Associations of asthma and psychiatric comorbidities on suicide mortality among community adolescents: A 20-year cohort study.

BACKGROUND: The role of psychiatric comorbidity as a confounder between asthma and subsequent suicide mortality in adolescents remained unclarified. METHODS: This study used a 20-year community-based cohort in Taiwan. Adolescents aged 11 to 16 from 123 schools were classified into three subgroups: current asthma (symptoms present in the past year), previous asthma (history of asthma but no symptoms in the past year), and no asthma. The mortality and medical care utilizations until the end of follow-up in 2015 were obtained. Cox proportional hazard and competing risk models were performed. Different adjustment models that included covariates of demographic status, allergy, cigarette smoking, psychiatric diagnoses, alcohol or substance misuse, and attention deficit and hyperactivity disorders were compared. RESULTS: During the follow-up, 285 out of 153,526 participants died from suicide. The crude hazard ratio for suicide was 1.95 (95 % CI=1.46∼2.60) in the current asthma subgroup and 2.01 (1.36∼2.97) in the previous asthma subgroup. The adjusted hazard ratios (aHR) attenuated to 1.67 (1.25∼2.24) and 1.72 (1.16∼2.54) respectively after further adjustment for all mental disorders, ADHD, substance, and alcohol use disorders. CONCLUSIONS: Our adjustment analyses stratified by different models highlight evidence of asthma as an independent risk factor that predicts suicide among adolescents. Depression and mental disorders were potential confounders and identifications of asthma and psychiatric disorders might help decrease suicide risk.

Patient Preference for Catheter-Based Hypertension Therapy and Subgroup Analysis: A Pilot Study Based on Taiwan Consensus on Renal Denervation.

Ojective: To understand hypertensive patients' preference for catheter-based therapy to manage hypertension. Methods: Survey data regarding catheter-based therapies performed at MacKay Memorial Hospital in Taipei, Taiwan, between 2019-2020 were analyzed. The questionnaire was circulated either in the clinics or during admission. A total of 46 patients completed the questionnaire. Results: A total of 46 patients (mean age 53.4 ± 13.5 years, 78.3% male) completed the questionnaire. In subgroup analysis according to Taiwan renal denervation (RDN) consensus, patients with drug intolerance (61.8% vs. 31.3%, p = 0.02) were more likely to choose RDN. Moreover, although lacking statistical significance, it is noteworthy that numerically more of the resistant hypertension group (55.6% vs. 28.0%, p = 0.09) and non-adherence group (38.5% vs. 30.0%, p = 0.20) were willing to undergo RDN. Conversely, numerically fewer patients with hypertension-mediated organ damage accepted RDN compared to those who did not have hypertension-mediated organ damage (26.1% vs. 43.5%, p = 0.21), although this disparity did not reach statistical significance. Conclusions: Approximately one-third of the patients expressed interest in considering RDN in this study. The most influential factor in patients' preference for RDN was drug intolerance due to medication-related side effects.

Lacticaseibacillus paracasei PS23 increases ghrelin levels and modulates microbiota composition: a post-hoc analysis of a randomized controlled study.

Muscle damage can occur due to excessive, high-intensity, or inappropriate exercise. It is crucial for athletes and sports enthusiasts to have access to ways that expedite their recovery and alleviate discomfort. Our previous clinical trial demonstrated the anti-inflammatory and muscle damage-ameliorating properties of Lacticaseibacillus paracasei PS23 (PS23), prompting us to further explore the role of this probiotic in muscle damage recovery. This post-hoc analysis of a randomized controlled study investigated potential mediators between the intake of PS23 and the prevention of strength loss after muscle damage. We recruited 105 students from a sports university who had participated in the previously published clinical trial. These participants were randomly allocated to three groups, receiving capsuled live PS23 (L-PS23), heat-treated PS23 (HT-PS23), or a placebo over a period of six weeks. Baseline and endpoint measurements were taken for the levels of circulating ghrelin and other blood markers, stress, mood, quality of life, and the fecal microbiota. A significant increase in ghrelin levels was recorded in the L-PS23 group compared to the other groups. Additionally, both L-PS23 and HT-PS23 interventions led to positive shifts in the gut microbiota composition, particularly in elevated Lacticaseibacillus, Blautia, and Lactobacillus populations. The abundance of these bacteria was positively correlated with exercise performance and inversely correlated with inflammatory markers. In conclusion, dietary supplementation with PS23 may enhance exercise performance and influence muscle damage by increasing ghrelin levels and modulating the gut microbiota composition. Further clarification of the possible mechanisms and clinical implications is required.

Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring.

Prenatal antidepressant exposure has been reported to be associated with adverse neurodevelopmental outcomes, yet studies considering confounding factors in Asian populations are lacking. This study utilized a nationwide data base in Taiwan, enrolling all liveborn children registered in the National Health Insurance system between 2004 and 2016. Subjects were divided into two groups: antidepressant-exposed (n = 55,707)) and antidepressant-unexposed group (n = 2,245,689). The effect of antidepressant exposure during different trimesters on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) was examined. Sibling controls and parallel comparisons by paternal exposure status were treated as negative controls. Additional sensitivity analyses were conducted to examine the effects of antidepressant exposure before and after pregnancy. Prenatal antidepressant exposure was associated with increased risks of ASD and ADHD in population-wide and adjusted analysis. However when comparing antidepressant-exposed children with their unexposed siblings, no differences were found for ASD (Hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.76-1.42 in first trimester; HR: 0.96, 95% CI 0.62-1.50 in second trimester; HR: 0.69, 95% CI 0.32-1.48 in third trimester) and ADHD (HR: 0.98, 95%CI 0.84-1.15 in first trimester; HR: 0.91, 95% CI 0.73-1.14 in second trimester; HR: 0.79, 95% CI 0.54-1.16 in third trimester). Increased risks for ASD and ADHD were also noted in paternal control, before and after pregnancy analyses. These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors.

The associates of anxiety among lung cancer patients: Dehydroepiandrosterone (DHEA) as a potential biomarker.

OBJECTIVE: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients. METHODS: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted. RESULTS: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (ß = 0.332, p < 0.001) and fatigue (ß = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA ß = 0.319, p = 0.004; PTSS ß = 0.396, p = 0.001; fatigue ß = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA ß = 0.346, p = 0.001; PTSS ß = 0.407, p = 0.001; fatigue ß = 0.326, p = 0.011). CONCLUSIONS: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.

PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Aims: Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods: Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results: The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion: The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

Stool microbiota analysis for abundance of genus Klebsiella among adults and children in endemic area for community Klebsiella pneumoniae infection.

BACKGROUND: Invasive Klebsiella pneumoniae syndrome is a significant endemic disease in Taiwan. Intestinal colonization of virulent clones that cause this phenomenon has been demonstrated in asymptomatic adults. Comparisons of healthy adults and children with stool K. pneumoniae colonization have rarely been reported. We aimed to evaluate the frequency and abundance of K. pneumoniae in the stool of adults and children by stool microbiota analysis. METHODS: Healthy volunteers and their children without antibiotic exposure within 3 months were recruited in a Taiwanese medical center. Stool samples were sent for gut microbiota analysis, using amplification of V3-V4 hypervariable regions of 16sRNA followed by high-throughput sequence. Rectal/stool swabs were sent for K. pneumoniae culture and identification by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: Fifty-five adults with a mean age of 46.9 years (range, 23.1-72.1 years) and 20 children with a mean age of 2.3 years (range, 0.9-5.8) were enrolled, and 29 adults and 6 children had positive K. pneumoniae swabs. Children had lower microbiota diversity than adults, including higher abundance of phylum Actinobacteria and Proteobacteria, and lower Bacteriodetes. For genus comparison, higher abundance of Escherichia, Streptococcus, Enterococcus and Bifidobacterium were found in children, but the composite abundance of Klebsiella in adults (median: 0.0156, range: 0-0.031) and in children (median: 0.0067, range: 0-0.043) were similar. Klebsiella abundance was significantly higher in participants with positive swabs (p < 0.0001). Klebsiella-positive swabs were strongly negatively correlated with Enterobacter spp. (p < 0.0001), but no known demographic factors correlated with Klebsiella-positive swabs. CONCLUSION: Klebsiella species are present in young children, and the abundance is similar in adults and children. Positive swabs correlate strongly with higher abundance in microbiota analysis.

