Which ICD-9 codes were assigned for malignant mesothelioma in the mortality data in the United States before the ICD-10 was introduced?

BACKGROUND: Malignant mesothelioma (MM) is rare and fatal; survival in most cases is only about one year. Mortality rate is, therefore, a good proxy measure of incidence rate. However, the specific International Classification of Diseases (ICD) code for MM was not available until the Tenth Revision ICD (ICD-10). Little is known on which Ninth Revision ICD (ICD-9) codes were assigned for MM in the ICD-9 era. METHODS: We used a 1996 double-coded mortality file compiled by the National Center for Health Statistics to calculate the detection rate (DR) and confirmation rate (CR) of selected ICD-9 codes. RESULTS: Of 2386 decedents whose underlying cause of death was MM (ICD-10 code C45), the DR (deaths) of corresponding ICD-9 code was 57% (1365) for code 199 "malignant neoplasm without specification of site;" 19% (448) for code 162.9 "malignant neoplasm of trachea, bronchus, and lung, unspecified;" 13% (310) for code 163 "malignant neoplasm of pleura;" and 11% (271) for other codes. The CR (deaths) for the aforementioned three ICD-9 codes were 4.0% (1365/33,942), 0.3% (448/150,342), and 70.8% (310/438), respectively. CONCLUSIONS: The three ICD-9 codes (199, 162.9, and 163) were the most commonly used codes for MM and composed nine-tenths of all MM deaths in the years before the ICD-10 was introduced. Using only ICD-9 code 163, the code most often used as the surrogate measure of MM in mortality studies in the ICD-9 era, capture may have been only 13% of all MM deaths in the US, and the estimated number of MM deaths missed in 1996 would be 2086.

Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in Heterozygous Disc1 Mutant Mice, a Putative Prodromal Schizophrenia Animal Model.

Symptoms of schizophrenia (SZ) typically emerge during adolescence to young adulthood, which gives a window before full-blown psychosis for early intervention. Strategies for preventing the conversion from the prodromal phase to the psychotic phase are warranted. Heterozygous (Het) Disc1 mutant mice are considered a prodromal model of SZ, suitable for studying psychotic conversion. We evaluated the preventive effect of chronic N-acetylcysteine (NAC) administration, covering the prenatal era to adulthood, on the reaction following the Amph challenge, which mimics the outbreak or conversion of psychosis, in adult Het Disc1 mice. Biochemical and morphological features were examined in the striatum of NAC-treated mice. Chronic NAC treatment normalized the Amph-induced activity in the Het Disc1 mice. Furthermore, the striatal phenotypes of Het Disc1 mice were rescued by NAC including dopamine receptors, the expression of GSK3s, MSN dendritic impairments, and striatal PV density. The current study demonstrated a potent preventive effect of chronic NAC treatment in Disc1 Het mice on the acute Amph test, which mimics the outbreak of psychosis. Our findings not only support the benefit of NAC as a dietary supplement for SZ prodromes, but also advance our knowledge of striatal dopamine receptors, PV neurons, and GSK3 signaling pathways as therapeutic targets for treating or preventing the pathogenesis of mental disorders.

Voluntary exercise ameliorates synaptic pruning deficits in sleep-deprived adolescent mice.

Adolescence is a critical period for brain development and adequate sleep during this period is essential for physical function and mental health. Emerging evidence has detailed the neurological impacts of sleep insufficiency on adolescents, as was unveiled by our previous study, microglia, one of the crucial contributors to synaptic pruning, is functionally disrupted by lack of sleep. Here, we provided evidence featuring the protective effect and the underlying mechanisms of voluntary exercise (VE) on microglial functions in an adolescent 72 h sleep deprivation (SD) model. We identified that the aberrant hippocampal neuronal activity and impaired short-term memory performance in sleep-deprived mice were prevented by 11 days of VE. VE significantly normalized the SD-induced dendritic spine increment and maintained the microglial phagocytic ability in sleep-deprived mice. Moreover, we found that the amendment of the noradrenergic signal in the central nervous system may explain the preventative effects of VE on the abnormalities of microglial and neuronal functions caused by SD. These data suggested that VE may confer protection to the microglia-mediated synaptic pruning in the sleep-deprived adolescent brains. Therefore, physical exercise could be a beneficial health practice for the adolescents that copes the adverse influence of inevitable sleep insufficiency.

Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a "Two-Hit" Non-Genetic Mouse Model of Schizophrenia.

Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28. After weaning, male offspring were randomly assigned into group-rearing and isolation-rearing groups. In their adulthood, we performed behavioral tests and characterized the histochemical features of their mesocorticolimbic structures. The sociability and anxiety levels were not affected by either manipulation, but synergistic effects of the two hits on stress-coping behavior was observed. Either of the single manipulations caused defects in sensorimotor gating, novel object recognition and spatial memory tests, but the combination of the two hits did not further exacerbate the disabilities. Prenatal infection increased the number of dopaminergic neurons in midbrain, whereas postweaning isolation decreased the GABAergic neurons in cortex. Single manipulation reduced the dendritic complexity and spine densities of neurons in the medial prefrontal cortex (mPFC) and dentate gyrus. Our results support the current perspective that disturbances in brain development during the prenatal or postnatal period influence the structure and function of the brain and together augment the susceptibility to mental disorders, such as schizophrenia.

Pathophysiology of Central Poststroke Pain: Motor Cortex Disinhibition and Its Clinical and Sensory Correlates.

Background and Purpose- Central poststroke pain (CPSP) is a disabling condition in stroke patients, and evidence suggests that altered corticospinal and motor intracortical excitability occurs in neuropathic pain. The objective of this study was to investigate changes in motor cortex excitability and sensorimotor interaction and their correlates with clinical manifestations and alterations in somatosensory systems in CPSP patients. Methods- Fourteen patients with CPSP but no motor weakness were compared with age- and sex-matched healthy controls for motor cortex excitability and sensorimotor interaction assessed by transcranial magnetic stimulation to measure resting motor thresholds, short-interval intracortical inhibition, intracortical facilitation, and afferent inhibitions. The sensory pathway was evaluated by quantitative sensory testing, contact heat evoked potential, and somatosensory evoked potentials. Clinical pain and quality of life were assessed with validated tools. Results- The duration of CPSP was 3.3±3.0 years (ranging 0.5-10 years), and pain significantly impaired quality of life. Compared with the unaffected hemisphere, the stroke hemisphere had higher thermal thresholds, lower contact heat evoked potential amplitudes, and prolonged cortical somatosensory evoked potential latencies. There was no difference in resting motor thresholds between the stroke and unaffected hemisphere or between patients and controls. CPSP patients had a reduction in short-interval intracortical inhibition in the stroke hemisphere compared with that in the unaffected hemispheres of patients and controls. No changes were noted in afferent inhibitions between the stroke and unaffected hemispheres. The short-interval intracortical inhibition of the stroke hemisphere was negatively correlated with self-rated health on a visual analog scale and positively correlated with cortical somatosensory evoked potential latencies. Conclusions- CPSP patients with intact corticospinal tracts showed reduced motor intracortical inhibition in the stroke hemisphere, suggesting defective gamma-aminobutyric acid-ergic inhibition. This disinhibition was associated with impaired quality of life and was related to dorsal column-medial lemniscus pathway dysfunction.

Upcoming epidemic of asbestos-related malignant pleural mesothelioma in Taiwan: A prediction of incidence in the next 30 years.

