What can we learn from experiences in general practice during the COVID-19 pandemic?:A qualitative study

Background: Experiences with organizational changes in daytime general practices and out-of-hours (OOH) services during the COVID-19 pandemic may help to address the challenges in general practice care that were already a concern before the crisis. This study aimed to describe these experiences and the potential usefulness of the organizational changes for future general practice care and any future pandemics.Methods: Semi-structured interviews were performed among 11 directors of OOH services, and 19 (locum) general practitioners (GPs) or practice managers, who were purposively sampled. Video or telephone interviews were performed in two rounds: between November 2020 and January 2021 and between May 2021 and August 2021. The data were analyzed using thematic analysis methods.Results: Three themes emerged from the data: (1) Changes in the triage procedures; in GP practices and OOH services, stricter triage criteria were implemented, and GPs were more actively involved in the triage process. These measures helped to reduce the number of ‘low urgency’ face-to-face consultations. (2) Changes in GP care; there was a shift towards video and telephone consultations, allowing GPs to spend more time with patients during the remaining face-to-face consultations. For chronic patients, the shift towards telemonitoring appeared to encourage self-care, and postponing face-to-face consultations for regular checkups appeared to be unproblematic for stable patients. (3) Coordination of GP care and information communication flow during the COVID-19 pandemic; OOH directors perceived a lack of consistency in the information from various governmental and non-governmental parties on containment measures and guidelines related to COVID-19, making it difficult to act on them. The COVID-19 pandemic intensified collaboration between GPs, OOH services, and other healthcare professionals.Conclusions: The results of this study indicate that some of the organizational changes, such as stricter triage, remote consultations, and changes in managed care of chronic patients, may help in tackling the pre-existing challenges in GP care from before the COVID-19 pandemic. However, more extensive research and continuous monitoring are necessary to establish the effects on patients and their health outcomes. To navigate future pandemics, the intensified collaboration between health professionals should be maintained, while there is considerable room for improvement in the provision of unambiguous information.</p

Creatinine, cystatin C, muscle mass, and mortality:Findings from a primary and replication population-based cohort

Background: Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of serum creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making. Methods: We included 8437 community-dwelling adults enrolled in the Dutch PREVEND study and 5033 in the US NHANES replication cohort. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification. Results: Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1–Q3) serum creatinine and cystatin C were 71 (61–80) and 80 (62–88) μmol/L and 0.87 (0.78–0.98) and 0.91 (0.80–1.10) mg/L, respectively. Higher serum creatinine was associated with greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1636 (19%) deaths were registered over a median follow-up of 12.9 (5.8–16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1–8.2%). In the NHANES, 1273 (25%) deaths were registered over a median follow-up of 17.9 (17.3–18.5) years with a 10-year mortality rate of 13.8% (12.8–14.7%). Both markers were associated with increased mortality. Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality, while the association between serum cystatin C and increased mortality strengthened. The shapes of the associations in the PREVEND study and NHANES were almost identical. Conclusions: The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.</p

Cigarette smoking is associated with higher thyroid hormone and lower TSH levels:The PREVEND study

PURPOSE: The extent to which smoking is associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) when taking account of clinical variables including alcohol consumption is unclear. We aimed to determine associations of TSH, FT4, and FT3 levels with current smoking. METHODS: A cross-sectional study was performed in 5766 euthyroid participants (Prevention of Renal and Vascular End-Stage Disease cohort). Current smoking was determined by self-report, categorized as never, former, and current (≤20 and >20 cigarettes per day). Smoke exposure was determined by urinary cotinine. RESULTS: Current smoking of ≤20 and >20 cigarettes per day was associated with lower TSH and higher FT3 levels. FT4 levels were higher in subjects smoking 20 cigarettes per day. In agreement, TSH was inversely, whereas FT4 and FT3 levels were positively associated with urinary cotinine (P 30 g per day conferred higher TSH and lower FT3 levels. CONCLUSIONS: Cigarette smoking is associated with modestly higher FT4 and FT3, and lower TSH levels, partly opposing effects of alcohol consumption

Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis

Background: Lung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality. Methods: This is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS). Results: A total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 – 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 – 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort. Conclusion: In this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS. Trial registration: ClinicalTrials.gov, ID NCT04482621

Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort:The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study

BACKGROUND: a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. METHODS: we measured plasma pyridoxal 5'-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1-57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8-8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47-0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51-1.01) and 0.74 (95% confidence interval, 0.53-1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27-0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65-1.51). CONCLUSIONS: in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women

