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2.
Pediatrics ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811179

RESUMO

BACKGROUND: A mother whose child has a chronic condition, such as a major congenital anomaly, often experiences poorer long-term health, including earlier mortality. Little is known about the long-term health of fathers of infants with a major congenital anomaly. METHODS: In this population-based prospective cohort study, we used individual-linked Danish registry data. Included were all mothers and fathers with a singleton infant born January 1, 1986, to December 31, 2015. Cox proportional hazards regression was used to generate hazard ratios for all-cause and cause-specific mortality among mothers and fathers whose infant had an anomaly and fathers of unaffected infants, relative to mothers of unaffected infants (referent), adjusted for child's year of birth, parity, parental age at birth, parental comorbidities, and sociodemographic characteristics. RESULTS: In total, 20 952 of 965 310 mothers (2.2%) and 20 655 of 951 022 fathers (2.2%) had an infant with a major anomaly. Median (interquartile range) of parental follow-up was 17.9 (9.5 to 25.5) years. Relative to mothers of unaffected infants, mothers of affected infants had adjusted hazard ratios (aHRs) of death of 1.20 (95% confidence interval [CI]: 1.09 to 1.32), fathers of unaffected infants had intermediate aHR (1.62, 95% CI: 1.59 to 1.66), and fathers of affected infants had the highest aHR (1.76, 95% CI: 1.64 to 1.88). Heightened mortality was primarily due to cardiovascular and endocrine/metabolic diseases. CONCLUSIONS: Mothers and fathers of infants with a major congenital anomaly experience an increased risk of mortality, often from preventable causes. These findings support including fathers in interventions to support the health of parental caregivers.

3.
J Diabetes Complications ; : 107873, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33627253

RESUMO

AIMS: In individuals at increased risk of infections, e.g., patients with type 2 diabetes, low MBL may have detrimental effects. We used the Mendelian randomization principle to examine whether genetically low MBL is a risk factor for developing infections in patients with type 2 diabetes. METHODS: Serum MBL (n = 7305) and MBL genotype (n = 3043) were determined in a nationwide cohort of patients with new type 2 diabetes and up to 8 years follow-up for hospital-treated infections and community-based antimicrobial prescriptions. The associations were examined in spline and Cox regression analyses. RESULTS: 1140 patients (16%) were hospitalized with an infection and 5077 patients (70%) redeemed an antimicrobial prescription. For low (≤100 µg/L) versus intermediate (101-1000 µg/L) serum MBL concentration, the adjusted hazard ratios (aHRs) were 1.13(95% confidence interval, 0.96-1.33) for any hospital-treated infections and 1.19(1.01-1.41) for bacterial infections. Low MBL expression genotype was not associated with risk of any hospital-treated infections except for diarrheal diseases (aHR 2.23[1.04-4.80]). Low MBL expression genotype, but not low serum MBL, was associated with increased risk for antimicrobial prescriptions (aHR 1.18[1.04-2.34] and antibacterial prescriptions 1.20[1.05-1.36]). CONCLUSIONS: Low MBL is a weak causal risk factor for developing infections in patients with type 2 diabetes.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33629103

