Decreased plasma cartilage acidic protein 1 in COVID-19.

Cartilage acidic protein-1 (CRTAC1) is produced by several cell types, including Type 2 alveolar epithelial (T2AE) cells that are targeted by SARS-CoV2. Plasma CRTAC1 is known based on proteomic surveys to be low in patients with severe COVID-19. Using an ELISA, we found that patients treated for COVID-19 in an ICU almost uniformly had plasma concentrations of CRTAC1 below those of healthy controls. Magnitude of decrease in CRTAC1 distinguished COVID-19 from other causes of acute respiratory decompensation and correlated with established metrics of COVID-19 severity. CRTAC1 concentrations below those of controls were found in some patients a year after hospitalization with COVID-19, long COVID after less severe COVID-19, or chronic obstructive pulmonary disease. Decreases in CRTAC1 in severe COVID-19 correlated (r = 0.37, p = 0.0001) with decreases in CFP (properdin), which interacts with CRTAC1. Thus, decreases of CRTAC1 associated with severe COVID-19 may result from loss of production by T2AE cells or co-depletion with CFP. Determination of significance of and reasons behind decreased CRTAC1 concentration in a subset of patients with long COVID will require analysis of roles of preexisting lung disease, impact of prior acute COVID-19, age, and other confounding variables in a larger number of patients.

Persistent blood DNA methylation changes one year after SARS-CoV-2 infection.

We recently reported the COVID-19-induced circulating leukocytes DNA methylation profile. Here, we hypothesized that some of these genes would persist differentially methylated after disease resolution. Fifteen participants previously hospitalized for SARS-CoV-2 infection were epityped one year after discharge. Of the 1505 acute illness-induced differentially methylated regions (DMRs) previously identified, we found 71 regions with persisted differentially methylated, with an average of 7 serial CpG positions per DMR. Sixty-four DMRs persisted hypermethylated, and 7 DMR persisted hypomethylated. These data are the first reported evidence that DNA methylation changes in circulating leukocytes endure long after recovery from acute illness.

Association between statin use and cognitive function: A systematic review of randomized clinical trials and observational studies.

The US Food and Drug Administration issued a black box warning in 2012 regarding the association of statin use with cognitive impairment. This may deter patients and practitioners from using statins for guideline-directed indications. Large studies have not shown an increase in cognitive impairment with statin use. MEDLINE, EMBASE, and Cochrane databases were searched up to October 2019. We present an up-to-date systematic review of randomized controlled trials (RCTs) and prospective observational studies examining the association between statin use and cognitive status in a population aged ≥60 years. Twenty-four studies with 1,404,459 participants were included in the review. Twenty-one were prospective observational studies, and 3 were RCTs. All 3 RCTs, which ranged from 3.2 to 5.6 years of follow-up, showed no significant association between statin use and adverse cognitive effects (odds ratio [OR] 1.03 [0.82-1.30]) and (OR 1.0 [0.61-1.65]). The mean difference in the Mini-Mental State Examination was insignificant (0.06 [-0.04 to 0.16]) in the third RCT. The follow-up for observational studies ranged from 3 to 15 years. Ten observational studies showed reduced incidence of dementia. Seven showed no association with incident dementia. Three studies showed decline in cognition was similar, whereas one showed slower decline with statin use. There was no evidence of adverse cognitive effects, including incidence of dementia, deterioration in global cognition, or specific cognitive domains associated with statin use in individuals aged ≥60 years. Future studies should examine this association in studies with longer follow-up periods.

Association of Educational Attainment With Incidence of CKD in Young Adults.

INTRODUCTION: Chronic kidney disease (CKD) is greatly affected by social determinants of health. Whether low educational attainment is associated with incident CKD in young adults is unclear. METHODS: We evaluated the association of education with incident CKD in 3139 Coronary Artery Risk Development in Young Adults participants. We categorized education into low (high school and less), medium (college), and high (master's and professional studies) groups. Incident CKD was defined as new development of estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2 or urine albumin to creatinine ratio (ACR) ≥30 mg/g. Change in eGFR over 20 years was a secondary outcome. RESULTS: At baseline, mean age was 35.0 ± 3.6 years, 47% were Black, and 55% were women. Participants with lower educational attainment were less likely to have high income and health insurance and to engage in a healthy lifestyle. Over 20 years, 407 participants developed CKD (13%). Compared with individuals with low educational attainment, those with medium and high educational attainment had an unadjusted hazard ratios for CKD of 0.79 (95% confidence interval [CI] 0.65-0.97) and 0.44 (95% CI, 0.30-0.63), respectively. This association was no longer significant after adjusting for income, health insurance, lifestyle, and health status. Low educational attainment was significantly associated with a change in eGFR in crude and adjusted analyses, although the association was attenuated in the multivariable models (low: -0.83 [95% CI, -0.91 to -0.75], medium: -0.80 (95% CI, -0.95 to -0.64), and high: -0.70 (95% CI, -0.89 to -0.52) ml/min per 1.73 m2 per yr). CONCLUSIONS: Health care access, lifestyle, and comorbid conditions likely help explain the association between low educational attainment and incident CKD in young adults.