BACKGROUND/PURPOSE: Globally, asbestos-related diseases (ARDs) keep rising over the coming decades. The epidemic of ARDs will be a burden on public health. We aimed to predict the malignant pleural mesothelioma (MPM) incidence in the next 30 years for Taiwan based on historical asbestos consumption. METHODS: We collected annual data on local asbestos consumption during 1939-2015 and sex-specific incidence of pleural cancer as a proxy for MPM during 1979-2013. We applied Poisson log-linear models to predict future MPM numbers under the assumption that latency periods between asbestos exposure and MPM incidence were between 25 and 45 years. RESULTS: Asbestos consumption reached a peak in the 1980s, with a total of 668 thousand metric tons during 1939-2015. The observed number of MPM incidence increased by 9- and 6-fold in males and females during 1979-2013, with a cumulative number of 907. Given a latency period of 31 years, MPM incidences were expected to peak around 2012-2016 for males and 2016-2020 for females. In 2017-2046, the predicted total number of new MPM might reach 659 cases (95% confidence interval = 579-749); and the male to female ratios ranged from 1.8 to 2.8. CONCLUSION: The MPM epidemic in Taiwan will likely peak in 2012-2020 as a result of local asbestos consumption. Approximately 659 new MPM cases in the next 30 years warrant an urgent need to implement a total asbestos ban and put more resources on a comprehensive surveillance, diagnosis, and follow-up health care system for ARDs.

Prognostic factors and treatment outcomes of malignant pleural mesothelioma in Eastern Asian patients - A Taiwanese study.

BACKGROUND/PURPOSE: There are scarce reports on the prognostic factors and treatment outcomes of patients with malignant pleural mesothelioma (MPM) in Asia. This study aimed to address these matters in a real-world setting. METHODS: Medical records of patients with histologically proven MPM diagnosed between 1977 and 2016 at the National Taiwan University Hospital were reviewed. Variables including age, gender, performance status, asbestos exposure, smoking history, histology subtype, staging, and treatment received were recorded. All patients were followed until death or March 1st, 2017. Survival and prognostic factors were analyzed by the Kaplan-Meir method and the Cox proportional hazard model. RESULTS: A total of 93 patients was identified, including 65 men and 28 women. An increasing trend of MPM cases diagnosed was observed in the past 40 years. Stage I/II disease (HR 0.24, 95% CI 0.13-0.46) and epithelioid histology (HR 0.42, 95% CI 0.23-0.75) were associated with favorable prognosis, whereas age ≥70 years (HR 2.66, 95% CI 1.36-5.22) and ECOG ≥2 (HR 5.03, 95% CI 2.69-9.4) were poor prognostic factors. After adjustment for prognostic factors, surgery in stage I-III MPM (HR 0.36, 95% CI 0.15-0.83) and systemic therapy in stage III/IV disease (HR 0.42, 95% CI 0.19-0.94) conferred a survival benefit. CONCLUSION: This is one of the largest case series of MPM reported in Asia outside of Japan. Prognostic factors in the study population included age, performance status, stage, and histology subtype. Surgery in potentially resectable disease and systemic therapy in advanced MPM confer a survival benefit in Asian patients.

Estimating lifetime medical costs from censored claims data.

Claims databases consisting of routinely collected longitudinal records of medical expenditures are increasingly utilized for estimating expected medical costs of patients with a specific condition. Survival data of the patients of interest are usually highly censored, and observed expenditures are incomplete. In this study, we propose a survival-adjusted estimator for estimating mean lifetime costs, which integrates the product of the survival function and the mean cost function over the lifetime horizon. The survival function is estimated by a new algorithm of rolling extrapolation, aided by external information of age- and sex-matched referents simulated from national vital statistics. The mean cost function is estimated by a weighted average of mean expenditures of patients in a number of months prior to their death, of which the number could be determined by observed costs in their final months, and the weights depend on extrapolated hazards. We evaluate the performance of the proposed approach in comparison with that of a popular method using simulated data under various scenarios and 2 cohorts of intracerebral hemorrhage and ischemic stroke patients with a maximum follow-up of 13 years and conclude that our new method estimates the mean lifetime costs more accurately.

Severe aortic arch calcification predicts mortality in patients undergoing peritoneal dialysis.

