scholarly journals Preterm delivery and long term mortality in women: national cohort and co-sibling study

BMJ ◽  
2020 ◽  
pp. m2533 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Kristina Sundquist

Abstract Objectives To examine the long term mortality associated with preterm delivery in a large population based cohort of women, and to assess for potential confounding by shared familial factors. Design National cohort study. Setting Sweden. Participants All 2 189 477 women with a singleton delivery in 1973-2015. Main outcome measures All cause and cause specific mortality up to 2016, identified from nationwide death records. Cox regression was used to calculate hazard ratios while adjusting for confounders, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and environmental) factors. Results In 50.7 million person years of follow-up, 76 535 (3.5%) women died (median age at death was 57.6). In the 10 years after delivery, the adjusted hazard ratio for all cause mortality associated with preterm delivery (<37 weeks) was 1.73 (95% confidence interval 1.61 to 1.87), and when further stratified was 2.20 (1.63 to 2.96) for extremely preterm delivery (22-27 weeks), 2.28 (2.01 to 2.58) for very preterm delivery (28-33 weeks), 1.52 (1.39 to 1.67) for late preterm delivery (34-36 weeks), and 1.19 (1.12 to 1.27) for early term delivery (37-38 weeks) compared with full term delivery (39-41 weeks). These risks declined but remained significantly raised after longer follow-up times: for preterm versus full term births, 10-19 years after delivery, the adjusted hazard ratio was 1.45 (95% confidence interval 1.37 to 1.53); 20-44 years after delivery, the adjusted hazard ratio was 1.37 (1.33 to 1.41). These findings did not seem to be attributable to shared genetic or environmental factors within families. Several causes were identified, including cardiovascular and respiratory disorders, diabetes, and cancer. Conclusions In this large national cohort of women, the findings suggested that preterm and early term delivery were independent risk factors for premature mortality from several major causes. These associations declined over time but remained raised up to 40 years later.

Stroke ◽  
2021 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Kristina Sundquist

Background and Purpose: Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort. Methods: A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. Results: In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12–1.43; P <0.001), and further stratified was 1.42 (1.11–1.81; P =0.005) for early preterm (22–33 weeks) and 1.22 (1.06–1.40; P =0.004) for late preterm (34–36 weeks), compared with full-term (39–41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: adjusted hazard ratio, 1.42 [95% CI, 1.04–1.94]; any preterm: 1.15 [0.97–1.35]) and ischemic stroke (early preterm: adjusted hazard ratio, 1.33 [95% CI, 0.87–2.03]; any preterm: 1.31 [1.07–1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families. Conclusions: In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.


2018 ◽  
Vol 8 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Patrick Sulzgruber ◽  
Sebastian Schnaubelt ◽  
Lorenz Koller ◽  
Georg Goliasch ◽  
Jan Niederdöckl ◽  
...  

Background: The development of cardiac arrhythmias resulting in cardiac arrest represents a severe complication in patients with acute myocardial infarction. While the worsening of the prognosis in this vulnerable patient collective is well known, less attention has been paid to its age-specific relevance from a long-term perspective. Methods: Based on a clinical acute myocardial infarction registry we analysed 832 patients with acute myocardial infarction within the current analysis. Patients were stratified into equal groups ( n=208 per group) according to age in less than 45 years, 45–64 years, 65–84 years and 85 years and older via propensity score matching. Multivariate Cox regression analysis was used to assess the age-dependent influence of cardiac arrest on mortality. Results: The total number of cardiac arrests differed significantly between age groups, demonstrating the highest incidence in the youngest population with 18.8% ( n=39), and a significantly lower incidence by increasing age (−11.6%; P=0.01). After a mean follow-up time of 8 years, a total of 264 patients (31.7%) died due to cardiovascular causes. While cardiac arrest was a strong and independent predictor for mortality within the total study population with an adjusted hazard ratio of 3.21 (95% confidence interval 2.23–4.61; P<0.001), there was no significant association with mortality independently in very young patients (<45 years; adjusted hazard ratio of 1.73, 95% confidence interval 0.55–5.53; P=0.35). Conclusion: We found that arrhythmias resulting in cardiac arrest are more common in very young acute myocardial infarction patients (<45 years) compared to their older counterparts, and were able to demonstrate that the prognostic value of cardiac arrest on long-term mortality in patients with acute myocardial infarction is clearly age dependent.