RESUMO

AIMS: To examine combined and sex-specific temporal changes in risks of adverse cardiovascular events and coronary revascularization in patients with chronic coronary syndrome undergoing coronary angiography. METHODS: We included all patients with stable angina pectoris and coronary artery disease examined by coronary angiography in Western Denmark from 2004 to 2016. Patients were stratified by examination year interval: 2004-2006, 2007-2009, 2010-2012, and 2013-2016. Outcomes were two-year risk of myocardial infarction, ischemic stroke, cardiac death, and all-cause death estimated by adjusted incidence rate ratios using patients examined in 2004-2006 as reference. RESULTS: A total of 29,471 patients were included, of whom 70% were men. The two-year risk of myocardial infarction (2.8% versus 1.9%, adjusted incidence rate ratio 0.65, 95% CI 0.53-0.81), ischemic stroke (1.8% versus 1.1%, adjusted incidence rate ratio 0.48, 95% CI 0.37-0.64), cardiac death (2.1% versus 0.9%, adjusted incidence rate ratio 0.38, 95% CI 0.29-0.51), and all-cause death (5.0% versus 3.6%, adjusted incidence rate ratio 0.65, 95% CI 0.55-0.76) decreased from the first examination interval (2004-2006) to the last examination interval (2013-2016). Coronary revascularizations also decreased (percutaneous coronary intervention: 51.6% versus 42.5%; coronary artery bypass grafting: 24.6% versus 17.5%). Risk reductions were observed in both men and women, however, women had a lower absolute risk. CONCLUSION: The risk for adverse cardiovascular events decreased substantially in both men and women with chronic coronary syndrome from 2004 to 2016. These results most likely reflect the cumulative effect of improvements in the management of chronic coronary artery disease.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33583126

RESUMO

BACKGROUND: Statins exert pleiotropic anti-inflammatory effects and may prevent diverticular disease. However, the association remains poorly understood with previous studies obtaining conflicting results. AIMS: To examine the effect of statin on the subsequent risk of diverticular disease. METHODS: We conducted a nested case-control study in Denmark among respondents (>18 years) of the 2010 or the 2013 Danish National Health Survey. Among these, we identified 8809 cases of hospital-diagnosed diverticular disease and risk-set sampled population controls without diverticular disease. Using complete prescription and hospital records, we used conditional logistic regression to compute odds ratios (ORs) associating statin use with diverticular disease. In adjusted analyses, we controlled for hospital-based diagnoses, medication use other than statins, and lifestyle and socioeconomic factors. RESULTS: The fully adjusted OR for diverticular disease associated with ever use (≥1 statin prescription filling) was 1.19 (95% CI: 1.12-1.27) compared with never use. However, we observed no dose-response relation. For example, among short-term users (<5 years), the OR was 1.18 (95% CI: 1.04-1.35) for low intensity users and 1.13 (95% CI: 1.01-1.26) for high intensity users. Among long-term users (≥5 years), the respective ORs were 1.25 (95% CI: 1.13-1.38) and 1.11 (95% CI: 0.98-1.24). In analyses restricting to cases and controls with a previous colonoscopy, associations were null (OR: 1.01 [95% CI: 0.85-1.20]). CONCLUSIONS: The observed association of a higher risk of diverticular disease associated with statins could be explained by diagnostic bias. Our study did not support a protective nor harmful effect of statins on the risk of diverticular disease.

6.
Am J Epidemiol ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33569573

RESUMO

The role of lifestyle in development of herpes zoster remains unclear. We examined whether smoking status, alcohol consumption, body mass index (BMI), or physical activity were associated with zoster risk. We followed a population-based cohort of 101,894 respondents to the 2010 Danish National Health Survey (baseline May 1, 2010) until zoster diagnosis, death, emigration, or July 1, 2014, whichever occurred first. We computed hazard ratios for zoster associated with each exposure, using Cox regression with age as the time-scale and adjusting for potential confounders. Compared with never smokers, hazards for zoster were increased in former smokers [1.17; 95% confidence interval (CI): 1.06, 1.30], but not in current smokers (1.00; 95% CI: 0.89, 1.13). Compared with low-risk alcohol consumption, neither intermediate-risk (0.95; 95% CI: 0.84, 1.07) nor high-risk alcohol consumption (0.99; 95% CI: 0.85, 1.15) were associated with zoster. We also found no increased hazard associated with weekly binge drinking vs. not (0.93; 95% CI: 0.77, 1.11). Risk of zoster varied little by BMI (referent=normal weight) and physical activity levels (referent=light level), with HRs between 0.96 and 1.08. We observed no dose-response association between the exposures and zoster. The examined lifestyle and anthropometric factors thus were not risk factors for zoster.

