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2.
PLoS Negl Trop Dis ; 15(1): e0009051, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406076

RESUMO

BACKGROUND: Until now, no antiviral treatment has been proven to be effective for the coronavirus disease 2019 (COVID-19). The timing of oxygen therapy was considered to have a great influence on the symptomatic relief of hypoxemia and seeking medical intervention, especially in situations with insufficient medical resources, but the evidence on the timing of oxygen therapy is limited. METHODS AND FINDINGS: Medical charts review was carried out to collect the data of hospitalized patients with COVID-19 infection confirmed in Tongji hospital, Wuhan from 30th December 2019 to 8th March 2020. In this study, the appropriate timing of oxygen therapy and risk factors associated with severe and fatal illness were identified and the effectiveness of antivirus on disease progression was assessed. Among 1362 patients, the prevalence of hypoxia symptoms was significantly higher in those patients with severe and fatal illness than in those with less severe disease. The onset of hypoxia symptoms was most common in the second to third week after symptom onset, and patients with critical and fatal illness experienced these symptoms earlier than those with mild and severe illness. In multivariable analyses, the risk of death increased significantly when oxygen therapy was started more than 2 days after hypoxia symptoms onset among critical patients (OR, 1.92; 95%CI, 1.20 to 3.10). Compared to the critically ill patients without IFN-a, the patients who were treated with IFN-a had a lower mortality (OR, 0.60; 95%CI, 0.39 to 0.91). CONCLUSIONS: Early initiation of oxygen therapy was associated with lower mortality among critical patients. This study highlighted the importance of early oxygen therapy after the onset of hypoxia symptoms. Our results also lend support to potentially beneficial effects of IFNα on critical illness.


Assuntos
Antivirais/uso terapêutico , Oxigênio/uso terapêutico , Adolescente , Adulto , Idoso , /epidemiologia , China/epidemiologia , Estado Terminal/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
3.
Int J Cancer ; 148(1): 28-37, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32621751

RESUMO

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer-specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer-specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer-specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow-up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer-specific mortality (95% CI 0%-65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer-specific mortality (95% CI 11%-82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%-12%) reduction in cancer-specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%-39%). Our findings suggest that underinsured patients face a higher risk of breast cancer-specific mortality in developing countries.

4.
Hum Reprod ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289027

RESUMO

STUDY QUESTION: Is pubertal timing associated with risk of premenstrual disorders (PMDs) in young adulthood? SUMMARY ANSWER: Late pubertal development is associated with decreased premenstrual symptom burden and risk of PMDs in young adulthood. WHAT IS KNOWN ALREADY: PMDs, including premenstrual syndrome and premenstrual dysphoric disorder, may begin during the teenage years. Few risk factors in early life have been identified for PMD development. STUDY DESIGN, SIZE, DURATION: A prospective cohort study of 6495 female participants during 1996-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included participants from the Growing Up Today Study (GUTS). Pubertal development was indicated by the timing of menarche, breast and pubic hair growth. Self-reported age at menarche was longitudinally assessed at enrollment (in 1996/2004 for GUTS I/II) and onwards, and classified as early (age ≤ mean - SD, 11.64 years), normative and late menarche (age ≥ mean + SD, 13.95 years). Timing of pubic hair and breast growth were assessed multiple times during follow-up via Tanner scales, and classified into early, normative and late development according to mean ± SD. Using a validated questionnaire based on the Calendar of Premenstrual Experiences, we assessed premenstrual symptoms and identified probable cases of PMDs in 2013. We examined the associations of timing of pubertal development with premenstrual symptom score and disorders using multivariable linear and logistic regressions, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In 2013 (mean age = 26), 1001 (15.4%) individuals met criteria for a PMD. An inverse association was found between age at menarche and premenstrual symptom z-score (ß -0.05 per year, 95% CI -0.07 to -0.03) and risk of PMDs (odds ratio (OR) 0.93 per year, 95% CI 0.88 to 0.99). Compared to individuals with normative menarche, individuals with late menarche had a lower risk of PMDs (OR 0.73, 95% CI 0.59 to 0.91), while individuals with early menarche had comparable odds (OR 0.98, 95% CI 0.81 to 1.18). Moreover, early growth of pubic hair was associated with increased premenstrual symptoms (z-score ß 0.09 per year, 95% CI 0.02 to 0.17) and PMD risk (OR 1.28, 95% CI 1.04 to 1.56), independent of age at menarche. No associations were noted for breast development. LIMITATIONS, REASONS FOR CAUTION: One major limitation is some misclassification of menarche due to recall. We, however, showed robust association among participants who were premenarcheal at baseline. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that pubertal timing, particularly timing of menarche, is inversely associated with the risk of developing premenstrual symptoms in young adulthood, and that women with later menarche have significantly lower risk of PMDs. Information on PMDs should be provided to teenage girls and their parents. If these findings are confirmed in independent populations, prevention strategies and early detection programs may be considered for women with early pubertal development. STUDY FUNDING/COMPETING INTEREST(S): The work is supported by the National Institutes of Health and Swedish Research Council. TRIAL REGISTRATION NUMBER: N/A.