2019 ◽  
Vol 14 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Francesca Mallamaci ◽  
Giovanni Tripepi ◽  
Graziella D’Arrigo ◽  
Silvio Borrelli ◽  
Carlo Garofalo ◽  
...  

Background and objectivesShort-term BP variability (derived from 24-hour ambulatory BP monitoring) and long-term BP variability (from clinic visit to clinic visit) are directly related to risk for cardiovascular events, but these relationships have been scarcely investigated in patients with CKD, and their prognostic value in this population is unknown.Design, setting, participants, & measurementsIn a cohort of 402 patients with CKD, we assessed associations of short- and long-term systolic BP variability with a composite end point of death or cardiovascular event. Variability was defined as the standard deviation of observed BP measurements. We further tested the prognostic value of these parameters for risk discrimination and reclassification.ResultsMean ± SD short-term systolic BP variability was 12.6±3.3 mm Hg, and mean ± SD long-term systolic BP variability was 12.7±5.1 mm Hg. For short-term BP variability, 125 participants experienced the composite end point over a median follow-up of 4.8 years (interquartile range, 2.3–8.6 years). For long-term BP variability, 110 participants experienced the composite end point over a median follow-up of 3.2 years (interquartile range, 1.0–7.5 years). In adjusted analyses, long-term BP variability was significantly associated with the composite end point (hazard ratio, 1.24; 95% confidence interval, 1.01 to 1.51 per 5-mm Hg higher SD of office systolic BP), but short-term systolic BP variability was not (hazard ratio, 0.92; 95% confidence interval, 0.68 to 1.25 per 5-mm Hg higher SD of 24-hour ambulatory systolic BP). Neither estimate of BP variability improved risk discrimination or reclassification compared with a simple risk prediction model.ConclusionsIn patients with CKD, long-term but not short-term systolic BP variability is related to the risk of death and cardiovascular events. However, BP variability has a limited role for prediction in CKD.


2014 ◽  
Vol 99 (5) ◽  
pp. 1599-1607 ◽  
Author(s):  
Tzu-Chieh Lin ◽  
Cheng-Han Lee ◽  
Chyun-Yu Yang ◽  
Yea-Huei Kao Yang ◽  
Swu-Jane Lin

Context: There was no clear evidence for the association between oral bisphosphonates or raloxifene and venous thromboembolism (VTE). There might also be ethnic differences in VTE risk. Objective: The purpose of this study was to compare the incidence and risk of VTEs for different classes of osteoporosis drugs in the Taiwanese osteoporotic fracture population. Design: This was a retrospective cohort study from 2003 to 2007, with up to 6 years follow-up. Setting: Enrollees were participants in Taiwan National Health Insurance. Patients: Patients older than 50 years who had vertebral or hip fractures and were new to osteoporosis therapy were recruited. Intervention: Patients were classified into the alendronate, calcitonin, or raloxifene group according to exposure after follow-up. Main Outcome Measure: The primary outcome of our study was all incident VTEs, including deep vein thrombosis and pulmonary embolism. Cox proportional hazard models were used to compare the relative VTE risk among alendronate, raloxifene, and calcitonin groups under an on-treatment scenario. Results: There were 25 443, 9642, and 31 900 patients in the alendronate, raloxifene, and calcitonin groups, and the mean age was 74.5 years (SD, 9.6). The incidence of VTE in the alendronate, raloxifene, and calcitonin groups was 11.2, 8.5, and 18.8 per 10 000 person-years. Results from Cox analyses showed that alendronate or raloxifene recipients did not have a higher risk for VTE than calcitonin recipients (adjusted hazard ratio for alendronate, 0.84; 95% confidence interval, 0.47–1.51; adjusted hazard ratio for raloxifene, 0.64; 95% confidence interval, 0.33–1.28). Conclusion: This retrospective analysis found that the incidence of VTE in Taiwanese patients with osteoporosis was low, and the risk of VTE was similar across alendronate, raloxifene, and calcitonin recipients in patients with osteoporotic fractures who were new to osteoporosis therapy.


Neurology ◽  
2016 ◽  
Vol 88 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Laura Licchetta ◽  
Francesca Bisulli ◽  
Luca Vignatelli ◽  
Corrado Zenesini ◽  
Lidia Di Vito ◽  
...  

Objective:To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).Methods:We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.Results:We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR.Conclusions:Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.