7.
Addiction ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620758

RESUMO

BACKGROUND AND AIMS: Persons with substance use disorders (SUDs) are at elevated risk of suicide death. We identified novel risk factors and interactions that predict suicide among men and women with SUD using machine learning. DESIGN: Case-cohort study. SETTING: Denmark. PARTICIPANTS: The sample was restricted to persons with their first SUD diagnosis during 1995 to 2015. Cases were persons who died by suicide in Denmark during 1995 to 2015 (n = 2774) and the comparison subcohort was a 5% random sample of individuals in Denmark on 1 January 1995 (n = 13 179). MEASUREMENTS: Suicide death was recorded in the Danish Cause of Death Registry. Predictors included social and demographic information, mental and physical health diagnoses, surgeries, medications, and poisonings. FINDINGS: Persons among the highest risk for suicide, as identified by the classification trees, were men prescribed antidepressants in the 4 years before suicide and had a poisoning diagnosis in the 4 years before suicide; and women who were 30+ years old and had a poisoning diagnosis 4 years before and 12 months before suicide. Among men with SUD, the random forest identified five variables that were most important in predicting suicide; reaction to severe stress and adjustment disorders, drugs used to treat addictive disorders, age 30+ years, antidepressant use, and poisoning in the 4 prior years. Among women with SUD, the random forest found that the most important predictors of suicide were prior poisonings and reaction to severe stress and adjustment disorders. Individuals in the top 5% of predicted risk accounted for 15% of all suicide deaths among men and 24% of all suicides among women. CONCLUSIONS: In Denmark, prior poisoning and comorbid psychiatric disorders may be among the most important indicators of suicide risk among persons with substance use disorders, particularly among women.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33627380

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD. METHODS: This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. RESULTS: Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (n = 28), ICC (n = 28), and ECC (n = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. CONCLUSIONS: Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC. IMPACT: Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.

9.
JAMA Netw Open ; 4(2): e2037053, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566109

RESUMO

Importance: Alpha 1-adrenergic receptor blocking agents (α1-blockers) have been reported to have protective benefits against hyperinflammation and cytokine storm syndrome, conditions that are associated with mortality in patients with coronavirus disease 2019 and other severe respiratory tract infections. However, studies of the association of α1-blockers with outcomes among human participants with respiratory tract infections are scarce. Objective: To examine the association between the receipt of α1-blockers and outcomes among adult patients hospitalized with influenza or pneumonia. Design, Setting, and Participants: This population-based cohort study used data from Danish national registries to identify individuals 40 years and older who were hospitalized with influenza or pneumonia between January 1, 2005, and November 30, 2018, with follow-up through December 31, 2018. In the main analyses, patients currently receiving α1-blockers were compared with those not receiving α1-blockers (defined as patients with no prescription for an α1-blocker filled within 365 days before the index date) and those currently receiving 5α-reductase inhibitors. Propensity scores were used to address confounding factors and to compute weighted risks, absolute risk differences, and risk ratios. Data were analyzed from April 21 to December 21, 2020. Exposures: Current receipt of α1-blockers compared with nonreceipt of α1-blockers and with current receipt of 5α-reductase inhibitors. Main Outcomes and Measures: Death within 30 days of hospital admission and risk of intensive care unit (ICU) admission. Results: A total of 528 467 adult patients (median age, 75.0 years; interquartile range, 64.4-83.6 years; 273 005 men [51.7%]) were hospitalized with influenza or pneumonia in Denmark between 2005 and 2018. Of those, 21 772 patients (4.1%) were currently receiving α1-blockers compared with a population of 22 117 patients not receiving α1-blockers who were weighted to the propensity score distribution of those receiving α1-blockers. In the propensity score-weighted analyses, patients receiving α1-blockers had lower 30-day mortality (15.9%) compared with patients not receiving α1-blockers (18.5%), with a corresponding risk difference of -2.7% (95% CI, -3.2% to -2.2%) and a risk ratio (RR) of 0.85 (95% CI, 0.83-0.88). The risk of ICU admission was 7.3% among patients receiving α1-blockers and 7.7% among those not receiving α1-blockers (risk difference, -0.4% [95% CI, -0.8% to 0%]; RR, 0.95 [95% CI, 0.90-1.00]). A comparison between 18 280 male patients currently receiving α1-blockers and 18 228 propensity score-weighted male patients currently receiving 5α-reductase inhibitors indicated that those receiving α1-blockers had lower 30-day mortality (risk difference, -2.0% [95% CI, -3.4% to -0.6%]; RR, 0.89 [95% CI, 0.82-0.96]) and a similar risk of ICU admission (risk difference, -0.3% [95% CI, -1.4% to 0.7%]; RR, 0.96 [95% CI, 0.83-1.10]). Conclusions and Relevance: This cohort study's findings suggest that the receipt of α1-blockers is associated with protective benefits among adult patients hospitalized with influenza or pneumonia.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Mortalidade Hospitalar , Hospitalização , Inflamação/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Unidades de Terapia Intensiva , Pneumonia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , /patologia , Estudos de Coortes , Dinamarca , Feminino , Humanos , Inflamação/etiologia , Influenza Humana/mortalidade , Influenza Humana/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia/mortalidade , Pneumonia/patologia , Pontuação de Propensão , Índice de Gravidade de Doença
10.
J Alzheimers Dis ; 79(4): 1601-1612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33459639