Excess Mortality in Individuals with Autism Spectrum Disorder: A Population-Based Cohort Study.

Purpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored. Patients and Methods: Using Taiwan's National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk. Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54-1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID. Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.

Psychiatric disorders in term-born children with marginally low birth weight: a population-based study.

BACKGROUND: Marginally low birth weight (MLBW) is defined as a birth weight of 2000 ~ 2499 g. Inconsistent findings have been reported on whether children with low birth weight had higher rates of neurological, attention, or cognitive symptoms. No studies have explored the occurrence of clinically diagnosed psychiatric disorders in term- born MLBW infants. We aimed to investigate the risk of subsequent psychiatric disorders in term-born children with MLBW. METHODS: This is a nationwide retrospective cohort study, by analysing the data from Taiwan's National Health Insurance Research Database from 2008 to 2018. The study population includes propensity-score-matched term-born infants with MLBW and those without MLBW (birth weight ≥ 2500 g). Cox proportional hazard analysis was used after adjustment for potential demographic and perinatal comorbidity confounders. Incidence rates and hazard ratios (HR) of 11 psychiatric clinical diagnoses were evaluated. RESULTS: A total of 53,276 term-born MLBW infants and 1,323,930 term-born infants without MLBW were included in the study. After propensity score matching for demographic variables and perinatal comorbidities, we determined that the term-born MLBW infants (n = 50,060) were more likely to have attention deficit and hyperactivity disorder (HR = 1.26, 95% confidence interval (CI) [1.20, 1.33]), autism spectrum disorder (HR = 1.26, 95% CI [1.14, 1.40]), conduct disorder (HR = 1.25, 95% CI [1.03, 1.51]), emotional disturbance (HR: = 1.13, 95% CI [1.02, 1.26]), or specific developmental delays (HR = 1.38, 95% CI [1.33, 1.43]) than term-born infants without MLBW (n = 50,060). CONCLUSION: MLBW was significantly associated with the risk of subsequent psychiatric disorder development among term-born infants. The study findings demonstrate that further attention to mental health and neurodevelopment issues may be necessary in term-born children with MLBW. However, possibilities of misclassification in exposures or outcomes, and risks of residual and unmeasured confounding should be concerned when interpreting our data.

Potential Benefits of Integrin αvß3 Antagonists in a Mouse Model of Experimental Dry Eye.

PURPOSE: The purpose of this study was to extensively evaluate the efficacy of integrin αvß3 antagonists for the treatment of experimental dry eye (EDE). METHODS: Vitronectin, an αvß3 ligand, was used to induce tumor necrosis factor-α gene expression in human THP-1 macrophages. To induce EDE, C57BL/6 mice were housed in a low-humidity controlled environment chamber and injected subcutaneously with scopolamine for 7 days. Subsequently, αvß3 antagonists, including RGDfD, c(RGDfD), c(RGDiD), c(RGDfK), ATN-161, SB273005, and cilengitide, were administered topically to EDE animals under controlled environment chamber conditions. Corneal epithelial damage in EDE was assessed by fluorescein staining. The density of conjunctival goblet cells and secretion of tears was measured by period acid-Schiff staining and phenol red-impregnated cotton threads, respectively. Inflammation markers, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-17A, and metalloproteinase (MMP)-9, in the pooled cornea and conjunctiva tissues were examined by real-time polymerase chain reaction. RESULTS: The inhibitory effects of αvß3 antagonists on the vitronectin-induced tumor necrosis factor-α gene expression and integrin-mediated inflammatory signaling were validated in THP-1 macrophages. αvß3 antagonists ameliorated the impairment of the corneal epithelial barrier with varying therapeutic efficacies, compared with vehicle-treated mice. c(RGDfD) and c(RGDiD) significantly protected against goblet cell loss, tear reduction, and proinflammatory gene expression in EDE. CONCLUSIONS: Topical applications of αvß3 antagonists yield therapeutic benefits in EDE by promoting corneal epithelial defect healing and reducing inflammation. Antagonistic targeting αvß3 may be a novel promising strategy to treat patients with dry eye disease.

