BMC Medicine最新文献

Background: Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia, fractures and death, depending on antidepressant class, drug, and dose.

Methods: This is a national cohort study. Patients with dementia registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem from May 1, 2007, until October 16, 2018, with at least one follow-up after dementia diagnosis, and who were new users of antidepressants, were included. Antidepressant use as a time varying exposure defined during the 6 months leading up to dementia diagnosis or each subsequent follow-up. We used linear mixed models to examine the association between antidepressant use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores. We used Cox proportional hazards models to calculate the hazard ratios for severe dementia (MMSE score < 10), fracture, and death. We compared antidepressant classes and drugs, and analyzed dose-response.

Results: We included 18740 patients (10 205 women [54.5%]; mean [SD] age, 78.2[7.4] years), of which 4271 (22.8%) received at least one prescription for an antidepressant. During follow-up, a total of 11912 prescriptions for antidepressants were issued, with selective serotonin reuptake inhibitors (SSRI) being the most common (64.8%). Antidepressant use was associated with faster cognitive decline (β (95% CI) = - 0.30(- 0.39, - 0.21) points/year), in particular sertraline (- 0.25(- 0.43, - 0.06) points/year), citalopram (- 0.41(- 0.55, - 0.27) points/year), escitalopram (- 0.76(- 1.09, - 0.44) points/year), and mirtazapine (- 0.19(- 0.34, - 0.04) points/year) compared with non-use. The association was stronger in patients with severe dementia (initial MMSE scores 0-9). Escitalopram showed a greater decline rate than sertraline. Compared with non-use, dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed.

Conclusions: In this cohort study, current antidepressant use was associated with faster cognitive decline; furthermore, higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality. These findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants use in patients with dementia.

Background: Tobacco industry activities and reduced smoking prevalence can foster under-appreciation of risks and under-investment in tobacco control. Reliable evidence on contemporary smoking impacts, including cause-specific mortality and attributable deaths, remains critical.

Methods: Prospective study of 178,169 cancer- and cardiovascular-disease-free individuals aged ≥ 45 years joining the 45 and Up Study in 2005-2009, with linked questionnaire, hospitalisation, cancer registry and death data to November 2017. Cause-specific mortality hazard ratios (HR) by smoking status, intensity and recency were estimated, adjusted for potential confounding factors. Population attributable fractions were estimated.

Results: There were 13,608 deaths during 9.3 years median follow-up (1.68 M person-years); at baseline, 7.9% of participants currently and 33.6% formerly smoked. Mortality was elevated with current versus never smoking for virtually all causes, including chronic lung disease (HR = 36.32, 95%CI = 26.18-50.40), lung cancer (17.85, 14.38-22.17) and oro-pharyngeal cancers (7.86, 4.11-15.02); lower respiratory infection, peripheral vascular disease, oesophageal cancer, liver cancer and cancer of unknown primary (risk 3-5 times as high); and coronary heart disease, cerebrovascular disease and cancers of urinary tract, pancreas, kidney, stomach and prostate (risk at least two-fold); former versus never-smoking demonstrated similar patterns with attenuated risks. Mortality increased with smoking intensity, remaining appreciable for 1-14 cigarettes/day (e.g. lung cancer HR = 13.00, 95%CI = 9.50-17.80). Excess smoking-related mortality was largely avoided with cessation aged < 45 years. In 2019, 24,285 deaths (one-in-every-six deaths, 15.3%), among Australians aged ≥ 45 years, were attributable to tobacco smoking.

Conclusions: Smoking continues to cause a substantial proportion of deaths in low-prevalence settings, including Australia, highlighting the importance of accelerated tobacco control.

Background: Systemic nutrition and inflammation status is recognized for its influence on cancer survival, yet its role in perioperative outcomes remains poorly defined. This study aimed to refine the assessment of systemic nutrition and inflammation status in non-small cell lung cancer (NSCLC) patients and to elucidate its impact on perioperative outcomes.

Methods: All patients underwent video-assisted thoracoscopic lobectomy, with their nutrition and inflammation status assessed based on preoperative blood tests. The development cohort, comprising 1497 NSCLC patients from two centers, evaluated the predictive value of systemic nutrition/inflammation indicators for perioperative endpoints and formulated the systemic nutrition-inflammation index (SNII). The tertiles of SNII were used to classify the nutrition/inflammation risk as high (< 15.6), moderate (15.6-23.1), and low (> 23.1). An external validation cohort of 505 NSCLC patients was utilized to confirm the effectiveness of SNII in guiding perioperative management.