RESUMO

BACKGROUND: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. OBJECTIVE: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer's disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). METHODS: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000-2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200-600 pmol/L). We used multivariable Cox regression to compute 0-15-year hazard ratios for dementia. RESULTS: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. CONCLUSION: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

11.
J Affect Disord ; 282: 712-716, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33445098

RESUMO

BACKGROUND: Posttraumatic stress disorder is a well-documented risk factor for cardiovascular disease. Whether non-specific stress-related psychopathology also increases risk is less well known. METHODS: In a cohort of adult Danish-born residents of Denmark with an incident diagnosis of unspecified reaction to severe stress ("unspecified stress reaction") between 1995 and 2011 (N = 24,534), we assessed incidence of seven arterial and venous cardiovascular events/conditions between 1996 and 2013. We calculated standardized incidence ratios (SIRs) comparing incidence of each outcome among the cohort to expected incidence based on sex-, age-, and calendar-time-specific national rates. We conducted stratified analyses by demographic characteristics, comorbidities, and length of follow-up time. RESULTS: Incidence over the study period ranged from 1.1% for provoked VTE to 5.7% for stroke, adjusting for competing risk of death. Unspecified stress reaction was associated with all outcomes (SIRs ranging from 1.3, 95% confidence interval (CI): 1.1-1.4 for atrial fibrillation/flutter to 1.9, 95% CI: 1.7-2.2 for unprovoked VTE and 1.9, 95% CI: 1.6-2.3 for provoked VTE). Associations persisted, but were attenuated, when restricting to persons without alcohol use disorder and to persons without physical health comorbidities. LIMITATIONS: Unspecified stress reaction has less precise criteria than other stress-related diagnoses, and we could not adjust for some potential confounders. CONCLUSIONS: Our results augment literature on stress disorders and cardiovascular disease by highlighting the additional importance of unspecified stress disorders. Further research on this diagnostic category, which may represent subsyndromal psychopathology, is warranted. These findings support considering persons with non-specific stress-related psychopathology in treatment and tertiary prevention activities.

