Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

The association of severe pain experienced in the pediatric intensive care unit and postdischarge health-related quality of life: A retrospective cohort study.

BACKGROUND: Pain may be a modifiable risk factor for lower health-related quality of life after pediatric critical illness. AIM: To evaluate the association between severe pain experienced in the (pediatrc intensive care unit) and postdischarge health-related quality of life. METHODS: This was a retrospective cohort study. Children aged 1 month to 18 years admitted to the pediatric intensive care unit and enrolled in the Seattle Children's Hospital Outcomes Assessment Program were included. Pain was assessed every 2 h by bedside nursing staff using a behavioral pain scale or numeric pain scale. A day of severe pain was defined as a pediatric intensive care unit day with ≥25% of pain scores ≥7/10. Baseline (preadmission) and postdischarge (median 6 weeks) health-related quality of life was assessed by the Pediatric Quality of Life Inventory (PedsQL™) or the Stein Jessop Functional Status II-R (FS II-R, for children with developmental disability). The cohort was stratified by diagnosis category (surgical vs. medical), and associations were measured using linear regression models. RESULTS: Among 546 patients, 11.9% experienced ≥1 day of severe pain. In multivariable linear regression, each day of severe pain was independently associated with a lower postdischarge health-related quality of life score by 3.6 points (95% CI -6.3 to -0.9) adjusted for baseline health-related quality of life score, age, baseline cognitive function, days with multi-organ dysfunction, pediatric intensive care unit length of stay, and decline in overall function. This association was stronger among surgical patients than medical patients with each day of severe pain resulting in a lower postdischarge health-related quality of life score by 5.3 points (95% CI -9.6 to -0.9) versus 2.6 points (95% CI -5.8 to 0.6). Surgical patients had lower postdischarge emotional functioning than physical functioning subdomain scores. CONCLUSIONS: Children who experience severe pain in the pediatric intensive care unit have lower postdischarge health-related quality of life adjusting for baseline health-related quality of life, particularly among children who have undergone surgery. Attention to pain management may be important to improve postdischarge health-related quality of life.

Outcomes of ß-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance.

BACKGROUND: ß-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. METHODS: Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of ß-hemolytic streptococci or clindamycin-resistant ß-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use-related etiology. RESULTS: Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. ß-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of ß-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07-3.01), as was the presence of clindamycin resistance among ß-hemolytic streptococci infections (1.86; 1.10-3.16). CONCLUSIONS: ß-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with ß-hemolytic streptococci-particularly clindamycin-resistant strains-may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.

Occurrence and Timing of Subsequent Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-transcription Polymerase Chain Reaction Positivity Among Initially Negative Patients.

Using data for 20 912 patients from 2 large academic health systems, we analyzed the frequency of severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction test discordance among individuals initially testing negative by nasopharyngeal swab who were retested on clinical grounds within 7 days. The frequency of subsequent positivity within this window was 3.5% and was similar across institutions.

Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B.

BACKGROUND & AIMS: Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB. METHODS: We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality. RESULTS: We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43). CONCLUSIONS: HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB. LAY SUMMARY: Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain. STUDY DESIGN: A multicenter, prospective, cohort study. SETTING & PARTICIPANTS: We evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study. EXPOSURES: Baseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography-tandem mass spectrometry (LC-MS/MS). OUTCOMES: Incident heart failure, myocardial infarction, and stroke events. ANALYTICAL APPROACH: We used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders. RESULTS: Participants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR. LIMITATIONS: Exclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances. CONCLUSIONS: In a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.

Association of Antidepressant Continuation in Pregnancy and Infant Birth Weight.