BACKGROUND/PURPOSE: Vascular calcification can predict cardiovascular (CV) morbidity and mortality in patients with end-stage renal disease. We evaluated the prevalence, association factors, and outcomes of chest X-ray-detected aortic arch calcification (AoAC) in patients undergoing peritoneal dialysis (PD). METHODS: We included 190 patients undergoing PD (mean age, 52.6 ± 14.3 years) for whom chest radiographs were available. AoAC revealed by chest X-ray was graded from 0 to 3 according to an AoAC score (AoACS). Multiple regression analyses were used to determine the factors associated with AoACS. After adjusting for age, sex, PD duration, diabetes mellitus, mean blood pressure, and history of CV disease, the association between AoAC grading and mortality were assessed using the Kaplan-Meier curve and Cox proportional hazard model. RESULTS: Age (p < 0.001), PD duration (p = 0.004), history of CV disease (p < 0.001), and renal Kt/V (p = 0.031) were associated with AoACS. After a mean follow-up of 55.1 ± 32.1 months, patients with Grade 2 (p = 0.011) or Grade 3 (p < 0.001) AoAC had higher all-cause mortality than patients with Grade 0 AoAC. In addition, patients with Grades 2 and 3 AoAC had higher CV-related mortality than those with Grades 0 and 1 AoAC (p = 0.013). Grade 2 [hazard ratio (HR) = 2.736; 95% confidence interval (CI), 1.038-7.211; p = 0.042] and Grade 3 AoAC (HR = 3.289; 95% CI, 1.156-9.359; p = 0.026) remained associated with all-cause mortality after adjustment. Similarly, Grades 2 and 3 AoAC (HR = 36.05; 95% CI, 3.494-372; p = 0.026) significantly correlated with CV mortality after adjustment. CONCLUSION: In patients undergoing PD, CXR-detected severe AoAC was an independent risk factor for all-cause and CV mortalities.

Health-related quality of life in patients with Barrett's esophagus.

BACKGROUND: Gastroesophageal reflux disease (GERD) has become a major health problem globally, affecting patients' health-related quality of life (HRQOL). Barrett's esophagus (BE) is a precancerous lesion associated with GERD. BE patients might not only suffer from HRQOL losses by GERD but also face psychological distress due to the increased risk of developing cancer. However, the majority of patients in Asia have shorter BE segment which is different from the West. This study aimed to determine whether the HRQOL in BE patients were worse than in healthy referents in Taiwan. METHODS: Patients who received referral esophagogastroduodenoscopy for various symptoms were evaluated for the existence of BE. Lesions were judged as endoscopically suspected esophageal metaplasia (ESEM) if they showed morphological resemblances to BE by endoscopy. The diagnosis of BE was confirmed by histology with intestinal metaplasia or gastric metaplasia based on the Montreal definition. The World Health Organization Quality of Life (WHOQOL-BREF) was administered to BE patients before treatment. For each BE patient, we selected 2 age-, sex-, educational background and municipality-matched healthy referents, sampled by simple randomization method from a national survey in Taiwan. Multiple linear regression models were constructed to control the potential confounders. RESULTS: A total of 84 patients diagnosed with BE were enrolled as BE group and then compared with 168 healthy referents. The BE group had significantly lower WHOQOL-BREF scores than those of healthy referents in the physical domain (P < 0.05) but higher scores in the environment domain (P < 0.05). In the physical domain, the BE group had significantly lower scores in various facets, including pain, discomfort, sleep and rest and dependence on medications or treatments. There was no significant difference in social and psychological domains between the BE group and healthy referents. CONCLUSIONS: BE patients suffer from poor sleep and rest and high dependence on medications, which significantly reduce their quality of life. Individual facets of each domain warrants a better clinical healthcare to improve quality of life of BE patients.

Quality of life and its determinants for heroin addicts receiving a methadone maintenance program: Comparison with matched referents from the general population.