2021 ◽  
Vol 25 (71) ◽  
pp. 1-174
Author(s):  
Jonathan Bedford ◽  
Laura Drikite ◽  
Mark Corbett ◽  
James Doidge ◽  
Paloma Ferrando-Vivas ◽  
...  

Background New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care. Objectives In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation. Methods We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK. Results Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses. Conclusions Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior. Future work Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken. Trial registration Current Controlled Trials ISRCTN13252515. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 71. See the NIHR Journals Library website for further project information.


2007 ◽  
Vol 106 (6) ◽  
pp. 1088-1095 ◽  
Author(s):  
Elisabeth Mahla ◽  
Anneliese Baumann ◽  
Peter Rehak ◽  
Norbert Watzinger ◽  
Martin N. Vicenzi ◽  
...  

Background Preoperative N-terminal pro-BNP (NT-proBNP) is independently associated with adverse cardiac outcome but does not anticipate the dynamic consequences of anesthesia and surgery. The authors hypothesized that a single postoperative NT-proBNP level provides additional prognostic information for in-hospital and late cardiac events. Methods Two hundred eighteen patients scheduled to undergo vascular surgery were enrolled and followed up for 24-30 months. Logistic regression and Cox proportional hazards model were performed to evaluate predictors of in-hospital and long-term cardiac outcome. The optimal discriminatory level of preoperative and postoperative NT-proBNP was determined by receiver operating characteristic analysis. Results During a median follow-up of 826 days, 44 patients (20%) experienced 51 cardiac events. Perioperatively, median NT-proBNP increased from 215 to 557 pg/ml (interquartile range, 83/457 to 221/1178 pg/ml; P&lt;0.001). The optimum discriminate threshold for preoperative and postoperative NT-proBNP was 280 pg/ml (95% confidence interval, 123-400) and 860 pg/ml (95% confidence interval, 556-1,054), respectively. Adjusted for age, previous myocardial infarction, preoperative fibrinogen, creatinine, high-sensitivity C-reactive protein, type, duration, and surgical complications, only postoperative NT-proBNP remained significantly associated with in-hospital (adjusted hazard ratio, 19.8; 95% confidence interval, 3.4-115) and long-term cardiac outcome (adjusted hazard ratio, 4.88; 95% confidence interval, 2.43-9.81). Conclusion A single postoperative NT-proBNP determination provides important additional prognostic information to preoperative levels and may support therapeutic decisions to prevent subsequent structural myocardial damage.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Tomoki Tanaka ◽  
Kyo Takahashi ◽  
Masahiro Akishita ◽  
Katsuya Iijima

Abstract Aim: For achieving healthy aging for all, multi-faceted frailty is serious problem in super-aged society such as Japan. We developed community-based frailty check-up program performed by trained senior volunteers. In this study, we aimed to validate the ability of the results of check-up to predict needing long-term support or care insurance or death in community-dwelling older population. Methods: A total of 1,536 older adults (mean age, 73.0±6.1 years; 74% women; non-eligible for long-term support or care) participated in the check-ups held from April, 2015 to March, 2018 in Kashiwa City, Japan. At check-ups cite, 21 items including nutrition, oral and physical functions, and social conditions were assessed; Outcome was needing long-term support or care insurance, or death from the day of check-ups until October, 2018. Results: During follow-up {median 678 days (inter-quartile range, 199-1263)}, 116 (7.6%) were newly needing for long-term support (n=50) or care (n=49), or death (n=18). The number of positive responses among 21 items was associated with decreased risks of outcome {age-sex adjusted hazard ratio (95% confidence interval), 0.87 (0.81-0.92)}. Compared those with &gt; 18 positive responses (third tertile), individuals with &lt; 14 positive responses (first tertile) were highly increased risks of outcome {age-sex adjusted hazard ratio (95% confidence interval), 2.44 (1.22-4.49)}. Conclusions: Community-based frailty check-ups program could predict the needing long-term support or care insurance or death in community-dwelling older population. The appropriate intervention for individuals with bad results of the check-up might contribute to serving as early prevention of multi-faceted frailty.


