The widely prescribed diabetes medicine metformin has been reported to lower the risk of incident breast cancer, but it is unclear whether it affects malignant progression after diagnosis. In this ...study, we conducted a retrospective cohort study using the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Women were included in the study if they were aged 66 to 80 years, newly diagnosed with stage I or II breast cancer, and enrolled in Medicare Parts A, B, and D during 2007 to 2011. Information on dispensed diabetes-related medications was obtained from Medicare Part D claims data. Our primary outcomes were second breast cancer events (SBCE), breast cancer recurrence, and breast cancer death. Time-varying Cox proportional hazard models were used to estimate HRs and their 95% confidence intervals (CI). Among 14,766 women included in the study, 791 experienced SBCE, 627 had a recurrence, and 237 died from breast cancer. Use of metformin (
= 2,558) was associated with 28% (95% CI, 0.57-0.92), 31% (95% CI, 0.53-0.90), and 49% (95% CI, 0.33-0.78) lower risks of an SBCE, breast cancer recurrence, and breast cancer death. Use of sulfonylureas or insulin was associated with 1.49- (95% CI, 1.00-2.23) and 2.58-fold (95% CI, 1.72-3.90) higher risks of breast cancer death. Further research may be warranted to determine whether metformin is a preferred treatment for diabetes among breast cancer survivors and whether it benefits breast cancer patients without diabetes.
.
To evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis.
Retrospective cohort study examining data from the Researching Severe Sepsis and Organ ...Dysfunction in Children: A Global Perspective trial (NCT00049764).
One hundred and four pediatric centers in 18 countries.
Children with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384).
None.
Poor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a "poor" functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and 2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6-8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0-9.
In this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an individual's clinical course are associated with poor functional outcome 28 days after onset of severe sepsis. These characteristics may provide opportunity for intervention in order to improve functional outcome in pediatric patients with severe sepsis. Decline in functional status 28 days after onset of severe sepsis is a frequent and potentially clinically meaningful event. Utilization of functional status as the primary outcome in future pediatric sepsis clinical trials should be considered.
Objective
Identification of characteristics associated with active disease in juvenile idiopathic arthritis (JIA) could inform early disease treatment strategies. This study evaluated characteristics ...associated with active disease at 12 and 24 months after JIA diagnosis in the era in which biologic disease‐modifying antirheumatic drugs (DMARDs) became available for JIA.
Methods
This single‐center retrospective study from 2004 through 2018 assessed characteristics associated with active nonsystemic categories of JIA at 12 and 24 months after diagnosis. Relative prevalence (RP) of disease activity was evaluated in relation to prespecified characteristics. Using RP, the effect of increasing biologic DMARD availability on these predictors was assessed at 12 months.
Results
A total of 1,151 patients with JIA were included. At 12 months, a 40% to 45% higher point prevalence of active disease was noted in older children (>5 years). Patients with active disease at 3 months had a greater prevalence of active disease at 12 months (RP 1.5, 95% confidence interval CI 1.2–1.8) and 24 months (RP 1.3, 95% CI 1–1.6). Compared to oligoarticular JIA, polyarticular RF‐negative, psoriatic, and enthesitis‐related JIA had a greater prevalence of active disease at 12 and 24 months. At 24 months, a greater prevalence of active disease was observed in children ≥10 years. RP of active disease was 25% lower in the late cohort (2013–2018) than in the earliest cohort (2004–2008; RP 0.75, 95% CI 0.62–0.92) when more biologic medications were available, but disease activity predictors were broadly similar over time.
Conclusion
Patients with JIA with active disease at 12 and 24 months were older at diagnosis, categorized as polyarticular RF‐negative, psoriatic, or enthesitis‐related JIA. Active disease at 3 months after diagnosis was associated with worse outcomes at 12 and 24 months.
Tubular Secretion in CKD Suchy-Dicey, Astrid M; Laha, Thomas; Hoofnagle, Andrew ...
Journal of the American Society of Nephrology,
07/2016, Letnik:
27, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular ...secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.
The frequency of overdiagnosis associated with breast cancer screening is a topic of controversy. Published estimates vary widely, but identifying which estimates are reliable is challenging. In this ...article we present an approach that provides a check on these estimates. Our approach leverages the close link between overdiagnosis and lead time by identifying the average lead time most consistent with a given overdiagnosis frequency. We consider a high-profile study that suggested that 31% of breast cancers diagnosed in the United States in 2008 were overdiagnosed and show that this corresponds to an average lead time of about nine years among localized cases. Comparing this estimate with the average lead time for invasive, screen-detected breast cancers of 40 months, around which there is a relative consensus, suggests the published estimate of overdiagnosis is excessive. This approach provides a novel way to appraise estimates of overdiagnosis given knowledge of disease natural history.