5.
JMIR Med Inform ; 8(11): e19069, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164899

RESUMO

BACKGROUND: Current online prognostic prediction models for breast cancer, such as Adjuvant! Online and PREDICT, are based on specific populations. They have been well validated and widely used in the United States and Western Europe; however, several validation attempts in non-European countries have revealed suboptimal predictions. OBJECTIVE: We aimed to develop an advanced breast cancer prognosis model for disease progression, cancer-specific mortality, and all-cause mortality by integrating tumor, demographic, and treatment characteristics from a large breast cancer cohort in China. METHODS: This study was approved by the Clinical Test and Biomedical Ethics Committee of West China Hospital, Sichuan University on May 17, 2012. Data collection for this project was started in May 2017 and ended in March 2019. Data on 5293 women diagnosed with stage I to III invasive breast cancer between 2000 and 2013 were collected. Disease progression, cancer-specific mortality, all-cause mortality, and the likelihood of disease progression or death within a 5-year period were predicted. Extreme gradient boosting was used to develop the prediction model. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUROC), and the model was calibrated and compared with PREDICT. RESULTS: The training, test, and validation sets comprised 3276 (499 progressions, 202 breast cancer-specific deaths, and 261 all-cause deaths within 5-year follow-up), 1405 (211 progressions, 94 breast cancer-specific deaths, and 129 all-cause deaths), and 612 (109 progressions, 33 breast cancer-specific deaths, and 37 all-cause deaths) women, respectively. The AUROC values for disease progression, cancer-specific mortality, and all-cause mortality were 0.76, 0.88, and 0.82 for training set; 0.79, 0.80, and 0.83 for the test set; and 0.79, 0.84, and 0.88 for the validation set, respectively. Calibration analysis demonstrated good agreement between predicted and observed events within 5 years. Comparable AUROC and calibration results were confirmed in different age, residence status, and receptor status subgroups. Compared with PREDICT, our model showed similar AUROC and improved calibration values. CONCLUSIONS: Our prognostic model exhibits high discrimination and good calibration. It may facilitate prognosis prediction and clinical decision making for patients with breast cancer in China.

6.
Am J Clin Nutr ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33236056

RESUMO

BACKGROUND: Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. OBJECTIVES: We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses' Health Studies (NHS and NHSII). METHODS: This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. RESULTS: We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8-42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7-52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. CONCLUSIONS: The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.

7.
BMJ Open ; 10(10): e041671, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082197

RESUMO

OBJECTIVES: The COVID-19 outbreak has caused enormous strain on healthcare systems, and healthcare trainees, which comprise the future healthcare workforce, may be a vulnerable group. It is essential to assess the psychological distress experienced by healthcare trainees during the COVID-19 outbreak. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study with 4184 healthcare trainees at Sichuan University in China was implemented during 7-13 February 2020. Participants were grouped by training programmes (medicine, medical technology and nursing) and training stages (undergraduate, postgraduate and residency). MAIN OUTCOMES: COVID-19-related psychological distress and acute stress reaction (ASR) were assessed using the Kessler 6-item Psychological Distress Scale and the Impact of Event Scale-Revised, respectively. We estimated the ORs of distress by comparing trainees across programmes and training stages using multivariable logistic regression. RESULTS: Significant psychological distress was found in 1150 (30.90%) participants and probable ASR in 403 (10.74%). Compared with the nursing trainees, the medical trainees (OR 1.54, 95% CI 1.22 to 1.95) reported a higher burden of psychological distress during the outbreak, while the medical technology trainees (OR 1.25, 95% CI 0.97 to 1.62) reported similar symptom scores. Postgraduates (OR 1.55, 95% CI 1.16 to 2.08) in medicine had higher levels of distress than their undergraduate counterparts did, whereas the nursing residents (OR 0.38, 95% CI 0.20 to 0.71) reported a lower burden than did nursing undergraduates. A positive association was found between having active clinical duties during the outbreak and distress (OR 1.17, 95% CI 0.98 to 1.39), particularly among the medical trainees (OR 1.85, 95% CI 1.47 to 2.33) and undergraduates (OR 4.20, 95% CI 1.61 to 11.70). No clear risk patterns of ASR symptoms were observed. CONCLUSIONS: Medical trainees, particularly postgraduates and those with active clinical duties, were at risk for psychological distress during the COVID-19 outbreak. Stress management may be considered for high-risk healthcare trainees.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Angústia Psicológica , Estresse Psicológico/epidemiologia , Adulto , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/psicologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/psicologia , Estresse Psicológico/etiologia , Adulto Jovem
8.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2230-2234, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33087343

