Sarcopenia has recently been included in the international classification of diseases despite lack of evidence to support essential diagnostic aspects. Christoffer Bjerre Haase and colleagues argue ...that the change is a step towards overdiagnosis
Background The aim of this study was to compare rate of onset, magnitude, and consistency of platelet inhibition after administration of prasugrel or clopidogrel and to relate platelet inhibition to ...systemic exposure to each active metabolite. Thienopyridines are prodrugs, metabolized in vivo to active metabolites that inhibit the platelet P2Y12 adenosine diphosphate (ADP) receptor. Methods This was an open-label, 2-way, crossover study that randomized healthy subjects (n = 68) to an oral loading dose (LD) of prasugrel 60 mg or clopidogrel 300 mg. Platelet aggregation response to 5 and 20 μmol/L of ADP was measured by turbidometric aggregometry. Plasma concentrations of the active metabolites of prasugrel and clopidogrel were quantified by liquid chromatography with tandem mass spectrometry detection methods. Results Inhibition of platelet aggregation (IPA) after prasugrel was significantly higher ( P < .01) than that after clopidogrel from 15 minutes through 24 hours (5 μmol/L ADP) and from 30 minutes through 24 hours (20 μmol/L ADP). For 20 μmol/L ADP, the median time to reach ≥20% IPA was 30 minutes for prasugrel and 1.5 hours for clopidogrel ( P < .001). The maximum IPA was 84.1% ± 9.5% with prasugrel versus 48.9% ± 27.0% with clopidogrel for 5 μmol/L ADP and 78.8% ± 9.2% versus 35.0% ± 24.5%, respectively, for 20 μmol/L ADP ( P < .001). Response to prasugrel was more consistent compared to clopidogrel ( P < .01). The lower IPA response to clopidogrel was associated with lower plasma concentrations of its active metabolite ( P < .001). Conclusions Prasugrel 60 mg LD results in more rapid, potent, and consistent inhibition of platelet function than clopidogrel 300 mg LD. Lower IPA responses to clopidogrel were associated with lower concentrations of its active metabolite.
The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to ...quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration’s risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated.
•Randomised cancer screening trials are rarely designed for estimating overdiagnosis.•Many trials were biased towards underestimating the degree of overdiagnosis.•Overdiagnosis was revealed in screening for lung, breast and prostate cancer.•The first overview and re-analysis of overdiagnosis in cancer screening trials.
In contemporary policy discourses, data are presented as key assets for improving health‐care quality: policymakers want health care to become ‘data driven’. In this article, we focus on a particular ...example of this ambition, namely a new Danish national quality development program for general practitioners (GPs) where doctors are placed in so‐called ‘clusters’. In these clusters, GPs are obliged to assess their own and colleagues’ clinical quality with data derived from their own clinics—using comparisons, averages and benchmarks. Based on semi‐structured interviews with Danish GPs and drawing on Science and Technology Studies, we explore how GPs understand these data, and what makes them trust—or question—a data analysis. The GPs describe how they change clinical practices based on these discussions of data. So, when and how do data for quality assurance come to influence their perceptions of quality? By exploring these issues, we carve out a role for a sociological engagement with evidence in everyday medical practices. In conclusion, we suggest a need to move from the aim of being data driven to one of being data informed.
Introduction
In Denmark, women are discontinued from mammography screening at age 69 due to decreased likelihood of benefits and increased likelihood of harm. The risk of harm increases with age and ...includes false positives, overdiagnosis and overtreatment. In a questionnaire survey, 24 women expressed unsolicited concerns about being discontinued from mammography screening due to age. This calls for further investigation of experiences related to discontinuation from screening.
Methods
We invited the women, who had left comments on the questionnaire, to participate in in‐depth interviews with the purpose to explore their reactions, preferences, and conceptions about mammography screening and discontinuation. The interviews lasted 1–4 h and were followed up with a telephone interview 2 weeks after the initial interview.
Results
The women had high expectations of the benefits of mammography screening and felt that participation was a moral obligation. Following that, they perceived the screening discontinuation as a result of societal age discrimination and consequently felt devalued. Further, the women perceived the discontinuation as a health threat, felt more susceptible to late diagnosis and death, and therefore sought out new ways to control their risk of breast cancer.
Conclusion
Our findings indicate that the age‐related discontinuation from mammography screening might be of more importance than previously assumed. This study raises important questions about screening ethics, and we encourage research to explore this in other settings.
Patient and Public Contribution
This study was conducted as a result of the women's unsolicited concerns about being discontinued from screening. This particular group contributed to the study with their own statements, interpretations and perspectives on the discontinuation of screening, and the initial analysis of data was discussed with the women during follow‐up interviews.
Cytochrome P-450 Polymorphisms and Response to Clopidogrel Mega, Jessica L; Close, Sandra L; Wiviott, Stephen D ...
New England journal of medicine/The New England journal of medicine,
01/2009, Letnik:
360, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The antiplatelet drug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes. This study shows that CYP polymorphisms that reduce clopidogrel activation result in reduced antiplatelet ...effect and less clinical benefit in patients with acute coronary syndromes.
The antiplatelet drug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes. This study shows that CYP polymorphisms that reduce clopidogrel activation result in reduced antiplatelet effect and less clinical benefit in patients with acute coronary syndromes.
Across the spectrum of acute coronary syndromes and in patients undergoing percutaneous coronary interventions (PCI) with stenting, dual antiplatelet therapy with aspirin and clopidogrel, a thienopyridine inhibitor of the platelet P2Y
12
adenosine diphosphate (ADP) receptor, is the standard of care.