Diabetologia ◽  
2019 ◽  
Vol 63 (3) ◽  
pp. 508-518 ◽  
Author(s):  
Casey Crump ◽  
Jan Sundquist ◽  
Kristina Sundquist

Abstract Aims/hypothesis Preterm birth (gestational age <37 weeks) has been associated with insulin resistance early in life. However, no large population-based studies have examined risks of type 1 and type 2 diabetes and potential sex-specific differences from childhood into adulthood. Clinicians will increasingly encounter adults who were born prematurely and will need to understand their long-term risks. We hypothesised that preterm birth is associated with increased risks of type 1 and type 2 diabetes into adulthood. Methods A national cohort study was conducted of all 4,193,069 singletons born in Sweden during 1973–2014, who were followed up for type 1 and type 2 diabetes identified from nationwide diagnoses and pharmacy data to the end of 2015 (maximum age 43 years; median age at the end of follow-up 22.5 years). Cox regression was used to adjust for potential confounders, and co-sibling analyses assessed the influence of shared familial (genetic and/or environmental) factors. Results In 92.3 million person-years of follow-up, 27,512 (0.7%) and 5525 (0.1%) people were identified with type 1 and type 2 diabetes, respectively. Gestational age at birth was inversely associated with both type 1 and type 2 diabetes risk. Adjusted HRs for type 1 and type 2 diabetes at age <18 years associated with preterm birth were 1.21 (95% CI, 1.14, 1.28) and 1.26 (95% CI, 1.01, 1.58), respectively, and at age 18–43 years were 1.24 (95% CI, 1.13, 1.37) and 1.49 (95% CI, 1.31, 1.68), respectively, compared with full-term birth. The associations between preterm birth and type 2 (but not type 1) diabetes were stronger among females (e.g. at age 18–43 years, females: adjusted HR, 1.75; 95% CI, 1.47, 2.09; males: 1.28; 95% CI, 1.08, 1.53; p < 0.01 for additive and multiplicative interaction). These associations were only partially explained by shared genetic or environmental factors in families. Conclusions/interpretation In this large national cohort, preterm birth was associated with increased risk of type 1 and type 2 diabetes from childhood into early to mid-adulthood. Preterm-born children and adults may need early preventive evaluation and long-term monitoring for diabetes.


2016 ◽  
Vol 26 (2) ◽  
pp. 189-198 ◽  
Author(s):  
J. Damián ◽  
R. Pastor-Barriuso ◽  
E. Valderrama-Gama ◽  
J. de Pedro-Cuesta

Background.Studies on depression and mortality in nursing homes have shown inconclusive findings, and none has studied the role of detection. We sought to measure the association of depression with long-term all-cause mortality in institutionalised older people and evaluate a potential modification in the association by its detection status.Methods.We selected a stratified cluster sample of 591 residents aged 75 years or older (mean age 84.5 years) living in residential and nursing homes of Madrid, Spain, who were free of severe cognitive impairment at the 1998–1999 baseline interview. Mortality was ascertained until age 105 years or September 2013 (median/maximum follow-up 4.8/15.2 years) through linkage to the Spanish National Death Index. Detected depression was defined at baseline as a physician's diagnosis or antidepressant use, undetected depression as significant depressive symptoms (score of 4 or higher on the ten-item version of the Geriatric Depression Scale) without documented diagnosis or treatment, and no depression as the absence of diagnosis, treatment, and symptoms. Constant and age-dependent hazard ratios for mortality comparing detected and undetected depression with no depression were estimated using Cox models, and absolute years of life gained and lost using Weibull models.Results.The baseline prevalences of detected and undetected depression were 25.9 and 18.8%, respectively. A total of 499 participants died during 3575 person-years of follow-up. In models adjusted for age, sex, type of facility, number of chronic conditions, and functional dependency, overall depression was not associated with long-term all-cause mortality (hazard ratio 0.87, 95% confidence interval (CI): 0.70–1.08). However, compared with no depression, detected depression showed lower mortality (hazard ratio 0.63, 95% CI: 0.46–0.86), while undetected depression registered higher, not statistically significant, mortality (hazard ratio 1.35, 95% CI: 0.98–1.86). The median life expectancy increased by 1.8 years (95% CI: −3.1 to 6.7 years) in residents with detected depression and decreased by 6.3 years (95% CI: 2.6–10.1 years) in those undetected. Results were more marked in women than men and they were robust to the exclusion of antidepressants from the definition of depression and also to the use of a stricter cut-off for the presence of depressive symptoms.Conclusions.The long-term mortality risk associated with depression in nursing homes depends on its detection status, with better prognosis in residents with detected depression and worse in those undetected. The absolute impact of undetected depressive symptoms in terms of life expectancy can be prominent.


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