12.
Cardiovasc Diabetol ; 20(1): 23, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478504

RESUMO

BACKGROUND: Diabetes patients without obstructive coronary artery disease as assessed by coronary angiography have a low risk of myocardial infarction, but their myocardial infarction risk may still be higher than the general population. We examined the 10-year risks of myocardial infarction, ischemic stroke, and death in diabetes patients without obstructive coronary artery disease according to coronary angiography, compared to risks in a matched general population cohort. METHODS: We included all diabetes patients without obstructive coronary artery disease examined by coronary angiography from 2003 to 2016 in Western Denmark. Patients were matched by age and sex with a cohort from the Western Denmark general population without a previous myocardial infarction or coronary revascularization. Outcomes were myocardial infarction, ischemic stroke, and death. Ten-year cumulative incidences were computed. Adjusted hazard ratios (HR) then were computed using stratified Cox regression with the general population as reference. RESULTS: We identified 5734 diabetes patients without obstructive coronary artery disease and 28,670 matched individuals from the general population. Median follow-up was 7 years. Diabetes patients without obstructive coronary artery disease had an almost similar 10-year risk of myocardial infarction (3.2% vs 2.9%, adjusted HR 0.93, 95% CI 0.72-1.20) compared to the general population, but had an increased risk of ischemic stroke (5.2% vs 2.2%, adjusted HR 1.87, 95% CI 1.47-2.38) and death (29.6% vs 17.8%, adjusted HR 1.24, 95% CI 1.13-1.36). CONCLUSIONS: Patients with diabetes and no obstructive coronary artery disease have a 10-year risk of myocardial infarction that is similar to that found in the general population. However, they still remain at increased risk of ischemic stroke and death.

13.
Dis Colon Rectum ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33496488

RESUMO

BACKGROUND: Patients undergoing total colectomy for inflammatory bowel disease (IBD) may develop cancer in the rectal remnant, but the association is poorly understood. OBJECTIVES: To examine risk and prognosis of rectal cancer after total colectomy for IBD. DESIGN: Nationwide population-based study. SETTING: Denmark 1977-2013. PATIENTS: Patients with IBD undergoing total colectomy. MAIN OUTCOME MEASURES: We examined incidence of rectal cancer among patients with IBD and total colectomy and compared cancer stage to that of other rectal cancer patients in Denmark. We used Kaplan-Meier methodology to estimate survival and Cox regression to estimate adjusted mortality rate ratios (aMRRs) following a rectal cancer diagnosis, comparing patients with and without IBD and a rectal remnant. RESULTS: We identified 4,703 patients with IBD (1,026 Crohn's disease; 3,677 ulcerative colitis) who underwent total colectomy with a rectal remnant. During 29,725 years of follow-up, 30 rectal cancers were observed, compared to 8 expected [standardized incidence ratio (SIR)=3.6, (95% confidence interval (CI): 2.4-5.1)]. Cancer stage distributions were similar. Risk of rectal cancer 35 years after total colectomy was 1.9% (95% CI:1.1%-2.9%). Five years after rectal cancer diagnosis, survival was 28% (95% CI: 12%-47%) and 38% (95% CI: 37%-38%) for patients with and without IBD and a rectal remnant, respectively. The aMRR 1-5 years after a rectal cancer diagnosis was 2.5 (95% CI: 1.6-3.9). Median time from last recorded non-diagnostic proctoscopy to rectal cancer diagnosis for patients with IBD and total colectomy was 1.1 years. LIMITATIONS: Few outcomes, use of administrative and not clinical data. CONCLUSION: Long-term risk of rectal cancer following total colectomy for IBD was low. Survival following a diagnosis of rectal cancer was poorer for patients with IBD and total colectomy than for rectal cancer patients without IBD and total colectomy. Endoscopic surveillance, as it appeared to be practiced in this cohort, may be inadequate. See Video Abstract at http://links.lww.com/DCR/B497 .