BACKGROUND/PURPOSE: Quality of life (QoL) is found to be lower in heroin addicts; however, few studies examine detailed QoL performance and related factors in heroin patients attending a methadone maintenance treatment program (MMTP). The study thus aimed to explore QoL and its determinants for publicly-funded and self-paid patients attending an MMTP. METHODS: Participants were recruited in Jianan Psychiatric Center, Tainan, Taiwan, during their first clinic visit for the MMTP. Age-, sex-, education-, and municipality-matched referents were collected from the 2001 Taiwan National Health Interview Survey database. The participants had a mean age of 38.29 years [standard deviation (SD) = 7.65 years] for publicly-funded (n = 129) and 37.97 years (SD = 7.16 years) for self-paid (n = 105) MMTP patients. Matched referents (n = 217) were 37.74 years (SD = 7.44 years). All participants were measured with the brief version of the World Health Organization's Quality of Life (WHOQOL-BREF) assessment. MMTP patients additionally went through tests for the hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV). RESULTS: Both publicly-funded and self-paid MMTP patients had lower QoL scores than their matched counterparts in the physical and psychological domains (p < 0.05) after control for confounding by age, sex, education, and municipality. Detailed individual item analyses showed that publicly-funded MMTP patients had lower scores for almost all items related to the physical, psychological, and social domains as compared to the referents because of HIV infection (p < 0.05). CONCLUSION: To improve the QoL of heroin users coming for MMTP, we recommend that clinicians pay attention to the comorbidity of HIV infection and individual items/facets.

Quality of life in polyneuropathy: association with biomarkers of small fiber impairment.

BACKGROUND: Polyneuropathy presumably lowers quality of life (QoL). However, there is a lack of systematic studies that assess QoL changes and biomarkers of polyneuropathy as determinants of QoL. We aimed to investigate the relationship between every specific aspect of QoL and the clinical parameters used to assess the impairment of motor, sensory (large and small fibers), and autonomic nerves in polyneuropathy. METHODS: Polyneuropathy patients were recruited from September 2013 to March 2014; QoL was assessed using (1) the WHO Quality of Life-BREF (WHOQoL), (2) the European Quality of Life-5 Dimensions, and (3) the Brief Pain Inventory Short Form. Neuropathy examinations included nerve conduction studies, autonomic function tests, quantitative sensory testing (QST), and intraepidermal nerve fiber (IENF) density assessment of skin biopsies. RESULTS: There were 61 polyneuropathy patients (male/female = 38/23, mean age 58.14 ± 12.95 years). Patients had a lower QoL than age-and gender-matched controls in the physical and psychological domains of the WHOQoL. Among the biomarkers for different nerve fiber categories, only the small fiber neuropathy assessments were significantly related to all domains of the WHOQoL. In contrast, the parameters of the large fiber neuropathy were independent of QoL. Patients with abnormal temperature thresholds and a lower IENF density had lower WHOQoL scores compared to patients with normal thresholds and IENF densities. Warm threshold of the foot in QST was linearly correlated with all domains of the WHOQoL. CONCLUSIONS: QoL scores were reduced in polyneuropathy, and biomarkers of small fiber neuropathy, i.e., warm threshold and IENF density were discriminating predictors of QoL.

Disease activity affects all domains of quality of life in patients with rheumatoid arthritis and is modified by disease duration.

OBJECTIVES: This study was conducted to determine how disease activity affects quality of life (QOL) and its interaction with functional impairments, and disease duration in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study enrolled 230 patients with RA from a rheumatology clinic in Taiwan and 227 healthy controls matched according to age, sex, marital status, and education. QOL was measured using the Taiwan version of the short form of the World Health Organisation Quality of Life (WHOQOL-BREF) questionnaire. Activity of RA was assessed by the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28). Functional disability was assessed by the Health Assessment Questionnaire (HAQ). Multiple regression analyses were performed to explore independent effects and interactions among DAS28, HAQ, and duration after controlling demographic factors. RESULTS: A higher HAQ score, longer duration of disease, and higher DAS28 score were independently associated with lower QOL scores. DAS28 score affected most items in all physical, psychological, environment, and social domains after controlling other factors. Besides, patients with longer disease duration showed aggravated scores on many facets of the physical and psychological domains, if their disease activity was elevated. CONCLUSIONS: Disease activity affects QOL of RA patients in all domains. It also aggravates scores in physical and physiological domains among those with a longer duration.