Results: In the development cohort, the SNII tool, calculated as the product of total cholesterol and total lymphocytes divided by total monocytes, demonstrated a stronger correlation with perioperative outcomes compared to 11 existing nutrition/inflammation indicators. A low SNII score, indicative of high nutrition/inflammation risk, was independently predictive of increased complication incidence and severity, as well as prolonged chest tube duration and hospital stay. These findings were corroborated in the validation cohort. Upon combining the development and validation cohorts, the superiority of the SNII in predicting perioperative outcomes was further confirmed over the existing nutrition/inflammation indicators. Additionally, comprehensive subgroup analyses revealed the moderately variable efficacy of SNII across different patient populations.

Conclusions: This study developed and validated the SNII as a tool for identifying systemic nutrition and inflammation risk, which can enhance perioperative managements in NSCLC patients. Patients identified with high risk may benefit from prehabilitation and intensive treatments, highlighting the need for further research.

Background: Acute coronary syndrome (ACS) patients without standard modifiable cardiovascular risk factors (SMuRFs) have a higher risk of early mortality. However, little is known about their long-term outcomes, especially for patients undergoing percutaneous coronary intervention (PCI). This study aims to explore the long-term outcomes and identify independent factors associated with adverse clinical outcomes in patients with ACS undergoing PCI without SMuRFs.

Methods: This study used data from Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) registry study. Clinical characteristics and outcomes of patients with and without SMuRFs were examined. The primary outcomes were major adverse cardia-cerebrovascular events (MACCE). The long-term (5 years) outcomes were compared between the without and with SMuRFs group in such cohort. An exploratory Cox proportional hazards regression was performed to identify the independent demographic and clinical predictors of the adverse clinical outcomes in the SMuRFs-absent cohort.

Results: Among 5688 patients with ACS undergoing PCI, 392 (6.9%) were in the absence of SMuRFs and 5296 (93.1%) were in the presence of SMuRFs. There were no significant differences in MACCE rates between the two cohorts (9.44% vs. 9.76%, log-rank P = 0.90). Cox proportional hazards regression indicated that age (HR, 1.06; 95% CI, 1.03-1.10; P = 0.001) and thrombus lesions (HR, 2.58; 95% CI, 1.24-5.40; P = 0.011) were independently associated with MACCE in the SMuRFs-absent cohort.

Conclusions: Among patients with ACS undergoing PCI, SMuRFs-absent patients had similar MACCE rates when compared with those with one or more SMuRFs at 5 years. This suggests that effective intervention strategies and updated risk assessment models are urgently needed in the SMuRFs-absent cohort.

Background: Respiratory distress is the main reason for the admission of infants to the neonatal intensive care unit (NICU). Rapid identification of the causes of respiratory distress and selection of appropriate and effective treatment strategies are important to optimise favourable short- and long-term patient outcomes. Lung ultrasound (LUS) technology has become increasingly important in this field. According to the scientific literature, LUS has high sensitivity (92-99%) and specificity (95-97%) in diagnosing neonatal respiratory distress syndrome. This diagnostic power helps guide timely interventions, such as surfactant therapy and mechanical ventilation.

Methods: Our objective was to outline consensus guidelines among an international panel of experts on the use of LUS to support the decision-making process in managing respiratory distress in the NICU. We used a three-round Delphi process. In each Delphi round, 28 panellists rated their level of agreement with each statement using a four-point Likert scale.

Results: In round 1, the panellists reviewed 30 initially proposed statements. In rounds 2 and 3, the statements were redeveloped based on the reviewers' comments, leading to the final approval of 18 statements. Among the 18 consensus statements, grade A was assigned a value of 10, grade B was assigned a value of 7, and grade C was assigned a value of 1.

Conclusions: A panel of experts agreed on 18 statements regarding managing infants with respiratory distress. Using LUS may help design future interventional studies and improve the benchmarking of respiratory care outcomes.

Background: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation with a high short-term mortality rate. Syndecan-1 (SDC-1) can independently predict the 90-day mortality of patients with septic shock. However, the role of SDC-1 in ACLF remains unknown.

Methods: In this study, serum SDC-1 levels were examined in 2 cohorts, which included 174 ACLF patients. And a mouse ACLF model induced by tetrachloride, lipopolysaccharide, and D-galactosamine was established, to evaluate the effects of sulodexide and heparan sulfate (side chains of SDC-1) on ACLF in vivo.