PURPOSE: The aim of the study was to evaluate the association of antidepressant continuation in pregnancy with infant birth weight among women using antidepressants before pregnancy. METHODS: This retrospective cohort study used electronic health data linked with state birth records. We identified singleton live births (2001-2014) to enrolled women with 1 or more antidepressant prescriptions filled 6 months or less before pregnancy, including "continuers" (≥1 antidepressant fills during pregnancy, n = 1775) and "discontinuers" (no fill during pregnancy, n = 1249). We compared birth weight, small or large for gestational age (SGA or LGA), low birth weight (LBW; <2500 g), and macrosomia (>4500 g) between the 2 groups, using inverse probability of treatment weighting to account for pre-pregnancy characteristics, including mental health conditions. RESULTS: After weighting, infants born to antidepressant continuers weighed 71.9 g less than discontinuers' infants (95% confidence interval [CI], -115.5 to -28.3 g), with a larger difference for female infants (-106.4 g; 95% CI, -164.6 to -48.1) than male infants (-48.5 g; 95% CI, -107.2 to 10.3). For female infants, SGA risk was greater in continuers than discontinuers (relative risk [RR],1.54; 95% CI, 1.02 to 2.32). Low birth weight risk was greater in continuers with 50% or more of days covered (RR, 1.69; 95% CI, 1.11 to 2.58) and exposure in the second trimester (RR, 1.53; 95% CI, 1.02 to 2.29), as compared with discontinuers. CONCLUSIONS: Depending on infant sex, as well as duration and timing of use, continuation of antidepressant use during pregnancy may be associated with lower infant birth weight, with corresponding increases in LBW and SGA.

Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Maternal Gestational Weight Gain in Relation to Antidepressant Continuation in Pregnancy.

OBJECTIVE: Both excessive and inadequate gestational weight gain (GWG) are associated with adverse health outcomes for the woman and her child. Antidepressant use in pregnancy could affect GWG, based on evidence in nonpregnant women that some antidepressants may cause weight gain and others weight loss. Previous studies of antidepressant use and GWG were small with limited ability to account for confounding, including by maternal mental health status and severity. We assessed the association of antidepressant continuation in pregnancy with GWG among women using antidepressants before pregnancy. STUDY DESIGN: Our retrospective cohort study included singleton livebirths from 2001 to 2014 within Kaiser Permanente Washington, an integrated health care system. Data were obtained from electronic health records and linked Washington State birth records. Among women with ≥1 antidepressant fill within 6 months before pregnancy, women who filled an antidepressant during pregnancy were considered "continuers;" women without a fill were "discontinuers." We calculated mean differences in GWG and relative risks (RR) of inadequate and excessive weight gain based on Institute of Medicine guidelines. Using inverse probability of treatment weighting with generalized estimating equations, we addressed differences in maternal characteristics, including mental health conditions. RESULTS: Among the 2,887 births, 1,689 (59%) were to women who continued antidepressants in pregnancy and 1,198 (42%) were to discontinuers. After accounting for confounding, continuers had similar weight gain to those who discontinued (mean difference: 1.3 lbs, 95% confidence interval [CI]: -0.1 to 2.8 lbs) and similar risks of inadequate and excessive GWG (RR: 0.95, 95% CI: 0.80-1.14 and RR: 1.06, 95% CI: 0.98-1.14, respectively). Findings were comparable for specific antidepressants and trimesters of exposure. CONCLUSION: We did not find evidence that continuation of antidepressants in pregnancy led to differences in GWG. KEY POINTS: · Antidepressant use is associated with weight change in nonpregnant populations.. · Prior evidence on whether antidepressant use in pregnancy affects gestational weight gain is sparse.. · We accounted for confounding by characteristics such as mental health conditions and their severity.. · We found no association between pregnancy antidepressant continuation and gestational weight gain..

Selection bias and misclassification in case-control studies conducted using the National Violent Death Reporting System.

Conducting case-control studies using the National Violent Death Reporting System (NVDRS) has the potential to introduce selection bias and misclassification through control selection. Some studies that use NVDRS compare groups of individuals who died by one mechanism, intent or circumstance, to individuals who died by another mechanism, intent or circumstance. For aetiological studies within NVDRS, the use of controls who had a different type of violent death has the potential to introduce selection bias, while relying on narrative summaries for exposure measurement may result in misclassification. We discuss these two methodological issues, and identify an unusual circumstance in which selection of live controls within NVDRS can be employed.