The interplay between tamoxifen and endoxifen plasma concentrations and coagulation parameters in patients with primary breast cancer

Background: Tamoxifen is an effective treatment for primary breast cancer but increases the risk for venous thromboembolism. Tamoxifen decreases anticoagulant proteins, including antithrombin (AT), protein C (PC) and tissue factor (TF) pathway inhibitor, and enhances thrombin generation (TG). However, the relation between plasma concentrations of both tamoxifen and its active metabolite endoxifen and coagulation remains unknown. Methods: Tamoxifen and endoxifen were measured in 141 patients from the prospective open-label intervention TOTAM-study after 3 months (m) and 6 m of tamoxifen treatment. Levels of AT and PC, the procoagulant TF, and TG parameters were determined at both timepoints if samples were available (n = 53–135 per analysis). Levels of coagulation proteins and TG parameters were correlated and compared between: 1) quartiles of tamoxifen and endoxifen levels, and 2) 3 m and 6 m of treatment. Results: At 3 m, levels of AT, PC, TF and TG parameters were not associated with tamoxifen nor endoxifen levels. At 6 m, median TF levels were lower in patients in the 3rd (56.6 [33] pg/mL), and 4th (50.1 [19] pg/mL) endoxifen quartiles compared to the 1st (lowest) quartile (76 [69] pg/mL) (P=0.027 and P=0.018, respectively), but no differences in anticoagulant proteins or TG parameters were observed. An increase in circulating TF levels (3 m: 46.0 [15] versus 6 m: 54.4 [39] pg/mL, P &lt; 0.001) and TG parameters was observed at the 6 m treatment timepoint, while AT and PC levels remained stable.Conclusions: Our results indicate that higher tamoxifen and endoxifen levels are not correlated with an increased procoagulant state, suggesting tamoxifen dose escalation does not further promote hypercoagulability.</p

Muscle mass and estimates of renal function:a longitudinal cohort study

BACKGROUND Creatinine is the most widely used test to estimate the glomerular filtration rate (GFR), but muscle mass as key determinant of creatinine next to renal function may confound such estimates. We explored effects of 24-h height-indexed creatinine excretion rate (CER index) on GFR estimated with creatinine (eGFRCr ), muscle mass-independent cystatin C (eGFRCys ), and the combination of creatinine and cystatin C (eGFRCr-Cys ) and predicted probabilities of discordant classification given age, sex, and CER index. METHODS We included 8076 adults enrolled in the PREVEND study. Discordant classification was defined as not having eGFRCr  <60 mL/min per 1.73 m2 when eGFRCys was <60 mL/min/1.73 m2 . Baseline effects of age and sex on CER index were quantified with linear models using generalized least squares. Baseline effects of CER index on eGFR were quantified with quantile regression and logistic regression. Effects of annual changes in CER index on trajectories of eGFR were quantified with linear mixed-effects models. Missing observations in covariates were multiply imputed. RESULTS Mean (SD) CER index was 8.0 (1.7) and 6.1 (1.3) mmol/24 h per meter in male and female participants, respectively (Pdifference  < 0.001). In male participants, baseline CER index increased until 45 years of age followed by a gradual decrease, whereas a gradual decrease across the entire range of age was observed in female participants. For a 70-year-old male participant with low muscle mass (CER index of 2 mmol/24 h per meter), predicted baseline eGFRCr and eGFRCys disagreed by 24.7 mL/min/1.73 m2 (and 30.1 mL/min/1.73 m2 when creatinine was not corrected for race). Percentages (95% CI) of discordant classification in male and female participants aged 60 years and older with low muscle mass were 18.5% (14.8-22.1%) and 15.2% (11.4-18.5%), respectively. For a 70-year-old male participant who lost muscle during follow-up, eGFRCr and eGFRCys disagreed by 1.5, 5.0, 8.5, and 12.0 mL/min/1.73 m2 (and 6.7, 10.7, 13.5, and 15.9 mL/min/1.73 m2 when creatinine was not corrected for race) at baseline, 5 years, 10 years, and 15 years of follow-up, respectively. CONCLUSIONS Low muscle mass may cause considerable overestimation of single measurements of eGFRCr . Muscle wasting may cause spurious overestimation of repeatedly measured eGFRCr . Implementing muscle mass-independent markers for estimating renal function, like cystatin C as superior alternative to creatinine, is crucial to accurately assess renal function in settings of low muscle mass or muscle wasting. This would also eliminate the negative consequences of current race-based approaches