RESUMO

BACKGROUND: Highly increased risk of injuries has been noted around the time of cancer diagnosis. Whether there is a similar increase in risk around the diagnosis of cervical cancer and its precursor lesions was unknown. METHODS: We performed a cohort study including 3,016,307 Swedish women that participated in cervical screening during 2001 to 2012. We calculated the incidence rates (IR) of hospitalized iatrogenic or noniatrogenic injuries during the diagnostic workup, and the time interval from smear or punch biopsy until surgical treatment or 2 months after the last smear or biopsy, among women with invasive cervical cancer (ICC) or its precursor lesions. We calculated the IRs of injuries during the 2 months after a normal smear among the other women as reference. IR ratios (IRR) and 95% confidence intervals (CI) were calculated using Poisson regression. RESULTS: Compared with other women, there was an increased rate of iatrogenic injuries during the diagnostic workup of women with ICC (IR, 0.58 per 1,000 person-months; IRR, 8.55; 95% CI, 3.69-19.80) as well as of women with cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ (IR, 0.09 per 1,000 person-months; IRR, 3.04; 95% CI, 1.73-5.34). We also found an increased rate of noniatrogenic injuries during the diagnostic workup of women with invasive cancer (IR, 0.65 per 1,000 person-months; IRR, 2.48; 95% CI, 1.30-4.47). CONCLUSIONS: Although rare, there was an increased risk of inpatient care for iatrogenic and noniatrogenic injuries during the diagnostic workup of women with ICC. IMPACT: Women experienced burden of medical complications and psychologic distress around diagnosis of a potential cervical cancer.

9.
Psychol Med ; : 1-8, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32972473

RESUMO

BACKGROUND: The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak. METHODS: We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents. RESULTS: There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th-26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5-371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%-2.3%). The epidemic phase (27th January-15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI -40.4 to -14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February-31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility. CONCLUSIONS: During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.

10.
Nat Commun ; 11(1): 4637, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934226

RESUMO

An association between schizophrenia and subsequent breast cancer has been suggested; however the risk of schizophrenia following a breast cancer is unknown. Moreover, the driving forces of the link are largely unclear. Here, we report the phenotypic and genetic positive associations of schizophrenia with breast cancer and vice versa, based on a Swedish population-based cohort and GWAS data from international consortia. We observe a genetic correlation of 0.14 (95% CI 0.09-0.19) and identify a shared locus at 19p13 (GATAD2A) associated with risks of breast cancer and schizophrenia. The epidemiological bidirectional association between breast cancer and schizophrenia may partly be explained by the genetic overlap between the two phenotypes and, hence, shared biological mechanisms.


Assuntos
Neoplasias da Mama/genética , Fatores de Transcrição GATA/genética , Esquizofrenia/genética , Idoso , Cromossomos Humanos Par 19/genética , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Suécia
11.
BMC Med ; 18(1): 238, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900363

RESUMO

BACKGROUND: Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown. METHODS: We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis. RESULTS: Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98). CONCLUSION: Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32799610

RESUMO

Childhood cancer survivors (CCS) are at increased risk of subsequent malignant neoplasms (SMNs). However, the impact of SMNs on long-term psychosocial functioning is unknown. In a cohort of 322 young adult CCS, survivors who developed a SMN (n = 43, 13.4%) did not report a significantly higher burden of fatigue, insomnia, depression, anxiety, or impaired quality of life on average 8 years after SMN diagnosis. They, however, endorsed significantly greater body image concerns. Our findings indicate that CCS with an SMN do not significantly differ from those without regarding most psychosocial outcomes in young adulthood, although clinicians may be vigilant for greater body image dissatisfaction.