COVID-19 mortality risk for older men and women.

BACKGROUND: Case-fatality from COVID-19 has been reported to be relatively high in patients age 65 years or older. We sought to determine the age-specific rates of COVID-19 mortality at the population level. METHODS: We obtained information regarding the total number of COVID-19 reported deaths for six consecutive weeks beginning at the 50th recorded death, among 16 countries that reported a relatively high number of COVID-19 cases as of April 12, 2020. We performed an ecological study to model COVID-19 mortality rates per week by age group (54 years or younger, 55-64 years, and 65 years or older) and sex using a Poisson mixed effects regression model. RESULTS: Over the six-week period of data, there were 178,568 COVID-19 deaths from a total population of approximately 2.4 billion people. Age and sex were associated with COVID-19 mortality. Compared with individuals ages 54 years or younger, the incident rate ratio (IRR) was 8.1, indicating that the mortality rate of COVID-19 was 8.1 times higher (95%CI = 7.7, 8.5) among those 55 to 64 years, and more than 62 times higher (IRR = 62.1; 95%CI = 59.7, 64.7) among those ages 65 or older. Mortality rates from COVID-19 were 77% higher in men than in women (IRR = 1.77, 95%CI = 1.74, 1.79). CONCLUSIONS: In the 16 countries examined, persons age 65 years or older had strikingly higher COVID-19 mortality rates compared to younger individuals, and men had a higher risk of COVID-19 death than women.

Observational Studies That Seek to Emulate a Randomized Trial of Screening to Reduce the Incidence of Cancer: Do They Address the Question to Which We'd Like to Have an Answer?

Some forms of cancer screening have the potential to reduce cancer incidence, if the screening modality can identify not only a malignancy but a treatable premalignant condition (such as a colon polyp) as well. Cohort studies of the efficacy of these forms of screening in reducing the incidence of cancer face many challenges, notably the difficulty in distinguishing whether a test performed in a given individual was screening or diagnostic in nature. Downward bias in the estimated efficacy of screening resulting from misclassification of test indication is a particular problem in cohort studies that seek to gauge cancer incidence beginning at the time of screening (and a corresponding point in time among unscreened persons). The downward bias is accentuated in those cohort studies that have sought to mimic the "intention-to-treat" analytical approach used in randomized trials, in which initially unscreened persons are retained in this category even if later they themselves undergo screening.

Point: Immortal Time Bias-What Are the Determinants of Its Magnitude?

In cohort studies, "immortal time" bias refers to a portion of time during which events cannot occur for a particular group of participants. Typically, immortal time bias occurs when: 1) Exposure can be initiated after follow-up of cohort members has begun; and 2) analytically, the preexposure experience is combined with that which takes place following exposure, rather than (correctly) as part of the experience of nonexposed individuals. Using the example of a cohort study of mortality in relation to receipt of cataract surgery, we sought to describe those study design and population characteristics that influence the magnitude of immortal time bias, so as to aid readers in gauging its impact on published research findings. These characteristics include the mean interval between cohort entry and when exposure criteria are met, the proportion of exposed study participants, and the length of study follow-up.

Case-Control Studies of the Efficacy of Screening Tests That Seek to Prevent Cancer Incidence: Results of an Approach That Utilizes Administrative Claims Data That Do Not Provide Information Regarding Test Indication.

