Identification of post-COVID-19 condition phenotypes, and differences in health-related quality of life and healthcare use: a cluster analysis.

The aim of this cross-sectional study was to identify post-COVID-19 condition (PCC) phenotypes and to investigate the health-related quality of life (HRQoL) and healthcare use per phenotype. We administered a questionnaire to a cohort of PCC patients that included items on socio-demographics, medical characteristics, health symptoms, healthcare use, and the EQ-5D-5L. A principal component analysis (PCA) of PCC symptoms was performed to identify symptom patterns. K-means clustering was used to identify phenotypes. In total, 8630 participants completed the survey. The median number of symptoms was 18, with the top 3 being fatigue, concentration problems, and decreased physical condition. Eight symptom patterns and three phenotypes were identified. Phenotype 1 comprised participants with a lower-than-average number of symptoms, phenotype 2 with an average number of symptoms, and phenotype 3 with a higher-than-average number of symptoms. Compared to participants in phenotypes 1 and 2, those in phenotype 3 consulted significantly more healthcare providers (median 4, 6, and 7, respectively, p < 0.001) and had a significantly worse HRQoL (p < 0.001). In conclusion, number of symptoms rather than type of symptom was the driver in the identification of PCC phenotypes. Experiencing a higher number of symptoms is associated with a lower HRQoL and more healthcare use.

Statin treatment and the risk of recurrent pulmonary embolism.

AIMS: Patients with idiopathic venous thromboembolism (VTE) have a high recurrence risk during and after stopping anticoagulant treatment. Several studies suggest that treatment with statins reduces the incidence of a first episode of VTE, but data on the effects in patients with a previous episode are lacking. We examined the effect of statin therapy on the risk of recurrent pulmonary embolism (PE). METHODS AND RESULTS: Using the PHARMO Record Linkage System, a Dutch population-based registry of pharmacy records linked with hospital discharge records, patients hospitalized with an acute episode of PE were identified between 1998 and 2008. Prescription-based use of statins and vitamin K antagonist (VKA) were identified starting at hospital discharge and during follow-up. The association between statin use (time-varying) and the incidence of recurrences, cardiovascular events, and death was assessed using Cox regression analysis. The mean (standard deviation) age was 61 (17) years. The median (range) duration of VKA treatment after acute PE was 199 (45-3793) days. Twenty-four per cent of the patients (n = 737) had at least one prescription of statins during the follow-up period and the median duration of statin therapy was 1557 (5-4055) days. During a median follow-up of 1529 (1-4155) days, 285 (9.2%) patients experienced a recurrence. Treatment with statins was associated with a reduced risk of recurrent PE [adjusted hazard ratio (HR) 0.50, 95% CI: 0.36-0.70], both during and after stopping VKA treatment. A dose-response relationship was shown for potency, with the largest reduction in those with the most potent statins. Finally, statin treatment also reduced the risk for cardiovascular events and all-cause mortality. CONCLUSION: Statin treatment decreases the risk of recurrent PE, irrespective of VKA treatment. Treatment with statins may be an attractive alternative for anticoagulant treatment in the long-term treatment of PE.

[An abdominal wall bulging: consider a neurological cause]. / Een uitstulping van de buik.

A patient with a swelling of the abdominal wall is a regular occurrence in general practice and hospital. The diagnosis can often be made with a thorough history and physical examination. An abdominal wall hernia is characterized by an increase in swelling on standing physical examination and Valsalva maneuver, which is often reducible, and a hernia defect is palpable. If no interruption of the abdominal wall is palpable and there is hypoesthesia, there may be an abdominal wall paresis because of thoracic paramedian hernia nuclei pulposi (HNP). Where an abdominal wall hernia is treated surgically in case of symptoms, this is conservatively treated with an HNP.

The prolonged impact of COVID-19 on symptoms, health-related quality of life, fatigue and mental well-being: a cross-sectional study.

Background: A subset of patients experience persisting symptoms after an acute COVID-19 infection, referred to as "post COVID-19 condition". This cross-sectional study aimed to compare symptoms, health-related quality of life (HRQoL), fatigue, mental well-being, and determinants of diminished HRQoL, between patients with post COVID-19 condition categorized by time since acute infection. Methods: We performed an online survey and analyzed responses of 10,194 adult respondents with a confirmed or suspected COVID-19 infection, who experienced persisting symptoms ≥3 months after the initial infection. The most debilitating symptoms and health outcomes were studied separately for respondents 3-6, 7-9, 10-12, 13-18, 19-24, and >24 months after acute infection. Results: At each time period, fatigue, sensory-processing problems, and concentration problems were the most debilitating symptoms reported by respondents, although the proportion of respondents who reported these symptoms differed significantly between time periods. Respondents 3-6 months post-acute infection had the lowest HRQoL (median EQ-5D utility score: 0.59), the highest fatigue level (median score: 110.0) and the highest proportion with a likely depressive disorder (32.4%), whereas respondents 13-18 months post-infection had the highest HRQoL (0.65), the lowest fatigue level (106.0), and the second lowest proportion with a likely depressive disorder (25.0%) (p = 0.000-0.007). Compared to those 13-18 and 19-24 months post-infection, respondents >24 months post-infection had a slightly lower HRQoL (0.60), lower fatigue level (108.0), and lower proportion with a likely depressive disorder (29.2%), although only the differences in HRQoL were statistically significant (p = 0.001-0.010). Younger age, female gender, lower level of education, not having paid work before COVID-19, comorbidity, and not being vaccinated, seemed to be associated with lower HRQoL. Conclusion: Regardless of time since infection, respondents considered fatigue, sensory processing problems and concentration problems the most debilitating symptoms. They experienced a low HRQoL and severe fatigue, even more than two years after acute COVID-19 infection. Respondents 3-6 months post-infection had the worst health outcomes, whereas respondents 13-18 months post-infection had the best outcomes, indicating that, at least for a subgroup of patients, health status may improve over time.

Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials.

BACKGROUND: It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78-1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72-1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76-1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82-1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80-1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary. CONCLUSIONS: The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out.

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with an increased risk of arterial thrombosis, but their effect on venous thrombotic events is less well established. The study aimed to assess the risk of symptomatic pulmonary embolism (PE) in patients using NSAIDs and to evaluate any effect of type, dose, and duration of therapy. METHODS: A case-control study was conducted using the PHARMO Record Linkage System, a Dutch population-based registry. Cases were patients hospitalized with a primary diagnosis of PE and were matched to controls without a history of PE. To exclude confounding by indication, the effect of painkillers without known hemostatic effects was assessed. RESULTS: The study population consisted of 4433 cases and 16,802 controls. After adjustment for surgery, trauma, and malignancy, current use of NSAIDs was associated with PE (odds ratio (OR) 2.39, 95% confidence interval (CI) 2.06-2.77). The risk was highest for traditional NSAIDs, and the overall risk for NSAIDs was highest in the first 30 days of exposure (OR 4.77, 95%CI 3.92-5.81), as compared with chronic (<1 year; OR 1.83, 95%CI 1.47-2.28) or long-term use (>1 year; OR 2.14, 95%CI 1.48-3.09). Use of acetaminophen and tramadol also increased the risk of PE (OR 1.74, 95%CI 1.42-2.14 and OR 4.07, 95%CI 2.86-5.75, respectively) with a similar time trend. CONCLUSIONS: Use of NSAIDs is associated with an increased risk of symptomatic PE. This association may be partially explained by underlying medical conditions, as suggested by a similarly increased thrombotic risk in patients receiving acetaminophen and tramadol.

Factor VIII deficiency does not protect against atherosclerosis.

BACKGROUND: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. OBJECTIVES: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. METHODS: Fifty-one obese (body mass index [BMI] ≥ 30 kg m(-2)) and 47 non-obese (BMI ≤ 25 kg m(-2)) hemophilia A patients, and 42 obese and 50 matched non-obese male controls were included. Carotid and femoral intima­media thickness [IMT] and brachial flow-mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. RESULTS: The overall population age was 50 ± 13 years. Carotid IMT was increased in obese subjects (0.77 ± 0.22 mm) as compared with non-obese subjects (0.69 ± 0.16 mm) [mean difference 0.07 mm (95% confidence interval [CI] 0.02­0.13, P = 0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02 mm [95% CI ) 0.07­0.11, P = 0.67], and mean difference of 0.06 mm [95% CI ) 0.13­0.25, P = 0.55], respectively). Thirty-five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P = 0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84% ± 3.24% and 5.32% ± 2.37%, P = 0.45). CONCLUSION: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary.

Cardiovascular risk assessment in haemophilia patients.

Haemophilia patients have a reduced cardiovascular mortality, which may be the result of a lifelong deficiency of factor VIII or IX. On the other hand, the prevalence of risk factors may differ in these chronically ill patients compared to the general population. The prevalence of risk factors and expected risk of cardiovascular disease was compared in haemophilia patients and healthy controls. In adult haemophilia A and B patients, body mass index, blood pressure, cholesterol levels and fasting glucose levels were measured and compared to healthy age-matched males. The expected risk of mortality due to cardiovascular disease was calculated using a European risk prediction algorithm (SCORE). A total of 100 haemophilia A and B patients and 200 healthy controls were analysed. The mean age of the patients was 47 years (range 18-83). The number of haemophiliacs with hyperglycaemia (24%) and hypertension (51%) was higher than in the controls (p-values 0.001 and 0.03, respectively). The mean low-density lipoprotein (LDL) cholesterol level in cases was lower than the controls (3.02 mM (0.69-6.57) and 3.60 mM (1.68-5.95), respectively, p < 0.001). Fewer cases had increased LDL levels (p=0.045). No difference was found in the 10-year cardiovascular mortality risk >10% between cases and controls (12% and 7%, respectively, p = 0.18). The prevalence of risk factors and expected risk of cardiovascular disease in haemophilia patients is comparable to the general population. This strengthens the hypothesis that hypocoagulability may reduce cardiovascular mortality in haemophilia patients.