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However, the pharmacodynamic response to clopidogrel has substantial interpatient variability,
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and patients with coronary disease with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk for cardiovascular events.
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Clopidogrel is a prodrug that requires biotransformation to an active metabolite by cytochrome P-450 (CYP) enzymes (Figure 1 in the Supplementary Appendix, available . . .
Research on the economic burden of air pollution has focused primarily on its macroeconomic impact. However, as some studies have found that air pollution can lead to avoidance behavior-for example, ...reducing the time spent outdoors-we hypothesize that it can also influence consumer spending activity. We combine high frequency data on ozone and fine particulate pollution with daily consumer spending in brick-and-mortar retail in 129 postal codes in Spain during 2014 to estimate the association between the two. Using a linear fixed effects model, we find that a 1-standard deviation increase in ozone concentration (20.97 μg/m3) is associated with 3.9 percent decrease in consumer spending (95% CI: -0.066, -0.012; p<0.01). The association of fine particulate matter with consumer spending is, however, not statistically significant (β: 0.005; 95% CI: -0.009, 0.018; p>0.10). Further, we do not observe a sufficiently strong bounce-back in consumer spending in the day-or even the week-following higher ozone concentration. Also, we find that the relationship between ozone concentration and consumer spending is heterogeneous, with those aged below 25 and those aged 45 or above exhibiting stronger negative association. This research informs policymakers about a plausibly unaccounted cost of ambient air pollution, even at concentrations lower than the WHO air quality guideline for short-term exposure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Escherichia coli O157:H7 is the leading cause of hemolytic uremic syndrome (HUS). Risk factors for development of this complication warrant identification. Methods. We enrolled children ...infected with E. coli O157:H7 within 1 week of the onset of diarrhea in this prospective cohort study. The study was conducted in 5 states over 9.5 years. The primary and secondary outcomes were HUS (hematocrit <30% with smear evidence of hemolysis, platelet count <150 × 103/μL, and serum creatinine concentration > upper limit of normal for age) and oligoanuric HUS. Univariate and multivariable and ordinal multinomial regression analyses were used to test associations between factors apparent during the first week of illness and outcomes. Results. Of the 259 children analyzed, 36 (14%) developed HUS. Univariate analysis demonstrated that children who received antibiotics during the diarrhea phase more frequently developed HUS than those who did not (36% vs 12%; P = .001). The higher rate of HUS was observed across all antibiotic classes used. In multivariable analysis, a higher leukocyte count (adjusted odds ratios aOR 1.10; 95% CI, 1.03—1.19), vomiting (aOR 3.05; 95% CI, 1.23—7.56), and exposure to antibiotics (aOR 3.62; 95% CI, 1.23—10.6) during the first week of onset of illness were each independently associated with development of HUS. Multinomial ordinal logistic regression confirmed that initial leukocyte count and antibiotic use were independently associated with HUS and, additionally, these variables were each associated with the development of oligoanuric HUS. Conclusions. Antibiotic use during E. coli O157:H7 infections is associated with a higher rate of subsequent HUS and should be avoided.
ObjectiveTo compare the long-term psychosocial consequences of mammography screening among women with breast cancer, normal results and false-positive results.DesignA matched cohort study with ...follow-up of 12–14 years.SettingDenmark from 2004 to 2019.Participants1170 women who participated in the Danish mammography screening programme in 2004–2005.InterventionMammography screening for women aged 50–69 years.Outcome measuresWe assessed the psychosocial consequences with the Consequences Of Screening–Breast Cancer, a condition-specific questionnaire that is psychometrically validated and encompasses 14 psychosocial dimensions.ResultsAcross all 14 psychosocial outcomes, women with false-positive results averagely reported higher psychosocial consequences compared with women with normal findings. Mean differences were statistically insignificant except for the existential values scale: 0.61 (95% CI (0.15 to 1.06), p=0.009). Additionally, women with false-positive results and women diagnosed with breast cancer were affected in a dose–response manner, where women diagnosed with breast cancer were more affected than women with false-positive results.ConclusionOur study suggests that a false-positive mammogram is associated with increased psychosocial consequences 12–14 years after the screening. This study adds to the harms of mammography screening. The findings should be used to inform decision-making among the invited women and political and governmental decisions about mammography screening programmes.
Recently, Schwartz et al. (J Am Soc Nephrol 20:629–637, 2009) used data from the National Institutes of Health-funded Chronic Kidney Disease in Children (CKiD) study to generate new equations for ...estimating the glomerular filtration rate (eGFR), including an update of the commonly used bedside equation. However, it is unclear if the equation can be generalized to a broader pediatric population. We have used the updated equation on a sample of pediatric patients with less impaired renal function to evaluate the correlation between the new Schwartz equation and measured GFR by iothalamate clearance. We retrospectively analyzed 738 iothalamate clearance tests from 503 patients with a mean serum creatinine of 0.50 mg/dl whose ages ranged from 1 to 16 years. We measured bias, precision, and accuracy and performed a Bland–Altman plot to determine the measure of agreement between the two methods. The mean GFR by iothalamate clearance was 110.6 ml/min/1.73 m
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and by the new Schwartz estimation 104.7 ml/min/1.73 m
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. The mean difference was 5.84 ml/min/1.73 m
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(95% CI 4.00–7.67). The newly purposed bedside Schwartz equation therefore demonstrated good agreement with the iothalamate renal clearances in our patient population and appears to be a valid bedside estimating equation for GFR in this sample of children.
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