Case-control studies evaluating a screening test's efficacy in reducing cancer mortality require accurate classification of test indication to obtain a valid result. However, for analogous studies of cancer incidence, determination of test indication is not as critical because, to define exposure, we need consider only tests that can identify precursor lesions whose treatment might prevent cancer, not tests leading to cancer diagnosis. This study utilizes US Surveillance, Epidemiology, and End Results (SEER)-Medicare data, which do not include information about colonoscopy indication, to evaluate the efficacy of colonoscopy in preventing colorectal cancer (CRC) incidence. Cases were Medicare enrollees diagnosed with CRC between 1996 and 2013; up to 3 controls were matched to each case. Colonoscopy receipt prior to presumed onset of occult cancer was associated with an approximately 60% reduction in CRC incidence (odds ratio = 0.41, 95% confidence interval: 0.40, 0.42). The association was robust to differing exposure windows and estimates of occult cancer duration and is similar to those from CRC incidence studies in which exam indication was available. Our results suggest that, when it is impractical/impossible to determine whether tests were conducted for screening, the efficacy of a test in preventing cancer incidence can still be estimated using a case-control study design.

Effectiveness of Intensive Endoscopic Screening for Esophageal Cancer in China: A Community-Based Study.

Evidence is required to evaluate the effectiveness of population-level endoscopic screening for esophageal cancer (EC). In this study, 5,632 permanent residents aged 25-65 years from 6 villages in Hua County, Henan Province, China, were defined as the screening cohort and were offered intensive endoscopic screening. Residents of all 914 remaining villages in Hua County were included as the control cohort, and age-sex standardization was used to calculate the expected numbers of EC and upper gastrointestinal (GI) tract cancer cases and deaths in the screening cohort. The effectiveness of screening was assessed by comparing observed numbers of cases and deaths with expected numbers after 9-year follow-up of these screened subjects (2007-2016). In the screening cohort, 23 upper GI cancers (including 16 ECs) and 10 upper GI cancer deaths (including 5 EC deaths) were identified, and 47% (standardized incidence ratio = 0.53, 95% confidence interval (CI): 0.33, 0.87) and 66% (standardized mortality ratio = 0.34, 95% CI: 0.14, 0.81) reductions in cumulative EC incidence and mortality were found. For upper GI cancers, incidence and mortality were lowered by 43% (standardized incidence ratio = 0.57, 95% CI: 0.38, 0.86) and 53% (standardized mortality ratio = 0.47, 95% CI: 0.25, 0.88), respectively. This study showed that upper GI tract endoscopy is an effective population-level screening test for EC in high-risk regions.

Transplant-Associated Thrombotic Microangiopathy Is a Multifactorial Disease Unresponsive to Immunosuppressant Withdrawal.

Transplant-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic cell transplantation (HCT) has not been well characterized in large population studies with clinically adjudicated cases. We performed a retrospective cohort study of adults who underwent allogeneic HCT between 2006 and 2015 to determine the incidence of and risk factors for TA-TMA and to describe its natural history and response to immunosuppressant withdrawal management. Among 2145 patients in this study, 192 developed TA-TMA with a cumulative incidence of 7.6% by 100days post-transplant. Independent pretransplant risk factors included the receipt of a second (or third) allogeneic HCT, HLA-mismatched donor, and myeloablative conditioning with or without total body irradiation; post-transplant risk factors included the antecedent development of acute graft-versus-host disease, diffuse alveolar hemorrhage, bacteremia, invasive aspergillosis, BK viremia, and higher sirolimus trough level. Among TA-TMA patients 27% achieved hematologic resolution and 57% remained alive as of 90days after diagnosis. Antecedent risk factors stratified patients into different survival groups, and immunosuppressant withdrawal alone did not improve patient outcomes. In conclusion, TA-TMA is a heterogenous disease that occurs after allogeneic transplantation. Management with immunosuppressant withdrawal does not impact patient outcomes. Until further evidence becomes available, the management of TA-TMA should focus on the treatment of underlying diseases.

No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis.

BACKGROUND & AIMS: Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case-control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of α-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis. METHODS: We defined cases (n = 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n = 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening. RESULTS: There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date. CONCLUSIONS: In a matched case-control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case-control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests.

CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy.