13.
World J Surg Oncol ; 18(1): 88, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375797

RESUMO

BACKGROUND: To explore overall survival (OS) and GISTs-specific survival (GSS) among cancer survivors developing a second primary gastrointestinal stromal tumors (GISTs). METHODS: We conducted a cohort study, where patients with GISTs after another malignancy (AM-GISTs, n = 851) and those with only GISTs (GISTs-1, n = 7660) were identified from the Surveillance, Epidemiology, and End Results registries (1988-2016). Clinicopathologic characteristics and survival were compared between the two groups. RESULTS: The most commonly diagnosed first primary malignancy was prostate cancer (27.7%), followed by breast cancer (16.2%). OS among AM-GISTs was significantly inferior to that of GISTs-1; 10-year OS was 40.3% vs. 50.0%, (p < 0.001). A contrary finding was observed for GSS (10-year GSS 68.9% vs. 61.8%, p = 0.002). In the AM-GISTs group, a total of 338 patients died, of which 26.0% died of their initial cancer and 40.8% died of GISTs. Independent of demographics and clinicopathological characteristics, mortality from GISTs among AM-GISTs patients was decreased compared with their GISTs-1 counterparts (HR, 0.71; 95% CI, 0.59-0.84; p < 0.001), whereas OS was inferior among AM-GISTs (HR, 1.11; 95% CI, 0.99-1.25; p = 0.085). CONCLUSIONS: AM-GISTs patients have decreased risk of dying from GISTs compared with GIST-1. Although another malignancy history does not seemingly affect OS for GISTs patients, clinical treatment of such patients should be cautious.

14.
Psychol Med ; : 1-3, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32389148

RESUMO

BACKGROUND: Due to the drastic surge of COVID-19 patients, many countries are considering or already graduating health professional students early to aid professional resources. We aimed to assess outbreak-related psychological distress and symptoms of acute stress reaction (ASR) in health professional students and to characterize individuals with potential need for interventions. METHODS: We conducted a prospective cohort study of 1442 health professional students at Sichuan University, China. At baseline (October 2019), participants were assessed for childhood adversity, stressful life events, internet addiction, and family functioning. Using multivariable logistic regression, we examined associations of the above exposures with subsequent psychological distress and ASR in response to the outbreak. RESULTS: Three hundred and eighty-four (26.63%) participants demonstrated clinically significant psychological distress, while 160 (11.10%) met the criterion for a probable ASR. Individuals who scored high on both childhood adversity and stressful life event experiences during the past year were at increased risks of both distress (ORs 2.00-2.66) and probable ASR (ORs 2.23-3.10), respectively. Moreover, internet addiction was associated with elevated risks of distress (OR 2.05, 95% CI 1.60-2.64) and probable ASR (OR 2.15, 95% CI 1.50-3.10). By contrast, good family functioning was associated with decreased risks of distress (OR 0.43, 95% CI 0.33-0.55) and probable ASR (OR 0.48, 95% CI 0.33-0.69). All associations were independent of baseline psychological distress. CONCLUSIONS: Our findings suggest that COVID-19 related psychological distress and high symptoms burden of ASR are common among health professional students. Extended family and professional support should be considered for vulnerable individuals during these unprecedented times.