14.
Eur J Endocrinol ; 184(4): R111-R122, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33449912

RESUMO

Glucocorticoids are, besides non-steroidal anti-inflammatory drugs, the most widely used anti-inflammatory medications. Prevalence studies indicate substantial use of both systemic and locally acting agents. A recognised adverse effect of glucocorticoid treatment is adrenal insufficiency, which is highly prevalent based on biochemical testing, but its clinical implications are poorly understood. Current evidence, including randomised trials and observational studies, indicates substantial variation among patients in both risk and course of glucocorticoid-induced adrenal insufficiency, but both are currently unpredictable. Oral and intra-articular formulations, as well as long-term and high-dose treatments, carry the highest risk of glucocorticoid-induced adrenal insufficiency defined by biochemical tests. However, no route of administration, treatment duration, or dose can be considered without risk. More research is needed to estimate the risk and temporal pattern of glucocorticoid-induced adrenal insufficiency, to investigate its clinical implications, and to identify predictors of risk and prognosis. Randomized trials are required to evaluate whether hydrocortisone replacement therapy mitigates risk and symptoms of glucocorticoid-induced adrenal insufficiency in patients discontinuing glucocorticoid treatment. This review aims to provide an overview of the available evidence, pointing to knowledge gaps and unmet needs.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/tratamento farmacológico , Glucocorticoides/efeitos adversos , Terapia de Reposição Hormonal , Insuficiência Adrenal/fisiopatologia , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiopatologia
15.
Clin Cancer Res ; 27(5): 1421-1428, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33334905

RESUMO

PURPOSE: Premenopausal women diagnosed with estrogen receptor (ER)-positive breast cancer are prescribed 5-10 years of endocrine therapy to prevent or delay recurrence. In this study, we evaluated the association between early discontinuation of endocrine therapy and breast cancer recurrence in a cohort of premenopausal women. EXPERIMENTAL DESIGN: We identified 4,503 patients with premenopausal ER-positive breast cancer who initiated adjuvant endocrine therapy and were registered in the Danish Breast Cancer Group clinical database (2002-2011). Women were excluded if they had a recurrence or were lost to follow-up less than 1.5 years after breast cancer surgery. Endocrine therapy was considered complete if the patient received at least 4.5 years of treatment or discontinued medication less than 6 months before recurrence. Exposure status was updated annually and modeled as a time-dependent variable. We accounted for baseline and time-varying confounders via time-varying weights, which we calculated from multivariable logistic regression models, and included in regression models to estimate HRs and 95% confidence intervals (CIs) associating early discontinuation with recurrence. RESULTS: Over the study follow-up, 1,001 (22%) women discontinued endocrine therapy. We observed 202 (20%) recurrences among those who discontinued endocrine therapy, and 388 (11%) among those who completed the recommended treatment. The multivariable-adjusted estimated rate of recurrence was higher in women who discontinued endocrine therapy relative to those who completed their treatment (hazard ratio, 1.67; 95% CI, 1.25-2.14). CONCLUSIONS: These results highlight the importance of clinical follow-up and behavioral interventions that support persistence of adjuvant endocrine therapy to prevent breast cancer recurrence.

16.
Lancet Diabetes Endocrinol ; 9(2): 94-105, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33347809

RESUMO

BACKGROUND: Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified. METHODS: In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs. RESULTS: Of the 2437 cases, 1967 (81·4%) had papillary carcinomas, 1880 (77·1%) were women, and 1384 (56·7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1·14 [95% CI 1·05-1·23]) and congenital hypothyroidism (4·55 [1·58-13·08]); maternal diabetes before pregnancy (OR 1·69 [0·98-2·93]) and postpartum haemorrhage (OR 1·28 [1·06-1·55]); and (from registry data in Denmark) maternal hypothyroidism (18·12 [10·52-31·20]), hyperthyroidism (11·91 [6·77-20·94]), goiter (67·36 [39·89-113·76]), and benign thyroid neoplasms (22·50 [6·93-73·06]) were each associated with an increased risk of thyroid cancer in offspring. INTERPRETATION: In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring. FUNDING: Intramural Research Program of the National Cancer Institute (National Institutes of Health).


Assuntos
Saúde Materna/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Gravidez , Fatores de Risco , Países Escandinavos e Nórdicos/epidemiologia , Neoplasias da Glândula Tireoide/etiologia
17.
BMJ ; 371: m4060, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268348

RESUMO

OBJECTIVE: To examine associations between birth defects and cancer from birth into adulthood. DESIGN: Population based nested case-control study. SETTING: Nationwide health registries in Denmark, Finland, Norway, and Sweden. PARTICIPANTS: 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014. MAIN OUTCOME MEASURES: Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models. RESULTS: Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk. CONCLUSIONS: The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.

