Associations were analysed using logistic regression analyses. Individual semi-structured interviews were conducted (n = 19) and analysed with qualitative content analysis. RESULTS: The result showed that 71% reported sufficient health literacy. Higher education, healthy lifestyle habits, better general health, and absence of widespread pain were associated with sufficient health literacy. Experiences regarding health literacy influencing the decision-making process toward a decision on action comprised: (1) searching for information actively or passively; (2) processing of the information included being informed, critical, and interpretive; and (3) taking a stand on the information based on trustfulness and motivation. CONCLUSION: Seven out of 10 reported sufficient health literacy. Despite this, unhealthy lifestyles were common, suggesting that having sufficient HL is not enough for a behavioural change and the decision-making process, including different phases such as searching, processing, and taking a stand on health information is important to consider. More research on health literacy is needed to gain knowledge of how best to develop health promotion in individuals with knee pain.

Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain.

OBJECTIVE: The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI. METHOD: This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed. RESULT: Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040. CONCLUSION: Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain. TRIAL REGISTRATION: clinicalTrials.gov Identifier: NCT04928170.

Abundance of Noncircular Intrahepatic Hepatitis B Virus DNA May Reflect Frequent Integration Into Human DNA in Chronically Infected Patients.

BACKGROUND: Hepatitis B virus (HBV) integration has implications for cancer development and surface antigen (HBsAg) production, but methods to quantify integrations are lacking. The aim of this study was to develop a droplet digital PCR (ddPCR) assay discriminating between circular and integrated HBV DNA, and to relate the distribution between the two forms to other HBV markers. METHODS: ddPCR with primers spanning the typical linearization breakpoint in the HBV genome allowed for quantification of the absolute copy numbers of total and circular HBV DNA, and calculation of linear HBV DNA. RESULTS: Analysis of 70 liver biopsies from patients with chronic HBV infection revealed that the fraction of linear HBV DNA, which includes integrations, was higher in HBeAg-negative patients than HBeAg-positive. The ratio between HBsAg and HBV DNA levels in serum correlated with the intrahepatic proportion of linear HBV DNA. Furthermore, ddPCR experiments on serum samples and experiments with nuclease indicated the contribution of encapsidated double-stranded linear DNA and replication intermediates to be limited. CONCLUSIONS: The degree of integration of intrahepatic HBV DNA in the HBeAg-negative stage may be higher than previously anticipated, and integrated DNA may explain the persistence of high HBsAg serum levels in patients with low HBV DNA levels.

Quantification of Viral RNA in Multiple Pieces of Explant Liver Tissue Shows Distinct Focal Differences in Hepatitis B Infection.

Hepatitis B virus (HBV) DNA and RNA were quantified by digital PCR assays in 20-30 tissue pieces from each of 4 liver explants with cirrhosis caused by HBV. The within-patient variability of HBV RNA levels between pieces was up to a 1000-fold. Core RNA and S RNA levels were similar and correlated strongly when replication was high, supporting that transcription was from covalently closed circular DNA (cccDNA). By contrast, enhanced expression of S RNA relative to cccDNA and core RNA in patients with medium-high or low replication supports that HBV surface antigen (HBsAg) can be expressed mainly from integrated HBV DNA in such patients.

Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar: an observational study.

BACKGROUND: The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. METHODS: Children (n = 677) with non-severe acute febrile illness aged 2-59 months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ("IMCI pneumonia") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia". RESULTS: Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. CONCLUSION: The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia. Trial registration Clinicaltrials.gov (NCT01094431).

Women´s experiences of preeclampsia as a condition of uncertainty: a qualitative study.

BACKGROUND: Preeclampsia is a severe condition that annually affects about 3-8% of pregnancies worldwide. Preeclampsia is thereby one of the most common pregnancy complications for both mother and child. Despite that, there is limited research exploring the women´s perspective of experiencing preeclampsia. AIM: The aim of this study was to describe women´s experiences of preeclampsia to improve the support and care given during and after pregnancy. METHODS: A qualitative descriptive interview study was undertaken. Nine women, diagnosed with preeclampsia, were recruited from a maternity unit in southern Sweden. The descriptive phenomenological method according to Amadeo Giorgi was used to analyse the data. RESULTS: The women´s experiences of PE were expressed as A condition of uncertainty, meaning that it was an unexpected and unknown situation. This main result consisted of 1) incomprehensible diagnosis message, 2) ambivalent feeling when the unexpected happens, 3) confusing contradictory messages, 4) appreciated support from the midwife, 5) need for continuous information. The nature of preeclampsia can sometimes deteriorate rapidly both for the mother and/or the child, often resulting in conversion from a planned vaginal spontaneous delivery to an emergency Caesarean section. The women narrated diffuse symptoms, and they experienced that they got contradictory information from different health care professionals regarding the severity of their disease. Detailed and continuous information is requested throughout the course of the disease, and the postpartum period. CONCLUSION: This qualitative study reveal a need for improved clinical management. Health care professionals must be aware that women and their partners need detailed, consistent and repeated information about severity and prognosis to diminish the condition of uncertainty, confusion and fearful experience. The clinical implication would be a standardized preeclampsia education for pregnant women early on in the pregnancy, to raise awareness of preeclamptic symptoms. Furthermore, there is a need for harmonized guidelines and individualized support to the woman and her partner both at the antenatal care and the maternity ward and inpatient care at the hospital.