At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol’s chromoendoscopy (LCE). In this study, we sought to determine ...the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions.
We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy.
LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored.
We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.
Background Albuminuria is a risk factor for chronic kidney disease progression, end-stage renal disease, cardiovascular events, and mortality. Animal studies suggested that vitamin D insufficiency ...may contribute to the pathogenesis of albuminuria. Study Design Cross-sectional study. Setting & Participants 15,068 adults participating in the Third National Health and Nutrition Examination Survey. Predictor Serum 25-hydroxyvitamin D concentration, examined in quartiles. Outcomes & Measurements Albuminuria, defined using established sex-specific cutoff values for urine albumin-creatinine ratio (25 to 2,999 mg/g for women, 17 to 2,999 mg/g for men). Results A stepwise increase in the prevalence of albuminuria was observed with decreasing quartiles of vitamin D concentration: 8.9%, 11.5%, 13.7%, and 15.8% ( P < 0.001). Adjusting for age, sex, race/ethnicity, region and season of measurement, smoking status, body mass index, and estimated glomerular filtration rate, relative risks for albuminuria by decreasing quartile of vitamin D concentration were 1.00 (reference group), 1.14 (95% confidence interval, 0.95 to 1.37), 1.22 (95% confidence interval, 1.03 to 1.45), and 1.37 (95% confidence interval, 1.10 to 1.71; P = 0.006). Additionally adjusting for blood pressure and diabetes mellitus, these risks were somewhat attenuated and retained statistical significance. Limitations The cross-sectional design of this study does not allow demonstration of temporal or causal relationships between vitamin D and albuminuria. Conclusions Additional studies are needed to clarify the relationship of vitamin D with albuminuria and determine whether vitamin D therapy prevents or improves markers of kidney and cardiovascular disease.
Given the high morbidity for mother and fetus associated with malaria in pregnancy, safe and efficacious drugs are needed for treatment. Artemisinin derivatives are the most effective antimalarials, ...but are associated with teratogenic and embryotoxic effects in animal models when used in early pregnancy. However, several organ systems are still under development later in pregnancy. We conducted a systematic review and meta-analysis of the occurrence of adverse pregnancy outcomes among women treated with artemisinins monotherapy or as artemisinin-based combination therapy during the 2nd or 3rd trimesters relative to pregnant women who received non-artemisinin antimalarials or none at all. Pooled odds ratio (POR) were calculated using Mantel-Haenszel fixed effects model with a 0.5 continuity correction for zero events. Eligible studies were identified through Medline, Embase, and the Malaria in Pregnancy Consortium Library. Twenty studies (11 cohort studies and 9 randomized controlled trials) contributed to the analysis, with 3,707 women receiving an artemisinin, 1,951 a non-artemisinin antimalarial, and 13,714 no antimalarial. The PORs (95% confidence interval (CI)) for stillbirth, fetal loss, and congenital anomalies when comparing artemisinin versus quinine were 0.49 (95% CI 0.24-0.97, I2 = 0%, 3 studies); 0.58 (95% CI 0.31-1.16, I2 = 0%, 6 studies); and 1.00 (95% CI 0.27-3.75, I2 = 0%, 3 studies), respectively. The PORs comparing artemisinin users to pregnant women who received no antimalarial were 1.13 (95% CI 0.77-1.66, I2 = 86.7%, 3 studies); 1.10 (95% CI 0.79-1.54, I2 = 0%, 4 studies); and 0.79 (95% CI 0.37-1.67, I2 = 0%, 3 studies) for miscarriage, stillbirth and congenital anomalies respectively. Treatment with artemisinin in 2nd and 3rd trimester was not associated with increased risks of congenital malformations or miscarriage and may be was associated with a reduced risk of stillbirths compared to quinine. This study updates the reviews conducted by the WHO in 2002 and 2006 and supports the current WHO malaria treatment guidelines malaria in pregnancy.
In Memoriam: Janet R. Daling, 1934–2022 Li, Christopher I; Weiss, Noel S; Madeleine, Margaret M ...
American journal of epidemiology,
07/2023, Letnik:
192, Številka:
7
Journal Article
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