Potential years of life lost (PYLL) caused by asbestos-related diseases in the world.

BACKGROUND: We applied the well-established, but rather under-utilized, indicator of Potential Years of Life Lost (PYLL) to estimate the global burden of mesothelioma and asbestosis. METHODS: We analyzed all deaths caused by mesothelioma and asbestosis that were reported by 82 and 55 countries, respectively, to the World Health Organization (WHO) from 1994 to 2010. RESULTS: The 128,015 and 13,885 persons who died of mesothelioma and asbestosis, potentially lost a total of 2.18 million and 180,000 years of life (PYLL), or, an annual average PYLL of 201,000 years and 17,000 years, respectively. The average PYLL per decedent were 17.0 and 13.0 years for mesothelioma and asbestosis, respectively. CONCLUSIONS: The current burden of asbestos-related diseases (ARDs) in terms of PYLL is substantial. The future burden of ARDs can be eliminated by stopping the use of asbestos.

Sleep Deprivation Induces Dopamine System Maladaptation and Escalated Corticotrophin-Releasing Factor Signaling in Adolescent Mice.

Sleep disruption is highly associated with the pathogenesis and progression of a wild range of psychiatric disorders. Furthermore, appreciable evidence shows that experimental sleep deprivation (SD) on humans and rodents evokes anomalies in the dopaminergic (DA) signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Since adolescence is a vital period for the maturation of the DA system as well as the occurrence of mental disorders, the present studies aimed to investigate the impacts of SD on the DA system of adolescent mice. We found that 72 h SD elicited a hyperdopaminergic status, with increased sensitivity to the novel environment and amphetamine (Amph) challenge. Also, altered neuronal activity and expression of striatal DA receptors were noticed in the SD mice. Moreover, 72 h SD influenced the immune status in the striatum, with reduced microglial phagocytic capacity, primed microglial activation, and neuroinflammation. The abnormal neuronal and microglial activity were putatively provoked by the enhanced corticotrophin-releasing factor (CRF) signaling and sensitivity during the SD period. Together, our findings demonstrated the consequences of SD in adolescents including aberrant neuroendocrine, DA system, and inflammatory status. Sleep insufficiency is a risk factor for the aberration and neuropathology of psychiatric disorders.

Estimation of benefit of prevention of occupational cancer for comparative risk assessment: methods and examples.

OBJECTIVES: To quantify the life years gained and financial savings by preventing a case of occupational cancer. METHODS: The authors retrieved data from the Taiwan Cancer Registry and linked them with the National Mortality Registry to estimate the survival functions for major occupational cancers: lung, pleural mesothelioma, urinary bladder and leukaemia. Assuming a constant excess hazard for each type of cancer, the authors extrapolated lifetime survival functions by the Monte Carlo method. For each patient with cancer, the authors simulated an age- and gender-matched person without cancer based on vital statistics of Taiwan to estimate life expectancy and expected years of life lost (EYLL). By using the reimbursement data from the National Health Insurance Research Database, the authors calculated the average monthly healthcare expenditures, which were summed to estimate the lifetime healthcare expenditures after adjusting for the corresponding monthly survival probability. RESULTS: A total of 51,408, 136, 12,891 and 5285 new cases of lung, pleural mesothelioma, bladder and leukaemia cancers, respectively, were identified during 1997-2005 and followed until the end of 2007. The EYLL was predicted to be 13.7±0.1, 18.9±0.7, 4.7±0.3 and 19.4±0.5 years for these cancers, respectively, and the lifetime healthcare expenditures with a 3% annual discount were predicted to be US$22,359, US$14,900, US$51,987 and US$59,741, respectively. CONCLUSIONS: The burden of these occupational cancers, in terms of EYLL and lifetime healthcare expenditures, was substantial. Such estimates may provide useful empirical evidence for comparative risk assessment that can be applied in health policy-making and clinical decision-making.