Associations between metabolic factors and radiographic knee osteoarthritis in early disease - a cross-sectional study of individuals with knee pain.

OBJECTIVE: Metabolic factors have been shown to be associated to severe radiographic knee osteoarthritis (RKOA). However, more knowledge is needed in early clinical knee osteoarthritis (KOA). The aim was to study associations between metabolic factors and radiographic knee osteoarthritis (OA) in individuals with knee pain. A second aim was to study associations between metabolic factors and RKOA in those with normal BMI and in those overweight/obese, respectively. METHOD: This cross-sectional study included 282 individuals with knee pain (without cruciate ligament injury) and aged 30-67 years, and 70% women. Waist circumference, body mass index (BMI), proportion of fat and visceral fat area (VFA) were assessed. RKOA was defined as Ahlbäck grade 1 in at least one knee. Fasting blood samples were taken and triglycerides, cholesterol (total, low density lipoprotein (LDL) and high density lipoprotein (HDL)), C-reactive protein (CRP), glucose, HbA1C were analysed. Metabolic syndrome was defined in accordance with the International Diabetes Federation (IDF). Associations were analysed by logistic regression. RESULTS: Individuals with RKOA were older, had higher BMI, higher VFA, larger waist circumference and had increased total cholesterol, triglycerides and LDL-cholesterol, but not fasting glucose. There was no difference between the group with RKOA vs. non-radiographic group regarding the presence of metabolic syndrome. In a subgroup analysis of individuals with normal BMI (n = 126), those with RKOA had higher VFA, more central obesity, higher levels of CRP and total cholesterol, compared with individuals without RKOA. In individuals with obesity, age was the only outcome associated to RKOA. CONCLUSION: There were clear associations between metabolic factors and RKOA in individuals with knee pain, also in those with normal BMI. In individuals with obesity age was the only variable associated to RKOA. TRIAL REGISTRATION: clinicalTrials.gov Identifier: NCT04928170.

The Meaning of Critical Illness for People Suffering From COVID-19: When a Frightening Unreality Becomes Reality.

The aim of this study was to elucidate the meaning of critical illness for people with COVID-19. This study used a qualitative design. Thirteen people who were critically ill with COVID-19 during 2020 and admitted to a COVID-19 intensive care unit in northern Sweden participated in the study. Data collection was conducted as individual interviews with a narrative approach, and data were analyzed with phenomenological hermeneutic interpretation. The participants did not think they would get critically ill with this unexpected illness. They experienced terrible nightmares where their relatives had been killed, and they missed their relatives both in their dreams and in reality, as they had not been allowed to be with them due to the virus. Gratefulness was described for surviving. Participants described thoughts of not being able to imagine going through this again. They felt fear and loneliness, as a terrifying unreality had become a reality.

Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019.

This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.

High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden, Brazil and Romania.

OBJECTIVES: Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world. PATIENTS AND METHODS: A total of 432 patients with OL from Sweden, Brazil and Romania were analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A real-time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58 and 59, was performed to detect HR-HPV in patients with OL. RESULTS: In the Swedish and Romanian cohorts, none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours. CONCLUSIONS: In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.

Changes in health-related quality of life among older adults aging with long-term spinal cord injury.

STUDY DESIGN: Cross-sectional and longitudinal. OBJECTIVES: To (i) describe health-related quality of life (HRQoL) and changes over 6 years in older adults aging with long-term spinal cord injury (SCI) and (ii) investigate how changes in HRQoL are associated with age, gender, and injury characteristics. SETTING: Community in southern Sweden. METHODS: From the initial 123 participants (years 2011-2012) in the Swedish Aging with Spinal Cord Injury Study (SASCIS), 77 individuals (32% women, C1-L3, AIS A-D, median age 66 years, median time since injury 31 years, 30% complete injuries) were assessed 6 years later. HRQoL was rated with the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23). Associations were investigated using multivariable linear regression analyses. RESULTS: The median rating of global QoL (scale range 0-100) was relatively high at both assessments (67 and 83, respectively). There was a large variability in all HRQoL-domains and no significant changes over 6 years. As compared to an AIS D injury, a tetraplegia AIS A-C injury and tetraplegia and paraplegia AIS A-C injuries were associated with positive change in depressive symptoms and global QoL, respectively. CONCLUSIONS: Older adults aging with long-term SCI show large variations in all HRQoL-domains and have the potential to maintain a high and stable level of HRQoL over time. Persons with AIS D injuries may need increased attention to mitigate negative changes in depressive symptoms and global QoL. Further studies are needed to identify modifiable factors associated with changes in HRQoL in older adults aging with long-term SCI.