18.
J Am Coll Cardiol ; 76(24): 2803-2813, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33303068

RESUMO

BACKGROUND: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value. OBJECTIVES: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC). METHODS: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease. RESULTS: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD. CONCLUSIONS: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33221243

RESUMO

OBJECTIVES: The authors sought to assess the distribution of 5-year risk of cardiovascular disease (CVD) events (myocardial infarction, revascularizations, ischemic stroke) and death among symptomatic patients with varying degrees of coronary artery disease (CAD) ascertained from computed tomography angiography (CTA). BACKGROUND: CTA is used increasingly as the first-line test for evaluating patients with symptoms suggestive of CAD. This creates the daily clinical challenge of best using the information available from CTA to guide appropriate downstream allocation of preventive treatments. METHODS: Among 21,275 patients from the Western Denmark Heart Registry, the authors developed a model predicting 5-year risk for CVD and death based on traditional risk factors and CAD severity. Only events occurring >90 days after CTA were included. RESULTS: During a median follow-up of 4.2 years, 1,295 CVD events and deaths occurred. The median 5-year risk for events was 4% (interquartile range: 3% to 8%), and ranged from <5% to >50% in individual patients. The degree of CAD severity was the strongest risk factor; however, traditional risk factors also contributed significantly to risk. Thus, risk distributions in patients with varying degree of CAD overlapped considerably, and patients with extensive nonobstructive CAD could have higher estimated risk than patients with obstructive CAD (stenosis >50%). Among patients with obstructive CAD, 12% had 5-year risk <10% whereas 24% had risk >20%. A similar large overlap in risk was found when revascularizations were excluded from the endpoint. CONCLUSIONS: The 5-year risk for CVD events and death varies substantially in symptomatic patients undergoing CTA, even in the presence of obstructive CAD. These results provide support for individual risk assessment to improve potential benefit when allocating preventive therapies following CTA.

20.
Endoscopy ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33241540

RESUMO

BACKGROUND AND STUDY AIMS: Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 50% of all colorectal cancers (CRCs) diagnosed in patients with inflammatory bowel disease (IBD). This may reflect a high colonoscopy frequency; however evidence remains limited. PATIENT AND METHODS: We conducted a cohort study of IBD and non-IBD patients undergoing colonoscopy. We calculated 6-36 months CIPs of PCCRC after first-time and subsequent colonoscopies. We also computed crude and adjusted HRs of PCCRC, comparing IBD with non-IBD patients undergoing first-time and subsequent colonoscopies. Separate analyses were conducted for consecutive colonoscopies. We calculated PCCRC-3 year rates to estimate the proportion of IBD and non-IBD CRC patients experiencing PCCRC. RESULTS: We observed 138 and 1,909 PCCRCs among 34,688 IBD and 358,217 non-IBD patients who underwent colonoscopy. The CIP of PCCRC after first-time colonoscopy was 0.21%, 95% confidence interval (CI): [0.17-0.27] for IBD patients and 0.37%, 95% CI: [0.35-0.39] for non-IBD patients. The adjusted HR of PCCRC after a first-time colonoscopy was 0.96, 95% CI: [0.75-1.22] and the adjusted HRs after subsequent colonoscopies had point estimates around 1.0. The PCCRC-3 year rate was 24.3%, 95% CI: [20.4-28.7] for IBD and 7.5%, 95% CI [7.2-7.8] for non-IBD patients. CONCLUSIONS: Although PCCRCs accounted for a substantial proportion of all IBD-related CRCs, IBD patients had a low CIP of PCCRC after colonoscopy. The elevated PCCRC-3 year rates may among other factors stem from increased colonoscopy frequency in IBD patients.

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