Results: Baseline serum SDC-1 levels in 101 ACLF patients (847.72, 499.79-1511.37 ng/ml) were significantly higher than in healthy controls (33.58, 27.08-43.34 ng/ml) (P < 0.0001). The baseline SDC-1 levels of patients who died or accepted a liver transplantation within 90 days were markedly higher than those of patients who survived (P < 0.05). A novel prognostic model (UIAS) based on upper gastrointestinal bleeding, INR, age, and SDC-1 was developed. The AUROC of the UIAS score for 28-day deterioration in ACLF patients was 0.884, indicating an obviously greater predictive performance for the outcomes of ACLF than those of the Child-Pugh (AUROC = 0.646), MELD (AUROC = 0.713), and COSSH-ACLF II scores (AUROC = 0.713). Moreover, we found that heparan sulfate and sulodexide could increase the expression of SDC-1 and attenuate liver injury, by promoting liver regeneration and inhibiting cell apoptosis through the activation of JAK1/STAT3 signalling.

Conclusions: Collectively, our findings suggest that SDC-1 represents a potential prognostic and therapeutic target for ACLF and should be further investigated.

Background: This study explored whether the prospective associations between muscle strength and incident type 2 diabetes (T2D) differ by varying levels of genetic susceptibility to T2D.

Methods: This study included 141,848 white British individuals from the UK Biobank. Muscle strength was expressed as the relative value of grip strength (measured by a hand dynamometer) divided by fat-free mass (measured via bioelectrical impedance analysis). Three categories of muscle strength (low, medium and high) were generated based on the sex- and age-specific tertiles. Genetic risk of T2D was estimated using a weighted polygenic risk score based on 138 independent single-nucleotide polymorphisms for T2D. During a median 7.4-year follow-up, 4,743 incident T2D cases were accrued. Cox regression with age as the underlying timescale was fit.

Results: High muscle strength was associated with a 44% lower hazard of T2D (HR:0.56, 95%CI:0.52-0.60), compared with low muscle strength, after adjustment for genetic risk of T2D. The inverse association between muscle strength and incident T2D was weaker in individuals with high genetic susceptibility. There was evidence of interaction between muscle strength and genetic susceptibility to T2D (p-additive = 0.010, p-multiplicative = 0.046). The estimated 8-year absolute risk of T2D was lower for high genetic risk-high muscle strength (2.47%), compared with low (2.89%) or medium (4.00%) genetic risk combined with low muscle strength.

Conclusions: Higher muscle strength was associated with lower relative risk of developing T2D, irrespective of genetic susceptibility to T2D, while such association was weaker in the high genetic risk group. Individuals at high genetic risk of T2D but with high muscle strength may have a lower 8-year absolute risk of developing T2D, compared with those at low or medium genetic risk but with low muscle strength. Our findings inform future clinical trials to prevent or delay the onset of T2D by implementing muscle-strengthening interventions among individuals of varying levels of genetic susceptibility to T2D, including those with high genetic risk.

Background: Smartphone screen time has risen sharply in recent years. Even though an association between smartphone use and mental health is well documented, it is still unclear whether this is simply a correlation or causality. The aim of this study is to investigate the effects of smartphone screen time reduction on mental health indicators.

Methods: This non-blinded, parallel randomized controlled trial (RCT) was performed to investigate the impact of a 3-week screen time reduction to ≤ 2 h/d in healthy students on stress (PSQ), well-being (WHO-5), depressive symptoms (PHQ-9), and sleep quality (ISI) at baseline (t0), post-intervention (t1), and at follow-up (t2 = 6 weeks after t1). For the intention to treat analysis, repeated measures ANOVAs and post-hoc tests (for time as well as group differences) were performed and effect sizes were presented as partial eta squared (η² = time × group) and group-mean differences.

Results: In total, 111 out of 125 healthy students (70 females; mean age = 22.68 ± 2.6 years; mean screen time = 276 ± 115.1 min/day) were randomly assigned to intervention-(n = 58; 3 weeks of screen time reduction to ≤ 2 h/day) or control group (n = 53). Although no differences were observed at baseline (t0), significant post-intervention (t1) effects of small to medium size were observed on well-being (η² = .053), depressive symptoms (η² = .109), sleep quality (η² = .048), and stress (η² = .085). Significant group differences (p ≤ .05) were found post-intervention (t1) for depressive symptoms (Mean Difference (MD) = 2.11, Standard Error (SE) = 0.63, 95% Confidence Interval (CI) [0.87, 3.36]), sleep quality (MD = 2.59, SE = 0.97, 95% CI [0.66, 4.51]), well-being (MD = -1.54, SE = 0.68, 95% CI [.-2.89, -0.18]), and stress (MD = 6.91, SE = 3.48, 95% CI [0.01, 13.81]). Screen time increased rapidly after the intervention and at follow-up the values were once again approaching the initial level.