PURPOSE: Tamoxifen is widely used to reduce the risk of breast cancer (BC) recurrence and extend disease-free survival among women with estrogen-sensitive breast cancers. Tamoxifen efficacy is thought to be attributable to its active metabolite, which is formed through a reaction catalyzed by the P450 enzyme, CYP2D6. Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications ("inhibitors") is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen. METHODS: The present cohort study of 960 women diagnosed with early-stage BC between 1993 and 1999 examined the association between concomitant use of CYP2D6 inhibitors and adjuvant tamoxifen and the risk of adverse BC outcomes (recurrence, second primary BC, BC mortality), both overall and according to CYP2D6 metabolic phenotype. RESULTS: Six or more months of CYP2D6 inhibitor use concomitant with tamoxifen was not associated with any appreciable increase in risk of recurrence or second primary BC or BC mortality, and there was no clear evidence of variation by CYP2D6 metabolic phenotype. CONCLUSIONS: These results are consistent with the relatively few other large, population-based studies conducted to date that have not observed an increased risk of adverse BC outcomes associated with CYP2D6 inhibition.

Post-diagnosis use of antihypertensive medications and the risk of death from ovarian cancer.

OBJECTIVE: To examine associations between post-diagnosis use of antihypertensive (AH) medications including thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACEIs), beta blockers (BBs) [both non-selective (NSBBs) and selective (SBBs)] and calcium channel blockers (CCBs) and ovarian cancer-specific survival. METHODS: This cohort study used SEER-Medicare data on 2195 women 66+ years of age who were diagnosed with ovarian cancer during 2007-2012 and who survived for at least 12 months. Use of an AH class was defined as two or more fills during the year after diagnosis. Ovarian cancer-specific death was assessed starting one year after diagnosis and continued through the end of 2013. Associations between AH use and ovarian cancer-specific mortality were assessed using Cox proportional hazard models, comparing users of a given class of AH to non-AH users. RESULTS: Overall, 718 (33%), 690 (31%), 521 (24%), 154 (7%) of women used a TD, ACEI, BB, or CCB, respectively, with some women (48%) using more than one class of drug. Ovarian cancer-specific mortality was found to be lower among women who used an ACEI (adjusted hazard ratio [aHR] 0.76, 95% confidence interval [CI] 0.63-0.92), a TD (aHR 0.82, 95%CI 0.68-0.99), or a NSBB (aHR 0.60, 95%CI 0.43-0.83), but no such association was seen in women who took a SBB or CCB. CONCLUSION: We observed that women who took certain forms of an AH medication during the year following a diagnosis of ovarian cancer were thereafter at a relatively reduced risk of dying from their disease. However, the potential for residual confounding by disease severity argues for a cautious interpretation.

Screening flexible sigmoidoscopy versus colonoscopy for reduction of colorectal cancer mortality.

PURPOSE: Colonoscopy and flexible sigmoidoscopy are both recommended colorectal cancer (CRC) screening strategies, but their relative effectiveness is unclear. We sought to evaluate the ability of each of these two modalities to reduce CRC mortality. METHODS: We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were persons aged 70-85 years who died of CRC and were matched to up to three non-CRC controls. Receipt of endoscopy was ascertained from Medicare claims and endoscopy indication assigned using a validated algorithm. Conditional logistic regression models were developed to estimate the association between screening colonoscopy or sigmoidoscopy and CRC mortality. We conducted secondary analyses by race, sex, and endoscopist characteristics, and with varying duration of the look-back period. RESULTS: In the initial analysis using all available look-back years, screening flexible sigmoidoscopy was associated with a 35% reduction in CRC mortality (OR 0.65, 95% CI 0.48, 0.89), while screening colonoscopy was associated with a 74% reduction (OR 0.26, 95% CI 0.23, 0.30). Sigmoidoscopy was not associated with any reduction in proximal CRC mortality. The association between colonoscopy and reduced CRC mortality was stronger in the distal than the proximal colon. Results were similar in analyses using a 5-year look-back period. CONCLUSIONS: Screening colonoscopy was associated with greater reductions in CRC mortality than screening sigmoidoscopy, and with a greater reduction in the distal than the proximal colon. These results provide additional information on the relative benefits of screening for CRC with sigmoidoscopy and colonoscopy.