Exercise or manual physiotherapy compared with a single session of physiotherapy for osteoporotic vertebral fracture: three-arm PROVE RCT.

BACKGROUND: A total of 25,000 people in the UK have osteoporotic vertebral fracture (OVF). Evidence suggests that physiotherapy may have an important treatment role. OBJECTIVE: The objective was to investigate the clinical effectiveness and cost-effectiveness of two different physiotherapy programmes for people with OVF compared with a single physiotherapy session. DESIGN: This was a prospective, adaptive, multicentre, assessor-blinded randomised controlled trial (RCT) with nested qualitative and health economic studies. SETTING: This trial was based in 21 NHS physiotherapy departments. PARTICIPANTS: The participants were people with symptomatic OVF. INTERVENTIONS: Seven sessions of either manual outpatient physiotherapy or exercise outpatient physiotherapy compared with the best practice of a 1-hour single session of physiotherapy (SSPT). MAIN OUTCOME MEASURES: Outcomes were measured at 4 and 12 months. The primary outcomes were quality of life and muscle endurance, which were measured by the disease-specific QUALEFFO-41 (Quality of Life Questionnaire of the European Foundation for Osteoporosis - 41 items) and timed loaded standing (TLS) test, respectively. Secondary outcomes were (1) thoracic kyphosis angle, (2) balance, evaluated via the functional reach test (FRT), and (3) physical function, assessed via the Short Physical Performance Battery (SPPB), 6-minute walk test (6MWT), Physical Activity Scale for the Elderly, a health resource use and falls diary, and the EuroQol-5 Dimensions, five-level version. RESULTS: A total of 615 participants were enrolled, with 216, 203 and 196 randomised by a computer-generated program to exercise therapy, manual therapy and a SSPT, respectively. Baseline data were available for 613 participants, 531 (86.6%) of whom were women; the mean age of these participants was 72.14 years (standard deviation 9.09 years). Primary outcome data were obtained for 69% of participants (429/615) at 12 months: 175 in the exercise therapy arm, 181 in the manual therapy arm and 173 in the SSPT arm. Interim analysis met the criteria for all arms to remain in the study. For the primary outcomes at 12 months, there were no significant benefits over SSPT of exercise [QUALEFFO-41, difference -0.23 points, 95% confidence interval (CI) -3.20 to 1.59 points; p = 1.000; and TLS test, difference 5.77 seconds, 95% CI -4.85 to 20.46 seconds; p = 0.437] or of manual therapy (QUALEFFO-41, difference 1.35 points, 95% CI -1.76 to 2.93 points; p = 0.744; TLS test, difference 9.69 seconds (95% CI 0.09 to 24.86 seconds; p = 0.335). At 4 months, there were significant gains for both manual therapy and exercise therapy over SSPT in the TLS test in participants aged < 70 years. Exercise therapy was superior to a SSPT at 4 months in the SPPB, FRT and 6MWT and manual therapy was superior to a SSPT at 4 months in the TLS test and FRT. Neither manual therapy nor exercise therapy was cost-effective relative to a SSPT using the threshold of £20,000 per quality-adjusted life-year. There were no treatment-related serious adverse events. CONCLUSIONS: This is the largest RCT to date assessing physiotherapy in participants with OVFs. At 1 year, neither treatment intervention conferred more benefit than a single 1-hour physiotherapy advice session. The focus of future work should be on the intensity and duration of interventions to determine if changes to these would demonstrate more sustained effects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49117867. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 44. See the NIHR Journals Library website for further project information.

Osteoporosis is a condition in which bones lose their strength and are more likely to break. It affects around 3 million people in the UK. Fractures of the spine are very common in people with osteoporosis. They can cause a change in body shape, back pain and difficulty with carrying out daily tasks. A treatment that may help people is physiotherapy. There is evidence that several different types of physiotherapy, such as exercise or manual (hands-on) therapy, may help. This was the largest trial of physiotherapy for people with osteoporotic vertebral fracture to date. Seven sessions of physiotherapy treatment based on either exercise or manual therapy were compared with a single 1-hour session of individualised advice from a physiotherapist. The outcome of these treatments was assessed using recognised measures of quality of life, back muscle strength, pain, function and activity at 4 months and 1 year after treatment. How safe the treatments were and whether or not they had any impact on falls or the costs of health and social care were also examined. Interviews were conducted with some of the participants in the trial to seek their opinion about the treatment that they had received. The results show that the participants tolerated all the treatments well, with no significant safety issues, and perceived treatment to be beneficial. The study did not find significant differences between the three treatments in terms of clinical effectiveness or cost-effectiveness at 1 year, although there were benefits in some areas at 4 months.