Explaining the Invisibility of Asbestos-Related Diseases in the Taiwan Workers' Compensation System.

Occupational asbestos exposure was prevalent in Taiwan, but asbestos-related diseases (ARDs) have rarely been recognized. We conducted in-depth face-to-face interviews with 16 patients with ARDs. All of them had worked in industries known for high asbestos exposure. However, only three patients had filed workers' compensation (WC) claims, and of them, only two patients were approved. Reasons for the low compensation rate of ARDs could be divided into institutional barriers related to the flaws of the WC system and non-institutional barriers related to the knowledge status, causal interpretation, and social situations of individual workers. The Labor Occupational Accident Insurance and Protection Act passed in April 2021 has responded to the under-compensation of occupational diseases. However, the new act's effects toward improving the recognition of ARDs remain questionable. Our findings indicated that additional efforts are needed to remove non-institutional barriers hindering workers' ability to ensure their compensation rights.

Polycystic kidney disease increases the stoke incidence in Taiwan: A retrospective population-based cohort study using National Health Insurance Database.

BACKGROUND: Few studies documented incidence rates of different types of stroke among patients with polycystic kidney disease (PKD). METHODS: We conducted a retrospective cohort study based on the National Health Insurance (NHI) Database of Taiwan. The PKD cohort comprised patients aged≥20 years diagnosed with PKD using inpatient claims from 1998 to 2011, excluding prior stroke. The reference cohort was established by inpatients without PKD using 1:4 frequency-matched with age, gender, and baseline comorbidities. The two cohorts were followed-up until stroke hospitalization, death, withdrawal from the NHI program, or the end of 2012. To account for competing risks of death, we used multivariable competing risks regression models to estimate sub-distribution hazard ratio (SHR) adjusted for age, gender, baseline comorbidities and end stage renal disease. RESULTS: 7837 PKD patients and 31,211 reference subjects were followed up through 2012. A total of 955 cases of stroke were identified in the PKD cohort, including 441 ischemic stroke (IS), 289 intracranial hemorrhage (ICH), 73 subarachnoid hemorrhage (SAH) and 232 other stroke. The incidence rates of overall stroke, IS, ICH, and SAH were 21.3, 10.2, 6.8, and 1.7 per 1000 person-years, respectively. The SHR for overall stroke was 1.39 [95% confidence interval (CI) 1.28-1.50]. SAH had the highest SHR, 4.55 [95% CI 3.26-6.37], followed by ICH (1.84), other stroke (1.24), and IS (1.22). CONCLUSION: This study illustrated the incidence rates of stroke among inpatient of PKD. The PKD patients had a significantly increased risk of all kinds of stroke after adjusting baseline comorbidities.

Impaired response to sleep deprivation in heterozygous Disc1 mutant mice.

OBJECTIVES: Sleep/circadian rhythm disturbances are environmental stress factors that might interact with genetic risk factors and contribute to the pathogenesis of psychiatric disorders. METHODS: In this study, the multiple-platform method was used to induce sleep deprivation (SD). We evaluated the impact of 72-hour SD in behavioural, anatomical, and biochemical aspects in heterozygous Disc1 mutant (Disc1 Het) mice, an animal model of schizophrenia. RESULTS: The sleep pattern and circadian activity were not altered in Disc1 Het mice. Yet, we observed differential responses to SD stress between genotypes. Increased microglial density and reduced neuronal proliferative activity were found in the dentate gyrus, a neurogenic niche, in Het-SD mice. Notably, SD-induced Bdnf mRNA elevations were evident in both WT and Het mice, while only in WT-SD mice did we observe increased BDNF protein expression. Our results suggested an SD-induced physical response featured by the elevation of BDNF protein expression to counteract the harmful influences of SD and sufficient DISC1 is required in this process. CONCLUSIONS: The present study proposes that sleep disturbance could be pathogenic especially in genetically predisposed subjects who fail to cope with the stress. Potential therapeutic strategies for psychiatric disorders targeting the mRNA translation machinery could be considered.