Short peptides derived from pigment epithelium-derived factor attenuate retinal ischemia reperfusion injury through inhibition of apoptosis and inflammatory response in rats.

Pigment epithelium-derived factor (PEDF) is widely recognized as a neuroprotective factor expressed in the retina and has shown therapeutic potential in several retinal diseases. Our study aimed to identify the neuroprotective fragment in PEDF and investigate its protective activity in retinas under ischemia-reperfusion (IR) condition. We synthesized a series of shorter synthetic peptides, 6-mer (Ser93-Gln98) and its d-form variant (6 dS) derived from the 44-mer (Val78-Thr121; a PEDF neurotrophic fragment), to determine their cytoprotective activity in IR injury, which was induced in rat retinas by injection of saline into the anterior chamber to increase the intraocular pressure (IOP) followed by reperfusion. We found the cytoprotective effect of 6-mer on glutamate-treated Neuro-2a cells and tert-butyl hydroperoxide (tBHP)-treated 661W cells were 2.6-fold and 1.5-fold higher than the 44-mer, respectively. The cytoprotective effect was blocked by a chemical inhibitor atglistatin and blocking antibody targeting PEDF receptor (PEDF-R). IR induced several impairments in retina, including cell apoptosis, activation of microglia/macroglia, degeneration of retinal capillaries, reduction in electroretinography (ERG) amplitudes, and retinal atrophy. Such IR injuries were ameliorated by treatment with 6-mer and 6 dS eye drops. Also, the neuroprotective activity of 6-mer and 6 dS in ischemic retinas were dramatically reversed by atglistatin preconditioning. Taken together, our data demonstrate smallest neuroprotective fragment of PEDF has potential to treat retinal degeneration-related diseases.

The Effect of the Knowledge, Skills, and Attitudes from Nurse Training Using In Situ Simulation in an Intensive Care Unit.

BACKGROUND: In situ simulation is the practice of using simulated scenarios to improve skill implementation, train critical thinking and problem-solving abilities, and enhance self-efficacy. This study aimed to enhance nursing knowledge, skills, and attitudes toward clinical work by applying in situ simulation training to improve the healthcare of critically ill patients. METHODS: This study was conducted from a medical center in northern Taiwan and included 86 trainees who received intensive care training courses from 1 June 2017 to 31 May 2019. The self-report knowledge assessment, empathetic self-efficacy scale, skill assessment, and attitudes of instructors before and after training were collected. The statistical analysis used the Wilcoxon test for knowledge and attitudes, and chi-square tests were used for skills to evaluate the learning effect. RESULTS: The results showed a statistically significant improvement in knowledge, skills, attitudes, and empathy in nursing care. CONCLUSIONS: In situ simulation learning can be an accepted method for nursing skills in the intensive care unit. Through this study, we understood that the in situ simulation method was beneficial to nurses' care and care thinking processes. It is worth developing and evaluating integrated simulation education to enhance learning, change behavior, and promote holistic care in the nursing field.

Antiosteoporosis medications and cardiovascular disease: a population-based nationwide nested case-control study.

