Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019.

Light-chain (AL) amyloidosis is a multisystem disorder with a high early mortality and diagnostic delays of >1 year from symptom onset. This retrospective observational study sought to characterize the clinical prodrome and diagnostic delay to inform early detection. We identified 1523 adults with newly diagnosed AL amyloidosis in the Optum de-identified Clinformatics® Datamart US healthcare claims database as those with ≥2 new diagnosis codes for AL or other amyloidosis in 90 days with ≥1 multiple myeloma treatment within 730 days, excluding patients with prior hereditary or secondary amyloidosis and Familial Mediterranean Fever. We considered 34 signs/symptoms using diagnosis codes in all observable time on or before AL amyloidosis diagnosis. Sign/symptom prevalence was compared to that of 1:4 matched population controls. The overlap and sequence of signs/symptoms and the median time from first sign/symptom to AL amyloidosis diagnosis were explored. Healthcare utilization was summarized. The most common individual AL amyloidosis signs/symptoms were malaise/fatigue (61%) and dyspnea (59%). Cardiac signs/symptoms were observed in 77% of patients, followed by renal (62%) and neurologic (59%) signs/symptoms. Multisystem involvement (≥3 systems) was present in 54%. Monoclonal gammopathy was detected in 29% before diagnosis. Median time from symptom onset to AL amyloidosis diagnosis was 2.7 years. Healthcare utilization was high between first AL amyloidosis signs/symptoms and diagnosis, with 50% visiting ≥5 physician types. AL amyloidosis patients have a lengthy and complex clinical prodrome. Novel approaches to early diagnosis are needed to improve outcomes.

Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis.

Antioxidant vitamins may reduce cancer risk by limiting oxidative DNA damage. To summarize and quantify the current epidemiologic evidence of an association between antioxidant vitamin intake and endometrial cancer, we conducted a systematic literature review and meta-analysis. One cohort and 12 case-control studies presenting relevant risk estimates were identified by conducting bibliographical searches through June 2008. Dose-response meta-analyses were conducted for beta-carotene, vitamin C, and vitamin E from food sources. Intake from supplements was not considered in the meta-analyses because of the few studies that reported relevant information. Based on case-control data, the random-effects summary odds ratios (OR) were, for beta-carotene: 0.88 (95% CI: 0.79-0.98) per 1,000 mcg/1,000 kcal (I2: 77.7%; p < 0.01); for vitamin C: 0.85 (95% CI: 0.73-0.98) per 50 mg/1,000 kcal (I2: 66.1%; p < 0.01); and, for vitamin E: 0.91 (95% CI: 0.84-0.99) per 5 mg/1,000 kcal (I2: 0.0%; p: 0.45). In contrast, the only prospective study identified provided little indication of an association. Although the current case-control data suggest an inverse relationship of endometrial cancer risk with dietary intakes of beta-carotene, vitamin C, and vitamin E from food sources, additional studies are needed, particularly cohort studies, to confirm an association.

Association between dietary fiber and endometrial cancer: a dose-response meta-analysis.

BACKGROUND: Endometrial cancer is the most common female gynecologic cancer in the United States. Excessive and prolonged exposure of the endometrium to estrogens unopposed by progesterone and a high body mass are well-established risk factors for endometrial cancer. Although dietary fiber has been shown to beneficially reduce estrogen concentrations and prevent obesity, its role in endometrial cancer has received relatively little attention. OBJECTIVE: The objective was to summarize and quantify the current evidence of a role of dietary fiber consumption in endometrial cancer risk and to identify research gaps in this field. DESIGN: We conducted a systematic literature review of articles published through February 2007 to summarize the current evidence of a relation between dietary fiber consumption and endometrial cancer risk and to quantify the magnitude of the association by conducting a dose-response meta-analysis. RESULTS: Ten articles representing 1 case-cohort study and 9 case-control studies that evaluated several aspects of fiber consumption and endometrial cancer risk were identified through searches in various databases. On the basis of 7 case-control studies, the random-effects summary risk estimate was 0.82 (95% CI: 0.75, 0.90) per 5 g/1000 kcal dietary fiber, with no evidence of heterogeneity (I(2): 0%, P for heterogeneity: 0.55). The random-effects summary estimate was 0.71 (95% CI: 0.59, 0.85) for the comparison of the highest with the lowest dietary fiber intake in 8 case-control studies, with little evidence of heterogeneity (I(2): 20.8%, P for heterogeneity: 0.26). In contrast, the only prospective study that evaluated this association did not find an association. CONCLUSIONS: Although the current evidence, based on data from case-control studies, supports an inverse association between dietary fiber and endometrial cancer, additional population-based studies, particularly cohort studies, are needed before definitive conclusions can be drawn.