Conclusions: The study highlights mental health improvements through smartphone screen time reduction. Three weeks of screen time reduction showed small to medium effect sizes on depressive symptoms, stress, sleep quality, and well-being. The results suggest a causal relationship, rather than a merely correlative one, between daily smartphone screen time and mental health.

Trial registration: The study was preregistered on Open Science Framework (trial registration number: A9K76) on November 8, 2023.

Background: Hypothyroidism in pregnancy is associated with obstetrical and fetal complications, such as prematurity. However, whether its management by levothyroxine affects the risk of prematurity is not yet clear.

Methods: We conducted a cohort study within the Quebec Pregnancy Cohort including pregnancies with hypothyroidism from January 1, 1998, through December 31, 2015. In primary analyses, we considered levothyroxine exposure (yes/no), total duration, mean daily dose, and cumulative dose in the 2-months period before delivery (for preterm deliveries) or before 37th weeks' gestation (for term deliveries). Secondly, levothyroxine dosage before and after the beginning of the second trimester were compared, and pregnancies were categorized in increased or constant dosage groups. Lastly, levothyroxine was also defined as a time-varying daily exposure from the 14th weeks' gestation until delivery or 37th weeks' gestation, whichever came first. Prematurity was defined as giving birth before the 37th weeks' gestation. Term pregnancies were censored at 37th weeks' gestation because they were no longer at risk of prematurity afterwards. Generalized estimating equations and Cox-proportional hazard models, adjusted for potential confounders, were used to calculate adjusted relative risks (aRRs) and hazard ratios (aHRs), respectively.

Results: A total of 9489 pregnant individuals with hypothyroidism were included. Among them, 6667 (70.3%) were exposed to levothyroxine in the 2-months time-window. Adjusting for potential confounders, no association was observed between levothyroxine exposure (aRR, 0.98; 95% CI, 0.81-1.20) and the risk of prematurity compared to non-exposed. Also, no association between levothyroxine duration (> 30 days: aRR, 0.99; 95% CI, 0.81-1.21), cumulative dose (> 7125 mcg: aRR, 0.97; 95% CI, 0.73-1.27) or mean daily dose (> 125 mcg/day: aRR, 0.95; 95% CI, 0.72-1.26) and the risk of prematurity was observed, compared to non-exposure. Finally, the risk of prematurity did not vary between increased or constant dosage groups (aRR, 0.84; 95% CI, 0.67-1.05). Similarly, time-varying exposure analysis did not show any association between levothyroxine exposure and prematurity risk (aHR, 0.95; 95% CI, 0.81-1.11).

Conclusions: Levothyroxine supplementation in late pregnancy among individuals with hypothyroidism was not associated with prematurity risk. Our findings support the safe use of levothyroxine during gestation and might be useful for the current guidelines.

Background: Duodenal adenocarcinoma (DA) has a high recurrence rate, making the prediction of recurrence after surgery critically important.

Methods: Our objective is to develop a machine learning-based model to predict the postoperative recurrence of DA. We conducted a multicenter, retrospective cohort study in China. 1830 patients with DA who underwent radical surgery between 2012 and 2023 were included. Wrapper methods were used to select optimal predictors by ten machine learning learners. Subsequently, these ten learners were utilized for model development. The model's performance was validated using three separate cohorts, and assessed by the concordance index (C-index), time-dependent calibration curve, time-dependent receiver operating characteristic curves, and decision curve analysis.

Results: After selecting predictors, ten feature subsets were identified. And ten feature subsets were combined with the ten machine learning learners in a permutation, resulting in the development of 100 predictive models, and the Penalized Regression + Accelerated Oblique Random Survival Forest model (PAM) exhibited the best predictive performance. The C-index for PAM was 0.882 (95% CI 0.860-0.886) in the training cohort, 0.747 (95% CI 0.683-0.798) in the validation cohort 1, 0.736 (95% CI 0.649-0.792) in the validation cohort 2, and 0.734 (95% CI 0.674-0.791) in the validation cohort 3. A publicly accessible web tool was developed for the PAM.

Conclusions: The PAM has the potential to identify postoperative recurrence in DA patients. This can assist clinicians in assessing the severity of the disease, facilitating patient follow-up, and aiding in the formulation of adjuvant treatment strategies.