15.
Cancer Epidemiol Biomarkers Prev ; 29(6): 1253-1263, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32238406

RESUMO

BACKGROUND: Although vitamin D inhibits breast tumor growth in experimental settings, the findings from population-based studies remain inconclusive. Our goals were to investigate the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer recurrence in prospective epidemiologic studies and to explore the molecular underpinnings linking 25(OH)D to slower progression of breast cancer in the Nurses' Health Studies (NHS, N = 659). METHODS: Plasma 25(OH)D was measured with a high-affinity protein-binding assay and a radioimmunoassay. We profiled transcriptome-wide gene expression in breast tumors using microarrays. Hazard ratios (HR) of breast cancer recurrence were estimated from covariate-adjusted Cox regressions. We examined differential gene expression in association with 25(OH)D and employed pathway analysis. We derived a gene expression score for 25(OH)D, and assessed associations between the score and cancer recurrence. RESULTS: Although 25(OH)D was not associated with breast cancer recurrence overall [HR = 0.97; 95% confidence interval (CI), 0.88-1.08], the association varied by estrogen-receptor (ER) status (P interaction = 0.005). Importantly, among ER-positive stage I to III cancers, every 5 ng/mL increase in 25(OH)D was associated with a 13% lower risk of recurrence (HR = 0.87; 95% CI, 0.76-0.99). A null association was observed for ER-negative cancers (HR = 1.07; 95% CI, 0.91-1.27). Pathway analysis identified multiple gene sets that were significantly (FDR < 5%) downregulated in ER-positive tumors of women with high 25(OH)D (≥30 ng/mL), compared with those with low levels (<30 ng/mL). These gene sets are primarily involved in tumor proliferation, migration, and inflammation. 25(OH)D score derived from these gene sets was marginally associated with reduced risk of recurrence in ER-positive diseases (HR = 0.77; 95% CI, 0.59-1.01) in the NHS studies; however no association was noted in METABRIC, suggesting that further refinement is need to improve the generalizability of the score. CONCLUSIONS: Our findings support an intriguing line of research for studies to better understand the mechanisms underlying the role of vitamin D in breast tumor progression, particularly for the ER-positive subtype. IMPACT: Vitamin D may present a personal-level secondary-prevention strategy for ER-positive breast cancer.

16.
Eur J Epidemiol ; 35(3): 273-282, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31788734

RESUMO

Children born small for gestational age have a higher risk of intellectual disability. We investigated associations of birth weight for gestational age percentile and gestational age with risk of intellectual disability in appropriate-for-gestational-age (AGA) children. We included 828,948 non-malformed term or post-term AGA singleton children (including 429,379 full siblings) born between 1998 and 2009 based on data from the Swedish Medical Birth Register. Diagnosis of intellectual disability after 3 years of age was identified through the Patient Register. Using Cox regression models, we calculated hazard ratios (HRs) with 95% confidence intervals (CIs) of intellectual disability among children with different birth weight percentiles and gestational age in the whole population and in a subpopulation of full siblings. A total of 1688 children were diagnosed with intellectual disability during follow-up. HRs (95% CIs) of intellectual disability for the low birth weight percentile groups (10th-24th and 25th-39th percentiles, respectively) versus the reference group (40th-59th percentiles) were 1.43 (1.22-1.67) and 1.28 (1.10-1.50) in population analysis and 1.52 (1.00-2.31) and 1.44 (1.00-2.09) in sibling comparison analysis. The increased risk for low birth weight percentiles in population analysis was stable irrespective of gestational age. A weak U-shaped association between gestational age and intellectual disability was observed in population analysis, although not in sibling comparison analysis. These findings suggest that among AGA children born at term or post-term, lower birth weight percentiles within the normal range are associated with increased risk of intellectual disability, regardless of gestational age.


Assuntos
Peso ao Nascer , Deficiência Intelectual/epidemiologia , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido de Baixo Peso , Masculino , Gravidez , Fatores de Risco , Irmãos , Suécia/epidemiologia
17.
Biol Psychiatry ; 87(8): 708-716, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31862157

RESUMO

BACKGROUND: Being adopted early in life, an indicator of exposure to early-life adversity, has been consistently associated with poor mental health outcomes in adulthood. Such associations have largely been attributed to stressful environments, e.g., exposure to trauma, abuse, or neglect. However, mental health is substantially heritable, and genetic influences may contribute to the exposure to childhood adversity, resulting in potential genetic confounding of such associations. METHODS: Here, we explored associations between childhood adoption and mental health-related outcomes in midlife in 243,797 UK Biobank participants (n adopted = 3151). We used linkage disequilibrium score regression and polygenic risk scores for depressive symptoms, schizophrenia, neuroticism, and subjective well-being to address potential genetic confounding (gene-environment correlations) and gene-environment interactions. As outcomes, we explored depressive symptoms, bipolar disorder, neuroticism, loneliness, and mental health-related socioeconomic and psychosocial measures in adoptees compared with nonadopted participants. RESULTS: Adoptees were slightly worse off on almost all mental, socioeconomic, and psychosocial measures. Each standard deviation increase in polygenic risk for depressive symptoms, schizophrenia, and neuroticism was associated with 6%, 5%, and 6% increase in the odds of being adopted, respectively. Significant genetic correlations between adoption status and depressive symptoms, major depression, and schizophrenia were observed. No evidence for gene-environment interaction between genetic risk and adoption on mental health was found. CONCLUSIONS: The association between childhood adoption and mental health cannot fully be attributed to stressful environments but is partly explained by differences in genetic risk between adoptees and those who have not been adopted (i.e., gene-environment correlation).