Purpose: Patients with osteoporosis are at an increased risk of cardiovascular disease (CVD). Several antiosteoporosis medications have been demonstrated with the benefit of preventing osteoporosis. Our aim is to assess the CVD risks associated with antiosteoporosis medications using the National Health Insurance Research Database in Taiwan between 2000 and 2016. Methods: Among 41,102 patients of 40+ years old with newly diagnosed osteoporosis, 69.1% (N = 28,387) of patients were included in the user cohort of antiosteoporosis medicines, of whom 13, 472 developed CVD by the end of 2016, while 14,915 did not. Using the nested case-control analysis in the user cohort (88.0% women and 77.4% elderly), we applied conditional logistic regression to estimate odds ratios (ORs) of eight types of CVD for the users of denosumab, bisphosphonate, teriparatide, and hormone replacement therapy (HRT). Results: The adjusted ORs of overall CVDs were 0.13 (95% CI: 0.12-0.15) for denosumab users, 0.52 (95% CI: 0.45-0.61) for teriparatide users, and 0.80 (95% CI: 0.76-0.85) for bisphosphonate users. The HRT users were at higher odds of coronary artery and peripheral artery diseases, heart failure, pulmonary embolism, and deep vein thrombosis. Conclusion: Denosumab, teriparatide, and bisphosphonate may have more protective effects against CVD than hormone therapy. Physicians may take subsequent cardiovascular risks into account when choosing an adequate antiosteoporosis medication for patients with osteoporosis.

Prevalence of bacillary layer detachment in diabetic macular edema and response to 3 anti-vascular endothelial growth factor treatment.

Spectral-domain optical coherence tomography is widely used in maculopathy, including diabetic macular edema (DME). Bacillary layer detachment (BALAD) is a novel optical coherence tomography finding, defined as the separation of the intraretinal layer between the inner segment myoids and ellipsoids. A total of 161 treatment-naïve eyes with centrally involved DME that underwent 3 monthly loading doses of anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections were enrolled and analyzed retrospectively. BALAD was found in 6.2% of eyes with concurrent subretinal fluid (SRF). All eyes were divided into 3 groups: no either group had neither SRF or BALAD; the SRF only group had SRF but no BALAD; and the BALAD group had both SRF and BALAD. A significant increase in baseline central foveal thickness (CFT) in the BALAD group was observed (no either vs SRF only vs BALAD, baseline CFT: 387.6 ±â€…74.29 vs 440.6 ±â€…106.79 vs 642.0 ±â€…188.86; P < .01). Total resolution of BALAD was noted after anti-VEGF therapy, along with a significant decrease in CFT in all groups (CFT decrease: 82.4 ±â€…87.07 vs 187.6 ±â€…138.88 vs 252.1 ±â€…127.63; P < .01). Eyes with BALAD tended to have the worst baseline visual acuity (baseline logarithm of the minimum angle of resolution VA: 0.76 ±â€…0.353 vs 0.63 ±â€…0.303 vs 1.15 ±â€…0.300; P = .046) but showed the most improvement after treatment (logarithm of the minimum angle of resolution VA change: -0.14 ±â€…0.235 vs -0.22 ±â€…0.275 vs -0.27 ±â€…0.250; P = .079). After resolution of BALAD, all eyes in the BALAD group exhibited ellipsoid zone and/or interdigitation zone disruption corresponding to the BALAD area. BALAD is a novel optical coherence tomography finding associated with a spectrum of diseases including DME. With anti-VEGF therapy, total resolution of BALAD and a significant decrease in CFT can be obtained. However, ellipsoid zone/interdigitation zone disruption tended to develop.

Reduction in the Incidence Density of Pressure Injuries in Intensive Care Units after Advance Preventive Protocols.

(1) Background: Patients who are critically ill or undergo major surgery are admitted to intensive care units (ICUs). Prolonged immobilization is the most likely cause of pressure injuries (PrIs) in the ICU. Previous studies of Western populations found that effective protocols could reduce the incidence of PrIs, and the efficacy of systemic targeted intervention protocols in preventing PrIs in the Chinese population needs to be surveyed. (2) Methods: We reviewed cases of PrIs in the ICUs of Taipei Veterans General Hospital from 2014 to 2019. The ICU nurses at the hospital began to implement targeted interventions in January 2017. The incidence density of PrIs was calculated by dividing the number of PrIs by person days of hospitalizations in the pre-bundle (2014-2016) and post-bundle (2017-2019) stages. Poisson regression was performed to compare the trend of incidence densities. (3) Results: The incidence density of PrIs was 9.37/1000 person days during the pre-bundle stage and 1.85/1000 person days during the post-bundle stage (p < 0.001). The relative risk (RR) was 0.197 (95% confidence interval: 0.149-0.26). The incidence densities of iatrogenic PrIs and non-iatrogenic PrIs decreased as the RRs decreased. (4) Conclusions: Targeted interventions could significantly reduce the incidence of PrIs. Healthcare providers must follow the bundle care protocol for PrI prevention to improve the quality of healthcare and promote patient health.