Consumption of animal foods and endometrial cancer risk: a systematic literature review and meta-analysis.

This article summarizes and quantifies the current evidence relating dietary intake of animal products and endometrial cancer. Literature searches were conducted to identify peer-reviewed manuscripts published up to December 2006. Twenty-two manuscripts from three cohort studies and 16 case-control studies were identified. One of these cohort studies evaluated only fried meat and another only milk consumption; they were not included in our meta-analyses. The third cohort study identified did not present exposure levels and could not be included in dose-response meta-analysis. This cohort study did not show an association with meat or red meat consumption. Random-effects dose-response summary estimates for case-control studies evaluating these foods were 1.26 (95% CI: 1.03-1.54) per 100 g/day of total meat, 1.51 (95% CI: 1.19-1.93) per 100 g/day of red meat, 1.03 (95% CI: 0.32-3.28) per 100 g/day of poultry, 1.04 (95% CI: 0.55-1.98) per 100 g/day of fish, and 0.97 (95% CI: 0.93-1.01) per serving of dairy. Our meta-analysis, based on case-control data, suggests that meat consumption, particularly red meat, increases endometrial cancer risk. The current literature does not support an association with dairy products, while the evidence is inconsistent for poultry, fish, and eggs. More studies, particularly prospective studies, are needed.

Dietary lipids and endometrial cancer: the current epidemiologic evidence.

BACKGROUND: Because dietary fat has been postulated to affect obesity and estrogen levels, two important risk factors for endometrial cancer, its association with this disease has received some attention. We summarize here the current evidence for several dietary lipids. METHODS: Searches were conducted to identify peer-reviewed manuscripts up to December 2006. Two cohort studies and nine case-control studies were included in meta-analyses. RESULTS: Random-effects summary estimates for case-control studies were 1.24 (95% CI: 1.10, 1.41) per 10% kcal from total fat and 1.28 (95% CI: 1.12, 1.47) per 10 g/1,000 kcal of saturated fat. The only cohort study evaluating total fat and saturated fat did not find an association. We estimated a 35% increased risk (95% CI: 0.96, 1.90) per 150 mg/1,000 kcal of cholesterol intake, based on six case-control studies. For animal fat (per 10 g/1,000 kcal) the summary estimates were 0.78 (95% CI: 0.63, 0.96) and 1.34 (95% CI: 1.06, 1.69) for two cohort and four case-control studies, respectively. CONCLUSIONS: Case-control data suggest an increased risk for total, saturated, and animal fat. However, the limited available cohort data do not support these associations. Additional data, particularly from prospective studies, are needed before conclusions can be drawn.

Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis.

Endometrial cancer is the most common female gynecological cancer in the United States. Although obesity is a well-established risk factor, the role of other dietary factors is not well understood. The purpose of this study was to summarize and quantify the current evidence for fruit and vegetable intake and endometrial cancer by conducting a systematic literature review and meta-analysis. Searches were conducted to identify relevant papers published up to June 2006 in various databases. We included peer-reviewed manuscripts published in any language. Random and fixed-effects pooled risk estimates were estimated. We found one cohort study and 16 case-control studies evaluating various aspects of consumption. The random-effects summary estimates (95% CI) comparing high vs. low categories of intake reported were 0.71 (0.55-0.91) for total vegetables based on 10 studies, 0.85 (0.74-0.97) for cruciferous vegetables based on seven studies, and 0.90 (0.72-1.12) for total fruit based on 14 studies. For 100 g/day intake, summary ORs were 0.90 (0.86-0.95) for total vegetables, 0.79 (0.69-0.90) for cruciferous vegetables, and 0.97 (0.92-1.02) for total fruit. Excluding studies not meeting certain quality criteria provided similar results. The current evidence, based solely on case-control studies, with less than half being population-based, suggests a modest inverse association with vegetable consumption, particularly for cruciferous vegetables. We did not find any cohort studies evaluating fruit and vegetables separately. No firm conclusion can be drawn at this time in the absence of additional well-conducted population-based studies and, particularly, prospective data.