18.
Elife ; 82019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31711568

RESUMO

While the rare occurrence of child loss is accompanied by reduced life expectancy of parents in contemporary affluent populations, its impact in developing societies with high child mortality rates is unclear. We identified all parents in Iceland born 1800-1996 and compared the mortality rates of 47,711 parents who lost a child to those of their siblings (N = 126,342) who did not. The proportion of parents who experienced child loss decreased from 61.1% of those born 1800-1880 to 5.2% of those born after 1930. Child loss was consistently associated with increased rate of maternal, but not paternal, death before the age of 50 across all parent birth cohorts; the relative increase in maternal mortality rate ranged from 35% among mothers born 1800-1930 to 64% among mothers born after 1930. The loss of a child poses a threat to the survival of young mothers, even during periods of high infant mortality rates.


Assuntos
Mortalidade Infantil/história , Mortalidade Prematura/história , Mães , Criança , Feminino , História do Século XIX , História do Século XX , Humanos , Islândia/epidemiologia , Lactente , Recém-Nascido , Pais
19.
BMJ ; 367: l5784, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645334

RESUMO

OBJECTIVE: To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections. DESIGN: Population and sibling matched cohort study. SETTING: Swedish population. PARTICIPANTS: 144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population. MAIN OUTCOME MEASURES: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections. RESULTS: The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios. CONCLUSION: In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.


Assuntos
Infecções Bacterianas/epidemiologia , Suscetibilidade a Doenças/imunologia , Transtornos de Estresse Traumático/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Anamnese , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Irmãos , Transtornos de Estresse Traumático/imunologia , Taxa de Sobrevida , Suécia/epidemiologia , Adulto Jovem
20.
Cancer Epidemiol Biomarkers Prev ; 28(12): 1977-1985, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31533938

RESUMO

BACKGROUND: The impact of the immune landscape of the microenvironment on cancer progression is not well understood for triple-negative breast cancer (TNBC). We, therefore, aimed to examine the association of immune cell enrichment scores as a proxy for immune profiles of tumor microenvironment with TNBC prognosis. METHODS: We included 76 patients with TNBC diagnosed between 2008 to 2016 in West China Hospital and 158 patients with TNBC from The Cancer Genome Atlas. On the basis of transcriptome data, we calculated the overall ImmuneScore and type-specific enrichment scores for 34 types of immune cells, using xCell, a gene signature-based method. HRs of recurrence-free survival (RFS) and overall survival (OS) were calculated by Cox proportional hazards models. RESULTS: During the median follow-up time of 2.8 (0.1-9.8) years, 42 patients had a recurrence, and 34 patients died. The overall ImmuneScore and most immune cell enrichment scores were relatively higher in tumors than normal tissues. A higher enrichment score of plasma cells was associated with favorable RFS [HR 0.45; 95% confidence interval (CI), 0.27-0.73] and OS (HR 0.32; 95% CI, 0.17-0.61). The score of CD4+ central memory T cell (Tcm) was negatively associated with RFS (HR 1.52; 95% CI, 1.17-1.97). Besides, CD4+ Tcm enrichment score was higher in invasive tumors that were not ductal/lobular carcinoma (OR 1.59; 95% CI, 1.06-2.37). CONCLUSIONS: Our findings suggest that plasma cells and CD4+ Tcm in the tumor microenvironment may play a role in the subsequent progression of TNBC. IMPACT: This study provides evidence of the role of immune cells in TNBC progression that may have clinical utility.


Assuntos
Biomarcadores/análise , Carcinoma Ductal de Mama/imunologia , Carcinoma Lobular/imunologia , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Neoplasias de Mama Triplo Negativas/imunologia , Microambiente Tumoral/imunologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/patologia , China , Estudos de Coortes , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Prognóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia
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