Substance use before or during pregnancy and the risk of child mortality, perinatal morbidities and congenital anomalies.

AIMS: We aimed to investigate child mortality, perinatal morbidities and congenital anomalies born by women with substance misuse during or before pregnancy (DP or BP). METHODS: Taiwan Birth Registration from 2004 to 2014 linking Integrated Illicit Drug Databases used to include substance misuse participates. Children born by mothers convicted of substance misuse DP or BP were the substance-exposed cohort. Two substance-unexposed comparison cohorts were established: one comparison cohort selected newborns from the rest of the population on a ratio of 1:1 and exact matched by the child's gender, child's birth year, mother's birth year and child's first use of the health insurance card; another comparison cohort matched newborns from exposed and unexposed mothers by their propensity scores calculated from logistic regression. RESULTS: The exposure group included 1776 DP, 1776 BP and 3552 unexposed individuals in exact-matched cohorts. A fourfold increased risk of deaths in children born by mothers exposed to substance during pregnancy was found compared to unexposed group (hazard ratio [HR] = 4.54, 95% confidence interval (CI): 2.07-9.97]. Further multivariate Cox regression models with adjustments and propensity matching substantially attenuated HRs on mortality in the substance-exposed cohort (aHR = 1.62, 95% CI: 1.10-2.39). Raised risks of perinatal morbidities and congenital anomalies were also found. CONCLUSIONS: Increased risks of child mortality, perinatal morbidities or congenital anomalies were found in women with substance use during pregnancy. From estimates before and after adjustments, our results showed that having outpatient visits or medical utilizations during pregnancy were associated with substantially attenuated HRs on mortality in the substance-exposed cohort. Therefore, the excess mortality risk might be partially explained by the lack of relevant antenatal clinical care. Our finding may suggest that the importance of early identification, specific abstinence program and access to appropriate antenatal care might be helpful in reducing newborn mortality. Adequate prevention policies may be formulated.

Substantia nigra nigrosome-1 imaging correlates with the severity of motor symptoms in Parkinson's disease.

BACKGROUND: Nigrosome-1 imaging has been used for assisting the diagnosis of Parkinson's disease (PD). We aimed to examine the diagnostic performance of loss of nigrosome-1 in PD and the correlation between the size of the nigrosome-1 and motor severity of PD. METHODS: We included 237 patients with PD and 165 controls. The motor severity of PD was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and Hoehn-Yahr staging. The 3 or 1.5 Tesla susceptibility-weighted imaging combined with a deep-learning algorithm was applied for detecting the loss and the size of nigrosome-1. Clinical correlations and diagnostic performance of size of nigrosome-1 were also investigated. RESULTS: The mean nigrosome-1 size was significantly smaller in PD patients than in controls (0.06 ± 0.07 cm2 vs. 0.20 ± 0.05 cm2, P < 0.001). The area under the receiver operating characteristic curve (AUC) of the established model showed 0.94 accuracy (95% confidence interval [CI]: 0.87, 1.01, P < 0.01) in differentiating between the PD and control groups. Moreover, the partial loss of nigrosome-1 detected with SWI had an AUC of 0.96 in discriminating early-stage PD from controls (95% CI: 0.88, 1.02, P < 0.001). After adjusting for age, sex, disease duration, and levodopa equivalent daily dose, the estimated size of nigrosome-1 was negatively associated with the UPDRS part III motor score (ρ = -0.433, P < 0.001), but not with Mini-Mental State Examination scores (ρ = 0.006, P = 0.894). CONCLUSIONS: The extent of loss and the size of nigrosome-1 may potentially assist in the diagnosis of PD. Nigrosome-1 size reflects the motor severity of PD.